FUNCTION: Part of the ABC transporter complex PstSACB involved in phosphate import; probably responsible for the translocation of the substrate across the membrane. FUNCTION: Part of the binding-protein-dependent transport system for phosphate; probably responsible for the translocation of the substrate across the membrane. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the binding-protein-dependent transport system permease family. CysTW subfamily.


FUNCTION: Regulates pectin lyase production in response to DNA damage. SIMILARITY: Belongs to the c/mor transcriptional regulatory family.


SUBCELLULAR LOCATION: Cell projection, cilium Note=Localizes to the base of the cilium. SIMILARITY: Belongs to the CCDC149 family.


SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor. SIMILARITY: Belongs to the M.pulmonis LipAB lipoprotein family.


FUNCTION: Acts as a component of the NMS (Ndc80-MIND-Spc7) super complex which has a role in kinetochore function during late meiotic prophase and throughout the mitotic cell cycle. Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. SUBCELLULAR LOCATION: Nucleus. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body. Note=Associated with kinetochores. SIMILARITY: Belongs to the NUF2 family.


FUNCTION: NAD-dependent lysine deacetylase that specifically removes acetyl groups on target proteins. Also acts as a protein-lysine deacylase by mediating protein desuccinylation and de-2- hydroxyisobutyrylation. Modulates the activities of several proteins which are inactive in their acylated form. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the sirtuin family. Class III subfamily.


SIMILARITY: Belongs to the troponin C family.


FUNCTION: May play a role in the regulation of plant growth and development. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.


FUNCTION: Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. Plays a role in intracellular vesicle trafficking. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. May be required for normal dopamine homeostasis in the cerebral cortex, hippocampus, and hypothalamus. Plays a role in the regulation of cell surface exposure of DRD2. Contributes to the regulation of dopamine signaling. May play a role in actin cytoskeleton reorganization and neurite outgrowth (By similarity). SUBCELLULAR LOCATION: Cytoplasm Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Endosome membrane; Peripheral membrane protein; Cytoplasmic side Melanosome membrane; Peripheral membrane protein; Cytoplasmic side Nucleus Postsynaptic density Endoplasmic reticulum Note=Detected at axon terminals and in dendrites. Detected at synapses, at postsynaptic density, at presynaptic vesicle membranes and microtubules. Detected at tubulovesicular elements in the vicinity of the Golgi apparatus and of melanosomes. Detected in neuron cell bodies, axons and dendrites (By similarity). SIMILARITY: Belongs to the dysbindin family.


FUNCTION: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc) residue from UDP-GalNAc to a serine or threonine residue on the protein receptor (By similarity). Generates GalNAc-O-Ser/Thr structure also known as Tn antigen, which itself is immunogenic but also serves as a precursor for the synthesis of different mucin-type O-glycan core structures (By similarity). Contributes to the synthesis of O-linked glycans on mucins and proteoglycans of the central nervous system (By similarity). Can glycosylate both unmodified peptides and glycopeptides that already contain an O-linked GalNAc sugar. Transfers GalNAc to Thr-/Ser-rich tandem repeats GTTPSPVPTTSTTSAP of MUC5AC. Transfers GalNAc to three consecutive serine/threonine residues on SDC3 forming a triplet-Tn epitope expressed in Purkinje cells of the developing brain (By similarity). May promote neurogenesis through glycosylation and stabilization of PDPN (By similarity). SUBCELLULAR LOCATION: Golgi apparatus membrane; Single- pass type II membrane protein. SIMILARITY: Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.


FUNCTION: Plays a role in regulating the structure of the Golgi apparatus. SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network Cell junction, tight junction Cell membrane; Peripheral membrane protein Note=Recruited to tight junctions (TJ) during late stages of maturation of the TJ complexes. Excluded from adherens junctions and desmosomes.


FUNCTION: Dual specificity protein kinase that phosphorylates ANN1, ANN2 and CP29B at serine and threonine residues, and ANN1, ANN2 and ANN4 at tyrosine residues. May regulate the phosphorylation status of annexin proteins (PubMed:26452715). Acts as positive regulator in abscisic acid (ABA)-mediated regulation of postgermination growth and drought response. May regulate the expression of ABA-responsive genes such as RD22, RD29A, LTI65/RD29B and RAB18 (PubMed:27264339). SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.


SUBCELLULAR LOCATION: Secreted. SUBCELLULAR LOCATION: Secreted.


SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the FAD-dependent glycerol-3-phosphate dehydrogenase family.


SUBCELLULAR LOCATION: Nucleus membrane; Single-pass membrane protein. SIMILARITY: Belongs to the RMD1/sif2 family.


FUNCTION: Aminopeptidase which cleaves preprotein intermediates that carry destabilizing N-ter amino acid residues after the mitochondrial processing peptidase (MPP) cleavage site and is thus critical for stabilization of the mitochondrial proteome. SUBCELLULAR LOCATION: Nucleus Mitochondrion inner membrane; Peripheral membrane protein; Matrix side Note=Has the same dual localization (mitochondrion and nucleus) as one of its substrate, NFS1. SIMILARITY: Belongs to the peptidase M24B family.


FUNCTION: NAD(P)H-dependent oxidoreductase involved in metabolic inactivation of pro- and anti-inflammatory eicosanoids: prostaglandins (PG), leukotrienes (LT) and lipoxins (LX). Catalyzes with high efficiency the reduction of the 13,14 double bond of 15-oxoPGs, including 15-oxo-PGE1, 15-oxo-PGE2, 15-oxo-PGF1-alpha and 15-oxo-PGF2- alpha (By similarity). Catalyzes with lower efficiency the oxidation of the hydroxyl group at C12 of LTB4 and its derivatives, converting them into biologically less active 12-oxo-LTB4 metabolites (By similarity). Reduces 15-oxo-LXA4 to 13,14 dihydro-15-oxo-LXA4, enhancing neutrophil recruitment at the inflammatory site (By similarity). Plays a role in metabolic detoxification of alkenals and ketones. Reduces alpha,beta- unsaturated alkenals and ketones, particularly those with medium-chain length, showing highest affinity toward (2E)-decenal and (3E)-3-nonen- 2-one (By similarity). May inactivate 4-hydroxy-2-nonenal, a cytotoxic lipid constituent of oxidized low-density lipoprotein particles (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the NADP-dependent oxidoreductase L4BD family.


FUNCTION: Involved in disulfide bond formation. Catalyzes a late, reductive step in the assembly of periplasmic c-type cytochromes, probably the reduction of disulfide bonds of the apocytochrome c to allow covalent linkage with the heme. Possible subunit of a heme lyase (By similarity). SUBCELLULAR LOCATION: Cell inner membrane; Single-pass membrane protein; Periplasmic side. SIMILARITY: Belongs to the thioredoxin family. DsbE subfamily.


FUNCTION: Required for the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Involved in the assembly of the distal region of complex I. SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the ATP synthase subunit s family.


FUNCTION: Magnesium transporter that mediates the influx/efflux of magnesium in a concentration-dependent manner. Plays a crucial role in male gametophyte development and male fertility. SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35.5) family.


FUNCTION: Catalyzes the reduction of the macrocycle of cobalt- precorrin-6A to cobalt-precorrin-6B. SIMILARITY: Belongs to the precorrin-6x reductase family.


FUNCTION: Probable transcription factor involved in the negative regulation of flowering, probably through the photoperiodic pathway. Prevents premature flowering. Downstream regulator of a subset of the MIKC* MADS-controlled genes required during pollen maturation. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Mediates the uptake of pyruvate into mitochondria. SUBCELLULAR LOCATION: Mitochondrion Mitochondrion inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.


SUBCELLULAR LOCATION: Plastid, chloroplast membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the Tic20 family.


FUNCTION: Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2 or ILF2 (PubMed:33009960). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (PubMed:20223979, PubMed:24328678, PubMed:25043012, PubMed:25108355). Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons (PubMed:18414909, PubMed:29530986). Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (PubMed:18414909). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (By similarity). Plays a negative role in TLR4 signaling by interacting with TRAF6 and ECSIT, leading to inhibition of ECSIT ubiquitination, an important step of the signaling (PubMed:31620128). SUBCELLULAR LOCATION: Cytoplasm Nucleus Membrane; Peripheral membrane protein. SIMILARITY: Belongs to the CRBN family.


