FUNCTION: Involved in the generation of biological rhythms. The biological cycle depends on the rhythmic formation and nuclear localization of the tim-per complex. Light induces the degradation of tim, which promotes elimination of per. Nuclear activity of the heterodimer coordinatively regulates per and tim transcription negative feedback loop. Behaves as a negative element in circadian transcriptional loop. Does not appear to bind DNA, suggesting indirect transcriptional inhibition (By similarity). Expression exhibits prominent circadian variation in adult heads and in particular in the photoreceptor nuclei. SUBCELLULAR LOCATION: Nucleus. Note=Nuclear at specific periods of the day. Interaction with TIM is required for nuclear localization (By similarity).


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: General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites. Contributes to the regulation of gene expression; functions as activator in the absence of oxidative stress. Down-regulates expression of target genes in response to oxidative stress. Overexpression protects cells against apoptosis in response to oxidative stress. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the TFIIB family.


FUNCTION: Part of an E3 ubiquitin ligase complex for neddylation. Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes. Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Involved in oxygen transport from the lung to the various peripheral tissues. FUNCTION: [Hemopressin]: Hemopressin acts as an antagonist peptide of the cannabinoid receptor CNR1. Hemopressin-binding efficiently blocks cannabinoid receptor CNR1 and subsequent signaling. SIMILARITY: Belongs to the globin family.


FUNCTION: Forms passive diffusion pores that allow small molecular weight hydrophilic materials across the outer membrane. SUBCELLULAR LOCATION: Cell outer membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the alphaproteobacteria porin family.


FUNCTION: Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the eIF-3 subunit C family.


FUNCTION: Envelope protein required for virus entry into host cell and for cell-cell fusion (syncytium formation). SUBCELLULAR LOCATION: Virion membrane; Single-pass type II membrane protein Note=Component of the intracellular mature virion (IMV) membrane. SIMILARITY: Belongs to the poxviridae A28 protein family.


FUNCTION: DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK4 functions in RET-mediated neurite outgrowth and plays a positive role in activation of the MAP kinase pathway (By similarity). Putative link with downstream effectors of RET in neuronal differentiation. May be involved in the regulation of the immune response induced by T-cells. SIMILARITY: Belongs to the DOK family. Type B subfamily.


FUNCTION: PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the FKBP-type PPIase family. FKBP1 subfamily.


FUNCTION: Could be a succinate-semialdehyde dehydrogenase (NADP(+)). SIMILARITY: Belongs to the aldehyde dehydrogenase family.


SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the UPF0283 family.


FUNCTION: May be involved in modulating the expression of photoreceptor specific genes. Binds to the Ret-1 and Bat-1 element within the rhodopsin promoter (By similarity). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Component of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), a complex that is involved in endosomal cargo sorting. SUBCELLULAR LOCATION: Cytoplasm Note=Punctate pattern. SIMILARITY: Belongs to the BLOC1S4 family.


FUNCTION: Involved in the biosynthesis of the anthracycline (aromatic polyketide) antibiotic nogalamycin (PubMed:8760909, PubMed:8668120). Catalyzes the oxygenation of 12-deoxy-nogalonic acid at position 12 to yield nogalonic acid (PubMed:19255477, PubMed:20052967).


FUNCTION: Plays an important role in deacetylating mercapturic acids in kidney proximal tubules. SUBCELLULAR LOCATION: Apical cell membrane; Peripheral membrane protein. Cytoplasm. SIMILARITY: Belongs to the AspA/AstE family. Aspartoacylase subfamily.


FUNCTION: Acts as a calcium sensor. May promote vacuolation of aleurone cells in response to signal induced by gibberellin. CBL proteins interact with CIPK serine-threonine protein kinases. Binding of a CBL protein to the regulatory NAF domain of a CIPK protein lead to the activation of the kinase in a calcium-dependent manner (By similarity). SUBCELLULAR LOCATION: Vacuole, aleurone grain membrane Note=Tonoplast. SIMILARITY: Belongs to the calcineurin regulatory subunit family.


FUNCTION: Snake venom phospholipase A2 (PLA2) that has only a weak enzymatic activity. It has a myotoxic activity in vivo (dystrophic effect). PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the phospholipase A2 family. Group I subfamily. D49 sub-subfamily.


FUNCTION: Modulates transcription in response to changes in cellular NADH/NAD(+) redox state. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the transcriptional regulatory Rex family.


FUNCTION: Plays a role in the control of the actin cytoskeleton via activation of the JNK pathway. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side Endosome membrane; Lipid-anchor; Cytoplasmic side Note=Treatment with TNF activates endosomal but not plasma membrane RHOV. SIMILARITY: Belongs to the small GTPase superfamily. Rho family.


FUNCTION: L-ornithine N(5)-monooxygenase; part of the gene cluster that mediates the biosynthesis of coprinoferrin, an acylated tripeptide hydroxamate siderophore (PubMed:31496254). The biosynthesis of coprinoferrin depends on the hydroxylation of ornithine to N(5)- hydroxyornithine, catalyzed by the monooxygenase cpf2 (PubMed:31496254). The second step, the acylation of N(5)-hydroxy-L- ornithine to yield N(5)-hexanoyl-N(5)-hydroxyl-L-ornithine is catalyzed by a not yet identified acyltransferase (Probable). Finally, assembly of coprinoferrin is catalyzed by the nonribosomal peptide synthase (NRPS) cpf1 via amide bond formation between three N(5)-hexanoyl-N(5)- hydroxyl-L-ornithine molecules to release the linear trimer (PubMed:31496254). Interestingly, proteins seemingly not directly related to biosynthesis, such as transcription factors, replication factors, and autophagy-related proteins, are conserved among the clusters homologous to the coprinoferrin cluster, suggesting that the cluster may also play developmental and cell biological functions (Probable). SIMILARITY: Belongs to the lysine N(6)-hydroxylase/L-ornithine N(5)- oxygenase family.


FUNCTION: Required for motile ciliogenesis and flagellar genesis by mediating the maturation of the glycolytic enzyme ENO4. SUBCELLULAR LOCATION: Cytoplasm Cell projection, cilium. SIMILARITY: Belongs to the HOATZ family.


FUNCTION: Involved in the production of the bacteriocin subtilosin. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.


SIMILARITY: Belongs to the UPF0325 family.


FUNCTION: Methylates the carboxyl group of the C-terminal leucine residue of protein phosphatase 2A catalytic subunits to form alpha- leucine ester residues. SIMILARITY: Belongs to the methyltransferase superfamily. LCMT family.


FUNCTION: Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; and the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.


SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor.


FUNCTION: The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Required for autophagy (By similarity). SUBCELLULAR LOCATION: Preautophagosomal structure membrane; Peripheral membrane protein Vacuole membrane; Peripheral membrane protein Note=Peripheral membrane protein of pre-autophagosomal structure (PAS) and vacuole. SIMILARITY: Belongs to the WD repeat PROPPIN family.


FUNCTION: Anti-apoptotic protein which can inhibit apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Can modulate both capacitative Ca2+ entry and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release. SUBCELLULAR LOCATION: Golgi apparatus membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the BI1 family. LFG subfamily.


FUNCTION: Involved in ammonium transport (PubMed:25841038). May be involved in arbuscular mycorrhizal (AM) symbiosis with AM fungi (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ammonia transporter channel (TC 1.A.11.2) family.


FUNCTION: As part of a BORC-like complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, this complex may couple lysosomes to microtubule plus-end-directed kinesin motor. SUBCELLULAR LOCATION: Lysosome membrane; Lipid-anchor; Cytoplasmic side. SIMILARITY: Belongs to the BORCS5 family.


FUNCTION: Beta-1,3-galactosyltransferase that transfers galactose from UDP-galactose to substrates with a terminal beta-N-acetylglucosamine (beta-GlcNAc) residue. Can also utilize substrates with a terminal galactose residue, albeit with lower efficiency. Involved in the biosynthesis of the carbohydrate moieties of glycolipids and glycoproteins. SUBCELLULAR LOCATION: Golgi apparatus membrane; Single- pass type II membrane protein. SIMILARITY: Belongs to the glycosyltransferase 31 family.


FUNCTION: Bifunctional enzyme that catalyzes both the deamination of dCTP to dUTP and the hydrolysis of dUTP to dUMP without releasing the toxic dUTP intermediate. SIMILARITY: Belongs to the dCTP deaminase family.


FUNCTION: Plays role in broad-spectrum disease resistance. Probably has no oxalate oxidase activity even if the active site is conserved. SUBCELLULAR LOCATION: Secreted, extracellular space, apoplast. SIMILARITY: Belongs to the germin family.


FUNCTION: Catalyzes the relaxation of negatively supercoiled DNA in the presence of ATP or dATP but not other nucleotides. Individual subunits have no activity. Not able to negatively supercoil DNA, it can however introduce positive supercoils in DNA. Relaxes positive supercoils in an ATP-dependent manner. Catenates and decatenates DNA. Generates dsDNA breaks in the presence of the quinolone antibiotic ciprofloxacin, showing it is a topoisomerase (PubMed:16313624). SIMILARITY: Belongs to the type II topoisomerase GyrA/ParC subunit family.


