FUNCTION: Required for correct export to the cell surface of some cell outer membrane lipoproteins (tested with PM1514) upon heterologous expression in E.coli and probably also in Pasteurella. SUBCELLULAR LOCATION: Cell outer membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the Slam family.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the conotoxin I2 superfamily.


FUNCTION: 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 Tim8- Tim13 complex mediates the import of some proteins while the predominant Tim9-Tim10 70 kDa complex mediates the import of much more proteins (By similarity). SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side. SIMILARITY: Belongs to the small Tim family.


FUNCTION: Alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. SIMILARITY: Belongs to the methyltransferase superfamily. NTM1 family.


FUNCTION: Acts in the same pathway as FANCM to restrain class II meiotic crossing over (CO), and acts with FANCM during meiosis to repair interstrand cross-links (ICLs). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the CENP-X/MHF2 family.


FUNCTION: Catalyzes the ketonization of 2-hydroxymuconate stereoselectively to yield 2-oxo-3-hexenedioate. SIMILARITY: Belongs to the 4-oxalocrotonate tautomerase family.


FUNCTION: Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is a respiratory chain that generates an electrochemical potential coupled to ATP synthesis. SUBCELLULAR LOCATION: Cell inner membrane; Single-pass membrane protein. SIMILARITY: Belongs to the Rieske iron-sulfur protein family.


FUNCTION: Receptor-like protein that regulates shoot meristem proliferation. Based on additive and synergistic phenotypes of double mutants, it is probable that unlike CLV1 and CLV2 in A.thaliana, FAE2 and TD1 do not function exclusively in a single pathway. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.


FUNCTION: Hexosyltransferase involved in N-glycan biosynthetic pathway that takes place under low-salt conditions (1.75 M instead of 3.4 M). Participates in the formation of the tetrasaccharide present at 'Asn- 532' of S-layer glycoprotein Csg, consisting of a sulfated hexose, 2 hexoses and rhamnose. Together with Agl6, mediates the addition of sugars 1 and 2 to dolichol phosphate in the tetrasaccharide. SIMILARITY: Belongs to the glycosyltransferase group 1 family.


FUNCTION: CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). In this organism endogenous ribonuclease 3 and Cas9 are required for correct coprocessing of pre-crRNA and the trans-encoded small RNA (tracrRNA). Cas9, crRNA and tracrRNA are required for cleavage of invading DNA (Probable). Complements pre-crRNA and tracrRNA coprocessing defects in an rnc deletion in S.pyogenes strain 370 (PubMed:24270795). FUNCTION: Digests double-stranded RNA. Involved in the processing of primary rRNA transcript to yield the immediate precursors to the large and small rRNAs (23S and 16S). Also processes some mRNAs, and tRNAs when they are encoded in the rRNA operon (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the ribonuclease III family.


FUNCTION: Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the potassium channel HCN family.


FUNCTION: Transcription factor that regulates the expression of the gene cluster that mediates the biosynthesis of Equisetin (PubMed:23614392). SUBCELLULAR LOCATION: Nucleus.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase S1 family.


FUNCTION: Catalytic component of the NuA4 histone acetyltransferase (HAT) complex which is involved in epigenetic transcriptional activation of selected genes principally by acetylation of nucleosomal histones H4, H3, H2B, H2A and H2A variant H2A.Z (By similarity). Acetylates histone H4 to form H4K5ac, H4K8ac, H4K12ac and H4K16ac, histone H3 to form H3K14ac, and histone H2A to form H2AK4ac and H2AK7ac (By similarity). The NuA4 complex is involved in the DNA damage response and is required for chromosome segregation. The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) through homologous recombination (By similarity). Recruitment to promoters depends on H3K4me. Also acetylates non-histone proteins (By similarity). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as 2-hydroxyisobutanoyl-CoA (2- hydroxyisobutyryl-CoA) or (2E)-butenoyl-CoA (crotonyl-CoA), and is able to mediate protein 2-hydroxyisobutyrylation and crotonylation, respectively (By similarity). SUBCELLULAR LOCATION: Nucleus Chromosome Note=Following DNA damage, localizes to sites of DNA damage, such as double stand breaks (DSBs). SIMILARITY: Belongs to the MYST (SAS/MOZ) family.


FUNCTION: Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) (PubMed:17977534, PubMed:17609214, PubMed:23530041, PubMed:26887952, PubMed:31916624). Can use other acyl donors, but with less efficiency (By similarity). N- acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:17977534, PubMed:23530041, PubMed:26887952, PubMed:31916624). Ceramides generated by CERS6 play a role in inflammatory response (By similarity). Acts as a regulator of metabolism and hepatic lipid accumulation (By similarity). Under high fat diet, palmitoyl- (C16:0-) ceramides generated by CERS6 specifically bind the mitochondrial fission factor MFF, thereby promoting mitochondrial fragmentation and contributing to the development of obesity (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein.


FUNCTION: Glycosylates the TibA adhesin.


FUNCTION: Capsid vertex-specific component that plays a role during viral DNA encapsidation, assuring correct genome cleavage and presumably stabilizing capsids that contain full-length viral genomes. Participates in the interaction between the capsid and the tegument through interaction with the large tegument protein/LTP. SUBCELLULAR LOCATION: Virion Host nucleus. SIMILARITY: Belongs to the herpesviridae CVC2 protein family.


FUNCTION: Catalyzes the formation of diacylglycerol from 2- monoacylglycerol and fatty acyl-CoA. Probably not involved in absorption of dietary fat in the small intestine. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the diacylglycerol acyltransferase family.


FUNCTION: Contributes to jasmonic acid biosynthesis by initiating the beta-oxidative chain shortening of its precursors (PubMed:16963437, PubMed:18267944). Converts 12-oxo-phytodienoic acid (OPDA) and 3-oxo-2- (2'-pentenyl)-cyclopentane-1-octanoic acid (OPC-8:0) into OPDA-CoA and OPC-8:0-CoA, respectively (PubMed:16963437, PubMed:18267944). Follows a two-step reaction mechanism, wherein the carboxylate substrate first undergoes adenylation by ATP, followed by a thioesterification in the presence of CoA to yield the final CoA thioester (By similarity). SUBCELLULAR LOCATION: Peroxisome. SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins (By similarity). SIMILARITY: Belongs to the peptidase S14 family.


FUNCTION: Phosphorylates 5-hydroxymethyluracil (5hmdU) into 5- phosphomethyl-2'-deoxyuridine (5-PmdU) on DNA as a step in the pathway leading to thymidine hypermodifications in the viral genome (PubMed:34522950). The phosphate is added internally to the DNA polymer (PubMed:34522950). Also transfers glutamate to 5- pyrophosphoryloxymethyldeoxyuridine (5-PPmdU) to produce 5-Nalpha- glyutamylthymidine (Nalpha-GluT). As a final result of the pathway of hypermodification, 5-aminoethyl-2'-deoxyuridine (5-NedU) substitutes for about 30% of thymidines in the viral DNA (PubMed:34522950, PubMed:29555775). These modifications probably prevent degradation of viral genome by the host restriction-modification antiviral defense system (PubMed:34522950). SIMILARITY: Belongs to the thymidylate kinase family. 5-hmdU DNA kinase subfamily.


FUNCTION: Catalyzes the conversion of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBPP) into a mixture of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Acts in the terminal step of the DOXP/MEP pathway for isoprenoid precursor biosynthesis. SIMILARITY: In the N-terminal section; belongs to the IspH family.


FUNCTION: Critical mediator, in cooperation with CASP4, of endoplasmic reticulum-stress induced apoptosis. Required or the activation of CASP4 following endoplasmic reticulum stress. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TMEM214 family.


FUNCTION: Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+). Critical component of the visual transduction cascade, controlling the calcium concentration of outer segments during light and darkness. Light causes a rapid lowering of cytosolic free calcium in the outer segment of both retinal rod and cone photoreceptors and the light-induced lowering of calcium is caused by extrusion via this protein which plays a key role in the process of light adaptation. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.


FUNCTION: 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. SUBCELLULAR LOCATION: Nucleus. Chromosome. SUBCELLULAR LOCATION: Nucleus Chromosome. SIMILARITY: Belongs to the histone H3 family.


FUNCTION: Catalyzes the ATP-dependent amidation of deamido-NAD to form NAD. Uses ammonia as a nitrogen source. SIMILARITY: Belongs to the NAD synthetase family. SIMILARITY: Belongs to the NAD synthetase family.


FUNCTION: Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the conotoxin O1 family.