FUNCTION: Involved in the repression of jasmonate (JA)-induced genes. Forms a ternary complex with TIFY11A/JAZ9 and BHLH094 to negatively regulate JA-responsive genes. Involved in transcriptional regulation in the root tip. Plays a regulatory role in root cell elongation. Regulates root cell elongation during salt stress. SUBCELLULAR LOCATION: Nucleus Cytoplasm.


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 involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37, together with TsaD and TsaB. TsaE seems to play an indirect role in the t(6)A biosynthesis pathway, possibly in regulating the core enzymatic function of TsaD (By similarity). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the TsaE family.


SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor. SIMILARITY: Belongs to the TP013X lipoprotein family.


FUNCTION: Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR- mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. In addition to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface. Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.


FUNCTION: Promotes mitotic spindle assembly. SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. NCD subfamily.


FUNCTION: Receptor for the bacteriocin pesticin and for the siderophore yersiniabactin. SUBCELLULAR LOCATION: Cell outer membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TonB-dependent receptor family.


FUNCTION: High-affinity transporter for external inorganic phosphate. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.


FUNCTION: DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (PubMed:27852435, PubMed:27871366, PubMed:27871365, PubMed:32649882, PubMed:30893605). DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde (PubMed:27852435, PubMed:27871366, PubMed:27871365, PubMed:32649882). Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis (PubMed:27852435, PubMed:27871366, PubMed:27871365, PubMed:32649882). Acts as a pleiotropic protease for DNA-binding proteins cross-linked with DNA, such as TOP1, TOP2A, histones H3 and H4 (PubMed:27871366). Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs (By similarity). SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs (By similarity). Involved in recruitment of VCP/p97 to sites of DNA damage (PubMed:22902628, PubMed:23042605, PubMed:23042607, PubMed:32152270). Also acts as an activator of CHEK1 during normal DNA replication by mediating proteolytic cleavage of CHEK1, thereby promoting CHEK1 removal from chromatin and subsequent activation (PubMed:31316063). Does not activate CHEK1 in response to DNA damage (PubMed:31316063). May also act as a 'reader' of ubiquitinated PCNA: recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA (PubMed:22681887, PubMed:22894931, PubMed:22902628, PubMed:22987070). Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis (PubMed:22681887). SUBCELLULAR LOCATION: Nucleus Chromosome Note=Localizes to sites of UV damage via the PIP-box (PubMed:22894931, PubMed:23042605). Recruited to stalled replication forks at sites of replication stress following deubiquitination (PubMed:22894931, PubMed:23042605, PubMed:22987070, PubMed:27871365, PubMed:32649882). CHEK1 stimulates recruitment to chromatin (PubMed:31316063). SIMILARITY: Belongs to the Spartan family.


FUNCTION: Inhibitor of protein-phosphatase 1. SIMILARITY: Belongs to the protein phosphatase inhibitor 2 family.


FUNCTION: [Latency-associated peptide]: Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix. Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1. Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia. Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency- associated peptide chain and subsequent release of the active TGF-beta- 1. FUNCTION: Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively. FUNCTION: [Transforming growth factor beta-1]: Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency- associated peptide (LAP) and Transforming growth factor beta-1 (TGF- beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix. At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus. TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin- binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1. Once activated following release of LAP, TGF- beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity). While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency- associated peptide chain (LAP) and 'milieu molecules'. Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells (By similarity). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus. Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (By similarity). SUBCELLULAR LOCATION: [Latency-associated peptide]: Secreted, extracellular space, extracellular matrix. SUBCELLULAR LOCATION: [Transforming growth factor beta-1]: Secreted. SIMILARITY: Belongs to the TGF-beta family.


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


FUNCTION: Converts choline-O-sulfate into choline. SIMILARITY: Belongs to the sulfatase family.


SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TMEM170 family.


FUNCTION: Serine protease inhibitor that specifically inhibits trypsin (Ki=73.8-78 nM) and chymotrypsin (Ki=993 nM) (PubMed:17886436, PubMed:17288251, PubMed:33802055). In vitro, it shows cytoprotective activity in the oxidative stress agent 6-hydroxydopamine (6-OHDA)- induced neurotoxicity model (PubMed:33802055). In this model, it decreases reactive oxygen species (ROS) level, and increases cell viability in a correlated manner (PubMed:33802055). It is possible that the observed effect is due to the ability of this peptides to act as free-radical scavenger (PubMed:33802055). SUBCELLULAR LOCATION: Secreted Nematocyst. SIMILARITY: Belongs to the venom Kunitz-type family. Sea anemone type 2 potassium channel toxin subfamily.


FUNCTION: Acts as a negative regulator for calcification in the shells of mollusks. May function both as a calcium concentrator and as a carbonic anhydrase required for production of carbonate ions, which are assembled to CaCO(3) at mineralization sites. Is important for shell formation in both the calcitic prismatic layer and the aragonitic nacreous layer (By similarity). SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix. SIMILARITY: Belongs to the alpha-carbonic anhydrase family.


FUNCTION: Muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites. Specifically binds phosphatidylserine. Acts as a sensor of oxidation: upon membrane damage, entry of extracellular oxidative environment results in disulfide bond formation and homooligomerization at the injury site. This oligomerization acts as a nucleation site for recruitment of TRIM72-containing vesicles to the injury site, leading to membrane patch formation. Probably acts upstream of the Ca(2+)- dependent membrane resealing process (By similarity). SUBCELLULAR LOCATION: Cell membrane, sarcolemma Cytoplasmic vesicle membrane Note=Tethered to plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. SIMILARITY: Belongs to the TRIM/RBCC family.


FUNCTION: Catalyzes the dephosphorylation of the nucleoside 5'- monophosphates deoxyadenosine monophosphate (dAMP), deoxycytidine monophosphate (dCMP), deoxyguanosine monophosphate (dGMP) and deoxythymidine monophosphate (dTMP). SIMILARITY: Belongs to the HDDC2 family.


FUNCTION: Phosphatase which shows a preference for 4'- phosphopantetheine and its oxidatively damaged forms (sulfonate or S- sulfonate), providing strong indirect evidence that the phosphatase activity pre-empts damage in the coenzyme A (CoA) pathway. Hydrolyzing excess 4'-phosphopantetheine could constitute a directed overflow mechanism to prevent its oxidation to the S-sulfonate, sulfonate, or other forms. Hydrolyzing 4'-phosphopantetheine sulfonate or S-sulfonate would forestall their conversion to inactive forms of CoA and acyl carrier protein. May play a role in the physiological regulation of CoA intracellular levels. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: In the N-terminal section; belongs to the type II pantothenate kinase family. SIMILARITY: In the C-terminal section; belongs to the damage-control phosphatase family. Phosphopantetheine phosphatase (II) subfamily.


FUNCTION: Probable transcription factor, which may be involved in embryonic patterning (PubMed:14711878). May be required for basal embryo development after fertilization (PubMed:14711878). Acts partially redundantly with STIP in promoting embryonic cell division and proliferation (PubMed:17706632). Promotes cotyledon boundary formation by maintaining the symmetry in CUC genes expression domains (PubMed:22827849). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the WUS homeobox family.


FUNCTION: Plays a central role as a glucosyl donor in cellular metabolic pathways. SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the UDPGP type 1 family.


FUNCTION: [Isoform 2]: In tooth development, may play a role in the recruitment and the differentiation of cells that contribute to cementum formation. May also bind hydroxyapatite and regulate its crystal nucleation to form cementum. FUNCTION: [Isoform 1]: Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum- bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the very long-chain fatty acids dehydratase HACD family.


FUNCTION: Binds ATP/ADP in vitro. Possesses low ATPase activity but high affinity for microtubules. SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KIN-7 subfamily.


FUNCTION: Catalyzes the sequential condensation of isopentenyl diphosphate (IPP) with (2E,6E)-farnesyl diphosphate (E,E-FPP) to yield (2Z,6Z,10Z,14Z,18Z,22Z,26Z,30Z,34E,38E)-undecaprenyl diphosphate (di- trans,octa-cis-UPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide. SIMILARITY: Belongs to the UPP synthase family.


FUNCTION: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene- specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity). May play a role in transcription elongation (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the Mediator complex subunit 26 family.


