FUNCTION: Transcription factor that plays an essential role in anti- viral immunity. It mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. IRF9/ISGF3G associates with the phosphorylated STAT1:STAT2 dimer to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the IRF family.


FUNCTION: Inhibitor of E2F-dependent transcription (PubMed:9689056, PubMed:9704927, PubMed:9501179). Binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' (PubMed:9501179). Has a preference for the 5'-TTTCCCGC-3' E2F recognition site (PubMed:9501179). E2F6 lacks the transcriptional activation and pocket protein binding domains (PubMed:9704927, PubMed:9501179). Appears to regulate a subset of E2F-dependent genes whose products are required for entry into the cell cycle but not for normal cell cycle progression (PubMed:9689056, PubMed:9501179). Represses expression of some meiosis-specific genes, including SLC25A31/ANT4 (By similarity). May silence expression via the recruitment of a chromatin remodeling complex containing histone H3-K9 methyltransferase activity. Overexpression delays the exit of cells from the S-phase (PubMed:9501179). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the E2F/DP family.


FUNCTION: Probably mediates the hydrolysis of some nucleoside diphosphate derivatives. SIMILARITY: Belongs to the Nudix hydrolase family. PCD1 subfamily.


FUNCTION: 7-dehydrocholesterol reductase of the cholesterol biosynthetic pathway reducing the C7-C8 double bond of cholesta-5,7- dien-3beta-ol (7-dehydrocholesterol/7-DHC) and cholesta-5,7,24-trien- 3beta-ol, two intermediates in that pathway. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ERG4/ERG24 family.


FUNCTION: Involved in cell adhesion and establishing epithelial cell polarity. FUNCTION: This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. Plays a role in innate immunity by enhancing virus-triggered induction of interferons (IFNs) and interferon stimulated genes (ISGs). Mechanistically, enhances the ubiquitination of TRAF3 and TRAF6 as well as the phosphorylation of TAK1 and TBK1. SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein Apical cell membrane; Single-pass type II membrane protein Cell membrane, sarcolemma Note=Colocalizes with OBSCN at the intercalated disk and sarcolemma in cardiomyocytes. Localizes in long striations at the level of Z and M lines. SIMILARITY: Belongs to the X(+)/potassium ATPases subunit beta family.


FUNCTION: Catalyzes the hydrolytic deamination of adenosine and 2- deoxyadenosine. SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. Adenosine deaminase subfamily.


FUNCTION: Binds with high affinity to muscular (alpha-1/CHRNA1) and neuronal (alpha-7/CHRNA7) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the snake three-finger toxin family. Long-chain subfamily. Type II alpha-neurotoxin sub-subfamily.


FUNCTION: Extracellular signaling peptide that may regulate primary root growth rate and systemic nitrogen (N)-demand signaling. SUBCELLULAR LOCATION: [C-terminally encoded peptide 10.3]: Secreted, extracellular space, apoplast Note=Accumulates in xylem sap. SUBCELLULAR LOCATION: [C-terminally encoded peptide 10.2]: Secreted, extracellular space, apoplast Note=Accumulates in xylem sap. SUBCELLULAR LOCATION: [C-terminally encoded peptide 10.1]: Secreted, extracellular space, apoplast Note=Accumulates in xylem sap. SIMILARITY: Belongs to the C-terminally encoded plant signaling peptide (CEP) family.


FUNCTION: May have GTPase activity. May also bind and hydrolyze ATP. May function as chaperone (By similarity). Likely to have a role in propionyl-CoA and adenosylcobalamin metabolism. SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the SIMIBI class G3E GTPase family. ArgK/MeaB subfamily.


SIMILARITY: To E.coli YfaT and P.aeruginosa PA4490.


FUNCTION: Lysosomal transporter which is essential for liver homeostasis. Required to maintain stability and lysosomal localization of GLMP. SUBCELLULAR LOCATION: Lysosome membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily.


FUNCTION: Global transcription factor that controls the expression of over 100 target genes in response to anoxia. It facilitates the adaptation to anaerobic growth conditions by regulating the expression of gene products that are involved in anaerobic energy metabolism. When the terminal electron acceptor, O(2), is no longer available, it represses the synthesis of enzymes involved in aerobic respiration and increases the synthesis of enzymes required for anaerobic respiration (By similarity). SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Required for the processing of the 27S pre-rRNA. SUBCELLULAR LOCATION: Nucleus, nucleolus. SIMILARITY: Belongs to the EBP2 family.


FUNCTION: ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (By similarity). Cycles between the cytoplasmic-open state (c- state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family.


FUNCTION: Involved in the biosynthesis of the compatible solute mannosylglucosylglycerate through a phosphorylating pathway. Catalyzes the dephosphorylation of mannosylglucosyl-3-phosphoglycerate (MGPG) to mannosylglucosylglycerate (MGG). Can also dephosphorylate UDP-glucose, ADP-glucose, GDP-mannose, glucosyl-3-phosphoglycerate (GPG), mannosyl- 3-phosphoglycerate (MPG), ADP, GDP and UDP. SIMILARITY: Belongs to the 5'-nucleotidase family.


FUNCTION: Transcription factor which regulates nonfermentable carbon utilization. Activator of gluconeogenetic genes (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ERT1/acuK family.


FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation. Sulfonates p-nitrophenol, a small phenolic compond. Does not sulfonate steroids, dopamine, acetaminophen, or alpha-naphthol. SUBCELLULAR LOCATION: Cytoplasm Lysosome. SIMILARITY: Belongs to the sulfotransferase 1 family.


FUNCTION: Acts as a virulence determinant. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.


FUNCTION: Poor inhibitor of platelet aggregation. The disintegrin inhibits the adhesion of cells expressing the RGD-dependent integrin alpha-5/beta-1 (ITGA5/ITGB1) to immobilized fibronectin. Inhibition on alpha-IIb/beta-3 (ITGA2B/ITGB3) is low, and there is no inhibition on alpha-1/beta-1 (ITGA1/ITGB1), alpha-2/beta-1 (ITGA2/ITGB1) and alpha- 6/beta-1 (ITGA6/ITGB1). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-II subfamily. P-IId sub-subfamily.


SUBCELLULAR LOCATION: Golgi apparatus. SIMILARITY: Belongs to the PRRC1 family.


SIMILARITY: Belongs to the aspartokinase family.


FUNCTION: Plays a critical role in M.tuberculosis ability to inhibit apoptosis of infected macrophages; thus helps the bacterium in its struggle to resist the host immune response (PubMed:17658950). In fact, via a NuoG-dependent mechanism, M.tuberculosis can neutralize NOX2- derived reactive oxygen species (ROS) in order to inhibit TNF-alpha- mediated host cell apoptosis (PubMed:20421951). Also mediates inhibition of neutrophil apoptosis, leading to delayed activation of naive CD4 T cells (PubMed:22264515). FUNCTION: NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be menaquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient (By similarity). SIMILARITY: Belongs to the complex I 75 kDa subunit family.


SIMILARITY: Belongs to the UPF0232 family.


FUNCTION: Catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid using ATP as a cosubstrate. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the shikimate kinase family. AroL subfamily.


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


SIMILARITY: Belongs to the UPF0231 family.


FUNCTION: The beta subunit is responsible for the synthesis of L- tryptophan from indole and L-serine. SIMILARITY: Belongs to the TrpB family.


SIMILARITY: Belongs to the UPF0146 family.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the scolopendra toxin 2 family.


FUNCTION: Repressor specific for genes preceded by a radiation/desiccation response motif (RDRM) site, which is present upstream of several radiation-induced genes.


SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the RING-type zinc finger family. ATL subfamily.


FUNCTION: NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be a menaquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient. SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein; Cytoplasmic side. SIMILARITY: Belongs to the complex I 30 kDa subunit family.


FUNCTION: Catalyzes the production of pinosylvin from cinnamoyl-CoA and malonyl-CoA, and dihydropinosylvin from dihydrocinnamoyl-CoA. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the thiolase-like superfamily. Chalcone/stilbene synthases family.


FUNCTION: Flagellin is the subunit protein which polymerizes to form the filaments of bacterial flagella. Flagella are an important component in the invasiveness of B.bacilliformis. SUBCELLULAR LOCATION: Secreted. Bacterial flagellum. SIMILARITY: Belongs to the bacterial flagellin family.


FUNCTION: Regulates the proliferation and migration of oligodendrocytes, a process essential for normal myelination and repair. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the tetraspanin (TM4SF) family.


FUNCTION: Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the transferase hexapeptide repeat family. LpxA subfamily.


FUNCTION: ATPase required for the post-translational delivery of tail- anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the membrane-bound receptor, and returning it to the cytosol to initiate a new round of targeting. SUBCELLULAR LOCATION: Cytoplasm Endoplasmic reticulum. SIMILARITY: Belongs to the arsA ATPase family.


