FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by pro-inflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Part of a non-canonical MAPK signaling pathway, composed of the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated transcription of APP in response to APOE (PubMed:28111074). SUBCELLULAR LOCATION: Nucleus. Cytoplasm. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.


FUNCTION: Probable ubiquitin-protein ligase which is mainly involved pre-mRNA splicing and DNA repair. Core component of the NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity (By similarity). Together with emb-4, necessary for interaction of rnp-4, a probable exon junction complex component, with mRNAs and spliceosomal snRNAs. Plays a role in nuclear retention of unspliced mRNAs. SUBCELLULAR LOCATION: Nucleus Nucleus, nucleoplasm. SIMILARITY: Belongs to the WD repeat PRP19 family.


FUNCTION: Catalyzes the reversible phosphorolytic breakdown of the N- glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1- phosphate. SIMILARITY: Belongs to the PNP/UDP phosphorylase family.


FUNCTION: Probable thiol-disulfide oxidoreductase that may participate in various redox reactions. SIMILARITY: Belongs to the nucleoredoxin family.


FUNCTION: Catalyzes oxidation of D-erythronate to 2-oxo-tetronate. Can use either NAD(+) or NADP(+) as cosubstrate, with a preference for NAD(+). SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase family.


FUNCTION: Probable GTPase that plays a role in the mitochondrial ribosomal small subunit assembly. Specifically binds the 12S mitochondrial rRNA (12S mt-rRNA) to a 33 nucleotide section delineating the 3' terminal stem-loop region. May act as a chaperone that protects the 12S mt-rRNA on the 28S mitoribosomal subunit during ribosomal small subunit assembly (By similarity). SUBCELLULAR LOCATION: Mitochondrion matrix Mitochondrion inner membrane; Peripheral membrane protein Note=Localizes on the matrix side on the mitochondrial inner membrane. SIMILARITY: Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Era GTPase family.


FUNCTION: As part of the KICSTOR complex may function in the amino acid-sensing branch of the TORC1 signaling pathway. SUBCELLULAR LOCATION: Lysosome membrane. SIMILARITY: Belongs to the KICS2 family.


FUNCTION: Plays an essential role in the regulation of neuronal differentiation and migration during development of the central nervous system. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: May be involved in the regulation of photosystem II. SUBCELLULAR LOCATION: Plastid, chloroplast thylakoid membrane. Note=Associated with the photosystem II complex. SIMILARITY: Belongs to the psbP family.


FUNCTION: Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy (By similarity). Has a role in cell trafficking notably of the Schwann cell and is necessary for the maintenance and development of the peripheral nerve myelin sheath. SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nucleus. Cell membrane Note=Mainly cytoplasmic but differentially localized to other regions. Associates with the plasma membrane in intestinal epithelia and lactating mammary gland. Translocated to the nucleus in a p53/TP53-dependent manner. In prostate epithelium and placental chorion, located in both the cytoplasm and in the nucleus. No nuclear localization in colon epithelium cells. In intestinal mucosa, prostate and renal cortex, located predominantly adjacent to adherens junctions. Cytoplasmic with granular staining in proximal tubular cells of the kidney and salivary gland ducts. Recruits to the membrane of recycling/sorting and late endosomes via binding to phosphatidylinositol 4-phosphate. Associates with microtubules. Colocalizes with TUBG1 in the centrosome. Cytoplasmic location increased with hypoxia. Phosphorylated form found associated with centromeres during S-phase of mitosis and with the plasma membrane (By similarity). SIMILARITY: Belongs to the NDRG family.


FUNCTION: Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Can mediate natural killer (NK) cell cytotoxicity dependent on SH2D1A and SH2D1B (By similarity). Increases proliferative responses of activated T-cells and SH2D1A/SAP does not seem be required for this process. Homophilic interactions enhance interferon gamma/IFNG secretion in lymphocytes and induce platelet stimulation via a SH2D1A-dependent pathway. May serve as a marker for hematopoietic progenitor cells (PubMed:11564780, PubMed:12115647, PubMed:12928397, PubMed:12962726, PubMed:16037392) Required for a prolonged T-cell:B-cell contact, optimal T follicular helper function, and germinal center formation. In germinal centers involved in maintaining B-cell tolerance and in preventing autoimmunity (By similarity). In mast cells negatively regulates high affinity immunoglobulin epsilon receptor signaling; independent of SH2D1A and SH2D1B but implicating FES and PTPN6/SHP-1 (PubMed:22068234). In macrophages enhances LPS-induced MAPK phosphorylation and NF-kappaB activation and modulates LPS-induced cytokine secretion; involving ITSM 2 (By similarity). Positively regulates macroautophagy in primary dendritic cells via stabilization of IRF8; inhibits TRIM21-mediated proteasomal degradation of IRF8 (PubMed:29434592). SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.


FUNCTION: May have the capacity to recognize and bind specific classes of odorants. May act as a carrier molecule, transporting odorants across the mucus layer to access receptor sites. May serve as a primary defense mechanism by recognizing and removing potentially harmful odorants or pathogenic microorganisms from the mucosa or clearing excess odorant from mucus to enable new odorant stimuli to be received (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.


SIMILARITY: Belongs to the mimivirus BTB/WD family.


FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of endogenous polyunsaturated fatty acids (PUFAs). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds, with preference for omega-2 position. Metabolizes (5Z,8Z,11Z,14Z)- eicosatetraenoic acid (arachidonate) toward 18-hydroxy arachidonate (PubMed:11162607). Catalyzes the epoxidation of double bonds of PUFAs such as docosapentaenoic and docosahexaenoic acids (PubMed:16112640). Has low omega-hydroxylase activity toward leukotriene B4 and arachidonate (PubMed:11162645). Involved in the metabolism of xenobiotics. Catalyzes the hydroxylation of the antihistamine drug ebastine (PubMed:11162645). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane Microsome membrane. SIMILARITY: Belongs to the cytochrome P450 family.


FUNCTION: Catalyzes the NAD(+)-dependent oxidative decarboxylation of D-malate into pyruvate. Is essential for aerobic growth on D-malate as the sole carbon source. But is not required for anaerobic D-malate utilization, although DmlA is expressed and active in those conditions. Appears to be not able to use L-tartrate as a substrate for dehydrogenation instead of D-malate. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the isocitrate and isopropylmalate dehydrogenases family.


FUNCTION: ADP-ribose glycohydrolase that hydrolyzes ADP-ribosyl- cysteine bonds (By similarity). Specifically reverses the SirTM- mediated mono-ADP-ribosylation of GcvH-L, by releasing ADP-ribose from the target protein. May be involved in the modulation of the response to host-derived oxidative stress.


FUNCTION: Catalyzes the formation of S-(methylsulfanyl)glutathione and 1-deoxy-D-xylulose 5-phosphate (DXP) from 1-methylthioxylulose 5- phosphate (MTXu-5P) (PubMed:23042035, PubMed:23035785). The S- (methylsulfanyl)glutathione is reductively cleaved to relase methanethiol in a second reaction. Involved in the MTA-isoprenoid shunt of the methionine salvage pathway (PubMed:23042035).


SUBCELLULAR LOCATION: Cytoplasm Note=Associates predominantly in the form of large cytoplasmic complexes.


FUNCTION: Secreted metalloproteinase that allows assimilation of proteinaceous substrates. Shows high activities on basic nuclear substrates such as histone and protamine (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase M35 family.


FUNCTION: Probable S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA (By similarity). May methylate the carboxyl group of leucine residues to form alpha-leucine ester residues. SIMILARITY: Belongs to the methyltransferase superfamily. LCMT family.


FUNCTION: Zeins are major seed storage proteins. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI- anchor. SIMILARITY: Belongs to the gliadin/glutenin family.


FUNCTION: Ice-binding adhesion protein that adsorbs this bacterium onto ice to maintain a favorable position in its aquatic habitat. Inhibits growth of the ice crystals. Has high thermal hysteresis (TH) activity, which is the ability to lower the freezing point of an aqueous solution below its melting point. The TH activity of this protein is approximately 1.4 degrees Celsius at 25 uM and little below 2 degrees Celsius at 80 uM. SUBCELLULAR LOCATION: Cell outer membrane; Lipid-anchor; Extracellular side. SIMILARITY: Belongs to the ice-binding protein family.


