FUNCTION: Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein) (PubMed:10521267). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein Golgi apparatus membrane; Multi-pass membrane protein Cytoplasmic granule Cell membrane Cell projection, axon Synapse Cell projection, neuron projection. SIMILARITY: Belongs to the peptidase A22A family.


FUNCTION: May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion. In mycobacteria-infected cells, its retention on the phagosomal membrane prevents fusion between phagosomes and lysosomes. SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton Cytoplasm, cell cortex Cytoplasmic vesicle, phagosome membrane Note=In non-infected macrophages, associated with the cortical microtubule network. In mycobacteria-infected macrophages, becomes progressively relocalized and retained around the mycobacterial phagosomes. Retention on the phagosomal membrane is strictly dependent on mycobacterial viability and not due to impaired acidification (By similarity). SIMILARITY: Belongs to the WD repeat coronin family.


SUBCELLULAR LOCATION: Cytoplasm, cytosol.


FUNCTION: Forms a water-specific channel. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.


FUNCTION: May have a role in autophagy. SUBCELLULAR LOCATION: Lysosome membrane Late endosome membrane. SIMILARITY: Belongs to the RMC1 family.


FUNCTION: Plays a role in male fertility (PubMed:23553430). May have a role in sperm migration or binding to zona-intact eggs (PubMed:23553430). Involved in the activation of the proacrosin/acrosin system (By similarity). SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome Secreted. SIMILARITY: Belongs to the peptidase S1 family.


FUNCTION: Mutations in this gene were selected in directed evolution experiments for resistance to intense ionizing radiation (3000 Gy). FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single- stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with LexA causing its activation and leading to its autocatalytic cleavage. FUNCTION: Required for homologous recombination and the bypass of mutagenic DNA lesions by the SOS response. Catalyzes ATP-driven homologous pairing and strand exchange of DNA molecules necessary for DNA recombinational repair. Catalyzes the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single- stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. The SOS response controls an apoptotic-like death (ALD) induced (in the absence of the mazE-mazF toxin-antitoxin module) in response to DNA damaging agents that is mediated by RecA and LexA (PubMed:22412352). FUNCTION: Plays a role in recovery after DNA ADP-ribosylation. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the RecA family.


FUNCTION: AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. AMPK also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. The AMPK gamma3 subunit is a non-catalytic subunit with a regulatory role in muscle energy metabolism. It mediates binding to AMP, ADP and ATP, leading to AMPK activation or inhibition: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive. SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma subunit family.


FUNCTION: Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono- and polyamines, thereby producing cross-linked or aminated proteins, respectively. Involved in many biological processes, such as bone development, angiogenesis, wound healing, cellular differentiation, chromatin modification and apoptosis. Acts as a protein-glutamine gamma-glutamyltransferase by mediating the cross- linking of proteins: under physiological conditions, the protein cross- linking activity is inhibited by GTP; inhibition is relieved by Ca(2+) in response to various stresses. When secreted, catalyzes cross-linking of proteins of the extracellular matrix, resulting in the formation of scaffolds. Plays a key role during apoptosis, both by (1) promoting the cross-linking of cytoskeletal proteins resulting in condensation of the cytoplasm, and by (2) mediating cross-linking proteins of the extracellular matrix, resulting in the irreversible formation of scaffolds that stabilize the integrity of the dying cells before their clearance by phagocytosis, thereby preventing the leakage of harmful intracellular components. In addition to protein cross-linking, can use different monoamine substrates to catalyze a vast array of protein post-translational modifications: mediates aminylation of serotonin, dopamine, noradrenaline or histamine into glutamine residues of target proteins to generate protein serotonylation, dopaminylation, noradrenalinylation or histaminylation, respectively (By similarity). Mediates protein serotonylation of small GTPases during activation and aggregation of platelets, leading to constitutive activation of these GTPases (By similarity). Plays a key role in chromatin organization by mediating serotonylation and dopaminylation of histone H3. Catalyzes serotonylation of 'Gln-5' of histone H3 (H3Q5ser) during serotonergic neuron differentiation, thereby facilitating transcription. Acts as a mediator of neurotransmission-independent role of nuclear dopamine in ventral tegmental area (VTA) neurons: catalyzes dopaminylation of 'Gln- 5' of histone H3 (H3Q5dop), thereby regulating relapse-related transcriptional plasticity in the reward system (By similarity). Also acts as a protein deamidase by mediating the side chain deamidation of specific glutamine residues of proteins to glutamate. May also act as an isopeptidase cleaving the previously formed cross-links. Also able to participate in signaling pathways independently of its acyltransferase activity: acts as a signal transducer in alpha-1 adrenergic receptor-mediated stimulation of phospholipase C-delta (PLCD) activity and is required for coupling alpha-1 adrenergic agonists to the stimulation of phosphoinositide lipid metabolism (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytosol Nucleus Chromosome Secreted, extracellular space, extracellular matrix Cell membrane Mitochondrion Note=Mainly localizes to the cytosol. Present at much lower level in the nucleus and chromatin. Also secreted via a non-classical secretion pathway to the extracellular matrix. SIMILARITY: Belongs to the transglutaminase superfamily. Transglutaminase family.


FUNCTION: Probable component of the endoplasmic reticulum-associated degradation (ERAD) pathway. SIMILARITY: Belongs to the LCL2 family.


SIMILARITY: Belongs to the TlyA family.


FUNCTION: Represses mngA and mngB. Regulates its own expression.


SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the UPF0324 family.


FUNCTION: Plays a role in the formation and organization of tight junctions during the establishment of polarity in epithelial cells. SUBCELLULAR LOCATION: Cytoplasm Cell junction, adherens junction Cell membrane; Peripheral membrane protein Photoreceptor inner segment.


FUNCTION: Complement inhibitor (PubMed:27018802). Prevents complement- mediated C5 activation by binding to C5 (PubMed:27018802). Binds C5 at a different binding site than the other tick complement inbibitors OmCI and CirpT1, and the drug eculizumab (PubMed:27018802, PubMed:31871188). Inhibits complement in human and guinea pig but not in other species tested (rabbit, rat, mouse, and pig) (PubMed:27018802). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the RaCI family.


FUNCTION: Has kinase activity and phosphorylates inositol-1,3,4,5,6- pentakisphosphate (Ins(1,3,4,5,6)P5) to produce 1,2,3,4,5,6- hexakisphosphate (InsP6), also known as phytate. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the IPK1 type 1 family.


FUNCTION: As part of the NSL complex it is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. The receptor returns to the cell membrane surface and the pathogen-derived antigens are presented to resting T-cells via MHC class II proteins to initiate the adaptive immune response. Probably recognizes in a calcium- dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens (By similarity). FUNCTION: On DCs it is a high affinity receptor for ICAM2 and ICAM3 by binding to mannose-like carbohydrates. May act as a DC rolling receptor that mediates transendothelial migration of DC presursors from blood to tissues by binding endothelial ICAM2. Seems to regulate DC-induced T- cell proliferation by binding to ICAM3 on T-cells in the immunological synapse formed between DC and T-cells (By similarity). SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein.


SIMILARITY: Belongs to the ZC2HC1 family.


FUNCTION: Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH or NADH to yield (R)-2,3-dihydroxy-isovalerate. SIMILARITY: Belongs to the ketol-acid reductoisomerase family.


FUNCTION: Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of scap and degradation of hmgcr. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs). Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with scap and retention of the SCAP-SREBP complex in the endoplasmic reticulum. In presence of oxysterol, interacts with scap, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing scap from escorting SREBPs to the Golgi. Sterol deprivation reduces oxysterol-binding, disrupting the interaction between insig1 and scap, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBPs. Also regulates cholesterol synthesis by regulating degradation of hmgcr. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the INSIG family.


SIMILARITY: Belongs to the phospholipase A2 family.