FUNCTION: Together with KRT19, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle. SUBCELLULAR LOCATION: Cytoplasm Nucleus, nucleoplasm Nucleus matrix. SIMILARITY: Belongs to the intermediate filament family.


FUNCTION: This protein is essential for plasmid replication; it is involved in copy control functions. In vitro, binds to the DNA repeat units, BCDD'D'', EFG and HIJ (By similarity). SIMILARITY: Belongs to the initiator RepB protein family.


FUNCTION: ATP-dependent DNA helicase important for chromosome transmission and normal cell cycle progression in G(2)/M (By similarity). May have a role in changing DNA topology to allow the loading of proteins involved in maintaining sister chromatid cohesion in the vicinity of the centromeres (By similarity). Has a specific role in chromosome segregation during meiosis II (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the DEAD box helicase family. DEAH subfamily. DDX11/CHL1 sub-subfamily.


FUNCTION: Catalyzes the reversible cyclization of carbamoyl aspartate to dihydroorotate. SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily. DHOase family. Class I DHOase subfamily.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the NPY family.


FUNCTION: Glucose-regulated GTPase-accelerating protein (GAP) for the GTP-bound self-activating heterotrimeric G alpha protein GPA1. Cooperates with G beta-gamma dimers to maintain an unactivated but fully functional pool of GPA1. Phosphorylation-dependent endocytosis of RGS1 physically uncouples the two proteins, resulting in signal activation. Free AGB1 is essential, but not sufficient, for RGS1 endocytosis. Modulates cell proliferation, abscisic acid (ABA) and drought stress signal transduction by acting in a hexokinase- independent glucose-signaling pathway (PubMed:26528314). Involved in the shapes of leaves, the development of floral buds, the elongation of stems, siliques, and hypocotyls, the time of flowering and the regulation of guard-cell K(+) and anion channels. Important for the kinetics of voltage activation of inward K(+) current but not for the current amplitude. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Endosome membrane; Multi-pass membrane protein Note=accumulates at the nascent cell plate during cytokinesis.


FUNCTION: Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway. The interaction with the membrane- bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the IL-6 superfamily.


FUNCTION: Involved in bacteriochlorophyll biosynthesis; introduces a magnesium ion into protoporphyrin IX to yield Mg-protoporphyrin IX. SIMILARITY: Belongs to the Mg-chelatase subunits D/I family.


FUNCTION: Catalyzes the hydrolysis of the adenine ring of phosphoribosyl-AMP. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the PRA-CH family.


FUNCTION: Key component of the proton channel; it plays a direct role in the translocation of protons across the membrane. SUBCELLULAR LOCATION: Cellular thylakoid membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ATPase A chain family.


FUNCTION: Involved in the isomerization of 5-deoxy-glucuronate (5DG) to 5-dehydro-2-deoxy-D-gluconate (DKG or 2-deoxy-5-keto-D-gluconate). SIMILARITY: Belongs to the isomerase IolB family.


FUNCTION: Catalyzes the cleavage of 2-amino-3-ketobutyrate to glycine and acetyl-CoA. FUNCTION: Catalyzes the cleavage of 2-amino-3-ketobutyrate to glycine and acetyl-CoA. SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.


FUNCTION: Catalyzes the coenzyme F420-dependent oxidation of glucose 6- phosphate (G6P) to 6-phosphogluconolactone. Appears to have a role in resistance to oxidative stress, via its consumption of G6P that serves as a source of reducing power to combat oxidative stress in mycobacteria. Cannot use NAD, NADP, FAD or FMN instead of coenzyme F420 as an electron acceptor. Exhibits nearly no activity with D-mannose-6- phosphate or D-fructose-6-phosphate as substrate. SIMILARITY: Belongs to the F420-dependent glucose-6-phosphate dehydrogenase family.


FUNCTION: Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (PubMed:19767744). In a neuroblastoma cell line, protects cells from ER stress-induced death (PubMed:17178827). In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827). SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding protein 3-like protein 2]: Nucleus Note=Upon ER stress, translocated into the nucleus. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type II membrane protein. Note=ER membrane resident protein. Upon ER stress, translocated to the Golgi apparatus where it is cleaved. The cytosolic N-terminal fragment (processed cyclic AMP-responsive element-binding protein 3-like protein 1) is transported into the nucleus. SIMILARITY: Belongs to the bZIP family. ATF subfamily.


FUNCTION: Catalyzes the decarboxylation of oxaloacetate coupled to Na(+) translocation.


SUBCELLULAR LOCATION: Lysosome. SIMILARITY: Belongs to the sulfatase family.


FUNCTION: Catalyzes the condensation of iminoaspartate with dihydroxyacetone phosphate to form quinolinate. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the quinolinate synthase family. Type 3 subfamily.


FUNCTION: Catalyzes the phosphorylation of N-acetylmannosamine (ManNAc) to ManNAc-6-P. SIMILARITY: Belongs to the ROK (NagC/XylR) family. NanK subfamily.


FUNCTION: Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine corresponding to position 914 in M.jannaschii 16S rRNA. It constitutes the last step in biosynthesis of the hypermodified N1-methyl-N3-(3-amino-3- carboxypropyl) pseudouridine (m1acp3-Psi). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the TDD superfamily. TSR3 family.


FUNCTION: Required for resistance to DNA-damaging agents. FUNCTION: Required for resistance to DNA-damaging agents. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the universal stress protein A 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 superfamily.


FUNCTION: Component of the ERMES/MDM complex, which serves as a molecular tether to connect the endoplasmic reticulum (ER) and mitochondria. Components of this complex are involved in the control of mitochondrial shape and protein biogenesis, and function in nonvesicular lipid trafficking between the ER and mitochondria. MDM12 is required for the interaction of the ER-resident membrane protein MMM1 and the outer mitochondrial membrane-resident beta-barrel protein MDM10. The MDM12-MMM1 subcomplex functions in the major beta-barrel assembly pathway that is responsible for biogenesis of all mitochondrial outer membrane beta-barrel proteins, and acts in a late step after the SAM complex. The MDM10-MDM12-MMM1 subcomplex further acts in the TOM40-specific pathway after the action of the MDM12-MMM1 complex. Essential for establishing and maintaining the structure of mitochondria and maintenance of mtDNA nucleoids. SUBCELLULAR LOCATION: Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side Note=The ERMES/MDM complex localizes to a few discrete foci (around 10 per single cell), that represent mitochondria-endoplasmic reticulum junctions. These foci are often found next to mtDNA nucleoids. SIMILARITY: Belongs to the MDM12 family.


FUNCTION: Key component of the F(0) channel; it plays a direct role in translocation across the membrane. A homomeric c-ring of between 10-14 subunits forms the central stalk rotor element with the F(1) delta and epsilon subunits. FUNCTION: F(1)F(0) ATP synthase produces ATP from ADP in the presence of a proton or sodium gradient. F-type ATPases consist of two structural domains, F(1) containing the extramembraneous catalytic core and F(0) containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ATPase C chain family.


FUNCTION: Chaperone involved in the maturation of iron-sulfur cluster- containing proteins. Has a low intrinsic ATPase activity which is markedly stimulated by HscB. SIMILARITY: Belongs to the heat shock protein 70 family.


FUNCTION: Protein with pleiotropic attributes mediated in a cell- compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors and sex steroid hormones in the nucleus. FUNCTION: In the mitochondria, together with PHB, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan. FUNCTION: In the nucleus, serves as transcriptional co-regulator. SUBCELLULAR LOCATION: Mitochondrion inner membrane Cytoplasm Nucleus Cell membrane. SIMILARITY: Belongs to the prohibitin family.


FUNCTION: [Annexin Ac2-26]: Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades. Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors. Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration. Promotes resolution of inflammation and wound healing. Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2. FUNCTION: Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity. Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response. Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells. Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (By similarity). Has no effect on unstimulated T-cells. Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (By similarity). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)- dependent binding to phospholipid membranes (By similarity). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Cell projection, cilium Basolateral cell membrane Lateral cell membrane Cell membrane; Peripheral membrane protein Apical cell membrane Membrane; Peripheral membrane protein Early endosome Cytoplasmic vesicle membrane; Peripheral membrane protein Endosome membrane; Peripheral membrane protein Secreted Secreted, extracellular space Cell membrane; Peripheral membrane protein; Extracellular side Secreted, extracellular exosome Cytoplasmic vesicle, secretory vesicle lumen Cell projection, phagocytic cup Note=Colocalizes with actin fibers at phagocytic cups. Secreted, at least in part via exosomes and other secretory vesicles. Detected in exosomes and other extracellular vesicles. Secretion is increased in response to wounding and inflammation (By similarity). Alternatively, the secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in the protein translocation from the cytoplasm into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (By similarity). Detected in gelatinase granules in resting neutrophils. Neutrophil adhesion to endothelial cells stimulates secretion via gelatinase granules, but foreign particle phagocytosis has no effect. Displays calcium-dependent binding to phospholipid membranes (By similarity). SIMILARITY: Belongs to the annexin family.


SIMILARITY: Belongs to the acylphosphatase family.