FUNCTION: Catalyzes the succinyl-CoA-dependent conversion of glutarate to glutaryl-CoA. Can use different dicarboxylic acids as CoA acceptors, the preferred ones are glutarate, succinate, adipate, and 3- hydroxymethylglutarate (By similarity). SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the CoA-transferase III family.


FUNCTION: Acts as a suppressor component of the dual wtf meiotic drive system, and can suppress but not confer meiotic drive by compatible poisons (By similarity). Wtf meiotic drive systems promote unequal transmission of alleles from the parental zygote to progeny spores by encoding a poison and an antidote from the same locus; the poison is trans-acting and forms toxic aggregates in all spores within an ascus, wherease the antidote is spore-specific and targets aggregates for degradation by the vacuole (By similarity). Meiotic drive by wtf systems therefore lead to poisoning of all progeny that do not inherit the dual poison/antidote allele, or express a compatible antidote (By similarity). SUBCELLULAR LOCATION: Spore membrane; Multi-pass membrane protein Vacuole membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the WTF family.


FUNCTION: May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitment of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits (By similarity). SIMILARITY: Belongs to the DENR family.


FUNCTION: ATP-binding RNA helicase involved in mitochondrial RNA metabolism. Required for maintenance of mitochondrial DNA (By similarity). SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the DEAD box helicase family. MRH4 subfamily.


FUNCTION: A humoral factor that plays a role in stress tolerance; gives increased resistance to the lethal effects of bacterial challenge and stress. Regulated by the JAK/STAT pathway and NF-KB-like Relish pathway in the fat body, upd3 in the hemocytes and Mekk1 in response to septic injury and consequent immune response (By similarity). SUBCELLULAR LOCATION: Secreted Note=Secreted from the fat body into the hemolymph. SIMILARITY: Belongs to the Turandot family.


FUNCTION: Required for several developmental events such as syncytial blastoderm formation and embryonic segmentation. Is involved in transcriptional regulation. Required for arm phosphorylation. Wg signaling operates by inactivating the sgg repression of en autoactivation. Negatively controls the neuromuscular junction (NMJ) growth in presynaptic motoneurons. Plays a role in the regulation of microtubule dynamics and actin cytoskeleton during embryogenesis. Required for phosphorylation of sra in activated eggs. Essential for completion of meiosis, possibly by triggering calcineurin activation via sra phosphorylation. Phosphorylates microtubule-associated protein futsch in axons. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cell cortex. Synapse. Cell projection, axon. Note=In syncytial embryos, detected at the centrosomes throughout the cell cycle, and in the mitotic spindle and pseudocleavage furrows invaginating from the cell cortex during mitosis. Concentrated at the growing end of membranes during the cellularization process. After cellularization, localized to the centrosomes during mitosis and to the nucleus at the end of telophase. Enriched in the presynaptic side of the neuromuscular junction, with some signal detected also in axonal branches. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.


SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. SIMILARITY: In the N-terminal section; belongs to the leguminous lectin family. SIMILARITY: In the C-terminal section; belongs to the protein kinase superfamily. Ser/Thr protein kinase family.


FUNCTION: ATP-dependent RNA helicase involved in mRNA turnover, and more specifically in mRNA decapping. SUBCELLULAR LOCATION: Cytoplasm, P-body Note=Is concentrated in several cytoplasmic foci called P bodies (or cytoplasmic processing bodies) which represent sites of mRNA decapping and 5' to 3' exonucleotidic decay. SIMILARITY: Belongs to the DEAD box helicase family. DDX6/DHH1 subfamily.


FUNCTION: Structural component of flagellum, the bacterial motility apparatus. Part of the rod structure of flagellar basal body (By similarity). SUBCELLULAR LOCATION: Bacterial flagellum basal body. SIMILARITY: Belongs to the flagella basal body rod proteins family.


FUNCTION: Lanthionine-containing peptide antibiotic (lantibiotic) that is probably active on Gram-positive bacteria, since its analog [Del1]Flvbeta.e shows antibacterial activity against Gram-positive bacteria (PubMed:27028884). This activity is not synergistically enhanced by [Del2]Flvalpha.a, an analog of Flvalpha.a, which is encoded by the same operon than Flvbeta.e (PubMed:27028884). The bactericidal activity of lantibiotics is based on depolarization of energized bacterial cytoplasmic membranes, initiated by the formation of aqueous transmembrane pores (By similarity). SUBCELLULAR LOCATION: Secreted.


FUNCTION: Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery. Required for maturation of extramitochondrial Fe-S proteins. Functions as Fe-S scaffold, mediating the de novo assembly of an Fe-S cluster and its transfer to target apoproteins. Essential for embryo development. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP1/NBP35 subfamily.


FUNCTION: Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C18:3(n-6) acyl-CoA. May participate in the production of monounsaturated and of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators (By similarity). In conditions where the essential linoleic and alpha linoleic fatty acids are lacking it is also involved in the synthesis of Mead acid from oleic acid (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein Cell projection, dendrite Note=In Purkinje cells, the protein localizes to the soma and proximal portion of the dendritic tree. SIMILARITY: Belongs to the ELO family. ELOVL5 subfamily.


FUNCTION: Receptor for chemokine SCYA25/TECK. Subsequently transduces a signal by increasing the intracellular calcium ions level (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 1 family.


FUNCTION: Inhibits the expression or activity of extracellular murein hydrolases by interacting, possibly with LrgB, with the holin-like protein CidA. The LrgAB and CidA proteins may affect the proton motive force of the membrane. May be involved in programmed cell death (PCD), possibly triggering PCD in response to antibiotics and environmental stresses. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the CidA/LrgA family. LrgA subfamily.


FUNCTION: May play a key role in alkaline pH tolerance. SIMILARITY: Belongs to the asp23 family.


FUNCTION: Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. SIMILARITY: Belongs to the glycosyl hydrolase 22 family.


SUBCELLULAR LOCATION: Vacuole.


FUNCTION: Early transcription factor that plays a key role in somitogenesis, paraxial mesoderm development and regulation of stem cell pluripotency. Essential for the mesenchymal to epithelial transition associated with somite formation. Required for somite morphogenesis, thereby regulating patterning of the axial skeleton and skeletal muscles. Required for proper localization of somite epithelium markers during the mesenchymal to epithelial transition. Also plays a key role in regulation of stem cell pluripotency. Promotes pluripotency exit of embryonic stem cells (ESCs) by priming ESCs for differentiation. Acts as a key regulator of self-renewal of hematopoietic stem cells (HSCs) by mediating HSCs quiescence and long- term self-renewal. Together with MEOX2, regulates transcription in heart endothelial cells to regulate fatty acid transport across heart endothelial cells. Acts by forming a heterodimer with another helix- loop-helix (bHLH) protein, such as TCF3/E12, that binds DNA on E-box motifs (5'-CANNTG-3') and activates transcription of target genes. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. Is a component of the KEOPS complex that is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. The Kae1 domain likely plays a direct catalytic role in this reaction. The Bud32 domain probably displays kinase activity that regulates Kae1 function. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: In the C-terminal section; belongs to the protein kinase superfamily. Tyr protein kinase family. BUD32 subfamily. SIMILARITY: In the N-terminal section; belongs to the KAE1 / TsaD family.


FUNCTION: Probably required to stimulate the proliferation, polarization and motility of imaginal disk cells. May act by stabilizing the binding of insulin-like peptides to its receptor through a simultaneous interaction with both molecules to form a multiprotein signaling complex (By similarity). SUBCELLULAR LOCATION: Secreted Note=Secreted in hemolymph. It is probably transported to target tissues via hemolymph. SIMILARITY: Belongs to the glycosyl hydrolase 18 family. IDGF subfamily.


FUNCTION: Prevents the interaction between CTNNB1 and TCF family members, and acts as negative regulator of the Wnt signaling pathway. SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the CTNNBIP1 family.