FUNCTION: Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (By similarity). Ceramides, sphingosine, and its phosphorylated form sphingosine-1- phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (By similarity). Has a higher catalytic efficiency towards C12-ceramides versus other ceramides (By similarity). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (By similarity). For the reverse synthetic reaction, the natural sphingosine D-erythro isomer is more efficiently utilized as a substrate compared to D-erythro- dihydrosphingosine and D-erythro-phytosphingosine, while the fatty acids with chain lengths of 12 or 14 carbons are the most efficiently used (By similarity). Has also an N-acylethanolamine hydrolase activity (By similarity). By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes (By similarity). Also indirectly regulates tumor necrosis factor/TNF-induced apoptosis (By similarity). By regulating the intracellular balance between ceramides and sphingosine, in adrenocortical cells, probably also acts as a regulator of steroidogenesis (By similarity). SUBCELLULAR LOCATION: Lysosome Secreted Note=Secretion is extremely low and localization to lysosomes is mannose-6-phosphate receptor-dependent. SIMILARITY: Belongs to the acid ceramidase family.


FUNCTION: Positive modulator of ATM response to DNA damage. SUBCELLULAR LOCATION: Cytoplasm Nucleus Note=Cytoplasmic under growth arrest conditions. Translocated into the nucleus when growth resumes at S phase and following DNA damage.


FUNCTION: Putative taste receptor. TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 3 family. TAS1R subfamily.


FUNCTION: Probable catalytic component of a complex displaying alpha (N-terminal) acetyltransferase activity. SIMILARITY: Belongs to the acetyltransferase family. MAK3 subfamily.


FUNCTION: Serine/threonine-protein kinase, which phosphorylates mlk-1. Involved in the stress response to heavy metals by activating the mlk- 1/mek-1/kgb-1 pathway (PubMed:20008556). In ventral cord commissural motoneurons, required for dorsal axon guidance downstream of unc- 6/netrin repulsion receptor unc-5 and probably of Rho GTPases ced-10 and mig-2. Plays a redundant role with mig-10 in orientating axonal growth of HSN neurons (PubMed:18499456). Plays a redundant role with pak-1 in P neuroblast migration and in distal tip cell (DTC)-mediated guidance of gonad elongation probably downstream of Rho GTPases (PubMed:17050621, PubMed:19023419, PubMed:23390595). In association with pak-2, plays a role in embryogenesis. In association with pak-1, may be involved in spermatogenesis (PubMed:23390595). SUBCELLULAR LOCATION: Perikaryon Cell projection, dendrite Cytoplasm. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.


FUNCTION: Regulates the processing of the mir-60 microRNA (miRNA), which in turn negatively regulates the expression of the transcription factor zip-10 (PubMed:29664006). Does not affect the splicing of zip-10 (PubMed:29664006). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ISY1 family.


FUNCTION: Potential transcription factor. May play a role in early mesoderm formation and later in lateral mesoderm differentiation and neurogenesis (By similarity). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the extracellular matrix via dystrophin glycoprotein complex. Plays an important role in synapse formation and in the organization of UTRN and acetylcholine receptors at the neuromuscular synapse. Binds to phosphatidylinositol 4,5-bisphosphate (By similarity). SUBCELLULAR LOCATION: Cell membrane, sarcolemma; Peripheral membrane protein; Cytoplasmic side Cell junction Cytoplasm, cytoskeleton Note=In skeletal muscle, it localizes at the cytoplasmic side of the sarcolemmal membrane and at neuromuscular junctions. SIMILARITY: Belongs to the syntrophin family.


SUBCELLULAR LOCATION: Cell surface Cell membrane; Lipid-anchor, GPI-anchor Note=Present on the surface of merozoite.


FUNCTION: Flavin-dependent monooxygenase; part of the gene cluster that mediates the biosynthesis of xenovulene A, an unusual meroterpenoid that has potent inhibitory effects on the human gamma-aminobutyrate A (GABAA) benzodiazepine receptor (PubMed:29773797). The first step of xenovulene A biosynthesis is the biosynthesis of 3-methylorcinaldehyde performed by the non-reducing polyketide synthase aspks1 (PubMed:17912413, PubMed:29773797, PubMed:20552126). The salicylate hydroxylase asL1 then catalyzes the oxidative dearomatization of 3- methylorcinaldehyde to yield a dearomatized hydroxycyclohexadione (PubMed:29773797). The 2-oxoglutarate-dependent dioxygenase asL3 further catalyzes the oxidative ring expansion to provide the first tropolone metabolite (PubMed:29773797). The cytochrome P450 monooxygenase asR2 allows the synthesis of tropolone hemiacetal (PubMed:29773797). In parallel, a previously unrecognised class of terpene cyclase, asR6, produces alpha-humulene from farnesylpyrophosphate (FPP) (PubMed:29773797). The putative Diels- Alderase asR5 probably catalyzes the formation of the tropolone- humulene skeleton by linking humulene and the polyketide moiety (PubMed:29773797). Oxidative-ring contractions catalyzed by asL4 and asL6 then processively remove carbon atoms from the polyketide to yield xenovulene A (PubMed:29773797). SIMILARITY: Belongs to the aromatic-ring hydroxylase family.


FUNCTION: Catalyzes the phosphorylation of 5-dehydro-2-deoxy-D- gluconate (2-deoxy-5-keto-D-gluconate or DKG) to 6-phospho-5-dehydro-2- deoxy-D-gluconate (DKGP). SIMILARITY: Belongs to the carbohydrate kinase PfkB family.


FUNCTION: Hydrolyzes galactomannan found in plant cell wall, by cleaving alpha-1,6-D-galactose side-chains from the mannan backbone. Appears to act in synergy with mannanase (ManA) to elicit hydrolysis of galactomannan. Has greater activity against galactomannans with decreased degree of polymerisation values. To a lesser extent, is also able to degrade other galactosides containing alpha-1,6-linked D- galactose, such as melibiose and stachyose. SIMILARITY: Belongs to the glycosyl hydrolase 27 family.


FUNCTION: Binds 16S rRNA, required for the assembly of 30S particles. SIMILARITY: Belongs to the universal ribosomal protein uS14 family. Zinc-binding uS14 subfamily.


FUNCTION: Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP- dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin- independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions. The interaction with EMAP2 increases the proteasome-mediated HIF-1A degradation under the hypoxic conditions. Plays a role in hepatitis C virus internal ribosome entry site-mediated translation. Mediates nuclear translocation of the androgen receptor (AR) and thereby enhances androgen-mediated transactivation. Promotes MAVS degradation and thereby negatively regulates MAVS-mediated innate immune response. SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the peptidase T1A family.


SUBCELLULAR LOCATION: Golgi apparatus, cis-Golgi network membrane; Multi-pass membrane protein Golgi apparatus, trans-Golgi network membrane Late endosome membrane Note=Mainly localizes within medial-/trans-Golgi and trans-Golgi network (TGN), while less so within cis-Golgi. SIMILARITY: Belongs to the YIP1 family.


FUNCTION: Synthesizes sorbitol-6-phosphate, a key intermediate in the synthesis of sorbitol which is a major photosynthetic product in many members of the Rosaceae family. SIMILARITY: Belongs to the aldo/keto reductase family.


FUNCTION: Receptor for cholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gastrin. It modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 1 family.


FUNCTION: Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Binds to the proximal enhancer region of NANOG (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency (By similarity). Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity). May function as a switch in neuronal development (By similarity). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Catalyzes the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA. The mechanism of action of the enzyme occurs in 3 steps: (A) adenylation of the enzyme by ATP; (B) transfer of adenylate to an RNA-N3'P to produce RNA-N3'PP5'A; (C) and attack of the adjacent 2'-hydroxyl on the 3'-phosphorus in the diester linkage to produce the cyclic end product. The biological role of this enzyme is unknown but it is likely to function in some aspects of cellular RNA processing (By similarity). SUBCELLULAR LOCATION: Nucleus, nucleoplasm. SIMILARITY: Belongs to the RNA 3'-terminal cyclase family. Type 1 subfamily.


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


FUNCTION: Antimicrobial peptide active against a variety of Gram- positive and some Gram-negative bacterial strains. Has antifungal activity against a slime mold isolate. Has hemolytic activity against human erythrocytes. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the frog skin active peptide (FSAP) family. Brevinin subfamily.


SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family.