FUNCTION: Promotes colloidosmotic lysis by binding to the midgut epithelial cells of both dipteran (Aedes aegypti) and lepidopteran (Manduca sexta) larvae. SIMILARITY: Belongs to the delta endotoxin family.


FUNCTION: Has a dual role in the assembly of mitochondrial ATPase. Acts as a protease that removes N-terminal residues of mitochondrial ATPase CF(0) subunit 6 at the intermembrane space side. Also involved in the correct assembly of the membrane-embedded ATPase CF(0) particle, probably mediating association of subunit 6 with the subunit 9 ring (By similarity). SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side. Note=Associates loosely with the inner membrane. SIMILARITY: Belongs to the peptidase M76 family.


FUNCTION: May function as a transcription factor. May be involved in the development of multiple embryonic organs. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein family.


FUNCTION: Activator of the mhpABCDFE operon coding for components of the 3-hydroxyphenylpropionate degradation pathway.


FUNCTION: Involved in ribosome biogenesis. Required for normal pre-rRNA processing in internal transcribed spacer 1 (ITS1). May be involved in the movements of the replication forks (By similarity). SUBCELLULAR LOCATION: Nucleus, nucleolus. SIMILARITY: Belongs to the SLX9 family.


FUNCTION: Thiol-disulfide oxidoreductase that participates in various redox reactions in the chloroplast. Mediates the reduction of PSI-N in the thylakoid lumen. May interact and probably reduce other target proteins of the thylakoid membrane, such as FTSH2, FTSH8, LHCB5, atpA, atpB, atpE, petA and petC. Involved in the biogenesis of the plastid cytochrome b6f complex. Reducing equivalents are provided by stromal M- type thioredoxins and probably transduced through the thylakoid membrane by CCDA. Possesses low insulin disulfide bonds reducing activity. SUBCELLULAR LOCATION: Plastid, chloroplast thylakoid membrane; Peripheral membrane protein; Lumenal side. SIMILARITY: Belongs to the thioredoxin family.


FUNCTION: Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules. SUBCELLULAR LOCATION: Nucleus Chromosome, centromere, kinetochore Note=Localizes to kinetochores from late prophase to anaphase. SIMILARITY: Belongs to the NUF2 family.


FUNCTION: Growth hormone plays an important role in growth control. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the somatotropin/prolactin family.


FUNCTION: May initiate with G7P the virion concomitant assembly-budding process, by interacting with the packaging signal of the viral genome. The assembly-budding takes place at the host inner membrane. In turn, G7P and G9P are present at the end of the filamentous virion that emerges first from the bacterial host (By similarity). SUBCELLULAR LOCATION: Virion Host membrane; Single-pass membrane protein Note=Prior to assembly, is found associated with the bacterial host inner membrane. There are about five copies of this protein per mature phage that are located on the tail side of the filamentous virion with G7P (By similarity). SIMILARITY: Belongs to the inovirus G9P protein family.


FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin specifically blocks mammalian neuronal nAChR of the alpha- 7/CHRNA7, alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-4-beta-2/CHRNA4-CHRNB2 subtypes (By similarity). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the conotoxin D superfamily.


FUNCTION: Hydrolyzes the N-acetamido groups of N-acetyl-D-glucosamine polymers in chitin to form chitosan and acetate (PubMed:15555935, PubMed:7592838, PubMed:8987657, PubMed:9373940, PubMed:16232493, PubMed:16878976). May play a role in evasion of the host immune response; plant chitinases liberate chitin molecules from the fungal cell wall which act as elicitors of the plant immune response, deacetylation of the liberated chitin neutralizes elicitor activity (PubMed:8987657, PubMed:10913295). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the polysaccharide deacetylase family.


FUNCTION: Converts 4-O-beta-D-mannopyranosyl-D-glucopyranose (Man-Glc) to mannose 1-phosphate (Man1P) and glucose. Involved in a mannan catabolic pathway which feeds into glycolysis. SIMILARITY: Belongs to the glycosyl hydrolase 130 family.


SUBCELLULAR LOCATION: Secreted. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 68 family.


FUNCTION: May function in a SRP (signal recognition particle) and GET (guided entry of tail-anchored proteins) independent pathway for targeting a broad range of substrate proteins to the endoplasmic reticulum (By similarity). Has a role in meiosis (PubMed:16303567). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the TMEM208 family.


FUNCTION: Although this protein associates with the 30S subunit of the ribosome it is not considered to be a bona fide ribosomal protein. SIMILARITY: Belongs to the SRA family.


FUNCTION: Putative variant histone H3 which may replace conventional H3 in a subset of nucleosomes. 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 (By similarity). SUBCELLULAR LOCATION: Nucleus Chromosome. SIMILARITY: Belongs to the histone H3 family.


FUNCTION: ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). ICAM3 is also a ligand for integrin alpha-D/beta-2. In association with integrin alpha-L/beta-2, contributes to apoptotic neutrophil phagocytosis by macrophages. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. SIMILARITY: Belongs to the immunoglobulin superfamily. ICAM family.


SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the SF3B4 family.


FUNCTION: Putative antitoxin component of a type IV toxin-antitoxin (TA) system; its cognate toxin is unknown. SIMILARITY: Belongs to the CbeA/YafW/YfjZ antitoxin family.


FUNCTION: Binds to the small latent transforming growth factor-beta complex, consisting of the N-terminal TGFB1 latency-associated peptide (LAP) and the mature form of TGFB1, thereby leading to the activation of TGFB1 (PubMed:27389696). The activation of TGFB1 leads to stimulation of naive CD4(+) T-cells to increase FoxP3 expression and to an increase in the number of FoxP3(+) regulatory T-cells (PubMed:27389696). Induces the differentiation of a suppressive CD4(+)LAP(+)FoxP3(-) T-cell subset (PubMed:27389696). Induces the secretion of TGFB1 in macrophages, but not in activated CD4(+) T-cells (PubMed:27389696). May reduce the expression of several pro- inflammatory cytokines and chemokines by CD4(+) T-cells, including IL2 and IL6 (PubMed:27389696). SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the immunoglobulin superfamily. CEA family.


FUNCTION: Forms part of a two-component regulatory system AfsQ1/AfsQ2 involved in secondary metabolism. May activate AfsQ1 by phosphorylation. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.


FUNCTION: Electroneutral divalent metal cation:bicarbonate symporter of the plasma membrane mediating the cellular uptake of zinc and manganese, two divalent metal cations important for development, tissue homeostasis and immunity (PubMed:16638970, PubMed:18037372, PubMed:22563477, PubMed:29337306). Transports an electroneutral complex composed of a divalent metal cation and two bicarbonate anions or alternatively a bicarbonate and a selenite anion (PubMed:16638970, PubMed:18037372, PubMed:22563477, PubMed:27166256). Thereby, it also contributes to the cellular uptake of selenium, an essential trace metal and micronutrient (PubMed:27166256). Also imports cadmium a non- essential metal which is cytotoxic and carcinogenic (PubMed:15722412, PubMed:16638970, PubMed:17108009, PubMed:18037372, PubMed:24529376). May also transport iron and cobalt through membranes (PubMed:16638970, PubMed:22898811, PubMed:24529376). Through zinc import, indirectly regulates the metal-dependent transcription factor MTF1 and the expression of some metalloproteases involved in cartilage catabolism and also probably heart development (PubMed:24529376, PubMed:29337306). Also indirectly regulates the expression of proteins involved in cell morphology and cytoskeleton organization (PubMed:29927450). Indirectly controls innate immune function and inflammatory response by regulating zinc cellular uptake which in turn modulates the expression of genes specific of these processes (PubMed:23403290). Protects, for instance, cells from injury and death at the onset of inflammation (By similarity). By regulating zinc influx into monocytes also directly modulates their adhesion to endothelial cells and arteries (PubMed:30015240). Reclaims manganese from the bile at the apical membrane of hepatocytes, thereby regulating the activity of the manganese-dependent enzymes through the systemic levels of the nutrient (PubMed:28481222). Also participates in manganese reabsorption in the proximal tubule of the kidney (By similarity). By mediating the extracellular uptake of manganese by cells of the blood-brain barrier, may also play a role in the transport of the micronutrient to the brain. With manganese cellular uptake also participates in mitochondrial proper function (By similarity). Finally, also probably functions intracellularly, translocating zinc from lysosome to cytosol to indirectly enhance the expression of specific genes during TCR- mediated T cell activation (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Apical cell membrane; Multi-pass membrane protein Basolateral cell membrane; Multi-pass membrane protein Lysosome membrane; Multi- pass membrane protein Note=Localizes to the lysosome of activated T-cells. A large fraction of the protein is found intracellularly in microvascular capillary endothelial cells that constitute the blood-brain barrier. Localized and functional at both apical and basolateral membranes of microvascular capillary endothelial cells that constitute the blood-brain barrier. SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family.