FUNCTION: Secreted protein that functions as cytokine and growth factor and mediates its signal through cell-surface proteoglycan and non- proteoglycan receptors (PubMed:18469519, PubMed:12573468, PubMed:12122009, PubMed:10212223, PubMed:24458438, PubMed:15466886, PubMed:12084985, PubMed:10772929). Binds cell-surface proteoglycan receptors via their chondroitin sulfate (CS) groups (PubMed:12084985, PubMed:10212223). Thereby regulates many processes like inflammatory response, cell proliferation, cell adhesion, cell growth, cell survival, tissue regeneration, cell differentiation and cell migration (PubMed:12573468, PubMed:12122009, PubMed:10212223, PubMed:10683378, PubMed:24458438, PubMed:22323540, PubMed:12084985, PubMed:15466886, PubMed:10772929). Participates in inflammatory processes by exerting two different activities. Firstly, mediates neutrophils and macrophages recruitment to the sites of inflammation both by direct action by cooperating namely with ITGB2 via LRP1 and by inducing chemokine expression (PubMed:10683378, PubMed:24458438). This inflammation can be accompanied by epithelial cell survival and smooth muscle cell migration after renal and vessel damage, respectively (PubMed:10683378). Secondly, suppresses the development of tolerogenic dendric cells thereby inhibiting the differentiation of regulatory T cells and also promote T cell expansion through NFAT signaling and Th1 cell differentiation (PubMed:22323540). Promotes tissue regeneration after injury or trauma. After heart damage negatively regulates the recruitment of inflammatory cells and mediates cell survival through activation of anti-apoptotic signaling pathways via MAPKs and AKT pathways through the activation of angiogenesis (By similarity). Also facilitates liver regeneration as well as bone repair by recruiting macrophage at trauma site and by promoting cartilage development by facilitating chondrocyte differentiation (By similarity). Plays a role in brain by promoting neural precursor cells survival and growth through interaction with heparan sulfate proteoglycans (By similarity). Binds PTPRZ1 and promotes neuronal migration and embryonic neurons survival (PubMed:10212223). Binds SDC3 or GPC2 and mediates neurite outgrowth and cell adhesion (PubMed:12084985, PubMed:1768439). Binds chondroitin sulfate E and heparin leading to inhibition of neuronal cell adhesion induced by binding with GPC2 (PubMed:12084985). Binds CSPG5 and promotes elongation of oligodendroglial precursor-like cells (By similarity). Also binds ITGA6:ITGB1 complex; this interaction mediates MDK-induced neurite outgrowth (PubMed:15466886, PubMed:1768439). Binds LRP1; promotes neuronal survival (PubMed:10772929). Binds ITGA4:ITGB1 complex; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation (PubMed:15466886). Binds anaplastic lymphoma kinase (ALK) which induces ALK activation and subsequent phosphorylation of the insulin receptor substrate (IRS1), followed by the activation of mitogen-activated protein kinase (MAPK) and PI3-kinase, and the induction of cell proliferation (PubMed:12122009). Promotes epithelial to mesenchymal transition through interaction with NOTCH2 (PubMed:18469519). During arteriogenesis, plays a role in vascular endothelial cell proliferation by inducing VEGFA expression and release which in turn induces nitric oxide synthase expression. Moreover activates vasodilation through nitric oxide synthase activation (By similarity). Negatively regulates bone formation in response to mechanical load by inhibiting Wnt/beta- catenin signaling in osteoblasts (By similarity). In addition plays a role in hippocampal development, working memory, auditory response, early fetal adrenal gland development and the female reproductive system (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the pleiotrophin family.


FUNCTION: Plays a role in the spread of virus to neighboring cells ex vivo. SUBCELLULAR LOCATION: Host cell membrane; Single-pass membrane protein Note=May localize at the surface of cytoplasmic extensions at the periphery of the cell. SIMILARITY: Belongs to the orthopoxvirus OPG049 family.


FUNCTION: Chemotactic-signal transducers respond to changes in the concentration of attractants and repellents in the environment, transduce a signal from the outside to the inside of the cell, and facilitate sensory adaptation through the variation of the level of methylation (Probable). Directly recognizes five C4-dicarboxylic acids: L-malic, citramalic, citraconic, bromosuccinic and methylsuccinic acids (PubMed:17933940, PubMed:29391435). Three of the identified ligands act as chemoattractants (L-malic, D,L-bromosuccinic and L-citramalic acids) whereas two of them (L-methylsuccinic and citraconic acids) behave as antagonists by inhibiting the downstream chemotaxis signaling cascade (PubMed:29391435). Antagonists compete with chemoattractants, thereby decreasing the affinity for chemoattractants and the subsequent chemotactic response (PubMed:29391435). Acts through the che chemosensory pathway (PubMed:29391435). SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the methyl-accepting chemotaxis (MCP) protein family.


FUNCTION: Phosphorylates the antiviral nucleoside analog ganciclovir. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. HCMV ganciclovir subfamily.


FUNCTION: Acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality control. SUBCELLULAR LOCATION: Mitochondrion outer membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the FUN14 family.


SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-independent O-methyltransferase family. COMT subfamily.


FUNCTION: E3 ubiquitin ligase that plays a role in several processes including innate immnity, autophagy or inflammation (PubMed:28594402, PubMed:34512673). Negatively regulates miRNAs by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA- mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (PubMed:24778252). This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy (PubMed:31160576). Upon enteroviral infection, promotes 'Lys-63'- mediated ubiquitination activation of IFIH1/MDA5 leading to innate signaling cascade (PubMed:28594402). Mechanistically, selectively recognizes MDA5 filaments that occur on dsRNAs (PubMed:33373584). Plays also a role in limitation of inflammation through different mechanisms. First, promotes 'Lys-48'-mediated ubiquitination of VCAM1 leading to its degradation and limitation of LPS-induced lung inflammation (PubMed:31310649). In addition, negatively regulates inflammasome activation by promoting 'lys48'-linked ubiquitination of NLRP3 which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages (PubMed:34512673). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the TRIM/RBCC family.


FUNCTION: Probable component of the tectonic-like complex (also named MKS complex), a complex localized at the transition zone of primary cilia (PubMed:27646273, PubMed:25447994, PubMed:27577095). Has a role in ciliary structure and function (PubMed:27646273). SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body Note=Localizes at the transition zone (TZ), a region between the basal body and the ciliary axoneme (PubMed:27646273). In spermatocytes, localizes in the transition zone and the migrating base of the spermatid ciliary cap (PubMed:25447994, PubMed:27577095). Co-localizes with the tectonic-like complex (PubMed:27646273). SIMILARITY: Belongs to the B9D family.


SIMILARITY: Belongs to the histidine acid phosphatase family.


FUNCTION: Non catalytic polymerase cofactor and regulatory protein that plays a role in viral transcription and replication. Stabilizes the RNA polymerase L to the N-RNA template and binds the soluble protein N, preventing it from encapsidating non-genomic RNA. Also inhibits host IFN-alpha and IFN-beta signaling by binding and retaining phosphorylated STAT1 in the cytoplasm or by inhibiting the DNA binding of STAT1 in the nucleus (By similarity). SUBCELLULAR LOCATION: [Isoform P2]: Host cytoplasm. SUBCELLULAR LOCATION: [Phosphoprotein]: Virion. Host cytoplasm. SUBCELLULAR LOCATION: [Isoform P5]: Host nucleus. SIMILARITY: Belongs to the lyssavirus protein P family.


FUNCTION: Has antimicrobial activity against the Gram-positive bacteria S.aureus (MIC=8 uM) and the yeast C.albicans (MIC=16 uM). Causes hemolysis on horse erythrocytes (64 uM for 100% hemolysis). Minimum bactericidal concentrations have also been tested against S.aureus and is four-fold higher (MBC=32 uM). SUBCELLULAR LOCATION: Secreted Target cell membrane Note=Forms a helical membrane channel in the prey. SIMILARITY: Belongs to the non-disulfide-bridged peptide (NDBP) superfamily. Short antimicrobial peptide (group 4) family.


SIMILARITY: Belongs to the CC2D1 family.


FUNCTION: Multicopper oxidase; part of the gene cluster that mediates the biosynthesis of cercosporin, a light-activated, non-host-selective toxin (PubMed:29844193). The perylenequinone chromophore of cercosporin absorbs light energy to attain an electronically-activated triplet state and produces active oxygen species such as the hydroxyl radical, superoxide, hydrogen peroxide or singlet oxygen upon reaction with oxygen molecules (PubMed:11701851). These reactive oxygen species cause damage to various cellular components including lipids, proteins and nucleic acids (PubMed:11701851). The first step of cercosporin biosynthesis is performed by the polyketide synthase CTB1 which catalyzes the formation of nor-toralactone (Probable). The starter unit acyltransferase (SAT) domain of CTB1 initiates polyketide extension by the selective utilization of acetyl-CoA, which is elongated to the heptaketide in the beta-ketoacyl synthase (KS) domain by successive condensations with six malonyl units introduced by the malonyl acyltransferase (MAT) domain. The product template (PT) domain catalyzes C4-C9 and C2-C11 aldol cyclizations and dehydrations to a trihydroxynaphthalene, which is thought to be delivered to the thioesterase (TE) domain for product release (Probable). The bifunctional enzyme CTB3 then methylates nor-toralactone to toralactone before conducting an unusual oxidative aromatic ring opening (Probable). The O-methyltransferase CTB2 further methylates the nascent OH-6 of the CBT3 product, blocking further oxidation at this site before the reductase CTB6 reduces the 2-oxopropyl ketone at position C7, giving naphthalene (Probable). The FAD-dependent monooxygenase CTB5 in concert with the multicopper oxidase CTB12 are responsible for homodimerization of naphthalene with CTB7 installing the dioxepine moiety, finally producing cercosporin (Probable). The fasciclin domain- containing protein CTB11 might act with CTB5 and CTB12 whereas the roles of CTB9 and CTB10 have still to be elucidated (By similarity). SIMILARITY: Belongs to the multicopper oxidase family.