FUNCTION: Required for Ca(2+) flux in immune cells and plays a role in T-cell proliferation and in T-cell and neutrophil migration (By similarity). Involved in endoplasmic reticulum-associated degradation (ERAD) of soluble glycosylated proteins (By similarity). Required for palmitoylation and cell surface expression of CD36 and involved in macrophage uptake of low-density lipoprotein and in foam cell formation (By similarity). Together with ZDHHC6, required for palmitoylation of ITPR1 in immune cells, leading to regulate ITPR1 stability and function. Plays a role in protection of cells from ER stress-induced apoptosis. Protects cells from oxidative stress when overexpressed in cardiomyocytes (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein Cell membrane; Single- pass membrane protein Note=Probably mainly localized in the ER. SIMILARITY: Belongs to the selenoprotein K family.


FUNCTION: Prevents cell to cell fusion by interacting with and directing the viral OPG040 protein on the host plasma membrane. The OPG185-OPG040 complex associates with components of the entry fusion complex (EFC) presumably to avoid superinfection and syncytium formation. Via its interaction with C3/VCP protein, protects the infected cell and probably also the extracellular enveloped virus from complement attack. SUBCELLULAR LOCATION: Virion membrane; Single-pass type I membrane protein Host membrane; Single-pass type I membrane protein Note=Component of extracellular enveloped virus (EEV) but not intracellular mature virus (IMV). Component of the outermost membrane of EEV. SIMILARITY: Belongs to the orthopoxvirus OPG185 family.


FUNCTION: Self-assembles to form the virion icosahedral capsid with a T=1 symmetry. This very small capsid (25 nm in diameter) allows the virus to be very stable in the environment and resistant to some disinfectants, including detergents. Essential for the initial attachment to host receptors. After attachment, the virus is endocytosed and traffics to the nucleus. The capsid protein binds and transports the viral genome and Rep across the nuclear envelope (By similarity). SUBCELLULAR LOCATION: Host nucleus Virion. SIMILARITY: Belongs to the gyrovirus capsid protein family.


FUNCTION: [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell- cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. SUBCELLULAR LOCATION: [Ubiquitin]: Cytoplasm Nucleus Mitochondrion outer membrane; Peripheral membrane protein. SIMILARITY: Belongs to the ubiquitin family.


FUNCTION: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Postsynaptic cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM4 sub-subfamily.


FUNCTION: Transcription factor; part of the gene cluster that mediates the biosynthesis of oxopyrrolidines, polyketide-amino acid hybrid compounds with feature structures of tetramic acid. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Probable transcription factor. Required for the establishment of a subset of imaginal tissues: the abdominal histoblasts and the salivary gland imaginal rings. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Plays a regulatory role in autophagic activity. In complex with BCAS3, associates with the autophagosome formation site during both non-selective and selective autophagy. SUBCELLULAR LOCATION: Cytoplasm Preautophagosomal structure Note=The BCAS3:PHAF1 complex is recruited to the preautophagosomal structures adjacent to the damaged mitochondria upon mitophagy in a PRKN-PINK1 dependent manner. SIMILARITY: Belongs to the PHAF1 family.


FUNCTION: Cytochrome c1 subunit of the cytochrome bc1 complex, an essential component of the respiratory electron transport chain required for ATP synthesis. The bc1 complex catalyzes the oxidation of menaquinol and the reduction of cytochrome c in the respiratory chain. The bc1 complex operates through a Q-cycle mechanism that couples electron transfer to generation of the proton gradient that drives ATP synthesis. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.


FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. NRPB3 is part of the core element with the central large cleft and the clamp element that moves to open and close the cleft. Component of RNA polymerases IV and V which mediate short-interfering RNAs (siRNA) accumulation and subsequent RNA-directed DNA methylation-dependent (RdDM) transcriptional gene silencing (TGS) of endogenous repeated sequences, including transposable elements. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family.


FUNCTION: Involved in the regulation of gene expression by stress factors and by components of stress signal transduction pathways. Transcription factor that binds to the GCC-box pathogenesis-related promoter element. Acts as a transcriptional inhibitor and may regulate other AtERFs (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the AP2/ERF transcription factor family. ERF subfamily.


FUNCTION: Required for the positioning and movement of chloroplasts. Interacts with profilin and actin independent of its polymerization status. Regulates chloroplast localization by anchoring chloroplasts to the plasma membrane and forming a bridge to the actin cytoskeleton. SUBCELLULAR LOCATION: Plastid, chloroplast outer membrane; Peripheral membrane protein; Cytoplasmic side.


FUNCTION: Thought to play a role in cellular copper homeostasis, mitochondrial redox signaling or insertion of copper into the active site of COX. Plays an essential role in embryo development. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Single-pass membrane protein. SIMILARITY: Belongs to the SCO1/2 family.


FUNCTION: As part of the MCIA complex, primarily participates in the assembly of the mitochondrial complex I and therefore plays a role in oxidative phosphorylation (PubMed:20816094, PubMed:24158852, PubMed:32320651). This moonlighting protein has also a dehydrogenase activity toward a broad range of substrates with greater specificity for long-chain unsaturated acyl-CoAs (PubMed:12359260, PubMed:16020546, PubMed:21237683, PubMed:24158852). However, in vivo, it does not seem to play a primary role in fatty acid oxidation (PubMed:20816094, PubMed:24158852). In addition, the function in complex I assembly is independent of the dehydrogenase activity of the protein (PubMed:24158852). SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side Note=Essentially associated with membranes. SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.


FUNCTION: Component of the phosphopantothenoylcysteine decarboxylase (PPCDC) involved in the coenzyme A synthesis. Acts as an inhibitory subunit of protein phosphatase PPZ1, which is involved in many cellular processes such as G1-S transition or salt tolerance. SIMILARITY: Belongs to the HFCD (homooligomeric flavin containing Cys decarboxylase) superfamily.


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 (By similarity). Acts as a scavenger of H(2)O(2) (PubMed:20356456). SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the peroxiredoxin family. BCP/PrxQ subfamily.


FUNCTION: Functions as a component of the DNA-binding general transcription factor complex TFIID. Binding of TFIID to a promoter (with or without TATA element) is the initial step in pre-initiation complex (PIC) formation. TFIID plays a key role in the regulation of gene expression by RNA polymerase II through different activities such as transcription activator interaction, core promoter recognition and selectivity, TFIIA and TFIIB interaction, chromatin modification (histone acetylation by TAF1), facilitation of DNA opening and initiation of transcription (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the TAF4 family.


FUNCTION: Negatively regulates the egg-laying rate by promoting retention of fertilized eggs. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the UPF0375 family.


FUNCTION: Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures. The histones H1.0 are found in cells that are in terminal stages of differentiation or that have low rates of cell division. SUBCELLULAR LOCATION: Nucleus Chromosome Note=The RNA edited version has been localized to nuclear speckles. During mitosis, it appears in the vicinity of condensed chromosomes. SIMILARITY: Belongs to the histone H1/H5 family.


FUNCTION: Provides oxygen to the bacteroids. This role is essential for symbiotic nitrogen fixation (By similarity). SIMILARITY: Belongs to the plant globin family.


FUNCTION: Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG- 3' repeats more tightly than the telomeric single-stranded DNA 5'- TTAGGG-3' repeats (By similarity). SUBCELLULAR LOCATION: Nucleus, nucleolus. Cytoplasm Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs.


SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the IIV-6 203L/325L family.


FUNCTION: Along with MDM2, contributes to TP53 regulation (PubMed:32300648). Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the MDM2/MDM4 family.


FUNCTION: Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Required for assembly and activity of the vacuolar ATPase (By similarity). Regulates the size of gut granules during embryonic development (PubMed:20148972). In neurons, required for necrotic cell death by promoting intracellular acidification (PubMed:16005300). Required for cell death induced by hypoxia (PubMed:16005300). Required for acidification of synaptic vesicles and the release of neurotransmitters from adult neurons (PubMed:22426883). SUBCELLULAR LOCATION: Membrane; Multi- pass membrane protein. SIMILARITY: Belongs to the V-ATPase 116 kDa subunit family.


FUNCTION: Cell wall formation. May be involved in outgrowth of the germinated spore or it could function in the synthesis of the germ cell wall. SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein. SIMILARITY: In the C-terminal section; belongs to the transpeptidase family. SIMILARITY: In the N-terminal section; belongs to the glycosyltransferase 51 family.


FUNCTION: Is required not only for elongation of protein synthesis but also for the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family. MetG type 2B subfamily.


SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TMEM205 family.


FUNCTION: Hydrolyzes glycosides and monolignol glucosides (PubMed:25219312). Can hydrolyze para-nitrophenyl beta-D- glucopyranoside (pNPGlc) in vitro (PubMed:23811195, PubMed:25219312). Hydrolyzes para-nitrophenyl beta-D-fucopyranoside, para-nitrophenyl beta-D-galactopyranoside and para-nitrophenyl beta-D-xylopyranoside in vitro (PubMed:25219312). Hydrolyzes the monolignol glucosides coniferin and syringin with high catalytic efficiencies (PubMed:25219312). SIMILARITY: Belongs to the glycosyl hydrolase 1 family.


FUNCTION: Negatively regulates periodontal ligament (PDL) differentiation and mineralization to ensure that the PDL is not ossified and to maintain homeostasis of the tooth-supporting system. Inhibits BMP2-induced cytodifferentiation of PDL cells by preventing its binding to BMPR1B/BMP type-1B receptor, resulting in inhibition of BMP-dependent activation of SMAD proteins (By similarity). Critical regulator of TGF-beta in articular cartilage and plays an essential role in cartilage homeostasis and osteoarthritis (OA) pathogenesis. Negatively regulates chondrogenesis in the articular cartilage by blocking the TGF-beta/receptor interaction on the cell surface and inhibiting the canonical TGF-beta/Smad signal. Binds calcium and plays a role in osteoblast-driven collagen biomineralization activity. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix. SIMILARITY: Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.


FUNCTION: Cleaves the polyglutamate sidechains of folate polyglutamates in the vacuole. Is important for polyglutamyl tail length determination before vacuolar exit. Plays a role on folate stability and intracellular folate content. Has endopeptidase activity against 4- amino-10-methylpteroyl penta-, tetra-, tri- and di-gamma-L-glutamate substrates and is responsible for the production of folic acid, also called pteroylglutamic acid (PteGlu) from teroylpolyglutamates. SUBCELLULAR LOCATION: Vacuole Secreted, extracellular space Secreted, cell wall Note=Extracellular or cell-wall bound. SIMILARITY: Belongs to the peptidase C26 family.


FUNCTION: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side. SIMILARITY: Belongs to the complex I 51 kDa subunit family.


FUNCTION: Inner membrane component of the type II secretion system required for the energy-dependent secretion of extracellular factors such as proteases and toxins from the periplasm. Plays a role in the complex assembly and recruits ExeL resulting in a stable complex in the inner membrane. Provides thus a link between the energy-providing ExeE protein in the cytoplasm and the rest of the T2SS machinery. SUBCELLULAR LOCATION: Cell inner membrane; Single-pass membrane protein. SIMILARITY: Belongs to the GSP M family.


FUNCTION: Required correct function and survival of retinal photoreceptors (PubMed:24691551). Required for retinal development (By similarity). In rod photoreceptors, facilitates stability and/or trafficking of guanylate cyclases and is required to maintain endoplasmic reticulum and mitochondrial homeostasis (By similarity). May play a role in clathrin-coated intracellular vesicle trafficking of proteins from the endoplasmic reticulum to the retinal rod plasma membrane (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein Cytoplasmic vesicle, clathrin-coated vesicle membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the DP1 family.


FUNCTION: Catalyzes quinol oxidation with the concomitant reduction of oxygen to water. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the cytochrome c oxidase bacterial subunit 4 family.


FUNCTION: [Fusion glycoprotein F0]: Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins. FUNCTION: [Fusion glycoprotein F2]: Major determinant of the species specificity of RSV infection. The trimer of F1-F2 (F protein) also facilitates the attachment and entry into the host cell. Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. FUNCTION: [Fusion glycoprotein F1]: Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post- fusion hairpin state. During viral and plasma cell membrane fusion, the coiled coil regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs at the plasma or endosomal membrane. The trimer of F1-F2 (F protein) also facilitates the attachment and entry into the host cell. Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. SUBCELLULAR LOCATION: [Fusion glycoprotein F1]: Virion membrane; Single-pass type I membrane protein Host cell membrane; Single-pass membrane protein Note=Localized at the host apical membrane. SUBCELLULAR LOCATION: [Fusion glycoprotein F2]: Virion membrane Host cell membrane Note=Localized at the host apical membrane. SUBCELLULAR LOCATION: [Fusion glycoprotein F0]: Host Golgi apparatus membrane; Single-pass membrane protein. SIMILARITY: Belongs to the paramyxoviruses fusion glycoprotein family.


FUNCTION: RNA-binding protein with binding specificity for poly(C). May play an important role in neural development (By similarity). SUBCELLULAR LOCATION: Cytoplasm Nucleus Note=Predominantly cytoplasmic. May shuttle between cytoplasm and nucleus.


FUNCTION: Probable lysosomal cobalamin transporter. Required to export cobalamin from lysosomes allowing its conversion to cofactors (By similarity). SUBCELLULAR LOCATION: Lysosome membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the LIMR family. LMBRD1 subfamily.


FUNCTION: Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells. Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes. Promotes initial tethering and rolling of leukocytes in endothelia. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. SIMILARITY: Belongs to the selectin/LECAM family.


FUNCTION: Endo-1,4-beta-xylanase involved in the hydrolysis of xylan, a major structural heterogeneous polysaccharide found in plant biomass representing the second most abundant polysaccharide in the biosphere, after cellulose. SUBCELLULAR LOCATION: Secreted. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 11 (cellulase G) family.


FUNCTION: Potential calcium sensor that binds calcium in vitro.


FUNCTION: Homocysteine S-methyltransferase involved in the conversion of S-adenosylmethionine (AdoMet) to methionine to control the methionine/AdoMet ratio. Also converts S-methylmethionine (SMM) to methionine. SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Activates hepatocyte growth factor (HGF) by converting it from a single chain to a heterodimeric form. SUBCELLULAR LOCATION: Secreted. Note=Secreted as an inactive single- chain precursor and is then activated to a heterodimeric form. SIMILARITY: Belongs to the peptidase S1 family.


FUNCTION: Probable component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:11861581, PubMed:15238519). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins (PubMed:11861581). Developmental role in early embryogenesis and the metaphase to anaphase transition in oocyte and spermatocyte meiosis and mitosis in germ cells (PubMed:11134076, PubMed:11861581, PubMed:15238519). Required for embryonic anterior-posterior axis formation (PubMed:11832245). Plays a role in regulating the abundance of glr-1 receptors in postmitotic neurons, which may in turn control animal locomotion (PubMed:15556870). Involved in regulating GABA neurotransmitter release at neuromuscular junctions in GABA motor neurons (PubMed:24321454). SIMILARITY: Belongs to the APC8/CDC23 family.


FUNCTION: Transcriptional repressor that plays a role in various developmental processes such as myogenesis and brain development. Specifically binds the consensus DNA sequence 5'-[AC]ACATCTG[GT][AC]-3' which contains the E box core, and acts by recruiting chromatin remodeling multiprotein complexes. Plays a key role in myogenesis by directly repressing the expression of ID2 and ID3, 2 inhibitors of skeletal myogenesis. Also involved in controlling cell division of progenitor cells and regulating the survival of postmitotic cortical neurons. May also play a role in the organization of chromosomes in the nucleus (By similarity). SUBCELLULAR LOCATION: Nucleus Note=Associates with condensed chromatin. SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein family. ZBTB18 subfamily.


FUNCTION: E3 ubiquitin-protein ligase that regulates cell proliferation. Involved in apoptosis regulation. Mediates ER stress- induced activation of JNK signaling pathway and apoptosis by promoting ERN1 activation and splicing of XBP1 mRNA. Also involved in protein trafficking and localization. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein Late endosome membrane; Single-pass type I membrane protein Lysosome membrane; Single-pass type I membrane protein Nucleus inner membrane; Single-pass type I membrane protein Note=Under certain conditions, relocalizes to recycling endosomes and to the inner nuclear membrane.


FUNCTION: Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the glutaredoxin family. CPYC subfamily.


FUNCTION: Catalyzes with low efficiency E and Z isomers of indole-3- acetaldoxime from tryptophan (Trp). SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the cytochrome P450 family.