FUNCTION: Hydrolyzes various peptides including beta-endorphin, insulin B chain, dynorphin A, and neurokinin A, with high specificity for the cleavage of the Phe-Xaa bonds. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase A1 family.


FUNCTION: NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be ubiquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient. SUBCELLULAR LOCATION: Cell inner membrane; Peripheral membrane protein. SIMILARITY: Belongs to the complex I 23 kDa subunit family.


FUNCTION: Involved in light-induced Na(+)-dependent proton extrusion. Also seems to be involved in CO(2) transport. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the Cema family.


FUNCTION: Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. Therefore, it is important in the regulation of neuronal excitability. KCNQ2-KCNQ3 channel is selectively permeable to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+). Associates with Na(+)-coupled myo-inositol symporter SLC5A3 forming a coregulatory complex that alters ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) permeation (PubMed:28793216). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.3/KCNQ3 sub-subfamily.


SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the peptidase M48B family.


FUNCTION: Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELFE. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co- transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation. Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity. SUBCELLULAR LOCATION: Nucleus Cytoplasm Nucleus, PML body Note=Accumulates on chromatin in response to replication stress. Complexed with CCNT1 in nuclear speckles, but uncomplexed form in the cytoplasm. The translocation from nucleus to cytoplasm is XPO1/CRM1-dependent. Associates with PML body when acetylated (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Nucleus, PML body Note=Accumulates on chromatin in response to replication stress. Complexed with CCNT1 in nuclear speckles, but uncomplexed form in the cytoplasm. The translocation from nucleus to cytoplasm is XPO1/CRM1-dependent. Associates with PML body when acetylated (By similarity). SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.


FUNCTION: Component of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery. Required for maturation of extramitochondrial Fe-S proteins. The nubp1-nubp2 heterotetramer forms a Fe-S scaffold complex, mediating the de novo assembly of an Fe-S cluster and its transfer to target apoproteins. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP2/CFD1 subfamily.


FUNCTION: Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling (PubMed:23929341, PubMed:9539740). Specifically recognizes PEX5 monoubiquitinated at 'Cys-11', and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel (By similarity). Extraction by the PEX1-PEX6 AAA ATPase complex is accompanied by unfolding of the TPR repeats and release of bound cargo from PEX5 (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytosol Peroxisome membrane Cell projection, cilium, photoreceptor outer segment Note=Associated with peroxisomal membranes; anchored by PEX26 to peroxisome membranes. Localized at the base of the outer segment of photoreceptor cells. SIMILARITY: Belongs to the AAA ATPase family.


FUNCTION: Probable alcohol acetyltransferase that uses acetyl-CoA to synthesize acetate esters from various alcohols (Probable). Not involved in the synthesis of ethyl acetate (PubMed:28356220). SIMILARITY: Belongs to the AB hydrolase superfamily.


FUNCTION: Selective transporter that mediates the uptake of Zn(2+) (PubMed:17202136, PubMed:22242765, PubMed:27321477, PubMed:28875161, PubMed:31164399, PubMed:31914589, PubMed:31979155, PubMed:33837739, PubMed:36473915). Plays an essential role for dietary zinc uptake from small intestine (By similarity). The Zn(2+) uniporter activity is regulated by zinc availability (PubMed:32348750, PubMed:17202136). Exhibits also polyspecific binding and transport of Cu(2+), Cd(2+) and possibly Ni(2+) but at higher concentrations (PubMed:22242765, PubMed:31914589). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Recycling endosome membrane; Multi-pass membrane protein Apical cell membrane; Multi-pass membrane protein Note=Colocalized with TFRC in the recycling endosomes. Cycles between endosomal compartments and the plasma membrane in response to Zn(2+) availability. Zn(2+) deficiency promotes accumulation of SLC39A4 on the surface membrane, whereas high extracellular Zn(2+) levels induce internalization of SLC39A4, but also trigger drastic removal of cellular SLC39A4 via proteasomal and lysosomal degradation pathways. SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family.


FUNCTION: Probable transcription activator for a number of lung- specific genes (PubMed:8626802). Mediates up-regulation of the E3 ligase IRF2BPL and drives ubiquitination and degradation of CTNNB1 (PubMed:29374064). SUBCELLULAR LOCATION: Nucleus.


SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein.


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


SIMILARITY: Belongs to the LarC family.


FUNCTION: Involved in the catabolism of quinolinic acid (QA). SIMILARITY: Belongs to the NadC/ModD family.


FUNCTION: Plays a role in the ovary in limiting the number of primordial germ cells (PGCs) that develop directly into gametes, allowing them instead to enter the developmental pathway that produces germline stem cells (GSCs) from PGCs and ensuring lifelong production of gametes from these GSCs. Negatively regulates epidermal growth factor receptor (Egfr) signaling. Probably down-regulates EGFR signaling on intermingled cells, a type of somatic stromal cell which contacts PGCs, and the resultant low level of signaling limits the proportion of PGCs which start gametogenesis, maintaining them in an undifferentiated proliferative state. SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein Note=Not uniformly present at the cell membrane but is concentrated at the interface between germ cells. SIMILARITY: Belongs to the peptidase M13 family.


FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of loline alkaloids, potent insecticidal agents composed of a pyrrolizidine ring system and an uncommon ether bridge linking carbons 2 and 7 (PubMed:15654104). Lolines are structurally differentiated by the various modifications of the L-amino group and include norloline, loline, N-methylloline, N-acetylloline, N- acetylnorloline, and N-formylloline (PubMed:15861432, PubMed:25531527). The first committed step is the condensation of O-acetyl-L-homoserine (derived from L-aspartic acid) and L-proline, probably catalyzed by the gamma-type pyridoxal 5'-phosphate(PLP)-dependent enzyme lolC, to give the diamino diacid, NACPP (PubMed:15861432, PubMed:16755627). Ensuing cyclization, decarboxylation, and acetylation steps yield 1-exo- acetamidopyrrolizidine (AcAP)(PubMed:24374065). LolO is required for installation of the ether bridge upon the pathway intermediate, 1-exo- acetamidopyrrolizidine (AcAP) (PubMed:29537853). In sequential 2- oxoglutarate- and O(2)-consuming steps, lolO removes hydrogens from C2 and C7 of AcAP to form both carbon-oxygen bonds in N-acetylnorloline (NANL), the precursor to all other lolines (PubMed:24374065, PubMed:29537853). The enzymes lolD, lolE, lolF and lolT have also been proposed to be involved in the ether-bridge installation (PubMed:15654104). Further processing of the exocyclic moiety of NANL by fungal N-acetamidase (LolN), methyltransferase (LolM), and cytochrome P450 (LolP) enzymes, with occasional involvement of a plant acetyltransferase, generates the other known lolines (PubMed:25531527, PubMed:18655839). LolN transforms NANL to norlonine which is monomethylated and dimethylated to respectively lonine and N- methyllonine (NML) by lolM (PubMed:25531527). LolP catalyzes hydroxylation of the methyl group in N-methylloline (NML) and further oxygenation to N-formylloline (NFL) (PubMed:18655839). A plant acetyltransferase is responsible for the acetylation of loline to form N-acetylloline (NAL) (PubMed:25531527). LolA might interact with aspartate kinase to prevent feedback inhibition of its activity by these end products and thereby promote production of L-homoserine from L-aspartate (PubMed:15654104). SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the cytochrome P450 family.


SIMILARITY: Belongs to the UPF0605 family.


FUNCTION: Functions as a PqqA binding protein and presents PqqA to PqqE, in the pyrroloquinoline quinone (PQQ) biosynthetic pathway. SIMILARITY: Belongs to the PqqD family.


FUNCTION: A highly abundant probable chromatin protein, it binds double-strand DNA without sequence specificity; there is approximately 1 Cren7 molecule for 12 bp of DNA. Constrains negative DNA supercoils, increases DNA stability against thermal denaturation. Binding does not require protein methylation. Binds single-strand DNA weakly. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the Cren7 family.


FUNCTION: Involved in cellular auxin homeostasis by regulating auxin metabolism. Regulates intracellular auxin accumulation at the endoplasmic reticulum and thus auxin availability for nuclear auxin signaling. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the auxin efflux carrier (TC 2.A.69.2) family.


FUNCTION: Involved in a secretory pathway responsible for the surface presentation of determinants needed for the entry of Salmonella species into mammalian cells. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the FliQ/MopD/SpaQ family.


FUNCTION: As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase S1 family.


FUNCTION: Metal-binding repressor for the cad operon. Involved in resistance to heavy metals, such as cadmium, bismuth, zinc or lead. Binds 2 metal ions per subunit. Metal binding to the N-terminal regulatory site causes the repressor to dissociate from the DNA.


