| IED ID | IndEnz0002001224 |
| Enzyme Type ID | protease001224 |
| Protein Name |
Replicase polyprotein 1ab pp1ab ORF1ab polyprotein Cleaved into: Host translation inhibitor nsp1 Leader protein Non-structural protein 1 nsp1 ; Non-structural protein 2 nsp2 p65 homolog ; Papain-like protease nsp3 PL-PRO EC 3.4.19.12 EC 3.4.22.- Non-structural protein 3 nsp3 PL2-PRO ; Non-structural protein 4 nsp4 ; 3C-like proteinase nsp5 3CL-PRO 3CLp EC 3.4.22.69 Main protease Mpro Non-structural protein 5 nsp5 SARS coronavirus main proteinase ; Non-structural protein 6 nsp6 ; Non-structural protein 7 nsp7 ; Non-structural protein 8 nsp8 ; Non-structural protein 9 nsp9 ; Non-structural protein 10 nsp10 Growth factor-like peptide GFL ; RNA-directed RNA polymerase nsp12 Pol RdRp EC 2.7.7.48 Non-structural protein 12 nsp12 ; Helicase nsp13 Hel EC 3.6.4.12 EC 3.6.4.13 Non-structural protein 13 nsp13 ; Proofreading exoribonuclease nsp14 ExoN EC 2.1.1.- EC 3.1.13.- Guanine-N7 methyltransferase Non-structural protein 14 nsp14 ; Uridylate-specific endoribonuclease nsp15 EC 4.6.1.- NendoU Non-structural protein 15 nsp15 ; 2'-O-methyltransferase nsp16 EC 2.1.1.57 Non-structural protein 16 nsp16 |
| Gene Name | rep 1a-1b |
| Organism | Severe acute respiratory syndrome coronavirus (SARS-CoV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Cornidovirineae Coronaviridae Orthocoronavirinae Betacoronavirus Sarbecovirus Severe acute respiratory syndrome coronavirus (SARS-CoV) |
| Enzyme Sequence | MESLVLGVNEKTHVQLSLPVLQVRDVLVRGFGDSVEEALSEAREHLKNGTCGLVELEKGVLPQLEQPYVFIKRSDALSTNHGHKVVELVAEMDGIQYGRSGITLGVLVPHVGETPIAYRNVLLRKNGNKGAGGHSYGIDLKSYDLGDELGTDPIEDYEQNWNTKHGSGALRELTRELNGGAVTRYVDNNFCGPDGYPLDCIKDFLARAGKSMCTLSEQLDYIESKRGVYCCRDHEHEIAWFTERSDKSYEHQTPFEIKSAKKFDTFKGECPKFVFPLNSKVKVIQPRVEKKKTEGFMGRIRSVYPVASPQECNNMHLSTLMKCNHCDEVSWQTCDFLKATCEHCGTENLVIEGPTTCGYLPTNAVVKMPCPACQDPEIGPEHSVADYHNHSNIETRLRKGGRTRCFGGCVFAYVGCYNKRAYWVPRASADIGSGHTGITGDNVETLNEDLLEILSRERVNINIVGDFHLNEEVAIILASFSASTSAFIDTIKSLDYKSFKTIVESCGNYKVTKGKPVKGAWNIGQQRSVLTPLCGFPSQAAGVIRSIFARTLDAANHSIPDLQRAAVTILDGISEQSLRLVDAMVYTSDLLTNSVIIMAYVTGGLVQQTSQWLSNLLGTTVEKLRPIFEWIEAKLSAGVEFLKDAWEILKFLITGVFDIVKGQIQVASDNIKDCVKCFIDVVNKALEMCIDQVTIAGAKLRSLNLGEVFIAQSKGLYRQCIRGKEQLQLLMPLKAPKEVTFLEGDSHDTVLTSEEVVLKNGELEALETPVDSFTNGAIVGTPVCVNGLMLLEIKDKEQYCALSPGLLATNNVFRLKGGAPIKGVTFGEDTVWEVQGYKNVRITFELDERVDKVLNEKCSVYTVESGTEVTEFACVVAEAVVKTLQPVSDLLTNMGIDLDEWSVATFYLFDDAGEENFSSRMYCSFYPPDEEEEDDAECEEEEIDETCEHEYGTEDDYQGLPLEFGASAETVRVEEEEEEDWLDDTTEQSEIEPEPEPTPEEPVNQFTGYLKLTDNVAIKCVDIVKEAQSANPMVIVNAANIHLKHGGGVAGALNKATNGAMQKESDDYIKLNGPLTVGGSCLLSGHNLAKKCLHVVGPNLNAGEDIQLLKAAYENFNSQDILLAPLLSAGIFGAKPLQSLQVCVQTVRTQVYIAVNDKALYEQVVMDYLDNLKPRVEAPKQEEPPNTEDSKTEEKSVVQKPVDVKPKIKACIDEVTTTLEETKFLTNKLLLFADINGKLYHDSQNMLRGEDMSFLEKDAPYMVGDVITSGDITCVVIPSKKAGGTTEMLSRALKKVPVDEYITTYPGQGCAGYTLEEAKTALKKCKSAFYVLPSEAPNAKEEILGTVSWNLREMLAHAEETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDYGVRFFFYTSKEPVASIITKLNSLNEPLVTMPIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGYLTSSSKTSEEHFVETVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLSLDKLKSLLSLREVKTIKVFTTVDNTNLHTQLVDMSMTYGQQFGPTYLDGADVTKIKPHVNHEGKTFFVLPSDDTLRSEAFEYYHTLDESFLGRYMSALNHTKKWKFPQVGGLTSIKWADNNCYLSSVLLALQQLEVKFNAPALQEAYYRARAGDAANFCALILAYSNKTVGELGDVRETMTHLLQHANLESAKRVLNVVCKHCGQKTTTLTGVEAVMYMGTLSYDNLKTGVSIPCVCGRDATQYLVQQESSFVMMSAPPAEYKLQQGTFLCANEYTGNYQCGHYTHITAKETLYRIDGAHLTKMSEYKGPVTDVFYKETSYTTTIKPVSYKLDGVTYTEIEPKLDGYYKKDNAYYTEQPIDLVPTQPLPNASFDNFKLTCSNTKFADDLNQMTGFTKPASRELSVTFFPDLNGDVVAIDYRHYSASFKKGAKLLHKPIVWHINQATTKTTFKPNTWCLRCLWSTKPVDTSNSFEVLAVEDTQGMDNLACESQQPTSEEVVENPTIQKEVIECDVKTTEVVGNVILKPSDEGVKVTQELGHEDLMAAYVENTSITIKKPNELSLALGLKTIATHGIAAINSVPWSKILAYVKPFLGQAAITTSNCAKRLAQRVFNNYMPYVFTLLFQLCTFTKSTNSRIRASLPTTIAKNSVKSVAKLCLDAGINYVKSPKFSKLFTIAMWLLLLSICLGSLICVTAAFGVLLSNFGAPSYCNGVRELYLNSSNVTTMDFCEGSFPCSICLSGLDSLDSYPALETIQVTISSYKLDLTILGLAAEWVLAYMLFTKFFYLLGLSAIMQVFFGYFASHFISNSWLMWFIISIVQMAPVSAMVRMYIFFASFYYIWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVAVKNGALHLYFDKAGQKTYERHPLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCDESASKSASVYYSQLMCQPILLLDQALVSDVGDSTEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLSTFVSAARQGVVDTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQVAKSHNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKGGKIVSTCFKLMLKATLLCVLAALVCYIVMPVHTLSIHDGYTNEIIGYKAIQDGVTRDIISTDDCFANKHAGFDAWFSQRGGSYKNDKSCPVVAAIITREIGFIVPGLPGTVLRAINGDFLHFLPRVFSAVGNICYTPSKLIEYSDFATSACVLAAECTIFKDAMGKPVPYCYDTNLLEGSISYSELRPDTRYVLMDGSIIQFPNTYLEGSVRVVTTFDAEYCRHGTCERSEVGICLSTSGRWVLNNEHYRALSGVFCGVDAMNLIANIFTPLVQPVGALDVSASVVAGGIIAILVTCAAYYFMKFRRVFGEYNHVVAANALLFLMSFTILCLVPAYSFLPGVYSVFYLYLTFYFTNDVSFLAHLQWFAMFSPIVPFWITAIYVFCISLKHCHWFFNNYLRKRVMFNGVTFSTFEEAALCTFLLNKEMYLKLRSETLLPLTQYNRYLALYNKYKYFSGALDTTSYREAACCHLAKALNDFSNSGADVLYQPPQTSITSAVLQSGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDTVYCPRHVICTAEDMLNPNYEDLLIRKSNHSFLVQAGNVQLRVIGHSMQNCLLRLKVDTSNPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVDILGPLSAQTGIAVLDMCAALKELLQNGMNGRTILGSTILEDEFTPFDVVRQCSGVTFQGKFKKIVKGTHHWMLLTFLTSLLILVQSTQWSLFFFVYENAFLPFTLGIMAIAACAMLLVKHKHAFLCLFLLPSLATVAYFNMVYMPASWVMRIMTWLELADTSLSGYRLKDCVMYASALVLLILMTARTVYDDAARRVWTLMNVITLVYKVYYGNALDQAISMWALVISVTSNYSGVVTTIMFLARAIVFVCVEYYPLLFITGNTLQCIMLVYCFLGYCCCCYFGLFCLLNRYFRLTLGVYDYLVSTQEFRYMNSQGLLPPKSSIDAFKLNIKLLGIGGKPCIKVATVQSKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINRLCEEMLDNRATLQAIASEFSSLPSYAAYATAQEAYEQAVANGDSEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKRAKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVVPDYGTYKNTCDGNTFTYASALWEIQQVVDADSKIVQLSEINMDNSPNLAWPLIVTALRANSAVKLQNNELSPVALRQMSCAAGTTQTACTDDNALAYYNNSKGGRFVLALLSDHQDLKWARFPKSDGTGTIYTELEPPCRFVTDTPKGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQAGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCHIDHPNPKGFCDLKGKYVQIPTTCANDPVGFTLRNTVCTVCGMWKGYGCSCDQLREPLMQSADASTFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNEKVAGFAKFLKTNCCRFQEKDEEGNLLDSYFVVKRHTMSNYQHEETIYNLVKDCPAVAVHDFFKFRVDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDFVENPDILRVYANLGERVRQSLLKTVQFCDAMRDAGIVGVLTLDNQDLNGNWYDFGDFVQVAPGCGVPIVDSYYSLLMPILTLTRALAAESHMDADLAKPLIKWDLLKYDFTEERLCLFDRYFKYWDQTYHPNCINCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNVAFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICSTMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVETPHLMGWDYPKCDRAMPNMLRIMASLVLARKHNTCCNLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQHRLYECLYRNRDVDHEFVDEFYAYLRKHFSMMILSDDAVVCYNSNYAAQGLVASIKNFKAVLYYQNNVFMSEAKCWTETDLTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQAVGACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLVLSVNPYVCNAPGCDVTDVTQLYLGGMSYYCKSHKPPISFPLCANGQVFGLYKNTCVGSDNVTDFNAIATCDWTNAGDYILANTCTERLKLFAAETLKATEETFKLSYGIATVREVLSDRELHLSWEVGKPRPPLNRNYVFTGYRVTKNSKVQIGEYTFEKGDYGDAVVYRGTTTYKLNVGDYFVLTSHTVMPLSAPTLVPQEHYVRITGLYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKCSRIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRTLLTKGTLEPEYFNSVCRLMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKGVITHDVSSAINRPQIGVVREFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKIGILCIMSDRDLYDKLQFTSLEIPRRNVATLQAENVTGLFKDCSKIITGLHPTQAPTHLSVDIKFKTEGLCVDIPGIPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEAIRHVRAWIGFDVEGCHATRDAVGTNLPLQLGFSTGVNLVAVPTGYVDTENNTEFTRVNAKPPPGDQFKHLIPLMYKGLPWNVVRIKIVQMLSDTLKGLSDRVVFVLWAHGFELTSMKYFVKIGPERTCCLCDKRATCFSTSSDTYACWNHSVGFDYVYNPFMIDVQQWGFTGNLQSNHDQHCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWSVEYPIIGDELRVNSACRKVQHMVVKSALLADKFPVLHDIGNPKAIKCVPQAEVEWKFYDAQPCSDKAYKIEELFYSYATHHDKFTDGVCLFWNCNVDRYPANAIVCRFDTRVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFTNLKQLPFFYYSDSPCESHGKQVVSDIDYVPLKSATCITRCNLGGAVCRHHANEYRQYLDAYNMMISAGFSLWIYKQFDTYNLWNTFTRLQSLENVAYNVVNKGHFDGHAGEAPVSIINNAVYTKVDGIDVEIFENKTTLPVNVAFELWAKRNIKPVPEIKILNNLGVDIAANTVIWDYKREAPAHVSTIGVCTMTDIAKKPTESACSSLTVLFDGRVEGQVDLFRNARNGVLITEGSVKGLTPSKGPAQASVNGVTLIGESVKTQFNYFKKVDGIIQQLPETYFTQSRDLEDFKPRSQMETDFLELAMDEFIQRYKLEGYAFEHIVYGDFSHGQLGGLHLMIGLAKRSQDSPLKLEDFIPMDSTVKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQDLSVISKVVKVTIDYAEISFMLWCKDGHVETFYPKLQASQAWQPGVAMPNLYKMQRMLLEKCDLQNYGENAVIPKGIMMNVAKYTQLCQYLNTLTLAVPYNMRVIHFGAGSDKGVAPGTAVLRQWLPTGTLLVDSDLNDFVSDADSTLIGDCATVHTANKWDLIISDMYDPRTKHVTKENDSKEGFFTYLCGFIKQKLALGGSIAVKITEHSWNADLYKLMGHFSWWTAFVTNVNASSSEAFLIGANYLGKPKEQIDGYTMHANYIFWRNTNPIQLSSYSLFDMSKFPLKLRGTAVMSLKENQINDMIYSLLEKGRLIIRENNRVVVSSDILVNN |
| Enzyme Length | 7073 |
| Uniprot Accession Number | P0C6X7 |
| Absorption | |
| Active Site | ACT_SITE 1651; /note="For PL-PRO activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00444, ECO:0000269|PubMed:16306590"; ACT_SITE 1812; /note="For PL-PRO activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00444, ECO:0000269|PubMed:16306590"; ACT_SITE 1826; /note="For PL-PRO activity"; /evidence="ECO:0000269|PubMed:16306590"; ACT_SITE 3281; /note="For 3CL-PRO activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"; ACT_SITE 3385; /note="For 3CL-PRO activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"; ACT_SITE 5128; /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"; ACT_SITE 5129; /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"; ACT_SITE 5130; /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"; ACT_SITE 5992; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 5994; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 6093; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 6170; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 6175; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 6663; /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"; ACT_SITE 6678; /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"; ACT_SITE 6718; /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"; ACT_SITE 6821; /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"; ACT_SITE 6905; /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"; ACT_SITE 6945; /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"; ACT_SITE 6978; /evidence="ECO:0000255|PROSITE-ProRule:PRU01300" |