SIMILARITY: Belongs to the OPA3 family.


FUNCTION: Component of the octopine active transport system probably consisting of four subunits: Q, M, P and T. SUBCELLULAR LOCATION: Periplasm. SIMILARITY: Belongs to the bacterial solute-binding protein 3 family.


FUNCTION: [Desert hedgehog protein B]: The C-terminal part of the desert hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (DhhN and DhhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated DhhN (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). FUNCTION: [Desert hedgehog protein B N-product]: The dually lipidated desert hedgehog protein N-product (DhhNp) is essential for a variety of patterning events during development (By similarity). Involved in the early induction and patterning of anterodorsal ectoderm, nervous system and somites. Induces ectopic cement gland formation in embryos (PubMed:7671800). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity). SUBCELLULAR LOCATION: [Desert hedgehog protein B]: Endoplasmic reticulum membrane Golgi apparatus membrane Secreted Cell membrane Note=Co-localizes with HHAT in the ER and Golgi membrane. SUBCELLULAR LOCATION: [Desert hedgehog protein B N-product]: Cell membrane; Lipid-anchor. SIMILARITY: Belongs to the hedgehog family.


FUNCTION: Has probably no intrinsic transporter activity but together with SLC30A5 forms a functional zinc ion:proton antiporter heterodimer, mediating zinc entry into the lumen of organelles along the secretory pathway (PubMed:15994300, PubMed:19366695, PubMed:19759014). As part of that zinc ion:proton antiporter, contributes to zinc ion homeostasis within the early secretory pathway and regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis (PubMed:15994300, PubMed:19759014, PubMed:35525268). SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.


FUNCTION: Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin- choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine- dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the nuclear hormone receptor family. NR2 subfamily.


FUNCTION: May be involved in the maintenance of active epigenetic status of target genes. May inhibit differentiation of embryonic stem (ES) cells into a primitive ectoderm lineage (By similarity). SUBCELLULAR LOCATION: Nucleus Note=Associated with transcriptionally active chromatin.


FUNCTION: Endogalactanase involved in the degradation of plant cell wall polysaccharides, and more particularly of hairy regions of pectin. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 53 family.


FUNCTION: This protein may play a role in equipping the seed for survival, maintaining a minimal level of hydration in the dry organism and preventing the denaturation of cytoplasmic components, or may play a role during imbibition by controlling water uptake. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the small hydrophilic plant seed protein family.


FUNCTION: Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems. SUBCELLULAR LOCATION: Cell membrane Plastid, chloroplast membrane. Plastid, chloroplast stroma. SIMILARITY: Belongs to the iron/manganese superoxide dismutase family.


FUNCTION: Catalytic subunit of the periplasmic nitrate reductase complex NapAB. Receives electrons from NapB and catalyzes the reduction of nitrate to nitrite. FUNCTION: Catalytic subunit of the periplasmic nitrate reductase complex NapAB. Receives electrons from NapB and catalyzes the reduction of nitrate to nitrite. SUBCELLULAR LOCATION: Periplasm. SUBCELLULAR LOCATION: Periplasm. SIMILARITY: Belongs to the prokaryotic molybdopterin-containing oxidoreductase family. NasA/NapA/NarB subfamily. SIMILARITY: Belongs to the prokaryotic molybdopterin-containing oxidoreductase family. NasA/NapA/NarB subfamily.


FUNCTION: Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein Cytoplasm, cytoskeleton, cilium basal body Note=Localizes at the transition zone, a region between the basal body and the ciliary axoneme.


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


FUNCTION: Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the NMT family.


FUNCTION: Involved in copy control of plasmid pIP501.


FUNCTION: Appears to function synergistically with RBM14 as a transcriptional coactivator. Isoform 1 and isoform 2 function in nuclear receptor coactivation. Isoform 1 and isoform 2 function in general transcriptional coactivation. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:29374058). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the SS18 family.


FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta- catenin signaling pathway (By similarity). Required for normal fusion of the chorion and the allantois during placenta development (By similarity). Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (By similarity). SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix Secreted. SIMILARITY: Belongs to the Wnt family.


FUNCTION: Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin-protein ligase complex that controls progression through mitosis and the G1 phase of the cell cycle. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the APC8/CDC23 family.


FUNCTION: Acts as a negative regulator for calcification in the shells of mollusks. May function both as a calcium concentrator and as a carbonic anhydrase required for production of carbonate ions, which are assembled to CaCO(3) at mineralization sites. Is important for shell formation in both the calcitic prismatic layer and the aragonitic nacreous layer. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix. SIMILARITY: Belongs to the alpha-carbonic anhydrase family.


FUNCTION: Has a role in meiosis and septation. SUBCELLULAR LOCATION: Cytoplasm Note=Localizes to the barrier septum.


FUNCTION: Acts as a transcriptional repressor. Involved in recruitment of functional SIN3A complexes to DNA. Represses transcription at least in part through the activity of an associated histone deacetylase (HDAC). May also repress transcription in a SIN3A-independent manner through recruitment of functional TLE5 complexes to DNA. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Hydrolyzes both oxacillin and methicillin. SIMILARITY: Belongs to the class-D beta-lactamase family.


FUNCTION: Binds the poly(A) tail of mRNA. Appears to be an important mediator of the multiple roles of the poly(A) tail in mRNA biogenesis, stability and translation. In the nucleus, involved in both mRNA cleavage and polyadenylation. Is also required for efficient mRNA export to the cytoplasm. Acts in concert with a poly(A)-specific nuclease (PAN) to affect poly(A) tail shortening, which may occur concomitantly with either nucleocytoplasmic mRNA transport or translational initiation. In the cytoplasm, stimulates translation initiation and regulates mRNA decay through translation termination- coupled poly(A) shortening, probably mediated by PAN (By similarity). SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the polyadenylate-binding protein type-1 family.


FUNCTION: Mediates the side-chain deamidation of N-terminal glutamine residues to glutamate, an important step in N-end rule pathway of protein degradation. Conversion of the resulting N-terminal glutamine to glutamate renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. Does not act on substrates with internal or C-terminal glutamine and does not act on non-glutamine residues in any position. SIMILARITY: Belongs to the NTAQ1 family.


FUNCTION: The MdtABC tripartite complex confers resistance against novobiocin and deoxycholate. SUBCELLULAR LOCATION: Cell inner membrane; Peripheral membrane protein. SIMILARITY: Belongs to the membrane fusion protein (MFP) (TC 8.A.1) family.


SIMILARITY: Belongs to the orthoreovirus sigma-1s protein family.


FUNCTION: Phosphatase that has high activity toward pyridoxal 5'- phosphate (PLP). Also active at much lower level toward pyrophosphate, phosphoethanolamine (PEA), phosphocholine (PCho), phospho-l-tyrosine, fructose-6-phosphate, p-nitrophenyl phosphate, and h-glycerophosphate. SIMILARITY: Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.


FUNCTION: May be involved in neural development. Involved in regulation of osteoblast function and bone formation. Involved in matrix vesicle release by osteoblasts; this function seems to involve maintenance of the actin cytoskeleton. May be involved in cellular trafficking of SERT and thereby in regulation of serotonin uptake. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Note=Colocalizes with SERT at the plasma membrane. SIMILARITY: Belongs to the myelin proteolipid protein family.


FUNCTION: Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the MCM 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. 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 Nucleus. SUBCELLULAR LOCATION: Cytoplasm. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the universal ribosomal protein uL2 family.


FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system. Its toxic effect is neutralized by coexpression with cognate antitoxin RelB2 but no other ParD or RelB antitoxin. SIMILARITY: Belongs to the RelE toxin family.


