Ligand for members of the frizzled family of seven transmembrane receptors.
Involved in the retrieval of endoplasmic reticulum membrane proteins from the early Golgi compartment.
Belongs to the glycosyl hydrolase 35 family.
Acts as a defensive agent. Recognizes blood group fucosylated oligosaccharides including A, B, H and Lewis B-type antigens. Does not recognize Lewis A antigen and has low affinity for monovalent haptens.
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 1-acyl-sn-glycerol-3-phosphate acyltransferase family.
Belongs to the Rieske iron-sulfur protein family.
The Rieske protein is a high potential 2Fe-2S protein.
Belongs to the autoinducer-2 exporter (AI-2E) (TC 2.A.86) family.
Component of the CSN complex, probably composed of cops1, cops2, cops3, cops4, cops5, cops6, cops7, cops8 and cops9.
Essential 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.
Belongs to the Mediator complex subunit 19 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.
Component of the origin recognition complex (ORC) that binds origins of replication.
Belongs to the apolipoprotein A1/A4/E family.
Lacks conserved residue(s) required for the propagation of feature annotation.
Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.
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.
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 palmitoyl-protein thioesterase family.
Belongs to the protein kinase superfamily.
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.
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.
Belongs to the Mediator complex subunit 1 family.
Cell autonomous antagonist of the canonical Wnt signaling pathway.
May play a role in the regulation of the epithelial-mesenchymal transition.
Double knockout of c3orf70a and c3orf70b resulted in significantly decreased expression of the mature neuron markers elavl3 and eno2 and the midbrain/hindbrain marker irx3b. Neurobehaviors related to circadian rhythm and altered light-dark conditions were significantly impaired.
Highly expressed in the gut, myotomes and brain, especially the midbrain and hindbrain, at 3 days post-fertilization (dpf).
Plays a role in neuronal and neurobehavioral development (PubMed:31623237). Required for normal expression of the postmitotic and mature neuron markers elavl3 and eno2 and neurobehaviors related to circadian rhythm and altered light-dark conditions (PubMed:31623237).
Belongs to the thioesterase PaaI family.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.
Belongs to the opioid neuropeptide precursor family.
Dynorphin peptides differentially regulate the kappa opioid receptor. Dynorphin A(1-13) has a typical opiod activity, it is 700 times more potent than Leu-enkephalin.
Leu-enkephalins compete with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress.
Leumorphin has a typical opiod activity and may have anti-apoptotic effect.
Belongs to the aldehyde dehydrogenase family.
Plays a role in valine and pyrimidine metabolism. Binds fatty acyl-CoA.
Belongs to the eukaryotic ribosomal protein eS10 family.
Belongs to the ligand-gated ion channel (TC 1.A.9) 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.
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.
Belongs to the tetraspanin (TM4SF) 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.
Belongs to the complex I NDUFA3 subunit family.
Complex I is composed of 45 different subunits.
Belongs to the G-protein coupled receptor 1 family.
Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system (By similarity). Required for proper retrograde ciliary transport (PubMed:26044572).
Belongs to the dynein light chain Tctex-type family.
Morpholino knockdown of the protein produces a dose dependent typical ciliopathy phenotype, with ventrally curved body axis, hydrocephalus, abnormal otoliths and small eyes. The few embryos surviving to 4 days post fertilization display severe generalized edema, pronephric cysts, and defects of the craniofacial cartilage.
After the mid-blastula transition (MBT), expressed throughout the deep cells, which give rise to the embryo proper. In adults, isoform 2 shows highest expression in the eye and liver. Expressed in adult gonads.
Belongs to the nuclear hormone receptor family. NR1 subfamily.
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Expressed both maternally and zygotically. Most abundant during early oogenesis during stages I and II, and expression levels drop by oocyte maturation. Expressed at the 1-cell stage and then again after the MBT from the blastula to early gastrula (shield) stages, during which expression levels decrease. Not detected after gastrulation until adults.
High affinity receptor for triiodothyronine (By similarity). In the absence of thyroid hormone during late blastula stage development, acts as a transcriptional repressor. Whereas in the presence of thyroid hormone, can act as an activator of transcription. In addition, represses retinoic acid (RA)-signaling during blastula and gastrula stages of development.
The C-terminal extension present in isoform 1 and absent in isoform 2 (the F-domain) regulates transcriptional activity by altering the selectivity of binding to cofactors.
Belongs to the natriuretic peptide family.
Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of different cellular processes.
Becomes activated when its major tyrosine phosphorylation site is not phosphorylated. It can also be activated by point mutations as well as by truncations at the C-terminal end or by other mutations. Heme regulates its activity by enhancing the phosphorylation on Tyr-528 (By similarity).
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.
Dephosphorylated at Tyr-528 by PTPRJ. Phosphorylated on Tyr-528 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-417. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-528, the SH3 domain engaged with the SH2-kinase linker, and Tyr-417 dephosphorylated. Dephosphorylation of Tyr-528 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-528, Tyr-417 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-528 by CSK allows this interaction to reform, resulting in SRC inactivation (By similarity).
Interacts with amotl2; this interaction promotes the translocation of phosphorylated src to peripheral cell-matrix adhesion sites.
Myristoylated at Gly-2, and this is essential for targeting to membranes.
Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each src kinase is very difficult. Src appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of src to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including ptk2/fak1 and paxillin (pxn) (By similarity). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Involved in anchorage-independent cell growth (By similarity).
S-nitrosylation is important for activation of kinase activity.
The SH2 and SH3 domains are important for the intramolecular and intermolecular interactions that regulate catalytic activity, localization, and substrate recruitment.
Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing.
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 alpha-carbonic anhydrase family.
Expressed during early cleavage, gastrulation and at 1 day post-fertilization.
Morpholino knockdown leads to phenotypes ranging in severity from weak to severe that are developmentally delayed with disturbed brain patterning, necrosis in areas of the brain, aberrant eye development, impaired somitogenesis resulting in stacked somites, perturbed yolk sac extension and posterior axis extension with a high mortality rate of 88% at 5 days post-fertilization.
Plays a role in nonsense-mediated mRNA decay (By similarity). Does not have RNase activity by itself (By similarity). Promotes dephosphorylation of UPF1 (By similarity). Together with SMG7 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation (By similarity). Necessary for TERT activity (By similarity). Required for normal embryonic development (PubMed:19414594).
Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.
Belongs to the SLAIN motif-containing family.
Belongs to the small GTPase superfamily. Ras family.
Belongs to the actinoporin family. Sea anemone subfamily.
Belongs to the PDGF/VEGF growth factor family.
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).
May be involved in different biological processes including transcription and apoptosis by sequestering specific proteins outside of the nucleus (By similarity). Involved in actin stress fibers formation probably through its interaction with ARHGDIA and the regulation of the Rho signaling pathway (By similarity). May thereby play a role in cell adhesion and migration, regulating for instance podocytes migration during development of the kidney (PubMed:25961457).
Morpholino knockdown of the protein results in an edematous phenotype and proteinuria (PubMed:25961457). Podocyte foot process effacement and disorganization, rarefaction of slit membranes, and disorganization of the glomerular basement membrane in glomeruli which are characteritic of nephrosis are observed (PubMed:25961457).
Regulates ciliary localization of the BBSome complex. Together with the BBSome complex, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. May play a role in neurite outgrowth. May have tumor suppressor function.
Self-associates. Interacts with BBS9; the interaction mediates the association of LZTL1 with the BBsome complex and regulates BBSome ciliary trafficking.
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.
Belongs to the small GTPase superfamily. Rab family.
Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (By similarity). Involved in protein transport. Plays a role in vesicular traffic. Mediates VEGFR2 endosomal trafficking to enhance VEGFR2 signaling (By similarity).
Belongs to the glycosyltransferase 31 family.
Belongs to the cytidine and deoxycytidylate deaminase family.
This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Belongs to the universal ribosomal protein uS17 family.
Belongs to the type I cytokine receptor family. Type 1 subfamily.
The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.
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.
Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.
Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex. MAEA is required for normal cell proliferation. The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1 (By similarity). Plays a role in erythroblast maturation and in the development of mature macrophages (By similarity). Mediates the attachment of erythroid cell to mature macrophages; this MAEA-mediated contact inhibits erythroid cell apoptosis (By similarity). Participates in erythroblastic island formation, which is the functional unit of definitive erythropoiesis. Associates with F-actin to regulate actin distribution in erythroblasts and macrophages (By similarity). May contribute to nuclear architecture and cells division events (By similarity).
Identified in the CTLH complex that contains at least MAEA, RMND5A, GID8, WDR26, and RANBP9 and/or RANBP10 as the catalytic core. Interacts with F-actin.
The expected RING-type zinc finger domain is highly divergent and most of the expected Cys residues are not conserved. Still, the protein is required for CTLH complex E3 ubiquitin-protein transferase activity. In addition, the conserved Cys-314 in this highly divergent region is required for ubiquitination by the yeast GID complex, suggesting a direct role in catalyzing ubiquitination.
Belongs to the GST superfamily. Theta family.
Acts as a glycogen-targeting subunit for PP1 and regulates its activity. Activates glycogen synthase, reduces glycogen phosphorylase activity and limits glycogen breakdown.
Interacts with PPP1CC catalytic subunit of PP1 and associates with glycogen. Forms complexes with glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity.
The N-terminal region is required for binding to PP1, the central region is required for binding to glycogen and the C-terminal region is required for binding to glycogen phosphorylase glycogen synthase and phosphorylase kinase.
Belongs to the glycosyltransferase 10 family.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
Belongs to the mitochondrial Rho GTPase family.
Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution (By similarity).
Ubiquitinated by PRKN in a PINK1-dependent manner, leading to its degradation.
Belongs to the neutral ceramidase family.
Detected in intestine (at protein level).
Expressed and active during embryonic development.
Fishes display severe embryonic morphological and cellular abnormalities such as abnormal morphogenesis in the head and tail, pericardial edema, defect of blood cell circulation, and an increase of apoptotic cells, especially in the head and neural tube regions, at 36 hours post-fertilization.
Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:15271994). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation. Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine. Together with sphingomyelinase, participates in the production of sphingosine and sphingosine-1-phosphate from the degradation of sphingomyelin, a sphingolipid enriched in the plasma membrane of cells (By similarity). Also participates in the hydrolysis of ceramides from the extracellular milieu allowing the production of sphingosine-1-phosphate inside and outside cells (By similarity).
Belongs to the Toll-like receptor family.
The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab may be involved in endocytic recycling and may regulate the transport to the plasma membrane of transmembrane proteins. May regulate the assembly and the activity of tight junctions. May play a role in angiogenesis through regulation of endothelial cells chemotaxis. May be involved in neurite outgrowth. Has also been proposed to play a role in post-Golgi membrane trafficking from the TGN to the recycling endosome. Finally, it has been involved in insulin-induced transport to the plasma membrane of glucose transporters.
Belongs to the RecA family. DMC1 subfamily.
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 (By similarity).
Plays a role in mitochondrial and peroxisomal fission. Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface.
Component of the pre-catalytic and catalytic spliceosome complexes. Component of the postcatalytic spliceosome P complex.
Maternally expressed. Expressed as early as the 1-cell stage and continued through the 8-cell and 32-cell stages and 15-hpf and 24-hpf stages.
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 (By similarity). Required for normal early embryogenesis (PubMed:20013661).
The C-terminal RRM domain and the zinc finger motif are necessary for RNA-binding.
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.
Component of the MAJIN-TERB1-TERB2 complex.
Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. Component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA. In the MAJIN-TERB1-TERB2 complex, TERB1 probably mediates association with the shelterin/telosome complex.
Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.
Monomer (By similarity). Homodimer (By similarity). Homooligomer (By similarity).
Morpholino knockdown of the protein alters the neural development in embryos.
Preferentially expressed in the adult brain, gills, pancreas, liver, pituitary, heart, kidney and gut (PubMed:21952246). Widely expressed in the nervous system. Expressed in the vascular system and in neurons (PubMed:23161551).
Specific thyroid hormone transmembrane transporter, that mediates both uptake and efflux of thyroid hormones across the cell membrane independently of pH or a Na(+) gradient (PubMed:21952246, PubMed:31436139). The substrate preference is 3,3-diiodothyronine (3,3'-T2) and T3 and to a lesser extentd T4 and rT3. Acts as a crucial regulator during embryonic development (PubMed:23161551).
Ubiquitous expression during the bud stage in 10-hpf embryos. Later, at 24 hpf, mct8 is most abundant in the forebrain, midbrain, hindbrain, spinal cord, notochord, and eyes. At 48 hpf, mct8 expression is mainly observed in the brain and along the spinal cord.
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.
GlcNAcylation at Ser-111 promotes monoubiquitination of Lys-119. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).
Monoubiquitination of Lys-119 by the BRE1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation.
Phosphorylated during apoptosis; which facilitates apoptotic chromatin condensation.
Probable E3 ubiquitin-protein ligase that acts as a negative regulator of double-strand breaks (DSBs) repair following DNA damage.
The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif also mediates interaction with ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs) (By similarity).
Heterodimer of 2 subunits, IMMPL1 and IMMPL2.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.
Dephosphorylates a range of proteins, and thereby regulates cellular signaling cascades.
Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate.
Part of the cohesin complex which is composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.
Belongs to the WD repeat peroxin-7 family.
Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.
Belongs to the TALE/IRO homeobox family.
Belongs to the thymidylate kinase family.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.
Belongs to the Integrator subunit 10 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 PI3/PI4-kinase family. Type III PI4K subfamily.
Belongs to the actin-binding proteins ADF family. GMF subfamily.
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.
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 DNA2/NAM7 helicase family. SDE3 subfamily.
Belongs to the glycosyltransferase 25 family.
Belongs to the 'GDXG' lipolytic enzyme family.
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.
Spatially restricted regions of the neural tube.
Transcription factor expressed in spatially restricted regions of the neural tube during embryonic development.
Associates with the cleavage and polyadenylation specificity factor (CPSF) complex.
Belongs to the DNA polymerase type-B-like family.
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.
Belongs to the AB hydrolase superfamily. Lipase family.
Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.
May be involved in calcium-dependent ubiquitination and subsequent proteasomal degradation of target proteins. Probably serves as a molecular bridge in ubiquitin E3 complexes. Participates in the ubiquitin-mediated degradation of beta-catenin (CTNNB1).
Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.
Contaminating sequence. Potential poly-A sequence.
Expressed throughout the blastoderm early in development. Highly expressed in the developing brain at 24 hours post-fertilization (hpf), and at lower levels in the rest of the embryo.
Transcription elongation factor that enhances transcription elongation by RNA polymerase II (RNAPII).
Transcription elongation factor which binds histone H3 and enhances transcription elongation by RNA polymerase II (RNAPII). Promotes the activation of the myogenic gene program by entailing erasure of the repressive H3K27me3 epigenetic mark through stabilization of the chromatin interaction of the H3K27 demethylase KDM6A. Plays an important role during early patterning and somitogenesis of the embryo.
Belongs to the ZIP transporter (TC 2.A.5) family.
Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
Transmembrane reductase that uses ascorbate as an electron donor in the cytoplasm and transfers electrons across membranes to reduce iron cations Fe(3+) into Fe(2+) in the lumen of the late endosome and lysosome. Reduced iron can then be extruded from the late endosome and lysosome to the cytoplasm by divalent metal-specific transporters. It is therefore most probably involved in endosomal and lysosomal cellular iron homeostasis.
Functions as component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A9 subfamily.
Belongs to the protein-tyrosine phosphatase family.
Belongs to the poly(ADP-ribose) glycohydrolase family.
Catalyzes the 2-oxoglutarate and iron-dependent C4-lysyl hydroxylation of ETF1 at 'Lys-63' thereby promoting the translational termination efficiency of ETF1.
Belongs to the spermidine/spermine synthase family.
Interacts with PHB2; the interaction associates DNAJC19 with the prohibitin complex. Interacts with TIMM16/PAM16 (By similarity). May be a component of the PAM complex at least composed of a mitochondrial HSP70 protein, GRPEL1 or GRPEL2, TIMM44, TIMM16/PAM16 and TIMM14/DNAJC19 (By similarity).
Mitochondrial co-chaperone which forms a complex with prohibitins to regulate cardiolipin remodeling (By similarity). May be a 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. May act as a co-chaperone that stimulate the ATP-dependent activity (By similarity).
Belongs to the organo anion transporter (TC 2.A.60) family.
Belongs to the pseudouridine synthase TruD family.
Belongs to the mitochondrial carrier (TC 2.A.29) family.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Very large inducible GTPase (VLIG) family.
Belongs to the integrin alpha chain family.
Belongs to the SLC12A transporter family.
Seems to correspond to a subunit of a multimeric transport system and thus, additional subunits may be required for its function.
Belongs to the ATPase epsilon chain family.
Belongs to the aconitase/IPM isomerase family.
Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.
Belongs to the ubiquitin-activating E1 family.
Heterodimer of SAE1 and UBA2/SAE2. The heterodimer corresponds to the two domains that are encoded on a single polypeptide chain in ubiquitin-activating enzyme E1. Interacts with UBE2I.
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-237 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, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.
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).
Belongs to the nucleosome assembly protein (NAP) family.
Belongs to the eukaryotic RPB4 RNA polymerase subunit family.
Catalyzes the exchange of ADP and ATP across the membrane.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
Structural component of the gap junctions and the hemichannels.
Belongs to the methyltransferase superfamily. PrmA family.
Catalytic subunit of a heterodimer with TRMT112, which specifically methylates the 6th position of adenine in position 1832 of 18S rRNA (By similarity). N6-methylation of adenine(1832) in 18S rRNA resides in the decoding center of 18S rRNA and is required for translation and embryonic stem cells (ESCs) pluripotency and differentiation (By similarity).
Expressed from 20 minutes after fertilization in embryos.
rRNA N6-adenosine-methyltransferase activity is inhibited by zinc.
Belongs to the small GTPase superfamily. Arf family.
Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family.
Belongs to the krueppel C2H2-type zinc-finger protein family.
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.
Belongs to the ubiquitin-conjugating enzyme family.
In muscle, parvalbumin is thought to be involved in relaxation after contraction. It binds two calcium ions (By similarity).
Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family.
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.
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.
Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.
Homodimer, and heterodimer with other family members.
Belongs to the threonine aldolase family.
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.
May confer resistance to the antitumor agent cisplatin. Binds to DNA and RNA (By similarity).
Belongs to the bacterial ribosomal protein bL34 family.
Belongs to the helicase family. RLR subfamily.
Belongs to the sulfotransferase 1 family.
Highly expressed in the testis and at lower levels in the ovary, kidney and head.
Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Mediates the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone (By similarity).
Belongs to the avidin/streptavidin family.
Belongs to the PTEN phosphatase protein family.
May be a regulator of keratinocyte proliferation or differentiation.
Belongs to the cyclic nucleotide phosphodiesterase family.
Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
Belongs to the WD repeat neurobeachin family.
Involved in thrombopoiesis. Plays a role in the development or secretion of alpha-granules, that contain several growth factors important for platelet biogenesis.
Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.
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.
At the 10-somite stage, expressed in the paraxial mesoderm with an anterior expression limit at somite 6. At the 20-somite stage, expressed in the developing CNS with an anterior expression limit adjacent to the somite 3/somite 4 boundary; also expressed in bilateral domains adjacent to the anterior spinal cord and ventrally along the trunk in the pronephric ducts.
Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
Belongs to the complex I NDUFA12 subunit family.
Belongs to the immunoglobulin superfamily. BTN/MOG family.
Belongs to the MIP/aquaporin (TC 1.A.8) family.
RNA-binding protein that plays a role in the regulation of alternative splicing.
Seems to be required for maximal rate of protein biosynthesis. Enhances ribosome dissociation into subunits and stabilizes the binding of the initiator Met-tRNA(I) to 40 S ribosomal subunits.
Belongs to the glycosyl hydrolase 23 family.
Belongs to the peptidase C69 family. Secernin subfamily.
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.
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.
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.
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.
At 3 days-post-fertilization (dpf), expressed strongly in neurons in the ventral hindbrain and tegmentum and diffusely in the dorsal hindbrain and optic tectum. Also expressed in the diencephalon and the prospective olfactory bulb. Expression in non-spiny type-XIV tectal neurons is mostly diffuse. Over the next 7 days, as the dendritic arbor develops, expression becomes progressively more punctate, becoming localized to sites of synapse formation. At 4 dpf, expressed in the inner and outer plexiform layers of the retina and in the optic chiasm.
L27 domain is required for targeting to postsynaptic density.
Palmitoylated. Palmitoylation is required for targeting to postsynaptic density, plasma membrane and synapses.
Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins.
Ubiquitinated by MDM2 in response to NMDA receptor activation, leading to proteasome-mediated degradation of DLG4 which is required for AMPA receptor endocytosis.
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.
Required for the assembly of axonemal inner and outer dynein arms. Involved in preassembly of dyneins into complexes before their transport into cilia.
Belongs to the class-I aminoacyl-tRNA synthetase family.
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily.
Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bodies. Required for normal nutrient assimilation, increase of white adipose tissue and body weight gain when on a high-fat diet. Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate, small molecules that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis.
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 phosphatase 2A regulatory subunit B family.
Belongs to the chondroitin N-acetylgalactosaminyltransferase family.
Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.
Homodimer. Heterodimer of an alpha (TPM1, TPM3 or TPM4) and a beta (TPM2) chain.
The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.
Belongs to the polyribonucleotide nucleotidyltransferase family.
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
In cyliated cells, dynein axonemal particle-specific protein required for deployment of ODA to the axoneme. Interacts with outer dynein arm (ODA) subunits.
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.
In the C-terminal section; belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family.
Peroxisomal trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities. Catalyzes two of the four reactions of the long straight chain fatty acids peroxisomal beta-oxidation pathway (By similarity). Can also use branched-chain fatty acids such as 2-methyl-2E-butenoyl-CoA as a substrate, which is hydrated into (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA (By similarity). Optimal isomerase for 2,5 double bonds into 3,5 form isomerization in a range of enoyl-CoA species. Also able to isomerize both 3-cis and 3-trans double bonds into the 2-trans form in a range of enoyl-CoA species (By similarity). Regulates the amount of medium-chain dicarboxylic fatty acids which are essential regulators of all fatty acid oxidation pathways (By similarity). Also involved in the degradation of long-chain dicarboxylic acids through peroxisomal beta-oxidation (By similarity).
Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translocase that uses the membrane potential as the external driving force.
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of timm10b from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane.
Belongs to the enoyl-CoA hydratase/isomerase family.
Belongs to the ATP-dependent AMP-binding enzyme family.
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.
Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Is not required for association of CNOT7 to the CCR4-NOT complex (By similarity).
Component of the CCR4-NOT complex. cnot10 and cnot11 form a subcomplex docked to the cnot1 scaffold (By similarity).
Belongs to the nuclear hormone receptor family.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.
Converts acetoacetate to acetoacetyl-CoA in the cytosol (By similarity). Ketone body-utilizing enzyme, responsible for the synthesis of cholesterol and fatty acids (By similarity).
Belongs to the major facilitator superfamily. Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.
Belongs to the engrailed homeobox family.
Phosphoinositide phosphatase which catalyzes the hydrolysis of phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 3-phosphate (PtdIns(3)P) and has low activity towards phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2).
Binds 2 divalent metal cations (By similarity). Shows activity with Mn(2+), Co(2+) and Mg(2+) but shows no activity with Zn(2+) (By similarity).
Catalyzes the dephosphorylation of the nucleoside 5'-monophosphates deoxyadenosine monophosphate (dAMP), deoxycytidine monophosphate (dCMP), deoxyguanosine monophosphate (dGMP) and deoxythymidine monophosphate (dTMP).
Belongs to the carotenoid oxygenase family.
Catalyzes both 11-cis retinol and 13-cis retinol, 2 stereoisomeric forms of retinoic acid from all-trans-retinyl ester. Acts as an alternative isomerohydrolase in retinal Mueller cells by catalyzing formation of 11-cis retinol, to meet the high demand for the chromophore by cones (PubMed:21676174). Capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid (By similarity).
Retinal Mueller cells. Detected in the inner retina near the ganglion cell layer, in a region where the Mueller end feet are located, and a weak signal is observed between the outer nuclear and ganglion cell layers (at protein level).
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) 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.
Adapter protein for the cul3 E3 ubiquitin-protein ligase complex. Promotes the export of zbtb16/plzf from the nucleus to the cytoplasm and targets zbtb16/plzf for ubiquitination and degradation. Up-regulates neurog1 expression and antagonizes zbtb16/plzf, to promote neurogenesis.
Expressed during primary neurogenesis. At the 3 somite stage (3s), expressed in rostrocaudal stripes in the posterior neural plate characteristic of the lateral zone, intermediate zone, and medial zone of primary neurogenesis. At 14s and 20 hpf, widely expressed in the spinal cord. By 24 hpf, becomes restricted to the posterior spinal cord. Expression also occurs in a dynamic segmental pattern in the hindbrain, at the mid-hindbrain boundary, cranial ganglia, midbrain, and forebrain. Isoform 1: Expressed throughout early development. Isoform 2: up-regulated from 9 hpf, when neurogenesis is initiated.
Expressed in the developing central nervous system.
Interacts with cul3. Interacts (via BTB domain) with zbtb16/plzf.
Morpholino knockdown of both isoform 1 and isoform 2 leads to a major decrease in the expression of neurog1 and downstream markers of neuronal differentiation. Knockdown of either isoform alone leads to a mild decrease in the expression of late markers of neurogenesis, but has no detectable effect on neurog1 expression.
Exhibits acyl-CoA:lysocardiolipin acyltransferase (ALCAT) activity; catalyzes the reacylation of lyso-cardiolipin to cardiolipin (CL), a key step in CL remodeling (By similarity). Recognizes both monolysocardiolipin and dilysocardiolipin as substrates with a preference for linoleoyl-CoA and oleoyl-CoA as acyl donors (By similarity). Also exhibits 1-acyl-sn-glycerol-3-phosphate acyltransferase activity (AGPAT) activity; converts 1-acyl-sn-glycerol-3- phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3- phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Possesses both lysophosphatidylinositol acyltransferase (LPIAT) and lysophosphatidylglycerol acyltransferase (LPGAT) activities (By similarity). Required for establishment of the hematopoietic and endothelial lineages (PubMed:18388326).
S-nitrosylation inhibits channel currents and ATP release.
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.
Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
Binds to membranes via its F-BAR domain and mediates membrane tubulation. Plays a role in cellular transport processes by recruiting dynamins to membranes. Plays a role in the reorganization of the actin cytoskeleton and in neuron morphogenesis via its interaction with cobl, and by recruiting cobl to the cell cortex. Plays a role in the regulation of neurite formation, neurite branching and the regulation of neurite length. Required for normal synaptic vesicle endocytosis; this process retrieves previously released neurotransmitters to accommodate multiple cycles of neurotransmission. Required for normal excitatory and inhibitory synaptic transmission (By similarity). Required for normal embryonic development, including normal development of laterality, normal body size and shape, as well as normal brain and heart development. Required for normal development of stereocilia and kinocilia in sensory hair cells of neuromasts in the posterior lateral line organ, and thus also for balance keeping and normal swimming behavior.
Highly expressed throughout embryogenesis, from fertilization to hatching. Detected in embryonic neuronal tissues, including forebrain, hindbrain, spinal cord and retina.
The F-BAR domain mediates membrane-binding and membrane tubulation.
Belongs to the protein kinase superfamily. Tyr protein kinase family. ROR subfamily.
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 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.
Appears to play a crucial role in the insertion of secretory and membrane polypeptides into the ER. It is required for assembly of membrane and secretory proteins. Found to be tightly associated with membrane-bound ribosomes, either directly or through adaptor proteins (By similarity).
Heterotrimeric complex composed of SEC61-alpha, SEC61-beta and SEC61-gamma.
Belongs to the glycosyl hydrolase 22 family.
Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.
Belongs to the beta type-B retroviral polymerase family. HERV class-II K(HML-2) pol subfamily.
Belongs to the eukaryotic diacylglycerol kinase family.
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.
May act as a specific coactivator for the mammalian TEFs.
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 DNA2/NAM7 helicase family.
Belongs to the complex I NDUFA2 subunit family.
Expressed from 1 dpf in the brain and pronephric tubules. At 3 dpf, expression expanded to the eyes and neuromasts, where mechanosensory hair cells exist, along the lateral line.
Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton (By similarity) (PubMed:26895965). Plays a central role in renal ciliogenesis and kidney development (PubMed:26895965).
The morphants contained multiple phenotypic defects, beginning with a downward-curled tail at 2 dpf. Additional ciliary defects after 3 dpf included small eyes, pericardial edema and hydrocephalus. These defects became more severe, leading to abdominal fluid accumulation, as well as abnormal pronephric kidneys at 5 dpf.
Belongs to the eIF-2B alpha/beta/delta subunits family.
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.
Proposed core component of the chromatin remodeling Ino80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding.
Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX.
Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes.
Belongs to the protein kinase superfamily. ADCK protein kinase family.
Belongs to the universal ribosomal protein uL15 family.
Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.
In muscle, parvalbumin is thought to be involved in relaxation after contraction. It binds two calcium ions.
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.
First expressed at the dorsal side of the blastula embryo. Expressed in the germ ring, shield and chordamesoderm during gastrulation and is restricted to the notochord and tailbud during somitogenesis (at protein level).
In the embryo, first expressed at the doming stage (4.2 hours). Highest expression is found between 5.2 and 9.5 hours (epiboly) after which levels gradually decrease, with expression becoming absent by 48 hours.
Involved in the transcriptional regulation of genes required for mesoderm differentiation, including itself. Indispensable for the formation of the notochord and the tail structure. Functions together with tbx16/spadetail in development of trunk and tail mesoderm. Functions by itself early in development to repress medial floor plate and promote notochord fate but at later times, functions together with tbx16/spadetail to promote medial floor plate formation. Acts in a parallel pathway to, but cooperates with, non-canonical wnt-signaling during tail formation. Required for the morphogenesis of Kupffer's vesicle and regulates left-right asymmetry.
Loss of notochord cells and posterior structures. Disrupts left-right development.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.
Belongs to the cyclin family. Cyclin L subfamily.
A pair of annexin repeats may form one binding site for calcium and phospholipid.
Plays a role in transport between endoplasmic reticulum and Golgi.
Probable sodium-dependent sugar transporter.
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.
Morpholino knockdown in embryos results in decreased red blood cells and an arrest in T-cell progenitors, as well as increased vascularity. The vascular defects could be rescued by wild-type gene and by thalidomide treatment.
Acetyltransferase required for the establishment of sister chromatid cohesion. Couples the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together (By similarity). Essential for early development (PubMed:15256591).
Belongs to the acetyltransferase family. ECO subfamily.
The N-terminal region seems to be responsible for association with chromosomes, thus excluding any involvement of the Zn finger in this process.
Homopentamer. May be part of a cullin-containing E3 ubiquitin-protein ligase complex.
Probable substrate-specific adapter of a cullin-containing E3 ubiquitin-protein ligase complex mediating the ubiquitination and subsequent proteasomal degradation of target proteins.
Belongs to the protein-tyrosine phosphatase family. Receptor class 8 subfamily.
The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits.
Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa1.1/KCNMA1 sub-subfamily.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin 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.
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. Glutathione depletion is an important factor for apoptosis initiation and execution. Acts as a pro-apoptotic component of the unfolded protein response pathway by mediating the pro-apoptotic effects of the ATF4-ATF3-DDIT3/CHOP cascade. Negative regulator of Notch signaling pathway involved in embryonic neurogenesis: acts by inhibiting Notch cleavage by furin, maintaining Notch in an immature inactive form, thereby promoting neurogenesis in embryos.
Expressed throughout the embryo including the shield. Strongly expressed in notochord and head regions from the bud to somite stages. Expressed in early born neurons in the telencephalic nucleus, the nuclei of the tract of the post-optic commissure and of the medial longitudinal fasciculus, and in segmental clusters of neurons in the hindbrain.
Functions as a positive effector of the Wnt signaling pathway regulating antero-posterior neural patterning.
Homomers. Interacts with dishevelled and axin1.
The DIX domain mediates self-interaction and interaction with dishevelled and axin1.
Cadherins are calcium-dependent cell adhesion proteins.
Belongs to the peptidase C19 family. USP12/USP46 subfamily.
Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action (By similarity). Has almost no deubiquitinating activity by itself and requires the interaction with wdr48 to have a high activity (By similarity).
Catalyzes the deubiquitination of SPDL1 (By similarity). Plays a role in the repair of UV-induced DNA damage via deubiquitination of ERCC1, promoting its recruitment to DNA damage sites (By similarity). May be involved in the maintenance of photoreceptor function (PubMed:30573563). May play a role in normal retinal development (PubMed:27613029).
Morpholino-treated larvae show a reduction in eye size and significantly fewers green cone photoreceptors compared to the wild-type (PubMed:30573563). Moderate to severe eye morphological defects, with a defective formation of the retinal structures (PubMed:27613029).
Belongs to the calcium channel subunit alpha-2/delta family.
Belongs to the heme-copper respiratory oxidase family.
Binds 2 heme A groups non-covalently per subunit.
Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity). As a newly synthesized protein, rapidly incorporates into a multi-subunit assembly intermediate in the inner membrane, called MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase) complex, whose core components are COA3/MITRAC12 and COX14. Within the MITRAC complex, interacts with COA3 and with SMIM20/MITRAC7; the interaction with SMIM20 stabilizes the newly synthesized MT-CO1 and prevents its premature turnover. Interacts with TMEM177 in a COX20-dependent manner (By similarity).
Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
Necessary for efficient adipogenesis. Does not show ion channel activity.
May be involved in actin-dependent nuclear movement. May be involved in the organization of the nuclear envelope. May recruit Ran GTPase to the nuclear periphery.
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).
Activated by RHOA binding. Inhibited by Y-27632.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
Protein kinase which is a key regulator of actin cytoskeleton and cell polarity.
Belongs to the glycosyltransferase 31 family. Beta3-Gal-T subfamily.
Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins.
Its primary function is the prevention of hypercalcemia. Upon release into the circulation, it lowers calcium transport by the gills, thereby reducing its rate of influx from the environment into the extracellular compartment. STC also stimulates phosphate reabsorption by renal proximal tubules. The consequence of this action is increased levels of plasma phosphate, which combines with excess calcium and promotes its disposal into bone and scales.
Probably part of the adaptor protein complex 5 (AP-5) a tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1.
Binds the telomeric double-stranded 5'-TTAGGG-3' repeat.
Palmitoylated. Undergoes rapid palmitoylation turnover. Palmitoylation regulates the cell membrane and nuclear shuttling and the regulation of GPCR signaling. Upon depalmitoylation, it is targeted from the plasma membrane into the nucleus. GPCR signaling inhibits depalmitoylation and promotes localization to the plasma membrane.
Regulator of G protein-coupled receptor (GPCR) signaling. Regulatory subunit of the R7-Gbeta5 complexes that acts by controlling the subcellular location of the R7-Gbeta5 complexes. When palmitoylated, it targets the R7-Gbeta5 complexes to the plasma membrane, leading to inhibit G protein alpha subunits. When it is unpalmitoylated, the R7-Gbeta5 complexes undergo a nuclear/cytoplasmic shuttling (By similarity).
Belongs to the multicopper oxidase family.
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 SEC23/SEC24 family. SEC24 subfamily.
Belongs to the transglutaminase superfamily. Transglutaminase family.
Endoplasmic reticulum-Golgi intermediate compartment membrane
Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:23091644). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (PubMed:23091644). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (By similarity). Upon binding of c-di-GMP or cGAMP, STING1 oligomerizes and is able to activate both NF-kappa-B and irf3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state (PubMed:30842662). In addition to promote the production of type I interferons, plays a direct role in autophagy (PubMed:30842662). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). The ERGIC serves as the membrane source for LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome. The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation. Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (By similarity).
Homodimer; forms a homodimer in absence of cyclic nucleotide (c-di-GMP or cGAMP) (By similarity). Homotetramer; in presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order oligomers through side-by-side packing (By similarity). Interacts (when phosphorylated) with irf3; following activation and phosphorylation by tbk1, recruits irf3 (By similarity).
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). The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (By similarity).
Phosphorylation by TBK1 leads to activation and production of IFN-beta. Following cyclic nucleotide (c-di-GMP or cGAMP)-binding, activation and translocation from the endoplasmic reticulum, STING1 is phosphorylated by tbk1, leading to recruitment of the transcription factor irf3 to induce type-I interferons and other cytokines.
The N-terminal domain interacts with glycerophospholipids and phospholipids.
Belongs to the LDH/MDH superfamily. MDH type 2 family.
Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family. Alanine aminotransferase subfamily.
Expressed at relatively high levels in both proximal and distal regions of the fin bud during pectoral fin development.
The C-terminal UBZ-type zinc fingers function as ubiquitin-binding domains.
Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR1/GRIN1 subfamily.
Belongs to the inositol monophosphatase superfamily.
Belongs to the gastrin/cholecystokinin family.
Expressed both maternally and zygotically (Ref.1). Expressed in the germ ring at the blastoderm margin during the shield stage of gastrulation, expression is higher dorsally than ventrally (PubMed:22406073). Expressed at the posterior dorsal midline at the four-somite stage and in the pectoral fin bud 48 hours post-fertilization (PubMed:22406073). Zygotic expression begins during somitogenesis and is confined to the mesenchyme of the developing tailbud, the posterior 4-5 somites and the ventrolateral mesenchyme of the head (Ref.1). In later stages, expressed in the pharyngeal arch mesenchyme and pectoral finbuds (Ref.1). Not detected in mature chondrocytes (Ref.1).
Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. Required during embryogenesis for extension of the primary anterior-posterior axis. Regulates convergent extension movements and hypaxial myogenesis during gastrulation via activation of non-canonical Wnt signaling (PubMed:22406073).
Morpholino knockdown results in convergent extension movement defects during gastrulation and an absence of myod1 expression in the majority of hypaxial muscle precursor cells.
Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.
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.
Dual specificity phosphatase able to dephosphorylate phosphotyrosine, phosphoserine and phosphothreonine residues, with a preference for phosphotyrosine as a substrate.
Belongs to the TNF receptor-associated factor family.
Belongs to the bZIP family. Jun subfamily.
A soluble form may be derived from the membrane form by proteolytic processing.
Expressed both maternally and throughout the zygotic stages, with highest expression at the bud stage. No evidence for a cyclic pattern of expression in the presomitic mesoderm during somitogenesis. Expressed weakly at the epiboly stage (4.5 hours) throughout the blastoderm. Expression clears from marginal region and localizes to the epiblast cells of the animal pole. As gastrulation proceeds, expressed in hypoblast cells that migrate towards the animal pole, in the prechordal plate and in forerunner cells. At 90% epiboly, expressed in the neural plate. At the three somite stage (11 hours), expressed in a small cluster of cells within the tailbud region and in future spinal cord. From the 8-14 somite stages, expressed in alternating pre-rhombomeres of the hindbrain, and more broadly in mid- and forebrain. Also expressed weakly in the anterior margins of the formed somites and in the anterior presomitic mesoderm. At the end of somitogenesis (22 hours), expressed strongly in the telencephalon and anterior midbrain, weakly in other parts of the midbrain and variably in the hindbrain.
Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Involved in the correct formation of boundaries in the somites and hindbrain (By similarity). Required for Delta-Notch-mediated induction of hypochord cells at the lateral borders of the midline precursor domain (PubMed:11429294, PubMed:14518000).
In the embryo, expressed along the A-P axis of the neural tube, within the lateral plate mesoderm, in the presomitic mesoderm and the somites, in specific rhombomeres of the hindbrain (even-numbered rhombomeres) and in the otic vesicles.
May play an essential role for the assembly of the mitochondrial F1-F0 complex.
Independently of its dipeptidase activity, acts as an adhesion receptor for neutrophil recruitment from bloodstream into inflamed lungs and liver.
Belongs to the tumor necrosis factor family.
Belongs to the transcription factor STAT family.
Belongs to the DEAD box helicase family. DDX47/RRP3 subfamily.
Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A subfamily.
May be involved in iron export and also in transfer of iron between maternal and fetal circulation.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.
Belongs to the phosphatidyl serine synthase family.
Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine (By similarity). Catalyzes mainly the conversion of phosphatidylcholine but also converts, in vitro and to a lesser extent, phosphatidylethanolamine (By similarity).
Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.
Belongs to the calycin superfamily. Lipocalin family.
Belongs to the small GTPase superfamily. SAR1 family.
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.
Belongs to the complex I NDUFS6 subunit family.
Autophosphorylates upon activation by efna5.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.
Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity).
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially efna5. Upon activation by efna5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation probably through activation by efna1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development (By similarity).
Widely expressed in the developing zebrafish nervous system.
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).
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Phosphorylated; in a cell-cycle dependent manner at mitosis.
Expressed in the germ plasm and the primordial germ cells (PGCs). At the onset of embryogenesis, maternal product is located in granules distributed throughout the cortex of the one-cell stage embryo. At 0.5 hour post fertilization (hpf) is expressed at the vegetal part of the blastomere. At 1 hpf expressed at the distal parts of the first two cleavage furrows. At 4 hpf expressed exclusively in PGCs. Expressed in PGCs during their migration and at their arrival in the presumptive gonade. At 5 days post-fertilization (dpf) still expressed in PGCs, albeit at a lower level.
RNA-binding factor that positively regulates gene expression by prohibiting miRNA-mediated gene suppression. Relieves miRNA repression in germline cells. Prohibits the function of several miRNAs by blocking the accessibility of target mRNAs (By similarity). Sequence-specific RNA-binding factor that binds to U-rich regions (URRs) in the 3'untranslated region (3'-UTR) of several mRNAs (By similarity). Does not bind to miRNAs (By similarity). Germline-specific protein required for the primordial germ cell (PGC) survival and migration during early embryonic development.
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.
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.
Functions as guanine nucleotide exchange factor (GEF) for RAB11A.
Interacts with GDP-bound and nucleotide-free forms of RAB11A.
The N-terminal half of the protein mediates interaction with RAB11A and functions as guanine nucleotide exchange factor. Four long alpha-helices (interrupted by a central kink) assemble into coiled coils, giving rise to a 'V' shape.
Belongs to the adaptor complexes small subunit 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.
Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.
Plays an important role in membrane trafficking through the secretory apparatus.
Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus.
Belongs to the SLC41A transporter family.
Belongs to the chloride channel CLIC family.
Highly expressed in hematopoietic organs, Expressed in the intermediate cell mass (ICM), a tissue equivalent to the mammalian extraembryonic yolk-sac blood islands. Colocalizes with gata1.
Mitochondrial iron transporter that specifically mediates iron uptake in developing erythroid cells, thereby playing an essential role in heme biosynthesis.
Morpholino knockdown results in embryos which are profoundly anemic.
May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
Belongs to the major facilitator superfamily. SLC46A family.
Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force (By similarity). Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (By similarity). Functions at acidic pH via alternate outward- and inward-open conformation states (By similarity). Protonation of residues in the outward open state primes the protein for transport (By similarity). Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate (By similarity). Also able to transport antifolate drugs, such as methotrexate and pemetrexed (By similarity). Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (By similarity). Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (By similarity).
Belongs to the vasopressin/oxytocin family.
Belongs to the FPP/GGPP synthase family.
Belongs to the protein prenyltransferase subunit beta family.
Belongs to the vinculin/alpha-catenin family.
Belongs to the UDP-glycosyltransferase family.
The small GTPases Rab are key regulators in vesicle trafficking.
Belongs to the 5-formyltetrahydrofolate cyclo-ligase family.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
Belongs to the adaptor complexes large subunit family.
Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
Belongs to the RNase H2 subunit B family.
Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.
The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C.
Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.
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 (By similarity).
Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.
In adults, weakly expressed in the intestine.
Belongs to the sulfotransferase 2 family.
Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of dermatan sulfate.
Regulates intra- and extracellular levels of inorganic pyrophosphate (PPi), probably functioning as PPi transporter.
Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. It stimulates division and differentiation of sympathetic and embryonic sensory neurons (By similarity).
Endoplasmic reticulum transmembrane protein involved in vesicle-mediated transport, which is required for neutrophil function.
Belongs to the G-protein coupled receptor 5 family.
Belongs to the heparin-binding growth factors 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 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.
Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.
The DHHC domain is required for palmitoyltransferase activity.
Belongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily.
Belongs to the G-protein coupled receptor 3 family.
Belongs to the phosphatidylethanolamine-binding protein family.
Belongs to the anion exchanger (TC 2.A.31) family.
Belongs to the glycosyltransferase 65 family.
Belongs to the mitochondrion-specific ribosomal protein mS29 family.
Belongs to the beta/gamma-crystallin family.
Belongs to the cAMP-dependent kinase regulatory chain family.
Belongs to the Arg-specific ADP-ribosyltransferase family.
Belongs to the peptidase C19 family. UBP8 subfamily.
Component of some SAGA transcription coactivator-HAT complexes.
Histone deubiquitinating component of the transcription regulatory histone acetylation (HAT) complex SAGA. Catalyzes the deubiquitination of both histones H2A and H2B, thereby acting as a coactivator. Recruited to specific gene promoters by activators, where it is required for transcription (By similarity).
Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex.
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). PAF1C seems to be required for multiple steps in cardiac formation. Involved in the migration of myocardial precursors to the midline and the differentiation of the atrioventricular boundary in the developing heart.
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). Interacts with ctr9 (PubMed:21338598).
Belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family.
Belongs to the TGF-beta family. GDNF subfamily.
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.
E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated proteins and mediates their ubiquitination and subsequent degradation.
The WWE domain mediates non-covalent poly(ADP-ribose)-binding.
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.
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC4 subfamily.
Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride.
First expressed at 48 hours post-fertilization (hpf). Expressed in dorsal midbrain and in retinal ganglion cells.
Homotrimer or heterotrimer with other ASIC proteins.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.
Belongs to the Antp homeobox family. Proboscipedia subfamily.
First expressed at the 1-somite stage in the presumptive rhombomeres 3 (r3) and 5 of the developing hindbrain. By the 3- to 4-somite stages, r5 expression has increased and there is weak expression in r4 and posterior to r6. From the 10- to 20-somite stages, confined to r3, r4 and r5 with highest levels in r3 and lowest levels in r5.
Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Plays an important role in the patterning of hindbrain and pharyngeal arches.
As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.
Expressed following gastrulation. At the 1-somite stage, expressed in the paraxial mesoderm. Subsequently expressed in the telencephalon, the otic vesicles, the somites and the anterior presomitic mesoderm.
Expression in the developing embryo is induced by activation of the Notch signaling pathway.
Transcriptional repressor which functions as a downstream effector of Notch signaling.
Cell surface proteoglycan that bears heparan sulfate.
Belongs to the adaptor complexes medium subunit family. Delta-COP subfamily.
Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits.
The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins.
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.
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.
Artifact. Missing internal sequence that doesn't correspond to an exon-intron boundary.
Component of the NDC80 complex, which is composed of ndc80, cdca1, spbc24 and spbc25.
Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1 (By similarity). Plays a role in neural tube closure.
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.
Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
Lysine deamination at Lys-5 (H3K4all) to form allysine only takes place on H3K4me3 and results in gene repression.
Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for tp53bp1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (cbx1, cbx3 and cbx5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120' (By similarity).
Monoubiquitinated by rag1 in lymphoid cells, monoubiquitination is required for V(D)J recombination.
Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by aurkb mediates the dissociation of HP1 proteins (cbx1, cbx3 and cbx5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by map3k20 isoform 1, rps6ka5 or aurkb during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by prkcb is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by lsd1/kdm1a. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by kdm4c/jmjd2c. Phosphorylation at Tyr-42 (H3Y41ph) by jak2 promotes exclusion of cbx5 (HP1 alpha) from chromatin (By similarity).
Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).
Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (By similarity). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (By similarity).
Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.
Exhibits ester hydrolase activity on the substrate p-nitrophenyl acetate.
May control cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton. Mediator of ERBB2 signaling (By similarity).
Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.
Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.
Plays a role in alternative splicing of pre-mRNAs, possibly by contributing to the selection of non-consensus donor sites.
Embryonic lethality, due to impaired S-phase progression and disruption of the S/M checkpoint, leading to premature mitotic entry and mitotic catastrophe.
Interacts with topbp1 (via BRCT domains); interaction takes place in a cdk2-dependent manner (By similarity). Component of the replisome complex (By similarity).
Regulator of DNA replication and S/M and G2/M checkpoints. Regulates the triggering of DNA replication initiation via its interaction with topbp1 by participating in cdk2-mediated loading of cdc45l onto replication origins. Required for the transition from pre-replication complex (pre-RC) to pre-initiation complex (pre-IC). Required to prevent mitotic entry after treatment with ionizing radiation.
Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG.
May be involved in fusion of ER-derived transport vesicles with the Golgi complex.
Belongs to the TRAPP small subunits family. BET3 subfamily.
Belongs to the terpene cyclase/mutase family.
Acts as guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases.
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 peroxiredoxin-like PRXL2 family. PRXL2A subfamily.
Belongs to the Nudix hydrolase family. NudC subfamily.
Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1.
Component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity.
Belongs to the dynein heavy chain family.
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. 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.
Component of the endosomal sorting complex required for transport II (ESCRT-II), composed of SNF8, VPS25 and VPS36.
Belongs to the RRM HNRPC family. RALY subfamily.
Belongs to the intermediate filament family.
Probable large-conductance Ca(2+)-activated chloride channel.
Belongs to the glycosyltransferase 29 family.
Homodimer and heterodimer; forms heterodimers with miga2.
Regulator of mitochondrial fusion: acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of pld6/MitoPLD dimers. May act by regulating phospholipid metabolism via pld6/MitoPLD.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS9 subfamily.
Belongs to the PNP/UDP phosphorylase family.
Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.
Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins.
Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members (By similarity).
Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions (By similarity).
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.
Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs).
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).
Barely detectable in adult somatic tissues. Expressed in immature germ cells that have not completed meiosis. In ovary, expressed predominantly in previtellogenic oocytes. In testis, expressed in primary and secondary spermatocytes, but not mature spermatozoa.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Mutants show anomalies in the chromosome number of male germ cells, leading to aneuploidy and severe developmental defects in their progeny.
Phosphorylates proteins on serine, threonine, and tyrosine (By similarity). Involved in mitotic cell cycle checkpoint control. Required for fin and heart regeneration. Required to prevent chromosome segregation errors during meiosis.
Strongly induced in a subpopulation of cells in the proximal blastema during regenerative outgrowth.
Acylated. Acylation may be a prerequisite for conversion of the monomeric 37 kDa laminin receptor precursor (37LRP) to the mature dimeric 67 kDa laminin receptor (67LR), and may provide a mechanism for membrane association.
Belongs to the universal ribosomal protein uS2 family.
Cleaved by stromelysin-3 (ST3) at the cell surface. Cleavage by stromelysin-3 may be a mechanism to alter cell-extracellular matrix interactions.
Monomer (37LRP) and homodimer (67LR). Component of the small ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S). Interacts with RPS21. Interacts with several laminins including at least LAMB1. Interacts with MDK.
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 GLI C2H2-type zinc-finger protein family.
Belongs to the U2 small nuclear ribonucleoprotein A family.
Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily.
Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state.
Belongs to the eukaryotic ribosomal protein eL42 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.
Belongs to the eukaryotic ribosomal protein eL39 family.
In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family.
In the N-terminal section; belongs to the ubiquitin family.
Ribosomal protein S27a is part of the 40S ribosomal subunit.
Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains. The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (By similarity). Involved in heart development (PubMed:20493459).
The RanBP2-type zinc finger (NZF) mediates binding to two consecutive 'Lys-63'-linked ubiquitins.
Homooligomer and heterooligomer. Core component of the 7SK RNP complex.
Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor. Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.
Belongs to the TALE/PBX homeobox family.
Belongs to the mitochondrion-specific ribosomal protein mL41 family.
Component of the mitochondrial ribosome large subunit. Also involved in apoptosis and cell cycle (By similarity).
Belongs to the quiescin-sulfhydryl oxidase (QSOX) family.
Catalyzes the oxidation of sulfhydryl groups in peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide.
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.
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.
Part of a SCF (SKP1-cullin-F-box) protein ligase complex.
Belongs to the GST superfamily. Mu 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 cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.
Catalyzes the hydrolysis of ATP coupled with the transport of calcium.
Highly expressed in the initial stages of development (4-cell up to 1k-2k cell stages). Expression slightly increases again between 24 hours and 5 dpf and after 20 dpf. Up-regulated during regeneration of the caudal fin after amputation.
May be involved in transcriptional regulation.
Widely expressed with highest levels in kidney, spleen and ovary.
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 tRNA methyltransferase O family.
Involved in formation of membrane ruffles and lamellipodia protrusions and in axon outgrowth. Binds to F-actin but not to RNA (By similarity).
Heterotetramer of two alpha chains and two beta chains.
Involved in oxygen transport from gills to the various peripheral tissues.
In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.
Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
At 24 hours post-fertilization, expressed predominantly in posterior blood island, posterior cardinal vein and circulating blood, as well as in somites, brain and retina. At 34 hours post-fertilization, becomes restricted to posterior blood island and circulating blood.
Belongs to the mitochondrial carrier (TC 2.A.29) family. SLC25A38 subfamily.
Fishes lacking both slc25a38a and slc25a38b display anemia.
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.
E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.
Possible contaminating sequence. The N-terminal 7 residues do not match the underlying genomic sequence.
Belongs to the SNF2/RAD54 helicase family.
Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins. Also able to mediate N-terminal lysine myristoylation of proteins.
Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.
The JAMM motif is essential for the protease activity.
Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains (By similarity). Functions at the endosome and is able to oppose the ubiquitin-dependent sorting of receptors to lysosomes (By similarity).
Belongs to the aspartyl/asparaginyl beta-hydroxylase family.
At the 10-somite stage, barely expressed in the paraxial mesoderm. At the 20-somite stage, expressed in the developing CNS with an anterior expression limit within rhombomere 7.
Belongs to the Antp homeobox family. Deformed subfamily.
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).
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.
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.
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.
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 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.
Activates eif2ak2/pkr in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of eif2s1/efi2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by dicer1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by dicer1 (By similarity).
Homodimer. Interacts with dicer1 and eif2ak2/pkr. Also able to interact with dsRNA (By similarity).
Ciliopathy phenotypes: appearance of 3 otoliths, kidney cysts and dilated kidney tubules at 2.5 days post-fertilization (dpf). Motile cilia in the kidney show disorganized cilia bundles with either severely reduced beat amplitude or paralysis. Olfactory motile cilia are nearly completely paralyzed.
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 (By similarity). May act by indirectly regulating transcription of dynein proteins (By similarity).
Belongs to the distal-less homeobox family.
Major acute phase reactant. Apolipoprotein of the HDL complex.
Belongs to the universal ribosomal protein uS19 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. A homomeric c-ring of probably 10 subunits is part of the complex rotary element.
Belongs to the phosphatase and actin regulator family.
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.
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.
Plays a role in migration and segregation of pigment cells (melanophores and xanthophores). Contributes to pigment stripe patterning in the epidermis.
Strongly expressed in melanophores and xanthophores. Also detected in eye, brain, heart, skin, fin, testis and ovary.
Belongs to the calcineurin regulatory subunit family.
Belongs to the V-ATPase E subunit family.
Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger family.
Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (By similarity).
Highly expressed in fertilized eggs as well as in all embryonic cells up to the end of gastrulation. Spatially restricted expression started after the onset of segmentation and was mainly localized in the developing pharyngeal arches. Transient expression was also detected in Kupffer's vesicle, a teleost-specific structure, and in lateral trunk and tail regions surrounding the neural keel, as well as areas of the developing pronephros.
Interacts with homodimeric pdgfa, pdgfb and pdgfc, and with heterodimers formed by pdgfa and pdgfb. Monomer in the absence of bound ligand. Interaction with dimeric pdgfa, pdgfb and/or pdgfc leads to receptor dimerization, where both pdgfra homodimers and heterodimers with pdgfrb are observed (By similarity).
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 (By similarity).
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. Required for normal development of the gastrointestinal tract. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric pdgfa, homodimeric pdgfb, heterodimers formed by pdgfa and pdgfb or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between pdgfra and pdgfrb. Phosphorylates pik3r1, plcg1, and ptpn11. Activation of plcg1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates pik3r1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of hras and of the MAP kinases mapk1/erk2 and/or mapk3/erk1. Promotes activation of STAT family members stat1, stat3 and stat5a and/or stat5b. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor (By similarity).
Ubiquitinated, leading to its internalization and degradation.
Calcium-dependent mitochondrial solute carrier. Mediates the reversible, electroneutral exchange of Mg-ATP or Mg-ADP against phosphate ions, catalyzing the net uptake or efflux of adenine nucleotides across the mitochondrial inner membrane. Nucleotide transport is inactive when cytosolic calcium levels are low, and is activated by an increase in cytosolic calcium levels. May play a role in protecting cells against oxidative stress-induced cell death, probably by promoting the formation of calcium-phosphate precipitates in the mitochondrial matrix, and thereby buffering calcium levels in the mitochondrial matrix (By similarity).
The N-terminal domain can bind calcium and regulates the ATP carrier activity of the transmembrane domain. The apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, leading to inhibition of the ATP carrier activity. Calcium binding leads to a major conformation change and abolishes the interaction with the transmembrane domain and the inhibition of the ATP carrier activity (By similarity).
Belongs to the glutathione peroxidase family.
Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class III subfamily.
Induces bone formation in conjunction with TGF-beta-1 or TGF-beta-2.
Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. Component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA.
Belongs to the Rab3-GAP catalytic subunit family.
Catalytic subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of rab3gap1 and rab3gap2, which has GTPase-activating protein (GAP) activity towards various Rab3 subfamily members (RAB3A, RAB3B, RAB3C and RAB3D), RAB5A and RAB43, and guanine nucleotide exchange factor (GEF) activity towards RAB18 (By similarity). As part of the Rab3GAP complex, acts as a GAP for Rab3 proteins by converting active RAB3-GTP to the inactive form RAB3-GDP (By similarity). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones (By similarity). The Rab3GAP complex, acts as a GEF for RAB18 by promoting the conversion of inactive RAB18-GDP to the active form RAB18-GTP (By similarity). Required for recruiting and activating RAB18 at the endoplasmic reticulum (ER) membrane where it maintains proper ER structure (By similarity). Required for normal eye and brain development (By similarity). May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters (By similarity).
The Rab3 GTPase-activating complex is a heterodimer composed of rab3gap1 and rab3gap2 (By similarity). The Rab3 GTPase-activating complex interacts with DMXL2 (By similarity). Interacts with LMAN1 (By similarity).
In the C-terminal section; belongs to the peptidase M41 family.
In the N-terminal section; belongs to the AAA ATPase family.
Expressed both maternally and zygotically. First expressed at 4 hpf. Expression is lower by 8 hpf and increases almost constantly thereafter.
Uniformly expressed in all embryonic cells at 4 and 8 hpf. At the 20-somite stage (18 hpf), ubiquitously expressed in the developing nervous system, in the tail bud and in the pronephric ducts. Also expressed in some placodes, including the anterior lateral line placode, otic vesicle and olfactory placode. At 27 hpf, strong expression persists in the central nervous system and the olfactory placode. Expressed strongly in the eyes and the pectoral fin buds. In the tail region, expressed in the spinal cord, in the posterior lateral line precursors, and persists in the pronephric ducts. At 48 hpf, expressed in all head territories including the developing brain, eyes, and pharyngeal arches. More caudally, expression persists in the pectoral fin buds, the spinal cord and, for the first time, appears in the intestine. At 72 hpf, expressed only in restricted regions of the brain, in pharyngeal arches region and in the amacrine cells and the horizontal cells of the retina.
Required for cis-Golgi integrity and efficient ER to Golgi transport.
The B box-type and RING-type zinc fingers although degenerate play a central role in function of the protein.
3D-structure analysis of the human homolog indicates that the membrane topology differs from the predictions. Contrary to predictions, the N-terminus contains two short helices that dip into the membrane, but do not cross it. The C-terminus contains the single transmembrane helix. This gives rise to a topology where the N-terminus is cytoplasmic and the C-terminus is lumenal.
Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins.
The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (psen1 or psen2), nicastrin (ncstn), aph1 (aph1a or aph1b) and psenen.
May be involved in iron transport and iron homeostasis.
Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).
Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
Expressed in brain regions that are known to control reproduction and sex behavior. Expressed in ovary, muscle and intestine. Expressed in early germ cells of the testis, including the spermatogonia, spermatocytes, and somatic cells such as Sertoli cells.
Expressed throughout early embryonic development from 0 hours post-fertilization (hpf) to 72 hpf. Expressed in blastomeres at 4 hpf. Expressed in the central nervous system at 18 hpf. Expressed in head including the anterior diencephalon, midbrain and hindbrain at 24 hpf. Expressed in trigeminal ganglia as well as in the heart, pancreas and intestinal bulb between 36 and 72 hpf (at protein level).
Membrane G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Plays a role in the embryonic development of sensory and motor neurons. Specifically induces apoptosis and reduces proliferation of brain cells. Involved in maintenance of meiotic arrest in oocytes.
Morpholino knockdown of the protein leads to growth retardation and developmental deformity.
Belongs to the complex I 23 kDa subunit family.
Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.
Involved in the maintenance of the Golgi structure. May play a role in hematopoiesis (By similarity).
Involved in the maintenance of the Golgi structure. May play a role in hematopoiesis.
Interacts with SHH via the cholesterol anchor of the dually lipid-modified SHH (ShhNp) (By similarity). Interacts with PTCH1 (By similarity). Forms homooligomers and heterooligomers with SCUBE1 and SCUBE3 (By similarity). Interacts with VEGFR2 (By similarity).
Lipid-binding protein required for SHH long-range signaling by binding to the dually lipid-modified SHH (ShhNp) and by promoting ShhNp mobilization, solubilization and release from the cell membrane. Acts by enhancing the proteolytic processing (shedding) of the lipid-modified N- and C- terminal of ShhNp at the cell surface. Synergizes with DISP1 to cause an increase in SHH secretion. Probable cell surface coreceptor for VEGFR2 involved in VEGFR2-mediated angiogenesis.
The CUB domain is important for the interaction with the cholesterol-anchor of SHH. The CUB domain regulates protease recruitment and activation during SHH shedding.
Zebrafish 'you class' developmental mutants are grouped together based on the anormal U-shaped morphology of the somites. Homozygous zebrafish mutants show disruption of the formation of hedgehog-sensitive muscle fates, with an altered myotomal morphology from a characteristic chevron shape to a more rounded U-shaped. One of these 'you class' mutant results from disruption of the Scube2 gene. These mutants lack slow twitch muscle and muscle pionneer cells, and PTCH1 expression within the myotome and neural tube is essentially absent.
Anchoring protein that mediates the subcellular compartmentation of cAMP-dependent protein kinase (PKA type II).
RII-binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.
Belongs to the G-protein coupled receptor 2 family.
Belongs to the inositol phosphokinase (IPK) family.
Belongs to the retinoblastoma protein (RB) family.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
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.
Embryos exhibit smaller eyes, a reduced brain and visceral skeleton, shortened fins and a lack of expansion of liver and gut, and die on day 6 of development.
Widely and highly expressed during the first 3 days of embryogenesis. Prominent sites of expression are the eyes and optic tectum on day 1, the fin buds, liver primordium, and gut on day 2, and the branchial arches on day 3.
First expressed at the 1-somite stage. At the 10-somite stage, weakly expressed in the paraxial mesoderm with an anterior expression limit at somite 1. At the 20-somite stage, expressed within the developing CNS with an anterior expression limit adjacent to the rhombomere 7/8 boundary.
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.
Ribosome biogenesis factor. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I.
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).
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 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 ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.
E3 ubiquitin-protein ligase that regulates selective mitochondrial autophagy by mediating 'Lys-63'-linked polyubiquitination. Acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation. Protects cells from ER stress-induced apoptosis. Responsible for the cotranslational ubiquitination and degradation of CFTR in the ERAD pathway. Also acts as a regulator of the innate antiviral response by catalyzing 'Lys-27'-linked polyubiquitination of CGAS, thereby promoting CGAS cyclic GMP-AMP synthase activity. Preferentially associates with the E2 enzymes UBE2J1 and UBE2J2 (By similarity).
The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity.
Belongs to the steroid 5-alpha reductase family.
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
Belongs to the PRAME family. LRRC14 subfamily.
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.
Interacts with G-actin; ADP-actin form and capping protein (CP).
Belongs to the glycosyltransferase 6 family.
Belongs to the intercrine beta (chemokine CC) family.
Belongs to the peptidase M28 family. M28B subfamily.
Belongs to the cysteine synthase/cystathionine beta-synthase family.
Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A6 subfamily.
Acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality control.
Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
Belongs to the DOK family. Type A subfamily.
Detected as early as 1 hour post-fertilization (hpf). Primarily localized in the head at 48 hpf.
Morpholino knockdown of the protein causes reduced brain and eye size and curved tails at 48 hpf.
Putative Rab GTPase-activating protein which plays a role in vesicular trafficking. Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles (By similarity). Plays a role in brain development (PubMed:28823706). May act as a general inhibitor of innate immunity signaling (By similarity).
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.
Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.
Belongs to the VPS10-related sortilin family. SORT1 subfamily.
Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Lysosomal proteins bind specifically to the receptor in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex. The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer. Also required for protein transport from the Golgi apparatus to the endosomes. May also mediate transport from the endoplasmic reticulum to the Golgi.
Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35; which is involved in retrograde trafficking of the receptor from endosomes to the Golgi apparatus (By similarity).
Palmitoylated. Undergoes cysteine S-palmitoylation which promotes the partitioning of the receptor into an endosomal membrane subdomain where it can interact with the retromer cargo-selective complex which mediates its retrograde trafficking to the Golgi apparatus.
Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Acts as a positive regulator of Wnt signaling pathway by promoting beta-catenin (CTNNB1) nuclear accumulation (By similarity). Required for normal Wnt signaling and normal dorsoventral patterning during embryogenesis (PubMed:28829046).
Expressed in the early developmental stages of embryos.
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 CTNNB1.
Morpholino knockdown produces morphants which exhibit loss or reduction of dorsal embryonic structures and Wnt signaling deficiency.
Belongs to the parathyroid hormone family.
Belongs to the prefoldin subunit beta family.
Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.
Heterohexamer of two PFD-alpha type and four PFD-beta type subunits.
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).
May be involved in vesicle transport between the ER and the Golgi complex.
Belongs to the 5'(3')-deoxyribonucleotidase family.
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 small heat shock protein (HSP20) family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM5/TYW2 family.
S-adenosyl-L-methionine-dependent transferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the transfer of the alpha-amino-alpha-carboxypropyl (acp) group from S-adenosyl-L-methionine to the C-7 position of 4-demethylwyosine (imG-14) to produce wybutosine-86 (By similarity).
Belongs to the glycosyl hydrolase 47 family.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.
Embryos show defects in branchial arch and ceratohyal development.
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 (By similarity). Plays an essential role in early embryonic development (PubMed:12006978).
First expressed at 11 hours post-fertilization (hpf) in the dorsal presomitic mesoderm and neural keel at posterior levels, extending into the ventral somitic mesoderm during budding. At 22-26 hpf, expression decreases in the lateral and ventral mesoderm, but is maintained in the neural rod. Expression decreases from posterior to anterior with an anterior expression limit at somite 9. At 24-26 hpf, posterior expression begins to weaken and is undetectable by 40-56 hpf.
Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation.
Detected in adult gill and in larval skin at 2 days post-fertilization (at protein level). In adult gill, strong expression is found in the basal regions of the secondary lamellae.
Expressed from 1 day post-fertilization.
Induced in larvae and adult gills by low salinity and repressed by high salinity.
May modulate the activity of a sodium/potassium-transporting ATPase.
Morpholino knockdown of the protein results in an increased number of sodium/potassium-transporting ATPase-expressing cells in larval skin.
Homopentamer. Pentaxin (or pentraxin) have a discoid arrangement of 5 non-covalently bound subunits.
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 protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.
Dimeric, linked by one or more disulfide bonds. Inhibin A is a dimer of alpha and beta-A. Inhibin B is a dimer of alpha and beta-B.
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 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.
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.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily.
Expressed during gastrulation in the ventral region of the embryo which includes tissue fated to form the non-neural ectoderm.
Belongs to the DEAD box helicase family.
Component of the DCX(AMBRA1) E3 ubiquitin ligase complex.
Expressed both maternally and zygotically. Present as maternal transcripts in the eggs and display a gradual decline until 8 hours post-fertilization (hpf), being replaced by zygotic mRNAs from 12 hpf onwards (PubMed:23348054). After 24 hpf, the transcripts are mainly localized in the brain and otic vesicles (PubMed:23348054).
Morpholino knockdown of ambra1a causes impaired dorso-ventral patterning in embryos (PubMed:23348054). Morpholino knockdown of ambra1a and ambra1b results in reduced autophagy and increased apoptosis during embryogenesis (PubMed:23348054). Morpholino knockdown of ambra1a and ambra1b results in impaired locomotion, caused by abnormal myogenesis (PubMed:24922546).
Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy (PubMed:23348054). The DCX(AMBRA1) complex specifically mediates the polyubiquitination of target proteins (By similarity). Acts as an upstream master regulator of the transition from G1 to S cell phase: ambra1a specifically recognizes and binds phosphorylated cyclin-D (ccnd1, ccnd2 and ccnd3), leading to cyclin-D ubiquitination by the DCX(AMBRA1) complex and subsequent degradation (By similarity). Acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (eloc) component of CRL5 complexes (By similarity). Acts as a key regulator of autophagy by modulating the BECN1-PIK3C3 complex: controls protein turnover during neuronal development, and regulates normal cell survival and proliferation (By similarity). In normal conditions, ambra1a is tethered to the cytoskeleton via interaction with dyneins light chains (By similarity). Upon autophagy induction, ambra1a is released from the cytoskeletal docking site to induce autophagosome nucleation by mediating ubiquitination of proteins involved in autophagy (By similarity). Also acts as an activator of mitophagy (By similarity). Required for skeletal muscle development (PubMed:24922546).
Belongs to the C/M/P thioester hydrolase family.
Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.
Belongs to the glucose-6-phosphatase family.
Detected in developing macrophages at 28 hours post-fertilization (PubMed:20424185). Continues to be expressed in macrophages at 2 and 6 days post-fertilization (dpf) (PubMed:25573892). Also detected in neutrophils at 2 and 6 dpf (PubMed:25573892).
Receptor for the C-X-C chemokines cxcl11.1 and cxcl11.6 (PubMed:25573892). Promotes macrophage chemotaxis to sites of bacterial infection (PubMed:20424185, PubMed:25573892).
Viable with no significant effect on survival (PubMed:25573892). Macrophage and neutrophil counts are normal (PubMed:25573892). Macrophage migration in response to cxcr3.2-independent stimuli is not affected, although the basal migration rate is reduced (PubMed:25573892). Macrophage migration to sites of bacterial infection by S.typhimurium or M.marinum is reduced (PubMed:20424185, PubMed:25573892). Dissemination of bacterial infection to distant sites and granuloma formation is also reduced (PubMed:25573892).
Belongs to the RIN (Ras interaction/interference) family.
Receptor for ATP that acts as a ligand-gated ion channel.
Belongs to the bacterial ribosomal protein bL20 family.
Belongs to the Mrp/NBP35 ATP-binding proteins family.
Belongs to the integrin beta chain family.
Belongs to the alkaline phosphatase family.
Belongs to the ELO family. ELOVL6 subfamily.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that elongates fatty acids with 12, 14 and 16 carbons with higher activity toward C16:0 acyl-CoAs. Catalyzes the synthesis of unsaturated C16 long chain fatty acids and, to a lesser extent, C18:0 and those with low desaturation degree. May participate in the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
The reaction is stimulated by the presence of HSD17B12, the enzyme catalyzing the second step of the elongation cycle.
Scaffold protein which mediates the formation of the PTW/PP1 phosphatase complex by providing a binding platform to each component of the complex. The PTW/PP1 phosphatase complex plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Mediates interaction of WDR82 and PPP1CA. Inhibitor of PPP1CA and PPP1CC phosphatase activities. Has inhibitory activity on PPP1CA only when phosphorylated. Binds to mRNA, single-stranded DNA (ssDNA), poly(A) and poly(G) homopolymers.
Belongs to the SMC family. RAD50 subfamily.
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.
This protein may be expected to contain an N-terminal transit peptide but none has been predicted.
The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity.
Belongs to the protein-tyrosine phosphatase family. Receptor class 5 subfamily.
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 secreted frizzled-related protein (sFRP) family.
Belongs to the POU transcription factor family. Class-2 subfamily.
Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.
Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin. Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Plays a central role in controlling thyroid cell metabolism.
Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.
Belongs to the G-alpha family. G(12) subfamily.
Negatively regulates TGF-beta signaling.
Belongs to the DHHC palmitoyltransferase family.
May be involved in the regulation of p53-dependent G2 arrest of the cell cycle.
Belongs to the DEAD box helicase family. DDX18/HAS1 subfamily.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type 2 subfamily.
Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.
Belongs to the gamma-glutamyltransferase family.
Cleaves the gamma-glutamyl peptide bond of glutathione and glutathione conjugates.
Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex (By similarity). Interacts with the poly-Gln domain of ATXN3; the interaction causes deubiquitination at Lys-399 and stabilizes BECN1 (PubMed:28445460).
Expanded poly-Gln tracts inhibit ATXN3-BECN1 interaction, decrease BECN1 levels and impair starvation-induced autophagy (PubMed:28445460).
Expressed during follicle development in the ovary (PubMed:23195281).
Plays a central role in autophagy (PubMed:24441423, PubMed:27467399, PubMed:28445460). 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).
Polyubiquitinated at Lys-399 with 'Lys-48'-linkages (PubMed:28445460). 'Lys-48'-linked polyubiquitination of Lys-399 leads to degradation (PubMed:28445460). Deubiquitinated by ATXN3, leading to stabilization (PubMed:28445460).
Results in defects in morphogenesis, increased numbers of dead cells, abnormal heart structure, and reduced organismal survival (PubMed:24441423). Reduces the regenerative response to muscle injury with accumulation of sarcomeric and nuclear debris (PubMed:27467399).
The C-terminal evolutionary conserved domain (ECD) contains poly-Gln-binding domains such as the ATXN3 poly-Gln motif, consistent with structural docking models revealing two highly scored poly-Gln-binding pockets in the ECD. As some binding is observed with BECN1 lacking the ECD, other domains of BECN1 may also interact with ATXN3.
The coiled coil domain can form antiparallel homodimers and mediates dimerization with the coiled coil domains of ATG14 or UVRAG involved in the formation of PI3K complexes.
Interacts with LRP4 (via the extracellular domain); the interaction facilitates the inhibition of Wnt signaling. Interacts with LRP5 (via the first two YWTD-EGF repeat domains); the interaction inhibits Wnt-mediated signaling. Interacts with LRP6.
Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SETD6 subfamily.
Belongs to the potassium channel HCN family.
Belongs to the V-ATPase V0D/AC39 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 (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). May play a role in coupling of proton transport and ATP hydrolysis (By similarity). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (By similarity). May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium (PubMed:21844891).
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity).
Belongs to the phosphohexose mutase family.
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).
Was originally thought to be the ortholog of mammalian DLG3.
During embryonic development, highly expressed at 8 hours post-fertilization (hpf) (PubMed:28402832). Expressed at the pharyngula stage at 24 hpf and expression is maintained 48 hpf, 72 hpf and to larval day 4 of development at 96 hpf (PubMed:29791492, PubMed:28402832). During this time, expressed in the pharyngeal arches, and in the intestinal bulb at 72 and 96 hpf (PubMed:29791492, PubMed:12464617). Also expressed in the epidermis and mouth at 48 and 72 hpf (PubMed:12464617).
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 10 kDa (p10) subunit (Probable). Interacts (via pyrin domain) with pycard (via pyrin domain) (PubMed:12464617, PubMed:29791979, PubMed:30150286). Interacts with caspb (PubMed:29791979). Component of NLRP1 inflammasomes (PubMed:30150286). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:30150286). The NLRP1 inflammasome is composed of the signal sensor nlrp1, and the adapter pycard (asc), which recruit effector pro-inflammatory caspases caspa and/or caspb (PubMed:30150286). The interaction between nlrp1 and pycard is required for the sequential recruitment of caspa and then caspb (PubMed:30150286). Caspa is preferentially recruited first and this causes the cleavage of pro-il1b into the midformed il1b (PubMed:30150286). This is followed by the recruitment of caspb, which is activated and cleaves the midformed il1b resulting in il1b maturation (PubMed:30150286). Interacts with caiap (PubMed:29123523).
Morpholino knockdown in early embryos results in abnormalities in the development of the cartilaginous pharyngeal skeleton and eventually results in death upon exhaustion of the yolk (PubMed:12464617). Abnormalities include deformed and thinned Meckel's and palatoquadrate cartilages, deformed ceratohyal cartilages and disorganized branchial cartilages (PubMed:12464617). Morpholino knockdown in one- to four-cell stage embryos results in an open mouth phenotype (PubMed:12464617). Morpholino knockdown in one-cell embryos results in reduced survival in response to bacterial infection with E.tarda, but does not decrease caspb activation (PubMed:30150286). Morpholino knockdown in larvae results in no abnormalities in the brain, eyes or pectoral fins (PubMed:12464617).
The two subunits are derived from the precursor sequence by an autocatalytic mechanism.
Thiol protease which cleaves IL-1 beta (il1b), releasing the mature cytokine which is involved in a variety of inflammatory processes, and mediates apoptosis (PubMed:12464617, PubMed:30150286). Component of the NLRP1 inflammasome, which plays a crucial role in innate immunity and inflammation (PubMed:30150286). In response to pathogens and other damage-associated signals, recruited to the NLRP1 inflammasome in its precursor form (PubMed:30150286). Its subsequent activation causes the cleavage of pro-il1b into the midformed il1b, which then evetually leads to il1b maturation and secretion in the extracellular milieu (PubMed:30150286). Required for the development of the cartilaginous pharyngeal skeleton (PubMed:12464617).
Up-regulated in response to pentachlorophenol (PCP), a toxic pollutant (PubMed:28402832). Up-regulated in response to bacterial infection with E.tarda (PubMed:30150286).
Belongs to the mitochondrion-specific ribosomal protein mS39 family.
Mitochondrial RNA-binding protein that may have a role in mitochondrial translation.
Belongs to the intercrine alpha (chemokine CxC) family.
Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
Component of the GPI transamidase complex. May be involved in the recognition of either the GPI attachment signal or the lipid portion of GPI.
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).
Proteolytically removes the C-terminal three residues of farnesylated proteins.
Belongs to the SIX/Sine oculis homeobox family.
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.
Belongs to the uroporphyrinogen-III synthase family.
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. 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 (By similarity).
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome (By similarity).
Belongs to the peptidase C78 family. ZUFSP subfamily.
Belongs to the sphingomyelin synthase family.
Promotes degradation of target mRNA species. Plays a role in the regulation of circadian mRNA stability. Binds GTP and has GTPase activity.
Belongs to the PPP phosphatase family. PP-2B subfamily.
Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles (By similarity).
Belongs to the MINDY deubiquitinase family. FAM188 subfamily.
Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.
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 protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
Belongs to the sulfotransferase 3 family.
According to a first report, morpholino-mediated knockdown of kctd13 leads to increased brain size and cell proliferation (PubMed:22596160). However, it was later shown that deletion of kctd13 does not cause any change in brain size or cell proliferation (PubMed:29088697). Experimental conditions used may explain discrepancies. A possible explanation being that morpholinos used in the first study, may have affected off-targets.
Increased levels of RHOA. N ochange in brain size or neural progenitor cell proliferation is observed.
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for synaptic transmission (By similarity). The BCR(KCTD13) E3 ubiquitin ligase complex mediates the ubiquitination of RHOA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and promoting synaptic transmission (PubMed:29088697).
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.
'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).
Belongs to the eukaryotic ribosomal protein eL8 family.
Common component of the spliceosome and rRNA processing machinery.
Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.
Mediates the uptake of pyruvate into mitochondria.
Belongs to the ClpA/ClpB family. Torsin subfamily.
Belongs to the liprin family. Liprin-alpha subfamily.
Belongs to the HAD-like hydrolase superfamily. EYA family.
Catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme.
In the C-terminal section; belongs to the PAPS reductase family. FAD1 subfamily.
In the N-terminal section; belongs to the MoaB/Mog family.
The molybdenum cofactor biosynthesis protein-like region may not be functional.
Belongs to the group II decarboxylase family.
Catalyzes the transfer of a dimethylallyl group onto the adenine at position 37.
Plays a role in the assembly or stability of the cytochrome c oxidase complex (COX).
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.
May be involved in podosome and invadosome formation.
Belongs to the CND3 (condensin subunit 3) family.
Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells.
Belongs to the L-aspartate dehydrogenase family.
Protease-inhibitor that contains multiple distinct protease inhibitor domains. Probably has serine protease- and metalloprotease-inhibitor activity (By similarity).
Belongs to the protease inhibitor I35 (TIMP) family.
After the very early developmental stages, the expression levels decrease and remain relatively constant until around 24 h, with the onset of an increase of expression that continues till the larval stages.
Neuronal cell surface protein that may be involved in cell recognition and cell adhesion.
Belongs to the sarcoglycan beta/delta/gamma/zeta family.
Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
Cross-link to form 2 major subcomplexes: one consisting of SGCB, SGCD and SGCG and the other consisting of SGCB and SGCD. The association between SGCB and SGCG is particularly strong while SGCA is loosely associated with the other sarcoglycans.
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.
Expressed zygotically. First detected at the tail bud stage and continues to be expressed for at least the first 48 hours of development.
First detected at the tail bud stage in the forebrain. At the 3-somite stage, also expressed weakly in the hindbrain. At the 12-somite stage, strongly expressed in the forebrain and weakly expressed throughout the central nervous system. At the 21-somite stage, also expressed in the lens.
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
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 WD repeat coronin family.
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.
Expressed maternally but largely absent later in embryonic development. Also expressed in adult.
Expressed strongly in ovary and more weakly in eye. Little expression in other tissues examined.
May play a role in apoptosis. Does not appear to show pro-apoptotic activity when expressed ectopically in early embryos.
Interacts with ODC1 and thereby sterically blocks ODC homodimerization.
Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimer, and targets the monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome.
Belongs to the eukaryotic initiation factor 4G family.
Phosphorylated on some or all of the serine and threonine residues present in the C-terminal region.
Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to cis-retinal.
Belongs to the amino acid/polyamine transporter 2 family.
Probable sodium-dependent amino acid/proton antiporter, could be a neuronal transporter for glutamate.
Belongs to the connexin family. Alpha-type (group II) subfamily.
Could function in transport of proteins into the mitochondrion.
Part of a large protein complex spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB) complex.
Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.
In the C-terminal section; belongs to the phosphoglycerate mutase family.
Females are almost sterile: only 7 of 3024 eggs derived from mutant females develop into cleavage-stage embryos, as opposed to the majority of eggs from wild-type (PubMed:30190407). Both male and female fishes develop normally and are overtly healthy (PubMed:30190407). Males are fertile (PubMed:30190407).
Highly expressed in oocytes (PubMed:30190407). Not expressed in testis (PubMed:30190407).
Oocyte-expressed fertilization factor that mediates sperm-egg binding and is essential for sperm entry into the egg (PubMed:30190407). Necessary and sufficient to mediate species-specific gamete recognition and fertilization, which is essential for vertebrate species performing external fertilization (PubMed:30190407). External fertilization cannot guarantee that only conspecific sperm reaches the egg by precopulatory mate choice: proteins such as Bouncer can therefore support the selection of conspecific sperm (PubMed:30190407).
Was named bouncer (bncr) in reference to the colloquial name of a security guard at a bar.
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.
Belongs to the glycosyltransferase 8 family.
Glycosyltransferase which elongates the O-linked glucose attached to EGF-like repeats in the extracellular domain of Notch proteins by catalyzing the addition of xylose.
Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes.
Belongs to the dynein light intermediate chain family.
Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs).
Belongs to the PUR DNA-binding protein family.
May bind repeated elements in single-stranded DNA and may participate in transcriptional and translational gene regulation.
Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
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.
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.
Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types.
Belongs to the complement C6/C7/C8/C9 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.
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides.
Belongs to the WD repeat G protein beta family.
Enhances GTPase-activating protein (GAP) activity of regulator of G protein signaling (RGS) proteins, hence involved in the termination of the signaling initiated by the G protein coupled receptors (GPCRs) by accelerating the GTP hydrolysis on the G-alpha subunits, thereby promoting their inactivation (Probable). Increases RGS9 GTPase-activating protein (GAP) activity, hence contributes to the deactivation of G protein signaling initiated by D(2) dopamine receptors (By similarity). Along with gnb5b, plays an important role in neuronal signaling, including in the parasympathetic, but not sympathetic, control of heart rate (PubMed:27523599).
May interact with RGS9; this interaction stabilizes both proteins and increases RGS9 GTPase-activating protein (GAP) activity, hence accelerating the deactivation of D(2) dopamine receptor-mediated signaling.
No visible phenotype; due to the redundancy with gnb5a. Simultaneous knockout of gnb5a and gnb5b results in no striking dysmorphologic features, but the larvae show impaired swimming activity, remain small, and generally die 7-14 days post fertilization (dpf), most likely as a result of their inability to feed.
Belongs to the eukaryotic NMN adenylyltransferase family.
Involved in transport of proteins from the cis/medial-Golgi to the trans-Golgi network.
Belongs to the SelWTH family. Selenoprotein T subfamily.
Expressed in embryonic olfactory vesicles and the photoreceptor cell layer of the embryonic retina. Low level in embryonic epiphysis.
May contain a selenide-sulfide bond between Cys-44 and Sec-47. This bond is speculated to serve as redox-active pair (By similarity).
Selenoprotein with thioredoxin reductase-like oxidoreductase activity.
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 nuclear hormone receptor family. NR3 subfamily.
Interacts with ribonucleoprotein complex components.
RNA-binding protein involved in deadenylation-dependent decapping of mRNAs, leading to the degradation of mRNAs. Acts as a scaffold protein that connects deadenylation and decapping machinery. Required for cytoplasmic mRNA processing body (P-body) assembly.
Belongs to the GST superfamily. Alpha family.
GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42 (By similarity).
Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.
Belongs to the CTL (choline transporter-like) family.
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 major facilitator superfamily.
Belongs to the protein kinase superfamily. RIO-type Ser/Thr kinase family.
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.
Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly.
Expressed zygotically. First detected at the mid-blastula transition. Confined to the future ectoderm by the shield stage, and to the presumptive neuroectoderm by the 75-80% epiboly stage. From the tail bud to the 3-somite stage, expressed throughout the neural plate, except in the anterior margin; strongest expression in the presumptive ventral diencephalon. At the 12- to 25-somite stage, expressed broadly in the central nervous system. From 24-30 hours post-fertilization, restricted to the ventral diencephalon, midbrain and hindbrain/anterior spinal cord region, and to the retina and lens.
Belongs to the SRC/p160 nuclear receptor coactivator family.
Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently.
Contains 3 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 (By similarity).
Expressed ubiquitously in the embryo and in many adult tissues including the brain, gills, liver, swim bladder and skin. Shows highest expression in the ovary and testis, and lower expression in the intestine, eye and skin. Only isoform E20b is expressed in the muscle and heart.
Interacts with the thyroid hormone receptors thraa and thrb (via the ligand-binding domain).
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) (By similarity). Has a role in primitive myelopoiesis in the differentiation of granulocytes and macrophages. May play a role in the positive regulation of the circadian clock (By similarity).
First observed at tailbud stage in the developing Kupffer's vesicle, the zebrafish laterality organ. At the 10 somites stage, it is expressed in the otic vesicle and the floorplate. At 18 somites it is expressed in the pronephros. From 23 somites, it is no longer detected.
Interacts with PIERCE1 and PIERCE2; the interactions link outer dynein arms docking complex (ODA-DC) to the internal microtubule inner proteins (MIP) in cilium axoneme.
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 beating of primary cilia and thereby be involved in the establishment of organ laterality during embryogenesis (PubMed:26531781).
Zebrafish mutants lacking cfap53 display total organ heterotaxia.
Heterohexamer; composed of 3 copies of TIMM8 (TIMM8A or TIMM8B) and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22 (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.
Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of some proteins while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins (By similarity).
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space.
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM13 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity).
F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel.
Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane.
Belongs to the chemokine-like receptor (CMKLR) family.
Belongs to the centaurin gamma-like family.
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.
Belongs to the splicing factor SR family.
Belongs to the WD repeat Groucho/TLE family.
May be important in protein trafficking and/or protein folding and stabilization.
Expression is restricted to the heart (at protein level).
May play an important role in cardiac development and function. May regulate cardiac conduction and the function of the gap junction protein GJA1. May contribute to the stability and proper localization of GJA1 to cardiac intercalated disk thereby regulating gap junction communication (PubMed:26403541). Regulates mitochondrial respiration and mitochondrial DNA copy number maintenance (By similarity).
Monomer. Homodimer. Interacts with GJA1.
Morpholino knockdown of the protein causes pericardial edema and altered cardiac morphology in 4 days post-fertilization (dpf) embryos and severity increases as embryos age. Morrphants are not viable by 7 dpf. Hearts showed abnormal cardiac looping in the morphants and a significant decline in heart beat rates seen in after 4.5 dpf and continue decreasing at 5 and 6 dpf. Ventricles show a significant reduction in amplitude of Ca(2+) transients in morphants between 4 and 6 dpf.
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.
Belongs to the class I-like SAM-binding methyltransferase superfamily. MenG/UbiE family.
Component of a multi-subunit COQ enzyme complex, composed of at least coq3, coq4, coq5, coq6, coq7 and coq9.
Methyltransferase required for the conversion of 2-polyprenyl-6-methoxy-1,4-benzoquinol (DDMQH2) to 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2).
Belongs to the proteasome subunit S5A family.
May be involved in N-linked oligosaccharide assembly.
Belongs to the galactose-3-O-sulfotransferase family.
Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway.
Binds 2 zinc divalent cations per subunit.
Homodimer. Bile acids promote the assembly of inactive monomers into an active dimer and enable catalysis.
Regulator of endoplasmic reticulum secretion that acts as a key determinant of brain size. Required for secretion of extracellular matrix proteins. Required for correct brain development by depositing sufficient extracellular matrix proteins for tissue integrity and the proliferation of neural progenitors (By similarity). Acts as a regulator of the unfolded protein response (UPR) (By similarity).
Belongs to the eukaryotic ribosomal protein eS17 family.
Belongs to the class I fructose-bisphosphate aldolase family.
Among the many cysteines in the lumenal domain, most are probably involved in disulfide bonds.
Belongs to the histone deacetylase family. HD type 2 subfamily.
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events.
Belongs to the beta-microseminoprotein family.
DNA binding protein that function as transcriptional activator. May play a role in the determination and function of cell types in the brain.
Belongs to the eukaryotic ribosomal protein eS12 family.
Belongs to the SWEET sugar transporter family.
Mediates sugar transport across membranes.
Transcriptional activator which activates the CDKN2A/ARF locus in response to Ras-Raf signaling, thereby promoting p53/TP53-dependent growth arrest. Binds to the consensus sequence 5'-CCCG[GT]ATGT-3'.
Activates an alternative mTOR signaling to regulate cell proliferation and migration.
Belongs to the carnitine/choline acetyltransferase family.
Acts as a ventralizing factor during embryogenesis. Inhibits axin-mediated JNK activation by binding axin and disrupting axin homodimerization. This in turn antagonizes a Wnt/beta-catenin-independent dorsalization pathway activated by axin/JNK-signaling.
At 24 hours post-fertilization, expressed in most tissues, with strongest expression in the brain and somites.
Expressed both maternally and zygotically.
Component of a multisubunit histone acetyltransferase complex (MSL).
Component of histone acetyltransferase complex. Within MSL complex, promotes ubiquitination of histone H2B.
C-terminus of translation can be extended by 1 residue.
Belongs to the activator 1 small subunits family.
Putative Notch ligand involved in the mediation of Notch signaling.
Component of a SNARE complex consisting of stx5, ykt6, gosr2 and bet1l.
Vesicle SNARE required for targeting and fusion of retrograde transport vesicles with the Golgi complex. Required for the integrity of the Golgi complex (By similarity).
Although it belongs to the DHHC palmitoyltransferase family, lacks the conserved active site cysteine residue at position 479 and may lack catalytic activity.
Belongs to the DHHC palmitoyltransferase family. AKR/ZDHHC17 subfamily.
Probably maternally supplied, the zygotic expression becomes significative at shield stage (6 hpf) and then decreases after 7.5 hpf but is still detected at 24 hpf.
Putative palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates.
May participate in suppression of cell proliferation and induces apoptotic cell death through activation of interleukin-1-beta converting enzyme (ICE)-like proteases.
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
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.
Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at least composed of cul3, klhl21 and rbx1.
Substrate-specific adapter of BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (By similarity).
Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.
E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated mdc1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of tp53bp1 and brca1 ionizing radiation-induced foci (IRIF). H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains, leading to degradation of substrate proteins. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation.
Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of the rnf8 homodimer and a E2 heterodimer of ube2n and ube2v2.
The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1.
Mediates the nuclear export of actin and profilin-actin complexes in somatic cells.
Belongs to the aspartate/ornithine carbamoyltransferase superfamily.
Belongs to the thiolase-like superfamily. Thiolase family.
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 AEBP2/jing C2H2-type zinc-finger family.
DNA-binding transcriptional repressor. May interact with and stimulate the activity of histone methyltransferase complexes.
Morpholino knockdown of the protein causes severe defects in motor neuron axonal outgrowth.
Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes. Has phospholipid scramblase activity toward cholesterol and phosphatidylserine, as well as phosphatidylethanolamine and phosphatidylcholine. Required for autophagosome formation: participates in early stages of autophagosome biogenesis at the endoplasmic reticulum (ER) membrane by reequilibrating the leaflets of the ER as lipids are extracted by atg2 (atg2a or atg2b) to mediate autophagosome assembly. In addition to autophagy, involved in other processes in which phospholipid scramblase activity is required (By similarity). Required for normal motor neuron development (PubMed:23063131).
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 cyclophilin-type PPIase family.
May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system.
Belongs to the nuclear hormone receptor family. NR5 subfamily.
Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex.
Belongs to the 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).
Catalyzes the first step in the biosynthesis of NAD from nicotinic acid, the ATP-dependent synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate.
Transiently phosphorylated on a His residue during the reaction cycle. Phosphorylation strongly increases the affinity for substrates and increases the rate of nicotinate D-ribonucleotide production. Dephosphorylation regenerates the low-affinity form of the enzyme, leading to product release.
Efficient DNA binding requires dimerization with another bHLH protein.
First detected at 10 hours post-fertilization (hpf) increasing over the next 24 hours, then decreasing between 48 and 72 hours. Not detected in adult.
In the 24 hours embryo, expressed in hindbrain close to the anterior and posterior boundaries of rhombomeres 2-6 and in ventral cells close to the floor plate of most rhombomeres. Also expressed in the telencephalon, diencephalon, tegmentum and spinal cord at sites distinct from those expressing ascl1a. Not expressed in the adenohypophysis.
Transcriptional regulator. May mediate transcription activation by binding to the E box-containing promoter (By similarity). Involved in neurogenesis. Involved in maintaining rhombomere boundaries in the hindbrain, probably via up-regulation of delta expression. May mediate transcription activation by binding to the E box-containing promoter.
Involved in the cell surface expression of neuronal nicotinic receptors (By similarity). Binds RNA (By similarity).
Belongs to the eukaryotic ribosomal protein eS8 family.
Binds long-chain acyl-coenzyme A molecules with a strong preference for unsaturated C18:1-CoA. Does not bind fatty acids (By similarity).
Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor.
Belongs to the peroxisomal membrane protein PXMP2/4 family.
Belongs to the teashirt C2H2-type zinc-finger protein family.
Acts as a mediator between the cap-binding complex (CBC) and the primary microRNAs (miRNAs) processing machinery during cell proliferation. Contributes to the stability and delivery of capped primary miRNA transcripts to the primary miRNA processing complex, thereby playing a role in RNA-mediated gene silencing (RNAi) by miRNAs (By similarity). Independently of its activity on miRNAs, necessary and sufficient to promote neural stem cell self-renewal. Does so by directly binding SOX2 promoter and positively regulating its transcription (By similarity).
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.
Belongs to the bacterial ribosomal protein bS18 family.
SUMO-specific isopeptidase involved in protein desumoylation. Specifically binds SUMO proteins with a higher affinity for sumo2 and sumo3 which it cleaves more efficiently. Also able to process full-length SUMO proteins to their mature forms (PubMed:22878415). Plays a key role in RNA polymerase-II-mediated snRNA transcription in the Cajal bodies (By similarity). Is a component of complexes that can bind to U snRNA genes (By similarity).
Centrosomal protein involved in centriole biogenesis. Acts as a scaffolding protein during early centriole biogenesis. Required for the targeting of centriole satellite proteins to centrosomes. Also required for centriole-centriole cohesion during interphase by acting as a platform protein for cep250 at the centriole (By similarity).
Belongs to the thymidylate synthase family.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives.
Belongs to the carbohydrate kinase PfkB 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 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 interleukin-1 receptor family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Morpholino knockdown of the protein results in profound anemia without affecting erythroid specification.
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.
Binding to PtdIns(3,5)P2 is not required for localization.
Required for normal morphology of late endosomes and/or lysosomes in neurons. Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (By similarity).
The CRAL-TRIO domain is required for targeting to the membrane and for binding PtdIns(3,5)P2.
Belongs to the protein disulfide isomerase family.
Belongs to the metallothionein superfamily. Type 1 family.
Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines.
Expressed both maternally and zygotically. Expressed ubiquitously during early embryogenesis, but becomes localized to the tail region during segmentation. During early larval development, expressed in discrete areas including the pronephric region, retina and cerebellum.
Metallothioneins have a high content of cysteine residues that bind various heavy metals.
Acts as the sensor component of the nlrp1 inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis (PubMed:30150286). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:30150286). Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, and mediates the formation of the inflammasome polymeric complex (By similarity). In response to pathogen-associated signals, the N-terminal part of nlrp1 is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes to initiate the formation of the inflammasome complex: the inflammasome recruits and activate pro-inflammatory caspases (caspa and/or caspb), leading to pyroptosis (By similarity).
Autocatalytically cleaved. Autocatalytic cleavage in FIIND region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating pro-inflammatory caspases (caspa and/or caspb) binding. Both N- and C-terminal parts remain associated non-covalently.
Constitutes the active part of the nlrp1 inflammasome (By similarity). In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of nlrp1 (NACHT, LRR and PYD domains-containing protein 1, N-terminus), preventing activation of the nlrp1 inflammasome (By similarity). In response to pathogen-associated signals, the N-terminal part of nlrp1 is degraded by the proteasome, releasing this form, which polymerizes to form the nlrp1 inflammasome complex: the nlrp1 inflammasome complex then directly recruits and activates pro-inflammatory caspases (caspa and/or caspb) activation, leading to subsequent pyroptosis (By similarity).
Constitutes the precursor of the nlrp1 inflammasome, which mediates autoproteolytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals.
Expressed in adult spleen, head kidney, gill and skin and also in the embryo.
In the embryo, highest expression at 2 hours post-fertilization (hpf) with levels decreasing in later stages.
Interacts with the C-terminal part of nlrp1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) in absence of pathogens and other damage-associated signals.
Interacts with the N-terminal part of nlrp1 (NACHT, LRR and PYD domains-containing protein 1, N-terminus) in absence of pathogens and other damage-associated signals (By similarity). Homomultimer; forms the nlrp1 inflammasome polymeric complex, a filament composed of homopolymers of this form in response to pathogens and other damage-associated signals (By similarity). The nlrp1 inflammasome polymeric complex associates with pycard/asc (PubMed:30150286). Interacts (via CARD domain) with pycard/asc (via CARD domain); leading to pro-inflammatory caspases (caspa and/or caspb) recruitment (PubMed:30150286). Pro-caspase-a and pro-caspase-b filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation. Active caspa and caspb then processes il1b and il18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (By similarity).
Morpholino knockdown in embryos 6 hours post-fertilization (hpf) results in reduced caspa and caspb activation following bacterial infection with E.tarda.
Regulatory part that prevents formation of the nlrp1 inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of nlrp1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus), preventing activation of the nlrp1 inflammasome (By similarity). In response to pathogen-associated signals, this part is ubiquitinated and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the nlrp1 inflammasome (By similarity).
The C-terminal part of nlrp1 oligomerizes to form the core of the nlrp1 inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments.
The CARD domain is involved in the interaction with pycard.
Ubiquitinated in response to pathogen-associated signals, leading to its degradation by the proteasome and subsequent release of the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and forms the nlrp1 inflammasome.
Up-regulated in response to infection with the bacteriim E.tarda.
nlrp1 inflammasome is activated by pathogens and other damage-associated signals: activation promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and forms the nlrp1 inflammasome.
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.
Belongs to the peptidase S9B family. DPPIV subfamily.
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 universal ribosomal protein uL30 family.