| Activity Regulation | ACTIVITY REGULATION: [Proofreading exoribonuclease nsp14]: Inhibited by Remdesivir (GS-5734). {ECO:0000269|PubMed:29511076}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: [RNA-directed RNA polymerase nsp12]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539, ECO:0000269|PubMed:14561748}; CATALYTIC ACTIVITY: [Helicase nsp13]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; Evidence={ECO:0000269|PubMed:22615777}; CATALYTIC ACTIVITY: [Helicase nsp13]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000269|PubMed:22615777}; CATALYTIC ACTIVITY: [3C-like proteinase nsp5]: Reaction=TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.; EC=3.4.22.69; Evidence={ECO:0000269|PubMed:12917450, ECO:0000269|PubMed:14561748}; CATALYTIC ACTIVITY: [Papain-like protease nsp3]: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:12917450, ECO:0000269|PubMed:17692280}; CATALYTIC ACTIVITY: [2'-O-methyltransferase nsp16]: Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167, Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609; EC=2.1.1.57; Evidence={ECO:0000269|PubMed:22022266, ECO:0000269|PubMed:28158275}; CATALYTIC ACTIVITY: [Uridylate-specific endoribonuclease nsp15]: Reaction=uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl-2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside-RNA; Xref=Rhea:RHEA:67732, Rhea:RHEA-COMP:13936, Rhea:RHEA-COMP:17334, Rhea:RHEA-COMP:17335, ChEBI:CHEBI:138284, ChEBI:CHEBI:173079, ChEBI:CHEBI:173080; Evidence={ECO:0000269|PubMed:16828802}; |
| DNA Binding | |
| EC Number | 3.4.19.12; 3.4.22.-; 3.4.22.69; 2.7.7.48; 3.6.4.12; 3.6.4.13; 2.1.1.-; 3.1.13.-; 4.6.1.-; 2.1.1.57 |
| Enzyme Function | FUNCTION: [Isoform Replicase polyprotein 1ab]: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein. {ECO:0000305}.; FUNCTION: [Host translation inhibitor nsp1]: Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371). {ECO:0000269|PubMed:23035226, ECO:0000269|PubMed:30943371}.; FUNCTION: [Non-structural protein 2]: May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2 (PubMed:19640993). Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses (PubMed:19640993). {ECO:0000269|PubMed:19640993}.; FUNCTION: [Papain-like protease nsp3]: Responsible for the cleavages located at the N-terminus of the replicase polyprotein (PubMed:16306590). In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:16306590, PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:23943763). Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF-kappa-B signaling (PubMed:19369340, PubMed:24622840). {ECO:0000269|PubMed:16306590, ECO:0000269|PubMed:17692280, ECO:0000269|PubMed:19369340, ECO:0000269|PubMed:23943763, ECO:0000269|PubMed:24622840, ECO:0000303|PubMed:24410069}.; FUNCTION: [Non-structural protein 4]: Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:23943763). Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV. {ECO:0000269|PubMed:23943763, ECO:0000303|PubMed:24410069}.; FUNCTION: [3C-like proteinase nsp5]: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH. {ECO:0000255|PROSITE-ProRule:PRU00772, ECO:0000269|PubMed:16226257}.; FUNCTION: [Non-structural protein 6]: Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:24991833, PubMed:24410069). Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24991833, PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833). {ECO:0000269|PubMed:24991833, ECO:0000303|PubMed:24410069}.; FUNCTION: [Non-structural protein 7]: Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers. {ECO:0000269|PubMed:22039154}.; FUNCTION: [Non-structural protein 8]: Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers. {ECO:0000269|PubMed:22039154}.; FUNCTION: [Non-structural protein 9]: Plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA. {ECO:0000269|PubMed:19153232}.; FUNCTION: [Non-structural protein 10]: Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation. {ECO:0000269|PubMed:22022266, ECO:0000269|PubMed:22635272}.; FUNCTION: [RNA-directed RNA polymerase nsp12]: Responsible for replication and transcription of the viral RNA genome. {ECO:0000269|PubMed:22791111}.; FUNCTION: [Helicase nsp13]: Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium. {ECO:0000269|PubMed:12917423, ECO:0000269|PubMed:22615777}.; FUNCTION: [Proofreading exoribonuclease nsp14]: Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity (PubMed:16549795, PubMed:20421945, PubMed:22635272). Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens (PubMed:23966862, PubMed:29511076, PubMed:21593585). {ECO:0000269|PubMed:16549795, ECO:0000269|PubMed:20421945, ECO:0000269|PubMed:21593585, ECO:0000269|PubMed:22635272, ECO:0000269|PubMed:23966862, ECO:0000269|PubMed:29511076}.; FUNCTION: [Uridylate-specific endoribonuclease nsp15]: Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (PubMed:28158275, PubMed:18045871). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (PubMed:16828802). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (PubMed:28158275, PubMed:18045871). {ECO:0000269|PubMed:16828802, ECO:0000269|PubMed:18045871, ECO:0000269|PubMed:28158275}.; FUNCTION: [2'-O-methyltransferase nsp16]: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs (PubMed:18417574, PubMed:22022266,PubMed:20421945). N7-methyl guanosine cap is a prerequisite for binding of nsp16 (PubMed:18417574). Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system (PubMed:18417574, PubMed:22022266,PubMed:20421945). {ECO:0000269|PubMed:18417574, ECO:0000269|PubMed:20421945, ECO:0000269|PubMed:22022266, ECO:0000305}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.0 for 3C-like proteinase activity. {ECO:0000269|PubMed:14561748}; |
| Pathway | |
| nucleotide Binding | NP_BIND 5583..5590; /note=ATP; /evidence=ECO:0000250 |
| Features | Active site (20); Beta strand (202); Chain (15); Compositional bias (1); Domain (28); Erroneous gene model prediction (6); Helix (166); Metal binding (32); Mutagenesis (12); Natural variant (87); Nucleotide binding (1); Region (7); Site (14); Topological domain (13); Transmembrane (12); Turn (47); Zinc finger (3) |
| Keywords | 3D-structure;ATP-binding;Activation of host autophagy by virus;Decay of host mRNAs by virus;Endonuclease;Eukaryotic host gene expression shutoff by virus;Eukaryotic host translation shutoff by virus;Exonuclease;Helicase;Host Golgi apparatus;Host cytoplasm;Host endoplasmic reticulum;Host endosome;Host gene expression shutoff by virus;Host mRNA suppression by virus;Host membrane;Host-virus interaction;Hydrolase;Inhibition of host ISG15 by virus;Inhibition of host NF-kappa-B by virus;Inhibition of host innate immune response by virus;Inhibition of host interferon signaling pathway by virus;Lyase;Membrane;Metal-binding;Methyltransferase;Modulation of host ubiquitin pathway by viral deubiquitinase;Modulation of host ubiquitin pathway by virus;Nuclease;Nucleotide-binding;Nucleotidyltransferase;Protease;RNA-binding;RNA-directed RNA polymerase;Reference proteome;Repeat;Ribosomal frameshifting;Thiol protease;Transferase;Transmembrane;Transmembrane helix;Ubl conjugation pathway;Viral RNA replication;Viral immunoevasion;Zinc;Zinc-finger |
