FUNCTION: Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9230079). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). FUNCTION: Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs). SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton Cell projection Nucleus. SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton Cell projection Nucleus. SIMILARITY: Belongs to the ARPC5 family.


FUNCTION: Binds with high affinity to muscle nicotinic acetylcholine receptor (nAChR) and hinders acetylcholine binding to the receptor, thereby impairing neuromuscular transmission. Causes muscle paralysis, spasms and increased respiration. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain subfamily. Type III alpha-neurotoxin sub-subfamily.


FUNCTION: Putative adenovirus Bcl-2 homolog that inhibits apoptosis induced by TNF or FAS pathways, as well as p53-mediated apoptosis. Without E1B 19K function, virus production is compromised because of premature death of host cell. Interacts with Bax protein in cell lysates (By similarity). SUBCELLULAR LOCATION: Host cell membrane Host nucleus envelope Host nucleus lamina Note=Associated with the plasma and nuclear membranes, and with the insoluble nuclear lamina. SIMILARITY: Belongs to the adenoviridae E1B 19 kDa protein family.


FUNCTION: Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3- kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration (By similarity). Has an essential role in the stimulation of B cell activation (By similarity). SUBCELLULAR LOCATION: Cytoplasm Cytoplasm, cytoskeleton Cytoplasmic vesicle membrane; Peripheral membrane protein Synapse, synaptosome Cell junction, focal adhesion Note=Localized in endocytic vesicles containing clustered receptors. Colocalizes with ASAP1 in vesicular structures. Colocalized with actin microfilaments and focal adhesions (By similarity). Colocalized with MAGI2 in synaptosomes (By similarity). Translocation to EGFR containing vesicles upon EGF stimulation is inhibited in the presence of SH3KBP1 (PubMed:21830225). Colocalizes with ZFP36 in the cytoplasm (By similarity).


FUNCTION: Paralytic toxin that inhibits insect voltage-gated sodium (Nav) and calcium (Cav) channels in P.americana (American cockroach) dorsal unpaired median (DUM) neurons, and inhibits the B.germanica (German cockroach) Nav channel (BgNaV1) (PubMed:28475112). Also shows a delay in fast inactivation when tested on BgNaV1 (PubMed:28475112). May act as a gating-modifier toxin on Nav and as a pore blocker on Cav (PubMed:28475112). In vivo, reversibly paralyzes both L.cuprina (Australian sheep blowfly) and M.domestica (housefly), but does not affect larvae of H.armigera (cotton bollworms) (PubMed:28475112). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 28 (Jztx-11) subfamily.


FUNCTION: Catalyzes the reversible retro-aldol cleavage of 2-keto-3- deoxy-L-rhamnonate (KDR) to pyruvate and lactaldehyde. SIMILARITY: Belongs to the HpcH/HpaI aldolase family. KDR aldolase subfamily.


FUNCTION: Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters.


FUNCTION: Snake venom phospholipase A2 (PLA2) that lacks enzymatic activity. Is myotoxic, induces edema, and causes systemic effects (renal changes that lead to proteinuria) on mice (PubMed:29170054). A model of myotoxic mechanism has been proposed: an apo Lys49-PLA2 is activated by the entrance of a hydrophobic molecule (e.g. fatty acid) at the hydrophobic channel of the protein leading to a reorientation of a monomer (By similarity). This reorientation causes a transition between 'inactive' to 'active' states, causing alignment of C-terminal and membrane-docking sites (MDoS) side-by-side and putting the membrane-disruption sites (MDiS) in the same plane, exposed to solvent and in a symmetric position for both monomers (By similarity). The MDoS region stabilizes the toxin on membrane by the interaction of charged residues with phospholipid head groups (By similarity). Subsequently, the MDiS region destabilizes the membrane with penetration of hydrophobic residues (By similarity). This insertion causes a disorganization of the membrane, allowing an uncontrolled influx of ions (i.e. calcium and sodium), and eventually triggering irreversible intracellular alterations and cell death (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily. K49 sub-subfamily.


FUNCTION: Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:18621711). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. Is also a component of the minor U12 spliceosome (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytosol Nucleus Note=SMN-mediated assembly into core snRNPs occurs in the cytosol before SMN-mediated transport to the nucleus to be included in spliceosomes. SIMILARITY: Belongs to the snRNP Sm proteins family.


FUNCTION: Pore-forming protein that forms cations-selective hydrophilic pores of around 1 nm and causes cardiac stimulation and cytolysis. Pore formation is a multi-step process that involves specific recognition of membrane sphingomyelin (but neither cholesterol nor phosphatidylcholine) using aromatic rich region and adjacent phosphocholine (POC) binding site, firm binding to the membrane (mainly driven by hydrophobic interactions) accompanied by the transfer of the N-terminal region to the lipid-water interface and finally pore formation after oligomerization of monomers. Cytolytic effects include red blood cells hemolysis, platelet aggregation and lysis, cytotoxic and cytostatic effects on fibroblasts. Lethality in mammals has been ascribed to severe vasospasm of coronary vessels, cardiac arrhythmia, and inotropic effects. SUBCELLULAR LOCATION: Secreted Nematocyst Target cell membrane Note=Forms an alpha-helical membrane channel in the prey. SIMILARITY: Belongs to the actinoporin family. Sea anemone subfamily.


FUNCTION: Involved in mercuric ion uptake. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein.


FUNCTION: Located at the top of the head of the small subunit, it contacts several helices of the 18S rRNA. SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the universal ribosomal protein uS13 family.


FUNCTION: Involved in pre-mRNA alternative splicing regulation. RNA- binding protein that binds to 5'ACACCC-3' core sequence (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm. SIMILARITY: Belongs to the muscleblind family.


FUNCTION: Part of the gene cluster that mediates the biosynthesis of squalestatin S1 (SQS1, also known as zaragozic acid A), a heavily oxidized fungal polyketide that offers potent cholesterol lowering activity by targeting squalene synthase (SS) (PubMed:28605916). SQS1 is composed of a 2,8-dioxobicyclic[3.2.1]octane-3,4,5-tricarboxyclic acid core that is connected to two lipophilic polyketide arms (PubMed:28605916). These initial steps feature the priming of an unusual benzoic acid starter unit onto the highly reducing polyketide synthase clz14, followed by oxaloacetate extension and product release to generate a tricarboxylic acid containing product (PubMed:28605916). The phenylalanine ammonia lyase (PAL) clz10 and the acyl-CoA ligase clz12 are involved in transforming phenylalanine into benzoyl-CoA (PubMed:28605916). The citrate synthase-like protein clz17 is involved in connecting the C-alpha-carbons of the hexaketide chain and oxaloacetate to afford the tricarboxylic acid unit (PubMed:28605916). The potential hydrolytic enzymes, clz11 and clz13, are in close proximity to pks2 and may participate in product release (PubMed:28605916). On the other side, the tetraketide arm is synthesized by a the squalestatin tetraketide synthase clz2 and enzymatically esterified to the core in the last biosynthetic step, by the acetyltransferase clz6 (By similarity). The biosynthesis of the tetraketide must involve 3 rounds of chain extension (By similarity). After the first and second rounds methyl-transfer occurs, and in all rounds of extension the ketoreductase and dehydratase are active (By similarity). The enoyl reductase and C-MeT of clz2 are not active in the final round of extension (By similarity). The acetyltransferase clz6 appears to have a broad substrate selectivity for its acyl CoA substrate, allowing the in vitro synthesis of novel squalestatins (By similarity). The biosynthesis of SQS1 requires several oxidative steps likely performed by oxidoreductases clz3, clz15 and clz16 (Probable). Finally, in support of the identification of the cluster as being responsible for SQS1 production, the cluster contains a gene encoding a putative squalene synthase (SS) clz20, suggesting a likely mechanism for self-resistance (Probable).


FUNCTION: CRISPR (clustered regularly interspaced short palindromic repeat), is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). Cas3 plus Cascade participate in CRISPR interference, the third stage of CRISPR immunity. Acts as a dsDNA and dsRNA endonuclease (in a fusion with Alicyclus caldarius esterase to increase solubility). SIMILARITY: Belongs to the CRISPR-associated nuclease Cas3-HD family.


SUBCELLULAR LOCATION: Nucleus, nucleolus. SIMILARITY: Belongs to the UPF0743 family.


FUNCTION: Alpha toxins bind voltage-independently at site-3 of sodium channels and inhibit the inactivation of the activated channels. The toxin affect mammalian sodium channels Nav1.7/SCN9A (EC(50)=4.5 nM), Nav1.4/SCN4A (EC(50)=9.6 nM), Nav1.6/SCN8A (EC(50)=30 nM), Nav1.5/SCN5A (only at micromolar concentrations), and insect sodium channel para/tipE (EC(50)=80 nM) (PubMed:16038905, PubMed:16641312, PubMed:23527544). In vivo, intraplantar administration of this toxin elicits pain behaviors, including licking and flinching of the hind paw (PubMed:26999206). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily.