Component of some SAGA transcription coactivator-HAT complexes. Within the SAGA complex, participates in a subcomplex of SAGA called the DUB module (deubiquitination module) (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.
Could coordinate an aspect of bone turnover.
Belongs to the tubulin polyglutamylase family.
Belongs to the glycosyltransferase 92 family.
Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues.
Belongs to the snRNP Sm proteins family.
Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
Belongs to the protein prenyltransferase subunit alpha 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.
Morpholino knockdown of the protein results in brain developmental defects. Morphants show a small head and seizure-like electroencephalography spikes. Additional defects include slow circulation, bend body and pericardial edema.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
Fish lacking cdk20 are viable during embryogenesis and early larval stages, but exhibit curvature of the body axis and curled cilia in distal kidney tubules.
Involved in cell growth. Activates cdk2, a kinase involved in the control of the cell cycle, by phosphorylating residue 'Thr-160' (By similarity). Required for high-level Shh responses in the developing neural tube. Together with tbc1d32, controls the structure of the primary cilium by coordinating assembly of the ciliary membrane and axoneme, allowing gli2 to be properly activated in response to SHH signaling.
Endonuclease that specifically degrades the RNA of RNA-DNA hybrids.
Ribosome biogenesis factor. May be required for both optimal rDNA transcription and pre-rRNA processing (By similarity).
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.
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.
Belongs to the repulsive guidance molecule (RGM) family.
Belongs to the WD repeat NOL10/ENP2 family.
Belongs to the sepiapterin reductase family.
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC1 subfamily.
Channel opening involves a conformation change that affects primarily the extracellular domain and the second transmembrane helix and its orientation in the membrane. In the open state, the second transmembrane helix is nearly perpendicular to the plane of the membrane; in the desensitized state it is strongly tilted. Besides, the second transmembrane domain is discontinuously helical in the open state. The GAS motif of the selectivity filter is in an extended conformation, giving rise to a distinct kink in the polypeptide chain. A domain swap between subunits gives rise to a full-length transmembrane helix (By similarity).
Expressed in central nervous system. Faintly expressed in the trunk, presumably in dorsal root ganglia.
First detected 48 hours post-fertilization (hpf) in the ventral thalamus, ventral midbrain, ventral cerebellum, ventral hindbrain, dorsal thalamus, hypothalamus, telencephalon, along the tract of the anterior commissure. Weakly expressed in the dorsal midbrain and olfactory bulb. Expression increases by 96 hpf and is detected in the tectum and trunk.
Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with asic1/accn2c.
Proton-gated sodium channel; it is activated by a drop of the extracellular pH and then becomes rapidly desensitized. Generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Can also transport potassium ions, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions.
Endoplasmic reticulum-Golgi intermediate compartment
May play a role in cell differentiation, proliferation and apoptosis. Binds cholesterol in cholesterol-containing plasma membrane microdomains and may play a role in the organization of the apical plasma membrane in epithelial cells. Involved in regulation of MAPK and Akt signaling pathways (By similarity).
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 extended synaptotagmin family.
Morpholino lockdown of the gene in 2 days post-fertilization (dpf) larvae show a dose-dependent significant reduction in the length of the terminal nerve axons, which provide the scaffold for migrating GnRH neurons towards the hypothalamus. In addition, there is a significant reduction in the size of the olfactory bulb.
Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3') (By similarity). May be involved in the functional network that regulates the development of the GnRH axis (PubMed:32620954).
Belongs to the paired homeobox family. Bicoid subfamily.
Plays a critical role in eye formation by regulating the initial specification of retinal cells and/or their subsequent proliferation.
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.
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. May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated protein aggregates. May also be involved in maintenance of normal mitochondrial structure and organization.
Highly expressed at 5 and 15 hpf. Expression is higher in brain and eye. The expression drops after 72 hpf.
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 G-alpha family. G(q) subfamily.
Associates with the cytoplasmic CCR4-NOT deadenylase complex to trigger ARE-containing mRNA deadenylation and decay processes.
Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis. Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery. Functions by recruiting the CCR4-NOT deadenylase complex and probably other components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes. Binds to 3'-UTR ARE of numerous mRNAs.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.4/KCNA4 sub-subfamily.
Expressed in the developing germ cells of both gonads, mainly in spermatogonia, spermatocytes and developing oocytes. Also expressed in embryonic olfactory placode and neural tube.
Expression increases gradually to a high level at pharyngula stage, which is restricted to the olfactory placode and the neural tube. In the juvenile zebrafish, the expression is first detected in undifferentiated gonad on 17 dpf.
Probable transcription factor that plays a role in configuring the spinal circuits controlling motion in vertebrates. Involved in neuronal specification within specific subdivision of spinal cord neurons and in the development of a coordinated locomotor network controlling movements. May regulate transcription (By similarity).
Belongs to the eukaryotic initiation factor 4E family.
Belongs to the universal ribosomal protein uS5 family.
Belongs to the eIF4E-binding protein family.
Belongs to the complex I subunit 2 family.
Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.
AO127 mutants were identified based on increased acridine orange uptake. AO127 mutants display enlarged lysosomes in brain and lysosomal accumulation of undigested ribosomal RNA in brain neurons, white matter lesions adjacent to brain ventricles, and frequent focal white matter anomalies throughout the brain. Nevertheless, mutants appear basically normal, reach normal adult size and length, are fertile and do not display obvious gross motor deficiencies.
Has ribonuclease activity, with higher activity at acidic pH. Probably is involved in lysosomal degradation of ribosomal RNA.
Belongs to the iron/ascorbate-dependent oxidoreductase 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.
Homodimer (By similarity). Component of the PET complex (By similarity).
RNA-binding component of the PET complex, a multiprotein complex required for the processing of piRNAs during spermatogenesis. The piRNA metabolic process mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposable elements, preventing their mobilization, which is essential for the germline integrity. The PET complex is required during the secondary piRNAs metabolic process for the piwil2 slicing-triggered loading of piwil4 piRNAs. In the PET complex, exd1 probably acts as an RNA adapter. Exd1 is an inactive exonuclease.
The 3'-5' exonuclease domain lacks the conserved Asp-Glu-Asp-Asp (DEDD) residues that coordinates divalent ions essential for exonuclease activity.
Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP synthases family.
GTP-binding protein involved in protein trafficking; modulates vesicle budding and uncoating within the Golgi apparatus.
Belongs to the ADP-ribosylglycohydrolase family.
Associates with the intermediate 315 kDa subcomplex of incompletely assembled complex I.
Belongs to the Tim17/Tim22/Tim23 family.
Chaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Participates in constructing the membrane arm of complex I (By similarity).
May function as a transcriptional repressor. May also function as a ubiquitin ligase. Functions in cell survival and proliferation through control of the cell cycle.
Positive regulator of amino acid starvation-induced autophagy.
Belongs to the SPEC3 family. Stum subfamily.
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.
In the C-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family.
Belongs to the universal ribosomal protein uL6 family.
Transferrins are iron binding transport proteins which bind Fe(3+) ion in association with the binding of an anion, usually bicarbonate.
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.
Hormone induced following exercise or cold exposure that promotes energy expenditure. Induced either in the skeletal muscle after exercise or in adipose tissue following cold exposure and is present in the circulation. Able to stimulate energy expenditure associated with the browning of the white fat depots and improves glucose tolerance (By similarity).
Receptor for the neuromedin-U and neuromedin-S neuropeptides.
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).
May be involved in cell differentiation.
Belongs to the aldo/keto reductase family.
Belongs to the ROX family. NO66 subfamily.
Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase (By similarity). Specifically demethylates 'Lys-4' (H3K4me) and 'Lys-36' (H3K36me) of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' (H3K4me3) and monomethylated H3 'Lys-4' (H3K4me1) residues, while it has weaker activity for dimethylated H3 'Lys-36' (H3K36me2). Also catalyzes demethylation of non-histone proteins (By similarity). Also catalyzes the hydroxylation of 60S ribosomal protein L8 on 'His-216', thereby playing a role in ribosome biogenesis (By similarity).
Ligand for cxcr3.2. Chemotactic for macrophages.
Up-regulated in response to bacterial infection by S.typhimurium or M.marinum.
Accessory component of the multisubunit proton-transporting vacuolar (V)-ATPase protein pump.
Accessory component of the proton-transporting vacuolar (V)-ATPase protein pump involved in intracellular iron homeostasis. May be involved in Golgi homeostasis.
Broad-scope metal ion transporter with a preference for zinc uptake. Also mediates cellular uptake of nontransferrin-bound iron.
Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (PubMed:27231142). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions (By similarity). Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (By similarity).
Embryos with CRISPR-induced slc39a14 null mutations display altered manganese homeostasis. This is associated with manganese deposition in the brain and altered locomotor activity. Mutants survived into adulthood without any obvious morphological or developmental defects.
Expressed at all stages of embryonic and early larval development.
Although the protein is present in a diversity of vertebrates ranging from bony fish to mammals, the mouse and rat orthologous proteins do not exist.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.
Impaired cone response recovery and delayed dark adaptation.
Phosphorylation at Ser-33 is regulated by light and activated by cAMP.
Retina-specific kinase involved in the shutoff of the photoresponse and adaptation to changing light conditions via cone opsin phosphorylation, including rhodopsin (RHO).
May associate with G-protein coupled receptors and regulate downstream signaling pathways.
Belongs to the metallo-dependent hydrolases superfamily. TatD-type hydrolase family.
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-35) blocks substrate entrance to Mg(2+) in the unliganded closed state. In presence of substrate, Glu-35 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.
Unlikely isoform. Aberrant splice sites.
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.
Belongs to the glycosyltransferase 39 family.
Detected throughout development (PubMed:18632251, PubMed:20466645). Highest expression levels are found at 0 hours post-fertilization (hpf), probably due to perdurance of maternal transcripts (PubMed:20466645). Expression levels remain high at 6 hpf and decrease rapidly by 12 hpf, followed by a second moderate peak in expression at 24 hpf (PubMed:20466645). Ubiquitously expressed during early stages of development (PubMed:18632251, PubMed:20466645). At 16-24 hpf, mainly found in eye, brain and somites (PubMed:18632251, PubMed:20466645). At 30 hpf, has strongest expression in forebrain, cerebellum and hindbrain (PubMed:18632251).
Morpholino knockdown of the protein results in developmental delays at 18 hours post fertilization (hpf). At 48-72 hpf the tail is abnormally twisted, and pericardium formation and eye pigmentation are also abnormal. Swim bladders are incompletely formed. Glycosylation of alpha-dystroglycan (dag1) is severely reduced.
Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is insufficient.
Widely expressed. Has particularly strong expression in ovary, testis, liver, brain, muscle, heart and eye.
Belongs to the Mediator complex subunit 30 family.
Expressed 30 hours post-fertilization (hpf) in the anterior and posterior lateral line ganglia where it persisted until at least 48 hpf. Also expressed between 30 and 72 hpf in the telencephalon. Expressed in the ventral thalamus, ventral midbrain, ventral cerebellum, and ventral hindbrain from 30 hpf. By 48 hpf, expressed also in the dorsal thalamus and hypothalamus. At 72 hpf, weak expression was apparent in the habenulae.
Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with ASIC1/ACCN2B.
ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability. Acts as an anti-recombinase to counteract toxic recombination and limit crossover during meiosis. Regulates meiotic recombination and crossover homeostasis by physically dissociating strand invasion events and thereby promotes noncrossover repair by meiotic synthesis dependent strand annealing (SDSA) as well as disassembly of D loop recombination intermediates. Also disassembles T loops and prevents telomere fragility by counteracting telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere.
Belongs to the helicase family. RAD3/XPD subfamily.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Trm1 family.
May play a role in motor coordination and exploratory behavior.
Belongs to the ABC transporter superfamily. ABCC family. CFTR transporter (TC 3.A.1.202) subfamily.
Causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones.
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).
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.
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.
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.
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.
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.
Homodimer (By similarity). Interacts with APOA1 (PubMed:23719382). Binds to HDL (PubMed:23719382).
Mutants do not show increased levels of free (unesterified) cholesterol.
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.
Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, efr3b probably acts as the membrane-anchoring component.
Component of a phosphatidylinositol 4-kinase (PI4K) complex.
Palmitoylated at its N-terminus, anchoring the protein to the plasma membrane.
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.
Belongs to the methyltransferase superfamily. ETFBKMT family.
Protein-lysine methyltransferase that selectively trimethylates the flavoprotein ETFB in mitochondria. Thereby, may negatively regulate the function of ETFB in electron transfer from Acyl-CoA dehydrogenases to the main respiratory chain.
Belongs to the acetyltransferase family. GNAT subfamily.
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).
Required for biogenesis of the 60S ribosomal subunit.
Protein transport. Probably involved in vesicular traffic.
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.
Devoided of intrinsic deacetylase activity, promotes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) by recruiting other histone deacetylases. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Represses MEF2-dependent transcription (By similarity).
Homodimer. Interacts with mef2 (By similarity).
Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.
Belongs to the AB hydrolase superfamily.
Basal body protein required in multiciliate cells to align and maintain cilia orientation in response to flow. May act by mediating a maturation step that stabilizes and aligns cilia orientation. Not required to respond to planar cell polarity (PCP) or flow-based orientation cues.
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.
Forms a complex with PIGT, PIGS, PIGU and GAA1.
Mediates GPI anchoring in the endoplasmic reticulum, by replacing a protein's C-terminal GPI attachment signal peptide with a pre-assembled GPI. During this transamidation reaction, the GPI transamidase forms a carbonyl intermediate with the substrate protein.
Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle.
Belongs to the heat shock protein 70 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.
Belongs to the mitochondrion-specific ribosomal protein mL49 family.
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.
Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling.
The D-box (destruction box) mediate the interaction with APC proteins, and may act as a recognition signal for degradation via the ubiquitin-proteasome pathway.
Belongs to the 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.
Belongs to the snRNP Sm proteins family. SmF/LSm6 subfamily.
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.
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.
Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity and in a phosphorylated-O-mannosyl trisaccharide dependent manner. Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide (By similarity). Supports the maturation of DAG1 more effectively than LARGE1 (By similarity). In addition, can modify both heparan sulfate (HS)- and chondroitin/dermatan sulfate (CS/DS)-proteoglycans (PGs), namely GPC4, with a glycosaminoglycan (GAG)-like polysaccharide composed of xylose and glucuronic acid to confer laminin binding (By similarity).
Binds 2 Mn(2+) ions per subunit. The xylosyltransferase part binds one Mn(2+) and the beta-1,3-glucuronyltransferase part binds one Mn(2+).
In the C-terminal section; belongs to the glycosyltransferase 49 family.
In the N-terminal section; belongs to the glycosyltransferase 8 family.
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 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.
Ubiquitously expressed throughout the embryo from fertilization onward. Accumulates at higher levels in cells of the telencephalon, the ventral hindbrain and the gut.
Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4.
Belongs to the mannose-6-phosphate isomerase type 1 family.
Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.
Regulates cell junction organization in epithelial cells.
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.
Belongs to the GST superfamily. Kappa family.
Belongs to the pyrroline-5-carboxylate reductase family.
First detected at 11.5 hours post-fertilization (hpf) in dorsal presomitic mesoderm and in the neural keel, extending to the ventral somitic mesoderm during tail budding. At 16-19 hpf, the rostral expression boundary is at somite 10. By the end of somitogenesis, expression decreases in the lateral and ventral mesoderm and becomes restricted to the neural rod. Also expressed in the developing pectoral fins from 34 hpf, with progressive localization to the periphery.
Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.
Belongs to the bZIP family. C/EBP subfamily.
Aquaporins facilitate the transport of water and small neutral solutes across cell membranes.
Belongs to the MIP/aquaporin (TC 1.A.8) family. AQP11/AQP12 subfamily.
Belongs to the WD repeat CDC20/Fizzy family.
First expressed at 12 hours post-fertilization (hpf) in the dorsal pre-somitic mesoderm and neural keel at posterior levels, extending into the ventral somitic mesoderm during budding. At 22-26 hpf, expression decreases in the lateral and ventral mesoderm, but is maintained in the neural rod. Expression decreases from posterior to anterior with an anterior expression limit at somite 11. At 24-26 hpf, posterior expression begin to weaken and is undetectable by 40-56 hpf.
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.
Belongs to the universal ribosomal protein uL22 family.
Component of the U11/U12 snRNPs that are part of the U12-type spliceosome.
Larval lethal with complete lethality by 10 days post-fertilization. Development of multiple organs is affected. Head, eye, lens, pancreas and liver are smaller than normal, and the swim bladder fails to inflate. The intestinal epithelium also remains thin and unfolded. U12-type introns are retained in mRNAs, whereas excision of U2-type introns is not affected. Assembly of both U12- and U11-containing snRNP complexes may be abnormal. Gene expression levels are broadly impacted; effects are not limited to U12-type intron-containing genes.
Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. U12-type introns comprise less than 1% of all non-coding sequences.
Widely expressed until 24 hours post-fertilization (hpf), probably due to inheritance of maternal transcripts. Expression becomes restricted to lens, pharyngeal region, liver/pancreas anlage and intestine at 48-72 hpf. Strongly expressed in pancreas and intestine at 96-120 hpf.
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.
By cocaine, which increases the levels of day-time expression.
High affinity receptor for melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibits adenylate cyclase activity (By similarity).
May negatively regulate cell cycle progression.
High affinity receptor for melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibits adenylate cyclase activity.
Belongs to the PIEZO (TC 1.A.75) family.
Expressed at high levels in kidney, and at low levels in eye, brain, gill and heart.
Expressed in diencephalon, mesencephalon, anterior hindbrain and otic vesicles at 24 hpf.
The PH domain is required for membrane targeting.
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.
Secreted scaffold protein that plays an essential role in dorsoventral patterning during early development. Stabilizes axial formation by restricting chordin (CHRD) activity on the dorsal side. Acts by facilitating the association between the tolloid proteases and their substrate chordin (CHRD), leading to enhance chordin (CHRD) degradation (By similarity).
Belongs to the Mediator complex subunit 6 family.
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. 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 euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Plays a role in promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes. Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (By similarity).
In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.
Belongs to the glycosyl hydrolase 30 family.
Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.
Belongs to the complex I NDUFB2 subunit family.
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 synaptophysin/synaptobrevin family.
Binds 1 divalent metal cation per subunit; can use either Mg(2+) or Mn(2+).
Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.
Morpholino knockdown of the protein does not apparently affect embryo development (PubMed:26232532). However, the motility of morphants is markedly reduced from 3 days post-fertilization onwards (PubMed:26232532). This is associated with a significant defect in the axonal outgrowth of spinal motor neurons without affecting neuron generation (PubMed:26232532).
Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes. Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (By similarity). Plays a role in axonogenesis (PubMed:26232532).
Probably maternally supplied, the zygotic expression becomes significative at 2.75 hpf and then decreases after 18 hpf but is still detected at 24 hpf (PubMed:26056731, PubMed:27235108). Highly expressed in the developing central nervous system from the presumptive telencephalon to the caudal tip of the spinal cord (PubMed:26232532).
Binds GDP/GTP and may possess intrinsic GTPase activity.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.
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 glycosyltransferase 2 family. GalNAc-T subfamily.
Belongs to the plakin or cytolinker family.
Expressed in the blastula and widely expressed in the gastrula from 3 hours post-fertilization (hpf) to 6 hpf (PubMed:29522173). Expressed in the epidermis from 16 hpf (PubMed:29522173). Expressed through the epidermis, lens, otic vesicle, pharynx, pectoral fin, and heart from 1 dpf to 5 dpf (PubMed:29522173).
Involved in the organization of desmosome cell-cell junctions (PubMed:29522173). Of particular importance in cell adhesion in the skin and during cardiac development (PubMed:29522173). May also play a role in the regulation of Wnt, TGF-beta and Hippo signaling pathways (PubMed:29522173).
Morpholino knockdowns show no general morphological differences however do show a slight developmental delay (PubMed:29522173). Abnormal skin surface, reduced numbers of desmosome cell-cell junctions and disorganization of remaining desmosome at 2 dpf (PubMed:29522173). Cardiac regions show reduced desmosome numbers, detached cells and pericardial effusion (PubMed:29522173). A cardiac reduction in Wnt and TGF-beta signaling is also evident, with an increase in Hippo signaling (PubMed:29522173).
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.
Component of the uniplex complex (By similarity). Homooligomer; forms a pentamer (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).
Inhibited by ruthenium red or its derivative Ru360.
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.
Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria. Constitutes the pore-forming and calcium-conducting subunit of the uniporter complex (uniplex). Activity is regulated by micu1 and micu2. At low Ca(2+) levels mcu activity is down-regulated by micu1 and micu2; at higher Ca(2+) levels micu1 increases mcu activity. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes. While dispensable for baseline homeostatic cardiac function, acts as a key regulator of short-term mitochondrial calcium loading underlying a 'fight-or-flight' response during acute stress: acts by mediating a rapid increase of mitochondrial calcium in pacemaker cells.
The N-terminal MCU domain is required for efficient Ca(2+) uptake and for interaction with MCUR1. It is not required for targeting to the mitochondria, oligomerization, interaction with MICU1 and MICU2, or assembly of the uniplex complex.
The critical DXXE motif connecting the transmembrane regions forms a pentameric barrel that constitutes the mouth of the pore. Inside the barrel, two acidic residues are in position to form two carboxylate rings. In absence of SMDT1/EMRE regulator, the calcium ions cannot exit the channel, suggesting that SMDT1/EMRE-binding induces conformational rearrangements to allow calcium to exit.
Belongs to the bZIP family. Maf subfamily.
Belongs to the flavin monoamine oxidase family.
Belongs to the selenoprotein M/F family.
Higher levels in polster, prechordal plate, axis, otic vesicle and somites. Lower levels in fin buds.
May be involved in redox reactions associated with the formation of disulfide bonds. May contribute to the quality control of protein folding in the endoplasmic reticulum (By similarity).
May bind and stabilize microtubules during myotubes formation.
Belongs to the glutamine synthetase family.
Belongs to the cytochrome c oxidase subunit 6A 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.
Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.
Belongs to the glycosyl hydrolase 31 family.
Belongs to the complexin/synaphin family.
Belongs to the bZIP family. ATF subfamily.
Arginine methyltransferase involved in the assembly or stability of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) (PubMed:24838397). Acts by mediating symmetric dimethylation of 'Arg-118' of ndufs2 after it assembles into the complex I, stabilizing the early intermediate complex.
Impaired NADH:ubiquinone oxidoreductase complex (complex I) assembly.
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.
Morpholino knockdown is associated with increased Erk phosphorylation levels and results in a high incidence of embryos showing delayed gastrulation, or delay in elongation during the segmentation stage, with reduced formation of the head and tailbud. Morphants show yolk elongation at 12 hours post-fertilization, indicating enhanced MAPK signaling.
Negatively regulates Ras signaling pathways and downstream activation of MAP kinases.
Belongs to the glycosyl hydrolase 59 family.
Hydrolyzes the galactose ester bonds of glycolipids such as galactosylceramide and galactosylsphingosine.
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 glycosyl hydrolase 18 family.
Detected in embryonic intermediate cell mass (site of hematopoiesis), liver and heart.
Lethal between 7 and 10 dpf. Embryos show hypochromia, and circulating blood cells are pale due to a defect in hemoglobin biosynthesis.
Monothiol glutaredoxin involved in mitochondrial iron-sulfur (Fe/S) cluster transfer (PubMed:16110529). Receives iron-sulfur clusters from scaffold protein ISCU and mediates their transfer to apoproteins, to the 4Fe/FS cluster biosynthesis machinery, or export from mitochondrion (PubMed:16110529). Required for normal hemoglobin biosynthesis (PubMed:16110529).
Belongs to the flagellar radial spoke RSP9 family.
Component of the axonemal radial spoke head which plays an important role in ciliary motility (PubMed:19200523). 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 (PubMed:27687975). Essential for both the radial spoke head assembly and the central pair microtubule stability in ependymal motile cilia (By similarity).
Dysmotile olfactory pit cilia which have a normal beat frequency but an ineffective circular beat pattern. Effect can be rescued by coinjection of mouse Rsph9 mRNA (PubMed:19200523). Embryos with CRISPR-induced rsph9 null mutations exhibit a greatly diminished olfactory and neural ciliary motility, structural defects in neural and pronephric ciliary axonemes and an impaired initiation of startle response to acoustic stimulation (PubMed:27687975).
Expressed in ciliated structures in the embryos namely, Kupffer's vesicle, pronephric ducts, otic placodes and ventral spinal cord (at protein level) (PubMed:27687975). Also expressed in the ventral midline of the midbrain primordium (at protein level) (PubMed:27687975).
Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.
Belongs to the TPT transporter family. SLC35C subfamily.
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. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
Functional P2XRs are organized as homomeric and heteromeric trimers.
Negative regulator of hepatic phosphatidylinositol 3-kinase (PI3K) activity.
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.
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).
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).
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Belongs to the sirtuin family. Class I subfamily.
Belongs to the fibroblast growth factor-binding protein family.
Photoreceptor implicated in non-image-forming responses to light. May be able to isomerize covalently bound all-trans retinal back to 11-cis retinal (By similarity).
Belongs to the glycosyl hydrolase 38 family.
Catalyzes the final step in the metabolic pathway of hydroxyproline.
Belongs to the inorganic phosphate transporter (PiT) (TC 2.A.20) family.
Sodium-phosphate symporter which plays a fundamental housekeeping role in phosphate transport.
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).
First appears at the end of gastrulation in the axial mesoderm. By the 5-somite stage, expressed in telencephalon and anterior diencephalon. From early segmentation stages until the end of tail elongation, found in the tail bud. Expression is maintained during somitogenesis. At the 10-somite stage, detected in the antero-medial aspect of the somites. At 20 hours of development expression is observed in the ventro-medial part of the somite as well as in a small population of cells located more dorsally, adjacent to the neural tube. As development proceeds, expression in the dorsal somite is progressively lost, while ventro-medial sclerotomal cells lining the developing axial vasculature continue to show expression until 30 hours of development. In the head, expression is maintained in the telencephalon and anterior diencephalon until late embryogenesis. At the 15-somite stage, expressed in the forebrain, dorsal hindbrain and dorsal caudal spinal cord. Until late stages of embryogenesis strong expression is observed in the dorsal hindbrain walls.
Inhibitor of bone morphogenetic proteins (BMP) signaling.
Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases.
This protein has four functional calcium-binding sites.
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.
E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation. Required for ribosomes to terminally stall during translation of poly(A) sequences by mediating monoubiquitination of a subset of 40S ribosomal subunits. Stalling precludes synthesis of a long poly-lysine tail and initiates the RQC pathway to degrade the potentially detrimental aberrant nascent polypeptide.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily.
Belongs to the phosphatase 2A regulatory subunit B56 family.
Expressed from 11 hours post-fertilization (hpf). Expression in the midbrain and optic primordia begins at the onset of segmentation and increases to 14 hpf, remaining strong during lateral migration of the optic primordia. Expressed in the neural tube and the oblongated retinal epithelium from 18 hpf. Expression within the differentiating eyes subsequently decreases from 22 hpf to 35 hpf, with only weak expression at the edge of the lens observed from 35 hpf to 48 hpf. Expressed in the branchial pouches from 22 hpf, and in the pharyngeal arches, ganglia and hindbrain and spinal cord neurons from 24 hpf. Expressed in the lens perimeter and the differentiated amacrine and ganglion cell layers at 72 hpf.
Required for eye morphogenesis. May promote the survival of proliferating retinal progenitor cells.
Severe lens and retinal defects leading to lethality.
Cofactor for the transcription factor TCF7. May be involved in lymphoid development.
mRNA-binding protein involved in proper cytoplasmic distribution of mitochondria.
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 complex I NDUFA11 subunit family.
Belongs to the threonine synthase family.
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.
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.
Expressed in the periderm and enveloping layer between 6 hours post-fertilization (hpf) to 16 hpf. Expressed in the epidermis, otic vesicle, gut, neural tube, pharynx, pectoral fin, and olfactory organ from 1 to 5 dpf. Expressed in the lens and cardiac region at 6 hpf to 5 dpf.
Morpholino knockdowns show no general morphological differences however do show a slight developmental delay (PubMed:29522173). Abnormal skin surface, reduced numbers of desmosome cell-cell junctions and disorganization of remaining desmosome at 2 dpf (PubMed:29522173). Cardiac regions show reduced desmosome numbers, detached cells and pericardial effusion. Reduced resting heart rate (PubMed:29522173). A cardiac reduction in Wnt and TGF-beta signaling is also evident, with an increase in Hippo signaling (PubMed:29522173).
Ubiquitous. Highest levels in ovary, high levels in heart, eye, kidney and brain, moderate levels in intestine and low levels in gill and skin.
Arginine hydroxylase involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) at early stages. Acts by mediating hydroxylation of 'Arg-111' of ndufs7. May also have methyltransferase activity.
Belongs to the methyltransferase superfamily.
Microtubule-binding protein that localizes to the microtubular manchette of elongating spermatids.
Fishes show ciliary defects. In retina, cilia are generated but not maintained, producing the absence of photoreceptor outer segments. A loss of cilia also occurs in auditory hair cells and olfactory sensory neurons. In all 3 sense organs, cilia defects are followed by degeneration of sensory cells.
Required for the formation of cilia. Essential for differentiation and survival of sensory neurons. May also have pro-apoptotic function.
In the C-terminal section; belongs to the Cu-Zn superoxide dismutase family.
Belongs to the endothelin/sarafotoxin family.
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.
First expressed at the 2-somite stage as a stripe in the region of the hindbrain that will give rise to rhombomeres 2 and 3. By the 10-somite stage, expression has expanded posteriorly to rhombomeres 4 and 5.
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.
By 7 somites, detected in the anterior brain and expression is strong within the optic stalks, preoptic area and telencephalon by 12 somites. By 16 somites, expression in the telencephalon is reduced but that in the preoptic area, optic stalk and ventral retina remains and this pattern of expression is similar at 24 hpf (hours post-fertilization). By 48 hpf, expression is restricted to the ventral preoptic area, anterior dorsal hypothalamus and ventral retina.
Expressed in the anterior neural keel and later in the preoptic area, optic stalk and ventral retina.
Transcription factor that may function in dorsoventral specification of the forebrain. Required for closure of the choroid fissure and together with vax1 is required for optic nerve differentiation and to limit retinal development to the optic cup.
Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation.
Phosphoinositides-binding protein that induces the formation of planar or gently curved membrane structures.
The IMD domain is predicted to have a helical structure. It may induce actin bundling and filopodia formation (By similarity).
Knockout leads to severe developmental defects in zebrafish embryos, including heart edema, insufficient cartilage, and skeletal dysplasia.
Required for mannose-6-phosphate-dependent trafficking of lysosomal enzymes (PubMed:36096887). 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 (By similarity).
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.
At 4 days post fertilization (dpf), it is expressed at low levels in the retina and brain, and at higher levels in the jaw mesenchyme.
Knockdown of both fbxw11a and fbxw11b results in abnormally developed pectoral fins and heart edema by day 3 post-fertilization (3 dpf). At 5 dpf, knocked-down embryos show periocular edema, small and misshapen eyes, and abnormal development of the jaw.
Self-associates. Component of the SCF(FBXW11) complex.
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 (By similarity). Participates in Wnt signaling regulation, and plays a role in eye and jaw development (PubMed:31402090).
The N-terminal D domain mediates homodimerization.
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.
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).
Belongs to the eukaryotic ribosomal protein eS28 family.
Component of the 40S small ribosomal subunit.
Belongs to the Mediator complex subunit 4 family.
Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization. Specifically recognizes growing microtubule minus-ends and stabilizes microtubules. Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization. In contrast to camsap2 and camsap3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation. Through interaction with spectrin may regulate neurite outgrowth.
Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity (By similarity).
eIF-5A seems to be the only eukaryotic protein to have a hypusine residue which is a post-translational modification of a lysine by the addition of a butylamino group.
mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. Critical for the efficient synthesis of peptide bonds between consecutive proline residues. Can resolve ribosomal stalling caused by consecutive prolines during translation. Involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity. Functions as a regulator of apoptosis.
Belongs to the FMN-dependent alpha-hydroxy acid dehydrogenase family.
Belongs to the exonuclease superfamily. TREX family.
Belongs to the peptidase M67A family. MYSM1 subfamily.
Binds double-stranded DNA via the SANT domain. The SWIRM domain does not bind double-stranded DNA (By similarity).
Metalloprotease that specifically deubiquitinates monoubiquitinated histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Preferentially deubiquitinates monoubiquitinated H2A in hyperacetylated nucleosomes. Deubiquitination of histone H2A leads to facilitate the phosphorylation and dissociation of histone H1 from the nucleosome. Acts as a coactivator by participating in the initiation and elongation steps of androgen receptor (AR)-induced gene activation (By similarity).
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.
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 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.
Leads to aberrant leukocyte development.
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.
Plays a role in cell division and in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats.
Belongs to the glycosyltransferase 14 family. XylT subfamily.
Belongs to the DNA polymerase type-B family.
Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.
Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization (By similarity).
Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.
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.
First detected at the shield stage of gastrulation in the involuting mesendoderm with levels being highest in the paraxial mesoderm and decline laterally to become undetectable in the ventral mesoderm. Expression spreads in the hypoblast towards the animal pole and converges dorsally. At the tail bud stage (9.5 hpf), transcripts are seen in adaxial cells flanking the future notochord and in the presomitic mesoderm (PSM). During early somitogenesis, expression also extends into the future head, in two stripes continuous with the adaxial cells. Expression continues under the hindbrain as far as the midbrain/hindbrain boundary, in the presomitic mesoderm (PSM), trunk adaxial cells and somites. Expression still found, in the early pharyngula stage. in the PSM and adaxial cells in the tail and, at 33 to 70 hpf, strong expression in the pharyngeal arches and saggital sections.
Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC).
Belongs to the G-protein coupled receptor T2R family.
Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.
Belongs to the TALE/MEIS homeobox family.
First expressed at 15 hours post-fertilization (hpf) in the presumptive proctodeum. At 22 hpf, expressed in the most distal part of the hindgut, the future rectum and the cloacal region; cloacal expression is still detectable until 64 hpf. First detected in the dorsal pre-somitic mesoderm and neural keel at 17 hpf. At 22-26 hpf, expression is restricted to the posterior tip of the trunk, begins to weaken and is undetectable by 40-56 hpf.
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 glycosyltransferase 47 family.
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).
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.
Is a receptor for the SMIM20 derived peptides Phoenixin-14 and Phoenixin-20 (By similarity). It mediates the Phoenixin-14 and Phoenixin-20 augmentation of gonadotropin-releasing hormone (GNRH) signaling in the hypothalamus and pituitary gland (By similarity). In the ovary, it mediates the effects of Phoenixin-14 and Phoenixin-20 induced granulosa cell proliferation during follicular growth (By similarity).
Critical regulator of endosomal recycling of numerous surface proteins, including integrins, signaling receptor and channels. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Associates with retriever and CCC complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGB1, ITGB5 and their associated alpha subunits. Also required for maintenance of normal cell surface levels of APP and LRP1. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)).
Monomer (By similarity). Interacts with CCDC22, CCDC93, DSCR3 and VPS35L; the interaction with DSCR3 is direct and associates SNX17 with the retriever and CCC complexes (By similarity).
The PTB-like F3 module within the FERM-like domain mediates cargo recognition via their NPxY sequences, while the F1 module (Ras-associating) is responsible for interaction with membrane-bound HRAS.
The PX domain mediates specific binding to phosphatidylinositol 3-phosphate (PtdIns(P3)). Required for association with endosomes.
Belongs to the type I cytokine receptor family. Type 2 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 phytoene/squalene synthase family.
Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP) moieties to form squalene.
Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7).
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.
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.
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 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.
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).
Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
Probable flavoprotein which may function in endoplasmic reticulum associated degradation (ERAD). May bind non-native proteins in the endoplasmic reticulum and target them to the ubiquitination machinery for subsequent degradation (By similarity).
Highly expressed in the developing midbrain and the eyes at 24 hpf. The expression becomes restricted afterwards to the posterior part of the midbrain and the midbrain-hindbrain boundary.
Belongs to the eukaryotic ribosomal protein P1/P2 family.
Heterodimer with RPLP1 at the lateral ribosomal stalk of the large ribosomal subunit.
Plays an important role in the elongation step of protein synthesis.
Belongs to the HAD-like hydrolase superfamily.
Activated by threonine and tyrosine phosphorylation.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. MAP kinase subfamily.
Expressed exclusively in the ovary, and protein localizes to the Balbiani body during oogenesis and with the germ plasm during early embryogenesis (PubMed:19249209). Accumulates at embryonic cleavage furrows (PubMed:26253407).
Mutant fails to form Balbiani body, and vegetal mRNAs are not localized in oocytes.
Prion-like protein required for the formation of Balbiani body (electron-dense aggregates in the oocyte) and germ plasm assembly, and for the establishment of oocyte polarity during early oogenesis (PubMed:18582455, PubMed:19249209). Mobility and aggregation properties are improved by tudor domain-containing protein tdrd6 through interaction with dimethylated arginines Tri-RG domains (PubMed:30086300). Establishes oocyte polarity through interactions with RNA-binding proteins rbpms2 and dazl, initiating a positive feedback loop amplification mechanism in the Balbiani body (PubMed:24496621). Interaction of BUC protein and mRNA with rbpms2 and dazl is required to mediate Balbiani body formation (PubMed:24496621). Involved in recruitment of germ plasm to embryonic cleavage furrows and dorsoventral patterning through interaction with Kinesin-1/KIF5BA (PubMed:26253407).
Specifically interacts (when methylated) with tdrd6 (via Tudor domain); interaction is responsible for recruitment of different protein complexes to germ plasm (PubMed:30086300). Interacts with rbpms2 and dazl; interaction mediates Balbiani body formation (PubMed:24496621). Interacts with kif5ba; interaction leads to buc enrichment at the embryonic cleavage furrows and mediates dorsoventral patterning (PubMed:26253407).
Symmetric dimethylarginine modification promotes interaction with tdrd6.
The dimethylated RG motifs (RG[X0-4]RG[X0-4]RG) motif mediates interaction with TDRD6 and is required for Balbiani body formation.
Belongs to the OHCU decarboxylase family.
Catalyzes the stereoselective decarboxylation of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) to (S)-allantoin.
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-70 and Arg-73) that bind to malonylated and succinylated substrates and define the specificity.
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-98 and Arg-101) 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.
Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (stim1 or stim2)-dependent SOCE activity (By similarity).
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.
Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs.
Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.
Acts as a molecular chaperone for G protein-coupled receptors, regulating their biogenesis and exit from the ER.
Belongs to the archaeal Rpo5/eukaryotic RPB5 RNA polymerase subunit family.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process.
Belongs to the acyl-CoA dehydrogenase family.
Belongs to the PX domain-containing GAP family.
Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and prevent repolymerization.
Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.
Required for N-linked oligosaccharide assembly.
Homotrimer. Forms a complex with activator 1 heteropentamer in the presence of ATP (By similarity). Component of the replisome complex (By similarity).
Monoubiquitinated by the ube2b-rad18 complex on Lys-164. Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the dcx(dtl) complex, leading to enhance PCNA-dependent translesion DNA synthesis (By similarity).
This protein is an auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand.
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.
Belongs to the AP endonuclease 2 family.
Expressed in several regions throughout the adult brain, including the mesencephalon.
May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion.
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Required for S phase entry 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.
Was originally thought to be located in the peroxisome. However, was later shown to be cytosolic.
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.
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.
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-44 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.
Death between 10 and 12 dpf. Thymus size is remarkably reduced and the pharyngeal arches are malformed. Eyes and swim bladder are also reduced.
Nucleolar protein that acts as a modulator of rRNA synthesis. Plays a central role during organogenesis (By similarity).
Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme.
Cleaved into an alpha and beta chain by autocatalysis; this activates the enzyme. The N-terminal residue of the beta subunit is responsible for the nucleophile hydrolase activity.
Has both L-asparaginase and beta-aspartyl peptidase activity. Does not have aspartylglucosaminidase activity and is inactive toward GlcNAc-L-Asn. Likewise, has no activity toward glutamine.
Heterodimer of an alpha and beta chain produced by autocleavage.
Belongs to the DOK family. Type B subfamily.
Involved in skeletal muscle development and differentiation.
Morphants exhibit leaner bodies, smaller eyes, and pericardial edema. At 3 dpf morphants show reduced birefringence in axial skeletal muscles suggesting disorganized skeletal muscle structure.
Ubiquitous expression during early development at 1 dpf, but by 2 dpf, transcripts are virtually undetectable in the major axial skeletal muscles.
Involved in the regulation of endocytosis and in several stages of intracellular trafficking. Together with snx4, involved in autophagosome assembly.
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).
Essential for sperm motility and is involved in the regulation of the beating frequency of motile cilia on the epithelial cells of the respiratory tract (By similarity). Required for the establishment of radial spokes in sperm flagella (By similarity).
May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity.
Involved in autophagy. May play a role in a late step of autophagy, such as clearance of autophagosomal cargo (By similarity).
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. Binds spliced mRNA upstream of exon-exon junctions (By similarity).
Morpholino knockdown results in a weakly abnormal brain patterning during development that does not affect embryo viability at 5 days post-fertilization.
Regulatory subunit of serine/threonine-protein phosphatase 4 (PP4).
Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits.
Belongs to the xanthine dehydrogenase family.
Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
Although the final Cys may be farnesylated, the terminal tripeptide is probably not removed, and the C-terminus is not methylated.
Belongs to the phosphorylase b kinase regulatory chain family.
Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin.
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.
At the 10-somite stage, expressed in the paraxial mesoderm with an anterior expression limit at somite 7. At the 20-somite stage, expressed in the developing CNS with an anterior expression limit adjacent to the somite 3/somite 4 boundary.
Interacts with odorant receptor proteins.
May enhance the cell surface expression of odorant receptors.
Belongs to the clathrin light chain family.
Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.
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 tubulin--tyrosine ligase family.
Fish display a lack of tubulin polyglutamylation and cilia formation in olfactory placodes.
Gln-174 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.
Polyglutamylase which modifies both tubulin and non-tubulin proteins, generating alpha-linked polyglutamate side chains on the gamma-carboxyl group of specific glutamate residues of target proteins (By similarity). Preferentially mediates ATP-dependent long polyglutamate chain elongation over the initiation step of the polyglutamylation reaction (By similarity). Preferentially modifies the alpha-tubulin tail over a beta-tail (By similarity). Mediates microtubule polyglutamylation in cilia axoneme, which is important for ciliary structural formation and motility (PubMed:17761526, PubMed:22246503). Polyglutamylates olfactory cilia, necessary for the regulation of ciliary sructure and beating (PubMed:17761526).
The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.
Belongs to the eukaryotic ribosomal protein eL30 family.
Belongs to the universal ribosomal protein uL2 family.
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 (By similarity).
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.
Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.
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 Mediator complex subunit 10 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). Negatively regulates the Wnt signaling pathway and positively regulates the Nodal signaling pathway. Required for cardiac cushion formation.
May regulate cell proliferation, growth, migration and epithelial to mesenchymal transition. May also be important for proper chromosome congression and alignment during mitosis.
At the 10-somite stage, barely detectable in the paraxial mesoderm. At the 20-somite stage, expressed within the developing CNS with an anterior expression limit at somite 1.
Belongs to the proteasome inhibitor PI31 family.
Plays an important role in control of proteasome function. Inhibits the hydrolysis of protein and peptide substrates by the 20S proteasome. Also inhibits the activation of the proteasome by the proteasome regulatory proteins PA700 and PA28.
Belongs to the copper type II ascorbate-dependent monooxygenase family.
Belongs to the dystrophin family. Dystrobrevin subfamily.
Belongs to the aldolase class II family. Adducin subfamily.
Belongs to the aldolase class II family. MtnB subfamily.
Catalyzes the dehydration of methylthioribulose-1-phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P). Functions in the methionine salvage pathway. May play a role in apoptosis.
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).
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide.
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 JHDM3 histone demethylase family.
May interfere with constitutive 5'-splice site selection.
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.
It is uncertain whether Met-1 or Met-2 is the initiator.
Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family.
Belongs to the ribonucleoside diphosphate reductase small chain family.
Belongs to the type-B carboxylesterase/lipase family.
Cofactor for serine ADP-ribosylation that confers serine specificity on parp1 and parp2 and plays a key role in DNA damage response. Initiates the repair of double-strand DNA breaks: recruited to DNA damage sites by parp1 and parp2 and switches the amino acid specificity of parp1 and parp2 from aspartate or glutamate to serine residues, licensing serine ADP-ribosylation of target proteins. Serine ADP-ribosylation of target proteins, such as histones, promotes decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Hpf1 acts by completing the active site of parp1 and parp2: forms a composite active site composed of residues from Hpf1 and parp1 or parp2. While hpf1 promotes the initiation of serine ADP-ribosylation, it restricts the polymerase activity of parp1 and parp2 in order to limit the length of poly-ADP-ribose chains. Hpf1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on parp1.
Expressed maternally: detected as early as 0 hour post-fertilization (hpf), before zygotic expression transcripts starts.
Interacts with PARP1 (via the PARP catalytic domain). Interacts with PARP2 (via the PARP catalytic domain). Interacts with core nucleosomes in a parp1- and parp2-dependent manner.
Morpholino knockdown of the protein causes malformation anbd delayed hatching.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.
A member of the basic liver-type FABPs, which are only found, thus far, in non-mammalian vertebrates.
Binds hydrophobic ligands, such as cholate, in the cytoplasm. May be involved in intracellular lipid transport (By similarity). Binds one cholate per subunit.
Expressed in the developing embryonic liver from 48 hpf. Also expressed in the liver of 5-day-old larvae. In adults, primarily expressed in the liver, with weak expression in the testis and intestine.
PubMed:12633865 reports expression in the ventral endoderm at 36 hpf, whereas PubMed:16857010 does not detect expression this early. The different timings may reflect strain-specific differences.
During early somitogenesis, first expressed in floor plate and somites. During mid-somitogenesis, expressed strongly in somites and more weakly in eye and hindbrain. During late somitogenesis, expressed in eye, hindbrain and posterior somites. At 24 hours post-fertilization (hpf), expressed in lens, forebrain, hindbrain, otic vesicle, anterior spinal cord neurons and posterior somites. At 36 hpf, expressed in the retinal ciliary marginal zone, brain, pancreas and weakly in pectoral fin. At 48 hpf, expressed in the retinal ciliary marginal zone, retinal ganglion cells, rhombomeres, otic vesicle and weakly in pectoral fin.
Expressed both maternally and zygotically. Expression is lost before gastrulation and begins again during early somitogenesis.
Activator of melanocortin receptor 4 (mc4r), a receptor involved in energy homeostasis. Plays a role after larval development in the control of energy homeostasis and body weight regulation by increasing ligand-sensitivity of mc4r and mc4r-mediated generation of cAMP once the zebrafish begins feeding, increasing the capacity for regulated feeding and growth.
Not expressed in embryos. Mainly expressed in adult.
Two paralogs of MRAP2 are present in zebrafish: mrap2a, which plays a role during larval development and mrap2b, which constitutes the ortholog of mammalian MRAP2.
Belongs to the YY transcription factor family.
Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.
Functions as an ammonia transporter. May play a role in the elimination of ammonia in the gill.
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'.
Embryos have a small head, eyes, jaw and an underdeveloped gut. Moreover many mutants display diminished yolk consumption and uninflated swim bladder as well as embryonic lethality. DNA methylation is impaired during embryogenesis and embryos display defects in lens development and maintenance. No fertility defects are noted for heterozygous animals.
Expressed in proliferating tissues. Highly expressed 24-48 hours after fertilization (hpf) in rapidly proliferating tissues, including the tectum, retina and brachial arches. Preferentially expressed in the liver bud and expression is maintained in the fully developed liver. Also expressed in the proximal gut. In adult, the highest expression is detected in testis.
Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits dnmt1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins. However, it is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo (By similarity). Required for pregastrula and lens development.
Phosphorylation at Ser-649 is required for gastrulation.
The RING finger is required for ubiquitin ligase activity.
The YDG domain (also named SRA domain) specifically recognizes and binds hemimethylated DNA at replication forks (DNA that is only methylated on the mother strand of replicating DNA).
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).
Belongs to the G-protein coupled receptor Fz/Smo family.
Acts as a transcriptional activator or repressor.
Expressed in the lens fiber cells during embryogenesis. During somitogenesis expressed in somitic cells (at protein level).
Homodimer or heterodimer. Binds DNA as a homodimer or a heterodimer (By similarity).
Belongs to the universal ribosomal protein uL3 family.
During larvae development, may be important for neurocranium morphogenesis.
Morpholino knockdown of the protein causes reduced cranial outgrowth and defects of the cartilaginous elements of the jaw.
Belongs to the PA-phosphatase related phosphoesterase family.
Plays a role as negative regulator of myoblast differentiation, in part through effects on MTOR signaling. Has no detectable enzymatic activity (By similarity).
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.
Binds 1 Mg(2+) or Mn(2+) ion per subunit.
Involved in early stages of the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.
Morpholino knockdown results in ciliopathy-related phenotypes, such as curved bodies, hydrocephalus, abnormal otolith, randomized left-right asymmetry, and pronephric cysts, accompanied with paralyzed pronephric cilia.
Part of the multisubunit axonemal dynein complex formed at least of two heavy chains and a number of intermediate and light chains.
Plays a critical role in the assembly of axonemal dynein complex (By similarity). Plays a key role in ciliary motility (PubMed:30060180).
Belongs to the shaker potassium channel beta subunit family.
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. Shows highest activity towards catecholestrogens and dobutamine. Also has lower activity towards L-DOPA, dopamine and epinephrine. Active towards the xenobiotic compounds methyl-DOPA, carbidopa, isoproterenol, and apomorphine.
Highly expressed in unfertilized eggs. Has low expression during embryogenesis. Expression then increases after hatching (48 hours post-fertilization), reaching maximum levels at 3 weeks of age.
Widely expressed (PubMed:28844929). Has higher expression in females compared to males (PubMed:21371608). Strongly expressed in liver and diencephalon (PubMed:28844929). Expressed at lower levels in hindbrain, spinal cord, eye, telencephalon, spleen, gut, gill and muscle (PubMed:28844929). Detected in ovary and testis (PubMed:28844929). In eye, detected in all layers of the retina with highest expression in the inner nuclear layer (PubMed:28844929). In gut, expressed in the lamina propria but has little or no expression in gut epithelium (PubMed:28844929). In brain, has strongest expression near the midline of the telencephalon, in the periventricular gray zone of the optic tectum, in the preglomerular nucleus, and near the walls of the diencephalic ventricle (PubMed:28844929).
Belongs to the pseudouridine synthase TruB family.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, and thus regulates transcriptional activity.
It is uncertain whether Met-1 or Met-10 is the initiator.
Potent suppressor of cytokine production that acts as a regulator of innate immune signaling and inflammation. Acts as a key negative regulator of select cytokine and chemokine responses elicited by TRIF-independent Toll-like receptors (TLRs), thereby limiting inflammatory cytokine responses to minor insults (By similarity). Has ribonuclease activity (By similarity).
Belongs to the calcium channel flower family.
May contain a selenide-sulfide bond between Cys-62 and Sec-65. This bond is speculated to serve as redox-active pair (By similarity).
Belongs to the pICln (TC 1.A.47) family.
Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin.
May be involved in the regulation of cellular senescence through a positive feedback loop with TP53.
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
May be involved in photoreceptor outer segment disk morphogenesis (By similarity).
Results in the cardinal features of Bardet-Biedl syndrome, including defects to the ciliated Kupffer's vesicle, delayed retrograde melanosome transport and impaired visual behavior.
Ubiquitously expressed during early development and in adult tissues including the eye, brain, heart and kidney (PubMed:27008867).
Stimulates the adrenal glands to release cortisol.
Heterotetramer of alpha and beta chains.
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).
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.
May bind zinc and other divalent cations and recruit them to vesicular organelles.
Belongs to the mitochondrion-specific ribosomal protein mL63 family.
Belongs to the ATPase alpha/beta chains family.
Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.
Promotes integrin-mediated cell adhesion.
Belongs to the vacuolar ATPase subunit S1 family.
Does not bind lactose, and may not bind carbohydrates.
Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
Expressed both maternally and zygotically (PubMed:21553381). Ubiquitous expression until the early somitogenesis stage (PubMed:21553381). In later embryonic stages, detected in the otic vesicles, hatching gland cells, pectoral fin, posterior tectum and swim bladder (PubMed:21553381).
Facilitative glucose transporter required for the development of the cardiovascular system.
Morpholino knockdown of the protein causes notochord and cardiovascular abnormalities (PubMed:22116938). Fishes display a reduced heart rate and blood flow, coupled with an incomplete and irregular vascular patterning (PubMed:22116938).
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly (By similarity).
In association with mitochondrial contact site and cristae organizing system (MICOS) complex components and mitochondrial outer membrane sorting assembly machinery (SAM) complex components may regulate mitochondrial dynamics playing a role in determining mitochondrial length, distribution and motility.
Belongs to the STXBP/unc-18/SEC1 family.
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 (By similarity).
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.
Belongs to the N-CoR nuclear receptor corepressors family.
Expressed exclusively in retinal ganglion cells during and after axogenesis.
Interacts with Bucky ball (BUC); to mediate Balbiani body formation and oocyte polarity during early oogenesis.
Knock-down leads to topographic missorting in the optic tract through the up-regulation of NRP1.
RNA-binding protein involved in the regulation of smooth muscle cell differentiation and proliferation in the gastrointestinal system (By similarity). RNA-binding protein localized in Balbiani body (electron-dense aggregates in the oocyte) and germ plasm during oogenesis, and may be required to maintain germ plasm mRNA translational repression (PubMed:18582455). Translational regulator during topographic map formation in the visual system (PubMed:27974617). Establishes oocyte polarity through interaction with Bucky ball (BUC) (Probable).
May be involved in fusion of retrograde transport vesicles derived from an endocytic compartment with the Golgi complex.
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.
Component of the multisubunit TRAPP II complex, which includes at least TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC4, TRAPPC5, TRAPPC6A/B, TRAPPC9, TRAPPC10 and TRAPPC14. TRAPPC9, TRAPPC10 and TRAPPC14 are specific subunits of the TRAPP II complex. Interacts with alpha-tubulin during mitosis.
Morpholino knockdown of the protein in early embryos results in curved bodies and small eyes. Morphants exhibit reduced ciliation in otic vesicles, neuromasts, and olfactory placodes (PubMed:31467083). In a knockout model mutant animals show head to body ratios lower than those of controls. They have decreased brain cell proliferation rate at 24 hpf (PubMed:30715179).
Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether (By similarity). TRAPP II complex has also GEF activity toward RAB1A (By similarity). TRAPPC14 is required for ciliogenesis (PubMed:30715179).
Belongs to the complex I 30 kDa subunit family.
Belongs to the PPase class C family. Prune subfamily.
Belongs to the dus family. Dus3 subfamily.
Belongs to the diacylglycerol acyltransferase family.
Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
Belongs to the eukaryotic/archaeal RNase P protein component 2 family.
Component of nuclear RNase P and RNase MRP ribonucleoproteins. RNase P consists of a catalytic RNA moiety and 10 different protein chains; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5.
Component of ribonuclease P, a protein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.
May act as a component of a corepressor complex that represses transcription.
Expression is initiated during early development throughout the notochord and extinguished between 24 and 48 hours after fertilization (PubMed:17543297). At 24 hours after fertilization, expressed ubiquitously throughout the embryo (PubMed:25959397).
Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine) (By similarity). Acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation (By similarity). 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) (By similarity). 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 (By similarity). LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency (By similarity). Involved in epithelial to mesenchymal transition (EMT) and participates in repression of E-cadherin, probably by mediating deamination of histone H3 (By similarity). 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 (By similarity). Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding (PubMed:21835952). Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation (By similarity). Required with loxl2a for correct expression of Sox2 and for neural differentiation (PubMed:25959397).
Morpholino knockdown of loxl2a and loxl2b in the embryo results in increased expression of Sox2 in the central nervous system, particularly in the eye, hindbrain and spinal cord. It also leads to impaired neural differentiation with morphological defects in the brain where the anterior brain is rounder than normal and the eyes present a flatter curvature. Embryo development is also compromised.
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.
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.
Belongs to the HIBADH-related family. 3-hydroxyisobutyrate dehydrogenase subfamily.
Belongs to the acetyltransferase family. NAA40 subfamily.
N-alpha-acetyltransferase that specifically mediates the acetylation of the N-terminal residues of histones H4 and H2A. In contrast to other N-alpha-acetyltransferase, has a very specific selectivity for histones H4 and H2A N-terminus and specifically recognizes the 'Ser-Gly-Arg-Gly sequence'.
Involved in ribosomal large subunit assembly.
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.
Belongs to the eukaryotic-type primase small subunit family.
Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily.
Serine/threonine kinase involved in cell cycle, nuclear condensation and transcription regulation. Involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation. Phosphorylates p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2. Phosphorylates KAT5 in response to DNA damage, promoting KAT5 association with chromatin and histone acetyltransferase activity. Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm. Phosphorylates ATF2 which activates its transcriptional activity.
Morpholino knockdown of the protein affects brain and neuromuscular development. Morphant embryos have small heads, small or absent eyes, truncated bodies, and reduced and damaged myofibers. Motor axons fail to migrate properly to the neuromuscular junctions. The brain has abnormal morphology, the cerebellum and hindbrain are absent.
Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs.
The six exosome core subunits containing a RNase PH-domain are not phosphorolytically active.
Acts as an adapter for the myotubularin phosphatase mtm1 to regulate mtm1 protein stability and possibly its intracellular location (PubMed:23818870). By stabilizing mtm1 protein levels, required for skeletal muscle maintenance but not for myogenesis (PubMed:23818870). In skeletal muscle cells, does not regulate mtm1 subcellular localization (PubMed:23818870).
Although it belongs to the non-receptor class myotubularin subfamily, lacks the conserved active site cysteine residue at position 378 in the dsPTPase catalytic loop and does not have phosphatase activity.
At 1 day post fertilization (dpf), expressed ubiquitously in developing eyes, brain, heart and skeletal muscles. Maternally expressed up to 8 hour post fertilization and zygotic expression starts at 1 dpf and continues until 5 dpf.
Heterodimer with lipid phosphatase mtm1 (By similarity). In skeletal muscles, the interaction stabilizes both mtmr12 and mtm1 protein levels (PubMed:23818870).
Morpholino knockdown results in early embryonic mortality between 3 to 5 days post fertilization. Causes a reduction in size with an abnormal dorsal curvature through the back and tail. Impaired motor function characterized by a delay in chorion hatching and a reduced motility. Some animals have pericardial edema. Defects in skeletal muscles including sarcomeric disorganization often with central nucleation and triad disorganization. In skeletal muscles, increased phosphatidylinositol 3-phosphate levels and severe reduction of mtm1 levels without affecting mtm1 subcellular localization. Double morpholino knockdown of mtmr12 and mtm1 results in a more severe phenotype.
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 osteocalcin/matrix Gla protein family.
Functions together with adgra2 to enable brain endothelial cells to selectively respond to Wnt7 signals (wnt7a or wnt7b) (PubMed:26051822, PubMed:26657775). Plays a key role in Wnt7-specific responses: required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (PubMed:26051822, PubMed:26657775). Acts as a Wnt7-specific coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by interacting specifically with the disordered linker region of Wnt7, thereby conferring ligand selectivity for Wnt7. Adgra2 is then required to deliver reck-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex. Also acts as a serine protease inhibitor (By similarity).
Interacts (via knot repeats) with wnt7a (via disordered linker region); the interaction is direct (By similarity). Interacts (via knot repeats) with wnt7b (via disordered linker region); the interaction is direct (By similarity). Interacts with adgra2; the interaction is direct (PubMed:26051822).
The Kazal-like domains mediate the serine protease inhibitor activity.
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.
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).
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 G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.
Belongs to the chloride channel (TC 2.A.49) family.
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in DNA repair.
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.
Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC.
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.
First detected at the 12-somite stage. From the 20-somite stage, expressed in the otic vesicle.
Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules.
Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker. In interphase, required for anchoring microtubule at the mother centriole subdistal appendages and for centrosome positioning. During mitosis, may be involved in spindle assembly and chromatin alignment by regulating the organization of spindle microtubules into a symmetrical structure. Plays a non-essential role in ciliogenesis.
The N-terminal 3D structure (head domain) resembles that of NHEJ1/XLF, PAXX, SASS6 and XRCC4.
The coiled-coil domain is involved in microtubule-binding.
Belongs to the PPP phosphatase family. PP-1 subfamily.
Belongs to the Mediator complex subunit 18 family.
RNA-binding protein that regulates alternative splicing events.
Belongs to the RBR family. Parkin subfamily.
Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.
May be involved in the calcium-dependent regulation of rhodopsin phosphorylation. Binds three calcium ions (By similarity).
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.
Binds calcium through the terminal sialic acids.
EPDs are synthesized in the meninx and secreted in the cerebrospinal fluid.
May play a role in neural plasticity. May be involved during axon regeneration.
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 methyltransferase superfamily. L-isoaspartyl/D-aspartyl protein methyltransferase family.
Initiates the repair of damaged proteins by catalyzing methyl esterification of L-isoaspartyl and D-aspartyl residues produced by spontaneous isomerization and racemization of L-aspartyl and L-asparaginyl residues in aging peptides and proteins.
Expressed from the 1-cell stage, before the onset of zygotic expression, then, during gastrulation, at 6 hours post-fertilization (hpf), expression is absent, and at 11-12 hpf, coincident with segmentation, expression returns until 72 hpf.
May be involved in transcriptional regulation (PubMed:23071114). Required for progression through late erythroid differentiation (PubMed:23071114). May be involved in vasculogenesis (PubMed:23071114).
Morpholino knockdown has no effect on overall morphology, and at the onset of blood circulation at 24 hours post-fertilization (hpf), blood cells are present, however between 33 and 48 hpf, blood cells are absent, and embryos develop cardiac edema (PubMed:23071114). Hemoglobin undetectable (PubMed:23071114). Some embryos recovered blood circulation at day 4 after knockdown, whereas others became severely edematous at day 4-5 and died by about 7 days (PubMed:23071114). At 28 and 48 hpf, expression of band3 almost abolished; embryonic alpha-globin1 also significantly reduced at 28 hpf (PubMed:23071114).
ATP-dependent microtubule severing protein. Severs microtubules along their length and depolymerizes their ends, primarily the minus-end, suppressing microtubule growth from and attachment to centrosomes. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome (By similarity).
Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.
Catalyzes the deamination of cytidine and deoxycytidine into uridine and deoxyuridine, respectively.
Belongs to the cytochrome c oxidase VIIb 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 an important role for the maintenance of myelin-axon integrity (By similarity). May affect intracellular Ca(2+) homeostasis (By similarity).
Choline transporter that seems to play a role in the choline-acetylcholine system and is required to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury.
Gene expression gradually increases from 36 to 96 hours post-fertilization (hpf). At 12 hpf, expressed broadly, but at 26 hpf, the expression clusters around the otic vesicle, pectoral fin, and midbrain.
Morpholino knockdown of the protein causes abnormal numbers of small, fused, and misplaced otoliths, and a smaller inner ear. Neuromasts of the morphants are smaller, and the number of lateral line neuromasts in the morphants is fewer than in the wild-type. Fewer hair cells per neuromast are found in both the anterior and posterior line of morpholino knockdown larvae (120 hpf) than in the wild-type. Knockdown larvae have a defective balance system, they show an abnormal swimming behavior by remaining stationary and resting in abnormal positions, they swim up and down and in circles. They also show some hearing loss.
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.
The UBA domain specifically recognizes and binds 'Lys-6'-linked polyubiquitin chains.
Ubiquitin-binding protein that specifically binds 'Lys-6'-linked polyubiquitin chains. 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).
DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing and transcription regulation (PubMed:30135188, PubMed:31399345). Binds preferentially to the 5'-[CU]CUGCG-3' RNA motif and specifically recognizes mRNA transcripts modified by C5-methylcytosine (m5C) (PubMed:31399345). Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting pabpc1a, thereby preventing mRNA decay (PubMed:31399345). Plays a role in the maternal-to-zygotic transition in early embryo by binding to m5C-containing maternal mRNAs and preventing their degradation (PubMed:31399345). Also promotes maternal-to-zygotic transition in oocytes and embryos by promoting translation repression; molecular mechanisms governing translation repression are unknown (PubMed:30135188). Plays a key role in RNA composition of extracellular exosomes by defining the sorting of small non-coding RNAs, such as tRNAs, Y RNAs, Vault RNAs and miRNAs. Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs (By similarity). Acts as a key effector of epidermal progenitors by preventing epidermal progenitor senescence: acts by regulating the translation of a senescence-associated subset of cytokine mRNAs, possibly by binding to m5C-containing mRNAs (By similarity). Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection (By similarity). Also able to bind DNA and regulate transcription. Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'). Promotes separation of DNA strands that contain mismatches or are modified by cisplatin. Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA, suggesting a role in DNA repair. The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation (By similarity).
Embryonic lethality caused by early gastrulation arrest: maternal mutant embryos fail to undergo normal cleavage and the maternal-to-zygotic transition (PubMed:30135188, PubMed:31399345). Early embryos show severe developmental arrest at the shield stage in maternal ybx1 knockout embryos, leading to lethality at 8 hours post-fertilization (hpf) (PubMed:31399345).
In the CSD domain, Trp-45 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring.
Interacts with pabpc1a; leading to pabpc1a recruitment on C5-methylcytosine (m5C)-containing mRNAs.
Activated by glycine and taurine. Inhibited by strychnine (PubMed:10188956, PubMed:26344198). Allosterically activated by ivermectin (PubMed:26344198). Inhibited by picrotoxinin (PubMed:26344198). Strychnine binding locks the channel in a closed conformation and prevents channel opening in response to extracellular glycine (PubMed:26344198). Can also be activated by GABA and inhibited by bicuculline, but this requires heterologous expression in human cells (PubMed:10188956).
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRA1 sub-subfamily.
Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:10188956, PubMed:26344198). Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents. Channel activity is potentiated by ethanol (By similarity).
Highly sensitive to activation by taurine despite the presence of Val in position 135. In mammals, Val-135 causes a drastic loss of taurine efficacy.
Homopentamer (in vitro) (PubMed:26344198). Heteropentamer composed of glra1 and glrb (By similarity). Both homopentamers and heteropentamers form functional ion channels (By similarity).
The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. Channel opening is effected by an outward rotation of the transmembrane domains that increases the diameter of the pore.
Expressed both maternally and zygotically. Expressed in oocytes and throughout embryogenesis, whereas expression in adults is undetectable.
Expressed in all cells until gastrulation, becoming restricted to the developing central nervous system later, where expression is in the forebrain, midbrain and hindbrain but maximally at the midbrain-hindbrain boundary.
May function as a switch in neuronal development (By similarity). Acts as a negative regulator of transcription. Plays a role in dorsoventral patterning of the embryo.
Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes.
Probably maternally supplied, the zygotic expression is detected early during development at the 512-cell stage.
Severe defects of trunk and tail development.
Transcriptional regulator that may act as an activator (By similarity). Plays a role for mesoderm patterning in early embryogenesis.
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).
May function as a homophilic cell adhesion molecule and be essential for tight junction integrity. May also be involved in transepithelial migration of leukocytes through adhesive interactions with jaml. The interaction between both receptors may also mediate the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair (By similarity).
Monomer. Probably homodimer formed by 2 molecules on adjacent cells (By similarity).
The Ig-like C2-type 1 domain may mediate homodimerization.
Involved in the histone deacetylase (HDAC1)-dependent transcriptional repression activity.
Belongs to the CDP-alcohol phosphatidyltransferase class-I family.
First expressed at the 1- to 2-somite stages posterior to rhombomere 5 (r5) of the developing hindbrain. By the 3- to 4-somite stages, the anterior expression limit is at the r4/r5 boundary. At 5- to 10-somite stages, expressed at high levels in r5 and r6. From the 20- to 30-somite stages, expressed weakly in r4.
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).
Belongs to the eukaryotic release factor 1 family.
Heterodimer with IL12A; disulfide-linked. The heterodimer is known as interleukin IL-12.
Belongs to the acid sphingomyelinase 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.
Cell surface proteoglycan that bears heparan sulfate (By similarity). Negatively regulates the hedgehog signaling pathway (By similarity). Positively regulates the canonical and non-canonical Wnt signaling pathways (By similarity). Binds to CD81 which decreases the availability of free CD81 for binding to the transcriptional repressor HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (By similarity). Inhibits the dipeptidyl peptidase activity of DPP4 (By similarity). Plays a role in limb patterning and skeletal development (By similarity). Modulates the effects of growth factors on renal branching morphogenesis (By similarity). Required for coronary vascular development (By similarity). Plays a role in regulating cell movements during gastrulation (PubMed:14610063).
Cleaved intracellularly by a furin-like convertase to generate 2 subunits, alpha and beta, which remain associated through disulfide bonds and are associated with the cell surface via the GPI-anchor (PubMed:14610063). This processing is essential for its role in inhibition of hedgehog signaling (By similarity). A second proteolytic event may result in cleavage of the protein on the cell surface, separating it from the GPI-anchor and leading to its shedding from the cell surface (By similarity).
Heterodimer; disulfide-linked. Cleavage by a furin-like convertase results in production of alpha and beta chains which form a disulfide-linked heterodimer.
Maternally expressed and is almost ubiquitous during blastula and gastrula stages but becomes restricted to the prospective hindbrain by 24 hours post-fertilization.
Morpholino knockdown results in severe defects during epiboly with most embryos arrested at 60-80% epiboly.
O-glycosylated; contains heparan sulfate.
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' (By similarity).
Interacts with RET in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex.
May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.
Belongs to the bZIP family. CNC subfamily.
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.
Plays a role in neuronal plasticity and the proteolytic action may subserve structural reorganizations associated with learning and memory operations.
Belongs to the formin homology family. Cappuccino subfamily.
Belongs to the eukaryotic-type primase large subunit family.
Regulatory subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands.
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 (By similarity).
Belongs to the glycosyl hydrolase 13 family.
Belongs to the immunoglobulin superfamily. ICAM family.
Morpholino knockdown leads to a phenotype ranging in severity from weak to severe that includes an elongated hindbrain, altered midbrain-hindbrain boundary, stacked somites in severe phenotypes and a mortality rate of 97% at 5 days post-fertilization.
Plays a role in nonsense-mediated mRNA decay (By similarity). Recruits UPF1 to cytoplasmic mRNA decay bodies (By similarity). Together with SMG5 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation (By similarity). Required for normal embryonic development (PubMed:19414594).
Enhances the tyrosine carboxypeptidase activity of vash1 and vash2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin. Also required to enhance the solubility and secretion of vash1 and vash2. May play a role in axon and excitatory synapse formation (By similarity).
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 adipolin/erythroferrone family.
Insulin-sensitizing adipocyte-secreted protein (adipokine) that regulates glucose metabolism in liver and adipose tissue.
Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.
Belongs to the poly(A) polymerase family.
Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:24561204). Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (By similarity). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:24561204).
Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as e2f1. Acts as a regulator of S-phase by recognizing and binding the E2-related site 5'-TTCCCGCC-3' and mediating repression of G1/S-regulated genes (By similarity). Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator and promoting expression of vegfa.
Embryos lacking both e2f7 and e2f8 contain multiple intersegmental arteries that completely fail to migrate from the dorsal aorta. Gross morphology of these embryos and initial formation of main axial vessels are unaltered.
Homodimer and heterodimer: mainly forms homodimers and, to a lesser extent, heterodimers with e2f8.
In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer (By similarity).
Heterodimer of PMPCA (alpha) and PMPCB (beta) subunits, forming the mitochondrial processing protease (MPP) in which PMPCA is involved in substrate recognition and binding and PMPCB is the catalytic subunit.
Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins.
Genetic defects resulting in MPV17 loss are responsible for the transparent (tra) mutant phenotype. 'tra' fishes display pigmentation abnormalities and lack of cells derived from the neural crest, such as iridophores and, at later stages of development, melanophores (PubMed:23862018). MPV17-null larvae show disruption of mitochondrial ultrastructure in liver cells with mitochondrial ballooning and disappearance of cristae, and impaired oxidative phosphorylation, insufficient pyrimidine synthesis, and mtDNA depletion (PubMed:30833296).
Involved in mitochondrial homeostasis, and control of oxidative phosphorylation and mitochondrial DNA (mtDNA) maintenance (PubMed:30833296). Non-selective channel that modulates the membrane potential under normal conditions and oxidative stress (By similarity).
Steroid membrane receptor. Binds progesterone. May be involved in oocyte maturation (By similarity).
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ11 subfamily.
Expression in the ocular lens starts at as early as 24 hours post fertilization (hpf).
Heat-shock transcription factor that specifically binds heat shock promoter elements (HSE) (PubMed:22528049). Required for denucleation and organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (PubMed:32061775, PubMed:33854238). In this process, may regulate denucleation of lens fiber cells in part by activating dnase1l1l and dnase2b transcription (PubMed:32061775). May be involved in DNA repair through the transcriptional regulation of rad51 (PubMed:22587838). May up-regulate TP53 protein in lens fiber cells, possibly through protein stabilization (PubMed:28981088). In the eye lens, controls the expression of alpha-crystallin B chain/CRYAB and consequently may be involved in the regulation of lysosomal acidification (PubMed:31786107).
In knockout animals, the eye lens grows normally, but during lens differentiation, denucleation is impaired and the degradation of mitochondria and endoplasmic reticulum is suppressed.
Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding.
Belongs to the 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.
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 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.
Can self-associate. Interacts with dynein, dynactin, NDE1 and NDEL1.
Dimerization mediated by the LisH domain may be required to activate dynein.
Enriched in the photoreceptor cell layer.
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.
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. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. May be required for proliferation of neuronal precursors and neuronal migration (By similarity). Involved in the positioning of nuclei in photoreceptor cells.
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.
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.
Expressed in the otic vesicle at 1 days post fertilization (dpf) (PubMed:26365339). Expressed in mesenchyme pectoral fins surrounding the cartilage of the endoskeletal disc, and in the epithelial cells of the oral cavity at 3 dpf (PubMed:26365339). Expressed weakly in the pronephric duct and the liver at 3 dpf (PubMed:26365339).
Plays a role in primary cilia formation (PubMed:26365339). Involved in cartilage and bone development (PubMed:26365339). May play a role in the differentiation of cranial neural crest cells (PubMed:26365339). May act as a downstream effector of hoxc8 during development (By similarity).
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.
Detected in embryo 24 to 48 hours after fertilization, and in intestinal bulb.
Homodimer in the absence of bound vitamin D3. Heterodimer with RXRA after vitamin D3 binding (By similarity). Interacts with ncoa1 and possibly other coactivators, leading to a strong increase of transcription of target genes (By similarity).
Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells. Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
Belongs to the CRF-binding protein family.
Binds CRF and inactivates it. May prevent inappropriate pituitary-adrenal stimulation in pregnancy.
Belongs to the methylthiotransferase family. MiaB subfamily.
E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. It thereby participates in many processes regulated by the Notch signaling pathway, such as midline cell fate specification prior to germ layer formation, patterning of sensory cell differentiation in the ear, neurogenesis of the hindbrain and commitment to a secretory fate in the intestine. Essential for early embryonic development.
Interacts with deltaA (dla) and deltaD (dld).
Mutants have a disorganized brain and neural tube, bent tail and very small or absent otoliths.
The ANK repeats are involved in Delta receptor internalization.
The N-terminal domain (1-440) mediates the interaction with Delta receptors.
The RING fingers mediate the E3 ligase activity. The third RING finger probably plays a central role in this process. The role of the other RING fingers remains unclear.
Belongs to the nucleotide-sugar transporter family. SLC35B subfamily.
At 3 dpf, mutant embryos show no visible abnormalities compared to wild-type embryos. They do not display any ocular abnormalities at 5 dpf. They nevertheless exhibit elevated levels of D-lactate, but not L-lactate compared to wild-type larvae.
Belongs to the FAD-binding oxidoreductase/transferase type 4 family.
Involved in D-lactate, but not L-lactate catabolic process.
Detected from 24 to 72 hours post-fertilization (hpf).
Involved in the control of cell movement by regulating actin cytoskeleton homeostasis and filopodium and lamellipodium formation.
Morpholino knockdown of the protein results in reduced head and eye size, a ventrally curved body, and enlarged brain vesicles. In the craniofacial cartilage, the ceratobranchial arches are reduced. Formation of ceratohyal cartilage is disrupted with an abnormal angle relative to wild-type. Morphogenesis of the developing neural tube is abnormal, with a smaller angle between the walls of the hindbrain neuroepithelium at 24 hours post-fertilization (hpf) and in some cases a partial opening in the dorsal region. Some deformation of the midbrain walls is also found. Retinal development is significantly delayed; no retinal ganglion cells (RGCs) are detected at 30 hpf and reduced numbers are found at 60 hpf. RGCs also appear to be mislocalized. In about a third of embryos, three instead of two otoliths are detected in the inner ear. Cilium length in Kupffer's vesicle is significantly reduced. Cilia in the olfactory placode also appear to be fewer in number and have reduced length. Double morpholino knockdown of marcksl1a and marckls1b results in a more pronounced developmental delay in the retina. Double morpholino knockdown of marcksb and marcksl1b results in retinal morphogenesis defects of increased severity. The optic cup structure is not apparent, and very few atoh7-positive retinal ganglion cell precursors are detected. Double morpholino knockdown of marcksb and marcksl1b also results in more severe defects in neural tube morphology, with partial duplications of the neural tube in the hindbrain region.
Strongly expressed in brain and eye. Also detected at lower levels in muscle.
Belongs to the methyltransferase superfamily. METTL16/RlmF family.
Methyltransferase activity is autoinhibited by the K-loop region that blocks S-adenosyl-L-methionine-binding. Upon activation, K-loop changes conformation, allowing S-adenosyl-L-methionine-binding and subsequent methyltransferase activity. mRNA N6-adenosine-methyltransferase activity is inhibited by zinc.
RNA N6-methyltransferase that methylates adenosine residues at the N(6) position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts. Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure. Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, impairing MAT2A splicing and protein expression. In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A. In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs.
The K-loop region occludes the S-adenosyl-L-methionine-binding pocket. Upon activation, conformation of the K-loop changes, allowing S-adenosyl-L-methionine-binding.
The VCR (vertebrate conserved) regions bind the first hairpin of MAT2A mRNAs. The VCR regions interact with the internal stem-loop within U6 snRNAs, inducing the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the methyltransferase region.
Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.
Appears to function predominantly as a heterodimeric complex with ILF3. This complex may function to regulate transcription of undefined genes (By similarity).
First detected at 12.5 hours post-fertilization, continuing through to adult stages. At the 10-somite stage, expressed in the paraxial mesoderm with an anterior expression at somite 1. At the 20-somite stage, expressed within the developing CNS with an anterior expression limit at the anterior-most region of somite 1.
Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
Plays an important role in regulating intracellular signaling events associated with erythroid terminal differentiation.
Fishes display embryonic cardiac hyperplasia with increased cell number and size by 72 hours post-fertilization. Gut and gut-derived organs are incapable of growth and differentiation after this time. The mutation enhances ATPase activity, rendering it DNA-independent and causes aggregation of the protein into large complexes.
Forms homohexameric rings (Probable). Can form a dodecamer with ruvbl1 made of two stacked hexameric rings (By similarity). Component of the chromatin-remodeling Ino80 complex (By similarity). Component of some MLL1/MLL complex (By similarity).
Has double-stranded DNA-stimulated ATPase activity (PubMed:12464178). Has ATP-dependent DNA helicase (5' to 3') activity suggesting a role in nuclear processes such as recombination and transcription (By similarity). Represses gene activation mediated by beta-catenin (PubMed:12464178). Proposed core component of the chromatin remodeling Ino80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (By similarity). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (By similarity). May act as a regulator of embryonic heart growth (PubMed:12464178).
Widely expressed in the embryo. After 60 hours post-fertilization there is increased expression in heart, liver, branchial arches, exocrine pancreas and intestine.
Belongs to the class-II aminoacyl-tRNA synthetase family.
Belongs to the PtdIns transfer protein family. PI transfer class IIA subfamily.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS11 subfamily.
Catalytic component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. Mediates the snRNAs 3' cleavage.
The HXHXDH motif is essential for the endoribonuclease activity of the CPSF complex.
Retinal double cone accessory photoreceptor cell outer segments.
Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.
Belongs to the PIGG/PIGN/PIGO family. PIGN subfamily.
Ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers ethanolamine phosphate to the first alpha-1,4-linked mannose of the glycosylphosphatidylinositol precursor of GPI-anchor.
Belongs to the D-glutamate cyclase family.
Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins.
Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response.
Expression is highest in adults. In the embryo, maternal transcript levels are reduced during blastula and gastrula stages. Expression increases during segmentation and later stages.
The intermediate domain (ID) is required for the phosphorylation and activation of IRAK.
Belongs to the Mediator complex subunit 23 family.
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).
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.
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Regulates calcium efflux at the endoplasmic reticulum.
May function in lipid transport from the endoplasmic reticulum and be involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. May regulate calcium efflux at the endoplasmic reticulum (By similarity).
Sigma receptors are classified into two subtypes (Sigma-1 and Sigma-2) based on their different pharmacological profile.
The C-terminal helices form a flat, hydrophobic surface that is probably tightly associated with the cytosolic surface of the endoplasmic reticulum membrane.
First detected at around 8 hours post-fertilization (hpf) within the prospective midbrain-hindbrain boundary (MHB). By 10 hpf, expressed in two stripes that converge at the dorsal midline. During somitogenesis, this expression domain extends to the prospective epiphysis and the dorsal midline of the hindbrain; unlike wnt10b, wnt1 is not detected in the prospective cerebellum. The hindbrain domain bifurcates along the midline to form two dorsolateral columns with transverse bands of up-regulation at rhombomere boundaries; these are refined into stripes which are maintained at least until at least 48 hpf. At 30 hpf, expressed in the epiphysis, the dorsal midline of the optic tectum, the anterior half of the MHB constriction and in the hindbrain walls. Not detected in adults.
In the embryo, expressed in the developing central nervous system (CNS), with an expression pattern very similar to that of wnt10b. During somitogenesis, expressed strongly in hindbrain boundary and roof plate cells.
Ligand for members of the frizzled family of seven transmembrane receptors. Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation (By similarity). Involved in neurogenesis. Performs a partially redundant function with wnt10b in the formation of the midbrain-hindbrain boundary (MHB) organizer. In the hindbrain, mediates lateral inhibition of boundary cell specification, probably via up-regulation of proneural and Delta gene expression in non-boundary cells; localized expression of wnt1 in boundary cells is maintained via rfng-mediated modulation of Notch activity.
Morpholino knockdown results in broadening of hindbrain boundary marker expression.
Palmitoleoylation is required for efficient binding to frizzled receptors. Palmitoleoylation is necessary for proper trafficking to cell surface (By similarity). Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway (By similarity).
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.
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.
Plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair.
Belongs to the small GTPase superfamily. RGK family.
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.
Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway. Probably involved in the binding of an intermediate of Fe/S cluster assembly.
Heterodimer; with an rxr molecule. Binds DNA preferentially as a rar/rxr heterodimer.
In the embryo, zygotic expression largely overlaps that of rarab, with high levels in hindbrain, lateral mesoderm and tail bud. In the adult, strong expression in brain and muscle, weaker expression in ovary, liver and digestive tract.
Not expressed maternally. First detected at 8 hours post-fertilization (hpf) during gastrulation, with expression being restricted to the posterior epiblast. Expression then increases, reaching a peak at 24 hpf and decreasing from 30-48 hpf. At 9 hpf, expressed throughout the dorsal epiblast except at the dorsal midline, and ventrally in prospective tail and head regions. At 10-11 hpf, expressed in presumptive hindbrain, posterior neural plate, lateral mesoderm and tail bud. At 12 hpf, strongly expressed in the neural epithelium and tail bud and expressed at low levels elsewhere including the eye. At 24 hpf, restricted to the hindbrain with an anterior border at rhombomere 6-7, to anterior spinal cord and to head mesenchyme just posterior to the otic vesicle. At 48 hpf, hindbrain expression remains and there is diffuse expression in non-neural tissue in the pharyngeal region.
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain patterning.
Belongs to the alpha/beta interferon family.
Acts as a ligand for Notch receptors and is involved in somitogenesis. Can activate Notch receptors. Required in somite segmentation to keep the oscillations of neighboring presomitic mesoderm cells synchronized.
Strongly expressed in the early retina, where it precedes other delta proteins. Also expressed in cranial ganglia, in sensory epithelia including ear and lateral line and in scattered epidermal cells. In the mesoderm, expression is visible by 50% epiboly; it is expressed subsequently in the tail bud, in stripes in the presomitic mesoderm and in the posterior half of each somite. Also expressed in notochord, blood vessels and pronephros. In contrast to other delta proteins, it is not expressed in the majority of nascent primary neurons. In somites, it marks the posterior part of each formed somite, while deltaD (dld) marks the anterior part.
Ubiquitinated by mib, leading to its endocytosis and subsequent degradation.
Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily.
Implicated in development of the cochlea.
Affects the left-right asymmetry of internal organs, but not their specification.
Belongs to the WD repeat IPI3/WDR18 family.
Component of the PELP1 complex, composed of at least PELP1, TEX10 and WDR18. The complex interacts with pre-60S ribosome particles.
Expressed from the 1-4 cell stage and in DFCs at 75%-epiboly stage. By the 6-somite stage, its expression in the Kupffer's vesicle is detectable in addition to some basal expression levels in other cells. Later at the 18-somite stage, detected ubiquitously throughout the embryo. After 2 dpf (days post fertilization), expressed in endodermal organs, including the pancreas and liver.
Involved in left-right determination through controlling the correct clustering and migration of dorsal forerunner cells (DFCs) and Kupffer's vesicle formation (PubMed:21876750). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (By similarity).
Belongs to the Golgi pH regulator (TC 1.A.38) family.
Homozygous for these mutant alleles complete embryogenesis normally, but manifest a cystic kidney phenotype during the early larval stages and die within a month of hatching. Elimination of maternally derived talpid3 activity by germline replacement resulted in embryonic lethality of talpid3 homozygotes. The phenotype of such maternal and zygotic mutant show absence of primary and motile cilia as well as aberrant Hedgehog signaling.
Required for ciliogenesis and sonic hedgehog/SHH signaling.
Ubiquitously distributed in embryos from early cleavage stages through to 2 dpf.
Component of the ER membrane protein complex (EMC).
Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
At the 20-somite stage (18 hpf), expressed on the dorsal side of the embryo in the developing central and peripheral nervous system (CNS and PNS), in the tail bud and the pronephric ducts. In the PNS, expressed in the otic vesicle, trigeminal ganglion and the anterior lateral line placode. Localized throughout the hindbrain, with highest expression in rhombomeres 3 and 4. In the head, expressed in the olfactory placode and in the diencephalic region. At the end of the segmentation period (20 hpf), expression begins in the newly forming endodermal pouches, and weakly in the pharyngeal arch precursor cells. During the early pharyngula period, expressed in the pectoral fin bud, the developing retina, and still present in the central nervous system and endodermal pouches. In the tail, expressed in the spinal cord and posterior lateral line precursors. Weakly expressed in the pronephric ducts, only in the corpuscles of Stanius. At 48 hpf, still expressed in the retina and brain, where expression is almost uniform. At this stage, expression is decreased in the spinal cord and is absent from the lateral line cells and pronephric ducts, but appears in the intestine and continues in the pharyngeal arches. In 72 hpf embryos, expression in the brain remains uniform but is restricted to amacrine cells in the retina. In the pharyngeal arches, expression continues to be limited to the ectodermal and endodermal covering cells.
Expression begins at 16 hpf and gradually increases up to 72 hpf.
Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.
Possible role in EGF receptor signaling.
Expressed in the mesoderm, including the intermediate mesoderm, the origin of the pronephros, at 90% epiboly (8.5 hpf) and early somitogenesis stages (11.5 hpf).
Morpholino knockdown of the protein causes abnormal morphology of the proximal kidney.
Plays a major role in early metanephros development.
Converts glycerol-3-phosphate to 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) by incorporating an acyl moiety at the sn-1 position of the glycerol backbone. Also converts LPA into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone. Protects cells against lipotoxicity.
Belongs to the beta-2-microglobulin family.
Belongs to the snRNP core protein family.
Belongs to the heat shock protein 90 family.
By heat shock during early embryogenesis.
Detected throughout the embryo and in low levels in the musculature. Expressed predominantly in the developing brain, tail bud and cells surrounding the posterior margin of the yolk tube.
Expressed throughout embryonic development.
In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state.
Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (By similarity). Not required for myofibril formation in skeletal muscles (PubMed:10364427, PubMed:17586488).
Monomer. Homodimer (By similarity). Interacts with unc45b (PubMed:17586488).
The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins.
Belongs to the glycosyl hydrolase 1 family.
Belongs to the eukaryotic RPA49/POLR1E RNA polymerase subunit family.
Expressed both maternally and zygotically, from ova through to 48 hours post-fertilization.
Belongs to the NADP-dependent oxidoreductase L4BD 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.
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.
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.
Component of the TIM23 complex, at least composed of TIM23, TIM17, TIM50 and TIM21.
Belongs to the copper transporter (Ctr) (TC 1.A.56) family. SLC31A subfamily.
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).
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 (PubMed:24360810).
Belongs to the DEAD box helicase family. eIF4A subfamily.
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.
Morpholino EIF4A3 knockdown results in multiple defects in craniofacial structures. Fish morphants staged at 24 hpf show eyes reduced in size, and dark and opaque zones in all brain structures. In addition, the otic vesicle and the midbrain/hindbrain border regions are barely detectable. Cartilage and bone staining reveals underdevelopment of craniofacial cartilage, bone alterations, and clefting of the lower jaw. The third through sixth pharyngeal arches are underdeveloped in morphants.
Somatostatin inhibits the release of somatotropin.
Belongs to the somatotropin/prolactin family.
Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.
Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade "E" sub-subfamily.
Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E' sub-subfamily.
Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.
Belongs to the Mediator complex subunit 26 family.
Nuclear monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin and regulates the srf signaling. Acts by modifying nuclear actin subunits through the addition of oxygen to form methionine-sulfoxide, leading to promote actin filament severing and prevent repolymerization (By similarity). Acts as a key regulator of the srf signaling pathway elicited by nerve growth factor and serum: mediates oxidation and subsequent depolymerization of nuclear actin, leading to increase mkl1/mrtf-a presence in the nucleus and promote srf:mkl1/mrtf-a-dependent gene transcription (PubMed:24440334).
Small hearts that fail to undergo normal looping at 24 hours post-fertilization (hpf) with thin, linear morphology compared to wild-type hearts at 48 hpf. moreover, cardiomyocytes hearts are spatially disorganized. Defects in srf:mkl1/mrtf-a-dependent gene transcription.
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.
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.
NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis and drug metabolism.
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 succinate/malate CoA ligase beta subunit family. GTP-specific subunit beta subfamily.
GTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.
Heterodimer of an alpha and a beta subunit. The beta subunit determines specificity for GTP.
Belongs to the methyltransferase superfamily. METL family.
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 mettl2a requires the N6-threonylcarbamoylation of tRNA (t6A37) by the EKC/KEOPS complex as prerequisite.
Cilium-specific protein required to control the microtubule-based, ciliary axoneme structure. May act by maintaining the association between IFT subcomplexes A and B. Binds GTP but is not able to hydrolyze it; the GTPase activity remains unclear. Required to pattern the neural tube. Involved in cerebral cortex development: required for the initial formation of a polarized radial glial scaffold, the first step in the construction of the cerebral cortex, by regulating ciliary signaling. Regulates the migration and placement of postmitotic interneurons in the developing cerebral cortex Required during embryogenesis for cilia formation in multiple organs such as the pronephric duct.
Detected at the 4- to 32-cell stage, suggesting it is expressed maternally.
Embryos have a ventrally curved tail, ciliary defects and cystic kidneys.
Interacts with EXOC2; regulates ARL13B localization to the cilium membrane.
Arg-210 acts as a selectivity gate, preventing misactivation of ubiquitin by this NEDD8-specific E1 complex.
Belongs to the ubiquitin-activating E1 family. UBA3 subfamily.
Catalytic subunit of the dimeric E1 enzyme, which activates NEDD8.
Catalytic subunit of the dimeric uba3-nae1 E1 enzyme. E1 activates nedd8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a nedd8-uba3 thioester and free AMP. E1 finally transfers nedd8 to the catalytic cysteine of ube2m (By similarity).
Heterodimer of uba3 and nae1. Interacts with nedd8, ube2f and ube2m (By similarity).
Belongs to the neutral sphingomyelinase family.
Belongs to the POU transcription factor family.
Belongs to the immunoglobulin superfamily. LISCH7 family.
Belongs to the cyclin family. Cyclin AB subfamily.
Initially ubiquitous expression at 12 hours post-fertilization (hpf), then strongly expressed in the central nervous system by 48 hpf (PubMed:28444311). Strongly expressed in the brain up to 5 days post-fertilization (dpf) (PubMed:28444311). Ongoing expression in whole brain tissue beyond 5 dpf into adulthood (PubMed:28444311).
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 (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). May play a role in motor neuron development and axonal outgrowth (PubMed:28444311).
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 multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.
Solute transporter for tetraethylammonium (TEA), cimetidine, metformin, guanidine, N-methylnicotinamide (NMN) and also the zwitterionic cephalosporin cephalexin. Responsible for the secretion of cationic drugs across the brush border membranes (By similarity).
Contains a degenerate basic motif not likely to bind DNA.
Morpholino knockdown of atoh8 causes two phenotypes. The severe phenotype displays a shrunken head, reduced eye size and fused somites and most embryos die within 3 days. The mild phenotype displays an abnormal brain shape with smaller eyes, a curved body axis with indistinct somite boundaries and frequently reduced or no circulation. In addition, the yolk extension is hardly visible starting at the beginning of tail straightening from the 17-somite stage.
Transcription factor that binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins (By similarity). During development, is required for heart looping and swim bladder formation by acting in concert with GATA4 and ZFPM1 (PubMed:23836893). During the development of both the retina and skeletal muscles is required for neural retinal cell through modulating PAX6 and NEUROG3 expression and myogenic differentiation (PubMed:20532172).
Weakly expressed in the heart tube at 30 hours post-fertilization (PubMed:23836893). Expressed at as early as epiboly stage, and is broadly distributed till early segmentation stage and in developing retina and skeletal muscle. In the eye, expression is detected in the optic primordium at the 6-somite stage and is steadily expressed during the invagination of the optic vesicle from its initiation to its expansion to the lens rudiment. In skeletal muscle, a faint signal is detected in muscle precursor cells at the early segmentation period, and in ventral somites from the 21-somite to 24 hour post fertilization stage. Expression decreases sharply during 36 to 48 hour post fertilization stage while it reaches its highest level at about 72 hour post fertilization stage. During this period, the distribution extends to the dorsal somites. In addition also appeared in the brain and neural crest cell (PubMed:20532172).
At 5 dpf, expressed in larvae brain and spinal cord.
Intrinsically disordered protein which may negatively regulate mTOR signaling pathway by stabilizing the mTOR complex component DEPTOR. Negatively regulates angiogenesis. Negatively regulates cell growth (By similarity). May play a role in neuronal development (PubMed:30080879).
MINAR1 topology is a matter of debate, some authors think the N-terminus is extracellular, while preliminary experimental results suggest a cytosolic location.
Mutant animals show no gross developmental abnormalities. They have enhanced fear-evoked freezing and compromised C-start responses. Mutant brains exhibit up-regulation of mTOR signaling.
Acts specifically as a negative regulator of skeletal muscle growth.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.
First detected at low levels in the blastula stage and begins to accumulate in the margin of the blastoderm. At the shield stage, when gastrulation starts, expression is higher on the dorsal site. As gastrulation proceeds, expressed at high levels in the anterior ectoderm. In the 1 day old embryo, at the early pharyngula stage, expression in the developing brain is very strong and expression extends in to the spinal cord.
Regulates independently canonical Wnt and Notch signaling by modulating LEF1 and Notch protein turnover. Stabilizes LEF1, a pivotal transcription factor in the Wnt signaling cascade, by blocking its ubiquitination. Involved in angiogenesis; involved in intersegmental vessel patterning during development.
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.
Belongs to the pseudouridine synthase Pus10 family.
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).
Component of the sarcomeric M-band which plays a role in myocyte response to biomechanical stress (By similarity). May regulate expression of other M-band proteins via an SRF-dependent pathway (By similarity). Important for normal contractile function in heart (PubMed:20847312).
Morpholino knockdown of the protein results in severe contractile dysfunction of the heart, leading to pericaridal edema and blood congestion. Heart development and gross cardiac morphology appear to be normal. Cardiomyocytes show some ultrastructural abnormalities including narrowing of the M-band and a poorly defined A-band/M-band transition.
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.
Both maternally and zygotically expressed. Expressed at all stages of early development. Expressed from 8-cell stage to 48 hours post-fertilization (hpf). Expressed in the eyes at 48 hpf.
Plays a role in pre-mRNA splicing by facilitating excision of a subset of introns (By similarity). May be involved in the regulation of innate immune response (By similarity). Plays a role during early embryonic development (PubMed:20348034). Involved in the formation of the anteroposterior axis with important roles also in neural development (PubMed:20348034).
Erythropoietin is the principal hormone involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass.
Functions as a polyspecific organic cation transporter, efficiently transporting many organic cations such as monoamine neurotransmitters 1-methyl-4-phenylpyridinium and biogenic amines including serotonin, dopamine, norepinephrine and epinephrine. May play a role in regulating central nervous system homeostasis of monoamine neurotransmitters. May be involved in luminal transport of organic cations in the kidney and seems to use luminal proton gradient to drive organic cation reabsorption. Does not seem to transport nucleoside and nucleoside analogs such as uridine, cytidine, thymidine, adenosine, inosine, guanosine, and azidothymidine (By similarity).
Homodimer and heterodimer; forms heterodimers with miga1.
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.
Regulates the GDP/GTP exchange reaction of most RAB proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP.
Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase NEP1 family.
Belongs to the SEC23/SEC24 family. SEC23 subfamily.
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.
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.
The Gelsolin-like repeat mediates interaction with proteins containing PPP motifs.
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).
As a subunit of eukaryotic initiation factor 2 (eIF-2), involved in the early steps of protein synthesis. In the presence of GTP, eIF-2 forms a ternary complex with initiator tRNA Met-tRNAi and then recruits the 40S ribosomal complex and initiation factors eIF-1, eIF-1A and eIF-3 to form the 43S pre-initiation complex (43S PIC), a step that determines the rate of protein translation. The 43S PIC binds to mRNA and scans downstream to the initiation codon, where it forms a 48S initiation complex by codon-anticodon base pairing. This leads to the displacement of eIF-1 to allow GTPase-activating protein (GAP) eIF-5-mediated hydrolysis of eIF2-bound GTP. Hydrolysis of GTP and release of Pi, which makes GTP hydrolysis irreversible, causes the release of the eIF-2-GDP binary complex from the 40S subunit, an event that is essential for the subsequent joining of the 60S ribosomal subunit to form an elongation-competent 80S ribosome. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must be exchanged with GTP by way of a reaction catalyzed by GDP-GTP exchange factor (GEF) eIF-2B (By similarity). Along with its paralog on chromosome Y, may contribute to spermatogenesis up to the round spermatid stage (By similarity).
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EIF2G subfamily.
Morpholino knockdown of eif2s3 produces morphants characterized by hypomotility and morphological deficits at 2 dpf. They are shorter with a curved tail. They also display a significant reduction of head size and small eyes.
The eukaryotic translation initiation factor 2 complex/eIF2 is a heterotrimer composed of an alpha, a beta and a gamma subunit.
Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.
Belongs to the methylmalonyl-CoA epimerase family.
Belongs to the nonaspanin (TM9SF) (TC 9.A.2) 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.
Defects in somite lineages. Secondary trunk myogenesis is reduced, as well as appendicular and hypaxial muscles and their progenitors. These cell types derive from the external cell layer (ECL) and ECL cell numbers are reduced. The endotome is expanded at the expense of a second somitic cell type. The resulting increase in endotome-derived cells that migrate to colonize the dorsal aorta generates a dramatic increase in chemokine-dependent hematopoietic stem cell (HSCs) induction.
Expressed within the early somite and then becomes restricted to the external cell layer (ECL) and consequently to appendicular muscle populations.
Mesodermal transcription factor that plays a key role in somitogenesis and is specifically required for sclerotome development. Required for maintenance of the sclerotome polarity and formation of the cranio-cervical joints. Binds specifically to the promoter of target genes and regulates their expression. Required for hematopoietic stem cell (HSCs) induction via its role in somitogenesis: specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the somite named endotome. Acts by mediating specification of endothelial cells of the endotome within the nascent somite, notably by repressing expression of cxcl12b.
Belongs to the WD repeat G protein beta family. Ribosomal protein RACK1 subfamily.
Involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes (By similarity). Required for VANGL2 membrane localization, inhibits Wnt signaling and regulates cellular polarization and oriented cell division during gastrulation.