FUNCTION: Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is responsible for the expression of sporulation specific genes. SIMILARITY: Belongs to the sigma-70 factor family.


FUNCTION: Omega-3 fatty acid desaturase that recognizes a range of 18- and 20-carbon omega-6 substrates. Introduces a double bond in the fatty acid chain three carbons away from terminal methyl group to biosynthesize n-3 (omega-3) polyunsaturated fatty acids (PUFAs) endogenously (PUFAs are essential for membrane structure and many cellular and physiological processes). Acts on a number of substrates like linoleoyl-CoA ((9Z,12Z)-octadecadienoyl-CoA, 18:2n-6), dihomo- gamma-linolenoyl-CoA ((8Z,11Z,14Z)-eicosatrienoyl-CoA, 20:3n-6), and arachidonoyl-CoA ((5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA, 20:4n-6), to generate alpha-linolenoyl-CoA ((9Z,12Z,15Z)-octadecatrienoyl-CoA, 18:3n-3), (8Z,11Z,14Z,17Z)-eicosatetraenoyl-CoA (20:4n-3) and (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA (20:5n-3) respectively (PubMed:9037020, PubMed:11972048, PubMed:14765186, PubMed:22041902, PubMed:24391980, PubMed:26806391). Unlike plants, Caenorhabditis elegans desaturases seem to use fatty acyl-CoAs as substrates (By similarity). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the fatty acid desaturase type 1 family.


FUNCTION: Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. Associated with KCNH2/HERG is proposed to form the rapidly activating component of the delayed rectifying potassium current in heart (IKr). May associate with KCNQ2 and/or KCNQ3 and modulate the native M-type current. May associate with HCN1 and HCN2 and increase potassium current. Interacts with KCNQ1; forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein Apical cell membrane; Single-pass membrane protein Note=Colocalizes with KCNB1 at the plasma membrane. SIMILARITY: Belongs to the potassium channel KCNE family.


FUNCTION: Reduces FMN, organic nitro compounds and disulfide DTNB. Involved in maintenance of the cellular redox state and the disulfide stress response. FUNCTION: Reduces FMN, organic nitro compounds and disulfide DTNB. Involved in maintenance of the cellular redox state and the disulfide stress response (By similarity). SIMILARITY: Belongs to the flavin oxidoreductase frp family.


FUNCTION: Required during biogenesis of c-type cytochromes (cytochrome c6 and cytochrome f) at the step of heme attachment. SUBCELLULAR LOCATION: Plastid, chloroplast thylakoid membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the CcmF/CycK/Ccl1/NrfE/CcsA family.


FUNCTION: Primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL). This HDL particle, termed trypanosome lytic factor-1 (TLF-1), mediates human innate immune protection against many species of African trypanosomes. Binds hemoglobin with high affinity and may contribute to the clearance of cell-free hemoglobin to allow hepatic recycling of heme iron. SUBCELLULAR LOCATION: Secreted Note=Secreted into blood plasma and associated with subtypes of high density lipoproteins (HDL). SIMILARITY: Belongs to the peptidase S1 family.


FUNCTION: Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in the PAF inactivation (PubMed:10542206). Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (PubMed:10542206). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. Also required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing (By similarity). Required for pronuclear migration during fertilization. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (By similarity). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Cytoplasm, cytoskeleton, spindle Nucleus membrane Note=Localizes to the plus end of microtubules and to the centrosome. Redistributes to axons during neuronal development. Also localizes to the microtubules of the manchette in elongating spermatids and to the meiotic spindle in spermatocytes (By similarity). May localize to the nuclear membrane. SIMILARITY: Belongs to the WD repeat LIS1/nudF family.


FUNCTION: Involved in pre-mRNA splicing as a component of the spliceosome (PubMed:9724750, PubMed:19592703, PubMed:28781166). May play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex (PubMed:9724750). SUBCELLULAR LOCATION: Nucleus Nucleus speckle.


FUNCTION: Plays a role in mitotic bipolar spindle formation. Binds mRNA. May function in nucleocytoplasmic transport and in directly or indirectly attaching cytoplasmic mRNPs to the cytoskeleton. SUBCELLULAR LOCATION: Cytoplasm Nucleus Cytoplasm, cytoskeleton, spindle pole Note=Recruited from interphase nuclei to spindle MTs during mitosis. SIMILARITY: Belongs to the WD repeat rae1 family.


FUNCTION: Able to depolarize frog skeletal muscle fibers, but has no effects on squid giant axons. Tetrodotoxin is able to partially antagonize the depolarization. Induces myonecrosis. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the true venom lectin family.


FUNCTION: Acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality control. SUBCELLULAR LOCATION: Mitochondrion outer membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the FUN14 family.


FUNCTION: Is probably involved in a pathway contributing to genomic integrity. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein. SIMILARITY: Belongs to the IRC22 family.


FUNCTION: Interacts with the core proteasome alpha-subunit (PrcA) through its C-terminal hydrophobic-tyrosine-X motif (HbYX motif) (PubMed:25469515). Interaction of Bpa with the proteasome stimulates proteasomal peptidase and casein degradation activity, which suggests Bpa could play a role in the removal of non-native or damaged proteins by influencing the conformation of the proteasome complex upon interaction (By similarity). SIMILARITY: Belongs to the Bpa family.


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


SIMILARITY: Belongs to the HGH1 family.


SUBCELLULAR LOCATION: Cell outer membrane; Lipid-anchor.


FUNCTION: Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein Golgi apparatus membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.


FUNCTION: Lytic transglycosylase with a strong preference for naked glycan strands that lack stem peptides. SIMILARITY: Belongs to the RlpA family.


FUNCTION: Transcription repressor. Interacts specifically with the W box (5'-(T)TGAC[CT]-3'), a frequently occurring elicitor-responsive cis-acting element. Regulates, probably indirectly, the activation of defense-related genes during defense response (By similarity). Regulates negatively basal innate immunity and XA21-mediated defense against X.oryzae pv. oryzae (Xoo) (By similarity). FUNCTION: Transcription repressor. Interacts specifically with the W box (5'-(T)TGAC[CT]-3'), a frequently occurring elicitor-responsive cis-acting element. Regulates, probably indirectly, the activation of defense-related genes during defense response (By similarity). Regulates negatively basal innate immunity and XA21-mediated defense against X.oryzae pv. oryzae (Xoo) (PubMed:19825552, PubMed:21961049). SUBCELLULAR LOCATION: Nucleus. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the WRKY group II-a family.


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


FUNCTION: Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways (By similarity). Believed to act in part as a component of the putative HOPS endosomal tethering complex which is proposed to be involved in the rab-5-to-rab-7 endosome conversion probably implicating sand-1, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion (PubMed:25273556). The HOPS complex is proposed to be recruited to rab-7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes (PubMed:24374177). Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes (By similarity). Required for fusion of endosomes (By similarity). In association with lgg-2 mediates the tethering of autophagosomes with lysosomes to form autolysosomes (PubMed:25126728, PubMed:24374177). Within the HOPS complex, contributes to the normal development of gut granules in embryonic and adult intestinal cells (PubMed:24501423). SUBCELLULAR LOCATION: Cytoplasm Lysosome membrane; Peripheral membrane protein Late endosome membrane; Peripheral membrane protein Late endosome Lysosome. SIMILARITY: Belongs to the VAM6/VPS39 family.


FUNCTION: Transcriptional regulator that plays a central role in lin- 12/Notch and glp-1/Notch signaling pathways, involved in cell-cell communication that regulate a broad spectrum of cell-fate determinations (PubMed:8625826). Binds directly to the 5'-[A/G]TGGGAA- 3' DNA consensus sequence, which is present in the regulatory region of several genes (PubMed:8625826, PubMed:18706403, PubMed:23615264, PubMed:15297877, PubMed:32196486, PubMed:21737278). Acts as a transcriptional repressor when it is not associated with Notch proteins (By similarity). When in a complex with a Notch intracellular domain (NICD) product of lin-12/Notch or glp-1/Notch, and transcription regulator lag-3, it may act as a transcriptional activator that activates transcription of target genes(PubMed:18381292, PubMed:10830967, PubMed:32196486, PubMed:9003776). Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively (By similarity). Autonomously required in the germline for the stem cell fate, acting in the glp-1-dependent transcriptional activation of genes, including lst-1 and sygl-1 (PubMed:32196486). Involved in cell-fate specification during reproductive system development, by positively autoregulating its own expression, in response to lin-12/Notch signaling (PubMed:23615264, PubMed:32839181). Plays a role in Notch-dependent induction of left-right asymmetry in interneurons and motoneurons (PubMed:21737278). May repress expression of hlh-6, in a lin-12/Notch-independent manner (PubMed:18706403). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the Su(H) family.