FUNCTION: Sperm surface membrane protein that may be involved in sperm- egg plasma membrane adhesion and fusion during fertilization. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor Cytoplasmic vesicle, secretory vesicle, acrosome Note=Expressed in acrosomal matrix and outer and inner acrosomal membranes. SIMILARITY: Belongs to the SPACA4/bouncer family.


FUNCTION: Transcriptional activator of nphA1 and nphA2 involved in the degradation of 4-nitrophenol (4-NP).


FUNCTION: May bind to RNA via its Arg/Ser-rich domain. SUBCELLULAR LOCATION: Nucleus speckle Nucleus, nucleoplasm Note=Colocalizes with SCNM1 and SNRNP70 in nuclear speckles. SIMILARITY: Belongs to the Luc7 family.


FUNCTION: Purine nucleoside enzyme that catalyzes the phosphorolysis of adenosine and inosine nucleosides, yielding D-ribose 1-phosphate and the respective free bases, adenine and hypoxanthine. Also catalyzes the phosphorolysis of S-methyl-5'-thioadenosine into adenine and S-methyl- 5-thio-alpha-D-ribose 1-phosphate. Also has adenosine deaminase activity. SIMILARITY: Belongs to the purine nucleoside phosphorylase YfiH/LACC1 family.


FUNCTION: Involved in chlorophyll synthesis and chloroplast protection against oxidative damage. SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the NAD kinase family.


FUNCTION: High affinity receptor for triiodothyronine. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 subfamily.


FUNCTION: Cell surface proteoglycan that bears both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix. Regulates exosome biogenesis in concert with SDCBP and PDCD6IP. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein Secreted Secreted, extracellular exosome Note=Shedding of the ectodomain produces a soluble form. SIMILARITY: Belongs to the syndecan proteoglycan family.


FUNCTION: FAD-linked oxidoreductase; part of the gene cluster that mediates the biosynthesis of fungal ergot alkaloid (PubMed:22403186). DmaW catalyzes the first step of ergot alkaloid biosynthesis by condensing dimethylallyl diphosphate (DMAP) and tryptophan to form 4- dimethylallyl-L-tryptophan (PubMed:22403186). The second step is catalyzed by the methyltransferase easF that methylates 4- dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine, resulting in the formation of 4-dimethylallyl-L-abrine (PubMed:22403186). The catalase easC and the FAD-dependent oxidoreductase easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is further oxidized by easD in the presence of NAD(+), resulting in the formation of chanoclavine-I aldehyde (PubMed:22403186). Chanoclavine-I aldehyde is the precursor of ergoamides and ergopeptines in Clavicipitaceae, and clavine-type alcaloids such as fumiclavine in Trichocomaceae (PubMed:22403186). However, the metabolites downstream of chanoclavine-I aldehyde in Arthrodermataceae have not been identified yet (PubMed:22403186). SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase family.


FUNCTION: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. SUBCELLULAR LOCATION: Nucleus Cell septum Cell tip Cytoplasm, cytoskeleton, spindle pole. SIMILARITY: Belongs to the SEC6 family.


FUNCTION: The phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS), a major carbohydrate active -transport system, catalyzes the phosphorylation of incoming sugar substrates concomitantly with their translocation across the cell membrane. This system is involved in sucrose transport. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the teretoxin H (TH) superfamily.


SIMILARITY: Belongs to the universal ribosomal protein uS7 family.


FUNCTION: Does not have nicotinamide-nucleotide (NMN) amidohydrolase activity. SIMILARITY: Belongs to the CinA family.


FUNCTION: Binds to membranes enriched in phosphatidylinositol 3- phosphate (PtdIns(P3)) and phosphatidylinositol 4,5-bisphosphate. May be involved in several stages of intracellular trafficking. SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. SIMILARITY: Belongs to the sorting nexin family.


FUNCTION: The specificity (S) subunit of a type I restriction enzyme; this subunit dictates DNA sequence specificity. This bacterium does not encode the associated endonuclease or methylase subunits. SIMILARITY: Belongs to the type-I restriction system S methylase family.


FUNCTION: During infection, this phosphoprotein probably modulates the structure of the red cell membrane to the advantage of the parasite, although its precise function is not known. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Peripheral membrane protein on the cytoplasmic face of the host erythrocyte membrane.


FUNCTION: Part of a non-canonical MAPK signaling pathway. Activated by APOE, enhances the AP-1-mediated transcription of APP, via a MAP kinase signal transduction pathway composed of MAP2K7 and MAPK1/ERK2 and MAPK3/ERK1. May be an activator of the JNK/SAPK pathway. SUBCELLULAR LOCATION: Cytoplasm Cell membrane Note=Behaves essentially as an integral membrane protein. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.


FUNCTION: Required for normal accumulation and movement of lipid- modified hedgehog (hh) morphogen. May act by stabilizing the interaction between heparan sulfate proteoglycans (HSPGs) and hh, HSPGs being required for diffusion of hh morphogen. Not involved in wingless (wg) morphogen movement, suggesting that it may provide HSPG specificity for Hh. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix Note=Colocalizes with HSPG.


FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:22496338). Catalyzes 'Lys-11'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit (PubMed:19820702, PubMed:19822757, PubMed:27259151). Also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is however unclear whether UBE2D1/UBCH5 acts as an E2 enzyme for the APC/C in vivo. Also involved in ubiquitination and subsequent degradation of VHL, resulting in an accumulation of HIF1A (PubMed:16819549). In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, except 'Lys-48'-linked polyubiquitination (PubMed:20061386, PubMed:20622874). SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.


SIMILARITY: Belongs to the asfivirus B354L family.


FUNCTION: Mediates influx of magnesium ions (By similarity). Alternates between open and closed states. Activated by low cytoplasmic Mg(2+) levels. Inactive when cytoplasmic Mg(2+) levels are high (By similarity). SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35) family.


FUNCTION: MFS transporter; part of the gene cluster that mediates the biosynthesis of itaconic acid and 2-hydroxyparaconate (PubMed:26639528, PubMed:27750034). Cis-aconitate is secreted by the mitochondrial tricarboxylate transporter MTT1. In the cytosol cis-aconitate is converted into trans-aconitate via isomerization by the aconitate- delta-isomerase ADI1 (PubMed:26639528). Decarboxylation of trans- aconitate by the trans-aconitate decarboxylase TAD1 then leads then to the production of itaconic acid (PubMed:26639528). The cytochrome P450 monooxygenase CYP3 further converts itaconate to 2-hydroxyparaconate via oxidation of the double bond, leading to a transient epoxide, which can subsequently be lactonized to produce 2-hydroxyparaconate (PubMed:27750034). Secretion of itaconate and possibly 2- hydroxyparaconate into the medium is mediated by the major facilitator ITP1 (PubMed:26639528, PubMed:27750034). The glyoxalase domain- containing protein RDO1 is not involved in the biosynthesis of itaconate and 2-hydroxyparaconate, however, it might play a role in the further conversion of 2-hydroxyparaconate to itatartarate (PubMed:27750034). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily.


FUNCTION: Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space to provide PA for CL synthesis in the inner membrane. Likewise, the TRIAP1:PRELID3A complex mediates the transfer of phosphatidic acid (PA) between liposomes (in vitro) and probably functions as a PA transporter across the mitochondrion intermembrane space (in vivo). Mediates cell survival by inhibiting activation of caspase-9 which prevents induction of apoptosis. SUBCELLULAR LOCATION: Mitochondrion Mitochondrion intermembrane space. SIMILARITY: Belongs to the TRIAP1/MDM35 family.


FUNCTION: DNA-dependent ATPase required for providing the needed energy to achieve the termination of early transcripts. Acts in concert with the RAP94 subunit of the virion RNA polymerase and the capping enzyme/VTF to catalyze release of UUUUUNU-containing nascent RNA from the elongation complex. NPH-I must bind ssDNA in order to exhibit ATPase activity (By similarity). SUBCELLULAR LOCATION: Virion Note=Virion core enzyme. SIMILARITY: Belongs to the helicase family. NPH I subfamily.