FUNCTION: Slow-binding inhibitor of serine proteases. The inhibitor rapidly binds to the protease forming a weak enzyme-inhibitor complex, and this is followed by a slow isomerization forming a tight-binding enzyme-inhibitor complex. Active against subtilisin A with a dissociation constant of 0.18 nM. Active against perkinsin. Not active against thermolysin, papain or pepsin. SUBCELLULAR LOCATION: Secreted.


FUNCTION: Enzyme catalyzing the degradation of lysoplasmalogen. Lysoplasmalogens are formed by the hydrolysis of the abundant membrane glycerophospholipids plasmalogens. May control the respective levels of plasmalogens and lysoplasmalogens in cells and modulate cell membrane properties. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein Cytoplasm. SIMILARITY: Belongs to the TMEM86 family.


FUNCTION: Component of the intraflagellar transport (IFT) complex B required for transport of proteins in the motile cilium (PubMed:28479320). May be required for ciliary entrance and transport of specific ciliary cargo proteins such as che-3 which are related to motility (PubMed:28479320). Required for sensory cilia biogenesis (PubMed:15713455). SUBCELLULAR LOCATION: Cell projection, axon Cell projection, cilium Cell projection, dendrite. SIMILARITY: Belongs to the CLUAP1 family.


FUNCTION: Co-chaperone that binds misfolded and hydrophobic patches- containing client proteins in the cytosol. Mediates their targeting to the endoplasmic reticulum but also regulates their sorting to the proteasome when targeting fails. Functions in tail-anchored/type II transmembrane proteins membrane insertion constituting with ASNA1 and the BAG6 complex a targeting module. Functions upstream of the BAG6 complex and ASNA1, binding more rapidly the transmembrane domain of newly synthesized proteins. It is also involved in the regulation of the endoplasmic reticulum-associated misfolded protein catabolic process via its interaction with BAG6: collaborates with the BAG6 complex to maintain hydrophobic substrates in non-ubiquitinated states. Competes with RNF126 for interaction with BAG6, preventing the ubiquitination of client proteins associated with the BAG6 complex (By similarity). Binds directly to HSC70 and HSP70 and regulates their ATPase activity (PubMed:12878599). SUBCELLULAR LOCATION: Cytoplasm Nucleus Note=Co-localizes with HSP90AB1 in the cytoplasm. Increased nuclear accumulation seen during cell apoptosis. SIMILARITY: Belongs to the SGT family.


FUNCTION: Serine/threonine protein kinase involved in the cytoplasm to vacuole transport (Cvt) and found to be essential in autophagy, where it is required for the formation of autophagosomes. Involved in the clearance of protein aggregates which cannot be efficiently cleared by the proteasome. Required for selective autophagic degradation of the nucleus (nucleophagy) as well as 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. Also involved in endoplasmic reticulum-specific autophagic process, in selective removal of ER- associated degradation (ERAD) substrates. Plays a key role in ATG9 and ATG23 cycling through the pre-autophagosomal structure and is necessary to promote ATG18 binding to ATG9 through phosphorylation of ATG9. Catalyzes phosphorylation of ATG4, decreasing the interaction between ATG4 and ATG8 and impairing deconjugation of PE-conjugated forms of ATG8. SUBCELLULAR LOCATION: Cytoplasm Preautophagosomal structure membrane; Peripheral membrane protein. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.


FUNCTION: Plays a role in mitotic spindle orientation and mitotic progression. Regulates the distribution of dynactin at the cell cortex in a PLK1-dependent manner, thus stabilizing cortical and astral microtubule attachments required for proper mitotic spindle positioning. May link microtubules to the actin cytospkeleton and focal adhesions. May be required for directed cell migration and centrosome orientation. May also be necessary for proper stacking of the Golgi apparatus (By similarity). SUBCELLULAR LOCATION: Cell junction, focal adhesion Cytoplasm, cytoskeleton Cytoplasm, cell cortex Note=Predominantly localizes to cortical actin structures during interphase and mitosis. Present in retraction fibers, which are formed at former adhesion sites during mitosis, and at spicular membrane protrusions in re-attaching cytokinetic cells. Partially colocalizes with cytoplasmic F-actin. Not detected at microtubules at interphase, nor at spindle during mitosis (By similarity). SIMILARITY: Belongs to the MISP family.


FUNCTION: Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity for phenylalanine. SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.


FUNCTION: Calmodulin-like protein which plays a role in the activation of calcineurin (CNA1).


FUNCTION: Extracellular dipeptidyl-peptidase which removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N- termini. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase S9C family.


SIMILARITY: Belongs to the Tdpoz family.


SIMILARITY: Belongs to the CoaE family.


FUNCTION: Part of a binding-protein-dependent transport system for an iron chelatin; probably responsible for the translocation of the substrate across the membrane. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the binding-protein-dependent transport system permease family. FecCD subfamily.


FUNCTION: 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). SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass type IV membrane protein Peroxisome Cytoplasmic vesicle, secretory vesicle, synaptic vesicle. SIMILARITY: Belongs to the Tango11 family.


SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein. SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the UPF0154 family.


FUNCTION: Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the serpin family.


FUNCTION: Inorganic phosphate and probable anion transporter. SUBCELLULAR LOCATION: Golgi apparatus membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. Sodium/anion cotransporter (TC 2.A.1.14) family.


FUNCTION: Catalyzes the displacement of the beta- and gamma-phosphates of CTP by phosphonoformate to produce CMP-5'-phosphonoformate, an intermediate in the biosynthesis of phosphinothricin tripeptide (PTT). PTT is both a natural-product antibiotic and potent herbicide.


FUNCTION: Has modulatory actions at skeletal neuromuscular junctions. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the FARP (FMRFamide related peptide) family.


FUNCTION: H(+)-stimulated, divalent metal cation uptake system. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the NRAMP family.


FUNCTION: Forms a chaperone-bound H2A.Z-H2B complex that acts as a source for SWR1 complex-dependent H2A to H2A.Z histone replacement in chromatin. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the CHZ1 family.


SIMILARITY: To B.subtilis YdcN C-terminal region.


FUNCTION: Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step that requires cell division, the PIC enters cell nucleus. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The last step is viral DNA integration into host chromosome (By similarity).


FUNCTION: The A chain is responsible for inhibiting protein synthesis through the catalytic inactivation of 60S ribosomal subunits by removing adenine from position 4,324 of 28S rRNA. The B chain binds to cell receptors and probably facilitates the entry into the cell of the A chain; B chains are also responsible for cell agglutination (lectin activity). Agglutination is inhibited by Neu5Ac(alpha2,6)lactose, and N-linked glycoproteins such as fetuin and orosomucoid. SIMILARITY: In the N-terminal section; belongs to the ribosome- inactivating protein family. Type 2 RIP subfamily.


FUNCTION: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Acts on the anterior body structures (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the Antp homeobox family. Labial subfamily.


FUNCTION: Plays a role in nuclear translocation of the viral pre- integration complex (PIC), thus is required for the virus to infect non-dividing cells. Targets specific host proteins for degradation by the 26S proteasome. Acts by associating with the cellular CUL4A-DDB1 E3 ligase complex through direct interaction with host VPRPB/DCAF-1. This change in the E3 ligase substrate specificity results in the degradation of host SAMHD1. In turn, SAMHD1 depletion allows viral replication in host myeloid cells by preventing SAMHD1-mediated hydrolysis of intracellular dNTPs necessary for reverse transcription (By similarity). SUBCELLULAR LOCATION: Virion. Host nucleus. Note=Nuclear just after virion uncoating, or if expressed in the absence of unprocessed GAG. SIMILARITY: Belongs to the lentivirus VPX protein family.


FUNCTION: [Isoform 1]: Choline/H+ antiporter, mainly in mitochodria (PubMed:10677542, PubMed:20665236, PubMed:33789160, PubMed:23651124). Also acts as a low-affinity ethanolamine/H+ antiporter, regulating the supply of extracellular ethanolamine (Etn) for the CDP-Etn pathway, redistribute intracellular Etn and balance the CDP-Cho and CDP-Etn arms of the Kennedy pathway (PubMed:33789160). FUNCTION: [Isoform 3]: Does not exhibit choline transporter activity. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Mitochondrion outer membrane; Multi-pass membrane protein Note=Mainly expressed in mitochondria. SIMILARITY: Belongs to the CTL (choline transporter-like) family.


FUNCTION: Transcription factor involved in the response to zinc ion deficiency. Binds to the consensus sequence 5'-[AG]TGTCGACA[CT]-3' also called zinc deficiency response element (ZDRE). The ZDRE sequence is conserved in the plant kingdom and present in the promoters of genes that constitute the primary response to zinc deficiency, comprising additional ZIP metal transporter genes (PubMed:20479230, PubMed:26306426). Required for zinc accumulation in roots. Mediates the expression of the zinc transporters ZIP3, ZIP4, ZIP5 and ZIP9 during growth in zinc-deficient conditions. ZIP9 transporter is involved in zinc uptake in roots (PubMed:26306426). SUBCELLULAR LOCATION: Nucleus.