FUNCTION: Probable oxidoreductase. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the prenylcysteine oxidase family.


SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the UPF0259 family.


FUNCTION: Catalyzes the attachment of valine to tRNA(Val). As ValRS can inadvertently accommodate and process structurally similar amino acids such as threonine, to avoid such errors, it has a 'posttransfer' editing activity that hydrolyzes mischarged Thr-tRNA(Val) in a tRNA- dependent manner. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family. ValS type 2 subfamily.


FUNCTION: Receptor for retinoic acid (PubMed:17205979). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:17205979). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:17205979). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (By similarity). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:17205979, PubMed:9230306, PubMed:19078967). Formation of heterocomplex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (By similarity). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (By similarity). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (PubMed:15901285). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (PubMed:15901285, PubMed:17905941). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (PubMed:10660575, PubMed:17905941). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (PubMed:19389355). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (By similarity). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Nuclear localization depends on ligand binding, phosphorylation and sumoylation (PubMed:10660575, PubMed:12079996). Translocation to the nucleus is dependent on activation of PKC and the downstream MAPK phosphorylation (PubMed:10660575, PubMed:12079996). Increased nuclear localization upon pulsatile shear stress (By similarity). SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 subfamily.


SIMILARITY: Belongs to the WD repeat WDR3/UTP12 family.


FUNCTION: Transcriptional regulator. SUBCELLULAR LOCATION: Nucleus.


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


FUNCTION: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively. SUBCELLULAR LOCATION: Cytoplasm, cytosol. SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.


FUNCTION: Functions as an electron carrier between membrane-bound cytochrome b6-f and photosystem I in oxygenic photosynthesis. SUBCELLULAR LOCATION: Cellular thylakoid lumen. SIMILARITY: Belongs to the cytochrome c family. PetJ subfamily.


FUNCTION: Plays an essential role in docking and fusion steps of regulated exocytosis (By similarity). At the presynaptic level, RPH3A is recruited by RAB3A to the synaptic vesicle membrane in a GTP- dependent manner where it modulates synaptic vesicle trafficking and calcium-triggered neurotransmitter release (By similarity). In the post-synaptic compartment, forms a ternary complex with GRIN2A and DLG4 and regulates NMDA receptor stability. Also plays a role in the exocytosis of arginine vasopressin hormone (By similarity). SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane Cell projection, dendritic spine Postsynaptic cell membrane Membrane; Peripheral membrane protein.


FUNCTION: V region of the variable domain of immunoglobulin light chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins- secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268). SUBCELLULAR LOCATION: Secreted Cell membrane.


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


FUNCTION: Involved in the biosynthesis of the antifungal antibiotic pyrrolnitrin. Catalyzes the chlorination of tryptophan (Trp) at C7 position to yield 7-chloro-L-tryptophan (7-CLT). The reaction between FADH2, Cl-, and O2 generates the powerful oxidant HOCl, which is presumed to carry out the chlorination reaction. The reaction of HOCl with the active site Lys-79 generates a lysine chloramine, which plays a key role in directing regiospecific chlorination of substrate in this important class of biosynthetic enzymes. It is also able to use bromide ions to generate monobrominated Trp. SIMILARITY: Belongs to the flavin-dependent halogenase family. Bacterial tryptophan halogenase subfamily.


FUNCTION: Epithelial intermediate filament protein. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the intermediate filament family.


FUNCTION: Digests double-stranded RNA. SIMILARITY: Belongs to the IIV-6 142R family.


FUNCTION: Probable transporter. Does not act in the transport of monocarboxylic acids across the plasma membrane. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.


FUNCTION: Catalyzes the conversion of the cyclic tetrahydrodipicolinate (THDP) into the acyclic N-succinyl-L-2-amino-6-oxopimelate using succinyl-CoA. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the type 2 tetrahydrodipicolinate N- succinyltransferase family.


FUNCTION: Protein-glutamine deamidase effector that inhibits the host cell cycle and other key cellular processes such as the actin network and programmed-cell death (PubMed:19308257, PubMed:19225106, PubMed:20870031). Acts by mediating the side chain deamidation of 'Gln- 40' of host NEDD8, converting it to glutamate, thereby abolishing the activity of cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL complexes) (By similarity). Inactivation of CRL complexes prevents ubiquitination and subsequent degradation of the cyclin-dependent kinase inhibitors CDKN1A/p21 and CDKN1B/p27, leading to G1 and G2 cell cycle arrests in host cells (PubMed:19308257). Deamidation of 'Gln-40' of host NEDD8 also triggers macrophage-specific programmed cell death (By similarity). Also able to catalyze deamidation of 'Gln-40' of host ubiquitin in vitro; however, NEDD8 constitutes the preferred substrate in vivo (By similarity). SUBCELLULAR LOCATION: Secreted Host nucleus Note=Secreted via the type III secretion system (TTSS). SIMILARITY: Belongs to the Cif family.


FUNCTION: Adhesin necessary for successful cytadherence and virulence. SUBCELLULAR LOCATION: Cell projection, attachment organelle membrane; Multi-pass membrane protein. Note=Integral and surface exposed membrane protein that localizes to the membrane at the attachment organelle.


FUNCTION: Catalyzes the irreversible cleavage of the glycosidic bond in both 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH/AdoHcy) to adenine and the corresponding thioribose, 5'- methylthioribose and S-ribosylhomocysteine, respectively. Also cleaves 5'-deoxyadenosine, a toxic by-product of radical S-adenosylmethionine (SAM) enzymes, into 5-deoxyribose and adenine. SIMILARITY: Belongs to the PNP/UDP phosphorylase family. MtnN subfamily.


FUNCTION: Acts at transfer of mannose group to a 3-deoxy-D-mono octulonic acid (KDO) via an alpha-1,5 linkage. SIMILARITY: Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.


FUNCTION: ATP-dependent DNA helicase required for initiation of viral DNA replication. It forms a complex with the viral E2 protein. The E1- E2 complex binds to the replication origin which contains binding sites for both proteins. SUBCELLULAR LOCATION: Host nucleus. SIMILARITY: Belongs to the papillomaviridae E1 protein family.


FUNCTION: ATP-dependent specificity component of the Clp protease. It directs the protease to specific substrates. Can perform chaperone functions in the absence of ClpP (By similarity). Probably the major protease that degrades proteins tagged by trans-translation (PubMed:11395451). SIMILARITY: Belongs to the ClpX chaperone family.


FUNCTION: Part of the high-affinity ATP-driven potassium transport (or Kdp) system, which catalyzes the hydrolysis of ATP coupled with the electrogenic transport of potassium into the cytoplasm. This subunit acts as a catalytic chaperone that increases the ATP-binding affinity of the ATP-hydrolyzing subunit KdpB by the formation of a transient KdpB/KdpC/ATP ternary complex. SUBCELLULAR LOCATION: Cell inner membrane; Single-pass membrane protein. SIMILARITY: Belongs to the KdpC family.


FUNCTION: Iron transporter involved in the uptake of iron from the rhizosphere across the plasma membrane in the root epidermal layer. May also transport other divalent cations. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family.


FUNCTION: Component of the methyl-coenzyme M reductase (MCR) I that catalyzes the reductive cleavage of methyl-coenzyme M (CoM-S-CH3 or 2- (methylthio)ethanesulfonate) using coenzyme B (CoB or 7- mercaptoheptanoylthreonine phosphate) as reductant which results in the production of methane and the mixed heterodisulfide of CoB and CoM (CoM-S-S-CoB). This is the final step in methanogenesis. SIMILARITY: Belongs to the methyl-coenzyme M reductase gamma subunit family.