Belongs to the eukaryotic ribosomal protein eS27 family.
Interacts (via C-terminus) with CCM2. Interacts (via N-terminus) with STK25 and STK26.
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 angiogenesis, vasculogenesis and hematopoiesis during embryonic development (By similarity). Required for normal cardiovascular development (PubMed:19370760).
Belongs to the Mediator complex subunit 11 family.
Belongs to the 2'-deoxynucleoside 5'-phosphate N-hydrolase 1 family.
Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases.
Belongs to the WD repeat PRL1/PRL2 family.
Expressed from 5 days post-fertilization onwards.
Metabolizes aflatoxin B1 (AFB1) to the cytotoxic derivative AFB1 exo-8,9-epoxide. Does not show activity towards lauric acid.
Belongs to the Orn/Lys/Arg decarboxylase class-II family.
Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO).
Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.
Embryonic brain. Not detected during blastula or gastrula stages. At the 4-5 somite stage, expressed in the diencephalon just posterior to the optic vesicles, and weakly in the hindbrain. By the 14 somite stage, there is widespread expression in the CNS, particularly in the ventral diencephalon, optic stalks and anterior hindbrain.
G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate.
Belongs to the universal ribosomal protein uS11 family.
Belongs to the tRNA pseudouridine synthase TruA family.
Monoubiquitination of Lys-120 (H2AXK119ub) by ring1 and rnf2/ring2 complex gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase ube2n and the E3 ligases rnf8 and rnf168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by rnf168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; rnf8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events (By similarity).
Phosphorylated. Phosphorylation of Ser-139 (H2AX139ph) occurs in response to DNA double strand breaks (DSBs) generated by exogenous genotoxic agents, by stalled replication forks and by meiotic recombination events. Phosphorylation is dependent on the DNA damage checkpoint kinases ATR and ATM, spreads on either side of a detected DSB site and may mark the surrounding chromatin for recruitment of proteins required for DNA damage signaling and repair. Widespread phosphorylation may also serve to amplify the damage signal or aid repair of persistent lesions. Dephosphorylation of Ser-139 is required for DNA DSB repair. Phosphorylation at Tyr-142 (H2AXY142ph) by baz1b/wstf determines the relative recruitment of either DNA repair or pro-apoptotic factors. Phosphorylation at Tyr-142 (H2AXY142ph) favors the recruitment of pro-apoptosis factors. In contrast, dephosphorylation of Tyr-142 by EYA proteins (eya1, eya2, eya3 or eya4) favors the recruitment of MDC1-containing DNA repair complexes to the tail of phosphorylated Ser-139 (H2AX139ph).
The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.
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 numerous proteins required for DNA damage signaling and repair when phosphorylated on Ser-139 (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. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation (By similarity).
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.
Belongs to the uracil-DNA glycosylase (UDG) superfamily. SMUG1 family.
May regulate membrane morphogenesis in the endoplasmic reticulum (ER) by promoting ER sheet formation at the expense of ER tubules.
Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development. May act via an interaction with SRF, leading to modulate the expression of SRF-dependent cardiac-specific genes and cardiac development (PubMed:12297045). May act as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and assist in chaperone-mediated protein refolding (By similarity).
Expressed in the margin of the pregastrula embryo destined to be the future mesoderm.
Expressed in the segmental plate and ventral mesoderm during early gastrulation and early somitogenesis (PubMed:25371059). Expressed in the marginal region and in a broad domain in the ventral region after 75% epiboly (PubMed:11703928). Expressed in the tailbud during the bud stage (PubMed:11703928).
Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Required for mesoderm and neural ectoderm patterning during gastrulation (PubMed:11703928). Involved in axis formation during embryonic development, via activation of canonical Wnt/CTNNB1 signaling (PubMed:11703928, PubMed:25371059). May be involved in the specification of the spatial patterns of expression of Gsc and other regulatory genes leading to the establishment of the embryonic axis (PubMed:7600994).
Palmitoleoylation is required for efficient binding to frizzled receptors (By similarity). Depalmitoleoylation leads to Wnt signaling pathway inhibition (By similarity).
Proteolytic processing by tiki1 and tiki2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of wnt8.
Belongs to the glycosyl hydrolase 56 family.
Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly (By similarity).
Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. Promotes the nucleation of microtubules from the spindle through recruitment of NEDD1 and gamma-tubulin (By similarity).
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
Monomer (By similarity). Homodimer (By similarity).
Morpholino knockdown of the protein causes a dramatic loss of cilia in Kupffer's vesicle.
Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration (By similarity). Required for Kupffer's vesicle ciliogenesis (PubMed:19164561).
Expressed very early in development. Expression levels drop until shield stage and increase again during gastrulation and later development. Expressed abundantly in the developing brain, and at lower levels throughout the embryo.
Required for neuronal survival during early development.
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. 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 (PubMed:7945937). 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).
Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death.
Belongs to the 5'-3' exonuclease family. XRN2/RAT1 subfamily.
Possesses 5'->3' exoribonuclease activity. May promote termination of transcription by RNA polymerase II.
Belongs to the ATP-dependent DNA ligase 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.
Belongs to the ubiquitin family. SUMO subfamily.
Cleavage of precursor form by a sentrin-specific protease is necessary for function.
Interacts with sae2, ube2i, ranbp2, pias1 and pias2 (By similarity). Covalently attached to a number of proteins (By similarity).
Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex sae1-sae2 and linkage to the E2 enzyme ube2i. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric sumo1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins.
Interacts with PPIF; the interaction is impaired by CsA.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.
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.
Ankrd45 mutants are viable and show no apparent defects. However mutant larvae developed enlarged livers when induced with liver specific expression of Kras G12V, one of the common mutations of KRAS that leads to cancer in humans.
Weakly detected in the dorsal forerunner cells at 80% epiboly to bud stages. At the 10-somite stage, strong expression is detected in the otic placodes, Kupffer's vesicles, and floor plate. Later, at 24 h post-fertilization, is mainly expressed in organs rich in motile cilia, including otic vesicles, pronephric ducts, and floor plates. At later stages, displays a ubiquitous expression pattern.
Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.
Morpholino knockdown of the protein causes no gross defects in embryos, with the exception of hypochromic blood due to decreased hemoglobin levels.
NAD(H)-dependent dehydrogenase/reductase with a preference for cyclic substrates (By similarity). Catalyzes stereoselective conversion of 4-oxo-L-proline to cis-4-hydroxy-L-proline, likely a detoxification mechanism for ketoprolines (By similarity). Mediates the formation of 2,5-dihydroxybenzoate (2,5-DHBA), a siderophore that chelates free cytoplasmic iron, thereby regulating iron transport and homeostasis while protecting cells against free radical-induced oxidative stress. The iron-siderophore complex is imported into mitochondria, providing an iron source for mitochondrial metabolic processes in particular heme synthesis (By similarity). May act as a 3-hydroxybutyrate dehydrogenase (By similarity).
Belongs to the alpha-ketoglutarate dehydrogenase family.
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.
Involved in stabilization of microtubules. May play a role in the regulation of lipogenesis (By similarity).
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.
Acts as an electroneutral and low-affinity sodium (Na(+))-dependent sodium-coupled solute transporter. Catalyzes the transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, nicotinate, propionate, butyrate and beta-D-hydroxybutyrate.
Expressed in brain and eye 24, 72 and 120 hours post-fertilization (hpf). At 72 hpf expressed in swim bladder and in pronephric tube. At 120 hpf expressed in brain, trabecular bar, eyes, otic capsule, stomach, gall bladder, gut and pancreas.
Belongs to the complex I NDUFS5 subunit family.
Mammalian complex I is composed of 45 different subunits. This is a component of the iron-sulfur (IP) fragment of the enzyme.
Belongs to the glycoprotein hormones subunit alpha family.
Heterodimer of an alpha and a beta chain.
Belongs to the selenophosphate synthase 1 family. Class II subfamily.
Synthesizes selenophosphate from selenide and ATP.
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.
A Gly-cisPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of L-amino acids.
D-aminoacyl-tRNA deacylase, with no observable activity on tRNAs charged with their cognate L-amino acid (By similarity). Hydrolyzes correctly charged, achiral, glycyl-tRNA(Gly) (PubMed:27224426). Deacylates mischarged D.melanogaster and E.coli glycyl-tRNA(Ala), protecting cells against glycine mischarging by AlaRS (PubMed:28362257). Acts via tRNA-based rather than protein-based catalysis; rejects L-amino acids rather than detecting D-amino acids in the active site (By similarity). By recycling D-aminoacyl-tRNA to D-amino acids and free tRNA molecules, this enzyme counteracts the toxicity associated with the formation of D-aminoacyl-tRNA entities in vivo and helps enforce protein L-homochirality (By similarity).
Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB. Together with ddx1, acts by facilitating the guanylylation of RTCB, a key intermediate step in tRNA ligation (By similarity).
Component of the tRNA-splicing ligase complex.
Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, but with relatively low efficiency.
Homodimer. Heterodimer with SPOP. Component of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL (By similarity).
Preferentially expressed in striated muscle.
Fish are viable during embryogenesis and early larval stages, but exhibit curvature of the body axis and hydrocephalus, and curled cilia in distal kidney tubules.
Interacts with cdk20, which promotes cdk20 stability and function.
Required for high-level Shh responses in the developing neural tube. Together with cdk20, controls the structure of the primary cilium by coordinating assembly of the ciliary membrane and axoneme, allowing gli2 to be properly activated in response to SHH signaling.
The Rab-GAP TBC domain appears to be inactive, probably due to a lack of the essential Arg and Gln in the catalytic finger motifs.
Required for proper progression of late cytokinetic stages.
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.
Belongs to the RNA 3'-terminal cyclase family. Type 2 subfamily.
Does not have cyclase activity. Plays a role in 40S-ribosomal-subunit biogenesis in the early pre-rRNA processing steps at sites A0, A1 and A2 that are required for proper maturation of the 18S RNA.
May contribute to the regulation of cell proliferation.
Belongs to the methyltransferase superfamily. RRP8 family.
Probable methyltransferase required to silence rDNA.
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.
Belongs to the SOS response-associated peptidase family.
Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites. Acts as an enzyme that recognizes and binds abasic sites in ssDNA at replication forks and chemically modifies the lesion by forming a covalent cross-link with DNA: forms a stable thiazolidine linkage between a ring-opened abasic site and the alpha-amino and sulfhydryl substituents of its N-terminal catalytic cysteine residue. The HMCES DNA-protein cross-link is then degraded by the proteasome. Promotes error-free repair of abasic sites by acting as a 'suicide' enzyme that is degraded, thereby protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks. Has preference for ssDNA, but can also accommodate double-stranded DNA with 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction.
Belongs to the major facilitator superfamily. MFSD6 family.
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 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.
Required for 60S pre-ribosomal subunits export to the cytoplasm.
Component of the transition zone in primary cilia. Required for ciliogenesis.
Fishes lacking both tmem237a and tmem237b display defects in midsomitic embryos, including shortening of the anterior-posterior axis and small anterior structures, kinking of the notochord, and broadening and thinning of the somite.
Belongs to the bZIP family. PAR subfamily.
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 sulfatase-modifying factor family.
Key transcription factor required for motile ciliogenesis. Activates genes essential for motile cilia formation and function.
Strongly expressed in the shield, the floor plate in early somitogenesis, the posterior neural plate, the otic vesicles and later in the otoliths, the pronephric ducts, diencephalon, olfactory pits, briefly in the trigeminal ganglion, and in an anterior brain region that overlaps the pineal gland and later corresponds to the anterior tectal ventricle.
Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways.
(Microbial infection) Glycosylated at Tyr-34 by Yersinia ruckeri toxin Afp18. Mono-O-GlcNAcylation by Afp18 inhibits RhoA activation by guanine nucleotide exchange factors and blocks RhoA signaling.
Belongs to the small GTPase superfamily. Rho family.
Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers.
Expressed specifically in the inner segments of cone photoreceptor cells of the retina (at protein level).
Morpholino knockdown of the protein display decreased eye size and formation of smaller mitochondria in cone ellipsoid photoreceptor cells.
Plays a role in promoting mitochondrial enlargement in cone photoreceptor cells in a fusion-independent and ATP-dependent manner.
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 eukaryotic ribosomal protein eL27 family.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.
Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:19423848). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:19423848). In the nucleus, binds to the vegfa core promoter and prevents myc binding and transcriptional activation by myc (PubMed:24940000). Thereby inhibits the production of vegfa and sprouting angiogenesis mediated by vegfa (PubMed:19423848, PubMed:19423847, PubMed:22353712, PubMed:24940000).
Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.
Morpholino knockdown causes aberrant angiogenesis with excessive intersegmental vessel branching, due to excessive expression of vegfa.
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.
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 (By similarity). Binding is pH dependent, and is optimal at pH 5-5.4 (By similarity).
Belongs to the protoporphyrinogen/coproporphyrinogen oxidase family. Protoporphyrinogen oxidase subfamily.
Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.
Involved in osteoblast cell differentiation. May play a role in inducing the cell cycle arrest (By similarity).
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).
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.
Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (By similarity). Protein transport. Probably involved in vesicular traffic (By similarity).
Belongs to the proteasome subunit S5B/HSM3 family.
Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. May be required for proliferation of neuronal precursors and neuronal migration.
Belongs to the major facilitator superfamily. Vesicular transporter family.
Involved in acetylcholine transport into synaptic vesicles.
Key regulator of mitochondrial quality that mediates the repairing or degradation of unhealthy mitochondria in response to mitochondrial damage. Mediator of mitochondrial protein catabolic process (also named MALM) by mediating the degradation of damaged proteins inside mitochondria by promoting the accumulation in the mitochondrial matrix of hydrolases that are characteristic of the lysosomal lumen. Also involved in mitochondrion degradation of damaged mitochondria by promoting the formation of vacuole-like structures (named MIV), which engulf and degrade unhealthy mitochondria by accumulating lysosomes (By similarity).
E3 ubiquitin-protein ligase that plays a role in the control of mitochondrial morphology. Promotes mitochondrial fragmentation and influences mitochondrial localization. Inhibits cell growth. 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.
The zinc finger domain is required for E3 ligase activity.
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).
Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX.
Binds DNA as a homodimer. Can form a heterodimer with ER-beta (By similarity).
Binds DNA as a homodimer. Can form a heterodimer with ER-beta.
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 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 requirement for H(+) efficiently prevents non-vesicular efflux across the plasma membrane. The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration.
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 a 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 therefore affects the proton electrochemical gradient and promotes synaptic vesicles acidification. Moreover, functions as a vesicular K(+)/H(+) antiport allowing to maintain the electrical gradient and to decrease chemical gradient and therefore sustain vesicular L-glutamate uptake. The vesicular H(+)/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). Also involved in the regulation of retinal hyaloid vessel regression during postnatal development (By similarity). May also play a role in the endocrine L-glutamatergic system of other tissues such as pineal gland and pancreas (By similarity).
Plays a role in skin pigmentation by antagonizing the action of melanotropin alpha. Induces melanin concentration within the melanophores. May participate in the control of the hypothalamo-pituitary adrenal gland axis by inhibiting the release of ACTH.
Beta-1,3-N-acetylglucosaminyltransferase that plays a key role in the synthesis of lacto- or neolacto-series carbohydrate chains on glycolipids.
Expressed in 2 distinct phases during the embryogenesis. The early phase extends from late blastulation to the completion of epiboly, during which the expression occurs in the superficial layer of the embryos. The second phase of expression starts during mid-segmentation and persists until day 3, during which the expression occurs prominently in the developing lens.
Hedgehog signaling is required for expression in embryonic lens.
Component of the ribosomal small subunit (SSU) processome.
Involved in nucleolar processing of pre-18S ribosomal RNA.
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 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 (By similarity).
Component of the nuclear pore complex (NPC).
Belongs to the iron/manganese superoxide dismutase family.
Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
Belongs to the universal ribosomal protein uL14 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 TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family.
May be involved in the ribosome maturation process.
Belongs to the phenylalanyl-tRNA synthetase beta subunit family. Type 2 subfamily.
Catalyzes the synthesis of lactosylceramide (LacCer) via the transfer of galactose from UDP-galactose to glucosylceramide (GlcCer) (By similarity). Required for proper patterning of the dorsoventral axis during embryogenesis through the regulation of BMP signaling (PubMed:16672343). Plays a role in proteoglycan glycosylation that is required for BMP-dependent specification of the dorsoventral axis (PubMed:16672343).
Expressed by the early epiboly stage and reaches a steady state level of expression by mid-somitogenesis (PubMed:16672343). Shows widespread expression throughout the embryo during the first 24 hours of development, with enhanced expression within several structures at the 20-somite stage (PubMed:16672343).
Morpholino knockdown results in dorsalized embryos which have ventrally expanded chordin expression and reduced activation of the Bmp-dependent transcription factors smad1/5/8 (PubMed:16672343). Proteoglycans exhibits defective glycosylation and a greatly reduced affinity for bmp2 (PubMed:16672343).
Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality.
Interacts with EF1A1, facilitates EF1A1 distribution to the membrane periphery and ruffles upon growth factor stimulation and suppresses cell migration.
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:15621520, PubMed:16917825). Preferentially oxidizes serotonin and tyramine (PubMed:15621520, PubMed:16917825). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity).
Inhibited by both clorgyline (selective MAOA inhibitor) and deprenyl (selective MAOB inhibitor).
Monomer, homo- or heterodimer (containing two subunits of similar size). Each subunit contains a covalently bound flavin. Enzymatically active as monomer (By similarity).
Strongest expression in brain and intestine, followed by liver, heart and gill. Little expression in spleen, eye or muscle. In brain, highest activity in noradrenergic and serotonergic cell groups and those of the habenulointerpeduncular pathway; moderate levels in dopaminergic cell clusters.
There appears to be only one form of this enzyme in zebrafish, whereas in mammals two forms (MAOA and MAOB) exist.
Oxidized purine nucleoside triphosphate hydrolase which is a prominent sanitizer of the oxidized nucleotide pool (PubMed:26862114, PubMed:30304478). Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-dATP) into 2-oxo-dAMP (PubMed:26862114). Has also a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP (PubMed:26862114, PubMed:30304478). Through the hydrolysis of oxidized purine nucleoside triphosphates, prevents their incorporation into DNA and the subsequent transversions A:T to C:G and G:C to T:A (PubMed:26862114, PubMed:30304478). Also catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA (PubMed:32144205, PubMed:30304478). Through this antimutagenic activity protects cells from oxidative stress (PubMed:32144205, PubMed:26862114, PubMed:30304478).
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.
Forms a tight complex with scap, the SCAP-SREBP complex, in the endoplasmic reticulum membrane.
Homodimer; efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein.
Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis. Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3'). Regulates transcription of genes related to cholesterol synthesis pathway (By similarity). Activated by mediated cholesterol efflux, transactivates NOTCH and promotes hematopoietic stem and progenitor cell emergence (PubMed:30705153).
Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane. Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis.
Processed in the Golgi apparatus, releasing the protein from the membrane (PubMed:30705153). At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum (By similarity). In the Golgi, complex SREBPs are cleaved sequentially by site-1 (mbtps1, S1P) and site-2 (mbtps2, S2P) protease. The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain, releasing the transcription factor from the Golgi membrane (By similarity).
Belongs to the casein kinase 2 subunit beta family.
Casein kinase II/CK2 is a tetramer composed of two alpha subunits and two beta subunits. The beta subunit dimerization is mediated by zinc ions.
Regulatory subunit of casein kinase II/CK2. As part of the kinase complex regulates the basal catalytic activity of the alpha subunit a constitutively active serine/threonine-protein kinase that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (By similarity). Participates in Wnt signaling (By similarity).
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.
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.
pH-dependent, voltage-insensitive, background potassium channel protein.
Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the actin family. ARP8 subfamily.
Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the DBINO domain of INO80. Exists as monomers and dimers, but the dimer is most probably the biologically relevant form required for stable interactions with histones that exploits the twofold symmetry of the nucleosome core (By similarity).
Plays an important role in the functional organization of mitotic chromosomes. Exhibits low basal ATPase activity, and unable to polymerize (By similarity).
Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Required for the recruitment of INO80 (and probably the INO80 complex) to sites of DNA damage Strongly prefer nucleosomes and H3-H4 tetramers over H2A-H2B dimers, suggesting it may act as a nucleosome recognition module within the complex (By similarity).
Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.
Involved in mitochondrial tRNA methylation (By similarity). Specifically methylates the N1 position of guanosine-37 in various 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.
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.
Component of the signal peptidase complex.
May be involved in modulating alternative pre-mRNA splicing.
Ensures normal bone formation, through the negative regulation of bone morphogenetic protein (BMP) signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of phosphorylated SMAD proteins.
Belongs to the Cu-Zn superoxide dismutase family.
Involved in the maintenance of the Golgi structure.
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.
Urotensin is found in the teleost caudal neurosecretory system. It has a suggested role in osmoregulation and as a corticotropin-releasing factor (By similarity).
Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1. 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 HMG-CoA reductase family.
Belongs to the Mediator complex subunit 25 family.
Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen.
Belongs to the bacterial ribosomal protein bL32 family.
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP/ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP/ATP hydrolysis.
Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor, but phosphorylates only AMP when using GTP as phosphate donor. Also displays broad nucleoside diphosphate kinase activity.
Belongs to the proteasome subunit S14 family.
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
The active site is a redox-active disulfide bond.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
Belongs to the AB hydrolase superfamily. ABHD16 family.
Could be involved in the unfolded protein response (UPR) pathway.
The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.
The N-terminal C2 domain associates with lipid membranes upon calcium binding.
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.
Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.
Belongs to the PI3/PI4-kinase family. ATM subfamily.
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.
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.
Belongs to the CMP-NeuNAc synthase family.
Catalyzes the activation of 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) to cytidine 5'-monophosphate 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (CMP-KDN), a substrate required for the addition of sialic acid. Also has weak activity towards N-acetylneuraminic acid (NeuNAc) and N-glycolylneuraminic acid (Neu5Gc).
During early stages of development (9-18 hours post fertilization, hpf) has weak and ubiquitous expression. Expression is restricted to brain at 24 hpf. At the hatching stage (48 hpf), detected in heart but not in brain.
N-alpha-acetyltransferase that acetylates the N-terminus of proteins that retain their initiating methionine (By similarity). Has a broad substrate specificity: able to acetylate the initiator methionine of most peptides, except for those with a proline in second position (By similarity). Also displays N-epsilon-acetyltransferase activity by mediating acetylation of the side chain of specific lysines on proteins (By similarity). The relevance of N-epsilon-acetyltransferase activity is however unclear (By similarity). Required for sister chromatid cohesion during mitosis by promoting binding of CDCA5/sororin to cohesin (By similarity). Essential in embryonic cell proliferation and survival (PubMed:16484612).
Until 48 hpf, highly expressed in developing vascular structures and epidermis. By 48 hpf, becomes restricted to the developing head. By 5 dpf, observed only in the epidermis.
Expressed in developing germ cells of both testis and ovary.
Transcription factor that plays a key role in sex determination and differentiation by controlling gonad development and germ cell proliferation. Acts both as a transcription repressor and activator (By similarity).
May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier.
Belongs to the pterin-4-alpha-carbinolamine dehydratase family.
Has deubiquitinating activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.
Caudal forebrain and neural keel, the floor plate, the gill slit and the developing pronephros.
First detected at the end of gastrulation in the anterior neuroectoderm. Expression increases in the developing brain during somitogenesis but has gone by 36 hours. Expression in the floor plate begins at the 10 somite stage and persists at 72 hours.
Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Plays an important role in embryonic development (PubMed:8541205).
Belongs to the protein-tyrosine phosphatase family. Non-receptor class CDC14 subfamily.
Belongs to the universal ribosomal protein uS7 family.
Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.
It is uncertain whether Met-1 or Met-3 is the initiator.
Plays a role in the regulation of retinal ganglion cell (RGC) maturation, neurite outgrowth, and hence in the development of the inner retina and optic nerve (PubMed:26593267). Appears to be a potent inhibitor of regeneration following spinal cord injury (By similarity).
Belongs to the class IV-like SAM-binding methyltransferase superfamily.
Belongs to the class I-like SAM-binding methyltransferase superfamily. EEF2KMT 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 90 and 114.
Involved in pre-mRNA splicing as a component of the spliceosome.
Regulator of histone methyltransferase complexes that plays an essential role in embryonic development. Acts by modulating histone methyltransferase activity and promoting the recruitment of histone methyltransferase complexes to their target genes. Binds DNA and mediates the recruitment of the PRC2 complex to target genes in embryonic stem cells. Does not have histone demethylase activity but regulates activity of various histone methyltransferase complexes. In embryonic stem cells, it associates with the PRC2 complex and inhibits trimethylation of 'Lys-27' of histone H3 (H3K27me3) by the PRC2 complex, thereby playing a key role in differentiation of embryonic stem cells and normal development (By similarity).
The ARID domain is required to target the PRC2 complex to its target genes.
Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3'-OH terminal group and enhances mRNA stability and gene expression.
The C-terminal part of the hedgehog protein precursor displays an autoproteolysis activity that results in the cleavage of the full-length protein into two parts (N-product and C-product). In addition, the C-terminal part displays a cholesterol transferase activity that results by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product.
The dually lipidated hedgehog protein N-product is a morphogen which is essential for a variety of patterning events during development.
Belongs to the VPS10-related sortilin family. SORCS subfamily.
Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by forming a channel that allows the retrotranslocation of misfolded proteins into the cytosol where they are ubiquitinated and degraded by the proteasome.
Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.
Component of the MMS22L-TONSL complex, a complex that promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication. It mediates the assembly of RAD51 filaments on single-stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs following histone replacement by histone chaperones and eviction of the replication protein A complex (RPA/RP-A) from DSBs. Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination. Within the complex, TONSL acts as histone reader, which recognizes and binds newly synthesized histones following their replacement by histone chaperones.
Component of the MMS22L-TONSL complex. Binds histones, with a strong preference for histone H3.1 (histones H3.1 and H3-4/H3.1t).
Tonsl deficiency causes growth deficits, vertebral abnormalities, reduced neutrophil numbers, and death at early stages of larvae development.
Belongs to the AB hydrolase superfamily. ABHD14 family.
Possible role in granule neuron development.
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. Homodimer; disulfide-linked. Occurs in both reduced and oxidized monomeric form. Oxidative conditions increase homodimerization.
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.
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.
May act as an adapter that regulates LRP2 function.
Glu-37 is present instead of the conserved Lys which is expected to be an active site residue. Lys-38 may fulfill that role.
DNA-binding protein which may repress cyclin D1 transcription by recruiting HDAC1 to its promoter, thereby diminishing H3K9ac, H3S10ph and H4K8ac levels. Promotes TP53 activation, which causes cell cycle arrest (By similarity).
Belongs to the DNA/RNA non-specific endonuclease family.
Has no ubiquitin ligase activity on its own. The ube2v2/ube2n heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage (By similarity).
Belongs to the UbiA prenyltransferase family.
Converts protoheme IX and farnesyl diphosphate to heme O.
General regulator of phagocytosis. Required to uptake Gram negative bacterium by macrophages.
Belongs to the ribonucleoside diphosphate reductase large chain family.
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Belongs to the 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.
Retinol dehydrogenase with a clear preference for NADP. Converts all-trans-retinal to all-trans-retinol. May play a role in the regeneration of visual pigment at high light intensity.
Homodimerization via the leucine zipper domains is required for autophosphorylation.
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).
ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. Seems to contact the pointed end of the daughter actin filament.
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.
Homodimer or heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked.
Has apparently no steroid dehydrogenase activity.
Belongs to the AB hydrolase superfamily. AB hydrolase 2 family.
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 complex I 75 kDa subunit family.
Required for nuclear and mitochondrial iron-sulfur protein biosynthesis.
Probably involved in transcriptional regulation.
Belongs to the liprin family. Liprin-beta subfamily.
Belongs to the nuclear hormone receptor family. NR2 subfamily.
Putative receptor that is required in photoreceptor cells precursors during eye development.
Belongs to the MsrB Met sulfoxide reductase family.
Methionine-sulfoxide reductase that specifically reduces methionine (R)-sulfoxide back to methionine. While in many cases methionine oxidation is the result of random oxidation following oxidative stress, methionine oxidation is also a post-translational modification that takes place on specific residues.
Belongs to the Mediator complex subunit 14 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.
Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis.
Heme 1 (or BL or b562) is low-potential and absorbs at about 562 nm, and heme 2 (or BH or b566) is high-potential and absorbs at about 566 nm.
The cytochrome bc1 complex contains 3 respiratory subunits (MT-CYB, CYC1 and UQCRFS1), 2 core proteins (UQCRC1 and UQCRC2) and probably 6 low-molecular weight proteins.
The full-length protein contains only eight transmembrane helices, not nine as predicted by bioinformatics tools.
A complete loss of mitochondrial respiratory chain complex III resulting in severe growth retardation, lactic acidosis and early death.
Essential for mitochondrial respiratory chain complex III (CIII) assembly and stability (PubMed:32161263). Also required for cytochrome c oxidase complex (complex IV) assembly (By similarity).
Highly expressed in skeletal and cardiac muscle (at protein level).
Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10521267). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins (By similarity).
Expressed both maternally and zygotically. Ubiquitously expressed during embryogenesis.
Heterogeneous proteolytic processing generates N-terminal (NTF) and C-terminal (CTF) fragments of approximately 35 and 20 kDa, respectively. During apoptosis, the C-terminal fragment (CTF) is further cleaved by a caspase.
Homodimer. The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity.
Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors.
Substrates, such as NOTCH1 and APP peptides, are bound between PSEN1 transmembrane domains and via the first lumenal loop and the cytoplasmic loop between the sixth and seventh transmembrane domains. Substrate binding causes a conformation change and formation of an intermolecular antiparallel beta-sheet between PSEN1 and its substrates.
The PAL motif is required for normal active site conformation.
Enhances Ca(2+)-mediated inhibition of inositol 1,4,5-triphosphate receptor (ITPR) Ca(2+) release.
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 bile acid:sodium symporter (BASS) (TC 2.A.28) family.
Belongs to the clathrin heavy chain family.
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).
Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity. Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure initiated by B4GAT1 by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide. Requires the phosphorylation of core M3 (O-mannosyl trisaccharide) by POMK to elongate the glucuronyl-beta-1,4-xylose-beta disaccharide primer (By similarity). Plays a key role in skeletal muscle function and regeneration (By similarity).
Can act both with Mn(2+) and Mg(2+) as cofactor in vitro, but Mn(2+) is the preferred cofactor in vivo.
DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them. Required to facilitate mitochondrial and nuclear replication fork progression by initiating de novo DNA synthesis using dNTPs and acting as an error-prone DNA polymerase able to bypass certain DNA lesions (By similarity). Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (By similarity). Provides different translesion synthesis alternatives when DNA replication is stalled: able to synthesize DNA primers downstream of lesions, such as UV lesions, R-loops and G-quadruplexes, to allow DNA replication to continue (By similarity). Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion. Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase. Also required for reinitiating stalled forks after ultraviolet (UV) damage during nuclear DNA replication. Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides. In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells (By similarity).
The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn(2+) ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis. Glu-119 is required to stabilize the incoming nucleotide at the 3'-site.
The zinc knuckle motif binds zinc and is required for the DNA primase activity. It facilitates the binding and selection of the 5'-nucleotide of the newly synthesized primer and the recognition of preferred initiation sites.
Plays an important role in the degradation of dermatan and keratan sulfates.
Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
Belongs to the Nudix hydrolase family. DCP2 subfamily.
May regulate a number of protein-protein interactions by competing for PDZ domain binding sites.
May play a role in keratin cytoskeleton disassembly.
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.
Branchiomotor neurons exhibit reduced axonal outgrowth and aberrant positioning of neuronal cell bodies. Outgrowth of motor axons from the spinal cord is impaired, the number and length of spinal motor neurons is reduced, and elevated levels of apoptosis are observed in the CNS. Thickened bundles of axonal microtubules are observed in the spinal cord. Longitudinal fascicles in the hindbrain are disordered. Most embryos are immotile and fail to hatch, while those that do exhibit reduced motility and swimming defects. Morpholino knockdown results in abnormal morphological features, including hydrocephalia, perturbed yolk sac extension and an arched-back phenotype, disorganized microtubule networks in the spinal cord and thinner microtubules in the spinal motor neuron axons, and in increased oxidative stress (PubMed:26744324). These phenotypes are rescued following exposure to the drugs methylene blue, guanabenz, salubrinal or phenazine (PubMed:26744324).
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.
Maternally expressed. Expressed at low levels throughout the embryo up to 24 hours post-fertilization (hpf).
As a component of the AMPAR complex, modifies AMPA receptor (AMPAR) gating.
Component of the putative class C core vacuole/endosome tethering (CORVET) complex (By similarity).
Plays a role in the TGF-beta signaling pathway.
Plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway. Believed to act as a component of the putative CORVET endosomal tethering complexes which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (By similarity).
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.
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). Required for the maturation of motor neuron axonal branches and dendrites (PubMed:29061699).
Reduced overall movement, decreased initiation of swim and turn movements and decreased mean body curvature change per swim half-cycle and mean number of swim half-cycles per swim (PubMed:29061699). At 2 and 4 dpf, decreased axonal branches and at 4 dpf, decreased dendrites in motor neurons (PubMed:29061699). Defects on motor neuron extensions persist at 26 dph (PubMed:29061699). Decreased GAP43 mRNA levels (PubMed:29061699).
May be involved in Golgi maintenance and protein secretion.
Belongs to the acetyltransferase family. MAK3 subfamily.
Belongs to the acetyltransferase family. ARD1 subfamily.
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.
Belongs to the actin family. ARP6 subfamily.
Belongs to the JARID1 histone demethylase family.
Activated by multiple phosphorylations on threonine and serine residues.
Forms a complex with either ERK1 or ERK2 in quiescent cells. Transiently dissociates following mitogenic stimulation (By similarity).
Serine/threonine kinase that may play a role in mediating the growth-factor and stress induced activation of the transcription factor CREB.
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).
Belongs to the cyclin family. Cyclin C subfamily.
Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Binds to and activates cyclin-dependent kinase CDK8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex.
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 (By similarity). Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine (By similarity).
Might carry two S-adenosyl-L-methionine binding sites with only one binding to the iron-sulfur cluster.
Interacts with the cohesin complex. Binds chromatin in a cohesin-dependent manner (By similarity).
May regulate sister chromatid cohesion during mitosis and couple it to DNA replication.
Functions as a redox-dependent negative regulator of the Wnt signaling pathway.
Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily.
Expressed specifically in the rostral-most somites at 24 hpf. At 48 hpf, expression continues in the rostral-most somites and also in the notochord. Somite expression was restricted to the vicinity of the horizontal myoseptum. In adults, expressed in the heart.
Mitochondrial solute carriers shuttle metabolites, nucleotides, and cofactors through the mitochondrial inner membrane. Specifically mediates the transport of S-adenosylmethionine (SAM) into the mitochondria (By similarity).
Belongs to the mitochondrion-specific ribosomal protein mL42 family.
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.
RNA-binding protein that may be involved in the regulation of pre-mRNA alternative splicing.
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.
Part of the tectonic-like complex (also named B9 complex).
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 biopterin-dependent aromatic amino acid hydroxylase family.
Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. Also acts as an inositol polyphosphate phosphatase that dephosphorylates Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain. Plays an important role in MLKL-mediated necroptosis. Produces highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL mediating the release of an N-terminal auto-inhibitory region leading to its activation. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis.
Autophosphorylated in response to CSF1 binding. autophosphorylation, leading to its degradation.
Monomer. Homodimer. Interacts with CSF1 (By similarity).
Present in an inactive conformation in the absence of bound ligand. CSF1 binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity).
The activation loop plays an important role in the regulation of kinase activity. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase (By similarity).
The juxtamembrane domain functions as autoinhibitory region. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase (By similarity).
Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Activates several signaling pathways in response to ligand binding (By similarity).
Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation (By similarity).
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.
O-glycosylated with heparan sulfate side chains.
Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-984 on the kinase activation loop.
Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner, where Tyr-984 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at additional tyrosine residues. Phosphorylation is important for interaction with scaffold proteins and effectors.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily.
Expressed in most populations of endothelial cells in 24 hours embryos. Not present in intersegmental vessels.
Tyrosine-protein kinase that acts as cell-surface receptor for angiopoietins and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Can activate or inhibit angiogenesis, depending on the context. Angiopoietin signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors (By similarity).
Guanine nucleotide exchange factor (GEF) which may be involved in the regulation of late endocytic pathway homeostasis, including endosomal positioning, maturation and secretion.
May be involved in proliferation and apoptosis in myeloid precursor cells.
Homodimer and heterodimer; heterodimerizes with keap1a (PubMed:18057000). Component of the BCR(KEAP1) E3 ubiquitin ligase complex, at least composed of 2 molecules of cul3, 2 molecules of keap1 (keap1a and/or keap1b), and rbx1 (By similarity). Interacts with nfe2l2/nrf2; the interaction is direct (By similarity).
Keap1 contains reactive cysteine residues that act as sensors for endogenously produced and exogenously encountered small molecules, which react with sulfhydryl groups and modify the cysteine sensors, leading to impair ability of the BCR(KEAP1) complex to ubiquitinate target proteins.
Non-enzymatic covalent modifications of reactive cysteines by electrophile metabolites inactivate the BCR(KEAP1) complex.
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting nfe2l2/nrf2 for ubiquitination (PubMed:18057000). Keap1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of nfe2l2/nrf2, a transcription factor regulating expression of many cytoprotective genes (PubMed:18057000). In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting nfe2l2/nrf2 nuclear accumulation and expression of phase II detoxifying enzymes (By similarity).
Ubiquitin ligase activity of the BCR(KEAP1) complex is inhibited by oxidative stress and electrophile metabolites such as sulforaphane. Electrophile metabolites react with reactive cysteine residues in keap1 and trigger non-enzymatic covalent modifications of these cysteine residues, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex.
Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity).
Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis.
Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization. May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity.
Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine with high efficiency (in vitro). Can catalyze the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction, but with low efficiency.
Probable acetyltransferase, which acetylates the inositol ring of phosphatidylinositol during biosynthesis of GPI-anchor.
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.
Protein glucosyltransferase that catalyzes the transfer of glucose from UDP-glucose to a serine residue within the consensus sequence peptide C-X-N-T-X-G-S-F-X-C. Can also catalyze the transfer of xylose from UDP-xylose but less efficiently.
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 dynactin 150 kDa subunit family.
May be signaling molecules that resemble neuropeptides.
In the C-terminal section; belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
Belongs to the adenylosuccinate synthetase family.
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 of purine nucleotide biosynthesis.
Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with psmg1.
Degraded by the proteasome upon completion of 20S proteasome maturation.
Defects in left-right asymmetry during embryogenesis, due to defects in ciliogenesis.
Required for ciliogenesis (PubMed:26389662). Acts as a tethering factor that facilitates recruitment of vcp/p97 to the intraflagellar transport complex B (IFT-B) in cilia (By similarity).
Golgi-localized palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and therefore functions in several unrelated biological processes (Probable). Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (Probable).
Probably maternally supplied. No zygotic expression is detected before 7.5 hpf.
As a component of the GATOR complex may function in the amino acid-sensing branch of the TORC1 signaling pathway.
Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). Probably part of the GATOR complex.
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.
Belongs to the universal ribosomal protein uL18 family.
Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA.
In the C-terminal section; belongs to the aldehyde dehydrogenase family. ALDH1L subfamily.
In the N-terminal section; belongs to the GART family.
Induces bone resorption, acting probably through a signaling cascade which results in the secretion of factor(s) enhancing osteoclast formation and activity.
Binds free fatty acids and their coenzyme A derivatives, bilirubin, and some other small molecules in the cytoplasm. May be involved in intracellular lipid transport.
Belongs to the complex I LYR family. LYRM9 subfamily.
At 4 days-post-fertilization (dpf), expressed strongly in the inner and outer plexiform layers and ganglion cell layer of the retina, in the tegmentum and in the hindbrain. Also expressed diffusely in the diencephalon.
May play a role in synapse assembly and function.
Belongs to the phosphoglycerate kinase family.
May play a role in early endosome fusion upstream of RAB5, hence regulating receptor trafficking and fluid-phase transport. Enhances cellular sensitivity to TNF-induced apoptosis.
The FYVE domain is important for binding to the endosomal membrane.
May be an activator of the JNK/SAPK pathway.
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA M5U methyltransferase family.
Mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine in tRNAs and 12S rRNA. Catalyzes the methylation of uridine at position 54 (m5U54) in all tRNAs. Specifically methylates the uridine in position 429 of 12S rRNA (m5U429). Does not affect RNA stability or mitochondrial translation.
May be involved in 20S pre-rRNA processing.
Catalyzes the hydrolysis of GTP bound to the 40S ribosomal initiation complex (40S.mRNA.Met-tRNA[F].eIF-2.GTP) with the subsequent joining of a 60S ribosomal subunit resulting in the release of eIF-2 and the guanine nucleotide. The subsequent joining of a 60S ribosomal subunit results in the formation of a functional 80S initiation complex (80S.mRNA.Met-tRNA[F]).
Belongs to the bZIP family. NFIL3 subfamily.
Regulates eif4e1a activity by preventing its assembly into the eIF4F complex.
Belongs to the glycosyl hydrolase 13 family. GlgB subfamily.
Prosaposin: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling.
Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.
Plays a role in vesicular protein sorting.
Homodimer and heterodimer: mainly forms homodimers and, to a lesser extent, heterodimers with e2f7.
Morpholino knockdown leads to both intermediate and severe phenotypes of abnormal embryonic development (PubMed:21227923, PubMed:19414594). Intermediate phenotypes show developmental delay, including aberrant formation of the head, tail, eye placodes and somites (PubMed:21227923, PubMed:19414594). Severe phenotypes show severe developmental arrest, including yolk extension defects, and lack of recognizable morphological development (PubMed:21227923, PubMed:19414594). High mortality rates of 80% to 85% at 5 days post-fertilization (PubMed:19414594). Increase in premature stop codon containing slc24a5 mRNA transcript levels in melanocytes (PubMed:21227923, PubMed:19414594).
RNA-dependent helicase and ATPase required for nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD. The formation of an upf1-upf2-upf3 surveillance complex is believed to activate NMD.
Endoribonuclease that cleaves single-stranded RNAs at 5' of uridylates and releases a product with a 2',3'-cyclic phosphate at the 3'-end. The UU and GU sites are more efficiently cleaved than CU and AU sites.
Conjugated to atg12 at Lys-246. 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.
By contrast to classical cadherins, homodimerization in trans is not mediated by cadherin EC1 domain strand-swapping, but instead through a homophilic adhesive interface which joins two elongated EC1-EC2 domains through a region near their Ca2+-binding sites to form a tetrahedral, X-like shape.
Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. May act as a negative regulator of neural cell growth.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily.
Belongs to the glycosyltransferase 16 (GT16) protein family.
Belongs to the glycosyltransferase 3 family.
Transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan.
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.
Catalyzes the hydrolysis of pseudosubstrates such as p-nitrocatechol sulfate and p-nitrophenyl sulfate (By similarity). Catalyzes the hydrolysis of the 2-sulfate groups of the 2-O-sulfo-D-glucuronate residues of chondroitin sulfate, heparin and heparitin sulfate (By similarity). Acts selectively on 2-sulfoglucuronate and lacks activity against 2-sulfoiduronate (By similarity).
Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily.
First detected at 14 hours post-fertilization (hpf) in the head and tail regions. Found mostly in the head region. Also detectable in the jaw of the embryo at 3 dpf.
Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Has activity toward H4K20Me1 only when nucleosome is used as a substrate and when not histone octamer is used as substrate (By similarity). Required for brain development, probably by regulating expression of neuron-specific genes.
Morpholino knockdown of the protein results in defects in brain and craniofacial development. Embryos show delays in brain development at 24 hpf and apoptosis in the developing brain and the neural tube at 30 hpf.
The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 promotes its access to H3K9me2 (By similarity).
The linker region is a critical determinant of demethylase specificity. It enables the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3 (By similarity).
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.
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.
Homophilic transmembrane adhesion molecule involved in various processes such as inflammation, cell death, axonal growth, cell chemotaxis and angiogenesis (By similarity). Promotes cell adhesion by mediating homophilic interactions via its extracellular N-terminal region (By similarity). Involved in the progression of the inflammatory stress by promoting cell-to-cell interactions between immune cells and endothelial cells (By similarity). Acts as a mediator of both programmed and necrotic cell death (By similarity). Plays a key role in the induction of plasma membrane rupture during programmed and necrotic cell death: oligomerizes in response to death stimuli to mediate plasma membrane rupture (cytolysis), leading to release intracellular molecules named damage-associated molecular patterns (DAMPs) that propagate the inflammatory response (By similarity). Acts as a regulator of angiogenesis (By similarity). Promotes the formation of new vessels by mediating the interaction between capillary pericyte cells and endothelial cells (By similarity). Also involved in striated muscle growth and differentiation (PubMed:31091274).
Morpholino knockdown of the protein results in impaired heart and skeletal muscle development.
May play a role in anchoring the cytoskeleton to the plasma membrane.
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.
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.
Functions as a calcium-regulated nucleotide exchange factor activating both Ras and rac1 through the exchange of bound GDP for GTP. May function in synaptic plasticity.
The DH (DBL-homology) domain is required for rac1 activation.
The IQ domain is dispensable for the Ras-GEF activity.
The Ras-GEF domain and the N-terminal Ras-GEF domain mediate Ras activation.
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 Cob(I)alamin adenosyltransferase family.
Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.
Component of the small nucleolar ribonucleoprotein particles containing H/ACA-type snoRNAs (H/ACA snoRNPs).
Required for ribosome biogenesis. Part of a complex which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Pseudouridine ("psi") residues may serve to stabilize the conformation of rRNAs.
Regulates the composition and fluidity of the plasma membrane (By similarity). Inhibits the incorporation of membrane-fluidizing phospholipids containing omega-3 long-chain polyunsaturated fatty acids (LCPUFA) and thereby promotes membrane rigidity (By similarity). Does not appear to have any effect on LCPUFA synthesis (By similarity).
Belongs to the grh/CP2 family. CP2 subfamily.
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This 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.
May act as a polo kinase kinase by mediating phosphorylation of plk1.
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).
May play a role in the regulation of neuronal activity.
First expressed at 14 hours post-fertilization (hpf) in the dorsal pre-somitic mesoderm and neural keel at posterior levels, extending into the ventral somitic mesoderm during budding. At 22-26 hpf, expression decreases in the lateral and ventral mesoderm, but is maintained in the neural rod. Expression decreases from posterior to anterior with an anterior expression limit at somite 17. Also expressed in the developing hindgut, except in the most distal portion. At 24-26 hpf, posterior expression begin to weaken and is undetectable by 40-56 hpf.
Belongs to the prenylcysteine oxidase family.
Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms.
Component of an ESCRT-I complex (endosomal sorting complex required for transport I).
Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs).
Impaired motor neuron outgrowth, leading to decreased mobility and shorter lifespan (PubMed:31203368). Axon lengths is significantly shorter in motor neurons (PubMed:30929741, PubMed:31203368).
The UMA domain mediates association with the ESCRT-I complex.
Although it belongs to the ADP-ribosylglycohydrolase family, lacks the metal-binding and substrate-binding residues, suggesting that it has no hydrolase activity.
Required for myofibril assembly and outgrowth of the cardiac chambers in the developing heart (By similarity). Appears to be catalytically inactive, showing no activity against O-acetyl-ADP-ribose (By similarity).
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 calcium channel alpha-1 subunit (TC 1.A.1.11) family. Two pore calcium channel subfamily.
Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position (By similarity).
Intracellular channel initially characterized as a non-selective Ca(2+)-permeable channel activated by NAADP (nicotinic acid adenine dinucleotide phosphate), it is also a highly-selective Na(+) channel activated directly by PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate). Localizes to the lysosomal and late endosome membranes where it regulates organellar membrane excitability, membrane trafficking, and pH homeostasis.
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.
Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate receptor. This signaling event requires the activity of the Fyn tyrosine kinase. Activates the epha3 receptor to regulate cell-cell adhesion and cytoskeletal organization. With the receptor epha2 may regulate lens fiber cells shape and interactions and be important for lens transparency maintenance. May function actively to stimulate axon fasciculation (By similarity). Controls axon growth and may be involved in the creation of the retino-tectal map.
Expressed in the presumptive midbrain of developing embryos from the six-somite stage. By 24 hours, strongly expressed in the midbrain caudal to the presumptive tectum. At later stages, maintained at the posterior margin of the tectum.
Belongs to the N-acylglucosamine 2-epimerase family.
Highly expressed in the yolk syncytial layer during embryonic (starting at the gastrula stage) and early larval development, an extraembryonic structure implicated in embryonic and larval nutrition.
Homodimer (By similarity). Interacts with NAXE and YJEFN3 (PubMed:23719382).
Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT).
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.
Translation initiation factor that is able to deliver tRNA to the P-site of the eukaryotic ribosome in a GTP-independent manner. The binding of Met-tRNA(I) occurs after the AUG codon finds its position in the P-site of 40S ribosomes, the situation that takes place during initiation complex formation on some specific RNAs. Its activity in tRNA binding with 40S subunits does not require the presence of the aminoacyl moiety. Possesses the unique ability to deliver non-Met (elongator) tRNAs into the P-site of the 40S subunit. In addition to its role in initiation, can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits.
Endoplasmic reticulum-localized palmitoyltransferase that could catalyze the addition of palmitate onto protein substrates.
Probably maternally supplied, the zygotic expression is detected early during development at the 512-cell stage and is stable until 24h hpf at least.
Expressed from 8 hours post-fertilization (hpf). Expressed in the midbrain and the optic primordia from 14 hpf and around the eyes, the branchial pouches and the neural tube at 24 hpf. By 48 hpf, expression in the midbrain, branchial pouches and the neural tube was reduced to a very low level.
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).
Belongs to the class-II aminoacyl-tRNA synthetase family. Phe-tRNA synthetase alpha subunit type 2 subfamily.
Heterotetramer; dimer of two heterodimers formed by alpha and beta subunits.
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.
Expressed both maternally and zygotically. Expressed ubiquitously in the developing embryo. Strongly expressed in the somites and brain at 16 to 26 hours post-fertilization (hpf).
Plays a role in embryonic development, including proper left-right asymmetry formation. Also required for proper cilia beating (PubMed:22493317). Plays a role in microtubule (MT) stabilization and this stabilization involves the maintenance of NUMA1 at the spindle poles. Colocalizes with polyglutamylated MTs to promote MT stabilization and regulate bipolar spindle formation in mitosis. Binding of CCSAP to centrosomes and the spindle around centrosomes during mitosis inhibits MT depolymerization, thereby stabilizing the mitotic spindle (By similarity).
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 (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).
Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment. Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity.
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (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).
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.
EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6.
Interacts with EGFR and promotes EGFR dimerization.
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).
Specifically required during spermatogenesis for flagellum morphogenesis and sperm motility.
Belongs to the polyadenylate-binding protein type-1 family.
Binds the poly(A) tail of mRNA (By similarity). Prevents mRNA deadenylation and confers poly(A) stability (By similarity). Binds to N6-methyladenosine (m6A)-containing mRNAs (By similarity). Stimulates the translation of mRNAs to which it is bound, acting, at least in part, with dazl (By similarity). Involved in the maternal-to-zygotic transition in early embryo via interaction with ybx1: interaction recruits pabpc1a on C5-methylcytosine (m5C)-containing maternal mRNAs, preventing their degradation (PubMed:31399345).
Interacts with ybx1; interaction recruits pabpc1a on C5-methylcytosine (m5C)-containing mRNAs, preventing their degradation.
RRM4, together with the C- and N-terminal regions, is sufficient for RNA-binding. RRM 1 has no RNA-binding activity itself, but improves discrimination between poly(A) and poly(U) in combination with the other repeats.
Binds to one of the cis-acting domain of the insulin gene enhancer. May be involved in the regional specification of the myotome and also in target recognition by the caudal primary neuron.
Expressed both maternally and zygotically. At 17 hours post-fertilization (hpf), expressed in dorsal Rohan-Beard neurons and strongly in the ventral myotomes. At 24 hpf, head expression is restricted to eyes, the tectal region of the midbrain, trigeminal ganglia and the ganglia anterior to the otic vesicles.
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of galactose (Gal) residues of keratan.
Belongs to the histidine acid phosphatase family. VIP1 subfamily.
Bifunctional inositol kinase that acts in concert with the IP6K kinases to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, may regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, and exocytosis. Phosphorylates inositol hexakisphosphate (InsP6).
Component of 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.
Endogenous ligand for the apelin receptor (aplnra and/or aplnrb) (PubMed:24316148, PubMed:24407481). Hormone required for mesendodermal differentiation, blood vessels formation and heart morphogenesis during early development and for adult cardiovascular homeostasis (PubMed:24316148, PubMed:24407481, PubMed:26017639, PubMed:29117894). Acts as a motogen by promoting mesendodermal cell migration during gastrulation by binding and activating the apelin receptor (PubMed:24316148, PubMed:24407481, PubMed:29117894). Acts as an early embryonic regulator of cellular movement with a role in migration and development of cardiac progenitor cells (PubMed:24316148, PubMed:24407481). May act as a chemoattractant for the activation of angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (PubMed:26017639). Positively regulates sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel sprouting. Involved in cardioprotective functions during heart failure. Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity).
Expressed from the mid-blastula transition (MBT) to 3 days post-fertilization (dpf) (PubMed:24316148). Ubiquitously expressed in dividing cells of the blastoderm before becoming restricted after gastrulation to axial structures, with most prominent expression in the neural tube (PubMed:24316148).
Expressed ubiquitously during late blastula and gastrula stages and becomes restricted to the lateral mesoderm, endoderm, and anterior and posterior notochord after gastrulation (PubMed:24407481).
Interacts with aplnra and aplnrb (PubMed:24316148).
Was named Toddler based on the phenotype.
Zinc-finger-nuclease (ZFN)- or TALEN-mediated apela gene inactivation induces embryonic lethality due to heart dysgenesis around 6 days post-fertilization (dpf) (PubMed:24316148, PubMed:24407481). Mutant embryos show cardiac dysplasia ranging from a rudimentary heart to no heart (PubMed:24316148, PubMed:24407481). Embryos have minimal blood circulation, with an excess of erythrocytes accumulating at the intermediate cell mass (ICM) (PubMed:24316148, PubMed:24407481). Larvae display variable posterior truncations and, at times, tailbud duplications (PubMed:24316148). Posterior tissue defects range from loss of the ventral fin to complete tail and trunk truncations (PubMed:24316148). Embryos also display malformed pharyngeal endoderm, abnormal left-right positioning and formation of the liver (PubMed:24407481). By mid-gastrulation, embryos show reduced endodermal cell numbers and endodermal and mesodermal progenitor cell migration toward the animal pole (PubMed:24316148, PubMed:24407481). CRISPR-induced apela null mutations show also reduced endodermal cell numbers, increased rates of endodermal cells death and reduced endodermal and mesodermal cell migration at mid-gastrulation (PubMed:29117894). Show a strong decrease in the angioblast migration to the embryonic midline during late gastrulation (PubMed:26017639).
Belongs to the ATP:guanido phosphotransferase family.
Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family.
Buffers cytosolic calcium. May stimulate a membrane Ca(2+)-ATPase and a 3',5'-cyclic nucleotide phosphodiesterase.
Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis.
Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion (By similarity). Required for embryogenesis, specifically for progression of epiboly and normal convergence-extension movements during gastrulation (PubMed:22235774).
Expressed at fertilization and up to 2 hours post-fertilization (hpf), expression then declines to low levels at 4 hpf before increasing at 6 hpf onwards until 96 hpf.
Morpholino knockdowns show increased embryonic lethality, with embryos that die developing one of two clear phenotypes following developmental arrest at 10 hpf (PubMed:22235774). The first group show severe epiboly arrest with the desmosomal cadherins and enveloping layer becoming detached from the external yolk syncytial layer that continues to undergo epiboly (PubMed:22235774). This results in a population of cells at the animal pole which maintain cell division and some gastrulation movements (PubMed:22235774). In the second phenotype the enveloping layer is attached to the yolk but does not progress through epiboly (PubMed:22235774). The enveloping layer remains attached in a ring to the base of the blastoderm until embryos arrest due to mechanical stress and detachment of the blastoderm from the yolk cell following extensive proliferation and blastoderm growth (PubMed:22235774). Embryos that survive to 14 hpf show morphological defects characteristic of altered gastrulation movements including a shorter embryonic axis, undulating notochord and somites that show either altered morphology or substantial disorganization (PubMed:22235774).
Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.
GTPase possibly involved in regulation of the MEK/ERK pathway.
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.
Maternally expressed from the 4-cell stage and ubiquitously expressed through early embryogenesis, with enriched expression in the brain region at 36 hpf (hours post fertilization).
Multiple developmental defects at 24 hpf (hours post fertilization) including smaller head and eyes, smaller brain ventricle, and curved notochord.
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.
Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by aurkb mediates the dissociation of HP1 proteins (cbx1, cbx3 and cbx5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by map3k20 isoform 1, rps6ka5 or aurkb during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by prkcb is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by lsd1/kdm1a. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by kdm4c/jmjd2c. Phosphorylation at Tyr-42 (H3Y41ph) by jak2 promotes exclusion of cbx5 (HP1 alpha) from chromatin. Phosphorylation on Ser-32 (H3S31ph) is specific to regions bordering centromeres in metaphase chromosomes.
Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).
Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with zmynd11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains.
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).
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.
Detectable at 4 hours post-fertilization (hpf), expression levels peaked at 24 hpf and gradually decreased afterwards. Expression become detectable when skeletal muscle differentiation commences at 14-16 somites with an anteropsterior gradient. Myocardial expression starts at 22 hpf in the forming heart tube and, at 24 hpf, is confined to differentiated cardiac muscles cells. At 24 hpf, is also expressed in the entire myotome. At 48 and 72 hpf, expression in the trunk muscle cells disappeares, but is present in muscles cells of the pectoral fin bud and facial muscles.
Expressed in the heart and, slightly, in skeletal muscle.
Important for striated muscle differentiation and cardiac morphogenesis. Is also required for cardiac conduction system development, plays a regulatory function in heart rate dynamics mediated, at least in part, through cAMP-binding.
Morpholino knockdown of the protein affects skeletal muscle development, resulting in abnormal facial and trunk muscle formation with defective aligment of muscle fibers and establishment of myotendinous junctions. A severe defect is observed in craniofacial muscle development, where many muscles are malformed or reduced in size. In the heart, pericardial edema is prevalent in the morphants with defective looping and misshaped chambers.
Expressed both maternally and zygotically. Expression increases between 1 dpf and 2 dpf when the exocrine pancreas starts to develop and is highest between 2 dpf and 5 dpf. Starts to express in the pancreatic area at 33 hpf. Later in development, the strongest domain of expression appears in the pancreas. Cells expressing are located about 1 somite anterior to the cluster of preproinsulin-positive cells, just before exocrine specification begins. By 36 hpf, expressing cells start to contact the preproinsulinpositive cells as a result of gut rotation. These expressing cells continue to grow posteriorly to form a typical pancreas-like shape at 3 dpf. From 33 hpf to 3 dpf, there is no overlap between expressing cells and preproinsulinpositive cells, indicating that expression is excluded from endocrine cells. Conversely, expression completely overlaps with trypsin expression at 3 dpf.
Expressed exclusively in the exocrine cells during pancreas development.
Expression is directly regulated by pancreas-specific transcription factor ptf1a. Probably also regulated by retinoic acid (RA).
Impaired exocrine cell differentiation and growth. Loss or significant reduction of exocrine cells are due to lineage-specific cell cycle arrest but not apoptosis. The endocrine cell mass appear normal. Cell cycle arrest is mediated by up-regulation of cell cycle inhibitor genes cdkn1a, cdkn1b, and cyclin gccng1.
Probable regulator of exocrine pancreas development.
Cytokine that acts as a physiological ligand for receptor tyrosine kinases LTK and ALK (PubMed:29078341, PubMed:29317532). Required for iridophore development in the adult eye by acting as a receptor for LTK (PubMed:29078341).
Expressed at low level in the notochord and iridophore stripes, the eye and the swim bladder.
Fishes show reduced iridophores in eyes and operculum, with no detectable phenotype in the trunk (PubMed:29317532). Fishes lacking both alkal1 and alkal2b show a complete loss of eye iridophores (PubMed:29317532). Fishes lacking alkal1, alkal2a and alkal2b are embryonic lethal and display total loss of iridophores (PubMed:29317532).
Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.
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.
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).
Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (By similarity). Seems to be involved in cell-fate decisions.
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.
Divalent metal cations. Prefers magnesium or manganese.
Involved in the mitochondrial division probably by regulating membrane fission. Loss-of-function leads to apoptosis (By similarity).
Detected at 1 to 7 days post-fertilization (dpf). Expressed in the forebrain and midbrain at 1 dpf, where it localizes to the ependymal cell layer of the dicephalic ventricle and midbrain ventricle. Expressed in the developing otic vesicle at 2-7 dpf, where it shows particularly strong expression in the epithelium of the semicircular canal projections.
Expressed in kidney, brain and gut. Also expressed weakly in eye, gill and skeletal muscle.
Proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
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.
Required for the localization of ZFYVE1 to lipid droplets and for its function in mediating the formation of endoplasmic reticulum-lipid droplets (ER-LD) contacts (By similarity). Plays a role in apical endocytosis/recycling (By similarity). Plays a key role in eye and brain development and neurodegeneration (PubMed:21473985).
The most common abnormalities observed at 3 days post-fertilization are microphthalmia, microcephaly, pericardial edema, delayed jaw formation, a reduced overall body size, and a general developmental delay. Further characterization revealed that the rab18b morphants have delayed retinal development and abnormal retinal lamination, residual nucleated lens fiber cells, widely open choroid fissure, and microphthalmia at day 3.
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 DEAD box helicase family. DDX54/DBP10 subfamily.
Belongs to the fatty acid desaturase type 1 family. DEGS subfamily.
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).
In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.
In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
Transposase-derived protein that may have nuclease activity (Potential). Does not have transposase activity.
Plays an important role in the removal of damaged mitochondria via mitophagy by controlling the stability and localization of RAB7A (By similarity). Required for the recruitment of RAB7A and ATG9A vesicles to damaged mitochondria and promotes the stability of RAB7A by inhibiting its proteasomal degradation during mitophagy (By similarity).
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 PDK/BCKDK protein kinase family.
May act as signaling molecule during development of the midbrain-hindbrain boundary (MHB) organizer, and be involved in patterning of the nervous system.
Not expressed during gastrulation. First detected at the 8-somite stage in the ventral region of the MHB and in the anterior somites. At the 14-somite stage, expressed in the anteromedial margins of the somites and in the optic stalks. At 24 hours, expression is lost in the somites but observed in the otic vesicle. At 30 hours, expressed in the hyoid and at 36 hours in the dorsal diencephalon.
Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate (By similarity).
Belongs to the glycosyl hydrolase 33 family.
Ubiquitin-like protein involved in autophagic vesicle formation.
Probable component of a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.
Scaffold protein for the de novo synthesis of iron-sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins.
Loss of neural tissue volume: neuronal cell death is associated with impaired autophagic degradation.
Plays a role in maintaining normal neuronal excitability and synaptic transmission. May be involved in several stages of intracellular trafficking (By similarity). Required for autophagosome clearance, possibly by mediating the fusion of lysosomes with autophagosomes (PubMed:25848753). Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a key component of late endosomes/lysosomes. Does not bind phosphatidylinositol 3-phosphate (PtdIns(3P)) (By similarity).
Belongs to the cyclophilin-type PPIase family. PPIL4 subfamily.
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).
Belongs to the purine/pyrimidine phosphoribosyltransferase 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.
Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane (PubMed:31367042). Plays a vital role in the regulation of ionic balance and cell volume (PubMed:31367042). Important for maintenance of endolymph volume in the otic vesicle, probably by regulating ion homeostasis (PubMed:19633174). Also plays a role in normal development of the swim bladder (PubMed:19633174).
Expressed in the otic vesicle at 6 days post-fertilization, with highest expression in the developing semicircular canals (at protein level). Detected in the notochord at the tailbud stage. Expressed in somites, notochord and intermediate mesoderm during early somitogenesis. Expressed in the otic vesicle from 24 hours post-fertilization onwards.
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).
Expressed in the central nervous system (CNS) (PubMed:26663717). Expressed in the developing forebrain, and especially in the telencephalon (PubMed:26663717).
Maternally expressed in the at four-cell stage. Highly expressed in the developing anterior neural plate since tailbud stage. During the segmentation period, 24 hour post fertilization (hpf), expression is still enriched in cell clusters at prosencephalon and mesencephalon.
Morpholino knockdown of the protein causes malformation in telencephalon (PubMed:26663717). Impaired neural stem/progenitor cells (NSPCs) proliferation in the telencephalon (PubMed:26663717).
Palmitoyl acyltransferase that mediates palmitoylation of proteins and is required during embryonic heart development. Involved in the proliferation of neural stem cells by regulating the FGF/ERK pathway (By similarity). Involved in the proliferation of neural stem cells by regulating the FGF/ERK pathway (PubMed:26663717).
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.
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.
Not expressed in blood or lymphatic endothelial cells, correlating spatially and temporally with the migration routes of endothelial cells that bud from the PCV, migrate in association with somite boundaries and seed the horizontal myoseptum region from where lymphatic precursors later migrate.
Required for lymphangioblast budding and angiogenic sprouting from venous endothelium during embryogenesis. Necessary for lymphangiogenesis, but is probably not part of either the vegfc-vegfr3 signaling or sox18-prox1 transcriptional pathways.
Restricted expression during development with expression in the pronephros and ventral mesenchyme at 24 hours post fertilization (hpf). By 36 hpf, expression is detected in discrete zones along each somitic boundary, between the PCV and the horizontal myoseptum, as well as along the horizontal myoseptum itself. At 48 hpf, expression is restricted along the horizontal myoseptum.
Putative sodium-dependent amino acid/proton antiporter.
Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain.
Belongs to the HAD-like hydrolase superfamily. SerB family.
Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2.
Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability (By similarity).
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.
RNA-binding protein involved in pre-mRNA splicing. Interacts with the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome. Involved in regulating splice site selection. Binds preferentially RNA with A/C rich sequences and poly-C stretches.
The C-terminal part is necessary for the interaction with the PRP19C/Prp19 complex/NTC/Nineteen complex.
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1B subfamily.
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group. They are involved in pain signaling. Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
The egy mutant embryos that lack detectable sart3 expression display microcephaly, microphthalmia and die by 7 to 8 dpf. Pharyngeal arch formation is defective resulting in a thymus devoid of lymphocytes and exocrine pancreas development is also impaired.
U6 snRNP-binding protein that functions as a recycling factor of the splicing machinery. Promotes the initial reassembly of U4 and U6 snRNPs following their ejection from the spliceosome during its maturation (PubMed:17416673). May also function as a substrate targeting factor for deubiquitinases and mediate the deubiquitination of components of the spliceosome and histones (By similarity).
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.
ATP-binding RNA helicase involved in translation initiation. Part of the 43S pre-initiation complex that is required for efficient initiation on mRNAs of higher eukaryotes with structured 5'-UTRs by promoting efficient NTPase-dependent 48S complex formation. Specifically binds to the 40S ribosome near the mRNA entrance. Does not possess a processive helicase activity.
Belongs to the DEAD box helicase family. DEAH subfamily.
Part of the 43S pre-initiation complex (PIC).
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.
Probable RNA helicase. Required for RNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (By similarity).
At 24 hours post-fertilization, expressed predominantly in posterior blood island, posterior cardinal vein and circulating blood. At 34 hours post-fertilization, becomes restricted to posterior blood island and circulating blood.
Mitochondrial glycine transporter that imports glycine into the mitochondrial matrix. Plays an important role in providing glycine for the first enzymatic step in heme biosynthesis, the condensation of glycine with succinyl-CoA to produce 5-aminolevulinate (ALA) in the miochondrial matrix. Required during erythropoiesis.
Belongs to the glycerophosphoryl diester phosphodiesterase family.
Reversible hydration of carbon dioxide. Its role in saliva is unknown.
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 copper/topaquinone oxidase family.
Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue.
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).
Expressed throughout the developing central nervous system, but excluded from the most medial ventricular zone (PubMed:26056227).
Larva with TALEN-induced zc4h2 null mutations show abnormally pectoral flexed fins, outward positioning of eyes, continuous swimming movements and balance problems at 5 days post-fertilization (dpf) (PubMed:26056227). Also exhibited an open mouth as well as continuous jaw movements (PubMed:26056227). Display a reduction in the number of V2 interneuron precursors in the hindbrain and spinal cord at 24 hours post-fertilization (hpf). Display a reduction in the number of GABAergic interneurons in the midbrain tegmentum at 35 hpf (PubMed:26056227).
Plays a role in GABAergic and V2 interneurons differentiation (PubMed:26056227). Involved in motoneuron development and in neuromuscular junction formation (PubMed:23623388).
Expressed both maternally and zygotically with continuous expression from the zygote to the early larva. Expression dramatically decreases at 30 and 50% epiboly stages, then increases from midgastrulaion onwards, being maintained at a high level until the protruding-mouth stage.
Shows complex and dynamic expression during early embryonic development. Prominent in many regions of the developing central nervous system, particularly in midbrain-hindbrain boundary, hindbrain and spinal cord. Strongly expressed in the retina, ear, branchial arches, hatching gland, heart, pronephric duct, gut, proctodeum, pectoral fin and swim bladder.
The leucine-zipper is required for dimerization and transcriptional repression.
60% of embryos die 7 days post-fertilization (PubMed:32075961). Embryos have cardiac developmental defects including a lack of cardiac looping and atrio-ventricular conduction defects with dysynchronous beating rhythms (PubMed:32075961). Increase in RTN4 protein expression levels (PubMed:32075961). Morpholino knockdown causes apparent sarcoplasmic reticulum membrane vacuolization in ventricular tissue along with structural discontinuity between sarcomeres (PubMed:32075961).
Expressed in embryos 48 to 96 hours post-fertilization (at protein level) (PubMed:32075961). Expressed in both ventricular and atrial cardiomyocytes (at protein level) (PubMed:32075961).
Plays an essential role in heart function and development by regulating the organization and function of the sarcoplasmic reticulum in cardiomyocytes.
The short lumenal loops between transmembrane domains 1 and 2 and between transmembrane domains 3 and 4 may impart a wedge-like configuration, thus deforming membranes.
Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles.
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.
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.
Belongs to the archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family.
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.
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).
Expressed maternally during early embryonic stages. Initially expressed throughout the embryo then expression is restricted to the brain region.
Scaffold protein involved in different aspects of polarized cells differentiation regulating epithelial and neuronal morphogenesis. Regulates the caudal migration of the nVII motor neurons. Required for convergent extension movements during gastrulation.
Associates with the pre-60S ribosomal particle.
Belongs to the universal ribosomal protein uL10 family.
Component of the ribosome assembly machinery. Nuclear paralog of the ribosomal protein P0, it binds pre-60S subunits at an early stage of assembly in the nucleolus, and is replaced by P0 in cytoplasmic pre-60S subunits and mature 80S ribosomes.
Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either laterally or terminally.
Interacts with SUPT5H to form the DSIF complex. DSIF interacts with RNA polymerase II and with the positive transcription elongation factor b complex (P-TEFb complex), which is composed of CDK9 and cyclin-T (By similarity).
May function as a component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates transcription elongation by RNA polymerase II. Probably enhances transcriptional pausing at sites proximal to the promoter, which may facilitate the assembly of an elongation competent RNA polymerase II complex. Also acts to stimulate transcriptional elongation at low nucleotide concentrations. Regulation of transcriptional elongation by this protein is required for the expression of genes which control neuronal development (By similarity).
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.
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).
Subunit of the heterotrimeric GatCAB amidotransferase (AdT) complex, composed of A (qrsl1), B (gatb) and C (gatc) subunits.
Belongs to the glycosyltransferase 61 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).
Syntaxin that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER.
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.
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 DEAD box helicase family. DEAH subfamily. DDX11/CHL1 sub-subfamily.
DNA-dependent ATPase and ATP-dependent DNA helicase that participates in various functions in genomic stability, including DNA replication, DNA repair and heterochromatin organization as well as in ribosomal RNA synthesis. Plays a role in DNA double-strand break (DSB) repair at the DNA replication fork during DNA replication recovery from DNA damage. Plays a role in the regulation of sister chromatid cohesion and mitotic chromosome segregation. Stimulates 5'-single-stranded DNA flap endonuclease activity of FEN1 in an ATP- and helicase-independent manner. Also plays a role in heterochromatin organization (By similarity). Involved in rRNA transcription activation through binding to active hypomethylated rDNA gene loci by recruiting UBTF and the RNA polymerase Pol I transcriptional machinery (PubMed:26089203). Plays a role in embryonic development (PubMed:26089203). Associates with chromatin at DNA replication fork regions. Binds to single- and double-stranded DNAs (By similarity).
Morpholino knockdown of the protein leads to abnormal craniofacial and vertebrate development with shortened and twisted torsos, smaller eyes and low mouth positions at 3 days post-fertilization (dpf).
Belongs to the tyrosyl-DNA phosphodiesterase family.
Identified in the spliceosome C complex.
Involved in pre-mRNA splicing as component of the spliceosome.
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-121 and Arg-124) that bind to malonylated and succinylated substrates and define the specificity.
Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine).
Belongs to the DNA photolyase class-1 family.
Binds 1 5,10-methenyltetrahydrofolate (MTHF) non-covalently per subunit.
May have a photoreceptor function (By similarity). Has weak cyclobutyl pyrimidine photolyase activity when expressed in E.coli and when tested in vitro.
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.
Potent stimulator of insulin secretion and relatively poor inhibitor of gastric acid secretion.
Belongs to the WD repeat striatin family.
Possible role in transport between endoplasmic reticulum and Golgi.
Belongs to the syndecan proteoglycan family.
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis.
RNA-binding protein that may be implicated in the regulation of pre-mRNA alternative splicing.
Required for DNA double-strand breaks (DSBs) formation in unsynapsed regions during meiotic recombination.
Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain (By similarity).
Detected in the early blastula, 2.5 hours post fertilization (hpf), before the onset of zygotic gene expression, and expression progressively increases, reaching a peak at late gastrula stages (9 hpf), before decreasing by 26 hpf. Maternal transcripts are detected throughout the blastoderm. Ubiquitous expression continues until early somitogenesis (12 hpf), after which transcript levels gradually decrease in the trunk (15-18 hpf), with strong expression becoming restricted to the head by 25 hpf.
May play a structural role in chromatin. Involved in sister chromatid cohesion, possibly by facilitating the cohesin complex loading (PubMed:22039349). Transcription factor, which may promote cortical neuron migration during brain development by regulating the transcription of crucial genes in this process (By similarity).
Scaffold protein that participates in the c-ring assembly of mitochondrial ATP synthase (F(1)F(0) ATP synthase or complex V) by facilitating the membrane insertion and oligomer formation of the subunit c/ATP5MC3. Participates in the incorporation of the c-ring into vestigial complexes. Additionally influences the incorporation of subunits MT-ATP6, MT-ATP8, ATP5MJ, and ATP5MK in the ATP synthase.
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.
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.
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.
Methylation at His-73 by SETD3. Methylation stabilizes actin filaments.
Oxidation of Met-44 and Met-47 by MICALs (mical1, mical2 or mical3) to form methionine sulfoxide promotes actin filament depolymerization. Mical1 and mical2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by msrb1 and msrb2, which promote actin repolymerization (By similarity).
Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix (By similarity). Each actin can bind to 4 others (By similarity).
Skeletal muscle, heart, gill, digestive tissue and brain (PubMed:9987040). Widespread expression throughout the brain, with highest levels in regions where neuronal proliferation is greatest (PubMed:9987040).
Belongs to the DNA mismatch repair MutL/HexB 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.
Belongs to the SMC family. SMC5 subfamily.
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).
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.
Belongs to the ADP-ribosyl cyclase family.
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.
Belongs to the eukaryotic ribosomal protein eL37 family.
Belongs to the universal ribosomal protein uS8 family.
Morpholino-injected embryos have a thin yolk sac, bent tail, and show a marked decrease of erythrocyte production.
Structural component of the ribosome (By similarity). Required for erythropoiesis during embryonic development (PubMed:27909223).
Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates.
Binds preferentially and cooperatively to pyrimidine rich single-stranded DNA (ss-DNA) (By similarity). May be required to maintain the copy number of mitochondrial DNA (mtDNA) and play a crucial role during mtDNA replication (PubMed:31550240). Required for retinal ganglion cell differentiation and retinal integrity (PubMed:31298765).
Morpholino-induced knockdown results in reduction in optic nerve size and mitochondrial depletion (PubMed:31550240, PubMed:31298765). Strongly reduced expression of the developmental regulator genes isl1 and atoh7 in retinal ganglion cell (RGC) precursors (PubMed:31298765). Nonphotoreceptor cells, both in the ganglion cell layer and in the inner nuclear layer, display compromised neuronal specification, whereas cell numbers in both layers are unaltered (PubMed:31298765).
Belongs to the pyridoxine kinase family.
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).
Translation initiation regulator which may repress non-AUG initiated translation and repeat-associated non-AUG (RAN) initiated translation by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function.
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type I family.
Belongs to the GSK-3-binding protein family.
Adopts an immunoglobulin-like beta-sandwich fold forming a hydrophobic cavity that capture N-terminally myristoylated target peptides. Phe residues within the hydrophobic beta sandwich are required for myristate binding (By similarity).
Detected in embryo. Detected in larvae four days after fertilization, in retina and neural tissues (at protein level). Detected in embryos at the sphere stage, during gastrulation, somitogenesis and in swimming larvae, both within and outside of the developing nervous system. Detected in adults.
Myristoyl-binding protein that acts as a cargo adapter: specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Plays a key role in localization of proteins to the primary cilium membrane.
Belongs to the complex I NDUFB3 subunit family.
First expressed in the inner cell mass (ICM) of embryos at 18 hpf (hours post fertilization) and continues to be expressed in the developing embryo until at least 48 hpf (PubMed:18941117). Expressed in the developing hematopoietic system, at 24 hpf and circulating primitive erythrocytes at 48 hpf (PubMed:11535513, PubMed:18941117). Expressed in the pronephros, and in circulating definitive erythrocytes in the heart lumen and vessels of the tail at 8 dpf (days post fertilization) (PubMed:11535513).
In adult heart myocardium upon injury (PubMed:33833125). Repressed in embryos by microRNA miR-144 (PubMed:18941117).
Morpholino knockdown causes significant reduction in expression of embryonic alpha globin e1 hbae1.1 in 22 hpf (hours post fertilization) and 36 hpf embryos.
Transcription regulator (PubMed:18941117, PubMed:33833125). Plays a role in erythropoiesis, binding to promoters and activating transcription of embryonic alpha globin e1 hbae1.1 and microRNA mir-144, in erythroid progenitors; perhaps acting as part of a negative feedback loop with mir-144 (PubMed:33833125, PubMed:18941117). May coordinate repression of genes controlling myocardial differentiation and mitochondrial metabolism with positive modulation of cell proliferation genes (PubMed:33833125). Required for regeneration of the myocardium after injury, probably acting by stimulating renewal of preexisting cardiomyocytes in adult hearts (PubMed:33833125).
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.
As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage.
Belongs to the replication factor A protein 1 family.
Component of the heterotrimeric canonical replication protein A complex (RPA).
Expressed in nonspecific cytotoxic cells (NCC).
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).
Ubiquitously expressed in embryos until eight hours after fertilization. Detected throughout the embryo, but particularly in the cephalic region, at 10 to 24 hours after fertilization. Detected in retina, tegmentum and myencephalon at 38 and 48 hours after fertilization.
Belongs to the dynein light chain family.
Essential for hematopietic stem cell development through the regulation of p53/TP53 pathway.
Expression in caudal hematopoietic tissue initiates during hematopietic stem cell expansion stages, and the expression level from 72 hours post-fertilization (hpf) to 96 hpf is much higher than that at 48 hpf.
Mutants show a notable decrease in the population of hematopietic stem cells in caudal hematopoietic tissue and early T-cells in thymus (PubMed:29470984). Compromised cell proliferation and excessive apoptosis are observed in the caudal hematopoietic tissue (PubMed:29470984).
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.
Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA.
Belongs to the immunoglobulin superfamily. DCC family.
Expression begins at 80% epiboly and is extinguished by 48 hours post-fertilization.
Expression begins in the posterior region of the embryo and this posterior restriction persists at the 4 s stage. At early somite stages, expressed along the neural tube with lower levels in the lateral and paraxial mesoderm. Expression decreases caudally and rostrally becomes restricted to the ventral part of the brain. Widespread in the spinal cord at 30 hours post-fertilization (hpf) and is also expressed in the lens from this time. At 40 hpf, expression is restricted to the lens.
May play a role in anteroposterior axis elongation.
Belongs to the proteasome subunit p27 family.
Component of some MLL1/MLL complex. Component of the PELP1 complex, composed of at least pelp1, tex10 and wdr18. The complex interacts with pre-60S ribosome particles.
Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit.
Belongs to the eukaryotic ribosomal protein eS6 family.
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (Caspase-6 subunit p18) and a 11 kDa (Caspase-6 subunit p11) subunit.
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).
Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth.
Does not exhibit calcium-activated chloride channel (CaCC) activity. Can inhibit the activity of ANO1 (By similarity).
The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology.
Myosin is a hexamer of 2 heavy chains and 4 light chains.
In the C-terminal section; belongs to the MoaC family.
In the N-terminal section; belongs to the radical SAM superfamily. MoaA family.
Expression is correlated temporally and spatially with somitogenesis. At late gastrula stage, expressed in the posterior presumptive neural plate. During somitogenesis, expression becomes restricted along the dorsoventral axis of the trunk neural tube in an anterior-to-posterior progression so that upon completion of somitogenesis, expression is seen exclusively in the ventral spinal cord with the exclusion of the floor plate and adjacent neural cells.
Belongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily.
Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May be responsible for glucose production through glycogenolysis and gluconeogenesis (By similarity).
Phosphorylates D-xylulose to produce D-xylulose 5-phosphate, a molecule that may play an important role in the regulation of glucose metabolism and lipogenesis.
3'-5' RNA exonuclease that trims the 3' end of oligo(U) and oligo(A) tracts of the pre-U6 small nuclear RNA (snRNA) molecule, leading to the formation of a mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate. Participates in the U6 snRNA 3' end processing that prevents U6 snRNA degradation. In addition also removes uridines from the 3' end of U6atac snRNA and possibly the vault RNA VTRNA1-1.
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 glycosyl hydrolase 63 family.
Cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor.
In the N-terminal section; belongs to the AlaDH/PNT family.
Component of the BCR(KBTBD8) E3 ubiquitin ligase complex.
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of neural crest specification (By similarity). The BCR(KBTBD8) complex acts by mediating monoubiquitination of target proteins (By similarity).
Calcium-dependent mitochondrial solute carrier.
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.
Belongs to the Integrator subunit 2 family.
May play a role in intracellular membrane fusion.
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 glycosyl hydrolase 79 family.
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones.
Strongly expressed in eye, diencephalon, spinal cord, hindbrain, liver, kidney and telencephalon. Also detected at very low levels in muscle, spleen, anterior gut and heart. In eye, expressed strongly in retina. In brain, expressed in the central part of the telencephalon, the periventricular gray zone of the optic tectum, the periglomerular nucleus, the olfactory bulb, and the region adjacent to the diencephalic ventricle in the hypothalamus. Expressed in gill, with strongest expression in gill filaments nearest the gill arch, and in esophageal epithelium.
Catalyzes the biosynthesis and metabolism of eicosanoids. Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2), a potent mediator of vasodilation and inhibitor of platelet aggregation (PubMed:18032380). Additionally, displays dehydratase activity, toward hydroperoxyeicosatetraenoates (HPETEs), especially toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) (By similarity).
Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2).
Belongs to the eukaryotic RPC7 RNA polymerase subunit family.
Component of the RNA polymerase III (Pol III) complex.
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.
Component of tight junction (TJ) strands.
Belongs to the calcium channel beta subunit family.
Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with max (By similarity).
Most abundant during early rapid cleavage, blastulation, and gastrulation. Reduced levels from time of establishment of the body plan (around 12 hours) and thereafter.
Expressed both maternally and zygotically. Expressed at 10 hours post-fertilization (hpf), reach peak levels at 48 hpf and is not detectable in adult tissues. Expressed during neurogenesis between 9 and 72 hpf and in ventral endoderm region where pancreatic progenitors originate.
May act as a transcriptional regulator. May play a role in neurogenesis and neuroendocrine cell differentiation during embryonic development (By similarity).
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.
Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.4/SCN4A subfamily.
Channel activity is regulated by ancillary beta subunits. Interaction with a beta subunit is required for rapid channel inactivation and rapid recovery after inactivation, and prevents decrease of channel activity in response to repetitive, high-frequency depolarizations.
Component of a voltage-sensitive sodium channel complex that consists of a pore-forming alpha subunit and one or more regulatory beta subunits.
Expressed in skeletal muscle, brain, spinal cord, and eye.
Pore-forming subunit of a voltage-gated sodium channel complex through which Na(+) ions pass in accordance with their electrochemical gradient. Alternates between resting, activated and inactivated states. Required for normal muscle fiber excitability, normal muscle contraction and relaxation cycles.
The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.
Belongs to the FAD-dependent oxidoreductase family.
Activated by autocatalytic proteolytical processing.
Expressed in retina at 48 hours post-fertilization (at protein level). Detected in all retinal cell layers but has particularly strong expression in the outer nuclear layer and ganglion cell layer (at protein level).
Lysosomal serine protease with tripeptidyl-peptidase I activity (PubMed:23587805). May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases (By similarity). Requires substrates with an unsubstituted N-terminus (By similarity).
Morpholino knockdown of the protein in embryos results in developmental defects from 48 hours post-fertilization onwards, including reduced eye and head size, a curved body, small jaw, and loss of the swim bladder.
Component of intercellular desmosome junctions (PubMed:22235774). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion (PubMed:22235774). Involved in the formation and structural organization of desmosome cell-cell junctions during embryonic development (PubMed:22235774). Required for embryogenesis, specifically for progression of epiboly and normal convergence-extension movements during gastrulation (PubMed:22235774). Required for the development of desmosomal-rich midlines in the heart (PubMed:17186466). Plays an important role in ventricular contraction and resulting heart stroke volume (PubMed:17186466, PubMed:33784018).
Expressed at fertilization and up to 2 hours post-fertilization (hpf), expression then declines to low levels at 4 hpf before increasing at 6 hpf onwards until 96 hpf (PubMed:22235774). Expressed in the atrium, ventricle, and both the inflow and outflow tracts at 48 hours post-fertilization (PubMed:17186466).
Expressed at low levels in the brain and heart.
Morpholino knockdowns show increased embryonic lethality, with embryos that die developing one of two clear phenotypes following developmental arrest at 10 hpf (PubMed:22235774). The first group show severe epiboly arrest with desmosomal cadherins and enveloping layer becoming detached from the external yolk syncytial layer that continued to undergo epiboly (PubMed:22235774). This results in a population of cells at the animal pole which maintain cell division and some gastrulation movements (PubMed:22235774). In the second phenotype the enveloping layer is attached to the yolk but does not progress through epiboly (PubMed:22235774). The enveloping layer remains attached in a ring to the base of the blastoderm until embryos arrest due to mechanical stress and detachment of the blastoderm from the yolk cell following extensive proliferation and blastoderm growth (PubMed:22235774). Embryos that survive to 14 hpf show morphological defects characteristic of altered gastrulation movements including a shorter embryonic axis, undulating notochord and somites that show either altered morphology or substantial disorganization (PubMed:22235774). Reduced abundance of desmosome cell junctions between cells at the shield stage at 6 hpf (PubMed:22235774). At the 8 somite stage (11 hpf) desmosomes are present however show poor structural organization with a wide intercellular space or unpaired plaques (PubMed:22235774). Bradycardia, chamber dilation, and abnormal cardiac contractility with progressive pericardial edema developing by 48 hpf (PubMed:17186466). Normal desmosomal midline fails to form in the myocardial tissue of the ventricle by 48 hpf (PubMed:17186466). Cardiac edema associated with blood accumulation around the yolk sac, accompanied by decreased cardiac stroke volumes and ventricular contraction at 3 days post-fertilization (PubMed:33784018).
Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
Belongs to the SLC35F solute transporter family.
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.
Binds calmodulin. Interacts with NDUFAF3.
Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Involved in nucleotide excision repair.
Belongs to the histidine acid phosphatase family. MINPP1 subfamily.
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 (By similarity).
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.
Sequence-specific RNA-binding protein that binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR. RNA binding results in a clear conformational change analogous to the Venus fly trap mechanism.
Involved in protein trafficking. May be involved in the down-regulation of membrane protein levels (By similarity).
Belongs to the PPP phosphatase family. PP-4 (PP-X) subfamily.
Protein phosphatase that regulates many processes such as microtubule organization at centrosomes.
During early stages of primary neurogenesis, expressed in the neural epithelium, with highest levels in the forebrain and midbrain. Also expressed in a posterior-to-anterior gradient in the caudal neural plate at the 3-6 somite stage.
Polyubiquitinated, leading to its proteasomal degradation.
Probable transcription factor. Probable substrate-recognition component of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Inhibits neurogenesis.
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.
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 NAD(P)-dependent epimerase/dehydratase family. UDP-glucuronic acid decarboxylase subfamily.
Catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid to UDP-xylose (PubMed:20226781). Necessary for the biosynthesis of the core tetrasaccharide in glycosaminoglycan biosynthesis (PubMed:20226781). Essential during embryogenesis for craniofacial development (PubMed:12006978, PubMed:16759393, PubMed:20226781).
Expressed both maternally and zygotically (PubMed:20226781). Present in one-cell embryos (PubMed:20226781). Levels decrease during epiboly and increase during segmentation stages (PubMed:20226781). At 24 hours post-fertilization (hpf), expressed in ventral craniofacial domains and along the yolk-endoderm boundary (PubMed:20226781). At 2 and 3 days post-fertilization (dpf), widely expressed throughout the head, appearing in the pharyngeal arches, eye, fin bud, neurocranium, notochord and brain (PubMed:20226781). At 5 dpf, expression localizes to the developing pharyngeal arch cartilages in both chondrocytes and perichondrium (PubMed:20226781).
Mutants show cartilage defects due to impaired chondrogenesis and have a reduced jaw size.
This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus. It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser.
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 carbon-nitrogen hydrolase superfamily. NIT1/NIT2 family.
Belongs to the zinc-containing alcohol dehydrogenase family.
May be a negative regulator of NF-kappa-B and p53-mediated gene transcription.
Expressed in the epidermis from 2 hours post-fertilization (hpf) to 16 hpf (PubMed:18164260). Expression is then restricted to the anterior of the embryo, in particular epidermal tissues of the neural structures at 24 hpf to 72 hpf (PubMed:18164260). Expressed in the heart, tissue ventral to the head and yolk at 48 hpf (PubMed:18164260).
Morpholino knockdown results in a range of cardiac phenotype severity from mild to severely affected (PubMed:23124967). Defects include slight to severe cardiac edema, blood pooling on the yolk, abnormal ventricles, heartstring and failure of cardiac looping (PubMed:23124967). Heart rate is decreased at 48 hours post-fertilization (48 hpf) from 138 beats per minute (bpm) to 110 (bpm), this decrease persists at 72 hpf (PubMed:23124967). Non-cardiac effects include kinked tail and disruption to the borders of anterior neural structures (PubMed:23124967). At 16 hpf abnormal expression and/or localization of cardiac precursor markers such as nkx2.5, lefty2, bmp4, spaw, lefty1 and tdgf1/oep (PubMed:23124967). Incomplete looping of the heart with displaced ventricle along the midline, above an enlarged atrium (PubMed:23124967). Expression of cardiac valve developmental proteins notch1b and bmp4 are abnormally expanded into the ventricle at 48 hpf (PubMed:23124967). The number of desmosomes is decreased at cell borders in the heart but those that are present show diminished intracellular elements and an increase in the intercellular gap width at 72 hpf (PubMed:23124967).
Required for development of the heart, potentially via cell-cell adhesion and modulation of expression of cardiac precursor genes (PubMed:23124967). Plays a role in desmosome cell-cell junctions and their intracellular connectivity (PubMed:23124967).
Belongs to the metallo-dependent hydrolases superfamily. Allantoinase family.
Belongs to the G-alpha family. G(s) subfamily.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.
Belongs to the GMC oxidoreductase family.
At 16 hours post-fertilization, expressed in the presumptive nucleus of the medial longitudinal fascicle, the presumptive trigeminal ganglion and the spinal cord. Expression in the spinal cord is strongest towards the rostral, more mature, spinal cord, and weaker towards the caudal spinal cord. At 24 hours post-fertilization, expressed in the olfactory placode, in the telencephalon and diencephalon but not in the proliferating ventricular zone. Expressed in the epiphysis, the nucleus of the medial longitudinal fascicle and in the area close to the nucleus of the posterior commissure. Expression in the hindbrain is restricted to reticulospinal neurons. In the cranial ganglia, expressed in the trigeminal, acoustic/anterior lateral line and posterior lateral line ganglion. In the spinal cord, expressed in the large dorsally-located Rohon-Beard neurons.
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).
Part of a specialized transcription system that mediates the transcription of most ribosomal proteins through the 5'-TCT-3' motif which is a core promoter element at these genes. Seems to also mediate the transcription of NF1. Does not bind the TATA box (By similarity). Members of the TBP family are differentially required to regulate transcription and development during early embryogenesis.
G protein-coupled receptor for follitropin, the follicle-stimulating hormone. Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways.
May mediate beneficial effects of muscular exercise.
The extracellular domain is cleaved and released from the cell membrane.
Belongs to the fatty acid desaturase type 1 family.
At the 10-somite stage, expressed in the paraxial mesoderm with an anterior expression limit at somite 6. At the 20-somite stage, expressed in the developing CNS with an anterior expression limit adjacent to the somite 3/somite 4 boundary.
Bridging factor that mediates the recruitment of cyld to the LUBAC complex, thereby regulating TNF-alpha-induced necroptosis. Required to activate the 'Met-1'- (linear) and 'Lys-63'-linked deubiquitinase activities of cyld.
Expressed both maternally and zygotically. Detected at two-cell stage. Ubiquitously expressed from the shield stage to 24 hours post-fertilization (hpf), and then becomes preferentially expressed in the central nervous system. From 5 days post-fertilization (dpf), expression becomes detectable in the gut and pronephric duct epithelium.
Transcription factor that can both act as an activator or a repressor depending on the context. Plays a central role in BMP signaling and olfactory neurogenesis. Associates with SMADs in response to bmp2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor involved in terminal olfactory receptor neurons differentiation. Involved in olfactory neurogenesis by participating in a developmental switch that regulates the transition from differentiation to maturation in olfactory receptor neurons (By similarity).
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.
May function in an early step of clathrin-mediated endocytosis.
Ribosomal protein P0 is the functional equivalent of E.coli protein L10.
Expression starts 11 hours post-fertilization (hpf) in the presumptive forebrain and becomes restricted to specific clusters of cells in the telencephalon and diencephalon at 24 hpf. Expressed in the neurons of the postoptic commissure at 30 hpf.
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.
Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters.
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.
The C-terminal di-lysine motif may confer endoplasmic reticulum localization.
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.
Belongs to the twisted gastrulation protein family.
Involved in dorsal-ventral patterning. Appears to function predominantly as a ventralizing factor, through its actions as a BMP signaling agonist, acting through both chd-dependent and chd-independent mechanisms. May also antagonize BMP signaling, probably via formation of ternary complexes with chd and BMPs, resulting in dorsalization.
Morpholino knockdown in embryos exhibits variable outcome. It may result in a weak ventralized phenotype (PubMed:11260716) or in dorsalization (PubMed:15525664 and PubMed:15604098).
Belongs to the universal ribosomal protein uL13 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.
Cargo transport protein that is required for apical transport from the trans-Golgi network (TGN) to the plasma membrane.
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.
Component of the Golgi to ER traffic (GET) complex, which is composed of GET1/WRB, CAMLG/GET2 and GET3/TRC40. Within the complex, GET1 and CAMLG form a heterotetramer which is stabilized by phosphatidylinositol binding and which binds to the GET3 homodimer.
Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (ER) (By similarity). Together with CAMLG/GET2, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol (By similarity). Required to ensure correct topology and ER insertion of CAMLG (By similarity).
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).
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.
GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).
Monoubiquitination of Lys-121 by the BRE1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation.
Phosphorylated on Ser-15 during apoptosis; which facilitates apoptotic chromatin condensation.
Autophosphorylation of CAMK2 plays an important role in the regulation of the kinase activity.
CAMK2 is composed of four different chains: alpha, beta, gamma, and delta. The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits (By similarity).
CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system.
First detected at 18 hpf. At 24 hpf, expressed in discrete anterior locations and along either side of the midline. At 48 hpf, expression is predominantly in the forebrain, and then accumulates in the forebrain, hindbrain, and retinal epithelium at 72 hpf.
Belongs to the myelin proteolipid protein family.
Belongs to the adenosylhomocysteinase family.
May be involved in chromatin assembly in DNA replication and DNA repair.
Involved in nucleolar processing of pre-18S ribosomal RNA. Has a role in the nuclear export of 40S pre-ribosomal subunit to the cytoplasm.
Plays a major role in tight junction-specific obliteration of the intercellular space.
Component of the LUBAC complex (linear ubiquitin chain assembly complex).
Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (By similarity). LUBAC conjugates linear polyubiquitin to ikbkg and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (By similarity). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (By similarity). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) to conjugate linear polyubiquitin to ikbkg and possibly other components contributing to the stability of the complex (By similarity). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (By similarity). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (By similarity). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (By similarity). Binds polyubiquitin of different linkage types (By similarity).
The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'Met-1'-linked polyubiquitins.
The UBL domain mediates association with RNF31 via interaction with its UBA domain.
Acts also as a negative regulator of osteoclast activity (PubMed:31173907). May be involved in interleukin-4-induced M2 macrophage polarization (By similarity).
Knockout zebrafish are viable and fertile and display no obvious morphological defects as adults (PubMed:31173907, PubMed:31036939). However deficient zebrafish have abnormal microglial with expended lysosomes (PubMed:31036939). They also display increased bone resorption (PubMed:31173907).
Lysosomal integral membrane protein that regulates the localization and activity of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (By similarity). Interacts with Rag GTPases and increases the lysosomial localization and activity of Rag GTPases and thereby regulates mTORC1 translocation and activity in lysosome (PubMed:31036939). Acts also as a negative regulator of osteoclast activity (PubMed:31173907). May be involved in interleukin-4-induced M2 macrophage polarization (By similarity).
Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
May play a role in the establishment and maintenance of neuronal transmission and plasticity via its ubiquitin ligase activity. 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.
Functions as cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration, via its role in the activation of AKT and FAK/PTK2. Plays a role in VEGFA signaling via its role in regulating the internalization of KDR/VEGFR2. Plays a role in intracellular vesicular transport processes, and is required for normal trafficking of the PMEL luminal domain that is essential for the development and maturation of melanocytes. Plays a role in the adhesion of leukocytes onto endothelial cells via its role in the regulation of SELP trafficking. May play a role in mast cell degranulation in response to Ms4a2/FceRI stimulation, but not in mast cell degranulation in response to other stimuli.
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.
During somitogenesis, first expressed in polster and presumptive forebrain. During mid-somitogenesis, expressed in eye, hindbrain and anterior spinal cord. During late somitogenesis, strong expression in eye and hindbrain, decreased levels in midbrain and anterior spinal cord. At 24 hours post-fertilization (hpf), expressed in neural retina and lens, brain and anterior spinal cord. At 36 hpf, retinal expression is confined to the ciliary marginal zone and there is strong expression in tectum, rhombomeres and otic vesicle. At 48 hpf, expressed in retinal ganglion cells and in tectum, rhombomeres and pectoral fin. Not detected in the vasculature during embryogenesis.
Expressed both maternally and zygotically. Expression is lost before gastrulation and begins again during somitogenesis.
Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
Belongs to the complex I subunit 5 family.
B30.2 box contains a microtubule-binding site.
May be involved in microtubule organization and stabilization.
Oligomerization is required for binding to microtubules.
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 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).
Expressed in kidney, heart and skin (PubMed:29123523). Not expressed in muscle, ovary, gills, eyes or brain (PubMed:29123523).
Morpholino knockdown results in reduced caspa activity and impairs caspa activity in response to bacterial infection with S.typhimurium (PubMed:29123523). In addition, larvae have increased susceptibility to the bacterium S.typhimurium (PubMed:29123523).
Probable inflammasome component which mediates inflammasome-dependent resistance to bacterial infection by S.typhimurium through association with activated caspa.
Self-associates (PubMed:29123523). Interacts with caspa (PubMed:29123523).
Up-regulated in response to bacterial infection with S.typhimurium (PubMed:29123523). Highly expressed in macrophages when infected with S.typhimurium (PubMed:29123523).
