FUNCTION: Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5- trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis (By similarity). Can phosphorylate inositol 2,4,5-triphosphate to inositol 2,4,5,6-tetraphosphate (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Shuttles actively between nucleus and cytoplasm with both nuclear import and nuclear export activity. SIMILARITY: Belongs to the inositol phosphokinase (IPK) family.


FUNCTION: Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (PubMed:18025219, PubMed:21551061, PubMed:24739961, PubMed:24715728). Hydrolyzes GTP to GMP in two consecutive cleavage reactions: GTP is first hydrolyzed to GDP and then to GMP in a processive manner (By similarity). Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and promotes both autophagy and inflammasome assembly (PubMed:21551061, PubMed:24739961, PubMed:24715728). Promotes host defense against bacterial infections by regulating bacteriolytic peptide generation via its interaction with ubiquitin-binding protein SQSTM1, which delivers monoubiquitinated proteins to autolysosomes for the generation of bacteriolytic peptides (PubMed:21551061). Also acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria (PubMed:24739961, PubMed:24715728). Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol (PubMed:24739961, PubMed:24715728). Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis, such as Gm12250/Irgb10: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (PubMed:24739961, PubMed:24715728). Confers protection to several pathogens, including the bacterial pathogens L.monocytogenes and M.bovis BCG as well as the protozoan pathogen T.gondii (PubMed:18025219, PubMed:21551061). Exhibits antiviral activity against influenza virus (By similarity). SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Lipid- anchor; Cytoplasmic side Golgi apparatus membrane; Lipid-anchor; Cytoplasmic side Cell membrane; Lipid-anchor; Cytoplasmic side Cytoplasm Secreted Note=Localizes to pathogen-containing vacuoles or to the cell surface of bacteria that escaped vacuoles. Secreted from endothelial cells in the cerebrospinal fluid, upon bacterial challenge and independently of IFNG induction. Golgi membrane localization requires isoprenylation and the presence of another IFNG- induced factor. SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.


FUNCTION: Involved in chromosome condensation, segregation and cell cycle progression. May participate in facilitating chromosome segregation by condensation DNA from both sides of a centrally located replisome during cell division. Not required for mini-F plasmid partitioning. Probably acts via its interaction with MukB and MukE. Overexpression results in anucleate cells. It has a calcium binding activity. FUNCTION: Involved in chromosome condensation, segregation and cell cycle progression. May participate in facilitating chromosome segregation by condensation DNA from both sides of a centrally located replisome during cell division. Not required for mini-F plasmid partitioning. Probably acts via its interaction with MukB and MukE. Overexpression results in anucleate cells. It has a calcium binding activity. SUBCELLULAR LOCATION: Cytoplasm, nucleoid Note=Restricted to the nucleoid region. SUBCELLULAR LOCATION: Cytoplasm, nucleoid. Note=Restricted to the nucleoid region. SIMILARITY: Belongs to the MukF family. SIMILARITY: Belongs to the MukF family.


FUNCTION: Ubiquitin-like modifier involved in autophagosomes formation. May mediate the delivery of the autophagosomes to the vacuole via the microtubule cytoskeleton. SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome membrane; Lipid-anchor Vacuole membrane; Lipid-anchor Cytoplasm, cytoskeleton. SIMILARITY: Belongs to the ATG8 family.


FUNCTION: Involved in the formation of 2-(5''-phosphoribosyl)-3'- dephosphocoenzyme-A, the prosthetic group of the acyl-carrier protein of the malonate decarboxylase. SIMILARITY: Belongs to the CitG/MdcB family.


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


FUNCTION: Specifically catalyzes the decarboxylation of L-arginine to agmatine. Has no S-adenosylmethionine decarboxylase (AdoMetDC) activity. SIMILARITY: Belongs to the prokaryotic AdoMetDC family. Type 1 subfamily.


FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system. Acts as an endoribonuclease on single-strand RNA, cleaving between the first and second bases in the sequence UCGCU. Neutralized by coexpression with cognate antitoxin MazE1. FUNCTION: Residues 29-56 inhibit ssDNA cleavage by DNA topoisomerase. This fragment does not have mRNA cleavage activity but it inhibits growth upon overexpression in M.smegmatis. FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system. Acts as an endoribonuclease (mRNA interferase) on single-strand mRNA, cleaving between the first and second bases in the sequence UCGCU. Overexpression in M.smegmatis but not E.coli inhibits growth, this effect is neutralized by coexpression with cognate toxin MazE4. FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system. Acts as an endoribonuclease on single-strand RNA, cleaving between the first and second bases in the sequence UCGCU. Neutralized by cognate antitoxin MazE4. SIMILARITY: Belongs to the PemK/MazF family.


FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down- regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4 (By similarity). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endosome Endoplasmic reticulum Note=Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.


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, chloroplast. SIMILARITY: Belongs to the universal ribosomal protein uL22 family.


FUNCTION: Protects the virus against cell antiviral state by blocking host interferon signaling. Mechanistically, targets host phosphorylated STAT1 (phospho-STAT1) for degradation, thereby inhibiting the interferon alpha signaling pathway (PubMed:12885886, PubMed:26859759). Plays a role in the inhibition of host apoptosis (PubMed:30290847). Interacts with and down-regulates the expression of host TXNL1. In turn, inhibits TXNL1-induced apoptosis through the BCL2-BAX-caspase 3 pathway (PubMed:30290847). Inhibits host apoptosis also by negatively regulating host CacyBP/SIP (PubMed:30234028). Promotes viral replication by activating the extracellular signal-regulated kinase (ERK) pathway (PubMed:30213106). SUBCELLULAR LOCATION: Host cytoplasm Host nucleus. SIMILARITY: Belongs to the paramyxoviruses V protein family.


FUNCTION: Maximin-H16 shows antimicrobial activity against bacteria and against the fungus C.albicans. Shows strong hemolytic activity (By similarity). FUNCTION: Maximin-y shows antimicrobial activity against bacteria and against the fungus C.albicans. It has little hemolytic activity (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the bombinin family.


FUNCTION: Appears to lack serine protease inhibitor activity in vitro when tested with bovine pancreatic alpha-chymotrypsin and elastase (PubMed:19716386). Involved in cuticle biosynthesis (PubMed:16500660, PubMed:19716386).


FUNCTION: Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. May anchor nucleoporins, but not NUP153 and TPR, to the NPC. During renal development, regulates podocyte migration and proliferation through SMAD4 signaling. SUBCELLULAR LOCATION: Nucleus membrane; Peripheral membrane protein Nucleus, nuclear pore complex Nucleus envelope Note=Localizes at the nuclear basket and at or near the nuclear entry to the gated channel of the pore. SIMILARITY: Belongs to the nucleoporin interacting component (NIC) family.


FUNCTION: Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Interacts with gangliosides GT1b and GD1b containing terminal alpha(2-8)-linked sialic acids on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis and traffics to the endoplasmic reticulum. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. In late phase of infection, neo- synthesized VP1 encapsulates replicated genomic DNA in the nucleus, and participates in rearranging nucleosomes around the viral DNA. SUBCELLULAR LOCATION: Virion. Host nucleus. SIMILARITY: Belongs to the polyomaviruses coat protein VP1 family.


FUNCTION: Hydrolysis of the deoxyribose N-glycosidic bond to excise 3- methyladenine, 3-methylguanine, 7-methylguanine, O2-methylthymine, and O2-methylcytosine from the damaged DNA polymer formed by alkylation lesions. SIMILARITY: Belongs to the alkylbase DNA glycosidase AlkA family.


FUNCTION: Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy. SUBCELLULAR LOCATION: Secreted, extracellular space. SIMILARITY: Belongs to the peptidase S1 family.


FUNCTION: Endonuclease that specifically degrades the RNA of RNA-DNA hybrids. FUNCTION: Endonuclease that specifically degrades the RNA of RNA-DNA hybrids. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the RNase H family. SIMILARITY: Belongs to the RNase H family.


FUNCTION: Specifically hydrolyzes gamma-D-glutamyl-L-lysine bonds in murein peptides, releasing L-Ala-D-Glu. SIMILARITY: Belongs to the peptidase C40 family.


FUNCTION: Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Required for normal platelet aggregation and blood coagulation. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 1 family.


FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals (PubMed:9250660, PubMed:9442090, PubMed:15911617). RAs exist as at least four different isomers: all- trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (By similarity). Catalyzes the hydroxylation of atRA primarily at C-4 and C-18, thereby contributing to the regulation of atRA homeostasis and signaling (PubMed:9250660, PubMed:9442090, PubMed:15911617). Hydroxylation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination (By similarity). Involved in the convertion of atRA to all-trans-4-oxo-RA (PubMed:15911617). Able to metabolize other RAs such as 9-cis, 13-cis and 9,13-di-cis RA (PubMed:9250660). Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4-hydroxy-DRA, all-trans- 5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA (Probable). May play a role in the oxidative metabolism of xenobiotics such as tazarotenic acid (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein. SIMILARITY: Belongs to the cytochrome P450 family.


FUNCTION: A leucine-specific metalloprotease that plays a role in controlling the amount of leupeptin during colony development. Degrades leupeptin into three components, acetyl-leucine, leucine and argininal. Has a strict preference for leucine at the P1 site. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase M28 family. M28A subfamily.


FUNCTION: Dermonecrotic toxins cleave the phosphodiester linkage between the phosphate and headgroup of certain phospholipids (sphingolipid and lysolipid substrates), forming an alcohol (often choline) and a cyclic phosphate (By similarity). This toxin acts on sphingomyelin (SM) with high activity (PubMed:18082635). It may also act on ceramide phosphoethanolamine (CPE), lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), but not on lysophosphatidylserine (LPS), and lysophosphatidylglycerol (LPG) (By similarity). It acts by transphosphatidylation, releasing exclusively cyclic phosphate products as second products (By similarity). Induces dermonecrosis, massive inflammatory response, platelet aggregation, increased vascular permeability, and causes edema and death in mice (PubMed:18082635). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the arthropod phospholipase D family. Class II subfamily. Class IIa sub-subfamily.


FUNCTION: Required for activity of the AHR. Upon ligand binding, AHR translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE). Not required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex initiates transcription of genes involved in the regulation of a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (By similarity). The heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters and functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity). The heterodimer ARNT:AHR binds to core DNA sequence 5'- TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (By similarity). SUBCELLULAR LOCATION: Nucleus.


SUBCELLULAR LOCATION: Spore wall. SIMILARITY: Belongs to the SWP12 family.


FUNCTION: Probably participates in a plant defense mechanism (Potential). Binds to and induces leakage in phospholipd membranes, particularly ones containing 1-palmitoyl-2-oleophosphatidylethanolamine (POPE) (PubMed:26322745). In vitro, displays cytotoxicity against cultured cells (PubMed:26322745). Not active against Gram-negative bacterium E.coli ATCC 25922 or Gram-positive bacterium S.aureus ATCC 25923 up to a concentration of 64 uM (PubMed:26322745). SIMILARITY: Belongs to the cyclotide family. Moebuis subfamily.


FUNCTION: Catalyzes the initial step in the synthesis of dolichol-P-P- oligosaccharides. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the glycosyltransferase 4 family.


FUNCTION: Mutations in this gene suppress deletion of PBP2b (penA); truncation at residue 168, undefined changes between residue Ile-447 and Ala-505, and mutation of Ala-505 suppress the penA deletion. Probably part of the elongasome which synthesizes peripheral peptidogylcan. FUNCTION: Functions as a peptidoglycan terminase that cleaves nascent peptidoglycan strands endolytically to terminate their elongation. SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein Note=Localizes to midcell in the presence and absence of khpB (also called eloR/jag). SIMILARITY: Belongs to the transglycosylase MltG family.


FUNCTION: Protein kinase that plays an important role in mitotic regulation. Seems to be phosphorylated and thereby activated by CDC2/cyclin B during mitotic activation. It is also required for spindle formation and for nuclear envelope breakdown. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.


FUNCTION: Tooth-associated epithelia protein that probably plays a role in odontogenesis, the complex process that results in the initiation and generation of the tooth. May be incorporated in the enamel matrix at the end of mineralization process. Involved in the induction of RHOA activity via interaction with ARHGEF and expression of downstream factors such as ROCK. Plays a role in attachment of the junctional epithelium to the tooth surface. SUBCELLULAR LOCATION: Secreted Cytoplasm Nucleus. SIMILARITY: Belongs to the ODAM family.


FUNCTION: Glutathione peroxidase-like protein that protects cells from phospholipid hydroperoxides and nonphospholipid peroxides during oxidative stress (PubMed:10480913, PubMed:11445588). Plays an important role in the oxidative stress-induced response in the presence of Ca(2+). Has peroxidase activity using preferentially thioredoxin as a reducing power. The redox state of the mitochondrial GPX2 is regulated by TRX1 and TRX2 (cytoplasmic thioredoxin), and by TRX3 (mitochondrial matrix thioredoxin) (PubMed:16251189). Involved in sporulation (PubMed:21763276). SUBCELLULAR LOCATION: Cytoplasm Nucleus Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side Mitochondrion inner membrane; Peripheral membrane protein; Matrix side. SIMILARITY: Belongs to the glutathione peroxidase family.


SUBCELLULAR LOCATION: Nucleus Cytoplasm.


SIMILARITY: Belongs to the aerolysin family.


FUNCTION: Molecular chaperone that assists in the folding or refolding of nascent or denatured proteins along with ATP hydrolysis (Probable). ATPase activity is highest in thermosome assemblies containing CCT1:CCT2, followed by assemblies containing CCT1:CCT2:CCT3. Seems to contribute to thermosome ATPase activity. Not required for growth. SIMILARITY: Belongs to the TCP-1 chaperonin family.


FUNCTION: This major extracellular protein may be involved in the invasion of non-professional phagocytic cells by Listeria. SUBCELLULAR LOCATION: Cell surface Secreted. SIMILARITY: Belongs to the peptidase C40 family.


SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the ycf45 family.


FUNCTION: Responsible for synthesis of pseudouridine from uracil-516 in 16S ribosomal RNA. SIMILARITY: Belongs to the pseudouridine synthase RsuA family.


FUNCTION: Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against rat Nav1.2/SCN2A and B.germanica Nav1. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily.


FUNCTION: Antimicrobial peptide active against Gram-positive bacteria and fungi but inactive against Gram-negative bacteria. Also inhibits growth of B.dendrobatidis zoospores at high concentrations. Shows anticancer activities. Shows hemolytic activity. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the frog skin active peptide (FSAP) family. Medusin subfamily.


FUNCTION: Could play a role in taste reception. Could be necessary for the concentration and delivery of sapid molecules in the gustatory system. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.


FUNCTION: Transcription factor that acts as a key regulator of ciliogenesis (PubMed:22233545). Specifically regulates expression of genes required for cilium assembly and function (PubMed:22233545). Recognizes and binds the X-box, a regulatory motif with DNA sequence 5'-GTNRCC(0-3N)RGYAAC-3' present on promoters (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Mainly expressed in the nucleus and at lower level in cytoplasm. SIMILARITY: Belongs to the RFX family.


FUNCTION: Regulates ATP-dependent protein translocation into the mitochondrial matrix. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side. SIMILARITY: Belongs to the TIM16/PAM16 family.


FUNCTION: Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of either ATP or GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and nucleotide specificity is provided by the beta subunit. SIMILARITY: Belongs to the succinate/malate CoA ligase alpha subunit family.


FUNCTION: Trans-acting transcriptional regulator of RuBisCO genes (rbcL and rbcS) expression. SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the LysR transcriptional regulatory family.


FUNCTION: Has weak lytic activity toward S.aureus cells. Full-length protein has no activity, but fusion of the Peptidase C51 domain to the lysostaphin SH3 cell wall binding domain yields an active chimeric enzyme, suggesting that PH may be functional.


FUNCTION: Seems to have esterase activity. Prefers ester of fatty acids from 4 to 16 carbon atoms. SUBCELLULAR LOCATION: Secreted, cell wall. Membrane; Lipid-anchor, GPI- anchor. Note=Covalently-linked GPI-modified cell wall protein (GPI-CWP) found only in mother cells. SIMILARITY: Belongs to the SRP1/TIP1 family.


FUNCTION: May be a component of a protein phosphatase type 2A (PP2A) complex. Negatively regulates SIT4 phosphatase, a modulators of caffeine sensitivity. SUBCELLULAR LOCATION: Cytoplasm Nucleus.


FUNCTION: Major acute phase reactant. Apolipoprotein of the HDL complex. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the SAA family.