FUNCTION: Multidrug efflux pump. Confers resistance to tetraphenylphosphonium (TPP), erythromycin, ethidium bromide, acriflavine, safranin O and pyronin Y (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the drug/metabolite transporter (DMT) superfamily. Small multidrug resistance (SMR) (TC 2.A.7.1) family. Mmr subfamily.


FUNCTION: Catalyzes the carbon skeleton rearrangement of L-glutamate to L-threo-3-methylaspartate ((2S,3S)-3-methylaspartate). SIMILARITY: Belongs to the methylaspartate mutase GlmS subunit family.


FUNCTION: Component of the DASH complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. The DASH complex mediates the formation and maintenance of bipolar kinetochore-microtubule attachments by forming closed rings around spindle microtubules and establishing interactions with proteins from the central kinetochore. May be necessary for growth under high osmotic stress. SUBCELLULAR LOCATION: Nucleus Cytoplasm, cytoskeleton, spindle Chromosome, centromere, kinetochore Note=Associates with the mitotic spindle and the kinetochore. Kinetochore association occurs only during mitosis (By similarity). SIMILARITY: Belongs to the DASH complex SPC19 family.


FUNCTION: Component of the COP9 signalosome (CSN) complex that acts as an regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunit of SCF-type E3 ubiquitin- protein ligase complexes (By similarity). The CSN complex seems to link protein degradation to sexual development. SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the peptidase M67A family. CSN6 subfamily.


FUNCTION: Interacts with EP300 and acts as a repressor of MYOD- dependent transcription and muscle differentiation. Inhibits EP300 histone acetyltransferase activity. Acts as a repressor of TGFB/SMAD transcriptional responses. May act as a repressor of the TGFB/SMAD3- dependent signaling by selectively blocking formation of TGFB-induced SMAD3-SMAD4 complex (By similarity). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Envelope glycoprotein that forms spikes at the surface of virion envelope. Essential for the initial attachment to heparan sulfate moieties of the host cell surface proteoglycans. Involved in fusion of viral and cellular membranes leading to virus entry into the host cell. Following initial binding to its host receptors, membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL. May be involved in the fusion between the virion envelope and the outer nuclear membrane during virion egress (By similarity). Also plays a role, together with gK, in virus-induced cell-to-cell fusion (syncytia formation). SUBCELLULAR LOCATION: Virion membrane; Single-pass type I membrane protein Host cell membrane; Single-pass type I membrane protein Host endosome membrane; Single-pass type I membrane protein Host Golgi apparatus membrane; Single-pass type I membrane protein Note=During virion morphogenesis, this protein probably accumulates in the endosomes and trans-Golgi where secondary envelopment occurs. It is probably transported to the cell surface from where it is endocytosed and directed to the trans-Golgi network (TGN). SIMILARITY: Belongs to the herpesviridae glycoprotein B family.


FUNCTION: Does not show any inhibitory activity against various snake venom PLA2s. Does not inhibit the endogenous PLA2 activities in various tissue homogenates prepared from this snake. SUBCELLULAR LOCATION: Secreted Note=Secreted in plasma. SIMILARITY: Belongs to the alpha-type phospholipase A2 inhibitor family.


SIMILARITY: Belongs to the peptidase S10 family.


FUNCTION: Structural component of the gap junctions. Essential for generation and/or maintenance of postembryonic neuroblasts and normal development of optic lobe. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Cell junction, gap junction. Basolateral cell membrane. Note=Accumulates in the basolateral membrane of follicle cells in oocytes and epithelial cells in embryonic salivary gland and hindgut. SIMILARITY: Belongs to the pannexin family.


FUNCTION: Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis. Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2A. Once all three components are bound together in a complex at the cell surface, ACVR2A phosphorylates and activates ACVR1. In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the TGF-beta family.


FUNCTION: Catalyzes the transfer of a methyl group from dimethylamine to the corrinoid cofactor of MtbC. SIMILARITY: Belongs to the dimethylamine methyltransferase family.


FUNCTION: May influence outgrowth by a variety of growth cones including those of the posterior lateral line ganglion. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the semaphorin family.


FUNCTION: Involved in pre-mRNA splicing as component of the spliceosome (By similarity). Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA (By similarity). In the germ line, has a role in oogenesis, by regulating spermatogenesis and nurse cell nuclei chromatin decondensation and dispersal, probably by regulating the splicing of proteins necessary for germline differentiation such as the meiotic protein mei-P26 (PubMed:27035939, PubMed:24244416). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the U2 small nuclear ribonucleoprotein A family.


FUNCTION: G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the G-protein coupled receptor 3 family.


FUNCTION: Plays a role as a mediator of E2F1-induced apoptosis in the absence of p53/TP53 (By similarity). Inhibits TLR9 response to nucelic acids and regulates TLR9-mediated innate immune response (PubMed:25917084). SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane protein Endoplasmic reticulum membrane; Multi-pass membrane protein Note=Colocalizes with COX4I1.


FUNCTION: Selenoprotein with thioredoxin reductase-like oxidoreductase activity (By similarity). Protects dopaminergic neurons against oxidative stress and cell death (PubMed:26866473). Involved in ADCYAP1/PACAP-induced calcium mobilization and neuroendocrine secretion (By similarity). Plays a role in fibroblast anchorage and redox regulation (By similarity). In gastric smooth muscle, modulates the contraction processes through the regulation of calcium release and MYLK activation (By similarity). In pancreatic islets, involved in the control of glucose homeostasis, contributes to prolonged ADCYAP1/PACAP- induced insulin secretion (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein. SIMILARITY: Belongs to the SelWTH family. Selenoprotein T subfamily.


FUNCTION: Integral part of various neural sensory systems in the antenna that provide the neural basis for the response to environmental changes in temperature (thermosensation), humidity (hygrosensation) and odor detection (PubMed:21220098, PubMed:27161501, PubMed:27656904). Required for odor-evoked electrophysiological responses in multiple neuron classes in the antenna and is likely to function as part of an olfactory receptor complex with Ir76a and Ir76b (PubMed:21220098). Together with Ir21a and Ir93a, mediates the response of the larval dorsal organ cool cells, a trio of cool-responsive neurons, to cooling and is required for cool avoidance behavior (PubMed:27126188, PubMed:27161501, PubMed:27656904). Required in chordonotal organ neurons for behavioral synchronization to low-amplitude temperature cycles and mediates circadian clock resetting by temperature (PubMed:26580016). Together with Ir40a and Ir93a, mediates the response of the hydrosensory sacculus neurons to changes in relative humidity, and is required for dry detection and humidiy preference behavior (PubMed:27161501, PubMed:27656904). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein Cell projection, axon Cell projection, dendrite Perikaryon Cell projection, cilium Note=Low levels detected in the axon segment adjacent to the perikaryon in some sensory neurons of the antenna but not detected along axons as they enter the brain or at synapses within antennal lobe glomeruli. In coeloconic neurons, prominently expressed both in the perikaryon and in the distal tip of the dendrite which corresponds to the ciliated outer dendritic segment innervating the sensory hair. Relatively low levels detected in inner dendrites (PubMed:19135896). Detected in dendritic bulbs of the dorsal organ cool cells (PubMed:27126188). SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.


FUNCTION: Plays a role in the inhibition of the host innate and adaptive immune responses. Possesses five immunoglobulin-binding domains that capture both the fragment crystallizable region (Fc region) and the Fab region (part of Ig that identifies antigen) of immunoglobulins (PubMed:2938951, PubMed:4163007, PubMed:10805799). In turn, Staphylococcus aureus is protected from phagocytic killing via inhibition of Ig Fc region. In addition, the host elicited B-cell response is prevented due to a decrease of antibody-secreting cell proliferation that enter the bone marrow, thereby decreasing long-term antibody production. Inhibits osteogenesis by preventing osteoblast proliferation and expression of alkaline phosphatase, type I collagen, osteopontin and osteocalcin. Acts directly as a pro-inflammatory factor in the lung through its ability to bind and activate tumor necrosis factor alpha receptor 1/TNFRSF1A (By similarity). SUBCELLULAR LOCATION: Secreted, cell wall; Peptidoglycan-anchor; Extracellular side Secreted Note=Cell wall anchoring is confered by the LPXTG motif and following sequences (PubMed:1638631). Anchored by sortase A (PubMed:10427003). SpA from strains A676 and V-I is secreted whereas SpA from Cowan 1 and 8325-4 is mostly attached to the cell wall (Probable). Newly synthesized protein is deposited at 2-4 foci/cell and eventually is distributed in a ring around the cell (PubMed:17416657). SIMILARITY: Belongs to the immunoglobulin-binding protein SpA family.