Morpholino knockdown of the protein results in ventral body curvature, hydrocephalus, and cystic kidneys.
Na(+)/Mg(2+) ion exchanger that acts as a predominant Mg(2+) efflux system at the plasma membrane (By similarity). Transporter activity is driven by the inwardly directed electrochemical gradient for Na(+) ions, thus directly depends on the extracellular Na(+) ion concentration set by Na(+)/K(+) pump (By similarity).
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).
Efficiently catalyzes the conversion of all-trans retinol (also called vitamin A1, the precursor of 11-cis retinal) to 3,4-didehydroretinol (also called vitamin A2, the precursor of 11-cis 3,4-didehydroretinal). Also acts on all-trans retinal and all-trans retinoic acid. The replacement of 11-cis retinal chromophore in photopigments with 11-cis 3,4-didehydroretinal enhances sensitivity to long-wavelength light. This may improve vision in fresh water which is often turbid.
Following L-thyroxine, expressed in the retinal pigment epithelium (at protein level).
In the retinal pigment epithelium, up-regulated by L-thyroxine (at protein level).
Mutant fish survive to adulthood without overt developmental abnormalities. Upon treatment with L-thyroxine, the mutant fish eyes fail to produce any vitamin A2 and their photoreceptors fail to undergo a red-shift in sensitivity.
Belongs to the band 7/mec-2 family. Flotillin subfamily.
Contaminating sequence. Sequence of unknown origin in the N-terminal part.
Heterooligomer; Heterooligomerizes with ic complex of flotillins 1 and 2.
May play a role in axon growth and regeneration. May be involved in epidermal cell adhesion and epidermal structure and function (By similarity).
Palmitoylation may be required for the formation of higher order complexes and for neurite outgrowth in cultured neural stem cells.
Morpholino knockdown of the protein causes reduced swim speed and abnormal touch-evoked escape response. Morphants exhibit abnormal cerebellar structure.
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.
F-actin regulator involved in anterograde Golgi to endosome transport: upon ubiquitination via 'Lys-33'-linked ubiquitin chains by the BCR(KLHL20) E3 ubiquitin ligase complex, interacts with EPS15 and localizes to the trans-Golgi network, where it promotes actin polymerization, thereby facilitating post-Golgi trafficking. May play a role in the maintenance of the Golgi apparatus morphology.
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.
Phosphatase that has a high activity toward phosphoethanolamine (PEA) and phosphocholine (PCho). Involved in the generation of inorganic phosphate for bone mineralization.
May play a role in promoting megakaryocyte differentiation by up-regulating RUNX1 expression.
Regulates (in vitro) the inhibition of rhodopsin phosphorylation in a calcium-dependent manner.
Belongs to the inositol 3,4-bisphosphate 4-phosphatase family.
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). Involved in the recruitment of macrophages in response to injury (PubMed:30659109). 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 (PubMed:22085962).
Morpholino knockdown increases the recruitment of macrophages in response to injury.
Regulates the macrophage function, by enhancing the resolution of inflammation and wound repair functions mediated by M2 macrophages. The regulation of macrophage function is, due at least in part, to the role of C5orf30 in regulating ability to inhibit glycolysis. Probably plays alaso a role in trafficking of proteins via its interaction with UNC119 and UNC119B cargo adapters: may help the release of UNC119 and UNC119B cargo or the recycling of UNC119 and UNC119B. May play a role in ciliary membrane localization via its interaction with UNC119B and protein transport into photoreceptor cells.
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 DNA polymerase type-X family.
Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator.
May play a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing.
Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.
Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.
Belongs to the mitochondrion-specific ribosomal protein mS33 family.
Belongs to the universal ribosomal protein uS13 family.
Embryos have a reduced forebrain, kinked tail and inflated hindbrain ventricle.
Located at the top of the head of the 40S subunit, it contacts several helices of the 18S rRNA (By similarity). Plays an essential role in early embryonic development.
Defects in ccdc103 are the cause of the schmalhans phenotype and show a curved body axis, randomized left-right asymmetry and pronephric kidney cysts, which are characteristic features of ciliopathies. Cilia completely lack both inner dynein arms (IDAs) and outer dynein arms (ODAs) while cilia length in these mutants is not altered.
Dynein-attachment factor required for cilia motility.
Expressed in all cells bearing motile cilia.
Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.
Homomultimers may associate with EGR1 bound to DNA.
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.
Monomer. Oligomerizes upon binding of cytochrome c and dATP (By similarity).
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 (By similarity).
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 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.
Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, sodium and phosphate. At the synaptic vesicle membrane, mainly functions as an uniporter that mediates the uptake of L-glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. The L-glutamate uniporter activity is electrogenic and is driven by the proton electrochemical gradient, mainly by the electrical gradient established by the vacuolar H(+)-ATPase across the synaptic vesicle membrane (By similarity). In addition, functions as a chloride channel that allows a chloride permeation through the synaptic vesicle membrane that affects the proton electrochemical gradient and promotes synaptic vesicles acidification (By similarity). At the plasma membrane, following exocytosis, functions as a symporter of Na(+) and phosphate from the extracellular space to the cytoplasm allowing synaptic phosphate homeostasis regulation. The symporter activity is electrogenic (By similarity). Moreover, operates synergistically with SLC18A3/VACHT under a constant H(+) gradient, thereby allowing striatal vesicular acetylcholine uptake (By similarity).
The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration. Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-), preventing non-vesicular L-glutamate release.
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 mitochondrion-specific ribosomal protein mL52 family.
Expressed both maternally and zygotically. Expressed widely in the embryo up to 24 hr post-fertilization (hpf). Expressed predominantly in the brain, branchial arches, and liver primordium between 24 to 72 hpf. Expressed in the midbrain at 7 days post-fertilization (dpf).
RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of pre-mRNAs. Associates with chromatin. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Binds non-specifically to pre-mRNAs (By similarity). Required for embryonic development, in particular of the brain.
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.
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.
First expressed in embryos between 5- and 7-somites. At 7 somites, expressed in discrete bilateral stripes both anteriorly and posteriorly, and in a transverse ectodermal stripe in the hindbrain. From 7-somites, expression seems to extend caudally from the head, and in both directions in the trunk region, until by 20-somites, expression is detected as a continuous band from the anterior head region to the tailbud. Concurrently, cells expressing kdrl in the mid- and posterior trunk regions converge medially. By 24 hours post-fertilization (hpf), expressed in all the endothelial cells lining the vasculature.
Interacts with isoform VEGF165 of vegfaa and isoform VEGF171 of vegfab.
Phosphorylated and activated by vegfaa and vegfab.
Receptor for VEGF or VEGFC. Has a tyrosine-protein kinase activity. Combinations of multiple VEGF receptors are required for development of different blood vessel types in the embryo. Involved in angiogenesis, specifically in VEGF-induced sprouting of new blood vessels. Particularly involved in artery formation. Does not appear to be required for hematopoiesis.
Was originally thought to be an ortholog of KDR, but PubMed:18516225 has shown that it represents a fourth vertebrate vascular endothelial growth factor receptor (VEGFR) that is not present in eutherian mammals (marsupials and placental mammals).
2-oxoadipate dehydrogenase (E1a) component of the 2-oxoadipate dehydrogenase complex (OADHC). Participates in the first step, rate limiting for the overall conversion of 2-oxoadipate (alpha-ketoadipate) to glutaryl-CoA and CO(2) catalyzed by the whole OADHC. Catalyzes the irreversible decarboxylation of 2-oxoadipate via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-residue succinyltransferase or DLST). Can catalyze the decarboxylation of 2-oxoglutarate in vitro, but at a much lower rate than 2-oxoadipate. Responsible for the last step of L-lysine, L-hydroxylysine and L-tryptophan catabolism with the common product being 2-oxoadipate.
The 2-oxoadipate dehydrogenase complex is composed of OADH (2-oxoadipate dehydrogenase; E1a), DLST (dihydrolipoamide succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3). E1a functional unit is a dimer.
The mitochondrial 2-oxoglutarate and 2-oxoadipate dehydrogenase complexes (OGDHC and OADHC, respectively) share their E2 (DLST) and E3 (dihydrolipoyl dehydrogenase or DLD) components, but the E1 component is specific to each complex (E1o and E1a, respectively).
NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors (By similarity). Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter (PubMed:24940000). Thereby contributes to regulate expression of vegfa, a key regulator of angiogenesis (PubMed:24940000). In addition to protein deacetylase activity, also has activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins (By similarity).
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).
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 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.
May have oxidoreductase activity. Regulates p38 MAP kinase activity by mediating stress activation of mapk14 and specifically regulating mapk14 signaling.
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.
A connexon is composed of a hexamer of connexins. Interacts with TMEM65.
Expressed both maternally and zygotically. Zygotic expression is initiated before gastrulation and persists through to day 5 of development. Levels increase in late somitogenesis, and late embryonic and early larval stages. Embryonic expression is observed in many developing tissues and organs, including the notochord and brain, and heart and vasculature. Detected throughout the lens at 24 hours post-fertilization (hpf), but by 3-4 days development, restricted to the lateral epithelium and differentiating cells in the equatorial region.
Expressed in adult ovary, heart, lens and liver. In growing caudal fins, expressed in cells flanking the germinal region of newly growing segments and in osteoblasts at segment boundaries.
Morpholino knockdown of the protein results in heart folding defects, reduced hematopoiesis and small eyes.
One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. Plays an essential role in gap junction communication in the ventricles (By similarity).
Plays a role in regulation of fin bone size and growth.
Belongs to the glycosyl hydrolase 27 family.
Belongs to the tenascin family. Teneurin subfamily.
Cap-specific adenosine methyltransferase activity is inhibited by zinc.
Cap-specific adenosine methyltransferase that catalyzes formation of N(6),2'-O-dimethyladenosine cap (m6A(m)) by methylating the adenosine at the second transcribed position of capped mRNAs (PubMed:30467178).
The role of N(6),2'-O-dimethyladenosine cap (m6A(m)) on transcripts is unclear and subject to discussion. According to a report, m6A(m) promotes the translation of capped mRNAs (PubMed:30467178). However, another study did not observe a clear effect on mRNA translation, but reported an increased stability of a subset of m6A(m) transcripts (By similarity). According to a third report, m6A(m) inhibits mRNA translation without affecting mRNA stability (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.
Mitochondrial electroneutral antiporter that exports citrate from the mitochondria into the cytosol in exchange for malate. Also able to mediate the exchange of citrate for isocitrate, phosphoenolpyruvate, cis-aconitate and to a lesser extend cis-aconitate, maleate and succinate (By similarity). Required for proper neuromuscular junction formation (PubMed:26870663).
Morpholino-injected embryos display altered tail morphology, impaired swimming and defective touch-evoked escape responses. Neuromuscular junction development is abnormal and motor axon terminals show short and erratic outgrowth toward the muscle fiber with no evidence of complete synapse formation. In addition, knockdown embryos often show edema of the hindbrain, heart, yolk sac and tail.
Possesses a short cleavable presequence, which, however, is found to be dispensable both for targeting to mitochondria and insertion into the inner membrane. However, the presequence is required to keep SLC25A1 in a soluble state and thus in an import-competent state. Mature SLC25A1 lacking the presequence is prone to aggregation.
Belongs to the argonaute family. Piwi subfamily.
Expressed exclusively in the adult gonads; expression in the ovary weaker than in the testis (at protein level). During neurogenesis and organogenesis, expression is detected in CNS (midbrain and eye) and fin buds. Starting from 24 hours post-fertilization, expression is found in the genital ridge.
Initially detected during embryonic segmentation which persists for at least 4 weeks post hatching.
Methylated on arginine residues; required for the interaction with Tudor domain-containing protein and subsequent localization to the meiotic nuage, also named P granule.
Plays a central role during gametogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:14516689, PubMed:17418787, PubMed:18833190). 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 (PubMed:14516689, PubMed:17418787, PubMed:18833190). Directly binds methylated piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements (PubMed:14516689, PubMed:17418787, PubMed:18833190). Has a strong preference for piRNAs with a uridine nucleotide at their 5'-end (g1U preference, also named 1U-bias) and binds piRNAs in an opposite direction compared to piwil2/zili (PubMed:14516689, PubMed:17418787, PubMed:18833190). Participates in a piRNA amplification loop with piwil2/zili (PubMed:14516689, PubMed:17418787, PubMed:18833190). Not involved in the piRNA amplification loop, also named ping-pong amplification cycle. Acts as an endoribonuclease that cleaves transposon messenger RNAs (By similarity).
Progressive loss of germ cells due to apoptosis during larval development.
The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs. The MID region is required for recognition of uridine in the first position of piRNAs (g1U preference, also named 1U-bias).
Positively regulates hepatic SREBP signaling pathway by modulating the proper localization of SCAP (SREBP cleavage-activating protein) to the endoplasmic reticulum, thereby controlling the level of functional SCAP.
At 2-3 days post-fertilization, detected in eye, forebrain, midbrain, hindbrain and anterior spinal cord.
Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily.
Expressed in eye, where it is found in the corneal epithelial layer and to a lesser extent in the stromal layer (at protein level).
Glycosylated. Contains keratan sulfate chains.
May be important in developing and maintaining corneal transparency and for the structure of the stromal matrix.
Morpolino knockdown of the protein results in increased apoptosis in eye, forebrain and midbrain, and reduced survival rate in embryos.
BC155304 contains a 74bp deletion, resulting in a frameshift.
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).
Belongs to the arylamine N-acetyltransferase family.
Putative regulator of protein phosphatase 1 (PP1) activity. May play a role in the endosomal sorting process or in endosome maturation pathway.
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.
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 (PubMed:18160536) (By similarity). Required for lipid droplet accumulation in liver and intestine during embryogenesis (PubMed:18160536). 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).
Belongs to the activator 1 large subunit family.
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)).
Cell autonomous antagonist of both the canonical and non-canonical Wnt signaling pathways.
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression.
Interacts with PDPK1 (via N-terminal region), RAD9A, CDCP1, MUC1 and VASP.
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine.
Belongs to the bacterial ribosomal protein bL33 family.
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. In the ESCRT-III complex, it probably serves as an acceptor for the ESCRT-II complex on endosomal membranes (By similarity).
Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.
Belongs to the low molecular weight phosphotyrosine protein phosphatase family.
Belongs to the YTHDF family. YTHDF2 subfamily.
Homozygous mutants from the first generation do not show any visible phenotype. Crossing homozygotes mutants together leads to lethality in around 70% of their progeny, because embryos do not developed past the one-cell stage. This lethality is probably mediated by defective sperm males. Defects are due to impaired decay of N6-methyladenosine (m6A)-modified maternal mRNAs, leading to impede zygotic genome activation. Embryos fail to initiate timely maternal-to-zygotic, undergo cell-cycle pause and remain developmentally delayed.
Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:28192787). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (By similarity). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs (By similarity). The YTHDF paralogs (ythdf1, ythdf2 and ythdf3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (By similarity). Plays a key role in maternal-to-zygotic transition during early embryonic development, the process during which maternally inherited mRNAs are degraded: acts by binding m6A-containing maternal mRNAs and promoting their degradation (PubMed:28192787). More than one-third of maternal mRNAs can be modified by m6A (PubMed:28192787). Binding to m6A-containing mRNAs results in mRNA degradation (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, such as notch1a, and promote their degradation (PubMed:28869969). The decreased Notch signaling following notch1a degradation promotes endothelial to hematopoietic transition (PubMed:28869969). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (By similarity). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (By similarity).
The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues. This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons.
Ubiquitously expressed throughout early embryogenesis.
Expressed in the developing eye and CNS prior to neuronal differentiation. First detected at around 18 hours post-fertilization (hpf) in the eye primordia and brain. At 24-42 hpf, expressed in most cells of the developing eyes, CNS and ears. At 48 hpf, also detected in the optic nerve and tracts. By 56 hpf, levels are barely detectable.
Homodimer. Binds DNA as a dimer (By similarity).
Probable transcription factor that is required for normal development of the outer retina.
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.
Binds directly to activin and functions as an activin antagonist. Specific inhibitor of the biosynthesis and secretion of pituitary follicle stimulating hormone (fsh) (By similarity). Inhibits bmp-signaling during later stages of development including late phases of dorsoventral patterning, to refine the early pattern set up by the interaction of chordino and bmp2/4. Not involved in organizer function or early phases of dorsoventral pattern formation.
Not expressed in the organizer region. Expression in gastrulating embryos is confined to anterior and paraxial regions, which give rise to head mesoderm and the first five somites. In addition, expressed transiently in a subset of cells in the posterior notochord anlage. Later, expression is seen in brain, eyes and somites.
Belongs to the nuclear hormone receptor family. NR0 subfamily.
Belongs to the ubiquitin-conjugating enzyme family. UEV subfamily.
Belongs to the RecA family. RAD51 subfamily.
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 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.
In contrast to the related histone demethylases jhdm1d and phf8, the conserved active His in position 321 is replaced by an Asn. However, the presence of an Asn residue neither affects binding to the catalytic iron nor abolishes demethylase activity.
Lysine demethylase that demethylates both histones and non-histone proteins. Mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2). Recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA (By similarity).
Belongs to the helicase family. SKI2 subfamily.
Belongs to the queuosine salvage protein family.
Catalyzes the conversion of 17-oxosteroids to 17beta-hydroxysteroids in the presence of NADPH (PubMed:16216911, PubMed:27927697). Favors the reduction of androstenedione to testosterone (PubMed:16216911, PubMed:27927697). Testosterone is the key androgen driving male development and function (By similarity). Among further tested androgens epiandrosterone and dehydroepiandrosterone are accepted as substrates and reduced at C-17 (PubMed:16216911). Can also reduce 11-ketoandrostenedione as well as 11beta-hydroxyandrostenedione at C-17 to the respective testosterone forms (PubMed:16216911, PubMed:27927697). Cannot use androsterone and androstanedione as substrates (PubMed:16216911).
Expressed in embryogenesis from sphere to 84 h post-fertilization.
Expression shows strong sexual dimorphism. In female, highly expressed in ovaries, and at lower levels in skin muscle, eyes and liver (PubMed:16216911). In males, strongly expresseed in liver and at lower levels in testis, spleen, kidney, intestine and muscle (PubMed:16216911).
First detected at 10 hpf (1-somite stage), with increased levels during subsequent embryonic development. Also expressed in adult.
In the embryo, expressed broadly in a subset of primary neurons in the brain and spinal cord. At 28 hours post-fertilization (hpf), regions of expression include telencephalon, olfactory placode, epiphysis, cranial ganglia, acoustic ganglia, Rohon-Beard mechano-sensory neurons and motoneurons. In 2 day postembryonic brain, expressed in many brain regions but absent from subpallium, the ventral preoptic region, ventral thalamus and hypothalamus; sites of expression extend laterally from the ventricular proliferative regions and correspond to freshly determined cell populations. In adult, expressed in all tissues examined with highest levels in brain.
May act as a transcriptional activator. Differentiation factor required for neurogenesis. Acts as an upstream activator of isl1.
Homodimer or homomultimer; disulfide-linked.
Mutants primary motor neurons have reduced axonal branching innervating the muscle fibers and secondary motor neurons have aberrant axonal structure. Mutants skeletal muscle show also an abnormal structure with disorganized myofibers and reduced synaptic formation at the neuromuscular junction. They show a progressive impairment of locomotor behavior and have smaller jaws and abnormal cartilage patterning compared to controls.
Promotes matrix assembly (By similarity). Involved in the organization of skeletal muscles and in the formation of neuromuscular junctions (PubMed:33559681).
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.
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.
Olfactory receptor that is activated by amino acids that act as potent odorants in fish. Displays preference for acidic amino acids such as Glu over basic amino acids.
Belongs to the GHMP kinase family. GalK subfamily.
Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase (By similarity). May play a role as a transcriptional coregulator in various cellular pathways (By similarity). Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage, facilitating repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (By similarity). Mediates sumoylation of PARP1 in response to PARP1 trapping to chromatin (By similarity). Negatively regulates induction of interferon phi 1 (ifnphi1) mediated by mavs and ticam1/trif. Also inhibits ifnphi1-mediated activation of the interferon-stimulated genes (ISGs) pkz and cd40, and to a lesser extent rsad2 and isg15 (PubMed:22345667). May inhibit ticam1/trif-mediated activation of NF-kappa-B (PubMed:22345667).
Highly expressed in early development (6 hours to 24 hours post fertilization), with lower expression thereafter.
Highly expressed in spleen, liver, and brain. Expressed at lower levels in heart, intestine, kidney, gill, skin, and muscle.
Sumoylated. Lys-35 is the main site of sumoylation.
The LXXLL motif is a coregulator signature that is essential for transcriptional corepression.
Up-regulated in response to polyinosinic-polycytidylic acid (poly(I:C)), and interferon phi 1 (ifnphi1).
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.
Belongs to the bombesin/neuromedin-B/ranatensin family.
First detected at 12.5 hours post-fertilization (hpf) in dorsal presomitic mesoderm and in the neural keel, extending to the ventral somitic mesoderm during tail budding. At 16-19 hpf, restricted to the posterior end of the somitic mesoderm. Also expressed in the developing pectoral fins from 34 hpf, with progressive localization to the periphery.
Belongs to the Mediator complex subunit 12 family.
First detected at the anterior position of the embryo at the first somite stage. From the late segmentation and pharyngula periods, expressed in a region ventral to the forebrain, and in the midbrain, hindbrain, and spinal cord. Expressed in the prospective extraocular muscles, mesencephalic neurons residing along the tract of the posterior commissure and interneurons in the spinal cord.
May participate in the energy homeostasis regulation.
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 endoribonuclease YbeY 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.
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.
Expressed at 10 hours post-fertilization (hpf), reach peak levels at 48 hpf and is not detectable in adult tissues. Expressed during neurogenesis between 9 and 72 hpf and in ventral endoderm region where pancreatic progenitors originate.
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.
Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells.
Expressed in the dorsal region of the neural keel as somatogenesis proceeds before 25 hpf. At 25 hpf, expression is highest in the neural plate, in the brain including telencephalon, diencephalon, tectum and the rhombomere boundary. Highly expressed in lens, germinal ganglion, otic capsule and rhombomeres 2-7. Weakly expressed in trunk and tail. Expression is particularly high in otic capsule at 48 hpf.
May function as a homophilic adhesion molecule.
Plays a key role in meiotic progression by ensuring that sufficient numbers of processed DNA double-strand breaks (DSBs) are available for successful homology search, promoting synaptonemal-complex formation independently and playing key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint.
Possible role in the regulation of cell death.
May play a role in the trafficking of a subset of G-protein coupled receptors.
Binds specifically to the 3'-terminal U-tract of U6 snRNA.
Acts as a negative regulator of transcription.
Expressed zygotically from the tailbud stage.
Belongs to the DNA mismatch repair MutS family.
Component of the post-replicative DNA mismatch repair system (MMR).
Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.
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 complex I NDUFC1 subunit family.
Belongs to the proteasome subunit S1 family.
Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP).
Acts as a negative regulator of transcription. May function as a switch in neuronal development (By similarity).
Binds 2 divalent metal cations per subunit.
Deoxyribonuclease which catalyzes (in vitro) the decatenation of kinetoplast DNA, which are circular DNA catenated to each other, producing linear DNA molecules (PubMed:23187801). Plays an important role in chromosomal segregation and cell cycle progression during eye development probably via its DNA decatenation activity (PubMed:23187801).
Morpholino knockdown in the embryo results in an abnormal cell cycle progression, formation of polyploidy and aberrant chromatin structures (PubMed:23187801). Consequently, the morphants have disordered eye cell layers and significantly smaller eyes compared to the wild-type counterpart (PubMed:23187801).
Predominantly expressed in the eye during embryonic development.
May have a role in the processing of DNA double strand breaks (DSBs) prior to their repair by the non homologous end joining (NHEJ) pathway. Probably exhibits both exonuclease and endonuclease activity (By similarity).
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.
Interacts with RAC1. Interacts with CORO1C.
Morpholino knockdown in single-cell embryos does not lead to gross anatomical defects, but causes subtle defects in the migration of neural crest cells, so that cells populate also the pharyngeal pouch, instead of being restricted to pharyngeal arches.
Multifunctional protein that may affect its functions by regulating the activity of small GTPases, such as RAC1 and RALA. Required for normal progress through the cell cycle, both during interphase and during mitosis. Required for normal attachment of kinetochores to mitotic spindles. Required for normal organization of the microtubule cytoskeleton in interphase cells. Interferes with the activation of RAC1 by guanine nucleotide exchange factors. Prevents accumulation of active, GTP-bound RAC1, and suppresses RAC1-mediated reorganization of the actin cytoskeleton and formation of membrane protrusions (By similarity). Required for normal cellular responses to contacts with the extracellular matrix of adjacent cells, and for directional cell migration (PubMed:25074804).
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.
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.
Expressed by serotonergic neurons in anterior and posterior raphe.
Expressed in post-mitotic raphe serotonergic neurons. First detected at the 20 somites stage.
Functions as a transcriptional regulator. Functions in the differentiation and the maintenance of the central serotonergic neurons. May play a role in cell growth (By similarity).
It is uncertain whether Met-1 or Met-14 is the initiator.
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.
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. Plays an important role in the assembly of the N-DRC linker (By similarity). Plays dual roles at both the primary (or non-motile) cilia to regulate hedgehog signaling and in motile cilia to coordinate cilia movement. Required for proper slow muscle development and positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway (PubMed:21659505). Required for tether cilia motility which is essential for normal otolith formation and localization in the developing inner ear (PubMed:19043402).
Component of the nexin-dynein regulatory complex (N-DRC). Interacts with microtubules.
Maternal transcripts are ubiquitous throughout the embryo during early development. By the 12-somite stage, expression becomes concentrated in the developing ears and this persists through the 18- to 20-somite stage. Transcripts are also present in the brain, neural tube and pronephric ducts.
Morpholino knockdown results in attenuated Hedgehog (Hh) transcriptional responses and impaired early muscle development (PubMed:21659505). Morphants exhibit developmental abnormalities, abnormal ear development and defective cilia motility (PubMed:19043402).
Plays a role in neuronal and neurobehavioral development (PubMed:31623237). Required for normal expression of neuronal markers elavl3 and eno2 and neurobehaviors related to circadian rhythm and changes in light-dark conditions (PubMed:31623237).
Plays a role in regulating cardiac sodium current.
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.
Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Can bind to fibrinogen, fibronectin, laminin and type V collagen (By similarity).
Expressed both maternally and zygotically. Present at the gastrulation and post-segmentation stages.
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.
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.
Belongs to the protein-tyrosine phosphatase family. Receptor class 3 subfamily.
Belongs to the fibrillar collagen family.
Expressed dynamically in the notochord from late epiboly, spreading to the anterior notochord by 24 hpf, and then throughout the notochord by 30 hpf. Subsequently, notochordal expression becomes restricted to the distal tip of the tail by 48 hpf and is no longer detectable by 72 hpf. Also expressed throughout the floor plate and hypochord at 24 hpf, and in forming head cartilages and the first forming tooth.
May play a role during the calcification of cartilage and the transition of cartilage to bone (By similarity). Together with col27a1b, plays a role in development of the notochord and axial skeleton.
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).
Belongs to the immunoglobulin superfamily.
Expressed in the somites of the embryo in a wave along the anterior-posterior axis.
Junctional adhesion protein that mediates heterotypic cell-cell interactions to regulate different cellular processes (By similarity). During myogenesis, it is involved in myocyte fusion through the binding of jam2a on neighboring myocytes (PubMed:22180726).
Morpholino knockdown impairs myocyte fusion during myogenesis.
Disrupted formation of the primitive heart tube.
Induced at the marginal cells of the blastoderm at dome stage. During gastrulation stages, it is predominantly expressed in the extraembryonic yolk syncytial layer (YSL) with a dorsal-to-ventral gradient. Expression in the YSL is strongly detected just below the developing myocardial precursors and maintained throughout segmentation period. This expression continues through early somitogenesis. However, as somitogenesis proceeds, expression domains become evident in the somitic mesoderm and in the endoderm adjacent to the yolk extension. By 24 hpf, it is strongly expressed in a distinct compartment of the somites, in the endoderm, and in the heart.
Lipid transporter that specifically mediates export of sphingosine-1-phosphate (sphing-4-enine 1-phosphate, S1P) and sphinganine-1-phosphate, which play critical roles in regulating heart development (PubMed:19062281, PubMed:19074308). Mediates the export of S1P from cells in the extraembryonic yolk syncytial layer (YSL), thereby regulating myocardial precursor migration (PubMed:19062281, PubMed:19074308).
Binds 5 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound to the C2 domain.
Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca(2+) from intracellular stores (By similarity).
The C2 domain is a Ca(2+)-dependent membrane-targeting module.
The PH domain mediates interaction with the surface membrane by binding to PIP2.
Morpholino knockdown results in severe defects in embryonic development. Nearly all embryos display pericardial edema. Most embryos display abnormal body shape and size, defects in heart morphogenesis, impaired mobility, and die at about 7 dpf. The embryonic cardiac muscle and skeletal muscle show defects in the association of the actin-myosin myofibers with the myocyte membrane (PubMed:18174465). Likewise, morpholino knockdown results in defective angiogenesis, with abnormally short and thin vessels and very little blood flow (PubMed:21378273).
Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling (By similarity). Required for normal embryonic development, including normal heart morphogenesis and normal angiogenesis.
The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain.
The N-terminal region displays a ubiquitin-type fold and mediates interaction with membranes containing negatively charged phosphatidylinositol phosphate via a surface enriched in positively charged residues.
The PH domain binds phospholipids. Binds preferentially phosphatidylinositol-3,4,5-trisphosphate, and has lower affinity for phosphatidylinositol-4,5-bisphosphate (By similarity).
Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle.
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.
Inhibited by Co(2+), Zn(2+), Cd(2+) and Pb(2+) ions. Inactivated by Hg(2+) and Cu(2+) ions.
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a variety of xenobiotic and endogenous compounds, including 2-naphthol, hydroxychlorobiphenyls, dopamine and T3 (triiodo-L-thyronine).
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.
Belongs to the immunoglobulin superfamily. AMIGO 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. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes.
Core component of at least two putative endosomal tethering complexes, the homotypic fusion and vacuole protein sorting (HOPS) complex and the class C core vacuole/endosome tethering (CORVET) complex.
Disruption of the gene results in melanocyte pigmentation defects, decreased body length, and bladder defects associated with abnormalities in surfactant production or distribution, consistent with abnormalities of lysosome-related organelles. Mutant animals also have defects in the optokinetic response and eye movement control system, suggesting cerebellar dysfunction. Microglia from mutant fish show morphologic abnormalities, with larger or more numerous lysosomal compartments and increased expression of acidic lysosomal markers compared to controls.
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.
Forms either a homodimer or a heterodimer with a related family member.
Up-regulated in B cells in response to runx1.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily.
Required for ciliogenesis. Also plays a role in mitochondrial metabolism where it may modulate complex IV activity (By similarity).
Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion (By similarity). Cadherins contribute to the sorting of heterogeneous cell types, and thereby play an important role during embryonic development (PubMed:12091300). Required for normal neural tube morphogenesis. Required to allow mid- and hindbrain neurons to reach and maintain their appropriate positions within the neural tube by restricting neuronal motility within the embryonic mid- and hindbrain (PubMed:12091300).
Expression in the embryo is initially found in all deep cells but later becomes restricted to various epithelial and neuronal tissues. Found in discrete areas of cell-cell adhesion when epiboly is nearly completed. Expressed in adult brain, eyes and trunk.
Expression is first detected in the embryo during gastrulation.
Homodimer (via extracellular region). Can also form heterodimers with other cadherins (via extracellular region). Dimerization occurs in trans, i.e. with a cadherin chain from another cell.
Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. Calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1.
Belongs to the mitochondrion-specific ribosomal protein mL43 family.
May modify the assembly dynamics of microtubules, such that microtubules are slightly longer, but more dynamic.
Belongs to the glycoprotein hormones subunit beta family.
DNA polymerase II participates in chromosomal DNA replication.
Expressed both maternally and zygotically, from ova through to 48 hours post-fertilization. At the 10-somite stage, expressed in the paraxial mesoderm with an anterior expression limit at somite 5. At the 20-somite stage, expressed in the developing CNS with an anterior expression adjacent to the somite 2/3 boundary.
Belongs to the SLC34A transporter family.
Probable component of a E3 ubiquitin ligase complex.
Belongs to the enhancer of polycomb family.
Although related to the Ser/Thr protein kinase family, has no protein kinase activity and acts as a mannose kinase instead.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. STKL subfamily.
Protein O-mannose kinase that specifically mediates phosphorylation at the 6-position of an O-mannose of the trisaccharide (N-acetylgalactosamine (GalNAc)-beta-1,3-N-acetylglucosamine (GlcNAc)-beta-1,4-mannose) to generate phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-1,3-N-acetylglucosamine-beta-1,4-(phosphate-6-)mannose). Phosphorylated O-mannosyl trisaccharide is a carbohydrate structure present in alpha-dystroglycan (dag1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Only shows kinase activity when the GalNAc-beta-3-GlcNAc-beta-terminus is linked to the 4-position of O-mannose, suggesting that this disaccharide serves as the substrate recognition motif (By similarity).
Co-chaperone that binds to numerous proteins and promotes their interaction with Hsp70 and Hsp90.
Belongs to the transferase hexapeptide repeat family.
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).
Belongs to the TAF9 family. CENP-S/MHF1 subfamily.
Interacts with MPDZ. Interacts with ARRB2.
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 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.
Downstream effector of Rap required for cell adhesion and migration of neural crest precursors during development.
Interacts with RAP1A; in a GTP-dependent manner.
Knockdown results in multiple defects in neural crest-derived lineages such as cartilage, pigment cells, and enteric neurons.
Present at very low level in one-cell embryos, suggesting the presence of maternally deposited transcripts. Increases upon the onset of zygotic transcription (around the 1000-cell stage), eventually peaking at 72 hpf.
Ubiquitously expressed and enriched in the anterior part of the embryos.
Highly expressed in the olfactory rosette where it localizes to a subset of olfactory sensory neurons, mainly in the apical region of the neuroepithelium. Not detected in other tissues tested.
Probable pheromone receptor. Shows high specificity for 4-hydroxyphenylacetic acid. Activation of the receptor stimulates intracellular calcium release.
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.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.
Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me) and activates transcription via chromatin remodeling.
Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins (By similarity). The protease activity is required for proteolytic activation of ATG8 family 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). Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, by catalyzing delipidation of ATG8 proteins conjugated to phosphatidylserine (PS) (By similarity). ATG4D plays a role in the autophagy-mediated neuronal homeostasis in the central nervous system (PubMed:25875846).
Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins.
Morpholino knockdown of the protein results in neurodegeneration in the central nervous system (CNS) (PubMed:25875846). Neurodegeneration is characterized by severe visible malformations in the developing CNS in regions that correspond to the midbrain-hindbrain boundary, the cerebellum and the hindbrain region (PubMed:25875846).
Detected in the presumptive hindbrain and notochord from the 3-somite stage onwards (PubMed:22252497). Expression in notochord becomes restricted to the posterior as development proceeds (PubMed:22252497, PubMed:22609016). Shows particularly strong expression at the hindbrain-rhombomere 1 boundary during the 12-18 somite stages (PubMed:22252497, PubMed:22609016). Expressed in ventral spinal cord neurons and ventral somite cells at 24 hours post-fertilization (hpf) (PubMed:22252497). Becomes restricted to trunk-tail motor neurons at 32 hpf (PubMed:22252497, PubMed:22609016). Detected in eye primordia from the 10-somite stage onwards (PubMed:22252497). At 24 hpf, expression in eye is found in the ventral retina and optic stalk, and also weakly in dorsal retina (PubMed:22252497). Expressed in the eye choroid fissure and ganglion cells at 32 hpf (PubMed:22252497, PubMed:22609016). Also found in thalamus, posterior tuberculum, head mesenchyme, pectoral fins and pronephric duct at 32 hpf (PubMed:22252497).
Interacts (via PDZ domain 1) with kidins220b (via PDZ-binding motif).
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.
Interacts (via its IQ motifs) with calm.
Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity).
Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1).
Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation.
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).
Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.
Complex of five different subunits; alpha, beta, gamma, delta and epsilon.
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.
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.
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 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.
Phosphatase that acts on lipids with a phosphoinositol headgroup (By similarity). Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate (By similarity).
Belongs to the glycosyl hydrolase 20 family.
May be involved in the regulation of excitatory synapses.
Belongs to the ALG10 glucosyltransferase family.
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).
Expressed in germ cells, being predominant in previtellogenic oocytes in the ovary and in spermatocytes in the testis.
Belongs to the PIGG/PIGN/PIGO family. PIGO subfamily.
Belongs to the myo-inositol oxygenase family.
Expressed in the embryo from 2 to 72 hours post-fertilization (hpf) (PubMed:22345307). Expressed in the embryonic heart and somites at 14, 20 and 24 hpf (PubMed:22345307). Expressed in myocardial progenitors from 18 to 24 hpf (PubMed:22345307). Expressed in the otic vesicle at 14 hpf (PubMed:22345307).
Morpholino knockdown of the protein leads to death at 6 days post-fertilization (dpf) due to heart growth defects and absence of blood circulation, despite the presence of a beating heart (PubMed:22345307). Show reduced heart contractility from 30 hours post-fertilization (hpf), onwards (PubMed:22345307). Display defects in sarcomere organization from 33 hpf, onwards (PubMed:22345307). Show altered expression of key genes necessary for sarcomere formation (PubMed:22345307).
Multifunctional RNA-binding protein involved in the regulation of pre-mRNA splicing, mRNA stability and mRNA translation important for cell fate decision and differentiation. Plays a major role in pre-mRNA alternative splicing regulation. Mediates preferentially muscle-specific exon inclusion in numerous mRNAs important for striated cardiac and skeletal muscle cell differentiation. Binds to intronic splicing enhancer (ISE) composed of stretches of GU-rich motifs localized in flanking intron of exon that will be included by alternative splicing. Involved in embryonic stem cell (ESC) transition to cardiac cell differentiation by promoting pre-mRNA alternative splicing events of several pluripotency and/or differentiation genes. Plays a role in the regulation of mRNA stability and mRNA translation to which it is bound. Involved in myogenic differentiation by regulating myog levels. Binds to a huge amount of mRNAs (By similarity). Required for embryonic heart development, sarcomer and M-band formation in striated muscles (PubMed:22345307).
The RRM domain is necessary for mRNA stability and mRNA translation regulation.
Expressed throughout embryogenesis from the blastula sphere stage (4 hours post fertilization).
Guanine nucleotide exchange factor (GEF) for Ras family proteins.
May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.
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).
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.
Potential NADPH-dependent oxidoreductase.
Atypical Ras-like protein that acts as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more resistant to degradation.
Belongs to the small GTPase superfamily. Ras family. KappaB-Ras subfamily.
In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 13 and 65, which are replaced by Ala and Leu residues, respectively, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins.
Serves as substrate adapter subunit in an E3 ubiquitin ligase complex zyg11-cul2-elongin BC. Targets substrates bearing N-terminal glycine degrons for proteasomal degradation.
Expression is not detected before the 3-somite stage at 10-11 hours post-fertilization. Earliest expression is detected during mid-neurulation.
Forms homodimers and homotetramers in vitro. In mixtures with other intermediate filament proteins such as vimentin and alpha-internexin, preferentially forms heterodimers (By similarity).
Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). Required for brain and eye development.
Widely expressed throughout the developing nervous system at 24 hours post-fertilization (hpf). As development progresses, expression becomes restricted to proliferative zones of the developing and postembryonic central nervous system. In the peripheral nervous system, expressed in the cranial ganglia. Also expressed in mesodermal muscle precursor cells and in cranial mesenchymal tissue.
Binds 1 divalent metal cation per subunit.
Component of the EKC/KEOPS complex composed of at least TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes.
Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. OSGEP likely plays a direct catalytic role in this reaction, but requires other protein(s) of the complex to fulfill this activity.
Embryos display primary microcephaly, leading to early lethality (PubMed:29346415, PubMed:28805828). Marked apoptosis is observed in the brain (telencephalon) (PubMed:28805828). Fishes do not show a renal phenotype, possibly as a result of early lethality (PubMed:28805828).
Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.
Belongs to the sterol desaturase family.
May catalyze the formation of 25-hydroxycholesterol from cholesterol.
Component of a PRC1-like complex. Homodimer. Interacts with cbx2 (By similarity).
Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. In the PRC1 complex, it is required to stimulate the E3 ubiquitin-protein ligase activity of rnf2 (By similarity).
Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.
This protein is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc.
ADP-ribosylated by tankyrase tnks and tnks2. Poly-ADP-ribosylated protein is recognized by rnf146, followed by ubiquitination and subsequent activation of the Wnt signaling pathway.
Component of the beta-catenin destruction complex required for regulating ctnnb1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (By similarity). Controls dorsoventral patterning by down-regulating ctnnb1 to inhibit the Wnt signaling pathway and ventralize embryos (PubMed:30467143).
Interacts with hwa; leading to promote the tankyrase-mediated degradation of axin1.
Ubiquitinated by rnf146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway.
Belongs to the peptidase C65 family. Otulin subfamily.
Protein-lysine 6-oxidase that mediates the oxidation of peptidyl lysine residues to allysine in target proteins. Catalyzes the post-translational oxidative deamination of peptidyl lysine residues in precursors of elastin and different types of collagens, a prerequisite in the formation of cross-links between collagens and elastin. Can mediate oxidation of lysine residues that are acetylated. Also able to catalyze deacetylation of lysine residues (By similarity).
Weakly expressed at 30 hours post fertilization (hpf) in the ventral head mesenchyme, but not spatially restricted after this time-point.
May be a component of the protein machinery at the inhibitory synapses, probably acting as a scaffold.
Belongs to the eukaryotic-type N-acetylglucosamine kinase family.
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).
Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) is replaced by L-serine.
Catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) to alpha-ketoglutarate (By similarity). Also catalyzes the oxidation of other D-2-hydroxyacids, such as D-malate (D-MAL) and D-lactate (D-LAC) (By similarity). Exhibits high activities towards D-2-HG and D-MAL but a very weak activity towards D-LAC (By similarity).
Belongs to the DEAD box helicase family. DDX59 subfamily.
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.
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.
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.
May be implicated in the regulation of the transcription as a repressor of the transcriptional activity of E4TF1.
Functions in mitochondrial and peroxisomal division. Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism. The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes. While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L filaments to curl into closed rings that are probably sufficient to sever a double membrane (By similarity). May play a role in the circadian control of mitochondrial ATP production (By similarity).
Homotetramer; dimerizes through the N-terminal GTP-middle region of one molecule binding to the GED domain of another DNM1L molecule. Oligomerizes in a GTP-dependent manner to form membrane-associated tubules with a spiral pattern.
The GED domain folds back to interact, in cis, with the GTP-binding domain and middle domain, and interacts, in trans, with the GED domains of other DNM1L molecules, and is thus critical for activating GTPase activity and for DNM1L dimerization.
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 eukaryotic ribosomal protein eL34 family.
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 TRAFAC class YlqF/YawG GTPase family. LSG1 subfamily.
GTPase required for the XPO1/CRM1-mediated nuclear export of the 60S ribosomal subunit. Probably acts by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm (By similarity).
In contrast to other GTP-binding proteins, this family is characterized by a circular permutation of the GTPase motifs described by a G4-G1-G3 pattern.
Ubiquitin-protein ligase which is mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome.
Component of the IFT complex B, at least composed of ift20, ift22, hspb11/ift25, ift27, ift46, ift52, traf3ip1/ift54, ift57, ift74, ift80, ift81, and ift88. Interacts with ift88 (By similarity). Interacts with il13ra1. Binds to microtubules, traf3 and disc1 (By similarity). Interacts with map4 (By similarity).
Plays an inhibitory role on IL13 signaling by binding to IL13RA1 and recruits TRAF3 and DISC1 to the microtubules. Involved in the regulation of microtubule cytoskeleton organization. Is a negative regulator of microtubule stability, acting through the control of MAP4 levels (PubMed:26487268). Involved in ciliogenesis (By similarity).
Expressed in all tissues examined with highest levels in brain, eye, gut and heart.
May have a protective function during conditions of oxidative stress. May be involved in intracellular oxygen storage or transfer.
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.
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.
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.
A short peptide sequence (termed the Stachel sequence) in the C-terminal part of the extra-cellular domain (ECD) functions as a tethered agonist. Upon structural changes within the ECD, e.g. due to extracellular ligand binding or mechanical movements, this intramolecular agonist is exposed to the 7TM domain, triggering G-protein activation.
Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.
Detected from 30 hours post-fertilization to 4 days post-fertilization in Schwann cells of the posterior lateral line nerve.
Expressed in Schwann cells of the posterior lateral line nerve and in brain.
G-protein coupled receptor which is activated by type IV collagen, a major constituent of the basement membrane. Couples to G(i)-proteins as well as G(s)-proteins (PubMed:25118328). Essential for normal differentiation of promyelinating Schwann cells and for normal myelination of axons (PubMed:19745155). Also plays a role in inner ear development (PubMed:24067352).
Morpholino knockdown of the protein results in defects in semicircular canal formation inner ear (PubMed:24067352).
Plays an important role in heart development (PubMed:24082093). Necessary and sufficient for axon sorting by Schwann cells independently of the ADGRG6-CTF (PubMed:25695270).
Has peptide-independent ATPase activity.
Belongs to the eukaryotic GSH synthase family.
May act as a negative regulator of osteoclast differentiation.
Belongs to the eukaryotic ribosomal protein eL18 family.
Belongs to the carotenoid/retinoid oxidoreductase family. CrtISO subfamily.
Catalyzes the saturation of all-trans-retinol to all-trans-13,14-dihydroretinol. In addition, saturates the 7-8 double bond of all-trans-retinol to produce all-trans-7,8-dihydroretinol. Can also use vitamin A2 (all-trans-3,4-didehydroretinol) as a substrate, to produce all-trans-13,14-dihydro-3,4-didehydroretinol or all-trans-7,8-dihydro-3,4-didehydroretinol. May play a role in vitamin A metabolism.
Expressed in liver at 72 hours post-fertilization (hpf) and gut at 96 hpf. Not detected at earlier stages of development.
Belongs to the eukaryotic ribosomal protein eS19 family.
This promotes the activity of RNA polymerase II.
Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.
Homodimer or homotetramer; both forms have similar enzymatic activities.
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.
Activator of the canonical Wnt signaling pathway by acting as a ligand for lgr4-6 receptors, which acts as a key regulator of angiogenesis. Upon binding to lgr4-6 (lgr4, lgr5 or lgr6), lgr4-6 associate with phosphorylated lrp6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Acts both in the canonical. Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway. Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells (By similarity). Can also amplify Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3 (By similarity).
The FU repeats are required for activation and stabilization of beta-catenin.
Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination.
Mitochondrial amino-acid transporter (By similarity). Does not act as a serine transporter: not able to mediate transport of serine into mitochondria (By similarity).
Morpholino knockdown of the protein causes erythroid abnormality and global defects in respiratory-chain activity. Morphant embryos exhibit erythrocytes with enlarged nuclei containing open chromatin, consistent with maturation arrest. The nuclear/cytoplasmic ratio is increased nearly 3-fold. Anemia cannot be rescued neither by exogenous folate or vitamin B12 supplementation, nor by N-acetylcysteine treatment.
Dimers and collagen-tailed forms, in which catalytic tetramers are associated with anchoring proteins that attach them to the basal lamina or to cell membranes. In the collagen-tailed forms, subunits are associated with a specific collagen, COLQ, which triggers the formation of isoform T tetramers from dimers.
First detected in the trunk, in discrete regions of paraxial mesodermal segmental plate at 12 h of devel-opment (6-somite stage). In older embryos a weak diffused staining is found, even in unsegmented presomitic mesoderm. Expression, probably located in myoblasts, proceeds in a rostro-caudal sequence according to the state of differentiation of the somites. Initial narrow staining progressively enlarged in the differentiating somite. At all stages, the ventral part of anterior somites showed more intense staining than the dorsal part. In the posterior brain expression and activity appear after 14 h. At 24h, detected in all primary neurons in the brain. Expression in cranial ganglia can be detected in whole embryo until about 36h. Expressed also in a sensory system in anterior and posteriorlateral line ganglia as seen in the embryo at 24h. In addition the heart shows strong expression from its early morphogenesis.
No other isoforms exist. This protein corresponds to the T isoform in other species.
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft.
Belongs to the mitochondrion-specific ribosomal protein mL46 family.
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.
Expression starts 30 hours post-fertilization (hpf) and is restricted to the anterior and posterior lateral line ganglia and the otic sensory neurons. At 48 hpf expression becomes also evident in the trigeminal ganglia. At 96 hpf expressed throughout most of the central nervous system. Excluded from the dorsal forebrain except for the habenula nuclei.
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.
The histidine box domains are involved in binding the catalytic metal ions.
Essential for maintaining normal cardiac rhythm in the developing heart and for neonatal survival (PubMed:33597309). Inhibits potassium and calcium currents in the cardiomyocytes, this assists in timely action potential repolarization and thereby maintains normal cardiac rhythm (PubMed:33597309).
Mutants display highly specific cardiac arrhythmia and die by 15 days post-fertilization (dpf) (PubMed:33597309). Exhibit skipped ventricular beats, irregular beats and slower heart rate but their hearts are morphologically indistinguishable from wild-type counterparts (PubMed:33597309). Increased potassium and calcium currents observed in isolated cardiomyocytes (PubMed:33597309).
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.
Probable component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network.
Homodimer; homodimerization is essential for catalytic activity.
Hydroxylates a specific Asn residue in the C-terminal transactivation domain (CAD) of HIF-1 alpha. The hydroxylation prevents interaction of HIF-1 with transcriptional coactivators. Also hydroxylates specific Asn, Asp and His residues within ankyrin repeat domain-containing proteins.
Belongs to the GST superfamily. Pi family.
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Belongs to the phospholipase B-like family.
Somewhat implicated in the biogenesis of peroxisomes.
Belongs to the eukaryotic ribosomal protein eL21 family.
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.
Belongs to the eukaryotic mitochondrial porin family.
Belongs to the alkaline ceramidase family.
Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid.
Belongs to the XPG/RAD2 endonuclease family. XPG subfamily.
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), 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.
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.
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.
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 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).
Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles.
Expressed in skeletal muscle, heart, brain, spinal cord, and eye.
Lacks the cysteine which covalently binds the conotoxin GVIIJ. This cysteine (position 719) is speculated in other sodium channel subunits alpha to be implied in covalent binding with the sodium channel subunit beta-2 or beta-4.
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.
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 BRAWNIN.
Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c.
The uracil binding region known from UPRTases is missing.
Expressed in neurons in the ventral area of the interpeduncular nucleus (IPN) where expression often overlaps with spx1.
In embryos, widely expressed in nerve cells innervating the central nervous system (CNS) in regions including the olfactory bulb, midbrain tegmentum, preoptic region, dorsal thalamus, posterior tuberculum, postoptic commissure, hindbrain, and lateral margin of the spinal cord (PubMed:27315774). In the spinal cord, expressed in various neuronal cell types throughout the dorsoventral axis, including motor neurons and interneurons (PubMed:27315774). In the postoptic commissure, anterior commissure, hypothalamus and pituitary gland, expression overlaps with gal (PubMed:27315774). In larvae, expressed in nerve cells in the dorsal spinal cord where expression often overlaps with spx1 (PubMed:30903017).
Receptor for the hormone galanin (PubMed:24517231). Receptor for the hormones spexin-1 and spexin-2 (PubMed:24517231, PubMed:31474838).
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.
Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation (By similarity). Also plays a role in primitive hematopoiesis, possibly by affecting the expression of genes critical for hematopoiesis.
Strongly expressed in the eye, gill, kidney, spleen, muscle, ovary and testis and weakly in the heart, liver, and gut. Expressed in the brain and lateral mesoderm at 12 hours post-fertilization (hpf).
The KA1 domain mediates binding to phospholipids and targeting to membranes.
From 28 hours post-fertilization (hpf) onward, embryos show an anterior-posterior gradient of pigmentation defects. While the head is fully pigmented, more posterior regions are decreasingly pigmented until midtrunk levels, where pigmentation is not detectable. Melanophores are present at midtrunk levels and migrate correctly, but are not properly pigmented. Embryos show severe reduction in pigmentation and widespread degeneration from 48 hpf onward. Failure to form perinotochordal basement membrane (PBM), without the loss of laminin immunoreactivity. Embryos are significantly shorter, because the notochord cells fail to differentiate and the notochord fails to lengthen properly. Vacuoles fail to inflate fully. Many notochord cells die by apoptosis. In 32 hpf embryos the endoplasmic reticulum is abnormally swollen and filled with a relatively electron dense material and the Golgi complex is fragmented into large vesicles throughout the cytoplasm. PBM is thin, disorganized and essentially lacks the medial layer. However, cells have a distinctive inner layer.
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 VPS10-related sortilin family. SORL1 subfamily.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type 1 subfamily.
Central scaffolding component of the centrioles ensuring their 9-fold symmetry (PubMed:21273447). Required for centrosome biogenesis and duplication: required both for mother-centriole-dependent centriole duplication and deuterosome-dependent centriole amplification in multiciliated cells (By similarity).
Nine homodimers form a cartwheel structure with an internal diameter of 23 nM and radial spokes connecting to the microtubule triplets.
The 35 nM long coiled-coil domain mediates homodimerization while the globular N-terminus links the dimers at an angle of 40 degrees to form the inner ring.
Belongs to the TRAPP small subunits family. Sedlin subfamily.
At 16 and 24 hpf, restricted to muscle precursor cells in somites. Also detected at 48 hpf.
Component of the BCR(KLHL40) E3 ubiquitin ligase complex.
Expressed in skeletal muscle. Detected in the eye at much lower levels.
Morpholino knockdown of the protein results in a curved trunk and small head at 48 hpf. Morphants show disruption of skeletal muscle patterning with an irregular, wavy appearance of the striated myofibers and extensive gaps between the myofibers. Myofibers show disorganized and irregular patterns with small aggregates of alpha-actinin, suggesting nemaline bodies. Animals exhibit sporadic muscle tremor and coordinated swimming is not observed.
ubstrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex (By similarity). Required for skeletal muscle development (PubMed:23746549).
At the 10-somite stage, expressed in the paraxial mesoderm with an anterior expression limit at somite 7. At the 20-somite stage, expressed in the developing CNS with an anterior expression limit adjacent to somite 4.
Belongs to the universal ribosomal protein uL5 family.
Belongs to the cytochrome c oxidase subunit 3 family.
Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).
Belongs to the glycosyltransferase 49 family.
Beta-1,4-glucuronyltransferase involved in O-mannosylation of alpha-dystroglycan (DAG1) (PubMed:23359570). Transfers a glucuronic acid (GlcA) residue onto a xylose (Xyl) acceptor to produce the glucuronyl-beta-1,4-xylose-beta disaccharide primer, which is further elongated by LARGE, during synthesis of phosphorylated O-mannosyl glycan (By similarity). Phosphorylated O-mannosyl glycan is 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). Required for axon guidance; via its function in O-mannosylation of alpha-dystroglycan (DAG1) (By similarity).
Muscular defects and reduced alpha-dystroglycan (dag1) glycosylation.
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 eukaryotic ribosomal protein eL13 family.
Component of the 60S large ribosomal subunit (LSU).
Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. As part of the LSU, it is probably required for its formation and the maturation of rRNAs.
Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction.
Belongs to the universal ribosomal protein uL23 family.
By dhama/boz downstream of canonical wnt-signaling.
Expressed in embryonic endothelial and blood lineages. From late-blastula stage, expression is restricted to the dorsal marginal region of the extraembryonic yolk syncytial layer (YSL). By the onset of gastrulation, expressed in the entire dorsal half of the YSL. Post-gastrulation, expression appears in both anterior and posterior lateral plate mesoderm by the 3-somite stage. Posteriorly, expression is in the intermediate cell mass (ICM), which contains both endothelial and blood precursors. Subsequently expressed in the developing endothelial cells including the endocardium until the onset of circulation (24 hpf) and disappears completely by 30 hpf, at which point expression is seen in the thyroid and liver primordia. Also expressed in the developing biliary tree and pancreas.
Recognizes the DNA sequence 5'-ATTAA-3' (By similarity). Transcriptional repressor. Regulates the differentiation of both endothelial and blood cells. Plays a role in embryonic dorsoventral patterning by regulating bmp expression. May establish anterior identity. Functions in the embryo to regulate liver development. Functions extraembryonically to generate organ chirality.
Belongs to the fatty acid desaturase CarF family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Glycine N-methyltransferase family.
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. PSMC4 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.
First detected at the shield stage of gastrulation in the involuting mesendoderm with levels being highest in the paraxial mesoderm and decline laterally to become undetectable in the ventral mesoderm. Expression spreads in the hypoblast towards the animal pole and converges dorsally. At the tail bud stage (9.5 hpf), transcripts are seen in adaxial cells flanking the future notochord and in the presomitic mesoderm (PSM). During early somitogenesis, expression also extends into the future head, in two stripes continuous with the adaxial cells. Expression continues around the developing eye, presomitic mesoderm (PSM), trunk adaxial cells and somites. In late somatogenesis, expression in the presumptive pronephric primodia lateral to the second and third somite. In the early pharyngula stage, expressed in the perioptic mesoderm. Expression continues in the PSM and adaxial cells in the tail.
Expression is limited to late stages of embryogenesis. First detected at 48 hours of development and restricted to regions of ongoing chondrogenesis. Expression is observed in the ethmoid plate and the trabeculae cranii of the neurocranium as well as in some presumptive cartilage cells of the pharyngeal arches. Expression is furthermore observed in the forming cartilage of the pectoral fins. At 72 hours of development, accumulates in the ceratobranchial and basibranchial parts of the gill arches.
May function as an inhibitor of bone morphogenetic proteins (BMP) signaling during later stages of development including late phases of dorsoventral patterning, to refine the early pattern set up by the interaction of chordino and BMP2/4. Not involved in organizer function or early phases of dorsoventral pattern formation.
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.
Acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit.
Associates with pre-60S ribosomal particles.
Homodimer; disulfide-linked, also forms higher order oligomers (By similarity). Interacts with mrap2a; decreasing ligand-sensitivity. Interacts with mrap2b; increasing ligand-sensitivity and generation of cAMP.
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).
Component of the chromatin-remodeling INO80 complex.
Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.
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.
Positively regulates dimethylation of two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA.
May play a role in anterograde transport of membrane proteins from the endoplasmic reticulum to the Golgi.
E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC). Regulates cell movements during gastrulation by acting downstream of fz7 to antagonize the frizzled-signaling pathway (By similarity).
Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively.
Barely detectable during embryogenesis at control temperatures. Distributed throughout the cytoplasm of early developing myocytes at 24 hours post fertilization (hpf).
Homodimer (By similarity). Interacts with unc45b and myosin.
Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (By similarity). Plays a key role in slow and fast muscle development in the embryo. Plays a role in myosin expression and assembly (PubMed:10364427, PubMed:17586488, PubMed:18182494, PubMed:18256191).
Strongly expressed in the early embryos within the somitic slow muscle progenitors, the adaxial cells that lie on either side of the notochord but not the notochord. Also expressed during the early differentiation of fast fibers. Detected in developing cardiac muscles and pectoral fin primordia. Not detected in mature muscle fibers.
Up-regulated by heat shock in embryos and larvae with highest levels of expression in 3 day old larvae.
Involved in the Hedgehog (Hh) signaling pathway, is essential for normal ciliogenesis (PubMed:29263200). Regulates the proteolytic processing of gli3 and cooperates with the transcription factor emx1 in the induction of downstream Hh pathway gene expression and gonadotropin-releasing hormone production. WDR11 complex facilitates the tethering of Adaptor protein-1 complex (AP-1)-derived vesicles.
Morpholino knockdown causes microphtalmia, microcephaly, melanocyte disorganization, curved body axis, motility defects and narrow trunk. Morphants also exhibit aberrant head cartilage formation and cranial-facial dysmorphology.
Acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyzes the transfer of UDP-D-xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan (By similarity). Participates in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (PubMed:27130732).
Embryos display mild to severe hydrocephalus and significantly reduced eye size, reminiscent of pathological defects in Walker-Warburg syndrome.
Expressed throughout early embryonic development.
Choline-specific glycerophosphodiesterase that hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and contributes to supplying choline to the cells. Has a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. In vitro, hydrolyzes only choline-containing lysophospholipids, such as sphingosylphosphorylcholine (SPC), platelet-activating factor (PAF) and lysoPAF, but not other lysophospholipids.
Belongs to the fructosamine kinase family.
Belongs to the AspA/AstE family. Aspartoacylase subfamily.
Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
Expressed in the ovary, where it localizes to nuage and to the Balbiani body (PubMed:30086300). Maternally provided and localized to the germ plasm in 4-cell stage embryos (PubMed:30086300). 24 hours post-fertilization, restricted to primordial germ cells, where it localizes to nuage (a peri-nuclear protein-RNA aggregate that associates closely with mitochondria) (PubMed:30086300).
Interacts (via Tudor domain) with buc (when dimethylated on arginine residues); and may be responsible for recruitment of different protein complexes to germ plasm.
Knockout oocytes exhibit significant defects in germ cell development, leading to reduction in primordial germ cell number in the offspring, irrespective of the genotype of the father (PubMed:30086300). Barely affects piRNA populations (PubMed:30086300).
The tudor domains recognize and bind to proteins with dimethylated arginine or lysine residues (Probable). Plays an important role in the protein functions through its direct binding to the target proteins (Probable).
Tudor domain-containing protein involved in germ cell development, more specifically the formation of chromatoid body (during spermiogenesis), Balbiani body (during oogenesis), germ plasm (upon fertilization), and for proper miRNA expression and spliceosome maturation (By similarity) (PubMed:30086300). Required for Balbiani body and germ plasm formation and mobility through interaction with dimethylated arginines in the prion-like protein Bucky ball (buc) (PubMed:30086300). Coordinates transcript deposition into future primordial germ cells (PubMed:30086300). Interacts with known germ plasm mRNAs such as vasa, dazl, nanos3 and hook2 (PubMed:30086300).
Degraded following binding to N(6)-methyladenosine methylated DNA (m6A).
Probable protease (By similarity). Acts as a sensor of N(6)-methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA, leading to its degradation (By similarity).
The RAMA domain recognizes and binds N(6)-methyladenosine methylation on DNA (m6A).
The GINS complex plays an essential role in the initiation of DNA replication.
Belongs to the helicase family. RecQ subfamily.
Detected in posterior lateral mesoderm, head mesenchyme and the intermediate cell mass in embryos 24 hours after fertilization.
Involved in transcriptional regulation. Represses the transcription of a number of genes. Required for primitive and definitive hematopoiesis during embryonic development.
Knock-down of the znf148 mRNA disrupts both primitive and definitive hematopoiesis, but does not affect primary blood vessel formation. Most embryos die before four days after fertilization.
Detected at 6-7 hours post-fertilization (hpf). Levels increase after 10 hpf and highest expression is seen at 24 hpf.
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 (PubMed:16581006). Acts as component of the EARP complex that is involved in endocytic recycling (By similarity).
Larvae are morphologically indistinguishable from wild-type sibling larvae, but their absorption of lipids is severely impaired.
Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA.
Homodimer; dimerizes via the coiled coil domain. Interacts with the MRN complex; the interaction links DNA sensing to resection (By similarity). Interacts with samhd1 (By similarity).
SNARE that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER.
Belongs to the Integrator subunit 3 family.
Belongs to the multiprotein complex Integrator. Component of the SOSS complex, composed of soss-b (soss-b1/nabp2 or soss-b2/nabp1), soss-a/ints3 and soss-c/inip.
Component of the Integrator complex. The Integrator complex is involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing (By similarity).
Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. The SOSS complex associates with single-stranded DNA at DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs). In the SOSS complex, it is required for the assembly of the complex and for stabilization of the complex at DNA damage sites (By similarity).
Autophosphorylated on tyrosine residues. Phosphorylated tyrosine residues are important for interaction with specific binding partners (By similarity).
Defects in the number and distribution of melanocytes.
Expressed in cells of the neural crest-melanocyte lineage. In the embryo, also expressed in mesodermal cells that give rise to hematopoietic precursors, notochord, neural crest-derived cells of the branchial arches, pineal gland, retina and mechanoreceptive sensory cells of lateral line neuromasts. Not detected in primordial germ cells or larval gut.
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine kitlg/scf and plays a role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, and in mast cell development, migration and function. Required for the migration of cells in the melanocyte lineage and the survival of embryonic melanocytes. Required for the differentiation of some, but not all, melanocytes. Not essential for hematopoiesis or primordial germ cell development.
Ubiquitinated. Rapidly ubiquitinated after autophosphorylation induced by kitlg/scf binding, leading to internalization and degradation.
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).
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.
Belongs to the glycosyl hydrolase 39 family.
Interacts with FGFR1 and FGFR2. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.
Plays an important role in the regulation of cell proliferation and cell differentiation. Required for normal regulation of the hair growth cycle. Functions as an inhibitor of hair elongation by promoting progression from anagen, the growth phase of the hair follicle, into catagen the apoptosis-induced regression phase.
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.
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.
Belongs to the gamma-glutamylcyclotransferase family.
May contribute to degradation of proteins cross-linked by transglutaminases by degrading the cross-link between a lysine and a glutamic acid residue. Catalyzes the formation of 5-oxo-L-proline from L-gamma-glutamyl-L-epsilon-lysine.
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 (By similarity).
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.
Belongs to the cytochrome c oxidase VIIa family.
Belongs to the mitochondrion-specific ribosomal protein mS23 family.
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).
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 protein arginine deiminase family.
Catalyzes the deimination of arginine residues of proteins.
Belongs to the universal ribosomal protein uS14 family.
Adapter protein that may provide a link between cell surface epidermal growth factor receptor and the MAPK/ERK signaling pathway. May promote cell proliferation (By similarity).
Belongs to the peroxisomal targeting signal receptor family.
Binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import.
Belongs to the Integrator subunit 8 family.
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 (By similarity).
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 glycosyltransferase 22 family. PIGB subfamily.
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the third alpha-1,2-mannose to Man2-GlcN-acyl-PI during GPI precursor assembly (By similarity).
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.
Expressed at low levels in brain, eye and muscle.
Morpholino knockdown of the protein results in reduced head and eye size and a ventrally curved body. No significant effect on formation of craniofacial cartilage. Formation of ceratohyal cartilage is disrupted with an abnormal angle relative to wild-type. Morphogenesis of the developing neural tube is abnormal, with a smaller angle between the walls of the hindbrain neuroepithelium at 24 hours post-fertilization (hpf). Retinal development is significantly delayed; no retinal ganglion cells (RGCs) are detected at 30 hours hpf and reduced numbers are found at 60 hpf. Cilium length in Kupffer's vesicle is significantly reduced. Double morpholino knockdown of marcksl1a and marckls1b results in a more pronounced developmental delay in the retina.
Belongs to the aldo/keto reductase family. Glutamate--cysteine ligase light chain subfamily.
Heterodimer of a catalytic heavy chain and a regulatory light chain.
Belongs to the protein phosphatase inhibitor 1 family.
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).
Reduced cerebellar and forebrain volume. The phenotype of these animals resemble that seen in those after bmi1 knockdown, supporting a link between chmp1a and bmi1. In chmp1a knockdown models, the internal granule and molecular layers were more severely affected than the Purkinje cells, which are consistent with the relatively preserved folia observed in humans with CHMP1A mutations.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.
Expressed in the vegetal cortex of the oocyte. Expressed uniformly in the embryo. Expressed in the vegetal pole at 0.08 hour post-fertilization (hpf). Expressed in the lens fiber cells at 24 hpf and in the blastodisc of the zygote at 30 hpf.
RNA-binding protein implicated in the regulation of several post-transcriptional events. May be involved in mRNA translation activation and stability (By similarity). Involved in the regulation of muscle-specific splicing of alpha actinin pre-mRNAs via the binding to the UR-repeat element (URE) at the branch point of the non-muscle (NM) exon.
Belongs to the trans-sulfuration enzymes family.
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.
TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation.
Essential component of glycosylphosphatidylinositol-mannosyltransferase 1 which transfers the first of the 4 mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis.
Converts big endothelin-1 to endothelin-1.
Heterohexamer; composed of 3 copies of TIMM8A and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22 (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 TIMM8A 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 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).
Belongs to the proteasome subunit S9 family.
Component of the lid subcomplex of the 19S proteasome regulatory particle complex (also named PA700 complex). The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits (By similarity).
Component of the lid subcomplex of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. In the complex, psmd11a is required for proteasome assembly (By similarity).
Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. May play a role in the prevention of cell senescence acting as a regulator of mitochondrial quality control.
The RING-CH-type zinc finger domain is required for E3 ligase activity.
Belongs to the actin-binding proteins ADF family.
Initially expressed during early gastrulation at 6 hours post-fertilization (hpf) with expression increasing from 8 hpf onwards.
Belongs to the homogentisate dioxygenase family.
Involved in the tethering of the SIN3 complex to core histone proteins.
Belongs to the 2-oxoacid dehydrogenase family.
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2).
Contributes to protect fish blood from freezing at subzero sea water temperatures. Lowers the blood freezing point. Binds to nascent ice crystals and prevents further growth.
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER).
Belongs to the multiprotein complex Integrator. Component of the SOSS complex, composed of soss-b (soss-b1/nabp2 or soss-b2/nabp1), soss-a/ints3 and soss-c/inip (By similarity).
Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. The SOSS complex associates with single-stranded DNA at DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) (By similarity).
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.
Belongs to the bacterial ribosomal protein bL12 family.
First detected in the posterior tail bud at around 16.5 hours post-fertilization (hpf), expression continuing through to 36 hpf. Expressed in the developing fin fold and neural tube from 48-72 hpf.
Expressed in photoreceptor cells of the outer nuclear layer of the retina and in the pinal gland.
Expressed in the retina 4 days post-fertilization (hpf).
Potential calcium-dependent cell-adhesion protein.
Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats.
Belongs to the POU transcription factor family. Class-7 subfamily.
Involved in early development of embryos, especially in the process of gastrulation. May play an important role in establishing and specifying rhombomeric segments. Seems to be required to maintain the cells in a highly undifferentiated state. In contrast to POU2, T-POU2 lacks DNA-binding activity because of its incomplete pou domain structure. Overexpression of POU2 does not have any effect on development, whereas overexpression of t-POU2 causes developmental retardation or arrest before gastrulation.
Maternally expressed. Present from the one-cell stage to the gastrula stage. Present in all blastomeres until the midblastula stage. The expression is restricted to the epiblast during gastrulation, and to the neural plate after gastrulation. In the adult, expression is limited to the ovary.
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 nucleoporin interacting component (NIC) family.
Mutants can be recognized on day 2 of embryogenesis by the presence of necrotic cells in the tectum and eyes. Dye mutants die on day 5 of development.
Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance.
Belongs to the glycosyltransferase 18 family.
May play a role in the regulation of centrosome and Golgi apparatus positioning.
S-adenosyl-L-methionine-dependent methyltransferase.
Belongs to the IMPDH/GMPR family. GuaC type 1 subfamily.
Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides.
Belongs to the class-II fumarase/aspartase family. Fumarase subfamily.
Catalyzes the dehydration of L-malate to fumarate. Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by-product of the urea cycle and amino-acid catabolism (By similarity). Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ). In response to DNA damage translocates to the nucleus and accumulates at DNA double-strand breaks (DSBs): acts by catalyzing formation of fumarate (By similarity).
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.
Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (By similarity). Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable).
There are 2 substrate-binding sites: the catalytic A site, and the non-catalytic B site that may play a role in the transfer of substrate or product between the active site and the solvent. Alternatively, the B site may bind allosteric effectors.
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.
Probably involved in the biogenesis of the COX complex.
Belongs to the protein kinase superfamily. BUD32 family.
Homodimer (By similarity). Heterodimer; with a rar molecule (By similarity). Binds DNA preferentially as a rar/rxr heterodimer (By similarity). Heterodimerizes with rarga.
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for rxrs is 9-cis retinoic acid (By similarity).
Shows uniform expression from the blastula to mid-gastrula stages. At 12 hours post-fertilization (hpf), expressed ubiquitously but more weakly. At 24 hpf, restricted to the ventral diencephalon, pharangeal endoderm and trunk and tail mesoderm; mesoderm expression is in medial cells of each somite along the dorsoventral axis, forming stripes. At 48 hpf, expressed in forebrain, eye, midbrain and anterior hindbrain.
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.
Chimeric cDNA. Contains sequence from chromosome 22 in the C-terminus.
Strongly inhibited by the divalent metal cations Fe(2+), Hg(2+), Co(2+), Zn(2+), Cu(2+) and Cd(2+).
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a variety of xenobiotic and endogenous compounds, including dopamine, T3 (triiodo-L-thyronine), T4 (thyroxine), flavonoids, isoflavonoids, and other phenolic compounds.
Belongs to the class I-like SAM-binding methyltransferase superfamily. BUD23/WBSCR22 family.
Morpholino knockdown of the protein increases jaw cartilage disorganization, decreases the size of brain structures and the lateral area and convolution of proximal renal tubules at 4 days post-fertilization (dpf) (PubMed:28264986). Embryos with CRISPR-induced cep55l null mutations display altered craniofacial patterning and atrophy of the proximal renal tubules (PubMed:28264986).
Plays a role in mitotic exit and cytokinesis. Recruits PDCD6IP and TSG101 to midbody during cytokinesis. Required for successful completion of cytokinesis. Not required for microtubule nucleation (By similarity). Plays a role in the development of the brain and kidney (PubMed:28264986).
Belongs to the complex I NDUFA8 subunit family.
At 2 dpf, strongly expressed in the developing eyes, as well as midbrain and hindbrain regions. In 3 dpf larvae, expressed in the upper rhombic lip. At 3 dpf, expression in the retina is weak and becomes spatially restricted in the inner nuclear layer. Weakly expressed in the forebrain region.
Expressed in the brain, in cerebellar-like structures, including Purkinje cells.
Morpholino knockdown of the protein results in a reduced cerebellar area and smaller optic tecta area compared to control larvae. At 3 dpf, transgenic larvae present with a significantly decreased size of Purkinje and granule cell layers compared to controls.
Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) (By similarity). Required for proper cerebellum development (PubMed:29656859).
Belongs to the DEAD box helicase family. DEAH subfamily. FANCM sub-subfamily.
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.
Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates, such as CGAS, HRAS and LCK.
Probably maternally supplied, the zygotic expression becomes significative at 4 hpf.
Expressed in the anterior neural keel and later in the preoptic area and optic stalk.
First detected in the anterior neural keel at 7 somites. By 12 somites, expression is more robust in the medial forebrain and forming eyes. By 16 somites, expression remains within the optic stalk and is predominantly restricted to tissue ventral to the optic stalk and ventral preoptic area. In addition to optic stalk and ventral preoptic area, weakly expressed in the ventral retina near the choroid fissure region by 24 hpf (hours post-fertilization). At 48 hpf, expression remains prominent in the ventral preoptic area but is much reduced in the choroid fissure and optic stalk.
Transcription factor that is required for closure of the choroid fissure and together with Vax2 is required for optic nerve differentiation and to limit retinal development to the optic cup.
Citrate synthase-lysine methyltransferase activity is inhibited by S-adenosylhomocysteine (AdoHcy) and oxaloacetate (OAA).
Protein-lysine methyltransferase that selectively trimethylates citrate synthase (CS) in mitochondria. Seems to conduct trimethylation in a highly distributive manner rather than in a processive manner, and thus introduces a single methyl group per binding event.
Fishes shown a severe reduction in the size of the pectoral fins.
Not clearly detected before 12 and 14 hpf. At 18 and 24 hpf, detected in the otic vesicle, telencephalon, and caudal fin. At 30 and 36 hpf, expressed in the otic vesicle, caudal fin, branchial arch, pectoral fin bud, and pituitary gland.
Plays a crucial role in pectoral fin bud outgrowth.
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.
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 pseudouridine synthase RluA family.
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.
Involved in regulation of actin and microtubule organization. Part of a WAVE complex that activates the Arp2/3 complex (By similarity).
Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.
Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.
Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs.
Monomer. Interacts with ANKRD16; the interaction is direct.
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.
Expressed maternally (PubMed:30467143). Transcripts are first distributed evenly in blastomeres (PubMed:30467143). During the early cleavage period, transcripts in the vegetal pole region are transported toward the animal pole from one side of the yolk (PubMed:30467143). Transcript levels decrease 2 hours post fertilization (PubMed:30467143). The protein is enriched in a small region of blastomeres, in which the dorsal organizer will form (at protein level) (PubMed:30467143).
Interacts with axin1; leading to promote the tankyrase-mediated degradation of axin (PubMed:30467143). Interacts with axin2; leading to promote the tankyrase-mediated degradation of axin (PubMed:30467143).
Key maternal determinant of the dorsal organizer and body axis formation in vertebrates that acts by promoting stabilization of beta-catenin (ctnnb1) (PubMed:30467143). Localizes on the plasma membrane of the future dorsal blastomeres in early blastulas and binds to and promotes the tankyrase-mediated degradation of axin (axin1 and axin2) (PubMed:30467143). Axin degradation results in stabilization and nuclear translocation of beta-catenin (ctnnb1) for activating organizer-specific target gene expression (PubMed:30467143).
Maternal mutant embryos lack the body axis: embryos develop normally during cleavage and blastula stages but lack the embryonic shield at the shield stage (PubMed:30467143). The dorsal organizer is absent and embryos fail to form the head and other dorsoanterior tissues (PubMed:30467143).
Was named huluwa after the Chinese animation TV series huluwa, known as Calabash Brothers in western countries.
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 H3 and H4 trimethylation marks H3K9me3 and H4K20me3.
Monomer. Homodimer. The monomeric form has a higher catalytic activity.
Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes. Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (By similarity).
Postsynaptic recycling endosome membrane
Probably maternally supplied, the zygotic expression is detected early during development at the 512-cell stage but decreases after 7.5 hpf.
Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions. May also function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock (By similarity).
Expressed in the ventricular zone of the brain at 28 hours post fertilization (hpf) and, at lower levels, in the posterior cardinal vein and in the posterior intermediate inner cell mass. At 48 hpf, still detected in the vein. At 28 and 48 hpf, expressed at low levels in a region near the dorsal aorta.
Part of a complex with MAP2K3, MAP3K3 and RAC1. Binds RAC1 directly and independently of its nucleotide-bound state (By similarity). Interacts with HEG1 and KRIT1; KRIT1 greatly facilitates the interaction with HEG1.
The C-terminal region constitutes an independently folded domain that has structural similarity with the USH1C (harmonin) N-terminus, despite very low sequence similarity.
The heart chambers in mutant animals are huge, constituted of a monolayered myocardium lined by endocardium.
Belongs to the eukaryotic ribosomal protein eL20 family.
Belongs to the POU transcription factor family. Class-3 subfamily.
Detected after completion of the gastrula period. Maximal expression after 1 to 2 days of development.
Predominantly expressed in the central nervous system, with strong expression in the cerebellum.
Transcription factor that may play important roles in patterning the embryonic brain.
Belongs to the 5'-3' exonuclease family.
At 24 hours post-fertilization (hpf), detected in the somites, tail bud region adjacent to the fin fold, pectoral fin buds and the head. A similar expression pattern is observed at 48 hpf, although levels are reduced. By 120 hpf, expression is almost completely undetectable.
Morpholino knockdown of the protein has no visible phenotype. Morpholino knockdown in animals homozygous for the c14 allele suppresses the c14 phenotype.
Belongs to the polyprenol kinase family.
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 MsrA Met sulfoxide reductase family.
Implicated in a number of cellular processes, including proliferation, differentiation, caspase-dependent and caspase-independent apoptosis, suppression of transformation (tumor suppressor), inhibition of protein phosphatase 2A, regulation of mRNA trafficking and stability, and inhibition of acetyltransferases as part of the INHAT (inhibitor of histone acetyltransferases) complex.
Component of the signal peptidase complex (SPC) composed of a catalytic subunit sec11a 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 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).
Belongs to the glycosyl hydrolase 85 family.
May play a role in the regulation of insulin-dependent IRS1 tyrosine phosphorylation in adipocytes.
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. Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT).
Belongs to the type II pantothenate kinase family.
In the N-terminal section; belongs to the type II pantothenate kinase family.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.
Morpholino knockdown causes severe defects in the development of the central nervous system, including enlarged hindbrain ventricles resembling a brain ventricular hydrocephalus-like edema phenotype (PubMed:21349154). Increased cell proliferation of glial fibrillary acidic protein (GFAP)-positive cells in the developing central nervous system (PubMed:21349154).
Probable hormone (By similarity). Required for the proper formation of the central nervous system by attenuating cell proliferation during development (PubMed:21349154).
Belongs to the glycosyltransferase 2 family.
Component of the dolichol-phosphate mannose (DPM) synthase complex.
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.
Belongs to the prickle / espinas / testin family.
Belongs to the aggrecan/versican proteoglycan family.
Adapter protein for the cul3 E3 ubiquitin-protein ligase complex. Promotes the export of zbtb16/plzf from the nucleus to the cytoplasm and targets zbtb16/plzf for ubiquitination and degradation. Up-regulates neurog1 expression and antagonizes zbtb16/plzf, to promote neurogenesis (By similarity).
In embryos, expressed in the cranial ganglia.
Interacts with cul3. Interacts (via BTB domain) with zbtb16/plzf (By similarity).
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 CoA-transferase III family.
Catalyzes the conversion of 4-hydroxyphenylpyruvic acid to homogentisic acid, one of the steps in tyrosine catabolism.
RNA-binding protein involved in pre-mRNA splicing.
Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptors and dopamine receptors. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Modulates the activity of potassium channels that are activated in response to G protein-coupled receptor signaling.
Belongs to the iodothyronine deiodinase family.
Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine).
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 (By similarity). Plays a role in the embryonic development.
Morpholino knockdown of the protein causes growth retardation, as evidenced by small fins, abnormal morphogenesis of the tail, and loss of heartbeat. Pericardial effusion was evident in 5-day-old morphant larvae.
Belongs to the DNA polymerase type-B-like family. GLD2 subfamily.
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. May not play a role in replication-dependent histone mRNA degradation (By similarity).
Binds oxysterols in a pocket within their transmembrane domains and interacts with SCAP via transmembrane domains 3 and 4.
Interacts with scap; interaction is direct and only takes place in the presence of sterols; it prevents interaction between scap and the coat protein complex II (COPII). Associates with the SCAP-SREBP complex; association is mediated via its interaction with scap and only takes place in the presence of sterols.
Mediates feedback control of cholesterol synthesis.
Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of scap and degradation of hmgcr. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs). Binds oxysterol, including 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.
The KxHxx motif mediates association with the coatomer complex.
Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. May act as a positive regulator of T-cell coactivation (By similarity).
Belongs to the complex I 51 kDa subunit family.
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
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.
Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-224 binds ATP and competes with ATP-binding at Arg-364, thereby preventing adenylyltransferase activity. Activation dissociates ATP-binding from Glu-224, 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).
Adenylyltransferase that mediates the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins.
The fido domain mediates the adenylyltransferase activity.
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.
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.
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 cytidylyltransferase family.
Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.
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.
Belongs to the chromogranin/secretogranin protein family.
Lipid-binding protein involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration.
Receptor for ghrelin, coupled to G-alpha-11 proteins. Stimulates growth hormone secretion. Binds also other growth hormone releasing peptides (GHRP) (e.g. Met-enkephalin and GHRP-6) as well as non-peptide, low molecular weight secretagogues (e.g. L-692,429, MK-0677, adenosine).
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).
Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (By similarity). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (By similarity). Interacts with the E2 enzymes UBE2D1, UBE2D3, UBE2E1 and UBE2L3 (By similarity). Plays a key role in neural development, probably by mediating ubiquitination of threonine residues on target proteins (By similarity). Involved in different processes such as regulation of neurite outgrowth, synaptic growth, synaptogenesis and axon degeneration (By similarity). Required in the visual system for correct fasciculation, targeting and mapping of retinal axons (PubMed:15590740). Acts as a regulator of pteridine synthesis (PubMed:15617681). May play a role in the regulation of the circadian clock gene expression (By similarity).
Belongs to the RING-Cys relay (RCR) family.
Fishes display defects in the projection of retinal axons as well as reduced yellow pigmentation (PubMed:15590740, PubMed:15617681). Mutants show failure of anterior axons to map to the posterior tectum: in wild types, retinal axons from the anterior eye remain unbranched and are fasciculated until reaching the posterior tectum, while in mutants, anterior axons branch in the anterior tectum (PubMed:15590740). The posterior tectum is very sparsely innervated (PubMed:15590740). Defects are also detectable in the dorsoventral axis (PubMed:15590740). Reduced yellow pigmentation is caused by a deficiency of sepiapterin, a yellow pteridine (PubMed:15617681).
The PHR domains are compact beta-sandwich folds composed of 11 antiparallel strands and decorated with conserved apical loops. They are likely to play a structural role and mediate interactions with substrates or partners.
The tandem cysteine domain region confers threonine specificity and contains the two essential catalytic cysteine residues that relay ubiquitin. It binds four zinc ions in a C5HC7HC2 configuration.
Widely expressed when the visual system begins developing. In the eye, expressed in all cells, including retinal ganglion cells, with no obvious gradient.
Belongs to the non-lysosomal glucosylceramidase family.
Non-lysosomal glucosylceramidase that catalyzes the hydrolysis of glucosylceramide (GlcCer) to free glucose and ceramide.
Deubiquitinating enzyme. Has almost no deubiquitinating activity by itself and requires the interaction with wdr48 to have a high activity.
Lysosomal transporter which is essential for liver homeostasis. Required to maintain stability and lysosomal localization of GLMP.
The dileucine internalization motif is required for lysosomal localization.
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.
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.
Belongs to the PPP phosphatase family. PP-5 (PP-T) subfamily.
Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs. CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation. The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs. Plays a role in mRNA export.
Component of the cleavage factor Im (CFIm) complex.
Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function.
Belongs to the bacterial ribosomal protein bL9 family.
May be involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors.
Belongs to the glutamate--cysteine ligase type 3 family.
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 bZIP family. Fos subfamily.
May play an important role in spermatogenesis and/or testis development.
Probably plays a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. Note=Localizes to the apical junction complex composed of tight and adherens junctions.
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.
Expression is predominantly seen in striated muscles, and strong expression in heart and skeletal muscles is observed throughout development to at least 5 dpf.
Involved in skeletal muscle development and maintenance.
Knockdown of klhl41b result in reduced disorganized muscle without any other significant abnormalities. Knockdown of both genes (klhl41a and klhl41b) is lethal by 3 dpf. Double knockdown fish exhibit severely disorganized muscle compared to controls and either of the single knockdowns.
Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Is required for the association of cnot10 with the CCR4-NOT complex. Seems not to be required for complex deadenylase function (By similarity).
Histone methyltransferase that sequentially mono-, di-, and tri-methylates both 'Lys-4' (H3K4) and 'Lys-36' (H3K36) of histone H3 to produce respectively trimethylated 'Lys-4' (H3K4me3) and trimethylated 'Lys-36' (H3K36me3) histone H3 and plays a key role in meiotic prophase by determining hotspot localization thereby promoting meiotic recombination. Can also methylate all four core histones with H3 being the best substrate and the most highly modified. Is also able, on one hand, to mono and di-methylate H4K20 and on other hand to trimethylate H3K9 with the di-methylated H3K9 as the best substrate. During meiotic prophase, binds specific DNA sequences through its zinc finger domains thereby determining hotspot localization where it promotes local H3K4me3 and H3K36me3 enrichment on the same nucleosomes through its histone methyltransferase activity. Thereby promotes double-stranded breaks (DSB) formation, at this subset of PRDM9-binding sites, that initiates meiotic recombination for the proper meiotic progression. During meiotic progression hotspot-bound PRDM9 interacts with several complexes; in early leptonema binds CDYL and EHMT2 followed by EWSR1 and CXXC1 by the end of leptonema. EWSR1 joins PRDM9 with the chromosomal axis through REC8. In this way, controls the DSB repair pathway, pairing of homologous chromosomes and sex body formation. Moreover plays a central role in the transcriptional activation of genes during early meiotic prophase thanks to H3K4me3 and H3K36me3 enrichment that represents a specific tag for epigenetic transcriptional activation. In addition performs automethylation. Acetylation and phosphorylation of histone H3 attenuate or prevent histone H3 methylation.
Mono-methylated; automethylated. Tri-methylated; automethylated.
The C2H2-type zinc fingers determines the hotspot localization through its binding to specific DNA sequences. Variations in their sequence affects affinity towards DNA-binding motif.
Binds DNA as a homodimer and as a heterodimer.
Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (By similarity). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress. During ISR, atf4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to eif2s1/eIF-2-alpha phosphorylation, and stress-induced atf4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (By similarity). Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity). In the absence of stress, atf4 translation is at low levels and it is required for normal metabolic processes such as embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (By similarity). Acts as a regulator of osteoblast differentiation by promoting expression of osteoblast-specific genes (By similarity). Regulates the circadian expression of the core clock components. Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor (By similarity).
First detected at 2.75 hours post-fertilization/hpf (PubMed:27235108). The expression increases at least till 24 hpf (PubMed:26056731). During the segmentation period expressed in the adaxial cells and the somites in a striping pattern (PubMed:14516702). By 24 hpf, expression in the somites decreases except in the tail region. In addition expression is also detected in lens placode and lens fiber cell from 18 hpf till 48 hpf and then decreases to disappear at 60 hpf (PubMed:14516702).
Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and therefore function in several unrelated biological processes.
Belongs to the metallophosphoesterase superfamily. MPPE1 family.
Metallophosphoesterase required for transport of GPI-anchor proteins from the endoplasmic reticulum to the Golgi. Acts in lipid remodeling steps of GPI-anchor maturation by mediating the removal of a side-chain ethanolamine-phosphate (EtNP) from the second Man (Man2) of the GPI intermediate, an essential step for efficient transport of GPI-anchor proteins (By similarity).
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.
Stimulates the secretion of gonadotropins.
Endoribonuclease which preferentially cleaves ApU and ApG phosphodiester bonds.
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).
Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context (By similarity).
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 universal ribosomal protein uS12 family.
Interacts with dvl2 (PubMed:18539122, PubMed:19395640). Interacts with kur (PubMed:26904945).
Maternally and zygotically expressed. Expressed in the embryo at the 256- and 512-cell, sphere and epiboly stages. Expressed in ciliated tissues, including Kupffer's vesicle, otic vesicle, pronephric duct and floor plate of the neural tube. Expressed in the floor plate and chordoneural hinge at 24 hpf. Expressed in the anteriormost tubules adjacent to the glomerular region at 36 hpf. Expressed in the pronephric tubules from mid-somitogenesis through 48 hpf.
Mutants show development of polycystic kidney disease and left-right (LR) asymmetry defects.
Plays a crucial role in regulating cilia motility in pronephric tubules, cloaca and neural tube. Required for establishing left-right asymmetry of the body plan; controls cell fate and convergent extension (CE) movements during gastrulation, respectively, via the Wnt and the planar cell polarity (PCP) signaling pathways. Required for the proper development of renal glomeruli and tubules.
Component of the multiprotein chromatin-remodeling complexes SWI/SNF.
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.
Belongs to the LDH/MDH superfamily. LDH family.
At the 10-somite stage, expressed in the paraxial mesoderm with an anterior expression limit at somite 4. At the 20-somite stage, expressed in the developing CNS with an anterior expression limit adjacent to the somite 1/somite 2 boundary, and also expressed in the presumptive pronephric ducts.
Auxiliary enzyme of beta-oxidation. Participates in the degradation of unsaturated fatty enoyl-CoA esters having double bonds in both even- and odd-numbered positions in peroxisome. Catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to yield trans-3-enoyl-CoA (By similarity).
Belongs to the short-chain dehydrogenases/reductases (SDR) family. 2,4-dienoyl-CoA reductase subfamily.
Does not appear to be a mRNA-cap-binding protein.
Expressed both maternally and zygotically. Levels decrease on oocyte maturation, increase during the midblastula transition, then decline again and are lost by 24 hours post-fertilization (hpf). Uniform distribution during gastrulation, but later becomes concentrated in mesodermal lineages, particularly those located ventrally.
Transposase-derived protein that may have nuclease activity (Potential). Does not have transposase activity (By similarity).
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.
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 (By similarity).
Belongs to the SRP receptor beta subunit family.
In the C-terminal section; belongs to the OMP decarboxylase family.
In the N-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family.
Has a role in nuclear-cytoplasmic transport of proteins and mRNAs.
Belongs to the MPDU1 (TC 2.A.43.3) family.
At the shield stage, expressed uniformly in the future ectoderm. At the 75-80% epiboly stage, becomes localized to the presumptive neuroectoderm; strong expression in the presumptive forebrain, weak expression in the presumptive spinal cord. At the tail bud to 3-somite stage, expressed in distinct regions of the future brain, the anterior margin of the neural plate and the future retina. At the 12-somite stage, strong expression in the central nervous system rostral to the hindbrain, including the optic vesicle. At the 21- to 25-somite stage, strong expression in the retina, otic placode and cerebellum. At 28-50 hours post-fertilization, restricted to the ventricular zone of the hindbrain. At 5 days, expressed in the esophageal endoderm.
Expressed zygotically. First detected at the 30% epiboly stage.
Transcriptional activator. May function as a switch in neuronal development (By similarity). Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity).
Mediates with IER2 FGF-signaling in Kupffer's vesicle ciliogenesis and in the establishment of laterality in the embryo (PubMed:19164561). May be involved in mitogenic function of FGF1 (By similarity).
Morpholino knockdown of the protein causes severe deficits in laterality (PubMed:19164561). Partial loss of Kupffer's vesicle cilia with the length of the remaining cilia reduced (PubMed:19164561). Double morpholino knockdown of IER2 and FIBPB causes an almost complete loss of Kupffer's vesicle cilia (PubMed:19164561).
Catalyzes the first step in the removal of the two C-4 methyl groups of 4,4-dimethylzymosterol.
The histidine box domains may contain the active site and/or be involved in metal ion binding.
Belongs to the transthyretin family. 5-hydroxyisourate hydrolase subfamily.
Belongs to the lipase maturation factor family.
Involved in the maturation of specific proteins in the endoplasmic reticulum.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.
Belongs to the class-IV pyridoxal-phosphate-dependent aminotransferase family.
Exhibits both acyltransferase and acetyltransferase activities (By similarity). Activity is calcium-dependent (By similarity). Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (By similarity). Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Involved in platelet-activating factor (PAF) biosynthesis by catalyzing the conversion of the PAF precursor, 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) into 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) (By similarity).
The HXXXXD motif is essential for acyltransferase activity.
Belongs to the chaperonin (HSP60) family.
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.
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.
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).
Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
Plays a role in promoting cell proliferation in response to pro-inflammatory stimuli.
Belongs to the protein-tyrosine phosphatase family. Receptor class 2B subfamily.
Belongs to the SMC family. SMC1 subfamily.
In the process of mRNA degradation, seems to play a role in mRNA decapping.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.
Adenine glycosylase active on G-A mispairs.
Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGCG-3'.
Belongs to the opioid growth factor receptor family.
Expressed in primary motor neurons from early stages of their differentiation (12 hpf) to at least 24 hpf.
Overexpression partially rescues the motor axon defects upon Smn-depleted.
Plays a role in the development of the nervous system such as in neurite outgrowth and elongation. Involved in motor axon growth and guidance. Required for correct interactions of motor axons with the horizontal myoseptum.
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.
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.
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.
Belongs to the eukaryotic ribosomal protein eL33 family.
Cytosolic CRABPs may regulate the access of retinoic acid to the nuclear retinoic acid receptors.
Isoform 2 is expressed both maternally and zygotically, and is the major isoform in adults. Isoform 1 and isoform 3 are expressed zygotically. Maximal expression is after 1 to 2 days of development and becomes down-regulated as cells differentiate.
Predominantly expressed in the embryonic and adult central nervous system. In adults, isoform 2 is expressed in the brain, ovary, basal cells of the skin and muscle satellite cells.
Embryos have various defects including smaller heads and eyes.
Plays an essential role in early embryonic development.
Belongs to the bacterial ribosomal protein bS18 family. Mitochondrion-specific ribosomal protein mS40 subfamily.
Produces ATP from ADP in the presence of a proton gradient across the membrane.
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.
Calcium-sensitive protein which reversibly blocks the barbed ends of actin filaments but does not sever preformed actin filaments. May play an important role in macrophage function. May play a role in regulating cytoplasmic and/or nuclear structures through potential interactions with actin. May bind DNA.
The [NKR]KIAxRE motif seems to be a cyclin-binding region.
Belongs to the methylthiotransferase family. CDKAL1 subfamily.
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.
Acts as an osmosensitive calcium-permeable cation channel (By similarity). Required for the functional integrity of the kidney glomerular filtration barrier (PubMed:30900988).
Morpholino knockdown induced a glomerular filtration barrier defect.
May promote appropriate targeting of ribosome-nascent polypeptide complexes.
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.
Belongs to the kynurenine formamidase family.
Catalyzes the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation. Kynurenine may be further oxidized to nicotinic acid, NAD(H) and NADP(H). Required for elimination of toxic metabolites.
The main chain amide nitrogen atoms of the second glycine and its adjacent residue in the HGGXW motif define the oxyanion hole, and stabilize the oxyanion that forms during the nucleophilic attack by the catalytic serine during substrate cleavage.
Belongs to the small G protein signaling modulator family.
Belongs to the glutaminyl-peptide cyclotransferase family.
Belongs to the TRAFAC class YlqF/YawG GTPase family. MTG1 subfamily.
Plays a role in the regulation of the mitochondrial ribosome assembly and of translational activity. Displays mitochondrial GTPase activity.
May play a role in vesicle trafficking and exocytosis.
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.
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.
Responsible for the 2-O-phosphorylation of xylose in the glycosaminoglycan-protein linkage region of proteoglycans thereby regulating the amount of mature 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 (By similarity).
Belongs to the protease inhibitor I47 (latexin) family.
Expressed both maternally and zygotically. Present throughout embryonic development, and in adults.
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis, and induces permeabilization of blood vessels. Acts both upstream of kdr and tie1 to stimulate endothelial cell differentiation, and upstream of gata1 to stimulate hematopoietic cell differentiation.
Homodimer; disulfide-linked (By similarity). Isoform VEGF165 binds kdr and kdrl.
Predominantly expressed in regions associated with active vascularization. From 15-16 hours post-fertilization (hpf), expressed in the anterior forebrain, the mesoderm underlying and lateral to the anterior hindbrain, the mesoderm underlying and lateral to the posterior hindbrain, and in the ventral medial portions of the somites. By 30-36 hpf, expression in the somites is decreased, while strong expression is observed in the region of the developing glomeruli and in the anterior portion of the pronephric ducts, the pharyngeal arches, and the brain. By 72 hpf, expression remains only in the pronephros region.
Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92.
May play a role in chaperone-mediated protein folding.
Belongs to the prokaryotic/mitochondrial release factor family.
In contrast to other members of the family, lacks the regions that come into close contact with the mRNA in the ribosomal A-site and determine the STOP codon specificity, suggesting a loss of codon specificity for translation release factor activity.
Interacts (via C-terminus) with MTRES1 (via S4 domain). Associates with mitoribosomal S39 large subunit, peptidyl tRNA and nascent chain.
Part of a mitoribosome-associated quality control pathway that prevents aberrant translation by responding to interruptions during elongation. As heterodimer with MTRES1, ejects the unfinished nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for MTRES1 and MTRF during mitoribosome rescue.
The GGQ domain interactS with the peptidyltransferase center (PTC) of the large ribosomal subunit to trigger nascent chain hydrolysis.
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).
Forms a complex composed of PDGFRL, TNK2 and GRB2.
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.
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.
May play a role in the development of the central system.
Embryos exhibit perturb cardiac looping as the result of a defect in left/right patterning.
Expressed throughout embryonic development. At 9- to 16-somites, transcripts are broadly expressed with specific staining observed in the developing nervous system, somites, and precardiac mesoderm. At later stages 1- to 3-days post-fertilization, transcripts become more localized within the dorsal diencephalon, the otic vesicles, and the fin buds.
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). Required in left/right patterning by modulating Ca(2+) levels in the cells surrounding the Kupffer vesicle.
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 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.
Expressed in hemopoietic and endothelial lineages. Isoform beta emerges first, expressing in the entire anterior and posterior lateral mesoderm (ALM and PLM respectively), and in the ventral wall of the dorsal aorta, where definitive hemopoiesis begins. Isoform alpha expresses later as two pairs of stripes in the PLM and ALM, and becomes restricted to the intermediate cell mass (ICM) by the 18-somite stage. The ICM is the key site of primitive hemopoiesis, giving rise to the erythroid lineage. Also expressed in all stages of endocardial cell migration and in the developing midbrain, hindbrain and spinal cord. In adults, expressed in the main hemopoietic organs, namely the kidney (where isoform alpha is the predominant isoform) and the spleen. Also expressed in the liver, gill and gonads.