FUNCTION: Involved in pyrimidine catabolism. Catalyzes the deamination of 3-aminoacrylate to malonic semialdehyde, a reaction that can also occur spontaneously. RutC may facilitate the reaction and modulate the metabolic fitness, rather than catalyzing essential functions. SIMILARITY: Belongs to the RutC family.


SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TMEM151 family.


FUNCTION: Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:8135828, PubMed:29915090, PubMed:30850536). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long- chain fatty acids (PubMed:30850536). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities, while the trifunctional enzyme subunit beta/HADHB described here bears the 3- ketoacyl-CoA thiolase activity (PubMed:8135828, PubMed:29915090, PubMed:30850536). SUBCELLULAR LOCATION: Mitochondrion Mitochondrion inner membrane Mitochondrion outer membrane Endoplasmic reticulum Note=Protein stability and association with membranes require HADHA. SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.


FUNCTION: Involved in the biosynthesis of the yellow-orange carotenoid staphyloxanthin, which plays a role in the virulence via its protective function against oxidative stress. Catalyzes the head-to-head condensation of two molecules of farnesyl diphosphate (FPP) into the colorless C(30) carotenoid 4,4'-diapophytoene (dehydrosqualene). SIMILARITY: Belongs to the phytoene/squalene synthase family. CrtM subfamily.


FUNCTION: In vitro, the TRIAP1:PRELID3A complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space. Phosphatidic acid import is required for cardiolipin (CL) synthesis in the mitochondrial inner membrane. SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the slowmo family.


FUNCTION: DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes. May also play a role in the response to DNA damage (DDR). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=May shuttle between cytoplasm and nucleus. SIMILARITY: Belongs to the CEF1 family.


FUNCTION: This is the catalytic subunit of the viral RNA-dependent RNA polymerase complex. This complex is involved in viral RNA replication that produces (+)-stranded genomes via a complementary, (-)-stranded intermediate. Binds RNA cooperatively with the host ribosomal protein S1.


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: Regulates exocytosis by functioning as a GAP for SEC4. Also required for efficient polarization of the actin patches. SUBCELLULAR LOCATION: Cytoplasm Bud Bud neck Note=Localizes to the presumptive bud site, the bud tip and the mother- bud neck.


FUNCTION: Functions as carrier for hydrophobic molecules in body fluids. Essential for the solubility and activity of lipidated Wnt family members, including WNT1, WNT2B, WNT3, WNT3A, WNT5A, WNT7A, WNT7B, WNT8, WNT9A, WNT9B, WNT10A and WNT10B (PubMed:26902720). Binds vitamin E. May transport vitamin E in body fluids under conditions where the lipoprotein system is not sufficient. May be involved in the transport of vitamin E across the blood-brain barrier (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the ALB/AFP/VDB family.


FUNCTION: Plays an essential role in chain termination during de novo fatty acid synthesis. High thioesterase activity for oleoyl-ACP versus other acyl-ACPs. SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the acyl-ACP thioesterase family.


FUNCTION: Plays a key role in the activation of the host resting B-cell and stimulation of B-cell proliferation. Acts by up-regulating the expression of viral EBNA1-6, LMP1, LMP2A and LMP2B genes, as well as several host genes including CD21, CD23 and MYC. Activates transcription by acting as an adapter molecule that binds to cellular sequence-specific DNA-binding proteins such as host CBF1, SMARCB1 and SPI1. Once EBNA2 is near promoter sites, its acidic activating domain recruits basal and activation-associated transcription factors TFIIB, TAF40, TFIIH components ERCC2 and ERCC3, and CBP in order to promote transcription. Alternatively, EBNA2 can affect activities of cell cycle regulators and retard cell cycle progression at G2/M phase. It also induces chromosomal instability, by disrupting mitotic checkpoints, multi-nucleation and formation of micronuclei in infected cells (By similarity). SUBCELLULAR LOCATION: Host nucleus matrix. Note=Associated with the nuclear matrix. SIMILARITY: Belongs to the herpesviridae EBNA2 family.


FUNCTION: ATP-dependent 5'-3' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to TFIIK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The ATP-dependent helicase activity of XPD/rad15 is required for DNA opening. In transcription, TFIIH has an essential role in transcription initiation. When the pre- initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module TFIIK controls the initiation of transcription. XPD/rad15 acts by forming a bridge between TFIIK and the core-TFIIH complex. Involved in the maintenance of the fidelity of DNA replication. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the helicase family. RAD3/XPD subfamily.


FUNCTION: Isoform 1, but not isoform 2 or isoform 3, may induce G2 arrest and apoptosis. May also increase cell sensitivity to apoptotic stimuli. FUNCTION: May induce G2 arrest and apoptosis. May also increase cell sensitivity to apoptotic stimuli. SUBCELLULAR LOCATION: Nucleus. SUBCELLULAR LOCATION: [Isoform 1]: Nucleus. SUBCELLULAR LOCATION: [Isoform 2]: Nucleus. SIMILARITY: Belongs to the FAM32 family.


FUNCTION: Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane resulting in collapse of the phospholipid asymmetry which leads to phosphatidylserine externalization on the cell surface (PubMed:9218461, PubMed:8663431, PubMed:10770950, PubMed:9572851, PubMed:9485382, PubMed:18629440, PubMed:23590222, PubMed:24648509, PubMed:24343571, PubMed:32110987, PubMed:23659204, PubMed:29748552). Mediates calcium- dependent phosphatidylserine externalization and apoptosis in neurons via its association with TRPC5 (By similarity). Also exhibits magnesium-dependent nuclease activity against double-stranded DNA and RNA but not single-stranded DNA and can enhance DNA decatenation mediated by TOP2A (PubMed:27206388, PubMed:17567603). Negatively regulates FcR-mediated phagocytosis in differentiated macrophages (PubMed:26745724). May contribute to cytokine-regulated cell proliferation and differentiation (By similarity). May play a role in the antiviral response of interferon (IFN) by amplifying and enhancing the IFN response through increased expression of select subset of potent antiviral genes (PubMed:15308695). Acts as an attachment receptor for HCV (PubMed:21806988). SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein Cell membrane; Lipid-anchor; Cytoplasmic side. Nucleus Cytoplasm Cytoplasm, perinuclear region Note=Localizes to the perinuclear region in the presence of RELT (PubMed:22052202). Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus (PubMed:12564925). SIMILARITY: Belongs to the phospholipid scramblase family.


FUNCTION: Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA- (5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). SIMILARITY: Belongs to the type IA topoisomerase family.


FUNCTION: Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the neutral ceramidase family.


FUNCTION: Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. SUBCELLULAR LOCATION: Apical cell membrane; Multi-pass membrane protein Basolateral cell membrane; Multi-pass membrane protein Cell membrane; Multi-pass membrane protein Cytoplasmic vesicle membrane; Multi-pass membrane protein Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane protein Note=Shuttles from vesicles to the apical membrane. Vasopressin-regulated phosphorylation is required for translocation to the apical cell membrane. PLEKHA8/FAPP2 is required to transport AQP2 from the TGN to sites where AQP2 is phosphorylated. SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.


FUNCTION: Lipid transporter that specifically mediates export of sphingosine-1-phosphate in red blood cells and platelets. Sphingosine- 1-phosphate is a signaling sphingolipid and its export from red blood cells into in the plasma is required for red blood cell morphology. Sphingosine-1-phosphate export from platelets is required for platelet aggregation and thrombus formation. In addition to export, also able to mediate S1P import. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Note=Localizes to the cell membrane and intracellular membranes. SIMILARITY: Belongs to the major facilitator superfamily.


FUNCTION: Catalyzes the reversible reduction of methenyl-H(4)MPT(+) to methylene-H(4)MPT. SIMILARITY: Belongs to the MTD family.


FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Preferentially eliminates organic peroxides rather than hydrogen peroxide (PubMed:10391912, PubMed:9988687, PubMed:10681558). Relays alkyl hydroperoxides as a signal to the transcription factor CAD1/YAP2 by inducing the formation of intramolecular disulfide bonds in CAD1, which causes its nuclear accumulation and activation (PubMed:20145245). Involved in cellular Mn(2+) homeostasis (PubMed:10635552). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the peroxiredoxin family. Prx5 subfamily.


FUNCTION: Calcium-dependent NADPH oxidase that generates superoxide. Involved in the massive phase II oxidative burst induced by pathogen infection. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the RBOH (TC 5.B.1.3) family.