FUNCTION: Multifunctional glycoprotein that acts as receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipidic nature such as oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids and bacterial diacylated lipopeptides. They are generally multivalent and can therefore engage multiple receptors simultaneously, the resulting formation of CD36 clusters initiates signal transduction and internalization of receptor- ligand complexes. The dependency on coreceptor signaling is strongly ligand specific. Cellular responses to these ligands are involved in angiogenesis, inflammatory response, fatty acid metabolism, taste and dietary fat processing in the intestine (By similarity). Binds long- chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption (By similarity). Mechanistically, binding of fatty acids activates downstream kinase LYN, which phosphorylates the palmitoyltransferase ZDHHC5 and inactivates it, resulting in the subsequent depalmitoylation of CD36 and caveolar endocytosis (By similarity). In the small intestine, plays a role in proximal absorption of dietary fatty acid and cholesterol for optimal chylomicron formation, possibly through the activation of MAPK1/3 (ERK1/2) signaling pathway (By similarity). Involved in oral fat perception and preferences (By similarity). Detection into the tongue of long-chain fatty acids leads to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions (By similarity). In taste receptor cells, mediates the induction of an increase in intracellular calcium levels by long-chain fatty acids, leading to the activation of the gustatory neurons in the nucleus of the solitary tract (By similarity). Important factor in both ventromedial hypothalamus neuronal sensing of long-chain fatty acid and the regulation of energy and glucose homeostasis (By similarity). Receptor for thrombospondins, THBS1 and THBS2, mediating their antiangiogenic effects (By similarity). As a coreceptor for TLR4:TLR6 heterodimer, promotes inflammation in monocytes/macrophages. Upon ligand binding, such as oxLDL or amyloid-beta 42, interacts with the heterodimer TLR4:TLR6, the complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion, through the priming and activation of the NLRP3 inflammasome. Selective and nonredundant sensor of microbial diacylated lipopeptide that signal via TLR2:TLR6 heterodimer, this cluster triggers signaling from the cell surface, leading to the NF-kappa-B-dependent production of TNF, via MYD88 signaling pathway and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Membrane raft Golgi apparatus Apical cell membrane Note=Upon ligand-binding, internalized through dynamin-dependent endocytosis. SIMILARITY: Belongs to the CD36 family.


FUNCTION: Bacterial hemolysins are exotoxins that attack blood cell membranes and cause cell rupture. Binds to eukaryotic membranes where it hydrolyzes phosphatidylcholine, sphingomyelin and phosphatidylethanolamine. The diacylglycerol produced can activate both the arachidonic acid pathway, leading to modulation of the inflammatory response cascade and thrombosis, and protein kinase C, leading to activation of eukaryotic phospholipases and further membrane damage (By similarity). This enzyme is hemolytic against horse erythrocytes. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the bacterial zinc-metallophospholipase C family.


FUNCTION: Caeridins show neither neuropeptide activity nor antibiotic activity. SUBCELLULAR LOCATION: Secreted.


FUNCTION: Oxidoreductase; 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 short-chain dehydrogenases/reductases (SDR) family.


FUNCTION: Component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling (PubMed:16113209, PubMed:16813573, PubMed:17478547, PubMed:19594707, PubMed:20679226, PubMed:23336935). The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane (By similarity). PEX12 also regulates PEX5 recycling by activating the E3 ubiquitin-protein ligase activity of PEX10 (By similarity). When PEX5 recycling is compromised, PEX12 stimulates PEX10-mediated polyubiquitination of PEX5, leading to its subsequent degradation (By similarity). SUBCELLULAR LOCATION: Peroxisome membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the pex2/pex10/pex12 family.


FUNCTION: Isochorismate synthase involved in the synthesis of salicylic acid (SA) required for both local and systemic acquired resistance (LAR and SAR) while SA synthesized through the phenylalanine ammonium lyase (PAL) pathway seems to potentiate plant cell death. Also involved in phylloquinone (vitamin K1) synthesis. Has no isochorismate pyruvate lyase (IPL) activity. SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the isochorismate synthase family.


FUNCTION: Activates erythroid-specific, globin gene expression. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the bZIP family. CNC subfamily.


FUNCTION: Has potent antibacterial activity against E.coli (ATCC 25922). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the beta-defensin family.


FUNCTION: Transporter that mediates the import of cysteine into melanosomes, thereby regulating skin/hair pigmentation. In melanosomes, cysteine import is required both for normal levels of cystine, the oxidized dimer of cysteine, and provide cysteine for the production of the cysteinyldopas used in pheomelanin synthesis, thereby regulating skin/hair pigmentation. Also catalyzes import of cysteine into lysosomes in non-pigmented cells. SUBCELLULAR LOCATION: Melanosome membrane; Multi-pass membrane protein Lysosome membrane; Multi- pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily.


FUNCTION: Affects cell viability at low temperatures. FUNCTION: Affects cell viability at low temperatures. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Plays a role in the regulation of cell expansion, root meristem patterning and auxin transport. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the ARG7 family.


FUNCTION: Plays a role in targeting the monocarboxylate transporters SLC16A1 and SLC16A7 to the cell membrane (By similarity). Plays a role in the outgrowth of motoneurons and in the formation of neuromuscular junctions. Following muscle denervation, promotes nerve terminal sprouting and the formation of additional acetylcholine receptor clusters at synaptic sites without affecting terminal Schwann cell number or morphology. Delays the retraction of terminal sprouts following re-innervation of denervated endplates. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein Synapse Note=Localizes to the neuromuscular junctions.


FUNCTION: In presence of calcium ions, it binds to surfactant phospholipids and contributes to lower the surface tension at the air- liquid interface in the alveoli of the mammalian lung and is essential for normal respiration. Enhances the expression of MYO18A/SP-R210 on alveolar macrophages. SUBCELLULAR LOCATION: Secreted Secreted, extracellular space, extracellular matrix Secreted, extracellular space, surface film. SIMILARITY: Belongs to the SFTPA family.


FUNCTION: May be involved in swimming motility.


FUNCTION: Catalyzes the cleavage of glutathione into 5-oxo-L-proline and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on other gamma-glutamyl peptides. SUBCELLULAR LOCATION: Cytoplasm, cytosol. SIMILARITY: Belongs to the gamma-glutamylcyclotransferase family. ChaC subfamily.


FUNCTION: Component of the chloroplast ribosome (chloro-ribosome), a dedicated translation machinery responsible for the synthesis of chloroplast genome-encoded proteins, including proteins of the transcription and translation machinery and components of the photosynthetic apparatus. SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the bacterial ribosomal protein bL17 family.


FUNCTION: NDH shuttles electrons from NAD(P)H:plastoquinone, via FMN and iron-sulfur (Fe-S) centers, to quinones in the photosynthetic chain and possibly in a chloroplast respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be plastoquinone. Couples the redox reaction to proton translocation, and thus conserves the redox energy in a proton gradient (By similarity). SUBCELLULAR LOCATION: Plastid, chloroplast thylakoid membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the complex I subunit 1 family.


FUNCTION: Possesses quercetin 3-O-glucosyltransferase and 7-O- glucosyltransferase activities in vitro. SIMILARITY: Belongs to the UDP-glycosyltransferase family.


FUNCTION: Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule. SIMILARITY: Belongs to the type II topoisomerase family. ParE type 1 subfamily.


FUNCTION: Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled repair (TCR) factor RAD26 fails to efficiently displace stalled RNA polymerase II. Also involved in telomere length regulation. Binds DNA. SUBCELLULAR LOCATION: Cytoplasm Nucleus Chromosome, telomere Note=During transcription stress, localizes to the nucleus following proteolytic cleavage by the proteasome. SIMILARITY: Belongs to the DEF1 family.


SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the L6 tetraspanin family.


FUNCTION: Controls the level of cAMP in yeast cells, together with the low-affinity cAMP phosphodiesterase (PDE1). SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.


FUNCTION: Catalyzes the transfer of a sulfur ion from a donor to cyanide or to other thiol compounds. Substrate preference is 3- mercaptopyruvate > thiosulfate. Involved in embryo and seed development. SUBCELLULAR LOCATION: Cytoplasm.


SIMILARITY: Belongs to the mimivirus R640 family.


FUNCTION: Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation. Represses RB1 transcription; this repression can be blocked by interaction with ZBTB49 isoform 3/ZNF509S1 (PubMed:25245946). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein family.


FUNCTION: Secreted, cytolytic toxin that forms pores in host membranes after proteolytic removal of a C-terminal propeptide, leading to destruction of the membrane permeability barrier and cell death. The pores are formed by transmembrane beta-strands and are approximately 3 nm in diameter. SUBCELLULAR LOCATION: Secreted Host cell membrane Note=Secreted as a soluble precursor. SIMILARITY: Belongs to the aerolysin family.


FUNCTION: Part of an ABC transporter complex involved in low-affinity glycine betaine uptake. Probably responsible for the translocation of the substrate across the membrane. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the binding-protein-dependent transport system permease family. CysTW subfamily.


FUNCTION: VIP causes vasodilation, lowers arterial blood pressure, stimulates myocardial contractility, increases glycogenolysis and relaxes the smooth muscle of trachea, stomach and gall bladder. FUNCTION: PHM-27 is a potent agonist of the calcitonin receptor CALCR, with similar efficacy as calcitonin (By similarity). PHI also causes vasodilation. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glucagon family.


FUNCTION: S-crystallins are structural components of squids and octopi eye lens. Contains relatively little if any GST activity. SIMILARITY: Belongs to the GST superfamily.


FUNCTION: Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (By similarity). May play a role during development (By similarity). SUBCELLULAR LOCATION: Nucleus, nucleolus Nucleus, nucleoplasm Cytoplasm Dynein axonemal particle Note=Mainly found in the nucleoplasm, with low levels detected in the cytoplasmic and chromatin fractions. SIMILARITY: Belongs to the WD repeat IPI3/WDR18 family.


FUNCTION: Converts cobyric acid to cobinamide by the addition of aminopropanol on the F carboxylic group. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the CobD/CbiB family.