Expression of isoform beta begins at the 1-2 somite stage, peaks at the 11-18 somite stage, and is maintained at a lower level in the adult kidney. Isoform alpha isn't expressed until the 4-somite stage, after which expression levels rapidly increase.
Transcription factor that plays a pivotal role in hemopoietic and endothelial development, acting synergistically with lmo2 and downstream of clo. Specifies mesodermal precursors to a hemangioblast cell fate. Hemangioblasts are bipotential precursors of blood and endothelium, and in the absence of hemopoietic induction cues such as gata1, tal1/scl-lmo2-induced hemangioblasts differentiate into endothelial cells. Isoform alpha and isoform beta are redundant for the initiation of primitive hemopoiesis but have distinct roles in the regulation of primitive erythroid differentiation and definitive hemopoietic stem cell specification, most likely due to differences in expression levels. Specification of definitive hemopoietic stem cells requires isoform beta. DNA binding is required for erythroid maturation, but not for its other hemopoietic functions. Endothelial roles include development of the dorsal aorta, the site of definitive hemopoiesis in the embryo. Required for angiogenesis but not angioblast specification. Has an additional role in endocardium formation during heart development. May play a role in central nervous system development.
Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 4,5-bisphosphate.
Belongs to the Mediator complex subunit 24 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). Required for proliferation of enteric nervous system precursors. Required for the development of dopaminergic amacrine cells and rod photoreceptor cells in the retina.
Maternally expressed. Ubiquitously expressed through the 10 somite stage. Expression subsequently decreases in the trunk and tail while remaining high in anterior parts of the embryo. By 24 hours post-fertilization (hpf) expression is no longer detectable in the trunk and tail, but is maintained in anterior parts of the embryo. At 48 hpf expression extends along almost the entire length of the gut and is particularly high in the dorsal forebrain, ventral midbrain, and the dorsal posterior part of the midbrain. At 60 hpf, expression in the gut is restricted to intestinal epithelial cells. At 72 hpf, expression in the CNS is limited to cells in the diencephalon, the ventral midbrain and the dorsal part of the midbrain, while expression outside the CNS is restricted to the pharyngeal endoderm. Expression in the pharyngeal endoderm persists through 96 hpf.
3'-UTR is sufficient for directing specific expression of this protein in the primordial germ cells (PGCs).
Acts as a translational repressor. Can mediate repression affecting different steps in the translation process: cap-driven, IRES-driven, polyadenylated RNAs or nonpolyadenylated RNAs (By similarity). Essential for the development of primordial germ cells (PGCs) by ensuring their proper migration and survival.
Present in oocytes and in embryos before the 4- and 256-cell stages. Levels decline and it is barely detectable by the fifth day of development.
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.
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.
May act as a repressor of nr2c2-mediated transactivation by suppressing the binding between nr2c2 and its response element in target genes.
Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes.
Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling.
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 sauvagine/corticotropin-releasing factor/urotensin I family.
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 ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily.
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 NUP186/NUP192/NUP205 family.
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.
May associate with CD21. May regulate the release of Ca(2+) from intracellular stores.
ATP-dependent chromatin remodeler that mediates chromatin-remodeling following DNA damage. Recruited to DNA damage sites through interaction with poly-ADP-ribose: specifically recognizes and binds histones that are poly-ADP-ribosylated on serine residues in response to DNA damage. Poly-ADP-ribose-binding activates the ATP-dependent chromatin remodeler activity, thereby regulating chromatin during DNA repair. Catalyzes nucleosome sliding away from DNA breaks in an ATP-dependent manner.
Adopts an inactive conformation in absence of DNA damage. Binding to poly-ADP-ribosylated histones activates the ATP-dependent chromatin remodeler activity.
Interacts with nucleosomes; interacts with the acidic patch of histones.
The macro domain mediates non-covalent poly(ADP-ribose)-binding and recruitment to DNA damage sites. Mediates auto-inhibition of ATPase activity by interacting with the N-terminal ATPase module, encompassing the helicase ATP-binding domain and helicase C-terminal domain. Binding to poly-ADP-ribosylated histones upon DNA damage releases the auto-inhibition by the macro domain and trigger ATPase activity. Does not bind monomeric ADP-ribose and mono-ADP-ribose fails to release the auto-inhibition of the ATPase module by the macro domain.
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.
Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors (By similarity). Involved in steering cell migration by controlling its directional persistence.
The acidic C-terminus is necessary and sufficient to inhibit ARP2/3 complex activity.
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.
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 BAF complex. Interacts with acetylated histones H3 and H4. Component of neuron-specific chromatin remodeling complex (nBAF complex), a subfamily of ATP-dependent SWI/SNF chromatin remodeling complexes (By similarity).
Muscle-specific component of the BAF complex, a multiprotein complex involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Specifically binds acetylated lysines on histone 3 and 4. In the complex, it acts as a tissue-specific anchor between histone acetylations and methylations and chromatin remodeling. Belongs to the neuron-specific chromatin remodeling complex (nBAF complex) and may play a role in neural development (By similarity). Plays an essential role in heart and skeletal muscle development.
The PHD-type zinc fingers mediate the binding to acetylated histones.
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).
Belongs to the ubiquitin-activating E1 family. UBA5 subfamily.
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 glycosyltransferase 22 family.
Belongs to the complex I subunit 4 family.
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.
Contains 2 Inka boxes (also named iBox or inca box). The Inka boxes bind and inhibit PAK4 by binding a substrate-like manner.
Dramatic reduction in craniofacial cartilage formation.
Expression is regulated by the transcription factor AP-2-alpha/tfap2a.
Inhibitor of the serine/threonine-protein kinase pak4/pak5 (By similarity). Acts by binding pak4/pak5 in a substrate-like manner, inhibiting the protein kinase activity (By similarity). Required for the proper migration of neural crest cells during embryonic development, probably by inhibiting pak4/pak5 (PubMed:17314132).
Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis.
Highly expressed in the olfactory rosette (PubMed:17717047). Specifically localizes to crypt neurons in the olfactory neuroepithelium (PubMed:22038944). Colocalizes with the inhibitory G-protein gnaia in crypt neurons (PubMed:22038944). Not detected in other tissues tested (PubMed:17717047).
Belongs to the carnosine N-methyltransferase family.
Guanine nucleotide exchange factor. May be involved in cytoskeletal organization.
The PH domain mediates binding to membranes.
Controls cell proliferation acting as a negative regulator of TOR signaling pathway mediated by mTORC1.
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).
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. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. 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 UTP23/FCF1 family. FCF1 subfamily.
Belongs to the glycosyltransferase 14 family.
Glycosyltransferase that mediates core 2 O-glycan branching, an important step in mucin-type biosynthesis.
Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
Adds the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation.
Belongs to the constitutive coactivator of PPAR-gamma family.
Belongs to the complex I NDUFA7 subunit family.
Belongs to the pancreatic ribonuclease family.
Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage.
Belongs to the tRNA(His) guanylyltransferase family.
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).
During centriole duplication, may play a role in the centriole elongation by promoting the recruitment of the microtubule-binding elongation machinery, leading to the centriole to centrosome conversion (By similarity). In addition may play a role in the primary cilia assembly (By similarity).
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.
May regulate phosphatase activity of protein phosphatase 1 (PP1) complexes.
Ubiquitously expressed in embryos until eight hours after fertilization. Highly expressed in the developing neural plate eight hours after fertilization. Detected in telencephalon, retina, diencephalon, mesencephalon, cerebellum and rhombomeres between 24 and 38 hours after fertilization. Detected in tegmentum, myencephalon and notochord 48 hours after fertilization.
tRNA hydroxylase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the hydroxylation of 7-(a-amino-a-carboxypropyl)wyosine (yW-72) into undermodified hydroxywybutosine (OHyW*). OHyW* being further transformed into hydroxywybutosine (OHyW) by LCMT2/TYW4. OHyW is a derivative of wybutosine found in higher eukaryotes.
Belongs to the acyl carrier protein (ACP) family.
Carrier of the growing fatty acid chain in fatty acid biosynthesis.
Belongs to the lyase 1 family. Argininosuccinate lyase 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).
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.
Morpholino knockdown of the protein causes delayed sound-induced startle response and circular swimming behavior. Morphants show significantly reduced extracellular receptor potentials and impaired mechanoelectrical transduction in hair cells of inner ear relative to controls.
Required for normal inner ear hair cell function and hearing.
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.
Expressed in brain and somites, and slight expression in cardiac primordium, at 18 hours post-fertilization (hpf) (PubMed:35039994). Expression is initiated at 22 hpf in the gut endoderm in an area known to be the origin of hepatic precursor cells and at 40 hpf, expands to the newly formed liver bud (PubMed:21471154). Expression is reduced after termination of primary liver formation (PubMed:21471154). Expressed in the brain, heart, and somites at 24 hpf (PubMed:35039994). Expression in somites becomes weaker, and is rarely detected from 48 hpf onwards (PubMed:35039994). Expressed in the cardiac region from 24 to 48 hpf (PubMed:35039994). At 48 hpf, expression is regionalized to the brain and heart (PubMed:21471154). At 96 hpf, almost no expression in heart, and expression is found to be accumulated in other tissues, such as the gill arch, swim bladder, and intestine (PubMed:35039994).
Involved in liver and heart organogenesis during embryo development (PubMed:21471154, PubMed:35039994). Plays a role in the migration of hepatoblasts from the intestinal endoderm during liver organogenesis; possibly by modulating actin polymerization during hepatoblast outgrowth (PubMed:21471154). May be involved in neuron regeneration (By similarity).
Severe deficiency in cardiac morphology and structure and 70% enbryonic lethality within 24 hpf (PubMed:35039994). Morpholino-mediated knockdown impairs the migration of hepatoblasts out from the gut endoderm, blocks liver bud formation, and results in a reduced liver size (PubMed:21471154). Also impairs development of pancreas and swim bladder (PubMed:21471154).
Acts as a positive regulator of ciliary hedgehog signaling (By similarity). Plays a role in ciliogenesis (By similarity). Plays an important role in the mitochondrial function and is essential for maintaining mitochondrial morphology and inner membrane ultrastructure (By similarity).
The BAR-like domain displays limited similarity to other BAR domains.
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.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB7 is part of a subcomplex with RPB4 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RBP4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity).
Part of the Ragulator complex composed of lamtor1, lamtor2, lamtor3, lamtor4 and lamtor5. The Ragulator complex interacts with slc38a9; the probable amino acid sensor. Component of the lysosomal folliculin complex (LFC).
Regulator of the TOR pathway, a signaling cascade that promotes cell growth in response to growth factors, energy levels, and amino acids. As part of the Ragulator complex, may activate the TOR signaling cascade in response to amino acids. Adapter protein that may regulate the MAP kinase cascade.
Belongs to the complex I NDUFB8 subunit family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.
Catalyzes the phosphorylation of thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), the immediate precursor for the DNA building block dTTP, with ATP as the preferred phosphoryl donor in the presence of Mg(2+).
The number of knockout embryos is obtained at the expected rate. Knockout embryos show microcephaly, neuronal cell death and early lethality. At 2 days post fertilization (dpf), forebrains in knockout animals exhibit higher amounts of apoptotic cells than control embryos. The head size is significantly smaller compared to sibling embryos of the same batch. From 3 dpf onwards, mutant embryos show markedly smaller eyes and prominent pericardiac edema. At 3 dpf, mutant embryos show twitching movements, reminiscent of epileptic seizures. In the brain, empty spaces, indicative of neurodegeneration, are apparent. Cartilage structures of the lower jaw (Meckels' cartilage) are absent in the mutant larvae. Severe underdevelopment of the eyes is prominent. The eyes of mutant embryos are smaller, have an irregular shape and only show the retinal pigmented epithelium (RPE) and photoreceptorlayer (PRL), whereas the other 4 layers are absent. From 4 dpf onwards, mutant embryos develop prominent edema of the brain and around the intestine. At 5 dpf, more than 40% of mutant embryos die.
Belongs to the universal ribosomal protein uL16 family.
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.
Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ).
In the C-terminal section; belongs to the sulfate adenylyltransferase family.
In the N-terminal section; belongs to the APS kinase family.
Craniofacial defects. Cartilage elements embryos do not mature and chondrocyte morphology and extracellular matrix are affected.
Expressed in the notochord from the 10 somite stage. Highly expressed in head mesenchyme and developing cartilages that will form the craniofacial skeleton.
Protein-lysine 6-oxidase that mediates the oxidation of peptidyl lysine residues to allysine in target proteins (By similarity). Catalyzes the post-translational oxidative deamination of peptidyl lysine residues in precursors of elastin and different types of collagens, a prerequisite in the formation of cross-links between collagens and elastin (By similarity). Can mediate oxidation of lysine residues that are acetylated (By similarity). Also able to catalyze deacetylation of lysine residues (By similarity). Required for maturation of neural crest derived cartilage elements (PubMed:21244857).
Belongs to the universal ribosomal protein uS3 family.
Regulatory subunit of protein phosphatase 1.
Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP).
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 (By similarity).
This sequence is encoded by a gene on chromosome 15 and is unlikely to be the med13 ortholog because it shows similarity but not synteny with human MED13. The chromosome 10 med13 gene identified by PubMed:17208216 is distinct from this entry.
May play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes. Mediates phagolysosomal fusion in macrophages. Proposed to be involved in endosomal maturation implicating vipas39. In epithelial cells, the vps33b:vipas39 complex may play a role in the apical recycling pathway and in the maintenance of the apical-basolateral polarity (By similarity). Plays a role in bile duct development.
Widely expressed from 4 hours post-fertilization (hpf) to 24 hpf. At 48 hpf, localized to brain, retina, ear, liver and proximal intestine. This expression pattern is more pronounced at 72 hpf and persists through 5 days post-fertilization (dpf). At 3 dpf and 4 dpf, expression in the liver is predominantly in developing biliary epithelial cells. No expression detected in kidney or spinal cord.
Belongs to the bacterial ribosomal protein bL19 family.
May function as a coactivator for aryl hydrocarbon and nuclear receptors.
Belongs to the cytochrome c oxidase VIII family.
Catalyzes the ferrous insertion into protoporphyrin IX.
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.
Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with terf2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'-TTAGGG-3' sites via its association with terf2 or other factors, and regulates gene expression.
Belongs to the eukaryotic ribosomal protein eL6 family.
Component of the super elongation complex (SEC). Associates with ccnt1/cyclin-T1, ccnt2/cyclin-T2 or ccnk/cyclin-K to form active P-TEFb.
Expressed from 24 hours post-fertilization (hpf) (PubMed:26542022). Expression increases between 24 and 72 hpf and then decreases towards 120 hpf (PubMed:26542022). In embryonic hearts expression peaks at 48 hpf and again at 96 hpf, decreasing at 120 hpf to levels then detected in adult hearts (PubMed:26542022).
Morpholino knockdown of the protein causes in larvae causes high levels of lethality.
Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) polr2a, supt5h and rdbp. This complex is inactive when in the 7SK snRNP complex form. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export.
Belongs to the eukaryotic ribosomal protein eS4 family.
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.
Expressed in the main insulin-sensitive tissues, such as cardiac muscle, skeletal muscle and adipose tissue.
Insulin-regulated facilitative glucose transporter.
Morpholino knockdown of the protein impairs the development of the embryonic heart resulting in abnormal valve formation (PubMed:25326603). Embryos also show poor glycemic control (PubMed:25326603).
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.
Belongs to the AVIT (prokineticin) family.
Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-1/CHRNA1 sub-subfamily.
One of the alpha chains that assemble within the acetylcholine receptor, a pentamer of two alpha chains, a beta, a delta, and a gamma or epsilon chains.
Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Essential for Golgi structural integrity.
May play a role in cell cycle regulation. Dual specificity phosphatase active toward substrates containing either phosphotyrosine or phosphoserine residues.
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.
Might be involved in growth regulation, and in myelinization in the peripheral nervous system.
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. Prefers complex-type N-glycans over hybrid-types. Has lower affinities for donors or acceptors than MGAT4A, suggesting that, under physiological conditions, it is not the main contributor in N-glycan biosynthesis.
Belongs to the DEAD box helicase family. DDX21/DDX50 subfamily.
Involved in the positive regulation of histone H3-K9 dimethylation.
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). May recruit the E2 ubiquitin-conjugating enzymes to the complex.
The APC/C is composed of at least 12 subunits.
Belongs to the formin homology family. Diaphanous subfamily.
Mitochondrial transporter that imports/exports pyrimidine nucleotides into and from mitochondria which participates in dendritic cell endocytosis.
First expressed in the paraxial mesoderm at the 90% epiboly stage, and subsequently confined to the presomitic mesoderm. Expressed in the rostral compartment of S-I and S-II.
Plays a role in somitogenesis. Required for somite segregation and establishment of rostrocaudal polarity in somites (By similarity).
The WRPW motif is required for binding to tle/groucho proteins.
The ripply homology domain is required for transcriptional repression.
Belongs to the metallo-dependent hydrolases superfamily. HutI family.
Expressed in the developing eye. In 48h embryos, enriched within the periocular mesenchyme (POM), in the branchial arch region and in the developing pancreas.
Transcription factor that regulates metabolic homeostasis in response to oxidative stress (By similarity). 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' (By similarity). Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (By similarity). May be involved in regulating cellular homeostasis in the eye (PubMed:17993506).
At 4 days post fertilization (dpf), it is widely expressed in the brain and eyes. There are high levels of expression in the retinal ganglion layer, the inner nuclear layer, the photoreceptor layer, the ciliary marginal zone, jaw mesenchyme, oral epithelia, and pectoral fins.
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.
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.
Component of the large ribosomal subunit (Probable). Plays a role in the formation of actively translating ribosomes (PubMed:25316788). Plays a role in the embryonic brain development (PubMed:25316788).
Expressed ubiquitously in the embryos. Strongly expressed at the midbrain and hindbrain boundary at 2 days post-fertilization (dpf).
Morpholino knockdown of the protein decreases head size, but not body length at 2 days post-fertilization (dpf) (PubMed:25316788). Show decreased formation of actively translating ribosomes (PubMed:25316788).
Component of the PAF1 complex, which at least consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8 (By similarity). The PAF1 complex interacts with PHF5A (By similarity).
Belongs to the chloride channel (TC 2.A.49) family. ClC-2/CLCN2 subfamily.
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.
Required for the processing of the 27S pre-rRNA.
Homodimer. Heterodimer; with a rar molecule. Binds DNA preferentially as a rar/rxr heterodimer.
Receptor for retinoic acid that acts as a transcription factor (PubMed:7565671). 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 (By similarity). The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (By similarity). The high affinity ligand for rxrs is 9-cis retinoic acid (By similarity). In the absence of ligand, the rar/rxr heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (By similarity). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (By similarity).
Uniform expression from the blastula to mid-gastrula stages. At 12 hours post-fertilization (hpf), expressed strongly in the tail and weakly elsewhere. At 24 hpf, weak expression in the forebrain, eyes and pharyngeal endoderm and continued expression in the tail mesoderm. At 48 hpf, anterior expression limited to ventral cells underlying the head, medial expression in the pectoral fin bud mesoderm and continued tail expression.
In the C-terminal section; belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.
Has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination.
Plays an important role in deacetylating mercapturic acids in kidney proximal tubules.
Belongs to the universal ribosomal protein uS15 family.
Expressed in the pre-gastrula embryo (at protein level).
Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site (By similarity). Relatively inactive in the unfertilized oocyte, undergoes rapid activation immediately following fertilization. Total activity increases progressively during later development and remains elevated during sphere and epiboly stage.
Tyrosine-protein kinase implicated in the control of cell growth. Plays a role in the regulation of intracellular calcium levels. Required in brain development and mature brain function with important roles in the regulation of axon growth, axon guidance, and neurite extension. Role in cntn1-mediated signaling (By similarity). Required for convergent extension cell movements during gastrulation, acting with yes via rhoa. May be required for epiboly to occur, possibly through its effects in calcium signaling.
Belongs to the MMS22 family. MMS22L subfamily.
Component of the MMS22L-TONSL complex, a complex that promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication. It mediates the assembly of RAD51 filaments on single-stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs following histone replacement by histone chaperones and eviction of the replication protein A complex (RPA/RP-A) from DSBs. Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination. Within the complex, MMS22L acts by binding ssDNA.
Detected throughout development (PubMed:18632251, PubMed:20466645). Highest expression levels are found at 0 hours post-fertilization (hpf), probably due to perdurance of maternal transcripts (PubMed:20466645). Ubiquitously expressed during early stages of development (PubMed:18632251, PubMed:20466645). At 16-24 hpf, mainly found in eye, brain and somites (PubMed:18632251, PubMed:20466645). At 30 hpf, has strongest expression in forebrain, cerebellum and hindbrain (PubMed:18632251).
Morpholino knockdown of the protein results in developmental delays at 18 hours post fertilization (hpf). At 48-72 hpf, the tail is slightly curved and somite boundaries are also abnormally curved. Swim bladders are incompletely formed. Glycosylation of alpha-dystroglycan (dag1) is severely reduced.
Widely expressed. Has particularly strong expression in testis, ovary, brain, liver and heart.
Directs RNA polymerase II nuclear import.
Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 and PEN2.
Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors. It may represent a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex (By similarity).
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.
G-protein coupled receptor for 5-hydroxytryptamine (serotonin).
Exhibits both phospholipase A1/2 and acyltransferase activities. Shows phospholipase A1 (PLA1) and A2 (PLA2) activity, catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids. Shows O-acyltransferase activity, catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid. Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE) which serves as precursor for N-acylethanolamines (NAEs) (By similarity). Required for complete organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (PubMed:33854238). Organelle membrane degradation is probably catalyzed by the phospholipase activity (PubMed:33854238) (By similarity).
Knockout animals exhibit normal growth of their body and eye lens. However, the disappearance of mitochondria and the endoplasmic reticulum in the lens is almost completely suppressed and membranous structures persisted in the lens central region.
The C-terminal transmembrane domain is required for the targeting of the protein to damaged organelles.
Required for proper homologous chromosome pairing and efficient cross-over and intragenic recombination during meiosis.
Required for proper homologous chromosome pairing and efficient cross-over and intragenic recombination during meiosis. Stimulates both DMC1- and RAD51-mediated homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks (By similarity).
Possible splicing regulator involved in the control of cellular survival.
First expressed at the 1-somite stage with an anterior expression limit in rhombomere 7 (r7) of the developing hindbrain. By the 15-somite stage, the anterior expression limit is at the r6/r7 boundary and this is maintained until at least 30 hours of development. At the 10-somite stage, weakly expressed in the paraxial mesoderm with an anterior expression limit at somite 1.
Probable transcriptional regulator involved in developmental processes.
The Ripply homology domain and the WRPW motif are both necessary for its transcriptional corepressor activity on the transcription activator TBX1.
Possible role in neuronal acetylcholine receptor transport.
Transcriptional activator that mediates FGF signaling during neural development (By similarity). Plays a role in the regulation of cell movement (PubMed:17980025). Does not bind DNA by itself (By similarity).
Up-regulated by FGF signaling in embryos at mid-gastrulation.
Contains miscellaneous N-terminal sequence and a possible frameshift.
Belongs to the eIF-2B gamma/epsilon subunits family.
Embryos arrest development shortly after the midblastula transition. During cleavage (2-, 64-, and 1,000-cell-stage embryos) all blastomeres of mutant embryos contain morphologically abnormal nuclei that appeared fragmented in formation of multiple micronuclei.
Has a similar domain organization and 27% homology to yeast kar5.
Required for nuclear membrane fusion during karyogamy.
May play a role in Golgi structure maintenance.
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).
May play a role in cilia formation and embryonic patterning.
Maternally provided it is detected at all tested stages of development.
May regulate secretion and presynaptic differentiation through inhibition of the activity of N-type voltage-gated calcium channel. During presynaptic differentiation may regulate both synaptic vesicle accumulation in axon terminals and subsequent axon terminal remodeling.
The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.
INPP5F has been initially described as an inositol polyphosphate 5-phosphatase.
Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a sequential dephosphorylation of phosphatidylinositol 4,5-bisphosphate at the 5 and 4 position of inositol, thus playing an important role in the endocytic recycling.
Component of intercellular bridges during meiosis. Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells. Not required for fertility (By similarity).
Contributes to nuclear envelope stiffness in germ cells (By similarity). Involved in male and female fertility (PubMed:32923640).
No discernible effect on morphology, viability or fecundity (PubMed:32923640). Simultaneous knockout of nemp1 and nemp2 results in viable healthy animals but both females and males have impaired fertility with females laying normal-sized clutches only for the first 3 weeks followed by a marked drop in fertility (PubMed:32923640).
Belongs to the uroporphyrinogen decarboxylase family.
Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway. Isomer I or isomer III of uroporphyrinogen may serve as substrate, but only coproporphyrinogen III can ultimately be converted to heme (By similarity). In vitro also decarboxylates pentacarboxylate porphyrinogen I (PubMed:9806541).
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.
Binds 3 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound to the C2 domain.
Belongs to the nucleobase:cation symporter-2 (NCS2) (TC 2.A.40) 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.
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.
At 12 hours post-fertilization, the expression is restricted to Kupffer's vesicle.
Morpholino knockdown of the protein results in randomnized heart looping at 48 hours post-fertilization.
Plays a specialized role in the generation of left-right asymmetry during embryogenesis. May act as a negative regulator of the NOTCH-signaling pathway.
The precursor is cleaved by a furin endopeptidase.
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.
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.
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.
Exports glutathione-coordinated iron-sulfur clusters such as [2Fe-2S]-(GS)4 cluster from the mitochondria to the cytosol in an ATP-dependent manner allowing the assembly of the cytosolic iron-sulfur (Fe/S) cluster-containing proteins and participates in iron homeostasis (By similarity). May play a role in cadmium, zinc and mercury detoxification (PubMed:27734548).
First expressed before epiboly in dorsal precursors. During epiboly, expressed in the enveloping layer, yolk syncytial layer and migrating mesendoderm. During segmentation stages, expressed in epithelial structures such as adaxial cells, border cells of the newly formed somites, developing lens, otic vesicles and venous vasculature.
Morpholino knockdown of the protein induces embryonic lethality due to cardiac dysplasia with little to no blood circulation around 6 days post-fertilization (dpf) (PubMed:24316148). Mutant embryos show pericardial edema and accumulation of erythrocytes in the intermediate cell mass (ICM) at 30 hours post-fertilization (hpf) (PubMed:24316148). Display decreased angioblast migration to the embryonic midline during late gastrulation (PubMed:24316148, PubMed:24407481, PubMed:26017639).
Receptor for apelin receptor early endogenous ligand (apela) and apelin (apln) hormones coupled to G proteins that inhibit adenylate cyclase activity (PubMed:17336906, PubMed:24316148, PubMed:24407481). 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 (PubMed:17336906, PubMed:24316148, PubMed:24407481, PubMed:26017639). Positively regulates angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (PubMed:26017639). May promote sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel development (By similarity). Required for cardiovascular development, particularly for intersomitic vein angiogenesis by acting as a receptor for apln hormone (By similarity). Also plays a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility, and heart failure (By similarity). Acts redundantly with agtrl1b in heart development (PubMed:17336906).
First expressed at early neurula stage (9-12 hours). Expression then increases greatly at the 16-somite stage, reached the maximum level at 36 hr of development, and thereafter decreased. Only expressed in adults in the brain.
Predominantly expressed in the central nervous system.
Functions in trans to edit the amino acid moiety from incorrectly charged tRNA(Ala).
Catalyzes the dehalogenation of halotyrosines such as 3,5-diiodo-L-tyrosine (PubMed:24153409). Likely to also catalyze the dehalogenation of other halotyrosines such as 3-bromo-L-tyrosine, 3-chloro-L-tyrosine and 3-iodo-L-tyrosine (By similarity).
Essential for Spemann-Mangold organizer formation and subsequent anterior head development in the embryo. Inhibits canonical Wnt signaling pathway by antagonizing nuclear import of beta-catenin (ctnnb1) during embryogenesis.
Interacts (via NLS1 and NLS2) with dvl2; the interaction is negatively regulated by Wnt stimulation. Interacts with csnk1a1. Interacts with ctnnb1; the interaction is positively regulated by Wnt stimulation.
Morpholino knockdown results in embryos with small eyes, head, and brain structures.
Named Custos for the Latin term for 'guard' or 'keeper'.
Interacts with the spliceosome. Part of a complex containing U4/U6 snRNPs (By similarity).
Participates in the second step of pre-mRNA splicing.
S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap2 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the second nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) (cap0) to produce m(7)GpppRmpNm (cap2).
Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.
Inhibitor of the serine/threonine-protein kinase pak4/pak5. Acts by binding pak4/pak5 in a substrate-like manner, inhibiting the protein kinase activity.
The Inka box (also named iBox or inca box) binds and inhibits PAK4 by binding a substrate-like manner.
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 (By similarity).
Key regulator of transforming growth factor beta-1 (TGFB1) specifically required for microglia function in the nervous system. Required for activation of latent TGF-beta-1 in macrophages and microglia: associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGFB1, and regulates integrin-dependent activation of TGF-beta-1. TGF-beta-1 activation mediated by lrrc33/nrros is highly localized: there is little spreading of TGF-beta-1 activated from one microglial cell to neighboring microglia, suggesting the existence of localized and selective activation of TGF-beta-1 by lrrc33/nrros.
Expressed in the developing eye. In 48h embryos, low levels in the developing eye. High levels in the branchial arch region and within the nasal epithelium. branchial arch region and in the developing pancreas.
Transcription factor that regulates metabolic homeostasis in response to oxidative stress (By similarity). 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' (By similarity). Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (By similarity).
Interacts with UBC9, RAN, RBM8A, eIF-1A and PAX6.
Expressed in the blastoderm margin. Expression shifts to the spinal cord and endodermal tissue at the somitogenesis stage.
Microtubule-associated protein with the capacity to bundle and stabilize microtubules. May associate with chromosomes and promote the organization of mitotic spindle microtubules around them (By similarity).
Belongs to the Integrator subunit 6 family.
Belongs to the indoleamine 2,3-dioxygenase family.
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).
Plasma membrane anion exchange protein of wide distribution.
Component of the swi5-sfr1 complex, a complex required for double-strand break repair via homologous recombination.
Belongs to the NADPH-dependent diflavin oxidoreductase NDOR1 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.
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.
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.
Belongs to the serpin family. Ov-serpin subfamily.
Maintains stem cell potency. Increases STAT3 phosphorylation and controls ERK phosphorylation. May act as a scaffold, increasing STAT3 recruitment onto endosomes.
The OCIA domain is necessary and sufficient for endosomal localization.
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. May antagonize BMP signaling (By similarity).
Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
LSm subunits form a heteromer with a doughnut shape.
Expressed in developing craniofacial tissues, intestine and lens.
Reduced melanisation 2 in embryos 2 days post-fertilization (dpf), misplaced pigment cells in the tail at 3 dpf, and abnormal jaw morphogenesis at 4 dpf and 5 dpf.
Acyltransferase which catalyzes the transfert of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoinositol or PI) and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle. Prefers arachidonoyl-CoA as the acyl donor, thus contributing to the regulation of free levels arachidonic acid in cell.
Belongs to the membrane-bound acyltransferase family.
Component of the ESCRT-I complex (endosomal sorting complex required for transport I).
Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (By similarity).
Impaired hinge point formation in the forebrain and midbrain cavities at 22 hours post-fertilization (hpf) in 95% of embryos (PubMed:30948426). Moderate curvature of the dorsal axis in 35% of embryos at 28 hpf which disappears at later stages (PubMed:30948426). Mild abnormalities in midbrain and forebrain ventricular cavities at 56 hpf (PubMed:30948426).
Positive regulator of Wnt signaling, acting synergistically with dvl2 (By similarity). Functions upstream of ctnnb1/beta-catenin in the canonical Wnt pathway, and also activates jnk in the Wnt/planar cell polarity (PCP) pathway (By similarity). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha (Gi-alpha) subunits (PubMed:30948426). This promotes apical cell constriction and subsequent bending of the neural plate during neurulation via arhgef18 (By similarity).
The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).
The PDZ domain is required for localization to apical junctions.
Undetectable at the gastrula stage at 7.5 hours post-fertilization (hpf) but readily observable during neurulation at 16 and 22 hpf where expression is restricted to the neural rod at 16 hpf and the neural tube at 22 and 28 hpf.
Plays a role in cortical progenitor cell proliferation and differentiation. May promote dendritic spine development of post-migratory cortical projection neurons by modulating the beta-catenin signaling pathway.
Expressed the retina, where expression is restricted to the outer nuclear layer.
Putative transcription factor that is required in photoreceptor cells precursors during eye development.
Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.
Component of the DREAM complex (By similarity). Binds directly to histone H4, probably via helix 1 of the histone fold, a region that is not accessible when histone H4 is in chromatin (By similarity).
Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA.
Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.
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 SWR1-like complex. Interacts with H2A.Z/H2AZ1 (By similarity).
Histone chaperone that specifically mediates the genome-wide removal of histone H2A.Z/H2AZ1 from the nucleosome: removes H2A.Z/H2AZ1 from its normal sites of deposition, especially from enhancer and insulator regions. Not involved in deposition of H2A.Z/H2AZ1 in the nucleosome. May stabilize the evicted H2A.Z/H2AZ1-H2B dimer, thus shifting the equilibrium towards dissociation and the off-chromatin state. Inhibits activity of protein phosphatase 2A (PP2A). Does not inhibit protein phosphatase 1. May play a role in cerebellar development and synaptogenesis (By similarity).
Phosphorylated. The phosphorylation is nuclear localization signal (NLS)-dependent (By similarity).
The H2A.Z-interacting domain (ZID) mediates a direct interaction with H2A.Z/H2AZ1.
Component of the nexin-dynein regulatory complex (N-DRC) (By similarity). Interacts (via IQ domain) with calmodulin when calcium levels are low. Does not interact with calmodulin in the presence of Ca(2+). Interacts with hsp70 and may form a complex with camk4 and hsp70 (PubMed:24787902).
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). Binds calmodulin when cellular Ca(2+) levels are low and thereby contributes to the regulation of calcium and calmodulin-dependent protein kinase IV (camk4) activity; contributes to the regulation of camk4 signaling cascades. Plays a role in the regulation of definitive hematopoiesis via its effects on camk4 (PubMed:24787902).
Detected in adult testis, and at lower levels in brain, kidney and ovary.
Morpholino knockdown of the protein leads to a severe reduction in the size of the caudal hematopoietic tissue at 72 hpf, a strong reduction in the number of myb-positive hematopoietic stem cells, and results in impaired definitive hematopoiesis. Contrary to wild-type, the expression of monocyte, macrophage and lymphoblast markers is strongly reduced. Likewise, hemoglobin levels are strongly reduced, suggesting impaired erythropoiesis.
The IQ domain mediates interaction with calmodulin when cellular Ca(2+) levels are low.
Belongs to the CDP-alcohol phosphatidyltransferase class-II family.
Functions in the biosynthesis of the anionic phospholipids phosphatidylglycerol and cardiolipin.
Belongs to the Odd C2H2-type zinc-finger protein family.
Contrary to PubMed:17011543, which shows pronephric expression during tailbud and somitogenesis stages, PubMed:18787069 report that osr1 is not expressed in kidney tissue. Similarly, in the absence of osr1, PubMed:17011543 report a complete absence of kidney tissue, and pericardial edemas characteristic of renal failure, whereas PubMed:18787069 report a segment-specific defect in the proximal nephron, with the distal nephron relatively unaffected, and a compensatory increase in angioblast cell numbers in the same trunk region.
Embryos show a down-regulation of early pronephric markers lhx1a/lim1 and pax2a/pax2.1, and subsequent kidney defects.
Expressed in the germ ring mesendoderm and subsequently in the endoderm and intermediate mesoderm, prior to the expression of definitive kidney or blood markers. At 60 hpf, expressed in the glomerulus, in some patches in the eye and brain, and weakly in the pectoral fin buds.
Transcriptional repressor (By similarity). Regulates mesoderm versus endoderm differentiation during gastrulation to regulate kidney versus vascular cell fate. Acts upstream of pax2a in kidney development and functions in glomerular maturation, after podocyte specification.
Protein kinase that may play an important role in cellular stress response. May be involved in the regulation of processes such as cell survival, neuronal excitability and renal sodium excretion (By similarity).
Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein. Major integral membrane glycoprotein of the erythrocyte membrane; required for normal flexibility and stability of the erythrocyte membrane and for normal erythrocyte shape via the interactions of its cytoplasmic domain with cytoskeletal proteins, glycolytic enzymes, and hemoglobin. Functions as a transporter that mediates the 1:1 exchange of inorganic anions across the erythrocyte membrane. Mediates chloride-bicarbonate exchange in the kidney, and is required for normal acidification of the urine.
Expression increases in response to prolonged fasting but decreases in response to growth hormone (GH).
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.
In embryos at 24 hpf, initially expressed in the lens and cranial region, and at 48 and 72 hpf in the brain boundary vasculature. Expression in these regions persists throughout the hatching period and by 96 hpf expression is most abundant in the liver. In both male and female adults, highest expression is in the liver with modest expression in the brain. In male but not females adults, expressed at a low level in muscle and gonad. Also expressed in the adult intestine.
Interacts equally well with igf1 and igf2.
Not expressed until 10 hpf. Expression gradually increases from 10 to 36 hpf and is maintained at high levels thereafter.
Binds 1 thiamine pyrophosphate per subunit.
Endoplasmic reticulum 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the fatty acid alpha-oxydation in a thiamine pyrophosphate (TPP)-dependent manner.
Symporter that selectively cotransports sodium ions and amino acids, such as L-glutamine and L-asparagine from the lysosome into the cytoplasm and may participates in mTORC1 activation. The transport activity requires an acidic lysosomal lumen.
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.
Component of the SKA1 complex, composed of ska1, ska2 and ska3.
DNA- and RNA-binding protein, involved in transcription repression and pre-mRNA splicing.
Morpholino-mediated knockdown of the gene results in embryos with reduced body length, microcephaly, retrognathia and heart edema.
The third RNA recognition motif, called PUMP domain, is atypical and may rather mediate homodimerization and/or protein-protein interactions.
Belongs to the complex I 20 kDa subunit family.
Belongs to the complex I NDUFA5 subunit family.
ATP-binding RNA helicase involved in the biogenesis of 60S ribosomal subunits.
Belongs to the DEAD box helicase family. DDX51/DBP6 subfamily.
The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis.
Expressed in the 2-somite stage (10 hpf) in the neural keel between rhombomere 7 (r7) and the anterior spinal cord. Between the 2- and 20-somite stages (10-19 hpf), expressed caudally in the developing spinal cord. At 25 somite stage (21 hpf), detected throughout the spinal cord with expression levels gradually decreasing from anterior to posterior. At the prim-5 stage (24 hpf), detected in the pectoral fin buds and in the dorsal forebrain. At the long-pec stage (48 hpf), expressed in the telecephalon, tectum opticum, hindbrain, cerebellum, in the first pharyngeal arch, in the eyes and at very low level in the olfactory placodes. Around the protruding mouth stage (72-96 hpf), some expression is still detected in the eyes and only scattered expression is seen in the tectum, midbrain/hindbrain boundary and hindbrain. By the early larval stage (120 hpf), no expression is detected in the first pharyngeal arch and only low expression is detectable in the telecephalon, midbrain/hindbrain boundary, hindbrain and along the edges of the tectum.
Probable transcriptional regulator involved in developmental processes. May act as a transcriptional repressor (Potential).
Up-regulated in embryos by all-trans retinoic acid at the prim-5 stage (24 hpf) in more anterior regions of the neural tube, especially in the midbrain, with weaker expression in the forebrain and in the eye primordium.
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.
Catalyzes the transfer of adenosine 5'-monophosphate (AMP) to Ser, Thr and Tyr residues of target proteins (AMPylation). May be a redox-active mitochondrial selenoprotein which interacts with a redox target protein.
Fam50a depletion results in early neurogenesis defects, abnormal anterior development impacting the brain, eyes and cartilage apparent at day 5 post-fertilization (5 dpf), and lethality occurring by 6 dpf.
Probably involved in the regulation of pre-mRNA splicing.
Widely expressed prior to and throughout gastrulation, and in mid-somitic embryos. From 24 hours post-fertilization (hpf) onward, and up to the latest time point assessed (72 hpf), expression is detected in anterior structures including the brain, eye and mandible.
Homodimer; disulfide-linked. Seems to also exist as monomers.
Scavenger receptor that displays several functions associated with host defense. Binds to carbohydrates (By similarity).
Belongs to the WD repeat PROPPIN family.
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.
Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of raf1 kinase and stimulate raf1 activity at specialized signaling complexes (By similarity).
Widely expressed. Higher levels of expression are detected in highly proliferative frontal regions of the embryo, e.g. brain, eye and anterior trunk.
Belongs to the apolipoprotein O/MICOS complex subunit Mic27 family.
Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.
Component of the mitochondrial contact site and cristae organizing system (MICOS) complex.
Belongs to the complex I NDUFB6 subunit 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.
Belongs to the methylmalonyl-CoA mutase family.
Catalyzes the reversible isomerization of methylmalonyl-CoA (MMCoA) (generated from branched-chain amino acid metabolism and degradation of dietary odd chain fatty acids and cholesterol) to succinyl-CoA (3-carboxypropionyl-CoA), a key intermediate of the tricarboxylic acid cycle.
Homodimer. Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin, APH1 and PEN2 (Probable).
Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors.
Protein expression is initiated from 6 and 12 hours of embryonic development.
While the protein appears only from 6 hours of development, the transcript is maternally derived and ubiquitously expressed during early embryonic development, suggesting that its translation is strictly regulated.
Accessory component of the STT3B-containing form of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. May be involved in substrate-specific N-glycosylation.
Accessory component of the STT3B-containing form of the oligosaccharyltransferase (OST) complex.
Heme transporter that regulates intracellular heme availability through the endosomal or lysosomal compartment.
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.
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.
First detected at low levels in the blastula stage and begins to accumulate in the margin of the blastoderm. At the shield stage, when gastrulation starts, expressed uniformly in the margin. As gastrulation proceeds, expressed at high levels in the posterior paraxial mesoderm. In the 1 day old embryo, at the early pharyngula stage, expression in the developing brain is very strong and expression is restricted to ventral domains of the brain. Expressed in endothelial cells of the intersegmantal vessels, between somite boundaries and in the dorsal aorta.
Belongs to the dermatan-sulfate isomerase family.
Chemorepulsive axon guidance protein required for the development of spinal cord and forebrain commissures. Acts as a chemorepulsive guidance protein for commissural axons during development. Able to inhibit or repel neurite outgrowth from dorsal spinal cord.
Belongs to the LAPTM4/LAPTM5 transporter family.
Tetrahedron-shaped homododecamer built from six homodimers.
C-terminal fragments could be released during apoptosis via caspase-3-dependent cleavage.
Plays a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein (CP).
Golgi-localized palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and regulates their association with membranes (Probable). Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (Probable).
Monomer. Homooligomers. The monomeric form has a higher catalytic activity. Forms heterooligomers with zdhhc7.
Probably maternally supplied, the zygotic expression is detected early during development at the sphere stage but decreases after 7.5 hpf.
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.
Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+) (By similarity). Involved in pigmentation, possibly by participating in ion transport in melanosomes (PubMed:16357253). Predominant sodium-calcium exchanger in melanocytes (PubMed:16357253).
Expressed in the retinal pigment epithelium and in the melanopore precursors at 1 day post-fertilization.
Fishes show a delayed and reduced development of pigmentation. They display a diminished number, size and density of melanosomes.
Highly expressed in melanin-producing cells. Colocalizes with melanin biosynthesis marker dct.
Belongs to the cyclophilin-type PPIase family. PPIase E subfamily.
Catalyzes the cis-trans isomerization of proline imidic peptide bonds in proteins.
Regulatory subunit of the dolichol-phosphate mannose (DPM) synthase complex; essential for the ER localization.
Expressed maternally and ubiquitously throughout the embryo across different developmental stages from early 8-cell stage to 24 hpf.
Mutant animals develop ventrally curved bodies visible at the end of 1 dpf, followed by bilateral kidney cysts in the glomerular-tubular region detectable at 2 dpf. Cilia in the anterior pronephric ducts are already visibly defective at 1 dpf and by 5 dpf, cilia are completely absent from these ducts. On the other hand, cilia from the posterior pronephric ducts remain unaffected. Cilia biogenesis is also defective in the retina, with the outer segments of photoreceptor cells having modified cilia. No visible cilia in the lateral line organ. Pericardial edema is also observed at 5 dpf.
Required for cilia biogenesis and maintenance in the kidney, the lateral line organ and eye. Appears to function within the multiple intraflagellar transport complex B (IFT-B).
Mitochondrial proton/calcium antiporter that mediates proton-dependent calcium efflux from mitochondrion (By similarity). Required for the maintenance of the tubular shape and cristae organization (By similarity).
Belongs to the actin family. ARP5 subfamily.
Belongs to the WD repeat DDB2/WDR76 family.
Belongs to the LDH/MDH superfamily. MDH type 1 family.
Belongs to the LanC-like protein family.
Functions as glutathione transferase. Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate (By similarity). Binds glutathione (By similarity).
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.
Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme.
Expressed in the nervous system during embryogenic stage 21. Expression decreases from stage 25 onwards.
Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as c-Jun and ATF2 and thus regulates AP-1 transcriptional activity. May play a role in the regulation of the circadian clock.
The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Catalyzes the formation of L-carnitine from gamma-butyrobetaine.
Involved in the early part of the secretory pathway.
Belongs to the ROX family. MINA53 subfamily.
Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase.
Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer (By similarity).
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity).
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway (By similarity).
Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated (By similarity).
Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport (By similarity).
Belongs to the potassium channel KCNE family.
Contrary to predictions, contains nine transmembrane helices, with an extracellular N-terminus and a cytoplasmic C-terminus. Besides, contains one long helix that dips into the membrane and then runs more or less parallel to the membrane surface.
Detected in embryos (at protein level). Detected in the yolk syncytium and in mesendodermal cells in the head and trunk region during early somitogenesis. Detected in the developing eyes, the anterior midbrain, the pineal gland and in anterior somites at 24 hpf. Detected only in the eyes and the pineal gland at 3 and 4 dpf. Detected in retinal pigment epithelium at 4 dpf.
Homodimer. Interacts (via C-terminus) with calmodulin.
Morpholino knockdown causes severe defects in embryonic development, with microphthalmia, a curved body axis and heart edema. The morphant hearts do not loop normally, heart atria are strongly dilated and blood circulation is severely impaired. Morphants have an altered morphology of the craniofacial skeleton, with malformation of the first and second arches and absence of the branchial arches. Embryonic heads at 4 dpf display reduced total retinyl ester levels and reduced levels of the visual pigment 11-cis-retinal. Morpholino knockdown of both stra6 and rbp4 alleviates the developmental impairment that is observed in stra6 morphants, suggesting the phenotype is due to impaired vitamin A homeostasis and excessive accumulation of retinoic acid.
Retinol transporter. Accepts retinol from the extracellular retinol-binding protein rbp4, mediates retinol transport across the cell membrane, and then transmits retinol to the cytoplasmic retinol-binding protein rbp1 (PubMed:27563101). Required for normal vitamin A homeostasis (PubMed:18316031).
Expressed ubiquitously at 18 hours post-fertilization (hpf).
Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to the luminal leaflet of the ER membrane, where it participates in the biosynthesis of glycosylphosphatidylinositol (GPI). GPI is a lipid glycoconjugate involved in post-translational modification of proteins. Can also translocate 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) (phosphatidylinositol or PI), as well as several other phospholipids (1,2-diacyl-sn-glycero-3-phosphocholine, 1,2-diacyl-sn-glycero-3-phosphoethanolamine), and N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI) in vitro.
Belongs to the eukaryotic AdoMetDC family.
Binds 1 pyruvoyl group covalently per subunit.
Essential for biosynthesis of the polyamines spermidine and spermine. Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels.
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 (By similarity).
Belongs to the bacterial ribosomal protein bL36 family.
Palmitoyl acyltransferase that mediates palmitoylation of proteins and is required during embryonic heart development. Involved in the proliferation of neural stem cells by regulating the FGF/ERK pathway (By similarity).
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.
Involved in the regulation of excitatory synapses.
Belongs to the glucosamine/galactosamine-6-phosphate isomerase family.
Involved in the regulation of both adhesion and cell morphology and cancer progression. Functions as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell-cell contacts in an integrin-dependent manner. Induces the formation of apical actin-dependent microvilli. Involved in the formation of a preapical plasma membrane subdomain to set up initial epithelial polarization and the apical lumen formation during renal tubulogenesis.
Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with psmg2.
At 4 days-post-fertilization (dpf), expressed in the inner and outer plexiform layers and the ganglion cell layer of the retina, the marginal zone of the tegmentum, and in the developing craniofacial cartilage.
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). May play a role in synapse assembly and function.
May have a roles as negative regulator of innate antiviral response.
Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.
Expressed in the ventral midline of the neural tube and brain. Also found in the notochord and in developing fin bud. In the developing brain, expression occurs in domains that include a discrete region in the floor of the diencephalon.
First detectable in the inner cell layer of the embryonic shield during gastrulation. By 9.5 hours of development, expressed in a continuous band that extends from the tail to the head, the anterior boundary of expression being positioned in the center of the animal pole anterior to the presumptive midbrain.
Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus (By similarity). Interacts with BOC and CDON (By similarity). Interacts with HHIP (By similarity). Interacts with DISP1 via its cholesterol anchor (By similarity). Interacts with SCUBE2 (By similarity).
N-palmitoylation by HHAT of ShhN is required for sonic hedgehog protein N-product multimerization and full activity (By similarity). It is a prerequisite for the membrane-proximal positioning and the subsequent shedding of this N-terminal peptide (By similarity).
The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (ShhN) (By similarity). Cholesterylation is required for the sonic hedgehog protein N-product targeting to lipid rafts and multimerization (By similarity). ShhN is the active species in both local and long-range signaling, whereas the C-product (ShhC) is degraded in the reticulum endoplasmic (By similarity).
The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Once cleaved, ShhC is degraded in the endoplasmic reticulum (By similarity).
The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhNp (By similarity). The N-terminal palmitoylated peptide is cleaved at the Heparan sulfate-binding Cardin-Weintraub (CW) motif site (By similarity). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (By similarity).
The dually lipidated sonic hedgehog protein N-product (ShhNp) is a morphogen which is essential for a variety of patterning events during development (By similarity). Involved in dorso-ventral patterning of the brain and in early patterning of the developing eyes (PubMed:7583153). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity). In the absence of SHH, PTCH1 represses the constitutive signaling activity of SMO (By similarity).
The lipidated N- and C-terminal peptides of ShhNp can be cleaved (shedding) (By similarity). The N-terminal palmitoylated peptide is cleaved at the Cardin-Weintraub (CW) motif site (By similarity). The cleavage reduced the interactions with heparan sulfate (By similarity). The cleavage is enhanced by SCUBE2 (By similarity).
The several steps and mechanisms that permit controlled Shh dispersion and gradient formation remain controversial. The Shh C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity resulting in the cleavage and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (ShhN). The protein is further modified by covalent addition of palmitate at the N-terminal of ShhN, resulting to the dual-lipidated Shh (ShhNp). ShhNp is firmly tethered to the cell membrane where it forms multimers. Further solubilization and release from the cell surface seem to be achieved through different mechanisms, including the interaction with DISP1 and SCUBE2, movement by lipoprotein particles, transport by cellular extensions called cytonemes or by proteolytic removal of both terminal lipidated peptides. Once released, the fully processed Shh can signal within embryonic tissues both at short and long-range.
At the 10-somite stage, expressed strongly in the paraxial mesoderm with an anterior expression limit at somite 6. At the 20-somite stage, expressed in the developing CNS with an anterior expression limit adjacent to the somite 2/somite 3 boundary.
Involved in several stages of intracellular trafficking.
Expressed from the oblong to the hatching stage.
May play a role in cell growth and maintenance of cell morphology.
Expressed in the hemato-vascular system: enriched in sorted endothelial cells and haemogenic endothelium (PubMed:28869969).
Gate loop 1 and gate loop 2 regions are adjacent to the S-adenosyl-L-homocysteine-binding site and display large conformational changes upon ligand-binding. They may play an important role in adenosine recognition. The interface loop contributes to the heterodimer interaction.
Heterodimer; heterodimerizes with mettl14 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.
Lethality 10 days post-fertilization (dpf) due to severe hematopoietic defects (PubMed:28869969). Levels of N6-methyladenosine (m6A)-containing mRNAs are significantly decreased and emergence of hematopoietic stem cells is blocked (PubMed:28869969).
Maternally expressed from the 4-cell stage and ubiquitously expressed through early embryogenesis, with enriched expression in the brain region at 36 hpf (hours post fertilization) (PubMed:24407421).
The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:28869969). In the heterodimer formed with mettl14, mettl3 constitutes the catalytic core (By similarity). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing and translation efficiency (By similarity). M6A is also involved in hematopoietic stem cells specification: m6A methylation and subsequent destabilization of mRNAs, such as notch1a, leads to decreased Notch signaling, promoting endothelial to hematopoietic transition (PubMed:28869969). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (By similarity). Mediates methylation of pri-miRNAs (By similarity).
Appears at 9 hours of development, and at 12 hours of development significant levels are found in the developing brain posterior to ocular vesicles. Distributed mainly in the midbrain, part of the diencephalon beneath the epiphysis and in the epiphysis at 18 hours of development. Found in the ventral part of the midbrain and in the dorsal part of the diencephalon at 24 hours of development.
May play a role in very early embryogenesis, gastrulation, and the development and subdivision of the diencephalon and the midbrain.
Belongs to the Mediator complex subunit 15 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. Required for cholesterol-dependent gene regulation (By similarity). Positively regulates the Nodal signaling pathway.
Component of the Mediator complex. Interacts with srebf1 and srebf2. Interacts with smad2, smad3 and smad4 (By similarity).
Specific and highly efficient GDP-D-glucose phosphorylase regulating the levels of GDP-D-glucose in cells.
The orthologs in A.thaliana are GDP-L-galactose phosphorylases catalyzing the first reaction of the Smirnoff-Wheeler pathway, the major route to ascorbate biosynthesis in plants.
May play a role as a nucleotide-sugar transporter.
May play an important role in centriole assembly and/or stability and ciliogenesis.
The CR1 and CR2 motifs mediate sequence-specific DNA binding.
Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
Belongs to the cyclin family. Cyclin E subfamily.
Essential for the control of the cell cycle at the G1/S (start) transition.
Interacts with CDK2 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex.
Phosphorylation by CDK2 triggers its release from CDK2 and degradation via the ubiquitin proteasome pathway.
May be involved in cytochrome c oxidase biogenesis.
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.
May play an important role in the formation of lipid droplets (LDs) which are storage organelles at the center of lipid and energy homeostasis (By similarity). May directly bind to diacylglycerol (DAGs) and triacylglycerol (By similarity).
Belongs to the eukaryotic ribosomal protein eL14 family.
First detected at sphere stage (4 hours) in a small group of cells at the margin of the blastoderm. As epiboly starts, it extends over the whole circumference of the margin of the blastoderm, while it is not detected in the yolk syncytial layer. Expression domain extends over 6 rows of cells, that is over a region that includes the precursors of mesoderm and endoderm. At the shield stage, it is also expressed in the invaginating axial mesendoderm. After the shield stage, the abundance of transcripts declines abruptly and only a weak expression is detected in embryos at 60% epiboly and no expression at 70% epiboly or later. Not detected in 4 day old embryos or in adult fish.
Probable transcription factor involved in the control of specification of mesoderm and endoderm. Acts in parallel with bonnie and clyde, faust and casanova in the Nodal signaling pathway.
Restricted to the mesendoderm precursors during gastrulation.
Belongs to the acetyltransferase family.
Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate.
Accelerates cholesterol efflux from endothelial cells to high-density lipoprotein (HDL) and thereby regulates angiogenesis (PubMed:23719382). Orchestrates hematopoietic stem and progenitor cell emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. YJEFN3-mediated cholesterol efflux activates endothelial SREBF2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates NOTCH and promotes hematopoietic stem and progenitor cell emergence (PubMed:30705153).
Expression in 24-36 hours post-fertilization (hpf) embryos shows a clear segmental pattern. By 48 hpf, when segmental angiogenesis is completed, is no longer expressed in somites.
Interacts with APOA1 (PubMed:23719382). Binds to HDL (PubMed:23719382).
Mutants appear morphologically normal and have no observable effect on dorsal aorta specification (PubMed:30705153). Mutants have reduced the number of nascent hematopoietic stem cells in the ventral dorsal aorta between 28 and 60 hours post-fertilization (hpf) (PubMed:30705153). Mutant embryos show increased cholesterol content (PubMed:30705153, PubMed:23719382).
G-protein coupled receptor for cannabinoids. Mediates many cannabinoid-induced effects in the central nervous system (CNS), as well as in peripheral tissues. Signaling typically involves reduction in cyclic AMP.
Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum.
As part of the spliceosome, plays a role in pre-mRNA splicing. Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity.
Despite the fact that it belongs to the cyclophilin-type PPIase family, it has probably no peptidyl-prolyl cis-trans isomerase activity.
Part of the activated spliceosome B/catalytic step 1 spliceosome, one of the forms of the spliceosome which has a well-formed active site but still cannot catalyze the branching reaction and is composed at least of 52 proteins, the U2, U5 and U6 snRNAs and the pre-mRNA. Recruited during early steps of activated spliceosome B maturation, it is probably one of the first proteins released from this complex as he matures to the spliceosome C complex.
Belongs to the hcp beta-lactamase family.
May be required for assembly of mitochondrial respiratory chain complexes.
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.
May play a role into cellular response to oxidative stress. May decrease cell proliferation (By similarity).
Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity requires interaction with HSP90alpha. Shows even higher methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at 'Lys-860'.
Belongs to the V-ATPase F subunit family.
Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments.
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 mitochondrion-specific ribosomal protein mS25 family.
At the 8-somite stage, expressed in the pronephros, with weak generalized expression elsewhere. At 24 hpf, expressed in the kidney tubules and the anterior duct, and also in the gut. At 60 hpf, expressed in the tubules and the pectoral fin buds.
Embryos show a down-regulation of early pronephric markers lhx1a/lim1 and pax2a/pax2.1, and subsequent defects in renal structures. In addition, embryos at 72 hpf display pericardial edemas and kidney cysts characteristic of kidney failure.
Transcriptional repressor (By similarity). Required for pronephric kidney development.
Probable S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA (By similarity).
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.
Expressed ubiquitously in 24 hours embryos, with highest levels in telencephalon, lens, retina, cerebellum and hindbrain primordia.
Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimers. Does not target the ODC monomers for degradation, which allows a protein synthesis-independent restoration of ODC activity.
Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). Required for normal cytokinesis and cilia signaling. Required for targeting proteins to the ciliary membrane by releasing myristoylated protein from unc119 cargo adapters into the cilium (By similarity).
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.
DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase. Functions as ATP-dependent DNA translocase. Can promote Holliday junction branch migration (in vitro).
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.
After the somite segmentation period, it is apparent throughout the embryo and the hatching gland. At the larval (3 dpf) stage, it is detected in the heart and kidney.
Dioxygenase that can both act as a arginine demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as u2af2/u2af65 and LUC7L2. Regulates RNA splicing by mediating 5-hydroxylation of u2af2/u2af65, affecting the pre-mRNA splicing activity of u2af2/u2af65. Hydroxylates its own N-terminus, which is required for homooligomerization. In addition to peptidyl-lysine 5-dioxygenase activity, may act as an RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which preferentially demethylates asymmetric dimethylation. Demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), including mono-, symmetric di- and asymmetric dimethylated forms, thereby playing a role in histone code. However, histone arginine demethylation may not constitute the primary activity in vivo. In collaboration with brd4, interacts with the positive transcription elongation factor b (P-TEFb) complex in its active form to regulate polymerase II promoter-proximal pause release for transcriptional activation of a large cohort of genes. Demethylates other arginine methylated-proteins such as esr1. Has no histone lysine demethylase activity (By similarity). Required for differentiation of multiple organs during embryogenesis. Acts as a key regulator of hematopoietic differentiation (By similarity).
Expressed in embryos from the one-cell developmental stage to the 3 days post-fertilization (dpf) larval stage.
Fishes display an accumulation of a large number of dead apoptotic cells in whole early embryo. These cells interfere with embryonic cell migration. In addition, normal development of the somite, brain, heart and notochord are sequentially disrupted up to 24 hours post-fertilization.
Hydroxylates its own N-terminus; hydroxylation is required for homooligomerization.
The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus.
Was initially thought to constitute the phosphatidylserine receptor, a receptor that mediates recognition of phosphatidylserine, a specific marker only present at the surface of apoptotic cells, and participates in apoptotic cell phagocytosis. However, some results strongly suggest that it does not constitute the receptor for phosphatidylserine and is not involved in apoptotic cell removal.
Belongs to the eukaryotic ribosomal protein eL31 family.
Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of type I collagen. By acting on collagen glycosylation, facilitates the formation of collagen triple helix.
Expressed at 16 hours post fertilization (hpf) in the pineal gland, a light-sensitive endocrine organ. Expression in the retinal pigment epithelium (RPE) is initiated in the ventronasal patch at 40 hpf, preceding photoreceptor differentiation by a few hours. During subsequent development, expression in the RPE becomes stronger and more widespread, covering the entire RPE except for the cilliary margin by 56 hpf.
Plays important roles in the production of 11-cis retinal and in visual pigment regeneration. Capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid (By similarity).
Belongs to the eukaryotic cobalamin transport proteins family.
Expressed along the tract of the anterior commissure between 24 and 30 hours post-fertilization (hpf). At 30 hpf, expressed in cells along the tract of the postoptic commissure. Expressed in preoptic area from 48 hpf until 96 hpf. Expressed in posterior hypothalamus, ventral midbrain, hindbrain and retinal ganglion cells by 48 hpf. These domains of expression persisted and strengthened in older embryos.
In vitro, has no proton-gated channel activity.
Probable cation channel with high affinity for sodium.
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.
Morpholino knockdown in embryos reducing the levels of grx3 protein to 40% severely impairs the synthesis of heme and the maturation of hemoglobin, and results in individuals with fewer red blood cells.
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 (By similarity). Required for hemoglobin maturation (PubMed:23615448). Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity (By similarity).
Belongs to the proteasome subunit p55 family.
According to a report, morpholino knockdown in embryos is lethal (PubMed:25078621). Other publications report that morpholino knockdown animals are viable (PubMed:28681861, PubMed:28161523, PubMed:30016436).
Homozygous knockout animals are viable (PubMed:28681861). While, larval and early juvenile fish show no overt phenotype, adult animals are small and develop craniofacial deformities (PubMed:28681861, PubMed:30016436). Mutant embryos lack fast-twitch myoblast fusion at 24 hours post-fertilization (hpf) (PubMed:25078621, PubMed:28681861, PubMed:28161523, PubMed:30016436). No alteration in the organization of slow-twitch myofibers, that do not fuse (PubMed:28681861, PubMed:30016436). In adults, fast-twitch musculature shows variably-sized hypotrophic fibers with variable degrees of fatty infiltration compared to wild-type siblings (PubMed:28681861, PubMed:30016436).
Myoblast-specific protein that mediates myoblast fusion, an essential step for the formation of multi-nucleated muscle fibers (PubMed:25078621, PubMed:28681861, PubMed:28161523, PubMed:30016436). Actively participates in the membrane fusion reaction by mediating the mixing of cell membrane lipids (hemifusion) upstream of mymx (By similarity).
Specifically expressed in the developing somites, concomitant with muscle differentiation.
Belongs to the SNF2/RAD54 helicase family. ISWI subfamily.
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).
Belongs to the D-glucuronyl C5-epimerase family.
Belongs to the fatty acyl-CoA reductase family.
Catalyzes the reduction of fatty acyl-CoA to fatty alcohols.
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.
Belongs to the complex I NDUFS4 subunit 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.
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).
In the N-terminal section; belongs to the calycin superfamily. Lipocalin family.
Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and may be involved in various processes including cellular proliferation, migration, adhesion and attachment. May play a role in ER stress response (By similarity).
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. It probably triggers the ubiquitin-mediated degradation of different substrates.
The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family.
Component of Polycomb group (PcG) multiprotein complexes; the complex class is required to maintain the transcriptionally repressive state of some genes.
Belongs to the peptidase C19 family. USP44 subfamily.
Deubiquitinase that plays a key role in the spindle assembly 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 U1 small nuclear ribonucleoprotein C family.
Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins snrpb, snrpd1, snrpd2, snrpd3, snrpe, snrpf and snrpg that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least 3 U1 snRNP-specific proteins snrnp70/U1-70K, snrpa/U1-A and snrpc/U1-C. snrpc/U1-C interacts with U1 snRNA and the 5' splice-site region of the pre-mRNA.
Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. SNRPC/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates commitment or early (E) complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.
Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. snrpc/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates E complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.
Still contains stable, but U1-C-deficient U1 snRNPs. Changes the alternative splicing patterns of a large set of specific target genes. Results in an early embryonic lethality at about 5 days post-fertilization.
U1 snRNP is composed of the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least 3 U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. SNRPC/U1-C interacts with U1 snRNA and the 5' splice-site region of the pre-mRNA.
Belongs to the nucleoporin Nup84/Nup107 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).
Negative regulator of sphingolipid synthesis.
Belongs to the universal ribosomal protein uS4 family.
Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs.
Belongs to the complex I NDUFB7 subunit 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.
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).
Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins. May play a regulatory role at the level of protein turnover.
Abundantly expressed at early developmental stages but decreases slightly when embryos proceed in development (PubMed:27377701). Expression is strongly detected from 0.25 to 3 hours post-fertilization (hpf) in embryos, but it is only weakly observed at 12 hpf (PubMed:27377701). At 24 and 36 hpf, signals are observed only around the eye with stronger intensities at 24 hpf than 36 hpf (PubMed:27377701).
Expressed at high levels in the ovary and at lower levels in the fin, testis and brain.
Histone methyltransferase that specifically trimethylates 'Lys-20' of histone H4 to form trimethylated histone H4 lysine 20 (H4K20me3) which represents a specific tag for epigenetic transcriptional repression (By similarity). Plays a crucial role in hematopoiesis during embryogenesis by negatively regulating expression of genes related to both primitive and definitive hematopoiesis (PubMed:27377701).
Morpholino knockdown results in embryos which show normal gross morphological development, including of heart and skeletal muscle (PubMed:27377701). However, an increased expression of genes related to both primitive and definitive hematopoiesis is seen (PubMed:27377701).
Mitochondrial GTPase involved in mitochondrial trafficking.
Belongs to the peptidase M67A family. BRCC36 subfamily.
Component of the BRCA1-A complex. Component of the BRISC complex. Both the BRCA1-A complex and the BRISC complex bind polyubiquitin.
Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the brca1-bard1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1.
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.
Detected 4 hours after fertilization with maximum levels seen in 6 hours embryos. Expression then declines during gastrulation (6-10 hours), but is still detectable in 24 and 30 hours embryos. The spatial distribution also varies during embryogenesis: at the beginning, expression is localized in deep cells and is absent from the enveloping layer. The pattern then becomes asymmetric, restricting to the forming embryonic shield. By the shield stage, it is highly localized in the axial hypoblast. As gastrulation proceeds, expression continues in the involuting cells, extending from the margin towards the anterior.
Seems to play a role in dorsal axis formation.
Belongs to the immunoglobulin superfamily. Contactin family.
Contactins mediate cell surface interactions during nervous system development.
In contrast to other members of the family, it lacks a canonical signal sequence; the existence of the signal sequence is therefore unsure.
Belongs to the Mediator complex subunit 21 family.
Expressed zygotically. Weak expression at 75% epiboly. At the 2-somite stage, expressed in the presumptive rhombomere 4 (r4) region partially overlapping with the r3 region. At the 10-somite stage, expressed in the r4, r3 and r2 regions. At the 14-somite stage, expression extends to the r5 and r6 regions and is observed in the diencephalon. At 24-48 hours post-fertilization (hpf), additionally expressed in the eye, midbrain-hindbrain boundary, cerebellum, pectoral fin and the pharyngeal arch primordia.
Involved in the metabolism of retinoic acid (RA), rendering this classical morphogen inactive through oxidation (PubMed:15661642). Appears to be involved in the inactivation of all-trans-retinoic acid (RA) (PubMed:15661642). Plays a role in skeletal development (PubMed:22019272).
Belongs to the universal ribosomal protein uL11 family.
Fishes display cysts in the glomerular-tubular region of the kidney similar to cystic kidney disease. Knockdown of the gene with 2 morpholino oligonucleotides leads to ventral body-axis curvature, formation of kidney cysts, otolith defects, and hydrocephalus, as well as cartilage defects of the craniofacial skeleton. Knockdown of the gene in a rhodopsin-GFP transgenic line demonstrates that the level of rhodopsin-GFP is lower in ift172 morphants than controls, suggesting retinal degeneration. Scanning electron microscopy of the olfactory placode reveales ciliogenesis defects in morphants, including shortened and truncated cilia.
Required for the maintenance and formation of cilia.
Belongs to the complex I NDUFB11 subunit family.
Belongs to the DNA polymerase epsilon subunit B family.
Participates in DNA repair and in chromosomal DNA replication.
Activated by dual phosphorylation on Ser-234 and Thr-238 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks (By similarity).
Dimer. Interacts (via its D domain) with its MAP kinase substrates. Interacts (via its DVD domain) with MAP3Ks activators.
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Phosphorylation by MAP2K6 asymmetrically activates p38 on one side of the blastodisc, an event which is necessary for blastomere cleavage.
Expressed both maternally and zygotically. Zygotic expression continues throughout development.
The D domain (residues 30-46) contains a conserved docking site and is required for the binding to MAPK substrates.
The DVD domain (residues 338-361) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation (By similarity).
Was originally thought to be a Map2k3 protein but sequence analysis shows closer similarity to the Map2k6 proteins.
Weakly autophosphorylated (By similarity). Phosphorylated at Ser-234 and Thr-238 by the majority of M3Ks.
Expressed during muscle development in adaxial cells, somites, cardiac precursors, finbuds and jaw muscle cells.
RNA-binding protein that regulates alternative splicing events by binding to 5'-GCAUG-3' elements. Regulates alternative splicing of tissue-specific exons.
Absence of sarm1 provides a level of protection against axon degeneration (PubMed:32001778). Schwann cells are protected from chemotoxicity by delaying axon degeneration (PubMed:32001778). Absence of Sarm1 does not promote axon resealing (PubMed:32728661).
Autoinhibited: in the inactive state, the enzymatic TIR domain is held apart by the autoinhibiting ARM repeats. NAD(+)-binding to ARM repeats maintains an inactive state by promoting interaction between ARM repeats and the TIR domain, thereby facilitating inhibition of the enzymatic TIR domain. Following activation, possibly by nicotinamide mononucleotide (NMN), auto-inhibitory interactions are released, allowing self-association of the TIR domains and subsequent activation of the NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is facilitated by the octamer of SAM domains.
Homooctamer; forms an octomeric ring via SAM domains.
NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism (PubMed:32001778). Acts as a negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway by promoting Wallerian degeneration, an injury-induced form of programmed subcellular death which involves degeneration of an axon distal to the injury site (By similarity). Wallerian degeneration is triggerred by NAD(+) depletion: in response to injury, SARM1 is activated and catalyzes cleavage of NAD(+) into ADP-D-ribose (ADPR), cyclic ADPR (cADPR) and nicotinamide; NAD(+) cleavage promoting cytoskeletal degradation and axon destruction (PubMed:28334607). Also able to hydrolyze NADP(+), but not other NAD(+)-related molecules (By similarity). Can activate neuronal cell death in response to stress (By similarity).
The ARM repeats inhibit the NAD(+) hydrolase (NADase) activity by binding to NAD(+): NAD(+)-binding to ARM repeats facilitates inhibition of the TIR domain NADase through their domain interface. In contrast to classical ARM repeats, the last helix of ARM 6 does not fold back to interact with the first two helices, but instead turns towards the N-terminus of SARM1. As a result, the two following motifs ARM 7 and ARM 8 reverse their directions and lie perpendicularly. Moreover, ARM repeats interact with different domains not only within each protomer but also of the adjacent ones.
Involved in spliceosome assembly (By similarity).
The Tudor domain mediates association with dimethylarginines, which are common in snRNP proteins.
As component of the WDR11 complex may act together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1.
May be a component of the WDR1 complex (By similarity). May interact with golgins.
Part of the postsynaptic scaffold in neuronal cells.
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.
Belongs to the WD repeat WDR12/YTM1 family.
Component of the PeBoW complex, composed of BOP1, PES1 and WDR12. Within the PeBoW complex BOP1 interacts directly with PES1 and WDR12. The PeBoW complex also associates with the 66S pre-ribosome.
Component of the PeBoW complex, 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).
Homodimer; binds DNA as homodimer. Heterodimer; heterodimerizes with other members of ATF family and with JUN family members.
Stress-responsive chromatin regulator that plays a role in various biological processes including innate immunological memory, adipocyte differentiation or telomerase regulation. In absence of stress, contributes to the formation of heterochromatin and heterochromatin-like structure by recruiting histone H3K9 tri- and di-methyltransferases thus silencing the transcription of target genes such as STAT1 in adipocytes, or genes involved in innate immunity in macrophages and adipocytes. Stress induces ATF7 phosphorylation that disrupts interactions with histone methyltransferase and enhances the association with coactivators containing histone acetyltransferase and/or histone demethylase, leading to disruption of the heterochromatin-like structure and subsequently transcriptional activation. In response to TNF-alpha, which is induced by various stresses, phosphorylated ATF7 and telomerase are released from telomeres leading to telomere shortening.
Lysosomal thiol reductase that can reduce protein disulfide bonds. May facilitate the complete unfolding of proteins destined for lysosomal degradation. Plays an important role in antigen processing.
Strongly expressed in spleen and kidney. Also detected at lower levels in heart, liver, intestine and muscle.
Up-regulated in spleen and kidney in response to bacterial lipopolysaccharide (LPS).
Belongs to the pectinacetylesterase family. Notum subfamily.
In contrast to other members of the family, lacks the active sites for palmitoleoyl-protein carboxylesterase activity, suggesting it has no activity.
Probable inactive palmitoleoyl-protein carboxylesterase.
As part of the exocyst, may play a role in regulated exocytosis.
Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes.
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 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 (By similarity). Controls gastrulation movements and left/right (L/R) axis determination via smad3-mediated regulation of cdh1/e-cadherin. Regulates the formation of Kupffer's vesicle, a signaling center essential for establishing L/R asymmetry. Modulates smad3 activity through modulating nodal-acvr1/akt4 signaling.
Expressed ubiquitously during blastula stages and throughout gastrulation. Shortly after shield formation, expressed weakly in dorsal forerunner cells (DFCs). Between somite stages 5 and 9, expressed in the tailbud and around the Kupffer's vesicle at a higher level than the more uniform expression in the embryo.
Composed of two structurally equivalent A and B domains that adopt a dual specificity protein phosphatase (DSP) fold.
Dual-specificity phosphatase. Required for centrosome separation and productive cytokinesis during cell division. Dephosphorylates SIRT2 around early anaphase. May dephosphorylate the APC subunit FZR1/CDH1, thereby promoting APC-FZR1 dependent degradation of mitotic cyclins and subsequent exit from mitosis.
Morpholino knockdown of the protein causes a shortening of the hair cell kinocilia in a larvae at 3 dpf. There are no other gross morphological defects in the inner ear.
Belongs to the prostaglandin G/H synthase family.
Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.
Tubulin-folding protein; involved in the second step of the tubulin folding pathway.
Embryos display defects such as small head, small eyes and dorsally bent body.
Plays an essential role in early embryonic development (PubMed:12006978). Plays an important role in the regulation of centriole duplication (By similarity).
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.
Gross morphology is normal. Expression of myelin basic protein (mbp) in the central nervous system at 5 dpf is strongly reduced. Expression of mpb in the peripheral nervous system is normal.
Probable transcription factor (Probable). Important for development and migration of oligodendrocyte precursor cells, and normal myelination of axons in the central nervous system (CNS) (PubMed:26459222). Functions autonomously in oligodendrocytes to promote CNS myelination (PubMed:26459222). Seems to act in parallel with notch3 during oligodendrocyte development (PubMed:26459222).
Acts as a negative regulator of autophagy.
The PHD-type zinc-finger domain is required for negative regulation of autophagy.
Mediates the nuclear export of proteins (cargos) with broad substrate specificity.
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.
Appears to play a crucial role in the insertion of secretory and membrane polypeptides into the ER. It is required for assembly of membrane and secretory proteins. Found to be tightly associated with membrane-bound ribosomes, either directly or through adapter proteins (By similarity). Necessary for the biogenesis and transport of multi-pass membrane proteins into the ER membrane (By similarity). Plays a role in the pronephric kidney tubule development (PubMed:27392076).
Heterotrimeric complex composed of SEC61-alpha, SEC61-beta and SEC61-gamma (By similarity). Component of the ribosome-associated ER translocon complex (By similarity).
Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.
Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate.
May be involved in gene regulation within neural lineage cells potentially by direct DNA binding or by binding to other transcription factors.
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.
Regulator of the TOR pathway, a signaling cascade that promotes cell growth in response to growth factors, energy levels, and amino acids. As part of the Ragulator complex, may activate the TOR signaling cascade in response to amino acids (By similarity).
Belongs to the pyrimidine 5'-nucleotidase family.
Can act both as nucleotidase and as phosphotransferase.
At the 3-somite stage, expressed in the forebrain. At the 12-somite stage, strongly expressed in the forebrain and weakly expressed throughout the central nervous system. At the 25-somite stage, also expressed in the lens.
At 26 hours post fertilization (hpf), expression is ubiquitous (PubMed:28972538). Later in development, expression is more pronounced in the anterior part (PubMed:28972538).
Belongs to the GTP-binding SRP family. SRP54 subfamily.
Binds to the signal sequence of presecretory protein when they emerge from the ribosomes and transfers them to TRAM (translocating chain-associating membrane protein) (By similarity). Plays a role in proliferation of granulocytic cells, neutrophils migration capacity and exocrine pancreas development (PubMed:28972538).
Has a two domain structure: the G-domain binds GTP; the M-domain binds the 7S RNA in presence of SRP19 and also binds the signal sequence.
Mutants show profound reductions in neutrophil counts and chemotaxis as well as a diminished exocrine pancreas size.
Signal recognition particle consists of a 7S RNA molecule and at least six protein subunits.
Belongs to the CND2 (condensin subunit 2) family.
Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes.
Belongs to the SMC family. SMC4 subfamily.
Essential for the assembly of the distal half of centrioles, required for centriole elongation.
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.
Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.
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 class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family.
Retinal short single cones, outer and inner segments.
Core component of the 7SK RNP complex. Associates with box C/D small nucleolar ribonucleoprotein (snoRNP) complexes.
Expression reaches a peak at 48 hours post-fertilization (hpf) and then decreases at 72, 96 and 120 hpf (PubMed:26542022). In embryonic hearts, expression slightly increases between 48 and 96 hpf, and then decreases at 120 hpf (PubMed:26542022). Expressed in the adult heart (PubMed:26542022).
Mild cardiac phenotype with increased phosphorylation of 'Ser-2' on RNA polymerase II.
RNA-binding protein that specifically binds distinct small nuclear RNA (snRNAs) and regulates their processing and function (PubMed:26542022). 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 (PubMed:26542022). 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 (PubMed:26542022). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (By similarity). 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 (By similarity). 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 (By similarity). 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 protein kinase superfamily. CMGC Ser/Thr protein kinase family.
Has a role in pre-mRNA splicing. Phosphorylates SF2/ASF.
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.
Mesendodermal expression at the blastoderm margin appears by 4.5 hpf. At early gastrulation, expression is maintained ventrolaterally while expression in dorsal cells and random deep cells declines. During gastrulation and segmentation, expression is maintained in adaxial, intermediate, and lateral plate mesoderm. During late segmentation, expressed in several regions including the forming heart. By 24 hpf, expressed in the dorsal aorta, caudal vein, and intersomitic blood vessels.
Receptor for apelin receptor early endogenous ligand (apela) and apelin (apln) hormones coupled to G proteins that inhibit adenylate cyclase activity (PubMed:17336905, PubMed:17336906, PubMed:24316148, PubMed:24407481). 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 (PubMed:17336905, PubMed:17336906, PubMed:24316148, PubMed:24407481, PubMed:26017639). Positively regulates angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (PubMed:26017639). May promote sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel development (By similarity). Required for cardiovascular development, particularly for intersomitic vein angiogenesis by acting as a receptor for apln hormone (By similarity). Plays a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility and heart failure (By similarity). Acts redundantly with agtrl1a in heart development (PubMed:17336906).
Belongs to the DEAD box helicase family. DDX52/ROK1 subfamily.
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).
Expressed both maternally and zygotically. Expressed in cleavage-stage embryos. Ubiquitously distributed throughout blastula stages of embryogenesis. At the onset of gastrulation, it is enriched in cells around the blastoderm margin. At shield stage, expression is detected in the deep involuted cells that contribute to mesendoderm. During mid and late gastrula stages, it is strongly expressed in axial mesendoderm. However, it is not present in the nascent tailbud at yolk plug closure (YPC) stage. Expression in axial mesendoderm is reduced at the 2 somite stage (SS). At 6 SS, it is expressed in cells surrounding Kupffer's vesicle, but apparently not within. By 10 SS, it is no longer detected as a specific signal above background.
Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate).
Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate). InsP6 is involved in many processes such as mRNA export, non-homologous end-joining, endocytosis and ion channel regulation. InsP6 also acts as a key regulator of left-right asymmetry in embryo, probably by regulating asymmetric Ca(2+) during left-right specification.
The EXKPK motif is conserved in inositol-pentakisphosphate 2-kinases of both family 1 and 2.
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. 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 (PubMed:12914916). 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 TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. TrmE GTPase family.
GTPase involved in the 5-carboxymethylaminomethyl modification (mnm(5)s(2)U34) of the wobble uridine base in mitochondrial tRNAs.
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).
Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy. In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation. The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and inhibiting its protein kinase activity.
Component of the C9orf72-SMCR8 complex. The C9orf72-SMCR8 complex associates with the ATG1/ULK1 kinase complex.
Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.
May be involved in collagen fiber assembly.
Belongs to the cyclin family. Cyclin Y subfamily.
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).
Belongs to the methyltransferase superfamily. Trimethylguanosine synthase family.
Acts as a regulator of cilium basal body docking and positioning in mono- and multiciliated cells.
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.
Was initially reported to have histone methyltransferase activity and methylate 'Lys-36' of histone H3 (H3K36me) (PubMed:21307598). However, this conclusion was based on mass spectrometry data wherin mass shifts were inconsistent with a bona fide methylation event and the histone methyltransferase activity could not be confirmed (By similarity).
Belongs to the eukaryotic/archaeal PrmC-related family.
Hydrolyzes the ester bond at the sn-1 position of glycerophospholipids and produces 2-acyl lysophospholipids. Hydrolyzes phosphatidylserine (PS) in the form of liposomes and 1-acyl-2 lysophosphatidylserine (lyso-PS), but not triolein, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA) or phosphatidylinositol (PI).
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).
Detected in primordial germ cells (PGCs) from 3 dpf. In adult, it is found in both the female and male gonad. In the ovary, it is present in all stages of germ cell differentiation. In testis, it is present in mitotic and meiotic germ cells. No protein has been detected in the fully differentiated sperm cell.
Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:18833190). Plays an essential role in germ cell differentiation and meiosis, independently of the function in transposable elements repression (PubMed:18833190). 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 (PubMed:18833190). 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 (By similarity). 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 (By similarity). Required for piwil4/miwi2 nuclear localization and association with secondary piRNAs antisense (By similarity). Represses circadian rhythms by promoting the stability and activity of core clock components BMAL1 and CLOCK (By similarity).
Progressive loss of germ cells due to apoptosis from 6 weeks of age.
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. ADGF subfamily.
Belongs to the proteasome subunit S10 family.
Belongs to the non-repetitive/WGA-negative nucleoporin family.
Part of the gamma-tubulin complex. Interacts with TUBG1 (By similarity).
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.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PDPK1 subfamily.
Required for normal spindle assembly. Plays a key role in mother-centriole-dependent centriole duplication. Plays a role in DNA damage response. Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression (By similarity).
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.
Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
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 (By similarity).
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.
Calretinin is a calcium-binding protein which is abundant in auditory neurons.
Belongs to the glycosyl hydrolase 65 family.
Catalyzes the hydrolysis of glucose from the disaccharide unit linked to hydroxylysine residues of collagen and collagen-like proteins.
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.
Embryos display defective melanosome transport and disruption of the ciliated Kupffer's vesicle phenotypes. BBIP1 morpholino knockdown results in bilateral cystic dilations of the pronephros. Pronephric cilia of morphants are abnormally short and fail to maintain a parallel orientation to the anteroposterior axis of the duct. Morphants also show increased frequency of situs inversus compared to wild-type and abnormal retinal development.
Belongs to the archaeal Rpo11/eukaryotic RPB11/RPC19 RNA polymerase subunit family.
Component of the RNA polymerase I (Pol I) and RNA polymerase III (Pol III) complexes consisting of at least 13 and 17 subunits, respectively.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common core component of RNA polymerases I and III which synthesize ribosomal RNA precursors and small RNAs, such as 5S rRNA and tRNAs, respectively (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.
A 90 degree bend between Pumilio repeats 3 and 4 gives rise to a L-shaped protein.
Expressed throughout embryogenesis. In the adult ovary, strong expression detected in primitive stage I ovarian follicles with levels declining sharply and becoming negligible in subsequent stages of oocyte development.
In adult, expressed at high levels in eye and ovary and at lower levels in brain, testis and head kidney. In the adult ovary, prominently expressed in early immature follicles.
Inhibits the poly(ADP-ribosyl)ation activity of PARP1 and the degradation of PARP1 by CASP3 following genotoxic stress (By similarity). Binds to double-stranded RNA or DNA without sequence specificity (By similarity). Involved in development of the eye and of primordial germ cells (PubMed:19319195).
Morpholino knockdown in embryos results in small eyes, small head and brain edema at 1 and 2 days post-fertilization (dpf). At 3 and 5 dpf, mutants exhibit features of an undifferentiated retina with loss of detailed architecture and a significant reduction in eye size. Structures such as the rod and cone layers are not concentrically organized and retinal ganglion cells and plexiform layers are not readily discernible. Mutants also show abnormal primordial germ cell migration.
Belongs to the cyclophilin-type PPIase family. PPIL2 subfamily.
Belongs to the V-ATPase D subunit family.
Promotes the survival of neuronal populations that are all located either in the central nervous system or directly connected to it.
Expressed in fast muscle fibers during skeletal muscle differentiation.
Morphant embryos have curved bodies, bent tails and a marked reduction in touch-evoked escape response. Muscle structure is altered and myofibers are sparse and disordered.
Myosin is a hexamer of 2 heavy chains and 4 light chains. Does not bind calcium.
Non-regulatory myosin light chain required for proper formation and/or maintenance of myofibers, and thus appropriate muscle function.
Required to protect lysosomal transporter MFSD1 from lysosomal proteolysis and for MFSD1 lysosomal localization.
Protects drg1 from proteolytic degradation.
Required for normal otolith growth and deposition of otolin-1 in the otolith.
Expression is activated at, or just after the midblastula stage, about 2 hours before the appearance of the embryonic shield. In early gastrulation, expression marks the anterior shield and by late gastrulation, expression is restricted to the rostral crescent and medial strip. Levels of GSC then decline and disappear at 12 hours post-fertilization.
Maternally expressed in oocytes and after fertilization, expressed in early embryos.
E3 ubiquitin ligase involved in the retrotranslocation and turnover of membrane and secretory proteins from the ER through a set of processes named ER-associated degradation (ERAD). This process acts on misfolded proteins as well as in the regulated degradation of correctly folded proteins (By similarity).
The C-terminal transmembrane domain is indispensable for the localization to the ER.
Depletion of ccdc32 using CRISPR-Cas9-mediated gene editing results in disrupted cardiac looping in embryos at 2 dpf, reduced number and length of cilia in Kupffer's vesicle, and in a significant reduction of head size at 3 dpf. Furthermore, ccdc32 crispants exhibit significant alterations in facial skeletal morphology and have hypoplastic cerebella.
Has a role in ciliogenesis and is required for proper cephalic and left/right axis development.
Belongs to the KIF-binding protein family.
Expressed maternally and is widely distributed in the early embryo (PubMed:8562427). Expressed in the posterior ventral and lateral mesodermal, and ectodermal cells during gastrulation (PubMed:25371059).
Key downstream component of the canonical Wnt signaling pathway (By similarity). In the absence of Wnt, forms a complex with axin1, axin2, apc, csnk1a1 and gsk3b that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of ctnnb1 and its subsequent degradation by the proteasome (By similarity). In the presence of Wnt ligand, ctnnb1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (By similarity). Plays a key role in dorsoventral patterning: in prospective ventral blastomeres, its down-regulation by axin1 and axin2 leads to inhibit the Wnt signaling pathway, while in prospective dorsal blastomeres, degradation of axin results in stabilization and nuclear translocation of ctnnb1 (PubMed:8562427, PubMed:30467143).
Phosphorylation by gsk3b promotes ubiquitination and subsequent degradation by the proteasome.
Ubiquitinated when phosphorylated by gsk3b, leading to its degradation.
Important for male fertility. With ROPN1, involved in fibrous sheath integrity and sperm motility, plays a role in PKA-dependent signaling processes required for spermatozoa capacitation.
Belongs to the cyclin family. Cyclin G subfamily.
May play a role in growth regulation. Is associated with G2/M phase arrest in response to DNA damage. May be an intermediate by which p53 mediates its role as an inhibitor of cellular proliferation.
Belongs to the complex I NDUFB4 subunit family.
Binds DNA as a dimer. Can form homodimer or heterodimer with HNF1-alpha (By similarity).
First expressed at stage 10 in the intermediate mesoderm. Expressed in rhombomere r5 by 14 hpf with expression diminishing by 18 hpf.
It is uncertain whether Met-1 or Met-5 is the initiator.
Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (By similarity). Acts downstream of hnf1ba but is not required for induction of rhombomere r5/r6 gene expression in the hindbrain.
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.
Heterodimer of a light chain and a heavy chain linked by a disulfide bond.
Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium.
Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs.
Component of the endosomal sorting complex required for transport II (ESCRT-II), 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).
Component of the endosomal sorting complex required for transport II (ESCRT-II).
Component of the endosomal sorting required for transport complex II (ESCRT-II), composed of SNF8, VPS25 and VPS36.
Plays a role in mitochondrial morphogenesis.
Homotrimer; disulfide-linked. Interacts with MASP1; probably triggers the lectin pathway of complement.
Lectin that plays a role in innate immunity, apoptosis and embryogenesis. Calcium-dependent lectin that binds self and non-self glycoproteins presenting high mannose oligosaccharides with at least one terminal alpha-1,2-linked mannose epitope. Primarily recognizes the terminal disaccharide of the glycan. Also recognizes a subset of fucosylated glycans and lipopolysaccharides. Plays a role in innate immunity through its ability to bind non-self sugars presented by microorganisms and to activate the complement through the recruitment of MAPS1. Also plays a role in apoptosis through its ability to bind in a calcium-independent manner the DNA present at the surface of apoptotic cells and to activate the complement in response to this binding (By similarity). Finally, plays a role in development, probably serving as a guidance cue during the migration of neural crest cells and other cell types during embryogenesis (PubMed:21258343).
Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide.
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.
Component of a transport protein particle (TRAPP) complex that may function in specific stages of inter-organelle traffic. Specifically involved in the early development of neural circuitry, likely by controlling the frequency and amplitude of intracellular calcium transients implicated in the regulation of neuron differentiation and survival.
Expressed in the central nervous system as early as 24 hours post-fertilization.
Homodimer (By similarity). Part of a TRAPP complex (By similarity).
Morpholino knockdown of the protein causes neurodevelopmental abnormalities associated with decreased survival rate. Morphants are characterized by microcephaly, brain hyperexcitability and lower seizure threshold.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.
Belongs to the Mediator complex subunit 7 family.
Belongs to the universal ribosomal protein uL24 family.
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 (By similarity).
Belongs to the connexin family. Beta-type (group I) subfamily.
Expressed in lens at 24 hours post-fertilization.
Has significant hemichannel activity. However, has only low-efficiency gap junction activity and probably does not function as a gap junction channel in vivo.
Belongs to the DZIP C2H2-type zinc-finger protein family.
Embryos show defects in otolith formation in the inner ear, but no other overt morphological changes.
Involved in primary cilium formation (PubMed:28530676). Probably acts as a transition zone protein required for localization of PKD1/PC1 and PKD2/PC2 to the ciliary membrane.
Maternally expressed. Ubiquitously expressed in embryos at 1 day post-fertilization (dpf), with a more discrete accumulation in the embryonic kidneys. In developing kidney, expressed in the midsections of the pronephric ducts, in a pattern consistent with the multiciliated cells.
Endocrine hormone of the central and peripheral nervous systems that binds and activates the G protein-coupled receptors GALR1 (galr1a and galr1b) and GALR2 (galr2a and galr2b). This small neuropeptide may regulate diverse physiologic functions including contraction of smooth muscle of the gastrointestinal and genitourinary tract, growth hormone and insulin release and adrenal secretion.
In embryos and larvae, detected mainly in nerve cells in the preoptic-hypothalamic regions and fibers innervating several brain regions (at protein level) (PubMed:22522977, PubMed:27315774). In embryos, detected in the anterior commissure, postoptic commissure, hypothalamus, pituitary gland, ventral hindbrain and the white matter of the ventral spinal cord (at protein level) (PubMed:27315774, PubMed:30903017). In larvae, detected in brain regions including telencephalon, hypothalamus, mesencephalon, medulla oblongata and pituitary at 30 hpf onwards (at protein level) (PubMed:22522977). Both isoforms are maternally expressed and detected throughout embryonic development (PubMed:22522977). Low-level expression detected throughout the developing embryo at 6-24 hours post-fertilization (hpf) with more focused expression detected in specific groups of neurons in the brain at 28 hpf onwards (PubMed:22522977).
Strongly expressed in brain and stomach, moderately in the eye, and very weakly in heart, kidney and gills. Not detected in liver.
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).
Strongly expressed in neurons and glia of the brain, the lamina propria, submucosa and serosa of the small intestine, in oocytes and on the fringes of the pancreas. Not expressed in the retina, eye lens, heart or bulbus arteriosus. Expressed in the yolk syncytial layer in gastrula stage embryos, in the yolk syncytial layer and mature somites in early segmentation embryos and in the yolk syncytial layer and the liver of long-pec stage (48 hours post-fertilization) embryos.
Widely expressed during maturation of oocytes. Also expressed in embryos from gastrulation onwards in the yolk syncytial layer and somites. Expression declines in the somites, but is up-regulated in the yolk syncytial layer throughout embryonic development.
Belongs to the WD repeat BOP1/ERB1 family.
Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules.
Interacts with ARMC12 in a TBC1D21-dependent manner.
Belongs to the 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.
May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment.
Microtubule-binding protein that negatively regulates centriole duplication. Binds to and stabilizes microtubules.
The N- and C-terminal barrels adopt an identical fold despite having only 13% of conserved residues.
The N-terminal region may be exposed to the interior of the granule, whereas the C-terminal portion may be embedded in the membrane. During phagocytosis and degranulation, proteases may be released and activated and cleave BPI at the junction of the N- and C-terminal portions of the molecule, providing controlled release of the N-terminal antibacterial fragment when bacteria are ingested.
The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope.
Belongs to the cytochrome c oxidase subunit 2 family.
Binds a dinuclear copper A center per subunit.
Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity). Found in a complex with TMEM177, COA6, COX18, COX20, SCO1 and SCO2. Interacts with TMEM177 in a COX20-dependent manner. Interacts with COX20. Interacts with COX16 (By similarity).
Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates. Catalyzes palmitoylation of Cys residues on protein substrates and has a preference for acyl-CoA with C16 fatty acid chains but may also utilize acyl-CoA with C14 and C18 fatty acid chains.
Expressed in skeletal muscle and heart. Detected, although at much lower levels, in brain, eye and fin.
Binds 2 magnesium ions. Also active with manganese.
Polymerase that creates the 3'-poly(A) tail of mRNA's.
Exhibits histone deacetylase (HDAC) enhancer properties. May play a role in progression through the cell cycle (By similarity).
Belongs to the UDP-glucose/GDP-mannose dehydrogenase family.
Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
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 'GDSL' lipolytic enzyme family. IAH1 subfamily.
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 (By similarity).
Belongs to the eukaryotic ribosomal protein eS24 family.
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.
May function to promote vesicle trafficking and/or fusion.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. NifS/IscS subfamily.
Detected in oocytes, and in embryos at 4 to 120 hours post-fertilization (hpf). Detected along marginal blastomeres at early epiboly stage and throughout the margin at the onset of gastrulation. At 60% epiboly, strongest expression is found in the dorsal shield region and is restricted to the epiblast. Detected in the anterior border of the presomitic mesoderm at the end of epiboly. Detected in adaxial cells, in the somites and in the nervous system during somitogenesis. Detected in diencephalon and hindbrain and in cells surrounding the notochord, including adaxial cells and ventral mesendoderm, in 15-somite stage embryos. At 48 hpf, detected mainly in the brain.
Guanine nucleotide exchange factor (GEF) for Ras family proteins (in vitro).
Although the OmpT protease is absent in Gram-positive bacteria, LF-ZF3 generated by a Gram-negative bacterium can penetrate a Gram-positive bacterium and exert its cytotoxicity.
Cleavage between Arg-55 and Arg-56 is catalyzed by a membrane-localized Gram-negative bacterium protease (OmpT in E.coli). The excised fragment is then transported to the bacterium cytosol for cleavage of the disulfide bridge linking Cys-48 and Cys-109, thus separating the N-terminal and LF-ZF3. LF-ZF3 but not the N-terminal peptide possesses bactericidal activity.
Ribonuclease. Angiogenic. Plays a role in host defense. Exhibits strong antibacterial activity against Gram-negative bacteria but mild antibacterial activity against Gram-positive bacteria. The RNase activity is not required for the bactericidal activity.
Strongly expressed in the adult liver and gut, and weakly in the heart and testis.
Belongs to the ELO family. ELOVL5 subfamily.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C18:3(n-6) acyl-CoA. May participate to the production of monounsaturated and of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
Belongs to the POU transcription factor family. Class-1 subfamily.
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.
Expressed in the germ ring at the blastoderm margin during the shield stage and when embryo reaches 80% epiboly stage of gastrulation, expression is higher dorsally than ventrally (PubMed:19216761, PubMed:22406073). Expressed in the paraxial mesoderm, posterior lateral mesoderm and adaxial cells at the end of the bud stage (PubMed:19216761, PubMed:22216300). Expressed in the segmental plate and ventral mesoderm during early gastrulation and early somitogenesis (PubMed:25371059). Expressed at the posterior dorsal midline at the three-somite stage and extends to the anterior region along the notochord, and to the trunk somites and cells lateral to them in the 24 hours post-fertilization (hpf) (PubMed:22406073). Expressed in both dorsal and ventral fast muscle cells in the late stages of segmentation (PubMed:19216761). Expressed in the hindbrain, a subpopulation of spinal cord interneurons, hypaxial muscles and in migrating muscle cells giving rise to the hyoid muscles and pectoral fin muscles at 24 hpf (PubMed:25371059). Expressed in the neural tube and hindbrain at 36 and 48 hpf with additional expression in the pectoral fin bud and fin muscles at 48 hpf (PubMed:19216761, PubMed:22406073). Expression is lost from the trunk at 48 hpf (PubMed:19216761).
Interacts (via N-terminus) with tle3a/gro2 (via C-terminus).
Morpholino knockdown results in circling swimming behavior at the larval stage (PubMed:22216300). Reduced fin bud formation and loss of myod1 expression in embryo hyoid muscles (PubMed:19216761, PubMed:22216300, PubMed:22406073). Disruption of cuboidal morphology of adaxial cell pseudo-epithelium, and failure of myod1-expressing cells to incorporate into the adaxial cell layer (PubMed:19216761). Slow muscle fibers are abnormally shaped at 24 hpf and 48 hpf and fast muscle cells form shorter myofibrils at 24 hpf and 48 hpf, in addition unfused fast muscles cells are present at 48 hpf (PubMed:19216761). Reduced expression of thin filament genes in skeletal muscles and thick filament genes in embryos (PubMed:19216761). Weak and discontinuous pattern of cxcl12a/sdf1a expression just before the posterior lateral line (PLL) begins to migrate in the posterior lateral mesoderm at the tail bud stage, and in adaxial cells at the 10-somite stage (PubMed:22216300). Disruption of myoseptum distribution as a result of abnormal differentiation of cxcl12a/sdf1a-expressing cells in the horizontal myoseptum at 24 hpf (PubMed:22216300). Increase in cell death rate in the PLL primordium and deposited neuromasts at 36 hpf (PubMed:22216300). Decrease in the number of PLL neuromasts with 15% of morphants showing complete loss of neuromasts at 48 hpf (PubMed:22216300). The speed of PLL primordium migration is reduced and neuromasts are deposited at inappropriate locations along the length of the posteriorly extending primordium (PubMed:22216300). Disruption of the discrete dorsoventral domains resulting in narrowing of the mediolateral region and slower extension of the expression domains towards the dorsal region at the shield stage (PubMed:22406073). Abnormal anterior-posterior axis, reduced dorsalward movement speed of lateral marginal cells and reduced wnt5b expression at the end of gastrulation. Embryos have a broader neural plate in the neuroectoderm with shorter and broader notochords, and reduced cell elongation (PubMed:22406073).