FUNCTION: May act as a growth inhibitor. May be involved in maintaining chromosomal stability. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the TBRG1 family.


FUNCTION: C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase S1 family.


FUNCTION: Binds to specific receptor at cellular surface, bringing about the attachment of the virus particle to the cell. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the viral nucleocapsid into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induce an irreversible conformational change in G, releasing a fusion hydrophobic peptide (By similarity). SUBCELLULAR LOCATION: Virion membrane; Single-pass type I membrane protein. SIMILARITY: Belongs to the novirhabdovirus glycoprotein family.


FUNCTION: Probable component of a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. SUBCELLULAR LOCATION: Nucleus Chromosome, centromere Note=Localizes exclusively in the centromeres. SIMILARITY: Belongs to the CENP-L/IML3 family.


FUNCTION: Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein Golgi apparatus membrane; Multi-pass membrane protein Note=Predominantly localized in the endoplasmic reticulum membrane. SIMILARITY: Belongs to the peptidase S54 family.


FUNCTION: Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells or in stabilizing the apical membrane through AUM/cytoskeletal interactions (By similarity). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the tetraspanin (TM4SF) family.


FUNCTION: Endoplasmic reticulum and mitochondria-associated protein that probably functions as a regulator of cellular redox state and thereby regulates protein post-translational modification, protein folding and mitochondrial activity. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein Mitochondrion membrane Note=Localizes to endoplasmic reticulum mitochondria-associated membrane (MAMs) that connect the endoplasmic reticulum and the mitochondria.


SUBCELLULAR LOCATION: Mitochondrion outer membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the carnitine/choline acetyltransferase family.


FUNCTION: Acts as a flagellar brake, regulating swimming and swarming in a bis-(3'-5') cyclic diguanylic acid (c-di-GMP)-dependent manner. When bound to c-di-GMP it binds to elements of the flagellar motor (MotA (PubMed:20303158) and/or FliG and FliM (PubMed:20346719), binding to FliM also occurs in the absence of c-di-GMP), causing the motor to slow down. Thus, increasing levels of c-di-GMP lead to decreased motility. Probably binds 1 c-di-GMP dimer per subunit. SUBCELLULAR LOCATION: Bacterial flagellum basal body. SIMILARITY: Belongs to the YcgR family.


FUNCTION: Probably involved in transcriptional regulation. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the TADA1 family.


FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of the insulin signaling pathway, modulating insulin sensitivity by limiting PIK3R1/p85alpha abundance in adipocytes. Targets PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase (PI3K), for 'Lys-48'-linked polyubiquitination and proteasome-mediated degradation.


FUNCTION: Serine protease inhibitor. SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, chromaffin granule Secreted. SIMILARITY: Belongs to the serpin family.


FUNCTION: Catalyzes the intermembrane transfer of phosphatidylglycerol and phosphatidylinositol. SUBCELLULAR LOCATION: Vacuole. SIMILARITY: Belongs to the NPC2 family.


FUNCTION: Imparts immunity to sakacin-A to naturally sensitive host strains.


FUNCTION: [Isoform 2]: Functional isoform capable of transporting TEA. FUNCTION: Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:7990927, PubMed:8955087, PubMed:10570053, PubMed:10997918, PubMed:10864577, PubMed:11502595, PubMed:11408531, PubMed:12395288, PubMed:16142924, PubMed:15640376, PubMed:16272756, PubMed:15662044, PubMed:16581093, PubMed:17567940). Functions as a pH- and Na(+)-independent, bidirectional transporter (PubMed:8955087, PubMed:16142924). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (PubMed:8955087, PubMed:9405386, PubMed:16142924, PubMed:17567940). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed in the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds from the blood by hepatic and renal clearance (PubMed:7990927, PubMed:9703985, PubMed:10997918). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal excretion and elimination of organic cations from the systemic circulation (By similarity). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, neurotransmitters dopamine, serotonin, noradrenaline, adrenaline and histamine, and quaternary ammonium compound such as choline (PubMed:8955087, PubMed:9776363, PubMed:10570053, PubMed:11502595, PubMed:11408531, PubMed:11758759, PubMed:15662044, PubMed:16581093, PubMed:17567940). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (By similarity). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (By similarity). Contributes to the influx and efflux of fatty acid carriers carnitines and acylcarnitines across the basolateral membrane of hepatocytes, from the liver to the systemic circulation and inversely and may be involved in regulating the systemic availability of hepatic acylcarnitines (By similarity). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (By similarity). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (By similarity). May contribute to the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Also mediates the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N- methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)- quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n- pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N- methylpyridinium (ASP) (PubMed:8955087, PubMed:10864577, PubMed:11408531, PubMed:12395288). SUBCELLULAR LOCATION: Basolateral cell membrane; Multi-pass membrane protein Apical cell membrane; Multi-pass membrane protein Lateral cell membrane; Multi-pass membrane protein Basal cell membrane; Multi-pass membrane protein Cell membrane; Multi-pass membrane protein Note=Localized to the sinusoidal/basolateral membrane of hepatocytes (PubMed:9703985). Mainly localized to the basolateral membrane of renal proximal tubular cells (PubMed:7990927, PubMed:9808712, PubMed:10997918, PubMed:11083459). Localized to the luminal/apical membrane of ciliated epithelial cells in the airway (PubMed:15817714). SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.


FUNCTION: Molecular chaperone capable of stabilizing a range of proteins. Seems to fulfill an ATP-independent, HSP70-like function in archaeal de novo protein folding. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the prefoldin alpha subunit family.


FUNCTION: Catalyzes the reduction of sulfopyruvate to (R)-sulfolactate much more efficiently than the reverse reaction. Also catalyzes the reduction of oxaloacetate, alpha-ketoglutarate, and to a much lower extent, KHTCA, but not pyruvate. Involved in the biosynthesis of both coenzyme M (with (R)-sulfolactate) and methanopterin (with alpha- ketoglutarate). SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the LDH2/MDH2 oxidoreductase family.


FUNCTION: May have a role in spermatogenesis where it promotes autophagy in response to serum starvation, via the NF-kappaB pathway. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Serine endoprotease which cleaves substrates at the RX(K/R)R consensus motif. SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.


FUNCTION: Voltage-gated chloride channel. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family.


SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side. SIMILARITY: Belongs to the small GTPase superfamily. Ras family.


SIMILARITY: Belongs to the EFCAB4 family.


FUNCTION: Folate-binding protein that interacts with the energy- coupling factor (ECF) ABC-transporter complex. Unlike classic ABC transporters this ECF transporter provides the energy necessary to transport a number of different substrates. The substrates themselves are bound by transmembrane, not extracytoplasmic soluble proteins (By similarity). SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.


FUNCTION: Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex. SUBCELLULAR LOCATION: Mitochondrion matrix. SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.


FUNCTION: Involved in cell cycle regulation. May be a regulatory subunit of CDKD-1/CAK-R2. SIMILARITY: Belongs to the cyclin family. Cyclin F subfamily.


FUNCTION: Contributes to histone modification (By similarity). May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4' (By similarity). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (By similarity). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (By similarity). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (By similarity). May regulate osteoblasts differentiation (By similarity). In association with RBBP5 and ASH2L, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the WD repeat WDR5/wds family.