FUNCTION: Catalyzes the dehydration of D-mannonate. SIMILARITY: Belongs to the mannonate dehydratase family.


FUNCTION: Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T- cells (Treg), in the suppression of tumor-associated antigen-specific T-cell immunity. Involved in promoting epithelial cell transformation. SUBCELLULAR LOCATION: Cell membrane; Lipid- anchor, GPI-anchor Note=Expressed at the cell surface. A soluble form has also been detected. SIMILARITY: Belongs to the immunoglobulin superfamily. BTN/MOG family.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the THEM6 family.


FUNCTION: Involved in the import of serine and threonine into the cell, with the concomitant import of sodium (symport system). SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.


FUNCTION: Part of the Sec protein translocase complex. Interacts with the SecYEG preprotein conducting channel. Has a central role in coupling the hydrolysis of ATP to the transfer of proteins into and across the cell membrane, serving as an ATP-driven molecular motor driving the stepwise translocation of polypeptide chains across the membrane. SUBCELLULAR LOCATION: Cell inner membrane; Peripheral membrane protein; Cytoplasmic side Cytoplasm Note=Distribution is 50- 50. SIMILARITY: Belongs to the SecA family.


SIMILARITY: Belongs to the ARG7 family.


SIMILARITY: Belongs to the UPF0339 family. Duplicated subfamily.


FUNCTION: Involved in both the arginine and lysine biosynthetic pathways. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family. ArgD subfamily.


FUNCTION: Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity). FUNCTION: By interacting with vestigial (vg), may control genes involved in DNA replication. SIMILARITY: Belongs to the dihydrofolate reductase family.


FUNCTION: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the Abd-B homeobox family.


FUNCTION: One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. SUBCELLULAR LOCATION: Plastid. SIMILARITY: Belongs to the universal ribosomal protein uS7 family.


FUNCTION: Receptor for the C-X-C chemokine cxcl12/sdf-1. Transduces a signal by increasing the intracellular calcium ion level. Signaling with cxcl12/sdf-1 mediates the directional movement of mesodermal cells during gastrulation. May play a role in the migration of embryonic presumptive primordial germ cells (pPGCs). May also be involved in regulating migration of hematopoietic stem cells into the larval liver (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Cytoplasm Nucleus Early endosome Late endosome Lysosome Note=Expressed in the cytoplasm of a small number of embryonic pPGCs from stage 24. Expressed in the nucleus of 3 lateral pPGCs (By similarity). SIMILARITY: Belongs to the G-protein coupled receptor 1 family.


FUNCTION: The presence of the two linear plasmids, termed pGKL1 and pGKL2, in strains of Kluyveromyces lactis confers the killer phenotype to the host cell, by promoting the secretion of a toxin able to inhibit the growth of sensitive strains.


FUNCTION: Covalent carrier of the coenzyme of citrate lyase. FUNCTION: Covalent carrier of the coenzyme of citrate lyase. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the CitD family. SIMILARITY: Belongs to the CitD family.


FUNCTION: Catalyzes the formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid (PA) in the mitochondrial inner membrane. Required for the biosynthesis of the dimeric phospholipid cardiolipin, which stabilizes supercomplexes of the mitochondrial respiratory chain in the mitochondrial inner membrane. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side. SIMILARITY: Belongs to the TAM41 family.


FUNCTION: Binds to actin and plays an important role in the assembly of the Z-disk. May functionally link sarcomeric actin to the desmin intermediate filaments in the heart muscle sarcomeres. Isoform 2 might play a role in the assembly of focal adhesion (By similarity). SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: In T-helper 2 (Th2) cells, regulates the magnitude of NFAT- driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=TRAF1 is associated with a fraction of NFATC2IP in the cytoplasm and prevents its translocation to the nucleus.


FUNCTION: Mannosyltransferase involved in glycosylphosphatidylinositol- anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN- acyl-PI during GPI precursor assembly (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the PIGM family.


FUNCTION: Golgi matrix protein playing a role in tethering of vesicles to Golgi membranes and in maintaining the overall structure of the Golgi apparatus. SUBCELLULAR LOCATION: Golgi apparatus membrane; Single-pass type II membrane protein Note=Probably located to cisternal rims of cis or medial Golgi.


FUNCTION: The VP2 protein is one of the two proteins (with VP5) which constitute the virus particle outer capsid. It is the major target of the host immunogenic response. Responsible for viral attachment to target host cell, probably by binding to sialic acid. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis (By similarity). SUBCELLULAR LOCATION: Virion. SIMILARITY: Belongs to the orbivirus VP2 family.


FUNCTION: Mediates the import of RPA complex into the nucleus, possibly via some interaction with importin beta. Isoform 2 is sumoylated and mediates the localization of RPA complex into the PML body of the nucleus, thereby participating in RPA function in DNA metabolism. SUBCELLULAR LOCATION: [Isoform 2]: Nucleus, PML body. SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Nucleus.


FUNCTION: Calcium- and diacylglycerol-independent serine/ threonine- protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI3K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Downstream of PI3K is required for insulin-stimulated glucose transport. Activates RAB4A and promotes its association with KIF3A which is required for the insulin-induced SLC2A4/GLUT4 translocation in adipocytes. Is essential in early embryogenesis and development of differentiating photoreceptors by playing a role in the establishment of epithelial and neuronal polarity (By similarity). Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (PubMed:27498875). SUBCELLULAR LOCATION: Cytoplasm Membrane Endosome Nucleus Note=Transported into the endosome through interaction with SQSTM1/p62. After phosphorylation by SRC, transported into the nucleus through interaction with KPNB1. Colocalizes with CDK7 in the cytoplasm and nucleus. Transported to vesicular tubular clusters (VTCs) through interaction with RAB2A. SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.


SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the UPF0756 family.


FUNCTION: Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis. SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the purine/pyrimidine phosphoribosyltransferase family.


FUNCTION: Catalyzes the attachment of proline to tRNA(Pro) in a two- step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family. ProS type 3 subfamily.


FUNCTION: May be involved in environmental stress response.


SIMILARITY: Belongs to the glycosyl hydrolase 23 family.


FUNCTION: Produces ATP from ADP in the presence of a proton gradient across the membrane. SIMILARITY: Belongs to the V-ATPase F subunit family.


FUNCTION: Part of a potassium transport system.


FUNCTION: Probable amino-acid or metabolite transport protein. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC) superfamily.


FUNCTION: Plasma membrane osmosensor that activates the high osmolarity glycerol (HOG) MAPK signaling pathway in response to high osmolarity. Detects changes in external osmolarity and activates PBS2 through the stimulation of STE11 and targets PBS2 to the plasma membrane. PBS2 activation leads to changes in glycerol production that helps to balance the intracellular and external osmotic pressures. Activates also HOG1 in response to heat stress and mediates resistance to oxidative stress. Involved in the regulation of the mating pathway. May be a receptor that feeds into the pseudohyphal growth pathway (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Bud Bud neck Cell projection Note=Localizes at the tip of the mating projection during conjugation. SIMILARITY: Belongs to the SHO1 family.


SIMILARITY: Belongs to the muconolactone Delta-isomerase family.


FUNCTION: Collagen VI acts as a cell-binding protein. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix Membrane; Peripheral membrane protein Note=Recruited on membranes by CSPG4. SIMILARITY: Belongs to the type VI collagen family.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the UPF0298 family.


FUNCTION: Probable transcription factor. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Redox regulated molecular chaperone. Protects both thermally unfolding and oxidatively damaged proteins from irreversible aggregation. Plays an important role in the bacterial defense system toward oxidative stress. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the HSP33 family.


FUNCTION: Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. Involved in DNA damage response by specifically recognizing activated CHEK1 (phosphorylated on 'Ser-345'), promoting its ubiquitination and degradation. Ubiquitination of CHEK1 is required to ensure that activated CHEK1 does not accumulate as cells progress through S phase, or when replication forks encounter transient impediments during normal DNA replication (By similarity). Involved in endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranslocated into the cytosol and promoting their ubiquitination and subsequent degradation. Able to recognize and bind denatured glycoproteins, which are modified with not only high-mannose but also complex-type oligosaccharides. Also recognizes sulfated glycans. SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Catalyzes the NAD(P)(+)-dependent oxidation of D-glucose to D-gluconate via gluconolactone. Can utilize both NAD(+) and NADP(+) as electron acceptor. Is involved in the degradation of glucose through a non-phosphorylative variant of the Entner-Doudoroff pathway. SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase family. Glucose 1-dehydrogenase subfamily.


FUNCTION: Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest activity towards 15-keto-PGE2. Overexpression represses transcriptional activity of PPARG and inhibits adipocyte differentiation. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the NADP-dependent oxidoreductase L4BD family.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the glycosyl hydrolase 32 family.