SIMILARITY: Belongs to the deoxyhypusine synthase family.


FUNCTION: 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. SIMILARITY: Belongs to the kynurenine formamidase family.


FUNCTION: Accessory component 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 (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein.


FUNCTION: Assists in the loading of diacylglycerol, generated from triacylglycerol stores in the fat body through the action of adipokinetic hormone, into lipophorin, the hemolymph lipoprotein. It increases the lipid carrying capacity of lipophorin by covering the expanding hydrophobic surface resulting from diacylglycerol uptake. It thus plays a critical role in the transport of lipids during flight in several species of insects (By similarity). Has hemagglutinating activity towards rabbit erythrocytes. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the insect apolipophorin-3 family.


FUNCTION: Extracellular fibrinogen-binding protein that plays an important role in virulence (PubMed:7934883). By interacting with the alpha chain of fibrinogen and its derivative fibrin, enhances a non- functional interaction between fibrinogen and platelets and is responsible for repression of fibrinogen-dependent platelet aggregation. In addition, assembles a fibrinogen protective shield around the bacteria which results in impaired phagocytic clearance by the host. Mechanistically, interacts with host complement C3b deposited on the surface of the bacterium via its C-terminal and then recruits fibrinogen via its N-terminal (By similarity). FUNCTION: Extracellular fibrinogen-binding protein that plays an important role in virulence. By interacting with the alpha chain of fibrinogen and its derivative fibrin, enhances a non-functional interaction between fibrinogen and platelets and is responsible for repression of fibrinogen-dependent platelet aggregation. In addition, assembles a fibrinogen protective shield around the bacteria which results in impaired phagocytic clearance by the host. Mechanistically, interacts with host complement C3b deposited on the surface of the bacterium via its C-terminal and then recruits fibrinogen via its N- terminal. SUBCELLULAR LOCATION: Secreted. SUBCELLULAR LOCATION: Secreted.


SIMILARITY: Belongs to the Schlafen family. Subgroup I subfamily.


FUNCTION: Catalyzes the specific phosphorylation of arginine residues in proteins (By similarity). Is required for stress tolerance and virulence in S.aureus. Acts as a modulator of the repressor activity of CtsR upon heavy metal and oxidative stress caused by these metal ions (PubMed:22902728). FUNCTION: Catalyzes the specific phosphorylation of arginine residues in proteins. SIMILARITY: Belongs to the ATP:guanido phosphotransferase family.


FUNCTION: NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be ubiquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the complex I subunit 2 family.


FUNCTION: Two distinct, membrane-bound, FAD-containing enzymes are responsible for the catalysis of fumarate and succinate interconversion; fumarate reductase is used in anaerobic growth, and succinate dehydrogenase is used in aerobic growth. Anchors the catalytic components of the fumarate reductase complex to the cell inner membrane, binds quinones. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the FrdD family.


FUNCTION: Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH. Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 2 family.


FUNCTION: Involved in the maintenance of the Golgi structure. May play a role in hematopoiesis. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cytoplasm. Golgi apparatus, cis-Golgi network membrane; Multi-pass membrane protein. Note=Localization to the cytoplasm or to the cell membrane is developmentally and ontogenetically regulated. SIMILARITY: Belongs to the YIP1 family.


FUNCTION: Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues (By similarity). Regulates the cellular cytoskeleton by enhancing actin stress fiber formation via phosphorylation of cofilin and by preventing microtubule breakdown via inhibition of TAOK1/MARKK kinase activity (By similarity). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Positively regulates integrin- mediated cell spreading, via phosphorylation of cofilin (PubMed:15584898). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of ciliary vesicle directional trafficking to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). Probably plays a central role at and after the meiotic phase of spermatogenesis (By similarity). SUBCELLULAR LOCATION: Cytoplasm Cytoplasm, perinuclear region Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Cell projection, lamellipodium Note=Colocalizes with SPRY4 in vesicular spots in the cytoplasm (PubMed:15584898). Localized to F- actin-rich lamellipodia at the cell periphery following fibronectin- mediated cell adhesion of Schwann cells (By similarity). SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.


FUNCTION: 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 (Potential). SUBCELLULAR LOCATION: Cell membrane Membrane, coated pit; Peripheral membrane protein; Cytoplasmic side Note=Component of the coat surrounding the cytoplasmic face of coated vesicles in the plasma membrane. SIMILARITY: Belongs to the adaptor complexes medium subunit family.


FUNCTION: May function to promote vesicle trafficking and/or fusion. May contribute to the establishment and maintenance of centrosome function (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Cytoplasm Cytoplasm, cytoskeleton. SIMILARITY: Belongs to the hook family.


SUBCELLULAR LOCATION: Periplasm. SIMILARITY: Belongs to the UPF0065 (bug) family.


FUNCTION: Fatty acyl-coenzyme A (CoA) diphosphatase that hydrolyzes fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'- bisphosphate (By similarity). Mediates the hydrolysis of a wide range of CoA esters, including choloyl-CoA and branched-chain fatty-acyl-CoA esters and at low substrate concentrations medium and long-chain fatty- acyl-CoA esters are the primary substrates (By similarity). Highest activity seen with medium-chain acyl-CoA esters and higher rates of activity seen with the unsaturated acyl-CoA esters compared with the saturated esters (By similarity). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (By similarity). SUBCELLULAR LOCATION: Peroxisome. SIMILARITY: Belongs to the Nudix hydrolase family.


SIMILARITY: Belongs to the eukaryotic ribosomal protein eL43 family.


FUNCTION: Replicates viral genomic DNA. This polymerase possesses two enzymatic activities: DNA synthesis (polymerase) and an exonucleolytic activity that degrades single-stranded DNA in the 3'-5' direction. SIMILARITY: Belongs to the DNA polymerase type-A family.


FUNCTION: Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites. 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 (By similarity). May act as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine (By similarity). SIMILARITY: Belongs to the SOS response-associated peptidase family.


FUNCTION: Binds to heparan sulfate proteoglycans on the surface of fibroblast cells. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. SIMILARITY: Belongs to the MHC class I family.


FUNCTION: Probable inward-rectifying potassium channel. Assuming opened or closed conformations in response to the voltage difference across the membrane, the channel is activated by hyperpolarization (By similarity). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the potassium channel family. Plant (TC 1.A.1.4) subfamily.


FUNCTION: Protein phosphatase that catalyzes the dephosphorylation of the C-terminal domain of RNA polymerase II. Plays a role in RNA processing and termination. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the SSU72 phosphatase family.


FUNCTION: Ethylene receptor related to bacterial two-component regulators. Acts as negative regulator of ethylene signaling. May play a role in the regulation of flowering by up-regulating GI (GIGANTEA) and RCN1 and regulate starch accumulation by down-regulating the alpha- amylase AMY3D. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ethylene receptor family.


FUNCTION: May have a regulatory bifunctional role. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein. SIMILARITY: Belongs to the CAP family.


FUNCTION: One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit. FUNCTION: One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit. SIMILARITY: Belongs to the universal ribosomal protein uL3 family. SIMILARITY: Belongs to the universal ribosomal protein uL3 family.


FUNCTION: Responsible for the polymerization of the main chain of the major teichoic acid by sequential transfer of ribitol phosphate units from CDP-ribitol to the second glycerol phosphate attached to the disaccharide linkage unit. Synthesizes polymers of more than 40 ribitol phosphate units in length. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein. SIMILARITY: Belongs to the CDP-glycerol glycerophosphotransferase family.


FUNCTION: May play a role in maturation and encapsidation of viral replicated genome, by promoting DNA homologous recombination. Exhibits endonuclease and 5'->3' exonuclease activities. The endonuclease activity displays a specificity for ssDNA in vitro (By similarity). SUBCELLULAR LOCATION: Host nucleus. SIMILARITY: Belongs to the baculo-herpesviridae alkaline nuclease family.


FUNCTION: Putative integrase that is involved in the insertion of the integrative and conjugative element ICEBs1. Required for the excision of ICEBs1 from the donor cell genome and subsequent integration in the recipient cell genome. Appears not to be transferred through the mating pore. Integration of ICEBs1 involves an attachment site in the chromosome, attB, and a site in the circular form of ICEBs1, attICEBs1. SIMILARITY: Belongs to the 'phage' integrase family.


FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up- regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down- regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells (By similarity). SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.


FUNCTION: Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2. DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase, predominantly CBR1 (By similarity). Facilitates the reduction of the catalytic iron-sulfur cluster found in the DPH1 subunit (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the DPH1/DPH2 family. DPH2 subfamily.


FUNCTION: Catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to an acceptor substrate and releases both CoA and the acetylated product. It prefers the antibiotic chloramphenicol.