| Interact With | Itself; P59637; Q9UQN3; P62942; Q9Y4W2; P62937; Q13427; O43447; Q9UKA8; P0C6U8; P59632; Itself; P0C6X7; P0C6X7; P05155; P59637; Itself; P0C6X7; P0C6X7; P0C6X7; Q13557; Q14653; P05161; Q64339; Q9H000; Q13064; Q96PM5; Q86WV6; P0CG48; Itself; P0C6X7; K9N638; P62942; P0C6X7; Itself; P0C6X7; O95865; A9UHW6; P59637; Q19QW5; Itself; Q9P0M6; P69849; P54274; P0C6X7; P0C6X7; P0C6X7; Itself; P0C6X7; Q9UQN3; Q5SQN1; P0C6X7; P0C6X7; P0C6X7; P0C6X7; O96017; Q8N488; P59636; P0C6X7; P0C6X7; P0C6X7; P0C6X7; P05155; P0C6X7; P06400; P0C6X7; P0C6X7; P0C6X7; P40337; P0C6X7 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Non-structural protein 2]: Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endosome {ECO:0000250|UniProtKB:P0DTD1}.; SUBCELLULAR LOCATION: [Papain-like protease nsp3]: Host membrane {ECO:0000305}; Multi-pass membrane protein. Host cytoplasm {ECO:0000269|PubMed:23943763}.; SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane; Multi-pass membrane protein. Host cytoplasm {ECO:0000269|PubMed:23943763}. Note=Localizes in virally-induced cytoplasmic double-membrane vesicles. {ECO:0000269|PubMed:17855519, ECO:0000269|PubMed:21345958, ECO:0000269|PubMed:23943763}.; SUBCELLULAR LOCATION: [3C-like proteinase nsp5]: Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host Golgi apparatus {ECO:0000250|UniProtKB:P0DTD1}.; SUBCELLULAR LOCATION: [Non-structural protein 6]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host perinuclear region {ECO:0000250}. Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.; SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host perinuclear region {ECO:0000269|PubMed:17532020}. Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.; SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host perinuclear region {ECO:0000250}. Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.; SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host perinuclear region {ECO:0000250}. Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.; SUBCELLULAR LOCATION: [Helicase nsp13]: Host endoplasmic reticulum-Golgi intermediate compartment {ECO:0000305}. Note=The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA.; SUBCELLULAR LOCATION: [Proofreading exoribonuclease nsp14]: Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum {ECO:0000250|UniProtKB:P0DTD1}.; SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease nsp15]: Host cytoplasm, host perinuclear region {ECO:0000250}. |
| Modified Residue | |
| Post Translational Modification | PTM: [Isoform Replicase polyprotein 1ab]: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins (PubMed:32083638, PubMed:16306590, PubMed:12917450, PubMed:15331731, PubMed:15564471). 3C-like proteinase nsp5 liberates nsps 6-16 from the polyprotein (PubMed:32083638). Papain-like and 3C-like proteinases are autocatalytically processed. {ECO:0000269|PubMed:12917450, ECO:0000269|PubMed:15331731, ECO:0000269|PubMed:15564471, ECO:0000269|PubMed:16306590, ECO:0000269|PubMed:32083638}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (11); Electron microscopy (2); X-ray crystallography (84) |
| Cross Reference PDB | 1Q2W; 1QZ8; 1UJ1; 1UK2; 1UK3; 1UK4; 1UW7; 1WOF; 1YSY; 1Z1I; 1Z1J; 2A5A; 2A5I; 2A5K; 2ACF; 2AHM; 2ALV; 2AMD; 2AMQ; 2BX3; 2BX4; 2C3S; 2D2D; 2DUC; 2FAV; 2FE8; 2FYG; 2G9T; 2GA6; 2GDT; 2GRI; 2GT7; 2GT8; 2GTB; 2GX4; 2GZ7; 2GZ8; 2GZ9; 2H2Z; 2H85; 2HOB; 2HSX; 2IDY; 2JZD; 2JZE; 2JZF; 2K7X; 2K87; 2OP9; 2OZK; 2PWX; 2Q6G; 2QC2; 2QCY; 2QIQ; 2RHB; 2RNK; 2V6N; 2VJ1; 2XYQ; 2XYR; 2XYV; 2Z3C; 2Z3D; 2Z3E; 2Z94; 2Z9G; 2Z9J; 2Z9K; 2Z9L; 3D62; 3E9S; 3EBN; 3R24; 4TWW; 4TWY; 4WY3; 4ZUH; 5B6O; 5C5N; 5C5O; 5C8S; 5C8T; 5C8U; 5E6J; 5F22; 5N19; 5N5O; 5NFY; 6JYT; 6LNQ; 6NUR; 6NUS; 6W79; 6WCO; 7LCP; 7LCQ; |