FUNCTION: Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. Extracytoplasmic function (ECF) sigma factors are held in an inactive form by a cognate anti-sigma factor (RshA) until released. This sigma factor is involved in heat shock and oxidative stress response; it is believed to control protein processing in the extracytoplasmic compartment (By similarity). FUNCTION: Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. Extracytoplasmic function (ECF) sigma factors are held in an inactive form by a cognate anti-sigma factor (RshA) until released. This sigma factor is involved in heat shock and oxidative stress responses; it positively regulates the expression of itself, sigE, sigB and a number of transcriptional regulators as well as other effectors of heat and oxidative stress, leading to direct and indirect control of up to 25% of the bacterial genome. Modulates expression of host genes for intercrine beta (chemokine CC) and apoptosis, altering the host immune response. FUNCTION: Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. Extracytoplasmic function (ECF) sigma factors are held in an inactive form by a cognate anti-sigma factor (RshA) until released. This sigma factor is involved in heat shock and oxidative stress responses; it positively regulates the expression of itself, sigE, sigB and a number of transcriptional regulators as well as other effectors of heat and oxidative stress, leading to direct and indirect control of up to 25% of the bacterial genome. Modulates expression of host genes for intercrine beta (chemokine CC) and apoptosis, altering the host immune response. SIMILARITY: Belongs to the sigma-70 factor family. ECF subfamily.


FUNCTION: Member of the two-component regulatory system SaeR/SaeS involved in the regulation of staphylococcal virulence factors in a strain-dependent fashion. Probably functions as a transcriptional regulator via a specific DNA-binding domain, recognizing motifs near the promoter sequences of target genes (By similarity). FUNCTION: Member of the two-component regulatory system SaeR/SaeS involved in the regulation of staphylococcal virulence factors in a strain-dependent fashion. Probably functions as a transcriptional regulator via a specific DNA-binding domain, recognizing motifs near the promoter sequences of target genes. SaeR/SaeS activates the expression of exoproteins involved in adhesion and invasion of host cells, including hemolysins (hla, Hlb, HlgC), Coa, DNase, Spa and cell wall-associated proteins (Emp, Eap, FnbA, FnbB, Efb). Represses the expression of type 5 capsular polysaccharide (cap operon). Also modulates the expression of several other genes. FUNCTION: Member of the two-component regulatory system SaeR/SaeS involved in the regulation of staphylococcal virulence factors in a strain-dependent fashion. Probably functions as a transcriptional regulator via a specific DNA-binding domain, recognizing motifs near the promoter sequences of target genes (By similarity). Modulates the expression of several genes. FUNCTION: Member of the two-component regulatory system SaeR/SaeS involved in the regulation of staphylococcal virulence factors in a strain-dependent fashion. Probably functions as a transcriptional regulator via a specific DNA-binding domain, recognizing motifs near the promoter sequences of target genes. SaeR/SaeS activates the expression of exoproteins involved in adhesion and invasion of host cells, including hemolysins (Hla, Hlb), Coa, DNase, Spa and cell wall- associated proteins (Emp, Eap, FnbA). Acts probably downstream of the Agr system in the regulatory cascade of virulence factors. SUBCELLULAR LOCATION: Cytoplasm.


SUBCELLULAR LOCATION: Plastid, chloroplast Mitochondrion. SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.


SIMILARITY: In the N-terminal section; belongs to the APS kinase family. SIMILARITY: In the C-terminal section; belongs to the sulfate adenylyltransferase family.


FUNCTION: F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. May play a role in the formation of epithelial cell junctions (By similarity). Forms, with CAPZB, the barbed end of the fast growing ends of actin filaments in the dynactin complex and stabilizes dynactin structure. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. SIMILARITY: Belongs to the F-actin-capping protein alpha subunit family.


FUNCTION: Binds as a heterodimer with protein bS6 to the central domain of the 16S rRNA, where it helps stabilize the platform of the 30S subunit. SIMILARITY: Belongs to the bacterial ribosomal protein bS18 family. SIMILARITY: Belongs to the bacterial ribosomal protein bS18 family.


FUNCTION: Not known; seems to contribute to the tellurium resistance (Ter) mechanism. SIMILARITY: Belongs to the CAPAB/TerDEXZ family.


FUNCTION: Involved in control of the biosynthesis of leucine.


FUNCTION: Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (By similarity). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). Required for cortical dynein-dynactin complex recruitment during metaphase (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Cell membrane; Peripheral membrane protein; Cytoplasmic side Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Cytoplasm, cell cortex Membrane; Lipid-anchor. SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.


FUNCTION: Not known, the gcv operon regulated by the E.coli homolog does not exist in H.influenzae, so it probably acts as a transcriptional regulator on some other operon. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the LysR transcriptional regulatory family.


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


FUNCTION: Catalyzes the proton-dependent transport of sialic acid. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the major facilitator superfamily. Sialate:H(+) symporter (SHS) (TC 2.A.1.12) family.


FUNCTION: Involved in cell wall biosynthesis and may also act as a sensor of external penicillins. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the beta-lactamase family.


FUNCTION: Phosphatidylinositol-4-phosphate-binding protein that may antagonize the action of GOLPH3 which is required for the process of vesicle budding at the Golgi and anterograde transport to the plasma membrane. SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane; Peripheral membrane protein; Cytoplasmic side Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein; Cytoplasmic side Note=Phosphatidylinositol 4-phosphate (PtdIns4P)- binding mediates recruitment to Golgi membranes. SIMILARITY: Belongs to the GOLPH3/VPS74 family.


FUNCTION: Important for the export of protein containing nuclear export signal (NES) out of the nucleus. Stimulates the GTPase activity of GSP1. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Maintains stem cell potency (By similarity). Increases STAT3 phosphorylation and controls ERK phosphorylation (By similarity). May act as a scaffold, increasing STAT3 recruitment onto endosomes (By similarity). SUBCELLULAR LOCATION: Endosome. SIMILARITY: Belongs to the OCIAD1 family.


FUNCTION: Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm. Polymerizes into longer and more stable actin filaments compared to ACT1/actin-1. Has ATPase activity. ATP hydrolysis leads to the formation of a stable intermediate ADP-inorganic phosphate (Pi) actin, which is followed by the release of Pi. ATP hydrolysis affects filament stability; ADP-bound actin depolymerizes much faster than ATP- or ADP- Pi-bound actin. Plays an essential role in male gametocyte development in the mosquito midgut, functioning in several processes including male gametocyte egress from host erythrocytes, formation of a beating flagellum and relocalization of ACT1/actin-1 to the cytoplasm. On the basal side of the mosquito midgut epithelium, required for the development of ookinetes into sporogonic oocysts. SUBCELLULAR LOCATION: Cytoplasm Cytoplasm, cytoskeleton Note=Prior to gametocyte activation in the mosquito midgut, localizes to the cytoplasm. Following gametocyte activation, localizes to a ring around the nucleus. SIMILARITY: Belongs to the actin family.


FUNCTION: Its physiological role is not yet clear. SIMILARITY: Belongs to the acylphosphatase family.


FUNCTION: Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L- serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate. FUNCTION: Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L- serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate. SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.


FUNCTION: Catalyzes the oxidative demethylation of sarcosine. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the MSOX/MTOX family. MSOX subfamily.


FUNCTION: Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing (By similarity). Participates in AID/AICDA-mediated somatic hypermutation (SHM) and class-switch recombination (CSR), 2 processes resulting in the production of high-affinity, mutated isotype-switched antibodies (PubMed:20585033). SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the paired homeobox family.


FUNCTION: Cytochrome c oxidase subunit which plays a role in assembly of respiratory supercomplexes. SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the RCF1 family.


FUNCTION: Transcriptional repressor for the nicCDEFTP and nicXR operons, encoding the lower aerobic nicotinate degradation pathway. Acts under non-induced conditions: repression of the nicCDEFTP and nicXR operons becomes alleviated in presence of 6-hydroxynicotinate (6HNA).


FUNCTION: Subunit I and II form the functional core of the enzyme complex. Electrons originating in cytochrome c are transferred via heme a and Cu(A) to the binuclear center formed by heme a3 and Cu(B). This cytochrome c oxidase shows proton pump activity across the membrane in addition to the electron transfer. SUBCELLULAR LOCATION: Cell inner membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the heme-copper respiratory oxidase family.


FUNCTION: Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells. Insufficient to induce tumorigenicity when overexpressed but contributes to MYC-mediated tumorigenesis. May play a role as transcriptional regulator (By similarity). SUBCELLULAR LOCATION: Nucleus Cytoplasm Note=Predominantly nuclear with some expression also seen in the cytoplasm. Predominantly cytoplasmic when phosphorylated at Thr-170 (By similarity).


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. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the phosphoglycerate kinase family.


