Entry
stringlengths 6
10
| Entry Name
stringlengths 5
11
| Sequence
stringlengths 2
35.2k
| EC number
stringlengths 7
118
⌀ | Cofactor
stringlengths 38
1.77k
⌀ | Gene Ontology (biological process)
stringlengths 18
11.3k
⌀ | Gene Ontology (cellular component)
stringlengths 17
1.75k
⌀ | Gene Ontology (molecular function)
stringlengths 24
2.09k
⌀ | Pfam
stringlengths 8
232
⌀ | Gene3D
stringlengths 10
250
⌀ | Protein families
stringlengths 9
237
⌀ | Post-translational modification
stringlengths 16
8.52k
⌀ | Subcellular location [CC]
stringlengths 29
6.18k
⌀ | Catalytic activity
stringlengths 64
35.7k
⌀ | Kinetics
stringlengths 69
11.7k
⌀ | Pathway
stringlengths 27
908
⌀ | pH dependence
stringlengths 64
955
⌀ | Temperature dependence
stringlengths 70
1.16k
⌀ | Function [CC]
stringlengths 17
15.3k
⌀ | Organism
stringlengths 8
196
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
P04394
|
NDUV2_BOVIN
|
MFLSAALRARAAGLAAHWGKHIRNLHKTAVQNGAGGALFVHRDTPENNPETPFDFTPENYKRIEAIVKNYPEGHKAAAVLPVLDLAQRQNGWLPISAMNKVAEILQVPPMRVYEVATFYTMYNRKPVGKYHIQVCTTTPCMLRNSDSILEAIQKKLGIKVGETTPDKLFTLIEVECLGACVNAPMVQINDNYYEDLTPKDIEEIIDELKAGKIPKPGPRSGRFSCEPAGGLTSLTEPPKGPGFGVQAGL
|
7.1.1.2
|
COFACTOR: Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135; Evidence={ECO:0000269|PubMed:27509854}; Note=Binds 1 [2Fe-2S] cluster. {ECO:0000269|PubMed:27509854};
|
mitochondrial electron transport, NADH to ubiquinone [GO:0006120]
|
mitochondrial inner membrane [GO:0005743]; mitochondrial respiratory chain complex I [GO:0005747]; mitochondrion [GO:0005739]
|
2 iron, 2 sulfur cluster binding [GO:0051537]; metal ion binding [GO:0046872]; NADH dehydrogenase (ubiquinone) activity [GO:0008137]
|
PF01257;
|
3.40.30.10;1.10.10.1590;
|
Complex I 24 kDa subunit family
| null |
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:10852722, ECO:0000269|PubMed:18721790, ECO:0000269|PubMed:25209663}; Peripheral membrane protein {ECO:0000305|PubMed:25209663}; Matrix side {ECO:0000305|PubMed:25209663}.
|
CATALYTIC ACTIVITY: Reaction=a ubiquinone + 5 H(+)(in) + NADH = a ubiquinol + 4 H(+)(out) + NAD(+); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA-COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2; Evidence={ECO:0000305|PubMed:10852722, ECO:0000305|PubMed:18721790, ECO:0000305|PubMed:25209663, ECO:0000305|PubMed:27509854}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29092; Evidence={ECO:0000305|PubMed:10852722, ECO:0000305|PubMed:18721790, ECO:0000305|PubMed:25209663, ECO:0000305|PubMed:27509854};
| null | null | null | null |
FUNCTION: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:10852722, PubMed:18721790, PubMed:25209663, PubMed:27509854). Parts of the peripheral arm of the enzyme, where the electrons from NADH are accepted by flavin mononucleotide (FMN) and then passed along a chain of iron-sulfur clusters by electron tunnelling to the final acceptor ubiquinone (PubMed:10852722, PubMed:25209663, PubMed:27509854). Contains one iron-sulfur cluster (PubMed:25209663, PubMed:27509854). {ECO:0000269|PubMed:10852722, ECO:0000269|PubMed:18721790, ECO:0000269|PubMed:25209663, ECO:0000269|PubMed:27509854}.
|
Bos taurus (Bovine)
|
P04395
|
3MG2_ECOLI
|
MYTLNWQPPYDWSWMLGFLAARAVSSVETVADSYYARSLAVGEYRGVVTAIPDIARHTLHINLSAGLEPVAAECLAKMSRLFDLQCNPQIVNGALGRLGAARPGLRLPGCVDAFEQGVRAILGQLVSVAMAAKLTARVAQLYGERLDDFPEYICFPTPQRLAAADPQALKALGMPLKRAEALIHLANAALEGTLPMTIPGDVEQAMKTLQTFPGIGRWTANYFALRGWQAKDVFLPDDYLIKQRFPGMTPAQIRRYAERWKPWRSYALLHIWYTEGWQPDEA
|
3.2.2.21
| null |
base-excision repair [GO:0006284]; base-excision repair, AP site formation [GO:0006285]; DNA damage response [GO:0006974]; DNA dealkylation involved in DNA repair [GO:0006307]; DNA repair [GO:0006281]
|
cytoplasm [GO:0005737]; protein-DNA complex [GO:0032993]
|
alkylated DNA binding [GO:0032131]; alkylbase DNA N-glycosylase activity [GO:0003905]; DNA-3-methyladenine glycosylase activity [GO:0008725]; DNA-3-methylguanine glycosylase activity [GO:0052822]; DNA-7-methyladenine glycosylase activity [GO:0052821]; DNA-7-methylguanine glycosylase activity [GO:0043916]
|
PF06029;PF00730;
|
3.30.310.20;1.10.1670.10;
|
Alkylbase DNA glycosidase AlkA family
| null | null |
CATALYTIC ACTIVITY: Reaction=Hydrolysis of alkylated DNA, releasing 3-methyladenine, 3-methylguanine, 7-methylguanine and 7-methyladenine.; EC=3.2.2.21;
| null | null | null | null |
FUNCTION: Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, 3-methylguanine, 7-methylguanine, O2-methylthymine, and O2-methylcytosine from the damaged DNA polymer formed by alkylation lesions.
|
Escherichia coli (strain K12)
|
P04397
|
GAL10_YEAST
|
MTAQLQSESTSKIVLVTGGAGYIGSHTVVELIENGYDCVVADNLSNSTYDSVARLEVLTKHHIPFYEVDLCDRKGLEKVFKEYKIDSVIHFAGLKAVGESTQIPLRYYHNNILGTVVLLELMQQYNVSKFVFSSSATVYGDATRFPNMIPIPEECPLGPTNPYGHTKYAIENILNDLYNSDKKSWKFAILRYFNPIGAHPSGLIGEDPLGIPNNLLPYMAQVAVGRREKLYIFGDDYDSRDGTPIRDYIHVVDLAKGHIAALQYLEAYNENEGLCREWNLGSGKGSTVFEVYHAFCKASGIDLPYKVTGRRAGDVLNLTAKPDRAKRELKWQTELQVEDSCKDLWKWTTENPFGYQLRGVEARFSAEDMRYDARFVTIGAGTRFQATFANLGASIVDLKVNGQSVVLGYENEEGYLNPDSAYIGATIGRYANRISKGKFSLCNKDYQLTVNNGVNANHSSIGSFHRKRFLGPIIQNPSKDVFTAEYMLIDNEKDTEFPGDLLVTIQYTVNVAQKSLEMVYKGKLTAGEATPINLTNHSYFNLNKPYGDTIEGTEIMVRSKKSVDVDKNMIPTGNIVDREIATFNSTKPTVLGPKNPQFDCCFVVDENAKPSQINTLNNELTLIVKAFHPDSNITLEVLSTEPTYQFYTGDFLSAGYEARQGFAIEPGRYIDAINQENWKDCVTLKNGETYGSKIVYRFS
|
5.1.3.2; 5.1.3.3
|
COFACTOR: Name=NAD(+); Xref=ChEBI:CHEBI:57540;
|
galactose catabolic process via UDP-galactose [GO:0033499]
|
cytosol [GO:0005829]
|
aldose 1-epimerase activity [GO:0004034]; carbohydrate binding [GO:0030246]; UDP-glucose 4-epimerase activity [GO:0003978]
|
PF01263;PF01370;
|
2.70.98.10;3.40.50.720;3.90.25.10;
|
NAD(P)-dependent epimerase/dehydratase family; Aldose epimerase family
| null | null |
CATALYTIC ACTIVITY: Reaction=UDP-alpha-D-glucose = UDP-alpha-D-galactose; Xref=Rhea:RHEA:22168, ChEBI:CHEBI:58885, ChEBI:CHEBI:66914; EC=5.1.3.2; CATALYTIC ACTIVITY: Reaction=alpha-D-glucose = beta-D-glucose; Xref=Rhea:RHEA:10264, ChEBI:CHEBI:15903, ChEBI:CHEBI:17925; EC=5.1.3.3; Evidence={ECO:0000255|PROSITE-ProRule:PRU10126};
| null |
PATHWAY: Carbohydrate metabolism; galactose metabolism.; PATHWAY: Carbohydrate metabolism; hexose metabolism.
| null | null |
FUNCTION: Mutarotase converts alpha-aldose to the beta-anomer. It is active on D-glucose, L-arabinose, D-xylose, D-galactose, maltose and lactose (By similarity). {ECO:0000250}.
|
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
|
P04401
|
IL5_MOUSE
|
MRRMLLHLSVLTLSCVWATAMEIPMSTVVKETLTQLSAHRALLTSNETMRLPVPTHKNHQLCIGEIFQGLDILKNQTVRGGTVEMLFQNLSLIKKYIDRQKEKCGEERRRTRQFLDYLQEFLGVMSTEWAMEG
| null | null |
cytokine-mediated signaling pathway [GO:0019221]; immune response [GO:0006955]; interleukin-5-mediated signaling pathway [GO:0038043]; positive regulation of B cell proliferation [GO:0030890]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of eosinophil differentiation [GO:0045645]; positive regulation of immunoglobulin production [GO:0002639]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of podosome assembly [GO:0071803]; positive regulation of receptor signaling pathway via JAK-STAT [GO:0046427]
|
extracellular space [GO:0005615]
|
cytokine activity [GO:0005125]; growth factor activity [GO:0008083]; interleukin-5 receptor binding [GO:0005137]
|
PF02025;
|
1.20.1250.10;
|
IL-5 family
| null |
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils (PubMed:10444455, PubMed:1873482). Acts also on activated and resting B-cells to induce immunoglobulin production, growth, and differentiation (PubMed:3128631). Mechanistically, exerts its biological effects through a receptor composed of IL5RA subunit and the cytokine receptor common subunit beta/CSF2RB. Binding to the receptor leads to activation of various kinases including LYN, SYK and JAK2 and thereby propagates signals through the RAS-MAPK and JAK-STAT5 pathways respectively (By similarity). {ECO:0000250|UniProtKB:P05113, ECO:0000269|PubMed:10444455, ECO:0000269|PubMed:1873482, ECO:0000269|PubMed:3128631}.
|
Mus musculus (Mouse)
|
P04404
|
CMGA_PIG
|
SAAALALLLCAGQVIALPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSQECFETLRGDERILSILRHQNLLKELQDLALQGAKERSHQQKKQSSYEDELSEVLEKQNDQAELKEGTEEASSKEAAEKRGDSKEVEKNDEDADGAKPQASLEPPXXXEAEDQTPGEEEAASTHPLASLPSKKRPGAQAEEDHEGPSQGPVDREKGPSAEQGPQAEREEEEEAEAGEKAVPEEEGPRSEAFDSHPSLGYKEMQRGWPQAPAMDGAGKTGAEEAQPPEGKGAREHSRQEEEEETAGAPQGLFRGGKRGEPAQEEEERLSEEWENAKRWSKMDRLAKELTAEKRLQGEEEEEEEEEDPDRSMKLSFRAPAYGFRGPGLQLRRGWRPSSREDSVEAGLPLQVRXYLEEKKEEEGSANRRPEDQELESLSAIEAELEKVAPQLQSLRRG
| null | null |
adenylate cyclase-activating adrenergic receptor signaling pathway involved in cardiac muscle relaxation [GO:0086030]; defense response to bacterium [GO:0042742]; defense response to Gram-negative bacterium [GO:0050829]; defense response to Gram-positive bacterium [GO:0050830]; mast cell activation [GO:0045576]; mast cell chemotaxis [GO:0002551]; mast cell degranulation [GO:0043303]; negative regulation of catecholamine secretion [GO:0033604]; negative regulation of insulin secretion [GO:0046676]; positive regulation of dense core granule biogenesis [GO:2000707]
|
chromaffin granule [GO:0042583]; extracellular space [GO:0005615]; neuronal dense core vesicle [GO:0098992]; transport vesicle [GO:0030133]
| null |
PF01271;
| null |
Chromogranin/secretogranin protein family
|
PTM: O-glycosylated; contains chondroitin sulfate (CS). CS attachment is pH-dependent, being observed at mildly acidic conditions of pH 5 but not at neutral pH, and promotes self-assembly in vitro. {ECO:0000250|UniProtKB:P10645}.; PTM: Parathyroid CHGA is sulfated on tyrosine residues, whereas adrenal CHGA seems to be mainly sulfated on oligosaccharide residues. {ECO:0000269|PubMed:2105940}.
|
SUBCELLULAR LOCATION: [Serpinin]: Secreted {ECO:0000250|UniProtKB:P26339}. Cytoplasmic vesicle, secretory vesicle {ECO:0000250|UniProtKB:P26339}. Note=Pyroglutaminated serpinin localizes to secretory vesicle. {ECO:0000250|UniProtKB:P26339}.; SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle {ECO:0000250|UniProtKB:P10354}. Cytoplasmic vesicle, secretory vesicle, neuronal dense core vesicle {ECO:0000250|UniProtKB:P10354}. Secreted {ECO:0000250|UniProtKB:P10354}. Note=Associated with the secretory granule membrane through direct interaction to SCG3 that in turn binds to cholesterol-enriched lipid rafts in intragranular conditions. In pituitary gonadotropes, located in large secretory granules. {ECO:0000250|UniProtKB:P10354}.
| null | null | null | null | null |
FUNCTION: [Pancreastatin]: Strongly inhibits glucose induced insulin release from the pancreas.; FUNCTION: [Parastatin]: Inhibits low calcium-stimulated parathyroid cell secretion.; FUNCTION: [Catestatin]: Inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist. Can induce mast cell migration, degranulation and production of cytokines and chemokines. {ECO:0000250|UniProtKB:P10645}.; FUNCTION: [Serpinin]: Regulates granule biogenesis in endocrine cells by up-regulating the transcription of protease nexin 1 (SERPINE2) via a cAMP-PKA-SP1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation. {ECO:0000250|UniProtKB:P26339}.
|
Sus scrofa (Pig)
|
P04405
|
GLYG2_SOYBN
|
MAKLVLSLCFLLFSGCFALREQAQQNECQIQKLNALKPDNRIESEGGFIETWNPNNKPFQCAGVALSRCTLNRNALRRPSYTNGPQEIYIQQGNGIFGMIFPGCPSTYQEPQESQQRGRSQRPQDRHQKVHRFREGDLIAVPTGVAWWMYNNEDTPVVAVSIIDTNSLENQLDQMPRRFYLAGNQEQEFLKYQQQQQGGSQSQKGKQQEEENEGSNILSGFAPEFLKEAFGVNMQIVRNLQGENEEEDSGAIVTVKGGLRVTAPAMRKPQQEEDDDDEEEQPQCVETDKGCQRQSKRSRNGIDETICTMRLRQNIGQNSSPDIYNPQAGSITTATSLDFPALWLLKLSAQYGSLRKNAMFVPHYTLNANSIIYALNGRALVQVVNCNGERVFDGELQEGGVLIVPQNFAVAAKSQSDNFEYVSFKTNDRPSIGNLAGANSLLNALPEEVIQHTFNLKSQQARQVKNNNPFSFLVPPQESQRRAVA
| null | null | null |
endoplasmic reticulum [GO:0005783]; protein storage vacuole [GO:0000326]
|
nutrient reservoir activity [GO:0045735]
|
PF00190;
|
2.60.120.10;
|
11S seed storage protein (globulins) family
|
PTM: During soybean germination, seed storage proteins are hydrolyzed by protease/26S proteasome. {ECO:0000269|PubMed:29037738}.
|
SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000250|UniProtKB:P04776}. Protein storage vacuole {ECO:0000250|UniProtKB:P04776}. Note=Hexamers are assembled in the endoplasmic reticulum and later sorted to the protein storage vacuoles. {ECO:0000250|UniProtKB:P04776}.
| null | null | null | null | null |
FUNCTION: Glycinin is the major seed storage protein of soybean (PubMed:2485233). Glycinin basic peptides (GBPs), and, to a lower extent, glycinin exhibit antibacterial activity against Gram-negative and Gram-positive bacteria (e.g. L.monocytogenes, B.subtilis, E.coli and S.enteritidis) by forming pores and aggregating in transmembranes, leading to membrane permeability and, eventually, cell death (PubMed:22236762, PubMed:28590128, Ref.21). {ECO:0000269|PubMed:22236762, ECO:0000269|PubMed:2485233, ECO:0000269|PubMed:28590128, ECO:0000269|Ref.21}.
|
Glycine max (Soybean) (Glycine hispida)
|
P04406
|
G3P_HUMAN
|
MGKVKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLNYMVYMFQYDSTHGKFHGTVKAENGKLVINGNPITIFQERDPSKIKWGDAGAEYVVESTGVFTTMEKAGAHLQGGAKRVIISAPSADAPMFVMGVNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGLMTTVHAITATQKTVDGPSGKLWRDGRGALQNIIPASTGAAKAVGKVIPELNGKLTGMAFRVPTANVSVVDLTCRLEKPAKYDDIKKVVKQASEGPLKGILGYTEHQVVSSDFNSDTHSSTFDAGAGIALNDHFVKLISWYDNEFGYSNRVVDLMAHMASKE
|
1.2.1.12; 2.6.99.-
| null |
antimicrobial humoral immune response mediated by antimicrobial peptide [GO:0061844]; cellular response to type II interferon [GO:0071346]; defense response to fungus [GO:0050832]; glucose metabolic process [GO:0006006]; glycolytic process [GO:0006096]; killing by host of symbiont cells [GO:0051873]; killing of cells of another organism [GO:0031640]; microtubule cytoskeleton organization [GO:0000226]; negative regulation of endopeptidase activity [GO:0010951]; negative regulation of translation [GO:0017148]; neuron apoptotic process [GO:0051402]; peptidyl-cysteine S-trans-nitrosylation [GO:0035606]; positive regulation of canonical NF-kappaB signal transduction [GO:0043123]; positive regulation of cytokine production [GO:0001819]; positive regulation of type I interferon production [GO:0032481]; protein stabilization [GO:0050821]; regulation of macroautophagy [GO:0016241]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]; GAIT complex [GO:0097452]; intracellular membrane-bounded organelle [GO:0043231]; lipid droplet [GO:0005811]; membrane [GO:0016020]; microtubule cytoskeleton [GO:0015630]; nuclear membrane [GO:0031965]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; ribonucleoprotein complex [GO:1990904]; vesicle [GO:0031982]
|
aspartic-type endopeptidase inhibitor activity [GO:0019828]; disordered domain specific binding [GO:0097718]; glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity [GO:0004365]; identical protein binding [GO:0042802]; microtubule binding [GO:0008017]; NAD binding [GO:0051287]; NADP binding [GO:0050661]; peptidyl-cysteine S-nitrosylase activity [GO:0035605]
|
PF02800;PF00044;
|
3.40.50.720;
|
Glyceraldehyde-3-phosphate dehydrogenase family
|
PTM: S-nitrosylation of Cys-152 leads to interaction with SIAH1, followed by translocation to the nucleus (By similarity). S-nitrosylation of Cys-247 is induced by interferon-gamma and LDL(ox) implicating the iNOS-S100A8/9 transnitrosylase complex and seems to prevent interaction with phosphorylated RPL13A and to interfere with GAIT complex activity (PubMed:22771119, PubMed:25417112). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:22771119, ECO:0000269|PubMed:25417112}.; PTM: ISGylated. {ECO:0000305|PubMed:16815975}.; PTM: Sulfhydration at Cys-152 increases catalytic activity. {ECO:0000250|UniProtKB:P16858}.; PTM: Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation. Such aggregates can be observed in vivo in the affected tissues of patients with Alzheimer disease or alcoholic liver cirrhosis, or in cell cultures during necrosis. Oxidation at Met-46 may play a pivotal role in the formation of these insoluble structures. This modification has been detected in vitro following treatment with free radical donor (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide. It has been proposed to destabilize nearby residues, increasing the likelihood of secondary oxidative damages, including oxidation of Tyr-45 and Met-105. This cascade of oxidations may augment GAPDH misfolding, leading to intermolecular disulfide cross-linking and aggregation. {ECO:0000305|PubMed:25086035}.; PTM: Succination of Cys-152 and Cys-247 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits glyceraldehyde-3-phosphate dehydrogenase activity. Fumarate concentration as well as succination of cysteine residues in GAPDH is significantly increased in muscle of diabetic mammals. It was proposed that the S-(2-succinyl)cysteine chemical modification may be a useful biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins by fumarate may contribute to the metabolic changes underlying the development of diabetes complications. {ECO:0000250|UniProtKB:P04797}.; PTM: (Microbial infection) Glycosylated by C.rodentium protein NleB, enteropathogenic E.coli protein NleB1 and S.typhimurium protein Ssek1: arginine GlcNAcylation prevents the interaction with TRAF2 and TRAF3 (PubMed:23332158, PubMed:27387501, PubMed:28522607). This leads to reduced ubiquitination of TRAF2 and TRAF3, and subsequent inhibition of NF-kappa-B signaling and type I interferon production, respectively (PubMed:23332158, PubMed:27387501). {ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:28522607}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12829261}. Nucleus {ECO:0000250|UniProtKB:P04797}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:12829261}. Membrane {ECO:0000269|PubMed:12829261}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P04797}. Note=Translocates to the nucleus following S-nitrosylation and interaction with SIAH1, which contains a nuclear localization signal (By similarity). Postnuclear and Perinuclear regions (PubMed:12829261). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:12829261}.
|
CATALYTIC ACTIVITY: Reaction=D-glyceraldehyde 3-phosphate + NAD(+) + phosphate = (2R)-3-phospho-glyceroyl phosphate + H(+) + NADH; Xref=Rhea:RHEA:10300, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540, ChEBI:CHEBI:57604, ChEBI:CHEBI:57945, ChEBI:CHEBI:59776; EC=1.2.1.12; Evidence={ECO:0000255|PROSITE-ProRule:PRU10009, ECO:0000269|PubMed:3170585}; CATALYTIC ACTIVITY: Reaction=L-cysteinyl-[protein] + S-nitroso-L-cysteinyl-[GAPDH] = L-cysteinyl-[GAPDH] + S-nitroso-L-cysteinyl-[protein]; Xref=Rhea:RHEA:66684, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:17089, Rhea:RHEA-COMP:17090, Rhea:RHEA-COMP:17091, ChEBI:CHEBI:29950, ChEBI:CHEBI:149494; Evidence={ECO:0000250|UniProtKB:P04797}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66685; Evidence={ECO:0000250|UniProtKB:P04797};
| null |
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.
| null | null |
FUNCTION: Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}.
|
Homo sapiens (Human)
|
P04409
|
KPCA_BOVIN
|
MADVFPAAEPAAPQDVANRFARKGALRQKNVHEVKNHRFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKQCVINVPSLCGMDHTEKRGRIYLKAEVTDEKLHVTVRDAKNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPRWDESFTFKLKPSDKDRRLSEEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKLLNQEEGEYYNVPIPEGDEEGNVELRQKFEKAKLGPAGNKVISPSEDRRQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKGTEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSICKGLMTKHPGKRLGCGPEGERDVREHAFFRRIDWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVNPQFVHPILQSAV
|
2.7.11.13
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE-ProRule:PRU00041}; Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain. {ECO:0000250|UniProtKB:P05696};
|
angiogenesis [GO:0001525]; apoptotic process [GO:0006915]; cell adhesion [GO:0007155]; intracellular signal transduction [GO:0035556]; negative regulation of glial cell apoptotic process [GO:0034351]; positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway [GO:0106071]; positive regulation of angiogenesis [GO:0045766]; positive regulation of cardiac muscle hypertrophy [GO:0010613]; positive regulation of cell adhesion [GO:0045785]; positive regulation of cell migration [GO:0030335]; positive regulation of dense core granule biogenesis [GO:2000707]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of endothelial cell proliferation [GO:0001938]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of lipopolysaccharide-mediated signaling pathway [GO:0031666]; positive regulation of macrophage differentiation [GO:0045651]; positive regulation of mitotic cell cycle [GO:0045931]; protein phosphorylation [GO:0006468]; regulation of platelet aggregation [GO:0090330]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; mitochondrial membrane [GO:0031966]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; photoreceptor disc membrane [GO:0097381]; plasma membrane [GO:0005886]
|
ATP binding [GO:0005524]; diacylglycerol-dependent serine/threonine kinase activity [GO:0004697]; PDZ domain binding [GO:0030165]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]; scaffold protein binding [GO:0097110]; zinc ion binding [GO:0008270]
|
PF00130;PF00168;PF00069;PF00433;
|
3.30.60.20;2.60.40.150;1.10.510.10;
|
Protein kinase superfamily, AGC Ser/Thr protein kinase family, PKC subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Mitochondrion membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.13;
| null | null | null | null |
FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascades involving MAPK1/3 (ERK1/2) and RAP1GAP. Depending on the cell type, is involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation. In cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Depending on the cell type, exhibits anti-apoptotic function and protects cells from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, or mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (By similarity). Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (By similarity). {ECO:0000250|UniProtKB:P17252, ECO:0000250|UniProtKB:P20444}.
|
Bos taurus (Bovine)
|
P04412
|
EGFR_DROME
|
MLLRRRNGPCPFPLLLLLLAHCICIWPASAARDRYARQNNRQRHQDIDRDRDRDRFLYRSSSAQNRQRGGANFALGLGANGVTIPTSLEDKNKNEFVKGKICIGTKSRLSVPSNKEHHYRNLRDRYTNCTYVDGNLKLTWLPNENLDLSFLDNIREVTGYILISHVDVKKVVFPKLQIIRGRTLFSLSVEEEKYALFVTYSKMYTLEIPDLRDVLNGQVGFHNNYNLCHMRTIQWSEIVSNGTDAYYNYDFTAPERECPKCHESCTHGCWGEGPKNCQKFSKLTCSPQCAGGRCYGPKPRECCHLFCAGGCTGPTQKDCIACKNFFDEAVSKEECPPMRKYNPTTYVLETNPEGKYAYGATCVKECPGHLLRDNGACVRSCPQDKMDKGGECVPCNGPCPKTCPGVTVLHAGNIDSFRNCTVIDGNIRILDQTFSGFQDVYANYTMGPRYIPLDPERREVFSTVKEITGYLNIEGTHPQFRNLSYFRNLETIHGRQLMESMFAALAIVKSSLYSLEMRNLKQISSGSVVIQHNRDLCYVSNIRWPAIQKEPEQKVWVNENLRADLCEKNGTICSDQCNEDGCWGAGTDQCLTCKNFNFNGTCIADCGYISNAYKFDNRTCKICHPECRTCNGAGADHCQECVHVRDGQHCVSECPKNKYNDRGVCRECHATCDGCTGPKDTIGIGACTTCNLAIINNDATVKRCLLKDDKCPDGYFWEYVHPQEQGSLKPLAGRAVCRKCHPLCELCTNYGYHEQVCSKCTHYKRREQCETECPADHYTDEEQRECFQRHPECNGCTGPGADDCKSCRNFKLFDANETGPYVNSTMFNCTSKCPLEMRHVNYQYTAIGPYCAASPPRSSKITANLDVNMIFIITGAVLVPTICILCVVTYICRQKQKAKKETVKMTMALSGCEDSEPLRPSNIGANLCKLRIVKDAELRKGGVLGMGAFGRVYKGVWVPEGENVKIPVAIKELLKSTGAESSEEFLREAYIMASEEHVNLLKLLAVCMSSQMMLITQLMPLGCLLDYVRNNRDKIGSKALLNWSTQIAKGMSYLEEKRLVHRDLAARNVLVQTPSLVKITDFGLAKLLSSDSNEYKAAGGKMPIKWLALECIRNRVFTSKSDVWAFGVTIWELLTFGQRPHENIPAKDIPDLIEVGLKLEQPEICSLDIYCTLLSCWHLDAAMRPTFKQLTTVFAEFARDPGRYLAIPGDKFTRLPAYTSQDEKDLIRKLAPTTDGSEAIAKPDDYLQPKAAPGPSHRTDCTDEMPKLNRYCKDPSNKNSSTGDDERDSSAREVGVGNLRLDLPVDEDDYLMPTCQPGPNNNNNMNNPNQNNMAAVGVAAGYMDLIGVPVSVDNPEYLLNAQTLGVGESPIPTQTIGIPVMGGPGTMEVKVPMPGSEPTSSDHEYYNDTQRELQPLHRNRNTETRV
|
2.7.10.1
| null |
behavioral response to ethanol [GO:0048149]; border follicle cell migration [GO:0007298]; cell projection assembly [GO:0030031]; chorion-containing eggshell pattern formation [GO:0030381]; compound eye cone cell differentiation [GO:0042675]; compound eye development [GO:0048749]; compound eye photoreceptor cell differentiation [GO:0001751]; determination of adult lifespan [GO:0008340]; determination of genital disc primordium [GO:0035225]; digestive tract morphogenesis [GO:0048546]; dorsal appendage formation [GO:0046843]; dorsal closure [GO:0007391]; dorsal closure, spreading of leading edge cells [GO:0007395]; embryo development ending in birth or egg hatching [GO:0009792]; embryonic pattern specification [GO:0009880]; epidermal growth factor receptor signaling pathway [GO:0007173]; epithelial cell proliferation involved in Malpighian tubule morphogenesis [GO:0061331]; establishment of epithelial cell apical/basal polarity [GO:0045198]; establishment or maintenance of apical/basal cell polarity [GO:0035088]; eye development [GO:0001654]; eye-antennal disc morphogenesis [GO:0007455]; germ-band shortening [GO:0007390]; germ-line stem cell population maintenance [GO:0030718]; gonad development [GO:0008406]; haltere development [GO:0007482]; heart process [GO:0003015]; imaginal disc development [GO:0007444]; imaginal disc-derived wing morphogenesis [GO:0007476]; imaginal disc-derived wing vein morphogenesis [GO:0008586]; imaginal disc-derived wing vein specification [GO:0007474]; leg disc proximal/distal pattern formation [GO:0007479]; lumen formation, open tracheal system [GO:0035149]; maintenance of epithelial integrity, open tracheal system [GO:0035160]; Malpighian tubule morphogenesis [GO:0007443]; maternal determination of dorsal/ventral axis, ovarian follicular epithelium, soma encoded [GO:0008071]; morphogenesis of an epithelium [GO:0002009]; morphogenesis of follicular epithelium [GO:0016333]; negative regulation of apoptotic process [GO:0043066]; negative regulation of apoptotic signaling pathway [GO:2001234]; negative regulation of compound eye retinal cell programmed cell death [GO:0046673]; negative regulation of G1/S transition of mitotic cell cycle [GO:2000134]; negative regulation of gene expression [GO:0010629]; neurogenesis [GO:0022008]; notum cell fate specification [GO:0035310]; notum development [GO:0007477]; oenocyte differentiation [GO:0001742]; olfactory learning [GO:0008355]; ommatidial rotation [GO:0016318]; oocyte axis specification [GO:0007309]; peripheral nervous system development [GO:0007422]; phosphorylation [GO:0016310]; photoreceptor cell differentiation [GO:0046530]; photoreceptor cell fate determination [GO:0043703]; positive regulation of border follicle cell migration [GO:1903688]; positive regulation of cell division [GO:0051781]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of gene expression [GO:0010628]; positive regulation of imaginal disc growth [GO:0045572]; positive regulation of phosphorylation [GO:0042327]; positive regulation of wound healing [GO:0090303]; R8 cell differentiation [GO:0045465]; regulation of tube length, open tracheal system [GO:0035159]; salivary gland development [GO:0007431]; second mitotic wave involved in compound eye morphogenesis [GO:0016330]; segment polarity determination [GO:0007367]; spiracle morphogenesis, open tracheal system [GO:0035277]; stem cell fate commitment [GO:0048865]; tracheal outgrowth, open tracheal system [GO:0007426]; wing and notum subfield formation [GO:0035309]; wing disc morphogenesis [GO:0007472]
|
apical plasma membrane [GO:0016324]; basal plasma membrane [GO:0009925]; plasma membrane [GO:0005886]; receptor complex [GO:0043235]
|
ATP binding [GO:0005524]; epidermal growth factor receptor activity [GO:0005006]; identical protein binding [GO:0042802]; transmembrane receptor protein tyrosine kinase activity [GO:0004714]
|
PF00757;PF14843;PF07714;PF01030;
|
3.80.20.20;1.10.510.10;
|
Protein kinase superfamily, Tyr protein kinase family, EGF receptor subfamily
|
PTM: Ubiquitination by Cbl in response to high spi, promotes its interaction with Graf and thus facilitates its GPI-enriched endocytic compartment (GEEC) mediated endocytosis and its subsequent degradation. {ECO:0000269|PubMed:28993397}.
|
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
|
CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
| null | null | null | null |
FUNCTION: Receptor tyrosine kinase, binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:22140578, PubMed:23579691, PubMed:8070664, PubMed:9882502). Known ligands include spitz, gurken, vein and giant-lens (PubMed:19718021, PubMed:20723758, PubMed:22140578, PubMed:9882502). Transduces the signal through the ras-raf-MAPK pathway (PubMed:9094709). Critical for the proliferation of imaginal tissues, and for the determination of both the antero-posterior and dorso-ventral polarities of the oocyte (PubMed:23579691, PubMed:34411095, PubMed:9882502). In the embryo, plays a role in the establishment of ventral cell fates, maintenance of amnioserosa and ventral neuroectodermal cells, germ band retraction, cell fate specification in the central nervous system, and production and repair of the cuticle (PubMed:22140578, PubMed:23029159, PubMed:23579691, PubMed:9094709). During dorsal closure (DC) functions with the dpp- and ACK-signaling pathways to regulate expression of the myosin zip in the embryonic epidermis and amnioserosa (AS), and thus coordinate the progression of epidermal cell shape changes required for correct DC (PubMed:23579691). In the embryonic epidermis, functions by negatively regulating dpp and consequently the dpp-dependent expression of the myosin zip (PubMed:23579691). In the AS, negatively regulates the production/ and or secretion of a diffusible signal which, is produced by the ACK-signaling pathway, and acts in the AS and epidermal cells to promote zip expression (PubMed:23579691). Also required in the AS to inhibit or delay apoptosis, and consequently slow the rate of DC (PubMed:23579691). Therefore functions at multiple levels to negatively regulate morphogenesis during DC, suggesting that it acts as a general brake mechanism for adjusting the rate of dorsal closure to ensure that closure proceeds smoothly and without loss of epidermal integrity (PubMed:23579691). During oogenesis, one of two tyrosine kinase chemoattractant receptors (Egfr and Pvr), that function in the border cells (BC) to detect guidance cues from the oocyte and transduce this information to the guidance pathway that regulate the collective migration of the BC cluster through the nurse cells to the oocyte (PubMed:24855950). {ECO:0000269|PubMed:19718021, ECO:0000269|PubMed:20723758, ECO:0000269|PubMed:22140578, ECO:0000269|PubMed:23029159, ECO:0000269|PubMed:23579691, ECO:0000269|PubMed:24855950, ECO:0000269|PubMed:34411095, ECO:0000269|PubMed:8070664, ECO:0000269|PubMed:9882502, ECO:0000303|PubMed:9094709}.
|
Drosophila melanogaster (Fruit fly)
|
P04413
|
US03_HHV11
|
MACRKFCRVYGGQGRRKEEAVPPETKPSRVFPHGPFYTPAEDACLDSPPPETPKPSHTTPPSEAERLCHLQEILAQMYGNQDYPIEDDPSADAADDVDEDAPDDVAYPEEYAEELFLPGDATGPLIGANDHIPPPCGASPPGIRRRSRDEIGATGFTAEELDAMDREAARAISRGGKPPSTMAKLVTGMGFTIHGALTPGSEGCVFDSSHPDYPQRVIVKAGWYTSTSHEARLLRRLDHPAILPLLDLHVVSGVTCLVLPKYQADLYTYLSRRLNPLGRPQIAAVSRQLLSAVDYIHRQGIIHRDIKTENIFINTPEDICLGDFGAACFVQGSRSSPFPYGIAGTIDTNAPEVLAGDPYTTTVDIWSAGLVIFETAVHNASLFSAPRGPKRGPCDSQITRIIRQAQVHVDEFSPHPESRLTSRYRSRAAGNNRPPYTRPAWTRYYKMDIDVEYLVCKALTFDGALRPSAAELLCLPLFQQK
|
2.7.11.1
| null |
modulation by virus of host chromatin organization [GO:0039525]; negative regulation of protein import into nucleus [GO:0042308]; negative regulation of protein localization to nucleus [GO:1900181]; phosphorylation [GO:0016310]; symbiont-mediated suppression of cytoplasmic pattern recognition receptor signaling pathway [GO:0039537]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity [GO:0039540]; symbiont-mediated suppression of host NF-kappaB cascade [GO:0085034]; symbiont-mediated suppression of host T-cell mediated immune response [GO:0052085]
|
host cell cytoplasm [GO:0030430]; host cell nucleus [GO:0042025]; viral tegument [GO:0019033]
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ATP binding [GO:0005524]; protein sequestering activity [GO:0140311]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]
|
PF00069;
|
1.10.510.10;
|
Protein kinase superfamily, Ser/Thr protein kinase family
|
PTM: Phosphorylated by UL13; this phosphorylation regulates subsequent phosphorylation of UL31 and UL34 by US3. Autophosphorylated. {ECO:0000269|PubMed:16415024}.