FUNCTION: Minor envelope protein. SUBCELLULAR LOCATION: Virion membrane; Single-pass type I membrane protein Host endoplasmic reticulum membrane; Single- pass type I membrane protein Host Golgi apparatus membrane; Single-pass type I membrane protein Secreted Note=Only a small fraction of GP3 synthesized in infected cells ends up in virions. The transmembrane region probably functions as an uncleaved signal (By similarity). SIMILARITY: Belongs to the arteriviridae GP3 protein family.


FUNCTION: The M ring may be actively involved in energy transduction. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein Bacterial flagellum basal body. SIMILARITY: Belongs to the FliF family.


FUNCTION: Involved in cytoplasm to vacuole transport (Cvt) and autophagic vesicle formation. Autophagy is essential for maintenance of amino acid levels and protein synthesis under nitrogen starvation. Required for selective autophagic degradation of the nucleus (nucleophagy). Also required for mitophagy, which eliminates defective or superfluous mitochondria in order to fulfill cellular energy requirements and prevent excess ROS production. 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 and ATG8 association to the vesicle membranes (By similarity). SUBCELLULAR LOCATION: Preautophagosomal structure membrane; Peripheral membrane protein. SIMILARITY: Belongs to the ATG5 family.


FUNCTION: Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis (PubMed:17494869, PubMed:11877457, PubMed:11877461, PubMed:12952931, PubMed:14617351, PubMed:25653444). Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1 (PubMed:17494869). Preferentially, may phosphorylate substrates on threonine residues (PubMed:11877457, PubMed:18657069). Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes (PubMed:12952931). Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes (PubMed:18657069). Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (PubMed:21464124). FUNCTION: (Microbial infection) By regulating clathrin-mediated endocytosis, AAK1 plays a role in the entry of hepatitis C virus as well as for the lifecycle of other viruses such as Ebola and Dengue. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein Membrane, clathrin-coated pit Presynapse Note=Active when found in clathrin- coated pits at the plasma membrane. In neuronal cells, enriched at presynaptic terminals. In non-neuronal cells, enriched at leading edge of migrating cells. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.


FUNCTION: Catalyzes the conversion of D-serine to pyruvate and ammonia (PubMed:17869212, PubMed:17937657). May play a role in D-serine detoxification (PubMed:17869212, PubMed:17937657). SIMILARITY: Belongs to the DSD1 family.


FUNCTION: Inactive kinase that suppresses ERK activity by promoting phosphatase activity of DUSP3 which specifically dephosphorylates and inactivates ERK in the nucleus. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily.


FUNCTION: 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. Can be blocked by external barium. SUBCELLULAR LOCATION: Membrane; Multi- pass membrane protein. SIMILARITY: Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ5 subfamily.


FUNCTION: Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP (By similarity). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency (By similarity). Can use triazofurin monophosphate (TrMP) as substrate (By similarity). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+) (By similarity). For the pyrophosphorolytic activity, prefers NAD(+) and NaAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively (By similarity). Involved in the synthesis of ATP in the nucleus, together with PARP1, PARG and NUDT5 (By similarity). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (By similarity). Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (By similarity). Also acts as a cofactor for glutamate and aspartate ADP- ribosylation by directing PARP1 catalytic activity to glutamate and aspartate residues on histones. Protects against axonal degeneration following mechanical or toxic insults. Delays axonal degeneration after axotomy. Results in a >10-fold increase in intact neurites 72 hours after injury (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase family.


FUNCTION: Component of the mitochondrial ribosome (mitoribosome), a dedicated translation machinery responsible for the synthesis of mitochondrial genome-encoded proteins, including at least some of the essential transmembrane subunits of the mitochondrial respiratory chain. The mitoribosomes are attached to the mitochondrial inner membrane and translation products are cotranslationally integrated into the membrane. SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the universal ribosomal protein uS2 family.


FUNCTION: Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto reductase 2 subfamily.


FUNCTION: Endo-1,4-beta-xylanase involved in the hydrolysis of xylan, a major structural heterogeneous polysaccharide found in plant biomass representing the second most abundant polysaccharide in the biosphere, after cellulose. Hydrolyzes birch-wood xylan, with a similar activity toward oat-spelt xylan. Also shows weak activities toward pNP-beta-D- cellobioside and pNP-beta-D-xylopyranoside, but no detectable activity toward carboxymethyl cellulose and pNP-beta-L-arabinofuranoside.-. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 10 (cellulase F) family.


FUNCTION: Acts as a semaphorin-like protein and binds to host plexin C1 receptor. May alter the movement of host plexin C1-expressing cells including dendritic cells, monocytes, or granulocytes in the proximity of infected cells. May also regulate host cell cytoskeleton of neighboring cells to improve viral infection (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the semaphorin family.


FUNCTION: 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). SUBCELLULAR LOCATION: Cytoplasm, cytosol Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Cell projection, cilium. SIMILARITY: Belongs to the RILPL family.


FUNCTION: [Neuromedin-C]: Induces an itch response through activation of receptors present on mast cells, triggering mast cell degranulation. FUNCTION: Stimulates the release of gastrin and other gastrointestinal hormones (PubMed:496973). Contributes to the perception of prurient stimuli and to the transmission of itch signals in the spinal cord that promote scratching behavior (By similarity). Contributes primarily to nonhistaminergic itch sensation (By similarity). In one study, shown to act in the amygdala as part of an inhibitory network which inhibits memory specifically related to learned fear (By similarity). In another study, shown to act on vasoactive intestinal peptide (VIP)-expressing cells in the auditory cortex, most likely via extrasynaptic diffusion from local and long-range sources, to mediate disinhibition of glutamatergic cells via VIP cell-specific GRPR signaling which leads to enhanced auditory fear memories (By similarity). Contributes to the regulation of food intake (By similarity). Inhibits voltage-gated sodium channels but enhances voltage-gated potassium channels in hippocampal neurons (By similarity). Induces sighing by acting directly on the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity (By similarity). SUBCELLULAR LOCATION: Secreted Cytoplasmic vesicle, secretory vesicle lumen Cell projection, neuron projection Note=In neurons of the retrotrapezoid nucleus/parafacial respiratory group, expressed on neuron projections which project into the pre-Botzinger complex. SIMILARITY: Belongs to the bombesin/neuromedin-B/ranatensin family.


FUNCTION: Transports viral genome to neighboring plant cells directly through plasmosdesmata, without any budding. The movement protein allows efficient cell to cell propagation, by bypassing the host cell wall barrier. Acts by forming tubules structures that increase the size exclusion limit (SEL) of plasmodesmata, thereby allowing viral ribonucleocapsids to spread directly to neighboring cells (By similarity). SUBCELLULAR LOCATION: Host cell junction, host plasmodesma. Note=Assembles in tubules that are embedded within modified plasmodesmata. SIMILARITY: Belongs to the caulimoviridae movement protein family.


FUNCTION: Required for proper maturation of seed storage proteins. Forms a complex with MAG2, ZW10/MIP1 and MIP2 on the endoplasmic reticulum that may be responsible for efficient transport of seed storage proteins. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. SIMILARITY: Belongs to the STXBP/unc-18/SEC1 family.


FUNCTION: Involved in the biosynthesis of sinapoylated anthocyanins. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase S10 family.


FUNCTION: Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. FUNCTION: Matrix protein p15 forms the outer shell of the core of the virus, lining the inner surface of the viral membrane. FUNCTION: Nucleocapsid protein p13 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers (By similarity). SUBCELLULAR LOCATION: [Nucleocapsid protein p13]: Virion. SUBCELLULAR LOCATION: [Matrix protein p15]: Virion. SUBCELLULAR LOCATION: [Capsid protein p24]: Virion. SIMILARITY: Belongs to the feline lentivirus group gag polyprotein family.


FUNCTION: Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells. SUBCELLULAR LOCATION: Peroxisome. SIMILARITY: Belongs to the catalase family.


FUNCTION: RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Prevents binding of U2AF2 to the 3'-splice site. Regulates alternative splicing of tissue- specific exons and of differentially spliced exons during erythropoiesis. Seems to act as a coregulatory factor of ER-alpha (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm.


FUNCTION: Unknown. In males lacking the Y chromosome, its strong overexpression leads to the appearance of proteinaceous star-shaped crystals in the primary spermatocytes causing meiotic drive, possibly by interfering with normal casein kinase 2 activity. SIMILARITY: Belongs to the casein kinase 2 subunit beta family.


FUNCTION: Probably involved in the control of the structural glucose backbone of osmoregulated periplasmic glucans (OPGs). SUBCELLULAR LOCATION: Periplasm. SIMILARITY: Belongs to the OpgD/OpgG family.


FUNCTION: Cell division protein that is involved in the assembly of the Z ring. May serve as a membrane anchor for the Z ring. SUBCELLULAR LOCATION: Cell inner membrane; Peripheral membrane protein; Cytoplasmic side Note=Localizes to the Z ring in an FtsZ-dependent manner. Targeted to the membrane through a conserved C-terminal amphipathic helix. SIMILARITY: Belongs to the FtsA/MreB family.