FUNCTION: May play a role in mitochondrial aerobic respiration essentially in the testis. Can also promote mitochondrial fission. SUBCELLULAR LOCATION: Mitochondrion Note=Associated with membranes. SIMILARITY: Belongs to the MTFR1 family.


FUNCTION: Possible glycosyltransferase that transfers an alpha-D- mannosyl residue from GDP-mannose into lipid-linked oligosaccharide, forming an alpha-(1->2)-D-mannosyl-D-mannose linkage. SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein. SIMILARITY: Belongs to the glycosyltransferase 15 family.


FUNCTION: Probable accessory potassium channel protein which modulates the activity of the pore-forming alpha subunit. SIMILARITY: Belongs to the shaker potassium channel beta subunit family.


FUNCTION: Required for secondary wall formation in fibers, especially in short days conditions. Promotes indole metabolism and transport (e.g. tryptophan, neoglucobrassicin and auxin (indole-3-acetic acid)). May prevent salicylic-acid (SA) accumulation. SUBCELLULAR LOCATION: Vacuole membrane; Multi-pass membrane protein Note=Also detected in transvacuolar strands. SIMILARITY: Belongs to the drug/metabolite transporter (DMT) superfamily. Plant drug/metabolite exporter (P-DME) (TC 2.A.7.4) family.


FUNCTION: Involved in pre-mRNA splicing process (PubMed:11991638, PubMed:12084575, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). SUBCELLULAR LOCATION: Nucleus Nucleus speckle Note=Colocalizes with core spliceosomal snRNP proteins (PubMed:12084575). SIMILARITY: Belongs to the crooked-neck family.


FUNCTION: ER (microsomal) omega-6 fatty acid desaturase introduces the second double bond in the biosynthesis of 18:3 fatty acids, important constituents of plant membranes. It is thought to use cytochrome b5 as an electron donor and to act on fatty acids esterified to phosphatidylcholine and, possibly, other phospholipids. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. SIMILARITY: Belongs to the fatty acid desaturase type 1 family.


FUNCTION: Converts adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to adenosine 5'-phosphosulfate (APS) and 3'(2')-phosphoadenosine 5'- phosphate (PAP) to AMP. Regulates the flux of sulfur in the sulfur- activation pathway by converting PAPS to APS. Involved in salt tolerance (By similarity). SIMILARITY: Belongs to the inositol monophosphatase superfamily.


FUNCTION: May play a protective role against oxidative stress. SUBCELLULAR LOCATION: Mitochondrion. SIMILARITY: Belongs to the small heat shock protein (HSP20) family.


FUNCTION: A likely role for the res protein would be to stabilize pCP13 by reducing the number of plasmid multimers resulting from homologous recombination. SIMILARITY: Belongs to the site-specific recombinase resolvase family.


FUNCTION: In the presence of arginine, coactivates the transcription of the arcABDC operon, with other regulatory proteins such as ArcR and CcpA. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: Belongs to the ArgR family.


FUNCTION: Involved in erythromycin resistance. SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family.


SIMILARITY: Belongs to the serpin family. Poxviruses subfamily.


FUNCTION: Transcription factor which regulates the transcription of multiple genes expressed in the intestinal epithelium (By similarity). Binds to the promoter of the intestinal sucrase-isomaltase SI and activates SI transcription (By similarity). Binds to the DNA sequence 5'-ATAAAAACTTAT-3' in the promoter region of VDR and activates VDR transcription (By similarity). Binds to and activates transcription of LPH (By similarity). Activates transcription of CLDN2 and intestinal mucin MUC2 (By similarity). Binds to the 5'-AATTTTTTACAACACCT-3' DNA sequence in the promoter region of CA1 and activates CA1 transcription (By similarity). Important in broad range of functions from early differentiation to maintenance of the intestinal epithelial lining of both the small and large intestine. Binds preferentially to methylated DNA (PubMed:28473536). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the Caudal homeobox family.


FUNCTION: Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. Acts as an adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:25349192). SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm. SUBCELLULAR LOCATION: [Isoform 2]: Nucleus. SIMILARITY: Belongs to the WD repeat CDC20/Fizzy family.


FUNCTION: Transcriptional repressor of genes that require a bHLH protein for their transcription. Plays an important role as neurogenesis negative regulator. SUBCELLULAR LOCATION: Nucleus.


FUNCTION: Required for biosynthesis of LAH modification in the post- translational modification of Campylobacter coli flagellin. SIMILARITY: Belongs to the CMP-NeuNAc synthase family.


SUBCELLULAR LOCATION: Secreted. SIMILARITY: Belongs to the glycosyl hydrolase 15 family.


FUNCTION: Regulates chordin (CHRD). May play a role in spatial programing within discrete embryonic fields or lineage compartments during organogenesis. In concert with NKX3-2, plays a role in defining the structural components of the middle ear; required for the development of the entire tympanic ring (By similarity). Probably involved in the regulatory networks that define neural crest cell fate specification and determine mesoderm cell lineages in mammals (By similarity). SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.


FUNCTION: Has exonuclease activity on both single-stranded and duplex templates bearing overhangs, but not blunt ended duplex DNA, and cleaves in a 3'-5' direction. Essential for the formation of DNA replication focal centers. Has an important role in maintaining genome stability. SUBCELLULAR LOCATION: Nucleus. SIMILARITY: Belongs to the WRNexo family.


FUNCTION: S-adenosyl-L-methionine-dependent transferase 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. Catalyzes the transfer of the alpha-amino-alpha-carboxypropyl (acp) group from S- adenosyl-L-methionine to the C-7 position of 4-demethylwyosine (imG-14) to produce wybutosine-86 (By similarity). SUBCELLULAR LOCATION: Cytoplasm Nucleus. SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM5/TYW2 family.


FUNCTION: [Isoform 2]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). FUNCTION: Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). Plays a key role in controlling cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288). The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage- independent growth, and epithelial mesenchymal transition (EMT) induction (PubMed:18579750). Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). FUNCTION: [Isoform 3]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). SUBCELLULAR LOCATION: Cytoplasm Nucleus Cell junction Note=Both phosphorylation and cell density can regulate its subcellular localization (PubMed:18158288, PubMed:20048001). Phosphorylation sequesters it in the cytoplasm by inhibiting its translocation into the nucleus (PubMed:18158288, PubMed:20048001). At low density, predominantly nuclear and is translocated to the cytoplasm at high density (PubMed:18158288, PubMed:20048001, PubMed:25849865). PTPN14 induces translocation from the nucleus to the cytoplasm (PubMed:22525271). Localized mainly to the nucleus in the early stages of embryo development with expression becoming evident in the cytoplasm at the blastocyst and epiblast stages (By similarity). SIMILARITY: Belongs to the YAP1 family.


FUNCTION: Involved in the biosynthesis of a molybdopterin-based tungsten cofactor. SIMILARITY: Belongs to the radical SAM superfamily.


FUNCTION: Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. May play a role in the prevention of cell senescence acting as a regulator of mitochondrial quality control. SUBCELLULAR LOCATION: Mitochondrion outer membrane; Multi-pass membrane protein Endoplasmic reticulum membrane; Multi-pass membrane protein.


FUNCTION: Lysosomal thiol reductase that can reduce protein disulfide bonds. May facilitate the complete unfolding of proteins destined for lysosomal degradation. SUBCELLULAR LOCATION: Secreted Lysosome. SIMILARITY: Belongs to the GILT family.


FUNCTION: Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA- precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. SUBCELLULAR LOCATION: Cell membrane Cytoplasm Nucleus Note=67LR is found at the surface of the plasma membrane, with its C-terminal laminin-binding domain accessible to extracellular ligands. 37LRP is found at the cell surface, in the cytoplasm and in the nucleus. SIMILARITY: Belongs to the universal ribosomal protein uS2 family.


FUNCTION: Diheme, high potential cytochrome c believed to be an intermediate electron donor to terminal oxidation systems. SUBCELLULAR LOCATION: Periplasm.


FUNCTION: Catalyzes three sequential steps of tetrahydrofolate biosynthesis. SUBCELLULAR LOCATION: Cytoplasm. SIMILARITY: In the N-terminal section; belongs to the DHNA family. SIMILARITY: In the central section; belongs to the HPPK family. SIMILARITY: In the C-terminal section; belongs to the DHPS family.