| Mapped Pubmed ID | 14585926; 15788388; 16128623; 16188992; 16219322; 16242152; 16250632; 16511208; 16821128; 16884309; 16912299; 16913704; 17189639; 17196984; 17409150; 17599357; 17605471; 17728234; 17855091; 17977841; 17981158; 18094151; 18305031; 18559270; 18611220; 19052085; 19319935; 19828617; 21203988; 21637813; 25614110; 26159422; 27128350; 27203180; 27799534; 29279395; 31131400; 31138817; 32391184; 33895266; |
| Motif | |
| Gene Encoded By | |
| Mass | 790,248 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.15 mM for peptide TSAVLQSGFRK-NH(2) {ECO:0000269|PubMed:14561748}; KM=0.58 mM for peptide SGVTFQGKFKK {ECO:0000269|PubMed:14561748}; KM=1.44 mM for peptide ATVRLQAGNAT {ECO:0000269|PubMed:14561748}; Note=The kinetic parameters are studied for the 3C-like proteinase domain.; |
| Metal Binding | METAL 4304; /note="Zinc 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297, ECO:0000269|PubMed:22022266"; METAL 4307; /note="Zinc 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297, ECO:0000269|PubMed:22022266"; METAL 4313; /note="Zinc 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297, ECO:0000269|PubMed:22022266"; METAL 4320; /note="Zinc 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297, ECO:0000269|PubMed:22022266"; METAL 4347; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297, ECO:0000269|PubMed:22022266"; METAL 4350; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297, ECO:0000269|PubMed:22022266"; METAL 4358; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297, ECO:0000269|PubMed:22022266"; METAL 4360; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297, ECO:0000269|PubMed:22022266"; METAL 5306; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5309; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5317; /note="Zinc 4"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5320; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5327; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5330; /note="Zinc 4"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5334; /note="Zinc 4"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5340; /note="Zinc 4"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5351; /note="Zinc 5"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5356; /note="Zinc 5"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5373; /note="Zinc 5"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5376; /note="Zinc 5"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 6109; /note="Zinc 6"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6112; /note="Zinc 6"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6128; /note="Zinc 6"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6131; /note="Zinc 6"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6159; /note="Zinc 7"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6163; /note="Zinc 7"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6166; /note="Zinc 7"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6181; /note="Zinc 7"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6354; /note="Zinc 8"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"; METAL 6375; /note="Zinc 8"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"; METAL 6386; /note="Zinc 8"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"; METAL 6389; /note="Zinc 8"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01299" |
| Rhea ID | RHEA:21248; RHEA:13065; RHEA:67020; RHEA:67732 |
| Cross Reference Brenda |