FUNCTION: High-capacity facilitative transporter for trehalose, required to induce anhydrobiosis. Anhydrobiotic larvae can survive almost complete dehydration. Does not transport maltose, sucrose or lactose. Mediates the bidirectional transfer of trehalose. Responsible for the transport of trehalose synthesized in the fat body and the incorporation of trehalose into other tissues that require a carbon source, thereby regulating trehalose levels in the hemolymph. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Trehalose transporter subfamily.


FUNCTION: Involved in the biosynthesis of carotenoids. Catalyzes the condensation of two molecules of geranylgeranyl diphosphate (GGPP) to give prephytoene diphosphate (PPPP) and the subsequent rearrangement of the cyclopropylcarbinyl intermediate to yield 15-cis-phytoene. SIMILARITY: Belongs to the phytoene/squalene synthase family.


FUNCTION: In molluscan muscle, calcium regulation is associated with myosin rather than with actin. Muscle myosin contains two types of light chains: the catalytic light chain, essential for ATPase activity, and the regulatory light chain, a calcium-binding protein responsible for Ca(2+) dependent binding and Ca(2+) dependent Mg-ATPase activity.


FUNCTION: Component of the AP2-containing clathrin coat that may regulate clathrin-dependent trafficking at plasma membrane, TGN and endosomal system (Probable). A possible serine/threonine-protein kinase toward the beta2-subunit of the plasma membrane adapter complex AP2 and other proteins in presence of poly-L-lysine has not been confirmed (PubMed:15809293, PubMed:16914521). By regulating the expression of excitatory receptors at synapses, plays an essential role in neuronal function and signaling and in brain development (By similarity). SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle Golgi apparatus, trans-Golgi network membrane Endosome membrane Note=Colocalizes to the trans-Golgi network (TGN) and to endosomal membranes with clathrin, transferrin and plasma membrane adapter AP1 and AP3 complexes. SIMILARITY: Belongs to the protein kinase superfamily.


FUNCTION: Gametocyte surface protein required for male fertility. SUBCELLULAR LOCATION: Cell surface Cell membrane; Lipid-anchor, GPI-anchor Note=Present on the surface of male and female gametocytes.


FUNCTION: Endoribonuclease that plays a central role in RNA processing and decay. Required for the maturation of 5S and 16S rRNAs and the majority of tRNAs. Also involved in the degradation of most mRNAs. SUBCELLULAR LOCATION: Cytoplasm Cell inner membrane; Peripheral membrane protein; Cytoplasmic side. SIMILARITY: Belongs to the RNase E/G family. RNase E subfamily.


FUNCTION: Catalyzes the first step in the biosynthesis of ornithine lipids, which are phosphorus-free membrane lipids. Catalyzes the 3- hydroxyacyl-acyl carrier protein-dependent acylation of ornithine to form lyso-ornithine lipid (LOL). SIMILARITY: Belongs to the acetyltransferase family. OlsB subfamily.


FUNCTION: Acts as a transcriptional regulator. Binds DNA and RNA (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm.


FUNCTION: Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. This is a prerequisite for the S-specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX. SUBCELLULAR LOCATION: Cytoplasm Mitochondrion. SIMILARITY: Belongs to the NnrE/AIBP family.


FUNCTION: Functions downstream of migratory protein mig-13 and may play a role in the control of Q neuroblast migration during larval development.


FUNCTION: Acts as a linker essential in the assembly of a core complex of PRK/GAPDH. Coordinates the reversible inactivation of chloroplast enzymes GAPDH and PRK during darkness in photosynthetic tissues. SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the CP12 family.


FUNCTION: Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. SUBCELLULAR LOCATION: Cytoplasm Cell junction, plasmodesma Note=Present in punctate particles with granular structure. SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.


FUNCTION: Functions at a post-ubiquitation step in the ubiquitin fusion degradation (UFD) pathway. It is required for vegetative growth (By similarity). SIMILARITY: Belongs to the UFD1 family.


FUNCTION: Component of the mst2 complex which is a highly specific H3 lysine 14 (H3K14) acetyltransferase that functions together with gcn5 to regulate global levels of H3K14 acetylation (H3K14ac), critical for DNA damage checkpoint activation. SUBCELLULAR LOCATION: Cytoplasm Nucleus.


FUNCTION: Part of the ABC transporter complex YbhFSR that could be involved in efflux of cefoperazone. Probably responsible for energy coupling to the transport system. FUNCTION: Part of the ABC transporter complex YbhFSR that could be involved in efflux of cefoperazone. Probably responsible for energy coupling to the transport system. SIMILARITY: Belongs to the ABC transporter superfamily.


FUNCTION: Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC) (PubMed:9635433, PubMed:14993212, PubMed:20129055, PubMed:24064211). It is degraded during the mitotic phase of the cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Its destruction at the metaphase- anaphase transition permits replication in the succeeding cell cycle (PubMed:9635433, PubMed:14993212, PubMed:24064211). Inhibits histone acetyltransferase activity of KAT7/HBO1 in a CDT1-dependent manner, inhibiting histone H4 acetylation and DNA replication licensing (PubMed:20129055). Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (PubMed:22615398). SUBCELLULAR LOCATION: Cytoplasm Nucleus Note=Mainly cytoplasmic but can be relocalized to the nucleus. SIMILARITY: Belongs to the geminin family.


FUNCTION: Subunit of malonate decarboxylase, it is an acyl carrier protein to which acetyl and malonyl thioester residues are bound via a 2'-(5''-phosphoribosyl)-3'-dephospho-CoA prosthetic group and turn over during the catalytic mechanism. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the MdcC family.


FUNCTION: This highly disulfide-bonded protein is a potent inhibitor of factor Xa. Facilitates digestion of tissues and may also protect the gastric tissues from its own digestive enzymes. May have therapeutic utility as an anticoagulant. Also exhibits a strong metastatic activity. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the protease inhibitor I15 (antistasin) family.


FUNCTION: Pectinesterase may play a role in cell wall metabolism during fruit growth and development prior to ripening and may be required for preparing cell walls for softening by polygalacturonase during fruit ripening. SUBCELLULAR LOCATION: Secreted, cell wall. SIMILARITY: In the C-terminal section; belongs to the pectinesterase family. SIMILARITY: In the N-terminal section; belongs to the PMEI family.


FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Plays a role in regulating dopamine-mediated locomotion behavior (PubMed:15378064). SIMILARITY: Belongs to the WD repeat G protein beta family.


SIMILARITY: Belongs to the UPF0292 family.


FUNCTION: GTPase-activating protein (GAP) for the ADP ribosylation factor 1 (ARF1). Involved in membrane trafficking and /or vesicle transport. Promotes hydrolysis of the ARF1-bound GTP and thus, is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles, a prerequisite for vesicle's fusion with target compartment. Probably regulates ARF1-mediated transport via its interaction with the KDELR proteins and TMED2. Overexpression induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, as when ARF1 is deactivated. Its activity is stimulated by phosphoinosides and inhibited by phosphatidylcholine (By similarity). SUBCELLULAR LOCATION: Cytoplasm Golgi apparatus Note=Associates with the Golgi complex.


FUNCTION: Exhibits lactonase activity. Acts in cells with perturbed membrane integrity and is possibly related to the membrane homeostasis (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the SMP-30/CGR1 family.


FUNCTION: Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre- rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre- ribosomal RNA by the RNA exosome. Participates in the 18S rRNA processing in growing oocytes, being essential for oocyte nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) transition. FUNCTION: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex that plays a key role in embryo preimplantation and is required for normal meiotic cycle progression in oocytes (By similarity). Acts as a maternal factor that regulates oocyte and zygotic chromatin tightness during maternal to zygotic transition (By similarity). Also involved in the transformation of the endometrium into the decidua, known as decidualization, providing a solid foundation for implantation of blastocysts. Recognizes the histone methyltransferases SUV39H1 and SUV39H2 and directs them to polyubiquitination and proteasomal degradation, which facilitates the H3K9me3 removal and early zygotic gene expression, essential steps for progressive genome reprogramming and the establishment of pluripotency during preimplantation embryonic development. Supports the spindle assembly and chromosome condensation during oocyte meiotic division by targeting the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation (By similarity). Targets PMP22 for polyubiquitination and proteasomal degradation (By similarity). SUBCELLULAR LOCATION: Nucleus, nucleolus Note=In the nucleolus, localizes predominantly in the granular component, but also detected in the fibrillar center and dense fibrillar component. SIMILARITY: Belongs to the WD repeat DCAF13/WDSOF1 family.