FUNCTION: Catalyzes the alpha,beta-elimination reaction of D-cysteine and of several D-cysteine derivatives. It could be a defense mechanism against D-cysteine. SIMILARITY: Belongs to the ACC deaminase/D-cysteine desulfhydrase family.


SIMILARITY: Belongs to the cornifelin family.


FUNCTION: Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism. SUBCELLULAR LOCATION: Mitochondrion matrix. SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Catalyzes the two-electron reduction of biliverdin IX-alpha to the tetrapyrrole chromophore phytochromobilin (PPhiB). SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the HY2 family.


SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the universal ribosomal protein uL2 family.


FUNCTION: Histone H5 performs the same function as H1, being necessary for the condensation of nucleosome chains into higher order structures, and replaces histone H1 in certain cells. SUBCELLULAR LOCATION: Nucleus. Chromosome. SIMILARITY: Belongs to the histone H1/H5 family.


SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the UPF0104 family.


FUNCTION: Translocates 4-amino-4-deoxy-L-arabinose-phosphoundecaprenol (alpha-L-Ara4N-phosphoundecaprenol) from the cytoplasmic to the periplasmic side of the inner membrane. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the ArnF family.


FUNCTION: Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moieties on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft- association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication. SUBCELLULAR LOCATION: Virion membrane Host apical cell membrane; Single-pass type II membrane protein Note=Preferentially accumulates at the apical plasma membrane in infected polarized epithelial cells, which is the virus assembly site. Uses lipid rafts for cell surface transport and apical sorting. In the virion, forms a mushroom-shaped spike on the surface of the membrane. SIMILARITY: Belongs to the glycosyl hydrolase 34 family.


FUNCTION: Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post- translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence. CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3'. The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3'. CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region. The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (By similarity). Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1 (By similarity). SUBCELLULAR LOCATION: Cytoplasm Nucleus Cytoplasm, cytosol Note=Localizes to sites of DNA damage in a H2AX-independent manner. Shuttling between the cytoplasm and the nucleus is under circadian regulation and is BMAL1-dependent. Sequestered to the cytoplasm in the presence of ID2.


FUNCTION: Encapsidates the genome, protecting it from nucleases. If expressed without protein P it binds non-specifically RNA and therefore can bind it's own mRNA. Interaction with protein P abolishes any non- specific RNA binding, and prevents phosphorylation. The soluble N-P complex encapsidates specifically the genomic RNA, with protein N protecting the genome like a pearl necklace. The encapsidated genomic RNA is termed the nucleocapsid (NC) and serves as template for viral transcription and replication. Protein N binds protein P in the NC through a different interaction, and can be phosphorylated. Subsequent viral replication is dependent on intracellular concentration of newly synthesized protein N. During replication, encapsidation by protein N is coupled to RNA synthesis and all replicative products are resistant to nucleases (By similarity). SUBCELLULAR LOCATION: Virion. Host cytoplasm. SIMILARITY: Belongs to the ephemerovirus nucleocapsid protein family.


FUNCTION: Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Able also to hydrolyzes the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. SUBCELLULAR LOCATION: Cytoplasm Cell membrane; Peripheral membrane protein Membrane raft Cytoplasm, cytoskeleton Note=Translocates to the plasma membrane when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.


FUNCTION: Seems to associate with BFR; could be a general redox and/or regulatory component participating in the iron storage mobilization functions of BFR. Could participate in the release or the delivery of iron from/to bacterioferritin (or other iron complexes) (By similarity).


FUNCTION: Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation. SUBCELLULAR LOCATION: Secreted, extracellular space. SIMILARITY: Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.


SIMILARITY: Belongs to the universal ribosomal protein uL22 family.


FUNCTION: Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton Cell projection, lamellipodium Cell projection, ruffle Cell projection, microvillus Cell projection, filopodium tip Cell projection, filopodium Note=Rapidly redistributed to ruffles and lamellipodia structures in response to autotaxin, lysophosphatidic acid (LPA) and epidermal growth factor (EGF) treatment. Redistributed to the leading edge of hepatocyte growth factor (HGF)-induced lamellipodia (By similarity). SIMILARITY: Belongs to the villin/gelsolin family.


FUNCTION: The heterodimer non-edited LVP1 induces lipolysis in rat adipocytes. Induction of lipolysis by LVP1 appears to be mediated through the beta-2 adrenergic receptor pathway (ADRB2) (By similarity). FUNCTION: The homodimer inhibits HMG-CoA reductase (HMGCR) (32% of inhibition produced by 0.6 uM), a glycoprotein involved in the control of cholesterol biosynthesis. The inhibitory effects of bumarsin are seen at much lower concentrations (0.6 uM) than that for statins such as atorvastatin (5 mM) and simvastatin (10 uM). In addition to inhibition of HMG-CoA reductase, this protein lowers cholesterol levels by inducing steroid hormone synthesis via StAR, and by increasing reverse cholesterol transport mediated by the induction of ABCA1 and APOA1 (By similarity). FUNCTION: The monomer edited version, similar to alpha-toxins, may modulate voltage-gated sodium channels (Nav) and may block voltage- gated potassium channels (Kv). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the long (3 C-C) scorpion toxin superfamily.


FUNCTION: Putative transporter. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TPT transporter family. SLC35E subfamily.


FUNCTION: Has antimicrobial activity. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the frog skin active peptide (FSAP) family. Dermaseptin subfamily.


FUNCTION: Cleaves the N-terminal amino acid of tripeptides. Has a broad specificity for tripeptides with no clear preference for a particular tripeptide. Tripeptides with proline in the second position are an exception and are not hydrolyzed. Does not hydrolyze dipeptides, tetrapeptides, or oligopeptides (By similarity). FUNCTION: Cleaves the N-terminal amino acid of tripeptides. FUNCTION: Cleaves the N-terminal amino acid of tripeptides. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the peptidase M20B family. SIMILARITY: Belongs to the peptidase M20B family.


FUNCTION: Transcription factor which regulates genes involved in hyphal development, cell adhesion, biofilm development, and virulence. Plays a role in the formation of 'finger' morphology, a unique multicellular morphology of C.albicans induced by carbon dioxide. Regulates gene expression during intestinal colonization. Required for the expression of the secreted aspartyl proteinases SAP4, SAP5, and SAP6; but also of BCR1, PGA4, and CDC24. Moreover, a positive feedback loop between CDC24 and TEC1 contributes to an increase in active CDC42 at the tip of the germ tube which is important for hyphae formation. Regulates also the pheromone response of the white cell phenotype. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the TEC1 family.


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


FUNCTION: Snake venom phospholipase A2 (PLA2) that shows very low inhibition of ADP-induced platelet aggregation in platelet-rich plasma of human, rabbit and guinea pig. In vivo, shows efficient edema- inducing activities in rat paws. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily. D49 sub-subfamily.


FUNCTION: Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to 'Lys-48'-linked polyubiquitin chains in a length-dependent manner and with a lower affinity to 'Lys-63'- linked polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome (By similarity). FUNCTION: Involved in nucleotide excision repair and is thought to be functional equivalent for RAD23B in global genome nucleotide excision repair (GG-NER) by association with XPC. In vitro, XPC:RAD23A dimer has NER activity. Can stabilize XPC (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the RAD23 family.


FUNCTION: Catalyzes the specific phosphorylation of arginine residues in proteins. SIMILARITY: Belongs to the ATP:guanido phosphotransferase family.


FUNCTION: Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.


FUNCTION: Plays a role in attracting adult male S.mansoni to females in vitro.


FUNCTION: In the male reproductive tract, binds to sperm heads where it modulates sperm capacitance by inhibiting calcium uptake and nitrogen oxide (NO) production. FUNCTION: Serine protease inhibitor which exhibits anti-trypsin activity (PubMed:3202973, PubMed:2110056). In the pancreas, protects against trypsin-catalyzed premature activation of zymogens (By similarity). SUBCELLULAR LOCATION: Secreted.