FUNCTION: Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. Plays a role in the regulation of cell proliferation. May act as a tumor suppressor (By similarity). SUBCELLULAR LOCATION: Cytoplasm Cell junction, focal adhesion Note=Detected along actin stress fibers. SIMILARITY: Belongs to the prickle / espinas / testin family.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the alpha-carbonic anhydrase family.


FUNCTION: Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. In the complex, it is required to regulate activity of mtHSP70 (SSC1) via its interaction with PAM18/TIM14. May act by positioning PAM18/TIM14 in juxtaposition to mtHSP70 at the translocon to maximize ATPase stimulation (By similarity). SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein. SIMILARITY: Belongs to the TIM16/PAM16 family.


FUNCTION: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). May down-regulate activation of NF- kappa-B (PubMed:15799966). SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Part of a multidrug efflux pump. Confers resistance to cationic lipophilic dyes such as ethidium bromide, acriflavine, pyronine Y and safranin O. The efflux is probably coupled to an influx of protons (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the drug/metabolite transporter (DMT) superfamily. Small multidrug resistance (SMR) (TC 2.A.7.1) family. EbrA/EbrB subfamily.


FUNCTION: Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity). SUBCELLULAR LOCATION: Cytoplasm Sarcoplasmic reticulum. SIMILARITY: Belongs to the FKBP-type PPIase family. FKBP1 subfamily.


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


FUNCTION: Snaclec that binds to von Willebrand factor (VWF) and induces its interaction with GPIbalpha (GP1BA) (via the vWF A1 domain), resulting in platelet aggregation. Intramuscular and intravenous injections in mice induce a dose-dependent drop in platelet count (thrombocytopenia). Pretreatment by intravenous injection by this protein in mice potentiates the hemorrhagic lesion in the skin provoked by the metalloproteinase BaP1 intradermally injected. This result is not observed when both BaP1 and this protein are injected simultaneously. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the snaclec family.


FUNCTION: Possesses some antifungal activity sensitive to inorganic cations and antibacterial activity against B.megaterium. SIMILARITY: Belongs to the DEFL family.


FUNCTION: The phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS), a major carbohydrate active transport system, catalyzes the phosphorylation of incoming sugar substrates concomitantly with their translocation across the cell membrane (PubMed:14645248, PubMed:9063979). This system is involved in mannosyl- D-glycerate transport (PubMed:14645248). Also involved in thermoinduction of ompC (PubMed:9063979). SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein.


FUNCTION: The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide substrates in the order PtdIns(4,5)P2 > PtdIns(3,5)P2 > PtdIns(3,4,5)P3. Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes. FUNCTION: Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Catalyzes the dephosphorylation of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) to form phosphatidylinositol 3-phosphate. Has serine- protein phosphatase activity acting on PIKfyve to stimulate its lipid kinase activity, its catalytically activity being required for maximal PI(3,5)P2 production. In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide and although displaying preferences for PtdIns(3,5)P2, it is capable of hydrolyzing PtdIns(3,4,5)P3 and PtdIns(4,5)P2, at least in vitro. SUBCELLULAR LOCATION: Endosome membrane Note=Localization requires VAC14 and PIKFYVE.


FUNCTION: Na(+)/H(+) antiporter that extrudes sodium in exchange for external protons. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: In the N-terminal section; belongs to the NhaA Na(+)/H(+) (TC 2.A.33) antiporter family.


FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site. FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site. SIMILARITY: Belongs to the bacterial ribosomal protein bL19 family. SIMILARITY: Belongs to the bacterial ribosomal protein bL19 family.


FUNCTION: Functions as an E3 ubiquitin ligase.


FUNCTION: Has aminomutase and, to a much lesser extent, ammonia-lyase activity. Primarily, catalyzes the rearrangement of L-tyrosine to S- beta-tyrosine, which is probably incorporated into secondary metabolite myxovalargin. The aminomutase activity exclusively produces S-beta- tyrosine. SIMILARITY: Belongs to the TAL/TAM family.


FUNCTION: Inhibits CBL-SH3KBP1 complex mediated down-regulation of EGFR signaling by sequestration of SH3KBP1. Binds to SH3KBP1 and prevents its interaction with CBL and inhibits translocation of SH3KBP1 to EGFR containing vesicles upon EGF stimulation. SUBCELLULAR LOCATION: Lysosome. SIMILARITY: Belongs to the KCTD3 family.


FUNCTION: May control digestion processes in crustaceans. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the gastrin/cholecystokinin family.


FUNCTION: Plays a role in valine and pyrimidine metabolism. Binds fatty acyl-CoA (By similarity). SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the aldehyde dehydrogenase family.


FUNCTION: Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with piP-bodies suggests a participation in the secondary piRNAs metabolic process. Required for the localization of germ-cell factors to the meiotic nuage (By similarity). SUBCELLULAR LOCATION: Cytoplasm Nucleus Note=Component of the meiotic nuage, also named P granule, a germ-cell-specific organelle required to repress transposon activity during meiosis. Specifically localizes to piP-bodies, a subset of the nuage which contains secondary piRNAs (By similarity). SIMILARITY: Belongs to the maelstrom family.


SIMILARITY: Belongs to the tfa family.


FUNCTION: Probable thiol protease. SIMILARITY: Belongs to the peptidase C1 family.


FUNCTION: A non-essential component of RNA polymerase (RNAP). SIMILARITY: Belongs to the RNA polymerase subunit epsilon family.


FUNCTION: Probable potassium channel subunit. No channel activity observed in vitro as protein remains in the endoplasmic reticulum. May need to associate with an as yet unknown partner in order to reach the plasma membrane. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.


FUNCTION: Part of the ABC transporter complex XylFGH involved in xylose import. Responsible for energy coupling to the transport system. SUBCELLULAR LOCATION: Cell inner membrane; Peripheral membrane protein. SIMILARITY: Belongs to the ABC transporter superfamily. Xylose importer (TC 3.A.1.2.4) family.


SIMILARITY: Belongs to the bacterial ribosomal protein bL33 family. SIMILARITY: Belongs to the bacterial ribosomal protein bL33 family.


FUNCTION: Orphan nuclear receptor. Component of a cascade required for the development of the hypothalamic-pituitary-adrenal-gonadal axis. Acts as a coregulatory protein that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions. May also have a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Shuttles between the cytoplasm and nucleus. Homodimers exits in the cytoplasm and in the nucleus (By similarity). SIMILARITY: Belongs to the nuclear hormone receptor family. NR0 subfamily.


FUNCTION: Part of the ABC transporter complex CysAWTP involved in sulfate/thiosulfate import. Responsible for energy coupling to the transport system. SUBCELLULAR LOCATION: Cell inner membrane; Peripheral membrane protein. SIMILARITY: Belongs to the ABC transporter superfamily. Sulfate/tungstate importer (TC 3.A.1.6) family.


FUNCTION: Converts the unstable imine alcohols produced by CYP71D1V2/T3O into 3-hydroxy-16-methoxy-2,3-dihydrotabersonine or 3- hydroxy-2,3-dihydrotabersonine. SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase family.


FUNCTION: Non-reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of the mycotoxin citrinin, a hepato- nephrotoxic compound to humans due to inhibition of respiration complex III (Ref.1). The pathway begins with the synthesis of a keto-aldehyde intermediate by the citrinin PKS (pksCT also named citS) from successive condensations of 4 malonyl-CoA units, presumably with a simple acetyl-CoA starter unit (Ref.1). Release of the keto-aldehyde intermediate is consistent with the presence of the C-terminal reductive release domain (Ref.1). CitA collaborates with citS by catalyzing the hydrolysis of ACP-bound acyl intermediates to free the ACP from stalled intermediates (PubMed:29189834). CitB then catalyzes the oxidation of the C-12 methyl of the ketone intermediate to an alcohol intermediate which is further oxidized by the oxidoreductase citC to produce a bisaldehyde intermediate (Ref.1). The fourth catalytic step is catalyzed by the citD aldehyde dehydrogenase (Ref.1). The final transformation is the reduction of C-3 by citE to provide the chemically stable citrinin nucleus (Ref.1). CitE appears highly selective for its substrate as its presence in any context other than a full complement of citS and citA-D does not result in observable new compounds (Ref.1). FUNCTION: Dehydrogenase; part of the gene cluster that mediates the biosynthesis of the mycotoxin citrinin, a hepato-nephrotoxic compound to humans due to inhibition of respiration complex III (PubMed:27913218, PubMed:19012408, PubMed:19111642, PubMed:28238725). The pathway begins with the synthesis of a keto-aldehyde intermediate by the citrinin PKS (pksCT) from successive condensations of 4 malonyl- CoA units, presumably with a simple acetyl-CoA starter unit (PubMed:28238725). Release of the keto-aldehyde intermediate is consistent with the presence of the C-terminal reductive release domain (PubMed:28238725). Mp11 collaborates with pksCT by catalyzing the hydrolysis of ACP-bound acyl intermediates to free the ACP from stalled intermediates (By similarity). Mpl2 then catalyzes the oxidation of the C-12 methyl of the ketone intermediate to an alcohol intermediate which is further oxidized by the oxidoreductase mpl7 to produce a bisaldehyde intermediate (PubMed:27913218). The fourth catalytic step is catalyzed by the mpl4 aldehyde dehydrogenase (PubMed:27913218). The final transformation is the reduction of C-3 by mpl6 to provide the chemically stable citrinin nucleus (PubMed:27913218). SIMILARITY: Belongs to the GMC oxidoreductase family.