FUNCTION: Involved in glycosylation steps downstream of mono-O-methyl- glycosyl-p-hydroxybenzoic acid derivative (p-HBAD I) and 2-O-methyl- rhamnosyl-phenolphthiocerol dimycocerosate (mycoside B) during the p- hydroxybenzoic acid derivatives (p-HBAD) and glycosylated phenolphthiocerol dimycocerosates (PGL) biosynthesis. FUNCTION: Involved in glycosylation steps downstream of mono-O-methyl- glycosyl-p-hydroxybenzoic acid derivative (p-HBAD I) and 2-O-methyl- rhamnosyl-phenolphthiocerol dimycocerosate (mycoside B) during the p- hydroxybenzoic acid derivatives (p-HBAD) and glycosylated phenolphthiocerol dimycocerosates (PGL) biosynthesis. SIMILARITY: Belongs to the glycosyltransferase 2 family.


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. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the TAF4 family.


FUNCTION: Putative acid-stable proteinase inhibitor. SUBCELLULAR LOCATION: Secreted.


FUNCTION: Catalyzes the degradation of L-methionine to alpha- ketobutyrate, methanethiol and ammonia. Exhibits a high activity toward L-methionine, L-ethionine, L-homocysteine and seleno-L-methionine, but not L-cysteine. Involved in an alternative cysteine biosynthesis pathway to the reverse trans-sulfuration pathway (methionine->homocysteine->cystathionine->cysteine) in which methanethiol is an intermediate. Mediates also an alternative isoleucine biosynthesis pathway in which 2-ketobutyrate is an intermediate. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the trans-sulfuration enzymes family.


FUNCTION: Effector that enhances P.infestans colonization of Nicotiana benthamiana leaves. SUBCELLULAR LOCATION: Secreted Host cytoplasm. SIMILARITY: Belongs to the RxLR effector family.


FUNCTION: Catalyzes the reduction of prostaglandin-ethanolamide H(2) (prostamide H(2)) to prostamide F(2alpha) with NADPH as proton donor. Also able to reduce prostaglandin H(2) to prostaglandin F(2alpha) (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytosol. SIMILARITY: Belongs to the peroxiredoxin-like PRXL2 family. Prostamide/prostaglandin F synthase subfamily.


FUNCTION: Key player in antiviral response. Induces expression of TLRs, including that of TLR3, TLR9 and TLR8a1, and that of cytosolic pattern recognition receptors, including RIGI, IFIH1/MDA5 and DHX58/LGP2. Also induces MX1 and its own expression. In the presence of intracellular IFNAR2 (iIFNAR2) and IFNAR1B, intracellular isoform 3 may mediate STAT1 and STAT2 phosphorylation and induction of EIF2AK2, MX1 and RSAD2. SUBCELLULAR LOCATION: [Isoform 1]: Secreted. SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, cytosol. SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm, cytosol. SIMILARITY: Belongs to the alpha/beta interferon family.


FUNCTION: Required for nuclear membrane fusion during karyogamy. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein Nucleus membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the KAR5 family.


SIMILARITY: To ORF5 in pFZ1.


SUBCELLULAR LOCATION: Cell inner membrane; Single-pass membrane protein Note=May be able to insert into the membrane in both orientations. Relies on YidC for insertion.


FUNCTION: Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation. Specifically binds the 5'- AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: sox5 and sox6 cooperatively bind with sox9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate sox9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes. Binds to the proximal promoter region of the myelin protein MPZ gene, and is thereby involved in the differentiation of oligodendroglia in the developing spinal tube. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Promotes the exchange of Ran(SPI1)-bound GDP by GTP. Involved in the control of mitosis. Regulates a variety of nuclear events, including mitotic check-point, chromosome decondensation and mRNA processing/transport (By similarity). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Acts as a ligand for C-C chemokine receptor CCR2 (By similarity). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions (By similarity). Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils (By similarity). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain (By similarity). Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.


FUNCTION: Required for genome encapsidation. Forms ribonucleoprotein complexes along with TGB1 helicase and viral RNA. SUBCELLULAR LOCATION: Virion. SIMILARITY: Belongs to the potexvirus capsid protein family.


FUNCTION: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the complex I subunit 4L family.


FUNCTION: Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (amyloid-beta precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex. Probably present in a minority of gamma-secretase complexes compared to APH1A. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the APH-1 family.


FUNCTION: Bifunctional nuclease with both RNase and DNase activities. Involved in basal defense response. Participates in abscisic acid- derived callose deposition following infection by a necrotrophic pathogen. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the bifunctional nuclease family.


FUNCTION: Acyl-ACP thioesterase involved in the production of fatty acids and beta-keto fatty acids. Can produce beta-keto fatty acids of medium chain (8:0 and 10:0) and small amounts of 8:0 fatty acid when expressed in a heterologous organism (E.coli). May play a role in suberin biosynthesis. SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the 4-hydroxybenzoyl-CoA thioesterase family.


FUNCTION: Histone lysine methyltransferase that specifically mono-, di-, and trimethylates 'Lys-37' of histone H3 to regulate sporulation. SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase superfamily.


FUNCTION: Protein kinase that acts downstream of the MPS1 MAPK cascade as a highly conservative signal modulator that dictates growth, conidiation and pathogenicity (PubMed:28424497). Phosphorylates HAT1 at 'Ser-8' to block its translocation from the nucleus to the cytoplasm where HAT1 positively regulates appressorium development and pathogenicity (PubMed:30776962). SUBCELLULAR LOCATION: Cytoplasm Note=Mainly localizes to the cytoplasm at the conidial stage. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.


FUNCTION: S-adenosyl-L-methionine-dependent and membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA) in proteins such as NIFK, myelin basic protein, histone H4, H2A and H2A/H2B dimer (PubMed:16051612, PubMed:17925405, PubMed:26876602, PubMed:26529540). Able to mono- and dimethylate EWS protein; however its precise role toward EWS remains unclear as it still interacts with fully methylated EWS (PubMed:18320585). SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side. SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT8 subfamily.


FUNCTION: Part of the ABC transporter complex TagGH involved in teichoic acids export. Responsible for energy coupling to the transport system. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein. SIMILARITY: Belongs to the ABC transporter superfamily. Teichoic acids exporter (TC 3.A.1.104.1) family.


FUNCTION: Plays a role in somitogenesis. Required for somite segregation and establishment of rostrocaudal polarity in somites (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ripply family.


FUNCTION: ATP-dependent RNA helicase involved in mRNA export from the nucleus. Rather than unwinding RNA duplexes, DDX19 functions as a remodeler of ribonucleoprotein particles, whereby proteins bound to nuclear mRNA are dissociated and replaced by cytoplasmic mRNA binding proteins. SUBCELLULAR LOCATION: Cytoplasm Nucleus, nucleoplasm Note=Associates with the nuclear pore complex cytoplasmic fibrils. SIMILARITY: Belongs to the DEAD box helicase family. DDX19/DBP5 subfamily.


FUNCTION: Plays a role in nucleocapsid assembly and serves an essential function during the final stages of the DNA packaging process. Participates in the processing of branched DNA molecules at the late stages of viral genome replication. SIMILARITY: Belongs to the 'phage' integrase family.


FUNCTION: Required for mitosis progression. Promotes the nucleation of microtubules from the spindle. SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome.


FUNCTION: Cytochrome P450 involved in the biosynthesis of the benzylisoquinoline alkaloid noscapine (PubMed:25485687, PubMed:27378283, PubMed:29610307). Converts (S)-1-hydroxy-N- methylcanadine to (13S,14R)-1,13-dihydroxy-N-methylcanadine (PubMed:25485687, PubMed:27378283). SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the cytochrome P450 family.


FUNCTION: ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand- specific manner. May regulate mitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters (PubMed:12198491, PubMed:15870080, PubMed:17420247, PubMed:8248235). Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein, helicase Twinkle (TWNK) and the large ribosomal subunit protein bL32m. bL32m is protected from degradation by LONP1 when it is bound to a nucleic acid (RNA), but TWNK is not (PubMed:17579211, PubMed:28377575). SUBCELLULAR LOCATION: Mitochondrion matrix. SIMILARITY: Belongs to the peptidase S16 family.


FUNCTION: Involved in the regulation of glucose homeostasis and lipid metabolism. FUNCTION: Involved in the regulation of glucose homeostasis and lipid metabolism. SUBCELLULAR LOCATION: Secreted.


FUNCTION: [Isoform 1]: Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner, with a preference for pyrimidines. Preferentially hydrolyzes UTP and TTP on UTP and TTP. AMP, ADP, ATP and UMP are not substrates. Preferentially activated by Ca(2+) over Mg(2+). FUNCTION: [Isoform 2]: Has a broad substrate specificity with the ability of cleaving all nucleotide di- and triphosphates with the exception of adenosine di- and triphosphate (ADP and ATP). Preferentially hydrolyzes CTP, UDP, CDP, GTP and GDP. Can use either Ca(2+) or Mg(2+) equally. SUBCELLULAR LOCATION: [Isoform 2]: Golgi apparatus membrane; Multi-pass membrane protein. SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasmic vesicle, autophagosome membrane; Multi-pass membrane protein Lysosome membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the GDA1/CD39 NTPase family.