FUNCTION: Probable proton-coupled zinc ion antiporter mediating the import of zinc from cytoplasm into synaptic vesicles and participating to cellular zinc ion homeostasis in the brain. SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Multi-pass membrane protein Synapse, synaptosome Late endosome membrane; Multi-pass membrane protein Lysosome membrane; Multi- pass membrane protein. SIMILARITY: Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.


FUNCTION: Involved in pre-mRNA splicing as component of the U5 snRNP complex that is involved in spliceosome assembly. SUBCELLULAR LOCATION: Cytoplasm Nucleus Note=Predominantly nuclear.


FUNCTION: Bifunctional terpene synthase; part of the gene cluster that mediates the biosynthesis of aspergiltriene A, aspergildienes A-D and aspergilols A-D (PubMed:33480256). The bifunctional terpene synthase AuAS converts isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) into sesterterpenes (PubMed:33480256). The C- terminal prenyltransferase (PT) domain of AuAS catalyzes formation of GFPP, whereas the N-terminal terpene cyclase (TC) domain catalyzes the cyclization of GFPP into 5 distinct sesterterpenes: aspergiltriene A, aspergildiene A, aspergildiene B, aspergildiene C and aspergildiene D (PubMed:33480256). The cytochrome P450 monooxygenase AP450 then hydroxylates the aspergildienes A, B, C and D to yield the corresponding sesterterpene alcohols, aspergilols A-D (PubMed:33480256). SIMILARITY: In the C-terminal section; belongs to the FPP/GGPP synthase family. SIMILARITY: In the N-terminal section; belongs to the terpene synthase family.


FUNCTION: FAD-linked oxidoreductase; part of the gene cluster that mediates the biosynthesis of aurofusarin, a red mycelium pigment which is acting as a mycotoxin (PubMed:15811992, PubMed:15809006, PubMed:16879655). The first step is performed by the polyketide synthase which condenses one acetyl-CoA and 6 malonyl-CoA units to form the first intermediate, the cyclic heptaketide and yellow pigment YWA1 (PubMed:21296881, PubMed:23557488). The C2 hydroxyl group in the pyrone ring of YWA1 is probably formed during ring closure by an aldol-type cyclization reaction (PubMed:21296881). The dehydratase aurZ then acts as the first tailoring enzyme in the aurofusarin biosynthetic pathway by converting YWA1 to nor-rubrofusarin (PubMed:21296881, PubMed:23557488). Nor-rubrofusarin is then methylated to rubrofusarin by the O-methyltransferase aurJ (PubMed:21296881, PubMed:23557488). Rubrofusarin is then transported across the plasma membrane by the rubrofusarin-specific pump aurT for further enzymatic processing by the extracellular complex composed of GIP1, aurF, aurO and aurS to yield aurofusarin (PubMed:21296881). SUBCELLULAR LOCATION: Secreted Secreted, extracellular space. SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase family.


FUNCTION: May play a role in a redox process. SIMILARITY: Belongs to the ETF beta-subunit/FixA family.


FUNCTION: Probably phosphorylates lipids; the in vivo substrate is unknown. FUNCTION: In vitro phosphorylates phosphatidylglycerol but not diacylglycerol; the in vivo substrate is unknown. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the diacylglycerol/lipid kinase family. YegS lipid kinase subfamily. SIMILARITY: Belongs to the diacylglycerol/lipid kinase family. YegS lipid kinase subfamily.


SUBCELLULAR LOCATION: Cellular thylakoid membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the PsaL family.


FUNCTION: Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane (PubMed:12730355). Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:11149946, PubMed:14622179, PubMed:15571673, PubMed:15777781, PubMed:23332758, PubMed:9425306, PubMed:9603192). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (PubMed:25678561). Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112 (PubMed:26792191). SUBCELLULAR LOCATION: Nucleus inner membrane Nucleus outer membrane Nucleus envelope Cytoplasmic vesicle Endoplasmic reticulum membrane Membrane; Single-pass membrane protein Lipid droplet Cell junction Cell membrane Cell projection, growth cone Postsynaptic density membrane Note=During interphase, detected at the inner and outer nuclear membrane and the endoplasmic reticulum. Detected on cytoplasmic vesicles during mitosis (By similarity). Targeted to lipid droplets, cholesterol and galactosylceramide-enriched domains of the endoplasmic reticulum (PubMed:12730355). Enriched at cell-cell communication regions, growth cone and postsynaptic structures. Localization is modulated by ligand-binding. In motor neurons it is enriched at cholinergic postsynaptic densities (PubMed:20167253). SIMILARITY: Belongs to the ERG2 family.


FUNCTION: Short-chain dehydrogenase/reductase; part of the gene cluster that mediates the biosynthesis of various drimane-type sesquiterpene esters, compounds that exhibit diverse biological activities and are widely present in eukaryotes (PubMed:34468074). The pathway begins with the synthesis of the backbone drimenol by the terpene cyclase drtB using farnesyl pyrophosphate (FPP) as substrate (PubMed:34468074). The cytochrome P450 monooxygenase drtD is then responsible for the hydroxylations at C-6, C-9 and C-12, as well as the oxidation of hydroxyl groups at C-6 and C-11 to a ketone and an aldehyde, respectively (PubMed:34468074). Then, the biosynthesis can go in two directions, either the hydroxylated drimenol is further hydroxylated at C-2 and C-3 by an enzyme(s) not associated with the drt cluster, or the FAD-binding oxidoreductase drtC further oxidizes C-11 or C-12 to form the butyrolactone ring (PubMed:34468074). DrtB, drtD and drtC are solely responsible for the formation of the different drimane structures observed during drimane sesquiterpenes biosynthesis (PubMed:34468074). The polyketide synthase drtA synthesizes different lengths (C6 and C8) of PKS chains, which are then oxidized to varying degrees by the short-chain dehydrogenase drtF (PubMed:34468074). Finally, these PKS chains are transferred onto drimane sesquiterpenes by the acyltransferase drtE, forming the sesquiterpene esters (PubMed:34468074). In addition to the different fatty acyl-CoA chains produced by drtA, drtE is also able to use cinnamoyl-CoA as a substrate (PubMed:34468074). SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) family.


FUNCTION: Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella. Involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the PIH1 family. Kintoun subfamily.


FUNCTION: Involved in peroxisome biogenesis and matrix protein import (PubMed:24510720). Required for pollen maturation and in vivo germination via its role in peroxisomal function, which partially involves jasmonic acid biosynthesis (PubMed:24510720). Transported to peroxisomes via the interaction with PEX19-1 (PubMed:21487094). Required for peroxisomal protein import by acting as an anchoring protein for the AAA ATPase complex, which consists of PEX1 and PEX6 (PubMed:21487094). SUBCELLULAR LOCATION: Peroxisome membrane; Multi-pass membrane protein.


FUNCTION: Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike (By similarity). FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates cell surface expression of CD4, CD28, CD3, and MHC-I or MHC-II molecules. FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. FUNCTION: Interferes with TCR signaling from the cell membrane. Interacts with CD247/TCRZ (TCR zeta chain) and exert potent down- regulation of cell surface TCR/CD3 complexes. FUNCTION: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. One of the earliest and most abundantly expressed viral proteins (By similarity). SUBCELLULAR LOCATION: Host cell membrane; Lipid-anchor; Cytoplasmic side Note=Associates with the inner plasma membrane through its N-terminal domain. SIMILARITY: Belongs to the lentivirus primate group Nef protein family.


FUNCTION: Catalyzes the hydrolysis of the 3'-5' phosphodiester bond of glycerophosphodiesters such as glycerophosphorylethanolamine (GPE), a typical phospholipid metabolite. SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase class- III family.


FUNCTION: Component of the cytochrome bc complex which donates electrons to the photosynthetic reaction center. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the cytochrome b family. PetB subfamily.


