| IED ID | IndEnz0002001222 |
| Enzyme Type ID | protease001222 |
| Protein Name |
Replicase polyprotein 1ab pp1ab ORF1ab polyprotein Cleaved into: Host translation inhibitor nsp1 nsp1 Leader protein ; Non-structural protein 2 nsp2 p65 homolog ; Papain-like proteinase PL-PRO EC 3.4.19.12 EC 3.4.22.- Non-structural protein 3 nsp3 ; Non-structural protein 4 nsp4 ; 3C-like proteinase 3CL-PRO 3CLp EC 3.4.22.- nsp5 ; 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 Pol RdRp EC 2.7.7.48 nsp12 ; Helicase Hel EC 3.6.4.12 EC 3.6.4.13 nsp13 ; Guanine-N7 methyltransferase ExoN EC 2.1.1.- EC 3.1.13.- nsp14 ; Uridylate-specific endoribonuclease EC 4.6.1.- NendoU nsp15 ; 2'-O-methyltransferase EC 2.1.1.57 nsp16 |
| Gene Name | rep 1a-1b |
| Organism | Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012) (MERS-CoV) (Betacoronavirus England 1) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Cornidovirineae Coronaviridae Orthocoronavirinae Betacoronavirus Merbecovirus Middle East respiratory syndrome-related coronavirus (MERS-CoV) Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012) (MERS-CoV) (Betacoronavirus England 1) |
| Enzyme Sequence | MSFVAGVTAQGARGTYRAALNSEKHQDHVSLTVPLCGSGNLVEKLSPWFMDGENAYEVVKAMLLKKEPLLYVPIRLAGHTRHLPGPRVYLVERLIACENPFMVNQLAYSSSANGSLVGTTLQGKPIGMFFPYDIELVTGKQNILLRKYGRGGYHYTPFHYERDNTSCPEWMDDFEADPKGKYAQNLLKKLIGGDVTPVDQYMCGVDGKPISAYAFLMAKDGITKLADVEADVAARADDEGFITLKNNLYRLVWHVERKDVPYPKQSIFTINSVVQKDGVENTPPHYFTLGCKILTLTPRNKWSGVSDLSLKQKLLYTFYGKESLENPTYIYHSAFIECGSCGNDSWLTGNAIQGFACGCGASYTANDVEVQSSGMIKPNALLCATCPFAKGDSCSSNCKHSVAQLVSYLSERCNVIADSKSFTLIFGGVAYAYFGCEEGTMYFVPRAKSVVSRIGDSIFTGCTGSWNKVTQIANMFLEQTQHSLNFVGEFVVNDVVLAILSGTTTNVDKIRQLLKGVTLDKLRDYLADYDVAVTAGPFMDNAINVGGTGLQYAAITAPYVVLTGLGESFKKVATIPYKVCNSVKDTLTYYAHSVLYRVFPYDMDSGVSSFSELLFDCVDLSVASTYFLVRLLQDKTGDFMSTIITSCQTAVSKLLDTCFEATEATFNFLLDLAGLFRIFLRNAYVYTSQGFVVVNGKVSTLVKQVLDLLNKGMQLLHTKVSWAGSNISAVIYSGRESLIFPSGTYYCVTTKAKSVQQDLDVILPGEFSKKQLGLLQPTDNSTTVSVTVSSNMVETVVGQLEQTNMHSPDVIVGDYVIISEKLFVRSKEEDGFAFYPACTNGHAVPTLFRLKGGAPVKKVAFGGDQVHEVAAVRSVTVEYNIHAVLDTLLASSSLRTFVVDKSLSIEEFADVVKEQVSDLLVKLLRGMPIPDFDLDDFIDAPCYCFNAEGDASWSSTMIFSLHPVECDEECSEVEASDLEEGESECISETSTEQVDVSHEISDDEWAAAVDEAFPLDEAEDVTESVQEEAQPVEVPVEDIAQVVIADTLQETPVVSDTVEVPPQVVKLPSEPQTIQPEVKEVAPVYEADTEQTQSVTVKPKRLRKKRNVDPLSNFEHKVITECVTIVLGDAIQVAKCYGESVLVNAANTHLKHGGGIAGAINAASKGAVQKESDEYILAKGPLQVGDSVLLQGHSLAKNILHVVGPDARAKQDVSLLSKCYKAMNAYPLVVTPLVSAGIFGVKPAVSFDYLIREAKTRVLVVVNSQDVYKSLTIVDIPQSLTFSYDGLRGAIRKAKDYGFTVFVCTDNSANTKVLRNKGVDYTKKFLTVDGVQYYCYTSKDTLDDILQQANKSVGIISMPLGYVSHGLDLIQAGSVVRRVNVPYVCLLANKEQEAILMSEDVKLNPSEDFIKHVRTNGGYNSWHLVEGELLVQDLRLNKLLHWSDQTICYKDSVFYVVKNSTAFPFETLSACRAYLDSRTTQQLTIEVLVTVDGVNFRTVVLNNKNTYRSQLGCVFFNGADISDTIPDEKQNGHSLYLADNLTADETKALKELYGPVDPTFLHRFYSLKAAVHKWKMVVCDKVRSLKLSDNNCYLNAVIMTLDLLKDIKFVIPALQHAFMKHKGGDSTDFIALIMAYGNCTFGAPDDASRLLHTVLAKAELCCSARMVWREWCNVCGIKDVVLQGLKACCYVGVQTVEDLRARMTYVCQCGGERHRQIVEHTTPWLLLSGTPNEKLVTTSTAPDFVAFNVFQGIETAVGHYVHARLKGGLILKFDSGTVSKTSDWKCKVTDVLFPGQKYSSDCNVVRYSLDGNFRTEVDPDLSAFYVKDGKYFTSEPPVTYSPATILAGSVYTNSCLVSSDGQPGGDAISLSFNNLLGFDSSKPVTKKYTYSFLPKEDGDVLLAEFDTYDPIYKNGAMYKGKPILWVNKASYDTNLNKFNRASLRQIFDVAPIELENKFTPLSVESTPVEPPTVDVVALQQEMTIVKCKGLNKPFVKDNVSFVADDSGTPVVEYLSKEDLHTLYVDPKYQVIVLKDNVLSSMLRLHTVESGDINVVAASGSLTRKVKLLFRASFYFKEFATRTFTATTAVGSCIKSVVRHLGVTKGILTGCFSFVKMLFMLPLAYFSDSKLGTTEVKVSALKTAGVVTGNVVKQCCTAAVDLSMDKLRRVDWKSTLRLLLMLCTTMVLLSSVYHLYVFNQVLSSDVMFEDAQGLKKFYKEVRAYLGISSACDGLASAYRANSFDVPTFCANRSAMCNWCLISQDSITHYPALKMVQTHLSHYVLNIDWLWFAFETGLAYMLYTSAFNWLLLAGTLHYFFAQTSIFVDWRSYNYAVSSAFWLFTHIPMAGLVRMYNLLACLWLLRKFYQHVINGCKDTACLLCYKRNRLTRVEASTVVCGGKRTFYITANGGISFCRRHNWNCVDCDTAGVGNTFICEEVANDLTTALRRPINATDRSHYYVDSVTVKETVVQFNYRRDGQPFYERFPLCAFTNLDKLKFKEVCKTTTGIPEYNFIIYDSSDRGQESLARSACVYYSQVLCKSILLVDSSLVTSVGDSSEIATKMFDSFVNSFVSLYNVTRDKLEKLISTARDGVRRGDNFHSVLTTFIDAARGPAGVESDVETNEIVDSVQYAHKHDIQITNESYNNYVPSYVKPDSVSTSDLGSLIDCNAASVNQIVLRNSNGACIWNAAAYMKLSDALKRQIRIACRKCNLAFRLTTSKLRANDNILSVRFTANKIVGGAPTWFNALRDFTLKGYVLATIIVFLCAVLMYLCLPTFSMVPVEFYEDRILDFKVLDNGIIRDVNPDDKCFANKHRSFTQWYHEHVGGVYDNSITCPLTVAVIAGVAGARIPDVPTTLAWVNNQIIFFVSRVFANTGSVCYTPIDEIPYKSFSDSGCILPSECTMFRDAEGRMTPYCHDPTVLPGAFAYSQMRPHVRYDLYDGNMFIKFPEVVFESTLRITRTLSTQYCRFGSCEYAQEGVCITTNGSWAIFNDHHLNRPGVYCGSDFIDIVRRLAVSLFQPITYFQLTTSLVLGIGLCAFLTLLFYYINKVKRAFADYTQCAVIAVVAAVLNSLCICFVASIPLCIVPYTALYYYATFYFTNEPAFIMHVSWYIMFGPIVPIWMTCVYTVAMCFRHFFWVLAYFSKKHVEVFTDGKLNCSFQDAASNIFVINKDTYAALRNSLTNDAYSRFLGLFNKYKYFSGAMETAAYREAAACHLAKALQTYSETGSDLLYQPPNCSITSGVLQSGLVKMSHPSGDVEACMVQVTCGSMTLNGLWLDNTVWCPRHVMCPADQLSDPNYDALLISMTNHSFSVQKHIGAPANLRVVGHAMQGTLLKLTVDVANPSTPAYTFTTVKPGAAFSVLACYNGRPTGTFTVVMRPNYTIKGSFLCGSCGSVGYTKEGSVINFCYMHQMELANGTHTGSAFDGTMYGAFMDKQVHQVQLTDKYCSVNVVAWLYAAILNGCAWFVKPNRTSVVSFNEWALANQFTEFVGTQSVDMLAVKTGVAIEQLLYAIQQLYTGFQGKQILGSTMLEDEFTPEDVNMQIMGVVMQSGVRKVTYGTAHWLFATLVSTYVIILQATKFTLWNYLFETIPTQLFPLLFVTMAFVMLLVKHKHTFLTLFLLPVAICLTYANIVYEPTTPISSALIAVANWLAPTNAYMRTTHTDIGVYISMSLVLVIVVKRLYNPSLSNFALALCSGVMWLYTYSIGEASSPIAYLVFVTTLTSDYTITVFVTVNLAKVCTYAIFAYSPQLTLVFPEVKMILLLYTCLGFMCTCYFGVFSLLNLKLRAPMGVYDFKVSTQEFRFMTANNLTAPRNSWEAMALNFKLIGIGGTPCIKVAAMQSKLTDLKCTSVVLLSVLQQLHLEANSRAWAFCVKCHNDILAATDPSEAFEKFVSLFATLMTFSGNVDLDALASDIFDTPSVLQATLSEFSHLATFAELEAAQKAYQEAMDSGDTSPQVLKALQKAVNIAKNAYEKDKAVARKLERMADQAMTSMYKQARAEDKKAKIVSAMQTMLFGMIKKLDNDVLNGIISNARNGCIPLSVIPLCASNKLRVVIPDFTVWNQVVTYPSLNYAGALWDITVINNVDNEIVKSSDVVDSNENLTWPLVLECTRASTSAVKLQNNEIKPSGLKTMVVSAGQEQTNCNTSSLAYYEPVQGRKMLMALLSDNAYLKWARVEGKDGFVSVELQPPCKFLIAGPKGPEIRYLYFVKNLNNLHRGQVLGHIAATVRLQAGSNTEFASNSSVLSLVNFTVDPQKAYLDFVNAGGAPLTNCVKMLTPKTGTGIAISVKPESTADQETYGGASVCLYCRAHIEHPDVSGVCKYKGKFVQIPAQCVRDPVGFCLSNTPCNVCQYWIGYGCNCDSLRQAALPQSKDSNFLKRVRGSIVNARIEPCSSGLSTDVVFRAFDICNYKAKVAGIGKYYKTNTCRFVELDDQGHHLDSYFVVKRHTMENYELEKHCYDLLRDCDAVAPHDFFIFDVDKVKTPHIVRQRLTEYTMMDLVYALRHFDQNSEVLKAILVKYGCCDVTYFENKLWFDFVENPSVIGVYHKLGERVRQAILNTVKFCDHMVKAGLVGVLTLDNQDLNGKWYDFGDFVITQPGSGVAIVDSYYSYLMPVLSMTDCLAAETHRDCDFNKPLIEWPLTEYDFTDYKVQLFEKYFKYWDQTYHANCVNCTDDRCVLHCANFNVLFAMTMPKTCFGPIVRKIFVDGVPFVVSCGYHYKELGLVMNMDVSLHRHRLSLKELMMYAADPAMHIASSNAFLDLRTSCFSVAALTTGLTFQTVRPGNFNQDFYDFVVSKGFFKEGSSVTLKHFFFAQDGNAAITDYNYYSYNLPTMCDIKQMLFCMEVVNKYFEIYDGGCLNASEVVVNNLDKSAGHPFNKFGKARVYYESMSYQEQDELFAMTKRNVIPTMTQMNLKYAISAKNRARTVAGVSILSTMTNRQYHQKMLKSMAATRGATCVIGTTKFYGGWDFMLKTLYKDVDNPHLMGWDYPKCDRAMPNMCRIFASLILARKHGTCCTTRDRFYRLANECAQVLSEYVLCGGGYYVKPGGTSSGDATTAYANSVFNILQATTANVSALMGANGNKIVDKEVKDMQFDLYVNVYRSTSPDPKFVDKYYAFLNKHFSMMILSDDGVVCYNSDYAAKGYIAGIQNFKETLYYQNNVFMSEAKCWVETDLKKGPHEFCSQHTLYIKDGDDGYFLPYPDPSRILSAGCFVDDIVKTDGTLMVERFVSLAIDAYPLTKHEDIEYQNVFWVYLQYIEKLYKDLTGHMLDSYSVMLCGDNSAKFWEEAFYRDLYSSPTTLQAVGSCVVCHSQTSLRCGTCIRRPFLCCKCCYDHVIATPHKMVLSVSPYVCNAPGCGVSDVTKLYLGGMSYFCVDHRPVCSFPLCANGLVFGLYKNMCTGSPSIVEFNRLATCDWTESGDYTLANTTTEPLKLFAAETLRATEEASKQSYAIATIKEIVGERQLLLVWEAGKSKPPLNRNYVFTGYHITKNSKVQLGEYIFERIDYSDAVSYKSSTTYKLTVGDIFVLTSHSVATLTAPTIVNQERYVKITGLYPTITVPEEFASHVANFQKSGYSKYVTVQGPPGTGKSHFAIGLAIYYPTARVVYTACSHAAVDALCEKAFKYLNIAKCSRIIPAKARVECYDRFKVNETNSQYLFSTINALPETSADILVVDEVSMCTNYDLSIINARIKAKHIVYVGDPAQLPAPRTLLTRGTLEPENFNSVTRLMCNLGPDIFLSMCYRCPKEIVSTVSALVYNNKLLAKKELSGQCFKILYKGNVTHDASSAINRPQLTFVKNFITANPAWSKAVFISPYNSQNAVARSMLGLTTQTVDSSQGSEYQYVIFCQTADTAHANNINRFNVAITRAQKGILCVMTSQALFESLEFTELSFTNYKLQSQIVTGLFKDCSRETSGLSPAYAPTYVSVDDKYKTSDELCVNLNLPANVPYSRVISRMGFKLDATVPGYPKLFITREEAVRQVRSWIGFDVEGAHASRNACGTNVPLQLGFSTGVNFVVQPVGVVDTEWGNMLTGIAARPPPGEQFKHLVPLMHKGAAWPIVRRRIVQMLSDTLDKLSDYCTFVCWAHGFELTSASYFCKIGKEQKCCMCNRRAAAYSSPLQSYACWTHSCGYDYVYNPFFVDVQQWGYVGNLATNHDRYCSVHQGAHVASNDAIMTRCLAIHSCFIERVDWDIEYPYISHEKKLNSCCRIVERNVVRAALLAGSFDKVYDIGNPKGIPIVDDPVVDWHYFDAQPLTRKVQQLFYTEDMASRFADGLCLFWNCNVPKYPNNAIVCRFDTRVHSEFNLPGCDGGSLYVNKHAFHTPAYDVSAFRDLKPLPFFYYSTTPCEVHGNGSMIEDIDYVPLKSAVCITACNLGGAVCRKHATEYREYMEAYNLVSASGFRLWCYKTFDIYNLWSTFTKVQGLENIAFNFVKQGHFIGVEGELPVAVVNDKIFTKSGVNDICMFENKTTLPTNIAFELYAKRAVRSHPDFKLLHNLQADICYKFVLWDYERSNIYGTATIGVCKYTDIDVNSALNICFDIRDNGSLEKFMSTPNAIFISDRKIKKYPCMVGPDYAYFNGAIIRDSDVVKQPVKFYLYKKVNNEFIDPTECIYTQSRSCSDFLPLSDMEKDFLSFDSDVFIKKYGLENYAFEHVVYGDFSHTTLGGLHLLIGLYKKQQEGHIIMEEMLKGSSTIHNYFITETNTAAFKAVCSVIDLKLDDFVMILKSQDLGVVSKVVKVPIDLTMIEFMLWCKDGQVQTFYPRLQASADWKPGHAMPSLFKVQNVNLERCELANYKQSIPMPRGVHMNIAKYMQLCQYLNTCTLAVPANMRVIHFGAGSDKGIAPGTSVLRQWLPTDAIIIDNDLNEFVSDADITLFGDCVTVRVGQQVDLVISDMYDPTTKNVTGSNESKALFFTYLCNLINNNLALGGSVAIKITEHSWSVELYELMGKFAWWTVFCTNANASSSEGFLLGINYLGTIKENIDGGAMHANYIFWRNSTPMNLSTYSLFDLSKFQLKLKGTPVLQLKESQINELVISLLSQGKLLIRDNDTLSVSTDVLVNTYRKLR |