FUNCTION: Involved in the ethylmalonyl-CoA pathway, a new acetyl-CoA assimilation strategy that operates in a number of bacteria and replaces the glyoxylate cycle. Catalyzes the oxidation of (2S)- methylsuccinyl-CoA to yield mesaconyl-(C1)-CoA. Highly specific for (S)-methylsuccinyl-CoA. SIMILARITY: Belongs to the acyl-CoA dehydrogenase family.


FUNCTION: Catalyzes a reversible aldol reaction between acetaldehyde and D-glyceraldehyde 3-phosphate to generate 2-deoxy-D-ribose 5- phosphate. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the DeoC/FbaB aldolase family. DeoC type 2 subfamily.


FUNCTION: Antifreeze proteins lower the blood freezing point. SUBCELLULAR LOCATION: Secreted.


FUNCTION: Beta toxins bind voltage-independently at site-4 of sodium channels (Nav) and shift the voltage of activation toward more negative potentials thereby affecting sodium channel activation and promoting spontaneous and repetitive firing (By similarity). In mice, causes intense writhing. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the long (3 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Beta subfamily.


FUNCTION: Cell adhesion molecule contributing to the interactive process required for myelination in the central nervous system. SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor.


FUNCTION: The transmembrane protein (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm (By similarity). FUNCTION: The leader peptide is a component of released, infectious virions and is required for particle budding. FUNCTION: The surface protein (SU) attaches the virus to the host cell by binding to the cell receptor. This interaction triggers the refolding of transmembrane protein (TM) and is thought to activate its fusogenic potential by unmasking its fusion peptide (By similarity). SUBCELLULAR LOCATION: [Envelope glycoprotein gp130]: Host endoplasmic reticulum membrane. Note=The polyprotein has a highly unusual biosynthesis for a retroviral glycoprotein. It is translated as a full- length precursor protein into the rough endoplasmic reticulum and initially has a type III protein configuration with both its N and C- termini located intracytoplasmically (By similarity). SUBCELLULAR LOCATION: [Transmembrane protein]: Virion membrane; Single-pass type I membrane protein Host endoplasmic reticulum membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: [Surface protein]: Virion membrane; Peripheral membrane protein Host endoplasmic reticulum membrane; Peripheral membrane protein. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. SUBCELLULAR LOCATION: [Leader peptide]: Virion membrane; Single-pass type II membrane protein Host endoplasmic reticulum membrane; Single-pass type II membrane protein Note=Its N-terminus is located inside the viral particle.


FUNCTION: N-methyltransferase that mediates the formation of anserine (beta-alanyl-N(Pi)-methyl-L-histidine) from carnosine. Anserine, a methylated derivative of carnosine (beta-alanyl-L-histidine), is an abundant constituent of vertebrate skeletal muscles. SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase superfamily. HNMT family.


FUNCTION: Transcriptional activator. Activates ectoderm, in addition to inhibiting mesoderm and endoderm formation; required at the blastula stage for normal formation of both the central nervous system and epidermis, the two early derivatives of the ectoderm. In addition, also required to maintain the regional identity of the animal cells of the blastula, the cells that are precursors of ectodermal structures. Also plays a role in differential adhesion, which limits cell mixing as primary germ layers become specified. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Selectively catalyzes the oxidative deamination of D- aspartate and its N-methylated derivative, N-methyl D-aspartate. SUBCELLULAR LOCATION: Peroxisome. SIMILARITY: Belongs to the DAMOX/DASOX family.


FUNCTION: Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the eukaryotic ribosomal protein eL40 family.


FUNCTION: Apoprotein for the two 4Fe-4S centers FA and FB of photosystem I (PSI); essential for photochemical activity. FB is the terminal electron acceptor of PSI, donating electrons to ferredoxin. The C-terminus interacts with PsaA/B/D and helps assemble the protein into the PSI complex. Required for binding of PsaD and PsaE to PSI. PSI is a plastocyanin/cytochrome c6-ferredoxin oxidoreductase, converting photonic excitation into a charge separation, which transfers an electron from the donor P700 chlorophyll pair to the spectroscopically characterized acceptors A0, A1, FX, FA and FB in turn. SUBCELLULAR LOCATION: Plastid, chloroplast thylakoid membrane; Peripheral membrane protein; Stromal side.


FUNCTION: Nematode cuticles are composed largely of collagen-like proteins. The cuticle functions both as an exoskeleton and as a barrier to protect the worm from its environment. Dose-dependent regulator of body length and shape. SIMILARITY: Belongs to the cuticular collagen family.


FUNCTION: Kinetochore- and microtubule-binding protein that plays a key role in spindle assembly (PubMed:24462186, PubMed:24462187, PubMed:26388440). ZNF207/BuGZ is mainly composed of disordered low- complexity regions and undergoes phase transition or coacervation to form temperature-dependent liquid droplets. Coacervation promotes microtubule bundling and concentrates tubulin, promoting microtubule polymerization and assembly of spindle and spindle matrix by concentrating its building blocks (PubMed:26388440). Also acts as a regulator of mitotic chromosome alignment by mediating the stability and kinetochore loading of BUB3 (PubMed:24462186, PubMed:24462187). Mechanisms by which BUB3 is protected are unclear: according to a first report, ZNF207/BuGZ may act by blocking ubiquitination and proteasomal degradation of BUB3 (PubMed:24462186). According to another report, the stabilization is independent of the proteasome (PubMed:24462187). SUBCELLULAR LOCATION: Nucleus Chromosome, centromere, kinetochore Cytoplasm, cytoskeleton, spindle Note=Localizes primarily to the nucleus in interphase, concentrates at kinetochores prior to nuclear envelope breakdown and during early prometaphase, and disappears from kinetochores upon microtubule-binding.


FUNCTION: Catalyzes the conversion of butyryl-CoA through butyryl phosphate to butyrate. SIMILARITY: Belongs to the phosphate acetyltransferase and butyryltransferase family.


FUNCTION: Component of the dark-operative protochlorophyllide reductase (DPOR) that uses Mg-ATP and reduced ferredoxin to reduce ring D of protochlorophyllide (Pchlide) to form chlorophyllide a (Chlide). This reaction is light-independent. The NB-protein (ChlN-ChlB) is the catalytic component of the complex. SIMILARITY: Belongs to the BchN/ChlN family.


FUNCTION: ATP-dependent serine protease that mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix. Necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing and facilitates peroxisome matrix protein import. SUBCELLULAR LOCATION: Peroxisome matrix. SIMILARITY: Belongs to the peptidase S16 family.


FUNCTION: Acyl-CoA ligase; part of the gene cluster that mediates the biosynthesis of the lipopeptides W493 A and B (PubMed:25412204). W493 A and B consist of six amino acid residues D-allo-thr, L-Ala, D-Ala, L- Gln, D-Tyr, and L-Val/L-Ile linked to a 3-hydroxy-4-methyltetradecanoic acid polyketide chain (PubMed:25412204). The biosynthesis starts with formation of the linear polyketide chain by the highly reducing polyketide synthase PKS40 (PubMed:25412204). The gene cluster contains a putative acyl-CoA ligase (FPSE_09184) for formation of a CoA thioester polyketide. The thiol bond could be hydrolyzed by the putative thioesterase (FPSE_09186) and then accepted by the first T domain in module 1 of NRPS32 (PubMed:25412204). The second T domain is responsible for accepting a threonine, which is adenylated by the A domain and epimerized to the D-allo-threonine formed by the E domain. The five successive modules incorporate Ala, Ala, Gln, Tyr, and Val/Ile into the final product, which is released by cyclization (PubMed:25412204). SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix. SIMILARITY: Belongs to the Wnt family.


SIMILARITY: Belongs to the peptidase M3B family.


FUNCTION: Catalyzes the reversible oxidation of malate to oxaloacetate. SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 2 family.


SIMILARITY: Belongs to the OAF family.


FUNCTION: Maximin-9 shows antimicrobial activity against bacteria and against the fungus C.albicans. It has little hemolytic activity (By similarity). FUNCTION: Maximin-H3 shows antibacterial activity against both Gram- positive and Gram-negative bacteria. It shows also antimicrobial activity against the fungus C.albicans. Shows strong hemolytic activity. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the bombinin family.