FUNCTION: The phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS), a major carbohydrate active transport system, catalyzes the phosphorylation of incoming sugar substrates concomitantly with their translocation across the cell membrane. The enzyme II complex composed of PtsG and Crr is involved in glucose transport. Also functions as a chemoreceptor monitoring the environment for changes in sugar concentration. It can also phosphorylate mannose, methyl alpha-glucoside and 2-deoxy-glucose. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein.


FUNCTION: May act as a metallochaperone involved in nitrous oxide reductase assembly. Specifically binds Cu(+). SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Periplasmic side. SIMILARITY: Belongs to the NosL family.


SIMILARITY: Belongs to the small GTPase superfamily. Rab family.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: In the C-terminal section; belongs to the imidazoleglycerol-phosphate dehydratase family. SIMILARITY: In the N-terminal section; belongs to the histidinol- phosphatase family.


FUNCTION: Plant lipoxygenase may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. Catalyzes the hydroperoxidation of lipids containing a cis,cis-1,4-pentadiene structure (By similarity). SIMILARITY: Belongs to the lipoxygenase family.


FUNCTION: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity). SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the complex I subunit 3 family.


SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the helicase family. DnaB subfamily.


FUNCTION: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (By similarity). Involved in regulation of the mitochondrial permeability transition pore (mPTP) (PubMed:8567677, PubMed:9309684, PubMed:9820802). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated (PubMed:8567677, PubMed:9309684, PubMed:9820802). In cooperation with mitochondrial p53/TP53 is involved in activating oxidative stress-induced necrosis (PubMed:8567677, PubMed:9309684, PubMed:9820802). Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels (PubMed:8567677, PubMed:9309684, PubMed:9820802). Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis (PubMed:19228691). SUBCELLULAR LOCATION: Mitochondrion matrix. SIMILARITY: Belongs to the cyclophilin-type PPIase family.


FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates effector caspases caspase-3 (CASP3) or caspase-7 (CASP7). Promotes DNA damage- induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP). SIMILARITY: Belongs to the peptidase C14A family.


FUNCTION: Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the beta-2-microglobulin family.


FUNCTION: Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c. Cytochrome c1 is a catalytic core subunit containing a c-type heme. It transfers electrons from the [2Fe-2S] iron-sulfur cluster of the Rieske protein to cytochrome c. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Single-pass membrane protein. SIMILARITY: Belongs to the cytochrome c family.


FUNCTION: Increases serum survival and confers group II surface exclusion.


FUNCTION: Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. Endogenous envelope proteins may have kept, lost or modified their original function during evolution. This endogenous envelope protein has lost its original fusogenic properties. FUNCTION: TM anchors the envelope heterodimer to the viral membrane through one transmembrane domain. The other hydrophobic domain, called fusion peptide, mediates fusion of the viral membrane with the target cell membrane (By similarity). FUNCTION: SU mediates receptor recognition. SUBCELLULAR LOCATION: [Endogenous retrovirus group K member 21 Env polyprotein]: Virion. SUBCELLULAR LOCATION: [Surface protein]: Cell membrane; Peripheral membrane protein Note=The surface protein is not anchored to the membrane, but localizes to the extracellular surface through its binding to TM. SUBCELLULAR LOCATION: [Transmembrane protein]: Cell membrane; Single-pass type I membrane protein. SIMILARITY: Belongs to the beta type-B retroviral envelope protein family. HERV class-II K(HML-2) env subfamily.


SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TrbL/VirB6 family.


SIMILARITY: Belongs to the UPF0125 (RnfH) family. SIMILARITY: Belongs to the UPF0125 (RnfH) family.


FUNCTION: Phosphatase active on para-nitrophenylphosphate (pNPP) and on various phosphoproteins such as myelin basic protein. Seems to act as a positive regulator of cryptochrome signaling involved in hypocotyl growth inhibition and cotyledon expansion under white and blue light conditions. Confers thermotolerance. Required for heat shock mediated- signaling pathway that leads to the expression of heat shock proteins (HSPs). SUBCELLULAR LOCATION: Nucleus, nucleoplasm. SIMILARITY: Belongs to the PPP phosphatase family. PP-7 subfamily.


FUNCTION: Could be a protease inhibitor. SUBCELLULAR LOCATION: Secreted.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase A1 family.


FUNCTION: Produces ATP from ADP in the presence of a proton gradient across the membrane. The archaeal alpha chain is a catalytic subunit. SIMILARITY: Belongs to the ATPase alpha/beta chains family.


FUNCTION: Beta subunit of the SNF1 kinase complex, which is required for transcriptional, metabolic, and developmental adaptations in response to glucose limitation. Has a structural role, mediating heterotrimer formation, and a regulatory role, defining carbon source- regulated subcellular location and substrate specificity of the SNF1 kinase complex. Promotes the PKA-regulated relocalization of the SNF1 kinase complex to the vacuolar membrane in response to various types of carbon stress (By similarity). SUBCELLULAR LOCATION: Cytoplasm Vacuole membrane; Peripheral membrane protein; Cytoplasmic side Note=Resides in the cytosol during growth in glucose and relocalizes to the vacuolar membrane in response to carbon stress. SIMILARITY: Belongs to the 5'-AMP-activated protein kinase beta subunit family.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the TACO1 family. YeeN subfamily.


FUNCTION: Catalyzes the esterification, concomitant with transport, of exogenous long-chain fatty acids into metabolically active CoA thioesters for subsequent degradation or incorporation into phospholipids. FUNCTION: Catalyzes the esterification, concomitant with transport, of exogenous long-chain fatty acids into metabolically active CoA thioesters for subsequent degradation or incorporation into phospholipids. Activity is the highest with fatty acid substrates of > 10 carbon atoms (PubMed:15213221). Is involved in the aerobic beta- oxidative degradation of fatty acids, which allows aerobic growth of E.coli on fatty acids as a sole carbon and energy source (PubMed:12535077). SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein Note=Partially membrane-associated. SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein Note=Partially membrane-associated. SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Subunits I and II form the functional core of the enzyme complex. Electrons originating in cytochrome c are transferred via heme a and Cu(A) to the binuclear center formed by heme a3 and Cu(B). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the cytochrome c oxidase subunit 2 family.


FUNCTION: Has antibacterial activity (Probable). Upon stimulation with lipoteichoic acid, promotes cytokines and chemokines production and secretion (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the beta-defensin family.


FUNCTION: [Bradykinin-potentiating peptide AP]: Acts as indirect hypotensive agent. Potently induces vasodilation of arterioles, with only a small increase in leukocyte rolling flux. FUNCTION: [Bradykinin-potentiating peptide 10c]: Peptide with several activities. It inhibits the activity of the angiotensin-converting enzyme (ACE) by a preferential interaction with its C-domain (PubMed:11994001). It evokes transient hypotension (-14 mmHg) similar to that evoked by 0.5 ug of bradykinin, when injected alone into rats. It has a high bradykinin-potentiating effect (120%), when 60 nmol of BPP-10c are coinjected with 0.5 ug of bradykinin into rats (PubMed:22869554). Does not affect angiotensin-1 pressor effects. Shows potent and long-lasting antihypertensive activity as well as a reduction of the heart rate (PubMed:17475904). It also binds and dose- dependently promotes the activation of cytosolic argininosuccinate synthase (ASS1), an enzyme that catalyzes the conversion of citrulline, L-aspartate and ATP to argininosuccinate, AMP and pyrophosphate. It also enhances ASS1-dependent arginine production in HEK 293 cells, as well as in spontaneous hypertensive rat (SHR) and Wistar rat plasma. In addition, it induces the production of nitric-oxide (NO) by HUVEC cells via the endothelial nitric-oxide synthase (NOS3), which use arginine as a substrate and produce NO. It has been shown to be internalized by ASS1-expressing endothelial (HUVEC) and kidney (HEK 293) cells, and is detected homogenously distributed within the cell cytoplasm for up to 2 hours (PubMed:19491403). FUNCTION: [Bradykinin-potentiating peptide 11e]: Acts as indirect hypotensive agent. Increases leukocyte rolling flux and adhesion by five-fold in post-capillary venules, without any increments in vasodilation of arterioles. SUBCELLULAR LOCATION: Secreted Cytoplasm, cytosol. Note=BPP-10c is internalized in the cytosol of prey cells. SIMILARITY: In the N-terminal section; belongs to the bradykinin- potentiating peptide family.


FUNCTION: Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing. SIMILARITY: Belongs to the AAR2 family.


FUNCTION: Mitochondrial amino-acid transporter (By similarity). Transports citrate (PubMed:12150972). Does not act as a serine transporter: not able to mediate transport of serine into mitochondria (By similarity) (PubMed:12150972). In brown adipose tissue, plays a role in the regulation of UCP1-dependent thermogenesis probably by supporting mitochondrial glycerol-3-phosphate utilization (By similarity). SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the sideroflexin family.


FUNCTION: ATP-binding RNA helicase involved in translation initiation. Remodels RNA in response to ADP and ATP concentrations by facilitating disruption, but also formation of RNA duplexes (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the DEAD box helicase family. DDX3/DED1 subfamily.