FUNCTION: DNA-binding component of a FANCM-MHF complex involved in DNA damage repair and genome maintenance (PubMed:20347428). FANCM-MHF promotes gene conversion at blocked replication forks, probably by reversal of the stalled fork (By similarity). Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere- associated network (CCAN), which serves as a structural platform for outer kinetochore assembly (PubMed:22561346). SIMILARITY: Belongs to the CENP-X/MHF2 family.


FUNCTION: Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, the type-2 receptors act as a primary activin receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin- A/INHA-INHBA). The type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor (By similarity). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.


FUNCTION: Involved in disulfide-bond formation. Acts by transferring its disulfide bond to other proteins (By similarity). SIMILARITY: Belongs to the thioredoxin family. DsbA subfamily.


FUNCTION: Putative regulatory subunit of serine/threonine-protein phosphatase 4. SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Putative protein methyltransferase using S-adenosyl-L- methionine as the methyl donor. May methylate a Gln residue in target proteins (By similarity). SIMILARITY: Belongs to the eukaryotic/archaeal PrmC-related family.


FUNCTION: Transcription factor (PubMed:17021039). Binds to specific DNA sequence motifs in regulatory elements, for example in the genes encoding transcription factor lin-48, apoptosis regulator ced-9 and neuropeptide-like protein nlp-2 (PubMed:17021039, PubMed:15923112, PubMed:11532910, PubMed:31398431). Specifies cell fate, playing an essential role in embryonic and larval development (PubMed:9374390, PubMed:10511553, PubMed:31398431, PubMed:17020758). Involved in morphogenesis of the vulva and uterus in hermaphrodites and of the rectal epithelium of the tail in males (PubMed:9374390, PubMed:15923112, PubMed:31398431, PubMed:17020758). Plays multiple roles in the development of the egg-laying system, acting in both lin- 3/EGF-pathway-dependent and -independent processes (PubMed:31398431, PubMed:17020758). Positively regulates expression of neuropeptide-like proteins nlp-2 and nlp-7 in uvl cells in an EGF-pathway-dependent manner (PubMed:31398431). Involved in negatively modulating apoptosis in germline and somatic cells, acting in partial redundancy with transcription factor pax-2, probably by directly regulating transcription of ced-9 (PubMed:17021039). Positively regulates transcription of lin-48 in hindgut cells and functions in the development of the hindgut (PubMed:11532910, PubMed:15923112, PubMed:10511553). SUBCELLULAR LOCATION: Nucleus Chromosome.


FUNCTION: Transcription factor. Binds optimally to the DNA consensus sequence 5'-YYTAATGRTTTTY-3'. May control the expression of neural adhesion molecules such as L1 or Ng-CAM during embryonic development of both the central and peripherical nervous system. May be involved in controlling adhesive processes in keratinizing epithelia. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the BAR homeobox family.


FUNCTION: Counteracts the innate antiviral activity of APOBEC3G. Forms a complex with host APOBEC3G thus preventing the entry of this lethally hypermutating enzyme into progeny virions. Functions as an adapter molecule, recruiting APOBEC3G to the ubiquitin-proteasome machinery. Targets APOBEC3G for degradation through the assembly with elongin BC complex, CUL5 and RBX1. Binds viral RNA and affects the stability of viral nucleoprotein core. May play a role in viral morphology (By similarity). SUBCELLULAR LOCATION: Host cytoplasm Host cell membrane; Peripheral membrane protein; Cytoplasmic side Virion Note=In the cytoplasm, seems to colocalize with intermediate filament vimentin. A fraction is associated with the cytoplasmic side of cellular membranes, presumably via the interaction with Pr55Gag precursor (By similarity). SIMILARITY: Belongs to the primate lentivirus group Vif protein family.


FUNCTION: Transcriptional activator involved in abiotic stress tolerance. Can directly regulate stress-related gene expression by binding to the DNA sequence 5'-[AG]CCGAC-3' (DRE element) of their promoter region. Involved in the regulation of stomatal closure movement under drought stress (PubMed:23625358). Acts as a positive regulator of drought stress response (PubMed:22095047). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the AP2/ERF transcription factor family. ERF subfamily.


FUNCTION: Catalyzes the formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle. Required for growth on ethanol or acetate, but dispensable when fermentable carbon sources are available. Acts also on 2- methylisocitrate. SUBCELLULAR LOCATION: Glyoxysome. SIMILARITY: Belongs to the isocitrate lyase/PEP mutase superfamily. Isocitrate lyase family.


SIMILARITY: To M.leprae ML2435 and S.coelicolor SCO3349.


FUNCTION: Secreted alpha-L-arabinofuranosidase that actively hydrolyzes p-NP-alpha-L-arabinofuranoside and is specific for furanose configuration of the carbohydrate ring. Exhibits also significant activity against polymeric arabinose-containing substrates such as arabinan and arabinoxylan, a major component of plant hemicellulose. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 54 family.


FUNCTION: RNA-dependent RNA polymerase that plays an essential role in the virus replication. SIMILARITY: Belongs to the tombusviridae RNA polymerase family.


FUNCTION: Endo-acting xylanase which specifically cleaves internal linkages on the xylan backbone, releasing xylooligosaccharides. Is able to hydrolyze glucuronoxylan and the arabinoxylan from wheat. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 11 (cellulase G) family.


FUNCTION: May play a role in male fertility. May act as a retinoid carrier protein within the epididymis. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.


FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of paspalitrems, indole-diterpene (IDT) mycotoxins that are potent tremorgens in mammals (PubMed:23468653, PubMed:29457197, PubMed:32077051). The geranylgeranyl diphosphate (GGPP) synthase idtG is proposed to catalyze the first step in IDT biosynthesis via catalysis of a series of iterative condensations of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP), geranyl diphosphate (GPP), and farnesyl diphosphate (FPP), to form GGPP (Probable). Condensation of indole-3-glycerol phosphate with GGPP by the prenyltransferase idtC then forms 3-geranylgeranylindole (3-GGI) (Probable). Epoxidation of the two terminal alkenes of the geranylgeranyl moiety by the FAD-dependent monooxygenase idtM, and cyclization by the terpene cyclase idtB then leads to the production of paspaline (Probable). The cytochrome P450 monooxygenase idtP then catalyzes oxidative elimination of the pendant methyl group at C-12 of paspaline and generates the C-10 ketone to yield 13-desoxypaxilline (PubMed:32077051). The cytochrome P450 monooxygenase idtQ may catalyze the C-13 oxidation of 13-desoxypaxilline to afford paxilline (Probable). Considering that both paspalicine and paxilline were detected in C.paspali, idtQ also catalyzes the formation of paspalinine from 13-desoxypaxilline via paspalicine as an intermediate (Probable). Finally, the alpha-prenyltransferase idtF prenylates paspalinine at the C-20 or the C-21 positions to yield paspalitrems A and C, respectively (PubMed:32077051). The hydroxylation of paspalitrem A at C-32 by a still unknown oxidase affords paspalitrem B (Probable). SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the cytochrome P450 family.


FUNCTION: Involved in the resistance to some abiotic stresses (e.g. high salt, hyperosmotic stress) in young seedlings, by regulating the expression of several stress-inducible genes (cold- and salt-induced genes but not drought-responsive genes). Required for the ABA response during germination. CIPK serine-threonine protein kinases interact with CBL proteins. Binding of a CBL protein to the regulatory NAF domain of CIPK protein lead to the activation of the kinase in a calcium- dependent manner. The CBL9/CIPK3 complex acts in the regulation of abscisic acid response in seed germination. SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.


FUNCTION: (Microbial infection) Probably transports the toxic C- terminal region of CdiA-2 from B.pseudomallei strain 1026b across the inner membrane to the cytoplasm, where CdiA has a toxic effect. Expression in E.coli makes the bacteria sensitive to the tRNase domain of B.pseudomallei strain 1026b CdiA-2. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein.


FUNCTION: Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (By similarity). SUBCELLULAR LOCATION: Nucleus, nucleolus Nucleus, Cajal body Note=Also localized to Cajal bodies (coiled bodies). SIMILARITY: Belongs to the eukaryotic ribosomal protein eL8 family.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the CDV3 family.