FUNCTION: Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis. SIMILARITY: Belongs to the annexin family.


FUNCTION: Probable transcription factor. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the ETS family.


FUNCTION: Involved in copper tolerance (PubMed:26396241, PubMed:34791351). Required for copper resistance under both aerobic and anaerobic photosynthetic growth conditions (PubMed:26396241). Binds copper (PubMed:26396241, PubMed:34791351). Could be an important defense against copper in the periplasm and may protect not only c type cytochromes but also other proteins with cysteine residues from copper ions that may catalyze nonnative disulfide bond formation (PubMed:26396241). SUBCELLULAR LOCATION: Periplasm. SIMILARITY: Belongs to the CopI family.


FUNCTION: Protein that can both mediate the addition of adenosine 5'- monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context (By similarity). The side chain of Glu-251 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (By similarity). Acts as a key regulator of the unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of Hsc70-3/BiP. In unstressed cells, acts as an adenylyltransferase by mediating AMPylation of Hsc70-3/BiP at 'Thr-518', thereby inactivating it. In response to endoplasmic reticulum stress, acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from Hsc70-3/BiP at 'Thr-518', leading to restore HSPA5/BiP activity (By similarity). SUBCELLULAR LOCATION: Membrane; Single- pass membrane protein. SIMILARITY: Belongs to the fic family.


FUNCTION: Hydrolyzes dipeptides containing N-terminal aspartate residues. May play a role in allowing the cell to use peptide aspartate to spare carbon otherwise required for the synthesis of the aspartate family of amino acids. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the peptidase S51 family.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the PPase class C family.


FUNCTION: Catalyzes the attachment of a first N-acetyl-N-hydroxylysine to a carboxylic group of citric acid to yield N-citryl-N-acetyl-N- hydroxylysine. Involved in the biosynthesis of the siderophore aerobactin which is a chelator that mediates the high-affinity iron transport systems induced under iron-stressed conditions. SIMILARITY: Belongs to the IucA/IucC family.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.


FUNCTION: Repressor involved in the biosynthesis of the osmoprotectant glycine betaine. It represses transcription of the choline transporter BetT and the genes of BetAB involved in the synthesis of glycine betaine (By similarity). FUNCTION: Repressor involved in the biosynthesis of the osmoprotectant glycine betaine. It represses transcription of the choline transporter BetT and the genes of BetAB involved in the synthesis of glycine betaine.


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


SIMILARITY: Belongs to the UPF0098 family.


FUNCTION: 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. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the PAM17 family.


FUNCTION: Catalyzes an exceptionally high rate of oxidation of a wide range of aldose sugars, including D-glucose, galactose, arabinose and xylose, and also the disaccharides lactose, cellobiose and maltose. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein; Periplasmic side. SIMILARITY: Belongs to the bacterial PQQ dehydrogenase family.


FUNCTION: Negative regulator of sigma-B activity. Phosphorylates and inactivates its specific antagonist protein, RsbV. Upon phosphorylation of RsbV, RsbW is released and binds to sigma-B, thereby blocking its ability to form an RNA polymerase holoenzyme (E-sigma-B). SIMILARITY: Belongs to the anti-sigma-factor family.


FUNCTION: Vacuolar metal transporter involved in intracellular metal homeostasis. Can transport iron (Fe), manganese (Mn) and cadmium (Cd). Regulates metal accumulation under Fe starvation. Acts redundantly with NRAMP3 to mobilize vacuolar Fe and provide sufficient Fe during seed germination. In association with NRAMP3, required for optimal growth and photosynthesis under Mn deficiency. Exports Mn from vacuoles in leaf mesophyll cells, making Mn available for functional photosystem II in chloroplasts. SUBCELLULAR LOCATION: Vacuole membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the NRAMP (TC 2.A.55) family.


FUNCTION: Proton-conducting pore forming subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the V-ATPase proteolipid subunit family.


FUNCTION: Catalyzes the decarboxylation of L-tyrosine to produce tyramine for methanofuran biosynthesis. Can also catalyze the decarboxylation of L-aspartate to produce beta-alanine for coenzyme A (CoA) biosynthesis. SIMILARITY: Belongs to the group II decarboxylase family. MfnA subfamily.


FUNCTION: Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides (By similarity). SIMILARITY: Belongs to the ribonucleoside diphosphate reductase small chain family.


SIMILARITY: Belongs to the Crescerin family.


SIMILARITY: Belongs to the Orn/Lys/Arg decarboxylase class-II family. SpeA subfamily.


FUNCTION: Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl- glutathione to form glutathione and D-lactic acid. SIMILARITY: Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.


SIMILARITY: Belongs to the [NiFe]/[NiFeSe] hydrogenase small subunit family.


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


FUNCTION: This protein specifically catalyzes the removal of signal peptides from prolipoproteins. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the peptidase A8 family.


FUNCTION: Has antifungal activity against C.albicans. Has antibacterial activity against the Gram-positive bacterium S.aureus and the Gram- negative bacterium E.coli. Lacks hemolytic activity against rabbit erythrocytes.


FUNCTION: Catalyzes the dephosphorylation of undecaprenyl diphosphate (UPP). Confers resistance to bacitracin. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the UppP family.


FUNCTION: May play a role in fatty acid biosynthesis and insulin sensitivity. SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the enoyl-CoA hydratase/isomerase family.


SIMILARITY: Belongs to the TRIM/RBCC family.


FUNCTION: May play a key role in the regulation of the intracellular concentration of adenosylhomocysteine. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the adenosylhomocysteinase family.


FUNCTION: May transfer electrons to the iron-sulfur centers of SerB. SUBCELLULAR LOCATION: Periplasm.


FUNCTION: Mitochondrial acyltransferase which transfers an acyl group to the N-terminus of glycine and glutamine, although much less efficiently. Can conjugate numerous substrates to form a variety of N- acylglycines, with a preference for benzoyl-CoA over phenylacetyl-CoA as acyl donors. Thereby detoxify xenobiotics, such as benzoic acid or salicylic acid, and endogenous organic acids, such as isovaleric acid. SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the glycine N-acyltransferase family.


FUNCTION: Component of antiviral defense system DISARM (defense island system associated with restriction-modification), composed of DrmE, DrmA, DrmB, DrmC and DrmMII. DISARM is probably a multi-gene restriction module, this subunit has an unknown function. Expression of DISARM in B.subtilis (strain BEST7003) confers resistance to phages Nf, phi29, phi105, phi3T, SPO1, SPR and SPP1. Protection is over 10(7)-fold against phi3T, 10(4)-10(5)-fold against Nf, phi29, phi105 and SPR, 100- fold against SPO1 and 10-fold against SPP1. DISARM does not interfere with phage adsorption, but instead interferes with (phi3T) DNA replication early in its cycle, preventing replication, circularization and lysogeny and probably causes phage DNA degradation (DNA is degraded in SPP1-infected cells). SUBCELLULAR LOCATION: Cytoplasm.


FUNCTION: Mediates the reversible addition of palmitate to target proteins, thereby regulating their membrane association and biological function. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the DHHC palmitoyltransferase family. PFA4 subfamily.


FUNCTION: May play a role in the proliferation or differentiation of keratinocytes. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.


FUNCTION: Acts by interacting with multiple viral and host proteins to enhance the activity of viral RNA-dependent RNA polymerase.


FUNCTION: Axonemal dynein assembly factor required for ciliary motility. Involved in neuronal migration during development of the cerebral neocortex. May regulate the stability and proteasomal degradation of the estrogen receptors that play an important role in neuronal differentiation, survival and plasticity. SUBCELLULAR LOCATION: Nucleus Cytoplasm Dynein axonemal particle Cell projection, neuron projection.