FUNCTION: Forms oxaloacetate, a four-carbon dicarboxylic acid source for the tricarboxylic acid cycle. SIMILARITY: Belongs to the PEPCase type 1 family.


FUNCTION: Probable palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes (By similarity). May play a role in cell proliferation (PubMed:28331227). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the DHHC palmitoyltransferase family.


FUNCTION: Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. VPS51 participates in retrograde transport of acid hydrolase receptors, likely by promoting tethering and SNARE-dependent fusion of endosome- derived carriers to the TGN. Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network Recycling endosome Note=Localizes to the trans-Golgi network as part of the GARP complex, while it localizes to recycling endosomes as part of the EARP complex. SIMILARITY: Belongs to the VPS51 family.


FUNCTION: Gluconolactonase with low activity towards other sugar lactones, including gulonolactone and galactonolactone. Catalyzes a key step in ascorbic acid (vitamin C) biosynthesis. Can also hydrolyze diisopropyl phosphorofluoridate and phenylacetate (in vitro). Calcium- binding protein. Modulates Ca(2+) signaling, and Ca(2+)-dependent cellular processes and enzyme activities (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the SMP-30/CGR1 family.


FUNCTION: The electron transfer flavoprotein serves as a specific electron acceptor for several dehydrogenases, including five acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF- ubiquinone oxidoreductase (ETF dehydrogenase) (By similarity). Involved in leucine catabolism and in phytol degradation. SUBCELLULAR LOCATION: Mitochondrion matrix. SIMILARITY: Belongs to the ETF beta-subunit/FixA family.


SIMILARITY: Belongs to the SlyX family.


FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'- linked polyubiquitination. Involved in endoplasmic reticulum-associated degradation (ERAD). Required for sterol-induced ubiquitination of 3- hydroxy-3-methylglutaryl coenzyme A reductase and its subsequent proteasomal degradation. FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:20061386). In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:20061386). Involved in endoplasmic reticulum-associated degradation (ERAD) (PubMed:22607976). Required for sterol-induced ubiquitination of 3- hydroxy-3-methylglutaryl coenzyme A reductase and its subsequent proteasomal degradation (PubMed:23223569). SUBCELLULAR LOCATION: Endoplasmic reticulum Lipid droplet. SUBCELLULAR LOCATION: Endoplasmic reticulum Lipid droplet. SUBCELLULAR LOCATION: Endoplasmic reticulum Lipid droplet. SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.


FUNCTION: Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. VPS51 participates in retrograde transport of acid hydrolase receptors, likely by promoting tethering and SNARE-dependent fusion of endosome- derived carriers to the TGN. Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane (By similarity). Required for vacuolar targeting and cellular trafficking. Involved in the regulation of vascular tissue patterning, probably by regulating PIN1 expression pattern, thus modulating auxin flux. Important to prevent PIN1 accumulation within margin cells, possibly by targeting PIN1 to the lytic vacuole. Regulates PIN1 and ATHB8 expression pattern in secondary veins (PubMed:24757006). SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network Recycling endosome Prevacuolar compartment Note=Localizes to the trans-Golgi network as part of the GARP complex, while it localizes to recycling endosomes as part of the EARP complex. SIMILARITY: Belongs to the VPS51 family.


FUNCTION: Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II (By similarity). SUBCELLULAR LOCATION: Nucleus Chromosome Note=Colocalizes with RNA polymerase II on chromatin. Recruited to actively transcribed loci. SIMILARITY: Belongs to the SSRP1 family.


FUNCTION: Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the eIF-3 subunit H family.


SUBCELLULAR LOCATION: Spore core. SIMILARITY: Belongs to the SspH family.


FUNCTION: May participate in leucine metabolism. May transport leucine or a compound related to leucine metabolism. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC) superfamily.


FUNCTION: Involved in catabolism of D-apiose. Catalyzes the phosphorylation of 3-oxo-isoapionate to 3-oxo-isoapionate 4-phosphate. SIMILARITY: Belongs to the four-carbon acid sugar kinase family.


FUNCTION: Required for endonucleolytic cleavage during polyadenylation- dependent pre-mRNA 3'-end formation. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the Clp1 family. Clp1 subfamily.


FUNCTION: Converts heme B (protoheme IX) to heme O by substitution of the vinyl group on carbon 2 of heme B porphyrin ring with a hydroxyethyl farnesyl side group. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the UbiA prenyltransferase family. Protoheme IX farnesyltransferase subfamily.


FUNCTION: Transcriptional repressor for the arsADRC operon.


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. Binds evenly across chromosome, does not display a preference for AT content (PubMed:21085634). SUBCELLULAR LOCATION: Cytoplasm, nucleoid Note=Evenly distributed in the nucleoid (PubMed:21085634). SIMILARITY: Belongs to the bacterial histone-like protein family.


FUNCTION: Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:19523396). Also acts as a receptor for the heterodimeric glycoprotein hormone thyrostimulin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Plays a central role in controlling thyroid cell metabolism (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Basolateral cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.


FUNCTION: Plays a role in efficient localization of neo-synthesized capsids to nuclear replication compartments, thereby controlling cleavage and packaging of virus genomic DNA. SUBCELLULAR LOCATION: Host cytoplasm. Host nucleus. SIMILARITY: Belongs to the herpesviridae UL32 protein family.


FUNCTION: ATPase required for the post-translational delivery of tail- anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors GET1 and GET2, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the GET1-GET2 receptor, and returning it to the cytosol to initiate a new round of targeting. Cooperates with the HDEL receptor ERD2 to mediate the ATP-dependent retrieval of resident ER proteins that contain a C-terminal H-D-E-L retention signal from the Golgi to the ER. Involved in low-level resistance to the oxyanions arsenite and arsenate, and in heat tolerance. SUBCELLULAR LOCATION: Cytoplasm Endoplasmic reticulum Golgi apparatus Note=GET1 and GET2 are required for targeting GET3 to the endoplasmic reticulum. SIMILARITY: Belongs to the arsA ATPase family.


FUNCTION: [Isoform 2]: Forms toxic aggregates that disrupt spore maturation. FUNCTION: Promotes unequal transmission of alleles from the parental zygote to progeny spores by acting as poison/antidote system where the poison and antidote proteins are produced from the same locus; the poison component is trans-acting and targets all spores within an ascus whereas the antidote component is spore-specific, leading to poisoning of all progeny that do not inherit the allele. FUNCTION: [Isoform 1]: Localizes isoform 2 to the vacuole thereby facilitating its degradation (By similarity). In addition to suppressing isoform 2, also suppresses S.pombe strain FY29033 wtf18 isoform 2 (PubMed:32032353). SUBCELLULAR LOCATION: [Isoform 2]: Ascus epiplasm Cytoplasm Spore membrane; Multi-pass membrane protein Vacuole membrane; Multi-pass membrane protein Endoplasmic reticulum membrane; Multi-pass membrane protein Note=Localizes in trans to all spores within an ascus. Localization to the spore vacuole is dependent on isoform 1. SUBCELLULAR LOCATION: [Isoform 1]: Spore membrane; Multi-pass membrane protein Vacuole membrane; Multi-pass membrane protein Note=Contained within spores expressing the isoform and localizes isoform 2 to the vacuole. SIMILARITY: Belongs to the WTF family.


FUNCTION: Exhibits holdase chaperone activity involved in the stabilization of POR proteins against photooxidative stress in chloroplasts. Required for chloroplast development. SUBCELLULAR LOCATION: Plastid, chloroplast envelope Plastid, chloroplast thylakoid membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the chaperone-like protein of POR1 protein family.


FUNCTION: May play a role in microtubule-dependent retrograde axonal transport. May function as the motor for the transport of multivesicular body (MVB)-like organelles in dendrites (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.


SIMILARITY: Belongs to the small heat shock protein (HSP20) family.


FUNCTION: Serves as a ruler that controls the length of tail by stopping the tail tube polymerization and is probably released from the tail shaft during infection to facilitate DNA translocation into the host cell (PubMed:2150582). Assembles into a multimeric linear form possibly stabilized by the covering tail assembly proteins G and GT (PubMed:23911548). Its C-terminus fixes the tail tip complex (J, I, L, K), thereby forming the tail assembly initiator complex (PubMed:23911548). Tail tube proteins polymerize around tape measure protein, displacing the tail assembly protein G and GT (PubMed:23911548). When the tail reaches the length specified by the tape measure protein, it stops and becomes capped by the tail terminator protein (Probable). Upon tail assembly, tape measure protein is cleaved into a form called H*, that plays a role later during virion entry in a new cell (Probable). Once assembled, the virion is released and can infect new cell by binding to the entry receptor LambB (Probable). After opening of a pore on the external membrane, the entry protein H* protein is probably released in the periplasmic space for successfull DNA injection (PubMed:23911548). SUBCELLULAR LOCATION: Virion Note=There are 6 copies of entry protein H* per mature phage. SIMILARITY: Belongs to the Lambdavirus tape measure protein family.


FUNCTION: Involved in the active transport across the outer membrane of iron complexed with catecholate siderophores such as dihydroxybenzoylserine and dihydroxybenzoate. It derives its energy for transport by interacting with the trans-periplasmic membrane protein TonB. Can also transport catechol-substituted cephalosporins. Receptor for microcins M, H47 and E492. SUBCELLULAR LOCATION: Cell outer membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TonB-dependent receptor family.