FUNCTION: Involved in acetate metabolism. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: In the C-terminal section; belongs to the phosphate acetyltransferase and butyryltransferase family. SIMILARITY: In the N-terminal section; belongs to the CobB/CobQ family.


FUNCTION: Oxygenase required for conversion of tetracenomycin F1 to tetracenomycin D3.


FUNCTION: Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). Requires the other members of the gamma- secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. May function in the cytoplasmic partitioning of proteins. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is involved in calcium homeostasis. Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein Golgi apparatus membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the peptidase A22A family.


FUNCTION: Serine/threonine-protein kinase. Needed for the initiation of DNA synthesis during mitosis as well as for synaptonemal complex formation and commitment to recombination during meiosis. Required for HTA1-HTB1 locus transcription repression. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC7 subfamily.


FUNCTION: Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds kainate > quisqualate > glutamate >> AMPA. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Postsynaptic cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK4 subfamily.


FUNCTION: Transcription factor (PubMed:15177025, PubMed:19386265). Binds to a sequence motif, 5'-TTATTGGCTTCGTTAA-3', which may be involved in AIY interneuron function, in the regulatory elements of target genes; binding is more efficient, in vitro, together with homeobox protein ceh-10 (PubMed:15177025). Required for specification of the AIA and AIY interneurons and the NSM neurons (PubMed:11493519, PubMed:24353061). Positively regulates the expression of a number of genes including ceh-10, ceh-23, kal-1, hen-1, ser-2, unc-17 and sra-11 in AIY neurons, and cat-4, flp-4, bas-1, ptps-1 and mgl-1 in NSM neurons (PubMed:11493519, PubMed:24353061, PubMed:19386265, PubMed:15177025). In concert with WNT/beta-catenin signaling, initiates expression of homeobox ceh-10 in AIY, but not in the sister cells, SMDD motor neurons (PubMed:19386265). Also acts in an autoregulatory feedback loop to maintain its own expression (PubMed:9292724, PubMed:19386265). Plays a role in the thermotactic response, olfactory imprinting, regulation of longevity, control of dauer formation and axon outgrowth and pathfinding (PubMed:9292724, PubMed:16051801, PubMed:21055415, PubMed:24353061). Not required for normal chemosensory behavior (PubMed:9292724). SUBCELLULAR LOCATION: Nucleus Perikaryon Cell projection, axon.


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


FUNCTION: Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme with higher activity toward C18 acyl-CoAs, especially C18:3(n-3) acyl-CoAs and C18:3(n-6)-CoAs. Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs, and weakly toward C20:0-CoA. Little or no activity toward C22:0-, C24:0-, or C26:0-CoAs. May participate in the production of saturated and polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ELO family. ELOVL7 subfamily.


FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of calidodehydroaustin, a fungal meroterpenoid (PubMed:28233494, PubMed:29076725). The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:28233494). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity). Acid-catalyzed keto- rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (By similarity). The cytochrome P450 monooxygenase ausG modifies austinolide to austinol (By similarity). Austinol is further acetylated to austin by the O-acetyltransferase ausP, which spontaneously changes to dehydroaustin (PubMed:28233494). The cytochrome P450 monooxygenase ausR then converts dehydroaustin is into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation catalyzed by ausR permits the O-acetyltransferase ausQ to add an additional acetyl group to the molecule, leading to the formation of acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase ausT catalyzes the reduction of the double bond present between carbon atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7- hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an acetylation reaction but also the addition of the PKS ausV diketide product to 1,2-dihydro-7-hydroxydehydroaustin, forming precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha- ketoglutarate-dependent dioxygenase converts precalidodehydroaustin into calidodehydroaustin (PubMed:28233494). SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the cytochrome P450 family.


FUNCTION: Catalyzes the isomerization of L-xylulose-5-phosphate to L- ribulose-5-phosphate. Is involved in the anaerobic L-ascorbate utilization. FUNCTION: Catalyzes the isomerization of L-xylulose-5-phosphate to L- ribulose-5-phosphate. Is involved in the anaerobic L-ascorbate utilization. SIMILARITY: Belongs to the L-ribulose-5-phosphate 3-epimerase family.


FUNCTION: Tubulin-folding protein; involved in the final step of the tubulin folding pathway. SUBCELLULAR LOCATION: Cytoplasm Note=Detected predominantly in the photoreceptor connecting cilium. SIMILARITY: Belongs to the TBCC family.


FUNCTION: Hydrolyzes the N-acetamido groups of N-acetyl-D-glucosamine residues in chitin to form chitosan and acetate (By similarity). Chitosan is required to anchor melanin to the cell wall, for maintenance of cell wall integrity, and for proper cytokinesis (By similarity). Chitosan offers an advantage during infection as it is less readily detected than chitin by host immunosurveillance mechanisms (By similarity). SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI- anchor. SIMILARITY: Belongs to the polysaccharide deacetylase family.


FUNCTION: AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:11882383, PubMed:21620960, PubMed:21432781). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:11882383, PubMed:21620960, PubMed:21432781). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:21620960, PubMed:21432781). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (PubMed:9632753, PubMed:10400692). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (By similarity). AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating the TORC1 signaling pathway, and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. Also regulates the TORC1 signaling pathway by catalyzing phosphorylation of CASTOR1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF- kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (By similarity). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (PubMed:12107176). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (PubMed:15546921). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth (By similarity). AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) (By similarity). AKT mediates the antiapoptotic effects of IGF-I (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (By similarity). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr- 384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53. Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility. Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation. Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (By similarity). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (By similarity). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (By similarity). Acts as a negative regulator of the cGAS- STING pathway by mediating phosphorylation of CGAS during mitosis, leading to its inhibition (By similarity). Acts as an inhibitor of tRNA methylation by mediating phosphorylation of the N-terminus of METTL1, thereby inhibiting METTL1 methyltransferase activity (By similarity). SUBCELLULAR LOCATION: Cytoplasm Nucleus Cell membrane Note=Nucleus after activation by integrin-linked protein kinase 1 (ILK1). Nuclear translocation is enhanced by interaction with TCL1A (By similarity). Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus. Colocalizes with WDFY2 in intracellular vesicles (By similarity). SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.


FUNCTION: Required for the morphogenesis and for the elongation of the flagellar filament by facilitating polymerization of the flagellin monomers at the tip of growing filament. Forms a capping structure, which prevents flagellin subunits (transported through the central channel of the flagellum) from leaking out without polymerization at the distal end (By similarity). SUBCELLULAR LOCATION: Secreted. Bacterial flagellum. SIMILARITY: Belongs to the FliD family.


SIMILARITY: Belongs to the CCM2 family.


FUNCTION: E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, leading to degradation of nascent peptide chains. ZNF598 is activated when ribosomes are stalled within an mRNA following translation of prematurely polyadenylated mRNAs. Acts as a ribosome collision sensor: specifically recognizes and binds collided di-ribosome, which arises when a trailing ribosome encounters a slower leading ribosome, leading to terminally arrest translation. Following binding to colliding ribosomes, mediates monoubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS3/uS3, and 'Lys-63'-linked polyubiquitination of RPS20/uS10. Polyubiquitination of RPS20/uS10 promotes recruitment of the RQT (ribosome quality control trigger) complex, which drives the disassembly of stalled ribosomes, followed by degradation of nascent peptides. E3 ubiquitin-protein ligase activity is dependent on the E2 ubiquitin-conjugating enzyme UBE2D3. Also acts as an adapter that recruits the 4EHP-GYF2 complex to mRNAs. Independently of its role in RQC, may also act as a negative regulator of interferon-stimulated gene (ISG) expression. SUBCELLULAR LOCATION: Cytoplasm, cytosol. SIMILARITY: Belongs to the ZNF598/HEL2 family.


FUNCTION: Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Stimulates the mitotic kinase activity of aurkb/aurora-B in the CPC. Does not appear to exhibit anti-apoptotic activity (By similarity). CPC. Does not appear to exhibit anti-apoptotic activity. SUBCELLULAR LOCATION: Cytoplasm Nucleus Chromosome, centromere Cytoplasm, cytoskeleton, spindle Note=Localizes on chromosome arms and inner centromeres from prophase through metaphase and then transferring to the spindle midzone and midbody from anaphase through cytokinesis. SIMILARITY: Belongs to the IAP family.