FUNCTION: Plays a role in migration and segregation of pigment cells (melanophores and xanthophores). Contributes to pigment stripe patterning in the epidermis. SUBCELLULAR LOCATION: Golgi apparatus membrane; Multi-pass membrane protein Endoplasmic reticulum membrane; Multi-pass membrane protein Note=Mainly found in the Golgi apparatus. SIMILARITY: Belongs to the tetraspanin (TM4SF) family.


FUNCTION: APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles. Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells. A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes. APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues. By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis. APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis. First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes. APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting. SUBCELLULAR LOCATION: Secreted Secreted, extracellular space Secreted, extracellular space, extracellular matrix Extracellular vesicle Endosome, multivesicular body Note=In the plasma, APOE is associated with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL lipoproteins. Lipid poor oligomeric APOE is associated with the extracellular matrix in a calcium- and heparan-sulfate proteoglycans- dependent manner. Lipidation induces the release from the extracellular matrix. Colocalizes with CD63 and PMEL at exosomes and in intraluminal vesicles within multivesicular endosomes. SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.


FUNCTION: Involved in lysis inhibition. Interacts with and inhibits the holin thereby delaying the host cell lysis timing. SUBCELLULAR LOCATION: Host cell inner membrane; Multi- pass membrane protein.


FUNCTION: Plays a role in spermiogenesis and fertilization. SUBCELLULAR LOCATION: Nucleus membrane Note=Located throughout the subacrosomal area.


FUNCTION: Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis. FUNCTION: Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export. SUBCELLULAR LOCATION: Cytoplasm Nucleus.


FUNCTION: Evades nuclear antiviral defenses triggered by dsDNA viruses. Acts during the initial stages of lytic infection and the reactivation of latent viral genome. Prevents the antiviral effect of nuclear bodies by degrading host PML and SP100. Prevents antiviral response to viral DNA induced by IFI16 by degrading it. Additionally, inhibits host IRF3 nuclear signaling to prevent interferon production by the infected cells.


FUNCTION: Transcription factor that may function in dorsoventral specification of the forebrain. Required for axon guidance and major tract formation in the developing forebrain. May contribute to the differentiation of the neuroretina, pigmented epithelium and optic stalk (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the EMX homeobox family.


FUNCTION: GTPase tethering membranes through formation of trans- homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis (PubMed:27619977). May also regulate Golgi biogenesis. May regulate axonal development. FUNCTION: GTPase tethering membranes through formation of trans- homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis. May also regulate Golgi biogenesis. May regulate axonal development. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein Golgi apparatus membrane; Multi-pass membrane protein Cell projection, axon Note=Localizes to endoplasmic reticulum tubular network. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein Golgi apparatus membrane; Multi-pass membrane protein Cell projection, axon Note=Localizes to endoplasmic reticulum tubular network (PubMed:27619977). SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.


FUNCTION: Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Cpsf4 binds RNA polymers with a preference for poly(U) (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the CPSF4/YTH1 family.


FUNCTION: Oxidoreductase; part of the gene cluster that mediates the biosynthesis of the bianthraquinone cladofulvin, a conidial pigment not required for virulence but that plays a role in fitness and resistance to environmental stresses including UV light and low-temperature stress (PubMed:24465762, PubMed:27274078). The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase (PKS) claG. The atrochrysone carboxyl ACP thioesterase claF then breaks the thioester bond and releases the atrochrysone carboxylic acid from claG (PubMed:27274078). This compound is decarboxylated by claH to yield emodin, which is further converted to chrysophanol hydroquinone by the reductase claC and the dehydratase claB (PubMed:27274078). The cytochrome P450 monooxygenase claM then catalyzes the dimerization of nataloe-emodin to cladofulvin (PubMed:27274078). SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) family.


FUNCTION: Ligand for the T-cell-specific cell surface receptor ICOS. Acts as a costimulatory signal for T-cell proliferation and cytokine secretion; induces also B-cell proliferation and differentiation into plasma cells. Could play an important role in mediating local tissue responses to inflammatory conditions, as well as in modulating the secondary immune response by co-stimulating memory T-cell function (By similarity). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. SIMILARITY: Belongs to the immunoglobulin superfamily. BTN/MOG family.


FUNCTION: Involved in endocytosis. SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle membrane Cell membrane Note=Colocalizes with AP-2 at the plasma membrane. SIMILARITY: Belongs to the NECAP family.


FUNCTION: Siderophore transporter; part of the gene cluster that mediates the biosynthesis of siderophore ferrichrome A which is contributing to organismal virulence (PubMed:17138696, Ref.4). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily.


FUNCTION: Catalyzes the coenzyme A-dependent oxidative decarboxylation of different 2-oxoacids such as 2-oxoglutarate, pyruvate and 2- oxobutyrate to form their CoA derivatives.


FUNCTION: Probable 3-methyl-2-oxobutanoate hydroxymethyltransferase required for pantothenic acid biosynthesis (PubMed:11154694). Acts downstream in the pantothenic acid pathway (PubMed:11154694). SIMILARITY: Belongs to the PanB family.


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. Has a highest activity toward Muc7, EA2 and Muc2, with a lowest activity than GALNT2. Glycosylates 'Thr-57' of SELPLG. SUBCELLULAR LOCATION: Golgi apparatus membrane; Single-pass type II membrane protein. SIMILARITY: Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.


FUNCTION: Probable transcription factor which exert its primary action widely during early neural development and in a very limited set of neurons in the mature brain. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the POU transcription factor family. Class-3 subfamily.


SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. FTS subfamily.


FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of radicicol, a resorcylic acid lactone (RAL) that irreversibly inhibits the HSP90 molecular chaperone, an important target for cancer chemotherapy (PubMed:19101477). The cluster encodes only two apparent post-PKS enzymes, a cytochrome P450 monooxygenase (radP) and a non-heme halogenase (radH) that introduce the epoxide and the chlorine, respectively (PubMed:19101477). If this cluster includes all the genes required for radicicol biosynthesis, the remaining structural features of radicicol are presumably generated by the PKSs rads1 and rads2 (PubMed:19101477). The C-2' ketone could arise if the R-PKS rads1 and NR-PKS rads2 each carry out four iterations, in contrast to the five iteration-three iteration split for the hypothemycin PKSs (PubMed:19101477). The origin of the cis 5',6' double bond is not known (By similarity). The radicicol R-PKS rads1 ER domain may catalyze either double bond isomerization or reduction in the third iteration (By similarity). SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the cytochrome P450 family.


FUNCTION: Regulator of short-term neuronal synaptic plasticity in the dentate gyrus. Associates with AMPA receptors (ionotropic glutamate receptors) in synaptic spines and promotes AMPA receptor desensitization at excitatory synapses (By similarity). SUBCELLULAR LOCATION: Cell projection, dendritic spine membrane; Single-pass type I membrane protein Synapse. SIMILARITY: Belongs to the shisa family. SHISA9 subfamily.


FUNCTION: Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Required for the cotranscriptional processing of 3'- ends of polyadenylated and histone pre-mRNA. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the metallo-beta-lactamase superfamily. RNA- metabolizing metallo-beta-lactamase-like family. CPSF2/YSH1 subfamily.


FUNCTION: The SPT4-SPT5 complex mediates both activation and inhibition of transcription elongation, and plays a role in pre-mRNA processing. This complex seems to be important for the stability of the RNA polymerase II elongation machinery on the chromatin template but not for the inherent ability of this machinery to translocate down the gene (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the SPT5 family.


FUNCTION: Required for plastid separation and partitioning during cell division (PubMed:22025705). Not involved in plastid constriction or in the organization of cytoplasmic actin cables (PubMed:22025705). Contributes to polar growth of root hairs (PubMed:28096376). SUBCELLULAR LOCATION: Cytoplasm Note=Localized to distinct foci in the cytoplasm, which frequently colocalize with the cell periphery and with chloroplasts.


FUNCTION: Antibacterial peptide (PubMed:30974767). Inhibits biofilm formation of A.baumannii and Staphylococcus spp. bacteria (PubMed:30974767). Also shows potent mast cell degranulation activity and potent hemolytic activity of rat erythrocytes (PubMed:15052574, PubMed:15225564). Does not show chemotaxis for polymorphonucleated leukocytes (PMNL) (PubMed:15052574, PubMed:15225564). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the MCD family. Mastoparan subfamily.