FUNCTION: Part of the MsrPQ system that repairs oxidized periplasmic proteins containing methionine sulfoxide residues (Met-O), using respiratory chain electrons. Thus protects these proteins from oxidative-stress damage caused by reactive species of oxygen and chlorine generated by the host defense mechanisms. MsrPQ is essential for the maintenance of envelope integrity under bleach stress, rescuing a wide series of structurally unrelated periplasmic proteins from methionine oxidation, including the primary periplasmic chaperone SurA and the lipoprotein Pal. The catalytic subunit MsrP is non- stereospecific, being able to reduce both (R-) and (S-) diastereoisomers of methionine sulfoxide. SUBCELLULAR LOCATION: Periplasm Note=Is attached to the inner membrane when interacting with the MsrQ subunit. SIMILARITY: Belongs to the MsrP family.


FUNCTION: Involved in tellurite resistance (PubMed:8981981). TerW binds specifically to the potential promoter region of the terZABCDE operon and probably regulates expression of the genes (By similarity). FUNCTION: Involved in tellurite resistance (Ref.2). TerW binds specifically to the potential promoter region of the terZABCDE operon and probably regulates expression of the genes (Ref.2).


FUNCTION: Catalyzes the oxidation of erythronate-4-phosphate to 3- hydroxy-2-oxo-4-phosphonooxybutanoate. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family. PdxB subfamily.


FUNCTION: Component of the DNA-directed RNA polymerase (RNAP) that catalyzes the transcription in the cytoplasm of viral DNA into RNA using the four ribonucleoside triphosphates as substrates. SUBCELLULAR LOCATION: Host cytoplasm Virion Note=Found in association with viral nucleoid. SIMILARITY: Belongs to the Asfivirus DNA-directed RNA polymerase RPB7 homolog family.


FUNCTION: Chaperone involved in the maturation of iron-sulfur cluster- containing proteins. Has a low intrinsic ATPase activity which is markedly stimulated by HscB. Involved in the maturation of IscU (By similarity). SIMILARITY: Belongs to the heat shock protein 70 family.


FUNCTION: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity). SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side. SIMILARITY: Belongs to the complex I NDUFA2 subunit family.


FUNCTION: Free serine kinase that uses ATP to phosphorylate L-serine to yield O-phospho-L-serine and ADP. O-phospho-L-serine serves as a substrate for SbnA and is a precursor for staphyloferrin B biosynthesis (PubMed:29483190). Is also a DNA-binding regulatory protein that senses heme to control gene expression for siderophore biosynthesis. Binds to DNA within the sbnC coding region and is required for expression of genes in the sbn operon from sbnD onward (PubMed:26534960).


FUNCTION: Possible function in sperm maturation. SUBCELLULAR LOCATION: Secreted.


FUNCTION: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. SUBCELLULAR LOCATION: Golgi apparatus membrane; Single- pass type II membrane protein. SIMILARITY: Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.


FUNCTION: ATP-dependent RNA helicase involved nonsense-mediated mRNA decay and ribosome biogenesis through rRNA processing. SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the DEAD box helicase family. DDX5/DBP2 subfamily.


FUNCTION: Involved in the maturation of [NiFe] hydrogenases. Required for nickel insertion into the metal center of the hydrogenase. SIMILARITY: Belongs to the HypA/HybF family.


SIMILARITY: Belongs to the HAD-like hydrolase superfamily.


FUNCTION: Catalyzes the conversion of lactate to pyruvate. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family.


FUNCTION: Involved in terpene biosynthesis in roots. Possesses sesquiterpene (C15) synthase activity and diterpene (C20) synthase activity in vitro. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the terpene synthase family. Tpsa subfamily.


FUNCTION: Required for cell fusion events during development including the fusion of anchor cells (AC), vulval A and vulval D rings, and late epidermal seam cells (PubMed:17488621). Required for amphid sheath cell fusion induced by entry into dauer stage (PubMed:21350017). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein Apical cell membrane. SIMILARITY: Belongs to the EFF/AFF cell fusogen family.


FUNCTION: Catalyzes the reversible transfer of the terminal phosphate of ATP to form a long-chain polyphosphate (polyP). SIMILARITY: Belongs to the polyphosphate kinase 1 (PPK1) family.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 5 (cellulase A) family.


FUNCTION: Probably participates in a plant defense mechanism. SIMILARITY: Belongs to the cyclotide family. Bracelet subfamily.


FUNCTION: Small GTPase that is essential for the correct formation of the tangential divisions in early embryos. Associates with microtubule during mitosis and may function in the positioning of the division plane. May participate in the patterning of the early embryo at the octant-dermatogen transition (PubMed:17419841). Is crucial for normal development of the plant (PubMed:28475733). SUBCELLULAR LOCATION: Cytoplasm Nucleus Cytoplasm, cytoskeleton, spindle Cytoplasm, cytoskeleton, phragmoplast Note=During interphase, mainly expressed in the cytoplasm and weakly in the nucleus. Associated with microtubules during cell division. SIMILARITY: Belongs to the GPN-loop GTPase family.


SIMILARITY: Belongs to the cytochrome P450 family.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the FPP/GGPP synthase family.


FUNCTION: Plays a role in protein import into the endoplasmic reticulum (ER). May function as chaperone docking protein during post- translational protein translocation into the ER. Chaperone receptor mediating Hsp70-dependent protein targeting to chloroplasts. Interacts specifically with some chloroplast precursors, but not with mitochondrial precursors. Able to select precursors for delivery to the chloroplast translocase independently of Hsp70. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein Plastid, chloroplast outer membrane; Single-pass membrane protein Note=Resides most likely exclusively in the ER membrane.


FUNCTION: RNA-binding protein involved in deadenylation-dependent decapping of mRNAs, leading to the degradation of mRNAs. Acts as a scaffold protein that connects deadenylation and decapping machinery. Required for cytoplasmic mRNA processing body (P-body) assembly. SUBCELLULAR LOCATION: Cytoplasm, P-body Nucleus Nucleus, PML body Nucleus speckle Note=Predominantly cytoplasmic. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. Enriched in splicing speckles. Localization to nuclear foci and speckles requires active transcription. Excluded from the nucleolus. SIMILARITY: Belongs to the PAT1 family.


FUNCTION: Septins are GTPases involved in cytokinesis. The septins localize to the site of cleavage and act as a structural scaffold that recruits different components involved in diverse processes at specific stages during the cell cycle. Septins are also involved in cell morphogenesis, chitin deposition, cell cycle regulation, cell compartmentalization and spore wall formation (By similarity). SIMILARITY: Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.


SIMILARITY: Belongs to the citrate synthase family.


FUNCTION: Catalyzes a trans-dehydration via an enolate intermediate. SIMILARITY: Belongs to the type-II 3-dehydroquinase family.


FUNCTION: ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the DEAD box helicase family. eIF4A subfamily.


SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the Cold-regulated 413 protein family.


FUNCTION: Acts as a suppressor of the SAPK signaling pathways by associating with and dephosphorylating MAP3K7/TAK1 and MAP3K5, and by attenuating the association between MAP3K7/TAK1 and MAP2K4 or MAP2K6. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. SIMILARITY: Belongs to the PP2C family.


SIMILARITY: Belongs to the phage P protein family.


FUNCTION: Microtubule-binding protein required to ensure proper cell division and nuclear envelope reassembly by sequestering the endoplasmic reticulum away from chromosomes during mitosis. Probably acts by clearing the endoplasmic reticulum membrane from metaphase chromosomes (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the DP1 family.


FUNCTION: Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors. NF-YA positively regulates the transcription of the core clock component BMAL1. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the NFYA/HAP2 subunit family.


FUNCTION: Catalyzes the ATP-dependent phosphorylation of a wide variety of beta-D-glucosides, to produce 6-phospho-beta-D-glucosides including cellobiose-6'-P, gentiobiose-6'-P, cellobiitol-6-P, salicin-6-P, and arbutin-6-P. Is not able to phosphorylate alpha-D-glucosides. May have a dual role of kinase and transcriptional regulator of the cellobiose- PTS operon. SIMILARITY: Belongs to the ROK (NagC/XylR) family.


FUNCTION: Involved in nucleolar processing of pre-18S ribosomal RNA. Has a role in the nuclear export of 40S pre-ribosomal subunit to the cytoplasm (By similarity). SUBCELLULAR LOCATION: Nucleus, nucleolus. SIMILARITY: Belongs to the NOP14 family.


FUNCTION: May be the site-specific invertase required for pilin gene inversion. Moraxella can express either a Q or I pilin; the inversion of 2 kb of DNA determines which pilin is expressed.