|
SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:24807716}. Host nucleus {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:24049179, ECO:0000269|PubMed:34935440}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:31801859};
| null | null | null | null |
FUNCTION: Multifunctional serine/threonine kinase that plays a role in several processes including egress of virus particles from the nucleus, modulation of the actin cytoskeleton and inhibition of host immune response (PubMed:25907557, PubMed:31249678, PubMed:34935440). Phosphorylates UL31 and UL34, two critical regulators of capsid budding from nucleus to endoplasmic reticulum, thereby facilitating virion egress (PubMed:15994828, PubMed:1656069). Modulates and redistributes host components of the nuclear envelope, including LMNA, emerin/EMD and the nuclear matrix protein MATR3 (PubMed:20962082). In turn, facilitates nuclear pore impairment and capsid release through impaired nuclear envelope (PubMed:31249678). Phosphorylates envelope glycoprotein B (gB), probably to direct it to the cell surface (PubMed:19846518). Promotes virus intracellular spread by restructuring host cell cytoskeleton. Blocks host apoptosis to extend cell survival and allow efficient viral replication. Promotes viral gene expression by phosphorylating host HDAC2 to reduce viral genome silencing (PubMed:20660201). Strongly inhibits TCR-activated signal transduction in T-cells by reducing the ubiquitination of LAT and TRAF6, leading to a suboptimal activation of LAT (PubMed:25907557). Subverts host antiviral innate immunity by inhibiting type I interferon production through hyperphosphorylation of beta-catenin/CTNNB1 (PubMed:31801859). In addition, phosphorylates the RNA sensor RIGI and the transcription factor IRF3 to prevent the RLR-mediated antiviral signaling pathway (PubMed:24049179, PubMed:34935440). Hyperphosphorylates host RELA and thereby dampens NF-kappa-B signaling (PubMed:24807716). {ECO:0000269|PubMed:15994828, ECO:0000269|PubMed:1656069, ECO:0000269|PubMed:17652388, ECO:0000269|PubMed:19279109, ECO:0000269|PubMed:19846518, ECO:0000269|PubMed:20660201, ECO:0000269|PubMed:20962082, ECO:0000269|PubMed:24049179, ECO:0000269|PubMed:24807716, ECO:0000269|PubMed:25907557, ECO:0000269|PubMed:31249678, ECO:0000269|PubMed:31801859, ECO:0000269|PubMed:34935440, ECO:0000269|PubMed:9223283}.
|
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
|
P04415
|
DPOL_BPT4
|
MKEFYISIETVGNNIVERYIDENGKERTREVEYLPTMFRHCKEESKYKDIYGKNCAPQKFPSMKDARDWMKRMEDIGLEALGMNDFKLAYISDTYGSEIVYDRKFVRVANCDIEVTGDKFPDPMKAEYEIDAITHYDSIDDRFYVFDLLNSMYGSVSKWDAKLAAKLDCEGGDEVPQEILDRVIYMPFDNERDMLMEYINLWEQKRPAIFTGWNIEGFDVPYIMNRVKMILGERSMKRFSPIGRVKSKLIQNMYGSKEIYSIDGVSILDYLDLYKKFAFTNLPSFSLESVAQHETKKGKLPYDGPINKLRETNHQRYISYNIIDVESVQAIDKIRGFIDLVLSMSYYAKMPFSGVMSPIKTWDAIIFNSLKGEHKVIPQQGSHVKQSFPGAFVFEPKPIARRYIMSFDLTSLYPSIIRQVNISPETIRGQFKVHPIHEYIAGTAPKPSDEYSCSPNGWMYDKHQEGIIPKEIAKVFFQRKDWKKKMFAEEMNAEAIKKIIMKGAGSCSTKPEVERYVKFSDDFLNELSNYTESVLNSLIEECEKAATLANTNQLNRKILINSLYGALGNIHFRYYDLRNATAITIFGQVGIQWIARKINEYLNKVCGTNDEDFIAAGDTDSVYVCVDKVIEKVGLDRFKEQNDLVEFMNQFGKKKMEPMIDVAYRELCDYMNNREHLMHMDREAISCPPLGSKGVGGFWKAKKRYALNVYDMEDKRFAEPHLKIMGMETQQSSTPKAVQEALEESIRRILQEGEESVQEYYKNFEKEYRQLDYKVIAEVKTANDIAKYDDKGWPGFKCPFHIRGVLTYRRAVSGLGVAPILDGNKVMVLPLREGNPFGDKCIAWPSGTELPKEIRSDVLSWIDHSTLFQKSFVKPLAGMCESAGMDYEEKASLDFLFG
|
2.7.7.7; 3.1.11.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_04100, ECO:0000269|PubMed:9665720};
|
base-excision repair, gap-filling [GO:0006287]; bidirectional double-stranded viral DNA replication [GO:0039686]; DNA replication proofreading [GO:0045004]; nucleotide-excision repair, DNA gap filling [GO:0006297]; SOS response [GO:0009432]
| null |
3'-5' exonuclease activity [GO:0008408]; 3'-5'-DNA exonuclease activity [GO:0008296]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; metal ion binding [GO:0046872]; nucleotide binding [GO:0000166]
|
PF00136;PF03104;
|
1.20.1280.300;3.30.342.10;3.40.1820.10;1.10.287.690;3.90.1600.10;3.30.420.10;
|
DNA polymerase type-B family
| null | null |
CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|HAMAP-Rule:MF_04100, ECO:0000269|PubMed:1332748};
| null | null | null | null |
FUNCTION: Replicates the viral genomic DNA. This polymerase possesses two enzymatic activities: DNA synthesis (polymerase) and an exonucleolytic activity that degrades single-stranded DNA in the 3'- to 5'-direction for proofreading purpose. {ECO:0000255|HAMAP-Rule:MF_04100, ECO:0000269|PubMed:1332748, ECO:0000269|PubMed:15037066}.
|
Enterobacteria phage T4 (Bacteriophage T4)
|
P04418
|
END5_BPT4
|
MTRINLTLVSELADQHLMAEYRELPRVFGAVRKHVANGKRVRDFKISPTFILGAGHVTFFYDKLEFLRKRQIELIAECLKRGFNIKDTTVQDISDIPQEFRGDYIPHEASIAISQARLDEKIAQRPTWYKYYGKAIYA
|
3.2.2.17; 4.2.99.18
| null |
DNA repair [GO:0006281]
| null |
class I DNA-(apurinic or apyrimidinic site) endonuclease activity [GO:0140078]; deoxyribodipyrimidine endonucleosidase activity [GO:0033959]; DNA-(apurinic or apyrimidinic site) endonuclease activity [GO:0003906]; endonuclease activity [GO:0004519]; pyrimidine dimer DNA N-glycosylase activity [GO:0000704]
|
PF03013;
|
1.10.440.10;
| null | null | null |
CATALYTIC ACTIVITY: Reaction=Cleaves the N-glycosidic bond between the 5'-pyrimidine residue in cyclobutadipyrimidine (in DNA) and the corresponding deoxy-D-ribose residue.; EC=3.2.2.17; Evidence={ECO:0000269|PubMed:6254991, ECO:0000269|PubMed:8347626}; CATALYTIC ACTIVITY: Reaction=2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)-2'-deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3-dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-phospho-2'-deoxyribonucleoside-DNA + H(+); Xref=Rhea:RHEA:66592, Rhea:RHEA-COMP:13180, Rhea:RHEA-COMP:16897, Rhea:RHEA-COMP:17067, ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:157695, ChEBI:CHEBI:167181; EC=4.2.99.18; Evidence={ECO:0000269|PubMed:6254991, ECO:0000269|PubMed:8347626};
| null | null | null | null |
FUNCTION: Participates in the repair of UV-damaged DNA by excising pyrimidine dimers that are the major UV-lesions (PubMed:6254991). DNA glycosylase activity hydrolyzes the glycosylic bond of the 5' pyrimidine of the dimer (PubMed:6254991). This leaves apurinic/apyrimidic (AP) sites in the DNA. These AP sites are removed by the AP lyase activity which cleaves the intrapyrimidine phosphodiester bond (PubMed:6254991). Catalysis proceeds via a protonated imine covalent intermediate between the alpha-amino group of the N-terminal threonine residue and the C1' of the deoxyribose sugar of the 5' pyrimidine at the dimer site (PubMed:16916523, PubMed:8347626). {ECO:0000269|PubMed:16916523, ECO:0000269|PubMed:6254991, ECO:0000269|PubMed:8347626}.
|
Enterobacteria phage T4 (Bacteriophage T4)
|
P04421
|
LYSC_BOVIN
|
MKALVILGFLFLSVAVQGKVFERCELARTLKKLGLDGYKGVSLANWLCLTKWESSYNTKATNYNPSSESTDYGIFQINSKWWCNDGKTPNAVDGCHVSCRELMENDIAKAVACAKHIVSEQGITAWVAWKSHCRDHDVSSYVEGCTL
|
3.2.1.17
| null |
defense response to Gram-negative bacterium [GO:0050829]; defense response to Gram-positive bacterium [GO:0050830]; digestion [GO:0007586]; killing of cells of another organism [GO:0031640]; metabolic process [GO:0008152]
| null |
lysozyme activity [GO:0003796]
|
PF00062;
|
1.10.530.10;
|
Glycosyl hydrolase 22 family
| null | null |
CATALYTIC ACTIVITY: Reaction=Hydrolysis of (1->4)-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins.; EC=3.2.1.17;
| null | null | null | null |
FUNCTION: Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents.
|
Bos taurus (Bovine)
|
P04424
|
ARLY_HUMAN
|
MASESGKLWGGRFVGAVDPIMEKFNASIAYDRHLWEVDVQGSKAYSRGLEKAGLLTKAEMDQILHGLDKVAEEWAQGTFKLNSNDEDIHTANERRLKELIGATAGKLHTGRSRNDQVVTDLRLWMRQTCSTLSGLLWELIRTMVDRAEAERDVLFPGYTHLQRAQPIRWSHWILSHAVALTRDSERLLEVRKRINVLPLGSGAIAGNPLGVDRELLRAELNFGAITLNSMDATSERDFVAEFLFWASLCMTHLSRMAEDLILYCTKEFSFVQLSDAYSTGSSLMPQKKNPDSLELIRSKAGRVFGRCAGLLMTLKGLPSTYNKDLQEDKEAVFEVSDTMSAVLQVATGVISTLQIHQENMGQALSPDMLATDLAYYLVRKGMPFRQAHEASGKAVFMAETKGVALNQLSLQELQTISPLFSGDVICVWDYGHSVEQYGALGGTARSSVDWQIRQVRALLQAQQA
|
4.3.2.1
| null |
ammonia assimilation cycle [GO:0019676]; arginine biosynthetic process [GO:0006526]; arginine biosynthetic process via ornithine [GO:0042450]; arginine metabolic process [GO:0006525]; locomotory behavior [GO:0007626]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; post-embryonic development [GO:0009791]; urea cycle [GO:0000050]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]
|
argininosuccinate lyase activity [GO:0004056]; identical protein binding [GO:0042802]
|
PF14698;PF00206;
|
1.10.40.30;1.20.200.10;1.10.275.10;
|
Lyase 1 family, Argininosuccinate lyase subfamily
|
PTM: Acetylation modifies enzyme activity in response to alterations of extracellular nutrient availability. Acetylation increased with trichostin A (TSA) or with nicotinamide (NAM). Glucose increases acetylation by about a factor of 3 with decreasing enzyme activity. Acetylation on Lys-288 is decreased on the addition of extra amino acids resulting in activation of enzyme activity. {ECO:0000269|PubMed:20167786}.
| null |
CATALYTIC ACTIVITY: Reaction=2-(N(omega)-L-arginino)succinate = fumarate + L-arginine; Xref=Rhea:RHEA:24020, ChEBI:CHEBI:29806, ChEBI:CHEBI:32682, ChEBI:CHEBI:57472; EC=4.3.2.1; Evidence={ECO:0000269|PubMed:11747432, ECO:0000269|PubMed:11747433, ECO:0000269|PubMed:2263616, ECO:0000269|PubMed:9045711}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24021; Evidence={ECO:0000305|PubMed:11747432, ECO:0000305|PubMed:11747433}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24022; Evidence={ECO:0000305|PubMed:11747433, ECO:0000305|PubMed:9045711};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.12 mM for 2-(N(omega)-L-arginino)succinate {ECO:0000269|PubMed:11747432, ECO:0000269|PubMed:11747433}; Vmax=10.36 umol/min/mg enzyme toward 2-(N(omega)-L-arginino)succinate {ECO:0000269|PubMed:11747432, ECO:0000269|PubMed:11747433};
|
PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine from L-ornithine and carbamoyl phosphate: step 3/3. {ECO:0000305|PubMed:11747433}.; PATHWAY: Nitrogen metabolism; urea cycle; L-arginine and fumarate from (N(omega)-L-arginino)succinate: step 1/1. {ECO:0000305|PubMed:11747433}.
| null | null |
FUNCTION: Catalyzes the reversible cleavage of L-argininosuccinate to fumarate and L-arginine, an intermediate step reaction in the urea cycle mostly providing for hepatic nitrogen detoxification into excretable urea as well as de novo L-arginine synthesis in nonhepatic tissues (PubMed:11747432, PubMed:11747433, PubMed:22081021, PubMed:2263616, PubMed:9045711). Essential regulator of intracellular and extracellular L-arginine pools. As part of citrulline-nitric oxide cycle, forms tissue-specific multiprotein complexes with argininosuccinate synthase ASS1, transport protein SLC7A1 and nitric oxide synthase NOS1, NOS2 or NOS3, allowing for cell-autonomous L-arginine synthesis while channeling extracellular L-arginine to nitric oxide synthesis pathway (PubMed:22081021). {ECO:0000269|PubMed:11747432, ECO:0000269|PubMed:11747433, ECO:0000269|PubMed:22081021, ECO:0000269|PubMed:9045711}.
|
Homo sapiens (Human)
|
P04425
|
GSHB_ECOLI
|
MIKLGIVMDPIANINIKKDSSFAMLLEAQRRGYELHYMEMGDLYLINGEARAHTRTLNVKQNYEEWFSFVGEQDLPLADLDVILMRKDPPFDTEFIYATYILERAEEKGTLIVNKPQSLRDCNEKLFTAWFSDLTPETLVTRNKAQLKAFWEKHSDIILKPLDGMGGASIFRVKEGDPNLGVIAETLTEHGTRYCMAQNYLPAIKDGDKRVLVVDGEPVPYCLARIPQGGETRGNLAAGGRGEPRPLTESDWKIARQIGPTLKEKGLIFVGLDIIGDRLTEINVTSPTCIREIEAEFPVSITGMLMDAIEARLQQQ
|
6.3.2.3
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000250};
|
glutathione biosynthetic process [GO:0006750]; protein homotetramerization [GO:0051289]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]
|
ATP binding [GO:0005524]; glutathione synthase activity [GO:0004363]; identical protein binding [GO:0042802]; magnesium ion binding [GO:0000287]
|
PF02955;PF02951;
|
3.40.50.20;3.30.1490.20;3.30.470.20;
|
Prokaryotic GSH synthase family
| null | null |
CATALYTIC ACTIVITY: Reaction=ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP + glutathione + H(+) + phosphate; Xref=Rhea:RHEA:13557, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57305, ChEBI:CHEBI:57925, ChEBI:CHEBI:58173, ChEBI:CHEBI:456216; EC=6.3.2.3;
| null |
PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione from L-cysteine and L-glutamate: step 2/2.
| null | null | null |
Escherichia coli (strain K12)
|
P04426
|
WNT1_MOUSE
|
MGLWALLPSWVSTTLLLALTALPAALAANSSGRWWGIVNIASSTNLLTDSKSLQLVLEPSLQLLSRKQRRLIRQNPGILHSVSGGLQSAVRECKWQFRNRRWNCPTAPGPHLFGKIVNRGCRETAFIFAITSAGVTHSVARSCSEGSIESCTCDYRRRGPGGPDWHWGGCSDNIDFGRLFGREFVDSGEKGRDLRFLMNLHNNEAGRTTVFSEMRQECKCHGMSGSCTVRTCWMRLPTLRAVGDVLRDRFDGASRVLYGNRGSNRASRAELLRLEPEDPAHKPPSPHDLVYFEKSPNFCTYSGRLGTAGTAGRACNSSSPALDGCELLCCGRGHRTRTQRVTERCNCTFHWCCHVSCRNCTHTRVLHECL
| null | null |
animal organ morphogenesis [GO:0009887]; animal organ regeneration [GO:0031100]; astrocyte-dopaminergic neuron signaling [GO:0036520]; BMP signaling pathway [GO:0030509]; bone development [GO:0060348]; branching involved in ureteric bud morphogenesis [GO:0001658]; canonical Wnt signaling pathway [GO:0060070]; cell fate commitment [GO:0045165]; cell population proliferation [GO:0008283]; cell proliferation in midbrain [GO:0033278]; cell-cell signaling [GO:0007267]; cellular response to peptide hormone stimulus [GO:0071375]; central nervous system morphogenesis [GO:0021551]; cerebellum development [GO:0021549]; cerebellum formation [GO:0021588]; diencephalon development [GO:0021536]; dopaminergic neuron differentiation [GO:0071542]; embryonic axis specification [GO:0000578]; embryonic brain development [GO:1990403]; fat cell differentiation [GO:0045444]; forebrain anterior/posterior pattern specification [GO:0021797]; hematopoietic stem cell proliferation [GO:0071425]; hepatocyte differentiation [GO:0070365]; inner ear morphogenesis [GO:0042472]; metencephalon development [GO:0022037]; midbrain development [GO:0030901]; midbrain dopaminergic neuron differentiation [GO:1904948]; midbrain-hindbrain boundary development [GO:0030917]; midbrain-hindbrain boundary maturation during brain development [GO:0022004]; myoblast fusion [GO:0007520]; myotube differentiation [GO:0014902]; negative regulation of BMP signaling pathway [GO:0030514]; negative regulation of cell differentiation [GO:0045596]; negative regulation of cell-cell adhesion [GO:0022408]; negative regulation of cell-substrate adhesion [GO:0010812]; negative regulation of cellular senescence [GO:2000773]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway [GO:1903377]; negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512]; negative regulation of ubiquitin-dependent protein catabolic process [GO:2000059]; neurogenesis [GO:0022008]; neuron differentiation [GO:0030182]; neuron fate commitment [GO:0048663]; neuron fate determination [GO:0048664]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of dermatome development [GO:0061184]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of hematopoietic stem cell proliferation [GO:1902035]; positive regulation of insulin-like growth factor receptor signaling pathway [GO:0043568]; positive regulation of lamellipodium assembly [GO:0010592]; positive regulation of Notch signaling pathway [GO:0045747]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of DNA-templated transcription [GO:0006355]; response to wounding [GO:0009611]; signal transduction [GO:0007165]; signal transduction in response to DNA damage [GO:0042770]; Spemann organizer formation [GO:0060061]; spinal cord association neuron differentiation [GO:0021527]; T cell differentiation in thymus [GO:0033077]; Wnt signaling pathway [GO:0016055]
|
cell surface [GO:0009986]; endoplasmic reticulum lumen [GO:0005788]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; Wnt signalosome [GO:1990909]
|
cytokine activity [GO:0005125]; frizzled binding [GO:0005109]; protein domain specific binding [GO:0019904]; receptor ligand activity [GO:0048018]; signaling receptor binding [GO:0005102]
|
PF00110;
|
3.30.2460.20;
|
Wnt family
|
PTM: Palmitoleoylation is required for efficient binding to frizzled receptors. Palmitoleoylation is necessary for proper trafficking to cell surface (By similarity). Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway (By similarity). {ECO:0000250|UniProtKB:P56704, ECO:0000250|UniProtKB:Q91029}.
|
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix {ECO:0000250|UniProtKB:P04628}. Secreted {ECO:0000250|UniProtKB:P04628}.
| null | null | null | null | null |
FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors. Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation (By similarity). In some developmental processes, is also a ligand for the coreceptor RYK, thus triggering Wnt signaling (PubMed:15454084, PubMed:16116452). Plays an essential role in the development of the embryonic brain and central nervous system (CNS) (PubMed:16116452, PubMed:2202907). Has a role in osteoblast function, bone development and bone homeostasis (By similarity). {ECO:0000250|UniProtKB:P04628, ECO:0000269|PubMed:15454084, ECO:0000269|PubMed:16116452, ECO:0000269|PubMed:2202907}.
|
Mus musculus (Mouse)
|
P04439
|
HLAA_HUMAN
|
MAVMAPRTLLLLLSGALALTQTWAGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDQETRNVKAQSQTDRVDLGTLRGYYNQSEAGSHTIQIMYGCDVGSDGRFLRGYRQDAYDGKDYIALNEDLRSWTAADMAAQITKRKWEAAHEAEQLRAYLDGTCVEWLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWELSSQPTIPIVGIIAGLVLLGAVITGAVVAAVMWRRKSSDRKGGSYTQAASSDSAQGSDVSLTACKV
| null | null |
antibacterial humoral response [GO:0019731]; antigen processing and presentation of endogenous peptide antigen via MHC class I [GO:0019885]; antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent [GO:0002485]; antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent [GO:0002486]; antigen processing and presentation of endogenous peptide antigen via MHC class Ib [GO:0002476]; antigen processing and presentation of exogenous peptide antigen via MHC class I [GO:0042590]; CD8-positive, alpha-beta T cell activation [GO:0036037]; defense response to Gram-positive bacterium [GO:0050830]; detection of bacterium [GO:0016045]; immune response [GO:0006955]; innate immune response [GO:0045087]; peptide antigen assembly with MHC class I protein complex [GO:0002502]; positive regulation of CD8-positive, alpha-beta T cell activation [GO:2001187]; positive regulation of CD8-positive, alpha-beta T cell proliferation [GO:2000566]; positive regulation of memory T cell activation [GO:2000568]; positive regulation of T cell cytokine production [GO:0002726]; positive regulation of T cell mediated cytotoxicity [GO:0001916]; positive regulation of type II interferon production [GO:0032729]; protection from natural killer cell mediated cytotoxicity [GO:0042270]; T cell mediated cytotoxicity [GO:0001913]; T cell mediated cytotoxicity directed against tumor cell target [GO:0002419]; T cell receptor signaling pathway [GO:0050852]
|
cell surface [GO:0009986]; early endosome membrane [GO:0031901]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum exit site [GO:0070971]; endoplasmic reticulum membrane [GO:0005789]; ER to Golgi transport vesicle membrane [GO:0012507]; external side of plasma membrane [GO:0009897]; extracellular exosome [GO:0070062]; extracellular space [GO:0005615]; Golgi apparatus [GO:0005794]; Golgi medial cisterna [GO:0005797]; Golgi membrane [GO:0000139]; lumenal side of endoplasmic reticulum membrane [GO:0098553]; membrane [GO:0016020]; MHC class I peptide loading complex [GO:0042824]; MHC class I protein complex [GO:0042612]; phagocytic vesicle membrane [GO:0030670]; plasma membrane [GO:0005886]; recycling endosome membrane [GO:0055038]
|
beta-2-microglobulin binding [GO:0030881]; CD8 receptor binding [GO:0042610]; peptide antigen binding [GO:0042605]; RNA binding [GO:0003723]; signaling receptor binding [GO:0005102]; T cell receptor binding [GO:0042608]; TAP binding [GO:0046977]; TAP complex binding [GO:0062061]
|
PF07654;PF00129;PF06623;
|
2.60.40.10;3.30.500.10;
|
MHC class I family
|
PTM: (Microbial infection) Polyubiquitinated in a post ER compartment by interaction with human herpesvirus 8 MIR1 protein. This targets the protein for rapid degradation via the ubiquitin system. {ECO:0000269|PubMed:12006494}.; PTM: N-linked glycosylation at Asn-110. {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:21263072}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21263072, ECO:0000269|PubMed:25880248, ECO:0000269|PubMed:8805302}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000305|PubMed:8805302}; Single-pass type I membrane protein {ECO:0000255}.
| null | null | null | null | null |
FUNCTION: Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:1402688, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:24395804, PubMed:2456340, PubMed:2784196, PubMed:28250417, PubMed:7504010, PubMed:7694806, PubMed:9862734). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:25880248, PubMed:7506728, PubMed:7679507). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:12796775, PubMed:18275829, PubMed:19542454, PubMed:28250417). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome or via endopeptidase IDE/insulin-degrading enzyme (PubMed:17079320, PubMed:17189421, PubMed:20364150, PubMed:26929325, PubMed:27049119). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:7504010, PubMed:9862734). {ECO:0000269|PubMed:10449296, ECO:0000269|PubMed:12138174, ECO:0000269|PubMed:12393434, ECO:0000269|PubMed:12796775, ECO:0000269|PubMed:1402688, ECO:0000269|PubMed:15893615, ECO:0000269|PubMed:17079320, ECO:0000269|PubMed:17189421, ECO:0000269|PubMed:18275829, ECO:0000269|PubMed:19542454, ECO:0000269|PubMed:19543285, ECO:0000269|PubMed:20364150, ECO:0000269|PubMed:21498667, ECO:0000269|PubMed:24192765, ECO:0000269|PubMed:24395804, ECO:0000269|PubMed:2456340, ECO:0000269|PubMed:25880248, ECO:0000269|PubMed:26929325, ECO:0000269|PubMed:27049119, ECO:0000269|PubMed:2784196, ECO:0000269|PubMed:28250417, ECO:0000269|PubMed:7504010, ECO:0000269|PubMed:7506728, ECO:0000269|PubMed:7679507, ECO:0000269|PubMed:7694806, ECO:0000269|PubMed:9862734}.; FUNCTION: Allele A*01:01: Presents a restricted peptide repertoire including viral epitopes derived from IAV NP/nucleoprotein (CTELKLSDY), IAV PB1/polymerase basic protein 1 (VSDGGPNLY), HAdV-11 capsid L3/hexon protein (LTDLGQNLLY), SARS-CoV-2 3a/ORF3a (FTSDYYQLY) as well as tumor peptide antigens including MAGE1 (EADPTGHSY), MAGEA3 (EVDPIGHLY) and WT1 (TSEKRPFMCAY), all having in common a canonical motif with a negatively charged Asp or Glu residue at position 3 and a Tyr anchor residue at the C-terminus (PubMed:1402688, PubMed:17189421, PubMed:19177349, PubMed:20364150, PubMed:24395804, PubMed:25880248, PubMed:26758806, PubMed:30530481, PubMed:32887977, PubMed:7504010). A number of HLA-A*01:01-restricted peptides carry a post-translational modification with oxidation and N-terminal acetylation being the most frequent (PubMed:25880248). Fails to present highly immunogenic peptides from the EBV latent antigens (PubMed:18779413). {ECO:0000269|PubMed:1402688, ECO:0000269|PubMed:17189421, ECO:0000269|PubMed:18779413, ECO:0000269|PubMed:19177349, ECO:0000269|PubMed:20364150, ECO:0000269|PubMed:24395804, ECO:0000269|PubMed:25880248, ECO:0000269|PubMed:26758806, ECO:0000269|PubMed:30530481, ECO:0000269|PubMed:7504010}.; FUNCTION: Allele A*02:01: A major allele in human populations, presents immunodominant viral epitopes derived from IAV M/matrix protein 1 (GILGFVFTL), HIV-1 env (TLTSCNTSV), HIV-1 gag-pol (ILKEPVHGV), HTLV-1 Tax (LLFGYPVYV), HBV C/core antigen (FLPSDFFPS), HCMV UL83/pp65 (NLVPMVATV) as well as tumor peptide antigens including MAGEA4 (GVYDGREHTV), WT1 (RMFPNAPYL) and CTAG1A/NY-ESO-1 (SLLMWITQC), all having in common hydrophobic amino acids at position 2 and at the C-terminal anchors. {ECO:0000269|PubMed:11502003, ECO:0000269|PubMed:12138174, ECO:0000269|PubMed:12796775, ECO:0000269|PubMed:17079320, ECO:0000269|PubMed:18275829, ECO:0000269|PubMed:19542454, ECO:0000269|PubMed:20619457, ECO:0000269|PubMed:22245737, ECO:0000269|PubMed:26929325, ECO:0000269|PubMed:2784196, ECO:0000269|PubMed:28250417, ECO:0000269|PubMed:7694806, ECO:0000269|PubMed:7935798, ECO:0000269|PubMed:8630735, ECO:0000269|PubMed:8805302, ECO:0000269|PubMed:8906788, ECO:0000269|PubMed:9177355}.; FUNCTION: Allele A*03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK), SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) as well as tumor peptide antigens including PMEL (LIYRRRLMK), NODAL (HAYIQSLLK), TRP-2 (RMYNMVPFF), all having in common hydrophobic amino acids at position 2 and Lys or Arg anchor residues at the C-terminus (PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977, PubMed:7504010, PubMed:7679507, PubMed:9862734). May also display spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119). {ECO:0000269|PubMed:19543285, ECO:0000269|PubMed:21943705, ECO:0000269|PubMed:2456340, ECO:0000269|PubMed:27049119, ECO:0000269|PubMed:7504010, ECO:0000269|PubMed:7679507, ECO:0000269|PubMed:9862734}.; FUNCTION: Allele A*11:01: Presents several immunodominant epitopes derived from HIV-1 gag-pol and HHV-4 EBNA4, containing the peptide motif with Val, Ile, Thr, Leu, Tyr or Phe at position 2 and Lys anchor residue at the C-terminus. Important in the control of HIV-1, EBV and HBV infections (PubMed:10449296). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) (PubMed:32887977). {ECO:0000269|PubMed:10449296, ECO:0000269|PubMed:32887977}.; FUNCTION: Allele A*23:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response. {ECO:0000269|PubMed:17182537}.; FUNCTION: Allele A*24:02: Presents viral epitopes derived from HIV-1 nef (RYPLTFGWCF), EBV lytic- and latent-cycle antigens BRLF1 (TYPVLEEMF), BMLF1 (DYNFVKQLF) and LMP2 (IYVLVMLVL), SARS-CoV nucleocapsid/N (QFKDNVILL), as well as tumor peptide antigens including PRAME (LYVDSLFFL), all sharing a common signature motif, namely an aromatic residue Tyr or Phe at position 2 and a nonhydrophobic anchor residue Phe, Leu or Iso at the C-terminus (PubMed:12393434, PubMed:20844028, PubMed:24192765, PubMed:9047241). Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response (PubMed:17182537, PubMed:18502829). {ECO:0000269|PubMed:12393434, ECO:0000269|PubMed:17182537, ECO:0000269|PubMed:18502829, ECO:0000269|PubMed:20844028, ECO:0000269|PubMed:24192765, ECO:0000269|PubMed:9047241}.; FUNCTION: Allele A*26:01: Presents several epitopes derived from HIV-1 gag-pol (EVIPMFSAL, ETKLGKAGY) and env (LVSDGGPNLY), carrying as anchor residues preferentially Glu at position 1, Val or Thr at position 2 and Tyr at the C-terminus. {ECO:0000269|PubMed:15893615}.; FUNCTION: Allele A*29:02: Presents peptides having a common motif, namely a Glu residue at position 2 and Tyr or Leu anchor residues at the C-terminus. {ECO:0000269|PubMed:8622959}.; FUNCTION: Allele A*32:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response. {ECO:0000269|PubMed:17182537}.; FUNCTION: Allele A*68:01: Presents viral epitopes derived from IAV NP (KTGGPIYKR) and HIV-1 tat (ITKGLGISYGR), having a common signature motif namely, Val or Thr at position 2 and positively charged residues Arg or Lys at the C-terminal anchor. {ECO:0000269|PubMed:1448153, ECO:0000269|PubMed:1448154, ECO:0000269|PubMed:2784196}.; FUNCTION: Allele A*74:01: Presents immunodominant HIV-1 epitopes derived from gag-pol (GQMVHQAISPR, QIYPGIKVR) and rev (RQIHSISER), carrying an aliphatic residue at position 2 and Arg anchor residue at the C-terminus. May contribute to viral load control in chronic HIV-1 infection. {ECO:0000269|PubMed:21498667}.
|
Homo sapiens (Human)
|
P04440
|
DPB1_HUMAN
|
MMVLQVSAAPRTVALTALLMVLLTSVVQGRATPENYLFQGRQECYAFNGTQRFLERYIYNREEFARFDSDVGEFRAVTELGRPAAEYWNSQKDILEEKRAVPDRMCRHNYELGGPMTLQRRVQPRVNVSPSKKGPLQHHNLLVCHVTDFYPGSIQVRWFLNGQEETAGVVSTNLIRNGDWTFQILVMLEMTPQQGDVYTCQVEHTSLDSPVTVEWKAQSDSARSKTLTGAGGFVLGLIICGVGIFMHRRSKKVQRGSA
| null | null |
adaptive immune response [GO:0002250]; antigen processing and presentation of exogenous peptide antigen via MHC class II [GO:0019886]; peptide antigen assembly with MHC class II protein complex [GO:0002503]; positive regulation of immune response [GO:0050778]; positive regulation of T cell activation [GO:0050870]; positive regulation of T cell proliferation [GO:0042102]; positive regulation of type II interferon production [GO:0032729]; T cell receptor signaling pathway [GO:0050852]
|
cell surface [GO:0009986]; clathrin-coated endocytic vesicle membrane [GO:0030669]; endocytic vesicle membrane [GO:0030666]; ER to Golgi transport vesicle membrane [GO:0012507]; Golgi membrane [GO:0000139]; late endosome membrane [GO:0031902]; lumenal side of endoplasmic reticulum membrane [GO:0098553]; lysosomal membrane [GO:0005765]; membrane [GO:0016020]; MHC class II protein complex [GO:0042613]; plasma membrane [GO:0005886]; trans-Golgi network membrane [GO:0032588]; transport vesicle membrane [GO:0030658]
|
MHC class II protein complex binding [GO:0023026]; peptide antigen binding [GO:0042605]
|
PF07654;PF00969;
|
2.60.40.10;
|
MHC class II family
| null |
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Note=The MHC class II complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation.
| null | null | null | null | null |
FUNCTION: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
|
Homo sapiens (Human)
|
P04441
|
HG2A_MOUSE
|
MDDQRDLISNHEQLPILGNRPREPERCSRGALYTGVSVLVALLLAGQATTAYFLYQQQGRLDKLTITSQNLQLESLRMKLPKSAKPVSQMRMATPLLMRPMSMDNMLLGPVKNVTKYGNMTQDHVMHLLTRSGPLEYPQLKGTFPENLKHLKNSMDGVNWKIFESWMKQWLLFEMSKNSLEEKKPTEAPPKVLTKCQEEVSHIPAVYPGAFRPKCDENGNYLPLQCHGSTGYCWCVFPNGTEVPHTKSRGRHNCSEPLDMEDLSSGLGVTRQELGQVTL
| null | null |
antigen processing and presentation [GO:0019882]; antigen processing and presentation of exogenous peptide antigen via MHC class II [GO:0019886]; chaperone cofactor-dependent protein refolding [GO:0051085]; defense response [GO:0006952]; immunoglobulin mediated immune response [GO:0016064]; intracellular protein transport [GO:0006886]; macrophage migration inhibitory factor signaling pathway [GO:0035691]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cell migration [GO:0030336]; negative regulation of DNA damage response, signal transduction by p53 class mediator [GO:0043518]; negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:1902166]; negative regulation of mature B cell apoptotic process [GO:0002906]; negative regulation of peptide secretion [GO:0002792]; negative regulation of T cell differentiation [GO:0045581]; negative thymic T cell selection [GO:0045060]; positive regulation of adaptive immune response [GO:0002821]; positive regulation of B cell proliferation [GO:0030890]; positive regulation of canonical NF-kappaB signal transduction [GO:0043123]; positive regulation of chemokine (C-X-C motif) ligand 2 production [GO:2000343]; positive regulation of cytokine-mediated signaling pathway [GO:0001961]; positive regulation of dendritic cell antigen processing and presentation [GO:0002606]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of innate immune response [GO:0045089]; positive regulation of interleukin-6 production [GO:0032755]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of macrophage cytokine production [GO:0060907]; positive regulation of macrophage migration inhibitory factor signaling pathway [GO:2000448]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of monocyte differentiation [GO:0045657]; positive regulation of neutrophil chemotaxis [GO:0090023]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of prostaglandin biosynthetic process [GO:0031394]; positive regulation of T cell differentiation [GO:0045582]; positive regulation of type 2 immune response [GO:0002830]; positive regulation of viral entry into host cell [GO:0046598]; positive thymic T cell selection [GO:0045059]; prostaglandin biosynthetic process [GO:0001516]; protein stabilization [GO:0050821]; protein trimerization [GO:0070206]; protein-containing complex assembly [GO:0065003]; response to type II interferon [GO:0034341]; T cell activation involved in immune response [GO:0002286]
|
cell surface [GO:0009986]; cytoplasm [GO:0005737]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; external side of plasma membrane [GO:0009897]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; Golgi apparatus [GO:0005794]; late endosome [GO:0005770]; lysosome [GO:0005764]; macrophage migration inhibitory factor receptor complex [GO:0035692]; MHC class II protein complex [GO:0042613]; multivesicular body [GO:0005771]; NOS2-CD74 complex [GO:0035693]; nucleus [GO:0005634]; plasma membrane [GO:0005886]
|
amyloid-beta binding [GO:0001540]; CD4 receptor binding [GO:0042609]; cytokine receptor activity [GO:0004896]; macrophage migration inhibitory factor binding [GO:0035718]; MHC class II protein binding [GO:0042289]; MHC class II protein binding, via antigen binding groove [GO:0042658]; nitric-oxide synthase binding [GO:0050998]; protein folding chaperone [GO:0044183]
|
PF09307;PF08831;PF00086;
|
1.10.870.10;4.10.800.10;
| null | null |
SUBCELLULAR LOCATION: [Isoform Long]: Late endosome {ECO:0000269|PubMed:11483509}. Lysosome {ECO:0000269|PubMed:11483509}.; SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P04233}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:P04233}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P04233}. Golgi apparatus, trans-Golgi network {ECO:0000250|UniProtKB:P04233}. Endosome {ECO:0000250|UniProtKB:P04233}. Lysosome {ECO:0000250|UniProtKB:P04233}. Secreted {ECO:0000250|UniProtKB:P04233}. Note=Transits through a number of intracellular compartments in the endocytic pathway. It can either undergo proteolysis or reach the cell membrane. {ECO:0000250|UniProtKB:P04233}.
| null | null | null | null | null |
FUNCTION: Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place. Enhance also the stimulation of T-cell responses through interaction with CD44. {ECO:0000269|PubMed:8343954, ECO:0000269|PubMed:8977190}.; FUNCTION: [Isoform Long]: Stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of antigen-presenting cells (APCs). {ECO:0000269|PubMed:11483509, ECO:0000269|PubMed:12417635}.; FUNCTION: [Class-II-associated invariant chain peptide]: Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome. {ECO:0000250|UniProtKB:P04233}.
|
Mus musculus (Mouse)
|
P04443
|
HBB0_MOUSE
|
MVHFTAEEKAAITSIWDKVDLEKVGGETLGRLLIVYPWTQRFFDKFGNLSSAQAIMGNPRIKAHGKKVLTSLGLAVKNMDNLKETFAHLSELHCDKLHADPENFKLLGNMLVIVLSSYFGKEFTAEAQAAWQKLVVGVATALSHKYH
| null | null |
hydrogen peroxide catabolic process [GO:0042744]
|
blood microparticle [GO:0072562]; haptoglobin-hemoglobin complex [GO:0031838]; hemoglobin complex [GO:0005833]
|
haptoglobin binding [GO:0031720]; heme binding [GO:0020037]; hemoglobin alpha binding [GO:0031721]; metal ion binding [GO:0046872]; organic acid binding [GO:0043177]; oxygen binding [GO:0019825]; oxygen carrier activity [GO:0005344]; peroxidase activity [GO:0004601]
|
PF00042;
|
1.10.490.10;
|
Globin family
| null | null | null | null | null | null | null |
FUNCTION: This is a minor early embryonic beta chain.
|
Mus musculus (Mouse)
|
P04444
|
HBBZ_MOUSE
|
MVHFTAEEKAAITSIWDKVDLEKVGGETLGRLLIVYPWTQRFFDKFGNLSSALAIMGNPRIRAHGKKVLTSLGLGVKNMDNLKETFAHLSELHCDKLHVDPENFKLLGNMLVIVLSTHFAKEFTPEVQAAWQKLVIGVANALSHKYH
| null | null |
carbon dioxide transport [GO:0015670]; hydrogen peroxide catabolic process [GO:0042744]; negative regulation of transcription by RNA polymerase II [GO:0000122]; oxygen transport [GO:0015671]
|
blood microparticle [GO:0072562]; haptoglobin-hemoglobin complex [GO:0031838]; hemoglobin complex [GO:0005833]
|
haptoglobin binding [GO:0031720]; heme binding [GO:0020037]; hemoglobin alpha binding [GO:0031721]; metal ion binding [GO:0046872]; organic acid binding [GO:0043177]; oxygen binding [GO:0019825]; oxygen carrier activity [GO:0005344]; peroxidase activity [GO:0004601]; protein-containing complex binding [GO:0044877]
|
PF00042;
|
1.10.490.10;
|
Globin family
| null | null | null | null | null | null | null |
FUNCTION: This is an embryonic beta-type chain.
|
Mus musculus (Mouse)
|
P04456
|
RL25_YEAST
|
MAPSAKATAAKKAVVKGTNGKKALKVRTSATFRLPKTLKLARAPKYASKAVPHYNRLDSYKVIEQPITSETAMKKVEDGNILVFQVSMKANKYQIKKAVKELYEVDVLKVNTLVRPNGTKKAYVRLTADYDALDIANRIGYI
| null | null |
cytoplasmic translation [GO:0002181]; ribosomal large subunit assembly [GO:0000027]
|
cytosol [GO:0005829]; cytosolic large ribosomal subunit [GO:0022625]; preribosome, large subunit precursor [GO:0030687]
|
RNA binding [GO:0003723]; rRNA binding [GO:0019843]; structural constituent of ribosome [GO:0003735]
|
PF00276;PF03939;
|
3.30.70.330;
|
Universal ribosomal protein uL23 family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22096102}.
| null | null | null | null | null |
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. uL23 is a major component of the universal docking site for these factors at the polypeptide exit tunnel. {ECO:0000305|PubMed:22096102}.
|
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
|
P04485
|
ICP22_HHV11
|
MADISPGAFAPCVKARRPALRSPPLGTRKRKRPSRPLSSESEVESDTALESEVESETASDSTESGDQDEAPRIGGRRAPRRLGGRFFLDMSAESTTGTETDASVSDDPDDTSDWSYDDIPPRPKRARVNLRLTSSPDRRDGVIFPKMGRVRSTRETQPRAPTPSAPSPNAMLRRSVRQAQRRSSARWTPDLGYMRQCINQLFRVLRVARDPHGSANRLRHLIRDCYLMGYCRARLAPRTWCRLLQVSGGTWGMHLRNTIREVEARFDATAEPVCKLPCLETRRYGPECDLSNLEIHLSATSDDEISDATDLEAAGSDHTLASQSDTEDAPSPVTLETPEPRGSLAVRLEDEFGEFDWTPQEGSQPWLSAVVADTSSVERPGPSDSGAGRAAEDRKCLDGCRKMRFSTACPYPCSDTFLRP
| null | null |
symbiont-mediated suppression of host mRNA transcription via inhibition of RNA polymerase II activity [GO:0039523]
|
host cell nucleus [GO:0042025]
| null |
PF02479;
| null |
Herpesviridae ICP22 family
|
PTM: Phosphorylated by serine/threonine-protein kinase UL13 (PubMed:1323829, PubMed:8393574). Tyrosine phosphorylated. {ECO:0000269|PubMed:12504549, ECO:0000269|PubMed:1323829, ECO:0000269|PubMed:8393574}.
|
SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:16877770, ECO:0000269|PubMed:24741100, ECO:0000269|PubMed:28611249}. Note=Localizes in small nuclear bodies early in infection then moves to a more diffuse distribution in viral compartments as infection progresses (PubMed:16877770). UL31 mediates the recruitment and anchorage of ICP22 at the nuclear membrane (PubMed:24741100). {ECO:0000269|PubMed:16877770, ECO:0000269|PubMed:24741100}.
| null | null | null | null | null |
FUNCTION: Transcriptional regulator that interacts with cellular elongation regulators to inhibit host cell transcription and promote viral gene expression in productive infection, mainly by mediating changes on the host RNA polymerase II (PubMed:17344289, PubMed:28611249, PubMed:34696162). One change, which is UL13 independent, is the rapid loss of Pol II forms bearing Ser-2 phosphorylation in the heptapeptides of the CTD leading to unproductive elongation of pol II (PubMed:17344289, PubMed:25233083). A second change, which is UL13 dependent, is the appearance of an intermediate form of Pol II that differs from the normal hypo- and hyperphosphorylated forms. These Pol II modifications immediately inhibit host genome transcription, leading to cell cycle deregulation and loss of efficient antiviral response (Probable). In opposition to its role in productive infection, inhibits transcription elongation of early viral genes, which can be beneficial because it reduces antisense and intergenic transcription (PubMed:23029222, PubMed:35019725). This regulatory function directly or indirectly helps to retain Pol activity on the viral genome later in infection (PubMed:35019725). The viral protein VP16 overcomes transcriptional inhibition by ICP22 to promote transcription of IE genes (PubMed:23029222, PubMed:34696162). Recruits FACT complexes to the viral genome by interacting with the FACT complex, which could allow Pol II to cross the nucleosome barrier on the viral genome and achieve efficient viral transcription elongation late in viral infection and ultimately infectious virion production (Probable). Plays a role in virion primary envelopment, possibly by interacting with and regulating UL31 and UL34 (PubMed:24741100). Essential for the recruitment of Hsc70 into virus induced chaperone enriched (VICE) domains in infected cells (PubMed:20032172). May function as a co-chaperone (J protein-like), functionning together with Hsc70 to recognize and manage aggregated and misfolded proteins (PubMed:31748398). {ECO:0000269|PubMed:17344289, ECO:0000269|PubMed:20032172, ECO:0000269|PubMed:23029222, ECO:0000269|PubMed:24741100, ECO:0000269|PubMed:25233083, ECO:0000269|PubMed:28611249, ECO:0000269|PubMed:31748398, ECO:0000269|PubMed:34696162, ECO:0000269|PubMed:35019725, ECO:0000305|PubMed:16571817, ECO:0000305|PubMed:26676778, ECO:0000305|PubMed:28611249}.
|
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
|
P04487
|
RNB_HHV11
|
MSQTQPPAPVGPGDPDVYLKGVPSAGMHPRGVHAPRGHPRMISGPPQRGDNDQAAGQCGDSGLLRVGADTTISKPSEAVRPPTIPRTPRVPREPRVPRPPREPREPRVPRAPRDPRVPRDPRDPRQPRSPREPRSPREPRSPREPRTPRTPREPRTARGSV
| null | null |
suppression by virus of host autophagy [GO:0039521]; symbiont-mediated perturbation of host cell cycle progression [GO:0044071]; symbiont-mediated perturbation of host transcription [GO:0052026]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity [GO:0039554]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity [GO:0039540]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity [GO:0039723]; symbiont-mediated suppression of host PKR/eIFalpha signaling [GO:0039580]; symbiont-mediated suppression of host toll-like receptor signaling pathway [GO:0039722]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]; host cell nucleus [GO:0042025]
|
DNA binding [GO:0003677]; endopeptidase activity [GO:0004175]; molecular sequestering activity [GO:0140313]; protein serine/threonine kinase inhibitor activity [GO:0030291]; RNA binding [GO:0003723]
| null | null |
Simplex virus US11 protein family
|
PTM: May be phosphorylated on Ser residues by host kinases. {ECO:0000269|PubMed:7498183}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000269|PubMed:20633584}. Host cytoplasm {ECO:0000269|PubMed:20633584}. Note=Following infection, it is released into the cell cytoplasm.
| null | null | null | null | null |
FUNCTION: Plays a role in the inhibition of host immune response. Participates in the inhibition of host autophagy by interacting with and inhibiting host PKR/EIF2AK2. This interaction also prevents the interferon-induced shut down of protein synthesis following viral infection. Downmodulates the host RLR signaling pathway via direct interaction with host RIGI and IFIH1. Associates with endogenous HSP90 to disrupt the HSP90-TBK1 complex and induces destabilization of host TBK1 through a proteasome-dependent pathway. May also participate in nuclear egress of viral particles through interactions with host NCL and regulation of the viral UL34 mRNA. {ECO:0000269|PubMed:22130536, ECO:0000269|PubMed:22301138, ECO:0000269|PubMed:23115300, ECO:0000269|PubMed:23773021, ECO:0000269|PubMed:29743370}.
|
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
|
P04488
|
GE_HHV11
|
MDRGAVVGFLLGVCVVSCLAGTPKTSWRRVSVGEDVSLLPAPGPTGRGPTQKLLWAVEPLDGCGPLHPSWVSLMPPKQVPETVVDAACMRAPVPLAMAYAPPAPSATGGLRTDFVWQERAAVVNRSLVIHGVRETDSGLYTLSVGDIKDPARQVASVVLVVQPAPVPTPPPTPADYDEDDNDEGEDESLAGTPASGTPRLPPPPAPPRSWPSAPEVSHVRGVTVRMETPEAILFSPGETFSTNVSIHAIAHDDQTYSMDVVWLRFDVPTSCAEMRIYESCLYHPQLPECLSPADAPCAASTWTSRLAVRSYAGCSRTNPPPRCSAEAHMEPVPGLAWQAASVNLEFRDASPQHSGLYLCVVYVNDHIHAWGHITISTAAQYRNAVVEQPLPQRGADLAEPTHPHVGAPPHAPPTHGALRLGAVMGAALLLSALGLSVWACMTCWRRRAWRAVKSRASGKGPTYIRVADSELYADWSSDSEGERDQVPWLAPPERPDSPSTNGSGFEILSPTAPSVYPRSDGHQSRRQLTTFGSGRPDRRYSQASDSSVFW
| null | null |
virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell Golgi membrane [GO:0044178]; host cell junction [GO:0044156]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
identical protein binding [GO:0042802]
|
PF02480;PF20418;
|
2.60.40.10;
|
Alphaherpesvirinae glycoprotein E family
|
PTM: Phosphorylated on serines within the acidic cluster. Phosphorylation determines whether endocytosed viral gE traffics to the trans-Golgi network or recycles to the cell membrane. {ECO:0000305}.; PTM: N-glycosylated, and sulfated. {ECO:0000269|PubMed:6310034}.
|
SUBCELLULAR LOCATION: Virion membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Host cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Host cell junction. Host Golgi apparatus membrane {ECO:0000250}; Single-pass membrane protein {ECO:0000250}. Host endosome membrane {ECO:0000250}; Single-pass membrane protein {ECO:0000250}. 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), maybe through an interaction with PACS-1 sorting protein. The heterodimer gE/gI then redistributes to cell junctions to promote cell-cell spread later in the infection.
| null | null | null | null | null |
FUNCTION: In epithelial cells, the heterodimer gE/gI is required for the cell-to-cell spread of the virus, by sorting nascent virions to cell junctions. Once the virus reaches the cell junctions, virus particles can spread to adjacent cells extremely rapidly through interactions with cellular receptors that accumulate at these junctions. Implicated in basolateral spread in polarized cells (By similarity). In neuronal cells, gE/gI is essential for the anterograde spread of the infection throughout the host nervous system. Together with US9, the heterodimer gE/gI is involved in the sorting and transport of viral structural components toward axon tips. {ECO:0000250, ECO:0000269|PubMed:14734541, ECO:0000269|PubMed:2831396}.; FUNCTION: The heterodimer gE/gI serves as a receptor for the Fc part of host IgG. Dissociation of gE/gI from IgG occurs at acidic pH. May thus be involved in anti-HSV antibodies bipolar bridging, followed by intracellular endocytosis and degradation, thereby interfering with host IgG-mediated immune responses.
|
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
|
P04499
|
TERM_ADE05
|
MALSVNDCARLTGQSVPTMEHFLPLRNIWNRVRDFPRASTTAAGITWMSRYIYGYHRLMLEDLAPGAPATLRWPLYRQPPPHFLVGYQYLVRTCNDYVFDSRAYSRLRYTELSQPGHQTVNWSVMANCTYTINTGAYHRFVDMDDFQSTLTQVQQAILAERVVADLALLQPMRGFGVTRMGGRGRHLRPNSAAAAAIDARDAGQEEGEEEVPVERLMQDYYKDLRRCQNEAWGMADRLRIQQAGPKDMVLLSTIRRLKTAYFNYIISSTSARNNPDRRPLPPATVLSLPCDCDWLDAFLERFSDPVDADSLRSLGGGVPTQQLLRCIVSAVSLPHGSPPPTHNRDMTGGVFQLRPRENGRAVTETMRRRRGEMIERFVDRLPVRRRRRRVPPPPPPPEEEEGEALMEEEIEEEEEAPVAFEREVRDTVAELIRLLEEELTVSARNSQFFNFAVDFYEAMERLEALGDINESTLRRWVMYFFVAEHTATTLNYLFQRLRNYAVFARHVELNLAQVVMRARDAEGGVVYSRVWNEGGLNAFSQLMARISNDLAATVERAGRGDLQEEEIEQFMAEIAYQDNSGDVQEILRQAAVNDTEIDSVELSFRLKLTGPVVFTQRRQIQEINRRVVAFASNLRAQHQLLPARGADVPLPPLPAGPEPPLPPGARPRHRF
| null | null |
DNA replication [GO:0006260]; viral DNA genome replication [GO:0039693]; viral DNA strand displacement replication [GO:0039687]
|
host cell nuclear matrix [GO:0044204]; host cell nucleus [GO:0042025]
|
DNA binding [GO:0003677]; double-stranded DNA binding [GO:0003690]; single-stranded DNA binding [GO:0003697]
|
PF02459;
| null |
Adenoviridae terminal protein family
|
PTM: Preterminal protein is used to replicate viral genome, upon genomic encapsidation it is processed first into iTP and finally into TP by adenovirus protease. {ECO:0000255|HAMAP-Rule:MF_04061}.
|
SUBCELLULAR LOCATION: Host nucleus matrix {ECO:0000255|HAMAP-Rule:MF_04061, ECO:0000269|PubMed:8416372, ECO:0000269|PubMed:8497057}.
| null | null | null | null | null |
FUNCTION: Protein covalently bound to the viral DNA that acts as a primer for viral genomic replication by DNA strand displacement. Assembles on the viral origin of replication in an initiation complex with viral polymerase, DBP, host NFIA and host POU2F1/OCT1. During initiation, the polymerase covalently couples the first dCTP with Ser-580 of pTP. The terminal protein stimulates the template activity over 20 fold compared to protein-free templates. Neo-synthesized viral genomes are linked to two preterminal proteins, one for each 5' end. These new genomes are encapsidated in the nucleus, and during capsid maturation by viral protease, preterminal protein is first cleaved into intermediary (iTP), then into mature TP. May play a role in host nuclear matrix localization of genomic DNA. {ECO:0000255|HAMAP-Rule:MF_04061, ECO:0000269|PubMed:11847120, ECO:0000269|PubMed:12747549, ECO:0000269|PubMed:15273278, ECO:0000269|PubMed:8416372, ECO:0000269|PubMed:8497057}.
|
Human adenovirus C serotype 5 (HAdV-5) (Human adenovirus 5)
|
P04509
|
VP6_ROTRF
|
MDVLYSLSKTLKDARDKIVEGTLYSNVSDLIQQFNQMIITMNGNEFQTGGIGNLPIRNWNFDFGLLGTTLLNLDANYVETARNTIDYFVDFVDNVCMDEMVRESQRNGIAPQSDSLIKLSGIKFKRINFDNSSEYIENWNLQNRRQRTGFTFHKPNIFPYSASFTLNRSQPAHDNLMGTMWLNAGSEIQVAGFDYSCAINAPANTQQFEHIVQLRRVLTTATITLLPDAERFSFPRVITSADGATTWYFNPVILRPNNVEIEFLLNGQIINTYQARFGTIIARNFDTIRLSFQLMRPPNMTPAVAALFPNAQPFEHHATVGLTLRIESAVCESVLADASETMLANVTSVRQEYAIPVGPVFPPGMNWTDLITNYSPSREDNLQRVFTVASIRSMLVK
| null | null |
fusion of virus membrane with host plasma membrane [GO:0019064]
|
T=13 icosahedral viral capsid [GO:0039621]; viral envelope [GO:0019031]; viral intermediate capsid [GO:0039626]
|
host cell surface receptor binding [GO:0046789]; metal ion binding [GO:0046872]; structural molecule activity [GO:0005198]
|
PF00980;
|
2.60.120.170;1.10.1350.10;
|
Rotavirus VP6 family
|
PTM: The N-terminus is blocked. {ECO:0000255|HAMAP-Rule:MF_04129, ECO:0000269|PubMed:12610135}.; PTM: Sumoylated with SUMO1 and SUMO2. Sumoylation of viral proteins seems to have a positive role on viral replication. {ECO:0000255|HAMAP-Rule:MF_04129}.
|
SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04129, ECO:0000269|PubMed:11285213, ECO:0000269|PubMed:12097594}. Note=Component of the intermediate capsid (PubMed:11285213). Also found in spherical cytoplasmic structures, called virus factories, that appear early after infection and are the site of viral replication and packaging (Potential). {ECO:0000255|HAMAP-Rule:MF_04129, ECO:0000269|PubMed:11285213}.
| null | null | null | null | null |
FUNCTION: Intermediate capsid protein that self assembles to form an icosahedral capsid with a T=13 symmetry, which consists of 230 trimers of VP6, with channels at each of its five-fold vertices (PubMed:11285213). This capsid constitutes the middle concentric layer of the viral mature particle (PubMed:11285213). The innermost VP2 capsid and the intermediate VP6 capsid remain intact following cell entry to protect the dsRNA from degradation and to prevent unfavorable antiviral responses in the host cell during all the replication cycle of the virus. Nascent transcripts are transcribed within the structural confines of this double-layered particle (DLP) and are extruded through the channels at the five-fold axes (By similarity). VP6 is required for the transcription activity of the DLP (PubMed:12097594). {ECO:0000255|HAMAP-Rule:MF_04129, ECO:0000269|PubMed:11285213, ECO:0000269|PubMed:12097594, ECO:0000269|PubMed:6292454}.
|
Rotavirus A (strain RVA/Cow/France/RF/1975/G6P6[1]) (RV-A)
|
P04512
|
NSP4_ROTS1
|
MEKLTDLNYTLSVITLMNNTLHTILEDPGMAYFPYIASVLTGLFALNKASIPTMKIALKTSKCSYKVVKYCIVTIFNTLLKLAGYKEQITTKDEIEKQMDRVVKEMRRQLEMIDKLTTREIEQVELLKRIYDKLTVQTTGEIDMTKEINQKNVRTLEEWESGKNPYEPREVTAAM
| null | null |
induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]
|
extracellular region [GO:0005576]; host caveola [GO:0044155]; host cell rough endoplasmic reticulum membrane [GO:0044169]; membrane [GO:0016020]
|
metal ion binding [GO:0046872]; monoatomic ion channel activity [GO:0005216]; toxin activity [GO:0090729]
|
PF01452;
|
1.20.5.430;
|
Rotavirus NSP4 family
|
PTM: The N-glycosyl content is primarily Man(9)GlcNAc, with a small amount of Man(8)GlcNAc. {ECO:0000255|HAMAP-Rule:MF_04091}.
|
SUBCELLULAR LOCATION: Host rough endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P08434, ECO:0000255|HAMAP-Rule:MF_04091}; Single-pass type III membrane protein {ECO:0000255|HAMAP-Rule:MF_04091}. Host membrane, host caveola {ECO:0000255|HAMAP-Rule:MF_04091, ECO:0000269|PubMed:17376898}; Single-pass type III membrane protein {ECO:0000255|HAMAP-Rule:MF_04091}. Secreted {ECO:0000255|HAMAP-Rule:MF_04091, ECO:0000269|PubMed:17035333}. Note=NSP4 localizes also in vesicular structures which contain autophagosomal markers and associate with viroplasms in virus-infected cells. Additionally, a soluble form of glycosylated NSP4 is secreted despite retention of its transmembrane domain. {ECO:0000255|HAMAP-Rule:MF_04091}.
| null | null | null | null | null |
FUNCTION: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca(2+) in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly. {ECO:0000255|HAMAP-Rule:MF_04091, ECO:0000269|PubMed:21151776, ECO:0000269|PubMed:7637021, ECO:0000269|PubMed:9108087}.; FUNCTION: The secreted form acts as an enterotoxin that causes phospholipase C-dependent elevation of the intracellular calcium concentration in host intestinal mucosa cells. Increased concentration of intracellular calcium disrupts the cytoskeleton and the tight junctions, raising the paracellular permeability. Potentiates chloride ion secretion through a calcium ion-dependent signaling pathway, inducing age-dependent diarrhea. To perform this enterotoxigenic role in vivo, NSP4 is released from infected enterocytes in a soluble form capable of diffusing within the intestinal lumen and interacting with host plasma membrane receptors on neighboring epithelial cells such as integrins ITGA1/ITGB1 and ITGA2/ITGB1. {ECO:0000255|HAMAP-Rule:MF_04091, ECO:0000269|PubMed:17035333, ECO:0000269|PubMed:18587047}.
|
Rotavirus A (strain RVA/SA11-Both/G3P5B[2]) (RV-A) (Simian Agent 11 (strain Both))
|
P04517
|
POLG_TEV
|
MALIFGTVNANILKEVFGGARMACVTSAHMAGANGSILKKAEETSRAIMHKPVIFGEDYITEADLPYTPLHLEVDAEMERMYYLGRRALTHGKRRKVSVNNKRNRRRKVAKTYVGRDSIVEKIVVPHTERKVDTTAAVEDICNEATTQLVHNSMPKRKKQKNFLPATSLSNVYAQTWSIVRKRHMQVEIISKKSVRARVKRFEGSVQLFASVRHMYGERKRVDLRIDNWQQETLLDLAKRFKNERVDQSKLTFGSSGLVLRQGSYGPAHWYRHGMFIVRGRSDGMLVDARAKVTFAVCHSMTHYSDKSISEAFFIPYSKKFLELRPDGISHECTRGVSVERCGEVAAILTQALSPCGKITCKRCMVETPDIVEGESGESVTNQGKLLAMLKEQYPDFPMAEKLLTRFLQQKSLVNTNLTACVSVKQLIGDRKQAPFTHVLAVSEILFKGNKLTGADLEEASTHMLEIARFLNNRTENMRIGHLGSFRNKISSKAHVNNALMCDNQLDQNGNFIWGLRGAHAKRFLKGFFTEIDPNEGYDKYVIRKHIRGSRKLAIGNLIMSTDFQTLRQQIQGETIERKEIGNHCISMRNGNYVYPCCCVTLEDGKAQYSDLKHPTKRHLVIGNSGDSKYLDLPVLNEEKMYIANEGYCYMNIFFALLVNVKEEDAKDFTKFIRDTIVPKLGAWPTMQDVATACYLLSILYPDVLRAELPRILVDHDNKTMHVLDSYGSRTTGYHMLKMNTTSQLIEFVHSGLESEMKTYNVGGMNRDVVTQGAIEMLIKSIYKPHLMKQLLEEEPYIIVLAIVSPSILIAMYNSGTFEQALQMWLPNTMRLANLAAILSALAQKLTLADLFVQQRNLINEYAQVILDNLIDGVRVNHSLSLAMEIVTIKLATQEMDMALREGGYAVTSEKVHEMLEKNYVKALKDAWDELTWLEKFSAIRHSRKLLKFGRKPLIMKNTVDCGGHIDLSVKSLFKFHLELLKGTISRAVNGGARKVRVAKNAMTKGVFLKIYSMLPDVYKFITVSSVLSLLLTFLFQIDCMIRAHREAKVAAQLQKESEWDNIINRTFQYSKLENPIGYRSTAEERLQSEHPEAFEYYKFCIGKEDLVEQAKQPEIAYFEKIIAFITLVLMAFDAERSDGVFKILNKFKGILSSTEREIIYTQSLDDYVTTFDDNMTINLELNMDELHKTSLPGVTFKQWWNNQISRGNVKPHYRTEGHFMEFTRDTAASVASEISHSPARDFLVRGAVGSGKSTGLPYHLSKRGRVLMLEPTRPLTDNMHKQLRSEPFNCFPTLRMRGKSTFGSSPITVMTSGFALHHFARNIAEVKTYDFVIIDECHVNDASAIAFRNLLFEHEFEGKVLKVSATPPGREVEFTTQFPVKLKIEEALSFQEFVSLQGTGANADVISCGDNILVYVASYNDVDSLGKLLVQKGYKVSKIDGRTMKSGGTEIITEGTSVKKHFIVATNIIENGVTIDIDVVVDFGTKVVPVLDVDNRAVQYNKTVVSYGERIQKLGRVGRHKEGVALRIGQTNKTLVEIPEMVATEAAFLCFMYNLPVTTQSVSTTLLENATLLQARTMAQFELSYFYTINFVRFDGSMHPVIHDKLKRFKLHTCETFLNKLAIPNKGLSSWLTSGEYKRLGYIAEDAGIRIPFVCKEIPDSLHEEIWHIVVAHKGDSGIGRLTSVQAAKVVYTLQTDVHSIARTLACINRRIADEQMKQSHFEAATGRAFSFTNYSIQSIFDTLKANYATKHTKENIAVLQQAKDQLLEFSNLAKDQDVTGIIQDFNHLETIYLQSDSEVAKHLKLKSHWNKSQITRDIIIALSVLIGGGWMLATYFKDKFNEPVYFQGKKNQKHKLKMREARGARGQYEVAAEPEALEHYFGSAYNNKGKRKGTTRGMGAKSRKFINMYGFDPTDFSYIRFVDPLTGHTIDESTNAPIDLVQHEFGKVRTRMLIDDEIEPQSLSTHTTIHAYLVNSGTKKVLKVDLTPHSSLRASEKSTAIMGFPERENELRQTGMAVPVAYDQLPPKNEDLTFEGESLFKGPRDYNPISSTICHLTNESDGHTTSLYGIGFGPFIITNKHLFRRNNGTLLVQSLHGVFKVKNTTTLQQHLIDGRDMIIIRMPKDFPPFPQKLKFREPQREERICLVTTNFQTKSMSSMVSDTSCTFPSSDGIFWKHWIQTKDGQCGSPLVSTRDGFIVGIHSASNFTNTNNYFTSVPKNFMELLTNQEAQQWVSGWRLNADSVLWGGHKVFMSKPEEPFQPVKEATQLMNELVYSQGEKRKWVVEALSGNLRPVAECPSQLVTKHVVKGKCPLFELYLQLNPEKEAYFKPMMGAYKPSRLNREAFLKDILKYASEIEIGNVDCDLLELAISMLVTKLKALGFPTVNYITDPEEIFSALNMKAAMGALYKGKKKEALSELTLDEQEAMLKASCLRLYTGKLGIWNGSLKAELRPIEKVENNKTRTFTAAPIDTLLAGKVCVDDFNNQFYDLNIKAPWTVGMTKFYQGWNELMEALPSGWVYCDADGSQFDSSLTPFLINAVLKVRLAFMEEWDIGEQMLRNLYTEIVYTPILTPDGTIIKKHKGNNSGQPSTVVDNTLMVIIAMLYTCEKCGINKEEIVYYVNGDDLLIAIHPDKAERLSRFKESFGELGLKYEFDCTTRDKTQLWFMSHRALERDGMYIPKLEEERIVSILEWDRSKEPSHRLEAICASMIEAWGYDKLVEEIRNFYAWVLEQAPYSQLAEEGKAPYLAETALKFLYTSQHGTNSEIEEYLKVLYDYDIPTTENLYFQSGTVDAGADAGKKKDQKDDKVAEQASKDRDVNAGTSGTFSVPRINAMATKLQYPRMRGEVVVNLNHLLGYKPQQIDLSNARATHEQFAAWHQAVMTAYGVNEEQMKILLNGFMVWCIENGTSPNLNGTWVMMDGEDQVSYPLKPMVENAQPTLRQIMTHFSDLAEAYIEMRNRERPYMPRYGLQRNITDMSLSRYAFDFYELTSKTPVRAREAHMQMKAAAVRNSGTRLFGLDGNVGTAEEDTERHTAHDVNRNMHTLLGVRQ
|
2.7.7.48; 3.4.-.-; 3.4.22.44; 3.4.22.45; 3.6.4.-
| null |
DNA-templated transcription [GO:0006351]; proteolysis [GO:0006508]; viral RNA genome replication [GO:0039694]; virus-mediated perturbation of host defense response [GO:0019049]
|
helical viral capsid [GO:0019029]; host cell cytoplasmic vesicle [GO:0044161]; host cell nucleus [GO:0042025]
|
ATP binding [GO:0005524]; cysteine-type endopeptidase activity [GO:0004197]; helicase activity [GO:0004386]; hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides [GO:0016818]; RNA binding [GO:0003723]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type peptidase activity [GO:0008236]; structural molecule activity [GO:0005198]
|
PF00270;PF00271;PF00863;PF00851;PF01577;PF00767;PF08440;PF13608;PF00680;
|
3.30.505.20;3.30.70.270;3.90.70.150;3.40.50.300;2.40.10.10;
|
Potyviridae genome polyprotein family
|
PTM: [Viral genome-linked protein]: VPg is uridylylated by the polymerase and is covalently attached to the 5'-end of the genomic RNA. This uridylylated form acts as a nucleotide-peptide primer for the polymerase (By similarity). {ECO:0000250|UniProtKB:P09814}.; PTM: [Genome polyprotein]: Potyviral RNA is expressed as two polyproteins which undergo post-translational proteolytic processing. Genome polyprotein is processed by NIa-pro, P1 and HC-pro proteinases resulting in the production of at least ten individual proteins. P3N-PIPO polyprotein is cleaved by P1 and HC-pro proteinases resulting in the production of three individual proteins. The P1 proteinase and the HC-pro cleave only their respective C-termini autocatalytically. 6K1 is essential for proper proteolytic separation of P3 from CI (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: [6 kDa protein 1]: Host cytoplasmic vesicle. Note=Probably colocalizes with 6K2-induced vesicles associated with host chloroplasts. {ECO:0000250|UniProtKB:P13529}.; SUBCELLULAR LOCATION: [6 kDa protein 2]: Host cytoplasmic vesicle {ECO:0000250|UniProtKB:P09814}. Note=6K-induced vesicles associate with host chloroplasts. {ECO:0000250|UniProtKB:P09814}.; SUBCELLULAR LOCATION: [Viral genome-linked protein]: Host nucleus {ECO:0000250|UniProtKB:P21231}. Note=Binds to host plant eIF4E proteins in the host nucleus. {ECO:0000250|UniProtKB:P21231}.; SUBCELLULAR LOCATION: [Capsid protein]: Virion {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=Hydrolyzes glutaminyl bonds, and activity is further restricted by preferences for the amino acids in P6 - P1' that vary with the species of potyvirus, e.g. Glu-Xaa-Xaa-Tyr-Xaa-Gln-|-(Ser or Gly) for the enzyme from tobacco etch virus. The natural substrate is the viral polyprotein, but other proteins and oligopeptides containing the appropriate consensus sequence are also cleaved.; EC=3.4.22.44; Evidence={ECO:0000269|PubMed:2475971}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes a Gly-|-Gly bond at its own C-terminus, commonly in the sequence -Tyr-Xaa-Val-Gly-|-Gly, in the processing of the potyviral polyprotein.; EC=3.4.22.45; Evidence={ECO:0000269|PubMed:2656254, ECO:0000269|PubMed:2688301};
| null | null | null | null |
FUNCTION: [Helper component proteinase]: Required for aphid transmission and also has proteolytic activity. Only cleaves a Gly-Gly dipeptide at its own C-terminus (PubMed:2656254). Interacts with virions and aphid stylets (PubMed:9880030). Acts as a suppressor of RNA-mediated gene silencing, also known as post-transcriptional gene silencing (PTGS), a mechanism of plant viral defense that limits the accumulation of viral RNAs (PubMed:11414807). May have RNA-binding activity. {ECO:0000269|PubMed:11414807, ECO:0000269|PubMed:2656254, ECO:0000269|PubMed:9880030}.; FUNCTION: [Cytoplasmic inclusion protein]: Has helicase activity. It may be involved in replication.; FUNCTION: [6 kDa protein 1]: Indispensable for virus replication. {ECO:0000250|UniProtKB:P13529}.; FUNCTION: [6 kDa protein 2]: Indispensable for virus replication. {ECO:0000250|UniProtKB:P09814}.; FUNCTION: [Viral genome-linked protein]: Mediates the cap-independent, EIF4E-dependent translation of viral genomic RNAs (Probable). Binds to the cap-binding site of host EIF4E and thus interferes with the host EIF4E-dependent mRNA export and translation (By similarity). VPg-RNA directly binds EIF4E and is a template for transcription (By similarity). Also forms trimeric complexes with EIF4E-EIF4G, which are templates for translation (By similarity). {ECO:0000250|UniProtKB:P18247, ECO:0000305|PubMed:22242134, ECO:0000305|PubMed:27655175}.; FUNCTION: [Nuclear inclusion protein A]: Has RNA-binding and proteolytic activities. {ECO:0000269|PubMed:2475971}.; FUNCTION: [Nuclear inclusion protein B]: An RNA-dependent RNA polymerase that plays an essential role in the virus replication.; FUNCTION: [Capsid protein]: Involved in aphid transmission, cell-to-cell and systemis movement, encapsidation of the viral RNA and in the regulation of viral RNA amplification.
|
Tobacco etch virus (TEV)
|
P04524
|
SIGML_BPT4
|
MSETKPKYNYVNNKELLQAIIDWKTELANNKDPNKVVRQNDTIGLAIMLIAEGLSKRFNFSGYTQSWKQEMIADGIEASIKGLHNFDETKYKNPHAYITQACFNAFVQRIKKERKEVAKKYSYFVHNVYDSRDDDMVALVDETFIQDIYDKMTHYEESTYRTPGAEKKSVVDDSPSLDFLYEAND
| null | null |
late viral transcription [GO:0019086]
| null |
DNA binding [GO:0003677]; nucleotidyltransferase activity [GO:0016779]; sigma factor activity [GO:0016987]
| null | null |
Tevenvirinae RNA polymerase sigma-like factor family
| null | null | null | null | null | null | null |
FUNCTION: Plays a role in the transcription of the viral late genes by acting as a late promoter recognition subunit (PubMed:33602900). Associates with host RNA polymerase (RNAP) core and thus replaces the host sigma-70/rpoD subunit in the complex (PubMed:33602900). May also play a role in DNA packaging by interacting with the terminase subunit gp17 (PubMed:12051907). {ECO:0000255|HAMAP-Rule:MF_04164, ECO:0000269|PubMed:12051907, ECO:0000269|PubMed:33602900}.
|
Enterobacteria phage T4 (Bacteriophage T4)
|
P04530
|
HELIC_BPT4
|
MVEIILSHLIFDQAYFSKVWPYMDSEYFESGPAKNTFKLIKSHVNEYHSVPSINALNVALENSSFTETEYSGVKTLISKLADSPEDHSWLVKETEKYVQQRAMFNATSKIIEIQTNAELPPEKRNKKMPDVGAIPDIMRQALSISFDSYVGHDWMDDYEARWLSYMNKARKVPFKLRILNKITKGGAETGTLNVLMAGVNVGKSLGLCSLAADYLQLGHNVLYISMEMAEEVCAKRIDANMLDVSLDDIDDGHISYAEYKGKMEKWREKSTLGRLIVKQYPTGGADANTFRSLLNELKLKKNFVPTIIIVDYLGICKSCRIRVYSENSYTTVKAIAEELRALAVETETVLWTAAQVGKQAWDSSDVNMSDIAESAGLPATADFMLAVIETEELAAAEQQLIKQIKSRYGDKNKWNKFLMGVQKGNQKWVEIEQDSTPTEVNEVAGSQQIQAEQNRYQRNESTRAQLDALANELKF
|
3.6.4.-
| null |
bidirectional double-stranded viral DNA replication [GO:0039686]; DNA replication, synthesis of RNA primer [GO:0006269]; DNA unwinding involved in DNA replication [GO:0006268]
|
cytosol [GO:0005829]
|
ATP binding [GO:0005524]; DNA binding [GO:0003677]; DNA helicase activity [GO:0003678]; hydrolase activity [GO:0016787]; single-stranded DNA helicase activity [GO:0017116]
|
PF03796;
|
3.40.50.300;
|
Helicase family, DnaB subfamily
| null | null | null | null | null | null | null |
FUNCTION: ATP-dependent DNA helicase essential for viral DNA replication and recombination (PubMed:10871615). The helicase moves 5' -> 3' on the lagging strand template, unwinding the DNA duplex ahead of the leading strand polymerase at the replication fork and generating ssDNA for both leading and lagging strand synthesis (PubMed:11459969, PubMed:23578280). Interaction with the primase allows the primase to initiate lagging strand synthesis and fully activates the helicase (PubMed:22869700, PubMed:23578280). Loaded by the helicase assembly factor on replication forks that begin at discrete replication origin sequences, as well as on forks that are created during recombination (PubMed:10871615). {ECO:0000255|HAMAP-Rule:MF_04155, ECO:0000269|PubMed:10871615, ECO:0000269|PubMed:22869700, ECO:0000269|PubMed:23578280, ECO:0000303|PubMed:11459969}.
|
Enterobacteria phage T4 (Bacteriophage T4)
|
P04545
|
M21_HRSVA
|
MSRRNPCKFEIRGHCLNGKRCHFSHNYFEWPPHALLVRQNFMLNRILKSMDKSIDTLSEISGAAELDRTEEYALGVVGVLESYIGSINNITKQSACVAMSKLLTELNSDDIKKLRDNEELNSPKIRVYNTVISYIESNRKNNKQTIHLLKRLPADVLKKTIKNTLDIHKSITINNPKESTVSDTNDHAKNNDTT
| null | null |
regulation of viral transcription [GO:0046782]; transcription antitermination [GO:0031564]; viral transcription [GO:0019083]
|
host cell cytoplasm [GO:0030430]; host cell nucleus [GO:0042025]; virion component [GO:0044423]
|
metal ion binding [GO:0046872]; RNA binding [GO:0003723]; structural molecule activity [GO:0005198]
|
PF06436;
|
1.20.120.1350;
|
Pneumoviridae M2-1 protein family
|
PTM: Phosphorylated by host in infected cells (PubMed:10846068, PubMed:11711610, PubMed:29489893, PubMed:3339328). Only dephosphorylated M2-1 is competent for viral mRNA binding (PubMed:29489893). Cyclic turnover of phosphorylation-dephosphorylation of M2-1 is required for efficient viral transcription (PubMed:29489893). {ECO:0000269|PubMed:10846068, ECO:0000269|PubMed:11711610, ECO:0000269|PubMed:29489893, ECO:0000269|PubMed:3339328}.
|
SUBCELLULAR LOCATION: Virion {ECO:0000269|PubMed:23776214, ECO:0000269|PubMed:24760890}. Host cytoplasm {ECO:0000269|PubMed:11907323, ECO:0000269|PubMed:22675274, ECO:0000269|PubMed:27194388, ECO:0000269|PubMed:28916773, ECO:0000269|PubMed:29489893, ECO:0000269|PubMed:31649314}. Host nucleus {ECO:0000269|PubMed:15629770}. Note=Localizes in cytoplasmic inclusion bodies substructures called inclusion bodies associated granules (IBAGs) (PubMed:22675274, PubMed:28916773, PubMed:29489893, PubMed:31649314). Forms a layer between the matrix and nucleocapsid (PubMed:23776214, PubMed:24760890). {ECO:0000269|PubMed:22675274, ECO:0000269|PubMed:23776214, ECO:0000269|PubMed:24760890, ECO:0000269|PubMed:28916773, ECO:0000269|PubMed:29489893, ECO:0000269|PubMed:31649314}.
| null | null | null | null | null |
FUNCTION: Acts as a tetrameric transcription processivity factor that binds in a competitive manner to RNA and the phosphoprotein (P) to prevent premature termination during transcription (PubMed:19386701, PubMed:22675274). Transcription anti-terminator that enhances readthrough of intergenic junctions during viral transcription (PubMed:10364337, PubMed:27194388, PubMed:8552680, PubMed:9420254). Preferentially binds to poly(A)-rich sequences (PubMed:24434552). Plays a role in the association of the matrix protein with the nucleocapsid, which initiates assembly and budding (PubMed:18579594). Also, can activate host NF-kappa-B through association with host RELA (PubMed:15629770). {ECO:0000269|PubMed:10364337, ECO:0000269|PubMed:15629770, ECO:0000269|PubMed:18579594, ECO:0000269|PubMed:19386701, ECO:0000269|PubMed:22675274, ECO:0000269|PubMed:24434552, ECO:0000269|PubMed:27194388, ECO:0000269|PubMed:8552680, ECO:0000269|PubMed:9420254}.
|
Human respiratory syncytial virus A (strain A2)
|
P04551
|
CDK1_SCHPO
|
MENYQKVEKIGEGTYGVVYKARHKLSGRIVAMKKIRLEDESEGVPSTAIREISLLKEVNDENNRSNCVRLLDILHAESKLYLVFEFLDMDLKKYMDRISETGATSLDPRLVQKFTYQLVNGVNFCHSRRIIHRDLKPQNLLIDKEGNLKLADFGLARSFGVPLRNYTHEIVTLWYRAPEVLLGSRHYSTGVDIWSVGCIFAEMIRRSPLFPGDSEIDEIFKIFQVLGTPNEEVWPGVTLLQDYKSTFPRWKRMDLHKVVPNGEEDAIELLSAMLVYDPAHRISAKRALQQNYLRDFH
|
2.7.11.22
| null |
cell division [GO:0051301]; G1/S transition of mitotic cell cycle [GO:0000082]; G2/M transition of mitotic cell cycle [GO:0000086]; mitotic DNA damage checkpoint signaling [GO:0044773]; mitotic G1 cell size control checkpoint signaling [GO:0031568]; mitotic intra-S DNA damage checkpoint signaling [GO:0031573]; negative regulation of anaphase-promoting complex-dependent catabolic process [GO:1905785]; negative regulation of attachment of mitotic spindle microtubules to kinetochore [GO:1902424]; negative regulation of cell cycle switching, mitotic to meiotic cell cycle [GO:0110045]; negative regulation of conjugation with cellular fusion [GO:0031138]; negative regulation of double-strand break repair via nonhomologous end joining [GO:2001033]; negative regulation of exit from mitosis [GO:0001100]; negative regulation of mitotic actomyosin contractile ring assembly [GO:1903500]; negative regulation of mitotic cytokinesis [GO:1902413]; negative regulation of mitotic DNA replication initiation [GO:1903467]; negative regulation of mitotic spindle elongation [GO:1902845]; negative regulation of mitotic telomere tethering at nuclear periphery [GO:1904537]; negative regulation of primary cell septum biogenesis [GO:1905757]; phosphorylation [GO:0016310]; positive regulation of exit from mitosis [GO:0031536]; positive regulation of initiation of premeiotic DNA replication [GO:1904514]; positive regulation of kinetochore assembly [GO:1905561]; positive regulation of meiotic cell cycle [GO:0051446]; positive regulation of meiotic DNA double-strand break formation involved in reciprocal meiotic recombination [GO:1905263]; positive regulation of mitotic cell cycle DNA replication [GO:1903465]; positive regulation of mitotic chromosome condensation [GO:1903380]; positive regulation of mitotic metaphase/anaphase transition [GO:0045842]; positive regulation of mitotic sister chromatid biorientation [GO:0140429]; positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436]; positive regulation of protein catabolic process [GO:0045732]; positive regulation of protein import into nucleus [GO:0042307]; positive regulation of septation initiation signaling [GO:0031031]; regulation of cell cycle switching, mitotic to meiotic cell cycle [GO:0110044]; regulation of cellular response to glucose starvation [GO:1904547]; regulation of establishment or maintenance of bipolar cell polarity [GO:2000099]; regulation of G2/M transition of mitotic cell cycle [GO:0010389]; regulation of gene expression [GO:0010468]; regulation of linear element maturation [GO:0062123]; response to meiotic DNA replication checkpoint signaling [GO:0072441]; response to mitotic DNA integrity checkpoint signaling [GO:1990820]; response to mitotic G2 DNA damage checkpoint signaling [GO:0072435]; response to organic substance [GO:0010033]; signal transduction [GO:0007165]
|
chromatin [GO:0000785]; chromosome, telomeric repeat region [GO:0140445]; cyclin-dependent protein kinase holoenzyme complex [GO:0000307]; cytoplasm [GO:0005737]; kinetochore [GO:0000776]; meiotic spindle [GO:0072687]; meiotic spindle pole body [GO:0035974]; mitotic spindle [GO:0072686]; mitotic spindle midzone [GO:1990023]; mitotic spindle pole body [GO:0044732]; new mitotic spindle pole body [GO:0071958]; nucleolar peripheral inclusion body [GO:0140602]; nucleus [GO:0005634]; old mitotic spindle pole body [GO:0071957]
|
ATP binding [GO:0005524]; cyclin binding [GO:0030332]; cyclin-dependent protein kinase activity [GO:0097472]; cyclin-dependent protein serine/threonine kinase activity [GO:0004693]; protein kinase activity [GO:0004672]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]; protein serine/threonine/tyrosine kinase activity [GO:0004712]
|
PF00069;
|
1.10.510.10;
|
Protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}.
|
CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22; Evidence={ECO:0000250|UniProtKB:P24941}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.22; Evidence={ECO:0000269|PubMed:11486016};
| null | null | null | null |
FUNCTION: Cyclin-dependent kinase that acts as a master regulator of the mitotic and meiotic cell cycles (PubMed:1896017, PubMed:2274045, PubMed:6581157, PubMed:7498766, PubMed:8087848, PubMed:9042863, Ref.6). Required to drive the G1-S and G2-M transitions, and initiation of premeiotic DNA replication and meiosis II (PubMed:1896017, PubMed:2274045, PubMed:6581157, PubMed:7498766, PubMed:8087848, PubMed:9042863, Ref.6). More than 200 substrates have been identified (PubMed:27984725). Substrate specificity is in part regulated by the bound cyclin protein (PubMed:27984725). When complexed with cyclin cig2, it drives the G1-S phase transition (PubMed:8087848). When complexed with cyclin cdc13, it drives the G2-M transition and initiation of meiosis II (PubMed:7498766, PubMed:8087848). Its activity rises throughout the cell cycle and substrate specificity is further influenced by activity thresholds with more sensitive substrates phosphorylated earlier in the cell cycle than less sensitive substrates (PubMed:27984725). Phosphorylates dis1 during metaphase to ensure proper microtubule dynamics and accurate chromosome segregation (PubMed:16920624). Phosphorylates the repetitive C-terminus of the large subunit of RNA polymerase II rpb1 (Probable). Inactivated by checkpoint signaling following detection of cellular damage, leading to cell cycle arrest to allow damage repair (PubMed:16049013, PubMed:9042863). Inactivated during G2 DNA damage checkpoint signaling (PubMed:9042863). Inactivated in response to defective RNA splicing (PubMed:16049013). {ECO:0000269|PubMed:16049013, ECO:0000269|PubMed:16920624, ECO:0000269|PubMed:1896017, ECO:0000269|PubMed:2274045, ECO:0000269|PubMed:27984725, ECO:0000269|PubMed:6581157, ECO:0000269|PubMed:7498766, ECO:0000269|PubMed:8087848, ECO:0000269|PubMed:9042863, ECO:0000269|Ref.6, ECO:0000305|PubMed:18257517}.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
P04553
|
HSP1_HUMAN
|
MARYRCCRSQSRSRYYRQRQRSRRRRRRSCQTRRRAMRCCRPRYRPRCRRH
| null | null |
chromosome condensation [GO:0030261]; chromosome organization [GO:0051276]; sperm DNA condensation [GO:0035092]; spermatogenesis [GO:0007283]
|
cytosol [GO:0005829]; nucleoplasm [GO:0005654]; nucleosome [GO:0000786]
|
DNA binding [GO:0003677]
|
PF00260;
| null |
Protamine P1 family
|
PTM: Phosphorylated by SRPK1. {ECO:0000269|PubMed:10390541}.
|
SUBCELLULAR LOCATION: Nucleus. Chromosome.
| null | null | null | null | null |
FUNCTION: Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex.
|
Homo sapiens (Human)
|
P04554
|
PRM2_HUMAN
|
MVRYRVRSLSERSHEVYRQQLHGQEQGHHGQEEQGLSPEHVEVYERTHGQSHYRRRHCSRRRLHRIHRRQHRSCRRRKRRSCRHRRRHRRGCRTRKRTCRRH
| null | null |
chromosome condensation [GO:0030261]; chromosome organization [GO:0051276]; nucleus organization [GO:0006997]; sequestering of metal ion [GO:0051238]; spermatid development [GO:0007286]; spermatogenesis [GO:0007283]
|
male germ cell nucleus [GO:0001673]; nucleoplasm [GO:0005654]; nucleosome [GO:0000786]; nucleus [GO:0005634]
|
cadmium ion binding [GO:0046870]; DNA binding [GO:0003677]; ion binding [GO:0043167]; zinc ion binding [GO:0008270]
|
PF00841;
| null |
Protamine P2 family
|
PTM: Proteolytic processing into mature chains is required for histone eviction during spermatogenesis. Transition proteins (TNP1 and TNP2) are required for processing. {ECO:0000250|UniProtKB:P07978}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P07978}. Chromosome {ECO:0000250|UniProtKB:P07978}.
| null | null | null | null | null |
FUNCTION: Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex. {ECO:0000250|UniProtKB:P07978}.
|
Homo sapiens (Human)
|
P04575
|
UCP1_MESAU
|
MVNPTTSEVHPTMGVKIFSAGVAACLADIITFPLDTAKVRLQIQGEGQISSTIRYKGVLGTITTLAKTEGLPKLYSGLPAGIQRQISFASLRIGLYDTVQEYFSSGKETPPTLGNRISAGLMTGGVAVFIGQPTEVVKVRLQAQSHLHGIKPRYTGTYNAYRIIATTESFSTLWKGTTPNLLRNVIINCVELVTYDLMKGALVNNQILADDVPCHLLSAFVAGFCTTFLASPADVVKTRFINSLPGQYPSVPSCAMTMLTKEGPTAFFKGFVPSFLRLASWNVIMFVCFEQLKKELSKSRQTVDCTT
| null | null |
adaptive thermogenesis [GO:1990845]; cellular response to fatty acid [GO:0071398]; cellular response to hormone stimulus [GO:0032870]; cellular response to reactive oxygen species [GO:0034614]; mitochondrial transmembrane transport [GO:1990542]; proton transmembrane transport [GO:1902600]; regulation of reactive oxygen species biosynthetic process [GO:1903426]; response to cold [GO:0009409]; response to nutrient levels [GO:0031667]; response to temperature stimulus [GO:0009266]
|
mitochondrial inner membrane [GO:0005743]
|
cardiolipin binding [GO:1901612]; long-chain fatty acid binding [GO:0036041]; oxidative phosphorylation uncoupler activity [GO:0017077]; purine ribonucleotide binding [GO:0032555]
|
PF00153;
|
1.50.40.10;
|
Mitochondrial carrier (TC 2.A.29) family
|
PTM: May undergo sulfenylation upon cold exposure. May increase the sensitivity of UCP1 thermogenic function to the activation by noradrenaline probably through structural effects. {ECO:0000250|UniProtKB:P12242}.; PTM: May undergo ubiquitin-mediated proteasomal degradation. {ECO:0000250|UniProtKB:P04633}.
|
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250|UniProtKB:P12242}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P04633}.
|
CATALYTIC ACTIVITY: Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378; Evidence={ECO:0000250|UniProtKB:P25874};
| null | null | null | null |
FUNCTION: Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and diet variations and more generally to the regulation of energy balance. Functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane. However, LCFAs remaining associated with the transporter via their hydrophobic tails, it results in an apparent transport of protons activated by LCFAs. Thereby, dissipates the mitochondrial proton gradient and converts the energy of substrate oxydation into heat instead of ATP. Regulates the production of reactive oxygen species/ROS by mitochondria. {ECO:0000250|UniProtKB:P12242}.
|
Mesocricetus auratus (Golden hamster)
|
P04577
|
ENV_HV2RO
|
MMNQLLIAILLASACLVYCTQYVTVFYGVPTWKNATIPLFCATRNRDTWGTIQCLPDNDDYQEITLNVTEAFDAWNNTVTEQAIEDVWHLFETSIKPCVKLTPLCVAMKCSSTESSTGNNTTSKSTSTTTTTPTDQEQEISEDTPCARADNCSGLGEEETINCQFNMTGLERDKKKQYNETWYSKDVVCETNNSTNQTQCYMNHCNTSVITESCDKHYWDAIRFRYCAPPGYALLRCNDTNYSGFAPNCSKVVASTCTRMMETQTSTWFGFNGTRAENRTYIYWHGRDNRTIISLNKYYNLSLHCKRPGNKTVKQIMLMSGHVFHSHYQPINKRPRQAWCWFKGKWKDAMQEVKETLAKHPRYRGTNDTRNISFAAPGKGSDPEVAYMWTNCRGEFLYCNMTWFLNWIENKTHRNYAPCHIKQIINTWHKVGRNVYLPPREGELSCNSTVTSIIANIDWQNNNQTNITFSAEVAELYRLELGDYKLVEITPIGFAPTKEKRYSSAHGRHTRGVFVLGFLGFLATAGSAMGAASLTVSAQSRTLLAGIVQQQQQLLDVVKRQQELLRLTVWGTKNLQARVTAIEKYLQDQARLNSWGCAFRQVCHTTVPWVNDSLAPDWDNMTWQEWEKQVRYLEANISKSLEQAQIQQEKNMYELQKLNSWDIFGNWFDLTSWVKYIQYGVLIIVAVIALRIVIYVVQMLSRLRKGYRPVFSSPPGYIQQIHIHKDRGQPANEETEEDGGSNGGDRYWPWPIAYIHFLIRQLIRLLTRLYSICRDLLSRSFLTLQLIYQNLRDWLRLRTAFLQYGCEWIQEAFQAAARATRETLAGACRGLWRVLERIGRGILAVPRRIRQGAEIALL
| null | null |
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; suppression by virus of host tetherin activity [GO:0039587]; virion attachment to host cell [GO:0019062]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;
| null |
PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R (By similarity). {ECO:0000250}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Host cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Host endosome membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000250}.; SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Host cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Host endosome membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag (By similarity). {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: The surface protein gp120 (SU) attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. This peculiar 2 stage receptor-interaction strategy allows gp120 to maintain the highly conserved coreceptor-binding site in a cryptic conformation, protected from neutralizing antibodies. Since CD4 also displays a binding site for the disulfide-isomerase P4HB/PDI, a P4HB/PDI-CD4-CXCR4-gp120 complex may form. In that complex, P4HB/PDI could reach and reduce gp120 disulfide bonds, causing major conformational changes in gp120. TXN, another PDI family member could also be involved in disulfide rearrangements in Env during fusion. These changes are transmitted to the transmembrane protein gp41 and are thought to activate its fusogenic potential by unmasking its fusion peptide (By similarity). {ECO:0000250}.; FUNCTION: The surface protein gp120 is a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they take up antigen, process it, and present it to T-cells following migration to lymphoid organs. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. Virion capture also seems to lead to MHC-II-restricted viral antigen presentation, and probably to the activation of HIV-specific CD4+ cells (By similarity). {ECO:0000250}.; FUNCTION: The transmembrane protein gp41 (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm (By similarity). {ECO:0000250}.; FUNCTION: The envelope glycoprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface. {ECO:0000250}.; FUNCTION: The gp120-gp41 heterodimer seems to contribute to T-cell depletion during HIV-1 infection. The envelope glycoproteins expressed on the surface of infected cells induce apoptosis through an interaction with uninfected cells expressing the receptor (CD4) and the coreceptors CXCR4 or CCR5. This type of bystander killing may be obtained by at least three distinct mechanisms. First, the interaction between the 2 cells can induce cellular fusion followed by nuclear fusion within the syncytium. Syncytia are condemned to die from apoptosis. Second, the 2 interacting cells may not fuse entirely and simply exchange plasma membrane lipids, after a sort of hemifusion process, followed by rapid death. Third, it is possible that virus-infected cells, on the point of undergoing apoptosis, fuse with CD4-expressing cells, in which case apoptosis is rapidly transmitted from one cell to the other and thus occurs in a sort of contagious fashion (By similarity). {ECO:0000250}.; FUNCTION: The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity). {ECO:0000250}.
|
Human immunodeficiency virus type 2 subtype A (isolate ROD) (HIV-2)
|
P04578
|
ENV_HV1H2
|
MRVKEKYQHLWRWGWRWGTMLLGMLMICSATEKLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLVNVTENFNMWKNDMVEQMHEDIISLWDQSLKPCVKLTPLCVSLKCTDLKNDTNTNSSSGRMIMEKGEIKNCSFNISTSIRGKVQKEYAFFYKLDIIPIDNDTTSYKLTSCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNNKTFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSVNFTDNAKTIIVQLNTSVEINCTRPNNNTRKRIRIQRGPGRAFVTIGKIGNMRQAHCNISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWSTEGSNNTEGSDTITLPCRIKQIINMWQKVGKAMYAPPISGQIRCSSNITGLLLTRDGGNSNNESEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKRAVGIGALFLGFLGAAGSTMGAASMTLTVQARQLLSGIVQQQNNLLRAIEAQQHLLQLTVWGIKQLQARILAVERYLKDQQLLGIWGCSGKLICTTAVPWNASWSNKSLEQIWNHTTWMEWDREINNYTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWFNITNWLWYIKLFIMIVGGLVGLRIVFAVLSIVNRVRQGYSPLSFQTHLPTPRGPDRPEGIEEEGGERDRDRSIRLVNGSLALIWDDLRSLCLFSYHRLRDLLLIVTRIVELLGRRGWEALKYWWNLLQYWSQELKNSAVSLLNATAIAVAEGTDRVIEVVQGACRAIRHIPRRIRQGLERILL
| null | null |
actin filament organization [GO:0007015]; clathrin-dependent endocytosis of virus by host cell [GO:0075512]; evasion of host immune response [GO:0042783]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; symbiont entry into host cell [GO:0046718]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;1.20.5.490;
|
HIV-1 env protein family
|
PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:7568235}.; PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:26972002, ECO:0000269|PubMed:28667249}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:12218052, ECO:0000269|PubMed:2450679, ECO:0000269|PubMed:31091448}.
|
SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
| null | null | null | null | null |
FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:1360148, ECO:0000269|PubMed:2450679, ECO:0000269|PubMed:31091448}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:11257134, ECO:0000269|PubMed:19410541}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:19410541, ECO:0000269|PubMed:2243396}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
|
P04579
|
ENV_HV1RH
|
MRVMEMRKNCQHLWKWGTMLLGMLMICSAAEDLWVTVYYGVPVWKEATTTLFCASEAKAYKTEVHNVWAKHACVPTDPNPQEVLLENVTENFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDANLNGTNVTSSSGGTMMENGEIKNCSFQVTTSRRDKTQKKYALFYKLDVVPIEKGNISPKNNTSNNTSYGNYTLIHCNSSVITQACPKVSFEPIPIHYCTPAGFAILKCNDKKFNGTGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSENFTDNVKTIIVQLNASVQINCTRPNNNTRKSITKGPGRVIYATGQIIGDIRKAHCNLSRAQWNNTLKQVVTKLREQFDNKTIVFTSSSGGDPEIVLHSFNCGGEFFYCNTTQLFNSTWNSTEGSNNTGGNDTITLPCRIKQIVNMWQEVGKAMYAPPISGQIKCISNITGLLLTRDGGEDTTNTTEIFRLGGGNMRDNWRSELYKYKVVRIEPLGVAPTRAKRRVVQREKRAVGTIGAMFLGFLGAAGSTMGAGSITLTVQARHLLSGIVQQQNNLLRAIEAQQHLLQLTVWGIKQLQARVLAVERYLRDQQLLGIWGCSGKLICTTTVPWNASWSNKSLNMIWNNMTWMQWEREIDNYTGIIYNLLEESQNQQEKNEQELLELDKWANLWNWFDITQWLWYIRIFIMIVGGLVGLKIVFAVLSIVNRVRQGYSPLSFQTHLPAPRGPDRPEGIEGEGGERDRDRSGGAVNGFLTLIWDDLWTLCSFSYHRLRDLLLIVVRIVELLGRRGWEALKYWWNLLQYWSQELKNSAVSLLNTTAIAVAEGTDRIIEVAQRILRAFLHIPRRIRQGLERALL
| null | null |
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;1.20.5.490;
|
HIV-1 env protein family
|
PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
| null | null | null | null | null |
FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate RF/HAT3) (HIV-1)
|
P04580
|
ENV_HV1Z6
|
MRAREIERNCPNLWKWGIMLLGILMICSAADNLWVTVYYGVPVWKEATTTLFCASDAKSYKTEAHNIWATHACVPTDPNPQEIELENVTENFNMWRNNMVEQIHEDIISLWDQSLKPCVKLTPLCVTLNCTDESDEWMGNVTGKNVTEDIRMKNCSFNITTVVRDKTKQVHALFYRLDIVPIDNDNSTNSTNYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCRDKRFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEIIIRSENLTNNAKIIIVQLNESVAINCTRPYKNTRQSTPIGLGQALYTTRGRTKIIGQAHCNISKEDWNKTLQRVAIKLGNLLNKTTIIFKPSSGGDAEITTHSFNCGGEFFYCNTSGLFNSTWNINNSEGANSTESDNKLITLQCRIKQIINMWQGVGKAMYAPPIEGQINCSSNITGLLLTRDGGTNNSSNETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVEREKRAIGLGAMFLGFLGAAGSTMGAASVTLTVQARQLMSGIVQQQNNLLRAIEAQQHLLQLTVWGIKQLQARILAVERYLKDQQLLGIWGCSGKLICTTTVPWNSSWSNRSLNDIWQNMTWMEWEREIDNYTGLIYRLIEESQTQQEKNEQELLELDKWASLWNWFNITQWLWYIKIFIMIVGGLIGLRIVFAVLSLVNRVRQGYSPLSFQTLLPAPREPDRPEGIEEEGGERGRDRSIRLVNGFSALIWDDLRNLCLFSYHRLRDLILIAARIVELLGRRGWEALKYLWNLLQYWSRELRNSASSLLDTIAIAVAEGTDRVIEIVRRTYRAVLNVPTRIRQGLERLLL
| null | null |
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;1.20.5.490;
|
HIV-1 env protein family
|
PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
| null | null | null | null | null |
FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
Human immunodeficiency virus type 1 group M subtype D (isolate Z6) (HIV-1)
|
P04581
|
ENV_HV1EL
|
MRARGIERNCQNWWKWGIMLLGILMTCSAADNLWVTVYYGVPVWKEATTTLFCASDAKSYETEAHNIWATHACVPTDPNPQEIALENVTENFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCSDELRNNGTMGNNVTTEEKGMKNCSFNVTTVLKDKKQQVYALFYRLDIVPIDNDSSTNSTNYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCRDKKFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVIIRSENLTNNAKNIIAHLNESVKITCARPYQNTRQRTPIGLGQSLYTTRSRSIIGQAHCNISRAQWSKTLQQVARKLGTLLNKTIIKFKPSSGGDPEITTHSFNCGGEFFYCNTSGLFNSTWNISAWNNITESNNSTNTNITLQCRIKQIIKMVAGRKAIYAPPIERNILCSSNITGLLLTRDGGINNSTNETFRPGGGDMRDNWRSELYKYKVVQIEPLGVAPTRAKRRVVEREKRAIGLGAMFLGFLGAAGSTMGARSVTLTVQARQLMSGIVQQQNNLLRAIEAQQHLLQLTVWGIKQLQARILAVERYLKDQQLLGIWGCSGKHICTTNVPWNSSWSNRSLNEIWQNMTWMEWEREIDNYTGLIYSLIEESQTQQEKNEKELLELDKWASLWNWFSITQWLWYIKIFIMIIGGLIGLRIVFAVLSLVNRVRQGYSPLSFQTLLPAPRGPDRPEGTEEEGGERGRDRSVRLLNGFSALIWDDLRSLCLFSYHRLRDLILIAVRIVELLGRRGWDILKYLWNLLQYWSQELRNSASSLFDAIAIAVAEGTDRVIEIIQRACRAVLNIPRRIRQGLERSLL
| null | null |
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;1.20.5.490;
|
HIV-1 env protein family
|
PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
| null | null | null | null | null |
FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
Human immunodeficiency virus type 1 group M subtype D (isolate ELI) (HIV-1)
|
P04582
|
ENV_HV1B8
|
MRVKEKYQHLWRWGWRWGTMLLGMLMICSATEKLWVTVYFGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLVNVTENFNMWKNDMVEQMHEDIISLWDQSLKPCVKLTPLCVSLKCTDLKNDTNTNSSSGRMIMEKGEIKNCSFNISTSKRGKVQKEYAFFYKLDIIPIDNDTTSYTLTSCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNNKTFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSVNFTDNAKTIIVQLDTSVEINCTRPNNNTRKKIRIQRGPGRAFVTIGKIGNMRQAHCNISRAKWNATLKQIDSKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWSTKGSNNTEGSDTITLPCRIKQIINMWQEVGKAMYAPPISGQIRCSSNITGLLLTRDGGNSNNESEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKRAVGIGALFLGFLGAAGSTMGAASMTLTVQARQLLSGIVQQQNNLLRAIEGQQHLLQLTVWGIKQLQARILAVERYLKDQQLLGIWGCSGKLICTTAVPWNASWSNKSLEQIWNNMTWMEWDREINNYTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWFNITNWLWYIKLFIMIVGGLVGLRIVFAVLSIVNRVRQGYSPLSFQTHLPNPRGPDRPEGIEEEGGERDRDRSIRLVNGSLALIWDDLRSLCLFSYHRLRDLLLIVTRIVELLGRRGWEALKYWWNLLQYWSQELKNSAVNLLNATAIAVAEGTDRVIELVQAAYRAIRHIPRRIRQGLERILL
| null | null |
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;1.20.5.490;
|
HIV-1 env protein family
|
PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
| null | null | null | null | null |
FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate BH8) (HIV-1)
|
P04583
|
ENV_HV1MA
|
MRVREIQRNYQNWWRWGMMLLGMLMTCSIAEDLWVTVYYGVPVWKEATTTLFCASDAKSYETEVHNIWATHACVPTDPNPQEIELENVTEGFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLNCTNVNGTAVNGTNAGSNRTNAELKMEIGEVKNCSFNITPVGSDKRQEYATFYNLDLVQIDDSDNSSYRLINCNTSVITQACPKVTFDPIPIHYCAPAGFAILKCNDKKFNGTEICKNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIMIRSENLTDNTKNIIVQLNETVTINCTRPGNNTRRGIHFGPGQALYTTGIVGDIRRAYCTINETEWDKTLQQVAVKLGSLLNKTKIIFNSSSGGDPEITTHSFNCRGEFFYCNTSKLFNSTWQNNGARLSNSTESTGSITLPCRIKQIINMWQKTGKAMYAPPIAGVINCLSNITGLILTRDGGNSSDNSDNETLRPGGGDMRDNWISELYKYKVVRIEPLGVAPTKAKRRVVEREKRAIGLGAMFLGFLGAAGSTMGAASLTLTVQARQLLSGIVQQQNNLLRAIEAQQHLLQLTVWGIKQLQARVLAVERYLQDQRLLGMWGCSGKHICTTFVPWNSSWSNRSLDDIWNNMTWMQWEKEISNYTGIIYNLIEESQIQQEKNEKELLELDKWASLWNWFSISKWLWYIRIFIIVVGGLIGLRIIFAVLSLVNRVRQGYSPLSLQTLLPTPRGPPDRPEGIEEEGGEQGRGRSIRLVNGFSALIWDDLRNLCLFSYHRLRDLLLIATRIVELLGRRGWEALKYLWNLLQYWGQELKNSAISLLNTTAIAVAECTDRVIEIGQRFGRAILHIPRRIRQGFERALL
| null | null |
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;1.20.5.490;
|
HIV-1 env protein family
|
PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
| null | null | null | null | null |
FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
Human immunodeficiency virus type 1 group M subtype A (isolate MAL) (HIV-1)
|
P04584
|
POL_HV2RO
|
MGARNSVLRGKKADELERIRLRPGGKKKYRLKHIVWAANKLDRFGLAESLLESKEGCQKILTVLDPMVPTGSENLKSLFNTVCVIWCIHAEEKVKDTEGAKQIVRRHLVAETGTAEKMPSTSRPTAPSSEKGGNYPVQHVGGNYTHIPLSPRTLNAWVKLVEEKKFGAEVVPGFQALSEGCTPYDINQMLNCVGDHQAAMQIIREIINEEAAEWDVQHPIPGPLPAGQLREPRGSDIAGTTSTVEEQIQWMFRPQNPVPVGNIYRRWIQIGLQKCVRMYNPTNILDIKQGPKEPFQSYVDRFYKSLRAEQTDPAVKNWMTQTLLVQNANPDCKLVLKGLGMNPTLEEMLTACQGVGGPGQKARLMAEALKEVIGPAPIPFAAAQQRKAFKCWNCGKEGHSARQCRAPRRQGCWKCGKPGHIMTNCPDRQAGFLRTGPLGKEAPQLPRGPSSAGADTNSTPSGSSSGSTGEIYAAREKTERAERETIQGSDRGLTAPRAGGDTIQGATNRGLAAPQFSLWKRPVVTAYIEGQPVEVLLDTGADDSIVAGIELGNNYSPKIVGGIGGFINTKEYKNVEIEVLNKKVRATIMTGDTPINIFGRNILTALGMSLNLPVAKVEPIKIMLKPGKDGPKLRQWPLTKEKIEALKEICEKMEKEGQLEEAPPTNPYNTPTFAIKKKDKNKWRMLIDFRELNKVTQDFTEIQLGIPHPAGLAKKRRITVLDVGDAYFSIPLHEDFRPYTAFTLPSVNNAEPGKRYIYKVLPQGWKGSPAIFQHTMRQVLEPFRKANKDVIIIQYMDDILIASDRTDLEHDRVVLQLKELLNGLGFSTPDEKFQKDPPYHWMGYELWPTKWKLQKIQLPQKEIWTVNDIQKLVGVLNWAAQLYPGIKTKHLCRLIRGKMTLTEEVQWTELAEAELEENRIILSQEQEGHYYQEEKELEATVQKDQENQWTYKIHQEEKILKVGKYAKVKNTHTNGIRLLAQVVQKIGKEALVIWGRIPKFHLPVEREIWEQWWDNYWQVTWIPDWDFVSTPPLVRLAFNLVGDPIPGAETFYTDGSCNRQSKEGKAGYVTDRGKDKVKKLEQTTNQQAELEAFAMALTDSGPKVNIIVDSQYVMGISASQPTESESKIVNQIIEEMIKKEAIYVAWVPAHKGIGGNQEVDHLVSQGIRQVLFLEKIEPAQEEHEKYHSNVKELSHKFGIPNLVARQIVNSCAQCQQKGEAIHGQVNAELGTWQMDCTHLEGKIIIVAVHVASGFIEAEVIPQESGRQTALFLLKLASRWPITHLHTDNGANFTSQEVKMVAWWIGIEQSFGVPYNPQSQGVVEAMNHHLKNQISRIREQANTIETIVLMAIHCMNFKRRGGIGDMTPSERLINMITTEQEIQFLQAKNSKLKDFRVYFREGRDQLWKGPGELLWKGEGAVLVKVGTDIKIIPRRKAKIIRDYGGRQEMDSGSHLEGAREDGEMA
|
2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.47
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
|
DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
|
host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; lipid binding [GO:0008289]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF00607;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
|
1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
| null |
PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.
|
SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=Endopeptidase for which the P1 residue is preferably hydrophobic.; EC=3.4.23.47; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
| null | null | null | null |
FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.
|
Human immunodeficiency virus type 2 subtype A (isolate ROD) (HIV-2)
|
P04585
|
POL_HV1H2
|
MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQILGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQAAADTGHSNQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVLAEAMSQVTNSATIMMQRGNFRNQRKIVKCFNCGKEGHTARNCRAPRKKGCWKCGKEGHQMKDCTERQANFLREDLAFLQGKAREFSSEQTRANSPTRRELQVWGRDNNSPSEAGADRQGTVSFNFPQVTLWQRPLVTIKIGGQLKEALLDTGADDTVLEEMSLPGRWKPKMIGGIGGFIKVRQYDQILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNFPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFRKQNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPPLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTNRGRQKVVTLTDTTNQKTELQAIYLALQDSGLEVNIVTDSQYALGIIQAQPDQSESELVNQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLVSAGIRKVLFLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGSNFTGATVRAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRNPLWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED
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2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.16
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COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
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DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; protein processing [GO:0016485]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral life cycle [GO:0019058]; viral penetration into host nucleus [GO:0075732]
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host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; identical protein binding [GO:0042802]; integrase activity [GO:0008907]; lipid binding [GO:0008289]; peptidase activity [GO:0008233]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF00540;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
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1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
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PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000255|PROSITE-ProRule:PRU00405, ECO:0000269|PubMed:10494040, ECO:0000269|PubMed:12477841, ECO:0000269|PubMed:15065874}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association (PubMed:17656588). {ECO:0000269|PubMed:17656588}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03366}.
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SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000269|PubMed:18722123}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
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CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275, ECO:0000269|PubMed:32053707, ECO:0000269|PubMed:33542150}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250|UniProtKB:P03366}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
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FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion (PubMed:8648689). Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (PubMed:12660176). Host restriction factors such as monkey TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species (PubMed:23785198). Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (PubMed:24554657). {ECO:0000250|UniProtKB:P12497, ECO:0000269|PubMed:12660176, ECO:0000269|PubMed:23785198, ECO:0000269|PubMed:24554657, ECO:0000269|PubMed:8648689}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000269|PubMed:11044125, ECO:0000269|PubMed:17070549, ECO:0000269|PubMed:18343475, ECO:0000269|PubMed:20828778, ECO:0000269|PubMed:9931246}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane (PubMed:11932404, PubMed:9573231). Cleavages take place as an ordered, step-wise cascade to yield mature proteins (PubMed:11932404, PubMed:9573231). This process is called maturation (PubMed:11932404, PubMed:9573231). Displays maximal activity during the budding process just prior to particle release from the cell (PubMed:11932404, PubMed:9573231). Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (PubMed:7835426). Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (PubMed:12660176, PubMed:19914170). Also mediates cleavage of host YTHDF3 (PubMed:32053707). Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (PubMed:33542150). {ECO:0000255|PROSITE-ProRule:PRU00275, ECO:0000269|PubMed:12505164, ECO:0000269|PubMed:19956697, ECO:0000269|PubMed:32053707, ECO:0000269|PubMed:33542150, ECO:0000269|PubMed:7835426}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000269|PubMed:16221683}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000269|PubMed:20554775, ECO:0000269|PubMed:2349226}.
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Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
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P04587
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POL_HV1B5
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MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQILGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQAAADTGHSSQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVLAEAMSQVTNSTTIMMQRGNFRNQRKIVKCFNCGKEGHIARNCKAPRKKGCWKCGKEGHQMKDCTERQANFLREDLAFLQGKAREFSSEQTRANSPTISSEQTRANSPTRRELQVWGRDNNSPSEAGADRQGTVSFNFPQITLWQRPLVTIKIGGQLKEALLDTGADDTVLEEMSLPGRWKPKMIGGIGGFIKVRQYDQILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNFPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNRRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGSGYQYNVLPQGWKGSPAIFQSSMTKILEPFRKQNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGFTTPDKKHQKEPPFLWMGYELHPDKWTIQPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPPLVKLWYQLEKEPIVGAETFYVDGAASRETKLGKAGYVTNRGRQKVVTLTHTTNQKTELQAIHLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLVSAGIRKILFLDGIDKAQEEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGSNFTSATVKAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRNPLWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED
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2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.16
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COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
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DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
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host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; lipid binding [GO:0008289]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF00540;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
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1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
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PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
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SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
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CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
| null | null | null | null |
FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate BH5) (HIV-1)
|
P04588
|
POL_HV1MA
|
MGARASVLSGGKLDAWEKIRLRPGGKKKYRLKHLVWASRELERFALNPGLLETGEGCQQIMEQLQSTLKTGSEEIKSLYNTVATLYCVHQRIDVKDTKEALDKIEEIQNKSRQKTQQAAAAQQAAAATKNSSSVSQNYPIVQNAQGQMIHQAISPRTLNAWVKVIEEKAFSPEVIPMFSALSEGATPQDLNMMLNIVGGHQAAMQMLKDTINEEAADWDRVHPVHAGPIPPGQMREPRGSDIAGTTSTLQEQIGWMTSNPPIPVGDIYKRWIILGLNKIVRMYSPVSILDIRQGPKEPFRDYVDRFFKTLRAEQATQEVKNWMTETLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPSHKARVLAEAMSQATNSTAAIMMQRGNFKGQKRIKCFNCGKEGHLARNCRAPRKKGCWKCGKEGHQMKDCTERQANFLRENLAFPQGKAREFPSEQTRANSPTSRELRVWGGDKTLSETGAERQGIVSFSFPQITLWQRPVVTVRVGGQLKEALLDTGADDTVLEEINLPGKWKPKMIGGIGGFIKVRQYDQILIEICGKKAIGTILVGPTPVNIIGRNMLTQIGCTLNFPISPIETVPVKLKPGMDGPRVKQWPLTEEKIKALTEICKDMEKEGKILKIGPENPYNTPVFAIKKKDSTKWRKLVNFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFRTKNPEIVIYQYMDDLYVGSDLEIGQHRTKIEELREHLLKWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIQLPDKESWTVNDIQKLVGKLNWASQIYPGIKVKQLCKLLRGAKALTDIVPLTAEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEQYKNLKTGKYARIKSAHTNDVKQLTEAVQKIAQESIVIWGKTPKFRLPIQKETWEAWWTEYWQATWIPEWEFVNTPPLVKLWYQLETEPIVGAETFYVDGAANRETKKGKAGYVTDRGRQKVVSLTETTNQKTELQAIHLALQDSGSEVNIVTDSQYALGIIQAQPDKSESEIVNQIIEQLIQKDKVYLSWVPAHKGIGGNEQVDKLVSSGIRKVLFLDGIDKAQEEHEKYHSNWRAMASDFNLPPIVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKIIIVAVHVASGYIEAEVIPAETGQETAYFILKLAGRWPVKVVHTDNGSNFTSAAVKAACWWANIKQEFGIPYNPQSQGVVESMNKELKKIIGQVREQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIIDMIATDIQTKELQKQITKIQNFRVYYRDNRDPIWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVAGGQDED
|
2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.16
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
|
DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
|
host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; lipid binding [GO:0008289]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
|
1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
| null |
PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
| null | null | null | null |
FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.
|
Human immunodeficiency virus type 1 group M subtype A (isolate MAL) (HIV-1)
|
P04589
|
POL_HV1EL
|
MGARASVLSGGKLDKWEKIRLRPGGKKKYRLKHIVWASRELERYALNPGLLETSEGCKQIIGQLQPAIQTGTEELRSLYNTVATLYCVHKGIDVKDTKEALEKMEEEQNKSKKKAQQAAADTGNNSQVSQNYPIVQNLQGQMVHQAISPRTLNAWVKVIEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIAWMTSNPPIPVGEIYKRWIIVGLNKIVRMYSPVSILDIRQGPKEPFRDYVDRFYKTLRAEQASQDVKNWMTETLLVQNANPDCKTILKALGPQATLEEMMTACQGVGGPSHKARVLAEAMSQATNSVTTAMMQRGNFKGPRKIIKCFNCGKEGHIAKNCRAPRKKGCWRCGKEGHQLKDCTERQANFLRENLAFPQGKAGELSPKQTRANSPTSRELRVWGRDNPLSKTGAERQGTVSFNFPQITLWQRPLVAIKIGGQLKEALLDTGADDTVLEEMNLPGKWKPKMIGGIGGFIKVRQYDQIPIEICGQKAIGTVLVGPTPVNIIGRNLLTQIGCTLNFPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALTEICTDMEKEGKISRIGPENPYNTPIFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTISSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFRKQNPEMVIYQYMDDLYVGSDLEIGQHRTKIEKLREHLLRWGFTRPDKKHQKEPPFLWMGYELHPDKWTVQSIKLPEKESWTVNDIQNLVERLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGHGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLAEAVQRISTESIVIWGRTPKFRLPIQKETWETWWAEYWQATWIPEWEFVNTPPLVKLWYQLEKEPIIGAETFYVDGAANRETKLGKAGYVTDRGRQKVVPLTDTTNQKTELQAINLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLVSQGIRKVLFLDGIDKAQEEHEKYHNNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKVVHTDNGSNFTSAAVKAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRRRGIGGYSAGERIIDIIATDIQTKELQKQIIKIQNFRVYYRDSRDPIWKGPAKLLWKGEGAVVIQDKSDIKVVPRRKVKIIRDYGKQMAGDDCVASRQDED
|
2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.16
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
|
DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
|
host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; lipid binding [GO:0008289]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
|
1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
| null |
PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
| null | null | null | null |
FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.
|
Human immunodeficiency virus type 1 group M subtype D (isolate ELI) (HIV-1)
|
P04590
|
GAG_HV2RO
|
MGARNSVLRGKKADELERIRLRPGGKKKYRLKHIVWAANKLDRFGLAESLLESKEGCQKILTVLDPMVPTGSENLKSLFNTVCVIWCIHAEEKVKDTEGAKQIVRRHLVAETGTAEKMPSTSRPTAPSSEKGGNYPVQHVGGNYTHIPLSPRTLNAWVKLVEEKKFGAEVVPGFQALSEGCTPYDINQMLNCVGDHQAAMQIIREIINEEAAEWDVQHPIPGPLPAGQLREPRGSDIAGTTSTVEEQIQWMFRPQNPVPVGNIYRRWIQIGLQKCVRMYNPTNILDIKQGPKEPFQSYVDRFYKSLRAEQTDPAVKNWMTQTLLVQNANPDCKLVLKGLGMNPTLEEMLTACQGVGGPGQKARLMAEALKEVIGPAPIPFAAAQQRKAFKCWNCGKEGHSARQCRAPRRQGCWKCGKPGHIMTNCPDRQAGFLGLGPWGKKPRNFPVAQVPQGLTPTAPPVDPAVDLLEKYMQQGKRQREQRERPYKEVTEDLLHLEQGETPYREPPTEDLLHLNSLFGKDQ
| null | null |
viral budding via host ESCRT complex [GO:0039702]
|
host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
RNA binding [GO:0003723]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF00607;PF19317;PF00098;
|
1.10.1200.30;1.10.375.10;1.10.150.90;1.20.5.760;4.10.60.10;
|
Primate lentivirus group gag polyprotein family
|
PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04591}.; PTM: Capsid protein p24 is phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: Nucleocapsid protein p7 is methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000250|UniProtKB:P12493}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion (By similarity). Most core are conical, with only 7% tubular (By similarity). The core is constituted by capsid protein hexamer subunits (By similarity). The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription (By similarity). Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species (By similarity). Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (By similarity). The capsid interacts with high affinity with human NONO, promoting detection of viral DNA by CGAS, leading to CGAS-mediated inmmune activation (By similarity). {ECO:0000250|UniProtKB:P04591, ECO:0000250|UniProtKB:P12493, ECO:0000250|UniProtKB:P18095}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
|
Human immunodeficiency virus type 2 subtype A (isolate ROD) (HIV-2)
|
P04591
|
GAG_HV1H2
|
MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQILGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQAAADTGHSNQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVLAEAMSQVTNSATIMMQRGNFRNQRKIVKCFNCGKEGHTARNCRAPRKKGCWKCGKEGHQMKDCTERQANFLGKIWPSYKGRPGNFLQSRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLRSLFGNDPSSQ
| null | null |
viral budding via host ESCRT complex [GO:0039702]
|
host cell nuclear membrane [GO:0044200]; host cell plasma membrane [GO:0020002]; host cellular component [GO:0018995]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
RNA binding [GO:0003723]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF00607;PF19317;PF08705;PF00098;
|
1.10.1200.30;6.10.250.390;1.10.375.10;1.10.150.90;1.20.5.760;4.10.60.10;
|
Primate lentivirus group gag polyprotein family
|
PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association (PubMed:17656588). {ECO:0000269|PubMed:17656588}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000269|PubMed:20828778}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular (PubMed:19914170, PubMed:8648689). The core is constituted by capsid protein hexamer subunits (PubMed:19914170, PubMed:8648689). The core is disassembled soon after virion entry (PubMed:12660176). The capsid promotes immune invasion by cloaking viral DNA from CGAS detection (PubMed:30270045). Host restriction factors such as host TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription (PubMed:23785198). Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species (PubMed:23785198). Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (PubMed:24554657). {ECO:0000250|UniProtKB:P12493, ECO:0000269|PubMed:12660176, ECO:0000269|PubMed:19914170, ECO:0000269|PubMed:23785198, ECO:0000269|PubMed:24554657, ECO:0000269|PubMed:30270045, ECO:0000269|PubMed:8648689}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000269|PubMed:11044125, ECO:0000269|PubMed:11932404, ECO:0000269|PubMed:17070549, ECO:0000269|PubMed:18343475, ECO:0000269|PubMed:20828778, ECO:0000269|PubMed:9931246}.; FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
|
P04592
|
GAG_HV1EL
|
MGARASVLSGGKLDKWEKIRLRPGGKKKYRLKHIVWASRELERYALNPGLLETSEGCKQIIGQLQPAIQTGTEELRSLYNTVATLYCVHKGIDVKDTKEALEKMEEEQNKSKKKAQQAAADTGNNSQVSQNYPIVQNLQGQMVHQAISPRTLNAWVKVIEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIAWMTSNPPIPVGEIYKRWIIVGLNKIVRMYSPVSILDIRQGPKEPFRDYVDRFYKTLRAEQASQDVKNWMTETLLVQNANPDCKTILKALGPQATLEEMMTACQGVGGPSHKARVLAEAMSQATNSVTTAMMQRGNFKGPRKIIKCFNCGKEGHIAKNCRAPRKKGCWRCGKEGHQLKDCTERQANFLGRIWPSHKGRPGNFLQSRPEPTAPPAESFGFGEEITPSQKQEQKDKELYPLTSLKSLFGNDPLSQ
| null | null |
viral budding via host ESCRT complex [GO:0039702]
|
host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
RNA binding [GO:0003723]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF19317;PF08705;PF00098;
|
1.10.1200.30;6.10.250.390;1.10.375.10;1.10.150.90;1.20.5.760;4.10.60.10;
|
Primate lentivirus group gag polyprotein family
|
PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04591}.; PTM: Capsid protein p24 is phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: Nucleocapsid protein p7 is methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000250|UniProtKB:P12493}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). The capsid promotes immune invasion by cloaking viral DNA from CGAS detection (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (By similarity). {ECO:0000250|UniProtKB:P04591, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
|
Human immunodeficiency virus type 1 group M subtype D (isolate ELI) (HIV-1)
|
P04593
|
GAG_HV1B5
|
MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQILGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQAAADTGHSSQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVLAEAMSQVTNSTTIMMQRGNFRNQRKIVKCFNCGKEGHIARNCKAPRKKGCWKCGKEGHQMKDCTERQANFLGKIWPSYKGRPGNFLQSRPEPTAPPFLQSRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLRSLFGNDPSSQ
| null | null |
viral budding via host ESCRT complex [GO:0039702]
|
host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
RNA binding [GO:0003723]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF00607;PF19317;PF08705;PF00098;
|
1.10.1200.30;6.10.250.390;1.10.375.10;1.10.150.90;1.20.5.760;4.10.60.10;
|
Primate lentivirus group gag polyprotein family
|
PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04591}.; PTM: Capsid protein p24 is phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: Nucleocapsid protein p7 is methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000250|UniProtKB:P12493}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). The capsid promotes immune invasion by cloaking viral DNA from CGAS detection (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (By similarity). {ECO:0000250|UniProtKB:P04591, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate BH5) (HIV-1)
|
P04594
|
GAG_HV1MA
|
MGARASVLSGGKLDAWEKIRLRPGGKKKYRLKHLVWASRELERFALNPGLLETGEGCQQIMEQLQSTLKTGSEEIKSLYNTVATLYCVHQRIDVKDTKEALDKIEEIQNKSRQKTQQAAAAQQAAAATKNSSSVSQNYPIVQNAQGQMIHQAISPRTLNAWVKVIEEKAFSPEVIPMFSALSEGATPQDLNMMLNIVGGHQAAMQMLKDTINEEAADWDRVHPVHAGPIPPGQMREPRGSDIAGTTSTLQEQIGWMTSNPPIPVGDIYKRWIILGLNKIVRMYSPVSILDIRQGPKEPFRDYVDRFFKTLRAEQATQEVKNWMTETLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPSHKARVLAEAMSQATNSTAAIMMQRGNFKGQKRIKCFNCGKEGHLARNCRAPRKKGCWKCGKEGHQMKDCTERQANFLGKIWPSHKGRPGNFLQSRPEPTAPPAESFGFGEEIKPSQKQEQKDKELYPLASLKSLFGNDQLSQ
| null | null |
viral budding via host ESCRT complex [GO:0039702]
|
host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
RNA binding [GO:0003723]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF19317;PF08705;PF00098;
|
1.10.1200.30;6.10.250.390;1.10.375.10;1.10.150.90;1.20.5.760;4.10.60.10;
|
Primate lentivirus group gag polyprotein family
|
PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04591}.; PTM: Capsid protein p24 is phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: Nucleocapsid protein p7 is methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000250|UniProtKB:P12493}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). The capsid promotes immune invasion by cloaking viral DNA from CGAS detection (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (By similarity). {ECO:0000250|UniProtKB:P04591, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
|
Human immunodeficiency virus type 1 group M subtype A (isolate MAL) (HIV-1)
|
P04601
|
NEF_HV1H2
|
MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC
| null | null |
suppression by virus of host autophagy [GO:0039521]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I [GO:0046776]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II [GO:0039505]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell Golgi membrane [GO:0044178]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; virion component [GO:0044423]
|
GTP binding [GO:0005525]; SH3 domain binding [GO:0017124]
|
PF00469;
|
4.10.890.10;3.30.62.10;
|
Lentivirus primate group Nef protein family
|
PTM: Phosphorylated on serine residues, probably by host PKCdelta and theta. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: The virion-associated Nef proteins are cleaved by the viral protease to release the soluble C-terminal core protein. Nef is probably cleaved concomitantly with viral structural proteins on maturation of virus particles. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
SUBCELLULAR LOCATION: Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04078}; Lipid-anchor {ECO:0000255|HAMAP-Rule:MF_04078}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_04078}. Virion {ECO:0000255|HAMAP-Rule:MF_04078}. Secreted {ECO:0000255|HAMAP-Rule:MF_04078, ECO:0000269|PubMed:19912576}. Host Golgi apparatus membrane {ECO:0000255|HAMAP-Rule:MF_04078}. Note=TGN localization requires PACS1. Associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the release of exosomes. Incorporated in virions at a rate of about 10 molecules per virion, where it is cleaved. {ECO:0000255|HAMAP-Rule:MF_04078, ECO:0000269|PubMed:19912576}.
| null | null | null | null | null |
FUNCTION: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. {ECO:0000255|HAMAP-Rule:MF_04078, ECO:0000269|PubMed:9450757}.; FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection). Down-regulates host SERINC3 and SERINC5 thereby excluding these proteins from the viral particles. Virion infectivity is drastically higher when SERINC3 or SERINC5 are excluded from the viral envelope, because these host antiviral proteins impair the membrane fusion event necessary for subsequent virion penetration. {ECO:0000255|HAMAP-Rule:MF_04078, ECO:0000269|PubMed:12526811, ECO:0000269|PubMed:24473078, ECO:0000269|PubMed:8124721}.; FUNCTION: Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of Bad. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078, ECO:0000269|PubMed:19912576}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
|
P04602
|
NEF_HV1Z6
|
MGGRWSKSSIVGWPAIRERIRRTDPRRTDPAADGVGAASRDLEKHGAITSSNTRDTNADCAWLEAQEESEEVGFPVRPQVPLRPMTYKLAVDLSHFLKEKGGLEGLIWSKKRQEILDLWVYNTQGIFPDWQNYTPGPGIRYPLTFGWCFELVPVDPREVEEATEGETNCLLHPVCQHGMEDTEREVLKWRFNSRLAFEHKAREMHPEFYKDC
| null | null |
suppression by virus of host autophagy [GO:0039521]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I [GO:0046776]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II [GO:0039505]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell Golgi membrane [GO:0044178]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; virion component [GO:0044423]
|
GTP binding [GO:0005525]; SH3 domain binding [GO:0017124]
|
PF00469;
|
4.10.890.10;3.30.62.10;
|
Lentivirus primate group Nef protein family
|
PTM: The virion-associated Nef proteins are cleaved by the viral protease to release the soluble C-terminal core protein. Nef is probably cleaved concomitantly with viral structural proteins on maturation of virus particles. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Phosphorylated on serine residues, probably by host PKCdelta and theta. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
SUBCELLULAR LOCATION: Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04078}; Lipid-anchor {ECO:0000255|HAMAP-Rule:MF_04078}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_04078}. Virion {ECO:0000255|HAMAP-Rule:MF_04078}. Secreted {ECO:0000255|HAMAP-Rule:MF_04078}. Host Golgi apparatus membrane {ECO:0000255|HAMAP-Rule:MF_04078}. Note=TGN localization requires PACS1. Associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the release of exosomes. Incorporated in virions at a rate of about 10 molecules per virion, where it is cleaved. {ECO:0000255|HAMAP-Rule:MF_04078}.
| null | null | null | null | null |
FUNCTION: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection). Down-regulates host SERINC3 and SERINC5 thereby excluding these proteins from the viral particles. Virion infectivity is drastically higher when SERINC3 or SERINC5 are excluded from the viral envelope, because these host antiviral proteins impair the membrane fusion event necessary for subsequent virion penetration. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of host BAD. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
Human immunodeficiency virus type 1 group M subtype D (isolate Z6) (HIV-1)
|
P04603
|
NEF_HV1MA
|
MGGKWSKSSIVGWPKIRERIRRTPPTETGVGAVSQDAVSQDLDKCGAAASSSPAANNASCEPPEEEEEVGFPVRPQVPLRPMTYKGAFDLSHFLKEKGGLDGLVWSPKRQEILDLWVYHTQGYFPDWQNYTPGPGIRFPLTFGWCFKLVPMSPEEVEEANEGENNCLLHPISQHGMEDAEREVLKWKFDSSLALRHRAREQHPEYYKDC
| null | null |
suppression by virus of host autophagy [GO:0039521]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I [GO:0046776]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II [GO:0039505]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell Golgi membrane [GO:0044178]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; virion component [GO:0044423]
|
GTP binding [GO:0005525]; SH3 domain binding [GO:0017124]
|
PF00469;
|
4.10.890.10;3.30.62.10;
|
Lentivirus primate group Nef protein family
|
PTM: The virion-associated Nef proteins are cleaved by the viral protease to release the soluble C-terminal core protein. Nef is probably cleaved concomitantly with viral structural proteins on maturation of virus particles. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Phosphorylated on serine residues, probably by host PKCdelta and theta. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
SUBCELLULAR LOCATION: Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04078}; Lipid-anchor {ECO:0000255|HAMAP-Rule:MF_04078}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_04078}. Virion {ECO:0000255|HAMAP-Rule:MF_04078}. Secreted {ECO:0000255|HAMAP-Rule:MF_04078}. Host Golgi apparatus membrane {ECO:0000255|HAMAP-Rule:MF_04078}. Note=TGN localization requires PACS1. Associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the release of exosomes. Incorporated in virions at a rate of about 10 molecules per virion, where it is cleaved. {ECO:0000255|HAMAP-Rule:MF_04078}.
| null | null | null | null | null |
FUNCTION: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection). Down-regulates host SERINC3 and SERINC5 thereby excluding these proteins from the viral particles. Virion infectivity is drastically higher when SERINC3 or SERINC5 are excluded from the viral envelope, because these host antiviral proteins impair the membrane fusion event necessary for subsequent virion penetration. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of host BAD. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
Human immunodeficiency virus type 1 group M subtype A (isolate MAL) (HIV-1)
|
P04604
|
NEF_HV1EL
|
MGGKWSKSSIVGWPAIRERIRRTNPAADGVGAVSRDLEKHGAITSSNTASTNADCAWLEAQEESDEVGFPVRPQVPLRPMTYKEALDLSHFLKEKGGLEGLIWSKKRQEILDLWVYNTQGIFPDWQNYTPGPGIRYPLTFGWCYELVPVDPQEVEEDTEGETNSLLHPICQHGMEDPERQVLKWRFNSRLAFEHKAREMHPEFYKN
| null | null |
suppression by virus of host autophagy [GO:0039521]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I [GO:0046776]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II [GO:0039505]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell Golgi membrane [GO:0044178]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; virion component [GO:0044423]
|
GTP binding [GO:0005525]; SH3 domain binding [GO:0017124]
|
PF00469;
|
4.10.890.10;3.30.62.10;
|
Lentivirus primate group Nef protein family
|
PTM: The virion-associated Nef proteins are cleaved by the viral protease to release the soluble C-terminal core protein. Nef is probably cleaved concomitantly with viral structural proteins on maturation of virus particles. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Phosphorylated on serine residues, probably by host PKCdelta and theta. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
SUBCELLULAR LOCATION: Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04078}; Lipid-anchor {ECO:0000255|HAMAP-Rule:MF_04078}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_04078}. Virion {ECO:0000255|HAMAP-Rule:MF_04078}. Secreted {ECO:0000255|HAMAP-Rule:MF_04078}. Host Golgi apparatus membrane {ECO:0000255|HAMAP-Rule:MF_04078}. Note=TGN localization requires PACS1. Associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the release of exosomes. Incorporated in virions at a rate of about 10 molecules per virion, where it is cleaved. {ECO:0000255|HAMAP-Rule:MF_04078}.
| null | null | null | null | null |
FUNCTION: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection). Down-regulates host SERINC3 and SERINC5 thereby excluding these proteins from the viral particles. Virion infectivity is drastically higher when SERINC3 or SERINC5 are excluded from the viral envelope, because these host antiviral proteins impair the membrane fusion event necessary for subsequent virion penetration. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of host BAD. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
Human immunodeficiency virus type 1 group M subtype D (isolate ELI) (HIV-1)
|
P04608
|
TAT_HV1H2
|
MEPVDPRLEPWKHPGSQPKTACTNCYCKKCCFHCQVCFITKALGISYGRKKRRQRRRAHQNSQTHQASLSKQPTSQPRGDPTGPKE
| null | null |
DNA-templated transcription [GO:0006351]; evasion of host immune response [GO:0042783]; modulation by virus of host chromatin organization [GO:0039525]; negative regulation of peptidyl-threonine phosphorylation [GO:0010801]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of viral transcription [GO:0050434]; symbiont-mediated suppression of host translation initiation [GO:0039606]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]; host cell nucleus [GO:0042025]
|
actinin binding [GO:0042805]; cyclin binding [GO:0030332]; metal ion binding [GO:0046872]; molecular sequestering activity [GO:0140313]; protein domain specific binding [GO:0019904]; protein serine/threonine phosphatase inhibitor activity [GO:0004865]; RNA-binding transcription regulator activity [GO:0001070]; trans-activation response element binding [GO:1990970]
|
PF00539;
|
4.10.20.10;
|
Lentiviruses Tat family
|
PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:17267505}.; PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:18480452}.; PTM: Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:12883554}.; PTM: Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:9079663}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:19888548}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:19888548, ECO:0000269|PubMed:23501106}. Secreted {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:19888548}. Note=Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type.
| null | null | null | null | null |
FUNCTION: Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:16687403, ECO:0000269|PubMed:17267505, ECO:0000269|PubMed:1756726, ECO:0000269|PubMed:22187158, ECO:0000269|PubMed:7608968, ECO:0000269|PubMed:9491887}.; FUNCTION: Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:10397733, ECO:0000269|PubMed:17360663, ECO:0000269|PubMed:9079663}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
|
P04609
|
TAT_HV1Z6
|
MDPVDPNLEPWNHPGSQPKTACNRCHCKKCCYHCQVCFITKGLGISYGRKKRRQRRRPSQGGQTHQDPIPKQPSSQPRGNPTGPKE
| null | null |
DNA-templated transcription [GO:0006351]; modulation by virus of host chromatin organization [GO:0039525]; negative regulation of peptidyl-threonine phosphorylation [GO:0010801]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of viral transcription [GO:0050434]; symbiont-mediated suppression of host translation initiation [GO:0039606]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
|
actinin binding [GO:0042805]; cyclin binding [GO:0030332]; metal ion binding [GO:0046872]; protein domain specific binding [GO:0019904]; protein serine/threonine phosphatase inhibitor activity [GO:0004865]; RNA-binding transcription regulator activity [GO:0001070]; trans-activation response element binding [GO:1990970]
|
PF00539;
|
4.10.20.10;
|
Lentiviruses Tat family
|
PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04079}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079}. Secreted {ECO:0000255|HAMAP-Rule:MF_04079}. Note=Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type. {ECO:0000255|HAMAP-Rule:MF_04079}.
| null | null | null | null | null |
FUNCTION: Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079}.; FUNCTION: Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
Human immunodeficiency virus type 1 group M subtype D (isolate Z6) (HIV-1)
|
P04610
|
TAT_HV1BR
|
MEPVDPRLEPWKHPGSQPKTACTTCYCKKCCFHCQVCFTTKALGISYGRKKRRQRRRPPQGSQTHQVSLSKQPTSQPRGDPTGPKE
| null | null |
DNA-templated transcription [GO:0006351]; membrane hyperpolarization [GO:0060081]; modulation by virus of host chromatin organization [GO:0039525]; negative regulation of cellular respiration [GO:1901856]; negative regulation of peptidyl-threonine phosphorylation [GO:0010801]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of protein localization to nucleus [GO:1900182]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of viral transcription [GO:0050434]; symbiont-mediated suppression of host translation initiation [GO:0039606]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; viral gene expression [GO:0019080]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
|
actinin binding [GO:0042805]; cyclin binding [GO:0030332]; metal ion binding [GO:0046872]; protein domain specific binding [GO:0019904]; protein serine/threonine phosphatase inhibitor activity [GO:0004865]; regulatory region RNA binding [GO:0001069]; RNA-binding transcription regulator activity [GO:0001070]; trans-activation response element binding [GO:1990970]
|
PF00539;
|
4.10.20.10;
|
Lentiviruses Tat family
|
PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079, ECO:0000269|PubMed:12883554}.; PTM: Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04079}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079}. Secreted {ECO:0000255|HAMAP-Rule:MF_04079}. Note=Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type. {ECO:0000255|HAMAP-Rule:MF_04079}.
| null | null | null | null | null |
FUNCTION: Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079}.; FUNCTION: Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI) (HIV-1)
|
P04611
|
TAT_HV1EL
|
MDPVDPNLEPWNHPGSQPRTPCNKCHCKKCCYHCPVCFLNKGLGISYGRKKRRQRRGPPQGGQAHQVPIPKQPSSQPRGDPTGPKEQKKKVESEAETDP
| null | null |
DNA-templated transcription [GO:0006351]; modulation by virus of host chromatin organization [GO:0039525]; negative regulation of peptidyl-threonine phosphorylation [GO:0010801]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of viral transcription [GO:0050434]; symbiont-mediated suppression of host translation initiation [GO:0039606]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; viral gene expression [GO:0019080]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
|
actinin binding [GO:0042805]; cyclin binding [GO:0030332]; metal ion binding [GO:0046872]; protein domain specific binding [GO:0019904]; protein serine/threonine phosphatase inhibitor activity [GO:0004865]; regulatory region RNA binding [GO:0001069]; RNA-binding transcription regulator activity [GO:0001070]; trans-activation response element binding [GO:1990970]
|
PF00539;
|
4.10.20.10;
|
Lentiviruses Tat family
|
PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04079}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079}. Secreted {ECO:0000255|HAMAP-Rule:MF_04079}. Note=Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type. {ECO:0000255|HAMAP-Rule:MF_04079}.
| null | null | null | null | null |
FUNCTION: Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079}.; FUNCTION: Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
Human immunodeficiency virus type 1 group M subtype D (isolate ELI) (HIV-1)
|
P04613
|
TAT_HV1MA
|
MDPVDPNLEPWNHPGSQPRTPCNKCYCKKCCYHCQMCFITKGLGISYGRKKRRQRRRPPQGNQAHQDPLPEQPSSQHRGDHPTGPKE
| null | null |
DNA-templated transcription [GO:0006351]; modulation by virus of host chromatin organization [GO:0039525]; negative regulation of peptidyl-threonine phosphorylation [GO:0010801]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of viral transcription [GO:0050434]; symbiont-mediated suppression of host translation initiation [GO:0039606]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; viral gene expression [GO:0019080]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
|
actinin binding [GO:0042805]; cyclin binding [GO:0030332]; metal ion binding [GO:0046872]; protein domain specific binding [GO:0019904]; protein serine/threonine phosphatase inhibitor activity [GO:0004865]; regulatory region RNA binding [GO:0001069]; RNA-binding transcription regulator activity [GO:0001070]; trans-activation response element binding [GO:1990970]
|
PF00539;
|
4.10.20.10;
|
Lentiviruses Tat family
|
PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04079}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079}. Secreted {ECO:0000255|HAMAP-Rule:MF_04079}. Note=Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type. {ECO:0000255|HAMAP-Rule:MF_04079}.
| null | null | null | null | null |
FUNCTION: Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079}.; FUNCTION: Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
Human immunodeficiency virus type 1 group M subtype A (isolate MAL) (HIV-1)
|
P04614
|
TAT_HV1A2
|
MEPVDPNLEPWKHPGSQPRTACNNCYCKKCCFHCYACFTRKGLGISYGRKKRRQRRRAPQDSQTHQASLSKQPASQSRGDPTGPTESKKKVERETETDPFD
| null | null |
DNA-templated transcription [GO:0006351]; modulation by virus of host chromatin organization [GO:0039525]; negative regulation of peptidyl-threonine phosphorylation [GO:0010801]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of viral transcription [GO:0050434]; symbiont-mediated suppression of host translation initiation [GO:0039606]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
|
actinin binding [GO:0042805]; cyclin binding [GO:0030332]; metal ion binding [GO:0046872]; protein domain specific binding [GO:0019904]; protein serine/threonine phosphatase inhibitor activity [GO:0004865]; RNA-binding transcription regulator activity [GO:0001070]; trans-activation response element binding [GO:1990970]
|
PF00539;
|
4.10.20.10;
|
Lentiviruses Tat family
|
PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04079}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079}. Secreted {ECO:0000255|HAMAP-Rule:MF_04079}. Note=Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type. {ECO:0000255|HAMAP-Rule:MF_04079}.
| null | null | null | null | null |
FUNCTION: Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079}.; FUNCTION: Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2) (HIV-1)
|
P04616
|
REV_HV1B1
|
MAGRSGDSDEDLLKAVRLIKFLYQSNPPPNPEGTRQARRNRRRRWRERQRQIHSISERILSTYLGRSAEPVPLQLPPLERLTLDCNEDCGTSGTQGVGSPQILVESPTVLESGAKE
| null | null |
mRNA transport [GO:0051028]; protein export from nucleus [GO:0006611]; viral process [GO:0016032]
|
host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
|
DNA-binding transcription factor activity [GO:0003700]; RNA binding [GO:0003723]
|
PF00424;
|
6.10.140.630;
|
HIV-1 REV protein family
|
PTM: Asymmetrically arginine dimethylated at one site by host PRMT6. Methylation impairs the RNA-binding activity and export of viral RNA from the nucleus to the cytoplasm. The methylation site is still unclear and either occurs at Arg-35, Arg-38 or Arg-39. {ECO:0000269|PubMed:17176473}.; PTM: Asymmetrically arginine dimethylated at one site by host PRMT6. Methylation impairs the RNA-binding activity and export of viral RNA from the nucleus to the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04077}.; PTM: Phosphorylated by protein kinase CK2. Presence of, and maybe binding to the N-terminus of the regulatory beta subunit of CK2 is necessary for CK2-mediated Rev's phosphorylation. {ECO:0000255|HAMAP-Rule:MF_04077}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04077}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04077}. Note=The presence of both nuclear import and nuclear export signals leads to continuous shuttling between the nucleus and cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04077}.
| null | null | null | null | null |
FUNCTION: Escorts unspliced or incompletely spliced viral pre-mRNAs (late transcripts) out of the nucleus of infected cells. These pre-mRNAs carry a recognition sequence called Rev responsive element (RRE) located in the env gene, that is not present in fully spliced viral mRNAs (early transcripts). This function is essential since most viral proteins are translated from unspliced or partially spliced pre-mRNAs which cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rev itself is translated from a fully spliced mRNA that readily exits the nucleus. Rev's nuclear localization signal (NLS) binds directly to KPNB1/Importin beta-1 without previous binding to KPNA1/Importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rev to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP dissociates Rev from KPNB1 and allows Rev's binding to the RRE in viral pre-mRNAs. Rev multimerization on the RRE via cooperative assembly exposes its nuclear export signal (NES) to the surface. Rev can then form a complex with XPO1/CRM1 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rev/RRE/XPO1/RAN complex, so that Rev can return to the nucleus for a subsequent round of export. Beside KPNB1, also seems to interact with TNPO1/Transportin-1, RANBP5/IPO5 and IPO7/RANBP7 for nuclear import. The nucleoporin-like HRB/RIP is an essential cofactor that probably indirectly interacts with Rev to release HIV RNAs from the perinuclear region to the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04077}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1)
|
P04618
|
REV_HV1H2
|
MAGRSGDSDEELIRTVRLIKLLYQSNPPPNPEGTRQARRNRRRRWRERQRQIHSISERILGTYLGRSAEPVPLQLPPLERLTLDCNEDCGTSGTQGVGSPQILVESPTVLESGTKE
| null | null |
mRNA transport [GO:0051028]; viral process [GO:0016032]
|
host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
|
DNA-binding transcription factor activity [GO:0003700]; identical protein binding [GO:0042802]; RNA binding [GO:0003723]
|
PF00424;
|
6.10.140.630;
|
HIV-1 REV protein family
|
PTM: Asymmetrically arginine dimethylated at one site by host PRMT6. Methylation impairs the RNA-binding activity and export of viral RNA from the nucleus to the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04077}.; PTM: Phosphorylated by protein kinase CK2. Presence of, and maybe binding to the N-terminus of the regulatory beta subunit of CK2 is necessary for CK2-mediated Rev's phosphorylation. {ECO:0000255|HAMAP-Rule:MF_04077, ECO:0000269|PubMed:10984616, ECO:0000269|PubMed:11827166, ECO:0000269|PubMed:8806671}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04077}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04077}. Note=The presence of both nuclear import and nuclear export signals leads to continuous shuttling between the nucleus and cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04077}.
| null | null | null | null | null |
FUNCTION: Escorts unspliced or incompletely spliced viral pre-mRNAs (late transcripts) out of the nucleus of infected cells. These pre-mRNAs carry a recognition sequence called Rev responsive element (RRE) located in the env gene, that is not present in fully spliced viral mRNAs (early transcripts). This function is essential since most viral proteins are translated from unspliced or partially spliced pre-mRNAs which cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rev itself is translated from a fully spliced mRNA that readily exits the nucleus. Rev's nuclear localization signal (NLS) binds directly to KPNB1/Importin beta-1 without previous binding to KPNA1/Importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rev to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP dissociates Rev from KPNB1 and allows Rev's binding to the RRE in viral pre-mRNAs. Rev multimerization on the RRE via cooperative assembly exposes its nuclear export signal (NES) to the surface. Rev can then form a complex with XPO1/CRM1 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rev/RRE/XPO1/RAN complex, so that Rev can return to the nucleus for a subsequent round of export. Beside KPNB1, also seems to interact with TNPO1/Transportin-1, RANBP5/IPO5 and IPO7/RANBP7 for nuclear import. The nucleoporin-like HRB/RIP is an essential cofactor that probably indirectly interacts with Rev to release HIV RNAs from the perinuclear region to the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04077}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
|
P04624
|
ENV_HV1H3
|
MRVKEKYQHLWRWGWRWGTMLLGMLMICSATEKLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHAGVPTDPNPQEVVLVNVTENFNMWKNDMVEQMHEDIISLWDQSLKPCVKLTPLCVSLKCTDLKNDTNTNSSSGRMIMEKGEIKNCSFNISTSIRGKVQKEYAFFYKLDIIPIDNDTTSYTLTSCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNNKTFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSVNFTDNAKTIIVQLNTSVEINCTRPNNNTRKKIRIQRGPGRAFVTIGKIGNMRQAHCNISRAKWNATLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWSTEGSNNTEGSDTITLPCRIKQFINMWQEVGKAMYAPPISGQIRCSSNITGLLLTRDGGNNNNGSEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQREKRAVGIGALFLGFLGAAGSTMGAASMTLTVQARQLLSGIVQQQNNLLRAIEAQQHLLQLTVWGIKQLQARILAVERYLKDQQLLGIWGCSGKLLCTTAVPWNASWSNKSLEQIWNHTTWMEWDREINNYTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWFNITNWLWYIKLFIMIVGGLVGLRIVFAVLSVVNRVRQGYSPLSFQTHLPIPRGPDRPEGIEEEGGERDRDRSIRLVNGSLALIWDDLRSLCLFSYHRLRDLLLIVTRIVELLGRRGWEALKYWWNLLQYWSQELKNSAVSLLNATAIAVAEGTDRVIEVVQEAYRAIRHIPRRIRQGLERILL
| null | null |
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;1.20.5.490;
|
HIV-1 env protein family
|
PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
| null | null | null | null | null |
FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
Human immunodeficiency virus type 1 group M subtype B (isolate HXB3) (HIV-1)
|
P04625
|
THA_CHICK
|
MEQKPSTLDPLSEPEDTRWLDGKRKRKSSQCLVKSSMSGYIPSYLDKDEQCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPTYSCKYDGCCVIDKITRNQCQLCRFKKCISVGMAMDLVLDDSKRVAKRKLIEENRERRRKEEMIKSLQHRPSPSAEEWELIHVVTEAHRSTNAQGSHWKQKRKFLPEDIGQSPMASMPDGDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFSELPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTLSGEMAVKREQLKNGGLGVVSDAIFDLGKSLSAFNLDDTEVALLQAVLLMSSDRTGLICVDKIEKCQETYLLAFEHYINYRKHNIPHFWPKLLMKVTDLRMIGACHASRFLHMKVECPTELFPPLFLEVFEDQEV
| null | null |
cell differentiation [GO:0030154]; mRNA transcription by RNA polymerase II [GO:0042789]; negative regulation of RNA polymerase II transcription preinitiation complex assembly [GO:0017055]; negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of thyroid hormone mediated signaling pathway [GO:0002157]; positive regulation of transcription by RNA polymerase II [GO:0045944]; retinoic acid receptor signaling pathway [GO:0048384]; thyroid hormone mediated signaling pathway [GO:0002154]
|
cytosol [GO:0005829]; nucleus [GO:0005634]; RNA polymerase II transcription regulator complex [GO:0090575]
|
nuclear receptor activity [GO:0004879]; protein domain specific binding [GO:0019904]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific double-stranded DNA binding [GO:1990837]; TBP-class protein binding [GO:0017025]; thyroid hormone binding [GO:0070324]; zinc ion binding [GO:0008270]
|
PF00104;PF00105;
|
3.30.50.10;1.10.565.10;
|
Nuclear hormone receptor family, NR1 subfamily
| null |
SUBCELLULAR LOCATION: Nucleus.
| null | null | null | null | null |
FUNCTION: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.
|
Gallus gallus (Chicken)
|
P04626
|
ERBB2_HUMAN
|
MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNLELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLALTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSANIQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLPDLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTVPWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARCPSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQGGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV
|
2.7.10.1
| null |
cell surface receptor signaling pathway [GO:0007166]; cellular response to epidermal growth factor stimulus [GO:0071364]; cellular response to growth factor stimulus [GO:0071363]; enzyme-linked receptor protein signaling pathway [GO:0007167]; ERBB2-EGFR signaling pathway [GO:0038134]; ERBB2-ERBB3 signaling pathway [GO:0038133]; ERBB2-ERBB4 signaling pathway [GO:0038135]; heart development [GO:0007507]; immature T cell proliferation in thymus [GO:0033080]; intracellular signal transduction [GO:0035556]; motor neuron axon guidance [GO:0008045]; myelination [GO:0042552]; negative regulation of apoptotic process [GO:0043066]; negative regulation of immature T cell proliferation in thymus [GO:0033088]; neurogenesis [GO:0022008]; neuromuscular junction development [GO:0007528]; neuron differentiation [GO:0030182]; neurotransmitter receptor localization to postsynaptic specialization membrane [GO:0099645]; oligodendrocyte differentiation [GO:0048709]; peptidyl-tyrosine phosphorylation [GO:0018108]; phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0043491]; positive regulation of cell adhesion [GO:0045785]; positive regulation of cell growth [GO:0030307]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of epithelial cell proliferation [GO:0050679]; positive regulation of MAP kinase activity [GO:0043406]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of protein targeting to membrane [GO:0090314]; positive regulation of Rho protein signal transduction [GO:0035025]; positive regulation of transcription by RNA polymerase I [GO:0045943]; positive regulation of translation [GO:0045727]; protein phosphorylation [GO:0006468]; regulation of angiogenesis [GO:0045765]; regulation of ERK1 and ERK2 cascade [GO:0070372]; regulation of microtubule-based process [GO:0032886]; Schwann cell development [GO:0014044]; semaphorin-plexin signaling pathway [GO:0071526]; signal transduction [GO:0007165]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]; wound healing [GO:0042060]
|
apical plasma membrane [GO:0016324]; basal plasma membrane [GO:0009925]; basolateral plasma membrane [GO:0016323]; cytosol [GO:0005829]; early endosome [GO:0005769]; endosome membrane [GO:0010008]; ERBB3:ERBB2 complex [GO:0038143]; membrane [GO:0016020]; myelin sheath [GO:0043209]; neuromuscular junction [GO:0031594]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; presynaptic membrane [GO:0042734]; receptor complex [GO:0043235]; ruffle membrane [GO:0032587]; semaphorin receptor complex [GO:0002116]
|
ATP binding [GO:0005524]; coreceptor activity [GO:0015026]; ErbB-3 class receptor binding [GO:0043125]; identical protein binding [GO:0042802]; protein heterodimerization activity [GO:0046982]; protein tyrosine kinase activity [GO:0004713]; receptor tyrosine kinase binding [GO:0030971]; RNA polymerase I core binding [GO:0001042]; signaling receptor binding [GO:0005102]; transmembrane receptor protein tyrosine kinase activity [GO:0004714]; transmembrane signaling receptor activity [GO:0004888]
|
PF00757;PF14843;PF07714;PF01030;PF21314;
|
1.20.5.100;4.10.1140.10;3.80.20.20;1.10.510.10;
|
Protein kinase superfamily, Tyr protein kinase family, EGF receptor subfamily
|
PTM: Autophosphorylated. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (Probable). Ligand-binding increases phosphorylation on tyrosine residues (PubMed:27134172, PubMed:33497358). Signaling via SEMA4C promotes phosphorylation at Tyr-1248 (PubMed:17554007). Dephosphorylated by PTPN12 (PubMed:27134172). {ECO:0000269|PubMed:17554007, ECO:0000269|PubMed:27134172, ECO:0000269|PubMed:33497358, ECO:0000305}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:32381043}; Single-pass type I membrane protein {ECO:0000255}. Cell projection, ruffle membrane {ECO:0000269|PubMed:34380438}; Single-pass type I membrane protein {ECO:0000255}. Note=Internalized from the cell membrane in response to EGF stimulation. {ECO:0000269|PubMed:32381043}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:31138794, ECO:0000269|PubMed:33497358}; Single-pass type I membrane protein {ECO:0000255}. Early endosome {ECO:0000269|PubMed:31138794}. Cytoplasm, perinuclear region. Nucleus. Note=Translocation to the nucleus requires endocytosis, probably endosomal sorting and is mediated by importin beta-1/KPNB1. Also detected in VPS35-positive endosome-to-TGN retrograde vesicles (PubMed:31138794). {ECO:0000269|PubMed:31138794}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Nucleus.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm. Nucleus.
|
CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:21454582};
| null | null | null | null |
FUNCTION: Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}.
|
Homo sapiens (Human)
|
P04627
|
ARAF_MOUSE
|
MEPPRGPPVSGAEPSRAVGTVKVYLPNKQRTVVTVREGMSVYDSLDKALKVRGLNQDCCVVYRLIKGRKTVTAWDTAIAPLDGEELIVEVLEDVPLTMHNFVRKTFFSLAFCDFCLKFLFHGFRCQTCGYKFHQHCSSKVPTVCVDMSTNRRQFYHSIQDLSGGSRQQEAPSNLSVNELLTPQGPSPFTQQRDQEHFSFPAPANPPLQRIRSTSTPNVHMVSTTAPMDSSLMQFTAQSFSTDAAGRGGDGAPRGSPSPASVSSGRKSPHSKLPSEQRERKSLADEKKKVKNLGYRDSGYYWEVPPSEVQLLKRIGTGSFGTVFRGRWHGDVAVKVLKVAQPTAEQAQAFKNEMQVLRKTRHVNILLFMGFMTRPGFAIITQWCEGSSLYHHLHVADTRFDMVQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLATVKTRWSGAQPLEQPSGSVLWMAAEVIRMQDPNPYSFQSDVYAYGVVLYELMTGSLPYSHIGSRDQIIFMVGRGYLSPDLSKIFSNCPKAMRRLLTDCLKFQREERPLFPQILATIELLQRSLPKIERSASEPSLHRTQADELPACLLSAARLVP
|
2.7.11.1
|
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
|
MAPK cascade [GO:0000165]; negative regulation of apoptotic process [GO:0043066]; phosphorylation [GO:0016310]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; Ras protein signal transduction [GO:0007265]; regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032434]; regulation of TOR signaling [GO:0032006]
|
cytosol [GO:0005829]; mitochondrion [GO:0005739]
|
ATP binding [GO:0005524]; MAP kinase kinase kinase activity [GO:0004709]; metal ion binding [GO:0046872]; protein serine kinase activity [GO:0106310]
|
PF00130;PF07714;PF02196;
|
3.30.60.20;1.10.510.10;
|
Protein kinase superfamily, TKL Ser/Thr protein kinase family, RAF subfamily
| null | null |
CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
| null | null | null | null |
FUNCTION: Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade (By similarity). Phosphorylates PFKFB2 (By similarity). {ECO:0000250|UniProtKB:P10398}.
|
Mus musculus (Mouse)
|
P04628
|
WNT1_HUMAN
|
MGLWALLPGWVSATLLLALAALPAALAANSSGRWWGIVNVASSTNLLTDSKSLQLVLEPSLQLLSRKQRRLIRQNPGILHSVSGGLQSAVRECKWQFRNRRWNCPTAPGPHLFGKIVNRGCRETAFIFAITSAGVTHSVARSCSEGSIESCTCDYRRRGPGGPDWHWGGCSDNIDFGRLFGREFVDSGEKGRDLRFLMNLHNNEAGRTTVFSEMRQECKCHGMSGSCTVRTCWMRLPTLRAVGDVLRDRFDGASRVLYGNRGSNRASRAELLRLEPEDPAHKPPSPHDLVYFEKSPNFCTYSGRLGTAGTAGRACNSSSPALDGCELLCCGRGHRTRTQRVTERCNCTFHWCCHVSCRNCTHTRVLHECL
| null | null |
animal organ regeneration [GO:0031100]; astrocyte-dopaminergic neuron signaling [GO:0036520]; bone development [GO:0060348]; branching involved in ureteric bud morphogenesis [GO:0001658]; canonical Wnt signaling pathway [GO:0060070]; cell fate commitment [GO:0045165]; cell proliferation in midbrain [GO:0033278]; cell-cell signaling [GO:0007267]; cellular response to peptide hormone stimulus [GO:0071375]; central nervous system morphogenesis [GO:0021551]; cerebellum formation [GO:0021588]; diencephalon development [GO:0021536]; embryonic axis specification [GO:0000578]; embryonic brain development [GO:1990403]; fat cell differentiation [GO:0045444]; forebrain anterior/posterior pattern specification [GO:0021797]; hematopoietic stem cell proliferation [GO:0071425]; hepatocyte differentiation [GO:0070365]; inner ear morphogenesis [GO:0042472]; midbrain development [GO:0030901]; midbrain dopaminergic neuron differentiation [GO:1904948]; midbrain-hindbrain boundary maturation during brain development [GO:0022004]; myoblast fusion [GO:0007520]; negative regulation of apoptotic process [GO:0043066]; negative regulation of BMP signaling pathway [GO:0030514]; negative regulation of cell-cell adhesion [GO:0022408]; negative regulation of cell-substrate adhesion [GO:0010812]; negative regulation of cellular senescence [GO:2000773]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway [GO:1903377]; negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512]; negative regulation of ubiquitin-dependent protein catabolic process [GO:2000059]; neuron differentiation [GO:0030182]; neuron fate determination [GO:0048664]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of dermatome development [GO:0061184]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of hematopoietic stem cell proliferation [GO:1902035]; positive regulation of insulin-like growth factor receptor signaling pathway [GO:0043568]; positive regulation of lamellipodium assembly [GO:0010592]; positive regulation of Notch signaling pathway [GO:0045747]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of transcription by RNA polymerase II [GO:0045944]; response to wounding [GO:0009611]; signal transduction in response to DNA damage [GO:0042770]; Spemann organizer formation [GO:0060061]; spinal cord association neuron differentiation [GO:0021527]; T cell differentiation in thymus [GO:0033077]; Wnt signaling pathway [GO:0016055]
|
cell surface [GO:0009986]; cytoplasm [GO:0005737]; endocytic vesicle membrane [GO:0030666]; endoplasmic reticulum lumen [GO:0005788]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; Golgi lumen [GO:0005796]; plasma membrane [GO:0005886]
|
cytokine activity [GO:0005125]; frizzled binding [GO:0005109]; morphogen activity [GO:0016015]; protein domain specific binding [GO:0019904]; receptor ligand activity [GO:0048018]
|
PF00110;
|
3.30.2460.20;
|
Wnt family
|
PTM: Palmitoleoylation is required for efficient binding to frizzled receptors. Palmitoleoylation is necessary for proper trafficking to cell surface (Probable). Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway (By similarity). {ECO:0000250|UniProtKB:P56704, ECO:0000250|UniProtKB:Q91029, ECO:0000305|PubMed:21244856}.
|
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix {ECO:0000305}. Secreted {ECO:0000269|PubMed:26902720}.
| null | null | null | null | null |
FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation (PubMed:23499309, PubMed:23656646, PubMed:26902720, PubMed:28528193). In some developmental processes, is also a ligand for the coreceptor RYK, thus triggering Wnt signaling (By similarity). Plays an essential role in the development of the embryonic brain and central nervous system (CNS) (By similarity). Has a role in osteoblast function, bone development and bone homeostasis (PubMed:23499309, PubMed:23656646). {ECO:0000250|UniProtKB:P04426, ECO:0000269|PubMed:23499309, ECO:0000269|PubMed:23656646, ECO:0000269|PubMed:26902720, ECO:0000269|PubMed:28528193, ECO:0000305}.
|
Homo sapiens (Human)
|
P04629
|
NTRK1_HUMAN
|
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQGPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYTLLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHARLQALAQAPPVYLDVLG
|
2.7.10.1
| null |
axon guidance [GO:0007411]; axonogenesis involved in innervation [GO:0060385]; B cell differentiation [GO:0030183]; behavioral response to formalin induced pain [GO:0061368]; cellular response to nerve growth factor stimulus [GO:1990090]; cellular response to nicotine [GO:0071316]; circadian rhythm [GO:0007623]; detection of mechanical stimulus involved in sensory perception of pain [GO:0050966]; detection of temperature stimulus involved in sensory perception of pain [GO:0050965]; learning or memory [GO:0007611]; mechanoreceptor differentiation [GO:0042490]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of neuron apoptotic process [GO:0043524]; nerve growth factor signaling pathway [GO:0038180]; neuron apoptotic process [GO:0051402]; neuron development [GO:0048666]; neuron projection development [GO:0031175]; neurotrophin TRK receptor signaling pathway [GO:0048011]; olfactory nerve development [GO:0021553]; peptidyl-tyrosine autophosphorylation [GO:0038083]; peptidyl-tyrosine phosphorylation [GO:0018108]; positive regulation of angiogenesis [GO:0045766]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of GTPase activity [GO:0043547]; positive regulation of neuron projection development [GO:0010976]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of programmed cell death [GO:0043068]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of Ras protein signal transduction [GO:0046579]; positive regulation of synapse assembly [GO:0051965]; positive regulation of synaptic transmission, glutamatergic [GO:0051968]; programmed cell death involved in cell development [GO:0010623]; protein autophosphorylation [GO:0046777]; protein phosphorylation [GO:0006468]; regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0051896]; response to axon injury [GO:0048678]; response to electrical stimulus [GO:0051602]; response to hydrostatic pressure [GO:0051599]; response to nutrient levels [GO:0031667]; response to xenobiotic stimulus [GO:0009410]; Sertoli cell development [GO:0060009]; sympathetic nervous system development [GO:0048485]
|
axon [GO:0030424]; cell surface [GO:0009986]; dendrite [GO:0030425]; early endosome [GO:0005769]; early endosome membrane [GO:0031901]; endosome membrane [GO:0010008]; late endosome [GO:0005770]; late endosome membrane [GO:0031902]; neuronal cell body [GO:0043025]; plasma membrane [GO:0005886]; protein-containing complex [GO:0032991]; receptor complex [GO:0043235]; recycling endosome membrane [GO:0055038]
|
ATP binding [GO:0005524]; GPI-linked ephrin receptor activity [GO:0005004]; identical protein binding [GO:0042802]; kinase binding [GO:0019900]; nerve growth factor binding [GO:0048406]; nerve growth factor receptor activity [GO:0010465]; neurotrophin binding [GO:0043121]; neurotrophin p75 receptor binding [GO:0005166]; neurotrophin receptor activity [GO:0005030]; protein homodimerization activity [GO:0042803]; protein tyrosine kinase activity [GO:0004713]; transmembrane receptor protein tyrosine kinase activity [GO:0004714]
|
PF13855;PF16920;PF07714;PF18613;
|
2.60.40.10;3.80.10.10;1.10.510.10;
|
Protein kinase superfamily, Tyr protein kinase family, Insulin receptor subfamily
|
PTM: Ligand-mediated autophosphorylation (PubMed:1281417, PubMed:15488758, PubMed:27676246, PubMed:28177573, PubMed:2927393, PubMed:7510697, PubMed:8155326, PubMed:8325889). Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1 (PubMed:15488758, PubMed:7510697, PubMed:8155326, PubMed:8325889). {ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:28177573, ECO:0000269|PubMed:2927393, ECO:0000269|PubMed:7510697, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.; PTM: N-glycosylated (PubMed:2927393). Isoform TrkA-I and isoform TrkA-II are N-glycosylated. {ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:2927393}.; PTM: Ubiquitinated (PubMed:27445338). Undergoes polyubiquitination upon activation; regulated by NGFR (PubMed:27445338). Ubiquitination by NEDD4L leads to degradation (PubMed:27445338). Ubiquitination regulates the internalization of the receptor (By similarity). {ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:27445338}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:2927393}; Single-pass type I membrane protein {ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758}. Early endosome membrane {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P35739}. Late endosome membrane {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P35739}. Recycling endosome membrane {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P35739}. Note=Rapidly internalized after NGF binding (PubMed:1281417). Internalized to endosomes upon binding of NGF or NTF3 and further transported to the cell body via a retrograde axonal transport. Localized at cell membrane and early endosomes before nerve growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Colocalized with RAPGEF2 at late endosomes. {ECO:0000250|UniProtKB:P35739, ECO:0000269|PubMed:1281417}.
|
CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:2927393};
| null | null | null | null |
FUNCTION: Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1281417, PubMed:15488758, PubMed:17196528, PubMed:1849459, PubMed:1850821, PubMed:22649032, PubMed:27445338, PubMed:8325889). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P35739, ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459, ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.; FUNCTION: [Isoform TrkA-III]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. {ECO:0000269|PubMed:15488758}.
|
Homo sapiens (Human)
|
P04631
|
S100B_RAT
|
MSELEKAMVALIDVFHQYSGREGDKHKLKKSELKELINNELSHFLEEIKEQEVVDKVMETLDEDGDGECDFQEFMAFVSMVTTACHEFFEHE
| null | null |
adaptive thermogenesis [GO:1990845]; astrocyte differentiation [GO:0048708]; cell adhesion [GO:0007155]; cellular response to hypoxia [GO:0071456]; learning or memory [GO:0007611]; long-term synaptic potentiation [GO:0060291]; memory [GO:0007613]; negative regulation of skeletal muscle cell differentiation [GO:2001015]; neuron projection extension [GO:1990138]; positive regulation of apoptotic process [GO:0043065]; positive regulation of canonical NF-kappaB signal transduction [GO:0043123]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of myelination [GO:0031643]; positive regulation of neuron differentiation [GO:0045666]; positive regulation of synaptic transmission [GO:0050806]; regulation of cell shape [GO:0008360]; regulation of neuronal synaptic plasticity [GO:0048168]; response to glucocorticoid [GO:0051384]; response to methylmercury [GO:0051597]; sympathetic neuron projection extension [GO:0097490]
|
cytoplasm [GO:0005737]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; neuronal cell body [GO:0043025]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; ruffle [GO:0001726]; sarcoplasmic reticulum [GO:0016529]
|
calcium ion binding [GO:0005509]; calcium-dependent protein binding [GO:0048306]; identical protein binding [GO:0042802]; ion binding [GO:0043167]; protein homodimerization activity [GO:0042803]; RAGE receptor binding [GO:0050786]; S100 protein binding [GO:0044548]; signaling receptor binding [GO:0005102]; tau protein binding [GO:0048156]; zinc ion binding [GO:0008270]
|
PF00036;PF01023;
|
1.10.238.10;
|
S-100 family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P04271}. Nucleus {ECO:0000250|UniProtKB:P04271}. Secreted {ECO:0000250|UniProtKB:P50114}. Note=Secretion into the medium is promoted by interaction with isoform CLSTN3beta of CLSTN3. {ECO:0000250|UniProtKB:P50114}.
| null | null | null | null | null |
FUNCTION: Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:14621986, PubMed:15823027, PubMed:18949447, PubMed:20351179). Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer (PubMed:15823027). Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites (By similarity). Acts as a neurotrophic factor that promotes astrocytosis and axonal proliferation (By similarity). Involved in innervation of thermogenic adipose tissue by acting as an adipocyte-derived neurotrophic factor that promotes sympathetic innervation of adipose tissue (By similarity). Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase (By similarity). Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (PubMed:19910580). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity). May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity (By similarity). {ECO:0000250|UniProtKB:P02638, ECO:0000250|UniProtKB:P04271, ECO:0000250|UniProtKB:P50114, ECO:0000269|PubMed:14621986, ECO:0000269|PubMed:15823027, ECO:0000269|PubMed:18949447, ECO:0000269|PubMed:19910580, ECO:0000269|PubMed:20351179}.
|
Rattus norvegicus (Rat)
|
P04632
|
CPNS1_HUMAN
|
MFLVNSFLKGGGGGGGGGGGLGGGLGNVLGGLISGAGGGGGGGGGGGGGGGGGGGGTAMRILGGVISAISEAAAQYNPEPPPPRTHYSNIEANESEEVRQFRRLFAQLAGDDMEVSATELMNILNKVVTRHPDLKTDGFGIDTCRSMVAVMDSDTTGKLGFEEFKYLWNNIKRWQAIYKQFDTDRSGTICSSELPGAFEAAGFHLNEHLYNMIIRRYSDESGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQEWLQLTMYS
| null | null |
positive regulation of cell population proliferation [GO:0008284]; proteolysis [GO:0006508]; regulation of macroautophagy [GO:0016241]
|
calpain complex [GO:0110158]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]; membrane [GO:0016020]; plasma membrane [GO:0005886]
|
calcium ion binding [GO:0005509]; calcium-dependent cysteine-type endopeptidase activity [GO:0004198]
| null |
1.10.238.10;
| null | null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Translocates to the plasma membrane upon calcium binding. {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Essential for embryonic development (By similarity). {ECO:0000250|UniProtKB:O88456}.
|
Homo sapiens (Human)
|
P04633
|
UCP1_RAT
|
MVSSTTSEVQPTMGVKIFSAGVSACLADIITFPLDTAKVRLQIQGEGQASSTIRYKGVLGTITTLAKTEGLPKLYSGLPAGIQRQISFASLRIGLYDTVQEYFSSGRETPASLGSKISAGLMTGGVAVFIGQPTEVVKVRMQAQSHLHGIKPRYTGTYNAYRVIATTESLSTLWKGTTPNLMRNVIINCTELVTYDLMKGALVNHHILADDVPCHLLSALVAGFCTTLLASPVDVVKTRFINSLPGQYPSVPSCAMTMYTKEGPAAFFKGFAPSFLRLGSWNVIMFVCFEQLKKELMKSRQTVDCTT
| null | null |
adaptive thermogenesis [GO:1990845]; brown fat cell differentiation [GO:0050873]; cellular response to cold [GO:0070417]; cellular response to dehydroepiandrosterone [GO:1903495]; cellular response to fatty acid [GO:0071398]; cellular response to hormone stimulus [GO:0032870]; cellular response to reactive oxygen species [GO:0034614]; diet induced thermogenesis [GO:0002024]; generation of precursor metabolites and energy [GO:0006091]; mitochondrial transmembrane transport [GO:1990542]; mitochondrial transport [GO:0006839]; positive regulation of cold-induced thermogenesis [GO:0120162]; positive regulation of metabolic process [GO:0009893]; proton transmembrane transport [GO:1902600]; regulation of reactive oxygen species biosynthetic process [GO:1903426]; regulation of transcription by RNA polymerase II [GO:0006357]; response to cold [GO:0009409]; response to nutrient levels [GO:0031667]; response to temperature stimulus [GO:0009266]
|
mitochondrial envelope [GO:0005740]; mitochondrial inner membrane [GO:0005743]; mitochondrion [GO:0005739]
|
cardiolipin binding [GO:1901612]; GDP binding [GO:0019003]; GTP binding [GO:0005525]; long-chain fatty acid binding [GO:0036041]; oxidative phosphorylation uncoupler activity [GO:0017077]; proton transmembrane transporter activity [GO:0015078]; purine ribonucleotide binding [GO:0032555]; transmembrane transporter activity [GO:0022857]
|
PF00153;
|
1.50.40.10;
|
Mitochondrial carrier (TC 2.A.29) family
|
PTM: May undergo ubiquitin-mediated proteasomal degradation. {ECO:0000269|PubMed:22531154}.; PTM: May undergo sulfenylation upon cold exposure. May increase the sensitivity of UCP1 thermogenic function to the activation by noradrenaline probably through structural effects. {ECO:0000250|UniProtKB:P12242}.
|
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250|UniProtKB:P12242}; Multi-pass membrane protein {ECO:0000269|PubMed:7691596}.
|
CATALYTIC ACTIVITY: Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378; Evidence={ECO:0000269|PubMed:12479871, ECO:0000269|PubMed:22952235};
| null | null | null | null |
FUNCTION: Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and diet variations and more generally to the regulation of energy balance (By similarity). Functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane. However, LCFAs remaining associated with the transporter via their hydrophobic tails, it results in an apparent transport of protons activated by LCFAs (PubMed:12479871, PubMed:16814247, PubMed:22952235). Thereby, dissipates the mitochondrial proton gradient and converts the energy of substrate oxydation into heat instead of ATP. Regulates the production of reactive oxygen species/ROS by mitochondria (By similarity). {ECO:0000250|UniProtKB:P12242, ECO:0000269|PubMed:12479871, ECO:0000269|PubMed:16814247, ECO:0000269|PubMed:22952235}.
|
Rattus norvegicus (Rat)
|
P04634
|
LIPF_RAT
|
MWLLLITSVISTFGGAHGLFGKLGPGNPEANMNISQMITYWGYPCQEYEVVTEDGYILGVYRIPHGKNNSENIGKRPVVYLQHGLIASATNWIANLPNNSLAFMLADAGYDVWLGNSRGNTWSRKNVYYSPDSVEFWAFSFDEMAKYDLPATINFIVQKTGQEKIHYVGHSQGTTIGFIAFSTNPTLAKKIKTFYALAPVATVKYTQSPLKKISFIPTFLFKLMFGKKMFLPHTYFDDFLGTEVCSREVLDLLCSNTLFIFCGFDKKNLNVSRFDVYLGHNPAGTSVQDFLHWAQLVRSGKFQAFNWGSPSQNMLHYNQKTPPEYDVSAMTVPVAVWNGGNDILADPQDVAMLLPKLSNLLFHKEILAYNHLDFIWAMDAPQEVYNEMISMMAED
|
3.1.1.3
| null |
lipid catabolic process [GO:0016042]; malate metabolic process [GO:0006108]
|
extracellular region [GO:0005576]; intracellular membrane-bounded organelle [GO:0043231]; mitochondrion [GO:0005739]
|
lipase activity [GO:0016298]; malate dehydrogenase activity [GO:0016615]; triglyceride lipase activity [GO:0004806]
|
PF04083;
|
3.40.50.1820;
|
AB hydrolase superfamily, Lipase family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P80035}.
|
CATALYTIC ACTIVITY: Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.3; Evidence={ECO:0000269|PubMed:3839077}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-sn-glycerol + H(+); Xref=Rhea:RHEA:39931, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:52333, ChEBI:CHEBI:53753; Evidence={ECO:0000250|UniProtKB:P07098}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39932; Evidence={ECO:0000250|UniProtKB:P07098}; CATALYTIC ACTIVITY: Reaction=1,2,3-trioctanoylglycerol + H2O = 1,2-dioctanoyl-sn-glycerol + H(+) + octanoate; Xref=Rhea:RHEA:40047, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:76978, ChEBI:CHEBI:76979; Evidence={ECO:0000250|UniProtKB:P07098}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40048; Evidence={ECO:0000250|UniProtKB:P07098};
| null | null | null | null |
FUNCTION: Catalyzes the hydrolysis of triacylglycerols to yield free fatty acids, diacylglycerol, monoacylglycerol, and glycerol (PubMed:3839077). Shows a preferential hydrolysis at the sn-3 position of triacylglycerol (By similarity). {ECO:0000250|UniProtKB:P07098, ECO:0000269|PubMed:3839077}.
|
Rattus norvegicus (Rat)
|
P04635
|
LIP_STAHY
|
MKETKHQHTFSIRKSAYGAASVMVASCIFVIGGGVAEANDSTTQTTTPLEVAQTSQQETHTHQTPVTSLHTATPEHVDDSKEATPLPEKAESPKTEVTVQPSSHTQEVPALHKKTQQQPAYKDKTVPESTIASKSVESNKATENEMSPVEHHASNVEKREDRLETNETTPPSVDREFSHKIINNTHVNPKTDGQTNVNVDTKTIDTVSPKDDRIDTAQPKQVDVPKENTTAQNKFTSQASDKKPTVKAAPEAVQNPENPKNKDPFVFVHGFTGFVGEVAAKGENHWGGTKANLRNHLRKAGYETYEASVSALASNHERAVELYYYLKGGRVDYGAAHSEKYGHERYGKTYEGVLKDWKPGHPVHFIGHSMGGQTIRLLEHYLRFGDKAEIAYQQQHGGIISELFKGGQDNMVTSITTIATPHNGTHASDDIGNTPTIRNILYSFAQMSSHLGTIDFGMDHWGFKRKDGESLTDYNKRIAESKIWDSEDTGLYDLTREGAEKINQKTELNPNIYYKTYTGVATHETQLGKHIADLGMEFTKILTGNYIGSVDDILWRPNDGLVSEISSQHPSDEKNISVDENSELHKGTWQVMPTMKGWDHSDFIGNDALDTKHSAIELTNFYHSISDYLMRIEKAESTKNA
|
3.1.1.3; 3.1.1.32
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:2611229};
|
lipid catabolic process [GO:0016042]; phosphatidylcholine catabolic process [GO:0034638]; triglyceride catabolic process [GO:0019433]
|
extracellular region [GO:0005576]
|
1-acyl-2-lysophosphatidylserine acylhydrolase activity [GO:0052740]; calcium ion binding [GO:0005509]; phosphatidylserine 1-acylhydrolase activity [GO:0052739]; phospholipase A1 activity [GO:0008970]; phospholipase activity [GO:0004620]; triglyceride lipase activity [GO:0004806]
|
PF04650;
|
3.40.50.1820;
|
AB hydrolase superfamily, Lipase family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2611229}.
|
CATALYTIC ACTIVITY: Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.3; Evidence={ECO:0000269|PubMed:2611229}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:18689, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:57643, ChEBI:CHEBI:57875; EC=3.1.1.32; Evidence={ECO:0000269|PubMed:2611229};
| null | null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH around 9. {ECO:0000269|PubMed:2611229};
| null |
FUNCTION: Has a broad substrate specificity hydrolyzing a variety of triglycerides and phosphatidylcholines. {ECO:0000269|PubMed:2611229}.
|
Staphylococcus hyicus
|
P04636
|
MDHM_RAT
|
MLSALARPVGAALRRSFSTSAQNNAKVAVLGASGGIGQPLSLLLKNSPLVSRLTLYDIAHTPGVAADLSHIETRANVKGYLGPEQLPDCLKGCDVVVIPAGVPRKPGMTRDDLFNTNATIVATLTAACAQHCPEAMICIISNPVNSTIPITAEVFKKHGVYNPNKIFGVTTLDIVRANTFVAELKGLDPARVNVPVIGGHAGKTIIPLISQCTPKVDFPQDQLATLTGRIQEAGTEVVKAKAGAGSATLSMAYAGARFVFSLVDAMNGKEGVIECSFVQSKETECTYFSTPLLLGKKGLEKNLGIGKITPFEEKMIAEAIPELKASIKKGEDFVKNMK
|
1.1.1.37
| null |
aerobic respiration [GO:0009060]; gluconeogenesis [GO:0006094]; malate metabolic process [GO:0006108]; NADH metabolic process [GO:0006734]; oxaloacetate metabolic process [GO:0006107]; tricarboxylic acid cycle [GO:0006099]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; membrane [GO:0016020]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
|
L-malate dehydrogenase activity [GO:0030060]; malate dehydrogenase (NADP+) activity [GO:0046554]; malate dehydrogenase activity [GO:0016615]; protein homodimerization activity [GO:0042803]; protein self-association [GO:0043621]
|
PF02866;PF00056;
|
3.90.110.10;3.40.50.720;
|
LDH/MDH superfamily, MDH type 1 family
|
PTM: Acetylation is enhanced after treatment either with trichostin A (TCA) or with nicotinamide (NAM) with the appearance of tri- and tetraacetylations. Glucose also increases acetylation. {ECO:0000250|UniProtKB:P40926}.
|
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:24098488}.
|
CATALYTIC ACTIVITY: Reaction=(S)-malate + NAD(+) = H(+) + NADH + oxaloacetate; Xref=Rhea:RHEA:21432, ChEBI:CHEBI:15378, ChEBI:CHEBI:15589, ChEBI:CHEBI:16452, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.37; Evidence={ECO:0000255|PROSITE-ProRule:PRU10004};
| null | null | null | null | null |
Rattus norvegicus (Rat)
|
P04637
|
P53_HUMAN
|
MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPGGSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD
| null |
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:14534297, ECO:0000269|PubMed:16793544, ECO:0000269|PubMed:17015838, ECO:0000269|PubMed:18650397, ECO:0000269|PubMed:19515728, ECO:0000269|PubMed:20142040, ECO:0000269|PubMed:20364130}; Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:14534297, ECO:0000269|PubMed:16793544, ECO:0000269|PubMed:17015838, ECO:0000269|PubMed:18650397, ECO:0000269|PubMed:19515728, ECO:0000269|PubMed:20142040, ECO:0000269|PubMed:20364130};
|
autophagy [GO:0006914]; B cell lineage commitment [GO:0002326]; bone marrow development [GO:0048539]; cardiac muscle cell apoptotic process [GO:0010659]; cardiac septum morphogenesis [GO:0060411]; cellular response to actinomycin D [GO:0072717]; cellular response to gamma radiation [GO:0071480]; cellular response to glucose starvation [GO:0042149]; cellular response to hypoxia [GO:0071456]; cellular response to ionizing radiation [GO:0071479]; cellular response to UV [GO:0034644]; cellular response to UV-C [GO:0071494]; cellular response to xenobiotic stimulus [GO:0071466]; cellular senescence [GO:0090398]; cerebellum development [GO:0021549]; chromosome organization [GO:0051276]; circadian behavior [GO:0048512]; determination of adult lifespan [GO:0008340]; DNA damage response [GO:0006974]; DNA damage response, signal transduction by p53 class mediator [GO:0030330]; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977]; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator [GO:0006978]; double-strand break repair [GO:0006302]; embryonic organ development [GO:0048568]; entrainment of circadian clock by photoperiod [GO:0043153]; ER overload response [GO:0006983]; fibroblast proliferation [GO:0048144]; gastrulation [GO:0007369]; glial cell proliferation [GO:0014009]; glucose catabolic process to lactate via pyruvate [GO:0019661]; hematopoietic progenitor cell differentiation [GO:0002244]; hematopoietic stem cell differentiation [GO:0060218]; in utero embryonic development [GO:0001701]; intrinsic apoptotic signaling pathway [GO:0097193]; intrinsic apoptotic signaling pathway by p53 class mediator [GO:0072332]; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:0042771]; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059]; intrinsic apoptotic signaling pathway in response to hypoxia [GO:1990144]; mitochondrial DNA repair [GO:0043504]; mitophagy [GO:0000423]; mitotic G1 DNA damage checkpoint signaling [GO:0031571]; mRNA transcription [GO:0009299]; multicellular organism growth [GO:0035264]; necroptotic process [GO:0070266]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cell growth [GO:0030308]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of DNA replication [GO:0008156]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of fibroblast proliferation [GO:0048147]; negative regulation of G1 to G0 transition [GO:1903451]; negative regulation of glial cell proliferation [GO:0060253]; negative regulation of glucose catabolic process to lactate via pyruvate [GO:1904024]; negative regulation of helicase activity [GO:0051097]; negative regulation of miRNA processing [GO:1903799]; negative regulation of mitophagy [GO:1901525]; negative regulation of neuroblast proliferation [GO:0007406]; negative regulation of pentose-phosphate shunt [GO:1905856]; negative regulation of proteolysis [GO:0045861]; negative regulation of reactive oxygen species metabolic process [GO:2000378]; negative regulation of stem cell proliferation [GO:2000647]; negative regulation of telomere maintenance via telomerase [GO:0032211]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512]; neuroblast proliferation [GO:0007405]; neuron apoptotic process [GO:0051402]; nucleotide-excision repair [GO:0006289]; oligodendrocyte apoptotic process [GO:0097252]; oxidative stress-induced premature senescence [GO:0090403]; positive regulation of apoptotic process [GO:0043065]; positive regulation of cardiac muscle cell apoptotic process [GO:0010666]; positive regulation of cellular senescence [GO:2000774]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of execution phase of apoptosis [GO:1900119]; positive regulation of gene expression [GO:0010628]; positive regulation of intrinsic apoptotic signaling pathway [GO:2001244]; positive regulation of miRNA transcription [GO:1902895]; positive regulation of mitochondrial membrane permeability [GO:0035794]; positive regulation of neuron apoptotic process [GO:0043525]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of programmed necrotic cell death [GO:0062100]; positive regulation of reactive oxygen species metabolic process [GO:2000379]; positive regulation of release of cytochrome c from mitochondria [GO:0090200]; positive regulation of RNA polymerase II transcription preinitiation complex assembly [GO:0045899]; positive regulation of thymocyte apoptotic process [GO:0070245]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein import into nucleus [GO:0006606]; protein localization [GO:0008104]; protein stabilization [GO:0050821]; protein tetramerization [GO:0051262]; protein-containing complex assembly [GO:0065003]; Ras protein signal transduction [GO:0007265]; reactive oxygen species metabolic process [GO:0072593]; regulation of apoptotic process [GO:0042981]; regulation of cell cycle [GO:0051726]; regulation of cell cycle G2/M phase transition [GO:1902749]; regulation of DNA damage response, signal transduction by p53 class mediator [GO:0043516]; regulation of DNA-templated transcription [GO:0006355]; regulation of fibroblast apoptotic process [GO:2000269]; regulation of intrinsic apoptotic signaling pathway by p53 class mediator [GO:1902253]; regulation of mitochondrial membrane permeability involved in apoptotic process [GO:1902108]; regulation of tissue remodeling [GO:0034103]; regulation of transcription by RNA polymerase II [GO:0006357]; release of cytochrome c from mitochondria [GO:0001836]; replicative senescence [GO:0090399]; response to antibiotic [GO:0046677]; response to gamma radiation [GO:0010332]; response to inorganic substance [GO:0010035]; response to ischemia [GO:0002931]; response to salt stress [GO:0009651]; response to X-ray [GO:0010165]; rRNA transcription [GO:0009303]; signal transduction by p53 class mediator [GO:0072331]; somitogenesis [GO:0001756]; stem cell proliferation [GO:0072089]; T cell differentiation in thymus [GO:0033077]; T cell lineage commitment [GO:0002360]; T cell proliferation involved in immune response [GO:0002309]; thymocyte apoptotic process [GO:0070242]; transcription initiation-coupled chromatin remodeling [GO:0045815]; transforming growth factor beta receptor signaling pathway [GO:0007179]; tumor necrosis factor-mediated signaling pathway [GO:0033209]; type II interferon-mediated signaling pathway [GO:0060333]; viral process [GO:0016032]
|
centrosome [GO:0005813]; chromatin [GO:0000785]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; endoplasmic reticulum [GO:0005783]; germ cell nucleus [GO:0043073]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]; nuclear matrix [GO:0016363]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; PML body [GO:0016605]; protein-containing complex [GO:0032991]; replication fork [GO:0005657]; site of double-strand break [GO:0035861]; transcription regulator complex [GO:0005667]; transcription repressor complex [GO:0017053]
|
14-3-3 protein binding [GO:0071889]; ATP-dependent DNA/DNA annealing activity [GO:0036310]; chromatin binding [GO:0003682]; cis-regulatory region sequence-specific DNA binding [GO:0000987]; copper ion binding [GO:0005507]; core promoter sequence-specific DNA binding [GO:0001046]; disordered domain specific binding [GO:0097718]; DNA binding [GO:0003677]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; enzyme binding [GO:0019899]; general transcription initiation factor binding [GO:0140296]; histone deacetylase binding [GO:0042826]; histone deacetylase regulator activity [GO:0035033]; identical protein binding [GO:0042802]; MDM2/MDM4 family protein binding [GO:0097371]; molecular function activator activity [GO:0140677]; mRNA 3'-UTR binding [GO:0003730]; p53 binding [GO:0002039]; promoter-specific chromatin binding [GO:1990841]; protease binding [GO:0002020]; protein heterodimerization activity [GO:0046982]; protein phosphatase 2A binding [GO:0051721]; protein self-association [GO:0043621]; protein-folding chaperone binding [GO:0051087]; receptor tyrosine kinase binding [GO:0030971]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; RNA polymerase II-specific DNA-binding transcription factor binding [GO:0061629]; TFIID-class transcription factor complex binding [GO:0001094]; transcription cis-regulatory region binding [GO:0000976]; ubiquitin protein ligase binding [GO:0031625]; zinc ion binding [GO:0008270]
|
PF00870;PF08563;PF07710;PF18521;
|
2.60.40.720;6.10.50.20;4.10.170.10;
|
P53 family
|
PTM: Acetylation of Lys-382 by CREBBP enhances transcriptional activity (PubMed:10656795, PubMed:15448695, PubMed:20228809, PubMed:23431171). Acetylation of Lys-382 by EP300 (PubMed:10656795, PubMed:15448695, PubMed:20228809, PubMed:23431171). Deacetylation of Lys-382 by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence (PubMed:10656795, PubMed:15448695, PubMed:20228809, PubMed:23431171). Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner (PubMed:10656795, PubMed:15448695, PubMed:20228809, PubMed:23431171, PubMed:29681526). Acetylation at Lys-381 increases stability (PubMed:29474172). Deacetylation at Lys-381 by SIRT6 decreases its stability, thereby regulating cell senescence (PubMed:29474172). Acetylated at Lys-120 by KAT5, KAT6A and KAT8; regulating its ability to induce proapoptotic program (PubMed:17189187, PubMed:19854137, PubMed:23431171). {ECO:0000269|PubMed:10656795, ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:19854137, ECO:0000269|PubMed:20228809, ECO:0000269|PubMed:23431171, ECO:0000269|PubMed:29474172, ECO:0000269|PubMed:29681526}.; PTM: Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylated by HIPK1 (By similarity). Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter. Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2 (PubMed:31527692, PubMed:10951572). Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2. Phosphorylated on Ser-20 by PLK3 in response to reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis. Phosphorylated on Thr-55 by TAF1, which promotes MDM2-mediated degradation. Phosphorylated on Ser-33 by CDK7 in a CAK complex in response to DNA damage. Phosphorylated on Ser-46 by HIPK2 upon UV irradiation. Phosphorylation on Ser-46 is required for acetylation by CREBBP. Phosphorylated on Ser-392 following UV but not gamma irradiation. Phosphorylated by NUAK1 at Ser-15 and Ser-392; was initially thought to be mediated by STK11/LKB1 but it was later shown that it is indirect and that STK11/LKB1-dependent phosphorylation is probably mediated by downstream NUAK1 (PubMed:21317932). It is unclear whether AMP directly mediates phosphorylation at Ser-15. Phosphorylated on Thr-18 by isoform 1 and isoform 2 of VRK2. Phosphorylation on Thr-18 by isoform 2 of VRK2 results in a reduction in ubiquitination by MDM2 and an increase in acetylation by EP300. Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at Ser-15, Ser-33 and Ser-46, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes. Phosphorylated by DYRK2 at Ser-46 in response to genotoxic stress. Phosphorylated at Ser-315 and Ser-392 by CDK2 in response to DNA-damage. Phosphorylation at Ser-15 is required for interaction with DDX3X and gamma-tubulin (PubMed:28842590). {ECO:0000250, ECO:0000269|PubMed:10570149, ECO:0000269|PubMed:10606744, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10951572, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:11447225, ECO:0000269|PubMed:11546806, ECO:0000269|PubMed:11551930, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11780126, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:14702041, ECO:0000269|PubMed:15053879, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:16377624, ECO:0000269|PubMed:16704422, ECO:0000269|PubMed:1705009, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:17967874, ECO:0000269|PubMed:18022393, ECO:0000269|PubMed:20041275, ECO:0000269|PubMed:20124405, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:2141171, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:28842590, ECO:0000269|PubMed:31527692, ECO:0000269|PubMed:9372954}.; PTM: Dephosphorylated by PP2A-PPP2R5C holoenzyme at Thr-55. SV40 small T antigen inhibits the dephosphorylation by the AC form of PP2A.; PTM: May be O-glycosylated in the C-terminal basic region. Studied in EB-1 cell line. {ECO:0000269|PubMed:8632915}.; PTM: Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal degradation (PubMed:10722742, PubMed:12810724, PubMed:15340061, PubMed:17170702, PubMed:19880522, PubMed:29681526). Ubiquitinated by RFWD3, which works in cooperation with MDM2 and may catalyze the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome (PubMed:10722742, PubMed:12810724, PubMed:20173098). Ubiquitinated by MKRN1 at Lys-291 and Lys-292, which leads to proteasomal degradation (PubMed:19536131). Deubiquitinated by USP10, leading to its stabilization (PubMed:20096447). Ubiquitinated by TRIM24, RFFL, RNF34 and RNF125, which leads to proteasomal degradation (PubMed:19556538). Ubiquitination by TOPORS induces degradation (PubMed:19473992). Deubiquitination by USP7, leading to stabilization (PubMed:15053880). Isoform 4 is monoubiquitinated in an MDM2-independent manner (PubMed:15340061). Ubiquitinated by COP1, which leads to proteasomal degradation (PubMed:19837670). Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (PubMed:25732823). Polyubiquitinated by C10orf90/FATS, polyubiquitination is 'Lys-48'-linkage independent and non-proteolytic, leading to TP53 stabilization (By similarity). Polyubiquitinated by MUL1 at Lys-24 which leads to proteasomal degradation (PubMed:21597459). Deubiquitinated by USP3, leading to stabilization (PubMed:28807825). Ubiquitinated by MSL2, promoting its cytoplasmic localization (PubMed:19033443). {ECO:0000250|UniProtKB:P02340, ECO:0000269|PubMed:10722742, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17170702, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:19033443, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19536131, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:25591766, ECO:0000269|PubMed:25732823, ECO:0000269|PubMed:28807825, ECO:0000269|PubMed:29681526}.; PTM: Monomethylated at Lys-372 by SETD7, leading to stabilization and increased transcriptional activation (PubMed:15525938, PubMed:16415881). Monomethylated at Lys-370 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity (PubMed:17108971). Lys-372 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-370 (PubMed:17108971). Dimethylated at Lys-373 by EHMT1 and EHMT2 (PubMed:20118233). Monomethylated at Lys-382 by KMT5A, promoting interaction with L3MBTL1 and leading to repress transcriptional activity (PubMed:17707234). Dimethylation at Lys-370 and Lys-382 diminishes p53 ubiquitination, through stabilizing association with the methyl reader PHF20 (PubMed:22864287). Demethylation of dimethylated Lys-370 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (PubMed:17805299). Monomethylated at Arg-333 and dimethylated at Arg-335 and Arg-337 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (PubMed:19011621). {ECO:0000269|PubMed:15525938, ECO:0000269|PubMed:16415881, ECO:0000269|PubMed:17108971, ECO:0000269|PubMed:17707234, ECO:0000269|PubMed:17805299, ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:20118233, ECO:0000269|PubMed:22864287}.; PTM: Sumoylated with SUMO1. Sumoylated at Lys-386 by UBC9. {ECO:0000269|PubMed:11124955, ECO:0000269|PubMed:22214662, ECO:0000269|Ref.37}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17170702, ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:19033443, ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:26634371}. Nucleus {ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17170702, ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:26634371}. Nucleus, PML body {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12810724}. Endoplasmic reticulum {ECO:0000269|PubMed:17170702}. Mitochondrion matrix {ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:25168243, ECO:0000269|PubMed:27323408}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:28842590}. Note=Recruited into PML bodies together with CHEK2 (PubMed:12810724). Translocates to mitochondria upon oxidative stress (PubMed:22726440). Translocates to mitochondria in response to mitomycin C treatment (PubMed:27323408). Competitive inhibition of TP53 interaction with HSPA9/MOT-2 by UBXN2A results in increased protein abundance and subsequent translocation of TP53 to the nucleus (PubMed:24625977). {ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:27323408}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000269|PubMed:23752197}. Cytoplasm. Note=Predominantly nuclear but localizes to the cytoplasm when expressed with isoform 4.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the cytoplasm.; SUBCELLULAR LOCATION: [Isoform 3]: Nucleus. Cytoplasm. Note=Localized in the nucleus in most cells but found in the cytoplasm in some cells.; SUBCELLULAR LOCATION: [Isoform 4]: Nucleus. Cytoplasm. Note=Predominantly nuclear but translocates to the cytoplasm following cell stress.; SUBCELLULAR LOCATION: [Isoform 7]: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the cytoplasm.; SUBCELLULAR LOCATION: [Isoform 8]: Nucleus. Cytoplasm. Note=Localized in both nucleus and cytoplasm in most cells. In some cells, forms foci in the nucleus that are different from nucleoli.; SUBCELLULAR LOCATION: [Isoform 9]: Cytoplasm.
| null | null | null | null | null |
FUNCTION: Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17189187, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:9840937). Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:9840937). One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (PubMed:12524540, PubMed:17189187). Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492). {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:17317671, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24051492, ECO:0000269|PubMed:24652652, ECO:0000269|PubMed:9840937}.
|
Homo sapiens (Human)
|
P04638
|
APOA2_RAT
|
MKLLAMVALLVTICSLEGALVRRQAAETDVQTLFSQYLQSLTDYGKDLMEKAQPSEIQNQAKAYFQNAQERLTPFVQRTGTNLMDFLSRLMSPEEKPAPAAK
| null | null |
animal organ regeneration [GO:0031100]; cholesterol efflux [GO:0033344]; cholesterol homeostasis [GO:0042632]; cholesterol metabolic process [GO:0008203]; cholesterol transport [GO:0030301]; diacylglycerol catabolic process [GO:0046340]; high-density lipoprotein particle assembly [GO:0034380]; high-density lipoprotein particle clearance [GO:0034384]; high-density lipoprotein particle remodeling [GO:0034375]; lipid transport [GO:0006869]; lipoprotein metabolic process [GO:0042157]; low-density lipoprotein particle remodeling [GO:0034374]; negative regulation of cholesterol import [GO:0060621]; negative regulation of cholesterol transport [GO:0032375]; negative regulation of cytokine production involved in immune response [GO:0002719]; negative regulation of lipid catabolic process [GO:0050995]; negative regulation of very-low-density lipoprotein particle remodeling [GO:0010903]; phosphatidylcholine biosynthetic process [GO:0006656]; phospholipid catabolic process [GO:0009395]; phospholipid efflux [GO:0033700]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of lipid catabolic process [GO:0050996]; positive regulation of phagocytosis [GO:0050766]; protein stabilization [GO:0050821]; regulation of intestinal cholesterol absorption [GO:0030300]; regulation of protein stability [GO:0031647]; response to estrogen [GO:0043627]; response to glucocorticoid [GO:0051384]; response to glucose [GO:0009749]; response to xenobiotic stimulus [GO:0009410]; reverse cholesterol transport [GO:0043691]; triglyceride-rich lipoprotein particle remodeling [GO:0034370]
|
blood microparticle [GO:0072562]; chylomicron [GO:0042627]; extracellular space [GO:0005615]; high-density lipoprotein particle [GO:0034364]; spherical high-density lipoprotein particle [GO:0034366]; very-low-density lipoprotein particle [GO:0034361]
|
apolipoprotein receptor binding [GO:0034190]; cholesterol binding [GO:0015485]; cholesterol transfer activity [GO:0120020]; enzyme binding [GO:0019899]; heat shock protein binding [GO:0031072]; high-density lipoprotein particle binding [GO:0008035]; high-density lipoprotein particle receptor binding [GO:0070653]; lipase inhibitor activity [GO:0055102]; lipid binding [GO:0008289]; lipid transporter activity [GO:0005319]; phosphatidylcholine binding [GO:0031210]; phosphatidylcholine-sterol O-acyltransferase activator activity [GO:0060228]; phospholipid binding [GO:0005543]; protein heterodimerization activity [GO:0046982]; protein homodimerization activity [GO:0042803]; signaling receptor binding [GO:0005102]
|
PF04711;
|
6.10.250.100;
|
Apolipoprotein A2 family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02652}.
| null | null | null | null | null |
FUNCTION: May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism.
|
Rattus norvegicus (Rat)
|
P04639
|
APOA1_RAT
|
MKAAVLAVALVFLTGCQAWEFWQQDEPQSQWDRVKDFATVYVDAVKDSGRDYVSQFESSTLGKQLNLNLLDNWDTLGSTVGRLQEQLGPVTQEFWANLEKETDWLRNEMNKDLENVKQKMQPHLDEFQEKWNEEVEAYRQKLEPLGTELHKNAKEMQRHLKVVAEEFRDRMRVNADALRAKFGLYSDQMRENLAQRLTEIKNHPTLIEYHTKASDHLKTLGEKAKPALDDLGQGLMPVLEAWKAKIMSMIDEAKKKLNA
| null | null |
acylglycerol homeostasis [GO:0055090]; adrenal gland development [GO:0030325]; animal organ regeneration [GO:0031100]; blood vessel endothelial cell migration [GO:0043534]; cholesterol biosynthetic process [GO:0006695]; cholesterol efflux [GO:0033344]; cholesterol homeostasis [GO:0042632]; cholesterol import [GO:0070508]; cholesterol metabolic process [GO:0008203]; cholesterol transport [GO:0030301]; endothelial cell proliferation [GO:0001935]; G protein-coupled receptor signaling pathway [GO:0007186]; glucocorticoid metabolic process [GO:0008211]; high-density lipoprotein particle assembly [GO:0034380]; high-density lipoprotein particle remodeling [GO:0034375]; integrin-mediated signaling pathway [GO:0007229]; lipid storage [GO:0019915]; lipoprotein biosynthetic process [GO:0042158]; negative chemotaxis [GO:0050919]; negative regulation of cell adhesion molecule production [GO:0060354]; negative regulation of cytokine production involved in immune response [GO:0002719]; negative regulation of heterotypic cell-cell adhesion [GO:0034115]; negative regulation of inflammatory response [GO:0050728]; negative regulation of interleukin-1 beta production [GO:0032691]; negative regulation of response to cytokine stimulus [GO:0060761]; negative regulation of tumor necrosis factor-mediated signaling pathway [GO:0010804]; negative regulation of very-low-density lipoprotein particle remodeling [GO:0010903]; peripheral nervous system axon regeneration [GO:0014012]; phosphatidylcholine biosynthetic process [GO:0006656]; phospholipid efflux [GO:0033700]; phospholipid homeostasis [GO:0055091]; phospholipid metabolic process [GO:0006644]; phospholipid transport [GO:0015914]; positive regulation of cholesterol efflux [GO:0010875]; positive regulation of cholesterol metabolic process [GO:0090205]; positive regulation of phagocytosis [GO:0050766]; positive regulation of phospholipid efflux [GO:1902995]; positive regulation of Rho protein signal transduction [GO:0035025]; positive regulation of stress fiber assembly [GO:0051496]; positive regulation of substrate adhesion-dependent cell spreading [GO:1900026]; protein stabilization [GO:0050821]; regulation of Cdc42 protein signal transduction [GO:0032489]; regulation of intestinal cholesterol absorption [GO:0030300]; regulation of protein phosphorylation [GO:0001932]; response to estrogen [GO:0043627]; response to nutrient [GO:0007584]; response to xenobiotic stimulus [GO:0009410]; reverse cholesterol transport [GO:0043691]; triglyceride homeostasis [GO:0070328]; vitamin transport [GO:0051180]
|
cell surface [GO:0009986]; chylomicron [GO:0042627]; cytoplasmic vesicle [GO:0031410]; discoidal high-density lipoprotein particle [GO:0034365]; endocytic vesicle [GO:0030139]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; extracellular vesicle [GO:1903561]; high-density lipoprotein particle [GO:0034364]; intermediate-density lipoprotein particle [GO:0034363]; low-density lipoprotein particle [GO:0034362]; spherical high-density lipoprotein particle [GO:0034366]; very-low-density lipoprotein particle [GO:0034361]
|
amyloid-beta binding [GO:0001540]; apolipoprotein A-I receptor binding [GO:0034191]; apolipoprotein receptor binding [GO:0034190]; chemorepellent activity [GO:0045499]; cholesterol binding [GO:0015485]; cholesterol transfer activity [GO:0120020]; enzyme binding [GO:0019899]; heat shock protein binding [GO:0031072]; high-density lipoprotein particle binding [GO:0008035]; high-density lipoprotein particle receptor binding [GO:0070653]; identical protein binding [GO:0042802]; lipase inhibitor activity [GO:0055102]; lipid binding [GO:0008289]; lipid transporter activity [GO:0005319]; lipoprotein particle binding [GO:0071813]; phosphatidylcholine-sterol O-acyltransferase activator activity [GO:0060228]; phospholipid binding [GO:0005543]; protein homodimerization activity [GO:0042803]; signaling receptor binding [GO:0005102]
|
PF01442;
|
1.20.5.20;6.10.140.380;1.20.120.20;
|
Apolipoprotein A1/A4/E family
|
PTM: Glycosylated. {ECO:0000250}.; PTM: Palmitoylated. {ECO:0000250}.; PTM: Phosphorylation sites are present in the extracellular medium. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility.
|
Rattus norvegicus (Rat)
|
P04640
|
OSTCN_RAT
|
MRTLSLLTLLALTAFCLSDLAGAKPSDSESDKAFMSKQEGSKVVNRLRRYLNNGLGAPAPYPDPLEPHREVCELNPNCDELADHIGFQDAYKRIYGTTV
| null | null |
biomineral tissue development [GO:0031214]; bone development [GO:0060348]; brain development [GO:0007420]; cellular response to BMP stimulus [GO:0071773]; cellular response to growth factor stimulus [GO:0071363]; cellular response to insulin stimulus [GO:0032869]; cellular response to vitamin D [GO:0071305]; cellular response to zinc ion starvation [GO:0034224]; cognition [GO:0050890]; dephosphorylation [GO:0016311]; glucose homeostasis [GO:0042593]; learning or memory [GO:0007611]; negative regulation of bone development [GO:1903011]; ossification [GO:0001503]; osteoblast development [GO:0002076]; osteoblast differentiation [GO:0001649]; positive regulation of neurotransmitter secretion [GO:0001956]; regulation of bone mineralization [GO:0030500]; regulation of cellular response to insulin stimulus [GO:1900076]; regulation of testosterone biosynthetic process [GO:2000224]; response to activity [GO:0014823]; response to estrogen [GO:0043627]; response to ethanol [GO:0045471]; response to glucocorticoid [GO:0051384]; response to gravity [GO:0009629]; response to hydroxyisoflavone [GO:0033594]; response to inorganic substance [GO:0010035]; response to insulin [GO:0032868]; response to macrophage colony-stimulating factor [GO:0036005]; response to mechanical stimulus [GO:0009612]; response to nutrient levels [GO:0031667]; response to organic cyclic compound [GO:0014070]; response to testosterone [GO:0033574]; response to vitamin D [GO:0033280]; response to vitamin K [GO:0032571]; response to xenobiotic stimulus [GO:0009410]; response to zinc ion [GO:0010043]; stem cell differentiation [GO:0048863]; type B pancreatic cell proliferation [GO:0044342]
|
cell projection [GO:0042995]; cytoplasm [GO:0005737]; dendrite [GO:0030425]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; perikaryon [GO:0043204]; vesicle [GO:0031982]
|
calcium ion binding [GO:0005509]; hormone activity [GO:0005179]; hydroxyapatite binding [GO:0046848]; structural constituent of bone [GO:0008147]
| null | null |
Osteocalcin/matrix Gla protein family
|
PTM: Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation by GGCX. These residues are essential for the binding of calcium (By similarity). Decarboxylation promotes the hormone activity (By similarity). {ECO:0000250|UniProtKB:P86546, ECO:0000255|PROSITE-ProRule:PRU00463}.
|
SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P86546}.
| null | null | null | null | null |
FUNCTION: The carboxylated form is one of the main organic components of the bone matrix, which constitutes 1-2% of the total bone protein: it acts as a negative regulator of bone formation and is required to limit bone formation without impairing bone resorption or mineralization. The carboxylated form binds strongly to apatite and calcium. {ECO:0000250|UniProtKB:P86546}.; FUNCTION: The uncarboxylated form acts as a hormone secreted by osteoblasts, which regulates different cellular processes, such as energy metabolism, male fertility and brain development. Regulates of energy metabolism by acting as a hormone favoring pancreatic beta-cell proliferation, insulin secretion and sensitivity and energy expenditure. Uncarboxylated osteocalcin hormone also promotes testosterone production in the testes: acts as a ligand for G protein-coupled receptor GPRC6A at the surface of Leydig cells, initiating a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner. Also acts as a regulator of brain development: osteocalcin hormone crosses the blood-brain barrier and acts as a ligand for GPR158 on neurons, initiating a signaling response that prevents neuronal apoptosis in the hippocampus, favors the synthesis of all monoamine neurotransmitters and inhibits that of gamma-aminobutyric acid (GABA). Osteocalcin also crosses the placenta during pregnancy and maternal osteocalcin is required for fetal brain development. {ECO:0000250|UniProtKB:P86546}.
|
Rattus norvegicus (Rat)
|
P04642
|
LDHA_RAT
|
MAALKDQLIVNLLKEEQVPQNKITVVGVGAVGMACAISILMKDLADELALVDVIEDKLKGEMMDLQHGSLFLKTPKIVSSKDYSVTANSKLVIITAGARQQEGESRLNLVQRNVNIFKFIIPNVVKYSPQCKLLIVSNPVDILTYVAWKISGFPKNRVIGSGCNLDSARFRYLMGERLGVHPLSCHGWVLGEHGDSSVPVWSGVNVAGVSLKSLNPQLGTDADKEQWKDVHKQVVDSAYEVIKLKGYTSWAIGLSVADLAESIMKNLRRVHPISTMIKGLYGIKEDVFLSVPCILGQNGISDVVKVTLTPDEEARLKKSADTLWGIQKELQF
|
1.1.1.27
| null |
cellular response to extracellular stimulus [GO:0031668]; glucose catabolic process to lactate via pyruvate [GO:0019661]; lactate metabolic process [GO:0006089]; liver development [GO:0001889]; NAD metabolic process [GO:0019674]; positive regulation of apoptotic process [GO:0043065]; pyruvate catabolic process [GO:0042867]; pyruvate metabolic process [GO:0006090]; response to cAMP [GO:0051591]; response to estrogen [GO:0043627]; response to glucose [GO:0009749]; response to hydrogen peroxide [GO:0042542]; response to hypoxia [GO:0001666]; response to nutrient [GO:0007584]; response to organic cyclic compound [GO:0014070]; response to xenobiotic stimulus [GO:0009410]; skeletal muscle tissue development [GO:0007519]
|
cytosol [GO:0005829]; mitochondrion [GO:0005739]; oxidoreductase complex [GO:1990204]; sperm fibrous sheath [GO:0035686]
|
identical protein binding [GO:0042802]; kinase binding [GO:0019900]; L-lactate dehydrogenase activity [GO:0004459]; lactate dehydrogenase activity [GO:0004457]; NAD binding [GO:0051287]
|
PF02866;PF00056;
|
3.90.110.10;3.40.50.720;
|
LDH/MDH superfamily, LDH family
|
PTM: ISGylated. {ECO:0000250|UniProtKB:P00338}.
|
SUBCELLULAR LOCATION: Cytoplasm.
|
CATALYTIC ACTIVITY: Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate; Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27; Evidence={ECO:0000250|UniProtKB:P00338}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23445; Evidence={ECO:0000250|UniProtKB:P00338}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23446; Evidence={ECO:0000250|UniProtKB:P00338};
| null |
PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1. {ECO:0000250|UniProtKB:P00338}.
| null | null |
FUNCTION: Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000250|UniProtKB:P00338}.
|
Rattus norvegicus (Rat)
|
P04653
|
CASA1_SHEEP
|
MKLLILTCLVAVALARPKHPIKHQGLSSEVLNENLLRFVVAPFPEVFRKENINELSKDIGSESIEDQAMEDAKQMKAGSSSSSEEIVPNSAEQKYIQKEDVPSERYLGYLEQLLRLKKYNVPQLEIVPKSAEEQLHSMKEGNPAHQKQPMIAVNQELAYFYPQLFRQFYQLDAYPSGAWYYLPLGTQYTDAPSFSDIPNPIGSENSGKITMPLW
| null | null |
response to 11-deoxycorticosterone [GO:1903496]; response to dehydroepiandrosterone [GO:1903494]; response to estradiol [GO:0032355]; response to progesterone [GO:0032570]
|
extracellular space [GO:0005615]
| null |
PF00363;
| null |
Alpha-casein family
| null |
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Important role in the capacity of milk to transport calcium phosphate.
|
Ovis aries (Sheep)
|
P04657
|
CYC1_DROME
|
MGSGDAENGKKIFVQKCAQCHTYEVGGKHKVGPNLGGVVGRKCGTAAGYKYTDANIKKGVTWTEGNLDEYLKDPKKYIPGTKMVFAGLKKAEERADLIAFLKSNK
| null | null |
mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]; mitochondrial electron transport, ubiquinol to cytochrome c [GO:0006122]; oxidative phosphorylation [GO:0006119]; regulation of compound eye retinal cell programmed cell death [GO:0046669]; sperm individualization [GO:0007291]
|
cytosol [GO:0005829]; mitochondrial intermembrane space [GO:0005758]; mitochondrion [GO:0005739]; respirasome [GO:0070469]
|
cysteine-type endopeptidase activator activity involved in apoptotic process [GO:0008656]; electron transfer activity [GO:0009055]; heme binding [GO:0020037]; metal ion binding [GO:0046872]
|
PF00034;
|
1.10.760.10;
|
Cytochrome c family
|
PTM: Binds 1 heme c group covalently per subunit.
|
SUBCELLULAR LOCATION: Mitochondrion intermembrane space. Note=Loosely associated with the inner membrane.
| null | null | null | null | null |
FUNCTION: Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.
|
Drosophila melanogaster (Fruit fly)
|
P04670
|
URIC1_SOYBN
|
MAQQEVVEGFKFEQRHGKERVRVARVWKTRQGQHFIVEWRVGITLFSDCVNSYLRDDNSDIVATDTMKNTVYAKAKECSDILSAEEFAILLAKHFVSFYQKVTGAIVNIVEKPWERVTVDGQPHEHGFKLGSEKHTTEAIVQKSGSLQLTSGIEGLSVLKTTQSGFVNFIRDKYTALPDTRERMVATEVTALWRYSYESLYSLPQKPLYFTEKYQEVKKVLADTFFGPPKGGVYSPSVQNTLYLMAKATLNRFPDIAYVSLKLPNLHFIPVNISNQDGPIVKFEDDVYLPTDEPHGSIQASLSRLWSKL
|
1.7.3.3
| null |
nodulation [GO:0009877]; purine nucleobase catabolic process [GO:0006145]; urate catabolic process [GO:0019628]
|
peroxisome [GO:0005777]
|
urate oxidase activity [GO:0004846]
|
PF01014;
|
3.10.270.10;
|
Uricase family
|
PTM: The N-terminus is blocked.
|
SUBCELLULAR LOCATION: Peroxisome.
|
CATALYTIC ACTIVITY: Reaction=H2O + O2 + urate = 5-hydroxyisourate + H2O2; Xref=Rhea:RHEA:21368, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17775, ChEBI:CHEBI:18072; EC=1.7.3.3;
| null |
PATHWAY: Purine metabolism; urate degradation; (S)-allantoin from urate: step 1/3.
| null | null |
FUNCTION: Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin.
|
Glycine max (Soybean) (Glycine hispida)
|
P04688
|
TBA1_SCHPO
|
MREVISVHVGQAGVQIGNACWELYCLEHGIGPDGFPTENSEVHKNNSYLNDGFGTFFSETGQGKFVPRSIYVDLEPNVIDQVRTGPYKDLFHPEQMVTGKEDASNNYARGHYTVGKEMIDSVLERIRRMADNCSGLQGFLVFHSFGGGTGSGLGALLLERLNMEYGKKSNLQFSVYPAPQVSTSVVEPYNSVLTTHATLDNSDCTFMVDNEACYDICRRNLDIERPTYENLNRLIAQVVSSITASLRFAGSLNVDLNEFQTNLVPYPRIHFPLVTYSPIVSAAKAFHESNSVQEITNQCFEPYNQMVKCDPRTGRYMATCLLYRGDVIPRDVQAAVTSIKSRRTIQFVDWCPTGFKIGICYEPPQHVPGSGIAKVNRAVCMLSNTTSIAEAWSRLDHKFDLMYSKRAFVHWYVGEGMEEGEFSEAREDLAALERDYEEVGQDSMDNEMYEADEEY
|
3.6.5.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P68363};
|
microtubule cytoskeleton organization [GO:0000226]; mitotic cell cycle [GO:0000278]; nuclear division [GO:0000280]; nuclear migration by microtubule mediated pushing forces [GO:0098863]
|
astral microtubule [GO:0000235]; cytoplasm [GO:0005737]; microtubule [GO:0005874]; nucleus [GO:0005634]; spindle [GO:0005819]
|
GTP binding [GO:0005525]; hydrolase activity [GO:0016787]; metal ion binding [GO:0046872]; structural constituent of cytoskeleton [GO:0005200]
|
PF00091;PF03953;
|
1.10.287.600;3.30.1330.20;3.40.50.1440;
|
Tubulin family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
|
CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000250|UniProtKB:P68363}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000250|UniProtKB:P68363};
| null | null | null | null |
FUNCTION: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
P04689
|
TBA2_SCHPO
|
MREIISIHVGQAGTQIGNACWELYCLEHGIQPNGYMNPETASQNSDGGFSTFFSETGQGKYVPRSIYVDLEPNVIDQVRTGPYRDLFHPEQLITGKEDASNNYARGHYTVGKELVDEVTDKIRRIADNCSGLQGFLVFHSFGGGTGSGFGALLLERLAMEYTKKSKLQFSVYPAPQVSTSVVEPYNSVLTTHATLDLADCTFMVDNESCYDICRRNLDIERPSYENLNRLIAQVVSSITASLRFEGSLNVDLAEFQTNLVPYPRIHFPLVTYAPIVSAAKAFHESNSVQEITNQCFEPYNQMVKCDPRAGRYMATCLLYRGDVIPRDVQAAVTTIKAKRTIQFVDWCPTGFKIGICDRPPQHIEGSEIAKVDRAVCMLSNTTSIAEAWSRLDHKFDLMYSKRAFVHWYVGEGMEEGEFSEAREDLAALERDYEEVGQDSMEVDYMEEEY
|
3.6.5.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P68363};
|
cytoplasmic microtubule organization [GO:0031122]; microtubule cytoskeleton organization [GO:0000226]; mitochondrion distribution [GO:0048311]; mitotic cell cycle [GO:0000278]; mitotic spindle organization [GO:0007052]; nuclear division [GO:0000280]; nuclear migration by microtubule mediated pushing forces [GO:0098863]
|
astral microtubule [GO:0000235]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; microtubule [GO:0005874]; nucleus [GO:0005634]; spindle [GO:0005819]; spindle microtubule [GO:0005876]
|
GTP binding [GO:0005525]; hydrolase activity [GO:0016787]; metal ion binding [GO:0046872]; structural constituent of cytoskeleton [GO:0005200]
|
PF00091;PF03953;
|
1.10.287.600;3.30.1330.20;3.40.50.1440;
|
Tubulin family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
|
CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000250|UniProtKB:P68363}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000250|UniProtKB:P68363};
| null | null | null | null |
FUNCTION: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
P04692
|
TPM1_RAT
|
MDAIKKKMQMLKLDKENALDRAEQAEADKKAAEDRSKQLEDELVSLQKKLKGTEDELDKYSEALKDAQEKLELAEKKATDAEADVASLNRRIQLVEEELDRAQERLATALQKLEEAEKAADESERGMKVIESRAQKDEEKMEIQEIQLKEAKHIAEDADRKYEEVARKLVIIESDLERAEERAELSEGKCAELEEELKTVTNNLKSLEAQAEKYSQKEDKYEEEIKVLSDKLKEAETRAEFAERSVTKLEKSIDDLEDELYAQKLKYKAISEELDHALNDMTSI
| null | null |
actin filament capping [GO:0051693]; actin filament organization [GO:0007015]; cardiac muscle contraction [GO:0060048]; cellular response to reactive oxygen species [GO:0034614]; in utero embryonic development [GO:0001701]; muscle contraction [GO:0006936]; muscle filament sliding [GO:0030049]; negative regulation of cell migration [GO:0030336]; negative regulation of vascular associated smooth muscle cell migration [GO:1904753]; negative regulation of vascular associated smooth muscle cell proliferation [GO:1904706]; positive regulation of ATP-dependent activity [GO:0032781]; positive regulation of cell adhesion [GO:0045785]; positive regulation of heart rate by epinephrine [GO:0003065]; positive regulation of stress fiber assembly [GO:0051496]; regulation of cell shape [GO:0008360]; ruffle organization [GO:0031529]; sarcomere organization [GO:0045214]; ventricular cardiac muscle tissue morphogenesis [GO:0055010]; wound healing [GO:0042060]
|
actin cytoskeleton [GO:0015629]; actin filament [GO:0005884]; bleb [GO:0032059]; cytoplasm [GO:0005737]; myofibril [GO:0030016]; protein-containing complex [GO:0032991]; ruffle membrane [GO:0032587]; stress fiber [GO:0001725]
|
actin binding [GO:0003779]; actin filament binding [GO:0051015]; cytoskeletal protein binding [GO:0008092]; disordered domain specific binding [GO:0097718]; identical protein binding [GO:0042802]; protein heterodimerization activity [GO:0046982]; protein homodimerization activity [GO:0042803]
|
PF00261;
|
1.20.5.170;1.20.5.340;
|
Tropomyosin family
|
PTM: Phosphorylated at Ser-283 by DAPK1 in response to oxidative stress and this phosphorylation enhances stress fiber formation in endothelial cells. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:7568216}. Note=Associates with F-actin stress fibers (PubMed:7568216). {ECO:0000269|PubMed:7568216}.
| null | null | null | null | null |
FUNCTION: Binds to actin filaments in muscle and non-muscle cells (PubMed:22812662, PubMed:7568216). Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction (PubMed:22812662). Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments. {ECO:0000269|PubMed:22812662, ECO:0000269|PubMed:7568216}.
|
Rattus norvegicus (Rat)
|
P04693
|
TYRB_ECOLI
|
MFQKVDAYAGDPILTLMERFKEDPRSDKVNLSIGLYYNEDGIIPQLQAVAEAEARLNAQPHGASLYLPMEGLNCYRHAIAPLLFGADHPVLKQQRVATIQTLGGSGALKVGADFLKRYFPESGVWVSDPTWENHVAIFAGAGFEVSTYPWYDEATNGVRFNDLLATLKTLPARSIVLLHPCCHNPTGADLTNDQWDAVIEILKARELIPFLDIAYQGFGAGMEEDAYAIRAIASAGLPALVSNSFSKIFSLYGERVGGLSVMCEDAEAAGRVLGQLKATVRRNYSSPPNFGAQVVAAVLNDEALKASWLAEVEEMRTRILAMRQELVKVLSTEMPERNFDYLLNQRGMFSYTGLSAAQVDRLREEFGVYLIASGRMCVAGLNTANVQRVAKAFAAVM
|
2.6.1.107; 2.6.1.57
|
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
|
aspartate biosynthetic process [GO:0006532]; L-phenylalanine biosynthetic process from chorismate via phenylpyruvate [GO:0033585]; leucine biosynthetic process [GO:0009098]; tyrosine biosynthetic process from chorismate via 4-hydroxyphenylpyruvate [GO:0019292]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]
|
aromatic-amino-acid:2-oxoglutarate aminotransferase activity [GO:0008793]; identical protein binding [GO:0042802]; L-leucine:2-oxoglutarate aminotransferase activity [GO:0050048]; L-phenylalanine:2-oxoglutarate aminotransferase activity [GO:0080130]; L-tyrosine:2-oxoglutarate aminotransferase activity [GO:0004838]; protein homodimerization activity [GO:0042803]; pyridoxal phosphate binding [GO:0030170]
|
PF00155;
|
3.90.1150.10;3.40.640.10;
|
Class-I pyridoxal-phosphate-dependent aminotransferase family
| null |
SUBCELLULAR LOCATION: Cytoplasm.
|
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + an aromatic L-alpha-amino acid = an aromatic oxo-acid + L-glutamate; Xref=Rhea:RHEA:17533, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:73309, ChEBI:CHEBI:84824; EC=2.6.1.57; Evidence={ECO:0000269|PubMed:19731276}; CATALYTIC ACTIVITY: Reaction=(2S,3S)-3-methylphenylalanine + 2-oxoglutarate = (3S)-2-oxo-3-phenylbutanoate + L-glutamate; Xref=Rhea:RHEA:39911, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:74119, ChEBI:CHEBI:76864; EC=2.6.1.107; Evidence={ECO:0000269|PubMed:19731276};
| null |
PATHWAY: Amino-acid biosynthesis; L-phenylalanine biosynthesis; L-phenylalanine from phenylpyruvate (ArAT route): step 1/1.; PATHWAY: Amino-acid biosynthesis; L-tyrosine biosynthesis; L-tyrosine from (4-hydroxyphenyl)pyruvate: step 1/1.
| null | null |
FUNCTION: Broad-specificity enzyme that catalyzes the transamination of 2-ketoisocaproate, p-hydroxyphenylpyruvate, and phenylpyruvate to yield leucine, tyrosine, and phenylalanine, respectively. In vitro, is able to catalyze the conversion of beta-methyl phenylpyruvate to the nonproteinogenic amino acid (2S,3S)-beta-methyl-phenylalanine, a building block of the antibiotic mannopeptimycin produced by Streptomyces hygroscopicus NRRL3085. {ECO:0000269|PubMed:19731276}.
|
Escherichia coli (strain K12)
|
P04694
|
ATTY_RAT
|
MDSYVIQTDVDDSLSSVLDVHVNIGGRNSVQGRKKGRKARWDVRPSDMSNKTFNPIRAIVDNMKVQPNPNKTVISLSIGDPTVFGNLPTDPEVTQAMKDALDSGKYNGYAPSIGYLSSREEVASYYHCHEAPLEAKDVILTSGCSQAIELCLAVLANPGQNILIPRPGFSLYRTLAESMGIEVKLYNLLPEKSWEIDLKQLESLIDEKTACLVVNNPSNPCGSVFSKRHLQKILAVAERQCVPILADEIYGDMVFSDCKYEPLANLSTNVPILSCGGLAKRWLVPGWRLGWILIHDRRDIFGNEIRDGLVKLSQRILGPCTIVQGALKSILQRTPQEFYHDTLSFLKSNADLCYGALAAIPGLQPVRPSGAMYLMVGIEMEHFPEFENDVEFTERLIAEQAVHCLPATCFEYPNFFRVVITVPEVMMLEACSRIQEFCEQHYHCAEGSQEECDK
|
2.6.1.5
|
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000269|PubMed:1682164, ECO:0000269|PubMed:2562840};
|
2-oxoglutarate metabolic process [GO:0006103]; amino acid metabolic process [GO:0006520]; biosynthetic process [GO:0009058]; glutamate metabolic process [GO:0006536]; L-phenylalanine catabolic process [GO:0006559]; response to dexamethasone [GO:0071548]; response to glucocorticoid [GO:0051384]; response to mercury ion [GO:0046689]; response to organic cyclic compound [GO:0014070]; response to oxidative stress [GO:0006979]; tyrosine catabolic process [GO:0006572]
| null |
amino acid binding [GO:0016597]; identical protein binding [GO:0042802]; L-tyrosine:2-oxoglutarate aminotransferase activity [GO:0004838]; pyridoxal phosphate binding [GO:0030170]
|
PF00155;PF07706;
|
3.90.1150.10;3.40.640.10;
|
Class-I pyridoxal-phosphate-dependent aminotransferase family
| null | null |
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-tyrosine = 3-(4-hydroxyphenyl)pyruvate + L-glutamate; Xref=Rhea:RHEA:15093, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:36242, ChEBI:CHEBI:58315; EC=2.6.1.5; Evidence={ECO:0000269|PubMed:1682164};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.2 mM for tyrosine {ECO:0000269|PubMed:1682164};
|
PATHWAY: Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 2/6.
| null | null |
FUNCTION: Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine. {ECO:0000269|PubMed:1682164}.
|
Rattus norvegicus (Rat)
|
P04695
|
GNAT1_BOVIN
|
MGAGASAEEKHSRELEKKLKEDAEKDARTVKLLLLGAGESGKSTIVKQMKIIHQDGYSLEECLEFIAIIYGNTLQSILAIVRAMTTLNIQYGDSARQDDARKLMHMADTIEEGTMPKEMSDIIQRLWKDSGIQACFDRASEYQLNDSAGYYLSDLERLVTPGYVPTEQDVLRSRVKTTGIIETQFSFKDLNFRMFDVGGQRSERKKWIHCFEGVTCIIFIAALSAYDMVLVEDDEVNRMHESLHLFNSICNHRYFATTSIVLFLNKKDVFSEKIKKAHLSICFPDYNGPNTYEDAGNYIKVQFLELNMRRDVKEIYSHMTCATDTQNVKFVFDAVTDIIIKENLKDCGLF
| null | null |
adenylate cyclase-modulating G protein-coupled receptor signaling pathway [GO:0007188]; detection of light stimulus involved in visual perception [GO:0050908]; negative regulation of cyclic-nucleotide phosphodiesterase activity [GO:0051344]; phototransduction [GO:0007602]; phototransduction, visible light [GO:0007603]; response to light stimulus [GO:0009416]
|
cytoplasm [GO:0005737]; G protein-coupled receptor complex [GO:0097648]; heterotrimeric G-protein complex [GO:0005834]; photoreceptor disc membrane [GO:0097381]; photoreceptor inner segment [GO:0001917]; photoreceptor outer segment membrane [GO:0042622]
|
acyl binding [GO:0000035]; G protein-coupled receptor binding [GO:0001664]; G-protein beta/gamma-subunit complex binding [GO:0031683]; GDP binding [GO:0019003]; GTP binding [GO:0005525]; GTPase activity [GO:0003924]; metal ion binding [GO:0046872]; protein kinase binding [GO:0019901]
|
PF00503;
|
1.10.400.10;3.40.50.300;
| null | null |
SUBCELLULAR LOCATION: Cell projection, cilium, photoreceptor outer segment {ECO:0000269|PubMed:23303210}. Membrane {ECO:0000269|PubMed:23303210, ECO:0000269|PubMed:28655769}; Peripheral membrane protein {ECO:0000269|PubMed:23303210, ECO:0000269|PubMed:28655769}. Photoreceptor inner segment {ECO:0000250|UniProtKB:P20612}. Note=Localizes mainly in the outer segment in the dark-adapted state, whereas is translocated to the inner part of the photoreceptors in the light-adapted state. During dark-adapted conditions, in the presence of UNC119 mislocalizes from the outer segment to the inner part of rod photoreceptors which leads to decreased photoreceptor damage caused by light. {ECO:0000250|UniProtKB:P20612}.
| null | null | null | null | null |
FUNCTION: Functions as a signal transducer for the rod photoreceptor RHO (PubMed:21285355, PubMed:23303210, PubMed:28655769, PubMed:8259210). Required for normal RHO-mediated light perception by the retina (By similarity). Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs), such as the photoreceptor RHO. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PubMed:21285355, PubMed:28655769, PubMed:7969474, PubMed:8208289, PubMed:8259210). Activated RHO promotes GDP release and GTP binding (PubMed:21285355, PubMed:28655769). Signaling is mediated via downstream effector proteins, such as cGMP-phosphodiesterase (PubMed:21285355). {ECO:0000250|UniProtKB:P11488, ECO:0000269|PubMed:21285355, ECO:0000269|PubMed:28655769, ECO:0000305|PubMed:23303210, ECO:0000305|PubMed:7969474, ECO:0000305|PubMed:8208289, ECO:0000305|PubMed:8259210}.
|
Bos taurus (Bovine)
|
P04696
|
GNAT2_BOVIN
|
MGSGASAEDKELAKRSKELEKKLQEDADKEAKTVKLLLLGAGESGKSTIVKQMKIIHQDGYSPEECLEYKAIIYGNVLQSILAIIRAMPTLGIDYAEVSCVDNGRQLNNLADSIEEGTMPPELVEVIRKLWKDGGVQACFDRAAEYQLNDSASYYLNQLDRITAPDYLPNEQDVLRSRVKTTGIIETKFSVKDLNFRMFDVGGQRSERKKWIHCFEGVTCIIFCAALSAYDMVLVEDDEVNRMHESLHLFNSICNHKFFAATSIVLFLNKKDLFEEKIKKVHLSICFPEYDGNNSYEDAGNYIKSQFLDLNMRKDVKEIYSHMTCATDTQNVKFVFDAVTDIIIKENLKDCGLF
| null | null |
adenylate cyclase-modulating G protein-coupled receptor signaling pathway [GO:0007188]; detection of chemical stimulus involved in sensory perception of bitter taste [GO:0001580]; visual perception [GO:0007601]
|
cytoplasm [GO:0005737]; heterotrimeric G-protein complex [GO:0005834]; photoreceptor inner segment [GO:0001917]; photoreceptor outer segment [GO:0001750]; photoreceptor outer segment membrane [GO:0042622]
|
G protein-coupled receptor binding [GO:0001664]; G-protein beta/gamma-subunit complex binding [GO:0031683]; GTP binding [GO:0005525]; GTPase activity [GO:0003924]; metal ion binding [GO:0046872]
|
PF00503;
|
1.10.400.10;3.40.50.300;
|
G-alpha family, G(i/o/t/z) subfamily
| null |
SUBCELLULAR LOCATION: Cell projection, cilium, photoreceptor outer segment {ECO:0000250|UniProtKB:P50149}. Photoreceptor inner segment {ECO:0000250|UniProtKB:P50149}. Note=Localizes mainly in the outer segment in the dark-adapted state, whereas is translocated to the inner part of the photoreceptors in the light-adapted state. During dark-adapted conditions, in the presence of UNC119 mislocalizes from the outer segment to the inner part of rod photoreceptors which leads to decreased photoreceptor damage caused by light. {ECO:0000250|UniProtKB:P50149}.
| null | null | null | null | null |
FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase. {ECO:0000269|PubMed:6586721}.
|
Bos taurus (Bovine)
|
P04710
|
ADT1_YEAST
|
MSHTETQTQQSHFGVDFLMGGVSAAIAKTGAAPIERVKLLMQNQEEMLKQGSLDTRYKGILDCFKRTATHEGIVSFWRGNTANVLRYFPTQALNFAFKDKIKSLLSYDRERDGYAKWFAGNLFSGGAAGGLSLLFVYSLDYARTRLAADARGSKSTSQRQFNGLLDVYKKTLKTDGLLGLYRGFVPSVLGIIVYRGLYFGLYDSFKPVLLTGALEGSFVASFLLGWVITMGASTASYPLDTVRRRMMMTSGQTIKYDGALDCLRKIVQKEGAYSLFKGCGANIFRGVAAAGVISLYDQLQLIMFGKKFK
| null | null |
aerobic respiration [GO:0009060]; heme biosynthetic process [GO:0006783]; heme transport [GO:0015886]; mitochondrial ADP transmembrane transport [GO:0140021]; mitochondrial ATP transmembrane transport [GO:1990544]; mitochondrial transport [GO:0006839]; negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway [GO:1901029]
|
cytosol [GO:0005829]; mitochondrial inner membrane [GO:0005743]; mitochondrial intermembrane space [GO:0005758]; mitochondrion [GO:0005739]
|
ATP:ADP antiporter activity [GO:0005471]
|
PF00153;
|
1.50.40.10;
|
Mitochondrial carrier (TC 2.A.29) family
| null |
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250|UniProtKB:P18239}; Multi-pass membrane protein {ECO:0000255}.
|
CATALYTIC ACTIVITY: Reaction=ADP(in) + ATP(out) = ADP(out) + ATP(in); Xref=Rhea:RHEA:34999, ChEBI:CHEBI:30616, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:2167309}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35000; Evidence={ECO:0000269|PubMed:2167309};
| null | null | null | null |
FUNCTION: ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:2167309). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). {ECO:0000250|UniProtKB:G2QNH0, ECO:0000269|PubMed:2167309}.
|
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
|
P04711
|
CAPP1_MAIZE
|
MASTKAPGPGEKHHSIDAQLRQLVPGKVSEDDKLIEYDALLVDRFLNILQDLHGPSLREFVQECYEVSADYEGKGDTTKLGELGAKLTGLAPADAILVASSILHMLNLANLAEEVQIAHRRRNSKLKKGGFADEGSATTESDIEETLKRLVSEVGKSPEEVFEALKNQTVDLVFTAHPTQSARRSLLQKNARIRNCLTQLNAKDITDDDKQELDEALQREIQAAFRTDEIRRAQPTPQAEMRYGMSYIHETVWKGVPKFLRRVDTALKNIGINERLPYNVSLIRFSSWMGGDRDGNPRVTPEVTRDVCLLARMMAANLYIDQIEELMFELSMWRCNDELRVRAEELHSSSGSKVTKYYIEFWKQIPPNEPYRVILGHVRDKLYNTRERARHLLASGVSEISAESSFTSIEEFLEPLELCYKSLCDCGDKAIADGSLLDLLRQVFTFGLSLVKLDIRQESERHTDVIDAITTHLGIGSYREWPEDKRQEWLLSELRGKRPLLPPDLPQTDEIADVIGAFHVLAELPPDSFGPYIISMATAPSDVLAVELLQRECGVRQPLPVVPLFERLADLQSAPASVERLFSVDWYMDRIKGKQQVMVGYSDSGKDAGRLSAAWQLYRAQEEMAQVAKRYGVKLTLFHGRGGTVGRGGGPTHLAILSQPPDTINGSIRVTVQGEVIEFCFGEEHLCFQTLQRFTAATLEHGMHPPVSPKPEWRKLMDEMAVVATEEYRSVVVKEARFVEYFRSATPETEYGRMNIGSRPAKRRPGGGITTLRAIPWIFSWTQTRFHLPVWLGVGAAFKFAIDKDVRNFQVLKEMYNEWPFFRVTLDLLEMVFAKGDPGIAGLYDELLVAEELKPFGKQLRDKYVETQQLLLQIAGHKDILEGDPFLKQGLVLRNPYITTLNVFQAYTLKRIRDPNFKVTPQPPLSKEFADENKPAGLVKLNPASEYPPGLEDTLILTMKGIAAGMQNTG
|
4.1.1.31
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
|
carbon fixation [GO:0015977]; leaf development [GO:0048366]; photosynthesis [GO:0015979]; response to ammonium ion [GO:0060359]; response to cytokinin [GO:0009735]; response to nitrate [GO:0010167]; tricarboxylic acid cycle [GO:0006099]
|
apoplast [GO:0048046]; chloroplast [GO:0009507]; cytosol [GO:0005829]
|
phosphoenolpyruvate carboxylase activity [GO:0008964]
|
PF00311;
|
1.20.1440.90;
|
PEPCase type 1 family
| null |
SUBCELLULAR LOCATION: Cytoplasm.
|
CATALYTIC ACTIVITY: Reaction=oxaloacetate + phosphate = hydrogencarbonate + phosphoenolpyruvate; Xref=Rhea:RHEA:28370, ChEBI:CHEBI:16452, ChEBI:CHEBI:17544, ChEBI:CHEBI:43474, ChEBI:CHEBI:58702; EC=4.1.1.31;
| null |
PATHWAY: Photosynthesis; C4 acid pathway.
| null | null |
FUNCTION: Through the carboxylation of phosphoenolpyruvate (PEP) it forms oxaloacetate, a four-carbon dicarboxylic acid source for the tricarboxylic acid cycle.
|
Zea mays (Maize)
|
P04717
|
RBL_PEA
|
MSPQTETKAKVGFKAGVKDYKLTYYTPDYQTKDTDILAAFRVTPQPGVPPEEAGAAVAAESSTGTWTTVWTDGLTSLDRYKGRCYEIEPVPGEDNQFIAYVAYPLDLFEEGSVTNMFTSIVGNVFGFKALRALRLEDLRIPYAYVKTFQGPPHGIQVERDKLNKYGRPLLGCTIKPKLGLSAKNYGRAVYECLRGGLDFTKDDENVNSQPFMRWRDRFLFCAEAIYKSQAETGEIKGHYLNATAGTCEEMLKRAVFARELGVPIVMHDYLTGGFTANTTLSHYCRDNGLLLHIHRAMHAVIDRQKNHGMHFRVLAKALRLSGGDHIHAGTVVGKLEGEREITLGFVDLLRDDYIKKDRSRGIYFTQDWVSLPGVIPVASGGIHVWHMPALTEIFGDDSVLQFGGGTLGHPWGNAPGAVANRVALEACVQARNEGRDLAREGNAIIREACKWSPELAAACEVWKEIKFEFPAMDTL
|
4.1.1.39
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_01338}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01338};
|
photorespiration [GO:0009853]; reductive pentose-phosphate cycle [GO:0019253]
|
chloroplast [GO:0009507]
|
magnesium ion binding [GO:0000287]; monooxygenase activity [GO:0004497]; ribulose-bisphosphate carboxylase activity [GO:0016984]
|
PF00016;PF02788;
|
3.20.20.110;3.30.70.150;
|
RuBisCO large chain family, Type I subfamily
|
PTM: The disulfide bond which can form in the large chain dimeric partners within the hexadecamer appears to be associated with oxidative stress and protein turnover. {ECO:0000250|UniProtKB:P11383}.
|
SUBCELLULAR LOCATION: Plastid, chloroplast {ECO:0000255|HAMAP-Rule:MF_01338}.
|
CATALYTIC ACTIVITY: Reaction=2 (2R)-3-phosphoglycerate + 2 H(+) = CO2 + D-ribulose 1,5-bisphosphate + H2O; Xref=Rhea:RHEA:23124, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57870, ChEBI:CHEBI:58272; EC=4.1.1.39; Evidence={ECO:0000255|HAMAP-Rule:MF_01338, ECO:0000305|PubMed:23295478, ECO:0000305|PubMed:26197050}; CATALYTIC ACTIVITY: Reaction=D-ribulose 1,5-bisphosphate + O2 = (2R)-3-phosphoglycerate + 2-phosphoglycolate + 2 H(+); Xref=Rhea:RHEA:36631, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57870, ChEBI:CHEBI:58033, ChEBI:CHEBI:58272; Evidence={ECO:0000255|HAMAP-Rule:MF_01338, ECO:0000305|PubMed:23295478, ECO:0000305|PubMed:26197050};
| null | null | null | null |
FUNCTION: RuBisCO catalyzes two reactions: the carboxylation of D-ribulose 1,5-bisphosphate, the primary event in carbon dioxide fixation, as well as the oxidative fragmentation of the pentose substrate in the photorespiration process. Both reactions occur simultaneously and in competition at the same active site (Probable). Binds to abscisic acid (ABA); only half of the possible binding sites are occupied in the crystal and there are indications this is a low affinity site (PubMed:26197050). {ECO:0000269|PubMed:26197050, ECO:0000305|PubMed:23295478, ECO:0000305|PubMed:26197050}.
|
Pisum sativum (Garden pea) (Lathyrus oleraceus)
|
P04718
|
RBL2_RHORU
|
MDQSSRYVNLALKEEDLIAGGEHVLCAYIMKPKAGYGYVATAAHFAAESSTGTNVEVCTTDDFTRGVDALVYEVDEARELTKIAYPVALFHRNITDGKAMIASFLTLTMGNNQGMGDVEYAKMHDFYVPEAYRALFDGPSVNISALWKVLGRPEVDGGLVVGTIIKPKLGLRPKPFAEACHAFWLGGDFIKNDEPQGNQPFAPLRDTIALVADAMRRAQDETGEAKLFSANITADDPFEIIARGEYVLETFGENASHVALLVDGYVAGAAAITTARRRFPDNFLHYHRAGHGAVTSPQSKRGYTAFVHCKMARLQGASGIHTGTMGFGKMEGESSDRAIAYMLTQDEAQGPFYRQSWGGMKACTPIISGGMNALRMPGFFENLGNANVILTAGGGAFGHIDGPVAGARSLRQAWQAWRDGVPVLDYAREHKELARAFESFPGDADQIYPGWRKALGVEDTRSALPA
|
4.1.1.39
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:1899197, ECO:0000269|Ref.4}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:1899197, ECO:0000269|Ref.4};
|
reductive pentose-phosphate cycle [GO:0019253]
| null |
magnesium ion binding [GO:0000287]; monooxygenase activity [GO:0004497]; ribulose-bisphosphate carboxylase activity [GO:0016984]
|
PF00016;PF02788;
|
3.20.20.110;3.30.70.150;
|
RuBisCO large chain family, Type II subfamily
| null | null |
CATALYTIC ACTIVITY: Reaction=2 (2R)-3-phosphoglycerate + 2 H(+) = CO2 + D-ribulose 1,5-bisphosphate + H2O; Xref=Rhea:RHEA:23124, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57870, ChEBI:CHEBI:58272; EC=4.1.1.39; CATALYTIC ACTIVITY: Reaction=D-ribulose 1,5-bisphosphate + O2 = (2R)-3-phosphoglycerate + 2-phosphoglycolate + 2 H(+); Xref=Rhea:RHEA:36631, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57870, ChEBI:CHEBI:58033, ChEBI:CHEBI:58272;
| null | null | null | null |
FUNCTION: RuBisCO catalyzes two reactions: the carboxylation of D-ribulose 1,5-bisphosphate, the primary event in carbon dioxide fixation, as well as the oxidative fragmentation of the pentose substrate. Both reactions occur simultaneously and in competition at the same active site.
|
Rhodospirillum rubrum
|
P04731
|
MT1A_HUMAN
|
MDPNCSCATGGSCTCTGSCKCKECKCTSCKKSCCSCCPMSCAKCAQGCICKGASEKCSCCA
| null | null |
cellular response to cadmium ion [GO:0071276]; cellular response to copper ion [GO:0071280]; cellular response to zinc ion [GO:0071294]; detoxification of copper ion [GO:0010273]; intracellular zinc ion homeostasis [GO:0006882]; negative regulation of growth [GO:0045926]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleus [GO:0005634]
|
metal ion binding [GO:0046872]; zinc ion binding [GO:0008270]
|
PF00131;
|
4.10.10.10;
|
Metallothionein superfamily, Type 1 family
| null | null | null | null | null | null | null |
FUNCTION: Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
|
Homo sapiens (Human)
|
P04732
|
MT1E_HUMAN
|
MDPNCSCATGGSCTCAGSCKCKECKCTSCKKSCCSCCPVGCAKCAQGCVCKGASEKCSCCA
| null | null |
cellular response to cadmium ion [GO:0071276]; cellular response to copper ion [GO:0071280]; cellular response to zinc ion [GO:0071294]; detoxification of copper ion [GO:0010273]; intracellular zinc ion homeostasis [GO:0006882]; negative regulation of growth [GO:0045926]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
|
metal ion binding [GO:0046872]; zinc ion binding [GO:0008270]
|
PF00131;
|
4.10.10.10;
|
Metallothionein superfamily, Type 1 family
| null | null | null | null | null | null | null |
FUNCTION: Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
|
Homo sapiens (Human)
|
P04733
|
MT1F_HUMAN
|
MDPNCSCAAGVSCTCAGSCKCKECKCTSCKKSCCSCCPVGCSKCAQGCVCKGASEKCSCCD
| null | null |
cellular response to cadmium ion [GO:0071276]; cellular response to copper ion [GO:0071280]; cellular response to zinc ion [GO:0071294]; detoxification of copper ion [GO:0010273]; intracellular zinc ion homeostasis [GO:0006882]; negative regulation of growth [GO:0045926]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
|
metal ion binding [GO:0046872]; zinc ion binding [GO:0008270]
|
PF00131;
|
4.10.10.10;
|
Metallothionein superfamily, Type 1 family
| null | null | null | null | null | null | null |
FUNCTION: Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
|
Homo sapiens (Human)
|
P04737
|
PIL1_ECOLI
|
MNAVLSVQGASAPVKKKSFFSKFTRLNMLRLARAVIPAAVLMMFFPQLAMAAGSSGQDLMASGNTTVKATFGKDSSVVKWVVLAEVLVGAVMYMMTKNVKFLAGFAIISVFIAVGMAVVGL
| null | null | null |
extracellular region [GO:0005576]; plasma membrane [GO:0005886]
| null |
PF05513;
| null |
TraA family
| null |
SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:1464628}; Multi-pass membrane protein {ECO:0000269|PubMed:1464628}. Secreted {ECO:0000269|PubMed:1464628}. Note=Propilin is directed to the inner membrane, where it is cleaved and acetylated. Mature pilin forms filaments that are secreted to form the conjugative pilus.
| null | null | null | null | null |
FUNCTION: Propilin is the precursor of the pilus subunit, pilin, that forms conjugative pili, the filamentous surface appendages required for cell-to-cell contact during the earlier stages of bacterial conjugation, and that retract after contact is established. Mature pilin is assembled with the help of TraQ and TraX (PubMed:1464628, PubMed:6090426). Functions as a receptor for CdiA-CT from E.cloacae and E.coli, although it is not clear if this is physiologically relevant (PubMed:24889811). {ECO:0000269|PubMed:1464628, ECO:0000269|PubMed:24889811, ECO:0000269|PubMed:6090426}.
|
Escherichia coli (strain K12)
|
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