FUNCTION: Catalyzes the double cyclization reaction which converts lycopene to beta-carotene and neurosporene to beta-zeacarotene. SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the lycopene cyclase family.


FUNCTION: EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP. SIMILARITY: Belongs to the EF-1-beta/EF-1-delta family.


FUNCTION: SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network. SUBCELLULAR LOCATION: Golgi apparatus membrane; Single- pass type IV membrane protein. SIMILARITY: Belongs to the syntaxin family.


FUNCTION: Catalyzes the reduction of a wide range of aldehydes into their corresponding alcohols. Has a strong preference for NADPH over NADH as the electron donor. Cannot use a ketone as substrate. Is a major source of NADPH-dependent aldehyde reductase activity in E.coli. The in vivo functions of YahK has yet to be determined. SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase family.


FUNCTION: May be involved in collagen fiber assembly. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix. SIMILARITY: Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.


SIMILARITY: Belongs to the GPATCH1 family.


FUNCTION: Required for efficient Cap- and IRES-mediated mRNA translation initiation. Not involved in the ribosome biogenesis (By similarity). SUBCELLULAR LOCATION: Cytoplasm Nucleus, nucleoplasm Nucleus envelope. SIMILARITY: Belongs to the ABC transporter superfamily. ABCF family. EF3 subfamily.


FUNCTION: This is one of three E.coli hydrogenases synthesized in response to different physiological conditions. HYD1 is believed to have a role in hydrogen cycling during fermentative growth. SUBCELLULAR LOCATION: Cell inner membrane; Single-pass type I membrane protein; Periplasmic side. SUBCELLULAR LOCATION: Cell inner membrane; Single-pass type I membrane protein; Periplasmic side. SIMILARITY: Belongs to the [NiFe]/[NiFeSe] hydrogenase small subunit family.


FUNCTION: Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm. SIMILARITY: Belongs to the eukaryotic initiation factor 4E family.


FUNCTION: Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. CGI121 acts as an allosteric effector that regulates the t(6)A activity of the complex. The EKC/KEOPS complex also promotes both telomere uncapping and telomere elongation. The complex is required for efficient recruitment of transcriptional coactivators. CGI121 is not required for tRNA modification (By similarity). SUBCELLULAR LOCATION: Nucleus Chromosome, telomere. SIMILARITY: Belongs to the CGI121/TPRKB family.


FUNCTION: Transcriptional activator that binds specifically to the DNA sequence 5'-[AG]CCGAC-3'. Binding to the C-repeat/DRE element mediates high salinity- and dehydration-inducible transcription (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the AP2/ERF transcription factor family. ERF subfamily.


FUNCTION: Catalyzes the NADPH-dependent reduction of glyoxylate and hydroxypyruvate (HP) into glycolate and glycerate. Mostly active in the presence of NADPH and glyoxylate. SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family. GyaR subfamily.


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


FUNCTION: Filament-forming cytoskeletal GTPase (Probable). Pro- apoptotic protein involved in LGR5-positive intestinal stem cell and Paneth cell expansion in the intestines, via its interaction with XIAP (By similarity). May also play a role in the regulation of cell fate in the intestine (By similarity). Positive regulator of apoptosis involved in hematopoietic stem cell homeostasis; via its interaction with XIAP (By similarity). Negative regulator of repair and hair follicle regeneration in response to injury, due to inhibition of hair follicle stem cell proliferation, potentially via its interaction with XIAP (By similarity). Plays an important role in male fertility and sperm motility (By similarity). During spermiogenesis, essential for the establishment of the annulus (a fibrous ring structure connecting the midpiece and the principal piece of the sperm flagellum) which is a requisite for the structural and mechanical integrity of the sperm (By similarity). Involved in the migration of cortical neurons and the formation of neuron leading processes during embryonic development (By similarity). Required for dopaminergic metabolism in presynaptic autoreceptors; potentially via activity as a presynaptic scaffold protein (By similarity). SUBCELLULAR LOCATION: Cytoplasm Cell projection, cilium, flagellum Cytoplasmic vesicle, secretory vesicle Cell projection, axon Cell projection, dendrite Perikaryon Synapse Note=In platelets, found in areas surrounding alpha-granules (By similarity). Found in the sperm annulus, a fibrous ring structure connecting the midpiece and the principal piece of the sperm flagellum (By similarity). Expressed and colocalized with SLC6A3 and SNCA in axon terminals, especially at the varicosities (By similarity). SIMILARITY: Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.


FUNCTION: As a component of the mitochondrial large ribosomal subunit, it plays a role in mitochondrial translation. Associates with mitochondrial RNA polymerase to activate transcription. SUBCELLULAR LOCATION: Mitochondrion matrix. SIMILARITY: Belongs to the bacterial ribosomal protein bL12 family.


FUNCTION: Plastidic transporter involved in the biosynthesis of aliphatic glucosinolates by translocating the biosynthetic intermediates of Met-derived glucosinolates across chloroplast membranes. Transports short chain (C2) alpha-keto acids, such as 4- methylsulfanyl-2-oxobutanoic acid, from the cytosol to the chloroplast where they are subjected to chain elongation cycles. Functions also in the transport of chain-elongated (C3 to C8) Met derivatives from the chloroplast to the cytosol. Does not seem to be involved in the transport of indole-derived glucosinolates. SUBCELLULAR LOCATION: Membrane; Multi- pass membrane protein Plastid, chloroplast envelope. SIMILARITY: Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.


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


FUNCTION: Snake venom serine protease that cleaves fibrinogen Aalpha chain (FGA), partially cleaves Bbeta chain (FGB) and has no activity on gamma chain. Is less potent than A1 and A2 alpha-fibrinogenases. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase S1 family. Snake venom subfamily.


FUNCTION: Transports viral genome to neighboring plant cells directly through plasmosdesmata, without any budding. The movement protein allows efficient cell to cell propagation, by bypassing the host cell wall barrier. Displays an RNA-binding activity (By similarity).


FUNCTION: Involved in acetylcholine transport into synaptic vesicles. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. Vesicular transporter family.


FUNCTION: Contributes to the transparency and refractive index of the lens. May act as a chaperone, preventing aggregation of various proteins under a wide range of stress conditions. SUBCELLULAR LOCATION: Cytoplasm Nucleus Note=Translocates to the nucleus during heat shock. SIMILARITY: Belongs to the small heat shock protein (HSP20) family.


FUNCTION: Part of a complex that catalyzes the reversible cleavage of acetyl-CoA, allowing autotrophic growth from CO(2). The alpha-epsilon subcomponent functions as a carbon monoxide dehydrogenase. The precise role of the epsilon subunit is unclear; it may have a stabilizing role within the alpha(2)epsilon(2) component and/or be involved in electron transfer to FAD during a potential FAD-mediated CO oxidation. SIMILARITY: Belongs to the CdhB family.


FUNCTION: It is involved in synaptogenesis and promotes excitatory synapse differentiation (PubMed:27273464, PubMed:27812321). Enhances neuronal dendrite outgrowth (PubMed:16224024, PubMed:19640509). SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein Secreted Synapse. SIMILARITY: Belongs to the SLITRK family.


FUNCTION: Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current (By similarity). Plays a role in shifting voltage dependencies of activation and inactivation of the channel (By similarity). May modulate G protein inhibition (By similarity). May contribute to beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force (PubMed:36424916). Involved in membrane targeting of the alpha-1 subunit CACNA1C (PubMed:17525370). SUBCELLULAR LOCATION: Cell membrane, sarcolemma; Peripheral membrane protein; Cytoplasmic side. SIMILARITY: Belongs to the calcium channel beta subunit family.


FUNCTION: IFN-induced antiviral protein which acts as an inhibitor of cellular as well as viral processes, cell migration, proliferation, signaling, and viral replication. Enhances MAVS-mediated host antiviral responses by serving as an adapter bridging TBK1 to MAVS which leads to the activation of TBK1 and phosphorylation of IRF3 and phosphorylated IRF3 translocates into nucleus to promote antiviral gene transcription. Exhibits an antiproliferative activity via the up-regulation of cell cycle negative regulators CDKN1A/p21 and CDKN1B/p27. Normally, CDKN1B/p27 turnover is regulated by COPS5, which binds CDKN1B/p27 in the nucleus and exports it to the cytoplasm for ubiquitin-dependent degradation. IFIT3 sequesters COPS5 in the cytoplasm, thereby increasing nuclear CDKN1B/p27 protein levels. Up-regulates CDKN1A/p21 by down-regulating MYC, a repressor of CDKN1A/p21. Can negatively regulate the apoptotic effects of IFIT2 (By similarity). SUBCELLULAR LOCATION: Cytoplasm Mitochondrion. SIMILARITY: Belongs to the IFIT family.


SUBCELLULAR LOCATION: Cell inner membrane; Single-pass membrane protein. SIMILARITY: Belongs to the peptidase S12 family. YfeW subfamily.