FUNCTION: Mediates the nuclear export of encapsidated genomic RNAs (ribonucleoproteins, RNPs). Acts as an adapter between viral RNPs complexes and the nuclear export machinery of the cell. Possesses no intrinsic RNA-binding activity, but includes a C-terminal M1-binding domain. This domain is believed to allow recognition of RNPs bound to the protein M1. Since protein M1 is not available in large quantities before late stages of infection, such an indirect recognition mechanism probably ensures that genomic RNPs are not exported from the host nucleus until sufficient quantities of viral mRNA and progeny genomic RNA have been synthesized. Furthermore, the RNPs enter the host cytoplasm only when associated with the M1 protein that is necessary to guide them to the plasma membrane. May down-regulate viral RNA synthesis when overproduced. SUBCELLULAR LOCATION: Virion Host nucleus. SIMILARITY: Belongs to the influenza viruses NEP family.


FUNCTION: Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine (PubMed:7592981, PubMed:9458785, PubMed:9856990). Transports various bile acids, unconjugated or conjugated, such as cholate and taurocholate (PubMed:7592981, PubMed:9458785, PubMed:9856990). Also responsible for bile acid transport in the renal proximal tubules, a salvage mechanism that helps conserve bile acids (Probable). Works collaboratively with the Na(+)-taurocholate cotransporting polypeptide (NTCP), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (PubMed:33222321). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.


FUNCTION: Catalyzes a mechanistically unusual reaction, the ATP- dependent insertion of CO2 between the N7 and N8 nitrogen atoms of 7,8- diaminopelargonic acid (DAPA, also called 7,8-diammoniononanoate) to form a ureido ring. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the dethiobiotin synthetase family.


FUNCTION: Endo-1,4-mannanase that catalyzes the random hydrolysis of (1->4)-beta-D-mannosidic linkages in mannans and heteromannans. It is a crucial enzyme for depolymerization of seed galactomannans and wood galactoglucomannans. Hydrolyzes structurally different mannan polysaccharides, such as galactomannans, glucomannans, and beta-1,4- mannans from different sources, yielding principally mannobiose (PubMed:21037302). Also has transglycosylation activity (PubMed:23558681). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 5 (cellulase A) family.


FUNCTION: Has two active sites that simultaneously bind and inhibit trypsin.


FUNCTION: Acts as a calcium sensor involved in the regulatory pathway for the control of intracellular Na(+) and K(+) homeostasis and salt tolerance. Binding of a CBL protein to the regulatory NAF domain of a CIPK serine-threonine protein kinase lead to the activation of the kinase in a calcium-dependent manner. Operates in synergy with CIPK24/SOS2 to activate the plasma membrane Na(+)/H(+) antiporter SOS1. Involved in salt stress responses by mediating calcium-dependent microfilament reorganization. The CBL4/CIPK6 complex mediates translocation of AKT2 from the endoplasmic reticulum to the plasma membrane. Both myristoylation and S-acylation are required for AKT2 activation. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor Cytoplasm Nucleus Note=The cell membrane localization is S-acylation dependent. SIMILARITY: Belongs to the calcineurin regulatory subunit family.


FUNCTION: Catalyzes the conversion of heme O to heme A by two successive hydroxylations of the methyl group at C8. The first hydroxylation forms heme I, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme A. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the COX15/CtaA family. Type 1 subfamily.


FUNCTION: This protein is probably a component of a manganese permease, a binding protein-dependent, ATP-driven transport system. Probably responsible for energy coupling to the transport system (By similarity). SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein. SIMILARITY: Belongs to the ABC transporter superfamily.


FUNCTION: Required for the transport of riboflavin to the developing oocyte. SIMILARITY: Belongs to the folate receptor family.


FUNCTION: Photoreceptor required for image-forming vision at low light intensity. Can use both retinal and 3-dehydroretinal as visual pigment. Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change that activates signaling via G-proteins. Signaling via GNAQ probably mediates the activation of phospholipase C. SUBCELLULAR LOCATION: Membrane; Multi- pass membrane protein Note=Detected on the rhabdomere membrane in the photoreceptor outer segment. SIMILARITY: Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.


FUNCTION: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.


FUNCTION: This protein binds specifically to 23S rRNA. FUNCTION: The globular domain of the protein is located near the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that lines the wall of the exit tunnel in the center of the 70S ribosome. SUBCELLULAR LOCATION: Plastid. SIMILARITY: Belongs to the universal ribosomal protein uL22 family.


FUNCTION: Component of the entry fusion complex (EFC), which consists of 11 proteins. During cell infection, this complex mediates entry of the virion core into the host cytoplasm by a two-step mechanism consisting of lipid mixing of the viral and cellular membranes and subsequent pore formation. SUBCELLULAR LOCATION: Virion membrane; Single-pass membrane protein Note=Localizes to the membrane surrounding the core of mature virus particles (MV). SIMILARITY: Belongs to the orthopoxvirus OPG095 family.


FUNCTION: Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re- epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. SUBCELLULAR LOCATION: Secreted.


SIMILARITY: Belongs to the HesB/IscA family.


FUNCTION: Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. SUBCELLULAR LOCATION: Nucleus, nucleolus.


FUNCTION: Ammonium transporter involved in the maintenance of acid-base homeostasis. Transports ammonium and its related derivative methylammonium across the plasma membrane of epithelial cells likely contributing to renal transepithelial ammonia transport and ammonia metabolism. Postulated to primarily mediate an electroneutral bidirectional transport of NH3 ammonia species according to a mechanism that implies interaction of an NH4(+) ion with acidic residues of the pore entry followed by dissociation of NH4(+) into NH3 and H(+). As a result NH3 transits through the central pore and is protonated on the extracellular side reforming NH4(+) (PubMed:16131648) (By similarity). May act as a CO2 channel providing for renal acid secretion (By similarity). SUBCELLULAR LOCATION: Apical cell membrane; Multi-pass membrane protein Note=Also detected at the basolateral membrane and in subapical vesicles. SIMILARITY: Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.


FUNCTION: Probable transcription factor required for the initiation of inflorescence trichomes in response to gibberellin (GA) (PubMed:16679458, PubMed:17507408). Mediates the induction of GL1 expression by GA in inflorescence organs and is antagonized in its action by the DELLA repressor GAI. Acts upstream of the trichome initiation regulators GL1 and GL3, and downstream of the GA signaling repressor SPINDLY (SPY) (PubMed:16679458). Does not play a significant role in the cytokinin response (PubMed:17507408). Controls trichome branching through GA signaling (PubMed:22210898, PubMed:23825141). Acts downstream of the key regulator STICHEL (STI) in an endoreduplication- independent pathway (PubMed:22210898). Controls trichome cell division indirectly by acting downstream of a key endoreduplication regulator SIAMESE (SIM) (PubMed:23825141). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromic PIII sequence, 5'-AGCTTGAGTCTAATTGAATTAACTGTAC-3'. HESX1 and PROP1 bind as heterodimers on this palindromic site, and, in vitro, HESX1 can antagonize PROP1 activation (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ANF homeobox family.


FUNCTION: 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein. Mitochondrion membrane; Single-pass membrane protein. SIMILARITY: Belongs to the 3-beta-HSD family.


SIMILARITY: Belongs to the autoinducer-regulated transcriptional regulatory protein family.


FUNCTION: F(1)F(0) ATP synthase produces ATP from ADP in the presence of a proton or sodium gradient. F-type ATPases consist of two structural domains, F(1) containing the extramembraneous catalytic core and F(0) containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. FUNCTION: Component of the F(0) channel, it forms part of the peripheral stalk, linking F(1) to F(0). SUBCELLULAR LOCATION: Cell inner membrane; Single-pass membrane protein. SIMILARITY: Belongs to the ATPase B chain family.


SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: To M.tuberculosis Rv0874c.


FUNCTION: Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. SIMILARITY: Belongs to the thioredoxin family.


FUNCTION: Catalyzes the attachment of O-phosphoserine (Sep) to tRNA(Cys). SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family. O-phosphoseryl-tRNA(Cys) synthetase subfamily.


FUNCTION: Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the complement C6/C7/C8/C9 family.


FUNCTION: Catalyzes the NADPH dependent reduction of D-ribulose 5- phosphate to D-ribitol 5-phosphate. SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase family.


SIMILARITY: Belongs to the dGTPase family. Type 2 subfamily.


FUNCTION: Specific class of high-redox-potential 4Fe-4S ferredoxins. Functions in anaerobic electron transport in most purple and in some other photosynthetic bacteria and in at least one genus (Paracoccus) of halophilic, denitrifying bacteria. SIMILARITY: Belongs to the high-potential iron-sulfur protein (HiPIP) family.


FUNCTION: Bifunctional enzyme that acts both as an endopeptidase and 2- oxoglutarate-dependent monooxygenase (PubMed:28847961) (By similarity). Endopeptidase that cleaves histones N-terminal tails at the carboxyl side of methylated arginine or lysine residues, to generate 'tailless nucleosomes', which may trigger transcription elongation (PubMed:28847961). Preferentially recognizes and cleaves monomethylated and dimethylated arginine residues of histones H2, H3 and H4. After initial cleavage, continues to digest histones tails via its aminopeptidase activity (PubMed:28847961). Additionally, may play a role in protein biosynthesis by modifying the translation machinery. Acts as Fe(2+) and 2-oxoglutarate-dependent monooxygenase, catalyzing (S)-stereospecific hydroxylation at C-3 of 'Lys-22' of DRG1 and 'Lys- 21' of DRG2 translation factors (TRAFAC), promoting their interaction with ribonucleic acids (RNA) (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm.