FUNCTION: Catalytic subunit of cellulose synthase terminal complexes ('rosettes'), required for beta-1,4-glucan microfibril crystallization, a major mechanism of the cell wall formation. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the glycosyltransferase 2 family. Plant cellulose synthase subfamily.


FUNCTION: Receptor potentially involved in both adhesion and signaling processes early after leukocyte activation. Plays an essential role in leukocyte migration. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SUBCELLULAR LOCATION: [Adhesion G protein-coupled receptor E5 subunit alpha]: Secreted, extracellular space. SIMILARITY: Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.


FUNCTION: Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity (PubMed:14560022, PubMed:21931631). Activates serine/threonine-protein kinase TBK1 and facilitates its oligomerization (PubMed:14560022, PubMed:21931631). Enhances the phosphorylation of NF-kappa-B p65 subunit RELA by TBK1 (PubMed:14560022, PubMed:21931631). Promotes TBK1-induced as well as TNF-alpha or PMA-induced activation of NF-kappa-B (PubMed:14560022, PubMed:21931631). Participates in IFNB promoter activation via TICAM1 (PubMed:15611223). SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Converts o-succinylbenzoyl-CoA (OSB-CoA) to 1,4-dihydroxy-2- naphthoyl-CoA (DHNA-CoA). SIMILARITY: Belongs to the enoyl-CoA hydratase/isomerase family. MenB subfamily.


FUNCTION: 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. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase family. Fucose synthase subfamily.


FUNCTION: Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Probable neurotoxin with ion channel impairing activity. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the neurotoxin 27 (Jztx-72) family. ICK-72 subfamily.


FUNCTION: Involved in protein ubiquitination and degradation during development. Mediates protein ubiquitination at the mound and finger stage required for subsequent development and may be an essential component of the developmental transition between the induction of postaggregative gene expression and subsequent cell-type differentiation and morphogenesis. ubcB and ubpB differentially control ubiquitination/deubiquitination and degradation of mkkA protein in a cell-type-specific and temporally regulated manner. SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.


FUNCTION: Required for the germination response to inosine. Has no role in L-alanine germination. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC) superfamily. Spore germination protein (SGP) (TC 2.A.3.9) family.


FUNCTION: Glycosylates the amino acid-related molecules isoleucic acid (2-hydroxy-3-methylpentanoic acid) and valic acid (2-hydroxy-3- methylbutyric acid). Acts as a negative regulator of salicylic acid (SA)-dependent plant defense in the absence of pathogens and promotes the jasmonate (JA) response. Negatively influences the onset of senescence. SIMILARITY: Belongs to the UDP-glycosyltransferase family.


FUNCTION: May form with the serine/threonine protein phosphatase l(1)G0269 an active complex dephosphorylating and activating lipin-like phosphatases. Lipins are phosphatidate phosphatases that catalyze the conversion of phosphatidic acid to diacylglycerol and control the metabolism of fatty acids at different levels (By similarity). SUBCELLULAR LOCATION: Nucleus membrane; Multi-pass membrane protein Cytoplasm. SIMILARITY: Belongs to the CNEP1R1 family.


FUNCTION: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (PubMed:36417862). Does not seem to have NDK kinase activity. Confers protection from cell death by Bax and alters the cellular levels of several antioxidant enzymes including Gpx5. May play a role in spermiogenesis by increasing the ability of late-stage spermatids to eliminate reactive oxygen species (PubMed:12788088). SUBCELLULAR LOCATION: Cell projection, cilium Cytoplasm, cytoskeleton, flagellum axoneme. SIMILARITY: Belongs to the NDK family.


FUNCTION: This isozyme seems to be implicated in olfaction. Active in the demethylation of erythromycin as well as benzphetamine. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein. SIMILARITY: Belongs to the cytochrome P450 family.


FUNCTION: Chloroplast omega-3 fatty acid desaturase introduces the third double bond in the biosynthesis of 16:3 and 18:3 fatty acids, important constituents of plant membranes. It is thought to use ferredoxin as an electron donor and to act on fatty acids esterified to galactolipids, sulfolipids and phosphatidylglycerol. SUBCELLULAR LOCATION: Plastid, chloroplast membrane; Peripheral membrane protein. SIMILARITY: Belongs to the fatty acid desaturase type 1 family.


SUBCELLULAR LOCATION: Secreted Plastid, amyloplast Secreted, cell wall. SIMILARITY: Belongs to the glycosyl hydrolase 28 family.


FUNCTION: Functions as an ammonia transporter. May play a role in the elimination of ammonia in the gill (By similarity). SUBCELLULAR LOCATION: Basolateral cell membrane; Multi- pass membrane protein Cytoplasmic vesicle membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.


SIMILARITY: Belongs to the opacity porin family.


FUNCTION: Involved in the germination response to the combination of glucose, fructose, L-asparagine, and KCl. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor. SIMILARITY: Belongs to the GerABKC lipoprotein family.


SIMILARITY: Belongs to the UPF0254 family.


FUNCTION: Catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP substrates to beta-hydroxyacyl-ACP products, the first reductive step in the elongation cycle of fatty acid biosynthesis. SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) family.


SIMILARITY: Belongs to the ComB family.


FUNCTION: Lectin that plays a role in innate immunity, apoptosis and embryogenesis. Calcium-dependent lectin that binds self and non-self glycoproteins presenting high mannose oligosaccharides with at least one terminal alpha-1,2-linked mannose epitope. Primarily recognizes the terminal disaccharide of the glycan. Also recognizes a subset of fucosylated glycans and lipopolysaccharides. Plays a role in innate immunity through its ability to bind non-self sugars presented by microorganisms and to activate the complement through the recruitment of MAPS1. Also plays a role in apoptosis through its ability to bind in a calcium-independent manner the DNA present at the surface of apoptotic cells and to activate the complement in response to this binding. Finally, plays a role in development, probably serving as a guidance cue during the migration of neural crest cells and other cell types during embryogenesis. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the COLEC10/COLEC11 family.


FUNCTION: Multifunctional protein which functions as a renin, prorenin cellular receptor and is involved in the assembly of the lysosomal proton-transporting V-type ATPase (V-ATPase) and the acidification of the endo-lysosomal system (By similarity). May mediate renin-dependent cellular responses by activating ERK1 and ERK2 (By similarity). By increasing the catalytic efficiency of renin in AGT/angiotensinogen conversion to angiotensin I, may also play a role in the renin- angiotensin system (RAS) (By similarity). Through its function in V- type ATPase (v-ATPase) assembly and acidification of the lysosome it regulates protein degradation and may control different signaling pathways important for proper brain development, synapse morphology and synaptic transmission (PubMed:26376863, PubMed:29127204, PubMed:30985297). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein Lysosome membrane; Single-pass type I membrane protein Cytoplasmic vesicle, autophagosome membrane; Single-pass type I membrane protein Cell projection, dendritic spine membrane; Single-pass type I membrane protein Cell projection, axon Endosome membrane; Single-pass type I membrane protein Cytoplasmic vesicle, clathrin-coated vesicle membrane; Single-pass type I membrane protein Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass type I membrane protein.


FUNCTION: Responsible for synthesis of pseudouridine from uracil at positions 1911, 1915 and 1917 in 23S ribosomal RNA. SIMILARITY: Belongs to the pseudouridine synthase RluA family.


FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins and plays a role in several biological processes such as cell cycle, cell proliferation, or maintenance of chromosome stability (PubMed:15145941, PubMed:34791250). Recognizes and ubiquitinates BIRC2 and the cell cycle regulator DLGAP5 (PubMed:15145941, PubMed:16510124, PubMed:22212761). Plays a role downstream of PINK1 in the clearance of damaged mitochondria via selective autophagy (mitophagy) by targeting PRKN to dysfunctional depolarized mitochondria. Promotes MFN1 ubiquitination. Mediates the ubiquitination and proteasomal degradation of UXT isoform 2, thereby impairing the NF-kappa-B signaling pathway (PubMed:33010352). Inhibits NF-kappa-B pathway also by promoting the ubiquitination of TRAF2 (PubMed:22212761). Affects the assembly state and activity of the proteasome in the cells including neurons by ubiquitinating the proteasomal subunit PSMA2 via 'Lys-63'-linked polyubiquitin chains (By similarity). Promotes 'Lys-48'-linked polyubiquitination SIRT7, leading to the hydrogen peroxide-induced cell death (PubMed:36646384). SUBCELLULAR LOCATION: Cytoplasm Nucleus Mitochondrion Cytoplasm, cytosol Note=Predominantly cytoplasmic (PubMed:16096642). A minor proportion is detected in the nucleus (PubMed:16096642). Relocates from the cytosol to depolarized mitochondria (PubMed:23933751).


FUNCTION: GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes. SUBCELLULAR LOCATION: Cytoplasm Golgi apparatus membrane; Peripheral membrane protein; Cytoplasmic side Note=Also found on peripheral punctate structures likely to be endoplasmic reticulum-Golgi intermediate compartment.


SIMILARITY: Belongs to the mimivirus L39/R874 family.