FUNCTION: HAD-like hydrolase that has a thiamine monophosphate phosphatase activity in a heterologous system (PubMed:26537753). Does not contribute to thiamine monophosphate phosphatase activity in planta (PubMed:27677881). SIMILARITY: Belongs to the HAD-like hydrolase superfamily.


FUNCTION: May be a heme chaperone, appears to bind heme. Homologous bacterial proteins do not have oxygen-independent coproporphyrinogen- III oxidase activity (By similarity). Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl- L-methionine (By similarity). SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the anaerobic coproporphyrinogen-III oxidase family. HemW subfamily.


FUNCTION: Plays a critical role in eye formation by regulating the initial specification of retinal cells and/or their subsequent proliferation. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.


FUNCTION: Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for S-phase checkpoint activation upon UV-induced damage. SUBCELLULAR LOCATION: Nucleus Chromosome Note=Associated with chromatin before the formation of nuclei and detaches from it as DNA replication progresses. SIMILARITY: Belongs to the MCM family.


SIMILARITY: Belongs to the TAF11 family.


FUNCTION: Catalyzes the adenylation of p-hydroxybenzoic acid (pHBA) to form p-hydroxybenzoic acid-AMP (pHBA-AMP), which is converted directly to p-hydroxybenzoyl-S-FadD22 (pHBA-S-FAdD22) thioester intermediate in a CoA-independent manner by attack of the phosphopantetheine thiol of FadD22. This intermediate primes the biosynthesis of the phenolphthiocerol (PPOL) by presenting the pHBA starter unit for elongation by Pks15/1. PPOL is an important intermediate in the biosynthesis of phenolic glycolipid (mycosid B). SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Involved in the high-affinity D-xylose membrane transport system. Binds with high affinity to xylose (By similarity). SUBCELLULAR LOCATION: Periplasm. SIMILARITY: Belongs to the bacterial solute-binding protein 2 family.


FUNCTION: Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. May play a role in insulin- stimulated glucose uptake (By similarity). SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase C2 family.


FUNCTION: Required to resist Gram-negative bacterial infections, regulated by Dredd. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the attacin/sarcotoxin-2 family.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the FAM24 family.


SIMILARITY: Belongs to the glyoxalase I family.


SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family.


FUNCTION: May be involved in microtubule polymerization, and spindle function by stabilizing microtubules and anchoring them at centrosomes. May play a role in cell migration (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton Note=Associated with the microtubule network. Accumulates at the plus end of microtubules. SIMILARITY: Belongs to the MAPRE family.


FUNCTION: ATPase component of the type III secretion system (T3SS), also called injectisome, which is used to inject bacterial effector proteins into eukaryotic host cells (PubMed:26947936, PubMed:27770024, PubMed:29595954). Acts as a molecular motor to provide the energy that is required for the export of proteins (Probable). Required for type III secretion apparatus (T3SA) formation, proper protein secretion, host cell invasion and virulence (PubMed:26947936, PubMed:27770024, PubMed:31162724). May play a critical role in T3SS substrate recognition, disassembly of the effector/chaperone complex and unfolding of the effector in an ATP-dependent manner prior to secretion (By similarity). FUNCTION: ATPase component of the type III secretion system (T3SS), also called injectisome, which is used to inject bacterial effector proteins into eukaryotic host cells (By similarity). Acts as a molecular motor to provide the energy that is required for the export of proteins (By similarity). Required for type III secretion apparatus (T3SA) formation, proper protein secretion, host cell invasion and virulence (By similarity). May play a critical role in T3SS substrate recognition, disassembly of the effector/chaperone complex and unfolding of the effector in an ATP-dependent manner prior to secretion (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the ATPase alpha/beta chains family. T3SS ATPase subfamily.


SUBCELLULAR LOCATION: Fimbrium.


SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the glycosyltransferase 58 family.


FUNCTION: Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase S1 family.


FUNCTION: Growth factor for endothelial cells. VEGF-B167 binds heparin and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is regulated by proteolysis (By similarity). SUBCELLULAR LOCATION: Secreted Note=Secreted but remains associated to cells or to the extracellular matrix unless released by heparin. SIMILARITY: Belongs to the PDGF/VEGF growth factor family.


FUNCTION: Catalyzes the hydrolysis of the internal glycosidic bonds in heteroxylans, releasing mainly xylobiose and xylotriose. Most active on oat-spelt xylan. SUBCELLULAR LOCATION: Secreted, extracellular space. SIMILARITY: Belongs to the glycosyl hydrolase 10 (cellulase F) family.


FUNCTION: Probable RNA-binding protein. Involved in the regular timing (plastochron) of lateral organs formation. May regulate the rate of leaf initiation and the duration of vegetative phase. Seems to be redundant to the function of PLASTOCHRON1, but to act in an independent pathway.


FUNCTION: Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched- chain amino acid-dehydrogenase complex) (PubMed:15888450). The 2- oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (By similarity). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (By similarity). In monomeric form may have additional moonlighting function as serine protease (By similarity). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (PubMed:14645106, PubMed:15888450). SUBCELLULAR LOCATION: Mitochondrion matrix Nucleus Cell projection, cilium, flagellum Cytoplasmic vesicle, secretory vesicle, acrosome Note=Mainly localizes in the mitochondrion. A small fraction localizes to the nucleus, where the 2- oxoglutarate dehydrogenase complex is required for histone succinylation. SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.


FUNCTION: Participates in transcription elongation, termination and antitermination. SIMILARITY: Belongs to the NusG family.


SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the terpene synthase family. Tpsb subfamily.


FUNCTION: Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190, PubMed:31586034, PubMed:35114100). In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190, PubMed:31586034, PubMed:35114100). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190, PubMed:35114100). This stress- inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via TORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the sestrin family.


FUNCTION: Integral membrane subunit of the KtrAB potassium uptake transporter. The 2 major potassium transporter complexes KtrAB and KtrCD confer resistance to both suddenly imposed and prolonged osmotic stress. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TrkH potassium transport family. Ktr (TC 2.A.38.4) subfamily.


FUNCTION: Catalyzes an oxidative deamination of predominantly hydrophobic and aromatic L-amino acids, thus producing hydrogen peroxide that may contribute to the diverse toxic effects of this enzyme. Exhibits diverse biological activities, such as hemorrhage, hemolysis, edema, apoptosis of vascular endothelial cells or tumor cell lines, antibacterial and antiparasitic activities, as well as regulation of platelet aggregation. Effects of snake L-amino oxidases on platelets are controversial, since they either induce aggregation or inhibit agonist-induced aggregation. These different effects are probably due to different experimental conditions. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the flavin monoamine oxidase family. FIG1 subfamily.


FUNCTION: More likely to influence phosphoinositide metabolism than actin assembly. SIMILARITY: Belongs to the profilin family.


FUNCTION: Part of the twin-arginine translocation (Tat) system that transports large folded proteins containing a characteristic twin- arginine motif in their signal peptide across the thylakoid membrane. Involved in delta pH-dependent protein transport required for chloroplast development, especially thylakoid membrane formation. TATC and TATB mediate precursor recognition, whereas TATA facilitates translocation (By similarity). SUBCELLULAR LOCATION: Plastid, chloroplast thylakoid membrane; Single-pass membrane protein Note=The C- terminus is located in the stroma. SIMILARITY: Belongs to the TatB family.


FUNCTION: Component of the elongator complex, a multiprotein complex which is required for multiple tRNA modifications, including mcm5U (5- methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2- thiouridine), and ncm5U (5-carbamoylmethyl uridine) (PubMed:15769872, PubMed:18755837). The elongator complex catalyzes formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:29332244). It functions as a gamma-toxin target (TOT); disruption of the complex confers resistance to Kluyveromyces lactis toxin zymocin (pGKL1 killer toxin) (PubMed:11296232). May also be involved in sensitivity to Pichia inositovora toxin (PubMed:13680368). SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the ELP4 family.


FUNCTION: This protein is one of the two subunits of integration host factor, a specific DNA-binding protein that functions in genetic recombination as well as in transcriptional and translational control. FUNCTION: This protein is one of the two subunits of integration host factor, a specific DNA-binding protein that functions in genetic recombination as well as in transcriptional and translational control. SIMILARITY: Belongs to the bacterial histone-like protein family. SIMILARITY: Belongs to the bacterial histone-like protein family.