FUNCTION: Mono-ADP-ribosylates eukaryotic muscle and non-muscle actin on 'Arg-177'. ADP-ribosylates all actins tested, has more activity on nonmuscle beta/gamma-actin than on muscle alpha-actin. Prefers monomeric G-actin but can weakly ADP-ribosylate F-actin. ADP- ribosylation prevents the polymerization of G-actin to F-actin, causing actin filament depolymerization, destruction of the cytoskeleton and cytotoxicity. Does not possess NAD(+)-glycohydrolase activity, unlike most mART enzymes. SUBCELLULAR LOCATION: Secreted. Note=Secreted via the type III secretion system 1 (SPI-2 TTSS). SIMILARITY: Belongs to the SpvB family.


FUNCTION: Putative adapter protein.


FUNCTION: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. SUBCELLULAR LOCATION: Nucleus. Chromosome. SUBCELLULAR LOCATION: Nucleus Chromosome. SIMILARITY: Belongs to the histone H3 family.


FUNCTION: Component of the cuticle of the larva of Tenebrio molitor.


FUNCTION: Outer membrane channel, which is required for the function of several efflux systems (By similarity). Required for virulence. SUBCELLULAR LOCATION: Cell outer membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the outer membrane factor (OMF) (TC 1.B.17) family.


FUNCTION: This protein is the basis of the ABO blood group system. The histo-blood group ABO involves three carbohydrate antigens: A, B, and H. A, B, and AB individuals express a glycosyltransferase activity that converts the H antigen to the A antigen (by addition of UDP-GalNAc) or to the B antigen (by addition of UDP-Gal), whereas O individuals lack such activity. SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane; Single- pass type II membrane protein. Secreted. Note=Membrane-bound form in trans cisternae of Golgi. Secreted into the body fluid. SIMILARITY: Belongs to the glycosyltransferase 6 family.


FUNCTION: Component of the regulatory network controlling carbon source utilization through ubiquitination and deubiquitination involving creA, creB, creC, creD and acrB. Required to prevent the proteolysis of the CreB deubiquitinating enzyme in the absence of carbon catabolite repression. CreB deubiquitinating enzyme stabilized in a complex with the CreC leads to the expression of genes such as those in the proline and quinate pathways (By similarity). SIMILARITY: Belongs to the WD repeat creC family.


FUNCTION: Plays a role in the regulation of phosphate uptake. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the PhoU family.


FUNCTION: Required for late and very late gene expression. SIMILARITY: Belongs to the baculoviridae LEF-5 family.


FUNCTION: Essential component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Suppresses G-protein- and mitogen-activated protein kinase-mediated signal transduction (By similarity). SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the CSN1 family.


FUNCTION: Alkylbase DNA glycosidase-like protein that shows no DNA glycosylase activity for alkylated bases (PubMed:23273506, PubMed:23245849). The molecular role of mag2 appears to be abasic (AP) site recognition and protection, while possibly facilitating damage signaling by structurally sculpting the DNA substrate (PubMed:18270439, PubMed:23245849). Stimulates AP site binding to mismatch repair protein mutS (PubMed:23245849). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the alkylbase DNA glycosidase AlkA family.


FUNCTION: Aquaglyceroporin that may modulate the water content and osmolytes during anhydrobiosis (PubMed:23761966). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.


FUNCTION: Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross- linking of the peptide subunits) (By similarity). SUBCELLULAR LOCATION: Cell inner membrane. SIMILARITY: In the C-terminal section; belongs to the transpeptidase family. SIMILARITY: In the N-terminal section; belongs to the glycosyltransferase 51 family.


FUNCTION: Catalyzes the first step of diphthamide biosynthesis, a post- translational modification of histidine which occurs in elongation factor 2. Dph1 and dph2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising dph3 and a NADH-dependent reductase, predominantly cbr1. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the DPH1/DPH2 family. DPH1 subfamily.


FUNCTION: Catalyzes the reduction of flavin by NADH. Subsequently, the reduced flavins is transferred to the tetracycline 7-halogenase CtcP. SIMILARITY: Belongs to the non-flavoprotein flavin reductase family.


SUBCELLULAR LOCATION: Secreted, cell wall. Note=Tightly bound to cell wall. SIMILARITY: Belongs to the glycosyl hydrolase 17 family.


FUNCTION: Broad substrate specificity glycosidase. Releases glucose from soluble glucooligomers, with a preference for longer oligomers; acts more readily on cellotetraose than on cellobiose. Displays similar activities towards the disaccharides lactose and cellobiose. Is also able to hydrolyze various aryl-beta-glycosides in vitro. SIMILARITY: Belongs to the glycosyl hydrolase 1 family.


FUNCTION: Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 1 family.


FUNCTION: Responsible for the transport of C4-dicarboxylates during anaerobic growth. Catalyzes the uptake of fumarate coupled to the export of succinate. FUNCTION: Responsible for the transport of C4-dicarboxylates during anaerobic growth (PubMed:8955408, PubMed:10368146). Catalyzes the uptake of fumarate coupled to the export of succinate (PubMed:8955408). Can also catalyze the uptake of fumarate and the efflux of succinate, without exchange (PubMed:8955408, PubMed:10368146). Shows low rates of transport, which are sufficient for succinate export during fermentation but not for fumarate-succinate exchange in fumarate respiration, indicating that it may function in vivo as the succinate efflux carrier for glucose fermentation, even if it is also able to operate as a fumarate-succinate antiporter (PubMed:10368146). SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the DcuC/DcuD transporter (TC 2.A.61) family.


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


FUNCTION: Could be involved in the secretion of the yop virulence proteins. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the FHIPEP (flagella/HR/invasion proteins export pore) family.


FUNCTION: May be involved in the O-acetylation of mannan (PubMed:22086088). May act as a bridging protein that binds pectin and other cell wall polysaccharides. Probably involved in maintaining esterification of pectins (By similarity). SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein. SIMILARITY: Belongs to the PC-esterase family. TBL subfamily.


FUNCTION: Catalyzes the retro-aldol cleavage of 4-hydroxy-2- oxopentanoate to pyruvate and acetaldehyde. Is involved in the meta- cleavage pathway for the degradation of p-cumate. SIMILARITY: Belongs to the 4-hydroxy-2-oxovalerate aldolase family.


FUNCTION: Protein tyrosine phosphatase that exhibits also a weak lipid phosphatase activity towards PtdIns(3)P. SIMILARITY: Belongs to the PTEN phosphatase protein family.


FUNCTION: Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells. Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3- responsive target genes (By similarity). Plays a central role in calcium homeostasis (By similarity). Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Localizes mainly to the nucleus. Translocated into the nucleus via both ligand-dependent and ligand- independent pathways; ligand-independent nuclear translocation is mediated by IPO4. SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 subfamily.


FUNCTION: Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not have activity toward 'Lys-48'-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys- 63'-linked ubiquitin in various substrates. Mediates the specific 'Lys- 63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (By similarity). Acts as a regulator of the NLRP3 inflammasome by mediating deubiquitination of NLRP3, leading to NLRP3 inflammasome assembly (By similarity). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (By similarity). Deubiquitinates HDAC1 and PWWP2B leading to their stabilization (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Cytoplasm, cytoskeleton, spindle pole Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). Interaction with ABRAXAS2 retains BRCC3 in the cytoplasm. SIMILARITY: Belongs to the peptidase M67A family. BRCC36 subfamily.


FUNCTION: Putative methylesterase. SUBCELLULAR LOCATION: Plastid, chloroplast. SIMILARITY: Belongs to the AB hydrolase superfamily. Methylesterase family.


FUNCTION: Cell surface receptor that plays a functionally redundant role in postnatal brain development and in regulating axon regeneration in the adult central nervous system (PubMed:22406547, PubMed:27339102). Contributes to normal axon migration across the brain midline and normal formation of the corpus callosum (PubMed:27339102). Protects motoneurons against apoptosis; protection against apoptosis is probably mediated by MAG (PubMed:26335717). Plays a role in inhibiting neurite outgrowth and axon regeneration via its binding to neuronal chondroitin sulfate proteoglycans (PubMed:22406547). Binds heparin (PubMed:22406547). Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200). SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor Membrane raft Perikaryon Cell projection Note=Localized to the surface of neurons, including axons. SIMILARITY: Belongs to the Nogo receptor family.