FUNCTION: Sesquiterpene cyclase catalyzing the production of beta- farnesene from farnesyl diphosphate. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the terpene synthase family.


FUNCTION: Reversible hydration of carbon dioxide. Its role in saliva is unknown. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the alpha-carbonic anhydrase family.


FUNCTION: Adds the second galactose to the lacto-N-tetraose chain in lipooligosaccharide (LOS). SIMILARITY: Belongs to the glycosyltransferase 25 family.


FUNCTION: Mediates a global response to leucine. Exogenous leucine affects the expression of a number of different operons; lrp mediates this effect for at least some of these operons. For example it is regulator of the branched-chain amino acid transport genes (By similarity).


FUNCTION: Chemotactic for monocytes and T-lymphocytes. Binds to CXCR3 (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the intercrine alpha (chemokine CxC) family.


FUNCTION: Inhibitor of serine proteases. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the serpin family.


SIMILARITY: Belongs to the intradiol ring-cleavage dioxygenase family.


FUNCTION: Essential for proper morphogenesis of the vacuole. May exist as structural reinforcement on the surface of the vacuolar membrane and be required for maintenance against rupture by osmotic pressure. SUBCELLULAR LOCATION: Vacuole.


FUNCTION: Accelerates GTPase activity of RHOA and CDC42, but not RAC1. Stimulates the hydrolysis of phosphatidylinositol 4,5-bisphosphate by PLCD1 (By similarity). SUBCELLULAR LOCATION: Cell junction, focal adhesion.


FUNCTION: Represses the transcription of fabB, involved in unsaturated fatty acid (UFA) biosynthesis. By controlling UFA production, FabR directly influences the physical properties of the membrane bilayer. SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Catalytic component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates the snRNAs 3' cleavage. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex. SUBCELLULAR LOCATION: Nucleus Cytoplasm. SIMILARITY: Belongs to the metallo-beta-lactamase superfamily. RNA- metabolizing metallo-beta-lactamase-like family. INTS11 subfamily.


FUNCTION: Binds to plexin family members and plays an important role in the regulation of developmental processes. Required for normal cardiovascular development during embryogenesis. Functions as attractant for growing axons, and thereby plays an important role in axon growth and axon guidance (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the semaphorin family.


FUNCTION: Histones H3 and H4 chaperone involved in the nucleosome formation and heterochromatin silencing. Required for the deposition of H3K56ac-carrying H3-H4 complex onto newly-replicated DNA. Plays a role in the transcriptional regulation of the cell-cycle dependent histone genes by directly recruiting the SWI/SNF and RSC chromatin remodeling complexes to the histone genes in a cell cycle dependent manner. In cooperation with HIR and ASF1, creates a repressive structure at the core histone gene promoter and contributes to their repression outside of S phase. Involved in regulation of Ty1 transposition. SUBCELLULAR LOCATION: Nucleus Chromosome Note=Localizes to the promoter region of histones HTA1-HTB1, HHT1-HHF1, and HHT2-HHF2,. SIMILARITY: Belongs to the RTT106 family.


FUNCTION: Required for synthesis of pyridoxal-5-phosphate from vitamin B6. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the pyridoxine kinase family.


FUNCTION: Fluoride-specific ion channel (PubMed:23991286, PubMed:26344196). Important for reducing fluoride concentration in the cell, thus reducing its toxicity (By similarity). Is highly specific for fluoride ions and cannot transport chloride ions (PubMed:23991286). SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein Note=Exhibits a dual-topology architecture: the two subunits are oriented antiparallel to each other within the membrane. SIMILARITY: Belongs to the fluoride channel Fluc/FEX (TC 1.A.43) family.


FUNCTION: Mediates visceral muscle contractile activity (myotropic activity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the pyrokinin family.


SIMILARITY: Belongs to the beta-lactamase family.


FUNCTION: Mitochondrial iron transporter that mediates iron uptake. Probably required for heme synthesis of hemoproteins and Fe-S cluster assembly. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.


FUNCTION: Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (By similarity). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (By similarity). The presence of selenocysteine (Sec) versus Cys at the active site is essential for life: it provides resistance to overoxidation and prevents cells against ferroptosis (By similarity). The presence of Sec at the active site is also essential for the survival of a specific type of parvalbumin-positive interneurons, thereby preventing against fatal epileptic seizures (By similarity). May be required to protect cells from the toxicity of ingested lipid hydroperoxides (By similarity). Required for normal sperm development and male fertility (By similarity). Essential for maturation and survival of photoreceptor cells (By similarity). Plays a role in a primary T-cell response to viral and parasitic infection by protecting T-cells from ferroptosis and by supporting T-cell expansion (By similarity). Plays a role of glutathione peroxidase in platelets in the arachidonic acid metabolism (By similarity). Reduces hydroperoxy ester lipids formed by a 15-lipoxygenase that may play a role as down- regulator of the cellular 15-lipoxygenase pathway (By similarity). SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm. SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion. SIMILARITY: Belongs to the glutathione peroxidase family.


FUNCTION: Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors. Active directional transport is assured by both, a Phe-Gly (FG) repeat affinity gradient for these transport factors across the NPC and a transport cofactor concentration gradient across the nuclear envelope (GSP1 and GSP2 GTPases associated predominantly with GTP in the nucleus, with GDP in the cytoplasm). SUBCELLULAR LOCATION: Nucleus, nuclear pore complex Nucleus membrane; Peripheral membrane protein; Cytoplasmic side Nucleus membrane; Peripheral membrane protein; Nucleoplasmic side Note=Symmetric distribution.


FUNCTION: Member of the two-component regulatory system RpfG/RpfC, which is involved in the perception and response to the diffusible signaling factor (DSF), which is essential for cell-cell signaling (PubMed:11123673, PubMed:12960398). Detection of DSF leads to the positive regulation of biofilm dispersal and the production of virulence factors (PubMed:12960398). Activated RpfG degrades cyclic di- GMP to GMP, leading to the activation of Clp, a global transcriptional regulator that regulates a large set of genes in DSF pathway. May also directly control genes involved in biofilm dispersal (PubMed:15158198, PubMed:17378922, PubMed:20231439). SUBCELLULAR LOCATION: Cytoplasm Note=Localizes predominantly at the cell poles.


FUNCTION: The specificity (S) subunit of a type I restriction enzyme; this subunit dictates DNA sequence specificity. The M and S subunits together form a methyltransferase (MTase) that methylates adenosines in the sequence 5'-RAACN(5)TAG-3'. Methylation protects against cleavage by HindI (PubMed:4591672) (Probable). In the presence of the R subunit the complex can also act as an endonuclease, binding to the same target sequence but cutting the DNA some distance from this site. Whether the DNA is cut or modified depends on the methylation state of the target sequence. When the target site is unmodified, the DNA is cut. When the target site is hemimethylated, the complex acts as a maintenance MTase modifying the DNA so that both strands become methylated (Probable) (PubMed:12654995). After locating a non-methylated recognition site, the enzyme complex serves as a molecular motor that translocates DNA in an ATP-dependent manner until a collision occurs that triggers cleavage (By similarity). SIMILARITY: Belongs to the type-I restriction system S methylase family.


FUNCTION: Essential for the maintenance of cell size and integrity in response to osmotic stress. SIMILARITY: Belongs to the PPP phosphatase family. PP-Z subfamily.


FUNCTION: Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins (By similarity). SIMILARITY: Belongs to the prefoldin subunit alpha family.


FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5- dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Cell projection, dendrite Cell projection, axon Cytoplasmic vesicle Membrane, caveola Presynapse. SIMILARITY: Belongs to the G-protein coupled receptor 1 family.


FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. Participates in the regulation of transepithelial sodium transport in renal cells. May be involved in cell growth arrest. FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination (By similarity). Participates in the regulation of transepithelial sodium transport in renal cells. May be involved in cell growth arrest. FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. Participates in the regulation of transepithelial sodium transport in renal cells. May be involved in cell growth arrest. SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Shuttles between the nucleus and cytoplasm in a IPO11-dependent manner. SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Shuttles between the nucleus and cytoplasm in a IPO11-dependent manner. SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between the nucleus and cytoplasm in a IPO11-dependent manner. SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.


SUBCELLULAR LOCATION: Plastid, chloroplast thylakoid membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the PsaG/PsaK family.


FUNCTION: 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. SUBCELLULAR LOCATION: Nucleus Chromosome, centromere, kinetochore Note=Associated with kinetochores (PubMed:12408861). SIMILARITY: Belongs to the NKP2 family.


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


FUNCTION: Probably part of an ABC transporter complex. Probably responsible for the translocation of the substrate across the membrane (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the binding-protein-dependent transport system permease family. FecCD subfamily.