FUNCTION: Involved in the biosynthesis of 2-methyl-3-n-amyl-pyrrole (MAP), one of the terminal products involved in the biosynthesis of the red antibiotic prodigiosin (Pig). Catalyzes the transfer of 2-methyl-3- n-amyl-pyrrole (MAP) to 4-methoxy-2,2'-bipyrrole-5-carbaldehyde (MBC) to yield prodigiosin. It is able to use substrates with a variety of monocyclic rings in place of the pyrrolic ring A of its natural substrate. SIMILARITY: Belongs to the PigC family.


FUNCTION: Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor Golgi apparatus, trans-Golgi network Endosome Endosome, multivesicular body Note=Localizes mainly to the plasma membrane. In the presence of SORL1, shifts to vesicular structures, including trans-Golgi network, endosomes and multivesicular bodies. SIMILARITY: Belongs to the GDNFR family.


FUNCTION: Plays a role as pro-apoptotic protein that induces caspase- dependent apoptosis. FUNCTION: Mitochondrial glycine transporter that imports glycine into the mitochondrial matrix. Plays an important role in providing glycine for the first enzymatic step in heme biosynthesis, the condensation of glycine with succinyl-CoA to produce 5-aminolevulinate (ALA) in the mitochondrial matrix. Required during erythropoiesis. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family. SLC25A38 subfamily.


FUNCTION: Catalyzes the formation of phosphoribosylamine from phosphoribosylpyrophosphate (PRPP) and glutamine. SIMILARITY: In the C-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family.


SUBCELLULAR LOCATION: Membrane; Single- pass type I membrane protein Note=Localizes in the intracellular space in testicular germ cells and sperm. Detected also on the cell surface in post-meiotic round spermatids. In cauda epididymal sperm relocates during the acrosome reaction from the inner-acrosomal membrane onto the equatorial segment surface, on which sperm-oocyte fusion occurs. Colocalizes with IZUMO1 at the inner-acrosomal membrane.


FUNCTION: Protein associated with the U5 snRNP, during its maturation and its post-splicing recycling and which is required for spliceosomal tri-snRNP complex assembly in the nucleus (PubMed:34131137, PubMed:35188580). Has a molecular sequestering activity and transiently hinders SNRNP200 binding sites for constitutive splicing factors that intervene later during the assembly of the spliceosome and splicing (PubMed:35188580). Together with its molecular sequestering activity, may also function as a molecular adapter and placeholder, coordinating the assembly of the U5 snRNP and its association with the U4/U6 di- snRNP (PubMed:34131137). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Shuttles between the cytoplasm and the nucleus, associated with the U5 snRNP. SIMILARITY: Belongs to the TSSC4 family.


FUNCTION: Catalyzes the conversion of 2-amino-2-deoxy-D-gluconate (GlcNA) to 2-keto-3-deoxy-D-gluconic acid (KDGA) and ammonia. SIMILARITY: Belongs to the class-II pyridine nucleotide-disulfide oxidoreductase family.


FUNCTION: Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation (PubMed:20667974). Involved in a variety of CNS functions, such as sedation, NREM sleep and PGE2-induced allodynia, and may have an anti-apoptotic role in oligodendrocytes. Binds small non- substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid and thyroid hormone, and may act as a scavenger for harmful hydrophobic molecules and as a secretory retinoid and thyroid hormone transporter. Possibly involved in development and maintenance of the blood-brain, blood-retina, blood-aqueous humor and blood-testis barrier. It is likely to play important roles in both maturation and maintenance of the central nervous system and male reproductive system (PubMed:20667974, PubMed:9475419). Involved in PLA2G3-dependent maturation of mast cells. PLA2G3 is secreted by immature mast cells and acts on nearby fibroblasts upstream to PTDGS to synthesize PGD2, which in turn promotes mast cell maturation and degranulation via PTGDR (By similarity). SUBCELLULAR LOCATION: Rough endoplasmic reticulum Nucleus membrane Golgi apparatus Cytoplasm, perinuclear region Secreted Note=Detected on rough endoplasmic reticulum of arachnoid and menigioma cells. Localized to the nuclear envelope, Golgi apparatus, secretory vesicles and spherical cytoplasmic structures in arachnoid trabecular cells, and to circular cytoplasmic structures in meningeal macrophages and perivascular microglial cells. In oligodendrocytes, localized to the rough endoplasmic reticulum and nuclear envelope. In retinal pigment epithelial cells, localized to distinct cytoplasmic domains including the perinuclear region. Also secreted. SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.


FUNCTION: Non-catalytic component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins and histones (By similarity). This modification targets Sm proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein core particles (By similarity). Might play a role in transcription regulation (By similarity). The methylosome complex also methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain- containing proteins and subsequent localization to the meiotic nuage (PubMed:19584108). FUNCTION: Substrate-recognition component of the DCX(WDR77) complex, which mediates ubiquitination and degradation of Irgm1 in intestinal cells. SUBCELLULAR LOCATION: Nucleus Cytoplasm.


FUNCTION: Hydrolyzes cytokinin glucosides thus liberating free cytokinins.


FUNCTION: High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:28083649, PubMed:22647630, PubMed:18701466). May have a residual high-affinity, low-capacity glucose and fructose transporter activity (PubMed:18842065, PubMed:18327257, PubMed:18701466). Transports urate at rates 45- to 60-fold faster than glucose (PubMed:18842065). Does not transport galactose (PubMed:28083649). May mediate small uptake of adenine but not of other nucleobases (PubMed:22647630). SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Multi-pass membrane protein. Basolateral cell membrane; Multi-pass membrane protein. SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane Apical cell membrane; Multi-pass membrane protein. Basolateral cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.


FUNCTION: Degrades abnormal exported proteins and responsible for the propeptide processing of a natural pro-protein and for the maturation of a native protein. It also plays a prominent role in stress (heat shock, ethanol, puromycin and NaCl) resistance during active exponential growth (Probable). SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein. SIMILARITY: Belongs to the peptidase S1C family.


FUNCTION: Catalyzes the conversion of acetate into acetyl-CoA (AcCoA), an essential intermediate at the junction of anabolic and catabolic pathways. Acs undergoes a two-step reaction. In the first half reaction, Acs combines acetate with ATP to form acetyl-adenylate (AcAMP) intermediate. In the second half reaction, it can then transfer the acetyl group from AcAMP to the sulfhydryl group of CoA, forming the product AcCoA. FUNCTION: Enables the cell to use acetate during aerobic growth to generate energy via the TCA cycle, and biosynthetic compounds via the glyoxylate shunt. Acetylates CheY, the response regulator involved in flagellar movement and chemotaxis. SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Beta-glucosidase highly specific for the cleavage of C-26- bound glucose moiety of furostanol glycosides torvosides A and H. Hydrolyzes only p-nitrophenyl-beta-glucoside, but not p-nitrophenyl- beta-D-fucoside, p-nitrophenyl-beta-L-fucoside, p-nitrophenyl-beta-D- xyloside, p-nitrophenyl-beta-D-galactoside, p-nitrophenyl-beta-D-NAc- glucosamine, p-nitrophenyl-beta-D-mannoside or any of the p- nitrophenyl-alpha-glycosides tested. SIMILARITY: Belongs to the glycosyl hydrolase 3 family.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the neurotoxin 20 family.


FUNCTION: Negative regulator of FtsZ ring formation; modulates the frequency and position of FtsZ ring formation. Inhibits FtsZ ring formation at polar sites. Interacts either with FtsZ or with one of its binding partners to promote depolymerization. SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein. Note=Colocalized with FtsZ to the nascent septal site. SIMILARITY: Belongs to the EzrA family.


FUNCTION: Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of target proteins (By similarity).


FUNCTION: Probable neurotoxin. SUBCELLULAR LOCATION: Secreted. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the conotoxin D superfamily.


FUNCTION: Cytoplasmic polyadenylation element binding protein that binds to and regulates the translation of specific mRNAs.


FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals (PubMed:15661642). RAs exist as at least four different isomers: all-trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (By similarity). Catalyzes the hydroxylation of atRA primarily at C-4 and C-18, thereby contributing to the regulation of atRA homeostasis and signaling (By similarity). Hydroxylation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination (By similarity). Involved in the convertion of atRA to all- trans-4-oxo-RA. Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4- hydroxy-DRA, all-trans-5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA (By similarity). Plays a role in skeletal development, both at the level of patterning and in the ossification of bone and the establishment of some synovial joints (PubMed:22019272). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein Microsome membrane; Peripheral membrane protein. SIMILARITY: Belongs to the cytochrome P450 family.