| Enzyme Length | 7078 |
| Uniprot Accession Number | K9N7C7 |
| Absorption | |
| Active Site | ACT_SITE 1592; /note=For PL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1759; /note=For PL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 3288; /note=For 3CL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00772; ACT_SITE 3395; /note=For 3CL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00772; ACT_SITE 5137; /evidence=ECO:0000255|PROSITE-ProRule:PRU01293; ACT_SITE 5138; /evidence=ECO:0000255|PROSITE-ProRule:PRU01293; ACT_SITE 5139; /evidence=ECO:0000255|PROSITE-ProRule:PRU01293; ACT_SITE 5998; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; ACT_SITE 6000; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; ACT_SITE 6099; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; ACT_SITE 6176; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; ACT_SITE 6181; /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 | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: [Helicase]: 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; CATALYTIC ACTIVITY: [Helicase]: 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; CATALYTIC ACTIVITY: [Papain-like proteinase]: 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; CATALYTIC ACTIVITY: [2'-O-methyltransferase]: 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:0000250|UniProtKB:P0C6X7}; CATALYTIC ACTIVITY: [Uridylate-specific endoribonuclease]: 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:0000250|UniProtKB:P0C6X7}; |
| DNA Binding | |
| EC Number | 3.4.19.12; 3.4.22.-; 3.4.22.-; 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: The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [Host translation inhibitor nsp1]: Promotes the degradation of host mRNAs by inducing an endonucleolytic RNA cleavage in template mRNAs, and inhibits of host mRNA translation, a function that is separable from its RNA cleavage activity. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response. {ECO:0000269|PubMed:26311885}.; 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. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [Papain-like proteinase]: Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates, together with nsp4, in the assembly of virally induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B. signaling. {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:25142582}.; FUNCTION: [Non-structural protein 4]: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [3C-like proteinase]: 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). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000255|PROSITE-ProRule:PRU00772}.; FUNCTION: [Non-structural protein 6]: 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. {ECO:0000250|UniProtKB:P0C6X7}.; 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:0000250|UniProtKB:P0C6X7}.; 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:0000250|UniProtKB:P0C6X7}.; FUNCTION: [Non-structural protein 9]: May participate in viral replication by acting as a ssRNA-binding protein. {ECO:0000250|UniProtKB:P0C6X7}.; 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:0000250|UniProtKB:P0C6X7}.; FUNCTION: [RNA-directed RNA polymerase]: Responsible for replication and transcription of the viral RNA genome. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [Helicase]: 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:0000250|UniProtKB:P0C6X7}.; FUNCTION: [Guanine-N7 methyltransferase]: 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. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [Uridylate-specific endoribonuclease]: Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (By similarity). 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) (By similarity). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (By similarity). {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [2'-O-methyltransferase]: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system. {ECO:0000250|UniProtKB:P0C6X7}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 5592..5599; /note=ATP; /evidence=ECO:0000250 |
| Features | Active site (19); Beta strand (27); Chain (15); Domain (25); Helix (20); Metal binding (39); Nucleotide binding (1); Region (5); Site (14); Transmembrane (17); Turn (4); 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 cytoplasm;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;Repeat;Ribosomal frameshifting;Thiol protease;Transferase;Transmembrane;Transmembrane helix;Ubl conjugation pathway;Viral RNA replication;Viral immunoevasion;Zinc;Zinc-finger |
| Interact With | P05161; Q96PM5; K9N7C7; Itself |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Papain-like proteinase]: Host membrane; Multi-pass membrane protein. Host cytoplasm {ECO:0000250|UniProtKB:P0C6X7}.; SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane; Multi-pass membrane protein. Host cytoplasm. Note=Localizes in virally-induced cytoplasmic double-membrane vesicles. {ECO:0000250|UniProtKB:P0C6X7}.; 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}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Helicase]: 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. {ECO:0000250}.; SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease]: Host cytoplasm, host perinuclear region {ECO:0000250}. |