FUNCTION: Involved in 'Cys-type' sulfatase maturation under anaerobic conditions. Catalyzes the post-translational modification of cysteine ('Cys-51' in the arylsulfatase CPF_0221) into 3-oxoalanine (also known as C(alpha)-formylglycine (FGly)), by a free radical chemical mechanism initiated via the reductive cleavage of S-adenosyl-L-methionine (SAM) (PubMed:18408004, PubMed:16766528, PubMed:17335281, PubMed:19489556, PubMed:23477283). Is also able to oxidize a serine residue in a synthetic substrate to FGly in vitro, and in a serine variant of a Cys- type sulfatase in vivo, but this activity is not physiological (PubMed:18408004, PubMed:23477283). Converts threonyl peptides to the corresponding ketone product, and also allo-threonyl peptides, but with a significantly reduced efficiency (PubMed:23477283). SIMILARITY: Belongs to the radical SAM superfamily. Anaerobic sulfatase-maturating enzyme family.


FUNCTION: Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems. FUNCTION: Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems. SIMILARITY: Belongs to the iron/manganese superoxide dismutase family.


FUNCTION: Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. May inhibit cell growth (By similarity). Regulates cranial neural crest migration. Acts together with prickle1 to control axial elongation (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cell cortex Cell junction, focal adhesion Note=Detected along actin stress fibers. SIMILARITY: Belongs to the prickle / espinas / testin family.


FUNCTION: O-methyltransferase that catalyzes the conversion of mycinamicin III to mycinamicin IV in the biosynthesis of mycinamicin, a 16-membered macrolide antibiotic. SIMILARITY: Belongs to the methyltransferase TylF/MycF family.


FUNCTION: Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta- D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose. Plays a central role in the degradation of complex lipids and the turnover of cellular membranes. Through the production of ceramides, participates in the PKC-activated salvage pathway of ceramide formation. Catalyzes the glucosylation of cholesterol, through a transglucosylation reaction where glucose is transferred from GlcCer to cholesterol. GlcCer containing mono- unsaturated fatty acids (such as beta-D-glucosyl-N-(9Z-octadecenoyl)- sphing-4-enine) are preferred as glucose donors for cholesterol glucosylation when compared with GlcCer containing same chain length of saturated fatty acids (such as beta-D-glucosyl-N-octadecanoyl-sphing-4- enine). Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl 3-beta-D- glucoside to ceramide. Can also hydrolyze cholesteryl 3-beta-D- glucoside producing glucose and cholesterol. Catalyzes the hydrolysis of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N- acylsphing-4-enine), as well as the transfer of galactose between GalCers and cholesterol in vitro, but with lower activity than with GlcCers. Contrary to GlcCer and GalCer, xylosylceramide/XylCer (such as beta-D-xyosyl-(1<->1')-N-acylsphing-4-enine) is not a good substrate for hydrolysis, however it is a good xylose donor for transxylosylation activity to form cholesteryl 3-beta-D-xyloside. SUBCELLULAR LOCATION: Lysosome membrane; Peripheral membrane protein; Lumenal side Note=Interaction with saposin-C promotes membrane association. Targeting to lysosomes occurs through an alternative MPR-independent mechanism via SCARB2. SIMILARITY: Belongs to the glycosyl hydrolase 30 family.


FUNCTION: Transcriptional factor that binds to the consensus sequence 5'-[GT][AG][AGT]GGGG-3' and acts as a repressor of autophagy. Specifically represses expression of genes involved in autophagy and lysosome biogenesis/function such as MAP1LC3B, ULK1 or WIPI2. Associates with chromatin at the ITGB4 and VEGF promoters (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Mainly localizes in the nucleus. Under starvation conditions translocates to the cytoplasm, allowing expression of target genes involved in autophagy and lysosome biogenesis/function (By similarity). SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein family.


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


FUNCTION: Catalyzes the hydrolysis of L-arginine to urea and L- ornithine. The latter can be utilized in the urea cycle or as a precursor for the synthesis of both polyamines and proline (By similarity). SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the arginase family.


FUNCTION: A potent inhibitor of RNA polymerase (RNAP) probably involved in viral defense. Destabilizes the transcription pre-initiation complex of TBP, TFB, DNA and RNAP, inhibits abortive transcription initiation, productive initiation and transcription elongation. Increases the RNAP KM for NTPs about 50-fold. Overexpression of TFS1-tip4 (TFS1 with the active tip of this protein, phenocopies this protein) in S.acidocaldarius MW001 leads to severe growth inhibition (PubMed:29203770). When bound to RNAP induces conformational changes that widen the DNA-binding channel, probably destabilizing the interaction of DNA with RNAP (PubMed:34535646). SIMILARITY: Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.


FUNCTION: Transcriptional repressor which negatively regulates transcription of FYV5 by binding to the promoter on the sense strand. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ADF1 family.


FUNCTION: Assembles to form an icosahedral capsid. SUBCELLULAR LOCATION: Virion.


FUNCTION: Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM (By similarity). In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and is cytotoxic for a wide range of tumor cells in vitro and in vivo. SUBCELLULAR LOCATION: Secreted Membrane Note=The homotrimer is secreted. The heterotrimer is membrane- associated. SIMILARITY: Belongs to the tumor necrosis factor family.


FUNCTION: Part of the UhpABC signaling cascade that controls the expression of the hexose phosphate transporter UhpT. Activates the transcription of the uhpT gene. Acts by binding specifically to the uhpT promoter region. FUNCTION: Part of the UhpABC signaling cascade that controls the expression of the hexose phosphate transporter UhpT. Activates the transcription of the uhpT gene. Acts by binding specifically to the uhpT promoter region. SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport across cell membranes. Appears to be the principal fatty acid transporter in small intestinal enterocytes. Also functions as an acyl-CoA ligase catalyzing the ATP- dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake (By similarity). Plays a role in the formation of the epidermal barrier. Required for fat absorption in early embryogenesis (By similarity). Probably involved in fatty acid transport across the blood barrier (By similarity). Indirectly inhibits RPE65 via substrate competition and via production of VLCFA derivatives like lignoceroyl-CoA. Prevents light-induced degeneration of rods and cones (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Involved in the organization of myofibers. Together with KRT8, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle (By similarity). SIMILARITY: Belongs to the intermediate filament family.


FUNCTION: Part of the ABC transporter complex MalEFGK involved in maltose/maltodextrin import. Binds maltose and higher maltodextrins such as maltotriose. FUNCTION: Part of the ABC transporter complex MalEFGK involved in maltose/maltodextrin import. Binds maltose and higher maltodextrins. SUBCELLULAR LOCATION: Periplasm. SUBCELLULAR LOCATION: Periplasm. SIMILARITY: Belongs to the bacterial solute-binding protein 1 family.


FUNCTION: Receptor for transcobalamin saturated with cobalamin (TCbl) (PubMed:18779389). Plays an important role in cobalamin uptake (PubMed:18779389, PubMed:20524213). Plasma membrane protein that is expressed on follicular dendritic cells (FDC) and mediates interaction with germinal center B cells (PubMed:10727470). Functions as costimulator to promote B cell responses to antigenic stimuli; promotes B cell differentiation and proliferation (PubMed:10727470, PubMed:11418631). Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC) (PubMed:11418631). CD320 augments the proliferation of PC precursors generated by IL-10 (PubMed:11418631). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.


FUNCTION: Putative aminopeptidase. SIMILARITY: Belongs to the peptidase M42 family.


FUNCTION: May be involved in a signaling pathway during male germ cell development or mature sperm function. SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.


FUNCTION: Component of the SWR1 complex which mediates the ATP- dependent exchange of histone H2A for the H2A variant HZT1 leading to transcriptional regulation of selected genes by chromatin remodeling. Involved in chromosome stability (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the SWC3 family.


FUNCTION: May associate with CadN and participate in the transmission of developmental information. Can associate with alpha-catenin. Accumulates through wg signaling; arm function in wg signal transduction is required early in development for determination of neuroblast fate. Arm and Abl proteins function cooperatively at adherens junctions in both the CNS and epidermis (By similarity). SUBCELLULAR LOCATION: Cytoplasm Cell membrane; Peripheral membrane protein; Cytoplasmic side Cell junction, adherens junction Note=Inner surface of cell membrane and adherens junction. SIMILARITY: Belongs to the beta-catenin family.


FUNCTION: Involved in protein N-glycosylation. Essential for the second step of the dolichol-linked oligosaccharide pathway (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum. SIMILARITY: Belongs to the glycosyltransferase 28 family.


FUNCTION: Heavy-metal-binding protein. Binds cadmium. May be involved in cadmium transport and play a role in cadmium detoxification. SUBCELLULAR LOCATION: Membrane. SIMILARITY: Belongs to the HIPP family.


FUNCTION: Does not function as a hemocyanin. SIMILARITY: Belongs to the tyrosinase family. Hemocyanin subfamily.


FUNCTION: Component of the replication protein A complex (RPA) required for DNA recombination, repair and replication. The activity of RPA is mediated by single-stranded DNA binding and protein interactions. Plays an essential role in meiotic and somatic DNA repair, but is dispensable for DNA replication and homologous recombination. Is essential for normal progression through meiosis in pollen mother cells. Is involved in repair of double-strand DNA breaks (DSBs) induced by genotoxic stresses. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the replication factor A protein 1 family.