Transcription factor required in several developmental processes (PubMed:19216761, PubMed:22216300, PubMed:25371059). Involved in axis formation during embryonic development by inhibiting tle3a/gro2 from binding to tcf7l1a, thereby facilitating ctnnb1-mediated transcription of canonical Wnt/CTNNB1 signaling target genes (PubMed:25371059). Regulates convergent extension movements and hypaxial myogenesis during gastrulation by activating non-canonical Wnt signaling via wnt5b (PubMed:19216761, PubMed:22406073). Required for the formation of myofibrils and fusion of fast muscle precursor cells, potentially via transcriptional regulation of genes specific to thick and thin myofilaments (PubMed:19216761). Regulates the migration of the posterior lateral line primordium during embryonic development, possibly via regulation of cxcl12a/sdf1a expression in the posterior lateral mesoderm, thereby modulating the deposition of neuromasts at correct intervals (PubMed:22216300).
Component of the ribosomal small subunit processome for the biogenesis of ribosomes, functions in pre-ribosomal RNA (pre-rRNA) processing (PubMed:28263972). Essential for embryonic development in part through the regulation of p53 pathway. Required for the expansion growth of intestine, liver and exocrine pancreas, but not endocrine pancreas. May not play a major role during the early stage of endodermal organogenesis. Also involved in the sympathetic neuronal development (PubMed:28263972). Triggers the degradation of p53/TP53 and Delta113p53 isoform in a ubiquitination pathway independent way (PubMed:23357851). Mediates, with CAPN3, the proteasome-independent degradation of p53/TP53 (PubMed:23357851, PubMed:27657329).
Confers hypoplastic digestive organs and selectively up-regulates the expression of the Delta113p53 isoform but not p53, resulting in compromised organ growth in def mutant fish. Loss of function affects sympathetic neuronal development (PubMed:27657329).
Highly expressed in the embryos at 12 hpf and 1 dpf and expressed at high level at 3 dpf and 4 dpf, but at a lower level at 5 dpf. At 2 dpf, ubiquitously expressed, but enriched in the mid and hindbrain boundary. Through 3-5 dpf, expressed mainly in the gut, liver, pancreas and pharynx.
Mainly expressed in digestive organs at the later stage of organogenesis. Expressed in liver, gut and exocrine pancreas, but not in the islets.
Phosphorylated. Phosphorylation is required to facilitate the nucleolar localzsation of CAPN3 and promote p53/TP53 degradation in the nucleolus which promotes cell cycle progression and liver development.
Belongs to the universal ribosomal protein uS9 family.
Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.
Binds 2 magnesium ions, but the ions interact each with only 1 or 2 residues.
Poly(A) nuclease with 3'-5' RNase activity. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression (By similarity).
Expressed both maternally and zygotically. Expressed ubiquitously in the cleavage, blastula, gastrula and early somitogenesis stages. Expression declines during gastrulation. At 26 hours, expressed weakly throughout the head, and more strongly in the mesenchymal neural crest cells behind the eyes and in the endoderm and haemangiogenic region of the tail.
Promotes differentiation of dorsal tissues. May be involved in the mediation of Ndr2 signaling during mesoderm and axis formation during embryogenesis.
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.
Functions as a transcriptional repressor. May inhibit the activity of CTNNB1 in a TP53-dependent manner and thus regulate cell growth (By similarity). May function in adipocyte differentiation, negatively regulating mitotic clonal expansion (By similarity). Plays a role in cell-cell adhesion and epithelium development through its interaction with proteins of the beta-catenin family (Probable).
Morpholino knockdown of the protein results in neural tube closure defects and a disorganization of the neuroepithelium (PubMed:25009281). This developmental phenotype is associated with an alteration of cell-cell junctions (PubMed:25009281).
E3 ubiquitin-protein ligase involved in ER-associated protein degradation, preferentially associates with the E2 enzyme UBE2J2.
Integral component of ER-resident dislocation complexes.
Transcription repressor. Involved in the development of the forebrain region (By similarity).
Belongs to the amidase family. GatA subfamily.
Involved in redox regulation of the cell. Acts as an antioxidant (By similarity).
The active site Cys-77 corresponds to one of the redox-active cysteines of peroxiredoxins.
Widely expressed in all embryonic tissues from all stages. Expression is already detectable at the early stages from gastrula and somitogenesis, but within the embryonic tissues only; there is no expression within the nutrient cells of the yolk syncytial layer. Later in development, expression remains high and nonrestricted.
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.
May activate transcription by interacting directly with the X-box.
Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P).
Belongs to the DNA polymerase delta/II small subunit family.
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).
Has a role in transport between endoplasmic reticulum and Golgi.
Component of the peroxisomal translocation machinery.
Expressed both maternally and zygotically. At 9 hpf, expressed in the dorsal epiblast and prospective tail regions, but absent from the ventral epiblast. At 10 hpf, expressed in presumptive diencephalon and hindbrain, in tissue lateral to the head, the posterior neural plate, tail bud and adjacent mesoderm. At 11-15 hpf, restricted expression along the A-P axis of the neural plate up to the rhobomere 1/2 boundary. During somitogenesis, head and tail expression remains. At 18 hpf, retained expression in the neural tube. At 24 hpf, low levels of ubiquitous expression with stronger expression in eyes, hindbrain and spinal cord; in hindbrain the anterior border is at rhombomeres 3-4. Also expressed in non-neural tissues including pharyngeal endoderm, mesenchyme and tail bud. At 48 hpf, expression is maintained in hindbrain, eyes, diencephalon and the pharyngeal region, and is also observed in forebrain, midbrain and pectoral fin bud.
In the embryo, zygotic expression largely overlaps that of raraa, with high levels in hindbrain, lateral plate mesoderm (LPM) and tail bud, but in later stages rarab is expressed more broadly in the brain, pectoral fin bud and pharyngeal arches.
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain development and, in lateral plate mesoderm, for specification of the pectoral fins.
Belongs to the glycine N-acyltransferase family.
Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.
VIP causes vasodilation, lowers arterial blood pressure, stimulates myocardial contractility, increases glycogenolysis and relaxes the smooth muscle of trachea, stomach and gall bladder.
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.
Transcription elongation factor which increases mitochondrial RNA polymerase processivity. Regulates transcription of the mitochondrial genome, including genes important for the oxidative phosphorylation machinery (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.
Guanine nucleotide exchange factor (GEF) which may activate the small GTPases Rab. May promote the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (By similarity).
Required for protein import into peroxisomes.
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.
First expressed in embryos between 5- and 7-somites in the bilateral stripes that contain the developing angioblasts, and then localized to the intermediate cell mass (ICM) and the developing vasculature. By 30 hpf, expressed in the major trunk, head and intersomitic vessels, persisting through 4 dpf when expression is seen in developing subintestinal veins and in the remaining vasculature.
Interacts with isoform VEGF165 of vegfaa and, to a lesser extent, with isoform VEGF171 of vegfab (PubMed:17698971). Interacts (via juxtamembrane region) with chaperone pdcl3 (via thioredoxin fold region); the interaction leads to increased vegfr2 abundance through inhibition of its ubiquitination and degradation (By similarity).
The first vegfr expressed during development.
This entry should not be confused with kdrl (AC Q8AXB3), which used to be called kdr.
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 (By similarity).
Defective cilia (PubMed:22718903, PubMed:24596149). Morpholino knockdown of the protein results in cilia defects in the pronephric kidney at 27 hpf and distension/dilation of pronephros at 5 dpf. In the eyes, the outer segments of photoreceptor cells appear shortened or absent, whereas cellular lamination seems normal in retinas at 5 dpf (PubMed:22718903). Left-right asymmetry defects with abnormal heart looping, hydrocephalus, pronephric cysts, abnormal ear otolith formation and curly body axis (PubMed:24596149).
May contribute to the regulation of translation during cell-cycle progression. May contribute to the regulation of cell proliferation (By similarity). The membrane form is involved in sterol-regulated ubiquitination and degradation of HMG-CoA reductase HMGCR. May be involved in centrosome assembly.
Active at low pH (under pH 4.6): proton channel activity is activated by luminal side protons. Polyunsaturated fatty acids, such as arachidonic acid, also activate the channel activity.
Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture. The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping. Forms a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues (Ile-62 in the first module and Ile-288 in the second module) in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, the same residues establish a constriction essential for potassium selectivity.
Proton-activated proton channel that catalyzes proton efflux from endosomes and lysosomes to maintain a steady-state pH. Activated at low pH (under pH 4.6) by luminal side protons: selectively mediates lysosomal proton release from lysosomes, eliciting a proton leak that balances V-ATPase activity to maintain pH homeostasis. Regulation of lumenal pH stability is required for autophagosome-lysosome fusion. May also act as a potassium channel at higher pH, regulating potassium conductance in endosomes and lysosomes. The potassium channel activity is however unclear as it was tested in non-physiological conditions for a lysosomal channel.
Deubiquitinase that antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of APC/C target proteins, thereby promoting S phase entry. Specifically mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex (By similarity).
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.
Belongs to the universal ribosomal protein uS10 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.
Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-12.
Mainly expressed in brainstem neurons, and in the telencephalon. Also expressed in intestinal endocrine cells.
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.
Interacts with PCNA. Three molecules of fen1 bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity (By similarity).
Phosphorylated. Phosphorylation upon DNA damage induces relocalization to the nuclear plasma (By similarity).
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 (By similarity).
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.
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. Binds to 5'-UGUA-3' elements localized upstream of pA signals that act as enhancers of pre-mRNA 3'-end processing. The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA. Plays a role in somatic cell fate transitions and pluripotency by regulating widespread changes in gene expression through an APA-dependent function. Binds to chromatin. Binds to, but does not hydrolyze mono- and di-adenosine nucleotides.
Homodimer (via N- and C-terminus); binds RNA as homodimer. Component of the cleavage factor Im (CFIm) complex.
Lacks the conserved metal-binding residues in the NUDIX motif and is not expected to have hydrolase activity.
Present in ooplasm of stage I, II, and III oocytes. Present in the vitelline envelope.
Present in ovary and brain but not in other tissues (at protein level).
Transcription regulator required for brain development. Probably acts as a transcription factor that binds to the promoter of target genes, leading to activate their expression (By similarity).
Essential for the initiation of pectoral fin bud formation. Potentially acts downstream of retinoic acid and Wnt signaling and is required for tbx5 expression in the lateral plate mesoderm of presumptive pectoral fin bud regions.
First detected in the notochord at 10 hours post fertilization (hpf). At 12 and 14 hpf (the 6- and 10-somite stages), expressed in the notochord, somites and tail. At 14 hpf, also expressed in the forebrain and the lateral plate mesoderm anterior to somite 1. At 18 and 24 hpf, predominantly expressed in the tail, presumptive pectoral fin bud regions and the alar plate of the hindbrain.
Homodimer; disulfide-linked. Seems to also exist as monomers (By similarity).
Regulatory component of the SET1 complex implicated in the tethering of this complex to transcriptional start sites of active genes. Facilitates histone H3 'Lys-4' methylation (H3K4me) via recruitment of the SETD1A or SETD1B to the 'Ser-5' phosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A). Part of a transcription termination checkpoint that promotes transcription termination of long non-coding RNAs (lncRNAs).
Belongs to the cyclin-dependent kinase 5 activator family.
Heterodimer of a catalytic subunit and a regulatory subunit.
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 bacterial ribosomal protein bL35 family.
By retinoic acid, in embryonic anterior brain and eye.
Expressed zygotically, with greatest expression at 24 hours post-fertilization (hpf). At 9 hpf, shows ubiquitous expression in the epiblast. At 10 hpf, expressed in anterior and posterior regions; not expressed in the presumptive hindbrain, and anterior expression is limited to mesoderm adjacent to the head. Between 11-15 hpf restricted expression in the cranial mesoderm and tailbud. At 12 hpf, expressed in anterior lateral mesenchyme, with strongest expression lateral to the future hindbrain, and in tailbud. At 24 hpf, also expressed in the hindbrain, neural crest cells and tail; not detected in spinal cord. At 48 hpf, hindbrain expression increases with an anterior border at rhombomere 3 and a posterior border at the spinal cord/hindbrain junction; expressed in stripes one rhombomere wide in dorsal hindbrain. At 48 hpf, also expressed in pharangeal arches 1-7, anterior neurocranium, cells separating the eyes and forebrain, pectoral fin buds and tailbud. Embryonic zygotic expression overlaps that of raraa and rarab, but there is stronger expression in the posterior hindbrain beginning in late somitogenesis, and in neural crest cells in the pharangeal arches. In the adult, strongly expressed in the ovary, brain and muscle, and weakly expressed in the liver and digestive tract.
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain development and for the development of pharyngeal arches.
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.
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).
Transcription factor, is involved in craniofacial development, and in stomach organogenesis.
Regulatory subunit of serine/threonine-protein phosphatase 4.
Morpholino knockdown of ambra1a and ambra1b results in reduced autophagy and increased apoptosis during embryogenesis (PubMed:23348054). Morpholino knockdown of ambra1a and ambra1b results in reduced autophagy and increased apoptosis during embryogenesis (PubMed:23348054). Morpholino knockdown of ambra1a and ambra1b results in impaired locomotion, caused by abnormal myogenesis (PubMed:24922546).
Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy (PubMed:23348054). The DCX(AMBRA1) complex specifically mediates the polyubiquitination of target proteins (By similarity). Acts as an upstream master regulator of the transition from G1 to S cell phase: ambra1b specifically recognizes and binds phosphorylated cyclin-D (ccnd1, ccnd2 and ccnd3), leading to cyclin-D ubiquitination by the DCX(AMBRA1) complex and subsequent degradation (By similarity). Acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (eloc) component of CRL5 complexes (By similarity). Acts as a key regulator of autophagy by modulating the BECN1-PIK3C3 complex: controls protein turnover during neuronal development, and regulates normal cell survival and proliferation (By similarity). In normal conditions, ambra1b is tethered to the cytoskeleton via interaction with dyneins light chains (By similarity). Upon autophagy induction, ambra1b is released from the cytoskeletal docking site to induce autophagosome nucleation by mediating ubiquitination of proteins involved in autophagy (By similarity). Also acts as an activator of mitophagy (By similarity). Required for skeletal muscle development (PubMed:24922546).
Belongs to the Antp homeobox family. Labial subfamily.
First expressed at 50% epiboly in the shield region. During somitogenesis, present in the spinal cord and endoderm with an anterior expression limit at around rhombomere 4.
Sequence-specific transcription factor. Part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Acts on the anterior body structures. Seems to act in the maintenance and/or generation of hindbrain segments.
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).
The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs.
Belongs to the pyridoxamine 5'-phosphate oxidase family.
Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP).
Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate.
ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen. Coupled to the ATP-dependent transporter activity has also a fatty acyl-CoA thioesterase activity (ACOT) and hydrolyzes VLCFA-CoA into VLCFA prior their ATP-dependent transport into peroxisomes, the ACOT activity is essential during this transport process. Thus, plays a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation, mitochondrial function and microsomal fatty acid elongation (By similarity). Involved in oligodendrocyte patterning and myelination (PubMed:28911205).
Expressed from 48 hpf in the nervous system, floor plate, and pronephros/interrenal gland. By 72 hpf and persisting through 96 hpf expression is present in the central nervous system (CNS), floorplate, interrenal glands/pronephros, and gut. At 72 hpf expressed in the brain and spinal cord.
abcd1 deficient zebrafish appear normal. By day of life five abcd1 mutants demonstrate impaired motor function, and overall survival to adulthood of heterozygous and homozygous mutants is decreased.
Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactate, pyruvate, acetate, propionate, valerate and butyrate), lactate, mocarboxylate drugs (nicotinate, benzoate, salicylate and 5-aminosalicylate) and ketone bodies (beta-D-hydroxybutyrate, acetoacetate and alpha-ketoisocaproate), with a Na(+):substrate stoichiometry of between 4:1 and 2:1. Catalyzes passive carrier mediated diffusion of iodide. Mediates iodide transport from the thyrocyte into the colloid lumen through the apical membrane.
Expressed in brain and eye 24 hours post-fertilization. In the 5 day old embryo, detected in swim bladder, pronephros (embryonic kidney), pronephric tube, and pronephric ducts, brain, trabecular bar, eyes, otic capsule, stomach, gall bladder, and gut.
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.
Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates.
Probably maternally supplied, the zygotic expression becomes significative at 4.0 hpf and remains constant until 24 hpf.
Morpholino knockdown of the protein causes defects in development, abnormal locomotion and increased mortality. At 3 days postfertilization morphants have abnormally (delayed) developed eyes.
Binds to the receptor tyrosine kinases epha2, epha3, epha4 and epha5. Interacts with epha8; activates epha8 (By similarity).
Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. With the epha2 receptor may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis (By similarity).
Expressed in the presumptive midbrain of developing embryos from the six-somite stage. By 24 hours, expressed throughout the midbrain including the region of the presumptive tectum. At later stages, expressed in a graded fashion throughout the tectum.
Serine hydrolase involved in the detoxification of formaldehyde.
Deglycase activity does not require glutathione as a cofactor, however, glycated glutathione constitutes a PARK7 substrate.
Glyoxalase activity has been reported. It may however reflect its deglycase activity.
Larval brain and gut from 96 hours post-fertilization (hpf). Ubiquitous in adult; most abundant in brain, eye, heart and muscle. Within brain, neuronal expression is widespread, particularly in the cerebellum, medullary reticular formation and diencephalon. Expressed in major forebrain and diencephalic dopaminergic cell groups.
Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease (PubMed:17166173). It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway. Has been described as a protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals. But this function is rebuted by other works. As a protein deglycase, repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage. Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair. Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin. Displays a very low glyoxalase activity that may reflect its deglycase activity. It is involved in neuroprotective mechanisms as well as cell growth and transformation. Its involvement in protein repair could also explain other unrelated functions. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (By similarity).
Present from tailbud stage (10 hpf) through to adult. Levels increase from 24-120 hpf.
Sumoylated on Lys-130 by pias2 or pias4; which is essential for cell-growth promoting activity and transforming activity.
The protein deglycation activity is controversial. It has been ascribed to a TRIS buffer artifact by a publication and as a result of the removal of methylglyoxal by glyoxalase activity that leads to a subsequent decomposition of hemithioacetals and hemianimals due to the shift in equilibrium position by another one. However, biochemical experiments showing that PARK7 is a bona fide deglycase have been performed.
Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.
Belongs to the eukaryotic ribosomal protein eS21 family.
tRNA nucleus export receptor which facilitates tRNA translocation across the nuclear pore complex.
Mainly expressed in brain. Also expressed in embryo and retina.
Prion-like protein that has PrP(C)-like neuroprotective activity.
May play a role in targeting proteins for ubiquitination and subsequent proteasomal degradation.
Associates with the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex).
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.
Belongs to the bacterial ribosomal protein bL17 family.
Heterotetramer of two type I and two type II keratins. Keratin-8 associates with keratin-18 (By similarity).
There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
Together with KRT19, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle.
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.
Non-catalytic component of the proteasome.
Plays a key role in maintaining the cardiac electrical stability by modulating cell surface expression of SCN5A.
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).
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.
Highly expressed in the developing brain, and less within intersomitic structures of the trunk.
Morpholino knockdown of RNF170 results in developmental defects visible by 48 hpf, including microphthalmia, microcephaly, and loss of motility. Neurogenesis in the cranium is remarkably reduced, specifically in the mid-hindbrain region.
Adds the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Man(9)GlcNAc(2)-PP-Dol.
Belongs to the ALG6/ALG8 glucosyltransferase family.
Belongs to the eukaryotic/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.
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 (By similarity). Binds phosphatidylinositol 3-phosphate (PtdIns3P) (By similarity).
The L/FRRG motif is required for recruitment to PtdIns3P.
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).
Expressed in brain, heart and eye. Isoform 2 is expressed only in the retina.
Expressed throughout all the development stages. Isoform 2 is not expressed until 48 hours post fertilization.
Probably involved in membrane protein trafficking at the base of the ciliary organelle. May function in cilia biogenesis. Isoform 2 is required for proper retinal function and organization.
Results in the cardinal features of Bardet-Biedl syndrome in zebrafish, including defects to the ciliated Kupffer's vesicle and delayed retrograde melanosome transport. Isoform 2 defects does not result in Kupffer vesicle or melanosome transport defects, but rather leads to impaired visual function and mislocalization of the photopigment green cone opsin. Isoform 2, but not isoform 1, is sufficient to rescue both the vision defect as well as green opsin localization in the retina.
Belongs to the round spermatid basic protein 1 family.
Acts as a regulator of programmed cell death, mediating both autophagy and apoptosis.
May play a role in microtubule-mediated transport or vesicle function.
Identified in the spliceosome A complex; remains associated with the spliceosome throughout the splicing process. Component of the spliceosome B complex. Identified in the spliceosome C complex. Identified in the spliceosome E complex. Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42. SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP).
Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex, a constituent of the spliceosome. SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. May also be involved in the assembly of the 'E' complex. Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron.
The core of the protein consists of three beta-propeller domains.
Belongs to the galactose-1-phosphate uridylyltransferase type 1 family.
Belongs to the prefoldin subunit alpha family.
Transcription factor involved in epidermis differentiation.
Phosphatase that hydrolyzes imidodiphosphate, 3-phosphohistidine and 6-phospholysine. Has broad substrate specificity and can also hydrolyze inorganic diphosphate, but with lower efficiency (By similarity).
Adapter molecule for tnfrsf1a that specifically associates with the cytoplasmic domain of activated tnfrsf1a mediating its interaction with fadd.
Requires the intact death domain to associate with tnfrsf1a.
Expressed in 10-somite stage embryos but not spatially restricted.
Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes. May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium.
The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate.
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 (By similarity). Dph1 and dph2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising dph3 and a NADH-dependent reductase (By similarity).
Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of dph1, dph2, dph3 and a NADH-dependent reductase.
Binds DNA as a dimer and can form a homodimer in the absence of DNA.
Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3').
Belongs to the mitochondrion-specific ribosomal protein mS26 family.
Belongs to the protein-tyrosine phosphatase family. Receptor class 2A subfamily.
Postsynaptic RAC1 GTPase activating protein (GAP) that plays a key role in neuronal morphogenesis and migration mainly during development of the cerebral cortex. Regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons. Mechanistically, acts by binding and deforming membranes, thereby regulating actin dynamics to regulate cell migration and differentiation.
The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions.
Involved in the second step of GPI biosynthesis. De-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol.
May play a role in CNS development by interacting with growth factors implicated in motor neuron differentiation and survival.
Component of the 4EHP-GYF2 complex (By similarity).
Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation.
Maternally expressed: detected from the 1-cell stage, prior to the onset of zygotic expression. From blastula until gastrula stages, strongly expressed throughout the blastoderm. At 28 hours post-fertilization (hpf), highly expressed in the central nervous system (CNS), whereas a weaker expression is found in the somites. At later stages of development (48 hpf), expression persists in well-defined structures of the CNS, such as the diencephalon, the mesencephalon, the cerebellum and the rhombencephalon, and remains detectable in the somites.
Morpholino knockdown show mild, intermediate, and severe phenotypes. Embryos with severe phenotype display a disrupted body pattern, embryos with intermediate phenotype show defects in the head and eye structures, while embryos with mild phenotype only show a twist in the terminal part of the tail. Embryos do not show important cell loss in diencephalic dopaminergic (DA) neuron clusters.
May play a role in an as yet undefined retina-specific signal transduction. Could bind to photoactivated-phosphorylated red/green opsins.
Homodimer. Does not require RNA to homodimerize (By similarity).
Maternally and zygotically expressed. Ubiquitously expressed during cleavage and blastula periods, and then it accumulates in the dorsal midline of the body trunk during gastrulation. During segmentation and pharyngula periods it is expressed in the neural tissue of the head region, and in the paraxial mesoderm of the body trunk. Subsequently expression diminishes until the hatching period, when it is expressed only in the cardiac sac and pectoral finbuds. Isoform 2 localizes in neural tissue in the head region, but not in the paraxial mesoderm in the body trunk.
RNA-binding protein that plays a central role in myelinization. Binds to the 5'-NACUAAY-N(1,20)-UAAY-3' RNA core sequence. Acts by regulating pre-mRNA splicing, mRNA export, mRNA stability and protein translation. Required to protect and promote stability of mRNAs which promotes oligodendrocyte differentiation. Participates in mRNA transport by regulating the nuclear export of MBP mRNA. Also involved in regulation of mRNA splicing of some pre-mRNA. Acts as a translational repressor (By similarity).
Belongs to the dynein intermediate chain family.
Acyltransferase required to remodel newly synthesized phospholipid cardiolipin (1',3'-bis-[1,2-diacyl-sn-glycero-3-phospho]-glycerol or CL), a key component of the mitochondrial inner membrane, with tissue specific acyl chains necessary for adequate mitochondrial function (By similarity). Its role in cellular physiology is to improve mitochondrial performance (By similarity). CL is critical for the coassembly of lipids and proteins in mitochondrial membranes, for instance, remodeling of the acyl groups of CL in the mitochondrial inner membrane affects the assembly and stability of respiratory chain complex IV and its supercomplex forms (By similarity). Catalyzes the transacylacion between phospholipids and lysophospholipids, with the highest rate being between phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) and CL. Catalyzes both 1-acyl-sn-glycero-3-phosphocholine (lysophosphatidylcholine or LPC) reacylation and PC-CL transacylation, that means, it exchanges acyl groups between CL and PC by a combination of forward and reverse transacylations. Also catalyzes transacylations between other phospholipids such as phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine or PE) and CL, between PC and PE, and between PC and phosphatidate (1,2-diacyl-sn-glycero-3-phosphate or PA), although at lower rate. Not regiospecific, it transfers acyl groups into any of the sn-1 and sn-2 positions of the monolysocardiolipin (MLCL), which is an important prerequisite for uniformity and symmetry in CL acyl distribution. Cannot transacylate dilysocardiolipin (DLCL), thus, the role of MLCL is limited to that of an acyl acceptor. CoA-independent, it can reshuffle molecular species within a single phospholipid class. Redistributes fatty acids between MLCL, CL, and other lipids, which prolongs the half-life of CL. Its action is completely reversible, which allows for cyclic changes, such as fission and fusion or bending and flattening of the membrane. Hence, by contributing to the flexibility of the lipid composition, it plays an important role in the dynamics of mitochondria membranes. Essential for the final stage of spermatogenesis, spermatid individualization (By similarity). Required for the initiation of mitophagy (By similarity). Required to ensure progression of spermatocytes through meiosis (By similarity).
At 10 hours post-fertilization (hpf), expressed ubiquitously, including in cardiac progenitor regions, with strongest expression in the head area. By 24 hpf, highly expressed in the head, eyes, and tail. By 30 hpf, expression is restricted to the head, heart, eyes, and the region next to the yolk corresponding to endodermal tissue. At 51 hpf, expression is restricted to the heart.
Before gastrulation, expression is barely detectable. At 7 hours post-fertilization (hpf), sharply up-regulated. High-level expression continues throughout the segmentation (12 hpf) and pharyngula (24 to 30 hpf) stages. At hatching at 51 hpf, expression declines dramatically.
Morpholino knockdown results in dose-dependent lethality, severe developmental and growth retardation, marked bradycardia and pericardial effusions, and generalized edema.
The enzyme was named after a masochistic character Tafazzi, once popular on Italian television, apparently due to the difficulty encountered for its identification and characterization.
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The order of potency for this receptor is dexmedetomidine > norepinephrine = epinephrine > oxymetazoline.
Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2D sub-subfamily.
Heterodimer; heterodimerizes with mettl3 to form an antiparallel heterodimer that constitutes an active methyltransferase. Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of mettl3 and mettl14.
The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis. In the heterodimer formed with mettl3, mettl14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability and processing.
Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA.
Belongs to the complex IV NDUFA4 subunit 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)) (By similarity). Interacts with RAB5IF (By similarity).
Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. NDUFA4 is required for complex IV maintenance.
Involved in the early steps of selenocysteine biosynthesis and tRNA(Sec) charging to the later steps resulting in the cotranslational incorporation of selenocysteine into selenoproteins.
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.
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.
Belongs to the XRCC4-XLF family. XLF subfamily.
DNA repair protein involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination. Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends. Associates with xrcc4 to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired. The xrcc4-nhej1/xlf subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other. The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors.
Homodimer. Interacts with xrcc4; the interaction is direct and is mediated via a head-to-head interaction between N-terminal head regions. Associates with the non-homologous end joining (NHEJ) complex which is at least composed of the core proteins xrcc5/Ku80, xrcc6/Ku70, prkdc/DNA-PKcs, nhej1/xlf, lig4 and xrcc4.
The Leu-lock (Leu-114) site inserts into a hydrophobic pocket in xrcc4.
The coiled-coil region mediates homodimerization.
By hedgehog signaling in the floor plate. In response to injury and stretch.
Expressed in floor plate, dorsal forerunner cells, Kupffers vesicle, the floor plate, pronephric ducts and kidney.
Key transcription factor required for motile ciliogenesis. Activates genes essential for motile cilia formation and function. Its activity is sufficient for ectopic development of cilia that resemble motile cilia.
Plays a role in the process of neurogenesis.
Belongs to the adenomatous polyposis coli (APC) family.
May be involved in B-cell and macrophage adhesion processes. May play a role in src signaling pathway (By similarity).
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).
Highly expressed in the central and outer tiers of the inner nuclear layer of the retina.
May be involved in maintenance as well as cellular differentiation of retinal interneurons, such as bipolar cells. May play a role in establishing interneuronal cell classes in nonsensory as well as sensory systems.
Significant levels were first detected at the 14-somite stage (16 hours post-fertization; hpf) and increased by the prim-11 stage (28 hpf). At 16 hpf expression is observed in a small subset of neurons in the spinal cord and at 18 hpf in the developing hindbrain. At 28-32 hpf, significant levels of expression is seen in presumptive neurons along the rostral-caudal axis of the hindbrain and the spinal cord. During later stages of development expression is restricted to the developing retina and no longer detected in the hindbrain or spinal cord.
Belongs to the bacterial ribosomal protein bL27 family.
Expressed in olfactory epithelium (at protein level). Detected in a sparse population of olfactory sensory neurons.
Olfactory receptor for medium length odd-chained diamines including cadaverine which is generated by bacterial decarboxylation of the basic amino acid lysine and contributes to the odor of decomposing tissue. Mediates pronounced innate aversion behavior to cadaverine.
Activates the Jnk signaling pathway. Dephosphorylates and deactivates p38 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) (By similarity).
Catalyzes the reversible isomerization between hydroxypyruvate and 2-hydroxy-3-oxopropanoate (also termed tartronate semialdehyde).
Expressed in the nascent hair cells of the developing ear as early as 1 day post fertilization (dpf), and expression in the inner ear continues throughout development. Expression is restricted to the upper hair cell layer of the neuroepithelium at 5 dpf.
In adults, expression is restricted to the hair cells of inner ear and lateral line organ. Expressed at higher levels in the larval inner ear than in the lateral-line neuromasts.
Interacts (via N-terminus) with both isoforms CD1 and CD3 of PCDH15A (via cytoplasmic domain); this interaction is required for mechanotransduction of the hair cells and correct localization of PCDH15A in hair bundles of the hair cells.
Probable ion channel required for the normal function of hair cells (By similarity). Component of the hair cell's mechanotransduction (MET) machinery. Involved in mechanosensitive responses of the hair cells (PubMed:25114259).
Expressed both maternally and zygotically. Zygotic expression persists into the pharyngula stage.
Expressed in all tissues examined, including gill, fin, heart, intestine, muscle, ovary and testis.
Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures.
Component of the ribosome-associated endoplasmic reticulum translocon complex.
Necessary for the translocation in the endoplasmic reticulum and the biogenesis of multi-pass membrane proteins.
Belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.
Detected at 13 hours post-fertilization (hpf) in the precursor cells of adaxial cells (slow twitch muscle fibers) of the paraxial mesoderm (PubMed:29888752). At 22 hpf, detected in the developing heart (PubMed:29888752).
Morpholino knockdown in the embryo causes reduced heart beating rates and cardiomyocyte numbers at 48 hours post-fertilization (hpf) (PubMed:29888752). At 72 hpf, embryos display pericardial and yolk sac effusion and pronounced cardiac malformation coupled with defects in posterior development (PubMed:29888752). Embryos also lack ventricular epicardium at 96 hpf (PubMed:29888752).
Protein kinase that recognizes phosphorylation sites in which the surrounding peptides have an alpha-helical conformation (By similarity). Regulates cardiac development and cardiomyocyte differentiation by negatively regulating Wnt/beta-catenin signaling (PubMed:29888752).
Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors.
Expressed ubiquitously in the embryo and adult.
Functions in the early steps of protein synthesis of a small number of specific mRNAs. Acts by directing the binding of methionyl-tRNAi to 40S ribosomal subunits. In contrast to the eIF-2 complex, it binds methionyl-tRNAi to 40S subunits in a codon-dependent manner, whereas the eIF-2 complex binds methionyl-tRNAi to 40S subunits in a GTP-dependent manner.
Belongs to the paired homeobox family. Unc-4 subfamily.
In the somite, it is restricted to the caudal half of the newly formed somite and sclerotome.
Marker of antero-posterior subdivisions of the somite.
Transcription factor involved in somitogenesis and neurogenesis.
Belongs to the short-chain dehydrogenases/reductases (SDR) family. ERG27 subfamily.
As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway.
Detected in one-cell-stage embryos, suggesting maternal expression. Detected in blastomeres at 2.5 to 4 hpf. Ubiquitous in embryos from 6 to 12 hpf. At 24 hpf, expression is ubiquitous, with higher levels of expression in the region of the brain and eyes. At 48 hpf, predominantly expressed in the brain area, but also detected in heart and fins.
May regulate the intracellular trafficking of RAN. Promotes guanine nucleotide release from RAN and inhibits binding of new GTP. Plays a role in the regulation of the levels of GTP-bound RAN in the nucleus (By similarity). Required for normal expression of the ion channel hcn4 and for normal expression of the cardiac transcription factors nkx2.5, gata4 and hand2 during embryonic development. Required for normal embryonic heart development and normal heart rate (PubMed:26903377).
Monomer. Interacts with ran (By similarity).
Morpholino knockdown of the protein causes bradycardia and weakened myocardial contraction. Expression of hcn4 is decreased, and this may be the cause for the decreased heart rate. Morpholino knockdown causes defects in heart looping during embryonic heart development, probably due to the decreased expression of cardiac transcription factors in the anterior lateral mesoderm.
Expressed in Kupffer's vesicle at 12 hours post fertilization (hpf). Expressed in brain, neural tube, pronephric ducts, olfactory placode and the eye at 28 hpf. Expressed in ciliated cells of the olfactory placode, ear, neuromasts and pronephric ducts at 48 hpf. Expressed in neuromasts, olfactory sensory neurons and in the ear at 96 hpf (at protein level).
Expressed in tissues rich in motile cilia.
Morpholino knockdown of the protein causes curved body, a lack of defined brain structures or necrosis in the developing brain, and eye formation defects at 24 hpf. At 48 hpf, show a reduction in number of ciliated cells within the olfactory organ.
Plays a role in primary ciliogenesis by modulating actin polymerization.
Amidase that catalyzes the last step of diphthamide biosynthesis using ammonium and ATP. Diphthamide biosynthesis consists in the conversion of an L-histidine residue in the translation elongation factor eEF-2 (EEF2) to diphthamide (By similarity).
Belongs to the Diphthine--ammonia ligase family.
Belongs to the eukaryotic ribosomal protein eS7 family.
Mutants show larval lethality around 9 days post fertilization and defects in autophagy. They also have lipoprotein accumulation in the intestine and liver.
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.
Stabilizer subunit of the dolichol-phosphate mannose (DPM) synthase complex; tethers catalytic subunit to the ER.
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).
Catalyzes the transfer of endogenously produced octanoic acid from octanoyl-acyl-carrier-protein onto the lipoyl domains of lipoate-dependent enzymes. Lipoyl-ACP can also act as a substrate although octanoyl-ACP is likely to be the physiological substrate.
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.
Detected in embryos at 2dpf (at protein level). Widely expressed during embryogenesis and in adults.
Functions as transcription repressor, probably via its interaction with histone deacetylase complexes (PubMed:22821512). Required for normal expression of numerous target genes (PubMed:22821512). 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 (By similarity).
Interacts with components of the histone deacetylase complex sin3a, hdac1 and hdac2. Binds histones and nucleosomes.
Morpholino knockdown causes defects in embryonic heart morphogenesis and pericardiac edema, with defects in heart function that are visible already at 3 dpf. In addition, erythrocytes appear pale due to decreased hemoglobin content.
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.
Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS).
Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates.
Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway (PubMed:22669824). Acts by specifically mediating depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors (By similarity).
First appears around the blastoderm margin prior to the onset of gastrulation. In later gastrulation, expressed in the lateral edges and midline of the posterior neural plate. During segmentation, expressed in stripes at the lateral edges and adjacent to the midline of the neural plate, throughout the hindbrain, with strong expression in rhombomeres 3 and 5, and at the midbrain-hindbrain boundary. At 24 hours post-fertilization (hpf), highly expressed in the central nervous system, including the dorsal neural tube and the midbrain-hindbrain boundary.
The molecular function of NOTUM family protein has remained unclear for many years. It was initially thought to hydrolyze glycosaminoglycan (GAG) chains of glypicans, thereby affecting glypicans ability to interact with Wnt ligands. It was later reported to trigger glypican shedding, by mediating cleavage of their GPI-anchor (PubMed:22669824). It was finally shown that it requires glypicans to suppress Wnt signaling, but does not cleave their GPI-anchor. It acts by mediating depalmitoleoylation of WNT proteins, impairing WNT binding to frizzled receptors.
Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure. During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters (By similarity).
Detected at all stages tested, including the fertilized egg stage (at protein level). Present in the fertilized egg before mid-blastula transition, and is expressed ubiquitously at relatively high levels from gastrulation to mid-somitogenesis stages. At the 20-somite stage, expression starts to decrease in the notochord, but remains high in the head and central nervous system. This expression pattern persists until approximately 24 hours post-fertilization (hpf). At 48 hpf, expression is dramatically reduced in the posterior part of the body, and becomes restricted to the head area.
The 2 bromo domains mediate specific binding to acetylated histones. The exact combination of modified histone tails required to recruit brd4 to target genes is still unclear. The first bromo domain has high affinity for acetylated histone H4 tail, whereas the second bromo domain recognizes multiply acetylated marks in histone H3 (By similarity).
Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity.
Phosphorylation at Ser-74 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).
Channel activity is regulated by phosphorylation. Channel activity is regulated by intracellular Ca(2+).
Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B. Can also form a functional, homotetrameric ion channel (By similarity). Functions as non-selective, voltage-gated cation channel (By similarity). Required for normal oscillation of Ca(2+) levels within cilia; these oscillations of the intraciliary Ca(2+) levels can trigger cytoplasmic Ca(2+) signaling cascades (PubMed:25660539). May contribute to the release of Ca(2+) stores from the endoplasmic reticulum (By similarity). Required for normal temporal variation of the intracellular Ca(2+) levels in the heart (PubMed:23376035). Plays a role in fluid-flow mechanosensation (By similarity). Required for normal specification of the body left-right axis during embryogenesis, most likely via its role in ciliary Ca(2+) oscillations in Kupffer's vesicle (PubMed:15269167, PubMed:16216239, PubMed:16943304, PubMed:17360770, PubMed:23376035, PubMed:25660539).
Detected along cilia and at the cilium basal body in Kupffer's vesicle at the 10 somite stage (PubMed:26432887). Detected in heart at 48hpf (PubMed:23376035). Detected in muscle and pronephric kidney at 48 hpf (PubMed:16943304). Detected on trunk muscle sarcolemma and sarcomere, on ependymal cell cilia in brain, at the apical cell membrane in epithelial cells in the ear, at the lateral line organ and olfactory placode at 56 hpf (PubMed:16943304). Detected in adult kidney (at protein level) (PubMed:16943304).
First detected at the onset of gastrulation in a band at the blastoderm margin (PubMed:16216239, PubMed:17360770). Ubiquitous during gastrulation, somatogenesis and at 48 hpf (PubMed:16943304). During gastrulation, detected at the hypoblast of the dorsal midline and in dorsal forerunner cells that form a ciliated Kupffer's vesicle later on (PubMed:16216239, PubMed:17360770, PubMed:26432887). Ubiquitous during early somite stages, with high levels of expression in Kupffer's vesicle (PubMed:16216239, PubMed:17360770). At subsequent stages, detected in pronephric duct primordia and neural floorplate (PubMed:16216239, PubMed:16943304, PubMed:17360770, PubMed:26432887). Highly expressed in brain at 24 hpf (PubMed:16216239). At 3 dpf, detected at pharyngeal arches and the pectoral fin bud (PubMed:16216239).
Homotetramer (By similarity). Heterotetramer with pkd1, giving rise to a complex formed by one pkd1 chain and three pkd2 chains (By similarity). Interacts with pkd1l1 (By similarity).
Morpholino knockdown of the protein impairs specification of the left-right axis during embryonic development and randomization of heart and gut looping, plus misexpression of left-side specific genes (PubMed:16216239, PubMed:16943304, PubMed:17360770, PubMed:26432887, PubMed:25660539). Morpholino knockdown of the protein causes body curvature, tail curling, hydrocephalus and kidney cysts (PubMed:15269167, PubMed:16216239, PubMed:16943304, PubMed:16551655, PubMed:17360770, PubMed:23376035, PubMed:26432887). Morpholino knockdown has no effect on number, length or motility of pronephric cilia, but the fluid flow through the pronephric ducts seems to be impaired due to physical obstruction of the ducts (PubMed:16943304). Likewise, morpholino knockdown of the protein has no effect on the motility of cilia in Kupffer's vesicle (PubMed:25660539). Morpholino knockdown of the protein leads to an increase of the volume of Kupffer's vesicle, without any change in the proliferation of the cells that line the vesicle (PubMed:26432887). Morpholino knockdown of the protein leads to impaired heart function, characterized by arrhytmia and frequently associated with pericardial and abdominal edema and atrioventricular block (PubMed:23376035).
N-glycosylated. The four subunits in a tetramer probably differ in the extent of glycosylation; simultaneous glycosylation of all experimentally validated sites would probably create steric hindrance.
Phosphorylated. Phosphorylation is important for protein function; a mutant human construct that lacks the N-terminal phosphorylation sites cannot complement a zebrafish pkd2-deficient mutant.
The C-terminal coiled-coil domain is involved in oligomerization. The coiled-coil domain binds calcium and undergoes a calcium-induced conformation change (in vitro).
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).
May act as an adapter protein to couple membrane receptors to intracellular signaling pathways.
Fatty acid desaturase with bifunctional delta-5 and delta-6 activities. Component of a lipid metabolic pathway that catalyzes the biosynthesis of polyunsaturated fatty acids (PUFA) with preference toward n-3 substrates and Delta-6 function.
The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes HXXXH, HXXHH, and QXXHH (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases.
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.
Plays a role in fertility. Involved in distal reproductive tract development.
Belongs to the eukaryotic ribosomal protein eL29 family.
Belongs to the eukaryotic release factor 1 family. Pelota subfamily.
Cotranslational quality control factor involved in the No-Go Decay (NGD) pathway. Required for 48S complex formation from 80S ribosomes and dissociation of vacant 80S ribosomes. Recognizes stalled ribosomes and promotes dissociation of elongation complexes assembled on non-stop mRNAs; this triggers endonucleolytic cleavage of the mRNA, a mechanism to release non-functional ribosomes and to degrade damaged mRNAs as part of the No-Go Decay (NGD) pathway. Upon mitochondrial damage is recruited to the ribosome/mRNA-ribonucleoprotein complex associated to mitochondrial outer membrane thereby enabling the recruitment of autophagy receptors and induction of mitophagy.
The N-terminal domain has the RNA-binding Sm fold. It harbors the endoribonuclease activity.
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.
Component of the homotypic fusion and vacuole protein sorting (HOPS) complex (By similarity).
Mutants display hepatomegaly associated with large, vesicle-filled hepatocytes. They also have defects in pigmentation with reduced numbers of melanophores and no iridophores.
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport pathways. Believed to act as a core component of the putative HOPS endosomal tethering complex which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion (By similarity). May be involved in vesicle trafficking to the hepatocyte apical membrane and play a role in development of the intra-hepatic biliary tree. May target endosomes to the pigment granule in melanocytes. Essential for early embryonic development.
Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.
Belongs to the acetyltransferase ATAT1 family.
Morpholino knockdown of the protein causes developmental defects at 48 hours post-fertilization (hpf), including cilia curved body shape, short body axis, hydrocephalus, small head and small eyes. Morphants often do not respond, or have slow startle response, when probed with a needle, consistent with neuromuscular defects.
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.
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. Acetylates alpha-tubulin in neurons, but not in cilia.
Probably mediates the hydrolysis of some nucleoside diphosphate derivatives.
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates.
Belongs to the flagellar radial spoke RSP3 family.
Catalyzes the 2-thiolation of uridine at the wobble position (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). Required for the formation of 5-taurinomethyl-2-thiouridine (tm5s2U) of mitochondrial tRNA(Lys), tRNA(Glu), and tRNA(Gln) at the wobble position. ATP is required to activate the C2 atom of the wobble base.
During the reaction, ATP is used to activate the C2 atom of U34 by adenylation. After this, the persulfide sulfur on the catalytic cysteine is transferred to the C2 atom of the wobble base (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards the activated C2 atom on U34. Subsequently, a transient disulfide bond is formed between the two active site cysteine residues (By similarity).
Belongs to the dienelactone hydrolase family.
Transcription factor that binds to DNA at the consensus sequence 5'-CAG[GC]TG-3' (By similarity). Involved in the differentiation of retinal ganglion cells, photoreceptor population and optic nerve development (PubMed:10985346, PubMed:11430806). Required for retinal circadian rhythm photoentrainment (By similarity).
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.
Non-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, the products of which support energy production in nonhepatic animal tissues.
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.
Detected in all tissues tested, with the highest levels in serum (at protein level). At mRNA level, only expressed in liver.
Expressed as early as 24 hours post fecondation (hpf), expressed at higher levels than leg1b.
Important for early development of liver, exocrine pancreas and intestine, probably through cell cycle regulation. In liver, its function is partially redundant with leg1b function.
Morpholino knockdown of the protein causes a small liver phenotype. Morpholino which can simultaneously block the translation of leg1a and leg1b, causes a more severe small liver phenotype with hypoplastic exocrine pancreas and intestinal tube as well.
Belongs to the acetyltransferase family. GCN5 subfamily.
Craniofacial cartilage and bone defects, characterized by shortening and hypoplastic nature of the cartilage elements and disruption of the posterior ceratobranchial cartilages (PubMed:30424580). Morpholino knockdown of kat2a and kat2b leads to impaired heart and limb development. Abnormal fin development is also observed (PubMed:29174768).
Functions as a histone acetyltransferase (HAT) to promote transcriptional activation (By similarity). Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles (By similarity). Also acetylates non-histone proteins (PubMed:29174768). Involved in heart and limb development by mediating acetylation of tbx5 (PubMed:29174768). Also acetylates spermidine (By similarity). Together with kat2a, required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (PubMed:30424580).
Widely expressed throughout the anterior head region, including the central nervous system, the eye and branchial arches at 24 hours post fertilization (hpf). Expressed strongly in the brain region, with expression extending posteriorly in the spinal cord. By 40-48 hpf, expression remains strongly expressed in the head region but is reduced throughout the rest of the embryo (PubMed:30424580). Expressed in the heart and tail regions throughout developmental stages (PubMed:29174768).
Specifically expressed in the hematopoietic lineage during embryogenesis; first expressed at the late blastula stage around the blastoderm margin. During gastrulation, restricted to the ventral mesoderm, the presumptive prechordal plate and the dorso-marginal cells of the organizer. At the 3-somite stage, strongly expressed in a caudal domain (marking the erythroid lineage) and a cephalic domain of the lateral mesoderm. At the 8- to 10-somite stage, caudal expression is in two bands of lateral mesoderm which later converge at the midline. Anterior expression is also in two bands of lateral mesoderm which converge as two patches at the midline by the 15-somite stage, with increased scattering of single cells (macrophage precursors) away from the midline to the yolksac. Once at the yolksac, expression is lost. By 20-24 hours post-fertilization (hpf), expressed in proerythroblasts in the erythroid blood island centered above the uro-genital opening. Expression persists in circulating erythroblasts but is lost in mature erythrocytes.
Accepts electrons from ETF and reduces ubiquinone.
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.
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.
Neuronal cell surface protein that may be involved in cell recognition and cell adhesion. May play a role in formation or maintenance of synaptic junctions.
Sequence-specific transcription factor. Part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis (By similarity).
Coexpression of ntl and spt is required for expression.
Expression is first detected in the marginal zone of the blastoderm. Expression becomes more apparent at the germ-ring stage. In the early gastrula, expressed only in hypoblast cells of the germ ring. At mid-gastrula stage, expressed in ventrolateral mesoderm and is subsequently restricted to the segmental plate at late gastrula stage. At the segmentation period, expressed in the presomitic mesoderm including the tailbud. Expression is also detected in the adaxial cells in the vicinity of the presomitic mesoderm.
Involved in specifying the paraxial, but not dorsal, mesoderm. May regulate the expression of T-box transcription factors required for mesoderm formation and differentiation (By similarity).
Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins. Interacts with MALSU1.
May form part of 2 intersubunit bridges in the assembled ribosome. Upon binding to MALSU1, intersubunit bridge formation is blocked, preventing ribosome formation and repressing translation.
During gastrulation, accumulates around the closing blastopore with greater expression ventrally. At the animal pole, expressed in the ectoderm flanking the anterior neural plate. At the 10-somite stage, expressed in the developing tailbud and cranial neural crest. At the 20-somite stage, also expressed in the hematopoietic system.
Required for patterning ventral tissues of the tail. May increase bone morphogenetic protein (BMP) activity at the end of gastrulation by proteolytic cleavage of chordin and release of BMP from inactive complexes.
Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide. It has a relevant role in the homeostasis of membrane sphingolipids, thereby influencing membrane integrity, and endoplasmic reticulum organization and function. May sensitize cells to DNA damage-induced apoptosis.
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.
Forms a heterodimer with the catalytic subunit METTL1.
Required for the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA. In the complex, it is required to stabilize and induce conformational changes of the catalytic subunit.
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.
May be involved in ciliary biogenesis or function.
Morpholino knockdown leads to the formation of pronephric cysts and hydrocephalus, features consistent with a ciliopathy.
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.
Results in a significant reduction in midbrain size. A wide spectrum of defects in gastrulation and formation of anterior structures are noticed, ranging from milder microcephaly to more severe anencephaly and early embryonic death.
Binds DNA as a homodimer or as a heterodimer with JUN or ATF2/CREBP1.
Binds to the cAMP response element and activates transcription.
Displays temperature-dependent chaperone activity.
Interacts with RLBP1; the interaction increases synthesis of chromophore-precursors by DEGS1.
Expressed ubiquitously during early stages of development. From bud stage onwards, the expression pattern becomes restricted to the axial structures and the developing Kupffer's vesicle.
Morpholino knockdown of the protein leads to defective left-right (LR) axis formation in the embryo. Cilia number and length are reduced in the Kupffer's vesicle (KV). Morpholino knockdown of the protein in Kupffer's vesicle alone is still able to generate the phenotype, indicating that Gpr22 regulates LR asymmetry through the KV.
Orphan G-protein coupled receptor that regulates cilia length and structure in the Kupffer's vesicle leading to the left-right asymmetry development by establishing a directional fluid flow.
Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Most spliceosomal snRNPs contain a common set of Sm proteins, snrpb, snrpd1, snrpd2, snrpd3, snrpe, snrpf and snrpg that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins snrpb, snrpd1, snrpd2, snrpd3, snrpe, snrpf and snrpg, and at least three U1 snRNP-specific proteins snrnp70/u1-70k, snrpa/u1-a and snrpc/u1-c. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least prpf3, prpf4, prpf6, prpf8, prpf31, snrnp200, txnl4a, snrnp40, snrpb, snrpd1, snrpd2, snrpd3, snrpe, snrpf, snrpg, ddx23, cd2bp2, ppih, snu13, eftud2, sart1 and usp39, plus lsm2, lsm3, lsm4, lsm5, lsm6, lsm7 and lsm8. Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least lsm10, lsm11, snrpb, snrpd3, snrpe, snrpf and snrpg; the complex does not contain snrpd1 and snrpd2. Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Part of the SMN-Sm complex that contains smn1, gemin2/sip1, ddx20/gemin3, gemin4, gemin5, gemin6, gemin7, gemin8, strap/unrip and the Sm proteins snrpb, snrpd1, snrpd2, snrpd3, snrpe, snrpf and snrpg; catalyzes core snRNPs assembly. Forms a 6S pICln-Sm complex composed of clns1a/pICln, snrpd1, snrpd2, snrpe, snrpf and snrpg; ring-like structure where clns1a/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP.
Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. Is also a component of the minor U12 spliceosome. As part of the U7 snRNP it is involved in histone 3'-end processing.
May play a role in vesicular transport from endoplasmic reticulum to Golgi.
Part of the multisubunit TRAPP (transport protein particle) complex.
At 48 hours post-fertilization (hpf), it is highly expressed in the CNS, particularly in the brain tissues. The pattern is the same at 72 hpf.
Component of the TIM23 complex at least composed of timm23, timm17 and timm50.
Massive apoptosis in the CNS, probably due to loss of mitochondrial function and increased cytochrome c release.
Catalyzes the prenylation of para-hydroxybenzoate (PHB) with an all-trans polyprenyl group. Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis, which is the condensation of the polyisoprenoid side chain with PHB, generating the first membrane-bound Q intermediate.
Belongs to the mitochondrion-specific ribosomal protein mL40 family.
Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Seems to regulate the assembly of both ODAs and their axonemal docking complex onto ciliary microtubules (By similarity). Regulates ciliary and flagellar motility and is required for cilia-driven determination of body laterality (PubMed:31240264).
Component of the outer dynein arm-docking complex along with ODAD1, ODAD2, ODAD3 and ODAD4.
Knockout mutants show situs invertus but normal formation of Kupffer's vesicle (KV) cilia (PubMed:31240264). However, many of the KV cilia in the mutant beat with an irregular cycle in contrast to the smooth rotary movement in wild-type fish (PubMed:31240264).
Regulates ciliary motility and is required for cilia-driven determination of body laterality.
First detected in the otic placode at 16.5 hours post-fertilization (hpf). Detected in the developing inner ear sensory epithelium at 24 hpf. Detected in hair cells of the sensory epithelium at 4 days post-fertilization (dpf). At 5 dpf, levels are much reduced in the otolith organs, and not detectable at 7 dpf. Detected in neuromasts and in the lateral line system at 5 dpf and 7 dpf.
Fishes display the backstroke phenotype. Mutant fish exhibit otolith agenesis without additional effects on the sensory epithelium or other inner ear structures. Otoliths are essential for the perception of gravity and acceleration. Larvae without otoliths are unable to orient dorsal side up and rest mostly on their side in contact with the ground.
Proton-selective channel that specifically transports protons into cells (By similarity). Proton channel activity is only weakly-sensitive to voltage (By similarity). Proton-selective channel activity is probably required in cell types that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes (By similarity). In the vestibular system of the inner ear, required for the formation and function of otoconia, which are calcium carbonate crystals that sense gravity and acceleration (PubMed:15480759, PubMed:15581873). Probably acts by maintaining the pH appropriate for formation of otoconia (By similarity). May be involved in sour taste perception in sour taste cells by mediating entry of protons within the cytosol (By similarity).
Tetramer of heterotrimers consisting of exclusion domain, heavy- and light chains.
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).
Coreceptor for class 3 semaphorins. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.
Detected in primary motor neurons in the embryonic nervous system.
Belongs to the replication factor A protein 3 family.
May play role in the regulation of alternative splicing. May have hydrolase activity.
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The order of potency for this receptor is norepinephrine > epinephrine.
Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.
Homodimer and heterodimer; heterodimerizes with keap1b (PubMed:18057000). Component of the BCR(KEAP1) E3 ubiquitin ligase complex, at least composed of 2 molecules of cul3, 2 molecules of keap1 (keap1a and/or keap1b), and rbx1 (By similarity). Interacts with nfe2l2/nrf2; the interaction is direct (By similarity).
Belongs to the universal ribosomal protein uL4 family.
Substrate-binding subunit of tRNA (adenine-N1-)-methyltransferase, which catalyzes the formation of N1-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA.
Morpholino knockdown alters craniofacial cartilage development.
Substrate adapter for ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, which plays a key role in reticulophagy (also called ER-phagy) (By similarity). In response to endoplasmic reticulum stress, promotes recruitment of the E3 ufm1-protein ligase ufl1 to the endoplasmic reticulum membrane, leading to ufmylation of target proteins and subsequent reticulophagy of endoplasmic reticulum sheets (By similarity). Plays a role in cartilage development through sox9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator (PubMed:28263186).
May be involved in primary cilium formation.
Belongs to the GatB/GatE family. GatB subfamily.
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.
RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Regulates alternative splicing of tissue-specific exons (By similarity).
Serine protease inhibitor which displays weak inhibitory activity against trypsin (By similarity). May play a role in facial patterning during embryonic development (By similarity).
Expressed in retina where it localizes between the retinal pigment epithelium and the outer nuclear layer (at protein level).
Progressive loss of cone photoreceptors in the retina from two months post-fertilization (mpf) onwards, with almost complete loss by 9 mpf. Rod photoreceptors also show signs of degeneration in older animals of 14 mpf. Photoreceptor degeneration is accompanied by increased apoptosis and mislocalization of outer segment proteins. At the ultrastructural level, morphology of the photoreceptor ciliary pocket is frequently abnormal with either complete collapse of the pocket, or presence of multiple membranous vesicles.
Required to maintain the integrity of photoreceptor cells (PubMed:27737822, PubMed:28378834, PubMed:30052645). Specifically required for normal morphology of the photoreceptor ciliary pocket, and might thus facilitate protein trafficking between the photoreceptor inner and outer segments via the transition zone (PubMed:27737822).
Carboxylesterase that mediates deacylation of target proteins (By similarity). Acts as a regulator of growth cone migration. Does not act as an inhibitor of Wnt signaling (PubMed:23365253).
In contrast to other members of the family, it apparently does not inhibit the Wnt signaling pathway, suggesting that it does not mediate depalmitoleoylation of WNT proteins (PubMed:23365253). However, additional evidence is required to confirm these data.
Specifically expressed in the muscle pioneers (MPs) during primary motor innervation.
Defects in nek8 are the cause of polycystic kidney disease.
Morpholino knockdown of the protein in the embryo causes ventral body curvature, pronephric cyst formation and laterality defects, including reversed heart looping.
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.
Anchored to cell periphery via its N-terminal PDZ domain.
May function as a scaffold on which the coordinated assembly of proteins can occur. May play a role as an adapter that, via its PDZ domain, localizes LIM-binding proteins to actin filaments of both skeletal muscle and nonmuscle tissues (By similarity).
The LIM zinc-binding 3 (LIM 3) domain provides the structural basis for recognition of tyrosine-containing tight turn structures.
Embryonic nervous system. Expressed transiently in neurogenic placodes prior to delamination and formation of cranial ganglia. Expressed early (6-somite stage) in Rohon-Beard spinal sensory neurons and later in neural crest-derived dorsal root ganglion neurons. At 24 hours post-fertilization (hpf), expressed in specific regions of the brain and spinal cord. In hindbrain, expressed in presumptive neuroblasts adjacent to the rhombomere boundaries. In basal forebrain, expressed in dopaminergic progenitor cells.
First detected at the late gastrulation stage (9 hpf). Strongly expressed in distinct domains in the neural plate at the 3-somite stage. First expressed in the epiphysis at around 14 hpf.
Transcriptional regulator. Activates transcription by binding to the E box-containing promoter (By similarity). Mediates neuronal differentiation. Required for the development of Rohon-Beard spinal sensory neurons and dorsal root ganglion neurons, but not for primary motoneurons or autonomic neurons. Required for development of all cranial ganglia but not associated glial cells. Regulates epiphysial neurogenesis, acting partially redundantly with ascl1a and downstream of flh. Required for the development of basal forebrain dopaminergic neurons; involved in the specification of dopaminergic progenitor cells. May be involved in maintaining rhombomere boundaries in the hindbrain.
Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by triming the ubiquitin chain on the associated substrate to facilitate their threading through the VCP/p97 pore. Ubiquitin moieties on substrates may present a steric impediment to the threading process when the substrate is transferred to the VCP pore and threaded through VCP's axial channel. Mediates deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin chains. Cleaves both polyubiquitin and di-ubiquitin.
Belongs to the complex I subunit 1 family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. EFM5 family.
Protein-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at 'Lys-79'.
Was originally thought to be an N(6)-adenine-specific DNA methyltransferase based on primary sequence and predicted secondary structure.
Decreased axonal branches and decreased dendrites in motor neurons (PubMed:29061699). Decreased GAP43 mRNA levels (PubMed:29061699). Morpholino knockdown of the protein causes severe defects in motor neuron axonal outgrowth, including truncations and abnormal branching (PubMed:23063131).
Homodimer. Component of an import snRNP complex composed of kpnb1, rnut1, smn1 and znf259. Part of the core SMN complex that contains smn1, gemin2/sip1, ddx20/gemin3, gemin4, gemin5, gemin6, gemin7, gemin8 and strap/unrip. Interacts with ddx20, fbl, nola1, rnut1, syncrip and with several spliceosomal snRNP core Sm proteins, including snrpb, snrpd1, snrpd2, snrpd3, snrpe and ilf3 (By similarity). Interacts with elavl4 (PubMed:29061699).
The SMN complex plays an essential role in spliceosomal snRNP assembly in the cytoplasm and is required for pre-mRNA splicing in the nucleus (PubMed:23063131). It may also play a role in the metabolism of snoRNPs (PubMed:23063131). Required in motor neurons and proprioceptive neurons to ensure correct U12 intron splicing and proper levels of tmem41b mRNA (PubMed:23063131). Required for the maturation of motor neuron axonal branches and dendrites (PubMed:23063131, PubMed:29061699).
May function as an adapter protein. Required for efficient phagocytosis of apoptotic cells. May play a role in the internalization and endosomal trafficking of various lrp1 ligands (By similarity).
May negatively regulate myogenesis and skeletal muscle regeneration.
Belongs to the class I-like SAM-binding methyltransferase superfamily. TrmB family.
Catalyzes the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA.
Methyltransferase 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 tRNA. Also acts as a methyltransferase for a subset of internal N(7)-methylguanine in mRNAs. Internal N(7)-methylguanine methylation of mRNAs regulates translation. Also methylates a specific subset of miRNAs.
Detected before the 1k-cell stage, suggesting that it is maternally supplied. At the sphere stage, stronger expression in the dorsal blastomeres. In the gastrula, expressed in the whole embryo, except in the evacuation zone. During segmentation and pharyngula period, expressed in many distinct domains, including the polster, telencephalon, trigeminal placodes, rhombomeres, trunk neurons, somites and axial vasculature. During the pharyngula period, additional expression observed in lateral line primordia and in intersegmental vessels.
Phosphorylation at Tyr-103 is necessary for efficient binding to SRC and synergistically functioning with SRC to activate the downstream MAPK pathway.
Regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Required for proper architecture of actin filaments and for cell movements during embryogenesis. Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. Participates in angiogenesis. May play a role in the polarity, proliferation and migration of endothelial cells. Selectively promotes FGF-induced MAPK activation through SRC.
Belongs to the glycerate kinase type-2 family.
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 TRAPP small subunits family.
Part of the multisubunit transport protein particle (TRAPP) complex.
Belongs to the deoxyhypusine hydroxylase family.
Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-lysine intermediate produced by deoxyhypusine synthase/DHPS on a critical lysine of the eukaryotic translation initiation factor 5A/eIF-5A. This is the second step of the post-translational modification of that lysine into an unusual amino acid residue named hypusine. Hypusination is unique to mature eIF-5A factor and is essential for its function.
Belongs to the cyclin family. Cyclin-like FAM58 subfamily.
May be an activating cyclin for the cyclin-associated kinase CDK10.
Catalyzes the NAD-dependent oxidation of 2-aminomuconic semialdehyde of the kynurenine metabolic pathway in L-tryptophan degradation.
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.
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.
Component of the ESCRT-I complex (endosomal sorting complex required for transport I), a regulator of vesicular trafficking process.
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 Glu/Leu/Phe/Val dehydrogenases family.
May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning.
Necessary for the biogenesis and transport of multi-pass membrane proteins into the endoplasmic reticulum membrane (By similarity). Antagonizes Nodal signaling and subsequent organization of axial structures during mesodermal patterning. Ectopic expression results in cyclopia, due to a defect in mesendoderm patterning (PubMed:15257293).
Strongly and ubiquitously expressed at early stage of somatogenesis. Later, expression is prominent in the developing retina, optic tectum and somites.
May function as a sodium-dependent glucose transporter. Potential channels for urea in the inner medulla of kidney.
Although it belongs to the SDR family, Phe-218 is present instead of the conserved Tyr which is an active site residue. It is therefore expected that this protein lacks oxidoreductase activity.
Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.
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.
Embryonic, larval and adult stages. Expression is weak from 10 to 48 hours post-fertilization (hpf) and increases from 72 hpf.
In adult, expressed strongly in brain and more weakly in skin, muscle, eye and ovary.
Transcriptional regulator. Appears to mediate neuronal differentiation (By similarity).
Belongs to the sirtuin family. Class II subfamily.
NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of acyl groups from lysine residues.
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).
Morpholino knockdown causes abnormal retinal lamination in the developing eye.
Required correct function and survival of retinal photoreceptors (PubMed:24691551). Required for retinal development (By similarity). In rod photoreceptors, facilitates stability and/or trafficking of guanylate cyclases and is required to maintain endoplasmic reticulum and mitochondrial homeostasis (By similarity). May play a role in clathrin-coated intracellular vesicle trafficking of proteins from the endoplasmic reticulum to the retinal rod plasma membrane (By similarity).
Belongs to the POU transcription factor family. Class-6 subfamily.
Transcription factor that binds with high affinity to the motif 5'-TAATGARAT-3'.
Ubiquitously expressed during embryogenesis.
Low-affinity, high capacity permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine).
First detected at around 8 hours post-fertilization (hpf) within the prospective midbrain-hindbrain boundary (MHB). By 10 hpf, expressed in two stripes that converge at the dorsal midline. During somitogenesis, this expression domain extends to the prospective epiphysis and the dorsal midline of the hindbrain; unlike wnt1, wnt10b is detected in the prospective cerebellum. The hindbrain domain bifurcates along the midline to form two dorsolateral columns with transverse bands of up-regulation at rhombomere boundaries; these are refined into stripes which are maintained at least until at least 48 hpf. At 30 hpf, expressed in the epiphysis, the dorsal midline of the optic tectum, the anterior half of the MHB constriction and in the hindbrain walls.
In the embryo, expressed in the developing central nervous system (CNS), with an expression pattern very similar to that of wnt1.
Member of the Wnt ligand gene family that encodes for secreted proteins, which activate the Wnt signaling cascade. Involved in neurogenesis. Performs a partially redundant function with wnt1 in the formation of the midbrain-hindbrain boundary (MHB) organizer.
Retinal long single cone outer segments.
Belongs to the DNA photolyase class-2 family.
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.
Endogenous ligand for the apelin receptor (aplnra and/or aplnrb) (PubMed:17336905). Drives internalization of the apelin receptor (By similarity). Hormone involved in the regulation of cardiac precursor cell movements during gastrulation and heart morphogenesis (PubMed:17336905). Plays a role in early coronary blood vessels formation. Mediates myocardial contractility in an ERK1/2-dependent manner. May also have a role in the central control of body fluid homeostasis (By similarity).
Expressed at the end of gastrulation (at protein level) (PubMed:24407481). Expressed in the embryo from 7 to 48 hours post-fertilization (hpf) (PubMed:17336905). Expressed in the axial mesoderm and its later derivative, the notochord at 11.5 hpf (PubMed:17336905). Expressed in the forming head and heart and in the posterior notochord at 18 hpf (PubMed:17336905).
Morpholino knockdown of the protein show impaired gastrulation and heart formation (PubMed:17336905). Embryos display reduced migration of anterior lateral plate mesoderm (LPM) cells and cardiac progenitor cells (angioblasts) toward the midline during late gastrulation (PubMed:17336905, PubMed:26017639). Embryos show altered cardiac gene expression (PubMed:17336905). Embryos with CRISPR-induced apelin and apela null mutations show a strong decrease in the angioblast migration to the embryonic midline during late gastrulation (PubMed:26017639).
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.
Belongs to the cyclin family. Cyclin D subfamily.
Interacts with the CDK4 and CDK6 protein kinases to form a serine/threonine kinase holoenzyme complex (By similarity). The cyclin subunit imparts substrate specificity to the complex (By similarity).
Phosphorylation at Thr-282 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex.
Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals.
Ubiquitinated by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation. The DCX(AMBRA1) complex represents the major regulator of CCND1 stability during the G1/S transition.
Belongs to the eukaryotic ribosomal protein eL36 family.
Heteromeric complex composed of WDR83OS/Asterix and CCDC47. Component of the ribosome-associated ER translocon complex.
Necessary for the biogenesis, correct folding and transport of multi-pass membrane proteins into the endoplasmic reticulum (ER) membrane. Involved in the regulation of calcium ion homeostasis in the ER. Required for proper protein degradation via the ERAD (ER-associated degradation) pathway.
Belongs to the peptidase M24 family. SPT16 subfamily.
Hydrolyzes ADP-ribose, IDP-ribose, CDP-glycerol, CDP-choline and CDP-ethanolamine, but not other non-reducing ADP-sugars or CDP-glucose.
Binds 2 magnesium or manganese ions per subunit.
Protein phosphatase which positively regulates biosynthesis of the ubiquinone, coenzyme Q (By similarity). Dephosphorylates the ubiquinone biosynthesis protein coq7 which is likely to lead to its activation (By similarity).
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).
Component of the DCX(DTL) E3 ubiquitin ligase complex, at least composed of cul4 (cul4a or cul4b), ddb1, dtl/cdt2 and rbx1.
General developmental defects, including apoptosis in the central nervous system and a dorsally curved tail, which appear by 28 hpf. Effects are due to general cell cycle defects, including defects in the G2/M checkpoint.
Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), KMT5A and SDE2. CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing. KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration. Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (By similarity). May play a role in the regulation of the circadian clock (By similarity).
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.
Detected at the cleavage and blastula stages, 1.75-4 hours post-fertilization (hpf) (PubMed:21880859). Expressed in forebrain, midbrain, hindbrain and cells lining the brain ventricles at 19-22 hpf (PubMed:21880859). Expressed in midbrain and otic vesicles at 26-36 hpf (PubMed:21880859). Detected in bilateral domains in brain near the hypothalamus, and in heart, at 48-72 hpf (PubMed:15297442, PubMed:21880859).
Plays a role as a potent and selective agonist of pth2r resulting in adenyl cyclase activation and intracellular calcium level elevation.
Up-regulated in the developing brain by shh signaling.
Plays a role as an effector of the ADP-ribosylation factor-like protein 2, ARL2.
Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-603 has an important role in the selective binding of succinyl-CoA over acetyl-CoA.
Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase or succinyltransferase, depending on the context (By similarity). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (By similarity). Succinylation of histones gives a specific tag for epigenetic transcription activation (By similarity). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (By similarity). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (By similarity). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (By similarity). Acetylation of histones gives a specific tag for epigenetic transcription activation (By similarity). Also acetylates non-histone proteins, such as tbx5 (PubMed:29174768). Involved in heart and limb development by mediating acetylation of tbx5 (PubMed:29174768). Together with kat2b, required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (PubMed:30424580). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (By similarity).
Widely expressed throughout the anterior head region, including the central nervous system, the eye and branchial arches at 24 hours post fertilization (hpf). Expressed strongly in the brain region. By 40-48 hpf, expression remains strongly expressed in the head region but is reduced throughout the rest of the embryo (PubMed:30424580). Expressed in the heart and tail regions throughout developmental stages (PubMed:29174768).
Abundantly expressed from the blastula period through early gastrulation. During early somitogenesis, transcripts are dorsally localized at the level of the segmental plate and the presumptive notochord. At the 18-somite stage, expression becomes largely detectable throughout the somitic tissue At late embryonic stages, expression is particularly evident in the tectum, cerebellum, hindbrain region, and eyes. After hatching, transcripts can also be detected in the myotomes and pectoral fins.
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.
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).
Acts as a ligand for Notch receptors and is involved in primary neurogenesis. Can activate Notch receptors, thereby playing a key role in lateral inhibition, a process that prevents the immediate neighbors of each nascent neural cell from simultaneously embarking on neural differentiation.
Expressed in the epiblast (the future neurectoderm) and in neuroblasts. Expressed in overlapping regions with deltaA (dla) and deltaD (dld), but differs in the neural plate: it is apparently confined to the scattered cells within those patches that differentiate as neurons, while dla and dld are expressed in patches of contiguous cells.
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.
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.
Belongs to the V-ATPase H subunit family.
Expressed in the ear and mesendodermal components of pharyngeal arches.
Expression first detected at 5.0 hours post fertilization (hpf) in the dorsal blastoderm margin. Through the stage of embryonic shield formation, expression is restricted to the hypoblast, in the region of cells fated to become head and lateral plate mesoderm and pharyngeal endoderm. At 18 hpf, when the heart tube is beginning to assemble, three domains of expression can be seen: cardiac precursors, pharyngeal arch precursors and otic vesicle. These three domains remain the sites of expression to varying degrees through at least 72 hpf. By 51 hpf, expression can be seen in the cardiac outflow tract, the ventricle and the atrium, although by 72 hpf cardiac expression is strongest in the cardiac outflow tract.
Fishes display defects in the ear, pharyngeal arches and associated structures such as the thymus.
Probable transcriptional regulator involved in developmental processes (By similarity). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence (By similarity). Is required for normal development of the pharyngeal arch arteries (By similarity). Acts cell autonomously in the pharyngeal mesendoderm and influences the development of neural crest-derived cartilages secondarily.
Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor.
At the 10-somite stage, expressed in the paraxial mesoderm with an anterior expression limit at somite 8. At the 20-somite stage, expressed within the developing CNS with an anterior expression limit adjacent to the somite 4/5 boundary.
Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
Morpholino knockdown of the protein causes strong ciliopathy phenotypes, including pronephric cysts, axis curvature, left-right asymmetry defects and hydrocephalus. Cilia length and number appear normal, but outer dynein arms are missing and cilia are paralyzed.
The glycine cleavage system catalyzes the degradation of glycine.
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.
Expressed throughout development. Weakly or not expressed in some adult organs.
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).
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.
May play some role in mitochondrial processes.
Involved in the interconversion between alpha- and beta-L-fucoses.
Belongs to the WD repeat DCAF13/WDSOF1 family.
Possible role in ribosomal RNA processing. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex (By similarity).
Homodimer; homodimerization requires the C4-type zinc finger motif and decreases during mitosis in a phosphorylation-dependent manner.
Plays a role in determining ER morphology.
The C4-type zinc finger motif is necessary both for its ER three-way tubular junction localization and formation.
Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (By similarity). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (By similarity).
Belongs to the glycosyltransferase 43 family.
Although highly related to the Ras family, lacks the conserved prenylation motif at the C-terminus, which serves to target Ras proteins to membrane compartments.
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).
Expressed in the dorsal optic cup of developing eye, pectoral fin buds and heart. At 31 hpf, when the pectoral fin buds have begun bulging outwards, restricted expression is detected throughout the mesenchyme of the early fin buds and these high levels of expression continue until later stages.
Monomer. Homodimer (via the T-box); binds DNA as homodimer.
Required for pectoral fin formation. Together with tbx5b, involved in eye and heart development. Required for the looping stage of heart development. May bind to the core DNA motif of promoters.
The T-Box domain binds to double-stranded DNA.
Belongs to the adrenodoxin/putidaredoxin family.
Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is an heterohexamer containing two copies of each monomer. Form an heterodimer complex with NFS1.
Electron donor, of the core iron-sulfur cluster (ISC) assembly complex, that acts to reduce the persulfide into sulfide during [2Fe-2S] clusters assembly on the scaffolding protein ISCU (By similarity). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity).
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.
Belongs to the peptidase M24A family. Methionine aminopeptidase eukaryotic type 2 subfamily.
Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site.
Binds EIF2S1 at low magnesium concentrations. Interacts strongly with the eIF-2 gamma-subunit EIF2S3.
Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) residues. O-glycosylation is required for EIF2S1 binding.
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val).
Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.
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.
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.
Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites.
Belongs to the MICOS complex subunit Mic60 family.
Belongs to the cholesterol 7-desaturase family.
Catalyzes the production of 7-dehydrocholesterol (7-DHC or cholesta-5,7-dien-3beta-ol) by inserting a double bond (desaturating) at the C7-C8 single bond of cholesterol. This reaction is the first step in the synthesis of the steroid hormone Delta(7)-dafachronic acid.
Cytokine that acts as a physiological ligand for receptor tyrosine kinases LTK and ALK (PubMed:29078341, PubMed:29317532). Required for neural crest cell differentiation and iridophore development during embryonic iridophore development and adult stripe development by acting as a receptor for LTK (PubMed:29078341, PubMed:29317532). Also required for iridophore formation in the adult eye (PubMed:29078341).
Highly expressed in the swim bladder and single cells of unknown identity in the head.
Reduced number of iridophores in the eye (PubMed:29078341). Fishes lacking alkal2b do not exhibit any defects in trunk iridophores in adults (PubMed:29317532). Fishes lacking both alkal1 and alkal2b show a complete loss of eye iridophores (PubMed:29317532). Fishes lacking alkal1, alkal2a and alkal2b are embryonic lethal and display total loss of iridophores (PubMed:29317532).
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.
Belongs to the methyltransferase superfamily. Fibrillarin family.
First expressed at the dorsal intermediate region of the neural tube at the 5-somite stage, expression is extended along the rostral caudal axis by the late stages of segmentation (PubMed:19216761). Expressed at the presumptive fin bud at 24 hours post-fertilization (hpf) and then at the fin bud at 48 hpf (PubMed:19216761).
Morpholino knockdown results in decreased myod1 expression in the fin bud of embryos.
Transcription factor required for the development of hypaxial muscles.
Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily.
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). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed.
Expression starts between 10 and 12 hours post fecondation and is highest between 2 and 3 days after fertilization.
Predominantly expressed in the embryonic and adult central nervous system.
Transcription factor that may play important roles in patterning the embryonic brain. Could directly respond to the reception of the sonic hedgehog (shh) signal.
Belongs to the MICOS complex subunit Mic19 family. Metazoan Mic25 subfamily.
Component of the mitochondrial contact site and cristae organizing system (MICOS) complex (also known as MINOS or MitOS complex).
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.
Plays a role in the formation and organization of tight junctions during the establishment of polarity in epithelial cells.
Binds to various extracellular matrix proteins.
Promotes cell adhesion and matrix assembly.
Belongs to the universal ribosomal protein uL29 family.
Mediator of sterol homeostasis involved in sterol uptake, trafficking and distribution into membranes.
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.
Binds medium- and long-chain acyl-CoA esters.
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.
Belongs to the ribose 5-phosphate isomerase family.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the F-actin-capping protein beta subunit family.
Expressed in the olfactory bulb, telencephalon, hypothalamus, midbrain tegmentum, retina, hindbrain and the spinal cord. Expressed in GnRH3 neurons within the olfactory epithelium and terminal nerve.
Stimulates outgrowth of olfactory axons and migration of hypophysiotropic gonadotropin-releasing hormone 3 (GnRH3) neurons. May couple NMDA-sensitive glutamate receptor signaling to the nucleus and trigger long-lasting changes in the cytoarchitecture of dendrites and spine synapse processes.
Belongs to the DPH1/DPH2 family. DPH2 subfamily.
Binds 1 [4Fe-4S] cluster per subunit. The cluster facilitates the reduction of the catalytic iron-sulfur cluster in the dph1 subunit.
Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (By similarity). Dph1 and dph2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising dph3 and a NADH-dependent reductase (By similarity). Facilitates the reduction of the catalytic iron-sulfur cluster found in the dph1 subunit (By similarity).
May play a role in the respiratory chain.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily.
Belongs to the potassium channel family. V (TC 1.A.1.2) subfamily. Kv8.1/KCNV1 sub-subfamily.
Heteromultimer with KCNB1 and KCNB2. Interacts with KCNC4 and KCND1.
Potassium channel subunit that does not form functional channels by itself. Modulates KCNB1 and KCNB2 channel activity by shifting the threshold for inactivation to more negative values and by slowing the rate of inactivation. Can down-regulate the channel activity of KCNB1, KCNB2, KCNC4 and KCND1, possibly by trapping them in intracellular membranes.
Widely expressed in the embryo. High level in embryonic blood at 24 hours post-fertilization (hpf).
Belongs to the proteasome subunit S3 family.
Morpholino knockdown of the protein results in marked vascular anomalies of the dorsal cranial vessels including both dorsal longitudinal and mesencephalic veins.
Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 is involved in the regulation of cell adhesion and cell migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability (PubMed:29444212). EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells (By similarity) (PubMed:29444212). Involved in somitogenesis (PubMed:9765210).
EF-1 is composed of four subunits: alpha, beta, delta, and gamma.
Probably plays a role in anchoring the complex to other cellular components.
Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system, facilitating the assembly of these organelles.
Light intermediate chain of the cytoplasmic dynein complex 2, a multisubunit complex composed at least of eleven different proteins. The cytoplasmic dynein 2 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs). Among them, a heavy chain (DYNC2H1), two intermediate chains (DYNC2I2 and DYNC2I1), a light intermediate chain (DYNC2LI1), and a light chain (DYNLT2B) are unique to the dynein-2 complex, but a subset of light chains are also shared by dynein-1 and dynein-2 complexes. Dynein-2 complex is built around two copies of cytoplasmic dynein 2 heavy chain 1 (DYNC2H1). The C-terminal region forms the motor domain, which converts the energy from ATP hydrolysis into movement. Its N-terminal region forms the tail, an extended structure that binds the other subunits and holds the two heavy chains in a homodimer.
Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport (By similarity).
The vault ribonucleoprotein particle is a huge (400 A x 670 A) cage structure of 12.9 MDa. It consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains, PARP4 and one or more vault RNAs (vRNAs) (By similarity).
Transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development.
Belongs to the mitochondrion-specific ribosomal protein mL54 family.
Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
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).
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.
Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione.
Belongs to the ribonuclease III family. Mitochondrion-specific ribosomal protein mL44 subfamily.
Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 is involved in the regulation of cell adhesion and cell migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells (By similarity). Involved in somitogenesis (PubMed:9765210).
Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament. Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. Required for asymmetric spindle positioning and asymmetric cell division during meiosis. Required for normal formation of the cleavage furrow and for polar body extrusion during female germ cell meiosis. Also acts in the nucleus: together with FMN2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. In addition, promotes innate immune signaling downstream of dsRNA sensing. Mechanistically, contributes to IRF3 phosphorylation and activation downstream of MAVS and upstream of TBK1.
Binds to actin monomers via the WH2 domain.
The Spir-box targets binding to intracellular membrane structures.
Involved in DNA damage response; activates kinases ATM, SMC1A and PRKDC by modulating their phosphorylation status following ionizing radiation (IR) stress.
Expressed in most developing organs which contain mucus-secreting cells, including the epidermis, olfactory bulbs, otic vesicles, pharynx, esophagus, pneumatic duct, swim bladder, and intestine. Expressed in the gill, pharynx/esophagus, swim bladder/pneumatic duct, and intestine in the adult.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Era GTPase family.
Probable GTPase that plays a role in the mitochondrial ribosomal small subunit assembly. Specifically binds the 12S mitochondrial rRNA (12S mt-rRNA) to a 33 nucleotide section delineating the 3' terminal stem-loop region. May act as a chaperone that protects the 12S mt-rRNA on the 28S mitoribosomal subunit during ribosomal small subunit assembly (By similarity).
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).
Seems to facilitate zinc transport from the cytoplasm into the Golgi apparatus. Partly regulates cellular zinc homeostasis (By similarity).
E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC) (By similarity). Regulates cell movements during gastrulation by acting downstream of fz7 to antagonize the frizzled-signaling pathway.
Expression starts early during embryogenesis and is maintained through late embryogenesis and in the adult.
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).
Expressed both maternally and zygotically. Localized to the prospective animal pole during oogenesis. Ubiquitous expression during the blastula stages. During early gastrulation, levels are higher ventrally and in the presumptive shield (organizer region). Later in gastrulation, expression is restricted to midline and ventral cells. At the start of somatogenesis, expression is restricted to notochord, lateral plate mesoderm and a stripe of anterior dorsal neuroectoderm. By the 19-somite stage, expression in the lateral plate and midline diminishes but forebrain expression persists. All expression is lost by 24 hours post-fertilization (hpf).
Fishes exhibit ventral body curvature, reduced spacing of the eyes, and absence or reduction of ventral neuroectoderm, including the floor plate.
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. Activates an activin response element (ARE). Recognizes and binds to the DNA sequence 5'-TGT[GT][GT]ATT-3'. Modulator of nodal signaling required for organizer formation. Also required for the development of dorsal axial structures and left-right symmetry.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ2 subfamily.
By the 5-somite stage, expressed in the anterior spinal cord. Expression becomes restricted to the ventral spinal cord and by 24 hpf, expression is low and restricted to the medial ventral spinal cord.
Collagen-like protein, which provides an organic scaffold for otoliths onto the sensory epithelium of the inner ear (PubMed:15905077, PubMed:29076638). Acts as a scaffold for biomineralization by sequestering calcium (PubMed:29076638).
Homooligomer; disulfide-linked; probably forms homotrimers (PubMed:29076638). Interacts with otomp (By similarity).
The C1q domain mediates calcium-binding.
Expressed as early as 24 hours post fecondation (hpf), expressed at lower levels than leg1a.
Involved in early development of liver, exocrine pancreas and intestine, probably through cell cycle regulation. In liver, its function is partially redundant with leg1a function.
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.
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 cyclic nucleotide phosphodiesterase family. PDE1 subfamily.
At 36 hpf, expressed predominantlyin the brain, including several discrete regions in the forebrain, midbrain and hindbrain.
May play a role in bone differentiation and matrix mineralization (By similarity). May play a role in neural development.
Belongs to the FAM175 family. Abraxas subfamily.
Component of the BRCA1-A complex. Component of the BRISC complex. Homodimer. Interacts directly (when phosphorylated at Ser-388) with brca1. 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-388 of the pSXXF motif by ATM or ATR constitutes a specific recognition motif for the BRCT domain of BRCA1.
Expressed in embryo throughout the early nervous system. Strongly expressed in differentiating neurons in the brain, spinal cord and retina. Not detected in the lens at any developmental stage tested.
May be involved in early neuronal development (By similarity). May play a role in promoting megakaryocyte differentiation (By similarity).
Morpholino knockdown of the protein disrupts both skeletal muscle development in the trunk and cranial muscle development. Disrupts myogenesis by interfering with the proliferation of dermomyotomal cells expressing pax7.
Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development. Depending on context, functions as transcriptional repressor or activator. Plays an important role in the development of the inner ear, where it promotes hair cell proliferation and inhibits proliferation of neural progenitor cells (By similarity). Required for normal myogenesis. Plays a role in the development of fast muscle fibers throughout the body, as well as the development of craniofacial muscles.
Ubiquitous during segmentation. Detected in otic vesicle and statoacoustic ganglion at later stages of development. At 24 hpf, detected in developing fast muscle throughout the trunk.
Zebrafish has two genes coding for six1 orthologs. This gene is called six1a by ZFIN, but has also been described as six1b (PubMed:18789916).
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 Rab3-GAP regulatory subunit family.
Expressed at the notochord and the somite around tailbud stage. At 14 hours post-fertilization (hpf), expressed in the somites, notochord, and the brain. Found in the rhombomere 3 (r3) and r5. Expressed in the optic vesicles and a region covering the caudal diencephalon and the mesencephalon with the strongest expression at its most anterior part. Mesodermal expression is observed in both forming and formed somites. In forming and newly formed somites, transcripts are distributed evenly. In contrast, distribution in somites located on more anterior trunk seems to be uneven, strongest in the ventral, intermediate in the dorsal, and weakest in the medial parts. At 23 hpf, there is no expression in the medial parts of somites. Expression in somites fades away by 36 hpf. At 20 hpf, additional expression is detected in the pharyngeal arches.
Expressed by retinal ganglion cells and their presynaptic amacrine and postsynaptic tectal cell targets.
Homodimer; disulfide-linked; to mediate homophilic cell adhesion.
Involved in neural development by regulating the establishment of proper connectivity within the nervous system (PubMed:24183672, PubMed:27374343). Acts in both pre- and postsynaptic neurons in the hippocampus to control the assembly of a precise topographic projection: required in both CA1 and subicular neurons for the precise targeting of proximal CA1 axons to distal subiculum, probably by promoting homophilic cell adhesion (By similarity). Required by retinal ganglion cells for acquisition of their correct morphological and functional connectivity, thereby playing a key role in the development of the visual pathway (PubMed:24183672, PubMed:27374343).
Morpholino knockdown of the protein causes retinal ganglion cell dendrite stratification defects within the inner plexiform layer, as well as mistargeting of dendritic processes into outer portions of the retina.
Probably catalyzes the deacetylation of acetylated carbohydrates an important step in the degradation of oligosaccharides.
Contains a RS region (arginine-serine dipeptide repeat) within the C-terminal domain which is the hallmark of the SR family of splicing factors. This region probably plays a role in protein-protein interactions (By similarity).
Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family. TRM7 subfamily.
Methylates the 2'-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs.
Forms pentamers. Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold by pentamerizing into a star-shaped structure, which can bind a single copy each of PIKFYVE and FIG4 and coordinates their activities. Interacts with NOS1.
Scaffold protein component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Pentamerizes into a star-shaped structure and nucleates the assembly of the complex. The pentamer binds a single copy each of PIKFYVE and FIG4 and coordinates both PIKfyve kinase activity and FIG4 phosphatase activity, being required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes.
The C-terminal domain (residues 523-782) mediates pentameric interactions and is necessary for the formation and maintenance of the PI(3,5)P2 regulatory complex.
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.
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.
Belongs to the mitochondrion-specific ribosomal protein mS31 family.
Belongs to the Mediator complex subunit 22 family.
Glycosyltransferase that participates in the transfer of N-acetylglucosamine (GlcNAc) to the core mannose residues of N-linked glycans. Catalyzes the formation of the GlcNAcbeta1-4 branch on the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans (By similarity).
Belongs to the RBR family. RNF19 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, such as UCKL1. Involved in the cytolytic activity of natural killer cells and cytotoxic T-cells. Protects against staurosporin-induced cell death.
Interacts with UBE2L3, UBE2L6 and UCKL1.
The first IBR-type zinc finger is the most crucial for interaction with UBE2L3, UBE2L6 and UCKL1.
Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA (By similarity).
Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA.
Belongs to the 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.
Functions as a chaperone necessary for a stable expression of the CYBA and CYBB subunits of the cytochrome b-245 heterodimer.
Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes.
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.
Belongs to the ANT/ATPSC lysine N-methyltransferase family.
Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/mbtps1 and S2P/mbtps2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis. May protect neuroblastoma cells from ER stress-induced death. In vitro activates transcription of target genes via direct binding to the CRE site.
Upon ER stress, translocated to the Golgi apparatus, where it is processed by regulated intramembrane proteolysis (RIP) to release the cytosol-facing N-terminal transcription factor domain. The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/mbtps1 and S2P/mbtps2).
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. Plays a critical role in the assembly of N-DRC and also stabilizes the assembly of multiple inner dynein arms and radial spokes. Coassembles with CCDC65/DRC2 to form a central scaffold needed for assembly of the N-DRC and its attachment to the outer doublet microtubules.
Component of the nexin-dynein regulatory complex (N-DRC).
Belongs to the aerobic coproporphyrinogen-III oxidase family.
Catalyzes the formation of 5-oxo-L-proline from L-gamma-glutamyl-L-epsilon-lysine.
Mutants generated by CRISPR-Cas9-mediated gene editing exhibit severe cardiac malformations, including defects in left-right patterning and looping and hypoplastic ventricles.
Plays a critical role in cardiac development (PubMed:30110327). Acts as a key epigenetic regulator of gene expression during cardiac development via its dual activities as a methyltransferase and negative regulator of HDAC1 (PubMed:30110327).
Ubiquitously expressed in early embryos and becomes enriched in the developing heart at 48 hours post-fertilization.
ATP-dependent 3'-5' DNA helicase, 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. The ATPase activity of XPB/ERCC3, but not its helicase activity, is required for DNA opening. 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. The ATP-dependent helicase activity of XPB/ERCC3 is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.
Belongs to the helicase family. RAD25/XPB subfamily.
Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with PUF60. Interacts with ATF7IP. Interacts with Epstein-Barr virus EBNA2.
Defects in s1pr2 are a cause of heart development abnormality named miles apart (mil). In all vertebrates, the myocardial progenitors involute early during gastrulation and come to occupy bilateral positions in the anterior lateral plate mesoderm (LPM). During somitogenesis, these cells undergo a second phase of migration toward the midline and fuse to form the definitive heart tube. Defects in S1PR2 disrupt this process, leading to the formation of two laterally positioned hearts (cardia bifida). The mil phenotype for which two recessive alleles exist, mil(m93) and mil(te273) are fully penetrant. Mil(m93)/mil(te273) transheterozygous embryos display the same phenotype as homozygotes for either single mutant allele. In addition to cardia bifida, mil mutants display epithelial tail blisters, indicative of a defect in epithelial integrity.
Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P) (PubMed:10910360). S1P receptor is critical for cell migration and epithelial integrity during vertebrate embryogenesis (PubMed:10910360). Receptor for the chemokine-like protein FAM19A5 (By similarity). Mediates the inhibitory effect of FAM19A5 on vascular smooth muscle cell proliferation and migration (By similarity).
The expression pattern is complex and dynamic. Maternal expression is found in a diffuse pattern throughout the blastoderm, and this pattern persists through the onset of gastrulation. More pronounced expression can be seen at tailbud stage in the anterior portion of the embryo and along the embryonic axis, and at the 16-somite stage in the midbrain/hindbrain boundary and the tip of the tail where blisters later develop in receptor mutants. At the 18-somite stage, expression appears just lateral to the midline, and as the myocardial precursors migrate to the midline, their location overlaps with this domain of receptor expression.
Small GTPase required for proper nuclear import of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import.
Belongs to the ATP synthase subunit s family.
Homotetramer. Associates with ATP synthase.
Involved in regulation of mitochondrial membrane ATP synthase. Necessary for H(+) conduction of ATP synthase. Facilitates energy-driven catalysis of ATP synthesis by blocking a proton leak through an alternative proton exit pathway.
From mid-gastrula to just before somite formation, expressed in cells adjacent to axial mesoderm. Subsequently, during the anterior-to-posterior wave of somite formation and maturation, expressed within particular regions of each somite. Expressed in both muscle and non-muscle cells.
May act as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation.
Belongs to the cytochrome c oxidase subunit 6c family.
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
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.
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.
Sterol-binding protein that mediates cholesterol transport from the endoplasmic reticulum to endosomes. Creates contact site between the endoplasmic reticulum and late endosomes: localizes to late endosome membranes and contacts the endoplasmic reticulum. Acts as a lipid transfer protein that redirects sterol to the endosome at the expense of the cell membrane and favors membrane formation inside endosomes.
The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol.
The START domain mediates lipid-transfer between membranes. It contains a hydrophobic cavity able to accommodate one lipid molecule, thereby serving as a 'hydrophobic bridge' across the aqueous gap between donor and acceptor organelle membranes.
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).
Negatively regulates nitric oxide production by inducing nitric oxide synthase translocation to actin cytoskeleton and inhibiting its enzymatic activity.
May play a role in fatty acid biosynthesis and insulin sensitivity.
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. Required for myoseptal integrity, myofiber attachment, motility and craniofacial development (PubMed:17189627, PubMed:17586488, PubMed:20440001, PubMed:20849610). Is necessary for normal early lens development (PubMed:24549050).
Expressed in striated muscle tissue including somites, heart and craniofacial muscle. Detected in mesoderm adjacent to the dorsal midline during the late gastrula stages and in somitic mesoderm during development of trunk skeletal muscle. Also expressed in cranial skeletal muscle and in cardiac and smooth muscle. Detected in somitic muscle and heart primordium of 24 hour embryos. At later stages, expressed in muscles of pectoral fins, jaw, branchial arches and eye.
First detected at the late gastrula stages around 9 hours post-fertilization (hpf). Expression intensifies by the end of gastrulation around 10 hpf, continues into early somitogenesis stages around 12 hpf and persists in the somites until 96 hpf when the somites give rise to the trunk skeletal muscle.
Interacts with apobec2a, apobec2b, hsp90a.1, hsp90a.2, hsp90ab1 and myosin.
Substrate-specific adapter for an E3 ubiquitin-protein ligase complex.
Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway (By similarity). Is required for the formation and maintenance of the zonula adherens during early epithelial development and plays a critical role in organ morphogenesis and in regulating the orientation of cell division.
Exhibits an elevated basal enzymatic activity and is not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-404 (activation loop of the kinase domain) and Thr-556 (turn motif), need to be phosphorylated for its full activation (By similarity).
It is uncertain whether Met-1 or Met-9 is the initiator.
The C1 zinc finger does not bind the diacylglycerol (DAG).
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).
Pseudouridine synthase that catalyzes pseudouridylation of mRNAs.
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.
Plays a role in U6 snRNP assembly and function. Binds to the 3' end of U6 snRNA.
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) (By similarity).
Part of the EJC core complex that contains casc3, eif4a3, magoh and rbm8a.
Adopts an atypical protein kinase-like fold: while it adopts a core fold similar to that of well-characterized protein kinase-like domains. The KxGQ motif completely occludes the typical substrate binding pocket. Nucleotide-binding opens the substrate binding pocket and flips the active site from inside the hydrophobic core into a catalytically competent, solvent-exposed posture.
Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration. Its substrate specificity is unclear: does not show any protein kinase activity. Probably acts as a small molecule kinase, possibly a lipid kinase that phosphorylates a prenyl lipid in the ubiquinone biosynthesis pathway, as suggested by its ability to bind coenzyme Q lipid intermediates. Shows an unusual selectivity for binding ADP over ATP.
Autoinhibited by the N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket. Nucleotide-binding relieves inhibition.
Homodimer; homodimerizes via its transmembrane region. Interacts with the multi-subunit COQ enzyme complex.
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.
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
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.
Involved in mitochondrial RNA maturation and mitochondrial respiratory chain function.
Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system (By similarity).
Heterodimer of an alpha chain and a beta chain. Beta-2-microglobulin is the beta-chain of major histocompatibility complex class I molecules (By similarity).
A Gly-transPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of most L-amino acids except L-Ala. The trans conformation of the motif is maintained by Arg-143.
Deacylates mischarged D-aminoacyl-tRNAs (By similarity). Also deacylates mischarged glycyl-tRNA(Ala), protecting cells against glycine mischarging by AlaRS (By similarity). Probably acts by rejecting L-amino acids from its binding site rather than specific recognition of D-amino acids (By similarity). Catalyzes the hydrolysis of D-tyrosyl-tRNA(Tyr), has no activity on correctly charged L-tyrosyl-tRNA(Tyr) (By similarity). By recycling D-aminoacyl-tRNA to D-amino acids and free tRNA molecules, this enzyme counteracts the toxicity associated with the formation of D-aminoacyl-tRNA entities in vivo and helps enforce protein L-homochirality. In contrast to DTD1, deacylates L-Ala mischarged on tRNA(Thr)(G4.U69) by alanine-tRNA ligase AARS (PubMed:29410408). Can deacylate L-Ala due to a relaxed specificity for substrate chirality caused by the trans conformation of the Gly-Pro motif in the active site (PubMed:29410408). Also hydrolyzes correctly charged, achiral, glycyl-tRNA(Gly) in vitro, although in vivo eef1a1a/EF-Tu may protect cognate achiral glycyl-tRNA(Gly) from DTD2-mediated deacetylation (By similarity).
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).
Seems to act as a signaling molecule involved in the maintenance of iron homeostasis. Seems to be required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages. May also have antimicrobial activity (By similarity).
Belongs to the FARP (FMRFamide related peptide) family.
Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin-protein ligase complex that controls progression through mitosis and the G1 phase of the cell cycle.