FUNCTION: Probable UDP-L-arabinose mutase involved in the biosynthesis of cell wall non-cellulosic polysaccharides (By similarity). Was initially shown to possess an autoglycosylating activity which is dependent on the presence of UDP-glucose and manganese (Probable) (PubMed:10580281). SUBCELLULAR LOCATION: Secreted, cell wall Cell junction, plasmodesma Golgi apparatus Note=Cell wall-associated, with highest concentrations on plasmodesmata. Also located in the Golgi apparatus (By similarity). SIMILARITY: Belongs to the RGP family.


SIMILARITY: Belongs to the bacterial ring-hydroxylating dioxygenase alpha subunit family.


FUNCTION: Aquaporins facilitate the transport of water and small neutral solutes across cell membranes. SUBCELLULAR LOCATION: Vacuole membrane; Multi-pass membrane protein Note=Tonoplast. SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family. TIP (TC 1.A.8.10) subfamily.


FUNCTION: When anaerobically expressed in wild-type E.coli K12 confers a hemolytic phenotype, but not in an sheA mutant. Suggests it affects the expression of the latent E.coli K12 hemolysin sheA under anaerobic conditions. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the Smp family.


FUNCTION: Proton-coupled chloride transporter. Functions as antiport system and exchanges two chloride ions for 1 proton. Probably acts as an electrical shunt for an outwardly-directed proton pump that is linked to amino acid decarboxylation, as part of the extreme acid resistance (XAR) response. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClcA subfamily.


FUNCTION: Component of the cleavage factor I (CF I) involved in pre- mRNA 3'-end processing. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the metallo-beta-lactamase superfamily. RNA- metabolizing metallo-beta-lactamase-like family. CPSF2/YSH1 subfamily.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the CRISP family. Venom allergen 5-like subfamily.


FUNCTION: DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:8798671, PubMed:9242410, PubMed:9809069, PubMed:12517771, PubMed:17290226). Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed (PubMed:9242410, PubMed:9809069, PubMed:12517771, PubMed:17290226). Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction (PubMed:9242410, PubMed:9809069, PubMed:12517771, PubMed:17290226). LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps (PubMed:17290226). Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4 (PubMed:9242410, PubMed:9809069). Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10854421). LIG4 regulates nuclear localization of XRCC4 (PubMed:24984242). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ATP-dependent DNA ligase family.


FUNCTION: Catalyzes the conversion of alpha-L-mycarosylerythronolide B into erythromycin D in the erythromycin biosynthesis pathway. SIMILARITY: Belongs to the glycosyltransferase 28 family.


FUNCTION: Catalyzes the reversible oxidation of malate to oxaloacetate. SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 3 family.


FUNCTION: Leucine-rich repeat protein that likely mediates protein interactions, possibly in the context of signal transduction. SIMILARITY: Belongs to the SHOC2 family.


FUNCTION: NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be ubiquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the complex I subunit 3 family.


FUNCTION: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca(2+) in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly. FUNCTION: The secreted form acts as an enterotoxin that causes phospholipase C-dependent elevation of the intracellular calcium concentration in host intestinal mucosa cells. Increased concentration of intracellular calcium disrupts the cytoskeleton and the tight junctions, raising the paracellular permeability. Potentiates chloride ion secretion through a calcium ion-dependent signaling pathway, inducing age-dependent diarrhea. To perform this enterotoxigenic role in vivo, NSP4 is released from infected enterocytes in a soluble form capable of diffusing within the intestinal lumen and interacting with host plasma membrane receptors on neighboring epithelial cells such as integrins ITGA1/ITGB1 and ITGA2/ITGB1. SUBCELLULAR LOCATION: Host rough endoplasmic reticulum membrane; Single-pass type III membrane protein Host membrane, host caveola; Single-pass type III membrane protein Secreted Note=NSP4 localizes also in vesicular structures which contain autophagosomal markers and associate with viroplasms in virus- infected cells. Additionally, a soluble form of glycosylated NSP4 is secreted despite retention of its transmembrane domain. SIMILARITY: Belongs to the rotavirus NSP4 family.


FUNCTION: Has deubiquitinating activity towards 'Lys-48'- and 'Lys-63'- linked polyubiquitin chains. Deubiquitinates 'Lys-48'-linked polyubiquitination of RPS7 leading to its stabilization. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the DeSI family.


FUNCTION: One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the head domain of the 30S subunit. Is located at the subunit interface close to the decoding center. SIMILARITY: Belongs to the universal ribosomal protein uS7 family.


FUNCTION: Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a specific lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue. SIMILARITY: Belongs to the deoxyhypusine synthase family.


FUNCTION: Transcriptional activator that binds to the RPG box and to telomeres. Involved in the regulation of the transition between yeast and filamentous forms and plays a role in virulence. Induces expression of HWP1, a major hyphal cell protein and virulence factor. SUBCELLULAR LOCATION: Nucleus. Chromosome, telomere. SIMILARITY: Belongs to the RBF1 family.


FUNCTION: NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be ubiquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient. SUBCELLULAR LOCATION: Cell inner membrane; Peripheral membrane protein; Cytoplasmic side. SIMILARITY: Belongs to the complex I 49 kDa subunit family.


FUNCTION: This calcium-binding protein is found in the basal body complexes (the functional homolog of the centrosome in animal cell). In mitotic cells it is specifically associated with the poles of the mitotic spindles at the sites of the duplicated basal body complexes. SIMILARITY: Belongs to the centrin family.


FUNCTION: Essential component of the mitochondrial outer membrane sorting assembly machinery (SAM or TOB) complex, which is required for the sorting of proteins with complicated topology, such as beta-barrel proteins, to the mitochondrial outer membrane after import by the TOM complex. SUBCELLULAR LOCATION: Mitochondrion outer membrane.


FUNCTION: Signaling molecule involved in the regulation of genetic competence development (PubMed:16816200). Secreted during production, but the mature peptide acts intracellularly, indicating that it needs to be imported into the cell to function (By similarity). Stimulates expression of the genes controlled by ComA, a transcriptional factor that regulates the development of genetic competence (PubMed:16816200). Acts by inhibiting RapK, which regulates the activity of ComA (PubMed:16816200). SUBCELLULAR LOCATION: Secreted Cytoplasm Note=Produced through an export-import maturation process. SIMILARITY: Belongs to the Phr family.


FUNCTION: Probable proton-dependent permease that transports dipeptides. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. Proton- dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family. DtpD subfamily.


FUNCTION: May play a role in the modulation of host immune response. SIMILARITY: Belongs to the influenza viruses PA-X family.


FUNCTION: Trans-acting protein required for termination of DNA replication. Binds to DNA replication terminator sequences (terA to terF) to prevent the passage of replication forks. The termination efficiency will be affected by the affinity of this protein for the terminator sequence. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the Tus family.


SIMILARITY: Belongs to the FAM76 family.


FUNCTION: Can induce apoptosis in a caspase-dependent manner and plays a role in p53/TP53-dependent apoptosis. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein Nucleus membrane. SIMILARITY: Belongs to the shisa family.


FUNCTION: Catalyzes the oxidation of cytokinins, a family of N(6)- substituted adenine derivatives that are plant hormones, where the substituent is an isopentenyl group. SUBCELLULAR LOCATION: Secreted, extracellular space. SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase family.


FUNCTION: Probable aminopeptidase. SIMILARITY: Belongs to the peptidase S33 family.


FUNCTION: Involved in endosomal protein transport. SUBCELLULAR LOCATION: Endosome membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the OB-RGRP/VPS55 family.


FUNCTION: Involved in the biosynthesis of ornithine lipids (OLs), which are phosphorus-free membrane lipids (PubMed:16353552, PubMed:21205018). Catalyzes the hydroxylation at the 2 position of the secondary fatty acid of OL (PubMed:21205018). Contributes to symbiotic performance and acid tolerance (PubMed:16353552, PubMed:21205018). SIMILARITY: Belongs to the aspartyl/asparaginyl beta-hydroxylase family.