FUNCTION: Sterigmatocystin 8-O-methyltransferase; part of the gene cluster that mediates the biosynthesis of aflatoxins, a group of polyketide-derived furanocoumarins, and part of the most toxic and carcinogenic compounds among the known mycotoxins (PubMed:8434913, PubMed:15006741). The four major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741). Within the aflatoxin pathway, the O-methyltransferase aflP uses both sterigmatocystin (ST) and dihydrosterigmatocystin (DHST) as substrates to yield O- methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin (DHOMST), respectively (PubMed:8434913). The biosynthesis of aflatoxins begins with the norsolorinic acid synthase aflC that combines a hexanoyl starter unit produced by the fatty acid synthase aflA/aflB and 7 malonyl-CoA extender units to synthesize the precursor NOR. The second step is the conversion of NOR to averantin and requires the norsolorinic acid ketoreductase aflD, which catalyzes the dehydration of norsolorinic acid to form (1'S)-averantin. The norsolorinic acid reductases aflE and aflF may also play a role in the conversion of NOR to AVN. The cytochrome P450 monooxygenase aflG then catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN). The next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by aflK that plays a dual role in the pathway, as a 5'- oxoaverantin cyclase that mediates conversion of 5'-oxoaverantin, as well as a versicolorin B synthase in a later step in the pathway. The averufin oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal acetate (VHA). VHA is then the substrate for the versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL). Versicolorin B synthase aflK then converts VAL to versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which is required for DNA- binding, thus giving to aflatoxin its activity as a mutagen. Then, the activity of the versicolorin B desaturase aflL leads to versicolorin A (VERA). A branch point starts from VERB since it can also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins B1 and G1, and DMDHST for aflatoxins B2 and G2. Next, the versicolorin reductase aflM and the cytochrome P450 monooxygenase aflN are involved in conversion of VERA to demethylsterigmatocystin (DMST). AflX and aflY seem also involved in this step, through probable aflX-mediated epoxide ring-opening step following versicolorin A oxidation and aflY-mediated Baeyer-Villiger oxidation required for the formation of the xanthone ring. The methyltransferase aflO then leads to the modification of DMST to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin (DHST). Both ST and DHST are then substrates of the O-methyltransferase aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O- methylsterigmatocystin (DHOMST), respectively. Finally OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2, via the action of several enzymes including O-methylsterigmatocystin oxidoreductase aflQ, the cytochrome P450 monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase nadA which is specifically required for the synthesis of AFG1 (PubMed:15006741). SUBCELLULAR LOCATION: Cytoplasm Vacuole. SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-independent O-methyltransferase family. COMT subfamily.


SIMILARITY: Belongs to the KNR4/SMI1 family.


FUNCTION: Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. May have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the heparin-binding growth factors family.


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


FUNCTION: Interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, D-loops, replication forks, nicked Holliday junctions and also intact Holliday junctions with a reduced efficiency. May be required in mitosis for the processing of stalled or collapsed replication fork intermediates. Plays a role in DNA repair and in genotoxic stress-induced homologous recombination (HR) in somatic cells. Mediates a subset of meiotic recombination events that are insensitive to crossover interference. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the EME1/MMS4 family.


FUNCTION: A P subtype restriction enzyme that recognizes the double- stranded sequence 5'-TCGA-3' and cleaves after T-1.


FUNCTION: Sesquiterpene synthase involved in the production after herbivore attack of a blend of volatiles that attracts natural enemies of herbivores (PubMed:15075399, PubMed:21607717). Converts farnesyl diphosphate to sesquithujene, (S)-beta-bisabolene, (Z)-alpha- bergamotene, sesquisabinene B and several minor products (PubMed:25940560, PubMed:15075399, PubMed:21607717). Can also act in vitro as a monoterpene synthase, converting geranyl diphosphate to (S)- (-)-limonene, beta-myrcene and 11 other monoterpenes (PubMed:25940560, PubMed:15075399). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the terpene synthase family.


FUNCTION: G-protein coupled receptor (GPCR) that forms a heterodimer with daf-38 to control dauer formation and behavior (PubMed:22665789, PubMed:23509272). Receptor for the ascaroside pheromone ascr#2 (PubMed:22665789). Required for the response to dauer inducing pheromones, specifically the ascaroside ascr#2 (PubMed:22665789, PubMed:23509272). May serve neuronal specific roles in response to ascr#2 with expression in ASI neurons controlling dauer formation in larvae, and expression in ASK neurons playing a role in longevity and hermaphrodite repulsion (PubMed:22665789, PubMed:23509272). May function upstream of the daf-11, daf-7 and daf-2 signaling pathways (PubMed:22665789). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Cell projection, cilium Golgi apparatus Note=Localizes to the cell membrane in the presence of daf-38, but localizes to the Golgi apparatus in the absence of daf-38. SIMILARITY: Belongs to the G-protein coupled receptor 1 family.


FUNCTION: Acyltransferase that catalyzes the formation of ester bonds between fatty alcohols and fatty acyl-CoAs to form wax monoesters (PubMed:15220349, PubMed:15671038, PubMed:16106050, PubMed:28420705). Shows a preference for medium chain acyl-CoAs from C12 to C16 in length and fatty alcohols shorter than C20, as the acyl donors and acceptors, respectively (PubMed:15220349, PubMed:15671038). Also possesses acyl- CoA retinol acyltransferase (ARAT) activity that catalyzes 11-cis- specific retinyl ester synthesis (PubMed:16106050, PubMed:24799687). Shows higher catalytic efficiency toward 11-cis-retinol versus 9-cis- retinol, 13-cis-retinol, and all-trans-retinol substrates (PubMed:24799687). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the diacylglycerol acyltransferase family.


FUNCTION: Forms part of the ribosomal stalk, playing a central role in the interaction of the ribosome with GTP-bound translation factors (such as IF-2, EF-Tu, EF-G and RF3). SIMILARITY: Belongs to the universal ribosomal protein uL10 family.


FUNCTION: Neurophysin 2 specifically binds vasopressin. FUNCTION: Vasopressin has a direct antidiuretic action on the kidney, it also causes vasoconstriction of the peripheral vessels. Acts by binding to vasopressin receptors (V1bR/AVPR1B, V1aR/AVPR1A, and V2R/AVPR2) (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the vasopressin/oxytocin family.


FUNCTION: Catalyzes the synthesis of ADP-glucose, a sugar donor used in elongation reactions on alpha-glucans. SIMILARITY: Belongs to the bacterial/plant glucose-1-phosphate adenylyltransferase family.


FUNCTION: Relaxes both positive and negative superturns and exhibits a strong decatenase activity. SIMILARITY: Belongs to the TOP6B family.


FUNCTION: Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. This receptor is a possible mediator of the immunomodulation properties of melanocortins. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 1 family.


FUNCTION: Involved in the biosynthesis of cannabinoids-related terpenophenolic natural products, which have pharmacological activity (PubMed:22353623). Acyl-activating enzyme that catalyzes the conversion of hexanoic acid to hexanoyl-CoA, precursor of the cannabinoid pathway (PubMed:22353623). Can also activate other fatty acids including heptanoate, octanoate and nonanoate (PubMed:22353623). SUBCELLULAR LOCATION: Cytoplasm, cytosol Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Probable GTPase-activating protein which stimulates the GTP hydrolysis rate by GYP5 of YPT1 and SEC4. Involved in ER to Golgi trafficking and polarized exocytosis. SUBCELLULAR LOCATION: Cytoplasm Bud Bud neck. SIMILARITY: Belongs to the GYP5 family.


FUNCTION: This protein is one of many from the eggshell of the silk moth. SIMILARITY: Belongs to the chorion protein family.


FUNCTION: Dehydratase; part of the gene cluster that mediates the biosynthesis of ustilaginoidins, dimeric gamma-naphthopyrones isolated from different fungal species (PubMed:31050129). The first step in the biosynthesis of ustilaginoidins is the production of gamma- naphthopyrone precursor YWA1 by the non-reducing polyketide synthase ustP, via condensation of one acetyl-CoA starter unit with 6 malonyl- CoA units (PubMed:31050129). YWA1 is then probably substrate of the ustZ to yield norrubrofusarin via a dehydration reaction (Probable). A key enzyme in the biosynthetic pathway is the laccase ustL, which catalyzes the oxidative dimerization of norrubrofusarin to ustilaginoidin A (PubMed:31050129). It can produce the M- and P- atropisomers in varying amounts, depending on the reaction conditions (PubMed:31050129). For the biosynthesis of 3-methylustilaginoid in derivatives such as chaetochromin A, a methylated derivative of YWA1 is required (Probable). The C-methylation is considered to be catalyzed by ustM, the phosphopantetheine attachment site of which indicates that it acts on the growing polyketide chain before release of the product (Probable). For the biosynthesis of chaetochromin A, it is assumed that saturation of the D2 double bond takes place before dimerization, and is probably catalyzed by an external reductase because no candidate gene was identified within the cluster (Probable). SIMILARITY: Belongs to the tpcK family.