FUNCTION: Histone-like DNA-binding protein which is capable of wrapping DNA to stabilize it, and thus to prevent its denaturation under extreme environmental conditions. FUNCTION: Histone-like DNA-binding protein which is capable of wrapping DNA to stabilize it, and thus to prevent its denaturation under extreme environmental conditions. SIMILARITY: Belongs to the bacterial histone-like protein family.


SIMILARITY: Belongs to the M.jannaschii MJ0150/MJ0739/MJ0745/MJ1460/MJ1642 family.


FUNCTION: Acts as component of the mcm2-7 complex (mcm complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the mcm2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. The existence of maternal and zygotic forms of mcm3 and mcm6 suggests that specific forms of mcm2-7 complexes may be used during different stages of development. May replace mmcm6 in the mcm2-7 complex (By similarity). SUBCELLULAR LOCATION: Nucleus Note=Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses. SIMILARITY: Belongs to the MCM family.


FUNCTION: Probable secreted venom toxin. SUBCELLULAR LOCATION: Secreted.


FUNCTION: Binds pheromones that are released from drying urine of males. These pheromones affect the sexual behavior of females (By similarity). Acts as a shuttle for pheromonal communication between individuals of the same species. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.


FUNCTION: Metallothioneins have a high content of cysteine residues that bind various heavy metals (Probable). Functions as metal chelator of copper (Cu) and zinc (Zn) (PubMed:18287486). Plays a role in storing and distributing Zn ion in seed (PubMed:22014117). SUBCELLULAR LOCATION: Cytoplasm Nucleus Cell membrane. SIMILARITY: Belongs to the metallothionein superfamily. Type 15 family.


FUNCTION: Involved in pollen mitosis II (PMII) regulation during male gametogenesis. SUBCELLULAR LOCATION: Endomembrane system; Multi-pass membrane protein Vacuole membrane; Multi- pass membrane protein.


FUNCTION: Exhibits natriuretic and vasodepressor activity. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the natriuretic peptide family.


FUNCTION: Involved in the transposition of the insertion sequence. SIMILARITY: Belongs to the transposase 32 family.


FUNCTION: Assembles to form a prolate capsid about 56 nm in length and 41 nm in width. SUBCELLULAR LOCATION: Virion.


FUNCTION: Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross- linking of the peptide subunits) (Probable). Required for vegetative growth (Probable). Has a partially redundant function with PBP-2A (pbpA) during spore outgrowth (PubMed:9851991). SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein Forespore inner membrane; Single-pass type II membrane protein Note=Probably found all over the whole cell at low concentrations. Also localizes to the division site in vegetative cells. SIMILARITY: In the C-terminal section; belongs to the transpeptidase family. SIMILARITY: In the N-terminal section; belongs to the glycosyltransferase 51 family.


FUNCTION: Major enzyme of the phenylpropanoid pathway that mediates the production of several precursors for numerous metabolites and regulates carbon flow (PubMed:26412334). Catalyzes the formation of CoA thioesters using 4-coumarate, ferulate, caffeate, and cinnamate as substrates (PubMed:8819324, PubMed:26412334). Follows a two-step reaction mechanism, wherein a (hydroxy)cinnamate substrate first undergoes adenylation by ATP leading to an acyl-AMP, followed by a thioesterification in the presence of CoA to yield the final (hydroxy)cinnamoyl-CoA product (PubMed:26412334). Almost inactive toward sinapate (PubMed:8819324, PubMed:26412334). SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Cell surface proteoglycan that may bear both heparan sulfate and chondroitin sulfate. The multiple functional domains provide potential sites for mediating the adhesive cell-matrix interactions and cytoskeletal reorganization involved in limb chondrogenesis. Interaction with other matrix ligands as well as phosphorylation and shedding of the ectodomain might be involved in cell shape changes that occur during chondrogenesis. Furthermore, shedding of the ectodomain might break the adhesive interactions that promoted condensation, thus facilitating the deposition of cartilage matrix molecules. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. SIMILARITY: Belongs to the syndecan proteoglycan family.


FUNCTION: Has a toxic effect on insects and mammals. On German cockroach larvae, it provokes contraction, paralysis and lethality (PubMed:26109302). Intracerebroventricular injection into mice causes severe neurotoxic symptoms (PubMed:26109302). It fully competes with the binding of the iodinated Css4 (AC P60266) on rat brain synaptosomes, with moderate affinity and in a concentration-dependent manner (EC(50)=25 nM). It may act on both site 3 and site 4 of voltage- gated sodium channels. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family.


FUNCTION: Replicates the viral genome, host DNA polymerases cannot substitute for the viral enzyme in this process. SIMILARITY: Belongs to the DNA polymerase type-B family.


FUNCTION: Component of the mitochondrial import inner membrane translocase that mediates the translocation of transit peptide- containing proteins across the mitochondrial inner membrane. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Single-pass membrane protein. SIMILARITY: Belongs to the TIM50 family.


FUNCTION: Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates to the cytoplasm following phosphorylation and activation. Interaction with ERK3/MAPK6 or ERK4/MAPK4 and phosphorylation at Thr-182, activates the protein kinase activity, followed by translocation to the cytoplasm. Phosphorylation by PKA/PRKACA at Ser-115 also induces nuclear export. SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.


FUNCTION: Complex that is thought to mediate chromatin assembly in DNA replication and DNA repair. Assembles histone octamers onto replicating DNA in vitro. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer. SUBCELLULAR LOCATION: Nucleus Note=DNA replication foci. SIMILARITY: Belongs to the CHAF1A family.


FUNCTION: Produces L-cysteine from O-acetyl-L-serine and hydrogen sulfide. Can also use pyrazole and 3,4-dihydroxypyridine instead of the hydrogen sulfide to produce two plant specific non-protein amino acids beta-pyrazolylalanine and L-mimosine. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the cysteine synthase/cystathionine beta- synthase family.


FUNCTION: Control of the last step in methionine biosynthesis; MetR is a positive activator of the metA, metE and metH genes. It is also a negative regulator of its own expression (By similarity). FUNCTION: Control of the last step in methionine biosynthesis; MetR is a positive activator of the metA, metE and metH genes. MetR is also a negative regulator of its own expression. Binds homocysteine as an inducer. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the LysR transcriptional regulatory family.


SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. Histidinol-phosphate aminotransferase subfamily.


FUNCTION: Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. SUBCELLULAR LOCATION: Secreted Host cytoplasm Note=Secreted via type III secretion system 2 (SPI-2 TTSS), and delivered into the host cytoplasm. Localizes to the Salmonella-containing vacuole (SCV) at early time points following invasion and subsequently traffics away from the SCV along Salmonella-induced filaments (Sifs) in epithelial cells. SIMILARITY: Belongs to the Sif family.


FUNCTION: Plant non-specific lipid-transfer proteins transfer phospholipids as well as galactolipids across membranes. May play a role in wax or cutin deposition in the cell walls of expanding epidermal cells and certain secretory tissues. SUBCELLULAR LOCATION: Secreted, cell wall. SIMILARITY: Belongs to the plant LTP family.


FUNCTION: Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by retaining it in the cytoplasm. Inhibits both TNFRSF6- and TNFRSF1A- mediated CASP8 activity and apoptosis. Regulates glucose transport by controlling both the content of SLC2A1 glucose transporters on the plasma membrane and the insulin-dependent trafficking of SLC2A4 from the cell interior to the surface (By similarity). SUBCELLULAR LOCATION: Cytoplasm Note=Associated with microtubules.


FUNCTION: Catalyzes the dehydration of L-arabonate to L-2-keto-3- deoxyarabonate (L-KDA). Is involved in a degradation pathway of L- arabinose that allows A.brasilense to grow on L-arabinose as a sole carbon source. To a lesser extent, can also use D-xylonate as substrate, but not D-galactonate, D-arabonate, and D-gluconate. SIMILARITY: Belongs to the IlvD/Edd family.


FUNCTION: Catalyzes N-methylation of phosphoethanolamine, phosphomonomethylethanolamine and phosphodimethylethanolamine, the three methylation steps required to convert phosphoethanolamine to phosphocholine. Required for root system development and epidermal cell integrity through its role in choline and phospholipid metabolism. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase superfamily. PEAMT family.


FUNCTION: Probable transcription factor involved in seed development (PubMed:21447172, Ref.1, PubMed:29853599). Plays a role in seed morphogenesis by promoting the correct development of endotesta cell layer, which directs the further development of the seed coat, the endosperm, and consequently the embryo (Ref.1, PubMed:29853599). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: May function as a transcriptional coregulator (By similarity). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (By similarity). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of quercetin, rhamnetin and isorhamnetin but not kaempferol. O-sulfation of position 3 of flavonol. May play a role in auxin transport. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the sulfotransferase 1 family.


FUNCTION: Part of a two-component antiporter that catalyzes the efflux of Na(+), Li(+) and K(+) in exchange for external protons. Shows a preference for Na(+), followed by K(+) and Li(+). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the UmpA/UmpB family.


FUNCTION: May cause loosening and extension of plant cell walls by disrupting non-covalent bonding between cellulose microfibrils and matrix glucans. No enzymatic activity has been found. May be required for rapid internodal elongation in deepwater rice during submergence (By similarity). SUBCELLULAR LOCATION: Secreted, cell wall Membrane; Peripheral membrane protein. SIMILARITY: Belongs to the expansin family. Expansin B subfamily.