FUNCTION: Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c (Probable). Cytochrome b is a catalytic core subunit containing 2 b-type hemes BL and BH topographically segregated in the quinone reduction (Qi) and quinol oxidation (Q0) sites on opposite sides of the membrane (PubMed:18390544). SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the cytochrome b family.


FUNCTION: Divisome component that associates with the complex late in its assembly, after the Z-ring is formed, and is dependent on DivIC and PBP2B for its recruitment to the divisome. Together with EzrA, is a key component of the system that regulates PBP1 localization during cell cycle progression. Its main role could be the removal of PBP1 from the cell pole after pole maturation is completed. Also contributes to the recruitment of PBP1 to the division complex. Not essential for septum formation. SUBCELLULAR LOCATION: Cytoplasm Note=Shuttles between the lateral wall and the division site in a cell cycle-dependent manner. SIMILARITY: Belongs to the GpsB family.


FUNCTION: Nonribosomal peptide synthetase that mediates the biosynthesis of phenguignardic acid (PubMed:26851300, PubMed:29305695). PngA alone is sufficient for phenguignardic acid synthesis (PubMed:26851300, PubMed:29305695). PngA first activates phenylpyruvic acid (PPA) through its A domain to AMP-PPA (PubMed:26851300, PubMed:29305695). The PPA unit is then loaded to the T domain and eventually transferred to the TE domain (PubMed:26851300, PubMed:29305695). Another PPA unit is then loaded onto the T domain (PubMed:26851300, PubMed:29305695). The TE domain likely promotes the enolate formation on the attached unit, followed by a nucleophilic attack on the carbonyl to yield an ether linkage between the two units (PubMed:26851300, PubMed:29305695). Finally, the TE domain probably catalyzes a similar reaction to give the cyclized dioxolanone core and releases phenguignardic acid (PubMed:26851300, PubMed:29305695). SIMILARITY: Belongs to the NRP synthetase family.


FUNCTION: Amino acid transporter importing serine, an essential substrate of the mitochondrial branch of the one-carbon pathway, into mitochondria. Mitochondrial serine is then converted to glycine and formate, which exits to the cytosol where it is used to generate the charged folates that serve as one-carbon donors. May also transport other amino acids including alanine and cysteine. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the sideroflexin family.


FUNCTION: Seems to promote the survival of visceral and proprioceptive sensory neurons. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the NGF-beta family.


FUNCTION: Could catalyze the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to an acceptor substrate and release both CoA and the acetylated product. SIMILARITY: Belongs to the UPF0039 (ElaA) family.


FUNCTION: Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity). SIMILARITY: Belongs to the ferritin family.


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


FUNCTION: Mediates the interaction of DNA replication initiator protein DnaA with DNA polymerase subunit beta sliding clamp (dnaN). Stimulates hydrolysis of ATP-DnaA to ADP-DnaA, rendering DnaA inactive for reinitiation, a process called regulatory inhibition of DnaA or RIDA (By similarity). SIMILARITY: Belongs to the DnaA family. HdA subfamily.


FUNCTION: Colicins are polypeptide toxins produced by and active against E.coli and closely related bacteria. FUNCTION: This colicin is a channel-forming colicin. This class of transmembrane toxins depolarize the cytoplasmic membrane, leading to dissipation of cellular energy. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the channel forming colicin family.


SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.


FUNCTION: Catalyzes the interconversion of 2-phosphoglycerate and 3- phosphoglycerate. SIMILARITY: Belongs to the BPG-independent phosphoglycerate mutase family. A-PGAM subfamily.


FUNCTION: Catalyzes the hydrolytic deamination of adenosine and 2- deoxyadenosine. FUNCTION: Catalyzes the hydrolytic deamination of adenosine and 2- deoxyadenosine. SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. Adenosine deaminase subfamily.


FUNCTION: Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is a respiratory chain that generates an electrochemical potential coupled to ATP synthesis. c1 functions as an electron donor to cytochrome c. SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein.


FUNCTION: Has a role in meiosis. SUBCELLULAR LOCATION: Golgi apparatus Vacuole membrane. SIMILARITY: Belongs to the UPF0300 family.


FUNCTION: Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid. SUBCELLULAR LOCATION: Mitochondrion outer membrane. SIMILARITY: Belongs to the aromatic-ring hydroxylase family. KMO subfamily.


FUNCTION: Serves as substrate adapter subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC. Acts redudantly with ZER1 to target substrates bearing N-terminal glycine degrons for proteasomal degradation (PubMed:33093214). Involved in the clearance of proteolytic fragments generated by caspase cleavage during apoptosis since N- terminal glycine degrons are strongly enriched at caspase cleavage sites. Also important in the quality control of protein N- myristoylation in which N-terminal glycine degrons are conditionally exposed after a failure of N-myristoylation (PubMed:31273098). SIMILARITY: Belongs to the zyg-11 family.


FUNCTION: Dehydrogenase, part of the gene cluster that mediates the biosynthesis of melleolides, a range of antifungal and phytotoxic polyketide derivatives composed of an orsellinic acid (OA) moiety esterified to various sesquiterpene alcohols (Probable). The first step in melleolides biosynthesis is performed by the delta(6)-protoilludene synthase PRO1 which catalyzes the cyclization of farnesyl diphosphate to protoilludene (PubMed:21148562). The orsellinic acid synthase armB produces OA by condensing acetyl-CoA with 3 malonyl-CoA units in a three-round chain elongation reaction folowed by a C2-C7 ring closure (By similarity). ArmB further catalyzes the trans-esterification of OA to the various sesquiterpene alcohols resulting from the hydroxylation of protoilludene (By similarity). The melleolides cluster also includes 5 cytochrome P450 monooxygenases, 4 NAD(+)-dependent oxidoreductases, one flavin-dependent oxidoreductase, and one O-methyltransferase (By similarity). The cytochrome P450 monooxygenases may be involved in protoilludene hydroxylation to elaborate melleolides with multiple alcohol groups, such as melleolide D, which carries alcohol functionalities at C-4, C-5, C-10, and C-13 (By similarity). The role of the NAD(+)-dependent enzymes remains unknown (By similarity). Numerous melleolides, including arnamial, show 5'-O-methylation of the aromatic moiety which may be catalyzed by the methyltransferase encoded in the cluster (By similarity). The flavin-dependent oxidoreductase might represent the dehydrogenase yielding the aldehyde in position 1 of arnamial and other melleolides (By similarity). Finally, several halogenase localized outside of the cluster, are able to catalyze the transfer of a single chlorine atom to the melleolide backbone, resulting in a 6'-chloromelleolide product (By similarity). SIMILARITY: Belongs to the GMC oxidoreductase family.


FUNCTION: Involved in ribosome biogenesis, probably through modulation of rDNA transcription. SUBCELLULAR LOCATION: Nucleus, nucleolus. SIMILARITY: Belongs to the RRT14 family.


FUNCTION: Catalyzes the conversion of dihydroorotate to orotate with NAD(+) as electron acceptor. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the dihydroorotate dehydrogenase family. Type 1 subfamily.


FUNCTION: Catalyzes hydrolysis of N-hexanoyl-(S)-homoserine lactone, but not the R-enantiomer. Hydrolyzes short- and long-chain N-acyl homoserine lactones with or without 3-oxo substitution at C3, has maximum activity on C10-AHL. FUNCTION: Catalyzes hydrolysis of N-hexanoyl-(S)-homoserine lactone, but not the R-enantiomer. Hydrolyzes short- and long-chain N-acyl homoserine lactones with or without 3-oxo substitution at C3, has maximum activity on C10-AHL (By similarity). FUNCTION: Catalyzes hydrolysis of N-hexanoyl-(S)-homoserine lactone, but not the R-enantiomer. Hydrolyzes short- and long-chain N-acyl homoserine lactones with or without 3-oxo substitution at C3, has maximum activity on C10-AHL. SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.


SIMILARITY: Belongs to the eukaryotic ribosomal protein eS8 family.


FUNCTION: Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex sae1-sae2 and linkage to the E2 enzyme ube2i. This post- translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric sumo1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. SUBCELLULAR LOCATION: Nucleus membrane Nucleus speckle Cytoplasm Nucleus, PML body Cell membrane Nucleus. SIMILARITY: Belongs to the ubiquitin family. SUMO subfamily.


FUNCTION: Component of the acetyl coenzyme A carboxylase (ACC) complex. Biotin carboxylase (BC) catalyzes the carboxylation of biotin on its carrier protein (BCCP) and then the CO(2) group is transferred by the transcarboxylase to acetyl-CoA to form malonyl-CoA. SUBCELLULAR LOCATION: Plastid, chloroplast stroma. SIMILARITY: Belongs to the AccD/PCCB family.


FUNCTION: Induces paralysis 5 minutes after injection into blowflies (L.caesar) (PubMed:32182430). In most cases is not lethal 24 hours after injection, but paralysis is irreversible (PubMed:32182430). May have antimicrobial properties, like most ant linear peptides (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the formicidae venom precursor-01 superfamily.