Catalyzes the pyridoxal-phosphate-dependent breakdown of phosphoethanolamine, converting it to ammonia, inorganic phosphate and acetaldehyde.
Does not seem to possess aminotransferase activity.
Detected first in each somite at the 7-somite stage (12 hpf). By 24 hpf, expressed in each newly formed somite. Expression persists at low levels in each maturing somite until after 35 hpf. At 20 hpf, detected in the hindbrain and in olfactory cells.
Transcription factor, possibly involved in transcription regulation during lens development, including that of crystallin genes (PubMed:11134968). Specifically binds to the alphaCE2 enhancer element of crystallin gene (PubMed:11134968).
Expressed in rhombomeres three and five, and in the posterior half of newly formed somites which is avoided by ventrally extending motor axons.
Might normally influence the midsegmental pathway choice of the ventrally extending motor axons by contributing to a repulsive domain in the posterior somite.
O-methyltransferase that specifically monomethylates 5'-monophosphate of cytoplasmic histidyl tRNA (tRNA(His)), acting as a capping enzyme by protecting tRNA(His) from cleavage by DICER1. Also able, with less efficiently, to methylate the 5' monophosphate of a subset of pre-miRNAs, acting as a negative regulator of miRNA processing. The 5' monophosphate of pre-miRNAs is recognized by DICER1 and is required for pre-miRNAs processing: methylation at this position reduces the processing of pre-miRNAs by DICER1. Was also reported to mediate dimethylation of pre-miR-145; however dimethylation cannot be reproduced by another group which observes a monomethylation of pre-miR-145.
Belongs to the sulfotransferase 1 family. NDST subfamily.
Endoglycosidase that releases N-glycans from glycoproteins by cleaving the beta-1,4-glycosidic bond in the N,N'-diacetylchitobiose core. Involved in the processing of free oligosaccharides in the cytosol (By similarity).
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).
Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER).
Belongs to the eukaryotic ribosomal protein eL24 family.
Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (By similarity). Plays an essential role in early embryonic development (PubMed:12006978).
Embryos show various defects including smaller head and eyes.
Restriction factor required to restrict infectivity of gammaretroviruses: acts by inhibiting early step of viral infection and impairing the ability of the viral particle to translocate its content to the cytoplasm (By similarity). Enhances the incorporation of serine into phosphatidylserine and sphingolipids (By similarity).
Embryonic expression is highly dynamic. Detected along the marginal zone of symmetric embryos at 5 hours of development and found at the shield, a primary morphological asymmetry at 6 hours of development. With the extension of the body axis, expression extends to neuroectodermal regions fated to become fore- and mid-brain; found in two stripes at the posterior side of the eye rudiments at 12 hours of development, distributed in the diencephalon, midbrain and the epiphysis at 18 hours of development, and found in the diencephalon and the midbrain at 24 hours of development.
Plays a role in very early embryogenesis, gastrulation, and the development and subdivision of the diencephalon and the midbrain. Establishes and positions the zona limitans intrathalamica (ZLI) in the diencephalon. May play a role in the organizer function. Probably acts redundantly with otx2 in early brain development.
Expressed from 1 post-fertilization (dpf) and expression increases until 4 dpf. Ubiquitously expressed at 5 dpf.
Inhibitor of melanocortin receptor 4 (mc4r), a receptor involved in energy homeostasis. Plays a role during larval development in the control of energy homeostasis and body weight regulation by decreasing ligand-sensitivity of mc4r and mc4r-mediated generation of cAMP, leading to stimulate growth during larval development. Acts by stabilizing an inactive conformation of mc4r during embryonic development, when all the energy consumed is obtained from the yolk sac, possibly to speed the rapid maturation to the mobile free-feeding juvenile stage reached at 5 dpf.
Belongs to the eukaryotic RPC34/RPC39 RNA polymerase subunit family.
Receptor for the chemotactic and inflammatory peptide anaphylatoxin C3a. This receptor stimulates chemotaxis, granule enzyme release and superoxide anion production.
May play a role in mitochondrial aerobic respiration. Can also promote mitochondrial fission (By similarity).
Plays a role in mitochondrial aerobic respiration. Regulates mitochondrial organization and fission.
Mediates high-affinity intracellular uptake of the rare oligo-element molybdenum.
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.
Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle.
Belongs to the complex I NDUFC2 subunit family.
Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA.
Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits.
In the N-terminal section; belongs to the FGAMS family.
Belongs to the universal ribosomal protein uL1 family.
Belongs to the phage and mitochondrial RNA polymerase family.
Deubiquitinase that mediates deubiquitination of target proteins and is involved in various processes such as autophagy and endoplasmic reticulum-associated degradation (ERAD).
Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to usp13 and inhibits deubiquitinase activity.
The UBA domains mediate binding to ubiquitin.
The UBP-type zinc finger has lost its ability to bind ubiquitin and usp13 is not activated by unanchored ubiquitin.
Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues. Regulates cell proliferation during embryonic development. May be involved in acetylating the N-terminus of mtor.
Expressed at high levels at 6 hpf. Expression levels remain high through 18 hpf and 28 hpf in many developing tissues suCh as vascular structures or epidermis. By 48 hpf, expression is restricted to the head. At 5 dpf, expression is restricted to epidermis.
PubMed:16484612 decribes a naa35/zEgap-containing complex as evolutionary conserved NatC complex; however, the zMak3 protein investigated in this context corresponds to mammalian NAA50 and not NAA30 and its interaction with NAA35 is ambiguous.
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).
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.
Isoform a and isoform c differentially regulate mesendoderm formation and asymmetric organ development. Both isoforms regulate left-right development, but isoform a has a stronger effect on heart laterality.
Isoform a and isoform c have distinct expression patterns during early mesendoderm development; isoform c is expressed symmetrically in presumptive mesendoderm during late blastula stages, and in both the anterior (polster) and posterior prechordal plate during late gastrulation. In contrast, isoform a expression begins at bud stage, in the anterior prechordal plate (polster). At 4- to 6-somite stages, isoform a and isoform c are both expressed in the polster, and weak isoform c expression remains in the posterior prechordal plate. Isoform a is also expressed in lateral head mesendoderm. Isoform a and isoform c are also expressed in different asymmetric domains during development of the diencephalon, gut and heart; isoform c is restricted to the dorsal diencephalon and left hand side of the developing gut, whereas isoform a shows left-sided asymmetric expression in the developing heart, with strongest expression in ther anterior regions.
Isoform c is expressed during dome stage, while isoform a is not expressed until bud stage, following gastrulation. Isoform a shows strong expression during heart looping stages (30-36 hpf) and at 48 hpf.
Isoform c is regulated by tgf-beta signaling in the early mesendoderm.
Expression peaks before the end of gastrulation and drops down by 24 hours post-fertilization, when the heart starts beating (PubMed:27411634). Expression precedes that of the earliest endothelial and haematopoietic markers etv2 and tal1 (PubMed:27411634).
Heterodimer; efficient DNA binding requires dimerization with another bHLH protein.
Loss of most endothelial and haematopoietic cells and a significant increase in cardiomyocyte numbers (PubMed:27411634, PubMed:7588049). Embryos show defects in the endothelial and hematopoietic lineages at a very early embryonic stage, characterized by the absence of the endocardium (PubMed:27411634). Early cardiac morphogenesis proceeds normally even in the absence of the endocardium (PubMed:27411634). The myocardial cells form a tube that is demarcated into chambers, beats rhythmically, but exhibits a reduced contractility (PubMed:27411634). Mutant embryos survive for one week of development (PubMed:27411634).
Specifically expressed in endothelial and hematopoietic precursor cells (PubMed:27411634).
Transcription factor specifically expressed in endothelial and hematopoietic precursor cells that acts as a key regulator of the endothelial differentiation cascade. Acts as an early-response transcription factor that regulates the expression of early regulators of endothelial and haematopoietic differentiation, such as etv2 and tal1.
Was named 'cloche', which means 'bell' in French, because of the bell-shaped heart in mutant embryos.
Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).
Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. In addition to its endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination (By similarity).
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.
First detected in the thymus during day 4 of development. Expression then increases in the thymus for at least three weeks.
Homodimer. Component of the RAG complex composed of core components rag1 and rag2 (By similarity).
In the adult, predominantly expressed in the thymus with lower levels in the pronephros, mesonephros and ovary.
The NBD (nonamer binding) DNA-binding domain mediates the specific binding to the nonamer RSS motif by forming a tightly interwoven homodimer that binds and synapses 2 nonamer elements, with each NBD making contact with both DNA molecules. Each RSS is composed of well-conserved heptamer (consensus 5'-CACAGTG-3') and nonamer (consensus 5'-ACAAAAACC-3') sequences separated by a spacer of either 12 bp or 23 bp.
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity.
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.
Belongs to the MICOS complex subunit Mic13 family.
Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Constituent of mature MICOS complex, it is required for the formation of cristae junction (CJ) and maintenance of cristae morphology. Required for the incorporation of MIC10 into the MICOS complex.
Homodimer; mediated via the coiled-coil region.
Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-179 (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.
Component of the 60S subunit of the ribosome.
In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family.
Involved in actively transporting phosphate into cells via Na(+) cotransport.
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.
Probable receptor for oxysterols that plays a central role during humoral immunity. Promotes activated B-cell localization in the outer follicle and interfollicular regions (By similarity).
Belongs to the metallo-dependent hydrolases superfamily. NagA family.
Hydrolyzes the N-glycolyl group from N-glycolylglucosamine 6-phosphate (GlcNGc-6-P) in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway.
Expressed in the developing ceratobranchials and abdomen from 3 to 6 dpf.
Morpholino knockdown of the protein results in increased incidence of agomphosis (absence of teeth).
The PH domain binds phosphoinositides with a broad specificity. It competes with the PH domain of akt1 and directly interferes with akt1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing akt1 association to membrane lipids and subsequent activation of akt1 signaling (By similarity).
p53/tp53-regulated repressor of Akt/akt1 signaling. Represses akt1 by preventing akt1-binding to membrane lipids, thereby inhibiting akt1 translocation to the cellular membrane and activation. Contributes to p53/tp53-dependent apoptosis by repressing akt1 activity. Its direct transcription regulation by p53/tp53 may explain how p53/tp53 can negatively regulate akt1. May act as a tumor suppressor (By similarity).
Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Plays an essential role for the assembly of ODA-DC and in the docking of ODA in ciliary axoneme.
Component of the outer dynein arm-docking complex along with ODAD1, ODAD2 and ODAD3.
Morpholino knockdown of the protein causes severe curvature of the body at 72 hpf. Morphants also exhibit hydrocephalus, abnormal otoliths and disturbed left-right asymmetry patterning. Some animals (17%) tend to develop pronephric cysts. At the 7-somite stage, cilia number and length are reduced in the Kupffer's vesicle. At 60 hpf, cilia motility is markedly impaired in the pronephric duct.
The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.
Belongs to the peptidase C19 family. USP10 subfamily.
May be required for efficient assembly of the mitochondrial complex I.
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. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity (By similarity).
Component of the MRN complex composed of two heterodimers rad50/mre11 associated with a single nbn.
The EEXXXDDL motif at the C-terminus is required for the interaction with atm and its recruitment to sites of DNA damage and promote the phosphorylation of atm substrates, leading to the events of DNA damage response.
Belongs to the Integrator subunit 12 family.
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).
Has a helix-hairpin-helix (HhH) structural motif conserved among proteins that bind non-specifically to DNA.
Non-specific DNA-binding protein that plays key roles in mitotic nuclear reassembly, chromatin organization, DNA damage response, gene expression and intrinsic immunity against foreign DNA. Contains two non-specific double-stranded DNA (dsDNA)-binding sites which promote DNA cross-bridging. Plays a key role in nuclear membrane reformation at the end of mitosis by driving formation of a single nucleus in a spindle-independent manner. Transiently cross-bridges anaphase chromosomes via its ability to bridge distant DNA sites, leading to the formation of a dense chromatin network at the chromosome ensemble surface that limits membranes to the surface. Also acts as a negative regulator of innate immune activation by restricting CGAS activity toward self-DNA upon acute loss of nuclear membrane integrity. Outcompetes CGAS for DNA-binding, thereby preventing CGAS activation and subsequent damaging autoinflammatory responses. Also involved in DNA damage response; acts by inhibiting the ADP-ribosyltransferase activity of PARP1. Involved in the recognition of exogenous dsDNA in the cytosol: associates with exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown and is required to avoid autophagy.
Belongs to the amino acid-polyamine-organocation (APC) superfamily.
Morpholino knockdown of the protein causes smaller eyes compared to wild-type animals and aberrant light-induced locomotor response.
Belongs to the importin beta family. Importin beta-1 subfamily.
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' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene (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).
Morpholino knockdown of the protein causes myelination defects and functional deficits, characterized by progressive ataxia and motor skill impairment (PubMed:27890673). A disruption of retina architecture and retinotectal projections is observed, together with an inhibition of lens clarification and a low number of mechanosensory hair cells in the inner ear and lateral line system (PubMed:27890673).
Ubiquitously expressed in adult tissues.
Homodimer. Heterodimer; heterodimerizes with other rfx proteins.
Reduced cilia length in the Kupffer's vesicle and impaired left-right asymmetry.
Transcription factor that acts as a key regulator of ciliogenesis (PubMed:22233545). Specifically regulates expression of genes required for cilium assembly and function (PubMed:22233545). Recognizes and binds the X-box, a regulatory motif with DNA sequence 5'-GTNRCC(0-3N)RGYAAC-3' present on promoters (By similarity).
Catalyzes phosphatidylcholine biosynthesis from CDP-choline. It thereby plays a central role in the formation and maintenance of vesicular membranes.
Associates primarily with CDK7 and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor.
Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle.
2-oxoglutarate(2OG)-dependent dioxygenase that catalyzes the conversion of 2-oxoglutarate to succinate and CO(2) in an iron-dependent manner. However, does not couple 2OG turnover to the hydroxylation of acyl-coenzyme A derivatives, implying that it is not directly involved in phytanoyl coenzyme-A metabolism. Does not show detectable activity towards fatty acid CoA thioesters.
Belongs to the PhyH family. PHYHD1 subfamily.
Activated by homooligomerization induced by direct binding to cytosolic LPS.
During embryonic development, highly expressed at 8 hours post-fertilization (hpf) (PubMed:28402832). Expressed at the pharyngula stage at 24 hpf and expression is maintained for 7 days post-fertilization (PubMed:29791492, PubMed:28402832, PubMed:30076291). During this time, expressed in the pharyngeal arches, and in the epidermis and proctoderm at 48 hpf, and in the epidermis at 72 hpf (PubMed:29791492, PubMed:12464617, PubMed:30076291). Also expressed in the mouth at 48 and 72 hpf (PubMed:12464617, PubMed:30076291).
Expressed in the spleen, kidney and liver, and highly expressed in the gills and gut.
Impaired pyroptosis in response to bacterial infection with E.piscicida (PubMed:30076291). Morpholino knockdown results in no observed phenotype (PubMed:30076291). Morpholino knockdown results in impaired gut bacterial clearance following bacterial infection with E.piscicida (PubMed:30076291). Morpholino knockdown results in pericardial edema, erosion of the tail fin and body axis, and impaired up-regulation of il1b, tnfa, il6, il8, il10 and ifng1 cytokines in response to bacterial lipopolysaccharides (LPS) (PubMed:30076291).
The Pyrin domain mediates LPS recognition and homooligomerization.
Thiol protease which cleaves IL-1 beta (il1b), releasing the mature cytokine which is involved in a variety of inflammatory processes, and mediates apoptosis (PubMed:12464617, PubMed:30150286). Component of the NLRP1 inflammasome, which plays a crucial role in innate immunity and inflammation (PubMed:30150286). In response to pathogens and other damage-associated signals, recruited to the NLRP1 inflammasome in its precursor form following the recruitment of caspase caspa (PubMed:30150286). Its subsequent activation causes the cleavage of the midformed pro-il1b and results in il1b maturation and secretion in the extracellular milieu (PubMed:30150286). Activated by direct binding to bacterial lipopolysaccharides (LPS), which causes non-canonical inflammasome activation and results in the pyroptosis of infected cells and their extrusion into the gut lumen, as well as in cytokine secretion (PubMed:30076291). Plays a crucial role in the restriction of bacterial infection to intestinal sites (PubMed:30076291). Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (By similarity). Promotes pyroptosis by bacterial infection by E.piscicida (PubMed:30076291).
Up-regulated in response to pentachlorophenol (PCP), a toxic pollutant (PubMed:28402832). Up-regulated in response to bacterial lipopolysaccharides (LPS) and bacterial infection with E.piscicida (PubMed:30076291). Up-regulated in response to bacterial infection with E.tarda (PubMed:30150286).
Upon direct LPS-binding, forms large homooligomers, resulting in its activation (PubMed:30076291). These oligomers are often referred to as 'non-canonical inflammasomes' (PubMed:30076291). Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 10 kDa (p10) subunit (Probable). Interacts with caspa (PubMed:29791979). Interacts with pycard; the interaction only occurs in the presence of nlrp1 (PubMed:30150286). Component of NLRP1 inflammasomes (PubMed:30150286). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:30150286). The NLRP1 inflammasome is composed of the signal sensor nlrp1, and the adapter pycard (asc), which recruit effector pro-inflammatory caspases caspa and/or caspb (PubMed:30150286). The interaction between nlrp1 and pycard is required for the sequential recruitment of caspa and then caspb (PubMed:30150286). Caspa is preferentially recruited first and this causes the cleavage of pro-il1b into the midformed il1b (PubMed:30150286). This is followed by the recruitment of caspb, which is activated and cleaves the midformed il1b resulting in il1b maturation (PubMed:30150286).
Involved in the sodium-independent uptake of dibasic amino acids and sodium-dependent uptake of some neutral amino acids.
Belongs to the type II (or gamma) interferon family.
Belongs to the eukaryotic ribosomal protein eL43 family.
Belongs to the glycosyl hydrolase 37 family.
Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor.
Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily.
Belongs to the deoxyhypusine synthase family.
Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner.
Required for replication-independent chromatin assembly and for the periodic repression of histone gene transcription during the cell cycle.
Associates with 90S and pre-40S pre-ribosomal particles.
Component of the 90S pre-ribosome involved in the maturation of rRNAs. Required for early cleavages of the pre-RNAs in the 40S ribosomal subunit maturation pathway.
Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing.
Dimer (By similarity). Can also form higher oligomers (By similarity).
May play a role in lymphocyte development by negatively regulating the canonical Wnt signaling pathway (By similarity). May act as a LCN1 receptor (By similarity).
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.
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.
In oocytes, expression is lowest in ovarian follicles at stages I and II but gradually increases after the onset of vitellogenic growth, peaking at vitellogenic stages (stage IIIB).
Steroid membrane receptor. Signals upon progestin binding, resulting in rapid activation of MAPK and down-regulation of adenylyl cyclase activity. Interacts with steroids with varying degrees of affinity, showing specificity for activation by the maturation-inducing steroid (MIS) 4-pregnen-17,20beta-diol-3-one (17,20beta-DHP). Capable of mediating progestin-induced oocyte maturation.
ppGpp hydrolyzing enzyme involved in starvation response.
Expressed in the retina and in the neural tube.
Plays a role in tight junction biogenesis and in the establishment of cell polarity in epithelial cells (By similarity). Also involved in adherens junction biogenesis (By similarity). Functions in cellular patterning of the retina (PubMed:11992120).
The PDZ domain is required for apical location.
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.
Localized to the inner segment and synapse in photoreceptor cells.
Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (By similarity). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity).
S-nitrosylation of Cys-150 leads to translocation to the nucleus.
Acts as a catabolic phospho-lyase on both gamma- and beta-phosphorylated substrates. Degrades O-phospho-threonine (PThr) to alpha-ketobutyrate, ammonia and phosphate (By similarity).
Plays a role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus.
SEC16A and SEC16B are each present in multiple copies in a heteromeric complex.
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.
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).
During embryonic development, regulates the integrity of the genome and therefore the cell cycle progression by preventing rereplication through an APC-Cdh1-dependent mechanism.
Abundant in ovaries and eggs, and equally distributed among all blastomeres.
Concentrated in the streaming cytoplasm in just-fertilized eggs. Evenly partitioned during cleavage among all blastomeres. Absent in the yolk cell during cleavage, blastula and gastrula stages. Distributed homogeneously among all cells of the gastrula.
Serves to facilitate the differentiation of either mesoderm or endoderm either as a cofactor in an instructive signal or by providing permissive environment.
By the fibroblast growth factor fgf8 in the MHB.
Expressed maternally from early cleavage stages until the shield stage. Expressed zygotically in the polster at the bud stage. Expressed in the midbrain-hindbrain boundary (MHB) at 12 hours post-fertilization (hpf). Expressed in the tail bud and the mesenchymal cells of the caudal fin primordia at 26 hpf.
Involved in the maintenance of the midbrain-hindbrain boundary (MHB) organizer. Contributes to a positive-feedback loop of FGF signaling in the MHB, enabling the MHB to exert its role as an organizer for the tectal and cerebellar development.
Endoplasmic reticulum palmitoyl acyltransferase that probably catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes (By similarity). Could also function as a stearoyltransferase (By similarity).
Probably maternally supplied, the zygotic expression becomes significative at 6 hpf and increases from 7.5 hpf to 24 hpf.
The C-terminal di-lysine motif confers endoplasmic reticulum localization.
Belongs to the complex I NDUFA1 subunit family.
Disulfide reductase. May participate in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyze dithiol-disulfide exchange reactions. Has peroxidase activity and may contribute to the elimination of cellular hydrogen peroxide (By similarity).
As zebrafish lack the enzyme catalyzing the reverse reaction (HSD11B1), cortisone cannot be recycled, it is metabolized and excreted (PubMed:27927697). To maintain glucocorticoid signaling a new cortisol molecule must be synthesized (PubMed:27927697).
Broadly expressed in peripheral (brain, gill, eye, heart, liver, head kidney, posterior kidney, and gut).
Catalyzes the conversion of biologically active 11beta-hydroxyglucocorticoids (11beta-hydroxysteroid) such as cortisol, to inactive 11-ketoglucocorticoids (11-oxosteroid) such as cortisone, in the presence of NAD(+) (PubMed:22796344, PubMed:23042946, PubMed:27927697, PubMed:33387577). Cortisol is the primary glucocorticoid in teleosts and is released to increase glucose bioavailability in order to meet the increased energy demands in response to stress (PubMed:23042946). Functions as a dehydrogenase (oxidase), thereby decreasing the concentration of active glucocorticoids, regulating the hypothalamus-pituitary-interrenal (HPI) axis function in adult fish (PubMed:23042946). Decreasing the excess glucocorticoids may be of relevance to brain function and neural proliferation (PubMed:23042946). Plays a key role by catalyzing the oxidation of 11beta-hydroxytestosterone (11beta,17beta-dihydroxyandrost-4-ene-3-one) to 11-ketotestosterone (17beta-hydroxyandrost-4-ene-3,11-dione), the major fish androgen, that activates androgen receptor transcriptional activity (PubMed:22796344, PubMed:27927697). Catalyzes the conversion of 11beta-hydroxyandrostenedione (11beta-hydroxyandrost-4-ene-3,17-dione) to 11-ketoandrostenedione (androst-4-ene-3,11,17-trione), which can be further metabolized to 11-ketotestosterone (PubMed:27927697). Exerts a dual role in fish by inactivating glucocorticoids and activating androgens (PubMed:22796344, PubMed:27927697).
Belongs to the eukaryotic ribosomal protein eL32 family.
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).
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.
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.
May be required for motile ciliogenesis and flagellar genesis.
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.
Cranial vascular hemorrhages and pericardial edema, leading to complete cardiac and vascular organ failure by 72 hpf. Defects are due to increased oxidative stress.
Prenyltransferase that mediates the formation of menaquinone-4 (MK-4) and coenzyme Q10 (PubMed:23374346). MK-4 is a vitamin K2 isoform required for endothelial cell development (By similarity). 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 (By similarity). 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 (PubMed:23374346). Mediates biosynthesis of coenzyme Q10 in the Golgi membrane, leading to protect cardiovascular tissues from nos3/eNOS-dependent oxidative stress (PubMed:23533172).
Ubiquitous expression at 24 hours post fertilization (hpf) in addition to a distinct expression in the heart at 48 hpf.
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).
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 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).
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.
Directly interacts with actin-capping proteins; this interaction decreases the binding of capping proteins to actin.
Involved in epithelial cell integrity by acting on the maintenance of the actin cytoskeleton. Positively regulates the actin polymerization, by inhibiting the interaction of actin-capping proteins with actin.
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.
Defective hindbrain central artery development due to impaired migration and proliferation of central artery cells (PubMed:29757409). Activation of the MAPK and PI3K/AKT pathways is inhibited (PubMed:29757409). Hindbrain arterial and venous network identities are not affected and there is no effect on the Notch or VEGF pathways (PubMed:29757409). Decreased courtship behaviors and reduced spawning success (PubMed:32467166). Reduced levels of gnrh3 in the hypothalamus and telencephalon and reduced levels of oxt and avp in the telencephalon (PubMed:32467166). Reduced levels of lhb, cga, fshb and gnrhr2 in the pituitary (PubMed:32467166). Simultaneous knockout of Scg2a and Scg2b results in greatly reduced ovulation in females (PubMed:32467166). Morpholino knockdown results in defective central artery development (PubMed:29757409).
In the embryo, levels are low at 10 hours post-fertilization, then increase over the 14-24 hpf period, and stabilize after 36 hpf (PubMed:29757409). Mainly expressed in the central nervous system at 24 and 36 hpf, and is concentrated in the brain by 45 hpf (PubMed:29757409). Widely distributed around central arteries in the developing hindbrain at 42-45 hpf (PubMed:29757409).
Neuroendocrine protein of the granin family that regulates the biogenesis of secretory granules (By similarity). Required for neurovascular modeling of the hindbrain (PubMed:29757409). Acts in a non-cell autonomous manner and is required for migration and proliferation of central artery endothelial cells (PubMed:29757409). Required for normal courting behavior and spawning (PubMed:32467166).
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.
Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. Plays a role in the assembly and function of the 40S ribosomal subunit. Mutations in this protein affects the control of translational fidelity. Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.
Binds and promotes bundling of vimentin filaments originating from the Golgi.
Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool.
Homooctamer, including four polyglutamate binding sites. The subunits are arranged as a tetramer of dimers, and form a planar ring-shaped structure.
In the C-terminal section; belongs to the cyclodeaminase/cyclohydrolase family.
In the N-terminal section; belongs to the formiminotransferase family.
Belongs to the mitochondrion-specific ribosomal protein mS35 family.
Single-stranded DNA-dependent ATP-dependent helicase.
Cleaved at the onset of anaphase; this cleavage is required for sister chromatid separation and cytokinesis. Cleaved by caspases at the beginning of apoptosis.
Component of the cohesin complex, which consists of an SMC1 and SMC3 heterodimer core and 2 non-Smc subunits RAD21 and STAG1/SA1, STAG2/SA2 or STAG3/SA3.
Detected at the oocyte stage. Expressed throughout the embryo in early embryogenesis, with particularly robust expression in the brain and posterior tail regions at 26 hpf. At 48 hpf, strongly expressed in discrete areas of the brain, the mandibular cartilage and branchial arches, the otic vesicle and developing pectoral fins.
Double-strand-break repair protein rad21 homolog: As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions. The cohesin complex may also play a role in spindle pole assembly during mitosis (By similarity). In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome (By similarity). May control RUNX gene expression, including that of RUNX1 and RUNX3 (PubMed:17567667). May play a role in embryonic gut development, possibly through the regulation of enteric neuron development (PubMed:25575569).
May be phosphorylated; may become hyperphosphorylated in M phase of cell cycle. The large dissociation of cohesin from chromosome arms during prophase may be partly due to its phosphorylation by PLK1.
Morpholino knockdown of the protein causes abnormal embryonic development (PubMed:17567667). At 5 dpf, morphants exhibit delayed food transit along the gut and depletion of enteric neurons (PubMed:25575569).
Belongs to the Sp1 C2H2-type zinc-finger protein family.
Detected in the forebrain, prospective midbrain/hindbrain boundary, tail bud, and neural keel and neural tube in the somitogenesis stages. Expressed in the pectoral fin bud, and the signal is restricted to the apical fold.
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.
Acts as an inhibitor of the small GTPase RHOA and plays several roles in the regulation of myoblast and hair cell differentiation, lymphocyte T proliferation and neutrophil polarization (By similarity). Plays a role in fetal mononuclear myoblast differentiation by promoting filopodia and myotube formation (PubMed:24958875). Maintains naive T lymphocytes in a quiescent state and prevents chemokine-induced T lymphocyte responses, such as cell adhesion, polarization and migration. Involved also in the regulation of neutrophil polarization, chemotaxis and adhesion. Required for normal development of inner and outer hair cell stereocilia within the cochlea of the inner ear. Plays a role for maintaining the structural organization of the basal domain of stereocilia. Involved in mechanosensory hair cell function (By similarity). Required for normal hearing (PubMed:24958875).
Expressed in the eye, nervous system, and skeletal muscles (PubMed:24687993). Expressed in the otic vesicle (PubMed:24958875).
FAM65B morpholino knockdown leads to significant reduction of numbers of saccular hair cells and neuromasts and to hearing loss (PubMed:24958875). FAM65B knockdown also results in abnormal muscle, with low birefringence, tears at the myosepta, and increased embryo lethality (PubMed:24687993).
Homooligomer; homooligomerization is regulated by RHOC and leads to the formation of concatemers through the association of N- and C-termini.
May act as a zinc transporter involved in intracellular zinc homeostasis. May play a role as nuclear receptor coactivator.
First detected at the 18-somite stage where expression is restricted to somite boundaries. At 24 hpf, expression is elevated in epidermal tissue and in the hatching gland. After 24 hpf, expression dimishes, but persists at low levels along the dorsal trunk. At 48 hpf, expression is restricted at a low level to the forebrain. At 72 hpf, weak expression reappears along the entire dorsal trunk in discrete cell bodies.
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).
Belongs to the archaeal Rpo10/eukaryotic RPB10 RNA polymerase subunit family.
Belongs to the AB hydrolase superfamily. LDAH family.
E3 ubiquitin-protein ligase, which catalyzes polyubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 ube2l3.
Belongs to the strictosidine synthase family.
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 (By similarity).
Isoform 1 expression is stronger at the posterior border than in the anterior region within individual somites; On the contrary, isoform 2 expression is higher at the posterior border.
Isoform 1 is expressed during the segmentation period and is initially detected at the 7-8 somite stage; Isoform 2 is expressed at all developmental stages and appears in the first somites.
May play a structural role in chromatin. Involved in sister chromatid cohesion, possibly by facilitating the cohesin complex loading. Transcription factor, which may promote cortical neuron migration during brain development by regulating the transcription of crucial genes in this process (By similarity).
Belongs to the iron-containing alcohol dehydrogenase family. Hydroxyacid-oxoacid transhydrogenase 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.
Thiol-dependent isopeptidase that recognizes and hydrolyzes the peptide bond at the C-terminal Gly of UFM1, a ubiquitin-like modifier protein bound to a number of target proteins. Does not hydrolyze SUMO1 or ISG15 ubiquitin-like proteins.
Component of the AP-1 transcription factor that represses transactivation mediated by the Jun family of proteins.
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). Involved in neurogenesis (PubMed:18996918). Involved in somite development (PubMed:32023806).
Catalytic tRNA acetyltransferase subunit of the elongator complex, which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). In the elongator complex, acts as a tRNA uridine(34) acetyltransferase by mediating formation of carboxymethyluridine in the wobble base at position 34 in tRNAs.
Morpholino knockdown in embryos results in reduced tRNA modification with decreased levels of mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine) (PubMed:32023806). Morphant larvae display a ventrally curved body where somites present a distortion of their typical chevron shape, being rounded with a different angle compared to controls (PubMed:32023806). Morphants also show disruption of the horizontal myoseptum, diminished somite area, disorganised muscle fibers, a small neural tube and reduced Shh signaling activity (PubMed:32023806). One study has shown that morpholino knockdown in embryos at 27 hpf results in abnormal motor neuron axonal branching and length (PubMed:18996918). However, another study observed shortening in only 5% of motor neurons at 27 hpf and normal length by 48 hpf (PubMed:32023806).
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).
Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.
Heterodimer of uba3 and nae1. The complex binds nedd8 and ube2m (By similarity).
Regulatory subunit of the dimeric uba3-nae1 E1 enzyme. E1 activates nedd8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a nedd8-uba3 thioester and free AMP. E1 finally transfers nedd8 to the catalytic cysteine of ube2m (By similarity).
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).
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.
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.
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).
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, such as regulation of organ-specific terminal differentiation during development.
Involved in trafficking and recycling of synaptic vesicles.
Required for zonula adherens biogenesis and maintenance.
Expressed in the yolk syncytial layer (YSL) and subsequently in the intestinal bulb in developing embryos and larvae. In adults, expressed in the intestine.
PubMed:16857010 reports that adult expression is restricted to the intestine and absent from the liver, whereas PubMed:19953126 detects expression in the liver, intestine, heart, testis, ovary, and gills.
The zebrafish genome contains duplicated fabp1b genes (fabp1b.1 and fabp1b.2) which probably arose from a tandem gene duplication event.
Belongs to the complex I NDUFB5 subunit family.
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.
Expressed in a subset of retinal horizontal cells.
Photoreceptor implicated in non-image-forming responses to light.
Accelerates the intermembrane transfer of various glycolipids. Catalyzes the transfer of various glycosphingolipids between membranes but does not catalyze the transfer of phospholipids. May be involved in the intracellular translocation of glucosylceramides (By similarity).
Adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which gives a specific tag for epigenetic transcription activation. May be required for the mitotic checkpoint and normal cell cycle progression (By similarity). May play a role in the formation and maintenance of the auditory system (PubMed:31231791).
Belongs to the PI3/PI4-kinase family. TRA1 subfamily.
Morpholino TRRAP knockdown results in defects in the inner ear. Morphant larvae show reduced lateral line neuromasts, decreased number of hair cells per neuromast, and fewer and thinner stereocilia on the hair cells. In addition, the acoustic startle response is decreased and sound-induced fast escape reflex is impaired.
Affects the rate of fibrils formation. May have a primary role in collagen fibrillogenesis.
Belongs to the metallo-dependent hydrolases superfamily. ATZ/TRZ family.
Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia.
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 (By similarity).
Transcriptional activator. Binds the cAMP response element (CRE). Activates transcription through box-B element and CRE. Seems to function synergistically with atf6 (By similarity). Regulates FGF21 transcription (By similarity).
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.
Expression is regulated by neuronal activity.
Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hippocampus. Plays a key role in the structural and functional plasticity of neurons. Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons to be modified by neuronal activity in a manner specific to their function within a circuit, thereby facilitating appropriate circuit responses to sensory experience.
Belongs to the metallophosphoesterase superfamily. CPPED1 family.
Protein phosphatase involved in the dephosphorylation of AKT kinase family.
May play a role in regulating axonal regeneration and plasticity in the adult central nervous system.
Mitochondrial tRNA methyltransferase that mediates methylation of cytosine to 5-methylcytosine (m5C) at position 34 of mt-tRNA(Met). mt-tRNA(Met) methylation at cytosine(34) takes place at the wobble position of the anticodon and initiates the formation of 5-formylcytosine (f(5)c) at this position. mt-tRNA(Met) containing the f(5)c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RMT2 methyltransferase family.
Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor.
Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor. Important in nervous system development.
Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. Involved in Rac1-signaling pathways leading to the modulation of gene expression.
Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity.
Belongs to the 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.
Belongs to the Mediator complex subunit 31 family.
No visible phenotype; due to the redundancy with gnb5b. Simultaneous knockout of gnb5a and gnb5b results in no striking dysmorphologic features, but the larvae show impaired swimming activity, remain small, and generally die 7-14 days post fertilization (dpf), most likely as a result of their inability to feed.
In the embryo, expressed in the polster, paraxial mesoderm, tectum, otic vesicle and liver.
Methionine-sulfoxide reductase that specifically reduces methionine (R)-sulfoxide back to methionine. While in many cases, methionine oxidation is the result of random oxidation following oxidative stress, methionine oxidation is also a post-translational modification that takes place on specific residue. Acts as a regulator of actin assembly by reducing methionine (R)-sulfoxide mediated by MICALs (mical1, mical2 or mical3) on actin, thereby promoting filament repolymerization. Plays a role in innate immunity by reducing oxidized actin, leading to actin repolymerization in macrophages.
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.
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.
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. Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress.
Belongs to the archaeal Rpo12/eukaryotic RPC10 RNA polymerase subunit family.
Plays a role in the control of cell shape and motility in the trabecular meshwork.
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.
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 (By similarity).
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.
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 (By similarity).
Belongs to the eukaryotic ribosomal protein eL22 family.
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.
Belongs to the VPS10-related sortilin family.
Belongs to the chloride channel (TC 2.A.49) family. ClC-3/CLCN3 subfamily.
Dynamin-related GTPase that is essential for normal mitochondrial morphology by regulating the equilibrium between mitochondrial fusion and mitochondrial fission. Binds lipid membranes enriched in negatively charged phospholipids, such as cardiolipin, and promotes membrane tubulation. The intrinsic GTPase activity is low, and is strongly increased by interaction with lipid membranes (By similarity). Plays a role in remodeling cristae and the release of cytochrome c during apoptosis (By similarity).
Inactive form produced by cleavage at S1 position by oma1 following stress conditions that induce loss of mitochondrial membrane potential, leading to negative regulation of mitochondrial fusion.
Oligomeric complex consisting of membrane-bound and soluble forms of OPA1. Binds PARL (By similarity).
PARL-dependent proteolytic processing releases an antiapoptotic soluble form not required for mitochondrial fusion. Cleaved by oma1 at position S1 following stress conditions.
Proteolytic processing produces an antiapoptotic soluble form Cleaved by oma1 at position S1 following stress conditions.
Major helicase player in mitochondrial RNA metabolism. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. ATPase and ATP-dependent multisubstrate helicase, able to unwind double-stranded (ds) DNA and RNA, and RNA/DNA heteroduplexes in the 5'-to-3' direction. Plays a role in the RNA surveillance system in mitochondria; regulates the stability of mature mRNAs, the removal of aberrantly formed mRNAs and the rapid degradation of non coding processing intermediates. Also implicated in recombination and chromatin maintenance pathways. May protect cells from apoptosis. Associates with mitochondrial DNA (By similarity).
Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits.
Embryos display a small head with smaller eyes than normal and fewer cartilages in the branchial arches. Marked increase in cell death in brain (PubMed:19393221). Incomplete epiboly at gastrulation, characterized by blastopore closure defects and impaired axis formation (PubMed:21687713).
Expressed in the notochord, brain, eyes, branchial arches and pectoral fins.
Maternally expressed in the embryo: maternal expression is ubiquitous.
Phosphorylated by lats1 and lats2; leading to cytoplasmic translocation and inactivation.
Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (By similarity). Required for expansion of the neural plate and neural plate border zone progenitor pools. Acts as a direct regulator of pax3 expression via interaction with tead1 (PubMed:21687713). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation (PubMed:25778702).
Catalyzes the transfer of sulfate to position 3 of terminal glucuronic acid of both protein- and lipid-linked oligosaccharides. Participates in biosynthesis of HNK-1 carbohydrate structure, a sulfated glucuronyl-lactosaminyl residue carried by many neural recognition molecules.
Detected in the otic placode and the pineal gland in embryos 24 hours after fertilization. Detected in the sensory hair epithelium along the entire length of the lateral line organ in larvae 72 hours post fertilization. Restricted mainly to neuroepithelial patches in the ear of larvae 72 hours post fertilization.
Essential for the formation of otoliths in the inner ear of developing larvae and for the perception of gravity and acceleration. May be one of the organic components of the ortholiths.
Otoliths are structures composed of proteins and calcium carbonate that are found in the fish inner ear in contact with the otic epithelium. They are essential for the perception of gravity and acceleration.
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.
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.
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 (By similarity).
May play a role in erythroid cell differentiation.
Belongs to the bacterial ribosomal protein bS16 family.
May play a role in Cajal bodies formation.
Belongs to the radical SAM superfamily. RSAD2 family.
By interferon type I, type II and LPS. Induced by infection with spring viremia of carp virus, presumably through type I interferon pathway.
Interferon-inducible iron-sulfur (4FE-4S) cluster-binding antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon.
Belongs to the peroxiredoxin family. Prx6 subfamily.
Belongs to the eukaryotic ribosomal protein eL38 family.
Belongs to the zinc-containing alcohol dehydrogenase family. Class-III subfamily.
Antiparallel disulfide-linked heterodimer of an alpha chain and a beta chain. Self-associates and forms higher oligomers.
Functions as extracellular chaperone that prevents aggregation of non native proteins. Prevents stress-induced aggregation of blood plasma proteins.
Belongs to the cytochrome c oxidase subunit 6B.
Involved in the 5-carboxymethylaminomethyl modification (mnm(5)s(2)U34) of the wobble uridine base in mitochondrial tRNAs.
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.
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).
Involved in an early step of the mitochondrial complex IV assembly process.
Belongs to the sodium channel auxiliary subunit SCN1B (TC 8.A.17) family.
Recombinant ZNT-7 was able to bind to the human p75 neurotrophin receptor/NGFR and to induce tyrosine phosphorylation of the rat NTRK1/TRKA receptor tyrosine kinase, albeit less efficiently than rat NGF. ZNT-7 did not interact with rat NTRK2/TRKB or NTRK3/TRKC, indicating a similar receptor specificity as NGF.
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).
At 4 days-post-fertilization (dpf), expressed in the inner and outer plexiform layers of the retina, the marginal zone of the tegmentum, the developing craniofacial cartilage and in the ventral spinal cord.
Nus1 seems to exist in two topological orientations, a minor glycosylated species with its C-terminus oriented towards the lumen regulating NPC2 stability, and a major fraction oriented with its C-terminus directed towards the cytosol where it regulates cis-IPTase activity.
With DHDDS, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery. Adds multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol. Acts as a specific receptor for the N-terminus of Nogo-B, a neural and cardiovascular regulator.
PP1 comprises a catalytic subunit, and one or several targeting or regulatory subunits.
PP1 comprises a catalytic subunit, and one or several targeting or regulatory subunits. Ppp1r12a mediates binding to myosin.
Belongs to the actin family. ARP3 subfamily.
May function in combinations with OTX1/2 to specify cell fates in the developing central nervous system.
Belongs to the acetyltransferase family. GNA1 subfamily.
Functions in hedgehog (Hh) signaling. Regulates the release and extracellular accumulation of cholesterol-modified hedgehog proteins and is hence required for effective production of the Hh signal (PubMed:15110707). Synergizes with SCUBE2 to cause an increase in SHH secretion (By similarity).
Interacts with SHH; via the cholesterol anchor of the dually lipid-modified SHH (ShhNp).
Ubiquitously expressed throughout the embryo from fertilization onward. Accumulates at higher levels in the notochord, the ventral floor of the brain as well as dorsal and ventral margins of the myotome.
Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35) family.
Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways. AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. Within AP-4, the mu-type subunit AP4M1 is directly involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos. The adaptor protein complex 4 (AP-4) may also recognize other types of sorting signal.
Belongs to the eukaryotic RPA43 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 I which synthesizes ribosomal RNA precursors. May be involved in recruitment of Pol I to rDNA promoters (By similarity).
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.
Component of the TSC-TBC complex (also named Rhebulator complex).
Component of the TSC-TBC complex, that contains tbc1d7 in addition to the TSC1-TSC2 complex and consists of the functional complex possessing GTPase-activating protein (GAP) activity toward rheb in response to alterations in specific cellular growth conditions. The small GTPase rheb is a direct activator of the protein kinase activity of mTORC1 and the TSC-TBC complex acts as a negative regulator of mTORC1 signaling cascade by acting as a GAP for RHEB (By similarity).
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.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ6 subfamily.
Binds to one of the cis-acting domain of the insulin gene enhancer. May be involved in subtype specialization of primary motoneurons.
First expressed at 15 hours post-fertilization (hpf), segmentally in the ventral region of the spinal cord (primary motoneurons) and then later in the dorsal regions (Rohan-Beard neurons). At 18 hpf, also expressed in tail bud and pronephric duct. At 24 hpf, expressed strongly in trigeminal ganglia. At 30 hpf, expressed transiently in pectoral fin bud.
Expressed from 10.5 hours post-fertilization (hpf). During embryogenesis, expression is restricted to developing somites and heart.
Strongly expressed in fast skeletal muscle, and weakly in heart. Not expressed in other tissues.
May be involved in cell cycle regulation.
Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+).
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 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 SOSS-B family. SOSS-B2 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 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.
Induces rhoa activation and activates nppa transcription and myofibrillar organization through the rho/rock signaling pathway.
Expressed in highly specific patterns within the developing embryo.
May influence outgrowth by a variety of growth cones including those of the posterior lateral line ganglion.
Expressed both maternally and zygotically, with expression peaking at the neurula stage.
Interacts with the PDZ domain of dvl2/dsh.
Plays a role in non-canonical Wnt/planar cell polarity (PCP) signaling to regulate convergent extension cell movements during gastrulation. Acts together with scrib and prickle1 and localizes prickle1 and dvl2/dsh to the plasma membrane. Has an overlapping role with kny during both convergent extension and eye development. In the eye, involved in establishing proper alignment of the anterior neural plate and midline cells expressing shha and shhb/twhh. Has indirect effects on a number of other developmental processes including notochord shape formation, neural progenitor cell morphogenesis, segregation of somites and adaxial cell development. Together with prickle1, required for the posterior (caudal) movement of branchiomotor neurons in the hindbrain independently of, and a few hours after, convergent extension (PubMed:11780127, Ref.2, PubMed:9007230, PubMed:9007234, PubMed:9007236, PubMed:9808788, PubMed:10996075, PubMed:10992326, PubMed:11820812, PubMed:12105418, PubMed:12874125, PubMed:15829519, PubMed:16407953, PubMed:17239849). May be required for cell surface localization of fzd3 and fzd6 in the inner ear (By similarity).
Sequence differs from that shown at the C-terminus, most likely because of a sequence artifact.
Ubiquitously expressed at the 4-cell stage. In early somitogenesis, becomes more abundant in anterior neural tissue where expression is seen in the neural tube but not in the notochord.
Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion and in the control of neurotransmitter release at these output synapses.
The N-terminal first 124 residues can be classified as C2 domain, based on their 3D-structure. They are not sufficient for calcium ion or phospholipid binding (By similarity).
Component of the multisubunit TRAPP (transport protein particle) complex.
Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.
Pronounced hepatomegaly accompanied by lipid accumulation in the liver.
Negatively regulates the PAK1 kinase. PAK1 is a member of the PAK kinase family, which has been shown to play a positive role in the regulation of signaling pathways involving MAPK8 and RELA. PAK1 exists as an inactive homodimer, which is activated by binding of small GTPases such as CDC42 to an N-terminal regulatory domain. PAK1IP1 also binds to the N-terminus of PAK1, and inhibits the specific activation of PAK1 by CDC42. May be involved in ribosomal large subunit assembly.
Acts specifically as a negative regulator of skeletal muscle growth. May down-regulate muscle-specific transcription factors such as myod and myog.
Expressed both maternally and zygotically. Weakly expressed ubiquitously in early stage embryos. Present transiently in the blastula with levels dropping almost completely during gastrulation. Expression peaks during late somitogenesis, decreases at the end of somitogenesis, and then rises again at and after hatching. Strongly expressed in swimming larvae, juveniles and adults.
Predominantly expressed in muscle. At hatching, expression is strongest in the skin epithelium, and is also found in the retina and brain. From day 28, expressed in skeletal muscle. In the adult, highest expression is seen in the gastrointestinal tract, brain, muscle, heart and testis. Also expressed in the adult pharynx, kidney, spleen, liver, gill, eyes, skin, swim bladder and ovary.
Repressed in adult muscle, and stimulated in adult spleen, when fish are grown in overcrowded conditions.
Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. Plays a role in intracellular vesicle trafficking. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. May be required for normal dopamine homeostasis in the cerebral cortex, hippocampus, and hypothalamus. Plays a role in the regulation of cell surface exposure of DRD2. Contributes to the regulation of dopamine signaling. May play a role in actin cytoskeleton reorganization and neurite outgrowth (By similarity).
Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).
Expression detected 24 hpf (hours post fertilization), in developing hindbrain, most abundant in rhombomeres 2 and 3. Neural expression peaks at 48 hpf, at which point transcripts are found in the hindbrain, rhombic lip, and optic precursors. The exocrine pancreas represents a population of cells encircling the embryonic islet. At 72 hpf, expressed throughout the endodermal region corresponding to the exocrine pancreas. Expression is restricted to the exocrine pancreas following an early period of transient neural expression. Positive exocrine precursors and insulin-positive endocrine elements are both temporally and spatially segregated during embryogenesis.
Transcription factor implicated in the cell fate determination in various organs. Binds to the E-box consensus sequence 5'-CANNTG-3'. Required for exocrine pancreatic development. Plays a central role in directing the differentiation of retinal progenitors towards horizontal and amacrine fates.
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.
Ciliary phenotypes such as pericardial effusion, curved or kinked tail, as well as gastrulation defects.
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).
Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.
Belongs to the thiamine pyrophosphokinase family.
Detected in embryo 24 to 48 hours after fertilization and in gastrula.
Homodimer in the absence of bound vitamin D3. Heterodimer with RXRA after vitamin D3 binding (By similarity). Interacts with ncoa1 and possibly other coactivators, leading to a strong increase of transcription of target genes (PubMed:17218092, PubMed:17346665).
Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Possesses RNA slicer activity but only on select RNAs bearing 5'- and 3'-flanking sequences to the region of guide-target complementarity.
Seems to promote the survival of visceral and proprioceptive sensory neurons.
Belongs to the complex I 49 kDa subunit family.
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.
Amino acid transport activity is increased by sodium (PubMed:29872228). Transport of L-glutamine, leucine and tyrosine is increased by arginine binding (By similarity).
Associated component of the Ragulator complex (By similarity). Associated component of the Rag GTPases heterodimers (RRAGA and RRAGC) (PubMed:33296665).
Belongs to the amino acid/polyamine transporter 2 family. SLC38A9 subfamily.
Expression is ubiquitous from the one-cell stage to 12 hours post-fertilization (hpf), restricted to the retina at 18, 24, and 30 hpf (PubMed:35457018). Expression encompasses the heart and midbrain region at 30 and 48 hpf. From 72 hpf to 5 dpf, the expression is restricted to the liver and gut (PubMed:35457018).
Homozygote knockout fishs for the SLC38A9 show no morphological difference at 12 and 24 hours post-fertilization (hpf) (PubMed:35457018). However, a quarter exhibit pericardial edema and small eyes at 48 hpf; the abnormal phenotypes became severe at 72 hpf (PubMed:35457018). The overall body length is decreased at 24 and 72 hpf (PubMed:35457018). While mutant larvae with development defects died at 4-7 dpf, those normally developed have the same viability as wide type and exhibit normal fertility (PubMed:35457018).
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 (By similarity). Acts as an arginine sensor (PubMed:33296665). 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 (PubMed:33296665). The transport is most active at acidic pH. 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 (By similarity).
The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex (By similarity). The cytosolic N-terminus part of the protein mediates interaction with the Rag GTPase heterodimer in a RRAGA GDP-loaded state dependent and leading to the GDP release and SLC38A9 dissociation from the activated Rag GTPase heterodimer, upon arginine binding (PubMed:33296665). 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) (PubMed:33296665).
Binds and hydrolyzes ATP via the two cytoplasmic ABC transporter nucleotide-binding domains. The two ATP-binding domains interact with each other, forming a head-to-tail dimer. Normal ATPase activity requires interaction between the two domains. The first ABC transporter nucleotide-binding domain has no ATPase activity by itself.
Considerable lethality around 10 dpf (PubMed:25592226). No effect on initial pancreas development, but at 16 dpf mutants display loss of pancreatic acinar tissue (PubMed:25592226). At 22 dpf, most pancreatic acinar tissue has disappeared and has been replaced by fibrotic tissue that surrounds dilated, mucus-filled ducts (PubMed:25592226). Morpholino knockdown of the protein in 48 hpf embryos leads to impaired resistance to P.aeruginosa strain PA14 and strain SMC573, as shown by the increased bacterial burden, but there is no effect on resistance to E.tarda, B.cenocepacia, S.aureus MZ100, E.coli XL-10 and H.influenzae Hib EAGAN (PubMed:20732993). Morpholino knockdown of the protein causes an important reduction of the volume of Kupffer's vesicle during embryonic development (PubMed:26432887).
Detected in gut epithelium (at protein level) (PubMed:20933420). Detected in kidney, spleen, intestine and liver (PubMed:20732993). Detected in pancreatic duct epithelium at 5 dpf and throughout adult life (PubMed:25592226).
Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:20933420, PubMed:23487313, PubMed:25592226). Mediates the transport of chloride ions across the cell membrane (By similarity). Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Contributes to the regulation of the pH and the ion content of the epithelial fluid layer (By similarity). Required for normal fluid homeostasis in the gut (PubMed:20933420). Required for normal volume expansion of Kupffer's vesicle during embryonic development and for normal establishment of left-right body patterning (PubMed:23487313, PubMed:26432887). Required for normal resistance to infection by P.aeruginosa strain PA14 and strain SMC573 (PubMed:20732993).
First detected in developing pancreatic duct at 3 dpf (PubMed:25592226). Detected on Kupffer's vesicle during embryonic development (PubMed:23487313, PubMed:26432887). Detected on neural floorplate, brain and pronephric duct primordia in embryos at the 10 somite stage (PubMed:26432887).
Monomer; does not require oligomerization for channel activity (By similarity). Interacts with cse1l; this interaction may down-regulate cftr activity (PubMed:20933420).
Mutations that lead to the production of a severely truncated protein that ends before the start of the fourth transmembrane domain disrupt normal left-right body patterning during embryogenesis and abolish lumen expansion of Kupffer's vesicle.
Phosphorylated; this activates the channel (PubMed:27912062). Dephosphorylation strongly decreases ATPase activity (PubMed:27912062). Phosphorylation at PKA sites activates the channel. Phosphorylation at PKC sites enhances the response to phosphorylation by PKA (By similarity).
The disordered R region mediates channel activation when it is phosphorylated, but not in the absence of phosphorylation.
Belongs to the AAA ATPase family. RarA/MGS1/WRNIP1 subfamily.
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). Required for structural integrity of granules in primordial germ cells (PGCs).
Down-regulated by miR-430 in somatic cells. Down-regulation is relieved by dnd that acts by protecting the 3'-UTR of tdrd7 from miR-430-mediated RNA deadenylation.
In embryos, expression is restricted to primordial germ cells (PGCs).
Homodimerizes, the dimers can polymerize end-to-end to form filamentous structures.
Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis.
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).
Component of the CTLH E3 ubiquitin-protein ligase complex that mediates ubiquitination and subsequent proteasomal degradation of target proteins.
Identified in the CTLH complex that contains at least MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10; ARMC8 has an ancillary role in the complex.
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar4-20 subfamily.
Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity. In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (By similarity). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Plays a role in myogenesis by regulating the expression of target genes, such as EID3. Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity).
Component of the small nucleolar ribonucleoprotein particle containing H/ACA-type snoRNAs (H/ACA snoRNPs). Component of the telomerase holoenzyme complex (By similarity).
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).
Acts as a ligand for galanin receptors galr2a and galr2b (PubMed:24517231). Brain administration of the peptide inhibits food consumption and elevates levels of glucose, triacylglycerol and cholesterol in the serum (PubMed:29116147). Likely to control food intake by regulating appetite related genes which includes the negative regulation of the orexigenic factor agrp (PubMed:29116147). By controlling food intake it may act as a satiety factor in energy metabolism (PubMed:29116147).
In embryos, first detected at the 1 cell stage but disappears by the 2 cell stage (PubMed:30903017). Expressed again from 24 hours post fertilization (hpf) (PubMed:30903017). At 24 hours post fertilization (hpf), detected in a few cells in the embryo hindbrain (PubMed:30903017). In larvae, expressed in the neurons and nerve fibers of the midbrain tegmentum and hindbrain (PubMed:30903017). In the hindbrain, expressed in reticulospinal neurons with spinal projections (PubMed:30903017). Axons of hindbrain neurons project into the dorsal spinal cord where expression often overlaps with galr2b (PubMed:30903017). In larvae, not detected in the hypothalamus and not detected outside of the brain (PubMed:30903017).
Mainly expressed in the brain and ovary (PubMed:23623870, PubMed:24517231). Detected bilaterally in the adult brainstem (PubMed:30903017). Expressed in neurons in the dorsal habenula (dHb) (PubMed:31474838, PubMed:30903017). In the dHb some neurons project into the interpeduncular nucleus (IPN) where expression often overlaps with galr2a and galr2b (PubMed:31474838, PubMed:30903017). Weakly expressed in the liver, intestine, kidney, heart and gill (PubMed:23623870).
Plays a role in the regulation of food intake and energy metabolism (PubMed:29116147). May also be involved in suppressing the anxiety response by promoting the expression of serotonin-related genes such as fev, tph2 and slc6a4a (PubMed:31474838).
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.
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 complex I 24 kDa subunit family.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.
Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin.
Belongs to the protein phosphatase inhibitor 2 family.
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.
Binds DNA as a homodimer; required for transcriptional activation.
Expression is initially detected at the tailbud stage, immediately after gastrulation, in the cephalic mesoderm. It is maintained in the mesoderm during early stages of development. Expression is initiated in the neural crest by the 5 somites stage, and is restricted to a rostral domain of cranial neural crest. Later during development it is still expressed in specific regions of the neural crest-derived facial mesenchyme. In 24 hpf stage embryos, expressed strongly in the periocular mesenchyme. By 48 hpf, expression is maintained in the periocular mesenchyme towards the anterior of the head, with weaker expression in the nasal region and the prospective palate. Also expressed in a discrete region at the distal tip of the mandible arch and in the pectoral fin bud primordia.
Morpholino-mediated knockdown causes severe craniofacial alterations including small, misshapen head, microphthalmia and loss of the jaw. It is associated with a more or less severe loss of the cartilaginous facial skeleton. Pericardial edema is also detected.
Sequence-specific DNA-binding transcription factor that binds palindromic sequences within promoters and may activate or repress the transcription of a subset of genes. Most probably regulates the expression of genes involved in the development of mesenchyme-derived craniofacial structures (By similarity). Required for proper neural crest cell migration into the frontonasal primordia during development (PubMed:23059813).
The OAR motif may negatively regulate DNA-binding and therefore transcriptional activity. It is found in the C-terminal transactivation domain that stimulates transcription.
Protects actin filaments from depolymerization.
Binds cholesterol in a hydrophobic pocket; there are no hydrogen bonds between the sterol and the protein.
Interacts with NPC1 (via the second lumenal domain) in a cholestrol-dependent manner.
Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment. Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1. May bind and mobilize cholesterol that is associated with membranes. NPC2 binds cholesterol with a 1:1 stoichiometry. Can bind a variety of sterols, including lathosterol, desmosterol and the plant sterols stigmasterol and beta-sitosterol.
Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin. Regulates cell adhesion and cell spreading. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6 (By similarity).
The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain.
The SH2 domain interacts with tyrosine phosphorylated forms of proteins.
Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli.
Lacks one Cys residue in the IBR-type zinc finger domain that is one of the conserved features of the family.
Might act as an E3 ubiquitin-protein ligase, or as part of E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates.
Belongs to the TTC30/dfy-1/fleer family.
Localizes to the cilia of many ciliated epithelial cell types including pronephric cells, olfactory placode, the brain ventricle and lateral line organs.
Maternally expressed. First detected in Kupffer's vesicle of seven somite embryos and the lateral mesoderm of 11 somite embryos. By 24 to 30 hours post-fertilization (hpf), expression becomes widespread within the central nervous system and the pronephros and parallels the development of multiciliated cells. During later stages of larval development (54 hpf), expression continues throughout the pronephros and intensifies in the olfactory placode and lateral line organs.
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 (By similarity). Required for polyglutamylation of axonemal tubulin, which is a prerequisite for correct assembly of cilia and for normal cilia beat amplitude. Does not seem to be required for neuronal microtubule polyglutamylation.
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.
Esterifies acyl-group from acyl-ACP to the sn-1 position of glycerol-3-phosphate, an essential step in glycerolipids biosynthesis such as triglycerides, phosphatidic acids and lysophosphatidic acids.
Belongs to the complex I subunit 6 family.
May be part of a signaling pathway that leads to NF-kappa-B activation.
Required for 40S ribosome biogenesis. Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.
All KH domains contribute binding to target mRNA. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 also contribute. They are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains seems not to be required for localization to stress granules.
Expressed in oocytes from stages I to III. Expressed in 8-cell embryo. Expressed in brain, eye, branchial arches and neural tube at 24 hours post-fertilization (hpf). Detected predominantly in the CNS, putative neural crest, the sensorial layer of the epidermal ectoderm and their derivatives until the tailbud stage.
RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation (By similarity). Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (By similarity). Involved in neuronal crest migration (PubMed:14522877).
Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA metabolism and genomic integrity. In the CIA complex, MMS19 acts as an adapter between early-acting CIA components and a subset of cellular target iron-sulfur proteins.
Belongs to the 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 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 ubiquitin-conjugating enzyme family. UFC1 subfamily.
E1-like enzyme which specifically catalyzes the second step in ufmylation. Accepts the ubiquitin-like modifier UFM1 from the E1 enzyme UBA5 and forms an intermediate with UFM1 via a thioester linkage. Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress.
Defects are the cause of the lok phenotype, a phenotype related to primary ciliary dyskinesia (PCD). PCD is characterized by curly-tail down phenotype, laterality defects and pronephric cysts, but without defects in sensory cilia and without the presence of hydrocephalus.
Expressed in tissues that contain motile cilia, including Kupffer's vesicle, the floorplate, the pronephric tubules and the otic vesicle.
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 ccdc39 to form a molecular ruler that determines the 96 nanometer (nm) repeat length and arrangements of components in cilia and flagella.
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. May also be involved in the biogenesis of lysosome-related organelles such as melanosomes.
High levels detected in liver and small intestine of larvae at 5 days post-fertilization.
Proposed to be involved in endosomal maturation implicating in part vps33b. In epithelial cells, the vps33b:vipas39 complex may play a role in the apical rab11a-dependent recycling pathway and in the maintenance of the apical-basolateral polarity. May play a role in lysosomal trafficking, probably via association with the core HOPS complex in a discrete population of endosomes; the functions seems to be independent of vps33b. May play a role in vesicular trafficking during spermatogenesis (By similarity). May be involved in direct or indirect transcriptional regulation of E-cadherin.
First expressed at the 1-2 somite stage. By the 3-4 somite stage, the anterior expression limit in the developing hindbrain is at the rhombomere 5/6 boundary, and this is maintained until the 20 somite stage. By 30 hours post-fertilization, there is also limited expression within rhombomere 5.
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.
Mitochondrial outer membrane protein which regulates mitochondrial fission. Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface independently of the mitochondrial fission FIS1 and MFF proteins. Regulates DNM1L GTPase activity and DNM1L oligomerization (By similarity).
Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex.
Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(FEM1C) complex specifically recognizes proteins with an arginine at the C-terminus: recognizes and binds proteins ending with -Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons, leading to their ubiquitination and degradation.
The first seven ANK repeats at the N-terminus (1-243) are essnetial for recognition of Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons.
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).
Morpholino knockdown of the protein causes severe development defects and accumulation of DNA damage.
The UBZ4-type zinc fingers mediate binding to 'Lys-48'- and 'Lys-63'-linked polyubiquitin.
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 bacterial ribosomal protein bS6 family.
Involved in ventralization. May mediate Bmp2b signaling during embryonic dorsal-ventral pattern formation, and may itself be a transcriptional target for Smad5-mediated Bmp2b signaling.
May form trimers with another Smad1 and the co-Smad Smad4.
Zygotically expressed. First detected 1 h after the midblastula transition. During gastrulation, expression is restricted to ventral regions. Later, expressed in the somites, eyes and a subset of dorsal cells in the hindbrain. Levels increase until the end of gastrulation and then remain high.
Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation.
Highly expressed in unsegmented paraxial mesoderm.
Increased DNA damage response, apoptosis and development of abnormalities such as kidney cysts.
Interacts with fancd2 (when monoubiquitinated).
Nuclease required for the repair of DNA interstrand cross-links (ICL) recruited at sites of DNA damage by monoubiquitinated FANCD2. Specifically involved in repair of ICL-induced DNA breaks by being required for efficient homologous recombination, probably in the resolution of homologous recombination intermediates. 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. Probably keeps excising with 3'-flap annealing until it reaches and unhooks the ICL. Acts at sites that have a 5'-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap and is augmented by a 3' flap. Also has endonuclease activity toward 5'-flaps.
The UBZ4-type zinc finger specifically binds monoubiquitinated fancd2.
As part of the KICSTOR complex may function in the amino acid-sensing branch of the TORC1 signaling pathway.
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).
Phosphorylated. Phosphorylation occurs during interphase. Phosphorylation occurs also during mitosis; these phosphorylations reduce both its homodimerization and the ER three-way tubular junction 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.
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2.
May regulate actin polymerization, filopodia dynamics and arborization of neurons.
Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits cdk1 and acts as a key 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).
Endoplasmic reticulum ceramidase that catalyzes the hydrolysis of ceramides into sphingosine and free fatty acids at alkaline pH. Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation. May also hydrolyze dihydroceramides to produce dihydrosphingosine.
Plays a central role in late thymocyte development by controlling both positive and negative T-cell selection. Required to sustain and/or integrate signals required for proper lineage commitment and maturation of T-cells. Regulates T-cell development through T-cell antigen receptor (TCR) signaling and in particular through the regulation of calcium influx and phosphorylation of Erk (By similarity).
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a variety of xenobiotic and endogenous compounds, including 2-naphthol, hydroxychlorobiphenyls, T3 (triiodo-L-thyronine), T4 (thyroxine), estrone and DOPA.
Belongs to the learning-associated protein family.
Regulates dendritic and spine growth and synaptic transmission.
Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate. Cyanocobalamin constitutes the inactive form of vitamin B12 introduced from the diet, and is converted into the active cofactors methylcobalamin (MeCbl) involved in methionine biosynthesis, and 5'-deoxyadenosylcobalamin (AdoCbl) involved in the TCA cycle. Forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin across the lysosomal membrane into the cytosol. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine. Also acts as a glutathione transferase by catalyzing the dealkylation of the alkylcob(III)alamins MeCbl and AdoCbl, using the thiolate of glutathione for nucleophilic displacement to generate cob(I)alamin and the corresponding glutathione thioether. The conversion of incoming MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to meet the cellular needs for both cofactors. Cysteine and homocysteine cannot substitute for glutathione in this reaction.
Monomer in the absence of bound substrate. Homodimer; dimerization is triggered by binding to FMN or adenosylcobalamin. Heterodimer with MMADHC.
Belongs to the Clp1 family. Clp1 subfamily.
Component of the tRNA splicing endonuclease complex. Component of pre-mRNA cleavage complex II (CF-II) (By similarity).
Lethality before 5 days post-fertilization (dpf). Mutants display abnormal swimming behavior, abnormal head shape and curved tail. Defects are due to neuromotor defects and cerebellar neurodegeneration.
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.
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. Required for muscle development and angiogenesis.
Expressed both maternally and zygotically throughout the cleavage, gastrulation and somitogenesis stages.
Expressed ubiquitously during gastrulation. During early somitogenesis, strong expression in head and presumptive brain. During mid-somitogenesis, strong expression in eye, hindbrain and somitic boundaries and weak expression in tail bud. During late somitogenesis, strong expression in eye, hindbrain, branchial arch primordia, spinal cord and ventral medial somites. At 24 hours post-fertilization (hpf), strong expression throughout the head, with expression receeding from the trunk spinal cord, ventral medial somites and somitic boundaries; expressed in cells surrounding vascular structures of the dorsal aorta and caudal vein in the tail. At 36 hpf, expressed in lens, optic stalk, hindbrain and pectoral fin. At 48 hpf, expressed in eye, brain, otic vesicle and branchial arches.
Morpholino knockdown results in defects in the branching morphogenesis of the caudal vein and defects in somite specification with impaired muscle differentiation.
Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins.
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.
Efficient DNA binding requires dimerization with another bHLH protein. Heterodimer with the aryl hydrocarbon receptor (AHR), SIM1 or HIF2A/EPAS-1.
Isoform 1 and isoform 2 are most highly expressed in the brain, eye and skeletal muscle and to a lower degree in liver, heart, kidney and swim bladder. Isoform 3 is most highly expressed in the eye, forebrain, midbrain, hindbrain, skeletal muscle, gills and brain but is barely detectable in liver, heart, kidney and swim bladder. Before the pharyngula period isoform 3 is expressed throughout the entire embryo and during this period extensively in the brain and eye.
Transcription factor that plays a role in the development of the hypothalamo-pituitary axis. Specifically recognizes the xenobiotic response element (XRE) (By similarity). Isoform 1 acts as a transcriptional activator (PubMed:11072074). Isoform 3 acts as a transcriptional repressor (PubMed:10960127, PubMed:11072074).
Binds 2 divalent metal cations per subunit with RNAase activity being higher in presence of Mn(2+) than of Mg(2+) or Co(2+).
Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. During miRNA-mediated repression the complex seems also to act as translational repressor during translational initiation. Additional complex functions may be a consequence of its influence on mRNA expression (By similarity).
Belongs to the small GTPase superfamily. Ran family.
Expression is low at 2 hpf and starts to increase steadily after 12 hpf to reach adult levels at 72 hpf.
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).
Ubiquitous, with the highest expression in ovary, muscle, eye and brain.
Found in low abundance in the two-cell through early somite stages (<1.5 through 12 hours) and increases during later stages of growth and organ development.
High levels are seen in the kidney, gills and uterus.
Ser-80 is present instead of the conserved Cys/Sec which is expected to be the active site residue.
Detected in 32-cell embryos, probably due to perdurance of maternal transcripts. Has low expression at the 90% epiboly and tailbud stages (9-10 hours post-fertilization, hpf). Moderately expressed from 24 hpf onwards, and strongly expressed at the adult stage.
Homodimer (By similarity). Homotetramer (PubMed:24465614).
Plays a role in the regulation of ureagenesis by producing the essential cofactor N-acetylglutamate (NAG), thus modulating carbamoylphosphate synthase I (cps1) activity.
The amino-acid kinase (AAK) domain mediates binding of L-arginine.
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 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.
Morpholino knockdown results in reduced slc24a5 expression in wild-type embryos however expression is still detectable in the body and retinal pigment epithelium (PubMed:19414594). In 50% of the embryos expression of slc24a5 is restricted to the retina (PubMed:19414594).
Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1.
At gastrulation, expression is absent within the axial mesoderm. After gastrulation is complete, expressed in the presomitic mesoderm, but expression in the tailbud doesn't begin until the six to seven somite stage, after which it becomes abundant. Expression is abundant throughout somitogenesis within the posterior half of the somites, but is absent from older somites. Also expressed in a dynamic manner within the neural plate.
Expressed both maternally and zygotically. Expression decreases from the mid-blastula stages onwards before increasing again at the start of gastrulation.
Transcriptional corepressor that binds to a number of transcription factors.
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.
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).
Acts as a GTPase-activating protein (GAP) involved in trafficking between the Golgi and the ciliary membrane (By similarity). Acts as a GTPase-activating protein (GAP) for tubulin in concert with tubulin-specific chaperone C, but does not enhance tubulin heterodimerization (By similarity). In the retina, required for maintenance of rod and cone photoreceptor cells (PubMed:26034134). May have a role in normal retinal localization of the transducins GNB1 and GNAT1, and the rhodopsin kinase GRK1 (PubMed:26034134).
Contaminating sequence. Sequence of unknown origin at the N terminus.
In the retina, detected in both rod and cone photoreceptors (at protein level) (PubMed:21282572, PubMed:26034134). Has strongest expression in the retinal outer nuclear layer (ONL) and weaker expression in the outer plexiform layer (OPL) and inner plexiform layer (IPL) (at protein level) (PubMed:26034134). Expressed in all tissues tested (PubMed:21282572).
Myristoylated on Gly-2; which may be required for membrane targeting.
Palmitoylated on Cys-3; which may be required for plasma membrane targeting.
Viable and fertile. Early retinal development appears to be grossly normal. Outer segments of rod and cone photoreceptors show progressive degeneration from 2 months of age, with rod cells more severely affected in the early stages.
May play a role during the calcification of cartilage and the transition of cartilage to bone (By similarity). Together with col27a1a, plays a role in development of the notochord and axial skeleton.
Weakly expressed in the notochord from the 6 somite stage. Expressed throughout the notochord at 13 somites, then becomes restricted to the distal tip of the notochord by 24 hpf. Also expressed in head cartilages by 48 hpf.
Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses. May play a role in the regulation of cell proliferation (By similarity).
E3 ubiquitin-protein ligase. 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 ERCC1/RAD10/SWI10 family.
Belongs to the bacterial ribosomal protein bL28 family.
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.
At 36-48 hpf, mutants exhibit pericardial edema due to dysmorphic hearts that fail to loop and form and atrioventricular (AV) canal. Hearts show continues peristatic pumping rather than coordinated and sequential beating of atrial and ventricular chambers. Endocardial cells remain squamous and AV myocardial cell shape fail to occur.
In embryo, expressed ubiquitously, but with decreasing intensity, from the one-cell through gastrula stages.
Isoform 1 is expressed mainly in adult thymus. Isoform 2 is detected in adult skin. Isoform 3 is expressed in adult brain and embryo. Prominent expression sites include the olfactory placode, the basal layer of the olfactory epithelium, the neuroepithelium of the developing retina, the germinal zone of the differentiated eye, regions of motoneuron development in the neural tube and periventricular regions of the brain.
Transcription factor essential for neural and some non-neural tissues development. Binds to an 11-bp consensus sequence containing the invariant tetranucleotide 5'-ACGC-3'. During development of the central nervous system, required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates. Drives commitment of p2 progenitors to the V2b interneuron fates during spinal cord neurogenesis. In development of non-neural tissues, plays an essential role in the specification of the atrioventricular canal.
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.
Morpholino knockdown of the protein induces cardiac contractile dysfunction and loss of motoneuron formation.
Heterodimer of a large and a small subunit.
In the central section; belongs to the metallo-dependent hydrolases superfamily. DHOase family. CAD subfamily.
Belongs to the SIMIBI class G3E GTPase family. ZNG1 subfamily.
Mutant fishes survive to adulthood under zinc-replete conditions, but display moderate developmental delay, characterized by reduced height at anterior anal fin, standard length and snout to vent length at 6 days post fertilization (dpf) (PubMed:35584702). They show impaired zinc homeostasis and cells show impaired activity of metap1 (PubMed:35584702).
Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them (PubMed:35584702). Catalyzes zinc insertion into the active site of methionine aminopeptidase METAP1, which function to cleave the initiator methionine from polypeptides during or after protein translation (PubMed:35584702). Mechanistically, the N-terminal psi-PxLVp motif binds to the C6H2-type zinc finger of inactive form of METAP1 (PubMed:35584702). After formation of the docked complex, zinc is transferred from the CXCC motif in the GTPase domain of ZNG1 to the zinc binding site in the peptidase domain of METAP1 in a process requiring GTP hydrolysis. GTP/GDP exchange is required for release of active METAP1 (By similarity).
Essential for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase. Acts as a chaperone in the early steps of cytochrome c oxidase subunit II (MT-CO2/COX2) maturation, stabilizing the newly synthesized protein and presenting it to metallochaperones SCO1/2 which in turn facilitates the incorporation of the mature MT-CO2/COX2 into the assembling CIV holoenzyme.
Catalyzes the formation of 25-hydroxycholesterol from cholesterol, leading to repress cholesterol biosynthetic enzymes. Plays a key role in cell positioning and movement in lymphoid tissues: 25-hydroxycholesterol is an intermediate in biosynthesis of 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC), an oxysterol that acts as a ligand for the G protein-coupled receptor GPR183/EBI2, a chemotactic receptor for a number of lymphoid cells. May play an important role in regulating lipid metabolism by synthesizing a corepressor that blocks sterol regulatory element binding protein (SREBP) processing. In testis, production of 25-hydroxycholesterol by macrophages may play a role in Leydig cell differentiation.
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.
Plays a role in phosphate homeostasis. Mediates phosphate export from the cell (PubMed:23791524). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7); these are important intracellular signaling molecules (By similarity).
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.
Expressed in spinal cord and retinal ganglion cells.
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 a 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 therefore affects the proton electrochemical gradient and promotes synaptic vesicles acidification. Moreover, functions as a vesicular K(+)/H(+) antiport allowing to maintain the electrical gradient and to decrease chemical gradient and therefore sustain vesicular L-glutamate uptake. The vesicular H(+)/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). Also involved in the regulation of retinal hyaloid vessel regression during postnatal development (By similarity). May also play a role in the endocrine L-glutamatergic system of other tissues such as pineal gland and pancreas (By similarity). Required for glutamate release by retinotectal synapses and visual acuity (PubMed:17196531).
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).
May act by regulating membrane trafficking and cellular morphogenesis.
Probably part of the TNF-alpha signaling pathway that can shift the equilibrium toward induction of cell death. May act by regulating membrane trafficking and cellular morphogenesis.
Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions.
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.
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 eukaryotic ribosomal protein eS26 family.
Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. In the TIM22 complex, it constitutes the voltage-activated and signal-gated channel. Forms a twin-pore translocase that uses the membrane potential as external driving force in 2 voltage-dependent steps.
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 ubiquitin conjugation factor E4 family.
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.
Belongs to the SIMIBI class G3E GTPase family. ArgK/MeaB subfamily.
Belongs to the MICOS complex subunit Mic10 family.
Expressed throughout development. Weakly expressed during early developmental stages from shield to tailbud.
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 ribulose-phosphate 3-epimerase family.
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.
Necessary for protein translocation in the endoplasmic reticulum.
Component of the PEX2-PEX10-PEX12 retrotranslocation channel.
E3 ubiquitin-protein ligase 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 (By similarity). The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane. PEX2 also regulates peroxisome organization by acting as a E3 ubiquitin-protein ligase (By similarity).
Mutant fishes show a loss of peroxisomal structure, associated with high-mortality (PubMed:34016526). Defects are similar to human Zellweger syndrome (ZS), characterized by developmental abnormalities in many organs, organ-specific accumulation and reduction of distinct fatty acid species, such as an accumulation of ultra-very-long-chain polyunsaturated fatty acids (ultra-VLC-PUFAs) (PubMed:34016526).
The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore. The RING-type zinc-fingers that catalyze PEX5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex.
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.
Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer and proceeds in a highly ordered manner. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation (By similarity).
Initially expressed in adaxial mesoderm with transcripts distinctly localized to the anterior portion of each half-somite. Hereupon, also strongly expressed in the otic vesicles, branchial arches and the brain, especially at the midbrain-hindbrain boundary (MHB).
Monomer. Homodimer after ligand binding (By similarity). Interacts with cnpy1.
N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus (By similarity).
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues (By similarity).
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains (By similarity).
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and normal skeletogenesis. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by ubiquitination, internalization and degradation (By similarity).
Ubiquitinated. FGFR1 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation (By similarity).
Expressed in oocytes (at protein level). During oocyte maturation becomes detectable at stage Ib, and remains ubiquitously distributed within the oocyte cytoplasm until stage II. It then follows a gradual accumulation to the future animal pole during stage III, and remains localized to this pole at stage IV (at protein level). Expressed in oocytes, blastomeres and pre-mid-blastula transition embryos. Its expression during oogenesis is ubiquitous at stages I and II, but gradually accumulated at the periphery of the oocyte in the presumptive animal pole during stage III. Expression was maintained in that region at stage IV, and then became delocalized at stage V to cover a much broader area presumably encompassing the future blastodisc.
Sequence-specific RNA-binding protein that regulates mRNA cytoplasmic polyadenylation and translation initiation during oocyte maturation and early development. Binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR (By similarity).
Belongs to the sarcoglycan alpha/epsilon family.
Belongs to the GTP cyclohydrolase I family.
Homodimer in soluble form. Forms an octameric pore-like structure in the membrane.
Pore-forming protein which might play a role in host defense. Exists as an antiparallel dimer in solution. Can also assemble into an octameric pore-like structure spanning the cell membrane. Oligomerization may be triggered by binding of the jacalin-type lectin domain to high-mannose cell-surface proteoglycans, and also requires a low pH environment. In vitro, shows high binding affinity for S.cerevisiae mannan and human HIV virus glycoprotein gp120.
The jacalin-type lectin domain has strong affinity for high-mannose glycans with terminal non-reducing ends of Man(alpha-1,2)Man or Man(alpha-1,3)Man.
Up-regulated in the presence of organophosphate pesticides and zinc.
During development, expressed in embryonic structures of both mesodermal and ectodermal origins, including the heart, cranial motor neurons and the roof of the dorsal aorta. Prominently associated with heart formation and continuously expressed in the myocardial lineage from the initiation of myocardial differentiation through to formation of the differentiated, two chambered heart. First detected in anterior lateral plate mesoderm (ALPM) and by the 5- to 10-somite stages, strongly expressed in ALPM and in two bilateral groups of mesenchymal cells close to the anterior notochord and in a crescent of lateral plate adjacent to the tail. At the 6- to 8- and 12- to 14-somite stages, expressed throughout the ALPM. Between the 10 and 15-somite stages, expressed throughout the myocardium. At the 18-somite stage, expressed in the loosely packed mesenchymal cells in the midline immediately anterior to the heart fields. Later expression seen in the cardiac cone, cardiac tube and ventricle.
Transcriptional regulator that may play a very early role in the differentiation of the cardiac precursors.
Essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).
Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle.
The two SXIP sequence motifs are important for targeting to the growing microtubule plus ends.
Two TOG regions display structural characteristics similar to HEAT repeat domains and mediate interaction with microtubules.
Regulates negatively FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling.
Catalyzes the activation of N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc), a substrate required for the addition of sialic acid. Also has activity towards N-glycolylneuraminic acid (Neu5Gc). Has weak activity towards 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN).
Detected in the axial mesoderm at 9 hours post-fertilization (hpf). Expressed in the central nervous system, somites, notochord and developing pronephric duct at 18 hpf. At later stages (48-72 hpf) expression decreases in the trunk but persists in the central nervous system, and is also found in liver and kidney primordia.
Sequence of unknown origin at N terminus.
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 TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. EngB GTPase family.
Does not appear to have detectable kinase activity.
Interacts with calmodulin, in the presence of calcium.
The protein kinase domain is predicted to be catalytically inactive.
Expressed prior to gastrulation and following gastrulation cell movements at 10 hours post fertilization (PubMed:21227923). Expressed ubiquitously during early development (PubMed:21227923).
Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER (By similarity). Required for normal embryonic development (PubMed:21227923). May play a role in the nonsense-mediated decay pathway of mRNAs containing premature stop codons (PubMed:21227923).
Morpholino knockdown leads to both intermediate and severe phenotypes of abnormal embryonic development (PubMed:21227923). Intermediate phenotypes show areas of necrosis in the brain and neural structures with abnormal stacking of somites (PubMed:21227923). Severe phenotypes show a small body with few recognizable structures on top of the yolk sac with necrotic tissue present in the anterior and posterior regions (PubMed:21227923). Increase in premature stop codon containing slc24a5 mRNA transcript levels in melanocytes (PubMed:21227923).
Most of the residues in the galectin domain that have been shown to be critical for carbohydrate-binding in other galectins are not conserved.
This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.
Negatively regulates axonal outgrowth and is essential for normal synaptic transmission. Not required for regulation of axon polarity. Promotes acetylation of alpha-tubulin.
Belongs to the peptidase C19 family. PAN2 subfamily.
Binds 2 metal cations per subunit in the catalytic exonuclease domain.
Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1.
Contains a pseudo-UCH domain. This ubiquitin C-terminal hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain is predicted to be catalytically inactive because it lacks the active site catalytic triad characteristic of thiol proteases, with residues at the equivalent structural positions that are incompatible with catalysis, and it cannot bind ubiquitin. It functions as a structural scaffold for intra- and intermolecular interactions in the complex.
Forms a heterotrimer with an asymmetric homodimer of the regulatory subunit PAN3 to form the poly(A)-nuclease (PAN) deadenylation complex.
Positively regulated by the regulatory subunit PAN3.
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with PAN3.
Belongs to the 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).
Co-chaperone required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Acts as a co-chaperone via its interaction with HSP90 and is required for the piRNA amplification process, the secondary piRNA biogenesis. May be required together with HSP90 in removal of 16 nucleotide ping-pong by-products from Piwi complexes, possibly facilitating turnover of Piwi complexes.
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.
Expressed in simple epithelia such as intestinal mucosa, bile duct, hepatocytes, renal tubules, endothelia, ocular lens epithelium, and in a variety of mesenchymally-derived cells such as blood vessel endothelia, pillar gill cells, optic nerve glial cells, fibroblasts, interstitial cells, chondrocytes and ovarian theca cells. Also expressed in epidermis, pharyngeal mucosa, mucosa of anterior esophagus, gill mucosa and cornea.
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.
When phosphorylated, plays a role in filament reorganization.
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.
Morpholino knockdown of the protein causes small head and a curled tail by day 2. Knockdown causes increased sensitivity to IR-induced apoptosis (PubMed:22952453). In double morpholino knockdown of TP53 and YJU2, TP53 deficiency rescues animals from developmental neurodegeneration observed on YJU2 mutants and radiosensitivity (PubMed:22952453).
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 (By similarity). May protect cells from TP53-dependent apoptosis upon dsDNA break damage through association with PRP19-CD5L complex (PubMed:22952453).
Interacts with PCNA. Three molecules of fen1 bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity.
Phosphorylated. Phosphorylation upon DNA damage induces relocalization to the nuclear plasma.
Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.
May play a role in lysosome motility. May play a role in chromosome segregation.
Toll-like receptor (TLR)-specific co-chaperone for HSP90B1. Required for proper TLR folding and hence controls TLR exit from the endoplasmic reticulum. Consequently, required for immune responses (By similarity).
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Required for the activation of aurka at the onset of mitosis.
Expressed both maternally and zygotically. Expressed ubiquitously throughout gastrulation. At the tailbud stage, expressed at higher levels in the anterior and tailbud. Also expressed in migrating cranial neural crest cells.
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain development.
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.
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 carbon-nitrogen hydrolase superfamily. BTD/VNN family.
Catalyzes the hydrolytic deamination of enamine/imine intermediates that form during the course of normal metabolism. May facilitate the release of ammonia from these potentially toxic reactive metabolites, reducing their impact on cellular components. It may act on enamine/imine intermediates formed by several types of pyridoxal-5'-phosphate-dependent dehydratases including L-threonine dehydratase.
Belongs to the Mediator complex subunit 27 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). Required for the development of dopaminergic amacrine cells in the retina. May also negatively regulate the development of rod photoreceptor cells.
Maternally expressed. Ubiquitously expressed throughout development.
Enzyme that catalyzes the last step in proline biosynthesis. Proline is synthesized from either glutamate or ornithine; both are converted to pyrroline-5-carboxylate (P5C), and then to proline via pyrroline-5-carboxylate reductases (PYCRs). PYCRL is exclusively linked to the conversion of ornithine to proline.
Expressed both maternally and zygotically. Transcripts localizes to the Balbiani body during oogenesis (PubMed:18582455).
RNA-binding protein involved in gametogenesis in both males and females (PubMed:12296827). Acts by binding to the 3'-UTR of mRNA, specifically recognizing GUU triplets, and promoting the translation of key transcripts (PubMed:12296827). Establishes oocyte polarity through interaction with Bucky ball (BUC) (Probable). Interacts with Bucky ball (BUC) mRNA to mediate Balbiani body formation and oocyte polarity during early oogenesis (By similarity).
Testis and ovary specific. In ovary, it is localized in the cortex of oocytes (PubMed:10330505). At the onset of embryogenesis, maternal product is located at the vegetal pole, before migrating toward blastomeres through cytoplasmic streams as early embryogenesis proceededs (PubMed:10330505).
The DAZ domain is essential for the translation activation activity.
Belongs to the thiolase-like superfamily. HMG-CoA synthase family.
Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA.
Expressed in the developing nervous system.
Morpholino knockdown of the gene results in early postnatal lethality.
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.
APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma.
Highly expressed in the yolk syncytial layer during embryonic (starting at the blastula stage) and early larval development, an extraembryonic structure implicated in embryonic and larval nutrition. Also observed in the deep cell layer during blastula stage, in numerous ectodermal derivatives after gastrulation, and after 3 days of development in a limited number of cells both in brain and in the eyes.
B regulatory subunit of protein phosphatase 2A (PP2A) that plays a key role in cell cycle by controlling mitosis entry and exit. The activity of PP2A complexes containing PPP2R2D (PR55-delta) fluctuate during the cell cycle: the activity is high in interphase and low in mitosis. During mitosis, activity of PP2A is inhibited via interaction with phosphorylated ENSA and ARPP19 inhibitors. Within the PP2A complexes, the B regulatory subunits modulate substrate selectivity and catalytic activity, and may also direct the localization of the catalytic enzyme to a particular subcellular compartment (By similarity).
PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with ENSA (when phosphorylated at 'Ser-74') and ARPP19 (when phosphorylated at 'Ser-62'), leading to inhibit PP2A activity (By similarity).
Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine.
A maternally expressed membrane and cytoskeletal linker protein, which is essential for attachment of the centrosome to the male pronucleus. Promotes male and female pronucleus congression and subsequent fusion after fertilization. Congression is mediated by the sperm aster microtubules.
Defects in irag2 are a cause of pronuclear congression/fusion and chromosomal segregation abnormalities in the zygote named futile cycle (fue), a lethal recessive maternal-effect mutant. Mutant embryos undergo several cycles of anucleate cleavage and die.
Expressed in embryos and early cleavage stages (at protein level). Maternally expressed. Expressed in early cleavage embryos, weakly at 4 hours post-fertilization (hpf) and undetected at 24 hpf.
Converts proline to delta-1-pyrroline-5-carboxylate.
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.
Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility. Involved in the regulation of the size and morphology of cilia. Required for axonemal microtubules polyglutamylation (By similarity). Plays a role in cilia stability (PubMed:24574454).
Display curved body axis, short somite length and defective heart-looping orientation.
Probable component of the NALCN channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability.
Probable dioxygenase that requires molecular oxygen, alpha-ketoglutarate and iron.
Belongs to the DEAD box helicase family. DDX1 subfamily.
Component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3. The FHF complex associates with the homotypic vesicular sorting complex (the HOPS complex).
Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell.
Together with NONO, required for the formation of nuclear paraspeckles. Acts as a coactivator during transcriptional activation. Binds to RNA. May act as a regulator the circadian clock (By similarity).
Expressed throughout development with low levels detected from 3-8 hpf and highest levels in developing brain and lens at 24 hpf. In the embryo, expressed in anterior neural plate and later in lens and pituitary cells. Detected in the forebrain, lens and pectoral fin buds at 24 hpf. Becomes restricted to the lens equatorial region by 48 hpf. Strongest expression detected in the diencephalon and pituitary at 48 hpf. Evident in the cartilage surrounding the mouth at 72 hpf, appearing in the iris of the eye, developing lower jaw and the branchial arches at 96 hpf and extending to developing musculature along the trunk. During lens development, exhibits widespread expression during the primary differentiation phase of lens formation and then restricted to the region of secondary fiber cell differentiation during the phase of lens growth. Expressed in both proliferating and early differentiating progenitor cells of the posterior tuberculum.
In the adult, high levels detected in the eye and much lower levels in internal organs such as liver, gastrointestinal system, heart, genitourinary system and pancreas.
Transcriptional regulator which may play a role in the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons (By similarity). Required for lens and retinal development and for pituitary pre-placode formation and cell specification.
Contaminating sequence. Potential poly-A sequence starting in position 264.
May act as a 'capping' or 'branching' protein for keratin filaments in the cell periphery. May regulate K8/K18 filament and desmosome organization mainly at the apical or peripheral regions of simple epithelial cells (By similarity).
Expressed predominantly in the developing neural structures. Levels gradually increases from 36 to 144 hpf.
May be involved in the control of neuronal proliferation or migration in the brain of embryos.
CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy.
5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by terf2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways (By similarity). Possesses beta-lactamase activity, catalyzing the hydrolysis of penicillin G and nitrocefin (By similarity). Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem) (By similarity).
Interacts with terf2; the interaction is direct.
The TBM domain mediates interaction with terf2.
May induce G2 arrest and apoptosis. May also increase cell sensitivity to apoptotic stimuli.
Catalyzes the hydrolysis of the free cytosolic methylated adenosine nucleotide N(6)-methyl-AMP (N6-mAMP) to produce inositol monophosphate (IMP) and methylamine. Is required for the catabolism of cytosolic N6-mAMP, which is derived from the degradation of mRNA containing N6-methylated adenine (m6A).
Belongs to the dynactin subunit 2 family.
Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes. May play a role in synapse formation during brain development (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. May play a role in synapse formation during brain development.
Subunit of dynactin, a multiprotein complex associated with dynein.
Belongs to the DEAD box helicase family. DDX46/PRP5 subfamily.
Plays an essential role in splicing, either prior to, or during A complex formation.
Belongs to the eukaryotic ribosomal protein eL19 family.
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.
First expressed in 11-12 hour embryos. In the rostral brain of 13 hour embryos, expressed within the anterior half of the midbrain and the posterior part of the diencephalon. In the presumptive hindbrain, expressed in a segment-like stripe in the anterior region, resembling the presumptive rhombomere units of the hindbrain. Also detected in the intermediate mesoderm, posterior to the first somite. As somitogenesis proceeds, expression extends posteriorly and flanks the 10 most anterior somites. Expression changes extensively both in level and expansion of domains between 13 and 20 hours. In the rostral brain, expression extends to include a major part of the diencephalon and a caudal portion of the telencephalon. Within the hindbrain, strongly expressed in the two most anterior rhombomeres, and a lower but uniform expression is seen to extend throughout rhombomere 7. In 28 hour embryos, higher and more uniform expression is seen in both rostral and hindbrain areas. Also expressed in the retina of the eye.
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.
Detected in blastomere, near the blastoderm margin in gastrula, and in forebrain, posterior hindbrain and throughout the length of the trunk at early segmentation stages.
Required for segmental gene expression during hindbrain development. May function as a transcriptional repressor.
Probably involved in the patterning of the nervous system, in particular in the early specification of the diencephalon.
Belongs to the XRCC4-XLF family. XRCC4 subfamily.
Associated with nucleolar and cytoplasmic pre-60S particles (By similarity). At the end of biogenesis it dissociates from cytoplasmic pre-60S particles and is likely to be exchanged for its ribosomal homolog, RPL24 (By similarity).
Involved in the biogenesis of the 60S ribosomal subunit. Ensures the docking of GTPBP4/NOG1 to pre-60S particles (By similarity).
Activated by threonine and tyrosine phosphorylation by the dual specificity kinase, MKK3.
Dually phosphorylated on Thr-181 and Tyr-183, which activates the enzyme.
Expressed as the predominant form of mapk14 both maternally and zygotically throughout development.
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Mapk14a is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. Required for cytokinesis on the future dorsal side of the blastodisc, suggesting a role in symmetrical and synchronous blastomere cleavage.
Centrosomal protein involved in regulation of centriole duplication. Required to limit centriole duplication to once per cell cycle by preventing centriole reduplication.
Embryonic expression is highly dynamic. In early gastrula embryos, expressed in the involuting presumptive anterior mesoderm. Found in the head rudiment at 9 hours of development, and at 12 hours of development expression increases at the caudal side but decreases at the rostral side. With the extension of the body axis, expression extends to neuroectodermal regions fated to become fore- and mid-brain; detected in the presumptive border between the midbrain and the hindbrain at 18 hours of development, and found in the diencephalon and the midbrain at 24 hours of development.
Found in embryos at 0-2 hours of development, levels decrease drastically at 6 hours of development but increase again at 12 hours of development.
Acts as a transcriptional activator. Acts by binding to sequences related to the consensus octamer motif 5'-ATGCAAAT-3' in the regulatory regions of its target genes. May play a role in specifying terminally differentiated neuronal phenotypes.
Belongs to the POU transcription factor family. Class-4 subfamily.
Expressed in the nervous system. Expressed in the otic vesicle during embryogenesis. Expressed in the adult retina in a subset of retinal ganglion cells (RGCs), and at a lower level in the adult tectum. Not expressed in the adult olfactory bulb.
Weakly expressed during embryogenesis, with stronger expression in the adult eye.
Nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits.
Belongs to the purine nucleoside phosphorylase YfiH/LACC1 family.
Complete absence of iridophores (PubMed:29078341, PubMed:29317532). Fishes do not survive past 6 days post-fertilization (dpf), possibly because the swim bladder cannot fill with air (PubMed:29317532).
Expressed in notochord from 18-24 hours post-fertilization (hpf) and prominently in brain and swim bladder from 3 days post-fertilization (dpf).
Homodimer; homodimerizes upon binding to alkal ligands (alkal1, alkal2a or alkal2b).
Mainly expressed in neural crest cells (NCCs) and iridophores (PubMed:18369445, PubMed:29317532). In adults, expressed in the head and iridophores of the trunk and eyes, as well as in the swim bladder (PubMed:29317532).
Receptor tyrosine kinase required for the establishment and proliferation of iridophores and their progenitors from multipotent neural crest cells (PubMed:18369445, PubMed:23821036, PubMed:26801003, PubMed:29078341, PubMed:29317532). Iridophores are the blue-tinted cells that reflect light to give fish their metallic shine and which, together with yellow xanthophore and black melanophores, generate the zebrafish's stripes (PubMed:18369445, PubMed:23821036, PubMed:26801003). Following activation by alkal ligands (alkal1, alkal2a or alkal2b) at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:29078341, PubMed:29317532). Ligand-binding to the extracellular domain induces tyrosine kinase activation, resulting in the activation of the mitogen-activated protein kinase (MAPK) pathway (By similarity). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (By similarity).
Required for gamma-tubulin complex recruitment to the centrosome.
Involved in muscle differentiation (myogenic factor). Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein (By similarity).
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).
During the blastula period expressed in all blastomeres. At the onset of gastrulation, expressed more in the embryonic shield than in other regions. As embryos elongate, expression in the shield migrates toward the animal pole and forms a longitudinal band in the dorsal midline. At late gastrulation, expressed in the dorsal midline extending from the tailbud to the animal pole. Expression is under the control of Nodal signals.
Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs.
Belongs to the oligoribonuclease family.
Component of pre-catalytic, catalytic and post-catalytic spliceosomes. Associates with the spliceosome prior to recognition of the 3'-splice site for step II, probably during catalysis of step I.
Required for pre-mRNA splicing as component of the spliceosome. Participates in the second catalytic step of pre-mRNA splicing, when the free hydroxyl group of exon I attacks the 3'-splice site to generate spliced mRNA and the excised lariat intron. Required for holding exon 1 properly in the spliceosome and for correct AG identification when more than one possible AG exists in 3'-splicing site region. May be involved in the activation of proximal AG. Probably also involved in alternative splicing regulation.
Expressed both maternally and zygotically. Distributed throughout the blastoderm at the blastua stage but becomes confined to the future ectoderm by the shield stage. Expressed in the presumptive neuroectoderm at the 75-80% epiboly stage. From the tail bud to the 3-somite stage, expressed throughout the neural plate, except in the anterior margin. At the 12- to 25-somite stage, expressed broadly in the central nervous system.
Catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. M6P residues are required to bind to the M6P receptors (MPR), which mediate the vesicular transport of lysosomal enzymes to the endosomal/prelysosomal compartment.
Decreased mannose phosphorylation of lysosomal acid hydrolases, craniofacial and cardiac defects. Impaired development of pectoral fins and otic vesicles. Craniofacial defects are due to changes in the timing and localization of both type II collagen and sox9 expression, suggestive of an accelerated chondrocyte differentiation program. Increased level of active cathepsin K (ctsk) 3 days post-fertilization (dpf) because of abnormal processing and activation, leading to morphologic cartilage defects.
Hexamer of two alpha, two beta and two gamma (GNPTG) subunits; disulfide-linked. The alpha and/or the beta subunits of the enzyme constitute the catalytic subunits.
Stealth proteins are part of a protein family that is conserved from bacteria to higher eukaryotes. Family members were first identified in microbes as proteins that help pathogens to elude the host innate immune system. Microbial stealth proteins are most likely involved in the biosynthesis of exopolysaccharides. Stealth proteins are predicted to function as hexose-1-phosphoryltransferases.
The DMAP1-binding domain mediates substrate recognition. It specifically recognizes a conformation-dependent protein determinant present in acid hydrolases.
The alpha- and beta-subunits are generated by a proteolytic cleavage by mbtps1 protease at the Gln-893-Asp-894 bond.
Belongs to the Integrator subunit 7 family.
Component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. May play a role in DNA damage response (DDR) signaling during the S phase (By similarity). Essential during embryogenesis for eye development.
Fishes have a defective lens structure and abnormally shaped jaw and neurocranium.