SUBCELLULAR LOCATION: Virion. SIMILARITY: Belongs to the nanoviridae capsid protein family.


SIMILARITY: Belongs to the coronaviruses ns2a protein family.


FUNCTION: Component of the endomembrane trafficking machinery that is involved in protein recycling to the plasma membrane. Forms a complex with BIG5/MIN7/BEN1 and actin to modulate the function of the trans- Golgi network /early endosome at the intersection of the exocytic and endocytic pathways. May be linking post-Golgi traffic with the actin cytoskeleton. SUBCELLULAR LOCATION: Cytoplasm Endomembrane system Golgi apparatus, trans-Golgi network Early endosome.


FUNCTION: Component of nuclear connecting fibers associated with the transport of ribonucleoprotein particles from either the chromosome to the nuclear pore complex or their transient retention in the nucleoplasm. SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm, cytoskeleton. SUBCELLULAR LOCATION: [Isoform 1]: Nucleus.


FUNCTION: Catalyzes the hydrolytic cleavage of a subset of L- isoaspartyl (L-beta-aspartyl) dipeptides. Used to degrade proteins damaged by L-isoaspartyl residues formation. The best substrate for the enzyme reported thus far is iso-Asp-Leu. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the peptidase M38 family.


FUNCTION: Required for vacuolar assembly and vacuolar traffic. SIMILARITY: Belongs to the VPS41 family.


SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TMEM82 family.


FUNCTION: Monooxygenase; part of the ergochrome gene cluster responsible for the typical purple-black color of the ergot sclerotia (Probable). The ergochrome gene cluster produces several ergot pigments including the yellow ergochrome secalonic acid and its derivatives, as well as the red anthraquinones endocrocin and clavorubin (PubMed:28955461). The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase (PKS) CPUR_05437 (By similarity). The atrochrysone carboxyl ACP thioesterase CPUR_05436 then breaks the thioester bond and releases the atrochrysone carboxylic acid from CPUR_05437 (By similarity). The atrochrysone carboxylic acid is then converted to atrochrysone which is further transformed into emodin anthrone (By similarity). The next step is performed by the anthrone oxygenase CPUR_05434 that catalyzes the oxidation of emodinanthrone to emodin (By similarity). Emodin is further modified to yield monodictyphenone via several steps involving CPUR_05427, CPUR_05428, CPUR_05429 and CPUR_05430 (By similarity). The short chain dehydrogenase/reductase CPUR_05418 then catalyzes the C-5 ketoreduction to give the xanthone skeleton of the monomeric units (PubMed:32105084). Ergochromes formation requires further dimerization steps of different xanthone units, probably catalyzed by the cytochrome P450 monooxygenase CPUR_05419 (PubMed:28955461). CPUR_05425, CPUR_05426 and CPUR_05431 are unique to Claviceps, thus it is likely that they are involved in further modification of xanthone units or in their dimerization (PubMed:28955461). The yellow ergochromes and the red anthraquinone pigments endocrocin and clavorubin are products from the same PKS derived precursors and the latter are likely shunt products in the pathway of xanthone biosynthesis (PubMed:28955461). It is proposed that atrochrysone carboxylic acid released from the PKS CPUR_05437 can also be converted to endocrocin anthrone which is further oxidized into endocrocin by CPUR_05435 (By similarity). Endocrocin could be then modified to clavorubin, possibly by CPUR_05423 and CPUR_05431 (PubMed:28955461). Clavorubin is the principal anthraquinone metabolite produced by the cluster with a much higher yield compared to endocrocin (PubMed:28955461). SIMILARITY: Belongs to the avfA family.


FUNCTION: Plays a role in intracellular protein trafficking and degradation (By similarity). May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels (By similarity). May also regulate the intracellular trafficking of the ADR1B receptor (By similarity). May play a role in autophagy (By similarity). Together with MARCHF2 mediates the ubiquitination and lysosomal degradation of CFTR (By similarity). Overexpression results in CFTR intracellular retention and degradation in the lysosomes (By similarity). SUBCELLULAR LOCATION: Cytoplasm Golgi apparatus membrane; Peripheral membrane protein Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein Synapse Postsynaptic density Cell projection, dendrite Note=Enriched in synaptosomal and postsynaptic densities (PSD) fractions. Expressed in cell bodies and dendrites of Purkinje cells. Localized at the trans-Golgi network (TGN) of spermatids and the medulla of round spermatides (By similarity).


FUNCTION: Functions as a modulator of initiation or reinitiation events during DNA polymerase delta-mediated DNA synthesis. In the presence of ATP, stimulation of DNA polymerase delta-mediated DNA synthesis is decreased. Also plays a role in the innate immune defense against viruses. Stabilizes the RIGI dsRNA interaction and promotes RIGI 'Lys- 63'-linked polyubiquitination. In turn, RIGI transmits the signal through mitochondrial MAVS. SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Colocalizes with WRN in granular structures in the nucleus. SIMILARITY: Belongs to the AAA ATPase family. RarA/MGS1/WRNIP1 subfamily.


SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the TPP enzyme family.


FUNCTION: Amidohydrolase that hydrolyzes specifically one of the carboamide linkages in D-pantetheine thus recycling pantothenic acid (vitamin B5) and releasing cysteamine. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. SIMILARITY: Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.


FUNCTION: 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 (PubMed:9090384, PubMed:19687296, PubMed:22471590, PubMed:11370741, PubMed:35768507). 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 (PubMed:35768507). PEX12 also regulates PEX5 recycling by activating the E3 ubiquitin-protein ligase activity of PEX10 (PubMed:35768507). When PEX5 recycling is compromised, PEX12 stimulates PEX10-mediated polyubiquitination of PEX5, leading to its subsequent degradation (PubMed:35768507). SUBCELLULAR LOCATION: Peroxisome membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the pex2/pex10/pex12 family.


FUNCTION: Ammonium/proton antiporter that mediates the efflux of ammonium ions. Can also transport potassium or rubidium, but not sodium or lithium. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the monovalent cation:proton antiporter 2 (CPA2) transporter (TC 2.A.37) family.


SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase family.


FUNCTION: Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer. May be involved in the process which maintains transcribable genes in a unique chromatin conformation. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the HMGN family.


FUNCTION: [Isoform 1]: Cytokine that induces the release of T-cell- attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells. Can induce allergic inflammation by directly activating mast cells. FUNCTION: [Isoform 2]: May act as an antimicrobial peptide in the oral cavity and on the skin. SUBCELLULAR LOCATION: Secreted.


FUNCTION: Catalyzes the reduction of Delta(1)-pyrroline-2-carboxylate (Pyr2C) to L-proline, using NADPH as the electron donor. May be involved in a degradation pathway that converts trans-3-hydroxy-L- proline (t3LHyp) to L-proline. SIMILARITY: Belongs to the ornithine cyclodeaminase/mu-crystallin family.


FUNCTION: Co-chaperone for HSPA8/Hsc70 (PubMed:10816573). Stimulates ATP hydrolysis, but not the folding of unfolded proteins mediated by HSPA1A (in vitro) (PubMed:24318877). Plays a role in protein transport into mitochondria via its role as co-chaperone. Functions as co- chaperone for HSPA1B and negatively regulates the translocation of BAX from the cytosol to mitochondria in response to cellular stress, thereby protecting cells against apoptosis (PubMed:14752510). Promotes apoptosis in response to cellular stress mediated by exposure to anisomycin or UV (PubMed:24512202). SUBCELLULAR LOCATION: Membrane; Lipid- anchor Cytoplasm Microsome Nucleus Cytoplasm, perinuclear region Mitochondrion Note=Primarily associated with microsomes. A minor proportion is associated with mitochondria (By similarity). Primarily cytoplasmic. A minor proportion is associated with nuclei.


FUNCTION: Part of the twin-arginine translocation (Tat) system that transports large folded proteins containing a characteristic twin- arginine motif in their signal peptide across membranes. Together with TatB, TatC is part of a receptor directly interacting with Tat signal peptides. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TatC family.


FUNCTION: Hydrolyzes UDP-glucose to glucose 1-phosphate and UMP and UDP-galactose to galactose 1-phosphate and UMP. Preferred substrate is UDP-glucose. SIMILARITY: Belongs to the Nudix hydrolase family.


FUNCTION: Antimicrobial activity against Gram-negative bacteria E.coli and P.aeruginosa. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the beta-defensin family. LAP/TAP subfamily.


FUNCTION: Transfers an acetyl group from acetyl-CoA to L-homoserine, forming acetyl-L-homoserine. FUNCTION: Transfers an acetyl group from acetyl-CoA to L-homoserine, forming acetyl-L-homoserine. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the MetA family.


FUNCTION: A beta subtype methylase, recognizes the double-stranded sequence 5'-CCCGGG-3', methylates C-2 on both strands, and protects the DNA from cleavage by the Cfr9I endonuclease. SIMILARITY: Belongs to the N(4)/N(6)-methyltransferase family. N(4) subfamily.