FUNCTION: Plays a role in vesicular transport from endoplasmic reticulum to Golgi. SUBCELLULAR LOCATION: Cytoplasm, perinuclear region Endoplasmic reticulum Golgi apparatus. SIMILARITY: Belongs to the TRAPP small subunits family. Sedlin subfamily.


FUNCTION: During interphase, required for microtubule organizing and anchoring activities. During mitosis, required for the organization and stabilization of the spindle pole. May promote cell cycle arrest and DNA repair. SUBCELLULAR LOCATION: Nucleus Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole Cytoplasm, cytoskeleton, spindle pole. SIMILARITY: Belongs to the BCP1 family.


FUNCTION: Joins adenosylcobinamide-GDP and alpha-ribazole to generate adenosylcobalamin (Ado-cobalamin). Also synthesizes adenosylcobalamin 5'-phosphate from adenosylcobinamide-GDP and alpha-ribazole 5'- phosphate. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the CobS family.


FUNCTION: Water channel required to facilitate the transport of water across cell membrane. Increases the capacity for root water uptake under water deficit. May play a role in drought avoidance in upland rice. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family. PIP (TC 1.A.8.11) subfamily.


FUNCTION: Facilitative glucose transporter that can also mediate the uptake of various other monosaccharides across the cell membrane. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Perikaryon Cell projection Note=Localized to densely spaced patches along neuronal processes. SIMILARITY: Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.


FUNCTION: Possesses RNA-binding and ribonuclease activities in vitro. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Probably a thiamine-binding protein that interacts with the energy-coupling factor (ECF) ABC-transporter complex. Unlike classic ABC transporters this ECF transporter provides the energy necessary to transport a number of different substrates. The substrates themselves are bound by transmembrane, not extracytoplasmic soluble proteins. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the vitamin uptake transporter (VUT/ECF) (TC 2.A.88) family. Thiamine transporter subfamily.


FUNCTION: Probable transcriptional activator which may play a role in neuronal differentiation. Able to bind DNA and activate expression in vitro (By similarity). SUBCELLULAR LOCATION: Nucleus matrix. SIMILARITY: Belongs to the AKAP95 family.


FUNCTION: Prenyltransferase; part of the gene cluster that mediates the biosynthesis of echinulin family alkaloid (PubMed:35843946). The pathway begins with the biosynthesis of the cyclic dipeptide cyclo-L- Trp-L-Ala (cyclo-TA) by the NRPS criC via condensation of L-alanine and L-tryptophan (PubMed:35843946). The prenyltransferase criA then catalyzes the first prenylation step, a reverse prenylation reaction at C2, to yield preechinulin (By similarity). Preechinulin is the substrate of the cytochrome P450 monooxygenase criE that catalyzes the formation of the double bond between C10 and C11 to produce neoechulin A (By similarity). The unique prenyltransferase criF functions as a competitive enzyme with criE for preechinulin metabolization and uses preechinulin for effective regiospecific prenylations. Preechinulin is prenylated by criF at C5 or C7. C7-prenylation leads to accumulation of tardioxopiperazine B without further modification by criF. In contrast, the C5-prenylated tardioxopiperazine A can be prenylated again by criF, predominantly at C7 to form echinulin or less frequently at C4 to give variecolorin L. CriF accepts also neoechilunin A to produce varlecolorin G (prenylation at C5) or isoechinulin A (prenylation at C7). CriF further converts isoechinulin A into dehydroechinulin. Moreover, a yet unidentified enzyme can also convert neoechilunin A into neoechilunin B by introducing a double bond between positions C14 and C17 and thus provides a further substrate to criF for C5 and C7 prenylation (By similarity). SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.


SUBCELLULAR LOCATION: Mitochondrion outer membrane; Peripheral membrane protein. SIMILARITY: Belongs to the FMP52 family.


FUNCTION: Secreted protein that acts as a virulence factor during infections. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the CRISP family.


FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (By similarity). Inhibits neurogenesis and axis formation during embryonic development by modulating the phosphatidylinositol 3-kinase (PI3K) pathway (PubMed:18198183). Acts downstream of PI3K and akt1 to up-regulate gsk3b mRNA expression (PubMed:18198183). SUBCELLULAR LOCATION: Cytoplasm Nucleus.


FUNCTION: Involved in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), two major building blocks of isoprenoid compounds. Catalyzes the conversion of 4-diphosphocytidyl-2- C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine 5-monophosphate (CMP). SIMILARITY: Belongs to the IspF family.


FUNCTION: Binds directly to 23S ribosomal RNA and is necessary for the in vitro assembly process of the 50S ribosomal subunit. It is not involved in the protein synthesizing functions of that subunit (By similarity). SUBCELLULAR LOCATION: Plastid. SIMILARITY: Belongs to the bacterial ribosomal protein bL20 family.


FUNCTION: High-affinity transporter for external inorganic phosphate. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. phosphate:H(+) symporter (TC 2.A.1.9) family.


FUNCTION: Methylesterase shown to have carboxylesterase activity, methyl indole-3-acetic acid (MeIAA) esterase activity, methyl salicylate (MeSA) esterase activity and methyl jasmonate (MeJA) esterase activity in vitro. SIMILARITY: Belongs to the AB hydrolase superfamily. Methylesterase family.


FUNCTION: Major component of the RACK1 regulatory proteins that play a role in multiple signal transduction pathways. Involved in multiple hormone responses and developmental processes (PubMed:16829549, PubMed:18715992, PubMed:18947417). MAPK cascade scaffolding protein involved in the protease IV and ArgC signaling pathway but not the flg22 pathway (PubMed:25731164). SUBCELLULAR LOCATION: Cytoplasm Nucleus Note=Detected in the cytoplasm and nucleus when interacting with NUDT7. SIMILARITY: Belongs to the WD repeat G protein beta family. Ribosomal protein RACK1 subfamily.


FUNCTION: Growth factor active in angiogenesis and endothelial cell growth, stimulating their proliferation and migration. It binds to the receptor FLT1/VEGFR-1. Also promotes cell tumor growth (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the PDGF/VEGF growth factor family.


FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides (By similarity). May be involved in chloroplast redox homeostasis (By similarity). SUBCELLULAR LOCATION: Plastid, chloroplast stroma. SIMILARITY: Belongs to the peroxiredoxin family. Prx5 subfamily.


FUNCTION: [Capsid protein]: Involved in aphid transmission, cell-to- cell and systemis movement, encapsidation of the viral RNA and in the regulation of viral RNA amplification. FUNCTION: [Nuclear inclusion protein B]: An RNA-dependent RNA polymerase that plays an essential role in the virus replication. SUBCELLULAR LOCATION: [Capsid protein]: Virion. SIMILARITY: Belongs to the potyviridae genome polyprotein family.


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


SIMILARITY: Belongs to the glycosyl hydrolase 11 (cellulase G) family.


FUNCTION: Component of nuclear coiled bodies, also known as Cajal bodies or CBs, which are involved in the modification and assembly of nucleoplasmic snRNPs. SUBCELLULAR LOCATION: Nucleus Nucleus, Cajal body. SIMILARITY: Belongs to the coilin family.


SIMILARITY: Belongs to the epstein-barr virus RPMS1 family.


FUNCTION: Catalyzes the S-adenosylmethionine monomethyl esterification of trans-aconitate. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the methyltransferase superfamily. Tam family.


FUNCTION: Regulates the auxin-related MAX (More Axillary Growth) pathway during the shoot branching. SUBCELLULAR LOCATION: Cell membrane; Single-pass membrane protein. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.


FUNCTION: Component of the molecular motor that translocates viral genomic DNA in empty capsid during DNA packaging. Forms a tripartite terminase complex together with TRM2 and TRM3 in the host cytoplasm. Once the complex reaches the host nucleus, it interacts with the capsid portal vertex. This portal forms a ring in which genomic DNA is translocated into the capsid. TRM1 carries an endonuclease activity that plays an important role for the cleavage of concatemeric viral DNA into unit length genomes. SUBCELLULAR LOCATION: Host nucleus Note=Found associated with the external surface of the viral capsid during assembly and DNA packaging, but seems absent in extracellular mature virions. SIMILARITY: Belongs to the herpesviridae TRM1 protein family.


FUNCTION: Snake venom phospholipase A2 (PLA2) that has anticoagulant activity and inhibits bactericial growth of the Gram-negative bacteria Xanthomonas axonopodis pv. passiflorae (in monomeric form). PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3- sn-phosphoglycerides. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily. D49 sub-subfamily.


SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the bacterial ribosomal protein bS18 family. Mitochondrion-specific ribosomal protein mS40 subfamily.