FUNCTION: Component of the peroxisomal and mitochondrial division machineries. Plays a role in promoting the fission of mitochondria and peroxisomes. SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass membrane protein. Peroxisome membrane; Single-pass membrane protein. SIMILARITY: Belongs to the FIS1 family.


SUBCELLULAR LOCATION: Nucleus, nucleolus. SIMILARITY: Belongs to the CBF/MAK21 family.


FUNCTION: Neutrophil and pancreatic elastase-specific inhibitor of skin. It may prevent elastase-mediated tissue proteolysis (By similarity).


SIMILARITY: Belongs to the PRORSD1 family.


FUNCTION: Acts as the sensor component of the NLRP6 inflammasome, which mediates inflammasome activation in response to various pathogen- associated signals, leading to maturation and secretion of IL1B and IL18 (PubMed:30392956, PubMed:34678144). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:30674671). Acts as a recognition receptor (PRR): recognizes and binds specific pathogens and other damage-associated signals, such as lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, or double stranded RNA (dsRNA) (PubMed:30392956, PubMed:34678144, PubMed:33377178). May also recognize and bind lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria; however, LPS is probably not a major activator of the NLRP6 inflammasome (PubMed:31932628, PubMed:34678144). Following LTA- or dsRNA-binding, NLRP6 undergoes liquid-liquid phase separation (LLPS), enhancing multivalent interactions, an essential step for the formation of the NLRP6 inflammasome polymeric complex (PubMed:34678144). The NLRP6 inflammasome acts by promoting recruitment of effector pro-inflammatory caspases (CASP1 and/or CASP4) that catalyze maturation and secretion of IL1B and IL18 in the extracellular milieu (PubMed:30674671, PubMed:12387869, PubMed:30392956, PubMed:34678144). The NLRP6 inflammasome plays a central role in the maintenance of epithelial integrity and host defense against microbial infections in the intestine (PubMed:30392956). Required to restrict infection against Gram-positive bacteria by recognizing lipoteichoic acid (LTA), leading to recruitment of CASP4 and CASP1, and subsequent maturation and secretion of IL1B and IL18 (PubMed:30392956, PubMed:33377178). Involved in intestinal antiviral innate immunity together with DHX15: recognizes and binds viral dsRNA to restrict infection by enteric viruses through the interferon pathway and GSDMD-dependent release of IL18 (PubMed:34678144, PubMed:34161762). Required to prevent infection by the apicomplexan parasite Cryptosporidium in enterocytes by promoting GSDMD-dependent release of IL18 (By similarity). The NLRP6 inflammasome may also regulate the gut microbiota composition by acting as a sensor of microbiota-associated metabolites to form a PYCARD/ASC-dependent inflammasome for downstream IL18 release and secretion of antimicrobial peptides (By similarity). Essential for gut mucosal self-renewal and proliferation (By similarity). Regulate mucus secretion in an inflammasome- and autophagy-dependent manner to prevent invasion by enteric bacteria, (By similarity). During systemic bacterial infections, the NLRP6 inflammasome negatively regulates neutrophil recruitment and neutrophil extracellular traps (NETs) formation (By similarity). May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytosol Inflammasome Cell membrane Nucleus membrane. SIMILARITY: Belongs to the NLRP family.


FUNCTION: May be involved in response to X-ray. Regulates p21 protein stability by binding to Hsp90 and p21.


FUNCTION: E3 ubiquitin-protein ligase that cooperates with the microRNAs (miRNAs) machinery and promotes embryonic stem cells proliferation and maintenance. Binds to miRNAs and participates in post-transcriptional repression of transcripts. Required to maintain proliferation and prevent premature differentiation of neural progenitor cells during early neural development. SUBCELLULAR LOCATION: Cytoplasm, P-body. SIMILARITY: Belongs to the TRIM/RBCC family.


FUNCTION: ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP- ribose and acts on different substrates, such as proteins ADP- ribosylated on serine and threonine, free poly(ADP-ribose) and O- acetyl-ADP-D-ribose. Specifically acts as a serine mono-ADP- ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds. Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (By similarity). Also hydrolyzes free poly(ADP- ribose) in mitochondria. Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins. Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl- ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers. SUBCELLULAR LOCATION: Nucleus Cytoplasm Chromosome Mitochondrion matrix Note=Recruited to DNA lesion regions following DNA damage; ADP-D-ribose-recognition is required for recruitment to DNA damage sites. SIMILARITY: Belongs to the ADP-ribosylglycohydrolase family.


FUNCTION: Microbicidal activity. Active against E.coli, Listeria monocytogenes and C.albicans, in vitro. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the cathelicidin family.


FUNCTION: Essential cell division protein that coordinates cell division and chromosome segregation. The N-terminus is involved in assembly of the cell-division machinery. The C-terminus functions as a DNA motor that moves dsDNA in an ATP-dependent manner towards the difSL recombination site, which is located within the replication terminus region. Required for activation of the XerS recombinase, allowing activation of chromosome unlinking by recombination (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Note=Located at the septum. SIMILARITY: Belongs to the FtsK/SpoIIIE/SftA family.


FUNCTION: A hormone that controls sex pheromone production in females and pheromone responsiveness in male. Also mediates visceral muscle contractile activity (myotropic activity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the pyrokinin family.


FUNCTION: Can constrain negative DNA supercoils. May be involved in maintaining the integrity of the genome at high temperature. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the 7 kDa DNA-binding/endoribonuclease P2 family.


FUNCTION: Catalyzes the reversible interconversion of fructoselysine with its C-3 epimer, psicoselysine. Allows E.coli to utilize psicoselysine for growth. Does not act on psicose or fructoselysine 6- phosphate. SIMILARITY: Belongs to the FrlC family.


FUNCTION: Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code (PubMed:16603238, PubMed:24685137). Demethylation of Lys residue generates formaldehyde and succinate. Involved in the negative regulation of lifespan in a germline-dependent fashion (PubMed:22212395). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the JHDM3 histone demethylase family.


FUNCTION: Catalyzes a cyclopropane ring-opening reaction, the irreversible conversion of 1-aminocyclopropane-1-carboxylate (ACC) to ammonia and alpha-ketobutyrate. SIMILARITY: Belongs to the ACC deaminase/D-cysteine desulfhydrase family.


FUNCTION: Short-chain dehydrogenase; part of the gene cluster that mediates the biosynthesis of virensols and trichoxide, fungal natural products that contain or are derived from a salicylaldehyde core (PubMed:31790246). The pathway begins with the synthesis of the reduced chain in virensol C by the highly reducing polyketide synthase virA via condensation of one acetate and 8 malonate units (PubMed:31790246). VirA has interesting programming rules since the first 2 ketides are fully reduced, the 3 following ketides undergo beta-dehydration, and the last 3 ketides are only reduced to beta-hydroxys to yield the trihydroxy portion (PubMed:31790246). The production of aldehyde virensol C by virA alone is surprising, since virA does not contain a reductase (R) domain that is typically associated with reductive product release in HRPKS (PubMed:31790246). The cupin-domain enzyme virC is involved in enhancing virA product turnover (PubMed:31790246). The short-chain dehydrogenase virB then oxidizes the C-7 alcohol of virensol C to a ketone, yielding virensol D (PubMed:31790246). Virensol D is further transformed to salicylaldehyde 5-deoxyaurocitrin by the short-chain dehydrogenase virD (PubMed:31790246). VirD catalyzes the dehydrogenation of C-3 to form the beta-ketone aldehyde, which is followed by the generation of the nucleophilic C-2 that is required for the intramolecular aldol condensation between C-2 and C-7, itself followed by dehydration and aromatization which leads to salicylaldehyde 5-deoxyaurocitrin (PubMed:31790246). While the dehydrogenation of virensol D is definitely catalyzed by virD, the aldol condensation and dehydration may be uncatalyzed or assisted by virD (PubMed:31790246). The short chain dehydrogenase virG then converts salicylaldehyde 5-deoxyaurocitrin into virensol B which is further hydroxylated by the cytochrome P450 monooxygenase virE to yield the hydroquinone virensol A (PubMed:31790246). VirI then may oxidize virensol A to form the quinone, while virH performs the epoxidation (PubMed:31790246). Finally, the two remaining short-chain dehydrogenases, virK and virL, are probably responsible for reducing the ketones to the corresponding alcohols to furnish the epoxycyclohexanol structure in trichoxide (PubMed:31790246). SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) family.