FUNCTION: Catalyzes the intermembrane transfer of phosphatidylglycerol and phosphatidylinositol. SUBCELLULAR LOCATION: Cytoplasm Cytoplasmic vesicle Golgi apparatus Note=Also associated with Golgi-like vesicles. SIMILARITY: Belongs to the NPC2 family.


FUNCTION: Has a role in vesicular trafficking and septation during cytokinesis. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein.


FUNCTION: A type III restriction enzyme that recognizes 2 inversely oriented double-stranded sequences 5'-CGAAG-3' and cleaves 25-27 base pairs downstream. After binding to one recognition site undergoes random one-dimensional diffusion along DNA until it collides with a stationary enzyme bound to the second DNA site, which is when DNA cleavage occurs. DNA restriction requires both the Res and Mod subunits (By similarity). SIMILARITY: Belongs to the type III restriction-modification system Res protein family.


FUNCTION: Binds the chemical odorant, 2-isobutyl-3-methoxypyrazine. SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.


FUNCTION: May play a general 'housekeeping role' in lipid metabolism. Exhibits both diacylglycerol pyrophosphate (DGPP) phosphatase and phosphatidate (PA) phosphatase activities with no preference for either substrate. May play a role downstream of the ABA signaling pathway during seed germination and in stomatal movement in leaves. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase family.


FUNCTION: Nucleoside triphosphate pyrophosphatase that hydrolyzes dTTP and UTP. May have a dual role in cell division arrest and in preventing the incorporation of modified nucleotides into cellular nucleic acids. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the Maf family. YhdE subfamily.


FUNCTION: Binds CLEC2I/Clr-g leading to activation of natural killer cells or stimulation of IL-2 production and proliferation of T-cells in response to antigen stimulation. May contribute to the formation of the immunological synapse between T-cells and antigen-presenting dendritic cells (By similarity). SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein.


FUNCTION: Promotes cell adhesion and matrix assembly. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix. SIMILARITY: Belongs to the CCDC80 family.


SUBCELLULAR LOCATION: Secreted, cell wall. SIMILARITY: Belongs to the plant proline-rich protein superfamily.


FUNCTION: [Isoform Mitochondrial]: Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH. FUNCTION: [Isoform Cytoplasmic]: Catalyzes the dehydration of L-malate to fumarate (PubMed:23643539). Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by- product of the urea cycle and amino-acid catabolism (PubMed:23643539). Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ) (By similarity). In response to DNA damage and phosphorylation by PRKDC, translocates to the nucleus and accumulates at DNA double- strand breaks (DSBs): acts by catalyzing formation of fumarate, an inhibitor of KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 'Lys-36' (H3K36me2) (By similarity). FUNCTION: Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (PubMed:23643539). Experiments in different species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable). SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion. SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm, cytosol Nucleus Chromosome Note=Translocates to the nucleus in response to DNA damage: localizes to DNA double-strand breaks (DSBs) following phosphorylation by PRKDC. SIMILARITY: Belongs to the class-II fumarase/aspartase family. Fumarase subfamily.


SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.


FUNCTION: Inhibits trypsin in vitro. Probably plays a protective role through inhibition of insect midgut proteases. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the protease inhibitor I6 (cereal trypsin/alpha- amylase inhibitor) family.


FUNCTION: Component of the origin recognition complex (ORC) that binds origins of replication. It has a role in both chromosomal replication and mating type transcriptional silencing. Binds to the ARS consensus sequence (ACS) of origins of replication. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ORC3 family.


FUNCTION: Negative regulator of sphingolipid synthesis. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ORM family.


FUNCTION: One of two assembly initiator proteins, it binds directly to the 5'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit. FUNCTION: Located at the polypeptide exit tunnel on the outside of the subunit. SIMILARITY: Belongs to the universal ribosomal protein uL24 family.


FUNCTION: Plays a role in the initiation of viral DNA replication. A dimer of E2 interacts with a dimer of E1 in order to improve specificity of E1 DNA binding activity. Once the complex recognizes and binds DNA at specific sites, the E2 dimer is removed from DNA. E2 also regulates viral transcription through binding to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory regions of the viral genome. Activates or represses transcription depending on E2RE's position with regards to proximal promoter elements including the TATA-box. Repression occurs by sterically hindering the assembly of the transcription initiation complex. SUBCELLULAR LOCATION: Host nucleus. SIMILARITY: Belongs to the papillomaviridae E2 protein family.


FUNCTION: Assembles around the rod to form the L-ring and probably protects the motor/basal body from shearing forces during rotation. SUBCELLULAR LOCATION: Periplasm Bacterial flagellum basal body. SIMILARITY: Belongs to the FlgI family.


SIMILARITY: Belongs to the UPF0457 family.


FUNCTION: May be a general steroid carrier protein. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the BetVI family.


FUNCTION: Bifunctional enzyme that catalyzes the reactions from geranylgeranyl diphosphate to phytoene (phytoene synthase) and lycopene to beta-carotene via the intermediate gamma-carotene (lycopene cyclase). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: In the C-terminal section; belongs to the phytoene/squalene synthase family. SIMILARITY: In the N-terminal section; belongs to the lycopene beta- cyclase family.


FUNCTION: C-type cytochrome. Part of the cbb3-type cytochrome c oxidase complex. CcoP subunit is required for transferring electrons from donor cytochrome c via its heme groups to CcoO subunit. From there, electrons are shuttled to the catalytic binuclear center of CcoN subunit where oxygen reduction takes place. The complex also functions as a proton pump (By similarity). SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the CcoP / FixP family.


FUNCTION: Multivalent adapter protein which may decrease NOS3 activity by inducing its translocation away from the plasma membrane. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein; Cytoplasmic side Cytoplasmic vesicle Cytoplasm, cytoskeleton Cytoplasm Nucleus Note=Enriched in selected actin structures.


FUNCTION: Induces caspases and apoptosis. Counters the protective effect of BCL2. FUNCTION: [BH3-interacting domain death agonist p15]: Induces caspase activation and apoptosis (By similarity). Allows the release of cytochrome c (By similarity). SUBCELLULAR LOCATION: Cytoplasm Mitochondrion membrane Mitochondrion outer membrane Note=When uncleaved, it is predominantly cytoplasmic (By similarity). SUBCELLULAR LOCATION: [BH3-interacting domain death agonist p13]: Mitochondrion membrane Note=Associated with the mitochondrial membrane. SUBCELLULAR LOCATION: [BH3-interacting domain death agonist p15]: Mitochondrion membrane Note=Translocates to mitochondria as an integral membrane protein.


FUNCTION: Catalyzes the production of hydrogen sulfide (H2S) from cysteine. SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the ACC deaminase/D-cysteine desulfhydrase family.


FUNCTION: The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Acts as a functional inhibitor of gH and maintains gH in an inhibited form. Upon binding to host integrins, gL dissociates from gH leading to activation of the viral fusion glycoproteins gB and gH (By similarity). In human cytomegalovirus, forms two distincts complexes to mediate viral entry, a trimer and a pentamer at the surface of the virion envelope. The gH-gL-gO trimer is required for infection in fibroblasts by interacting with host PDGFRA. The gH-gL- UL128-UL130-UL131A pentamer is essential for viral entry in epithelial, endothelial and myeloid cells via interaction with host NRP2 (By similarity). SUBCELLULAR LOCATION: Virion membrane; Peripheral membrane protein; Extracellular side Host cell membrane; Peripheral membrane protein; Extracellular side Host Golgi apparatus, host trans- Golgi network Note=gL associates with the extravirion surface through its binding to gH. During virion morphogenesis, this protein probably accumulates in the host trans- Golgi where secondary envelopment occurs. SIMILARITY: Belongs to the herpesviridae glycoprotein L family.


FUNCTION: Catalyzes the conversion of homogentisate to maleylacetoacetate. SIMILARITY: Belongs to the homogentisate dioxygenase family.


FUNCTION: Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration (By similarity). SUBCELLULAR LOCATION: Cytoplasm Cell projection, growth cone Note=Colocalizes with synaptic vesicle protein 2 in the central region of the growth cone. SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.


FUNCTION: Orphan receptor. Signals via G(s)-alpha family of G-proteins. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.


FUNCTION: Binds to DNA and alters its conformation. May be involved in global regulation of gene expression. Binds specifically and non- specifically to DNA, preferentially to the 4 bp broken palindrome 5'- GTnAC-3'. Affects expression of a wide variety of genes, encoding both structural and metabolic proteins. SUBCELLULAR LOCATION: Cytoplasm, nucleoid. SIMILARITY: Belongs to the YbaB/EbfC family.


FUNCTION: Part of the energy-coupling factor (ECF) transporter complex CbiMNOQ involved in cobalt import. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the CbiN family.


FUNCTION: Dynein-attachment factor required for cilia motility. SUBCELLULAR LOCATION: Cytoplasm Cell projection, cilium, flagellum. SIMILARITY: Belongs to the CCDC103/PR46b family.