FUNCTION: Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions (By similarity). Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb (By similarity). Couples to apoptosis-inducing pathways such as those mediated by G(o) and JIP (By similarity). Inhibits G(o)-alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). May be involved in copper homeostasis/oxidative stress through copper ion reduction (By similarity). In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation (By similarity). Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1 (By similarity). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein Membrane; Single-pass type I membrane protein Perikaryon Cell projection, growth cone Membrane, clathrin-coated pit Early endosome Cytoplasmic vesicle Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. Only a minor proportion is present at the cell membrane; most of the protein is present in intracellular vesicles. During maturation, the immature APP (N- glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. SIMILARITY: Belongs to the APP family.


FUNCTION: Plays a role in skin pigmentation by antagonizing the action of melanotropin alpha. Induces melanin concentration within the melanophores. May participate in the control of the hypothalamo- pituitary adrenal gland axis by inhibiting the release of ACTH. SIMILARITY: Belongs to the melanin-concentrating hormone family.


FUNCTION: Key virulence factor required for mycobacterial survival within host macrophages (PubMed:16085396, PubMed:18474358, PubMed:22087003, PubMed:25187516, PubMed:25642820, PubMed:27698396). Exhibits protein tyrosine phosphatase activity (PubMed:10986245, PubMed:12066895, PubMed:17975835, PubMed:23102706, PubMed:25187516, PubMed:32142609). Shows no detectable activity towards substrates containing phosphoserine/threonine residues (PubMed:10986245, PubMed:12066895). FUNCTION: Key virulence factor required for mycobacterial survival within host macrophages (By similarity). Exhibits protein tyrosine phosphatase activity (By similarity). FUNCTION: Supports mycobacteria survival during infection by modulation of the phagosome maturation and modulation of the normal host signaling pathways, including host innate immune responses and cell apoptosis. FUNCTION: Supports mycobacteria survival during infection by modulation of the phagosome maturation and modulation of the normal host signaling pathways, including host innate immune responses and cell apoptosis (PubMed:18474358, PubMed:22087003, PubMed:25187516, PubMed:25642820, PubMed:27698396). Affects the phagocytosis process by preventing phagosome acidification and maturation in the macrophage (PubMed:22087003, PubMed:16085396, PubMed:18474358). This inhibition depends on both PtpA phosphatase activity and its ability to bind to host vacuolar-H(+)-ATPase (V-ATPase) machinery (PubMed:22087003). Enters into the host cytosol and binds to subunit H of the human V- ATPase machinery to block V-ATPase trafficking and phagosome acidification (PubMed:22087003). Dephosphorylates and inactivates host VPS33B protein, which inhibits phagosome maturation, fusion with the lysosome and promotes bacteria survival (PubMed:18474358, PubMed:22087003). Dephosphorylation of VPS33B requires interaction of PtpA with host V-ATPase and ubiquitin (PubMed:22087003, PubMed:25642820). Binding to host ubiquitin also leads to the dephosphorylation of phosphorylated Jnk and MAPK p38, leading to suppression of innate immunity (PubMed:25642820). Dephosphorylates host GSK-3 alpha on Tyr-279, which leads to modulation of GSK-3 alpha anti- apoptotic activity, promoting pathogen survival early during infection (PubMed:25187516). In vitro, dephosphorylates two subunits of the trifunctional enzyme TFP (ECHA/ ECHB), which means that it may also affect pathways involved in cell energy metabolism (PubMed:25743628). Furthermore, blocks innate immune system responses mediated by the host adapter TAB3 and dependent on NF-kappa-B by competitively binding the ubiquitin-interacting domain of TAB3, in a phosphatase activity- independent manner (PubMed:25642820). Antagonizes TRIM27-promoted JNK/p38 MAPK pathway activation and cell apoptosis through competitively binding to the RING domain of TRIM27 (PubMed:27698396). In addition, PtpA enters the nucleus of host cells and regulates the expression of several host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration, either by directly binding to the promoters of its target genes, or in an indirect manner (PubMed:28811474). In vitro, can bind directly to the promoter region of GADD45A, a gene encoding a protein involved in cell division, cell death and senescence, and DNA-damage repair (PubMed:28811474). SUBCELLULAR LOCATION: Secreted Host cytoplasmic vesicle, host phagosome Host cytoplasm Host nucleus Note=Translocates into the host cytosol by crossing the host phagosomal membrane during human macrophage infection. Colocalizes with host VPS33B in macrophage cytosol and associates with phagosomes. SIMILARITY: Belongs to the low molecular weight phosphotyrosine protein phosphatase family.


FUNCTION: Endo-1,4-beta-xylanase involved in the hydrolysis of xylan, a major structural heterogeneous polysaccharide found in plant biomass representing the second most abundant polysaccharide in the biosphere, after cellulose. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 10 (cellulase F) family.


FUNCTION: C-4 methylsterol oxidase; part of the third module of ergosterol biosynthesis pathway that includes the late steps of the pathway (PubMed:10783002). ERG25 is a catalytic component of the C-4 demethylation complex that catalyzes the conversion of 4,4- dimethylfecosterol into fecosterol via 4-methylfecosterol (PubMed:10783002). Catalyzes the three-step monooxygenation required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols (PubMed:10783002). The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to form squalene, which is the precursor of all steroids. Squalene synthase is crucial for balancing the incorporation of farnesyl diphosphate (FPP) into sterol and nonsterol isoprene synthesis. Secondly, the squalene epoxidase ERG1 catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, which is considered to be a rate-limiting enzyme in steroid biosynthesis. Then, the lanosterol synthase ERG7 catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol core. In the next steps, lanosterol is transformed to zymosterol through a complex process involving various demethylation, reduction and desaturation reactions. The lanosterol 14-alpha-demethylase ERG11 (also known as CYP51) catalyzes C14-demethylation of lanosterol to produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol, which is critical for ergosterol biosynthesis. The C-14 reductase ERG24 reduces the C14=C15 double bond of 4,4-dimethyl-cholesta-8,14,24-trienol to produce 4,4- dimethyl-cholesta-8,24-dienol. 4,4-dimethyl-cholesta-8,24-dienol is substrate of the C-4 demethylation complex ERG25-ERG26-ERG27 in which ERG25 catalyzes the three-step monooxygenation required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols, ERG26 catalyzes the oxidative decarboxylation that results in a reduction of the 3- beta-hydroxy group at the C-3 carbon to an oxo group, and ERG27 is responsible for the reduction of the keto group on the C-3. ERG28 has a role as a scaffold to help anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum and ERG29 regulates the activity of the iron- containing C4-methylsterol oxidase ERG25. Then, the sterol 24-C- methyltransferase ERG6 catalyzes the methyl transfer from S-adenosyl- methionine to the C-24 of zymosterol to form fecosterol. The C-8 sterol isomerase ERG2 catalyzes the reaction which results in unsaturation at C-7 in the B ring of sterols and thus converts fecosterol to episterol. The sterol-C5-desaturase ERG3 then catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol. The C-22 sterol desaturase ERG5 further converts 5-dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double bond in the sterol side chain. Finally, ergosta-5,7,22,24(28)-tetraen- 3beta-ol is substrate of the C-24(28) sterol reductase ERG4 to produce ergosterol (Probable). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein. SIMILARITY: Belongs to the sterol desaturase family.


FUNCTION: D-aminoacyl-tRNA deacylase with broad substrate specificity. By recycling D-aminoacyl-tRNA to D-amino acids and free tRNA molecules, this enzyme counteracts the toxicity associated with the formation of D-aminoacyl-tRNA entities in vivo. SIMILARITY: Belongs to the DtdA deacylase family.


SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase family.


FUNCTION: Antiproliferative and proapoptotic protein involved in cell stress response which acts as a dual regulator of transcription and autophagy. Acts as a positive regulator of autophagy. In response to cellular stress or activation of autophagy, relocates to autophagosomes where it interacts with autophagosome-associated proteins GABARAP, GABARAPL1/L2, MAP1LC3A/B/C and regulates autophagy. Acts as an antioxidant and plays a major role in p53/TP53-driven oxidative stress response. Possesses both a p53/TP53-independent intracellular reactive oxygen species (ROS) regulatory function and a p53/TP53-dependent transcription regulatory function. Positively regulates p53/TP53 and p73/TP73 and stimulates their capacity to induce apoptosis and regulate cell cycle. In response to double-strand DNA breaks, promotes p53/TP53 phosphorylation on 'Ser-46' and subsequent apoptosis. Acts as a tumor suppressor by inducing cell death by an autophagy and caspase-dependent mechanism. Can reduce cell migration by regulating the expression of SPARC. SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm, cytosol Nucleus Nucleus, PML body Cytoplasmic vesicle, autophagosome Note=Shuttles between the nucleus and the cytoplasm, depending on cellular stress conditions, and re-localizes to autophagosomes on autophagy activation.