Belongs to the eukaryotic/archaeal RNase P protein component 3 family.
Expressed in the neural plate border, Kupffer's vesicle, neural tube, otic vesicles, midbrain, eyes, forebrain and brain ventricular zone by 24 hours post-fertilization (hpf). From 36 to 96 hpf, expression is detected in the midbrain-hindbrain boundary, otic vesicles, pharyngeal arches, cranial cartilages such as Meckel's cartilages, palatoquadrates, and ceratohyals, cranial cavity, pectoral fin buds, brain ventricular zone, ciliary marginal zone, and digestive organs such as the intestine, liver and pancreas.
Morpholino knockdown results in disorganization of the olfactory bulbs with a significant reduction of GnRH neuronal development compared with uninjected embryos.
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. Required for proper development of GnRH neurons (gonadotropin-releasing hormone expressing neurons) that control the release of reproductive hormones from the pituitary gland (PubMed:32493844).
Probable guanine nucleotide exchange factor (GEF). May promote the exchange of GDP to GTP, converting inactive GDP-bound small GTPases into their active GTP-bound form.
Belongs to the proton-activated chloride channel family.
Morpholino-induced knockdown affects tail morphology, and causes cardiac edema and abnormal swimming in response to tactile stimulation. Morphants show aberrant axons, either short or over-extended, with some axons appearing to branch to the adjacent myotome.
Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Regulates Rho by stimulating it's GTPase activity in neurons (By similarity). Required for the regulation of neurite branching and motor neuron axon guidance (PubMed:27259756).
Enriched in testis but hardly detectable in the ovary (at protein level).
Expressed both maternally and zygotically. Expression is very low in the zygote, increasing from morula stage onward to reach a peak during early gastrulation. Levels then rapidly decline during neurula and organogenesis stages (at protein level). There is an inverse correlation between mRNA and protein levels at the late blastula and early gastrula stages.
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 (By similarity). Members of the TBP family are differentially required for transcription and development during early embryogenesis. Regulates mRNA levels in the early embryo by both transcriptional and post-transcriptional mechanisms. Required for transcription of a subset of genes at the mid-blastula transition (MBT). Negatively regulates the expression of other embryonic genes, including autoregulation of the tbp promoter itself. Also functions within a transcription-dependent mechanism to direct the temporally-regulated degradation of a subset of maternal mRNAs after the MBT. This is part of a general mechanism to regulate the maternal to zygotic transition and is required for normal embryonic development. Binds to promoters of a subset of genes. Required for gastrulation.
Belongs to the TRAFAC class YlqF/YawG GTPase family.
May play a role in regulating cellular proliferation.
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.
Belongs to the Mediator complex subunit 28 family.
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).
Morpholino knockdown of the protein produces embryos with a curly tail morphology and impaired swimming, suggesting dysfunction of neural circuits (PubMed:26168012). Spinal motor neurons have shortened axon tracts due to degeneration of neuronal processes (PubMed:27543974). Mitochondria in knockdown embryos show incomplete fission, abnormal aggregation and abnormal cell localization (PubMed:26168012, PubMed:27543974).
Transmembrane protein of the mitochondrial outer membrane that controls mitochondrial organization (By similarity) (PubMed:27543974). May regulate the biogenesis and dynamics of mitochondrial cristae, the inwards folds of the inner mitochondrial membrane (By similarity). Could regulate mitochondrial lipid homeostasis and thereby mitochondrial fission (By similarity).
DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. May be involved in subtype specialization of primary motoneurons. May bind to insulin gene enhancer sequences. Essential for heart development (By similarity).
Expressed immediately after gastrulation in the polster, cranial ganglia, rohan-beard neurons and in ventromedial cells of the spinal cord at 12 hours post-fertilization (hpf). Expressed in cells slightly anterior to the segment border at 16 hpf.
Morpholino knockdown of the protein results in abnormal contractility and looping in developing heart. Morphants show prolonged duration of cardiac action potentials, occasional 2:1 atrioventricular block and slowed conduction velocity (PubMed:25281747).
Plays a role in cardiac repolarization possibly by stabilizing membrane expression of the potassium channel kcnh6a/zerg, or by assisting its synthesis, folding or export from the endoplasmic reticulum, in a heat shock protein-dependent manner.
Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores.
Belongs to the AB hydrolase superfamily. ABHD17 family.
Hydrolyzes fatty acids from S-acylated cysteine residues in proteins. Has depalmitoylating activity towards nras.
Palmitoylated on cysteine residues located in a cysteine cluster at the N-terminus which promotes membrane localization.
Agents that activate cftr increase the size of Kupffer's vesicle in myo1d mutants (PubMed:29769531, PubMed:30139971). Expansion of the lumen size is not sufficient to restore the normal spherical shape of Kupffer's vesicle and rescue laterality defects (PubMed:29769531, PubMed:30139971). Heterologous expression of rat Myo1d can complement the defects in Kupffer's vesicle lumen size and anterior-posterior cell shape changes (PubMed:30139971).
Binds a calmodulin chain via each of the two IQ domains. IQ domain 1 mediates interaction with calmodulin both in the presence and in the absence of Ca(2+). IQ domain 2 mediates interaction with calmodulin in the presence of Ca(2+).
Expressed both maternally and zygotically (PubMed:29769531). Ubiquitous in embryos at the four cell stage (PubMed:30139971). Detected at the eight cell stage. Detected at low levels throughout the embryo at the six somite stage, with higher levels in the developing notochord (PubMed:29769531).
Interacts (via the two IQ motifs) with calmodulin. Interacts with F-actin.
Morpholino knockdown of the protein causes situs inversus, a left-right asymmetry defect where organs are placed at a position corresponding to the mirror image of the normal body plan. Causes laterality defects at the level of the heart, viscera and brain (PubMed:29769531). Morpholino knockdown of the protein leads to the formation of a Kupffer's vesicle with reduced volume and dismorphic shape. Morpholino knockdown of the protein interferes with the normal cellular remodeling that gives rise to anterior-posterior asymmetry of Kupffer's vesicle. Cells with a columnar shape persist at the posterior end of the vesicle, contrary to wild-type, where cells display columnar shape at the anterior part of the vesicle, and squamous or cuboidal shape at the posterior end of Kupffer's vesicle. Epithelial cells lining Kupffer's vesicle display an increased number of vacuoles, and disruption of the normal, directed vacuolar trafficking toward the apical cell membrane (PubMed:30139971).
Represents an unconventional myosin that should not be confused with the conventional myosin-1.
The TH1 domain is required for activity in complementing zebrafish defects in Kupffer's vesicle lumen size.
Unconventional myosin that functions as actin-based motor protein with ATPase activity (By similarity). Plays a role in the formation of Kupffer's vesicle, an organ that functions as left-right organizer during embryogenesis (PubMed:29769531, PubMed:30139971). Plays a role in vesicular trafficking events that are required for normal lumen expansion of Kupffer's vesicle (PubMed:30139971). Required for normal orientation of cilia in Kupffer's vesicle, and thus for normal, unidirectional circular flow and normal angular flow velocity, which then mediates asymmetric gene expression and left-right asymmetric development (PubMed:29769531). Plays a role in endosomal protein trafficking, and especially in the transfer of cargo proteins from early to recycling endosomes (By similarity). Required for normal planar cell polarity in ciliated cells, for normal rotational polarity of cilia, and for coordinated, unidirectional ciliary movement (By similarity).
In the C-terminal section; belongs to the gamma-glutamyl phosphate reductase family.
In the N-terminal section; belongs to the glutamate 5-kinase family.
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).
Expressed in the cranial paraxial mesoderm from 20 hpf and subsequently becomes restricted to the pharyngeal mesoderm that will form the muscle. Expression in the proepicardial organ is first seen at 40hpf in a cluster of cells between the myocardium and yolk. Also expressed in the developing arches. Expression begins to surround the heart by day 3 of development, and by 96 hpf, expression is restricted to the outer epicardial layer surrounding the myocardium.
Involved in epithelial-mesenchymal interactions in kidney and lung morphogenesis that include epithelial differentiation and branching morphogenesis.
E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress. In response to endoplasmic reticulum stress, recruited to the endoplasmic reticulum membrane, and mediates ufmylation of proteins, thereby promoting reticulophagy of endoplasmic reticulum sheets. Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response. Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 (By similarity). Required for hematopoietic stem cell function and hematopoiesis (By similarity).
Expressed in both embryos and adult fish, and the expression is specifically in fast skeletal muscle.
Knockout myl11a mutant have reduced trunk contractile force and complete pectoral fin paralysis. Muscle weakness is most pronounced in an appendicular muscle and is explained by reduced myosin activity and fiber degeneration.
Myosin regulatory subunit that plays a role to maintain muscle integrity during early development (PubMed:32707087). Plays a role in muscle contraction (PubMed:32707087).
Probable component of complexes involved in histone modification such as the NSL complex.
May play a role in protection against oxidative stress.
Belongs to the DEAD box helicase family. DEAH subfamily. DDX15/PRP43 sub-subfamily.
Transcription elongation factor implicated in the maintenance of proper chromatin structure in actively transcribed regions.
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 75-107, 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).
Differentiation factor required for neurogenesis (By similarity). Does not act as an upstream activator of isl1.
Embryonic olfactory bulbs and olfactory placodes. In adult, expressed in brain and eye.
Embryonic, larval and adult stages. First detected at 22 hours post-fertilization (hpf).
Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRID2 subfamily.
Expressed in cerebellar Purkinje cells, in crest cells in the medial octavolateral nucleus and in type I neurons of the optic tectum.
Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists (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).
Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB7 displays a trypsin-like activity.
The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.
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'.
ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism. In absence of activation signal, parp1 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, such as DNA strand breaks. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition. Poly-ADP-ribosyltransferase activity is tightly regulated and parp1 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences. A number of factors or post-translational modifications (auto-poly-ADP-ribosylation) promote parp1 removal from chromatin.
Homodimer; PARP-type zinc-fingers from separate parp1 molecules form a dimer module that specifically recognizes DNA strand breaks.
Poly-ADP-ribosylated on serine, glutamate and aspartate residues by autocatalysis. Auto-ADP-ribosylation on serine takes place following interaction with HPF1. Auto poly-ADP-ribosylation on serine residues promotes its dissociation from chromatin.
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:34798058). Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (By similarity). Specificity for the different amino acids is conferred by interacting factors, such as hpf1 and nmnat1 (By similarity). Following interaction with hpf1, catalyzes serine ADP-ribosylation of target proteins; hpf1 confers serine specificity by completing the parp1 active site. Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with hpf1 (By similarity). Following interaction with nmnat1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; nmnat1 confers glutamate and aspartate specificity (By similarity). Parp1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits hpf1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair. Mediates the poly-ADP-ribosylation of a number of proteins. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (By similarity). Parp1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (PubMed:34798058). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (By similarity). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II. Acts both as a positive and negative regulator of transcription elongation, depending on the context (By similarity). Poly-ADP-ribose chains generated by parp1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos. Also acts as a negative regulator of the cGAS-STING pathway by mediating poly-ADP-ribosylation and inactivation of cgas. Acts as a negative regulator of adipogenesis by catalyzing poly ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) (By similarity).
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.
The BRCT domain is able to bind intact DNA without activating the poly-ADP-ribosyltransferase activity. The BRCT domain mediates DNA intrastrand transfer (named 'monkey-bar mechanism') that allows rapid movements of parp1 through the nucleus.
The PADR1-type (also named Zn3) zinc-finger mediates an interdomain contact and is required for the ability of parp1 to regulate chromatin structure.
The PARP alpha-helical domain (also named HD region) prevents effective NAD(+)-binding in absence of activation signal. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition.
The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation. The bridging induces structural changes in parp1 that signal the recognition of a DNA break to the catalytic domain of parp1.
The two PARP-type zinc-fingers (also named Zn1 and Zn2) specifically recognize DNA strand breaks: PARP-type zinc-finger 1 binds PARP-type zinc-finger 2 from a separate parp1 molecule to form a dimeric module that specifically recognizes DNA strand breaks.
Chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). Acts as a modulator of the Wnt pathway, since some LDLRs are coreceptors for the canonical Wnt pathway (By similarity).
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 (By similarity). Mediates nuclear localization of vsx1. Required for progression through mitosis during organogenesis.
Forms a tight complex with rangap1 and ranbp2 (By similarity). Interacts with vsx1.
Part of TORC1 complex. Part of the TORC2 complex.
Subunit of TORC1 and TORC2, which regulate cell growth and survival in response to nutrient and hormonal signals.
At 3 dpf, mutant animals exhibit cerebellar hypoplasia, a reduction in the anterior structures, including the optic tecta, and an increase in cell proliferation in the head (PubMed:30609410). At 2 dpf, aberrant mitotic cell-cycle progression and an increase in cell death (PubMed:30609410). At 4 dpf, renal defects including renal aplasia, hypoplasia and enlargment of the proximal renal convolution tubule are observed (PubMed:30609410). Morpholino knockdown results in reduced head size, increased cell proliferation in the head, increased cell death and increased renal-tubule diameter (PubMed:30609410). In a double morpholino knockdown together with nphp1, the increase in renal-tubule diameter is exacerbated (PubMed:30609410).
Component of the condensin-2 complex, which contains the smc2 and smc4 heterodimer, and three non SMC subunits that probably regulate the complex: ncaph2, ncapd3 and ncapg2.
Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis (By similarity). Plays a role in the embryonic development of the head and kidney structures (PubMed:30609410).
Catalyzes ghrelin acylation at 'Ser-3' using preferentially octanoyl-CoA, hexanoyl-CoA and decanoyl-CoA as acyl-CoA donors leading to ghrelin activity (By similarity) (PubMed:18443287). In vitro uses also acyl-CoA donors of different lengths from short-chain (C2) to long-chain fatty acids (C16) knowing that acyl-CoA donors from butanoyl-CoA (C4) to dodecanoyl-CoA (C12) are more efficient compared to longer acyl-CoA donors, such as myristoyl-CoA (C14) and palmitoyl-CoA (C16) that are not efficient (By similarity).
Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome.
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.
Regulates leading edge dynamics and cell motility in fibroblasts. May be involved in cytokinesis and signal transduction.
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).
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.
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.
The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription.
Binds to the receptor tyrosine kinase ephb4.
Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with ephb4 may play a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration (By similarity).
Inducible phosphorylation of tyrosine residues in the cytoplasmic domain.
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 functions as deacetylase for non-histone proteins.
Mutarotase that catalyzes the interconversion of beta-D-galactose and alpha-D-galactose during galactose metabolism.
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.
Exhibits phosphohistidine phosphatase activity.
Homotrimer (By similarity). Binds F-actin. Interacts with RCC2. Interacts preferentially with nucleotide-free and GDP-bound RAC1. Interacts with VIM (via head domain) (By similarity).
Morpholino knockdown of the protein causes subtle defects in mesenchymal cell migration, but no gross anatomical defects. The migration of neural crest cells towards the pharyngeal arches is altered, resulting in no clear separation between the first and second pharyngeal arch cells.
Plays a role in directed cell migration by regulating the activation and subcellular location of RAC1 (Probable). Increases the presence of activated RAC1 at the leading edge of migrating cells. Required for normal organization of the cytoskeleton, including the actin cytoskeleton, microtubules and the vimentin intermediate filaments. Plays a role in endoplasmic reticulum-associated endosome fission: endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane. Required for normal cell proliferation, cell migration, and normal formation of lamellipodia. Required for normal distribution of mitochondria within cells (By similarity).
Involved in the specification of isotocin cells. Required for the specification of dopaminergic neurons in the developing hypothalamus and posterior tuberculum.
Isoform 1 and isoform 2 are expressed during embryonic development. At 16 hpf, expressed in a few cells in the ventral dieencephalon. At 48 hpf, present in the preoptic area and ventral hypothalamus (at protein level).
Isoform 1 and isoform 2 are expressed in brain and testis.
Expressed throughout the embryo, including the central nervous system.
Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Required for normal bone development. Inhibits Wnt signaling (By similarity).
Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity).
Belongs to the aminoglycoside phosphotransferase family.
Catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-lysine.
In the central section; belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.
Adults display microphthalmia, with eyes obscured by overgrown skin and misshapen irides. Mutants at 2 weeks of age show profound alterations in the morphology of individual photoreceptor subtypes and UV cones. At later timepoints loss of normal retinal lamination is observed, together with a disorganization of Mueller glia cells. Adults, cone photoreceptors are dysmorphic and reduced in abundance.
Expressed both maternally and zygotically. Expressed from early cleavage stage until blastula sphere stage. Expression is then barely detectable until the end of gastrulation (tailbud stage) when expression is resumed.
First expressed in late gastrula stage embryos (9.5 hours post fertilization (hpf)) in anterior neuroectoderm corresponding to the future dorsal part of the brain. Shortly after tailbud formation (11 hpf), expression expands to the entire neural region and is subsequently expressed in derivatives of the lateral neural plate and migrating neural crest cells, with the future midbrain and hindbrain showing strong expression. Also expressed weakly and transiently in the posterior embryo from 11.5 hpf to 15 hpf in the lateral mesoderm, and in ectoderm above the neural keel. At 14 hpf, expressed along the entire length of the embryo and starting around the 16-somite stage, expressed in the dorsal quadrant of the retina, representing the distal tip of the eye anlage. At this stage, also expressed in the hatching gland and the hypochord. At 24 hpf, expressed in the roof plate outlining the fourth brain ventricle, in the posterior hypochord, the primitive gut endoderm, the ventral tail mesenchyme, the dorsal part of the neural tube and the dorsal fin. Weakly expressed in the dorsal part of the posterior spinal cord and in blood cell precursors.
Growth factor that controls proliferation and cellular differentiation in the retina. Plays a key role in regulating apoptosis during retinal development. Establishes dorsal-ventral positional information in the retina and controls the formation of the retinotectal map. Functions maternally in dorsal/ventral patterning to induce the expression of the zygotic bmp2b and bmp4 genes and ventralize embryos. Zygotic expression does not appear to regulate axis specification, but instead functions to establish the integrity of the axial vessels during embryonic development. May be involved in maintaining the identity of cells of the dorsal-most neural tube and of at least a subset of neural crest 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.
Component of a PRC1-like complex (By similarity). Homodimer. Interacts with cbx2.
Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. In the PRC1 complex, it is required to stimulate the E3 ubiquitin-protein ligase activity of rnf2.
Maternally derived transcript is detected at high levels at 1 and 3 hours post-fertilization (hpf). Not detectable at 6 and 9 hpf. Detected at intermediate levels at 12 and 15 hpf. Highly expressed at 18 and 24 hpf, after which expression decreases again. Detected in the anterior embryo at the 6 somites stage. Detected in hindbrain, rhombomeres and telencephalon at the 18 somites stage. Restricted to the anterior embryo, including brain, otic vesicles, and optic stalks in 24 hpf embryo. Detected in pectoral fin buds in 48 hpf embryo.
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 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.
Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a. This receptor stimulates chemotaxis, granule enzyme release and superoxide anion production.
In adults, expression is restricted to the hair cells of inner ear and lateral line organ. Expressed at higher levels in the larval lateral-line neuromasts than in the larval inner ear.
Expressed in the embryonic neural tube, brain, pectoral fins and the pronephric glomerulus (at protein level).
Involved in vesicular recycling, probably as a GTPase-activating protein for Rab family protein(s).
Morpholino knockdown of the protein causes pericardial edema, retracted glomerulus in an enlarged Bowman's capsule and glomerular permeability defects.
The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.
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.
Expressed for a short period in the cells that will produce the enveloping layer (EVL).
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.
UTP--glucose-1-phosphate uridylyltransferase catalyzing the conversion of glucose-1-phosphate into UDP-glucose, a crucial precursor for the production of glycogen.
Involved in the lipid remodeling steps of GPI-anchor maturation.
Detected in larval gut, liver, exocrine pancreas and part of the brain and retina at 96 hpf.
Export receptor for importin alpha. Mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates have been released into the nucleoplasm (By similarity). Negatively regulates fluid secretion and plays a role in fluid homeostasis by down-regulating cftr activity (PubMed:20933420).
Morpholino knockdown of the protein causes strong expansion of the gut lumen, due to excessive fluid accumulation.
At 24 hpf, expression almost entirely restricted to the endothelial cells of the developing vasculature, with high levels in the major head and trunk vessels and also in the intersomitic vessels.
Morpholino knockdown of the protein causes profound defects in angiogenesis. Although sprouting of the intersomitic vessels occurs, the endothelial cells fail to extend fully across the intersomic region and there is no apparent formation of the dorsal longitudinal anastomosing vessel. No other obvious defect is observed in the developing morphant.
Required for developmental angiogenesis, but not for vasculogenesis.
Belongs to the arginase family. Agmatinase subfamily.
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).
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.
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.
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 (By similarity).
Detected in the presumptive ectoderm at the late blastula stage. During the gastrula stage, expression refines to the ventrolateral ectoderm and the dorsal-midline ectoderm. Expressed in primary neurons during the segmentation stage, with strongest expression in primary motoneurons and interneurons and lower expression in Rohon-Beard neurons. The expression domain is restricted to regions posterior of rhombomere 4. During the late segmentation and pharyngula stages, expression decreases in an anterior-to-posterior direction and is largely absent by 48 hours post-fertilization.
Morpholino knockdown of the protein results in impaired neurogenesis in posterior regions. Expression of the neural precursor marker ngn1 is reduced at the one- to three-somite stage. At later stages, there is a significant reduction in islet1-expressing primary motoneurons and defective axon outgrowth from motoneurons. Formation of Rohon-Beard neurons is initially abnormal but later recovers. Development of secondary neurons is not affected.
Transcriptional repressor. Activity as a repressor is enhanced by binding to the corepressor tle3a.
Carbohydrate-binding protein with a strong ligand preference for Glc2-N-glycan. May play a role in the early steps of protein N-glycosylation (By similarity).
Involved in the regulation of mitochondrial distribution and morphology. Required for mitochondrial fusion and mitochondrial network formation.
Belongs to the Mediator complex subunit 9 family.
Autophagy factor required for autophagosome formation.
May be involved in MAP kinase activation, epithelial sodium channel (ENaC) down-regulation and cell cycling.
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 metallophosphoesterase superfamily. LOC643853 family.
Belongs to the apolipoprotein C1 family.
Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
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.
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.
Probable component of the multiprotein Integrator (INT) complex.
Expressed at low levels during embryogenesis. Expressed in the ventral fin fold of the forming and extending tailbud and in the ventral regions of the neural tube.
Belongs to the eukaryotic ribosomal protein eL28 family.
Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (By similarity). Plays an essential role in early embryonic development (PubMed:12006978). May act as a haploinsufficient tumor suppressor (PubMed:15138505).
Embryos show various defects including an inflated hindbrain ventricle and smaller head and eyes. Mutant adults show an increased incidence of cancer, notably malignant peripheral nerve sheath tumors.
Acylglycerol lipase activity is activated upon binding to progesterone.
Progesterone-dependent acylglycerol lipase that catalyzes hydrolysis of endocannabinoid arachidonoylglycerol (AG) from cell membrane. Acts as a progesterone receptor: progesterone-binding activates the acylglycerol lipase activity, mediating degradation of 1-arachidonoylglycerol (1AG) and 2-arachidonoylglycerol (2AG) to glycerol and arachidonic acid (AA). Also displays an ester hydrolase activity against acetyl ester, butanoate ester and hexadecanoate ester. Plays a key role in sperm capacitation in response to progesterone by mediating degradation of 2AG, an inhibitor of the sperm calcium channel CatSper, leading to calcium influx via CatSper and sperm activation (By similarity). May also play a role in smooth muscle cells migration (By similarity).
Functions as an ammonia transporter. May play a role in the elimination of ammonia in the gill (By similarity).
Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes.
Binds DNA as a homotetramer. Isoform composition of the tetramer may determine transactivation activity.
May play a role in the regulation of microtubule organization and dynamics.
Interacts with XAF1, the interaction increases XAF1 stability and proapoptotic effects, and may regulate IFN signaling.
Expressed both maternally and zygotically. Uniform distribution at the cleavage, blastula, gastrula and early somitogenesis stages. Levels decline during the early gastrula stages. At 26 hours, still expressed in the head, forming gut and dorsal neural tube.
Involved in ventralization. May mediate Bmp2b signaling during early phases of embryonic dorsal-ventral pattern formation. Required for initiation of Smad1 expression during gastrulation.
May form trimers with the co-SMAD SMAD4.
May have a palmitoyltransferase activity toward substrates like ncdn, thereby regulating their association with membranes.
At 24 hours post-fertilization, expression is restricted to the tip of the developing tail.
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).
E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (By similarity). Recognizes and binds to proteins bearing specific N-terminal residues, leading to their ubiquitination and subsequent degradation (By similarity). Positively regulates hedgehog/shh-signaling pathways that function in eye development, neuronal specification and somite development (PubMed:27195754). Activation of shh up-regulates transcription of ubr3, which in turn promotes hedgehog/shh signaling possibly by controlling negative regulators such as Kif7 (PubMed:27195754).
Expressed in the embryonic retina, central nervous system and trunk (at the protein level).
Heterozygotes fail to form cohesive and stratified epithelium in their optic vesicles. Average somite angle is increased by 30% and the posterior central nervous system displays a gain of Rohon-Beard sensory neurons. Defects are the result of decreased Hh/shh-signaling demonstrated by the reduced expression of the Hh/shh target gene ptch2.
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.
NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.
C-terminus is a mobile self-inhibitory loop which interferes directly with active site.
Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products (By similarity). Contributes significantly to heme formation during erythropoiesis (By similarity).
May play a role in the regulation of the cation channel TRPM8 activity.
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.
In the C-terminal section; belongs to the NAD synthetase family.
Belongs to the PIGG/PIGN/PIGO family. PIGG subfamily.
Expressed both maternally and zygotically. Already present in fertilized eggs. Expression levels increase until the sphere stage and reduce gradually toward 24 hpf (at protein level).
In adults, expressed in the gonads, with expression much higher in the ovary than the testis (at protein level). Shows a small amount of expression in other adult organs, including the brain and kidney. Embryonic expression is mostly ubiquitous except in early gastrula embryos where expression is asymmetric.
TATA box-binding transcription factor (By similarity). Members of the TBP family are differentially required to regulate transcription and development during early embryogenesis. Commits mesoderm to the hematopoietic lineage during hemopoiesis, acting via mespa. Binds to the mespa promoter.
Heterodimer of KIF3A and KIF3B. KIF3A/KIF3B heterodimer interacts with KIFAP3 forming a heterotrimeric (KIF3A/KIF3B/KIFAP3) complex.
Loss of function of Kif3b only results in ciliogenesis defects in a subset of cilia. Robust cilia are still present in the central nervous system. Mutant have rapid rod degeneration and delayed outer segment genesis, but cones appear normal. The mild phenotype of kif3b mutants may be related to the presence of the kif3c protein.
Microtubule-based molecular motor that transport intracellular cargos, such as vesicles, organelles and protein complexes. Uses ATP hydrolysis to generate force to bind and move along the microtubule (By similarity). Plays a role in cilia formation. Required for photoreceptor development (PubMed:22308397, PubMed:28855254).
In embryos, expressed in mesencephalon with strongest expression ventrally. In adult, expressed in midbrain.
Not expressed maternally. Low levels from 13-24 hours post-fertilization (hpf). Also expressed in adult.
Morpholino knockdown of the gene results in early postnatal lethality and microcephaly.
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC2 subfamily.
First expressed by 30 hours post-fertilization (hpf) along the tract of the anterior commissure, where it persisted until 48 hpf. Detected at 48 hpf in the preoptic area, ventral thalamus, and ventral midbrain and weakly in the ventral hindbrain. At 72 and 96 hpf, expressed throughout most of the brain except the dorsal forebrain. Expressed in the retinal ganglion cells.
Probable cation channel with high affinity for sodium. In vitro, has no proton-gated channel activity.
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.
Adapter protein involved in invadopodia and podosome formation and extracellular matrix degradation.
The PX domain is required for podosome localization because of its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser extent, phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 domain (By similarity).
In embryos, expressed in mesencephalon with strongest expression dorsally, diencephalon, and rhombencephalon. During somitogenesis, anterior expression which partly overlaps the future eye field, gradually decreases while midbrain expression intensifies and becomes restricted to the presumptive tectum. In adult, strong expression in forebrain, midbrain and cerebellum.
Not expressed maternally. First detected at 9 hours post-fertilization (hpf), with high levels until 24 hpf. Also expressed in adult.
Required for eye and tectum development. May act as a transcriptional repressor.
Expressed at 10 hours and 12 hours in presumptive diencephalon. Expressed transiently at 12 hours in caudal telencephalon. Later expression in floor plate and somites, followed by rostral telencephalon and ventral thalamus. Expressed at 40 hours in hypothalamus.
Transcription factor (By similarity). Appears to be indispensable for the central nervous system development. May have a role in the neuronal differentiation of the ganglionic eminence and ventral thalamus. May also be involved in axonal guidance in the floor plate.
May regulate intracellular cholesterol transport.
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.
Morpholino knockdown of the protein in embryos results in severe disruption of muscle fibers.
Morpholino knockdown results in a dorsalized phenotype, with enlargement of the telencephalon and reduction of the tail at 24 hours post-fertilization. Expression of the dorsal marker goosecoid is expanded, whereas expression of the ventral markers eve1 and tbx6 is reduced. In addition, expression of the telencephalon marker opl and the midbrain/hindbrain boundary marker pax2.1 is expanded posteriorly.
Promotes phosphorylation of the Wnt coreceptor LRP6, leading to increased activity of the canonical Wnt signaling pathway. Facilitates constitutive LRP6 phosphorylation by CDK14/CCNY during G2/M stage of the cell cycle, which may potentiate cells for Wnt signaling. May regulate the transport and translation of mRNAs, modulating for instance the expression of proteins involved in synaptic plasticity in neurons. Involved in regulation of growth as erythroblasts shift from a highly proliferative state towards their terminal phase of differentiation. May be involved in apoptosis.
The C1q domain is essential for the function in Wnt signaling.
C2H2-type zinc-finger domains 6 and 9 are important for binding to the GGGGG motif in target DNA, and for the interaction with sox9a.
Detected in the notochord at 22-48 hours post-fertilization (hpf). Expressed in otic vesicles and pectoral fin at 48 hpf. Expressed in the hindbrain and midbrain-hindbrain boundary at 48-96 hpf.
Highly expressed in heart and brain. Also detected at lower levels in muscle and testis.
Morpholino knockdown of the protein results in a curved body axis (PubMed:24155663). Expression of col2a1a and sncgb in the developing notochord at 24 hours post-fertilization is significantly reduced (PubMed:24155663, PubMed:24269816).
Transcriptional regulator (PubMed:24155663, PubMed:24269816). Recognizes and binds to the core DNA sequence motif 5'-GGGGG-3' (PubMed:24155663, PubMed:24269816). Binds to the col2a1a promoter and activates col2a1a expression (PubMed:24155663). Binds to the sncgb promoter and activates sncgb expression, as part of a complex with sox9a (PubMed:24269816).
Calcium-regulated non-lysosomal thiol-protease.
Belongs to the GST superfamily. Zeta family.
Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to cysteines occuring in specific C-terminal amino acid sequences.
Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and RAB7A.
Belongs to the phosphatidylserine decarboxylase family. PSD-B subfamily. Eukaryotic type I sub-subfamily.
Catalyzes the formation of phosphatidylethanolamine (PtdEtn) from phosphatidylserine (PtdSer). Plays a central role in phospholipid metabolism and in the interorganelle trafficking of phosphatidylserine.
Heterodimer of a large membrane-associated beta subunit and a small pyruvoyl-containing alpha subunit.
Is synthesized initially as an inactive proenzyme. Formation of the active enzyme involves a self-maturation process in which the active site pyruvoyl group is generated from an internal serine residue via an autocatalytic post-translational modification. Two non-identical subunits are generated from the proenzyme in this reaction, and the pyruvate is formed at the N-terminus of the alpha chain, which is derived from the carboxyl end of the proenzyme. The autoendoproteolytic cleavage occurs by a canonical serine protease mechanism, in which the side chain hydroxyl group of the serine supplies its oxygen atom to form the C-terminus of the beta chain, while the remainder of the serine residue undergoes an oxidative deamination to produce ammonia and the pyruvoyl prosthetic group on the alpha chain. During this reaction, the Ser that is part of the protease active site of the proenzyme becomes the pyruvoyl prosthetic group, which constitutes an essential element of the active site of the mature decarboxylase.
Cell adhesion molecule involved in the establishment and/or maintenance of cell integrity. Involved in skeletal muscle and heart development as well as in the maintenance of heart function (PubMed:26642364). May play a role in vamp3-mediated vesicular transport and recycling of receptor molecules. 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 also be involved in striated muscle regeneration and in the regulation of cell spreading (By similarity).
Expressed in skeletal muscle (at protein level).
Morpholino knockdown of the protein causes cardiac edema in 70% of the injected morphants. They show malformed myotendinous junction and, in 80% of the morphants, skeletal muscle is characterized by myofibrillar misalignment and fiber detachment.
Sodium-independent transporter of chloride and iodide.
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(FEM1A) complex specifically recognizes proteins with an arginine at the C-terminus: recognizes and binds proteins ending with -Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons, leading to their ubiquitination and degradation.
Plays an important role in retinal cone photoreceptor survival (By similarity). May play a role in cone cell viability, slowing down cone degeneration, does not seem to play a role in degenerating rods (By similarity).
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.
Originally thought to be a histone deacetylase and shown in vitro to have this activity (By similarity). Has also been shown to be involved in MSH2 deacetylation (By similarity). However, protein deacetylase activity is a matter of debate, as 3D structure analysis shows that a glutamate gatekeeper and a sterically constricted active site confer specificity for N(8)-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. Supporting this observation, has been shown to exhibit only very low activity, if any, towards acetyl-lysine peptide substrates (By similarity).
Polyamine deacetylase (PDAC), which acts preferentially on N(8)-acetylspermidine, and also on acetylcadaverine and acetylputrescine (PubMed:28516954). Exhibits attenuated catalytic activity toward N(1),N(8)-diacetylspermidine and very low activity, if any, toward N(1)-acetylspermidine (PubMed:28516954). Has a very weak lysine deacetylase, if any (PubMed:28516954).
5'->3' double-stranded DNA exonuclease which may also contain a cryptic 3'->5' double-stranded DNA exonuclease activity. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for DNA mismatch repair (MMR) (By similarity).
Belongs to the XPG/RAD2 endonuclease family. EXO1 subfamily.
Belongs to the nucleoporin NSP1/NUP62 family.
Component of the BCR(KLHL12) E3 ubiquitin ligase complex.
Expressed ubiquitously throughout development.
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport. The BCR(KLHL12) complex is 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). Negatively regulates the Wnt signaling pathway, possibly via the targeted ubiquitination and subsequent proteolysis of dvl2 and dvl3 (PubMed:16547521). Regulates convergent-extension movements during early embryonic development (PubMed:16547521).
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.
Deubiquitinating enzyme that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN).
Belongs to the methyltransferase superfamily. RsmH family.
Plays an important role in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking. May catalyze the remodeling of phosphatidylglycerol and be involved in the transacylation-acylation reaction to produce phosphatidylglycerol-36:1. May be involved in bis(monoacylglycerol)phosphate biosynthetic pathway (By similarity).
Defects in circulating erythroid cells. Embryos are anemic despite normal expression of the erythroid cell markers. The erythrocytes from embryos that survive to adult stage exhibit hypochromic, microcytic anemia. Histological analysis of adult haematopoietic tissues does not show morphological defects. Defects are due to changes in the mitochondrial pH-and consequently the redox potential-to change to a level that reduces [2Fe-2S] cluster-containing fech activity, thereby reducing heme synthesis, resulting in hypochromic anemia.
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 (PubMed:23135403).
Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil composed of residues 73-105, leaving each N-terminal inhibitory region (residues 22-51) accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region (residues 22-51) 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).
A reversible disulfide bond can be formed between the two subunits in the homodimer; this has no effect on gdf2 activity.
Morpholino knockdown of the protein causes slight decreases in both anterior-posterior and dorsal-ventral axes, while trunk and tail anatomy are otherwise normal. Vascular patterning is relatively normal, although defects are detected in maturation of the caudal vein: the caudal venous plexus fails to resolve and both dorsal and ventral veins continue to carry blood flow.
Potent circulating inhibitor of angiogenesis. Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/eng.
Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC1 sub-subfamily.
Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Seems to be also activated by intracellular calcium store depletion.
Belongs to the 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.
Emrbyos show disruption of muscle architecture and greatly reduced motility. Embryonic muscle tissue display disorganization of the sarcomere and myofiber attachment defects (PubMed:17123513). Embryos show a defect in the generation and development of slow muscle fibers and a decrease in the expression of myogenic lineage genes in slow muscle cell precursors (PubMed:18713863).
Expressed in the anteroposterior axis and the notochord at 5 hours post-fertilization (hpf). Expressed in the eye inner cell layer of the retina at 48 hpf (PubMed:12915322). In the embryo expressed at high levels in the notochord, the tailbud, the presomitic mesoderm and the emerging somites. As the notochord and somitic muscle differentiate overtly, expression in these tissues is greatly reduced (PubMed:18713863).
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 (By similarity). Acts as a modulator of ryanodine receptor (RyR) activity: protects RyR from oxidation due to increased oxidative stress, or directly controls the RyR redox state, regulating the RyR-mediated calcium mobilization required for normal muscle development and differentiation (PubMed:18713863). Plays an important role in muscle development and differentiation during early development. Required for development of the slow muscle fiber lineage (PubMed:18713863). Required for the correct organization and attachment of the myofibrils, as well as for the continuity and integrity of the connective tissue that forms the myoseptum (PubMed:17123513).
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.
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 metallo-dependent hydrolases superfamily. Phosphotriesterase family.
Expressed in the forebrain, and in the prospective midbrain/hindbrain boundary during early somitogenesis. As development proceeds, also detected in the hindbrain, as well as in the apical fold of the developing pectoral fin, and this expression extends proximally.
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP9, the motif is inactive.
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.
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.
Required for ciliation. Recruits the RABL2B GTPase to the ciliary base to initiate ciliation.
Component of a DCX (DDB1-CUL4-X-box) protein ligase complex.
Highly expressed in brain, head, vasculature otic vesicles and developing pectoral fins.
Specific defects in fin and otic vesicle development.
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 (PubMed:20223979). 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).
Thalidomide is teratogenic in human, chicken and zebrafish, but not in mice. Binding of thalidomide and related drugs changes the substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, leading to decreased degradation of endogenous target proteins and increased degradation of other proteins that are not normal substrates. This is probably the underlying cause of the teratogenic activity of thalidomide, possibly due to abnormal regulation of the BMP and FGF8 signaling pathways.
May function as a co-chaperone towards HSPA9/mortalin which, by itself, is prone to self-aggregation.
Component of the lid subcomplex of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. In the complex, psmd11b is required for proteasome assembly (By similarity).
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). Plays a critical role in the assembly of N-DRC and also stabilizes the assembly of multiple inner dynein arms and radial spokes. Coassembles with DRC1 to form a central scaffold needed for assembly of the N-DRC and its attachment to the outer doublet microtubules.
Morpholino knockdown of the protein causes strong ciliopathy phenotypes, including pronephric cysts, axis curvature, left-right asymmetry defects and hydrocephalus. Cilia length and number appear normal, but cilia are dyskinetic.
Involved in pre-mRNA splicing, specifically in spliceosome disassembly during late-stage splicing events.
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).
Belongs to the replication factor A protein 2 family.
Modulates postsynaptic dendritic arbor elaboration and synaptic maturation.
May act as a GTPase-activating protein for Rab family protein(s).
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. CPSF2/YSH1 subfamily.
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).
By triiodothyronine (T3) and L-thyroxine (T4).
Expressed both maternally and zygotically. Expressed at the 1 cell stage (0 hpf) but disappears by the 2 cell stage. Expressed again from the 16 cell stage onwards. Embryonic expression increases dramatically around the hatching period. High expression then continues until 6 dpf, before declining.
In contrast to PubMed:10687864 and PubMed:11963654, PubMed:17418841 found that triiodothyronine (T3) did not induce expression in the embryo.
Interacts (via the ligand-binding domain) with ncoa2.
Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for the thyroid gland hormone triiodothyronine (T3). Transactivating activity is ligand-dependent, and is repressed in the absence of T3.
Widely expressed in a range of adult tissues including the brain, eye, fin, gill, intestine, liver, swim bladder and ovary. In the eye, expressed in the outer nuclear layer of the retina.
Interacts with TIMELESS, which impairs TIMELESS self-association.
Plays an important role in the control of DNA replication and the maintenance of replication fork stability.
Plays an important role in the control of DNA replication and the maintenance of replication fork stability. Important for cell survival after DNA damage or replication stress. May be required fin the replication checkpoint induced by hydroxyurea or ultraviolet light (By similarity).
Belongs to the bacterial ribosomal protein bS21 family.
Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM2 sub-subfamily.
At 24 and 48 hours post fertilization, expressed only in the heart.
Kinase that phosphorylates MYL2 in vitro (By similarity). Increases cardiomyocyte contractility (By similarity). Required for sarcomere formation in the developing heart.
Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity. Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac), regulating DNA replication initiation, regulating DNA replication initiation.
The 2 PHD-type zinc fingers are required for transcriptional activity.
Homohexamer (PubMed:30961891). Interacts with RAD51 (PubMed:30961891).
Phosphorylated. Phosphorylations at Ser-566 and Ser-567 allow efficient removal of RAD51 filaments from DNA.
Plays an essential role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks (PubMed:30961891). Acts as a molecular motor during the homology search and guides RAD51 ssDNA along a donor dsDNA thereby changing the homology search from the diffusion-based mechanism to a motor-guided mechanism. Also plays an essential role in RAD51-mediated synaptic complex formation which consists of three strands encased in a protein filament formed once homology is recognized. Once DNA strand exchange occured, dissociates RAD51 from nucleoprotein filaments formed on dsDNA (By similarity).
Appears to function in the signal transduction from Ras activation to actin cytoskeletal remodeling.
Regulator which is able to repress transcription, possibly via its interaction with a multiprotein chromatin remodeling complex that modifies the chromatin.
Activated by phosphorylation on a serine residue.
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response.
Stimulated by agonists such as ATP, EGF, thrombin and bradykinin as well as by cytosolic Ca(2+).
The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca(2+) (By similarity).
Mitochondrial GTPase that catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. Does not mediate the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis.
Belongs to the Mediator complex subunit 16 family.
Probable GTP-binding protein that possesses GTPase activity. May play a role in endothelial cell polarity and endothelial barrier function (By similarity).
G-protein coupled receptor expressed in lymphocytes that acts as a chemotactic receptor for B-cells, T-cells, splenic dendritic cells, monocytes/macrophages and astrocytes (By similarity). Receptor for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and other related oxysterols (By similarity). Mediates cell positioning and movement of a number of cells by binding the 7-alpha,25-OHC ligand that forms a chemotactic gradient (By similarity). Binding of 7-alpha,25-OHC mediates the correct localization of B-cells during humoral immune responses (By similarity).
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.
Although it is highly related to enolase enzyme family, lacks the conserved Glu active site.
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.
Detectable from a late gastrula stage (10 hpf). Very weakly expressed in the midbrain region at the 14-somite stage. Expression in the midbrain intensifies and extends along the anterior- posterior axis as embryogenesis proceeded. At 2 dpf, strongly expressed in the developing eyes and midbrain region. At 3 dpf, expressed in the retina.
Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) (By similarity). Required for proper cerebellum development (By similarity).
Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.
Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively (By similarity). Phosphorylates ceramide but not sphingosine (By similarity). Phosphorylates 1,2-dioleoylglycerol more rapidly than 2,3-dioleoylglycerol (By similarity). Independently of its lipid kinase activity, acts as a component of the TIM22 complex (By similarity). The TIM22 complex mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane by forming a twin-pore translocase that uses the membrane potential as the external driving force (By similarity).
Belongs to the glycosyl hydrolase 99 family.
Mediates sulfate transport with high affinity. Mediates oxalate transport. Mediates bicarbonate transport. Does not accept succinate as cosubstrate.
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.
Probably maternally supplied, the zygotic expression becomes significative at the 512-cell stage and increases until 10 hpf and then decreases but is still detected at 24 hpf.
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions.
Calcium-selective channel required to prevent calcium stores from overfilling, thereby playing a key role in calcium homeostasis (PubMed:27212239). In response to endoplasmic reticulum (ER) overloading, assembles into a homotetramer, forming a functional calcium-selective channel, regulating the calcium content in endoplasmic reticulum store (By similarity). Necessary for the biogenesis and transport of multi-pass membrane proteins into the ER membrane (By similarity).
Homodimer and homotetramer. Component of the ribosome-associated ER translocon complex.
Belongs to the SMC family. SMC2 subfamily.
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Inhibited by ketoconazole. May also be inhibited to a lesser extent by propiconazole.
Strongly expressed in intestine. Moderately expressed in liver, with higher levels in females compared to males. Also detected at low levels in brain, eye, kidney and testis.
Interacts with DDX4, PIWIL1, RANBP9 and TDRD1.
Belongs to the NAD(P)-dependent epimerase/dehydratase family. GDP-mannose 4,6-dehydratase subfamily.
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 potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily.
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.
Although this protein contains the conserved Asp-262 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 class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT8 subfamily.
Homodimer. Tetramer; individual homodimers associates to form a homotetramer. Homooctamer; individual homodimers associates to form a homooctamer and homooligomerization is required for proper localization to the cell membrane.
S-adenosyl-L-methionine-dependent and membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA).
The N-terminal region (1-60) inhibits the arginine N-methyltransferase activity.
Belongs to the NADPH--cytochrome P450 reductase 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.
Isomerase activity is increased by sulfhydril compounds. Dithiothreitol (DTT) is most effective, followed by glutathione (GSH) and 2-mercaptoethanol.
Isomerase that catalyzes the conversion of PGH2 into the more stable prostaglandin E2 (PGE2) (in vitro). The biological function and the GSH-dependent property of PTGES2 is still under debate (By similarity). In vivo, PTGES2 could form a complex with GSH and heme and would not participate in PGE2 synthesis but would catalyze the degradation of prostaglandin E2 H2 (PGH2) to 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid (HHT) and malondialdehyde (MDA) (By similarity).
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA1 sub-subfamily.
Belongs to the helicase family. Dicer subfamily.
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.
Expressed maternally and throughout embryogenesis. Expressed in the dorsal mesoderm at 6 hours post fertilization (6 hpf), and this expression is maintained in the axial mesoderm during gastrulation and early somitogenesis. Strongly expressed in the prospective neuroectoderm at 8 hpf. Expression persists in the neuroectoderm and increases in the tail bud at the end of gastrulation, at 10 hpf. Enriched in the prechordal mesoderm and developing notochord and in ventromedial regions of the brain and neural tube during the early somite stages. Expression remains elevated within the tail bud, forebrain, the midbrain-hindbrain boundary and in the developing otic vesicles as somitogenesis progresses.
Participates in the Wnt signaling pathway. Probably binds to DNA and acts as a repressor in the absence of ctnnb1, and possibly as an activator in its presence. Required early in development for dorsal specific gene activation and during gastrulation for repression of dorsal-specific genes in the marginal zone. Required for head formation and forebrain specification. Regulates anterior-posterior patterning in the neuroectoderm by repressing posterior neural fates.
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).
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. Mitochondrial glutathione is required for the activity and stability of proteins containing iron-sulfur clusters, as well as erythropoiesis (By similarity). Involved in the early steps of heme biosynthesis (PubMed:19656490).
Morpholino knockdown of the protein results in profound anemia without affecting erythroid specification. No porphyric phenotype detected.
Cell surface hyaluronidase that mediates the initial cleavage of extracellular high-molecular-weight hyaluronan into intermediate-size hyaluronan (PubMed:28118600). Acts as a regulator of angiogenesis in embryos by mediating degradation of extracellular hyaluronan, thereby promoting VEGF signaling (PubMed:28118600). Acts as a regulator of heart development during myocardial and endocardial morphogenesis: involved in the looping stage of heart morphogenesis (PubMed:21896629). Stimulates migration of endocardial cells and increases both myocardial and endocardial fusion (PubMed:21896630). Involved in the restriction of endocardial cushions (ECs) formation to the atrioventricular canal (AVC) (PubMed:21896630). Also required for muscle fiber attachment (PubMed:27471259). Is very specific to hyaluronan; not able to cleave chondroitin sulfate or dermatan sulfate (By similarity).
Embryos show defects in heart morphogenesis: while heart development is normal at the linear heart tube stage, cardiac looping is lost at later developmental stages (PubMed:21896629). Defects during the endocardial morphogenesis, characterized by the formation of ectopic atrioventricular canal in the ventricular myocardium and endocardium (PubMed:21896630). Maternal-zygotic mutants also display muscle fiber detachment, associated with impaired laminin organization and ineffective fibronectin degradation at the myotendinous junction (PubMed:27471259). Defects in angiogenesis, characterized by embryos with no venous sprouting (PubMed:28118600).
Expressed both maternally and zygotically. Expressed at the 2 cell stage. Ubiquitously expressed at the 22-somite stage. Expressed in the brain and head mesenchyme, otic vesicles, fin buds, caudal vein and the heart (both myocardial and endocardial cells) at 24 hours post fertilization (hpf).
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 (By similarity).
Acts as a regulator of Wnt signaling pathway by regulating beta-catenin (ctnnb1) nuclear localization (PubMed:25183871). Required for appendage regeneration by regulating cell proliferation (PubMed:19014929).
Following amputation, expressed in regenerating tissues (PubMed:19014929).
Loss of posterior structures and beta-catenin (ctnnb1)-dependent gene transcription due to the absence of accumulation of beta-catenin (ctnnb1) in the nucleus (PubMed:25183871). Fishes show reduced regenerative outgrowth following amputation due to decreased cell proliferation (PubMed:19014929).
Mainly expressed in proliferating tissues (PubMed:19014929).
Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters. May play a role in the establishment of polarity in the nervous system.
Proteolytic processing by tiki1 and tiki2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of wnt8b.
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 chchd4/mia40 in mitochondria.
Localized to the lens of early embryos (48 hpf), particularly in lens fiber cells (at protein level). In the adult, expression is highest in the eye but is also present in oocytes, brain and intestine.
The galectin domain, in contrast to the one in mammalian ortholog, is a functional carbohydrate-binding galectin.
Weakly expressed in embryos as early as 21 hpf, and strongly expressed at least up to 7 dpf.
Belongs to the Mediator complex subunit 17 family.
Belongs to the polypeptide deformylase family.
Removes the formyl group from the N-terminal Met of newly synthesized proteins.
Microtubule inner protein involved in the attachment of outer dynein arms (ODAs) to dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. Functions at the initial step of left-right asymmetry specification of the visceral organs.
Kinase activity is activated upon binding to GTP-bound Rho/Rac GTPases. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-809 (activation loop of the kinase domain) and Thr-951 (turn motif), may be needed to be phosphorylated for its full activation (By similarity).
Pkc-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. May play a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion and transcription activation signaling processes (By similarity).
Belongs to the myelin basic protein family.
Belongs to the eukaryotic ribosomal protein eL15 family.
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). PAF1C seems to be required for multiple steps in cardiac formation. Involved in heart development and required for differentiation of the atrioventricular boundary. Required for neural crest cell development.
Cholesterylation is required for N-product targeting to lipid rafts and multimerization.
First detectable at the mid-gastrula stage. Disappears at the end of the somitogenesis.
Interacts with BOC and CDON. Interacts with PTCH1 (By similarity). Interacts with glypican GPC3 (By similarity).
N-palmitoylation by HHAT of N-product is required for indian hedgehog protein N-product multimerization and full activity.
The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity). The N-product is the active species in both local and long-range signaling, whereas the C-product is degraded in the reticulum endoplasmic (By similarity).
The C-terminal part of the indian hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity). Both activities occur in the reticulum endoplasmic (By similarity).
The dually lipidated indian hedgehog protein N-product is a morphogen which is essential for a variety of patterning events during development. Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity). In the notochord, induces somite patterning and muscle pioneer differentiation (PubMed:8684485).
In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gln residues in position and 65, which is replaced by a Leu residue, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins.
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.
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).
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.
Activated by the phospholipids cardiolipin, phosphatidylserine, and phosphatidylethanolamine. Strongest activation with cardiolipin.
Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide.
Expressed both maternally and zygotically. Zygotic expression occurs in two stages: late blastulation/early gastrulation with greatest expression in the embryonic shield; and during segmentation with expression in the somites and presomitic mesoderm.
Involved in dorsal-ventral embryonic patterning, by promoting expression of bone morphogenetic protein (BMP) antagonists such as chd. Also involved in anterior-posterior neural patterning and in mesoderm induction.
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.
Highly expressed during early development and then ubiquitously expressed at very low levels at later larval stages.
Interacts (via PDZ-binding motif) with disheveled proteins; leading to the localization of dishevelled proteins to specific membrane subdomains.
Morpholino knockdown of the protein exacerbated the convergence/ extension (C/E) phenotypes of other planar cell polarity (PCP) family member mutants (vangl2, scribbled).
Most adhesion GPCRs proteins undergo autoproteolysis at the GPS domain. ADGRA3 is predicted non-cleavable because of the lack of a consensus catalytic triad sequence within GPS domain.
Orphan receptor that acts as a critical modulator of planar cell polarity during gastrulation. Controls the localization of dishevelled.
Ubiquitously expressed at very low levels.
Essential for hemidesmosome formation and maintenance of the cytoskeleton elements as well as cellular morphology in the basal epidermis during development. Also involved in regulating growth of the basal epidermis.
In larvae, basal epidermal cells migrate to ectopic places and hyper-proliferate.
Despite its name, the human homolog of this protein appears to lack measurable glycerol-3-phosphate acyltransferase activity under some conditions (PMID:19318427).
May transfer the acyl-group from acyl-coA to the sn-1 position of glycerol-3-phosphate, an essential step in glycerolipid biosynthesis. Also transfers the acyl-group from acyl-coA to the sn-2 position of 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid, or LPA), forming 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid, or PA) (By similarity).
During embryonic development, expressed dynamically in the developing hindbrain, kidney (pronephros), gut, liver and pancreas; expressed in both intermediate mesoderm (precursor to the kidney) and the caudal hindbrain (including rhombomeres r5 and r6) at 10 hpf with expression diminishing caudally by 14 hpf. Strongly expressed in adult kidney, gut, liver and swim bladder; weakly expressed in brain, eye, testis, ovary and heart.
Expressed both maternally and zygotically. Significantly expressed after the onset of gastrulation and throughout embryonic development.
Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (By similarity). Required for induction of rhombomere r5/r6 gene expression in the hindbrain.
Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins.
Catalyzes the transport of triglyceride between phospholipid surfaces (PubMed:17924655). Catalyzes the transport of cholesteryl ester, and phospholipid between phospholipid surfaces (By similarity). Required for the assembly and secretion of plasma lipoproteins that contain apolipoprotein B (PubMed:22581286, PubMed:17924655). Required for yolk lipid utilization and absorption of dietary lipids in larvae (PubMed:17176039).
Detected in the blastoderm margin by 4 hours post-fertilization (hpf). Expressed in the yolk syncytial layer (YSL) from 9 hpf to 24 hpf. By 48 hpf expression decreases in the extraembryonic YSL and is detected in the embryonic liver primordium and intestinal tube in which strongly expressed by 4 days post-fertilization (dpf). At 6 and 15 dpf expression is restricted to the two main liver lobes and the anterior part of the intestine including the intestinal bulb, but not detected in the pharynx or posterior intestine. Expressed in the enterocytes of the anterior part of intestine as well as in the hepatic cells in 15 dpf larvae. The total level of expression is very small before 2 hpf, increasing significantly between 2 and 5 hpf, and remaining high at 6 and 9 hpf. A significant decrease in the expression level is detected at 12 hpf and low level remains until the end of embryogenesis, which occurs by 72 hpf.
Expression is strongly up-regulated in the anterior intestine and to a lesser extent in liver in response to feeding in both larvae and adults (at protein level) (PubMed:15614773). Protein levels are not changed in 1 or 6 hours after feeding (PubMed:17176039).
Heterodimer; heterodimerizes with the protein disulfide isomerase.
Highest expression in the proximal part of the anterior intestine. Lower expression in the distal part of the anterior intestine, in the posterior portion of the intestinal tube and liver. Very low expression levels in heart, brain, ovary, testis and kidney.
Larvae do not absorb dietary neutral lipids, consume very little yolk, are small and die by 6 days post-fertilization (dpf) with pronounced edema. No defects in intestinal absorption of short chain fatty acids. Loss of visualization of neutral lipids in the vasculature, heart and head structures by oil red o staining. Levels of apolipoprotein B, vitellogenin and lipovitellin unchanged. No cardiovascular defects or global intestinal function impairment. Increased expression of Foza2 and Pgc1 proteins (PubMed:17176039). Leads to excess angiogenesis and yolk absorption defects. Decreased mRNA levels of flt1 at 24 hours post-fertilization (hpf) with no change in the mRNA levels of kdrl or flt4 or in other vascular genes (PubMed:22581286).
Belongs to the 'GDSL' lipolytic enzyme family. Phospholipase B1 subfamily.
Involved in teeth and skeletal development (PubMed:29878199). Has an essential role in the biosynthesis and trafficking of glycosaminoglycans and glycoproteins to produce a proper functioning extracellular matrix (By similarity). Required for extracellular matrix mineralization (PubMed:29878199). Also involved in the regulation of cellular calcium homeostasis (By similarity). Does not show transport activity towards bile acids or steroid sulfates.
Morphants have reduced head and eyes, a curled body, tooth cartilage that is bent downwards, reduced Meckel cartilage, absence of the fourth ceratobranchial cartilage, shortened or absent palate cartilage, widened palatal skeleton, reduced cleithrum, notochord, and lack of bone mineralization.
By phenylethyl alcohol (PEA) in the olfactory sensory epithelium.
Expressed specifically in Purkinje cells in the brain.
Belongs to the methyltransferase superfamily. HEN1 family.
Defects in germ cell development due to reduced piRNAs levels.
Expression in gonads starts around 3 weeks of age, which corresponds to the start of sex determination. Expression remains present in the adult gonads, both in males and females, although expression is weaker in testis.
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 and adenylation activities and subsequent degradation. Stabilization of piRNAs is essential for oocyte development.
Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts. Promotes T-cell activation and proliferation via its interactions with CD6 (By similarity). Contributes to the formation and maturation of the immunological synapse via its interactions with CD6 (By similarity). Mediates homotypic interactions with cells that express ALCAM. Mediates attachment of dendritic cells onto endothelial cells via homotypic interaction. Inhibits endothelial cell migration and promotes endothelial tube formation via homotypic interactions. Required for normal organization of the lymph vessel network. Required for normal hematopoietic stem cell engraftment in the bone marrow. Plays a role in hematopoiesis; required for normal numbers of hematopoietic stem cells in bone marrow. Promotes in vitro osteoblast proliferation and differentiation (By similarity). Promotes neurite extension, axon growth and axon guidance; axons grow preferentially on surfaces that contain ALCAM (By similarity). Mediates outgrowth and pathfinding for retinal ganglion cell axons (By similarity).
Expressed during axonogenesis in a subset of developing sensory and motor neurons that fasciculate with each other in the central nervous system (PubMed:8089660). Expressed in the retinotectal system of both embryos and adults, with expression in all retinal ganglion cells (RGC) during embryogenesis but only some RGCs in adults (at protein level) (PubMed:8026643).
Homodimer. Interacts (via extracellular domain) with CD6 (via extracellular domain). Homodimerization and interaction with CD6 involve the same region and cannot occur simultaneously. The affinity for CD6 is much higher than the affinity for self-association.
The CD6 binding site is located in the N-terminal Ig-like domain.
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The order of potency for this receptor is dexmedetomidine > norepinephrine > epinephrine.
Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2C sub-subfamily.
May function as a negative regulator of endoplasmic reticulum-stress induced autophagy.
May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols.
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.
Involved in the biogenesis of the 60S ribosomal subunit in the nucleus.
Belongs to the selenophosphate synthase 1 family.
In the embryo, expressed in retina, olfactory vesicles, tectum, pronephros ducts and myotomes at 24 hours post-fertilization and in retina, tectum, liver and intestinal bulb 3 days after fertilization.
Expressed just before gastrulation in a narrow region on the dorsal side of the embryo. Expression can be detected in the involuted cells comprising the mesendoderm of the developing axis. At the end of gastrulation expression is turned on in the ventral neural plate in cells adjacent to the axial-expressing mesodermal cells.
May play a crucial role in specification of both the axial mesendoderm and the ventral nervous system.
Mediates the hydrolysis of oxidized nucleoside diphosphate derivatives. Hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. Hydrolyzes 8-oxo-dGDP and 8-oxo-GDP with the same efficiencies. Hydrolyzes also 8-OH-dADP and 2-OH-dADP. Probably removes oxidized guanine nucleotides from both the DNA and RNA precursor pools (By similarity).
At the 10-somite stage, expressed in the paraxial mesoderm with an anterior expression limit posterior to the last somite. At the 20-somite stage, expressed within the developing CNS with an anterior expression limit adjacent to the somite 10/11 boundary.
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).
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.
Sulfate transporter. May play a role in endochondral bone formation.
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.
Heterodimer of a catalytic subunit qtrt1 and an accessory subunit qtrt2.
Expressed from the late gastrulation/early segmentation stage in the midbrain/hindbrain boundary (MHB) and in the posterior trunk region. Subsequently, its expression is restricted in the tail bud region and notochord. At 22 hrs after fertilization (hpf), high level expression is observed in the notochord and MHB. The tail bud expression declined by 30 hpf. Notochord expression declines at 48 hpf and disappears by 72 hpf although low level MHB expression remains until 72 hpf (PubMed:19874420).
May specifically influence certain angiogenesis process (PubMed:19874420).
Morpholino knockdown of the protein causes disorganized intersegmental vessels in the trunk.
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily.
Belongs to the RFamide neuropeptide family.
Expressed in a caudal domain whose anterior boundary expands from the r3/r4 boundary during late gastrulation to r2 during somitogenesis stages. Also expressed at the midbrain to hindbrain boundary by the 3-somite stage, where expression intensifies by the 6 somite stage. Also expressed in the spinal cord and tailbud.
Self-associates. Interacts with nlz2. May interact with Groucho corepressor proteins.
Transcriptional corepressor which does not bind directly to DNA and may regulate transcription through recruitment of histone deacetylases to gene promoters. Required for segmental gene expression during hindbrain development. May regulate cell adhesion, migration and proliferation.
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.
Acts as an important regulator of embryogenesis through its enhancement of Wnt/beta-catenin signaling. Positively regulates Wnt/beta-catenin signaling by ensuring phosphorylation of lrp6 specifically in plasma membrane rafts and its subsequent internalization into signaling-competent vesicles. Essential for the wnt8-mediated patterning of the mesoderm and neuroectoderm during gastrulation (PubMed:23987510).
Initially detected in mesendodermal cells at late blastula stages. During gastrulation, expressed in a broad marginal domain and becomes excluded from the ventral animal pole at late gastrula stages. During segmentation, initially exclusively detected in the somitic mesoderm but later also in the otic and optic vesicles. During organogenesis, expression is largely down-regulated in the somites but maintained in the otic vesicles and the retina.
Interacts with fzd8 and lrp6 (PubMed:23987510).
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.
Utilization of purines as secondary nitrogen sources, when primary sources are limiting.
Catalyzes the aminoacylation of histidyl-tRNA.
Danio rerio genome encodes a single hars gene which undergoes alternative splicing to produce both a cytoplasmic and mitochondrial enzyme, while humans have two separate genes.
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.
Component of a calcium channel complex with CACNA1S.
Expressed during embryogenesis (at protein level).
Expressed in muscles at the muscle triad.
Required for normal excitation-contraction coupling in skeletal muscle and for normal muscle contraction in response to membrane depolarization (PubMed:23736855). 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 (By similarity).
The mutants mi34 that do not express the protein exhibit altered motor behavior most probably due to a defect in the coupling between the electrophysiological activation and the muscular response. The nervous system, the neuromuscular junction or the skeletal muscles seem normal.
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.
Autophosphorylation at Tyr-429 maintains enzyme activity.
Expressed in unfertilized eggs (at protein level). Most highly enriched in the cortex of the newly fertilized egg. Becomes concentrated in the blastodisc by 30 minutes post-insemination and remains distributed among all regions of the embryo, excluding yolk. In the pharyngula stage (24 hours post-fertilization), observed all over the embryo, with highest levels in the eyes and central nervous system and somites (at protein level).
Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, differentiation, G2/M progression and cytokinesis (By similarity). Required for convergent extension cell movements during gastrulation, acting with fyna via rhoa. May be required for epiboly to occur, possibly through its effects in calcium signaling. During embryonic development, phosphorylates ptk2.1/fak.
Palmitoylation at Cys-3 promotes membrane localization.
Abnormalities in the brain starting at midsomitogenesis stages.
Ribosome biogenesis factor. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I. Required for cell survival in the CNS through its role in rRNA synthesis and processing.
Belongs to the PC-esterase family. CASD1 subfamily.
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).
Maintains high levels of reduced glutathione in the cytosol.
Component of the small nucleolar ribonucleoprotein particle containing H/ACA-type snoRNAs (H/ACA snoRNPs) (By similarity). Component of the telomerase holoenzyme complex (By similarity).
In the N-terminus possesses a conserved OCA domain for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif (5'-ATGAAAT-3').
Transcriptional coactivator that may regulate cell type-specific differentiation pathways.
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).
Expressed in the embryonic anterior presomitic mesoderm and in newly formed somites.
Named after the expression pattern, which decreases in a posterior to anterior direction in somites like a ripple.
Plays a role in somitogenesis. Essential for transcriptional repression of the segmental patterning genes, thus terminating the segmentation program in the presomitic mesoderm, and also required for the maintenance of rostrocaudal polarity in somites.
Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP2/CFD1 subfamily.
Belongs to the IspD/TarI cytidylyltransferase family. IspD subfamily.
Cytidylyltransferase required for protein O-linked mannosylation (PubMed:22522421). Catalyzes the formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate (By similarity). 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).
Hydrocephalus and incomplete brain folding by 48 hours post fertilization (h.p.f.), as well as significantly reduced eye size reminiscent of microphthalmia in patients suffering of muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies in human.
Adenosyl-L-methionine (AdoMet)-dependent tRNA (uracil-O(2)-)-methyltransferase.
Expressed in intermediate to anterior presomitic mesoderm.
Morpholino knockdown of the protein results in a complete inhibition of the segmentation of the presomitic mesoderm.
T-box transcription factor involved in the development of paraxial mesoderm.
Expression in elevated in ciliated tissues/organs, including brain, spinal cord, kidney, eyes, ears and lateral line.
Interacts with PCM1. Interacts with the complex TPGC. Binds to alpha-tubulin.
Mutants survive to adulthood and produce offspring (PubMed:34782749). Embryos show a significant defect in heart looping, with an increased proportion of embryos without a looped heart (PubMed:34782749). the They have an increased percentage of ciliated cells and ciliary length in Kupffer's Vesicle, although these alterations are not observed in the ear, pronephros or neural tube (PubMed:34782749).
Regulator of the tubulin polyglutamylase complex (TPGC) that controls cytoskeletal organization, nuclear shape, and cilium disassembly by balancing microtubule and actin assembly. Regulates the assembly and stability of the TPGC and thereby modulates polyglutamylation of the microtubule, which antagonizes MAP4 binding.
In double morpholino knockdown of tp53 and yju2, tp53 deficiency rescues animals from developmental neurodegeneration observed on yju2 mutants and radiosensitivity.
Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Interacts with SQSTM1.
First detected in the retina at 51 hours post fertilization (hpf) along the nasal edge of the choroid fissure. By 55 hpf expression has extended into the nasal region and by 72 hpf it covers the whole retina.
Retinal double cone principal photoreceptor cell outer segments.
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.
May be a centrosome-associated protein. Interacts with MYOC; affects its secretion and its aggregation.
Belongs to the AAA ATPase family. BCS1 subfamily.
Chaperone necessary for the assembly of mitochondrial respiratory chain complex III.
Belongs to the NAD(P)H dehydrogenase (quinone) family.
Inhibited competitively by AMP and IMP and non-competitively by fructose 1,6-bisphosphate.
Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.
Involved in protein trafficking. May serve as a receptor for ARFRP1.
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 ARISC complex. Component of the BRCA1-A complex. Component of the BRISC complex. Binds polyubiquitin.
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.
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.
Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase) (By similarity).
The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one.
Belongs to the Mediator complex subunit 20 family.
Embryos display peripheral heart edema and tail defects along with ciliopathy-related phenotypes, including hydrocephalus, abnormal ear otolith formation and smaller eyes.
Expressed in various ciliary organs, including Kupffer's vesicle, ear and heart, as well as brain and kidney.
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.
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.
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.
Involved in calcium binding and microtubule stabilization.
Detected in embryos just before the bud stage, in an oval patch in the polster (anterior prechordal plate) (PubMed:9108332). At the 3-somite stage, found in a horseshoe-shaped cluster of cells surrounding the head primordium (PubMed:9108332). From 24 hours post-fertilization (hpf) onwards, expressed in a belt-like shape on the anterior surface of the yolk sac (PubMed:9108332, PubMed:19021768). Little or no expression detected after hatching (PubMed:9108332, PubMed:19021768).
Expressed in cells of the hatching gland.
Metalloendopeptidase which participates in the breakdown of the egg envelope at the time of hatching. Cleaves the N-terminal regions of the zona pellucia glycoproteins ZP2 and ZP3, where it specifically recognizes the peptide sequences TVQQS-|-DYLIK (major site) and KLMLK-|-APEPF (minor site).
Expression increases between 20 and 48 hours after fertilization and is detected in sprouting intersegmental vessels (PubMed:21835952). At 24 hours after fertilization, expressed throughout the embryo with high levels in eye, mesencephalon and hindbrain boundaries (PubMed:25959397).
Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine) (By similarity). Acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation (By similarity). 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) (By similarity). 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 (By similarity). LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency (By similarity). Involved in epithelial to mesenchymal transition (EMT) and participates in repression of E-cadherin, probably by mediating deamination of histone H3 (By similarity). 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 (By similarity). Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding (PubMed:21835952). Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation (By similarity). Required with loxl2b for correct expression of Sox2 and for neural differentiation (PubMed:25959397).
Morpholino knockdown in the embryo prevents the formation of intersegmental blood vessels (PubMed:21835952). Morpholino knockdown of loxl2a and loxl2b in the embryo results in increased expression of Sox2 in the central nervous system, particularly in the eye, hindbrain and spinal cord (PubMed:25959397). It also leads to impaired neural differentiation with morphological defects in the brain where the anterior brain is rounder than normal and the eyes present a flatter curvature (PubMed:25959397). Embryo development is also compromised (PubMed:25959397).
Expressed in the axial mesoderm, notably, in the notochordal precursor cells immediately before formation of the notochord and in the chordoneural hinge of the tail bud, after the notochord is formed. In addition, its expression is detected in the ventral forebrain, sensory neurons, fin buds and excretory system.
Expression seen in many tissues of ectodermal and mesodermal origin during embryogenesis. First detected at bud stage in the ventral prosencephalon and along the length of the notochord. As segmentation proceeds, expressed in the optic primordia, otic placodes and diffusely in cells over the yolk lying ventrally to the tail bud. Midway through the segmentation period, expression also seen in the acostic and lateral line sensory ganglia. At 22 hpf, found in the most posterior portion of the pronephric ducts (PubMed:10664151). At the end of gastrulation, expression seen in the prospective ventral forebrain, single eye field and the presumptive notochord. At 12 hpf, expression in the midline found only at the posterior end of the notochord where it can be detected until the end of segmentation. At 20 hpf, expression in the eye is restricted to the dorsal retina and also found in the epiphysis, otic vesicles and sensory neurons of cranial ganglia. At 22 hpf, expressed in bud of pectoral fins and at 30 hpf, in a subset of interneurons in the anterior spinal cord (PubMed:10331981).
Loss of atrioventricular canal formation and cardiac looping.
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). Involved in the transcriptional regulation of genes required for mesoderm differentiation. Plays a role in the specification of late notochordal precursor cells and formation of the differentiated notochord. Required for cardiac atrioventricular canal formation.
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 H2AZ1 forms a heterodimer with H2B (By similarity).
Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. May be involved in the formation of constitutive heterochromatin. May be required for chromosome segregation during cell division (By similarity).
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.
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 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.
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). May play a role in differentiation during retinal development.
Isoform 1 is predominantly expressed in neural tissues. Isoform B is expressed ubiquitously. In the developing retina, it is expressed in progenitors throughout the retina at early stages and becomes restricted to the ganglion cell layer and ciliary marginal zone as differentiation proceeds.
Differentiation factor required for neurogenesis. Acts as an upstream activator of isl1.
Embryonic olfactory bulbs. In adult, expressed in brain, eye, intestine, muscle, ovary and skin.
Maternally expressed. At 24 hours post-fertilization (hpf), expressed mainly in head region.
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 (By similarity). Required for dorsal/ventral pattern formation.
Carbamylation allows a single lysine to coordinate two divalent metal cations.
Catalyzes the synthesis of beta-citryl-L-glutamate and N-acetyl-L-aspartyl-L-glutamate. Beta-citryl-L-glutamate is synthesized more efficiently than N-acetyl-L-aspartyl-L-glutamate.
N-acetyl-L-aspartyl-L-glutamate (NAAG) is the most abundant dipeptide present in vertebrate central nervous system (CNS). Beta-citryl-L-glutamate, a structural analog of NAAG, is present in testis and immature brain.
First detected in the developing viscera at 30 hours. Expression is gone by 5 days.
Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (By similarity).
Expressed both maternally and zygotically. Maternal expression is weak and zygotic expression is strong by the 30% epiboly stage. At the gastrula stage, expressed in all prospective neural tissue with the exception of a band of cells in the prospective midbrain and hindbrain. At the tail bud to 3-somite stage, expressed in distinct regions of the future brain, the anterior margin of the neural plate and the primordia of the epibranchial placodes. At the 12-somite stage, broad expression in the central nervous system (CNS), with weakest expression at the forebrain-midbrain and midbrain-hindbrain boundaries and in the posterior CNS. At the 21- to 25-somite stage, broad expression in the CNS and the lens.
Detectable in migrating neural crest cells during somitogenesis. At early larval stages, expression is visible in the ventricular zone, the upper and lower jaw and the developing pectoral fins. At later larval stages, expression fades out.
Predominantly expressed in brain. Expressed at a low level in the eye.
Specifically generates 13-cis retinol, a stereoisomeric form of retinoic acid. Capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid (By similarity).
Inhibited by phosphorylation of Tyr-538 by leukocyte common antigen and activated by dephosphorylation of this site.
Tyrosine-protein kinase implicated in the control of cell growth. Plays a role in the regulation of intracellular calcium levels. Required in brain development and mature brain function with important roles in the regulation of axon growth, axon guidance, and neurite extension. Role in CNTN1-mediated signaling (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.
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.
Homodimer; disulfide-linked. Interacts with PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB.
May play a role in cellular stress response.
Belongs to the peptidase S26 family. IMP2 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.
Expressed both maternally and zygotically during embryonic development.
May play a role in mitochondrial aerobic respiration. May also regulate mitochondrial organization and fission (By similarity).
Rab9 effector required for endosome to trans-Golgi network (TGN) transport.
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.
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.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft.
By activation of the Notch signaling pathway.
Expressed from the first somite stage. Expressed in lateral plate mesoderm before vessel formation, and thereafter in the aorta but not in the vein. At the 6-somite stage expression is seen in the lateral mesoderm of the head and trunk. While expression in the trunk lateral mesoderm is initially uniform, at the 16-somite stage, expression is restricted to angioblast precursors that have not yet migrated dorsally. At the 16-somite stage expression is also seen in the telencephalon, dorsal midbrain, neural crest and in the dorsal aorta and its vascular progenitors.
Transcriptional repressor (By similarity). Downstream effector of Notch signaling which regulates cell fate choice in angioblasts. Represses the venous cell fate, thereby promoting the arterial cell fate and aorta formation.
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).
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.
Essential for the organization of sarcomeric thin filaments in skeletal muscle.
Morpholino knockdown of the protein causes short bodies, bent tails, and reduced tail birefringence, consistent with abnormal skeletal muscle organization, in fish larvae, 3 days after fertilization. Larvae exhibit reduced trunk size, that generate less force than that of wild-type counterparts, and aberrant accumulation of alpha-actinin. Mutant embryos show abnormal motor function, with reduced spontaneous coiling and diminished touch-evoked escape responses.
Detected at the 1-cell embryo stage, probably due to inheritance of maternal transcripts. At the 50% ebiboly stage, detected in dorsal forerunner cells. At the 3-somite stage, found in Kupffer's vesicle. At the 8-somite stage, expressed in the pronephros, the floorplate of the neural tube, and otic vesicles. Expression in the pronephros continues to the 24-somite stage.
Interacts with dnaaf1/swt. Interacts with lrrc6/sea. Interacts with dvl (via DEP and PDZ domains).
Larval lethal (PubMed:26904945). Animals show strong ciliopathy phenotypes, including pronephric cysts, axis curvature, left-right asymmetry defects and hydrocephalus (PubMed:26904945). Kidney tubules are dilated and polarity of cilia in the epithelium is disorganized (PubMed:26904945). Cilia length and number appear normal, but outer dynein arms are missing and cilia are paralyzed (PubMed:26904945). Morpholino knockdown of the protein results in similar phenotypes (PubMed:24094744, PubMed:26904945).
Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly (PubMed:24094744, PubMed:26904945). Seems to be important for initiation rather than maintenance of cilium motility (PubMed:26904945). Required for correct positioning of cilia at the apical cell surface, suggesting an additional role in the planar cell polarity (PCP) pathway (PubMed:26904945). May suppress canonical Wnt signaling activity (PubMed:26904945).
Strongly expressed in ciliated tissues of the embryonic trunk, including the pronephric ducts and spinal canal.
Component of some chromatin complex recruited to chromatin sites methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3).
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.
It is uncertain whether Met-1 or Met-21 is the initiator.
May be involved in endoplasmic reticulum (ER) stress-induced cell death pathway.
Histone-binding protein (PubMed:34365506). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (PubMed:34365506). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity).
The N-terminal region, including the PHD-type 1 and 2 zinc fingers and the C2HC pre-PHD-type zinc finger, is required for binding to histone H3.
Mitochondrial ribosome-associated protein involved in the first steps of cytochrome c oxidase complex (complex IV) biogenesis. Stimulates the translation of MT-CO1 mRNA and is a constituent of early MT-CO1 assembly intermediates.
Palmitoyltransferase that could catalyze the addition of palmitate onto protein substrates.
Probably maternally supplied, the zygotic expression becomes significative at 6 hpf and is stable from 7.5 hpf to 24 hpf.
Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors.
ADP-ribosylated by tankyrase tnks and tnks2. Poly-ADP-ribosylated protein is recognized by rnf146, followed by ubiquitination at 'Lys-48' and subsequent activation of the Wnt signaling pathway.
Component of the beta-catenin destruction complex required for regulating ctnnb1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (PubMed:17681137). Controls dorsoventral patterning via two opposing effects: down-regulates ctnnb1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway (PubMed:17681137, PubMed:30467143).
Homodimer (By similarity). Interacts with dixdc1 (PubMed:12526749). Interacts with hwa; leading to promote the tankyrase-mediated degradation of axin1 (PubMed:30467143).
The DIX domain mediates interaction with dixdc1.
Calcium-binding protein that acts as an adapter that bridges unrelated proteins or stabilizes weak protein-protein complexes in response to calcium. Acts as a negative regulator of ER-Golgi transport (By similarity).
Heterodimer; heterodimerizes (via the EF-hand 5) with pdcd6.
Interacts with psen1 and psen2. Binds opa1 (By similarity).
Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of opa1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (By similarity).
Belongs to the glycosyltransferase 68 family.
Belongs to the eukaryotic ribosomal protein eS8 family. Ribosome biogenesis protein NSA2 subfamily.
Component of the pre-66S ribosomal particle.
Involved in the biogenesis of the 60S ribosomal subunit. May play a part in the quality control of pre-60S particles.
Citrate synthase is found in nearly all cells capable of oxidative metabolism.
Belongs to the methylenetetrahydrofolate reductase family.
Belongs to the chloride channel MCLC family.
Expressed in the hindbrain, swim bladder and the eye at 1 day post fertilization (dpf) with increased expression at 3 dpf (PubMed:30157172). At 3 dpf, most prominent expression in the retina, with strong exxpression in the ganglion cell layer, outer nuclear layer and the retinal pigmented epithelium (PubMed:30157172).
Knockout leads to lethality at 11 dpf, with knockout larvae exhibiting abnormalities in various retinal layers including the inner plexiform layer, the outer nuclear layer and the rod photoreceptor layer and decreased function of the photoreceptor cone cells (PubMed:30157172). Morpholino knockdown results in reduced eye size with proportionately decreased lens size, thinner inner plexiform layer and outer nuclear layer after 36 hours post fertilization (hpf) (PubMed:30157172). No change in the inner nuclear layer, but increased apparent thickness of the ganglion cell layer (PubMed:30157172). Reduced number of rod cells, with existing rod cells exhibiting an abnormal morphology or pyknotic appearance, decreased opsin levels and disrupted photoreceptor cell bodies (PubMed:30157172).
Seems to act as a chloride ion channel (By similarity). Plays a role in retina development (PubMed:30157172).
Mitochondrial carrier mediating the transport of coenzyme A (CoA) in mitochondria in exchange for intramitochondrial (deoxy)adenine nucleotides and adenosine 3',5'-diphosphate.
Morphant embryos show morphological anomalies including dorsal curvature and bent tails, severe muscle disorganization, early motor defects, and mitochondrial abnormalities.
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.
Belongs to the complex I LYR family. SDHAF1 subfamily.
Expressed during embryogenesis in the kidney, optic stalk, midbrain, otic vesicle and a row of cells along the spinal cord and the hindbrain.
First seen during the formation of neural keel. At 9-10 hours of development expression seen in two laterally located transverse stripes of cells in the rostral 1/3 of the embryo, and the two areas subsequently move towards the midline and form the posterior portion of the midbrain. Detected in the otic placode, Wolffian duct including the nephritic primordium and optic stalk at 10-12 hours. At 14-15 hours expression seen in the single cells along the spinal cord, presumably interneurons.
Probable transcription factor involved in the development of the midbrain/hindbrain boundary (MHB) organizer and specification of neuronal cell fates. Required for establishment of eng2 and eng3 gene expression in the midbrain and MHB primordium during late gastrulation.
Hydrolase highly specific for thiamine triphosphate (ThTP).
Exhibits both acyltransferase and acetyltransferase activities (By similarity). Activity is calcium-independent (By similarity). Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (By similarity). Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity).
The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphocholine.
The di-lysine motif may confer endoplasmic reticulum localization.
Expressed in all cells in pregastrulation stages. During gastrulation is differentially expressed, accumulating predominantly in the prechordal mesoderm and notochord. At the end of gastrulation, expressed along the anterior-posterior axis including the developing neural plate and differentiating mesoderm. Also present in the developing brain and head regions.
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) (By similarity).
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) (By similarity).
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 Mediator complex subunit 29 family.
Belongs to the complex I subunit 4L family.
Sodium- and proton-independent thyroid hormones and aromatic acids transporter. Mediates both uptake and efflux of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) with high affinity, suggesting a role in the homeostasis of thyroid hormone levels (By similarity). Responsible for low affinity bidirectional transport of the aromatic amino acids, such as phenylalanine, tyrosine, tryptophan and L-3,4-dihydroxyphenylalanine (L-dopa). Plays an important role in homeostasis of aromatic amino acids (By similarity).
In early somitogenesis, expressed in presumptive forebrain and midbrain, tail bud and Kupffer's vesicle. During mid-somitogenesis, ubiquitous expression which is strongest in the somites and eye. During late somitogenesis, predominantly expressed in eye, hindbrain and ventral somites. At 24 hours post-fertilization (hpf), restricted to lens and neural retina, brain, otic vesicle and somites. At 36 hpf, brain expression is restricted to telencephalon. At 48 hpf, restricted to telencephalon and pectoral fin.
Belongs to the P-Pant transferase superfamily. AcpS family.
Expressed during all stages of embryonic development, from 1-cell to 72 hours post-fertilization (hpf) (PubMed:23071114). Expressed in the forebrain, the midbrain, the mid-hindbrain boundary and eye area at 24 hpf (PubMed:23071114).
Knockout is viable, without apparent morphological defects, but, in an adnpb mutant background, some embryos have axis formation defects and at 36-48 hours post-fertilization (hpf), have abnormal body morphology with significant brain neuron death (PubMed:32533114). Expression of neural genes such as dlx5a, neurod1, and phox2a is greatly reduced in day 2 embryos in an adnpb mutant background (PubMed:23071114). Beta-catenin ctnnb1 levels reduced in an adnpb mutant background (PubMed:32533114). Morpholino knockdown reduces numbers of blood cells in circulation from 28 hours hpf (PubMed:23071114). Significant reduction in hemoglobin content at 48 and 72 hpf (PubMed:23071114). Developmental delay, distorted tail morphology, and much smaller head and eyes (PubMed:23071114). Some embryos recovered blood circulation at day 4 after knockdown, whereas others became severely edematous at day 4-5 and died by about 7 days (PubMed:23071114).
May be involved in transcriptional regulation (PubMed:23071114, PubMed:32533114). Positively modulates wnt-beta-catenin/ctnnb1 signaling (PubMed:32533114). Required for embryonic neurogenesis (PubMed:32533114). Required for progression through late erythroid differentiation (PubMed:23071114).
Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. Tprkb acts as an allosteric effector that regulates the t(6)A activity of the complex.
Contaminating sequence. Sequence of unknown origin.
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).
Endoplasmic reticulum cargo receptor that mediates the export of lipoproteins by recruiting cargos into COPII vesicles to facilitate their secretion. Acts as a cargo receptor for lipoproteins bearing both APOB and APOA1, thereby regulating lipoprotein delivery and the maintenance of lipid homeostasis.
Belongs to the eukaryotic ribosomal protein eS25 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. Minor subunit located with subunit a in the membrane (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).
Critical component of the guidance pathway underlying endothelial cell migration and blood vessel patterning. Involved in mediating membrane localization of ephrin proteins, which have been shown to provide guidance cues for endothelial cell migration.
Specifically expressed in subsets of neuronal tissues, epithelial cells, and developing somites through which vascular endothelial cells migrate from large ventral axial vessels to form stereotypic intersegmental blood vessels (ISV).
Belongs to the TFIIE beta subunit family.
Tetramer of two alpha and two beta chains.
Belongs to the mitochondrion-specific ribosomal protein mL53 family.
First detected at mid-gastrulation. After the onset of segmentation, detected in cranial placode. At later stages of development, detected in the olfactory, otic, and lateral line placodes, in the developing inner ear and in neuromasts. After 48 hpf, no longer detected in the inner ear, but continues to be expressed in lateral line neuromasts. In addition, detected in the pituitary, branchial arches, somites, pectoral fin, ventral abdomen muscle, and the cranial muscles of the eye and lower jaw. Detected in developing fast muscle.
Morpholino knockdown of the protein increases both cell proliferation and apoptosis in the otocyst. Increases proliferation of neuronal cells and decreases the number of cells destined to form hair cells. Disrupts myogenesis by interfering with the proliferation of dermomyotomal cells expressing pax7 and loss of myog expression.
Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development. Depending on context, functions as transcriptional repressor or activator. Transcriptional activation is enhanced by eya1 (in vitro). Plays an important role in the development of the inner ear, where it promotes hair cell proliferation and inhibits proliferation of neural progenitor cells. Required for normal myogenesis. Plays a role in the development of fast muscle fibers throughout the body, as well as the development of craniofacial muscles. Required for normal expression of myod1 and myog during myogenesis.
Zebrafish has two genes coding for six1 orthologs. This gene is called six1b by ZFIN and in PubMed:23444384, but has also been described as six1 (PubMed:17035528) and as six1a (PubMed:15254912, PubMed:18789916, PubMed:19409884).
First detected at 12 hours post-fertilization (hpf), increasing over the next 24 hours, then decreasing between 48 and 72 hours. Not detected in adult.
In pituitary absent (pia) mutants, adenohypophyseal cells fail to express hormone genes and some become apoptotic.
In the 24 hours embryo, expressed in the dorsal hindbrain in two bilaterally symmetrical lines of cells marking the boundary between the alar and basal plates, and ventrally in rhombomere 1 near the floor plate. Also expressed in embryonic adenohypophysis, telencephalon, diencephalon, epiphysis, ventral tegmentum, neural retina and spinal cord, in discrete regions distinct from those expressing ascl1b. In the 30 hours embryo, hindbrain expression is in stripes adjacent to rhombomere boundaries.
Transcriptional regulator. May mediate transcription activation by binding to the E box-containing promoter (By similarity). Involved in neurogenesis. Required for the development of neurons in the epiphysis, acting partially redundantly with neurog1 and downstream of flh. Involved in maintaining rhombomere boundaries in the hindbrain, probably via up-regulation of delta expression. Also involved in pituitary development; required cell-autonomously in adenohypophyseal cells for endocrine differentiation and for survival of a subset of cells.
Converts D-glucuronic acid residues adjacent to N-sulfate sugar residues to L-iduronic acid residues, both in maturing heparan sulfate (HS) and heparin chains (PubMed:16156897, PubMed:25568314). Plays a role in dorso-ventral axis specification during early development, together with glcea, where it may potentiate signaling via the BMP pathway (PubMed:16156897).
Detected from 0.5 to 48 hours post-fertilization (hpf) (PubMed:16156897). At 24-36 hpf, expressed in adaxial mesoderm, somites, notochord, floorplate, hypochord, tail bud, eye, telencephalon, diencephalon, midbrain, hindbrain and otic vesicle (PubMed:17195182).
Double morpholino knockdown of both glcea and glceb results in dorsalized embryos, with reduced ventral tail fin, kinked tail and an enlarged heart cavity. In severe cases there is significant shortening of the body and tail coiling. Epimerase activity is reduced. Expression of the dorsalizing factor chordin is expanded, whereas expression of bmp2b is reduced, notably in the tail. Expression of gata1 in blood islets is also reduced.
Inhibited by O-sulfated heparin, which is produced by a downstream step in the heparin biosynthesis pathway.
Arg-345 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 (By similarity). Preferentially glycylates a beta-tail peptide over the alpha-tail, although shifts its preference toward alpha-tail as beta-tail glutamylation increases (By similarity). Competes with polyglutamylases for modification site on beta-tubulin substrate, thereby creating an anticorrelation between glycylation and glutamylation reactions (By similarity). Not involved in elongation step of the polyglycylation reaction (By similarity).
Shortening and loss of cilia in several organs, including the Kupffer's vesicle and olfactory placode.
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 type I cytokine receptor family. Type 4 subfamily.
Belongs to the SPTSS family. SPTSSA subfamily.
Interacts with sptlc1; the interaction is direct. Component of the serine palmitoyltransferase (SPT) complex (By similarity).
Stimulates the activity of serine palmitoyltransferase (SPT). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (By similarity).
ATP-binding RNA helicase which 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. Acts downstream of piRNA biogenesis: exclusively required for transposon silencing in the nucleus, suggesting that it acts as a nuclear effector in the nucleus together with piwil4.
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).
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-395 in response to transcription stress; this promotes efficient transfer of TFIIH to stalled RNA polymerase II.
Morpholino knockdown of the protein alters the migration of gonadotropin-releasing hormone (GnRH) expressing neurons.
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 (PubMed:31883645). 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).
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.
Belongs to the transglutaminase-like superfamily. PNGase family.
Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins (By similarity).
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.
In the C-terminal section; belongs to the saccharopine dehydrogenase family.
May monitor slit diaphragm protein assembly, a specialized adherens junction characteristic of podocytes. In case of podocyte injury, it shuttles into the nucleus and acts as a transcription regulator. Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Acts as a transcriptional corepressor for snai1 and snai2/slug and plays a role in regulating neural crest development (By similarity).
Belongs to the nucleoporin Nup133 family.
Forms part of the Nup160 subcomplex in the nuclear pore which is composed of NUP160, NUP133, NUP107 and Nup96. This complex plays a role in RNA export and in tethering Nup98 and NUP153 to the nucleus.
Involved in poly(A)+ RNA transport (By similarity). Involved in nephrogenesis (PubMed:30427554).
Morpholino knockdown of the protein results in anomalies of the head, brain and kidney. Morphant embryos show decreased head sizes, reduced axonal numbers in the forebrain and midbrain, and disorganization in the hindbrain. As for the renal tissues, morphants show underdeveloped glomeruli with hypoplastic capillary vessels, and abnormal podocytes.
Widely expressed in the embryo and in adult tissues. Higher expression is observed in the brain, testes, ovary, skin, and kidney.
Belongs to the ETF beta-subunit/FixA family.
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.
Monomer. Component of the conserved oligomeric Golgi (COG) complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.
Required for normal Golgi function (PubMed:30290151). Plays a role in the vesicular trafficking between the endoplasmic reticulum and the Golgi apparatus (By similarity).
Widely expressed, including in larval inner ear anterior macula, brain, retina and ceratobranchial arches (PubMed:30290151). Expressed in larval chondrocytes and hair cells of the anterior macula (at protein level) (PubMed:30290151).
Zebrafish mutants are significantly shorter than their wild-type counterparts. Mutants have craniofacial defects with a smaller jaw, smaller inner ears, slightly smaller eyes, and stubby pectoral fins. They exhibit malformation of the inner ear, with abnormally shaped semicircular canals. Mechanosensory hair cells in the inner ear and neuromasts have reduced numbers of hair bundles. Response to auditory stimuli is greatly reduced. Animals show defects in proteoglycan secretion and reduced collagen COL1A2 expression in fins, but normal collagen type II expression in the jaw. Golgi apparatus structure is disrupted in mutant cells, with defects in the processing of N- and O-linked glycans and decreased glycosphingolipid complexity.
Acts as component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrins. The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes. In the endosomes, 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. May be involved in copper-dependent atp7a trafficking between the trans-Golgi network and vesicles in the cell periphery.
Component of the heterotrimeric retriever complex.
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).
Acts downstream of smo as an intracellular repressor of hedgehog signaling pathway, mainly through the suppression of gli1 activity. This negative regulatory effect is enhanced in conjunction with the suppressor of fused (sufu) protein. Positively regulates gli2a activity by promoting its dissociation from sufu. Involved in the regulation of microtubular dynamics.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KIF27 subfamily.
Binds microtubules. Interacts with gli1 and sufu.
Belongs to the queuine tRNA-ribosyltransferase family. QTRT2 subfamily.
Non-catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine).
Belongs to the SPTSS family. SPTSSB subfamily.
Detectable at 24 hpf and gradually increases through development. Detected in the nervous system in olfactory placode, olfactory bulb, telencephalon and tectum.
Carboxypeptidase which preferentially cleaves C-terminal acidic residues from peptides and proteins. Can also cleave C-terminal hydrophobic amino acids, with a preference for small residues over large residues.
Detected in intestine from 3 days post-fertilization onwards.
Strongly inhibited by potato carboxypeptidase inhibitor, and the chelating agents EDTA and 1,10-phenanthroline. Also inhibited by compounds with multiple carboxylic acid groups such as citrate and succinate, and to a lesser exent the amino acids aspartate and glutamate. Not significantly inhibited by benzylsuccinic acid.
Belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.
Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate.
Belongs to the SSU72 phosphatase family.
May be involved in the C-terminal domain of RNA polymerase II dephosphorylation, RNA processing and termination.
In the embryonic brain expressed in specific subtypes of neurons. Found in the tectal region, hindbrain, neurons in the nucleus of the anterior commissure, posterior commissure, postoptic commissure, medial lateral fascile and epiphysis. Localized to both central and peripheral axons of the primary sensory neurons.
Involved in the development of primary sensory neurons especially in branching of the peripheral axons. Interacts with the SLIT2 signaling specifically to promote axonal branching of Rohon-Beard neurons and the trigeminal sensory ganglion neurons.
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).
By ets transcription factors including ets1.
During embryogenesis, expressed in hematopoietic and endothelial precursors, including the two stripes of posterior and anterior lateral plate mesoderm at the 1-somite stage that give rise to the primitive blood.
Transcription factor that acts synergistically with tal1/scl in primitive and definitive hematopoiesis, and in endothelial development. Specifies mesodermal precursors to a hemangioblast cell fate. Hemangioblasts are bipotential precursors of blood and endothelium, and in the absence of hematopoietic induction cues such as gata1, tal1/scl-lmo2-induced haemangioblasts differentiate into endothelial cells.
Required for KRAS signaling regulation and modulation of cell proliferation (PubMed:31406347). 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).
May be a carrier that transport small solutes by using chemiosmotic ion gradients.
Acts as a negative regulator of hedgehog signaling probably by promoting internalization and subsequent degradation of smoothened protein (SMO) present in the ciliary membrane. Plays a role in sonic hedgehog (SHH)-induced spinal neural progenitor cells differentiation.
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.
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.
Dephosphorylates 26S nuclear proteasomes, thereby decreasing their proteolytic activity. The dephosphorylation may prevent assembly of the core and regulatory particles (CP and RP) into mature 26S proteasome (By similarity).
Dephosphorylates 26S nuclear proteasomes, thereby decreasing their proteolytic activity. The dephosphorylation may prevent assembly of the core and regulatory particles (CP and RP) into mature 26S proteasome.
The Ubiquitin-like domain mediates interaction with proteasomes.
Microprotein involved in mitochondrial respiratory chain complex III (ubiquinol-cytochrome c oxidoreductase) and complex IV (mitochondrial cytochrome c oxidase complex) assembly (By similarity). Required for the formation of mitochondrial supercomplexes (SCs) (By similarity). Also required for the activation of the NLRP3 inflammasome (By similarity).
Morpholino knockdown of the protein leads to various development defects, including smaller eye, abnormal head shape, malformations of the jaw, cardiac edema and a delayed yolk sac resorption (PubMed:23073385). Most animals die by 1 week of age (PubMed:23073385).
Stable expression throughout embryogenesis with more abundance after 5 days post-fertilization (dpf).
Widely expressed. Expressed more abundantly in brain compared with other tissues such as heart, muscle and liver.
Belongs to the eukaryotic RPC9 RNA polymerase subunit family.
By hypoxia. Expression is significantly up-regulated by severe hypoxia in brain but not in eye.
Detected in brain, eye and gill, but not in muscle and blood (at protein level). Particularly high expression in the periventral zone of tectum opticum, with significant expression detected in white matter, preglomerular nucleus, posterior tubular nucleus, torus longitudinalis, hypothalamus, pituitary gland, posterior tuberculum, hypothalamus, synencephalon and formatio reticularis. Detected also in brain regions of the visual system, predominantly in parts of tectum opticum and torus semicircularis, area dorsalis telencephali and medulla oblongata. Strong expression observed in sensory epithelium of peripheral olfactory organ, and outer and inner nuclear layers and ganglion cell layer of retina.
Expressed at low levels during the early stages of development, with levels increasing strongly around hatching period at 72 hours post-fertilization. Expression levels remain high in the adult stage.
Involved in oxygen transport in the brain (By similarity). Hexacoordinate globin, displaying competitive binding of oxygen or the distal His residue to the iron atom. Capable of penetrating cell membranes.
Contains one covalently linked retinal chromophore.
First detected at 51 hours post-fertilization (hpf) in the ventral retina. At 60 hpf, expressed in a strip across the ventrotemporal retina. By 96 hpf, also expressed in the dorsal retina.
Photoreceptor required for image-forming vision at low light intensity. While most salt water fish species use retinal as chromophore, most freshwater fish use 3-dehydroretinal, or a mixture of retinal and 3-dehydroretinal (By similarity). Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change that activates signaling via G-proteins. Subsequent receptor phosphorylation mediates displacement of the bound G-protein alpha subunit by arrestin and terminates signaling (By similarity).
Retinal rod photoreceptor cells, predominantly in the outer segments (at protein level) (PubMed:10349976). Retinal rod photoreceptor cells (PubMed:8327475, PubMed:8603882).
Was originally (PubMed:8327475 and PubMed:8924413) thought to be an ultraviolet-sensitive opsin present in short single cones.
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.
Found in a signaling complex consisting of at least ARHGEF2, NOD2 and RIPK2.
Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains.
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling (By similarity).
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. PYROXD1 subfamily.
Morpholino-injected embryos show severe disruption of the musculature with fragmentation of the muscle fibers, altered sarcomeric structure, loss of fiber integrity and accumulation of actin at the myosepta (PubMed:27745833). Disintegration of the myofibrils with mitochondrial infiltration of the resulting space, loss of Z-disk structures, and electron dense, nemaline-like bodies are observed by electron microscopy (PubMed:27745833).
Probable FAD-dependent oxidoreductase; involved in the cellular oxidative stress response (By similarity). Required for normal sarcomere structure and muscle fiber integrity (PubMed:27745833).
Belongs to the glycosyltransferase 28 family.