| Modified Residue | |
| Post Translational Modification | PTM: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed (By similarity). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (3) |
| Cross Reference PDB | 4WUR; 5HOL; 5KO3; |
| Mapped Pubmed ID | 27245450; 28079137; 29128390; |
| Motif | |
| Gene Encoded By | |
| Mass | 789,563 |
| Kinetics | |
| Metal Binding | METAL 4311; /note=Zinc; METAL 4311; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4314; /note=Zinc; METAL 4314; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4320; /note=Zinc; METAL 4320; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4327; /note=Zinc; METAL 4327; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4354; /note=Zinc; METAL 4354; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4357; /note=Zinc; METAL 4357; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4365; /note=Zinc; METAL 4365; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4367; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 5315; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5318; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5326; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5329; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5336; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5339; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5343; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5349; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5360; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5365; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5382; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5385; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 6115; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6118; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6134; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6137; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6165; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6169; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6172; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6187; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6356; /note=Zinc 8; /evidence=ECO:0000255|PROSITE-ProRule:PRU01299; METAL 6378; /note=Zinc 8; /evidence=ECO:0000255|PROSITE-ProRule:PRU01299; METAL 6389; /note=Zinc 8; /evidence=ECO:0000255|PROSITE-ProRule:PRU01299; METAL 6392; /note=Zinc 8; /evidence=ECO:0000255|PROSITE-ProRule:PRU01299 |
| Rhea ID | RHEA:21248; RHEA:13065; RHEA:67020; RHEA:67732 |
| Cross Reference Brenda |