FUNCTION: The central subunit of the protein translocation channel SecYEG. Consists of two halves formed by TMs 1-5 and 6-10. These two domains form a lateral gate at the front which open onto the bilayer between TMs 2 and 7, and are clamped together by SecE at the back. The channel is closed by both a pore ring composed of hydrophobic SecY resides and a short helix (helix 2A) on the extracellular side of the membrane which forms a plug. The plug probably moves laterally to allow the channel to open. The ring and the pore may move independently. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the SecY/SEC61-alpha family.


SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto reductase 13 subfamily.


FUNCTION: Bifunctional enzyme that catalyzes the enolization of 2,3- diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P) into the intermediate 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate (HK- MTPenyl-1-P), which is then dephosphorylated to form the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene). SIMILARITY: Belongs to the HAD-like hydrolase superfamily. MasA/MtnC family.


FUNCTION: Functions by promoting the formation of the first peptide bond. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the eIF-5A family.


FUNCTION: Structural component of the T=16 icosahedral capsid. The capsid is composed of pentamers and hexamers of major capsid protein/MCP, which are linked together by heterotrimers called triplexes. These triplexes are formed by a single molecule of triplex protein 1/TRX1 and two copies of triplex protein 2/TRX2. Additionally, TRX1 is required for efficient transport of TRX2 to the nucleus, which is the site of capsid assembly. SUBCELLULAR LOCATION: Virion Host nucleus. SIMILARITY: Belongs to the herpesviridae TRX2 protein family.


FUNCTION: Involved in the biosynthesis of the antimalarial endoperoxide artemisinin (PubMed:11032404, PubMed:11185551, PubMed:11289612, PubMed:10626375, PubMed:27488942). Catalyzes the formation of both olefinic and oxygenated sesquiterpenes, with amorpha-4,11-diene being the major product (PubMed:11032404, PubMed:11185551, PubMed:11289612, PubMed:10626375). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the terpene synthase family.


FUNCTION: Enhances the ribosomal termination-reinitiation event leading to the translation of major open reading frames on the polycistronic viral RNAs. SUBCELLULAR LOCATION: Host cytoplasm. Note=Found in cytoplasmic occlusion bodies. SIMILARITY: Belongs to the caulimoviridae viroplasmin family.


FUNCTION: Phosphotransfer between the C1 and C5 carbon atoms of pentose. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the phosphopentomutase family.


FUNCTION: Multicopper oxidase involved in copper homeostasis and copper tolerance under both aerobic and anaerobic conditions (PubMed:12442888, PubMed:17768242). Is responsible for the oxidation of Cu(+) to the less harmful Cu(2+) in the periplasm, thereby preventing Cu(+) from entering the cytoplasm (By similarity). SUBCELLULAR LOCATION: Periplasm. SIMILARITY: Belongs to the multicopper oxidase family.


FUNCTION: Component of the sulfite reductase complex that catalyzes the 6-electron reduction of sulfite to sulfide. This is one of several activities required for the biosynthesis of L-cysteine from sulfate. SIMILARITY: Belongs to the nitrite and sulfite reductase 4Fe-4S domain family.


SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase family.


FUNCTION: Catalyzes the conversion of 8-oxo-dGTP to 8-oxo-dGDP, and 8- oxo-GTP to 8-oxo-GDP. FUNCTION: Catalyzes the conversion of 8-oxo-dGTP to 8-oxo-dGDP, and 8- oxo-GTP to 8-oxo-GDP (PubMed:23463507, PubMed:16585780). Functions in concert with Rv1700 to detoxify 8-oxo-dGTP to 8-oxo-dGMP and plays an important role in supporting cellular growth under oxidative stress (PubMed:23463507). SIMILARITY: Belongs to the Nudix hydrolase family.


FUNCTION: Localized to zymogen granules, where it functions in trypsinogen activation (PubMed:12401800). May indirectly regulate cell motility, cell-cell and cell/extracellular matrix interactions (By similarity). SUBCELLULAR LOCATION: Zymogen granule membrane; Single-pass type I membrane protein.


FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors. Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation (By similarity). Involved in neurogenesis. Performs a partially redundant function with wnt10b in the formation of the midbrain-hindbrain boundary (MHB) organizer. In the hindbrain, mediates lateral inhibition of boundary cell specification, probably via up-regulation of proneural and Delta gene expression in non-boundary cells; localized expression of wnt1 in boundary cells is maintained via rfng-mediated modulation of Notch activity. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix Secreted. SIMILARITY: Belongs to the Wnt family.


SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.


FUNCTION: RING-type zinc finger-containing E3 ubiquitin ligase that assembles with melanoma antigen protein (MAGE) to catalyze the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. Within MAGE-RING ubiquitin ligase complex, MAGE stimulates and specifies ubiquitin ligase activity likely through recruitment and/or stabilization of the E2 ubiquitin-conjugating enzyme at the E3:substrate complex. Involved in maintenance of genome integrity, DNA damage response and DNA repair. SUBCELLULAR LOCATION: Nucleus Chromosome, telomere. SIMILARITY: Belongs to the NSE1 family.


FUNCTION: Transfers the glycosyl residue from UDP-Glc to the non- reducing end of alpha-1,4-glucan. SIMILARITY: Belongs to the glycosyltransferase 3 family.


FUNCTION: Involved in phosphonate degradation. SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. PhnW subfamily.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the UPF0291 family.


FUNCTION: Member of the two-component regulatory system NtrB/NtrC, which controls expression of the nitrogen-regulated (ntr) genes in response to nitrogen limitation. Phosphorylated NtrC binds directly to DNA and stimulates the formation of open promoter-sigma54-RNA polymerase complexes. SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Componement of the CCZ1-MON1 RAB7A guanine exchange factor (GEF). Acts as a positive regulator of CCZ1-MON1A/B function necessary for endosomal/autophagic flux and efficient RAB7A localization. SUBCELLULAR LOCATION: Lysosome membrane Late endosome membrane. SIMILARITY: Belongs to the RMC1 family.


SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the glycosyltransferase 2 family. GtrB subfamily.


SIMILARITY: Belongs to the eukaryotic ribosomal protein eL34 family.


FUNCTION: Involved in resistance to arsenate. Catalyzes the reduction of arsenate [As(V)] to arsenite [As(III)]. SIMILARITY: Belongs to the ArsC family.


SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the bacterial ribosomal protein bL27 family.


FUNCTION: PsaA and PsaB bind P700, the primary electron donor of photosystem I (PSI), as well as the electron acceptors A0, A1 and FX. PSI is a plastocyanin-ferredoxin oxidoreductase, converting photonic excitation into a charge separation, which transfers an electron from the donor P700 chlorophyll pair to the spectroscopically characterized acceptors A0, A1, FX, FA and FB in turn. Oxidized P700 is reduced on the lumenal side of the thylakoid membrane by plastocyanin. SUBCELLULAR LOCATION: Plastid, chloroplast thylakoid membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the PsaA/PsaB family.


FUNCTION: Is able to convert N-methyl-3,4-dihydroxy-DL-phenylalanine (N-methyl-DOPA) directly into cyclic isoquinoline, in vitro (PubMed:27065235, PubMed:30194285). The absence of the meta-hydroxyl group, as in L-N-methyl-tyrosine, leads to a 25-fold lower rate of reduction and the formation of the demethylated product L-tyrosine, instead of a cyclic product (PubMed:30194285). Does not accept the D- stereoisomer of N-methyltyrosine, in contrast to N-methyl-DOPA, for which both stereoisomers are oxidized with similar rates (PubMed:30194285). FUNCTION: Amino acid oxidase; part of the gene cluster that mediates the biosynthesis of the isoquinoline alkaloids fumisoquin A, fumisoquin B and fumisoquin C; as well as small amounts of fumipyrrole as a shunt metabolite (PubMed:25582336, PubMed:27065235, PubMed:30194285). The products of the cluster lead to a brown coloration and are important for growth and conidiation (PubMed:25582336). The nonribosomal peptide synthetase-like protein fsqF, which lacks a canonical condensation domain, is required for addition of a serine-derived dehydroalanine moiety to activated tyrosine but is not essential for the subsequent steps leading to isoquinoline formation (PubMed:27065235). A different enzyme, most likely the ATP-grasp enzyme fsqD, is responsible for activation of tyrosine (Probable). Three additional enzymes encoded by the fsq cluster, the N-methyltransferase fsqC, the phenol 2- monooxygenase fsqG and the FAD-dependent oxidase fsqB, catalyze the formation of the isoquinoline ring system in the fumisoquins (PubMed:27065235, PubMed:30194285). FsqB converts the fspF thiolation domain-bound (2S,4S,5S)-2-amino-6-(3,4-dihydroxyphenyl)-4-hydroxy-5- (methylamino)hexanoyl into isoquinoline (PubMed:27065235, PubMed:30194285). The cyclization most likely proceeds via a two-step mechanism, beginning with FAD-dependent oxidation of the methyl group to an iminium species followed by electrophilic attack on the deprotonated phenol (Probable). SIMILARITY: Belongs to the MSOX/MTOX family.


FUNCTION: Could be involved in insertion of integral membrane proteins into the membrane. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein; Cytoplasmic side. SIMILARITY: Belongs to the UPF0161 family.