FUNCTION: Vasotocin is an antidiuretic hormone. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the vasopressin/oxytocin family.


SIMILARITY: Belongs to the chlamydial CPn_0658/CT_538/TC_0825 family.


FUNCTION: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ORC3 family.


FUNCTION: Class-IV neuronal intermediate filament that is able to self- assemble. It is involved in the morphogenesis of neurons. It may form an independent structural network without the involvement of other neurofilaments or it may cooperate with NEFL to form the filamentous backbone to which NEFM and NEFH attach to form the cross-bridges (By similarity). May also cooperate with the neuronal intermediate filament protein PRPH to form filamentous networks (By similarity). SIMILARITY: Belongs to the intermediate filament 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 (PubMed:3129430, PubMed:17158705). The enzyme II complex composed of PtsG and Crr is involved in glucose transport (PubMed:2657735). The non-phosphorylated EIII-Glc is an inhibitor for uptake of certain sugars such as maltose, melibiose, lactose, and glycerol. Phosphorylated EIII-Glc, however, may be an activator for adenylate cyclase. It is an important regulatory protein for cell metabolism (PubMed:789369). 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. SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Part of the ABC transporter complex LsrABCD involved in autoinducer 2 (AI-2) import. Responsible for energy coupling to the transport system. SUBCELLULAR LOCATION: Cell inner membrane; Peripheral membrane protein. SIMILARITY: Belongs to the ABC transporter superfamily. AI-2 autoinducer porter (TC 3.A.1.2.8) family.


FUNCTION: Protein phosphatase which positively regulates biosynthesis of the ubiquinone, coenzyme Q (By similarity). Dephosphorylates the ubiquinone biosynthesis protein coq7 which is likely to lead to its activation (By similarity). SUBCELLULAR LOCATION: Mitochondrion matrix. SIMILARITY: Belongs to the PP2C family.


FUNCTION: Mediates an active uptake of hexoses, probably by sugar/hydrogen symport. Can transport glucose, galactose, mannose, xylose and 3-O-methylglucose, but not fructose and ribose. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.


SIMILARITY: Belongs to the TabA/YiaL family.


FUNCTION: Cysteine protease that plays an important role in the inhibition of host innate immune response. Degrades host elastin, fibrogen, fibronectin and kininogen. Blocks phagocytosis of opsonised S.aureus by neutrophils and monocytes by inducing their death in a proteolytic activity-dependent manner. Decreases surface expression of the 'don't eat me' signal CD31 on neutrophils. Cleaves host galectin- 3/LGALS3, thereby inhibiting the neutrophil-activating ability of the lectin. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase C47 family.


FUNCTION: ABC-type transporter; part of the cla gene cluster that produces clavatol and ortho-quinone methide (PubMed:30811183). The clavatol biosynthesis cluster cla and the terrestric acid cluster tra are both involved in the production of peniphenones and penilactones (PubMed:30811183). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family.


FUNCTION: Regulatory subunit of the error prone DNA polymerase zeta. Involved in damage-tolerance mechanisms through translesion DNA synthesis (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the MAD2 family.


FUNCTION: Repressor of photomorphogenesis in the light. Probably part of the COP1/SPA E3 ubiquitin-protein ligase complex. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Catalytic subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis (PubMed:6773966, PubMed:6806812, PubMed:6812052, PubMed:6403945, PubMed:6409898). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit PolA1, an accessory subunit PolA2 and two primase subunits, the catalytic subunit Prim1 and the regulatory subunit Prim2) is recruited to DNA at the replicative forks (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (By similarity). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit (By similarity). Can add both ribo- and deoxynucleotides during elongation of the primers (PubMed:6812052). Binds single stranded DNA (By similarity). SIMILARITY: Belongs to the eukaryotic-type primase small subunit family.


FUNCTION: Plays a critical role in cardiac development (PubMed:30110327). Acts as a key epigenetic regulator of gene expression during cardiac development via its dual activities as a methyltransferase and negative regulator of HDAC1 (PubMed:30110327). SUBCELLULAR LOCATION: Nucleus Cytoplasm. SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase superfamily.


SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the SVP26 family.


FUNCTION: Catalyzes the conversion of 2-hydroxypentadienoic acid (enolic form of 2-oxopent-4-enoate) to 4-hydroxy-2-ketopentanoic acid. SIMILARITY: Belongs to the hydratase/decarboxylase family. MhpD subfamily.


FUNCTION: NDH-1 shuttles electrons from an unknown electron donor, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory and/or the photosynthetic chain. The immediate electron acceptor for the enzyme in this species is believed to be plastoquinone. Couples the redox reaction to proton translocation, and thus conserves the redox energy in a proton gradient. Cyanobacterial NDH-1 also plays a role in inorganic carbon-concentration. SUBCELLULAR LOCATION: Cellular thylakoid membrane; Peripheral membrane protein; Cytoplasmic side. SIMILARITY: Belongs to the complex I 49 kDa subunit 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. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Single-pass membrane protein. SIMILARITY: Belongs to the UQCR10/QCR9 family.


FUNCTION: Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans. SUBCELLULAR LOCATION: Lysosome. SIMILARITY: Belongs to the glycosyl hydrolase 35 family.


FUNCTION: Component of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration (By similarity). SUBCELLULAR LOCATION: Cell membrane Membrane, coated pit; Peripheral membrane protein; Cytoplasmic side Note=Component of the coat surrounding the cytoplasmic face of the plasma membrane coated vesicles. SIMILARITY: Belongs to the adaptor complexes small subunit family.


FUNCTION: Snake venom zinc metalloproteinase that inhibits platelet aggregation by cleaving platelet glycoprotein Ib alpha (GP1BA) at Glu- 298/Asp-299, and abolishes binding of von Willebrand factor (VWF) to GPIBA. Cleaves P-selectin glycoprotein ligand-1 (PSGL-1/SELPLG) at Tyr- 51/Asp-52, and completely abolishes the binding of PSGL-1 to P- selectin. Anionic amino acid sequences containing sulfated tyrosines are needed for cleavages. Inhibits the thrombin-induced platelet aggregation, and the thrombin-induced release of ATP and ADP. Has lectin activity (inhibited by heparin). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III subfamily. P-IIIa sub-subfamily.


FUNCTION: Sequence-specific transcriptional activator. Recognizes the DNA sequence 5'-C[CA]GGAAGT-3'. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ETS family.


SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the peptidase M50B family.


FUNCTION: May be involved in cooperative interactions with calmodulins or calmodulin-like proteins (By similarity). Recruits calmodulin proteins to microtubules, thus being a potential scaffold in cellular signaling and trafficking (By similarity). May associate with nucleic acids and regulate gene expression at the transcriptional or post- transcriptional level (By similarity). SUBCELLULAR LOCATION: Nucleus Nucleus, nucleolus. SIMILARITY: Belongs to the IQD family.


FUNCTION: Catalyzes the conversion of methylthioalkyl glucosinolates of any chain length into methylsulfinylalkyl glucosinolates. SIMILARITY: Belongs to the FMO family.


FUNCTION: Antibacterial activity against Gram-positive bacterium S.aureus. Weak activity against Gram-negative bacterium E.coli and C.albicans. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the frog skin active peptide (FSAP) family. Temporin subfamily.


FUNCTION: The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. The TFIID complex structure can be divided into 3 modules TFIID- A, TFIID-B, and TFIID-C. TAF8 is involved in forming the TFIID-B module, together with TAF5. Mediates both basal and activator-dependent transcription. Plays a role in the differentiation of preadipocyte fibroblasts to adipocytes, however, does not seem to play a role in differentiation of myoblasts. Required for the integration of TAF10 in the TAF complex (By similarity). May be important for survival of cells of the inner cell mass which constitute the pluripotent cell population of the early embryo (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Localized in the cytoplasm and transported from the cytoplasm to the nucleus in some cells, possibly depending on the functional or developmental state of the cell. SIMILARITY: Belongs to the TAF8 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. This system is involved in D-mannitol transport (PubMed:368051, PubMed:6427236, PubMed:2123863). Also able to use D-mannonic acid (PubMed:6427236). SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein.