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O88890
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SH21A_MOUSE
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SH2 domain-containing protein 1A (Signaling lymphocytic activation molecule-associated protein) (SLAM-associated protein) (T-cell signal transduction molecule SAP)
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MDAVTVYHGKISRETGEKLLLATGLDGSYLLRDSESVPGVYCLCVLYQGYIYTYRVSQTETGSWSAETAPGVHKRFFRKVKNLISAFQKPDQGIVTPLQYPVEKSSGRGPQAPTGRRDSDICLNAP
|
Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as SLAMF1, CD244, LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with SH2D1B/EAT-2. Initially it has been proposed that association with SLAMF1 prevents SLAMF1 binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2. However, by simultaneous interactions, recruits FYN which subsequently phosphorylates and activates SLAMF1 (By similarity). Positively regulates CD244/2B4- and CD84-mediated natural killer (NK) cell functions. Can also promote CD48-, SLAMF6 -, LY9-, and SLAMF7-mediated NK cell activation. In the context of NK cell-mediated cytotoxicity enhances conjugate formation with target cells. May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.
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O88895
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HDAC3_MOUSE
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Histone deacetylase 3 (HD3) (EC 3.5.1.98) (Protein deacetylase HDAC3) (EC 3.5.1.-) (Protein deacylase HDAC3) (EC 3.5.1.-)
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MAKTVAYFYDPDVGNFHYGAGHPMKPHRLALTHSLVLHYGLYKKMIVFKPYQASQHDMCRFHSEDYIDFLQRVSPTNMQGFTKSLNAFNVGDDCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFCYVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHLFQPVISQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPYSEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYDGDHDNDKESDVEI
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Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression. Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation. Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (By similarity). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner. During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1. The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver. Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and RARA (By similarity). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (By similarity). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (By similarity). In addition to protein deacetylase activity, also acts as protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively. Catalyzes decrotonylation of MAPRE1/EB1 (By similarity).
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O88898
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P63_MOUSE
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Tumor protein 63 (p63) (Transformation-related protein 63) (TP63) (Tumor protein p73-like) (p73L)
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MNFETSRCATLQYCPDPYIQRFIETPAHFSWKESYYRSAMSQSTQTSEFLSPEVFQHIWDFLEQPICSVQPIELNFVDEPSENGATNKIEISMDCIRMQDSDLSDPMWPQYTNLGLLNSMDQQIQNGSSSTSPYNTDHAQNSVTAPSPYAQPSSTFDALSPSPAIPSNTDYPGPHSFDVSFQQSSTAKSATWTYSTELKKLYCQIAKTCPIQIKVMTPPPQGAVIRAMPVYKKAEHVTEVVKRCPNHELSREFNEGQIAPPSHLIRVEGNSHAQYVEDPITGRQSVLVPYEPPQVGTEFTTVLYNFMCNSSCVGGMNRRPILIIVTLETRDGQVLGRRCFEARICACPGRDRKADEDSIRKQQVSDSAKNGDGTKRPFRQNTHGIQMTSIKKRRSPDDELLYLPVRGRETYEMLLKIKESLELMQYLPQHTIETYRQQQQQQHQHLLQKQTSMQSQSSYGNSSPPLNKMNSMNKLPSVSQLINPQQRNALTPTTMPEGMGANIPMMGTHMPMAGDMNGLSPTQALPPPLSMPSTSHCTPPPPYPTDCSIVSFLARLGCSSCLDYFTTQGLTTIYQIEHYSMDDLASLKIPEQFRHAIWKGILDHRQLHDFSSPPHLLRTPSGASTVSVGSSETRGERVIDAVRFTLRQTISFPPRDEWNDFNFDMDSRRNKQQRIKEEGE
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Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Activates transcription of the p21 promoter (By similarity). Activates RIPK4 transcription. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. {ECO:0000250, ECO:0000269|PubMed:10227293, ECO:0000269|PubMed:10227294, ECO:0000269|PubMed:11932750, ECO:0000269|PubMed:14729569, ECO:0000269|PubMed:22197488}.
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O88900
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GRB14_RAT
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Growth factor receptor-bound protein 14 (GRB14 adapter protein)
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MTTSLQDGQSAAGRAGAQDSPLAVQVCRVAQGKGDAQDPAQVPGLHALSPASDATRRGAMDRRKAKDLEVQETPSIPNPFPELCCSPLTSVLSAGLFPRSNSRKKQVIKVYSEDETSRALEVPSDVTARDVCQLLILKNHYVDDNSWTLFEHLSHTGVERTVEDHELLTEVLSHWVMEEDNKLYLRKNYAKYEFFKNPMYFFPEHMVSFATEMNGDRSLTQIPQVFLSSNTYPEIHGFLHAKEQGKKSWKKAYFFLRRSGLYFSTKGTSKEPRHLQFFSEFSTSNVYMSLAGKKKHGAPTPYGFCFKPTKAGGPRDLKMLCAEEDQSRMCWVTAIRLLKYGMQLYQNYMHPSQARSACSSQSVSPMRSVSENSLVAMDFSGQKTRVIDNPTEALSVAVEEGLAWRKKGCLRLGNHGSPTAPSQSSAVNMALHRSQPWFHHRISRDEAQQLITRQGPVDGVFLVRDSQSNPRTFVLSMSHGQKIKHFQIIPVEDDGEVFHTLDDGHTKFTDLIQLVEFYQLNKGVLPCKLKHYCARMAV
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Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal (By similarity).
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O88902
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PTN23_RAT
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Tyrosine-protein phosphatase non-receptor type 23 (EC 3.1.3.48) (His domain-containing protein tyrosine phosphatase) (HD-PTP) (Protein tyrosine phosphatase TD14) (PTP-TD14)
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LNVNLMLGQAQECLLEKSMLDNRKSFLVARISAQVVDYYKEACRALENPDTASLLGRIQKDWKKLVQMKIYYFAAVAHLHMGKQAEEQQKFGERVAYFQSALDKLNEAIKLAKGQPDTVQDALRFAMDVIGGKYNSAKKDNDFIYHEAVPALDTLQPVKGAPLVKPLPVNPTDPAVTGPDIFAKLVPMAAHEASSLYSEEKAKLLREMLAKIEDKNEVLDQFMDSMQLDPDTVDNLDAYNHIPPQLMEKCAALSVRPDTVKNLVQSMQVLSGVFTDVEASLKDIRDLLEEDELQEQKLQETLGQAGAGPGPSVTKAELGEVRREWAKYTEVHEKASFTNSELHRAMNLHVGNLRLLSGPLDQVRAALPTPALTPEDKAVLQNLKRILAKVQEMRDQRVSLEQQLRELIQKDDITASLVTTDHSEMKKLFEEQLKKYDQLKVYLEQNLAAQDNVLRALTEANVQYAAVRRVLSELDQKWNSTLQTLVASYEAYEDLMKKSQEGKDFYADLESKVAALLERAQSLCRAQEAARQQLLDRELKKKAPPPRPTAPKPLLSRREEGEAAEAGDQPEELRSLPPDMMAGPRLPDPFLGTAAPLHFSPGPFPGSTGPATHYLSGPLPPGTYSGPTQLMQPRAAVPMAPGPVLYPAPVYTSELGLVPRSSPQHGIVSSPYAGVGPPQPIVGLPSAPPPQFSGPELAMDVRPATTTVDSVQAPISSHMALRPGPAPAPPQPCFPVPQPVPQSVPQPQPLPTPYTYSIGTKQHLTGPLPQHHFPPGIPTSFPAPRIGPQPPPQLQPQPQPQPQPQPPPQPQPQPQPQPQPQPQPQPQRPVFGPQPTQQPLPFQHPHLFPSQAPGILTPPPPYPFTPQPGVLGQPPPTRHTQLYPGPPPDTLPPHSGALPFPSPGPPHPHPTLAYGPAPSPRPLGPQATPVSIRGPPPANQPAPSPHLVPSPAPSPGPGPVPSRPPTAEPPPCLRRGAAAADLLSSSPESQHGGTQPPGGGQPLLQPTKVDAAERPTAQALRLIEQDPYEHPERLQKLQQELESFRGQLGDAGALDAVWRELQEAQEHDARGRSIAIARCYSLKNRHQDVMPYDSNRVVLRSGKDDYINASCVEGLSPYCPPLVATQRPLPGTAADFWLMVHEQKVSVIVMLVSEAEMEKQKVARYFPIERGQPMVHGALSVALSSVRTTDTHVERVLSLQFRDQSLKRSLVHLHFPTWPELGLPDSPGNLLRFIQEVHAHYLHQRPLHTPIVVHCSSGVGRTGAFALLYAAVQEVEAGSRIPELPQLVRRMRQQRKHMLQEKLHLKFCHEALVRHVEQVLQRHGVPPPGKPVASMSVSQKSHLPQDSQDLVLGGDVPISSIQATIAKLSIRPLGGLDSPAASLPSLVEPPGLPPASLPEPTPAPPSSPPPPSSPLPEPPQPEEEPSVPEAPSLGPPSSSLELLASLTPEAFSLDSSLRGKQRMSKQNFLQAHNGQGLRAAQPTDDPLSLLDPLWTLNKT
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Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes. May act as a negative regulator of Ras-mediated mitogenic activity. Plays a role in ciliogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:9694860}.
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O88904
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HIPK1_MOUSE
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Homeodomain-interacting protein kinase 1 (EC 2.7.11.1) (Nuclear body-associated kinase 2) (Protein kinase Myak)
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MASQLQVFSPPSVSSSAFCSAKKLKIEPSGWDVSGQSSNDKYYTHSKTLPATQGQASSSHQVANFNLPAYDQGLLLPAPAVEHIVVTAADSSGSAATATFQSSQTLTHRSNVSLLEPYQKCGLKRKSEEVESNGSVQIIEEHPPLMLQNRTVVGAAATTTTVTTKSSSSSGEGDYQLVQHEILCSMTNSYEVLEFLGRGTFGQVAKCWKRSTKEIVAIKILKNHPSYARQGQIEVSILSRLSSENADEYNFVRSYECFQHKNHTCLVFEMLEQNLYDFLKQNKFSPLPLKYIRPILQQVATALMKLKSLGLIHADLKPENIMLVDPVRQPYRVKVIDFGSASHVSKAVCSTYLQSRYYRAPEIILGLPFCEAIDMWSLGCVIAELFLGWPLYPGASEYDQIRYISQTQGLPAEYLLSAGTKTTRFFNRDPNLGYPLWRLKTPEEHELETGIKSKEARKYIFNCLDDMAQVNMSTDLEGTDMLAEKADRREYIDLLKKMLTIDADKRITPLKTLNHQFVTMSHLLDFPHSSHVKSCFQNMEICKRRVHMYDTVSQIKSPFTTHVAPNTSTNLTMSFSNQLNTVHNQASVLASSSTAAAATLSLANSDVSLLNYQSALYPSSAAPVPGVAQQGVSLQPGTTQICTQTDPFQQTFIVCPPAFQTGLQATTKHSGFPVRMDNAVPIVPQAPAAQPLQIQSGVLTQGSCTPLMVATLHPQVATITPQYAVPFTLSCAAGRPALVEQTAAVLQAWPGGTQQILLPSAWQQLPGVALHNSVQPAAVIPEAMGSSQQLADWRNAHSHGNQYSTIMQQPSLLTNHVTLATAQPLNVGVAHVVRQQQSSSLPSKKNKQSAPVSSKSSLEVLPSQVYSLVGSSPLRTTSSYNSLVPVQDQHQPIIIPDTPSPPVSVITIRSDTDEEEDNKYKPNSSSLKARSNVISYVTVNDSPDSDSSLSSPHPTDTLSALRGNSGTLLEGPGRPAADGIGTRTIIVPPLKTQLGDCTVATQASGLLSSKTKPVASVSGQSSGCCITPTGYRAQRGGASAVQPLNLSQNQQSSSASTSQERSSNPAPRRQQAFVAPLSQAPYAFQHGSPLHSTGHPHLAPAPAHLPSQPHLYTYAAPTSAAALGSTSSIAHLFSPQGSSRHAAAYTTHPSTLVHQVPVSVGPSLLTSASVAPAQYQHQFATQSYIGSSRGSTIYTGYPLSPTKISQYSYL
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Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. Phosphorylates PAGE4 at 'Thr-51' which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (By similarity).
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O88907
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PIAS1_MOUSE
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E3 SUMO-protein ligase PIAS1 (EC 2.3.2.27) (DEAD/H box-binding protein 1) (Protein inhibitor of activated STAT protein 1) (RING-type E3 ubiquitin transferase PIAS1)
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MADSAELKQMVMSLRVSELQVLLGYAGRNKHGRKHELLTKALHLLKAGCSPAVQMKIKELYRRRFPQKIMTPADLSIPNVHSSPMPPTLSPSTIPQLTYDGHPASSPLLPVSLLGPKHELELPHLTSALHPVHPDIKLQKLPFYDLLDELIKPTSLASDNSQRFRETCFAFALTPQQVQQISSSMDISGTKCDFTVQVQLRFCLSETSCPQEDHFPPNLCVKVNTKPCSLPGYLPPTKNGVEPKRPSRPINITSLVRLSTTVPNTIVVSWTAEIGRTYSMAVYLVKQLSSTVLLQRLRAKGIRNPDHSRALIKEKLTADPDSEIATTSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHLIIDGLFMEILKYCTDCDEIQFKEDGSWAPMRSKKEVQEVTASYNGVDGCLSSTLEHQVASHNQSSNKNKKVEVIDLTIDSSSDEEEEEPPAKRTCPSLSPTSPLSNKGILSLPHQASPVSRTPSLPAVDTSYINTSLIQDYRHPFHMTPMPYDLQGLDFFPFLSGDNQHYNTSLLAAAAAAVSDDQDLLHSSRFFPYTSSQMFLDQLSAGGSTSLPATNGSSSGSNSSLVSSNSLRESHGHGVASRSSADTASIFGIIPDIISLD
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Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53 pathway and the steroid hormone signaling pathway. In vitro, binds A/T-rich DNA (By similarity). The effects of this transcriptional coregulation, transactivation or silencing, may vary depending upon the biological context. Sumoylates PML (at'Lys-65' and 'Lys-160') and PML-RAR and promotes their ubiquitin-mediated degradation. PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 which in turn promotes PML phosphorylation and degradation. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation. Plays a dynamic role in adipogenesis by promoting the SUMOylation and degradation of CEBPB.
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O88908
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SOAT2_MOUSE
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Sterol O-acyltransferase 2 (EC 2.3.1.26) (Acyl-coenzyme A:cholesterol acyltransferase 2) (ACAT-2) (Cholesterol acyltransferase 2)
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MQPKVPQLRRREGLGEEQEKGARGGEGNARTHGTPDLVQWTRHMEAVKTQFLEQAQRELAELLDRALWEAMQAYPKQDRPLPSAAPDSTSKTQELHPGKRKVFITRKSLIDELMEVQHFRTIYHMFIAGLCVLIISTLAIDFIDEGRLMLEFDLLLFSFGQLPLALMTWVPMFLSTLLVPYQTLWLWARPRAGGAWMLGASLGCVLLAAHAVVLCVLPVHVSVRHELPPASRCVLVFEQVRLLMKSYSFLRETVPGIFCVRGGKGISPPSFSSYLYFLFCPTLIYRETYPRTPSIRWNYVAKNFAQVLGCLLYACFILGRLCVPVFANMSREPFSTRALLLSILHATGPGIFMLLLIFFAFLHCWLNAFAEMLRFGDRMFYRDWWNSTSFSNYYRTWNVVVHDWLYSYVYQDGLWLLGRRARGVAMLGVFLVSAVVHEYIFCFVLGFFYPVMLMLFLVFGGLLNFTMNDRHTGPAWNILMWTFLFMGQGIQVSLYCQEWYARRHCPLPQTTFWGMVTPRSWSCHP
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Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. Utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) and linolenoyl-CoA ((9Z,12Z,15Z)-octadecatrienoyl-CoA) as substrates. May provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa.
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O88909
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S22A8_MOUSE
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Organic anion transporter 3 (mOat3) (Organic anion/dicarboxylate exchanger) (Reduced in osteosclerosis transporter) (Roct) (Solute carrier family 22 member 8)
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MTFSEILDRVGSMGPFQYLHVTLLALPILGIANHNLLQIFTATTPDHHCRPPPNASLEPWVLPLGPNGKPEKCLRFVHLPNASLPNDTQGATEPCLDGWIYNSTRDTIVTEWDLVCGSNKLKEMAQSVFMAGILVGGPVFGELSDRFGRKPILTWSYLLLAASGSSAAFSPSLTVYMIFRFLCGCSISGISLSTIILNVEWVPTSTRAISSTTIGYCYTIGQFILPGLAYAVPQWRWLQLSVSAAFFIFSLLSWWVPESIRWLVLSGKFSKALKTLQRVATFNGKKEEGEKLTVEELKFNLQKDITSAKVKYGLSDLFRVSILRRVTFCLSLAWFATGFAYYSLAMGVEEFGVNIYILQIIFGGVDIPAKFITILSISYLGRRITQGFLLILAGVAILALIFVSSEMQLLRTALAVFGKGCLSGSFSCLFLYTSELYPTVLRQTGMGISNIWARVGSMIAPLVKITGELQPFIPNVIFGTMTLLGGSAAFFLLETLNRPLPETIEDIQDWYQQTKKTKQEPEAEKASQTIPLKTGGP
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Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (By similarity). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain. E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange. Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule. Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate. Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (By similarity). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (By similarity). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (By similarity). May contribute to the release of cortisol in the adrenals (By similarity). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile. Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB) (By similarity). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (By similarity). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity).
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O88910
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MPP3_MOUSE
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MAGUK p55 subfamily member 3 (Discs large homolog 3) (Protein MPP3)
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MPVLSEDSGLHETLALLTSQLRPDSNHREEMGFLRDVFSEKSLSYLMKIHEKLRYYERQSPTPVLHSAMALAEDVMEELQAASVHSDERELLQLLSTPHLRAVLMVHDTVAQKNFDPVLPPLPDNIDEDFEEESVKIVRLVKNKEPLGATIRRDEHSGAVVVARIMRGGAADRSGLVHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKIIPATQEEDRFKDSKVFMRALFHYDPREDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRVGDTNLRAGLIPSKQFQERRLSYRRTTGTLPSPQNFKKPPYDQPCDKETCDCDGYFKGHYVAGLRRSFRLGCRERLGGSQEAKVPTGAESQVLLTYEEVARYQHQPGERPRLVVLIGSLGAHLHELKQRVVAEDPQQFAVAVPHTTRPRKSHERDGVEYHFVSKQAFEADVHHNKFLEHGEYKENLYGTSLEAIQAVMAKNKVCLVDVEPEALRHLRTPEFKPYVIFVKPAIQERRKTPPVSPDSEDIASSLDEQQQEMAASAAFIDQHYGHLIDTVLVRQDLQEPAASSELS
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Participates in cell spreading through the phosphoinositide-3-kinase (PI3K) pathway by connecting CADM1 to DLG1 and the regulatory subunit of phosphoinositide-3-kinase (PI3K) (By similarity). Stabilizes HTR2C at the plasma membrane and prevents its desensitization. May participates in the maintenance of adherens junctions.
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O88917
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AGRL1_RAT
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Adhesion G protein-coupled receptor L1 (Calcium-independent alpha-latrotoxin receptor 1) (CIRL-1) (Latrophilin-1)
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MARLAAALWSLCVTTVLVTSATQGLSRAGLPFGLMRRELACEGYPIELRCPGSDVIMVENANYGRTDDKICDADPFQMENVQCYLPDAFKIMSQRCNNRTQCVVVAGSDAFPDPCPGTYKYLEVQYDCVPYKVEQKVFVCPGTLQKVLEPTSTHESEHQSGAWCKDPLQAGDRIYVMPWIPYRTDTLTEYASWEDYVAARHTTTYRLPNRVDGTGFVVYDGAVFYNKERTRNIVKYDLRTRIKSGETVINTANYHDTSPYRWGGKTDIDLAVDENGLWVIYATEGNNGRLVVSQLNPYTLRFEGTWETGYDKRSASNAFMVCGVLYVLRSVYVDDDSEAAGNRVDYAFNTNANREEPVSLAFPNPYQFVSSVDYNPRDNQLYVWNNYFVVRYSLEFGPPDPSAGPATSPPLSTTTTARPTPLTSTASPAATTPLRRAPLTTHPVGAINQLGPDLPPATAPAPSTRRPPAPNLHVSPELFCEPREVRRVQWPATQQGMLVERPCPKGTRGIASFQCLPALGLWNPRGPDLSNCTSPWVNQVAQKIKSGENAANIASELARHTRGSIYAGDVSSSVKLMEQLLDILDAQLQALRPIERESAGKNYNKMHKRERTCKDYIKAVVETVDNLLRPEALESWKDMNATEQVHTATMLLDVLEEGAFLLADNVREPARFLAAKQNVVLEVTVLSTEGQVQELVFPQEYASESSIQLSANTIKQNSRNGVVKVVFILYNNLGLFLSTENATVKLAGEAGTGGPGGASLVVNSQVIAASINKESSRVFLMDPVIFTVAHLEAKNHFNANCSFWNYSERSMLGYWSTQGCRLVESNKTHTTCACSHLTNFAVLMAHREIYQGRINELLLSVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLVGIDKTQYEVACPIFAGLLHYFFLAAFSWLCLEGVHLYLLLVEVFESEYSRTKYYYLGGYCFPALVVGIAAAIDYRSYGTEKACWLRVDNYFIWSFIGPVSFVIVVNLVFLMVTLHKMIRSSSVLKPDSSRLDNIKSWALGAIALLFLLGLTWAFGLLFINKESVVMAYLFTTFNAFQGVFIFVFHCALQKKVHKEYSKCLRHSYCCIRSPPGGAHGSLKTSAMRSNTRYYTGTQVPGQGRHIHQVSLGPRGRSALPESQKDPGGQSGPGDPLTFGLCPSRIRRMWNDTVRKQTESSFMAGDINSTPTLNRGTMGNHLLTNPVLQPRGGTSPYNTLIAESVGFNPSSPPVFNSPGSYREPKHPLGGREACGMDTLPLNGNFNNSYSLRSGDFPPGDGGPEPPRGRNLADAAAFEKMIISELVHNNLRGASGGAKGPPPEPPVPPVPGVSEDEAGGPGGADRAEIELLYKALEEPLLLPRAQSVLYQSDLDESESCTAEDGATSRPLSSPPGRDSLYASGANLRDSPSYPDSSPEGPNEALPPPPPAPPGPPEIYYTSRPPALVARNPLQGYYQVRRPSHEGYLAAPSLEGPGPDGDGQMQLVTSL
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Calcium-independent receptor of high affinity for alpha-latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor probably implicated in the regulation of exocytosis. [Isoform 2]: Receptor for TENM2 that mediates heterophilic synaptic cell-cell contact and postsynaptic specialization.
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O88923
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AGRL2_RAT
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Adhesion G protein-coupled receptor L2 (Calcium-independent alpha-latrotoxin receptor 2) (CIRL-2) (Latrophilin-2)
|
MVSSGCRMRSLWFIMIISFSPNTEGFSRAALPFGLVRRELSCEGYSIDLRCPGSDVIMIESANYGRTDDKICDADPFQMENTDCYLPDAFKIMTQRCNNRTQCVVVTGSDVFPDPCPGTYKYLEVQYECVPYMEQKVFVCPGTLKAIVDSPSIYEAEQKAGAWCKDPLQAADKIYFMPWTPYRTDTLIEYASLEDFQNSRQTTTYKLPNRVDGTGFVVYDGAVFFNKERTRNIVKFDLRTRIKSGEAIINYANYHDTSPYRWGGKTDIDLAVDENGLWVIYATEQNNGMIVISQLNPYTLRFEATWETTYDKRAASNAFMICGVLYVVRSVYQDNESEAGKNVIDYIYNTRLSRGEHVDVPFPNQYQYIAAVDYNPRDNQLYVWNNNFILRYSLEFGPPDPAQVPTTAVTITSSAELFKTTVSTTSSTSQRGPVSSTVAGPQEGSRGTKPPPAVSTTKIPPVTNIFPLPERFCEALEMKGIKWPQTQRGMMVERPCPKGTRGTASYLCMASTGTWNPKGPDLSNCTSHWVNQLAQKIRSGENAASLANELAKHTKGTVFAGDVSSSVRLMEQLVDILDAQLQELKPSEKDSAGRSYNKLQKREKTCRAYLKAIVDTVDNLLRAETLDCWKHMNSSEQAHTATMLLDTLEEGAFVLADNLLEPTRVSMPTDNIVLEVAVLSTEGQVQDFTFHLGFKGAFSSIQLSANTVKQNSRNGLAKVVFIIYRSLGPFLSTENATVKLGADLLGRNSTIAVNSHVLSVSINKESSRVYLTDPVLFSMPHIDSDNYFNANCSFWNYSERTMMGYWSTQGCKLVDTNKTRTTCACSHLTNFAILMAHREIVYKDGVHKLLLTVITWVGIVVSLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIGIDKTQYTIACPVFAGLLHFFFLAAFSWMCLEGVQLYLMLVEVFESEYSRKKYYYVAGYLFPATVVGVSAAIDSKSYGTLEACWLHVDNYFIWSFIGPVTFIILLNIIFLVITLCKMVKHSNTLKPDSSRLENINNYRVCDGYYNTDLPGYEDNKPFIKSWVLGAFALLCLLGLTWSFGLLFVNEETVVMAYLFTAFNAFQGLFIFIFHCALQKKVRKEYAKCFRHWYCCGGLPTESPHSSVKASTSRTSARYSSGTQSRIRRMWNDTVRKQSESSFISGDINSTSTLNQGMTGNYLLTNPLLRPHGTNNPYNTLLAETVVCNAPSAPVFNSPGHSLNNTRDTSAMDTLPLNGNFNNSYSLRKADYHDGVQVVDCGLSLNDTAFEKMIISELVHNNLRGSNKTHNLELKLPVKPVIGGSSSEDDAIVADASSLMHGDNPGLEFRHKELEAPLIPQRTHSLLYQPQKKVKPEATDSYVSQLTAEADEHLQSPNRDSLYTSMPNLRDSPYPESSPDMAEDLSPSRRSENEDIYYKSMPNLGAGRQLQMCYQISRGNSDGYIIPINKEGCIPEGDVREGQMQLVTSL
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Calcium-independent receptor of low affinity for alpha-latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor probably implicated in the regulation of exocytosis.
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O88935
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SYN1_MOUSE
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Synapsin-1 (Synapsin I)
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MNYLRRRLSDSNFMANLPNGYMTDLQRPQPPPPPPSAASPGATPGSATASAERASTAAPVASPAAPSPGSSGGGGFFSSLSNAVKQTTAAAAATFSEQVGGGSGGAGRGGAAARVLLVIDEPHTDWAKYFKGKKIHGEIDIKVEQAEFSDLNLVAHANGGFSVDMEVLRNGVKVVRSLKPDFVLIRQHAFSMARNGDYRSLVIGLQYAGIPSVNSLHSVYNFCDKPWVFAQMVRLHKKLGTEEFPLIDQTFYPNHKEMLSSTTYPVVVKMGHAHSGMGKVKVDNQHDFQDIASVVALTKTYATAEPFIDAKYDVRVQKIGQNYKAYMRTSVSGNWKTNTGSAMLEQIAMSDRYKLWVDTCSEIFGGLDICAVEALHGKDGRDHIIEVVGSSMPLIGDHQDEDKQLIVELVVNKMTQALPRQPQRDASPGRGSHSQSSSPGALTLGRQTSQQPAGPPAQQRPPPQGGPPQPGPGPQRQGPPLQQRPPPQGQQHLSGLGPPAGSPLPQRLPSPTAAPQQSASQATPVTQGQGRQSRPVAGGPGAPPAARPPASPSPQRQAGAPQATRQASISGPAPTKASGAPPGGQQRQGPPQKPPGPAGPTRQASQAGPGPRTGPPTTQQPRPSGPGPAGRPAKPQLAQKPSQDVPPPITAAAGGPPHPQLNKSQSLTNAFNLPEPAPPRPSLSQDEVKAETIRSLRKSFASLFSD
|
Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton. Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pre-synaptic terminal (By similarity). Also involved in the regulation of axon outgrowth and synaptogenesis. The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxide functions at a presynaptic level (By similarity).
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O88939
|
ZBT7A_MOUSE
|
Zinc finger and BTB domain-containing protein 7A (Leukemia/lymphoma-related factor) (POZ and Krueppel erythroid myeloid ontogenic factor) (POK erythroid myeloid ontogenic factor) (Pokemon)
|
MAGGVDGPIGIPFPDHSSDILSGLNEQRTQGLLCDVVILVEGREFPTHRSVLAACSQYFKKLFTSGAVVDQQNVYEIDFVSAEALTALMDFAYTATLTVSTANVGDILSAARLLEIPAVSHVCADLLERQILAADDVGDASQPDGAGPTDQRNLLRAKEYLEFFRSNPMNSLPPTAFPWSGFGAPDDDLDATKEAVAAAVAAVAAGDCNGLDFYGPGPPADRPPAGDGDEGDSTPGLWPERDEDAPPGGLFPPPTAPPATTQNGHYGRAGAGTGEEEAAALSEAAPEPGDSPGFLSGAAEGEDGDAADVDGLAASTLLQQMMSSVGRAGDSDEESRTDDKGVMDYYLKYFSGAHEGDVYPAWSQKGEKKIRAKAFQKCPICEKVIQGAGKLPRHIRTHTGEKPYECNICKVRFTRQDKLKVHMRKHTGEKPYLCQQCGAAFAHNYDLKNHMRVHTGLRPYQCDSCCKTFVRSDHLHRHLKKDGCNGVPSRRGRKPRVRGVPPDVPAGAGAPPGLPDAPRNGQEKHFKDEEEDEEEASPDGSGRLNVAGSGGDDGAGGPAVATAEGNFAT
|
Transcription factor that represses the transcription of a wide range of genes involved in cell proliferation and differentiation. Directly and specifically binds to the consensus sequence 5'-[GA][CA]GACCCCCCCCC-3' and represses transcription both by regulating the organization of chromatin and through the direct recruitment of transcription factors to gene regulatory regions. Negatively regulates SMAD4 transcriptional activity in the TGF-beta signaling pathway through these two mechanisms (By similarity). That is, recruits the chromatin regulator HDAC1 to the SMAD4-DNA complex and in parallel prevents the recruitment of the transcriptional activators CREBBP and EP300 (By similarity). Collaborates with transcription factors like RELA to modify the accessibility of gene transcription regulatory regions to secondary transcription factors. Also directly interacts with transcription factors like SP1 to prevent their binding to DNA (By similarity). Functions as an androgen receptor/AR transcriptional corepressor by recruiting NCOR1 and NCOR2 to the androgen response elements/ARE on target genes (By similarity). Thereby, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (By similarity). Involved in the switch between fetal and adult globin expression during erythroid cells maturation. Through its interaction with the NuRD complex regulates chromatin at the fetal globin genes to repress their transcription. Specifically represses the transcription of the tumor suppressor ARF isoform from the CDKN2A gene. Efficiently abrogates E2F1-dependent CDKN2A transactivation. Regulates chondrogenesis through the transcriptional repression of specific genes via a mechanism that also requires histone deacetylation. Regulates cell proliferation through the transcriptional regulation of genes involved in glycolysis (By similarity). Involved in adipogenesis through the regulation of genes involved in adipocyte differentiation (By similarity). Plays a key role in the differentiation of lymphoid progenitors into B and T lineages. Promotes differentiation towards the B lineage by inhibiting the T-cell instructive Notch signaling pathway through the specific transcriptional repression of Notch downstream target genes. Also regulates osteoclast differentiation (By similarity). May also play a role, independently of its transcriptional activity, in double-strand break repair via classical non-homologous end joining/cNHEJ. Recruited to double-strand break sites on damage DNA, interacts with the DNA-dependent protein kinase complex and directly regulates its stability and activity in DNA repair. May also modulate the splicing activity of KHDRBS1 toward BCL2L1 in a mechanism which is histone deacetylase-dependent and thereby negatively regulates the pro-apoptotic effect of KHDRBS1 (By similarity).
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O88940
|
MUSC_MOUSE
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Musculin (Myogenic repressor)
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MSTGSVSDPEDSEMRGLQRVYPAPASKRPPLLRMERGYGSPSDISSAEEEDGEEEPGSLGAAGGCKRKRLRGADAGGAGGRAGGAGKKPLPPKGSAAECKQSQRNAANARERARMRVLSKAFSRLKTSLPWVPPDTKLSKLDTLRLASSYIAHLRQLLQEDRYEDSYVHPVNLTWPFVVSGRPDSDSKDVSAANRLCGTSA
|
Transcription repressor that blocks myogenesis and activation of E-box dependent muscle genes.
|
O88942
|
NFAC1_MOUSE
|
Nuclear factor of activated T-cells, cytoplasmic 1 (NF-ATc1) (NFATc1) (NFAT transcription complex cytosolic component) (NF-ATc) (NFATc)
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MPNTSFPVPSKFPLGPPAAVCGSGETLRPAPPSGGTMKAAEEEHYSYVSPSVTSTLPLPTAHSALPAACHDLQTSTPGISAVPSANHPPSYGGAVDSGPSGYFLSSGNTRPNGAPTLESPRIEITSYLGLHHGSGQFFHDVEVEDVLPSCKRSPSTATLHLPSLEAYRDPSCLSPASSLSSRSCNSEASSYESNYSYPYASPQTSPWQSPCVSPKTTDPEEGFPRSLGACHLLGSPRHSPSTSPRASITEESWLGARGSRPTSPCNKRKYSLNGRQPSCSPHHSPTPSPHGSPRVSVTEDTWLGNTTQYTSSAIVAAINALTTDSTLDLGDGVPIKSRKTALEHAPSVALKVEPAGEDLGTTPPTSDFPPEEYTFQHLRKGAFCEQYLSVPQASYQWAKPKSLSPTSYMSPSLPALDWQLPSHSGPYELRIEVQPKSHHRAHYETEGSRGAVKASAGGHPIVQLHGYLENEPLTLQLFIGTADDRLLRPHAFYQVHRITGKTVSTTSHEIILSNTKVLEIPLLPENNMRAIIDCAGILKLRNSDIELRKGETDIGRKNTRVRLVFRVHIPQPNGRTLSLQVASNPIECSQRSAQELPLVEKQSTDSYPVIGGKKMVLSGHNFLQDSKVIFVEKAPDGHHVWEMEAKTDRDLCKPNSLVVEIPPFRNQRITSPAQVSFYVCNGKRKRSQYQRFTYLPANGNSVFLTLSSESELRGGFY
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Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (By similarity). Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function.
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O88943
|
KCNQ2_RAT
|
Potassium voltage-gated channel subfamily KQT member 2 (KQT-like 2) (Potassium channel subunit alpha KvLQT2) (Voltage-gated potassium channel subunit Kv7.2)
|
MVQKSRNGGVYPGTSGEKKLKVGFVGLDPGAPDSTRDGALLIAGSEAPKRGSVLSKPRTGGAGAGKPPKRNAFYRKLQNFLYNVLERPRGWAFIYHAYVFLLVFSCLVLSVFSTIKEYEKSSEGALYILEIVTIVVFGVEYFVRIWAAGCCCRYRGWRGRLKFARKPFCVIDIMVLIASIAVLAAGSQGNVFATSALRSLRFLQILRMIRMDRRGGTWKLLGSVVYAHSKELVTAWYIGFLCLILASFLVYLAEKGENDHFDTYADALWWGLITLTTIGYGDKYPQTWNGRLLAATFTLIGVSFFALPAGILGSGFALKVQEQHRQKHFEKRRNPAAGLIQSAWRFYATNLSRTDLHSTWQYYERTVTVPMISSQTQTYGASRLIPPLNQLEMLRNLKSKSGLTFRKEPQPEPSPSQKVSLKDRVFSSPRGVAAKGKGSPQAQTVRRSPSADQSLDDSPSKVPKSWSFGDRSRARQAFRIKGAASRQNSEEASLPGEDIVEDNKSCNCEFVTEDLTPGLKVSIRAVCVMRFLVSKRKFKESLRPYDVMDVIEQYSAGHLDMLSRIKSLQSRVDQIVGRGPTITDKDRTKGPAETELPEDPSMMGRLGKVEKQVLSMEKKLDFLVSIYTQRMGIPPAETEAYFGAKEPEPAPPYHSPEDSRDHADKHGCIIKIVRSTSSTGQRKYAAPPVMPPAECPPSTSWQQSHQRHGTSPVGDHGSLVRIPPPPAHERSLSAYSGGNRASTEFLRLEGTPACRPSEAALRDSDTSISIPSVDHEELERSFSGFSISQSKENLNALASCYAAVAPCAKVRPYIAEGESDTDSDLCTPCGPPPRSATGEGPFGDVAWAGPRK
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Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. Therefore, it is important in the regulation of neuronal excitability. KCNQ2 current is blocked by barium and tetraethylammonium whereas 4-aminopyridine and charybdotoxin have no effect on KCNQ2 current. Tyrosine kinase inhibitors genistein or herbimycin a markedly down-regulate KCNQ2 current. As the native M-channel, the potassium channel composed of KCNQ2 and KCNQ3 is also suppressed by activation of the muscarinic acetylcholine receptor CHRM1. KCNQ2-KCNQ3 channel is selectively permeable to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+). Associates with Na(+)-coupled myo-inositol symporter SLC5A3 forming a coregulatory complex that alters ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) permeation (By similarity).
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O88944
|
KCNQ3_RAT
|
Potassium voltage-gated channel subfamily KQT member 3 (KQT-like 3) (Potassium channel subunit alpha KvLQT3) (Voltage-gated potassium channel subunit Kv7.3)
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MGLKARRAAGAAGGGGGEGGGGGGGAANPAGGDSAVAGDEERKVGLAPGDVEQVTLALGTGADKDGTLLLEGGGREEGQRRTPQGIGLLAKTPLSRPVKRNNAKYRRIQTLIYDALERPRGWALLYHALVFLIVLGCLILAVLTTFKEYETVSGDWLLLLETFAIFIFGAEFALRIWAAGCCCRYKGWRGRLKFARKPLCMLDIFVLIASVPVVAVGNQGNVLATSLRSLRFLQILRMLRMDRRGGTWKLLGSAICAHSKELITAWYIGFLTLILSSFLVYLVEKDVPEMDAQGEEMKEEFETYADALWWGLITLATIGYGDKTPKTWEGRLIAATFSLIGVSFFALPAGILGSGLALKVQEQHRQKHFEKRRKPAAELIQAAWRYYATNPNRLDLVATWRFYESVVSFPFFRKEQLEAAASQKLGLLDRVRLSNPRGSNTKGKLFTPLNVDAIEESPSKEPKPVGLNNKERFRTAFRMKAYAFWQSSEDAGTGDPMTEDRGYGNDFLIEDMIPTLKAAIRAVRILQFRLYKKKFKETLRPYDVKDVIEQYSAGHLDMLSRIKYLQTRIDMIFTPGPPSTPKHKKSQKGSAFTYPSQQSPRNEPYVARAATSETEDQSMMGKFVKVERQVHDMGKKLDFLVDMHMQHMERLQVHVTEYYPTKGASSPAEGEKKEDNRYSDLKTIICNYSESGPPDPPYSFHQVPIDRVGPYGFFAHDPVKLTRGGPSSTKAQANLPSSGSTYAERPTVLPILTLLDSCVSYHSQTELQGPYSDHISPRQRRSITRDSDTPLSLMSVNHEELERSPSGFSISQDRDDYVFGPSGGSSWMREKRYLAEGETDTDTDPFTPSGSMPMSSTGDGISDSIWTPSNKPT
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Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. Therefore, it is important in the regulation of neuronal excitability. KCNQ2-KCNQ3 channel is selectively permeable to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+). Associates with Na(+)-coupled myo-inositol symporter SLC5A3 forming a coregulatory complex that alters ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) permeation (By similarity).
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O88947
|
FA10_MOUSE
|
Coagulation factor X (EC 3.4.21.6) (Stuart factor) [Cleaved into: Factor X light chain; Factor X heavy chain; Activated factor Xa heavy chain]
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MGSPVQLSLLCVVLASLLLPGKGVFINRERANNVLARTRRANSFFEEFKKGNLERECMEEICSYEEVREIFEDDEKTKEYWTKYKDGDQCESSPCQNQGACRDGIGGYTCTCSEGFEGKNCELFVRKLCRLDNGDCDQFCREEQNSVVCSCASGYFLGNDGKSCISTAPFPCGKITTGRRKRSVALNTSDSELDLEDALLDEDFLSPTENPIELLNLNETQPERSSDDLVRIVGGRECKDGECPWQALLINEDNEGFCGGTILNEFYILTAAHCLHQARRFKVRVGDRNTEKEEGNEMVHEVDVVIKHNKFQRDTYDYDIAVLRLKTPITFRMNVAPACLPQKDWAESTLMTQKTGIVSGFGRTHEKGRQSNILKMLEVPYVDRNTCKLSTSFSITQNMFCAGYEAKLEDACQGDSGGPHVTRFKNTYYVTGIVSWGEGCARKGKYGIYTKVTTFLKWIDRSMKARVGPTAETPRTAGPPN
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Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
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O88951
|
LIN7B_MOUSE
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Protein lin-7 homolog B (Lin-7B) (Mammalian lin-seven protein 2) (MALS-2) (Vertebrate lin-7 homolog 2) (Veli-2)
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MAALVEPLGLERDVSRAVELLERLQRSGELPPQKLQALQRVLQSRFCSAIREVYEQLYDTLDITGSAEVRAHATAKATVAAFTASEGHAHPRVVELPKTDEGLGFNIMGGKEQNSPIYISRVIPGGVADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGSVKLVVRYTPRVLEEMEARFEKMRSARRRQQHHSYTSLESRG
|
Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules. This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells. May increase the amplitude of ASIC3 acid-evoked currents by stabilizing the channel at the cell surface.
|
O88952
|
LIN7C_MOUSE
|
Protein lin-7 homolog C (Lin-7C) (mLin7C) (Mammalian lin-seven protein 3) (MALS-3) (Vertebrate lin-7 homolog 3) (Veli-3)
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MAALGEPVRLERDICRAIELLEKLQRSGEVPPQKLQALQRVLQSEFCNAVREVYEHVYETVDISSSPEVRANATAKATVAAFAASEGHSHPRVVELPKTEEGLGFNIMGGKEQNSPIYISRIIPGGIADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGKVKLVVRYTPKVLEEMESRFEKMRSAKRRQQT
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Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules. This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells.
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O88956
|
PLPP1_CAVPO
|
Phospholipid phosphatase 1 (EC 3.1.3.-) (EC 3.1.3.106) (EC 3.1.3.4) (EC 3.6.1.75) (Lipid phosphate phosphohydrolase 1) (PAP2-alpha) (Phosphatidate phosphohydrolase type 2a) (Phosphatidic acid phosphatase 2a) (PAP-2a) (PAP2a)
|
MFDKARLPYVALDVLCVVLAGLPFAILTSRHTPFQRGIFCNDESIKYPYKEDTIPYALLGGIMIPFSIVVMIIGETLSVYCNLLHSNSFIRNNYIATIYKSIGTFLFGAAASQSLTDIAKYSIGRLRPHFLSVCDPDWSKVNCSDGYIEYYVCRGNAEKVKEGRLSFYSGHSSFSMYCMVFVALYLQARMKGDWARLLRPTLQFGLVAASIYVGLSRISDYKHHWSDVLTGLIQGAIVAILVAVYVSDFFKARNSPFQERKEEDSHTTLHETPTAGNHYRSNHQP
|
Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P. Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound (By similarity). Through its extracellular phosphatase activity allows both the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes (By similarity). It is for instance essential for the extracellular hydrolysis of S1P and subsequent conversion into intracellular S1P (By similarity). Involved in the regulation of inflammation, platelets activation, cell proliferation and migration among other processes (By similarity). May also have an intracellular activity to regulate phospholipid-mediated signaling pathways (By similarity).
|
O88958
|
GNPI1_MOUSE
|
Glucosamine-6-phosphate isomerase 1 (EC 3.5.99.6) (Glucosamine-6-phosphate deaminase 1) (GNPDA 1) (GlcN6P deaminase 1) (Oscillin)
|
MKLIILEHYSQASEWAAKYIRNRIIQFNPGPDKYFTLGLPTGSTPLGCYQKLIEYYKNGDLSFQYVKTFNMDEYVGLPRDHPESYHSFMWNNFFKHIDIHPENTHILDGNAADLQAECDAFEEKIQAAGGIELFVGGIGPDGHIAFNEPGSSLVSRTRVKTLAMDTILANARFFDGDLAKVPTMALTVGVGTVMDAKEVMILITGAHKAFALYKAIEEGVNHMWTVSAFQQHPRTVFVCDEDATLELKVKTVKYFKGLMLVHNKLVDPLYSIKEKEIQKSQSAKKPYSD
|
Catalyzes the reversible conversion of alpha-D-glucosamine 6-phosphate (GlcN-6P) into beta-D-fructose 6-phosphate (Fru-6P) and ammonium ion, a regulatory reaction step in de novo uridine diphosphate-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc) biosynthesis via hexosamine pathway. Deamination is coupled to aldo-keto isomerization mediating the metabolic flux from UDP-GlcNAc toward Fru-6P. At high ammonium level can drive amination and isomerization of Fru-6P toward hexosamines and UDP-GlcNAc synthesis (By similarity). Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and their effects on hyaluronan synthesis that occur during tissue remodeling (By similarity). Seems to trigger calcium oscillations in mammalian eggs. These oscillations serve as the essential trigger for egg activation and early development of the embryo (By similarity).
|
O88962
|
CP8B1_MOUSE
|
7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase (EC 1.14.14.139) (7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase) (CYPVIIIB1) (Cytochrome P450 8B1) (Sterol 12-alpha-hydroxylase)
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MTLWCTVLGALLTVVGCLCLSLLLRHRRPWEPPLDKGFVPWLGHSMAFRKNMFEFLKGMRAKHGDVFTVQLGGQYFTFVMDPLSFGPIIKNTEKALDFQSYAKELVLKVFGYQSVDGDHRMIHLASTKHLMGQGLEELNQAMLDSLSLVMLGPKGSSLGASSWCEDGLFHFCYRILFKAGFLSLFGYTKDKQQDLDEADELFRKFRRFDFLFPRFVYSLLGPREWVEVSQLQRLFHQRLSVEQNLEKDGISCWLGYMLQFLREQGIASSMQDKFNFMMLWASQGNTGPTCFWVLLFLLKHQDAMKAVREEATRVMGKARLEAKKSFTFTPSALKHTPVLDSVMEESLRLCATPTLLRVVQEDYVLKMASGQEYQIRRGDKVALFPYLSVHMDPDIHPEPTAFKYDRFLNPDGTRKVDFYKSGKKIHHYSMPWGSGVSKCPGRFFALSEMKTFVLLMIMYFDFKLVDPDIPVPPIDPRRWGFGTSQPSHEVRFLYRLKPVQ
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A cytochrome P450 monooxygenase involved in primary bile acid biosynthesis. Catalyzes the 12alpha-hydroxylation of 7alpha-hydroxy-4-cholesten-3-one, an intermediate metabolite in cholic acid biosynthesis (By similarity). Controls biliary balance of cholic acid and chenodeoxycholic acid, ultimately regulating the intestinal absorption of dietary lipids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR NADPH--hemoprotein reductase) (By similarity).
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O88967
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YMEL1_MOUSE
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ATP-dependent zinc metalloprotease YME1L1 (EC 3.4.24.-) (ATP-dependent metalloprotease FtsH1) (YME1-like protein 1)
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MFSLSSTVQPQVTIPLSHLINAFHSPKNISVSVNTPVSQKQHRDTVPEHEAPSSEPVLNLRDLGLSELKIGQIDKMVENLLPGFYKDKRVSSCWHTSHISAQSFFENKYGHLDMFSTLRSSSLYRQHPKTLRSICSDLQYFPVFIQSRGFKTLKSRTRRLQSTSERLVEAQNIAPSFVKGFLLRDRGTDLESLDKLMKTKNIPEAHQDAFKTGFAEGFLKAQALTQKTNDSLRRTRLILFVLLLFGIYGLLKNPFLSVRFRTTTGLDSAVDPVQMKNVTFEHVKGVEEAKQELQEVVEFLKNPQKFTVLGGKLPKGILLVGPPGTGKTLLARAVAGEADVPFYYASGSEFDEMFVGVGASRIRNLFREAKANAPCVIFIDELDSVGGKRIESPMHPYSRQTINQLLAEMDGFKPNEGVIIIGATNFPEALDNALIRPGRFDMQVTVPRPDVKGRTEILKWYLNKIKFDKSVDPEIIARGTVGFSGAELENLVNQAALKAAVDGKEMVTMKELEFSKDKILMGPERRSVEIDNKNKTITAYHESGHAIIAYYTKDAMPINKATIMPRGPTLGHVSLLPENDRWNETRAQLLAQMDVSMGGRVAEELIFGTDHITTGASSDFDNATKIAKRMVTKFGMSEKLGVMTYSDTGKLSPETQSAIEQEIRILLRESYERAKHILKTHAKEHKNLAEALLTYETLDAKEIQIVLEGKKLEVR
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ATP-dependent metalloprotease that catalyzes the degradation of folded and unfolded proteins with a suitable degron sequence in the mitochondrial intermembrane region (By similarity). Plays an important role in regulating mitochondrial morphology and function by cleaving OPA1 at position S2, giving rise to a form of OPA1 that promotes maintenance of normal mitochondrial structure. Ensures cell proliferation, maintains normal cristae morphology and complex I respiration activity, promotes antiapoptotic activity and protects mitochondria from the accumulation of oxidatively damaged membrane proteins (By similarity). Required for normal, constitutive degradation of PRELID1. Catalyzes the degradation of OMA1 in response to membrane depolarization. Required to control the accumulation of nonassembled respiratory chain subunits (NDUFB6, OX4 and ND1) (By similarity).
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O88974
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SETB1_MOUSE
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Histone-lysine N-methyltransferase SETDB1 (EC 2.1.1.366) (ERG-associated protein with SET domain) (ESET) (SET domain bifurcated 1)
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MSSLPGCMSLAAAPAAADSAEIAELQQAVVEELGISMEELRQYIDEELEKMDCIQQRKKQLAELETWVLQKESEVAYVDRLFDDASREVTNCESLVKDFYSKLGLQYHDSSSEDEASRPTEIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRKSAQDVQKFMDAVNKKSSSQDLHKGTLGQVSGELSKDGDLIVSMRILGKKRTKTWHKGTLIAIQTVGLGKKYKVKFDNKGKSLLSGNHIAYDYHPPADKLFVGSRVVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDGYASYVTQSELYPICRPLKKTWEDIEDSSCRDFIEEYITAYPNRPMVLLKSGQLIKTEWEGTWWKSRVEEVDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASAMEKKQGGQLRTRPNMGAVRSKGPVVQYTQDLTGTGIQFKPMEPLQPIAPPAPLPIPPLSPQAADTDLESQLAQSRKQVAKKSTSFRPGSVGSGHSSPTSSTLSENVSAGKLGINQTYRSPLASVTSTPASAAPPVPPVPPGPPTPPGPPAPPGPLAPPAFHGMLERAPAEPSYRAPMEKLFYLPHVCSYTCLSRIRPMRNEQYRGKNPLLVPLLYDFRRMTARRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCLDPYVLVDRKFQPFKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFINTGPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQVNPNSGYQYKRLEECLPTGVYECNKRCNCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILTDDFADKEGLEMGDEYFANLDHIESVENFKEGYESDVPTSSDSSGVDMKDQEDGNSGSEDPEESNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENELSEMTSKDSRPPDLGPPHVPIPSSVSVGGCNPPSSEETPKNKVASWLSCNSVSEGGFADSDSRSSFKTSEGGDGRAGGGRGEAERASTSGLSFKDEGDNKQPKKEDPENRNKMPVVTEGSQNHGHNPPMKSEGLRRPASKMSVLQSQRVVTSTQSNPDDILTLSSSTESEGESGTSRKPTAGHTSATAVDSDDIQTISSGSDGDDFEDKKNLSGPTKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKNTRQFYDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTELTWDYNYEVGSVEGKELLCCCGAIECRGRLL
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Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (By similarity). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (By similarity). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway. Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (By similarity).
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O88978
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DAA11_MOUSE
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Dynein axonemal assembly factor 11 (DNAAF11) (Leucine-rich repeat-containing protein 6) (Leucine-rich testis-specific protein) (Protein tilB homolog) (Testis-specific leucine-rich repeat protein)
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MGRITEDLIRRNAEHNDCVIFSLEELSLHQQEIERLEHIDKWCRDLKILYLQNNLIGKIENVSKLKKLEYLNLALNNIERIENLEGCEWLTKLDLTVNFIGELSSVKTLTHNIHLKELFLMGNPCADFDGYRQFVVVTLQQLKWLDGKEIERSERIQALQNYTSVEQQIREQEKAYCLRRAKEKEEAQRKLEEENESEDKKKSSTGFDGHWYTDIHTACPSATENQDYPQVPETQEEQHNTKESDDIEDDLAFWNKPSLFTPESRLETLRHMEKQRKAQDKLSEKKKKAKPPRTLITEDGKVLNVNEAKLDFSLKDDEKHNQIILDLAVYRYMDTSLIEVDVQPTYVRVMVKGKPFQLALSTEVQPDRSSAKRSQTTGHLLICMPKVGEMITGGQRTPTSVKTTSTSSREQTNPRKKQIERLEVDPSKHSCPDVSTIVQEKRHRPKRMESQPRDEPSEEDPDFEDNPEVPPLI
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Involved in dynein arm assembly, is important for expression and transporting outer dynein arm (ODA) proteins from the cytoplasm to the cilia. Acts as a crucial component in the formation and motility of spermatozoal flagella (By similarity).
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O88983
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STX8_MOUSE
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Syntaxin-8 (Syntaxin-like protein 3I35)
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MAPDPWFSTYDSTCQIAQEIAEKIQERNQCERRGEKTPKLTLTIRTLLKNLKVKIDLLKDLLLRAVSTRQITQLEGDRRQNLLDDLVTRERLLLASFKNEGAEPDLIRSSLMSEEAKRGTPNPWLCEEPEETRGLGFDEIRQQQQKIIQEQDAGLDALSSIISRQKQMGQEIGNELDEQNEIIDDLANLVENTDEKLRTEARRVTLVDRKSTSCGMIMVILLLLVAIVVVAVWPTN
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Vesicle trafficking protein that functions in the early secretory pathway, possibly by mediating retrograde transport from cis-Golgi membranes to the ER.
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O88984
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NXF1_RAT
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Nuclear RNA export factor 1 (Tip-associated protein) (Tip-associating protein) (mRNA export factor TAP)
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MADEGKSYNEHDDRVSFPQRRKKGRGPFRWKCGVGNRRSGRGGSGIRSSRFEEDDGDVAMNDPQDGPRVRFNPYTTRPNRRRDTWHDRDRIHVTVRRDRAPQERGGAGTSQDGTTKNWFKITIPYGKKYDKMWLLSMIQSKCSVPFNPIEFHYENTRAHFFVENATTASALKAVNYKIQDRENGRISIIINSSAPPYIVQNELKPEQVEQLKLIMSKRYDGSQQALDLKGLRSDPDLVAQNIDVVLNRRGCMAAALRIIEENIPELLSLNLSNNRLYKLDDMSSIVQKAPNLKILNLSGNELKSEWELDKIKGLKLEELWLDRNPMCDTFLDQSTYISTIRERFPKLLRLDGHELPPPIAFDVEAPTMLPPCKGSYFGTENLKSLVLHFLQQYYAIYDSGDRQGLLDAYHDGACCSLSTPSNPQNPVRHNLAKYFNDSRNVKKIKDTTTRFRLLKHTRLNVVAFLNELPKTHHDVNSFVVDISAQTSTLLCFSVNGVFKEVDGKSRDSLRAFTRTFIAVPASNSGLCIVNDELFVRNASPEEIQRAFAMPAPTPSSSPVPTLSQEQQDMLQAFSTQSGMNLEWSQKCLQDNNWDYTRSAQAFTHLKAKGEIPEVAFMK
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Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex. ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export. Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export.
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O88987
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AKAP3_MOUSE
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A-kinase anchor protein 3 (AKAP-3) (A-kinase anchor protein 110 kDa) (AKAP 110) (Protein kinase A-anchoring protein 3) (PRKA3)
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MADRVDWLQSQSGVCKVGVYSPGDNQHQDWKMDTSTDPVRVLSWLRKDLEKSTAGFQDSRFKPGESSFVEEVAYPVDQRKGFCVDYYNTTNKGSPGRLHFEMSHKENPSQGLISHVGNGGSIDEVSFYANRLTNLVIAMARKEINEKIHGAENKCVHQSLYMGDEPTPHKSLSTVASELVNETVTACSKNISSDKAPGSGDRASGSSQAPGLRYTSTLKIKESTKEGKCPDDKPGTKKSFFYKEVFESRNAGDAKEGGRSLPGDQKLFRTSPDNRPDDFSNSISQGIMTYANSVVSDMMVSIMKTLKIQVKDTTIATILLKKVLMKHAKEVVSDLIDSFMKNLHGVTGSLMTDTDFVSAVKRSFFSHGSQKATDIMDAMLGKLYNVMFAKKFPENIRRARDKSESYSLISTKSRAGDPKLSNLNFAMKSESKLKENLFSTCKLEKEKTCAETLGEHIIKEGLHMWHKSQQKSPGLERAAKLGNAPQEVSFECPDPCEANPPHQPQPPENFANFMCDSDSWAKDLIVSALLLIQYHLAQGGKMDAQSFLEAAASTNFPTNKPPPPSPVVQDECKLKSPPHKICDQEQTEKKDLMSVIFNFIRNLLSETIFKSSRNCESNVHEQNTQEEEIHPCERPKTPCERPITPPAPKFCEDEEATGGALSGLTKMVANQLDNCMNGQMVEHLMDSVMKLCLIIAKSCDSPLSELGEEKCGDASRPNSAFPDNLYECLPVKGTGTAEALLQNAYLTIHNELRGLSGQPPEGCEIPKVIVSNHNLADTVQNKQLQAVLQWVAASELNVPILYFAGDDEGIQEKLLQLSATAVEKGRSVGEVLQSVLRYEKERQLDEAVGNVTRLQLLDWLMANL
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May function as a regulator of both motility- and head-associated functions such as capacitation and the acrosome reaction.
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O88989
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MDHC_RAT
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Malate dehydrogenase, cytoplasmic (EC 1.1.1.37) (Aromatic alpha-keto acid reductase) (KAR) (EC 1.1.1.96) (Cytosolic malate dehydrogenase)
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MSEPIRVLVTGAAGQIAYSLLYSIGNGSVFGKDQPIILVLLDITPMMGVLDGVLMELQDCALPLLQDVIATDKEEVAFKDLDVAVLVGSMPRREGMERKDLLKANVKIFKSQGAALEKYAKKSVKVIVVGNPANTNCLTASKSAPSIPKENFSCLTRLDHNRAKSQIALKLGVTADDVKNVIIWGNHSSTQYPDVNHAKVKLQGKEVGVYEALKDDSWLKGEFITTVQQRGAAVIKARKLSSAMSAAKAISDHIRDIWFGTPEGEFVSMGVISDGNSYGVPDDLLYSFPVVIKNKTWKFVEGLPINDFSREKMDLTAKELTEEKETAFEFLSSA
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Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH. Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation.
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O88990
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ACTN3_MOUSE
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Alpha-actinin-3 (Alpha-actinin skeletal muscle isoform 3) (F-actin cross-linking protein)
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MMMVMQPEGLGAGEGPFSGGGGGEYMEQEEDWDRDLLLDPAWEKQQRKTFTAWCNSHLRKAGTQIENIEEDFRNGLKLMLLLEVISGERLPRPDKGKMRFHKIANVNKALDFIASKGVKLVSIGAEEIVDGNLKMTLGMIWTIILRFAIQDISVEETSAKEGLLLWCQRKTAPYRNVNVQNFHTSWKDGLALCALIHRHRPDLIDYAKLRKDDPIGNLNTAFEVAEKYLDIPKMLDAEDIVNTPKPDEKAIMTYVSCFYHAFAGAEQAETAANRICKVLAVNQENEKLMEEYEKLASELLEWIRRTVPWLENRVGEPSMSAMQRKLEDFRDYRRLHKPPRVQEKCQLEINFNTLQTKLRLSHRPAFMPSEGKLVSDIANAWRGLEQVEKGYEDWLLSEIRRLQRLQHLAEKFQQKASLHEAWTRGKEEMLNQHDYESASLQEVRALLRRHEAFESDLAAHQDRVEHIAALAQELNELDYHEAASVNSRCQAICDQWDNLGTLTQKRRDALERMEKLLETIDQLQLEFARRAAPFNNWLDGAIEDLQDVWLVHSVEETQSLLTAHEQFKATLPEADRERGAILGIQGEIQKICQTYGLRPKSGNPYITLSSQDINNKWDTVRKLVPSRDQTLQEELARQQVNERLRRQFAAQANAIGPWIQGKVEEVGRLAAGLAGSLEEQMAGLRQQEQNIINYKSNIDRLEGDHQLLQESLVFDNKHTVYSMEHIRVGWEQLLTSIARTINEVENQVLTRDAKGLSQEQLNEFRASFNHFDRKRNGMMEPDDFRACLISMGYDLGEVEFARIMTMVDPNAAGVVTFQAFIDFMTRETAETDTAEQVVASFKILAGDKNYITPEELRRELPAEQAEYCIRRMAPYKGSGAPSGALDYVAFSSALYGESDL
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F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (By similarity).
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O88992
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C1QRF_MOUSE
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C1q-related factor (C1q and tumor necrosis factor-related protein 14) (C1q/TNF-related protein 14) (CTRP14) (Complement component 1 Q subcomponent-like 1)
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MLLVLVVLIPVLVSSGGPDGHYEMLGTCRMVCDPYPARGPGAGARSDGGDALSEQSGAPPPSTLVQGPQGKPGRTGKPGPPGPPGDRGPPGPVGPPGEKGEPGKPGPPGLPGSGGSGAISTATYTTVPRVAFYAGLKNPHEGYEVLKFDDVVTNLGNNYDAASGKFTCNIPGTYFFTYHVLMRGGDGTSMWADLCKNGQVRASAIAQDADQNYDYASNSVILHLDAGDEVFIKLDGGKAHGGNSNKYSTFSGFIIYSD
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May regulate the number of excitatory synapses that are formed on hippocampus neurons. Has no effect on inhibitory synapses.
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O88998
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NOE1_MOUSE
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Noelin (Neuronal olfactomedin-related ER localized protein) (Olfactomedin-1) (Pancortin)
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MSVPLLKIGVVLSTMAMITNWMSQTLPSLVGLNTTRLSAASGGTLDRSTGVLPTNPEESWQVYSSAQDSEGRCICTVVAPQQTMCSRDARTKQLRQLLEKVQNMSQSIEVLDRRTQRDLQYVEKMENQMKGLETKFKQVEESHKQHLARQFKAIKAKMDELRPLIPVLEEYKADAKLVLQFKEEVQNLTSVLNELQEEIGAYDYDELQSRVSNLEERLRACMQKLACGKLTGISDPVTVKTSGSRFGSWMTDPLAPEGDNRVWYMDGYHNNRFVREYKSMVDFMNTDNFTSHRLPHPWSGTGQVVYNGSIYFNKFQSHIIIRFDLKTEAILKTRSLDYAGYNNMYHYAWGGHSDIDLMVDENGLWAVYATNQNAGNIVISKLDPVSLQILQTWNTSYPKRSAGEAFIICGTLYVTNGYSGGTKVHYAYQTNASTYEYIDIPFQNKYSHISMLDYNPKDRALYAWNNGHQTLYNVTLFHVIRSDEL
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Contributes to the regulation of axonal growth in the embryonic and adult central nervous system by inhibiting interactions between RTN4R and LINGO1. Inhibits RTN4R-mediated axon growth cone collapse. May play an important role in regulating the production of neural crest cells by the neural tube (By similarity). May be required for normal responses to olfactory stimuli.
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O89000
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DPYD_RAT
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Dihydropyrimidine dehydrogenase [NADP(+)] (DHPDHase) (DPD) (EC 1.3.1.2) (Dihydrothymine dehydrogenase) (Dihydrouracil dehydrogenase)
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MAGVLSRDAPDIESILALNPRIQAHATLRSTMAKKLDKKHWKRNTDKNCFICEKLENNFDDIKHTTLGERGALREAVRCLKCADAPCQKSCPTSLDIKSFITSIANKNYYGAAKLIFSDNPLGLTCGMVCPTSDLCVGGCNLHATEEGPINIGGLQQFATEVFKAMNIPQIRSPLLPPPEHMPEAYSAKIALFGAGPASISCASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDVVNFEIELMKDLGVKIICGKSISTDEMTLSTLKENGYKAAFIGIGLPEPKKDHIFQGLTQVQGFYTSKDFLPLVAKGSKPGMCACHSPLPSVRGAVIVLGAGDTAFDCATSALRCGARRVFIVFRKGFANIRAVPEEMELAKEEKCEFLPFLSPRKVIVKDGKIVGMQFVRTEQDETGNWVEDEEQIVRLKADVVISPFGSVLDDPKVIEALSPIKFNRWGLPEVNPETMQTSEPWVFAGGDVVGMANTTVESVNDGKQASWYIHEYIQAQYGALVPSQPTLPLFYTPVDLVDISVEMAGLRFPNPFGLASATPATSTPMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIIRGTTSGPLYGPGQSSFLNIELISEKTAAYWCHSVTELKADFPDNILIASIMCSYNKNDWMELSKMAEASGADALELNLSCPHGMGERGMGLACGQDPELVRNICRWVRQSVRVPFFAKLTPNVTDIVSIARAAKEGGADGVTATNTVSGLMGLKADGSPWPSVGSGKRTTYGGVSGTTIRPIALRAVTAIARALPGFPILATGGIDSAESGLQFLHSGASVLQVCSAIQNQDFTVIEDYCTGLKALLYLKSIEELSDWDGQSPPTMSHQKGKPVPHIAELMGQKLPSFGPYLERRKKILAASKIRENDQNRACSPLQRKHFNSQKPIPAIKDVIGKSLQYLGTFGELNIMEQVVALIDEEMCINCGKCYMTCNDSGYQAIQFDPETHLPTVSDTCTGCTLCLSVCPIMDCIRMVSRATPYEPKRGLPLAVKPVC
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Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
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O89016
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ABCD4_MOUSE
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Lysosomal cobalamin transporter ABCD4 (EC 7.6.2.8) (ATP-binding cassette sub-family D member 4) (PMP70-related protein) (P70R) (Peroxisomal membrane protein 1-like) (PXMP1-L) (Peroxisomal membrane protein 69) (PMP69)
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MAVPGPTARAGARPRLDLQLVQRFVRIQKVFFPSWSSQNVLMFMTLLCVTLLEQLVIYQVGLIPSQYYGVLGNKDLDGFKALTLLAVTLIVLNSTLKSFDQFTCNLLYVSWRKDLTEHLHHLYFRARVYYTLNVLRDDIDNPDQRISQDVERFCRQLSSVTSKLIISPFTLTYYTYQCFQSTGWLGPVSIFGYFIVGTMVNKTLMGPIVTKLVQQEKLEGDFRFKHMQIRVNAEPAAFYRAGLVEHMRTDRRLQRLLQTQRELMSRELWLYIGINTFDYLGSILSYVVIAIPIFSGVYGDLSPTELSTLVSKNAFVCIYLISCFTQLIDLSTTLSDVAGYTHRIGELQEALLDMSRKSQDCEALGESEWDLDKTPGCPTTEPSDTAFLLDRVSILAPSSDKPLIKDLSLKICEGQSLLITGNTGTGKTSLLRVLGGLWEGMKGSVQMLADFGPHGVLFLPQKPFFTDGTLREQVIYPLKEIYPDSGSADDERIVRFLELAGLSSLVARTGGLDQQVDWNWYDVLSPGEMQRLSFARLFYLQPKYAVLDEATSALTEEAESELYRIGQQLGMTFISVGHRPSLEKFHSWVLRLHGGGSWELTRIKLE
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Lysosomal membrane protein that transports cobalamin (Vitamin B12) from the lysosomal lumen to the cytosol in an ATP-dependent manner. Targeted by LMBRD1 lysosomal chaperone from the endoplasmic reticulum to the lysosomal membrane. Then forms a complex with lysosomal chaperone LMBRD1 and cytosolic MMACHC to transport cobalamin across the lysosomal membrane.
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O89017
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LGMN_MOUSE
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Legumain (EC 3.4.22.34) (Asparaginyl endopeptidase) (Protease, cysteine 1)
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MTWRVAVLLSLVLGAGAVPVGVDDPEDGGKHWVVIVAGSNGWYNYRHQADACHAYQIIHRNGIPDEQIIVMMYDDIANSEENPTPGVVINRPNGTDVYKGVLKDYTGEDVTPENFLAVLRGDAEAVKGKGSGKVLKSGPRDHVFIYFTDHGATGILVFPNDDLHVKDLNKTIRYMYEHKMYQKMVFYIEACESGSMMNHLPDDINVYATTAANPKESSYACYYDEERGTYLGDWYSVNWMEDSDVEDLTKETLHKQYHLVKSHTNTSHVMQYGNKSISTMKVMQFQGMKHRASSPISLPPVTHLDLTPSPDVPLTILKRKLLRTNDVKESQNLIGQIQQFLDARHVIEKSVHKIVSLLAGFGETAERHLSERTMLTAHDCYQEAVTHFRTHCFNWHSVTYEHALRYLYVLANLCEAPYPIDRIEMAMDKVCLSHY
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Has a strict specificity for hydrolysis of asparaginyl bonds. Can also cleave aspartyl bonds slowly, especially under acidic conditions. May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system. Required for normal lysosomal protein degradation in renal proximal tubules. Required for normal degradation of internalized EGFR. Plays a role in the regulation of cell proliferation via its role in EGFR degradation.
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O89019
|
INVS_MOUSE
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Inversin (Inversion of embryo turning protein) (Nephrocystin-2)
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MNISEDVLSTGSSLASQVHAAAVNGDKGALQRLIVGNSALRDKEDRFGRTPLMYCVLADRVDCADALLKAGADVNKTDHSRRTALHLAAQKGNYRFMKLLLTRRANWMQKDLEEMTPLHLSTRHRSPKCLALLLKFMAPGEVDTQDKNKQTALHWSAYYNNPEHAKLLIKHDSNIGIPDVEGKIPLHWAANHKDPSAVHTVRCILDAAPTESLLNWQDYEGRTPLHFAVADGNLTVVDVLTSYESCNITSYDNLFRTPLHWAALLGHAQIVHLLLERNKSGTIPSDSQGATPLHYAAQSNFAETVKVFLQHPSVKDDSDLEGRTSFMWAAGKGNDDVLRTMLSLKSDIDINMSDKYGGTALHAAALSGHVSTVKLLLDNDAQVDATDVMKHTPLFRACEMGHRDVIQTLIKGGARVDLVDQDGHSLLHWAALGGNADVCQILIENKINPNVQDYAGRTPLQCAAYGGYINCMAVLMENNADPNIQDKEGRTALHWSCNNGYLDAIKLLLDFAAFPNQMENNEERYTPLDYALLGERHEVIQFMLEHGALSIAAIQDIAAFKIQAVYKGYKVRKAFRDRKNLLMKHEQLRKDAAAKKREEENKRKEAEQQKGQLDTDPPRSHCSSSAPVLPCPPSPQNEGSKQDATPSKQPPASHTVQSPDPEHSRLPGRCPGRASQGDSSIDLQGTASRKPSETPIEHCRGPSACVHPRSWEGGNSSKNQGTSSVEKRRGETNGKHRRCEEGPSSARQPLCTGSGRPAEKGEDSSPAVASASQQDHPRKPNKRQDRAARPRGASQKRRTHQLRDRCSPAGSSRPGSAKGEVACADQSSLHRHTPRSKVTQDKLIGGVSSGLPLSTEASRSGCKQLYEDICASPETGVAHGPPPGQCMNIHLLPVEQRLLIIQRERSRKELFRRKNKAAAVIQRAWRSYQLRKHLSRLLHLKQLGAREVLRCTQVCTALLLQVWRKELELKFPKSISVSRTSKSPSKGSSATKYARHSVLRQIYGCSQEGKGHHPIKSSKAPAVLHLSSVNSLQSIHLDNSGRSKKFSYNLQPSSQSKNKPKL
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Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling (By similarity). Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8. Does not seem to be strictly required for ciliogenesis. {ECO:0000250, ECO:0000269|PubMed:21565611, ECO:0000269|PubMed:9744276, ECO:0000269|PubMed:9771707}.
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O89020
|
AFAM_MOUSE
|
Afamin (Alpha-albumin) (Alpha-Alb)
|
MRHLKLTGFIFFLLPLTESLALPTKPQDVDHFNATQKFIDENTTYLAIIAFSQYVQEASFDEVETLVKVMLDYRDRCWADNTLPECSKTANDAIQDMLCDMEGLPQKHNFSHCCGKAGFPRRLCFFYNKKANVGFLPPFPTLDPEEKCQAYKNNSESFLHLYMYEVARRNPFVFAPVLLAVAAWFEEAATTCCEQQQKATCFQAKAAPITQYLKASSSYQRNVCGALIKFGPKVLNSINVAVFSKKFPKIGFKDLTTLLEDVSSMYEGCCEGDVVHCIRSQSQVVNHICSKQDSISSKIKVCCEKKTLEREACIINANKDDRPEGLSLREAKFTESENVCQERDSDPDKFFAEFIYEYSRRHPDLSTPELLRITKVYMDFLEDCCSRENPAGCYRHVEDKFNETTQRSLAMVQQECKQFQELGKDTLQRHFLVKFTKAAPQLPMEELVSLSKEMVAALTTCCTLSDEFACVDNLADLVLGELCGVNTNRTINPAVDHCCKTDFAFRRHCFEHLKADTTYELPSVSALVSALHTDWCQPRKEDLQNKKHRFLVNLVKWMPGITDEEWLCLFTKFTAAREECSEVQEPESCFSPESSKTGDESQATEKQR
|
Functions as carrier for hydrophobic molecules in body fluids. Essential for the solubility and activity of lipidated Wnt family members, including WNT1, WNT2B, WNT3, WNT3A, WNT5A, WNT7A, WNT7B, WNT8, WNT9A, WNT9B, WNT10A and WNT10B. Binds vitamin E. May transport vitamin E in body fluids under conditions where the lipoprotein system is not sufficient. May be involved in the transport of vitamin E across the blood-brain barrier.
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O89023
|
TPP1_MOUSE
|
Tripeptidyl-peptidase 1 (TPP-1) (EC 3.4.14.9) (Lysosomal pepstatin-insensitive protease) (LPIC) (Tripeptidyl aminopeptidase) (Tripeptidyl-peptidase I) (TPP-I)
|
MGLQARLLGLLALVIAGKCTYNPEPDQRWMLPPGWVSLGRVDPEEELSLTFALKQRNLERLSELVQAVSDPSSPQYGKYLTLEDVAELVQPSPLTLLTVQKWLSAAGARNCDSVTTQDFLTCWLSVRQAELLLPGAEFHRYVGGPTKTHVIRSPHPYQLPQALAPHVDFVGGLHRFPPSSPRQRPEPQQVGTVSLHLGVTPSVLRQRYNLTAKDVGSGTTNNSQACAQFLEQYFHNSDLTEFMRLFGGSFTHQASVAKVVGKQGRGRAGIEASLDVEYLMSAGANISTWVYSSPGRHEAQEPFLQWLLLLSNESSLPHVHTVSYGDDEDSLSSIYIQRVNTEFMKAAARGLTLLFASGDTGAGCWSVSGRHKFRPSFPASSPYVTTVGGTSFKNPFLITDEVVDYISGGGFSNVFPRPPYQEEAVAQFLKSSSHLPPSSYFNASGRAYPDVAALSDGYWVVSNMVPIPWVSGTSASTPVFGGILSLINEHRILNGRPPLGFLNPRLYQQHGTGLFDVTHGCHESCLNEEVEGQGFCSGPGWDPVTGWGTPNFPALLKTLLNP
|
Lysosomal serine protease with tripeptidyl-peptidase I activity. May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases (By similarity). Requires substrates with an unsubstituted N-terminus (By similarity).
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O89026
|
ROBO1_MOUSE
|
Roundabout homolog 1
|
MIAEPAHFYLFGLICLCSGSRLRQEDFPPRIVEHPSDLIVSKGEPATLNCKAEGRPTPTIEWYKGGERVETDKDDPRSHRMLLPSGSLFFLRIVHGRKSRPDEGVYICVARNYLGEAVSHNASLEVAILRDDFRQNPSDVMVAVGEPAVMECQPPRGHPEPTISWKKDGSPLDDKDERITIRGGKLMITYTRKSDAGKYVCVGTNMVGERESEVAELTVLERPSFVKRPSNLAVTVDDSAEFKCEARGDPVPTVRWRKDDGELPKSRYEIRDDHTLKIRKVTAGDMGSYTCVAENMVGKAEASATLTVQEPPHFVVKPRDQVVALGRTVTFQCEATGNPQPAIFWRREGSQNLLFSYQPPQSSSRFSVSQTGDLTITNVQRSDVGYYICQTLNVAGSIITKAYLEVTDVIADRPPPVIRQGPVNQTVAVDGTLILSCVATGSPAPTILWRKDGVLVSTQDSRIKQLESGVLQIRYAKLGDTGRYTCTASTPSGEATWSAYIEVQEFGVPVQPPRPTDPNLIPSAPSKPEVTDVSKNTVTLSWQPNLNSGATPTSYIIEAFSHASGSSWQTAAENVKTETFAIKGLKPNAIYLFLVRAANAYGISDPSQISDPVKTQDVPPTSQGVDHKQVQRELGNVVLHLHNPTILSSSSVEVHWTVDQQSQYIQGYKILYRPSGASHGESEWLVFEVRTPTKNSVVIPDLRKGVNYEIKARPFFNEFQGADSEIKFAKTLEEAPSAPPRSVTVSKNDGNGTAILVTWQPPPEDTQNGMVQEYKVWCLGNETKYHINKTVDGSTFSVVIPSLVPGIRYSVEVAASTGAGPGVKSEPQFIQLDSHGNPVSPEDQVSLAQQISDVVRQPAFIAGIGAACWIILMVFSIWLYRHRKKRNGLTSTYAGIRKVPSFTFTPTVTYQRGGEAVSSGGRPGLLNISEPATQPWLADTWPNTGNNHNDCSINCCTAGNGNSDSNLTTYSRPADCIANYNNQLDNKQTNLMLPESTVYGDVDLSNKINEMKTFNSPNLKDGRFVNPSGQPTPYATTQLIQANLSNNMNNGAGDSSEKHWKPPGQQKPEVAPIQYNIMEQNKLNKDYRANDTIPPTIPYNQSYDQNTGGSYNSSDRGSSTSGSQGHKKGARTPKAPKQGGMNWADLLPPPPAHPPPHSNSEEYNMSVDESYDQEMPCPVPPAPMYLQQDELQEEEDERGPTPPVRGAASSPAAVSYSHQSTATLTPSPQEELQPMLQDCPEDLGHMPHPPDRRRQPVSPPPPPRPISPPHTYGYISGPLVSDMDTDAPEEEEDEADMEVAKMQTRRLLLRGLEQTPASSVGDLESSVTGSMINGWGSASEEDNISSGRSSVSSSDGSFFTDADFAQAVAAAAEYAGLKVARRQMQDAAGRRHFHASQCPRPTSPVSTDSNMSAVVIQKARPAKKQKHQPGHLRREAYADDLPPPPVPPPAIKSPTVQSKAQLEVRPVMVPKLASIEARTDRSSDRKGGSYKGREALDGRQVTDLRTNPSDPREAQEQPNDGKGRGTRQPKRDLPPAKTHLGQEDILPYCRPTFPTSNNPRDPSSSSSMSSRGSGSRQREQANVGRRNMAEMQVLGGFERGDENNEELEETES
|
Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1. In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its interaction with MYO9B inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (By similarity). May be required for lung development.
|
O89032
|
SPD2A_MOUSE
|
SH3 and PX domain-containing protein 2A (Five SH3 domain-containing protein) (SH3 multiple domains protein 1) (Tyrosine kinase substrate with five SH3 domains)
|
MLAYCVQDATVVDVEKRRSPSKHYVYIINVTWSDSTSQTIYRRYSKFFDLQMQLLDKFPIEGGQKDPKQRIIPFLPGKILFRRSHIRDVAVKRLKPIDEYCRALVRLPPHISQCDEVFRFFEARPEDVNPPKEDYGSSKRKSVWLSSWAESPKKDVTGADTNAEPMILEQYVVVSNYKKQENSELSLQAGEVVDVIEKNESGWWFVSTSEEQGWVPATYLEAQNGTRDDSDINTSKTGEVSKRRKAHLRRLDRRWTLGGMVNRQHSREEKYVTVQPYTSQSKDEIGFEKGVTVEVIRKNLEGWWYIRYLGKEGWAPASYLKKAKDDLPTRKKNLAGPVEIIGNIMEISNLLNKKASGDKEAPAEGEGSEAPITKKEISLPILCNASNGSALAIPERTTSKLAQGSPAVARIAPQRAQISSPNLRTRPPPRRESSLGFQLPKPPEPPSVEVEYYTIAEFQSCISDGISFRGGQKAEVIDKNSGGWWYVQIGEKEGWAPASYIDKRKKPNLSRRTSTLTRPKVPPPAPPSKPKEAEENPVGACESQGSPLKVKYEEPEYDVPAFGFDSEPEMNEEPSGDRGSGDKHPAQPRRISPASSLQRAHFKVGESSEDVALEEETIYENEGFRPYTEDTLSARGSSGDSDSPGSSSLSLAVKNSPKSDSPKSSSLLKLKAEKNAQAELGKNQSNISFSSSVTISTTCSSSSSSSSLSKNNGDLKPRSASDAGIRDTPKVGTKKDPDVKAGLASCARAKPSVRPKPVLNRAESQSQEKMDISSLRRQLRPTGQLRGGLKGSRSEDSELPPQMASEGSRRGSADIIPLTATTPPCVPKKEWEGQGATYVTCSAYQKVQDSEISFPEGAEVHVLEKAESGWWYVRFGELEGWAPSHYLVAEENQQPDTASKEGDTGKSSQNEGKSDSLEKIEKRVQALNTVNQSKRATPPIPSKPPGGFGKTSGTVAVKMRNGVRQVAVRPQSVFVSPPPKDNNLSCALRRNESLTATDSLRGVRRNSSFSTARSAAAEAKGRLAERAASQGSESPLLPTQRKGIPVSPVRPKPIEKSQFIHNNLKDVYISIADYEGDEETAGFQEGVSMEVLEKNPNGWWYCQILDEVKPFKGWVPSNYLEKKN
|
Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide (By similarity). {ECO:0000250, ECO:0000269|PubMed:18417249, ECO:0000269|PubMed:19755709}.
|
O89033
|
CDC6_MOUSE
|
Cell division control protein 6 homolog (CDC6-related protein) (p62(cdc6))
|
MPQTRSQTQATIGFPKKKLSNTLKKPNSRDCEVKLRNVQPVPTTPCVDVKLLPLSPRKRLGDDNLCNTPRLSPCSPPKLGKKENGPPRSHTWKGCRLVFDDEPTFKASPPKEQDRVRQHQIRSSSAQRSPESKADPEQKCPPEKESVCIRLFKQEGTCYQQAKLVLNTAVPDRLPAREQEMGVIRNFLKEHICGKKAGSLYLSGAPGTGKTACLSRILQDFKKEVKGFKSILLNCMSLRSAQAVFPAIAQEIGREELCRPAGKDLMRKLEKHLTAEKGPMIVLVLDEMDQLDSKGQDVLYTLFEWPWLSNSRLVLIGIANTLDLTDRILPRLEARENCKPQLLNFPPYTRNQIAAILQDRLSQVSKDQVLDSAAIQFCARKVSAVSGDIRKALDVCRRAIEIVESDVRSQTVLKPLSECKSPSESPVPKRVGLAHISQVISEVDGNRVTLSQENTQDSLPLQQKILVCSLLLLTRRLKIKEVTLGKLYEAYSSICRKQQVTAVDQSECLSLSGLLESRGLVGLKKNKESRLTKVSLKIEEKEIEHVLNGKAFTGNILAAGLP
|
Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
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O89035
|
DIC_RAT
|
Mitochondrial dicarboxylate carrier (DIC) (Solute carrier family 25 member 10)
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MAEARTSRWYFGGLASCGAACCTHPLDLLKVHLQTQQEVKLRMTGMALQVVRTDGFLALYNGLSASLCRQMTYSLTRFAIYETMRDYMTKDSQGPLPFYSKVLLGGISGLTGGFVGTPADLVNVRMQNDMKLPLSQRRNYSHALDGLYRVAREEGLKKLFSGATMASSRGALVTVGQLSCYDQAKQLVLSTGYLSDNIFTHFLSSFIAGGCATFLCQPLDVLKTRLMNSKGEYQGVFHCAVETAKLGPQAFFKGLVPAGVRLVPHTVLTFMFLEQLRKHFGIKVAT
|
Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across mitochondrial inner membrane. Plays an important role in gluconeogenesis, fatty acid metabolism, urea synthesis, and sulfur metabolism, particularly in liver, by supplying the substrates for the different metabolic processes. Regulates fatty acid release from adipocytes, and contributes to systemic insulin sensitivity (By similarity).
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O89038
|
MEF2D_RAT
|
Myocyte-specific enhancer factor 2D
|
MGRKKIQIQRITDERNRQVTFTKRKFGLMKKAYELSVLCDCEIALIIFNHSNKLFQYASTDMDKVLLKYTEYNEPHESRTNADIIETLRKKGFNGCDSPEPDGEDSLEQSPLLEDKYRRASEELDGLFRRYGSSVPAPNFAMPVTVPVSNQSSMQFSNPSSSLVTPSLVTSSLTDPRLLSPQQPALQRNSVSPGLPQRPASAGAMLGRDLNSANGACPNPVGNGYVSARASPGLLPVANGNGLNKVIPAKSPPPPTHNTQLGAPSRKPDLRVITSQGGKGLMHHLNNAQRLGVSQSTHSLTTPVVSVATPSLLSQGLPFSSMPTAYNTDYQLPSAELSSLPAFSSPAGLALGNVTAWQQPQQPQQPQPPQPPQSQPQPPQPQPQQPPQQQPHLVPVSLSNLIPGSPLPHVGAALTVTTHPHISIKSEPVSPSRERSPAPPPPAVFPAARPEPGEGLSSPAGGSYETGDRDDGRGDFGPTLGLLRPAPEPEAEGSAVKRMRLDTWTLK
|
Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific, growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. Plays a critical role in the regulation of neuronal apoptosis (By similarity).
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O89039
|
ACKR3_RAT
|
Atypical chemokine receptor 3 (C-X-C chemokine receptor type 7) (CXC-R7) (CXCR-7) (Chemokine orphan receptor 1) (G-protein coupled receptor RDC1 homolog) (RDC-1)
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MDVHLFDYVEPGNYSDINWPCNSSDCIVVDTVQCPAMPNKNVLLYTLSFIYIFIFVIGMIANSVVVWVNIQAKTTGYDTHCYILNLAIADLWVVITIPVWVVSLVQHNQWPMGELTCKITHLIFSINLFGSIFFLACMSVDRYLSITYFTSTSSYKKKMVRRVVCVLVWLLAFFVSLPDTYYLKTVTSASNNETYCRSFYPEHSIKEWLIGMELVSVILGFAVPFTIIAIFYFLLARAMSASGDQEKHSSRKIIFSYVVVFLVCWLPYHFVVLLDIFSILHYIPFTCQLENVLFTALHVTQCLSLVHCCVNPVLYSFINRNYRYELMKAFIFKYSAKTGLTKLIDASRVSETEYSALEQNTK
|
Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1 (By similarity). Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Regulates axon guidance in the oculomotor system through the regulation of CXCL12 levels (By similarity).
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O89040
|
PLCB2_RAT
|
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 (EC 3.1.4.11) (Phosphoinositide phospholipase C-beta-2) (Phospholipase C-beta-2) (PLC-beta-2)
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MSLLNPVLLPPKVKAYLSQGERFIKWDDETSIASPVILRVDPKGYYLYWTHQSKEMEFLDVTSIRDTRFGKFAKIPKSQKLREVFNMDFPDNHFLLKTFTVVSGPDMVGLTFHNFVSYKENVGKDWAEDVLALAKHPMTANASRSTFLDKILVKLKMQLSPEGKIPVKNFFQMFPADRKRVEAALSACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFTSYHAKAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQALIDKYEPSGINVQRGQLSPEGMVWFLCGPENSVLAHDTLRIHQDMTQPLNHYFINSSHNTYLTAGQFSGPSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTDILFKEAVEAIAESAFKTSPYPVILSFENHVDSPRQQAKMAEYCRTMFGETLLTEPLENFPLKPGMPLPSPEDLRGKILIKNKKNQFSGPASPNKKPDGVSEGGFPSSVPVEEDTGWTAEDRTEVEEGEEEEEVEEEEEEESGNLDEEEIKKMQSDEGTAGLEVTAYEEMSSLVNYIQPTKFISFEFSAQKNRSYLVSSFTELKAYELLSKASMQFVDYNKRQMSRVYPKGTRMDSSNYMPQMFWNAGCQMVALNFQTMDLPMQQNMALFEFNGQSGYLLKHEFMRRQDKQFNPFSVDRIDVVVATTLSITVISGQFLSERSVRTYVEVELFGLPGDPKRRYRTKLSPTANSINPVWKEEPFIFEKILVPELASLRIAVMEEGGKFIGHRIIPINALHSGYHHLCLRSESNMPLTMPALFVFLEMKDYVPDTWADLTVALANPIKYFSAHDKKSVKLKEVTGSLPEKLFSGIPVASQSNGAPVSAGNGSTAPGTKAKEEATKEVAEPQTTSLEELRELKGVVKLQRRHEKELRELERRGARRWEELLQRGAAQLAELQDPAASCKLRPGKGSRKKRIVPCEETIVVPREVLEGPDPRVQDLKDRLEQELQQQGEEQYRSVLKRKEQHVTEQIAKMMELAREKQAAELKSFKETSETDTKEMKKKLEAKRLERIQAMTKVTTDKVAQERLKREINNSHIQEVVQAVKQMTETLERHQEKLEEKQTACLEQIQAMEKQFQEKALAEYEAKMKGLEAEVKESMRACFKACFPTEAEEKPERPCEASEESCPQEPLVNKTDTQESRL
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The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. This protein may be involved in the transduction of bitter taste stimuli.
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O89042
|
DPOLA_RAT
|
DNA polymerase alpha catalytic subunit (EC 2.7.7.7) (DNA polymerase alpha catalytic subunit p180)
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MAPVHGDDCKLETSAVSDSGSFVASRARREKKSKKGRQEALERLKKAKAGEKYKYEVEDLTSVYEEVDEEQYSKLVQARQDDDWIVDDDGIGYVEDGREIFDDDLEDDALDTCGEGSDGKAHRKDRKDVKKPSVTKPNNIKAMFIASAGKKTTDKTVDLSKDDLLGDILQDLNTETPQIAPPPVLIPKKKRSTGASPNPFSVHTATAVPSGKIASPVSRKEPPLTPVPLKRAEFAGDLAQPECPEDEQESGVIEFEDGDFDEPMDTEEVDEEEPVTAKIWDQESEPVEGVKHEADPETGTTSFLDSFLPDVSCWDIDQKDENSFLLQEVQVDSNHLPLVKGADDEQVFQFYWLDAYEDPYNQPGVVFLFGKVWVESAKTHVSCCVMVKNIERTLYFLPREMKIDLNTGKETATPITMKDVYEEFDSKISAKYKIMKFKSKIVEKNYAFEIPDVPEKSEYLEVRYSAEVPQLPQNLKGETFSHVFGTNTSSLELFLMNRKIKGPCWLEVKNPQLLNQPISWCKFEAMALKPDLVNVIKDVSPPPLVVMSFSMKTMQNVQNHQHEIIAMAALVHHNFPLDKAPPKPPFQTHFCVVSKPKDCIFPCAFKEVIKKKNMEVEVAATERTLLGFFLAKVHKLDPDILVGHNICGFELEVLLQRINECKVPFWSKIGRLRRSNMPKLGSRSGFGERNATCGRMICDVEISVKELIHCKSYHLSELVQQILKTERIVIPTENIRNMYSEPSHLLYLLEHIWKDARFILQIMCELNVLPLALQITNIAGNIMSRTLMGGRSERNEFLLLHAFYENNYIVPDKQIFRKPQQKPGDEDEEIDGDTNKYKKGRKKAAYAGGLVLDPKVGFYDKFILLLDFNSLYPSIIQEFNICFTTVQRVASETLKATEDEEQEQIPELPDPNLDMGILPREIRKLVERRKQVKQLMKQQDLNPDLVLQYDIRQKALKLTANSMYGCLGFSYSRFYAKPLAALVTYKGREILMHTKEMVQKMNLEVIYGDTDSIMINTNSTNLEEVFKLGNKVKNEVNKLYKLLEIDIDGVFKSLLLLKKKKYAALVVEPTSDGNYITKQELKGLDIVRRDWCDLAKDTGNFVIGQILSDQSRDTIVENIQKRLIEIGENVLNGSVPVSQFEINKALTKDPQDYPDKKSLPHVHVALWINSQGGRKVKAGDTVSYVICQDGSNLPATQRAYAPEQLQKQDNLAIDTQYYLAQQIHPVVARICEPIDGIDAVLIALWLGLDSTQFRVHQYHKDEENDALLGGPAQLTDEEKYKDCEKFKCLCPSCGTENIYDNVFEGSGMDMEPSLNRCSNIDCKASPATFMVQLSNKLIMDIRRCIKKYYDGWLICEEPTCRNRIRRLPLHFSRNGPLCPACMKAVLRPEYSDKSLYTQLCFYRYIFDADCALEKLPEHEKDKLKKQFFTPRVLQDYRKVKNIAEHFLSWSG
|
Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and two primase subunits PRIM1 and PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses (By similarity).
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O89046
|
COR1B_RAT
|
Coronin-1B (Coronin-2)
|
MSFRKVVRQSKFRHVFGQPVKNDQCYEDIRVSRVTWDSTFCAVNPKFLAVIVEASGGGAFMVLPLNKTGRIDKAYPTVCGHTGPVLDIDWCPHNDEVIASGSEDCTVMVWQIPENGLTSPLTEPVVVLEGHTKRVGIITWHPTARNVLLSAGCDNVVLIWNVGTAEELYRLDSLHPDLIYNVSWNHNGSLFCTACKDKSVRIIDPRRGTLVAEREKAHEGARPMRAIFLADGKVFTAGFSRMSERQLALWDPENFEEPMALQELDSSNGALLPFYDPDTSVVYVCGKGDSSIRYFEITDEPPYIHFLNTFTSKEPQRGMGSMPKRGLEVSKCEIARFYKLHERKCEPIVMTVPRKSDLFQDDLYPDTAGPDAALEAEDWVSGQDADPILISLREAYVPSKQRDLKVSRRNVLSDSKPAGYSRSGVSTATAITDIPSGNLAGSGEAGKLEEVMHGLRALRVLVKEQGERISRLEEHLGRMENGDT
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Regulates leading edge dynamics and cell motility in fibroblasts. May be involved in cytokinesis and signal transduction (By similarity).
|
O89047
|
KCNH3_RAT
|
Potassium voltage-gated channel subfamily H member 3 (Brain-specific eag-like channel 1) (BEC1) (Ether-a-go-go-like potassium channel 2) (ELK channel 2) (rElk2) (Voltage-gated potassium channel subunit Kv12.2)
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MPAMRGLLAPQNTFLDTIATRFDGTHSNFVLGNAQVAGLFPVVYCSDGFCDLTGFSRAEVMQRGCACSFLYGPDTSELVRQQIRKALDEHKEFKAELILYRKSGLPFWCLLDVIPIKNEKGEVALFLVSHKDISETKNRGGPDNWKERGGGRRRYGRAGSKGFNANRRRSRAVLYHLSGHLQKQPKGKHKLNKGVFGEKPNLPEYKVAAIRKSPFILLHCGALRATWDGFILLATLYVAVTVPYSVCVSTAREPSAARGPPSVCDLAVEVLFILDIVLNFRTTFVSKSGQVVFAPKSICLHYVTTWFLLDVIAALPFDLLHAFKVNVYVGAHLLKTVRLLRLLRLLPRLDRYSQYSAVVLTLLMAVFALLAHWVACVWFYIGQQEIENSESELPEIGWLQELARRLETPYYLVSRSPDGGNSSGQSENCSSSGGGSEANGTGLELLGGPSLRSAYITSLYFALSSLTSVGFGNVSANTDTEKIFSICTMLIGALMHAVVFGNVTAIIQRMYARRFLYHSRTRDLRDYIRIHRIPKPLKQRMLEYFQATWAVNNGIDTTELLQSLPDELRADIAMHLHKEVLQLPLFEAASRGCLRALSLALRPAFCTPGEYLIHQGDALQALYFVCSGSMEVLKGGTVLAILGKGDLIGCELPQREQVVKANADVKGLTYCVLQCLQLAGLHESLALYPEFAPRFSRGLRGELSYNLGAGGVSAEVDTSSLSGDNTLMSTLEEKETDGEQGHTISPAPADEPSSPLLSPGCTSSSSAAKLLSPRRTAPRPRLGGRGRPSRAGVLKPEAGPSAHPRTLDGLQLPPMPWNVPPDLSPRVVDGIEDGCGSDQHKFSFRVGQSGPECSSSPSPGTESGLLTVPLVPSEARNTDTLDKLRQAVTELSEQVLQMREGLQSLRQAVQLILVPQGEGQCPRVSGEGPCPATASGLLQPLRVDTGASSYCLQPPAGSVLSGTWPHPRPGHPPPLMAPWPWGPPASQSSPWPRATALWTSTSDSEPPGSGDLCSEPSTPASPPPPEEGARTGTPAPVSQAEATSTGEPPPGSGGRALPWDPHSLEMVLIGCHGPGSVQWTQEEGTGV
|
Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits an outward current with fast inactivation. Channel properties may be modulated by cAMP and subunit assembly.
|
O89049
|
TRXR1_RAT
|
Thioredoxin reductase 1, cytoplasmic (TR) (EC 1.8.1.9) (NADPH-dependent thioredoxin reductase) (Peroxidase TXNRD1) (EC 1.11.1.2) (Thioredoxin reductase TR1)
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MNDSKDAPKSYDFDLIIIGGGSGGLAAAKEAAKFDKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALKDSRNYGWKLEDTVKHDWEKMTESVQNHIGSLNWGYRVALREKKVVYENAYGKFIGPHKIMATNNKGKEKVYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLAGIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPTKIEQIEAGTPGRLKVTAKSTNSEETIEDEFNTVLLAVGRDSCTRTIGLETVGVKINEKTGKIPVTDEEQTNVPYIYAIGDILEGKLELTPVAIQAGRLLAQRLYGGSTVKCDYDNVPTTVFTPLEYGCCGLSEEKAVEKFGEENIEVYHSFFWPLEWTVPSRDNNKCYAKVICNLKDNERVVGFHVLGPNAGEVTQGFAAALKCGLTKQQLDSTIGIHPVCAEIFTTLSVTKRSGGDILQSGCUG
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Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form. Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis. Also has reductase activity on hydrogen peroxide (H2O2).
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O89050
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MKLN1_MOUSE
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Muskelin
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MAAGGAVAVAPECRLLPYALHKWSSFSSTYLPENILVDKPNDQSSRWSSESNYPPQYLILKLERPAIVQNITFGKYEKTHVCNLKKFKVFGGMNEENMTELLSSGLKNDYNKETFTLKHKIDEQMFPCRFIKIVPLLSWGPSFNFSIWYVELSGIDDPDIVQPCLNWYSKYREQEAIRLCLKHFRQHNYTEAFESLQKKTKIALEHPMLTDMHDKLVLKGDFDACEELIEKAVNDGLFNQYISQQEYKPRWSQIIPKSTKGDGEDNRPGMRGGHQMVIDVQTETVYLFGGWDGTQDLADFWAYSVKENQWTCISRDTEKENGPSARSCHKMCIDIQRRQIYTLGRYLDSSVRNSKSLKSDFYRYDIDTNTWMLLSEDTAADGGPKLVFDHQMCMDSEKHMIYTFGGRILTCNGSVDDSRASEPQFSGLFAFNCQCQTWKLLREDSCNAGPEDIQSRIGHCMLFHSKNRCLYVFGGQRSKTYLNDFFSYDVDSDHVDIISDGTKKDSGMVPMTGFTQRATIDPELNEIHVLSGLSKDKEKREENVRNSFWIYDIVRNSWSCVYKNDQATKDNLSKSLQEEEPCPRFAHQLVYDELHKVHYLFGGNPGKSCSPKMRLDDFWSLKLCRPSKDYLLRHCKYLIRKHRFEEKAQMDPLSALKYLQNDLYITVDHSDPEETKEFQLLASALFKSGSDFTALGFSDVDHTYAQRTQLFDTLVNFFPDSMTPPKGNLVDLITL
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Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (By similarity). Required for internalization of the GABA receptor GABRA1 from the cell membrane via endosomes and subsequent GABRA1 degradation. Acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component THBS1.
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O89051
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ITM2B_MOUSE
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Integral membrane protein 2B (Immature BRI2) (imBRI2) (Protein E25B) (Transmembrane protein BRI) (Bri) [Cleaved into: BRI2, membrane form (Mature BRI2) (mBRI2); BRI2 intracellular domain (BRI2 ICD); BRI2C, soluble form; Bri23 peptide (Bri2-23) (ABri23) (C-terminal peptide) (P23 peptide)]
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MVKVTFNSALAQKEAKKDEPKSSEEALIVPPDAVAVDCKDPGDVVPVGQRRAWCWCMCFGLAFMLAGVILGGAYLYKYFALQPDDVYYCGLKYIKDDVILNEPSADAPAARYQTIEENIKIFEEDAVEFISVPVPEFADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPKNLLELLINIKAGTYLPQSYLIHEHMVITDRIENVDNLGFFIYRLCHDKETYKLQRRETIRGIQKREASNCFTIRHFENKFAVETLICS
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Plays a regulatory role in the processing of the amyloid-beta A4 precursor protein (APP) and acts as an inhibitor of the amyloid-beta peptide aggregation and fibrils deposition. Plays a role in the induction of neurite outgrowth. Functions as a protease inhibitor by blocking access of secretases to APP cleavage sites (By similarity). Mature BRI2 (mBRI2) functions as a modulator of the amyloid-beta A4 precursor protein (APP) processing leading to a strong reduction in the secretion of secretase-processed amyloid-beta protein 40 and amyloid-beta protein 42. Bri23 peptide prevents aggregation of APP amyloid-beta protein 42 into toxic oligomers.
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O89053
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COR1A_MOUSE
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Coronin-1A (Coronin-like protein A) (Clipin-A) (Coronin-like protein p57) (Tryptophan aspartate-containing coat protein) (TACO)
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MSRQVVRSSKFRHVFGQPAKADQCYEDVRVSQTTWDSGFCAVNPKFMALICEASGGGAFLVLPLGKTGRVDKNVPLVCGHTAPVLDIAWCPHNDNVIASGSEDCTVMVWEIPDGGLVLPLREPVITLEGHTKRVGIVAWHPTAQNVLLSAGCDNVILVWDVGTGAAVLTLGPDVHPDTIYSVDWSRDGALICTSCRDKRVRVIEPRKGTVVAEKDRPHEGTRPVHAVFVSEGKILTTGFSRMSERQVALWDTKHLEEPLSLQELDTSSGVLLPFFDPDTNIVYLCGKGDSSIRYFEITSEAPFLHYLSMFSSKESQRGMGYMPKRGLEVNKCEIARFYKLHERKCEPIAMTVPRKSDLFQEDLYPPTAGPDPALTAEEWLGGRDAGPLLISLKDGYVPPKSRELRVNRGLDSARRRATPEPSGTPSSDTVSRLEEDVRNLNAIVQKLQERLDRLEETVQAK
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May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion. In mycobacteria-infected cells, its retention on the phagosomal membrane prevents fusion between phagosomes and lysosomes.
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O89084
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PDE4A_MOUSE
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cAMP-specific 3',5'-cyclic phosphodiesterase 4A (EC 3.1.4.53)
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MEPPAAPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERSEPERSPHRPIERADAVDTGDRPGLRTTRMSWPSSFHGTGTGGGSSRRLEAENGPTPSPGRSPLDSQASPGLMLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVASEAHGEDLIVTPFAQVLASLRNVRSNFSLLTNVPIPSNKRSPLGGPPSVCKATLSEETCQQLARETLEELDWCLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISNTFLDKQHEVEIPSPTPRQRPFQQPPPAAVQQAQPMSQITGLKKLVHTGSLNINVPRFGVKTDQEDLLAQELENLSKWGLNIFCVSEYAGGRSLSCIMYTIFQERDLLKKFHIPVDTMMTYMLTLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGVSNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEENCDIFQNLSKRQRQSLRKMVIDMVLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLELYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADLVHPDAQDILDTLEDNRDWYHSAIRQSPSPTLEEEPGVLSDPALPDKFQFELTLEEEDEEDSLEVPGLPCTEETLLAPHDTRAQAMEQSKVKGQSPAVVEVAESLKQETASAHGAPEESAEAVGHSFSLETSILPDLRTLSPSEEAQGLLGLPSMAAEVEAPRDHLAAMRACSACSGTSGDNSAVISAPGRWGSGGDPA
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Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes.
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O89086
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RBM3_MOUSE
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RNA-binding protein 3 (RNA-binding motif protein 3)
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MSSEEGKLFVGGLNFNTDEQALEDHFSSFGPISEVVVVKDRETQRSRGFGFITFTNPEHASDAMRAMNGESLDGRQIRVDHAGKSARGSRGGAFGGRGRSYSRGGGDQGYGSGRYDSRPGGYGYGYGRSRDYSGSQGGYDRYSGGNYRDNYDN
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Cold-inducible mRNA binding protein that enhances global protein synthesis at both physiological and mild hypothermic temperatures. Reduces the relative abundance of microRNAs, when overexpressed. Enhances phosphorylation of translation initiation factors and active polysome formation.
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O89090
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SP1_MOUSE
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Transcription factor Sp1 (Specificity protein 1)
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MSDQDHSMDEVTAVVKIEKDVGGNNGGSGNGGGAAFSQTRSSSTGSSSSSGGGGGQESQPSPLALLAATCSRIESPNENSNNSQGPSQSGGTGELDLTATQLSQGANGWQIISSSSGATPTSKEQSGNSTNGSNGSESSKNRTVSGGQYVVAATPNLQNQQVLTGLPGVMPNIQYQVIPQFQTVDGQQLQFAATGAQVQQDGSGQIQIIPGANQQIIPNRGSGGNIIAAMPNLLQQAVPLQGLANNVLSGQTQYVTNVPVALNGNITLLPVNSVSAATLTPSSQAGTISSSGSQESSSQPVTSGTAISSASLVSSQASSSSFFTNANSYSTTTTTSNMGIMNFTSSGSSGTSSQGQTPQRVGGLQGSDSLNIQQNQTSGGSLQGSQQKEGEQSQQTQQQQILIQPQLVQGGQALQALQAAPLSGQTFTTQAISQETLQNLQLQAVQNSGPIIIRTPTVGPNGQVSWQTLQLQNLQVQNPQAQTITLAPMQGVSLGQTSSSNTTLTPIASAASIPAGTVTVNAAQLSSMPGLQTINLSALGTSGIQVHQLPGLPLAIANTPGDHGTQLGLHGSGGDGIHDETAGGEGENSSDLQPQAGRRTRREACTCPYCKDSEGRASGDPGKKKQHICHIQGCGKVYGKTSHLRAHLRWHTGERPFMCNWSYCGKRFTRSDELQRHKRTHTGEKKFACPECPKRFMRSDHLSKHIKTHQNKKGGPGVALSVGTLPLDSGAGSEGTATPSALITTNMVAMEAICPEGIARLANSGINVMQVTELQSINISGNGF
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Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter Plays an essential role in the regulation of FE65 gene expression (By similarity). Positively regulates the transcription of the core clock component BMAL1. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112.
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O89091
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KLF10_MOUSE
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Krueppel-like factor 10 (GDNF-inducible factor) (Transcription factor GIF) (mGIF) (Transforming growth factor-beta-inducible early growth response protein 1) (TGFB-inducible early growth response protein 1) (TIEG-1)
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MLNFGASLQQASEGKMELISEKPREGMHPWDKAEQSDFEAVEALMSMSCDWKSHFKKYLENRPVTPVSDTSEDDSLLPGTPDLQTVPAFCLTPPYSPSDFEPSQGSNLTASAPSTGHFKSFSDAAKPPGATPFKEEEKNPLAAPPLPKAQATSVIRHTADAQLCNHQSCPVKAASILNYQDNSFRRRTHGNVEATRKNIPCAAVSPNRSKPEPSTVSDGDEKAGAALYDFAVPSSETVICRSQPAPSSPVQKSVLVSSPTVSTGGVPPLPVICQMVPLPANNSLVSTVVPSTPPSQPPAVCSPVLFMGTQVPEGTVVFVVPQPVVQSPRPPVVSPSGTRLSPIAPAPGFSPSAARVTPQIDSSRVRSHICSHPGCGKTYFKSSHLKAHVRTHTGEKPFSCSWKGCERRFARSDELSRHRRTHTGEKKFACPMCDRRFMRSDHLTKHARRHLSAKKLPNWQMEVSKLNDIALPPTPASAQ
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Transcriptional repressor which binds to the consensus sequence 5'-GGTGTG-3'. May play a role in the cell cycle regulation (By similarity). Plays a role in the regulation of the circadian clock binds to the GC box sequence in the promoter of the core clock component ARTNL/BMAL1 and represses its transcriptional activity. Regulates the circadian expression of genes involved in lipogenesis, gluconeogenesis, and glycolysis in the liver. Represses the expression of PCK2, a rate-limiting step enzyme of gluconeogenesis.
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O89093
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CCL20_MOUSE
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C-C motif chemokine 20 (Beta-chemokine exodus-1) (CC chemokine LARC) (CC chemokine ST38) (Liver and activation-regulated chemokine) (Macrophage inflammatory protein 3 alpha) (MIP-3-alpha) (Small-inducible cytokine A20)
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MACGGKRLLFLALAWVLLAHLCSQAEAASNYDCCLSYIQTPLPSRAIVGFTRQMADEACDINAIIFHTKKRKSVCADPKQNWVKRAVNLLSLRVKKM
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Acts as a ligand for C-C chemokine receptor CCR6. Signals through binding and activation of CCR6 and induces a strong chemotactic response and mobilization of intracellular calcium ions. The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and autoimmune diseases. CCL20 acts as a chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes (By similarity). Involved in the recruitment of both the pro-inflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for optimal migration of thymic natural regulatory T cells (nTregs) and DN1 early thymocyte progenitor cells. Positively regulates sperm motility and chemotaxis via its binding to CCR6 which triggers Ca2+ mobilization in the sperm which is important for its motility. May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells.
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O89094
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CASPE_MOUSE
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Caspase-14 (CASP-14) (EC 3.4.22.-) (Mini-ICE) (MICE) [Cleaved into: Caspase-14 subunit p17, mature form; Caspase-14 subunit p10, mature form; Caspase-14 subunit p20, intermediate form; Caspase-14 subunit p8, intermediate form]
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MESEMSDPQPLQEERYDMSGARLALTLCVTKAREGSEVDMEALERMFRYLKFESTMKRDPTAQQFLEELDEFQQTIDNWEEPVSCAFVVLMAHGEEGLLKGEDEKMVRLEDLFEVLNNKNCKALRGKPKVYIIQACRGEHRDPGEELRGNEELGGDEELGGDEVAVLKNNPQSIPTYTDTLHIYSTVEGYLSYRHDEKGSGFIQTLTDVFIHKKGSILELTEEITRLMANTEVMQEGKPRKVNPEVQSTLRKKLYLQ
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Non-apoptotic caspase which is involved in epidermal differentiation. Seems to play a role in keratinocyte differentiation and is required for cornification. Regulates maturation of the epidermis by proteolytically processing filaggrin. In vitro is equally active on the synthetic caspase substrates WEHD-ACF and IETD-AFC. Involved in processing of prosaposin in the epidermis. May be involved in retinal pigment epithelium cell barrier function (By similarity).
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O89098
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CYTF_MOUSE
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Cystatin-F (Cystatin-7) (Cystatin-like metastasis-associated protein) (CMAP) (Leukocystatin)
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MWLAILLALCCLTSDTHGARPPDFCSKDLISSVKPGFPKTIETNNPGVLKAARHSVEKFNNCTNDIFLFKESHVSKALVQVVKGLKYMLEVKIGRTTCRKTMHHQLDNCDFQTNPALKRTLYCYSEVWVIPWLHSFEVPVLLCQ
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Inhibits papain and cathepsin L but with affinities lower than other cystatins. May play a role in immune regulation through inhibition of a unique target in the hematopoietic system.
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O89100
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GRAP2_MOUSE
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GRB2-related adaptor protein 2 (Adapter protein GRID) (GADS protein) (GRB-2-like protein) (GRB2L) (GRB-2-related monocytic adapter protein) (MONA) (Monocytic adapter) (GRBLG) (Growth factor receptor-binding protein) (Hematopoietic cell-associated adaptor protein GrpL)
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MEATAKFDFMASGEDELSFRTGDILKILSNQEEWLKAELGSQEGYVPKNFIDIEFPEWFHEGLSRHQAENLLMGKDIGFFIIRASQSSPGDFSISVRHEDDVQHFKVMRDTKGNYFLWTEKFPSLNKLVDYYRTTSISKQKQVFLRDGTQDQGHRGNSLDRRSQGGPHPSGTVGEEIRPSVNRKLSDHLPLGPQQFHPHQQPSPQFTPGPQPPQQQRYLQHFHQDRRGGSLDINDGHCGLGSEVNATLMHRRHTDPVQLQAAGRVRWARALYDFEALEEDELGFRSGEVVEVLDSSNPSWWTGRLHNKLGLFPANYVAPMMR
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Interacts with SLP-76 to regulate NF-AT activation. Binds to tyrosine-phosphorylated shc.
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O89101
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FGF18_MOUSE
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Fibroblast growth factor 18 (FGF-18) (zFGF5)
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MYSAPSACTCLCLHFLLLCFQVQVLAAEENVDFRIHVENQTRARDDVSRKQLRLYQLYSRTSGKHIQVLGRRISARGEDGDKYAQLLVETDTFGSQVRIKGKETEFYLCMNRKGKLVGKPDGTSKECVFIEKVLENNYTALMSAKYSGWYVGFTKKGRPRKGPKTRENQQDVHFMKRYPKGQAELQKPFKYTTVTKRSRRIRPTHPG
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Plays an important role in the regulation of cell proliferation, cell differentiation and cell migration. Required for normal ossification and bone development. Stimulates hepatic and intestinal proliferation (By similarity).
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O89103
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C1QR1_MOUSE
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Complement component C1q receptor (C1q/MBL/SPA receptor) (C1qR(p)) (C1qRp) (Cell surface antigen AA4) (Complement component 1 q subcomponent receptor 1) (Lymphocyte antigen 68) (Ly-68) (CD antigen CD93)
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MAISTGLFLLLGLLGQPWAGAAADSQAVVCEGTACYTAHWGKLSAAEAQHRCNENGGNLATVKSEEEARHVQQALTQLLKTKAPLEAKMGKFWIGLQREKGNCTYHDLPMRGFSWVGGGEDTAYSNWYKASKSSCIFKRCVSLILDLSLTPHPSHLPKWHESPCGTPEAPGNSIEGFLCKFNFKGMCRPLALGGPGRVTYTTPFQATTSSLEAVPFASVANVACGDEAKSETHYFLCNEKTPGIFHWGSSGPLCVSPKFGCSFNNGGCQQDCFEGGDGSFRCGCRPGFRLLDDLVTCASRNPCSSNPCTGGGMCHSVPLSENYTCRCPSGYQLDSSQVHCVDIDECQDSPCAQDCVNTLGSFHCECWVGYQPSGPKEEACEDVDECAAANSPCAQGCINTDGSFYCSCKEGYIVSGEDSTQCEDIDECSDARGNPCDSLCFNTDGSFRCGCPPGWELAPNGVFCSRGTVFSELPARPPQKEDNDDRKESTMPPTEMPSSPSGSKDVSNRAQTTGLFVQSDIPTASVPLEIEIPSEVSDVWFELGTYLPTTSGHSKPTHEDSVSAHSDTDGQNLLLFYILGTVVAISLLLVLALGILIYHKRRAKKEEIKEKKPQNAADSYSWVPERAESQAPENQYSPTPGTDC
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Receptor (or element of a larger receptor complex) for C1q, mannose-binding lectin (MBL2) and pulmonary surfactant protein A (SPA). May mediate the enhancement of phagocytosis in monocytes and macrophages upon interaction with soluble defense collagens. May play a role in intercellular adhesion. Marker for early multipotent hematopoietic precursor cells. May play a role in cell-cell interactions during hematopoietic and vascular development.
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O89106
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FHIT_MOUSE
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Bis(5'-adenosyl)-triphosphatase (EC 3.6.1.29) (AP3A hydrolase) (AP3Aase) (Adenosine 5'-monophosphoramidase FHIT) (EC 3.9.1.-) (Adenylylsulfatase) (EC 3.6.2.1) (Adenylylsulfate-ammonia adenylyltransferase) (EC 2.7.7.51) (Diadenosine 5',5'''-P1,P3-triphosphate hydrolase) (Dinucleosidetriphosphatase) (Fragile histidine triad protein)
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MSFRFGQHLIKPSVVFLKTELSFALVNRKPVVPGHVLVCPLRPVERFRDLHPDEVADLFQVTQRVGTVVEKHFQGTSITFSMQDGPEAGQTVKHVHVHVLPRKAGDFPRNDNIYDELQKHDREEEDSPAFWRSEKEMAAEAEALRVYFQA
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Possesses dinucleoside triphosphate hydrolase activity (By similarity). Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP (By similarity). Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP (By similarity). Exhibits adenylylsulfatase activity, hydrolyzing adenosine 5'-phosphosulfate to yield AMP and sulfate (By similarity). Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (By similarity). Exhibits adenylylsulfate-ammonia adenylyltransferase, catalyzing the ammonolysis of adenosine 5'-phosphosulfate resulting in the formation of adenosine 5'-phosphoramidate (By similarity). Also catalyzes the ammonolysis of adenosine 5-phosphorofluoridate and diadenosine triphosphate (By similarity). Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5 (By similarity). Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways (By similarity). Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis (By similarity). Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity (By similarity). Functions as tumor suppressor.
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O89107
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DNSL3_RAT
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Deoxyribonuclease gamma (DNase gamma) (EC 3.1.21.-) (DNaseY) (Deoxyribonuclease I-like 3) (DNase I-like 3)
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MSLYPASPYLASLLLFILALHGALSLRLCSFNVRSFGESKKENHNAMDIIVKIIKRCDLILLMEIKDSNNNICPMLMEKLNGNSRRSTTYNYVISSRLGRNTYKEQYAFLYKEKLVSVKAKYLYHDYQDGDTDVFSREPFVVWFQAPFTAAKDFVIVPLHTTPETSVKEIDELADVYTDVRRRWKAENFIFMGDFNAGCSYVPKKAWKNIRLRTDPNFVWLIGDQEDTTVKKSTSCAYDRIVLRGQEIVNSVVPRSSGVFDFQKAYELSEEEALDVSDHFPVEFKLQSSRAFTNSRKSVSLKKKKKGSRS
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Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends. Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA. Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis. The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells. Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (By similarity). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (By similarity).
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O89109
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KCNN4_MOUSE
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Intermediate conductance calcium-activated potassium channel protein 4 (SK4) (SKCa 4) (SKCa4) (IK1) (KCa3.1) (KCa4)
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MGGELVTGLGALRRRKRLLEQEKRVAGWALVLAGTGIGLMVLHAEMLWFLGCKWVLYLLLVKCLITLSTAFLLCLIVVFHAKEVQLFMTDNGLRDWRVALTRRQVAQILLELLVCGVHPVPLRSPHCALAGEATDAQPWPGFLGEGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYRSIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLTDTLWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHNFMMDIHYAKEMKESAARLLQEAWMYYKHTRRKDSRAARRHQRKMLAAIHTFRQVRLKHRKLREQVNSMVDISKMHMILCDLQLGLSSSHRALEKRIDGLAGKLDALTELLGTALQQQQLPEPSQEAT
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Forms a voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. Plays a role in the late stages of EGF-induced macropinocytosis (By similarity).
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O89110
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CASP8_MOUSE
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Caspase-8 (CASP-8) (EC 3.4.22.61) [Cleaved into: Caspase-8 subunit p18; Caspase-8 subunit p10]
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MDFQSCLYAIAEELGSEDLAALKFLCLDYIPHKKQETIEDAQKLFLRLREKGMLEEGNLSFLKELLFHISRWDLLVNFLDCNREEMVRELRDPDNAQISPYRVMLFKLSEEVSELELRSFKFLLNNEIPKCKLEDDLSLLEIFVEMEKRTMLAENNLETLKSICDQVNKSLLGKIEDYERSSTERRMSLEGREELPPSVLDEMSLKMAELCDSPREQDSESRTSDKVYQMKNKPRGYCLIINNHDFSKAREDITQLRKMKDRKGTDCDKEALSKTFKELHFEIVSYDDCTANEIHEILEGYQSADHKNKDCFICCILSHGDKGVVYGTDGKEASIYDLTSYFTGSKCPSLSGKPKIFFIQACQGSNFQKGVPDEAGFEQQNHTLEVDSSSHKNYIPDEADFLLGMATVKNCVSYRDPVNGTWYIQSLCQSLRERCPQGDDILSILTGVNYDVSNKDDRRNKGKQMPQPTFTLRKKLFFPP
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Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood. Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (By similarity). Binding to the adapter molecule FADD recruits it to either receptor TNFRSF6/FAS mediated or TNFRSF1A. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (By similarity). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (By similarity). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (By similarity). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-325', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response. Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-D (GSDMD): GSDMD cleavage promoting release of the N-terminal moiety (Gasdermin-D, N-terminal) that binds to membranes and forms pores, triggering pyroptosis. Initiates pyroptosis following inactivation of MAP3K7/TAK1. Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production. May participate in the Granzyme B (GZMB) cell death pathways (By similarity). Cleaves PARP1 and PARP2.
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O89112
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LANC1_MOUSE
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Glutathione S-transferase LANCL1 (EC 2.5.1.18) (40 kDa erythrocyte membrane protein) (p40) (LanC-like protein 1)
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MAQRAFPNPYADYNKSLAENYFDSTGRLTPEFSHRLTNKIRELLQQMERGLKSADPRDGTGYTGWAGIAVLYLHLHNVFGDPAYLQMAHSYVKQSLNCLSRRSITFLCGDAGPLAVAAVLYHKMNSEKQAEECITRLIHLNKIDPHVPNEMLYGRIGYIFALLFVNKNFGEEKIPQSHIQQICENILTSGENLSRKRNLAAKSPLMYEWYQEYYVGAAHGLAGIYYYLMQPSLQVNQGKLHSLVKPSVDFVCRLKFPSGNYPPCLDDTRDLLVHWCHGAPGVIYMLIQAYKVFKEERYLCDAQQCADVIWQYGLLKKGYGLCHGAAGNAYAFLALYNLTQDLKYLYRACKFAEWCLDYGEHGCRTADTPFSLFEGMAGTIYFLADLLVPTKAKFPAFEL
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Functions as glutathione transferase. Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate. Mitigates neuronal oxidative stress during normal postnatal development and in response to oxidative stresses probably through GSH antioxidant defense mechanism. May play a role in EPS8 signaling. Binds glutathione (By similarity).
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O89116
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VTI1A_MOUSE
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Vesicle transport through interaction with t-SNAREs homolog 1A (Vesicle transport v-SNARE protein Vti1-like 2) (Vti1-rp2)
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MSSDFEGYEQDFAVLTAEITSKIARVPRLPPDEKKQMVANVEKQLEEARELLEQMDLEVREIPPQSRGMYSNRMRSYKQEMGKLETDFKRSRIAYSDEVRNELLGDAGNSSENQRAHLLDNTERLERSSRRLEAGYQIAVETEQIGQEMLENLSHDREKIQRARDRLRDADANLGKSSRILTGMLRRIIQNRILLVILGIIVVIAILTAIAFFVKGH
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V-SNARE that mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane. These interactions are proposed to mediate aspects of the specificity of vesicle trafficking and to promote fusion of the lipid bilayers. Involved in vesicular transport from the late endosomes to the trans-Golgi network. Along with VAMP7, involved in an non-conventional RAB1-dependent traffic route to the cell surface used by KCNIP1 and KCND2. May be concerned with increased secretion of cytokines associated with cellular senescence.
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O89290
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POL_HV193
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Gag-Pol polyprotein (Pr160Gag-Pol) [Cleaved into: Matrix protein p17 (MA); Capsid protein p24 (CA); Spacer peptide 1 (SP1) (p2); Nucleocapsid protein p7 (NC); Transframe peptide (TF); p6-pol (p6*); Protease (EC 3.4.23.16) (PR) (Retropepsin); Reverse transcriptase/ribonuclease H (EC 2.7.7.49) (EC 2.7.7.7) (EC 3.1.26.13) (Exoribonuclease H) (EC 3.1.13.2) (p66 RT); p51 RT; p15; Integrase (IN) (EC 2.7.7.-) (EC 3.1.-.-)]
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MGARASVLSGGKLDAWEKIRLRPGGKKKYRLKHLVWASRELERFALDPGLLETSEGCRKIIGQLQPSLQTGSEELKSLYNTIAVLYYVHQKVEVKDTKEALEKLEEEQNKGRQKTQQATAEKGVSQNYPIVQNLQGQMVHQSLSPRTLNAWVKVIEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKDTINEEAAEWDRLHPTQAGPIPPGQIREPRGSDIAGTTSTLQEQIQWMTGNPPVPVGEMYKRWIILGLNKIVRMYSPVGILDIRQGPKEPFRDYVDRFFKTLRAEQATQEVKGWMTDTLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPSHKARVLAEAMSQATNTAIMMQKSNFKGQRRIVKCFNCGKEGHIAKNCRAPRKKGCWKCGREGHQMKDCTERQAKFFRENLAFQQGEARKLHPEQARAVSPASRELQVRGGDNPISEAGAERRGTVPSLSFPQITLWQRPLVTIRVGGQLKEALLDTGADDTVLEDVNLPGKWKPKMIGGIGGFIKVKQYDSILIEICGHRAIGTVLVGPTPVNIIGRNMLTQIGCTLHFPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALTEICMEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDKDFRKYTASTIPSTNNETPGVRYQYNVLPQGWKGSPAIFQYSMTKILDPFRAKNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELREHLLKWGLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIQLPDKDSWTVNDIQKLVGKLNWASQIYPGIKVKQLCKLLRGAKALTDIVPLTTEAELELAENREILKEPVHGAYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYAKMRSAHTNDVKQLTEAVQKISLESIVIWGKTPKFRLPILKETWDTWWTEYWQATWIPEWEFVNTPPLVKLWYQLETEPIVGAETFYVDGASNRETKKGKAGYVTDRGRQKAVSLTETTNQKAELQAIQLALQDSGSEVNIVTDSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLSWVPAHKGIGGNEQVDKLVSAGIRKVLFLDGIDKAQEEHEKYHNNWRAMASDFNIPAVVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKIILVAVHVASGYLEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGTNFTSATVKAACWWAGIQQEFGIPYNPQSQGVVESMNKELKKIIGQIRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERTIDIIATDIQTRELQKQIIKIQNFRVYYRDSRDPVWKGPAKLLWKGEGAVVIQDNSEIKVVPRRKAKIIRDYGKQMAGDDCVAGRQDED
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[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. [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. [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. [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. [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). [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. 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.
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O89291
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GAG_HV193
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Gag polyprotein (Pr55Gag) [Cleaved into: Matrix protein p17 (MA); Capsid protein p24 (CA); Spacer peptide 1 (SP1) (p2); Nucleocapsid protein p7 (NC); Spacer peptide 2 (SP2) (p1); p6-gag]
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MGARASVLSGGKLDAWEKIRLRPGGKKKYRLKHLVWASRELERFALDPGLLETSEGCRKIIGQLQPSLQTGSEELKSLYNTIAVLYYVHQKVEVKDTKEALEKLEEEQNKGRQKTQQATAEKGVSQNYPIVQNLQGQMVHQSLSPRTLNAWVKVIEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKDTINEEAAEWDRLHPTQAGPIPPGQIREPRGSDIAGTTSTLQEQIQWMTGNPPVPVGEMYKRWIILGLNKIVRMYSPVGILDIRQGPKEPFRDYVDRFFKTLRAEQATQEVKGWMTDTLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPSHKARVLAEAMSQATNTAIMMQKSNFKGQRRIVKCFNCGKEGHIAKNCRAPRKKGCWKCGREGHQMKDCTERQANFLGKIWPSNKGRPGNFIQNRPEPSAPPAESFRFGEETTPSPKQEQKDEGLYPPLASLKSLFGNDP
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[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). [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}. [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). [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.
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O89292
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ENV_HV193
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Envelope glycoprotein gp160 (Env polyprotein) [Cleaved into: Surface protein gp120 (SU) (Glycoprotein 120) (gp120); Transmembrane protein gp41 (TM) (Glycoprotein 41) (gp41)]
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MRVRGMQRNWQHLGKWGLLFLGTLIICNAAENLWVTVYYGVPVWKEATTTLFCASDAKSYEKEAHNVWATHACVPTDPNPQEVVLENVTERFNMWENNMVEQMHTDIISLWDQSLKPCVKLTPLCVTLDCRNIATNGTNDTIAINDTLKEDPEAIQNCSFNTTTEIRDKQLKVHALFYKLDIVQINKDDNRTYRLINCDASTITQACPKVSWDPIPIHYCAPAGYAILKCNEKNFTGTGSCKNVSTVQCTHGIKPVVSTQLLLNGSLAEGEIVIRSQNISDNAKTIIVHLNESVQINCTRPNNNTRKRISLGPGRVFYTTGEIIGDIRKAHCNVSGTQWRNTLAKVKAKLGSYFPNATIKFNSSSGGDLEITRHNFNCMGEFFYCNTDELFNDTKFNDTGFNGTITLPCRIKQIVNMWQEVGRAMYANPIAGNITCNSNITGLLLTRDGGLNSTNETFRPGGGNMKDNWRSELYKYKVVEIEPLGVAPTKAKRQVVKRERRAVGLGALFLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAIEAQQHLLQLTVWGIKQLQARVLAVERYLKDQQLLGLWGCSGKLICTTNVPWNSSWSNKSLEEIWGNMTWMEWEKEVSNYSKEIYRLIEDSQNQQEKNEQELLALDKWASLWNWFDITQWLWYIKIFIMIVGGLIGLRIVFTVLSIVNRVRKGYSPLSFQTHIPSPREPDRPEGIEEGGGEQGKDRSVRLVTGFLALAWDDLRNLCLFSYRHLRDFILIAARIVDRGLKRGWEALKYLGNLTQYWGQELKNSAISLLNATAIAVAEWTDRVIEALQRAGRAILNIPRRIRQGLERALL
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[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}. [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}. [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}.
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O89293
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NEF_HV193
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Protein Nef (3'ORF) (Negative factor) (F-protein) [Cleaved into: C-terminal core protein]
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MGGKWSKSSIVGWPAIRERMRRTPPTPPAAEGVGAVSQDLERRGAITSSNTRANNPDLAWLEAQEEDEVGFPVRPQVPLRPMTYKGAVDLSHFLKEKGGLEGLIYSKRRQEILDLWVYHTQGYFPDWQNYTPGPGIRYPLTMGWCFKLVPVDPEEVEKANEGENNCLLHPMSQHGMEDEDKEVLKWEFDSRLALRHIARERHPEYYQD
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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}. 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}. 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}. 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}. Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
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O89939
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GAG_HV1SE
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Gag polyprotein (Pr55Gag) [Cleaved into: Matrix protein p17 (MA); Capsid protein p24 (CA); Spacer peptide 1 (SP1) (p2); Nucleocapsid protein p7 (NC); Spacer peptide 2 (SP2) (p1); p6-gag]
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MGARASVLTGGKLDAWEKIRLRPGGRKSYKIKHLVWASRELERFALNPDLLETAEGCQQIMRQLQPSLQTGTEEIKSLYNAVATLYCVHQRIEVKDTKEALEEVEKIQKKSQEKIQQAAMDKGNSNQVSQNYPIVQNAQGQMVHQAITPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNLMLNTVGGHQAAMQMLKDTINEEAAEWDRMHPQQAGPFPPGQIREPRGSDIAGTTSSLQEQITWMTGNPPIPVGEIYKRWIILGLNKIVRMYSPVSILDIRQGPKEPFRDYVDRFFKCLRAEQASQDVKGWMTDTLLVQNANPDCKTILRALGQGASLEEMMTACQGVGGPSHKARVLAEAMSQASGAAAAIMMQRSNFKGPRRTIKCFNCGKEGHLARNCRAPRKKGCWKCGKEGHQMKDCTERQANFLGKIWPSNKGRPGNFLQNRTEPTAPPAESLGFGEEIAPSPKQEMKEKELYPSLKSLFGSDP
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[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). [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}. [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). [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.
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O89940
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POL_HV1SE
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Gag-Pol polyprotein (Pr160Gag-Pol) [Cleaved into: Matrix protein p17 (MA); Capsid protein p24 (CA); Spacer peptide 1 (SP1) (p2); Nucleocapsid protein p7 (NC); Transframe peptide (TF); p6-pol (p6*); Protease (EC 3.4.23.16) (PR) (Retropepsin); Reverse transcriptase/ribonuclease H (EC 2.7.7.49) (EC 2.7.7.7) (EC 3.1.26.13) (Exoribonuclease H) (EC 3.1.13.2) (p66 RT); p51 RT; p15; Integrase (IN) (EC 2.7.7.-) (EC 3.1.-.-)]
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MGARASVLTGGKLDAWEKIRLRPGGRKSYKIKHLVWASRELERFALNPDLLETAEGCQQIMRQLQPSLQTGTEEIKSLYNAVATLYCVHQRIEVKDTKEALEEVEKIQKKSQEKIQQAAMDKGNSNQVSQNYPIVQNAQGQMVHQAITPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNLMLNTVGGHQAAMQMLKDTINEEAAEWDRMHPQQAGPFPPGQIREPRGSDIAGTTSSLQEQITWMTGNPPIPVGEIYKRWIILGLNKIVRMYSPVSILDIRQGPKEPFRDYVDRFFKCLRAEQASQDVKGWMTDTLLVQNANPDCKTILRALGQGASLEEMMTACQGVGGPSHKARVLAEAMSQASGAAAAIMMQRSNFKGPRRTIKCFNCGKEGHLARNCRAPRKKGCWKCGKEGHQMKDCTERQANFFRENLAFQQGEAREFSSEQDRTNSPTCRKPRVRRGDSPLPEAGDEGKGAISLPQITLWQRPLVTVKIGGQLIEALLDTGADDTVLEEINLPGRWKPKMIGGIGGFIKVRQYDQVPIEISGKKAIGTILVGPTPINIIGRNMLTQIGCTLNFPISPIETVPVKLKPGMDGPRVKQWPLTEEKIKALTEICKEMEEEGKISKIGPENPYNTPIFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGVRYQYNVLPQGWKGSPAIFQSSMTRILEPFRANNPEMVIYQYMDDLYVGSDLEIGQHRAKIEELREHLLKWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIQLPDKESWTVNDIQKLVGKLNWASQIYPGIKVTHLCKLLRGAKALTDIVSLTAEAEMELAENREILREPVHGVYYDPSKELIAEVQKQGLDQWTYQIYQEPYKNLKTGKYAKRGSAHTNDVKQLTEVVQKIATESIVIWGKTPKFKLPIRKETWEIWWTDYWQATWIPEWEFVNTPPLVKLWYRLETEPIPGAETYYVDGAANRETKLGKAGYVTDKGKQKIITLTETTNQKAELQAIQLALQDSRSEVNIVTDSQYALGIIQAQPDRSEAELVNQIIEQLIKKEKVYLSWVPAHKGIGGNEQVDKLVSSGIRKVLFLDGIDKAQEEHERYHNNWRAMASDFNLPPIVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKIIIVAVHVASGYIEAEVIPAETGQETAYFILKLAGRWPVTVIHTDNGSNFTSAAVKAACWWANITQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIIDIIASDIQTKELQKQITKIQNFRVYYRDSRDPVWKGPAKLLWKGEGAVVIQDNNEIKVVPRRKAKIIRDYGKQMAGDDCVAGRQDED
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[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. [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. [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. [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. [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). [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. [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.
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O89943
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TAT_HV1SE
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Protein Tat (Transactivating regulatory protein)
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MDPVDPNLEPWNHPGSQPKTPCNKCFCKVCCWHCQVCFLNKGLGISYGRKKRKHRRGTPQSSKGHQDPVPKQPLPTTRGNPTGPKESKKEVASKAEADQCD
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Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. 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}. 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}.
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O89945
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NEF_HV1SE
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Protein Nef (3'ORF) (Negative factor) (F-protein) [Cleaved into: C-terminal core protein]
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MGGKWSKSSIVGWPEVRERIRNTPTAAEGVGAVSQDLDRHGAITSSNTAANNPDCAWLEAQEEDSEVGFPVRPQVPLRPMTFKGAFDLSFFLKEKGGLDGLIYSKKRQEILDLWVYNTQGYFPDWQNYTPGPGTRFPLTFGWCFKLVPMDPAEVEEANKGENNSLLHPICQHGMEDEDREVLVWRFDSSLARRHIARELHPEYYKDC
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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}. 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}. 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}. 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}. Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
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O90304
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SPIKE_BRV1
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Spike glycoprotein (S glycoprotein) (E2) (Peplomer protein)
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MFLCFCTAPILCLWINSGGAVVVSNESLVVCEPVSYPYSLQVLRSFSQRVNLRTKRAVTTDAWSFAYQISTSSLNVNGWYVNFTSPLGWSYPNGKLFGIVLGSDAMMRASVSTFTYDVISYVGQRPNLDCQINDLANGGLESRYSTVRVDNCGNYPCHGGGKPGCSIGHPYMANGVRTRVLLTTQSPGIQYEIYSGQDYAVYQITPYTQYTVTMPSGTSGYCQQTPLYVECGSWTPYRVHAYGCDKATQSCNYTISSDWVVAFKSKASAIILRSQLIVALAQKLSRTVGVNKAVYFWFLKQPYHYLSLVNFSPNYALFSPLCKSLRQQSATYSALSYGSPFFVAQECYNNALYLPDCCLYTLFSILFSWDYQVNYPVNNVLQANETFLQLPTTGYLGQTVSQGRMLNLFKDAIVFLDFYDTKFYRTNDGPGGDIFAVVVKQVPVIAYSAFRIEQQTGYLAVKCNGVIQATLAPHSSRVVLLARHMSMWSIAAANSTTIYCPIYTLTSFVRLDISTSWYFHTLAQPSGPIQQVSMPVLSTGAAGVYMHPMIEHWVTLLAQSSVYQPSMFNMGVNKSVTLTTQLQAYAQVYTAWFLSILYTRLPESRRLTLGAQLTPFIQALLSFKQADIDATDVDTVARYNVLILMWGRKYAAVIYNQLPEWSYPLFKGGVGDSMWFRKKFLVTTKIHQTASHFPFIAGYLDFLDYKYIPKYKDVACPLSTMVPSILQVYETPQLFVIIVQCVSTTYSWYPGLRNPHTIYRSYKLGTICVLVPYSSPTDVYSSFGFFFQSALTIPTVQTTDDILPGCVGFVQDSVFTPCHPSGCPVRNSYDNYIICPGSSASNYTLRNYYRTTTPVTNVPIEEVPLQLEIPTVSLTSYELKQSESVLLQDIEGGIVVDHNTGSIWYPGGQAYDVSFYVSVIIRYAPPKLELPSTLANFTSCLDYICFGNQQCRGEAQTFCTSMDYFEQVFNKSLTSLITALQDLHYVLKLVLPETTLELTEDTRRRRRAVDEFSDTISLLSESFERFMSPASQAYMANMMWWDEAFDGISLPQRTGSILSSAPSLSSISSWHSYSSRTPLISNVKTPKTTFNVKLSMPKLPKASTLSTIGSVLSSGLSIASLGLSIFSIIEDRRVIELTQQQIMALEDQITILAGYTTKNFEEIQSSLNTLGQQVQDFSQTSALSLQQLSNGFEQITQQLDKSIYYVMAVQQYATYMSSLVNQLNELSQAVYKTQDMYITCIHSLQSGVLSPNCITPFQICHLYQVAKNLSSGECQPILSEREISRFYSLPLVTDAMVHNDTYWFSWSIPITCSNILGSVYKVQPGYIVNPHHPTSLQYDVPTHVVTSNAGALIFDEHYCDRYNQVYLCTKSAFDLAEASYLTMLYSNQTDNSSLTFHPAPRPDPCVYLSASALYCYYSDECHQCVIAVGNCTNRTVTYENYTYPIMDPQCRGFDQITISSPIAIGADFTALPSRPPLPLHLSYVNVTFNVTLPNELNWTDLVLDYSFKDKVYEISKNITQLHEQILQVSNWASGWFQRLRDFLYGLIPAWITWLTLGFSLFSILISGVNIILFFEMNGKVKKS
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Mediates the binding of virions to the host cell receptor and is involved in membrane fusion.
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O90368
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POLN_ONNVS
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Polyprotein P1234 (P1234) (Non-structural polyprotein) [Cleaved into: Polyprotein P123' (P123'); Polyprotein P123 (P123); mRNA-capping enzyme nsP1 (EC 2.1.1.-) (EC 2.7.7.-) (Non-structural protein 1); Protease nsP2 (EC 3.4.22.-) (EC 3.6.1.15) (EC 3.6.1.74) (EC 3.6.4.13) (Non-structural protein 2) (nsP2); Non-structural protein 3' (nsP3') (EC 3.1.3.84); Non-structural protein 3 (nsP3) (EC 3.1.3.84); RNA-directed RNA polymerase nsP4 (EC 2.7.7.19) (EC 2.7.7.48) (Non-structural protein 4) (nsP4)]
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MDSVYVDIDADSAFLKALQRAYPMFEVEPKQVTPNDHANARAFSHLAIKLIEQEIDPDSTILDIGPAPARRMMSDRKYHCVCPMRSAEDPERLANYARKLASAAGKVTDKNISGKINDLQAVMAVPNMETSTFCLHTDATCKQRGDVAIYQDVYAVHAPTSLYHQAIKGVRVAYWIGFDTTPFMYNAMAGAYPSYSTNWADEQVLKAKNIGLCSTDLSEGRRGKLSIMRGKKLKPCDRVLFSVGSTLYPESRKLLQSWHLPSVFHLKGKLSFTCRCDTIVSCEGYVVKRVTMSPGIYGKTSGYAVTHHADGFLMCKTTDTVDGERVSFSVCTYVPATICDQMTGILATEVTPEDAQKLLVGLNQRIVVNGRTQRNTNTMKNYLLPIVAQAFSKWAKECRKDMEDEKLLGVRERTLTCCCLWAFRKHKTHTVYKRPDTQSIQKVPAEFDSFVIPSLWSSGLSIPLRTRIKWLLSKAPKHEQLPHSGNAEEAAQAEMDAAEEREAELTREAMPPLQATQDDVQVEIDVEQLEDRAGAGIVETPRGAIKVTAQPSDRVVGEYLVLTPQAVLRSQKLSLIHALAEQVKTCTHSGRAGRYAVEAYDGRVLVPSGYAIPQEDFQSLSESATMVFNEREFVNRKLHHIAMHGPALNTDEESYELVRVEKTEHEYVYDVDQKKCCKREEATGLVLVGDLTSPPYHEFAYEGLKIRPACPYKTAVIGVFGVPGSGKSAIIKNLVTRQDLVTSGKKENCQEISNDVMRQRKLEISARTVDSLLLNGCNKPVEVLYVDEAFACHSGTLLALIAMVRPRQKVVLCGDPKQCGFFNMMQMKVNYNHNICTQVYHKSISRRCTLPVTAIVSSLHYESKMRTTNEYNQPIVVDTTGITKPEPGDLVLTCFRGWVKQLQIDYRGNEVMTAAASQGLTRKGVYAVRQKVNENPLYASTSEHVNVLLTRTEGKLIWKTLSGDPWIKILQNPPKGNFKATIKEWEAEHASIMAGICNHQMAFDTFQNKANVCWAKCLVPILDTAGIKLSDRQWSQIVQAFKEDRAYSPEVALNEICTRIYGVDLDSGLFSKPLISVYYADNHWDNRPGGKMFGFNPEVALMLEKKYPFTKGKWNINKQICITTRKVDEFNPETNIIPANRRLPHSLVAEHHTVRGERMEWLVNKINGHHMLLVSGYNLILPTKRVTWVAPLGTRGADYTYNLELGLPATLGRYDLVVINIHTPFRIHHYQQCVDHAMKLQMLGGDSLRLLKPGGSLLIRAYGYADRTSERVISVLGRKFRSSRALKPQCITSNTEMFFLFSRFDNGRRNFTTHVMNNQLNAVYAGLATRAGCAPSYRVKRMDIAKNTEECVVNAANPRGVPGDGVCKAVYRKWPESFRNSATPVGTAKTIMCGQYPVIHAVGPNFSNYSEAEGDRELASVYREVAKEVSRLGVSSVAIPLLSTGVYSGGKDRLLQSLNHLFTAMDSTDADVVIYCRDKEWEKKITEAISLRSQVELLDDHISVDCDIVRVHPDSSLAGRKGYSTVEGALYSYLEGTRFHQTAVDMAEIYTMWPKQTEANEQVCLYALGESIESVRQKCPVDDADASFPPKTVPCLCRYAMTPERVARLRMNHTTSIIVCSSFPLPKYKIEGVQKVKCSKALLFDHNVPSRVSPRTYRPADEIIQTPQIPTEACQDAQFVQSITDEAVPVPSDLEACDATMDWPSIDIVPTRQRSDSFDSEYSSRSNIQLVTADVHAPMYANSLASSGGSVLSLSSEQAQNGIMILPDSEDTDSISRVSTPIAPPRRRLGRTINVTCDEREGKILPMASDRLFTAKPYTVALGVSTADITAYPIQAPLGSTQPPALEQITFGDFAEGEIDNLLTGALTFGDFEPGEVEELTDSEWSTCSDTDEELXLDRAGGYIFSSDTGQGHLQQKSVRQTTLPVNIVEEVHEEKCYPPKLDEIKEQLLLKRLQESASTANRSRYQSRKVENMKATIIHRLKEGCRLYLASDTPRVPSYRITYPAPVYSPSISIKLNNPETAVAVCNEFLARNYPTVASYQVTDEYDAYLDMVDGSESCLDRATFNPSKLRSYPKQHSYHAPTIRSAVPSPFQNTLQNVLAAATKRNCNVTQMRELPTMDSAVFNVECFKKYACNQEYWREFASSPIRVTTENLTMYVTKLKGPKAAALFAKTHNLLPLQEVPMDRFTMDMKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLNAVLLPNVHTLFDMSAEDFDAIISTHFKPGDAVLETDIASFDKSQDDSLALTAMMLLEDLGVDQPILDLIEAAFGEISSCHLPTGTRFKFGAMMKSGMFLTLFVNTLLNITIASRVLEERLTTSACAAFIGDDNIIHGVVSDALMAARCATWMNMEVKIIDAVVSEKAPYFCGGFILHDTVTGTSCRVADPLKRLFKLGKPLAAGDEQDEDRRRALADEVTRWQRTGLITELEKAVYSRYEVQGITAVITSMATFASSKENFKKLRGPVVTLYGGPK
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[Polyprotein P1234]: Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2. [Polyprotein P123']: The early replication complex formed by the polyprotein P123' and nsP4 synthesizes minus-strand RNAs (Probable). Polyprotein P123' is a short-lived polyprotein that accumulates during early stage of infection (Probable). As soon P123' is cleaved into mature proteins, the plus-strand RNAs synthesis begins (Probable). [Polyprotein P123]: The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By similarity). As soon P123 is cleaved into mature proteins, the plus-strand RNAs synthesis begins (By similarity). [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and nsP1 guanylyltransferase (By similarity). mRNA-capping is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus (Probable). The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP (Probable). nsP1 capping consists in the following reactions: GTP is first methylated into 7-methyl-GMP and then is covalently linked to nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure (By similarity). NsP1 is also needed for the initiation of the minus-strand RNAs synthesis (By similarity). Probably serves as a membrane anchor for the replication complex composed of nsP1-nsP4 (By similarity). Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell (By similarity). [Protease nsP2]: Multifunctional protein whose N-terminus is part of the RNA polymerase complex and displays NTPase, RNA triphosphatase and helicase activities (By similarity). NTPase and RNA triphosphatase are involved in viral RNA capping and helicase keeps a check on the dsRNA replication intermediates (By similarity). The C-terminus harbors a protease that specifically cleaves the polyproteins and releases the mature proteins (By similarity). Required for the shutoff of minus-strand RNAs synthesis (By similarity). Specifically inhibits the host IFN response by promoting the nuclear export of host STAT1 (By similarity). Also inhibits host transcription by inducing the rapid proteasome-dependent degradation of POLR2A, a catalytic subunit of the RNAPII complex (By similarity). The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity). [Non-structural protein 3']: Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (By similarity). Displays mono-ADP-ribosylhydrolase activity (Probable). ADP-ribosylation is a post-translational modification that controls various processes of the host cell and the virus probably needs to revert it for optimal viral replication (Probable). Binds proteins of FXR family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs (Probable). The nsp3'-FXR complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of FXR family members to self-assemble and bind DNA (Probable). [Non-structural protein 3]: Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (By similarity). Displays mono-ADP-ribosylhydrolase activity (By similarity). ADP-ribosylation is a post-translational modification that controls various processes of the host cell and the virus probably needs to revert it for optimal viral replication (By similarity). Binds proteins of G3BP family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs (By similarity). The nsp3-G3BP complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of G3BP family members to self-assemble and bind DNA (By similarity).
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O90369
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POLS_ONNVS
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Structural polyprotein (p130) [Cleaved into: Capsid protein (EC 3.4.21.90) (Coat protein) (C); Precursor of protein E3/E2 (p62) (pE2); Assembly protein E3; Spike glycoprotein E2 (E2 envelope glycoprotein); 6K protein; Spike glycoprotein E1 (E1 envelope glycoprotein)]
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MEFIPAQTYYNRRYQPRPWTQRPTIQVIRPKPRRSRPAGQLAQLISAVSRLALRTVPQKPRRTRKTKKQKQVKQEQQSTRNQKKKAPKQKQTQKKKRPGRRERMCMKIENDCIFEVKHEGKITGYACLVGDKVMKPAHVKGTIDNADLAKLAFKRSSKYDLECAQIPVHMKSDASKFTHEKPEGYYNWHHGAVQYSGGRFTIPTGAGKPGDSGRPIFDNKGRVVAIVLGGANEGTRTALSVVTWNKDIVTKITPEGSVEWSLALPVMCLLANTTFPCSQPPCAPCCYEKKPEETLRMLEDNVMQPGYYQLLDSALACSQHRQRRNARENFNVYKVTRPYLAHCPDCGEGHSCHSPIALERIRSEATDGTLKIQVSLQIGIKTDDSHDWTKLRYMDSHTPVDADRSGLFVRTSAPCTITGTMGHFILARCPKGETLTVGFVDSRRISHTCMHPFHHEPPLIGREKFHSRPQHGKELPCSTYVHTTAATTEEIEVHMPPDTPDYTLMTQQAGNVKITVDGQTVRYKCKCDGSNEGLITTDKVINNCKVDQCHTAVTNHKKWQYNSPLTPRNSEQGDRKGKIHIPFPLVNTTCRVPKARNPTITYGKNRVTLLLYPDHPTLLSYRSMGRIPDYHEEWITSKKEISITVPAEGLEVTWGNNDPYKYWPQLSTNGTAHGHPHEIILYYYELYPTTTIAVLAAASIVVASLVSLSLGMCICARRRCITPYELTPGATIPFLLGVLCCVKTAKAASYYEAATYLWNEQQPLFWLQLLIPLSAAIVACNCLKLLPCCCKTLTFLAVMSIGARTVSAYEHATVIPNTVGVPYKTLVSRPGYSPMVLEMELQSVTLEPTLFLDYITCEYKTITPSPYVKCCGTAECKAKNLPDYNCKVFTGVYPFMWGGAYCFCDAENTQLSEAHVEKSESCKTEFASAYRAHTASVSAKLRVFYQGNNITVSAYANGDHAVTVKDAKFVIGPLSSAWSPFDNKIVVYKGEVYNMDYPPFGAGRPGQFGDIQSRTPDSKDVYANTQLILQRPAAGAIHVPYSQAPSGFKYWLKEKGASLQHTAPFGCQIATNPVRAVNCAVGNIPVSIDIPDAAFTRVTDAPSVTDMSCEVASCTHSSDFGGAAVVKYTASKKGKCAVHSLTNAVTIREPNVDVEGTAQLQIAFSTALASAEFKVQICSTQVHCSATCHPPKDHIVNYPSPHTTLGVQDISTTAMSWVQKITGGVGLVVAIAALILIIVLCVSFSRH
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[Capsid protein]: Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions. In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding. [Spike glycoprotein E2]: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane. [6K protein]: Constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins. [Spike glycoprotein E1]: Class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.
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O90370
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POLN_ONNVI
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Polyprotein P1234 (P1234) (Non-structural polyprotein) [Cleaved into: Polyprotein P123 (P123); mRNA-capping enzyme nsP1 (EC 2.1.1.-) (EC 2.7.7.-) (Non-structural protein 1); Protease nsP2 (EC 3.4.22.-) (EC 3.6.1.15) (EC 3.6.1.74) (EC 3.6.4.13) (Non-structural protein 2) (nsP2); Non-structural protein 3 (nsP3) (EC 3.1.3.84); RNA-directed RNA polymerase nsP4 (EC 2.7.7.19) (EC 2.7.7.48) (Non-structural protein 4) (nsP4)]
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MDSVYVDIDADSAFLKALQRAYPMFEVEPKQVTPNDHANARAFSHLAIKLIEQEIDPGSTILGIGSAPARRMMSDRKYHCVCPMRSAEDPERLANYARKLASAAGKVTDKNISGKINDLQAVMAVPNMETSTFCLHTDATCKQRGDVAIYQDVYAVHAPTSLYHQAIKGVHVAYWIGFDTTPFMYNAMAGAYPSYSTNWADEQVLKAKNIGLCSTDLSEGRRGKLSIMRGKKFKPCDRVLFSVGSTLYPESRKLLQSWHLPSVFHLKGKLSFTCRCDTIVSCEGYVVKRVTMSPGIYGKTSGYAVTHHADGFLMCKTTDTVDGERVSFSVCTYVPATICDQMTGILATEVTPEDAQKLLVGLNQRIVVNGRTQRNTNTMKNYLLPIVAQAFSKWAKECRKDMEDEKLLGVRERTLTCCCLWAFRKHKTHTVYKRPDTQSIQKVPAEFDSFVIPSLWSSGLSIPLRTRIKWLLSKAPKHEQLPHSGNAEEAAQAETDAVEEREAELTREAMPPLQATQDDVQVEIDVEQLEDRAGAGIVETPRGAIKVTAQPSDLVVGEYLVLTPQAVLRSQKLGLIHALAEQVKTCTHSGRAGRYAVEAYDGRVLVPSGYAIPQEDFQSLSESATMVFNEREFVNRKLHHIAMHGPALNTDEESYELVRVEKTEHEYVYDVDQKKCCKREEATGLVLVGDLTSPPYHEFAYEGLKIRPACPYKTAVIGVFGVPGSGKSAIIKNLVTRQDLVTSGKKENCQEISNDVMRQRKLEISARTVDSLLLNGCNKPVEVLYVDEAFACHSGTLLALIAMVRPRQKVVLCGDPKQCGFFNMMQMKVNYNHNICTQVYHKSISRRCTLPVTAIVSSLHYESKMRTTNEYNQPIVVDTTGTTKPEPGDLVLTCFRGWVKQLQIDYRGNEVMTAAASQGLTRKGVYAVRQKVNENPLYASTSEHVNVLLTRTEGKLIWKTLSGDPWIKILQNPPKGNFKATIKEWEAEHASIMAGICNYQMAFDTFQNKANVCWAKCLVPILDTAGIKLSDRQWSQIVQAFKEDRAYSPEVALNEICTRIYGVDLDSGLFSKPLISVYYADNHWDNRPGGKMFGFNPEVALMLEKKYPFTKGKWNINKQICITTRKVDEFNPETNIIPANRRLPHSLVAEHHSVRGERMEWLVNKINGHHMLLVSGYNLILPTKRVTWVAPLGTRGADYTYNLELGLPATLGRYDLVVINIHTPFRIHHYQQCVDHAMKLQMLGGDSLRLLKPGGSLLIRAYGYADRTSERVISVLGRKFRSSRALKPQCITSNTEMFFLFSRFDNGRRNFTTHVMNNQLNAVYAGLATRAGCAPSYRVKRMDIAKNTEECVVNAANPRGVPGDGVCKAVYRKWPESFRNSATPVGTAKTIMCGQYPVIHAVGPNFSNYSEAEGDRELASAYREVAKEVSRLGVSSVAIPLLSTGVYSGGKDRLLQSLNHLFAAMDSTDADVVIYCRDKEWEKKITEAISLRSQVELLDDHISVDCDIVRVHPDSSLAGRKGYSTVEGALYSYLEGTRFHQTAVDMAEIYTMWPKQTEANEQVCLYALGESIESVRQKCPVDDADASFPPKTVPCLCRYAMTPERVARLRMNHTTSIIVCSSFPLPKYKIEGVQKVKCSKALLFDHNVPSRVSPRTYRPADEIIQTPQISTEACQDAQLVQSINDEAVPVPSDLEACDATMDWPSIGTVPTRQRHDSFDSEYSSRSNIQLVTADVHAPMYANSLASSGGSMLSLSSEPAQNGIMILPDSEDTDSISRVSTPIAPPRRRLGRTINVTCDEREGKILPMASDRFFTAKPYTVALSVSTADITAYPIQAPLGLTQPPTLEQITFGDFAEGEIDNLLTGALTFGDFEPGEVEELTDSEWSTCSDTDEELRLDRAGGYIFSSDTGQGHLQQKSVRQTTLPVNIVEEVHEEKCYPPKLDETKEQLLLKRLQESASTANRSRYQSRKVENMKATIIHRLKEGCRLYLASDTPRVPSYRITYPAPVYSPSINIKLSNPETAVAVCNEFLARNYPTVASYQVTDEYDAYLDMVDGSESCLDRATFNPSKLRSYPKQHSYHAPTIRSAVPSPFQNTLQNVLAAATKRNCNVTQMRELPTMDSAVFNVECFKKYACNQEYWREFASSPIRVTTENLTMYVTKLKGPKAAALFAKTHNLLPLQEVPMDRFTMDMKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLNAVLLPNVHTLFDMSAEDFDAIIATHFKPGDAVLETDIASFDKSQDDSLALTAMMLLEDLGVDQPILDLIEAAFGEISSCHLPTGTRFKFGAMMKSGMFLTLFVNTLLNITIASRVLEERLTTSACAAFIGDDNIIHGVVSDALMAARCATWMNMEVKIIDAVVSEKAPYFCGGFILHDTVTGTSCRVADPLKRLFKLGKPLAAGDEQDEDRRRALADEVTRWQRTGLVTELEKAVYSRYEVQGITAVITSMATFASSKENFKKLRGPVVTLYGGPK
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[Polyprotein P1234]: Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2. [Polyprotein P123]: The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By similarity). As soon P123 is cleaved into mature proteins, the plus-strand RNAs synthesis begins (By similarity). [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and nsP1 guanylyltransferase (By similarity). mRNA-capping is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus (Probable). The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP (Probable). nsP1 capping consists in the following reactions: GTP is first methylated into 7-methyl-GMP and then is covalently linked to nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure (By similarity). NsP1 is also needed for the initiation of the minus-strand RNAs synthesis (By similarity). Probably serves as a membrane anchor for the replication complex composed of nsP1-nsP4 (By similarity). Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell (By similarity). [Protease nsP2]: Multifunctional protein whose N-terminus is part of the RNA polymerase complex and displays NTPase, RNA triphosphatase and helicase activities (By similarity). NTPase and RNA triphosphatase are involved in viral RNA capping and helicase keeps a check on the dsRNA replication intermediates (By similarity). The C-terminus harbors a protease that specifically cleaves the polyproteins and releases the mature proteins (By similarity). Required for the shutoff of minus-strand RNAs synthesis (By similarity). Specifically inhibits the host IFN response by promoting the nuclear export of host STAT1 (By similarity). Also inhibits host transcription by inducing the rapid proteasome-dependent degradation of POLR2A, a catalytic subunit of the RNAPII complex (By similarity). The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity). [Non-structural protein 3]: Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (By similarity). Displays mono-ADP-ribosylhydrolase activity (By similarity). ADP-ribosylation is a post-translational modification that controls various processes of the host cell and the virus probably needs to revert it for optimal viral replication (By similarity). Binds proteins of G3BP family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs (By similarity). The nsp3-G3BP complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of G3BP family members to self-assemble and bind DNA (By similarity).
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O90371
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POLS_ONNVI
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Structural polyprotein (p130) [Cleaved into: Capsid protein (EC 3.4.21.90) (Coat protein) (C); Precursor of protein E3/E2 (p62) (pE2); Assembly protein E3; Spike glycoprotein E2 (E2 envelope glycoprotein); 6K protein; Spike glycoprotein E1 (E1 envelope glycoprotein)]
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MEFIPAQTYYNRRYQPRPWTQRPTIQVIRPKPRRRRPAGQLAQLISAVSRLALRTVPQKPRRTRKIKKQKQVKQEQQSTRNQKKKAPKQKQTQKKKRPGRRERMCMKIENDCIFEVKHEGKVTGYACLVGDKVMKPAHVKGTIDNADLAKLAFKRSSKYDLECAQIPVHMKSDASKFTHEKPEGYYNWHHGAVQYSGGRFTIPTGAGKPGDSGRPIFDNKGRVVAIVLGGANEGTRTALSVVTWNKDIVTKITPEGSVEWSLALPVMCLLANTTFPCSQPPCAPCCYEKKPEETLRMLEDNVMQPGYYQLLDSALACSQHRQRRNARENFNVYKVTRPYLAHCPDCGEGHSCHSPIALERIRSEATDGTLKIQVSLQIGIKTADSHDWTKLRYMDSHTPVDADRSGLFVRTSAPCTITGTMGHFILARCPKGETLTVGFVDSRRISHTCMHPFHHEPPLIGREKFHSRPQHGKELPCSTYVHTTAATTEEIEVHMPPDTPDYTLMTQQAGNVKITVDGQTVRYKCKCDGSNEGLITTDKVINNCKVDQCHTAVTNHKKWQYNSPLTPRNSEQGDRKGKIHIPFPLVNTTCRVPKARNPTVTYGKNRVTLLLYPDHPTLLSYRAMGRIPDYHEEWITSKKEISITVPAEGLEVTWGNNDPYKYWPQLSTNGTAHGHPHEIILYYYELYPTTTIAVLAAASIVVASLVGLSLGMCICARRRCITPYELTPGATIPFLLGILCCVKTAKAASYYEAATYLWNEQQPLFWLQLLIPLSAAIVVCNCLKLLPCCCKTLTFLAVMSIGARTVSAYEHATVIPNTVGVPYKTLVSRPGYSPMVLEMELQSVTLEPTLFLDYITCEYKTITPSPYVKCCGTAECKAKNLPDYNCKVFTGVYPFMWGGAYCFCDAENTQLSEAHVEKSESCKTEFASAYRAHTASVSAKLRVFYQGNNITVSAYANGDHAVTVKDAKFVIGPLSSAWSPFDNKIVVYKGEVYNMDYPPFGAGRPGQFGDIQSRTPDSKDVYANTQLILQRPAAGAIHVPYSQAPSGFKYWLKEKGASLQHTAPFGCQIATNPVRAVNCAVGNIPVSIDIPDAAFTRVTDAPSVTDMSCEVASCTHSSDFGGAAVIKYTASKKGKCAVHSLTNAVTIREPNVDVEGTAQLQIAFSTALASAEFKVQICSTQVHCSATCHPPKDHIVNYPSPHTTLGVQDISTTAMSWVQKITGGVGLVVAIAALILIIVLCVSFSRH
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[Capsid protein]: Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein surrounded by a lipid membrane through which penetrate 80 spikes composed of trimers of E1-E2 heterodimers (By similarity). The capsid protein binds to the viral RNA genome at a site adjacent to a ribosome binding site for viral genome translation following genome release (By similarity). Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein (By similarity). Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles (By similarity). The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions (By similarity). In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane (By similarity). This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible (By similarity). The uncoating might be triggered by the interaction of capsid proteins with ribosomes (By similarity). Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding (By similarity). Specifically inhibits interleukin-1 receptor-associated kinase 1/IRAK1-dependent signaling during viral entry, representing a means by which the alphaviruses may evade innate immune detection and activation prior to viral gene expression (By similarity). [Assembly protein E3]: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Furin-cleaved E3 remains associated with spike glycoprotein E1 and mediates pH protection of the latter during the transport via the secretory pathway. After virion release from the host cell, the assembly protein E3 is gradually released in the extracellular space. [Spike glycoprotein E2]: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane. [6K protein]: Constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins. [Spike glycoprotein E1]: Class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.
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O91079
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GAG_HV1YF
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Gag polyprotein (Pr55Gag) [Cleaved into: Matrix protein p17 (MA); Capsid protein p24 (CA); Spacer peptide 1 (SP1) (p2); Nucleocapsid protein p7 (NC); Spacer peptide 2 (SP2) (p1); p6-gag]
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MGARASVLTGGKLDQWESIYLRPGGKKKYRMKHLVWASRELERFACNPGLMDTADGCAKLLNQLEPALKTGSEELRSLYNALAVLYCVHSRIQIHNTQEALDKIKEKQEQHKPEPKNPEAGAAAATDSNISRNYPLVQTAQGQMVHQPLTPRTLNAWVKVIEEKAFSPEVIPMFMALSEGATPSDLNTMLNTVGGHQAAMQMLKEVINEEAADWDRTHPVPVGPLPPGQLRDPRGSDIAGTTSTLAEQVAWMTANPPVPVGDIYRRWIVLGLNRIVRMYSPVSILEIKQGPKEPFRDYVDRFYKTLRAEQATQEVKNWMTETLLVQNANPDCKQLLKALGPGATLEEMMTACQGVGGPAHKARVLAEAMSQVQQPTTSVFAQRGNFKGIRKPIKCFNCGKEGHLARNCKAPRRGGCWKCGQEGHQMKDCKNEGRQANFLGKSWSPFKGRPGNFPQTTTRKEPTAPPLESYGFQEEKSTQGKEMQENQERTENSLYPPLTSLRSLFGNDPSSQ
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[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). [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}. [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). [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.
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O91080
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POL_HV1YF
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Gag-Pol polyprotein (Pr160Gag-Pol) [Cleaved into: Matrix protein p17 (MA); Capsid protein p24 (CA); Spacer peptide 1 (SP1) (p2); Nucleocapsid protein p7 (NC); Transframe peptide (TF); p6-pol (p6*); Protease (EC 3.4.23.16) (PR) (Retropepsin); Reverse transcriptase/ribonuclease H (EC 2.7.7.49) (EC 2.7.7.7) (EC 3.1.26.13) (Exoribonuclease H) (EC 3.1.13.2) (p66 RT); p51 RT; p15; Integrase (IN) (EC 2.7.7.-) (EC 3.1.-.-)]
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MGARASVLTGGKLDQWESIYLRPGGKKKYRMKHLVWASRELERFACNPGLMDTADGCAKLLNQLEPALKTGSEELRSLYNALAVLYCVHSRIQIHNTQEALDKIKEKQEQHKPEPKNPEAGAAAATDSNISRNYPLVQTAQGQMVHQPLTPRTLNAWVKVIEEKAFSPEVIPMFMALSEGATPSDLNTMLNTVGGHQAAMQMLKEVINEEAADWDRTHPVPVGPLPPGQLRDPRGSDIAGTTSTLAEQVAWMTANPPVPVGDIYRRWIVLGLNRIVRMYSPVSILEIKQGPKEPFRDYVDRFYKTLRAEQATQEVKNWMTETLLVQNANPDCKQLLKALGPGATLEEMMTACQGVGGPAHKARVLAEAMSQVQQPTTSVFAQRGNFKGIRKPIKCFNCGKEGHLARNCKAPRRGGCWKCGQEGHQMKDCKNEGRQFFREELVSLQRETRKLPPDNNKERAHSPATRELWVSGGEEHTGEGDAGEPGEDRELSVPTFNFPQITLWQRPVITVKIGKEVREALLDTGADDTVIEELQLEGKWKPKMIGGIGGFIKVRQYDNITVDIQGRKAVGTVLVGPTPVNIIGRNLLTQIGCTLNFPISPIETVPVKLKPGMDGPKVKQWPLTTEKIEALREICTEMEKEGKISRIGPENPYNTPIFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKQKKSVTVLDVGDAYFSCPLDKDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSTMTKILEPFREKHPEIIIYQYMDDLYVGSDLELAQHREAVEDLRDHLLKWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIKLPEKDVWTVNDIQKLVGKLNWASQIYPGIRVKQLCKLIRGTKALTEVVNFTEEAELELAENREILKEPLHGVYYDPGKELVAEIQKQGQGQWTYQIYQELHKNLKTGKYAKMRSAHTNDIKQLVEVVRKVATESIVIWGKTPKFRLPVQKEVWEAWWTDHWQATWIPEWEFVNTPPLVKLWYQLETEPISGAETFYVDGAANRETKLGKAGFVTDRGRQKVVSIADTTNQKAELQAILMALQESGRDVNIVTDSQYAMGIIHSQPDKSESELVSQIIEELIKKERVYLSWVPAHKGIGGNEQVDKLVSSGIRKILFLDGIEKAQEDHDRYHSNWKAMASDFNLPPIVAKEIVASCDKCQLKGEAMHGQVNCSPGVWQLDCTHLEGKIILVAVHVASGYLEAEVIPAETGQETAYFILKLAGRWPVKVIHTDNGSNFTSATVKAACWWANIKQEFGIPYNPQSQGAVESMNKELKKIIGQIRDQAEHLKTAVQMAVFIHNFKRKGGIGGYTAGERIIDIIATDIQTTNLQTQILKVQNFRVYYRDSRDPIWKGPAKLLWKGEGAVVIQDNGDIKVVPRRKAKIIRDYGKQMAGDGCVASGQDENQEME
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[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. [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. [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. [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. [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). [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. [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.
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O91083
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TAT_HV1YF
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Protein Tat (Transactivating regulatory protein)
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MEPVDPRLEPWNHPGSQPKTACNNCYCKRCCYHCLYCFTKKGLGISYGRKKRSQRRRTPQSSKSHQDLIPEQPLSQQQGDQTGQKKQKEALESKTEADPCD
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Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. 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}. 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}.
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O91086
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ENV_HV1YF
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Envelope glycoprotein gp160 (Env polyprotein) [Cleaved into: Surface protein gp120 (SU) (Glycoprotein 120) (gp120); Transmembrane protein gp41 (TM) (Glycoprotein 41) (gp41)]
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MGMKSGWLLFYLLVSLIKVIGSEQHWVTVYYGVPVWREAETTLFCASDAKAHSTEAHNIWATQACVPTDPNPQEVLLPNVTEKFNMWENKMADQMQEDIISLWEQSLKPCVKLTPLCVTMLCNDSYGEERNNTNMTTREPDIGYKQMKNCSFNATTELTDKKKQVYSLFYVEDVVPINAYNKTYRLINCNTTAVTQACPKTSFEPIPIHYCAPPGFAIMKCNEGNFSGNGSCTNVSTVQCTHGIKPVISTQLILNGSLNTDGIVIRNDSHSNLLVQWNETVPINCTRPGNNTGGQVQIGPAMTFYNIEKIVGDIRQAYCNVSKELWEPMWNRTREEIKKILGKNNITFRARERNEGDLEVTHLMFNCRGEFFYCNTSKLFNEELLNETGEPITLPCRIRQIVNLWTRVGKGIYAPPIRGVLNCTSNITGLVLEYSGGPDTKETIVYPSGGNMVNLWRQELYKYKVVSIEPIGVAPGKAKRRTVSREKRAAFGLGALFLGFLGAAGSTMGAASITLTVQARTLLSGIVQQQNILLRAIEAQQHLLQLSIWGIKQLQAKVLAIERYLRDQQILSLWGCSGKTICYTTVPWNETWSNNTSYDTIWNNLTWQQWDEKVRNYSGVIFGLIEQAQEQQNTNEKSLLELDQWDSLWSWFGITKWLWYIKIAIMIVAGIVGIRIISIVITIIARVRQGYSPLSLQTLIPTARGPDRPEETEGGVGEQDRGRSVRLVSGFSALVWEDLRNLLIFLYHRLTDSLLILRRTLELLGQSLSRGLQLLNELRTHLWGILAYWGKELRDSAISLLNTTAIVVAEGTDRIIELAQRIGRGILHIPRRIRQGLERALI
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[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}. [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}. [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}.
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O91087
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NEF_HV1YF
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Protein Nef (3'ORF) (Negative factor) (F-protein) [Cleaved into: C-terminal core protein]
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MGKIWSKSSLVGWPEIRERMRRQTQEPAVEPAVGAGAASQDLANRGAITIRNTRDNNESIAWLEAQEEEEEVGFPVRPQVPLRPITYKQAFDLSFFLKDKGGLEGLVWSRKRQDILDLWMYHTQGILPDWHNYTPGPGIRYPVTFGWCFKLVPLSAEEVEEANEGDNNALLHPICQHGADDDHKEVLVWRFDSSLARRHVARELHPEFYKNC
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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}. 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}. 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}. 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}. Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
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O91464
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POLG_AIVA8
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Genome polyprotein [Cleaved into: Leader protein (L); Capsid protein VP0; Capsid protein VP3 (P1C) (Virion protein 3); Capsid protein VP1 (P1D) (Virion protein 1); Protein 2A (P2A); Protein 2B (P2B); Protein 2C (P2C) (EC 3.6.4.13); Protein 3A (P3A); VPg (P3B) (Protein 3B); Protein 3CD (EC 3.4.22.28); Protease 3C (EC 3.4.22.28) (Picornain 3C) (P3C); RNA-directed RNA polymerase (RdRp) (EC 2.7.7.48) (3D polymerase) (3Dpol) (Protein 3D) (3D)]
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MAATRVSRSVLAAVAHSAAHRTYHTVLDCYDRLYLNTNPHLSYPLPKNSSFPCPFCQYDEQNEVLSPESLRGEGAEPCWKCSQDKPRRKYNTTPPEDWLYDSDVQSWFYPETYYSDLQQKFFDKLALLSLPGAYQAKTPEERALAGALTQLLNFPSTPPLTLPTTNLQRQGNSVTNIYGNGNNVTTDVGANGWAPTVSTGLGDGPVSASADSLPGRSGGASSEKTHTVSGSSNKVGSRFSKWWEPAAARASESATDSAIEGIDAAGKAASKAITRKLDRPAAPSSTANPQPSLIALNPSATQSGNASILTGSTAPSLLAYPTATPVPLPNPDEPSQPGPSGDRTWLLDTVTWSQEFTRGWNIAGSNGMQWTGLESLIFPVSTDTNWTSTSSPTAYPLPFSFVRAYPDSSWAAMYNTHSMWNCGWRVQVTVNGSQFHAGALILYMVPEATTHAIQTARDNAGFVFPYVILNLYESNTATIEVPYISPTPNTSSGLHAPWTFYLQVLSPLNPPPSLPTSLSCSIYVTPVDSSFHGLRYLAPQHWKTRAVPGAGTFGSAVAGQELPLCGVRAYYPPNAYIPAQVRDWLEFAHRPGLMATVPWTMADEPAERLGIFPVSPSAIAGTGAPISYVISLFSQWRGELAAHLLFTGSAQHYGRLVVCYTPAAPQPPSTMQEAMRGTYTVWDVNAASTLEFTIPFISNSYWKTVDVNNPDALLSTTGYVSIWVQNPLVGPHTAPASALVQAFISAGESFNVRLMQNPALTSQTLTEDLDAPQDTGNIENGAADNSPQPRTTFDYTGNPLPPDTKLENFFSFYRLLPMGGSGAPSLSFPADEGTIIPLNPINWLKGADVSGIAAMLSCFTYIAADLRITLRFSNPNDNPATMLVAFAPPGATIPLKPTRQMLSNFYMAEVPVSAATSTMVSFSIPYTSPLSAIPTSYFGWEDWSGTNFGQLSSGSWGNLMLIPSLSVDSAIPFDFQLSCWVAFGNFKAWVPRPPPPLPPLPTPAANAERTVAVIKQGAASATPDVDPDDRVYIVRAQRPTYVHWAIRKVAPDGSAKQISLSRSGIQALVALEPPEGEPYLEILPSHWTLAELQLGNKWEYSATNNCTHFVSSITGESLPNTGFSLALGIGALTAIAASAAVAVKALPGIRRQGLLTLSADTETNQTLNKITESVNQAAQVVSQFDLSGPANSVSLAASDIREAAHKVASSLNGFTDVIADIKDSLFTRVSDAVESGVATFLTWLVKLFGYLLVLFGSPTPMSISGLLVIICADLAPHAREFFTASGNVLSSLYYWIASKLGLSVTPQECERATLEPQGLKDFNDGALAMRNVEWIGETAWKWAHRLLDWIRGKAKTDPQAKLADVHDEIMLHYSDSILALGSEKLPIDHITKSISRCRELVSIAQEAKSGPHSSFLNQAIKNYTLAISQHRKCQTGPRPEPVVVYLYGPPGTGKSLLASLLAQTLSQRLAGTPDDVYSPSSASCEYFDGYTGQTVHFIDDIGQDPEGRDWANFPNLVSSAPFIVPMASLEEKGTHYTSKVIVVTSNFHEPNERAARSMGALRRRVHLRINVTSNGVPFDPTNALNPIPGTQSKYFTAQTPLTLFQSNTVRLDRDSIWTPTFTNMDELVDAIVTRLDRSTGVSNSLASLIRRQGNRVIDAEPREIPLEYADDLLEAMAHHRPVPCSLGLSQAIANNTPIQQISETFWKYRKPIFTCTTFLAVLGFLCSVIPLARSLWKSKQDTPQEPQAAYSAISHQKPKPKSQKPVPTRHIQRQGISPAVPGISNNVVHVESGNGLNKNVMSGFYIFSRFLLVPTHLREPHHTTLTVGADTYDWATLQTQEFGEITIVHTPTSRQYKDMRRFIGAHPHPTGLLVSQFKAAPLYVRISDNRILDLDFPGVVVCKQAYGYRAATFEGLCGSPLVTDDPSGVKILGLHVAGVAGTSGFSAPIHPILGQITQFATTQQSLIVPTAEVRPGVNVNRMSRLHPSPAYGAFPVKKQPAPLKRNDKRLQEGVDLDTQLFLKHGKGDVTEPWPGLEAAADLYFSTFPTSLPVLTQEQAIHGTPNMEGLDMGQAAGYPWNTLGRSRRSLFDEVEPGVFVPKPELQAEINQTLEDPDYVYSTFLKDELRPTAKVEQGLTRIVEAAPIHAIVAGRMLLGGLIDYMQGRPGEHGSAVGCNPDVHWTSFFYAFSEFSQVYDLDYKCFDATLPSAVFTLVADHLTRITGDPRVGRYIHSIRHSHHIYGNRMYDMIGGNPSGCVATSILNTIINNICVLSALIQHPDFSPSRFHILAYGDDVIYATEPPIHPSFLREFYQKHTPLVVTPANKGQDFPPTSTIYEVTFLKRWFVPDDVRPIYIHPVMDPDTYEQSVMWLRDGDFQDVVTSLCHLAFHSGPKTYAAWCMKVREQCLKSGFAPNFLPYSYLQLRWLNLLAA
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[Leader protein]: Inhibits the integrated stress response (ISR) in the infected cell by preventing the sequestration of eIF2B by phosphorylated EIF2S1/eIF-2alpha. Stress granule formation in response to EIF2S1/eIF-2alpha phosphorylation is thus inhibited, which allows protein synthesis and viral replication. Does not have any proteolytic activity. Required for viral RNA replication and viral RNA encapsidation. [Capsid protein VP1]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP3. Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. [Capsid protein VP0]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP1 and VP3. Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. [Capsid protein VP3]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP1. Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. [Protein 2C]: Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3. [Protein 3A]: Serves as membrane anchor via its hydrophobic domain. Plays an essential role in viral RNA replication by recruiting PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place. Stimulates the enzymatic activity of PI4KB, this activation is sensitized by ACBD3. [VPg]: Forms a primer, VPg-pU, which is utilized by the polymerase for the initiation of RNA chains. [Protease 3C]: Cysteine protease that generates mature viral proteins from the precursor polyprotein (By similarity). In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate cooperatively bind to the protease (By similarity).
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O91532
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HBEAG_HBVA7
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External core antigen (HBeAg) (Precore protein) (p25)
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MQLFHLCLIISCTCPTVQASKLCLGWLWGMDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAILCWVELMTLATWVGNNLQDPASRDLVVNYVNTNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRDRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC
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May regulate immune response to the intracellular capsid in acting as a T-cell tolerogen, by having an immunoregulatory effect which prevents destruction of infected cells by cytotoxic T-cells. This immune regulation may predispose to chronicity during perinatal infections and prevent severe liver injury during adult infections. {ECO:0000255|HAMAP-Rule:MF_04076}.
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O91534
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HBSAG_HBVA7
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Large envelope protein (L glycoprotein) (L-HBsAg) (LHB) (Large S protein) (Large surface protein) (Major surface antigen)
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MGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGFTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQTLQDPRVRGLYLPAGGSSSGTVNPAPNIASHISSISARTGDPVTNMENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSPVCLGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSSWAFAKFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMMWYWGPSLYSIVRPFIPLLPIFFCLWVYI
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The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches the virus to cell receptors and thereby initiating infection. This interaction determines the species specificity and liver tropism. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis. The large envelope protein also assures fusion between virion membrane and endosomal membrane. In its internal conformation the protein plays a role in virion morphogenesis and mediates the contact with the nucleocapsid like a matrix protein. {ECO:0000255|HAMAP-Rule:MF_04075}. The middle envelope protein plays an important role in the budding of the virion. It is involved in the induction of budding in a nucleocapsid independent way. In this process the majority of envelope proteins bud to form subviral lipoprotein particles of 22 nm of diameter that do not contain a nucleocapsid. {ECO:0000255|HAMAP-Rule:MF_04075}.
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O91734
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POLG_EC01F
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Genome polyprotein [Cleaved into: P1; Capsid protein VP0 (VP4-VP2); Capsid protein VP4 (P1A) (Virion protein 4); Capsid protein VP2 (P1B) (Virion protein 2); Capsid protein VP3 (P1C) (Virion protein 3); Capsid protein VP1 (P1D) (Virion protein 1); P2; Protease 2A (P2A) (EC 3.4.22.29) (Picornain 2A) (Protein 2A); Protein 2B (P2B); Protein 2C (P2C) (EC 3.6.1.15); P3; Protein 3AB; Protein 3A (P3A); Viral protein genome-linked (VPg) (Protein 3B) (P3B); Protein 3CD (EC 3.4.22.28); Protease 3C (EC 3.4.22.28) (Picornain 3C) (P3C); RNA-directed RNA polymerase (RdRp) (EC 2.7.7.48) (3D polymerase) (3Dpol) (Protein 3D) (3D)]
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MGAQVSTQKTGAHETSLSATGNSIIHYTNINYYKDAASNSANRQDFTQDPGKFTEPMKDVMIKTLPALNSPTVEECGYSDRVRSITLGNSTITTQECANVVVGYGEWPEYLSDNEATAEDQPTQPDVATCRFYTLDSVQWENGSPGWWWKFPDALRDMGLFGQNMYYHYLGRAGYTIHVQCNASKFHQGCILVVCVPEAEMGSAQTSGVVNYEHISKGEIASRFTTTTTAEDHGVQAAVWNAGMGVGVGNLTIFPHQWINLRTNNSATIVMPYVNSVPMDNMYRHHNFTLMIIPFVPLDFSAGASTYVPITVTVAPMCAEYNGLRLAGHQGLPTMNTPGSNQFLTSDDFQSPSAMPQFDVTPEMHIPGEVRNLMEIAEVDSVMPINNDSAAKVSSMEAYRVELSTNTNAGTQVFGFQLNPGAESVMNRTLMGEILNYYAHWSGSIKITFVFCGSAMTTGKFLLSYAPPGAGAPKTRKDAMLGTHVVWDVGLQSSCVLCIPWISQTHYRFVEKDPYTNAGFVTCWYQTSVVSPASNQPKCYMMCMVSACNDFSVRMLRDTKFIEQTSFYQGDVQNAVEGAMVRVADTVQTSATNSERVPNLTAVETGHTSQAVPGDTMQTRHVINNHVRSESTIENFLARSACVFYLEYKTGTKEDSNSFNNWVITTRRVAQLRRKLEMFTYLRFDMEITVVITSSQDQSTSQNQNAPVLTHQIMYVPPGGPIPVSVDDYSWQTSTNPSIFWTEGNAPARMSIPFISIGNAYSNFYDGWSHFSQAGVYGFTTLNNMGQLFFRHVNKPNPAAITSVARIYFKPKHVRAWVPRPPRLCPYINSTNVNFEPKPVTEVRTNIITTGAFGQQSGAVYVGNYRVVNRHLATHIDWQNCVWEDYNRDLLVSTTTAHGCDTIARCQCTTGVYFCLSRNKHYPVSFEGPGLVEVQESEYYPKRYQSHVLLAAGFSEPGDCGGILRCEHGVIGIVTMGGEGVVGFADVRDLLWLEDDAMEQGVKDYVEQLGNAFGSGFTNQICEQVNLLKESLVGQDSILEKSLKALVKIISALVIVVRNHDDLITVTATLALIGCTSSPWRWLKQKVSQYYGIPMAERQNNGWLKKFTEMTNACKGMEWIAIKIQKFIEWLKVKILPEVKEKHEFLNRLKQLPLLESQIATIEQSAPSQGDQEQLFSNVQYFAHYCRKYAPLYAAEAKRVFSLEKKMSNYIQFKSKCRIEPVCLLLHGSPGAGKSVATNLIGRSLAEKLNSSVYSLPPDPDHFDGYKQQAVVIMDDLCQNPDGKDVSLFCQMVSSVDFVPPMAALEEKGILFTSPFVLASTNAGSINAPTVSDSRALARRFHFDMNIEVISMYSQNGKINMPMSVKTCDEDCCPVNFKKCCPLVCGKAIQFIDRKTQVRYSLDMLVTEMFREYNHRHSVGATLEALFQGPPVYREIKISVAPETPPPPAIADLLKSVDSEAVREYCKEKGWLVPEISSTLQIEKHVSRAFICLQALTTFVSVAGIIYIIYKLFAGFQGAYTGMPNQKPKVPTLRQAKVQGPAFEFAVAMMKRNASTVKTEYGEFTMLGIYDRWAVLPRHAKPGPTILMNDQEVGVLDAKELVDKDGTNLELTLLKLNRNEKFRDIRGFLAREEAEVNEAVLAINTSKFPNMYIPVGQVTDYGFLNLGGTPTKRMLMYNFPTRAGQCGGVLMSTGKVLGIHVGGNGHQGFSAALLRHYFNEEQGEIEFIESSKDAGFPVINTPSKTKLEPSVFHQVFEGNKEPAVLRNGDPRLKVNFEEAIFSKYIGNVNTHVDEYMQEAVDHYAGQLATLDISTEPMKLEDAVYGTEGLEALDLTTSAGYPYVALGIKKRDILSKKTKDLTKLKECMDKYGLNLPMVTYVKDELRSAEKVAKGKSRLIEASSLNDSVAMRQTFGNLYKTFHLNPGIVTGSAVGCDPDVFWSKIPVMLDGHLIAFDYSGYDASLSPVWFACLKLLLEKLGYTNKETNYIDYLCNSHHLYRDKHYFVRGGMPSGCSGTSIFNSMINNIIIRTLMLKVYKGIDLDQFRMIAYGDDVIASYPWPIDASLLAEAGKDYGLIMTPADKGECFNEVTWTNVTFLKRYFRADEQYPFLVHPVMPMKDIHESIRWTKDPKNTQDHVRSLCLLAWHNGEHEYEEFIRKIRSVPVGRCLTLPAFSTLRRKWLDSF
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[Capsid protein VP1]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Capsid protein VP1 mainly forms the vertices of the capsid (By similarity). Capsid protein VP1 interacts with host ITGA2/ITGB1 to provide virion attachment to target host cells (By similarity). This attachment induces virion internalization predominantly through caveolin-mediated endocytosis. Tyrosine kinases are probably involved in the entry process (By similarity). After binding to its receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized (By similarity). Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm (By similarity). [Capsid protein VP2]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). [Capsid protein VP3]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). [Capsid protein VP4]: Lies on the inner surface of the capsid shell (By similarity). After binding to the host receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm (By similarity). [Capsid protein VP0]: Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity). Allows the capsid to remain inactive before the maturation step (By similarity). [Protease 2A]: Cysteine protease that cleaves viral polyprotein and specific host proteins (By similarity). It is responsible for the autocatalytic cleavage between the P1 and P2 regions, which is the first cleavage occurring in the polyprotein (By similarity). Cleaves also the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA translation (By similarity). Inhibits the host nucleus-cytoplasm protein and RNA trafficking by cleaving host members of the nuclear pores (By similarity). Counteracts stress granule formation probably by antagonizing its assembly or promoting its dissassembly (By similarity). [Protein 2B]: 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 Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication. [Protein 2C]: Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3. [Protein 3AB]: Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity. [Protein 3A]: Localizes the viral replication complex to the surface of membranous vesicles (By similarity). It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction (By similarity). This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface (By similarity). Plays an essential role in viral RNA replication by recruiting ACBD3 and PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (By similarity). [Viral protein genome-linked]: Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU (By similarity). The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome (By similarity). Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity). During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions (By similarity). [RNA-directed RNA polymerase]: Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated. [Protease 3C]: Major viral protease that mediates proteolytic processing of the polyprotein (By similarity). Cleaves host EIF5B, contributing to host translation shutoff (By similarity). Cleaves also host PABPC1, contributing to host translation shutoff (By similarity). Cleaves host NLRP1, triggers host N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment (By similarity).
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O91936
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POLG_HCVSA
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Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core protein (p21); Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); Viroporin p7; Protease NS2 (p23) (EC 3.4.22.-) (Non-structural protein 2) (NS2); Serine protease/helicase NS3 (EC 3.4.21.98) (EC 3.6.1.15) (EC 3.6.4.13) (Hepacivirin) (NS3 helicase) (NS3 protease) (NS3P) (Viroporin p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56/58); RNA-directed RNA polymerase (EC 2.7.7.48) (NS5B) (p68)]
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MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPTGRSWGQPGYPWPLYANEGLGWAGWLLSPRGSRPNWGPNDPRRKSRNLGKVIDTLTCGFADLMGYIPLVGGPVGGVARALAHGVRVLEDGVNYATGNLPGCSFSIFILALLSCLTVPTSAVPYRNASGVYHVTNDCPNSSIVYEAEDLILHAPGCVPCVRQGNVSRCWVQITPTLSAPSLGAVTAPLRRAVDYLAGGAALCSALYVGDACGAVFLVGQMFTYSPRRHNVVQDCNCSIYSGHITGHRMAWDMMMNWSPTTALVMAQLLRIPQVVIDIIAGAHWGVLFAAAYYASAANWAKVVLVLFLFAGVDANTRTVGGSAAQGARGLASLFTPGPQQNLQLINTNGSWHINRTALNCNDSLQTGFVAGLLYYHKFNSTGCPQRMASCRPLAAFDQGWGTISYAAVSGPSDDKPYCWHYPPRPCGIVPARGVCGPVYCFTPSPVVVGTTDRKGNPTYSWGENETDIFLLNNTRPPTGNWFGCTWMNSTGFVKTCGAPPCNLGPTGNNSLKCPTDCFRKHPDATYTKCGSGPWLTPRCLVHYPYRLWHYPCTLNYTIFKVRMYIGGLEHRLEVACNWTRGERCDLEDRDRAELSPLLHTTTQWAILPCSFTPTPALSTGLIHLHQNIVDTQYLYGLSSSIVSWAVKWEYIVLAFLLLADARICTCLWIMLLVCQAEAALENVIVLNAAAAAGTHGFFWGLLVICFAWHFKGRLVPGATYLCLGIWPLLLLLFLLPQRALALDSSDGGTVGCLVLTILTIFTLTPGYKKMVVLVIWWLQYFIARVEAFIHVWVPPLQVRGGRDAIIMLTCLFHPALGFEVTKILLGILGPLYLLQYSLIKLPYFIRARALLRACLLAKHLACGRYVQAALLHLGRLTGTYIYDHLAPMKDWAASGLRDLAVATEPIIFSPMETKVITWGADTAACGDILAGLPVSARRGHEIFLGPADDIREAGWRLLAPITAYAQQTRGVLGAIIVSLTGRDKNEAEGEVQVLSTATQTFLGTCINGVMWTVFHGAGAKTLAGPKGPVVQMYTNVDKDLVGWPTPPGTRSLTPCTCGSADLYLVTRHADVVPARRRGDTRASLLSPRPISYLKGSSGGPVMCPSGHVVGVFRAAVCTRGVAKALDFIPVENLETTMRSPVFTDNSTPPAVPHEFQVGHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSRAYGVDPNIRTGVRTVTTGAAITYSTYGKFLADGGCSGGAYDVIICDECHSQDATTILGIGTVLDQAETAGARLVVLATATPPGSVTTPHPNIEEVALPSEGEIPFYGRAIPLALIKGGRHLIFCHSKKKCDELAKQLTSQGVNAVAYYRGLDVAVIPATGDVVVCSTDALMTGFTGDFDSVIDCNTTVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRHGIYRYVSSGERPSGIFDSVVLCECYDAGCAWYDLTPAETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGLTNIDAHMLSQTKQGGENFPYLVAYQATVCVRAKAPPPSWDTMWKCMLRLKPTLTGPTPLLYRLGAVQNEITLTHPITKYIMACMSADLEVITSTWVLVGGVVAALAAYCLTVGSVAIVGRIILSGRPAIIPDREVLYQQFDEMEECSASLPYMDEARAIAEQFKEKVLGLIGTAGQKAETLKPAATSMWNRAEQFWAKHMWNFVSGIQYLAGLSTLPGNPAVATLMSFTAAVTSPLTTQQTLLFNILGGWVASQIAPPTAATAFVVSGMAGAAVGSIGLGRVLIDILAGYGAGVAGALVAFKIMCGEKPTAEDLVNLLPSILCPGALVVGVICAAVLRRHIGPGEGAVQWMNRLIAFASRGNHVSPTHYVPETDASAKVTQLLSSLTVTSLLKRLHTWIGEDYSTPCDGTWLRAIWDWVCTALTDFKAWLQAKLLPQLPGVPFLSCQRGYRGVWRGDGVNSTKCPCGATISGHVKNGTMRIVGPKLCSNTWHGTFPINATTTGPSVPAPAPNYKFALWRVGAADYAEVRRVGDYHYITGVTQDNLKCPCQVPSPEFFTELDGVRIHRYAPPCNPLLREEVCFSVGLHSFVVGSQLPCEPEPDVTVLTSMLSDPAHITAETAKRRLDRGSPPSLASSSASQLSAPSLKATCTTQGHHPDADLIEANLLWRQCMGGNITRVEAENKVVILDSFEPLKADDDDREISVSADCFRRGPAFPPALPIWARPGYDPPLLETWKQPDYDPPQVSGCPLPPAGLPPVPPPRRKRKPVVLSDSNVSQVLADLAHARFKADTQSIEGQDSAVGTSSQPDSGPEEKRDDDSDAASYSSMPPLEGEPGDPDLSSGSWSTVSDEDSVVCCSMSYSWTGALITPCSAEEEKLPINPLSNTLLRHHNLVYSTSSRSAGQRQKKVTFDRLQVLDDHYREVVDEMKRLASKVKARLLPLEEACGLTPPHSARSKYGYGAKEVRSLDKKALNHIKGVWQDLLDDSDTPLPTTIMAKNEVFAVEPSKGGKKPARLIVYPDLGVRVCEKRALYDIAQKLPTALMGPSYGFQYSPAQRVEFLLKTWRSKKTPMAFSYDTRCFDSTVTEHDIMTEESIYQSCDLQPEARAAIRSLTQRLYCGGPMYNSKGQQCGYRRCRASGVFTTSMGNTMTCYIKALASCRAAKLRDCTLLVCGDDLVAICESQGTHEDEASLRAFTEAMTRYSAPPGDPPVPAYDLELVTSCSSNVSVAHDASGNRVYYLTRDPQVPLARAAWETAKHSPVNSWLGNIIMYAPTLWARIVLMTHFFSVLQSQEQLEKALAFEMYGSVYSVTPLDLPAIIQRLHGLSAFTLHSYSPSEINRVSSCLRKLGVPPLRAWRHRARAVRAKLIAQGGKAAICGIYLFNWAVKTKRKLTPLADADRLDLSSWFTVGAGGGDIYHSMSRARPRCILLCLLLLTVGVGIFLLPAR
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[Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity).
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O91940
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L_BRSVA
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RNA-directed RNA polymerase L (Protein L) (Large structural protein) (Replicase) (Transcriptase) [Includes: RNA-directed RNA polymerase (EC 2.7.7.48); GTP phosphohydrolase (EC 3.6.1.-); GDP polyribonucleotidyltransferase (EC 2.7.7.88) (PRNTase); mRNA cap methyltransferase (EC 2.1.1.375) (mRNA (guanine-N(7)-)-methyltransferase) (G-N7-MTase) (mRNA (nucleoside-2'-O-)-methyltransferase) (N1-2'-O-MTase)]
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MDTLIHENSTNVYLTDSYLKGVISFSECNALGSYLLDGPYLKNDYTNIISRQKPLIEHINLKKLSIIQSFVTKYNKGELGLEEPTYFQSLLMTYKSLSTSELITTTTLFKKIIRRAIEISDVKVYAILNKLGLKEKGKVDRCDDTNTTLSNIVRDNILSVISDNTPSTKKPNNSSCKPDQPIKTTILCKLLSSMSHPPTWLIHWFNLYTKLNDILTQYRTNEARNHGYILIDTRTLGEFQFILNQYGCIVYHKKLKKITITTYNQFLTWKDISLSRLNVCMITWISNCLNTLNKSLGLRCEFNNVTLSQLFLHGDCILKLFHNEGYYIIKEVEGFIMSLILNLTEEDQFRKRFFNSMLNNITDAAARAQQDLLSRARHTILDKTISDNILNGKWLILLGKFLKLIKLAGANNLNNLSELYFLFRIFGHPMVDERQAMDAVRLNCNETKFYLLSSLSMLSGAFIYRIIKGFVNTYNRWPTLRNAIVLPLRWINYYKLNTYPSLLELTEADLIILSGLRFYREFHLPKKVDLEVIINDKAISPPKNLIWTSFPKNYMPSHIQIYIEHERLKFTESDRSRRVLEYYLRNNRFSESDLYNCIVNQEYLNNPNHVISLTGKERELSVGRMFAMQPGMFRQVQIMAEKLIAENILQFFPESLTRYGDLELQKILELKAGISNKANRCNDNYNNYISKCSIITDLSKFNQAFRYETSCICSDVLDELHGVQSLFSWLHLTIPFATVICTYRHAPPYIRNHITDLNKVDEQSGLYRYHMGGIEGWCQKLWTIEAITLLDLISIKGKFSITALINGDNQSIDISKPIKLNEGQTHAQADYLLALKSLKLLYKEYASIGHKLKGTETYISRDMQFMSKTIQHNGVYYPASIKKVLRVGPWINTILDDFKVSMESIGSLTQELEYRGESLLCSLIFRNVWLYNQIALQLKNHALCHNKLYLDILKVLAHLKMFFNLDNIDTALTLYMNLPMLFGGGDPNLLYRSFYRRTPDFLTEAIAHSVFVLSYYTGHDLQDKLQDLPDDKLNKFLTCIITFDKNPNAEFVTLMRDPQALGSERQAKVTSEINRLAVTEVLSNAPNKIFAKSAQHYTTTEVDLNDVMQKIEPTYPHGLRVVYESLPFYKAEKIVNLISGTKSITNILEKTSAIDYTDIERAIDMMRKNITLLIRILPLDYNKAKLGLLSLNNLSITDISKYVRERSWSLSNIVGITSPSILYTMDIKYTTSTITSGIIIEKYNSNFLTRGERGPTKPWVGSSTQEKKTMPVYNRQVLTKKQKDQIDLLAKLDWVYASIDNKDEFMEVLCLGTLGLSYEKAKKLFPQYLSVNYLHRLTVSSRPCEFPASIPAYRTTNYHFDTSPINRILTEKYGDEDIDIVFQNCISFGLSLMSVVEQFTNVCPNRIILIPKLNEIHLMKPPIFTGDVDICKLNQVIQKQHMFLPDKISLSQYVELFLSNKTLKNSPHISSNLVLVHKMSDYFLHKYVLSTNLAGHWIMIIQLMKDSKGIFEKDWGEGYITDHMFLDLNVFFDAYKTYLLCFHKGYGKAKLECDMNTSDLFCTLELIDISYWKSMSKVFLEQKVVKHIINQDSSLHRVRGCHSFKLWFLKRLNTSKFIVCPWVVNIDYHPTHMKAILTYMELTTMGLVHVDKLYTDQKHKLNDGFYTSNLFYINYNFSDNTHLLTKQIRVANSELIDNYNTLYHPSPESLESILKRSNQSNNVIELKDYPIDKFQSPKGRGVSDITCISSNQKIKQGYNNQDLYNLFPAVIIDKIVDHSGNIANINQMYTITPNQLTLISNGTSLYCMLPWHHINRFNFVFSSTGCKISTKLILKDLKIKDPHCIAFIGEGAGNLLLRTVVELHPDIKYIYRSLKDCNDHSLPIEFLRLYNGHISIDYGENLTIPATDATNAIHWSYLHIRYAEPINLFVCDAELPDLTNWSRIVSEWYKHVRCCKYCSTIDRSKLIVKYHAQDITDFKLNNISIVKTYVCLGSKLKGSEVYLVLTVGPSNIFPSFNVVQNAKLILSRTQNFPMPKKIDKDSVDANIKSLIPFLCYPITKKGIKAALSKLKDVVDGNILSYSIAGRNEVYSNKLINYKLLNILKWLDHILNFRSLEFSYNHLYMIESTYPFLSELLNSLTTNELKKLIKVTGSVLYSLQHEL
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Responsible for RNA synthesis (replicase and transcriptase), cap addition, and cap methylation. Performs also the polyadenylation of subgenomic mRNAs by a stuttering mechanism at a slipery stop site present at the end of viral genes. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at two different sites in the 3' leader promoter thereby initiating either genome replication or mRNA transcription. In the transcription mode, the polymerase performs the sequential transcription of all mRNAs using a termination-reinitiation mechanism responding to gene start and gene end signals. Some polymerase disengage from the template at each gene junction, resulting in a decreasing abundance of transcripts from the 3' to the 5' end of the genome. The first gene is the most transcribed, and the last the least transcribed. Needs as cofactors the phosphoprotein for processivity and the M2-1 anti-termination protein. Polyribonucleotidyl transferase (PRNTase) adds the cap structure when the nascent RNA chain length has reached few nucleotides (By similarity). Ribose 2'-O methylation of viral mRNA cap precedes and facilitates subsequent guanine-N-7 methylation (By similarity). In the replication mode, the polymerase replicates the whole viral genome without recognizing the gene end transcriptional signals. The ability of the polymerase to override the gene end signals as it is producing the antigenome is probably due to replicative RNA becoming encapsidated with nucleoprotein as it is synthesized (By similarity).
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O92446
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VP91_NPVBM
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Capsid-associated protein Vp91
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MMSGVMLLVFAIFLIIAFTLIYLAIYFKFDETTYTKRLQVMIEYIKRTNADEPTPNVIGYVSDITQNTYTVTWFNTVDLSTYQESVHDDRNEIFDFLNQKLQPVDRIVHDRVRANDENPNEFILSGDKDDVTMKCPAYFNFDYAQLKCVPVPPCDNKPAGRYPMDERLLDTLVLNQHLDKDYSSNEHLYHPTFYLRCFANGAHAVEECPDNYTFDAKTRQCKVNELCENRPDGYILSYFPSNLLVNQFMQCVSGRHVVRECPANKIFDRNLMSCVEAHPCTFNGAGHTYITADISDAQYFKCLNNNESQLMTCINRIRNSDNQYECSGDSRCIDLPNGTGQQVFKHADDDISYNSGQLVCDNFEIISNIECDQSNVFENKLFMDKFRLNMQFPTEVFDGTACVPATADNVNFLRSTFAIENIPNHYDIDMQTSMLGKIEMIKQLVSKDLSLNNDAIFAQWLLYARDKNAIGLNPLTGEPIDCFGNNLYDVFDARRANVCKDLGKSVLKTLNFGDGEFLNVLSDTLTGKDEDYRQFCAISYENGQKIVENEHFQRRILTNILQSDVCANIYTTLYQKYTTLNPKYTTTPLQYNRILVKRPKNIEIYGANTRLKNATIPKNATTISPVFNPFENQPNNRQNDSISPLFNPFQTTDAVWYSEPDGDEAVAPPPTAPPPPSEPEPEPEPELPSPLILDNKDLFYSCHYSVPFFKLTSCHAENDVIINALNELRNNVKVDADCESAKDLSHVLNAYAYVGNGIGCRSAYDGDAIVVKKEAVPSHVYANLNTQSNDGVKYNRWLHVKNDQYMACPEELYDNDEFKCNVESDKLYYLDNLQEDSIV
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Probable capsid-associated protein.
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O92529
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POLG_HCVT5
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Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core protein (p21); Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); Viroporin p7; Protease NS2 (p23) (EC 3.4.22.-) (Non-structural protein 2) (NS2); Serine protease/helicase NS3 (EC 3.4.21.98) (EC 3.6.1.15) (EC 3.6.4.13) (Hepacivirin) (NS3 helicase) (NS3 protease) (NS3P) (Viroporin p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56/58); RNA-directed RNA polymerase (EC 2.7.7.48) (NS5B) (p68)]
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MSTLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARPSQGRTWGQPGYPWPLYGNEGCGWAGWLMSPRGSRPSWGPNDPRRRSRNLGKVIDTLTCGLADLMGYIPVVGGPLGGVAAALAHGVRAIEDGINYATGNLPGCSFSIFILALLSCLTTPASALTYGNSSGLYHLTNDCPRSSIVLEAEAMILHLAGCVPCVRAGNISRCWHPVSPTLAVPNASVPASGFRKHVDLLAGAAVVCSSMYIGDLCGAVFLAGQLATFSPRIHDITQDCNCSVYTGHVTGHRMAWDMMMNWSPTTTLVLSSILRVPEIVLEVFAGGHWGVLIAIAYFGMSGNWLKVIAVLFLFAGVEATTTVGRAAGRSAYLFTSIFSSGPNQKIQLINTNGSWHINRTALNCIDSLQTGFLSALFYRSNFNSTGCSERLGACKPLEHFQQGWGPITHKSNITGPSEDRPYCWHYAPRECSVVPASSVCGPVYCFTPSPVVVGTTDRLGNPTYNWGENETDVFMLESLRPPQGGWFGCTWMNSTGFTKTCGAPPCQLIPGDYNSSSNQLLCPTDCFRKHPEATYQKCGSGPWLTPRCLVDYPYRLWHYPCTVNYTIHKVRMFIGGVEHRFDAACNWTRGDRCDLYDRDRIEMSPLLFSTTQLAILPCSFTTMPALSTGLIHLHQNIVDVQYLYGVSSSIVSWAVKWEYVVLMFLVLADARICTCLWLMLLVGKVEAALERLVVLNAASAAGTAGWCWTLIFLCCVWHVKGRLVPACTYTALGMWPILLVILALPQRAYAWDNSQAASLGVVALLVLTIFTLSPMYKQLLTHAIWWNQYMLARAEAMIHDWVPDLRVRGGRDAIILLTCLLHPHLGFEVTKILLAILAPLYILQHSLLKVPYFVRAHILLRACMFFRKVAAGKYVQACLLRLGAWTGTYIYDHLAPLSEWASDGLRDLAVAVEPVIFSPMEKKIITWGADTAACGDILRGLPVSARLGDLVLLGPADDMRHGGWKLLAPITAYAQQTRGLVGTIVTSLTGRDKNEAEGEVQVVSTATQSFLATTINGVLWTVYHGAGSKNLAGPKGPVCQMYTNVDQDLVGWPAPLGARSLAPCTCGSSDLYLVTRGADVIPARRRGDTRAALLSPRPISTLKGSSGGPLMCPSGHVVGLFRAAVCTRGVAKALDFIPVENMDTTMRSPVFTDNSSPPAVPQTYQVGYLHAPTGSGKSTRVPAAYATQGYKVLVLNPSVAATLSFGAYMSKAHGIDPNIRTGVRTITTGGPVTYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGVRLTVLATATPPGSVTVPHPNITETALPTTGEIPFYGKCIPLEFIKGGRHLIFCHSKKKCDELSKQLTSLGLNAVAFYRGVDVAVIPTSGDVVVCATDALMTGYTGDFDSVIDCNVAVTQVVDFSLDPTFSIETTTVPQDAVSRSQRRGRTGRGKPGVYRFVSQGERPSGMFDSVVLCEAYDTGCAWYELTPAETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQGGENFAYLVAYQATVCARAKAPPPSWDVMWKCLTRLKPTLTGPTPLLYRLGAVQNEIVTTHPITKYIMTCMSADLEVITSTWVIVGGVLAALAAYCLTVGCVVICGRIVTSGKPAVVPDREVLYQQFDEMEECSKHIPYLVEGQQIAEQFKQKVLGLLQAGTKHAEELKPAIHSTWPRVEEFWRKHMWNFVSGIQYLAGLSTLPGSPAVASLMSFTASLTSPLRTSQTLLLNILGGWIASQVAPPSASTAFVVSGLAGATVASIGLGRVIVDILAGYGAGVAGALVAFKIMSGECPSTEDMVNLLPALLSPGALVVGVVCAAILRRHVGPSEGANQWMNRLIAFASRGNHVSPTHYVPETDASNKVTQILSSLTITSLLRRLHQWIHEDTSTPCASSWLRDVWDWVCTVLSDFKTWLKAKITPRIPGIPFISCQAGYRGVWAGDGVCHTTCSCGAQIAGHVKNGSMKITGPRMCSNTWHGTFPINATTTSPSVPVPAPNYKRALWRVSAEEYVEVERHGDRHYVVGVTADGLKCPCQVPGPEFFTEVDGVRIHRYAPPCKPLLRDEVSFSVGLLEFVVGSQLPCEPEPDVTVVTSMLTDPSHITAETASRRLKRGSPPSLASSSASQLSAPSLKATCTANGDHPDAELIEANLLWRQEMGSNITRVESETKVVILDSFDPLVAEYDDREISVSAECHRPPRPKFPPALPIWARPDYNPPLLQKWQMPGYEPPVVSGCALPPAKPTPIPPPRRKRLIQLDESAVSQALQQLADKVFVEDTSTSEPSSGLGGSIAGPSSPDPTTADDTCSDAGSFSSMPPLEGEPGDPDLSTGSWSTVSEEDDVVCCSMSYTWTGALITPCAAEEEKLPINPLSNSLIRHHNMVYSTTSRSAGLRQKKVTFDRLQVVDQHYQDVLKEIKLRASTVHARLLSTEEACSLTPPHSARSRYGYGARDVRSHTSKAVKHIDSVWEDLLEDNATPIPTTIMAKNEVFCVDPSKGGRKPARLIVYPDLSVRVCEKMALYDVTQKLPKTVMGSAYGFQYSPSQRVEYLLKMWRSKKTPMGFSYDTRCFDSTVTERDIRTEEDIYQSCQLDPTARKAISSLTERLYCGGPMFNSKGESCGYRRCRASGVLTTSLGNTLTCYLKAQAACRAANIKNFDMLVCGDDLVVICESAGVQEDVVALRAFTDAMIRYSAPPGDAPQPTYDLELITSCSSNVSVAHDGTGQRYYYLTRDCTTPLARAAWETARHTPVNSWLGNIIMYAPTIWVRMVLMTHFFSILQCQEQLEAALNFDMYGVTYSVTPLDLPAIIQRLHGMAAFSLHGYSPTELNRVGASLRKLGAPPLRAWRHRARAVRAKLIAQGGKAAICGKYLFNWAVKTKLKLTPLAAASQLDLSGWFVAGYDGGDIYHSVSRARPRLLLLGLLLLTVGVGIFLLPAR
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[Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity).
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O92530
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POLG_HCVVN
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Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core protein (p21); Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); Viroporin p7; Protease NS2 (p23) (EC 3.4.22.-) (Non-structural protein 2) (NS2); Serine protease/helicase NS3 (EC 3.4.21.98) (EC 3.6.1.15) (EC 3.6.4.13) (Hepacivirin) (NS3 helicase) (NS3 protease) (NS3P) (Viroporin p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56/58); RNA-directed RNA polymerase (EC 2.7.7.48) (NS5B) (p68)]
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MSTLPKPQKRNQRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRQTGRTWAQPGYPWPLYGNEGCGWMGWLLSPRGSRPHWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPVVGAPLGGVAAALAHGVRAVEDGINYATGNLPGCSFSIFLLALLSCLTTPASAVHYANKSGIYHLTNDCPNSSIVYEAEDFIMHLPGCVPCIKSGNGSSCWLPATLTIAVPNASIPVRGFRRHVDLMVGAAAFCSAMYVGDLCGGIFLVGQLFSFNPRRHWVVQDCNCSIYVGHITGHRMAWDMMMNWSPTATLVLSYVMRIPQVIMDIFTGGHWGILAGILYYSMVANWAKVLCILFLFAGVDATTRTTGAQAARATLGFTGLFQTGAKQNIHLINTNGSWHINRTALNCNDSLNTGFMAALFYLHKFNSTGCPERLSACKSITQFAQGWGPVTYANVSGSSEDRPYCWHYAPRPCGVVSARSVCGPVYCFTPSPVVVGTTDRRGVPTYTWGENESDVFLLESLRPPAGAWYGCTWMNSTGYTKTCGAPPCHIGPPDQFCPTDCFRKHPEATYRKCGSGPWLTPRCLVDYPYRLWHYPCTVNYTIHKVRLFINGLEHRFDAACNWTRGERCELEDRDRIEMSPLLFSTTELAILPCSFTTMPALSTGLVHLHQNIVDIQYLYGLAPALVSWAVRWEYVVLAFLLLADARICACLWMVLLISQVEAALENLIVLNAASAASSQGWIYCLVFICCAWYIKGRVVPGATYAILHLWPLLLLVLALPQRAYAQDREQGASIGVVVIAAITIFTLTPAYKTMLVHFLWWNQYFIARSEALIQQWVPSLRVRGGRDAVILLTCLLHPSLGFDITKMLLALLGPLYLLQVSLLRVPYYVRAHALLRVCILVRRVAGGKYIQAALLKLGAWTGTYIYDHLAPLSTWASDGLRDLAVAVEPVTFSPMEKKIITWGADTAACGDILAGLPVSARLGHLLFLGPADDMKSMGWRLLAPITAYCQQTRGLLGTIVTSLTGRDRNVVEGEIQVLSTATQSFLGTAINGVMWTVYHGAGSKTLAGPKGPVCQMYTNVDQDMVGWPAPPGTRSLTPCTCGASDLYLVTRNADVIPARRRGDTRAGLLSPRPLSTLKGSSGGPLMCPSDHVVGLFRAAVCTRGVAKALDFVPVENMETTMRSPVFTDNSTPPAVPQTYQVGYLHAPTGSGKSTKVPAAYASQGYKVLVLNPSVAATLGFGSYMSTAHGIDPNIRTGVRTITTGGPITYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGVRLTVLATATPPGSVTVPHPNITETALPSTGEVPFYGKAIPLECIKGGRHLIFCHSKKKCDELAKQLRTLGLNAVAFYRGVDVSVIPTAGDVVVCATDALMTGYTGDFDSVIDCNVAVTQIVDFSLDPTFSIETTTVPQDAVARSQRRGRTGRGKPGVYRYVSQGERPSGMFDTVVLCEAYDVGCAWYELTPSETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGMTHIDAHFLSQTKQGGENFAYLVAYQATVCARAKAPPPSWDTMWKCLIRLKPMLTGPTPLLYRLGAVQNEIITTHPITKYIMTCMAADLEVITSTWVLAGGIVAALAAYCLTVGSVVICGRIVTSGKPVPLPDREVLYRQFDEMEECSRHIPYLAEGQQIAEQFKQKILGLLQNTAKQAEDLKPAVQSAWPKLEQFWQKHLWNFVSGVQYLAGLSTLPGNPAVASLMSFSAALTSPLSTSTTLLLNILGGWVASQLAPPTASTAFVVSGLAGAAVGSIGLGKVIIDILAGYGAGVSGALVAFKIMSGEAPAVEDMVNLLPALLSPGALVVGVVCAAVLRRHVGPSEGATQWMNRLIAFASRGNHVSPTHYVPETDASRAVTTILSSLTITSLLRRLHEWISGDWSAPCSCSWLKDVWDWVCTVLSDFKTWLRAKLVPTLPGIPFISCQRGFRGVWRGDGVNYTTCSCGANITGHVKNGSMKIVGPKMCSNVWNNRFPINAITTGPSVPVPEPNYHKALWRVSAEDYVEVVRVNDHHYIVGATADNLKCPCQVPAPEFFTEVDGVRLHRFAPPCRPLMRDDITFSVGLSTYVVGSQLPCEPEPDVVILTSMLTDPDHITAETAARRLARGSPPSLASSSASQLSAPSLKATCTTAGKHPDAELIEANLLWRQEVGGNITRVESENKIIVLDSFDPLIAETDDREISVGAECFNPPRPKFPPALPVWARPDYNPPLLQPWKAPDYEPPLVHGCALPPKGLPPVPPPRKKRVVQLDEGSAKRALAELAQTSFPPSTATLSEDSGRETSTLSSDMTPPREEADRASDDGSYSSMPPLEGEPGDPDLSSGSWSTVSEDHDSVVCCSMSYSWTGALITPCAAEEEKLPISPLSNALIRHHNLVYSTTSRSASLRQKKVTFDRVQVVDQHYYDVLKEIKTKASGVSAKLLSVEEACALTPPHSARSKFGYGAKEVRGLASKAVNHINSVWEDLLEDNSTPIPTTIMAKNEVFCVDAQKGGRKPARLIVYPDLGVRVCEKRALYDVTQKLPIAVMGAAYGFQYSPKQRVDYLLKMWRSKKTPMGFSYDTRCFDSTVTERDIRTEEDIYQCCQLDPVAKKAITSLTERLYCGGPMYNSRGQSCGYRRCRASGVLTTSLGNTLTCYLKAQAACRAAKLKDFDMLVCGDDLVVISESMGVAEDASALRAFTEAMTRYSAPPGDDPQPEYDLELITSCSSNVSVAHDGAGQRYYYLTRDPLTPLSRAAWETARHTPVNSWLGNIIMYAPTIWVRMVLMTHFFAILQSQEILHKALDFDMYGVTYSVTPLDLPYIIQRLHGMAAFSLHGYSPGELNRVASCLRKLGAPPLRAWRHRARAVRAKLIAQGGKHAICGKYLFNWAVRTKLKLTPLRGAANLDLSGWFVSGGSGGDIFHSVSRARPRNLLLCLLLLTVGVGIFLLPAR
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[Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity).
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O92531
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POLG_HCVVO
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Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core protein (p21); Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); Viroporin p7; Protease NS2 (p23) (EC 3.4.22.-) (Non-structural protein 2) (NS2); Serine protease/helicase NS3 (EC 3.4.21.98) (EC 3.6.1.15) (EC 3.6.4.13) (Hepacivirin) (NS3 helicase) (NS3 protease) (NS3P) (Viroporin p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56/58); RNA-directed RNA polymerase (EC 2.7.7.48) (NS5B) (p68)]
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MSTLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQSQGRHWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPNWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPVVGAPLGGVAAALAHGVRAIEDGINYATGNLPGCSFSIFLLALLSCLTTPASAVHYRNISGIYHLTNDCPNSSIIYEADNIIMHTPGCVPCVKTGNKSQCWVPVAPTLAVANASVPIRGFRSHVDLLVGSAAACSALYIGDLCGGVFLVGQLFTFRPRQHTTVQECNCSIYTGHITGHRMAWDMMMNWSPTVTFITSSLLRVPQLLLEIALEGHWGVIGALLYYSMVANWAKVFAVLLLFAGVDATTHIGSSASATTNRLTSFFSPGSKQNVQLIKTNGSWHINRTALNCNDSLHTGFIAGLLYAHRFNSSGCPERLSSCRPLHAFEQGWGPLTYANISGPSNDKPYCWHYPPRPCDIVPARSVCGPVYCFTPSPVVVGTTDRKGLPTYTWGANESDVFLLRSTRPPRGSWFGCTWMNSTGFVKTCGAPPCNTRPVGSGNDTLVCPTDCFRKHPEATYARCGSGPWLTPRCLVNYPYRLWHYPCTVNYTIHKVRMFVGGIEHRFEAACNWTRGERCELDDRDRVEMSPLLFSTTQLSILPCSFTTMPALSTGLIHLHQNIVDVQYLYGVSSAVVSWAVKWEYIVLAFLVLAVARVCACLWLMFLVGQAEAALENLIVLNATSAAGSQGWVWGVVFICAAWYIRGRAAPITTYAILQLWPLLLLVLALPRRAYAYNGEEAASLGMLAIVIITIFTLTPAYKTLLISTLWWIQYYIARAEAMLYVWVPSLQVRGGRDAVILLTCLLHPQLGFEVTKAILALLGPLYILQYSLLKTPYFVRAHILLRVCMFLRGVAGGKYVQAALLRLGAWTGTYIYDHLTPLSDWACDGLRDLAVAVEPVVFSPMEKKVITWGADTVACGDIISGLPVSARRGNLIFLGPADDIRDGGWRLLAPITAYAQQTRGLVGTIVTSLTGRDKNEVEGEIQVVSTATQSFLATTVNGVLWTVYHGAGSKTLAGPKGPICQMYTNVDQDLVGWPAPPGARSLTPCTCGSSDLYLVTRNADVIPARRRGDTRAALLSPRPISTLKGSSGGPMLCPSGHVAGIFRAAVCTRGVAKSLDFVPVENMQSTARSPSFSDNTTPPAVPQTYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGSYMSTAHGIDPNIRTGVRTITTGGAITYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGVRLTVLATATPPGSVTVPHPNITEVALSSTGEVPFYGKAIPLEYIKGGRHLIFCHSKKKCDELAKQLTSLGLNAVAFYRGVDVSVIPTSGDVVVCATDALMTGYTGDFDSVIDCNVSVTQVVDFSLDPTFTIETTTMPQDAVSRSQRRGRTGRGKHGVYRYVSQGERPSGIFDTVVLCEAYDTGCAWYELTPSETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGLTHIDAHLLSQTKQGGENFAYLVAYQATVCARAKAPPPSWDTMWKCLIRLKPMLTGPTPLLYRLGAVQNEITTTHPITKYIMTCMSADLEVITSTWVLVGGVLAALAAYCLSVGCVVVCGRISTTGKPVLIPDREVLYQQFDEMEECSRHIPYLVEGQHLAEQFKQKVLGLIQTTTRQAEEIEPVVHSAWPKLEQFWQKHLWNFVSGIQYLAGLSTLPGNPAVASLMSFSASLTSPLSTSTTLLLNILGGWVASQLANPTASTAFVVSGLAGATVGSIGLGRVLVDIIAGYGAGVSGALVAFKIMSGETPSAEDMVNLLPALLSPGALVVGVVCAAILRRHAGPAEGATQWMNRLIAFASRGNHVSPTHYVPETDTSRQVMAILSSLTVTSLLRKLHEWINSDWSTPCSGSWLRDIWDWVCTVLSDFKVWLKSKLVPALPGVPFLSCQRGFRGVWRGDGICRTTCPCGADIVGHVKNGSMRISGSRWCSNIWHGTFPINATTTGPSVPIPEPNYKRALWRVSAEEYVEVARVGDSHFVVGATNQDLKCPCQVPAPEFFTEVDGVRLHRFAPACKPLLRDEISFLVGLNSYAIGSQLPCEPEPDVTVVTSMLVDPSHLTAEAAARRLARGSPPSCASSLASQLSAPSLKATCTTHCAHPDADLIEANLLWRQEVGGNITRVESENKVIVLDSFDPLVPEYDDREPSVPAECHRPNRPKFPPALPIWARPDYNPPLLETWKKPDYAPPLVHGCALPSPVQPPVPPPRRKSVVHLDDSTVATALAELAEKSFPTQPASTPDSDSGHPTTSKSSDQADEGEDTPSEAGSYSSMPPLEGEPGDPDLSSGSWSTVSEEGDSVVCCSMSYSWTGALVTPCAAEEEKLPINPLSNSLIRHHNLVYSTTTRSAAMRQKKVTFDRLQILDQHYNNVVKEVKLRASGVTAKLLSVEEACSLTPPHSARSKFGYGAKDVRSHTSKAINHINSVWEDLLEDNQTPIPTTIMAKNEVFCADVSKGGRKPARLIVYPDLGVRVCEKRALYDVTRKLPTAIMGDAYGFQYSPKQRVDQLLKMWRSKKTPMGFSYDTRCFDSTVTEHDIKTERDVYLSCKLDPVARKAIESLTERLYIGGPMYNSRGQLCGTRRCRASGVLTTSLGNTMTCFIKAEAACRAAGLTNYDMLVCGDDLVVIAESAGVQEDASNLRAFTEAMTRYSAPPGDEPHPAYDLELITSCSSNVSVAHDHTGQRYYYLTRDPTTPLSRAAWETARHTPVNSWLGNIIMYAPAIWVRMVLMTHFFQILQAQEQLDKVLDFDMYGVTYSVSPLQLPAIIQRLHGMAAFSLHGYSPTELNRVGACLRKLGAPPLRAWRHRARAVRAKLIAQGGGAAICGKYLFNWAVKTKLKLTPIPDAARLDLSGWFISGFSGGDIYHSVSRARPRIFLLCLLLLSVGVGIFLLPAR
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[Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity).
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O92532
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POLG_HCVVP
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Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core protein (p21); Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); Viroporin p7; Protease NS2 (p23) (EC 3.4.22.-) (Non-structural protein 2) (NS2); Serine protease/helicase NS3 (EC 3.4.21.98) (EC 3.6.1.15) (EC 3.6.4.13) (Hepacivirin) (NS3 helicase) (NS3 protease) (NS3P) (Viroporin p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56/58); RNA-directed RNA polymerase (EC 2.7.7.48) (NS5B) (p68)]
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MSTLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPIGRSWGQPGYPWPLYGNEGCGWAGWLLSPRGSRPNWGPNDPRRRSRNLGKVIDTLTCGLADLMGYIPVLGGPLGGVAAALAHGVRAIEDGVNYATGNLPGCSFSIFLLALLSCLTTPASAIQVRNASGIYHLTNDCSNNSIVFEAETIILHLPGCVPCIKVGNGSRCWLSVSPTLAVPNSSVPIHGFRRHVDLLVGAAAFCSAMYIGDLCGSVFLVGQLFTFRPKHHQVTQDCNCSIYAGHITGHRMAWDMMLNWSPTVSYVVSSALRVPQLLLEVITGAHWGVLGALLYFSMVANWAKVIAVLFLFAGADATTYTGSAVSSTTGAFVSLFSPGPTQNLQLVNSNGSWHINRTALNCNDSLQTGFIAGLFARYKFNSTGCPERMSKCRPLHSFEQGWGPISYVNISGSSEDKPYCWHYAPRPCGIVPARNVCGPVYCFTPSPVVVGTTDQRGIPTYTWGENVSDVFLLHSARPPLGAWFGCTWMNSSGFVKTCGAPPCRIKPTINETDLVCPTDCFRKHPDASFVKCGSGPWLTPRCMVDYPYRLWHYPCTVNFTIHKVRVFVGGVEHRFNAACNWTRGDRCELDDRDRFEMSPLLFSTTQLAILPCSFTTMPALSTGLIHLHQNIVDIQYLYGVSTAVVSWAMKWEYVVLAFLVLADARVCACLWLMFLVGQAEAALENVIVLNAASAASCQGLLWGLIFICCAWHVRGRAVPVTTYALLQLWPLLLLILALPRRAYAFDSEQAASAGLLVLGLITIFTLTPAYKQLLISMLWWIQYFIALTEAQLHQWVPSLLVRGGRDAVILLACLFHPQLGFEVTKILLALLGPLYLLQYSLLKTPYFVRAHILLRACMFFRGMARGRYAQAILLRIGAWTGTYIYDHLAPLSDWACDGLRDLAVAVEPVVFSPMEKKVITWGADTAACGDIIAGLPVAARRGNLLFLGPADDVKGKGWRLLAPITAYAQQTRGIVGTIVTSLTGRDKNEVEGEIQVVSTATQSFLATAVNGVLWTVYYGAGSKTLAGPKGPVCQMYTNVDQDLVGWPAPAGARSLTPCSCGSSDLYLVTRNADVIPARRRGDNRAALLSPRPISTLKGSSGGPMLCPSGHVAGIFRAAVCTRGVAKSLDFAPVESMQSSQRSPSFSDNTSPPAVPQTYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGSYMSTSHGIDPNIRTGVRTITTGGAITYSTYGKFLADGGCSGGAYDVIICDECHSTDPTTVSGIGTVLDQAETSGVRLTVLATATPPGSVTVPHPNITESALPTTGEIPFYGKAVPLEYIKGGRHLIFCHPKKKCDELAKQLVSLGLNAVAFYRGVDVSVIPTSGDVVVCATDALMTGYTGDFDSVIDCNVTVTQVVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGKHGVYRYVSQGERPSGMFDSVILCEAYDTGCAWYELTPAETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQAEENFAYLVAYQATVCARAKAPPPSWDTMWKCLIRLKPMLTGPTPLLYRLGPVQNEVVTTHPITKYIMTCMSADLEVITSTWVLVGGVVAALAAYCLSVGCVVICGRISTSGKPVLIPDREVLYQQFDEMEECSRHIPYLAEGHLIAEQFKQKVLGLIQSTSKQAEELKPAVHAAWPKLEQFWQKQLWNFVSGIQYLAGLSTLPGNPAIASLMSFSASLTSPLSTHQTLLLNILGGWVASQLANPTASTAFVVSGLAGAAVGSIGLGRVIVDVLAGYGAGVSGALVAFKIMCGETPSAEDMVNLLPALLSPGALVVGVVCAAILRRHAGPSEGATQWMNRLIAFASRGNHVSPTHYVPETDTSRQIMTILSSLTVTSLLRKLHEWINTDWSTPCSSSWLRDIWDWVCEVLSDFKTWLKAKLVPALPGVPFLSCQRGFRGTWRGDGICHTTCPCGSEITGHVKNGTMKISGPRWCSNVSHRTFPINATTTGPSVPIPEPNYTRALWRVSAEEYVEVKRVGDSHFVVGATTDNLKCPCQVPAPEFFTEVDGVRLHRYAPRCKPLLRDEVSFSVGLSSYAVGSQLPCEPEPDVTVVTSMLIDPSHVTAEAAARRLARGSPPSLASSSASQLSAPSLKATCTMHGAHPDAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVPEFEEREMSVPAECHRPRRPKFPPALPIWATPGYNPPVLETWKSPTYEPPVVHGCALPPSGPPPIPPPRRKKVVQLDSSNVSAALAQLAAKTFETPSSPTTGYGSDQPDHSTESSEHDRDDGVASEAESYSSMPPLEGEPGDPDLSSGSWSTVSEEGDSVVCCSYSYSWTGALVTPCAAEEEKLPINPLSNSLIRHHNLVYSTSSRSAATRQKKVTFDRVQLLDQHYYDTVKEIKLRASHVKAQLLSTEEACDLTPPHSARSKFGYGAKDVRSHASKAINHINSVWADLLEDTQTPIPTTIMAKNEVFCVDASKGGRKSARLIVYPDLGVRVCEKRALFDVTRKLPTAIMGDAYGFQYSPQQRVDRLLKMWRSKKTPMGFSYDTRCFDSTVTERDIRTEQDIYLSCQLDPEARKVIESLTERLYVGGPMYNSKGQLCGQRRCRASGVLPTSMGNTVTCFLKATAACRAAGFTDYDMLVCGDDLVVVTESAGVNEDIANLRAFTEAMTRYSATPGDEPSPTYDLELITSCSSNVSVAHDGDGRRYYYLTRDPVTPLARAAWETARHTPVNSWLGNIIMYAPTIWVRMVLMTHFFQILQAQETLDRALDFDIYGVTYSITPLDLPVIIQRLHGMAAFSLHGYSPDELNRVASCLRKLGAPPLRAWRHRARAVRAKLIAQGGKAAVCGKYLFNWAIKTKLRLTPLRGASALDLSGWFTSGYGGGDVYHSASRARPRFLLLCLLLLSVGVGIFLLPAR
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[Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity).
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O92815
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POL_WDSV
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Gag-Pol polyprotein [Cleaved into: Matrix protein p10 (MA); p20; Capsid protein p25 (CA); Nucleocapsid protein p14 (NC-pol); Protease p15 (PR) (EC 3.4.23.-); Reverse transcriptase/ribonuclease H p90 (RT) (EC 2.7.7.49) (EC 2.7.7.7) (EC 3.1.26.4); Integrase p46 (IN) (EC 2.7.7.-) (EC 3.1.-.-)]
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MGNSSSTPPPSALKNSDLFKTMLRTQYSGSVKTRRINQDIKKQYPLWPDQGTCATKHWEQAVLIPLDSVSEETAKVLNFLRVKIQARKGETARQMTAHTIKKLIVGTIDKNKQQTEILQKTDESDEEMDTTNTMLFIARNKRERIAQQQQADLAAQQQVLLLQREQQREQREKDIKKRDEKKKKLLPDTTQKVEQTDIGEASSSDASAQKPISTDNNPDLKVDGVLTRSQHTTVPSNITIKKDGTSVQYQHPIRNYPTGEGNLTAQVRNPFRPLELQQLRKDCPALPEGIPQLAEWLTQTMAIYNCDEADVEQLARVIFPTPVRQIAGVINGHAAANTAAKIQNYVTACRQHYPAVCDWGTIQAFTYKPPQTAHEYVKHAEIIFKNNSGLEWQHATVPFINMVVQGLPPKVTRSLMSGNPDWSTKTIPQIIPLMQHYLNLQSRQDAKIKQTPLVLQLAMPAQTMNGNKGYVGSYPTNEPYYSFQQQQRPAPRAPPGNVPSNTCFFCKQPGHWKADCPNKTRNLRNMGNMGRGGRMGGPPYRSQPYPAFIQPPQNHQNQYNGRMDRSQLQASAQEWLPGTYPAXDPIDCPYEKSGTKTTQDVITTKNAEIMVTVNHTKIPMLVDTGACLTAIGGAATVVPDLKLTNTEIIAVGISAEPVPHVLAKPTKIQIENTNIDISPWYNPDQTFHILGRDTLSKMRAIVSFEKNGEMTVLLPPTYHKQLSCQTKNTLNIDEYLLQFPDQLWASLPTDIGRMLVPPITIKIKDNASLPSIRQYPLPKDKTEGLRPLISSLENQGILIKCHSPCNTPIFPIKKAGRDEYRMIHDLRAINNIVAPLTAVVASPTTVLSNLAPSLHWFTVIDLSNAFFSVPIHKDSQYLFAFTFEGHQYTWTVLPQGFIHSPTLFSQALYQSLHKIKFKISSEICIYMDDVLIASKDRDTNLKDTAVMLQHLASEGHKVSKKKLQLCQQEVVYLGQLLTPEGRKILPDRKVTVSQFQQPTTIRQIRAFLGLVGYCRHWIPEFSIHSKFLEKQLKKDTAEPFQLDDQQVEAFNKLKHAITTAPVLVVPDPAKPFQLYTSHSEHASIAVLTQKHAGRTRPIAFLSSKFDAIESGLPPCLKACASIHRSLTQADSFILGAPLIIYTTHAICTLLQRDRSQLVTASRFSKWEADLLRPELTFVACSAVSPAHLYMQSCENNIPPHDCVLLTHTISRPRPDLSDLPIPDPDMTLFSDGSYTTGRGGAAVVMHRPVTDDFIIIHQQPGGASAQTAELLALAAACHLATDKTVNIYTDSRYAYGVVHDFGHLWMHRGFVTSAGTPIKNHKEIEYLLKQIMKPKQVSVIKIEAHTKGVSMEVRGNAAADEAAKNAVFLVQRVLKKGDALASTDLVMEYSETDEKFTAGAELHDGVFMRGDLIVPPLEMLHAILLAIHGVSHTHKGGIMSYFSKFWTHPKASQTIDLILGHCQICLKHNPKYKSRLQGHRPLPSRPFAHLQIDFVQMCVKKPMYALVIIDVFSKWPEIIPCNKEDAKTVCDILMKDIIPRWGLPDQIDSDQGTHFTAKISQELTHSIGVAWKLHCPGHPRSSGIVERTNRTLKSKIIKAQEQLQLSKWTEVLPYVLLEMRATPKKHGLSPHEIVMGRPMKTTYLSDMSPLWATDTLVTYMNKLTRQLSAYHQQVVDQWPSTSLPPGPEPGSWCMLRNPKKSSNWEGPFLILLSTPTAVKVEGRPTWIHLDHCKLLRSSLSSSLGGPVNQLLS
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[Matrix protein p10]: Targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the pre-integration complex (By similarity). Capsid protein p25 forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex. [Nucleocapsid protein p14]: Involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization (By similarity). [Protease p15]: 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 (By similarity). [Reverse transcriptase/ribonuclease H p90]: Is a multifunctional enzyme that converts the viral dimeric 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 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 a polypurine tract (PPT) situated at the 5' end 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 PPT that has not been removed by RNase H as primers. PPT 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 (By similarity). [Integrase p46]: 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 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 that requires cell division, the PIC enters cell nucleus. 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 last step is viral DNA integration into host chromosome.
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