| IED ID | IndEnz0002001921 |
| Enzyme Type ID | protease001921 |
| 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 | Bat coronavirus HKU9 (BtCoV) (BtCoV/HKU9) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Cornidovirineae Coronaviridae Orthocoronavirinae Betacoronavirus Nobecovirus Bat coronavirus HKU9 (BtCoV) (BtCoV/HKU9) |
| Enzyme Sequence | MEGVPDPPKLKSMVVTTLKWCDPFANPNVTGWDIPIEEALEYAKQQLRTPEPQLVFVPYYLSHAPGISGDRVVITDSIWYATNFGWQPIRELAMDKDGVRYGRGGTHGVLLPMQDPSFIMGDIDIQIRKYGIGANSPPDVLPLWDGFSDPGPDVGPYLDFPDNCCPTKPKAKRGGDVYLSDQYGFDNNGILVEPVMKLLGVIKSDFTLEQLLAALGKYRTEDGYDLPDGYVKVAIKVGRKAVPVLKQSIFTVVGVTEQLVPGYYYPFSTSSVVEHTKPTRGGPVGKTVEAVMLSLYGTNNYNPATPVARLKCSYCDYYGWTPLKDIGTVNCLCGAEFQLTSSCVDAESAGVIKPGCVMLLDKSPGMRLIPGNRTYVSFGGAIWSPIGKVNGVTVWVPRAYSIVAGEHSGAVGSGDTVAINKELVEYLIEGIRVDADTLDNPTCATFIANLDCDTKAPVVHTVESLQGLCLANKIMLGDKPLPTDEFHPFIVGLAYHVQRACWYGALASRTFEAFRDFVRTEEERFAQFFGKVCAPINGCVYLAYTTGRVTLFSAYQVLNTAIAKSKDAFGGVAAIVVDMLKPILEWVLKKMSIAKGAWLPYAEGLLALFKAQFTVVKGKFQFLRASLNSKCHSLCDLLTTIMSKLLTSVKWAGCKVDALYTGTYYYFSRKGVLTEVQLCAKRLGLLLTPKQQKMEVEVLDGDFDAPVTLTDLELEECTGVLEEVFGASDVKLVKGTLVSLASKLFVRTEDGFLYRYVKSGGVLGKAFRLRGGGVSKVTFGDEEVHTIPNTVTVNFSYDVCEGLDAILDKVMAPFQVEEGTKLEDLACVVQKAVYERLSDLFSDCPAELRPINLEDFLTSECFVYSKDYEKILMPEMYFSLEDAVPVDDEMVDDIEDTVEQASDSDDQWLGDEGAEDCDNTIQDVDVATSMTTPCGYTKIAEHVYIKCADIVQEARNYSYAVLVNAANVNLHHGGGVAGALNRATNNAMQKESSEYIKANGSLQPGGHVLLSSHGLASHGILHVVGPDKRLGQDLALLDAVYAAYTGFDSVLTPLVSAGIFGFTVEESLCSLVKNVACTTYVVVYDRQLYERALATSFDVPGPQSSVQHVPAIDWAEAVEVQESIVDQVETPSLGAVDTVDSNADSGLNETARSPENVVGSVPDDVVADVESCVRDLVRQVVKKVKRDKRPPPIVPQQTVEQQPQEISSPGDCNTVLVDVVSMSFSAMVNFGKEKGLLIPVVIDYPAFLKVLKRFSPKEGLFSSNGYEFYGYSRDKPLHEVSKDLNSLGRPLIMIPFGFIVNGQTLAVSAVSMRGLTVPHTVVVPSESSVPLYRAYFNGVFSGDTTAVQDFVVDILLNGARDWDVLQTTCTVDRKVYKTICKRGNTYLCFDDTNLYAITGDVVLKFATVSKARAYLETKLCAPEPLIKVLTTVDGINYSTVLVSTAQSYRAQIGTVFCDGHDWSNKNPMPTDEGTHLYKQDNFSSAEVTAIREYYGVDDSNIIARAMSIRKTVQTWPYTVVDGRVLLAQRDSNCYLNVAISLLQDIDVSFSTPWVCRAYDALKGGNPLPMAEVLIALGKATPGVSDDAHMVLSAVLNHGTVTARRVMQTVCEHCGVSQMVFTGTDACTFYGSVVLDDLYAPVSVVCQCGRPAIRYVSEQKSPWLLMSCTPTQVPLDTSGIWKTAIVFRGPVTAGHYMYAVNGTLISVYDANTRRRTSDLKLPATDILYGPTSFTSDSKVETYYLDGVKRTTIDPDFSKYVKRGDYYFTTAPIEVVAAPKLVTSYDGFYLSSCQNPQLAESFNKAINATKTGPMKLLTMYPNVAGDVVAISDDNVVAHPYGSLHMGKPVLFVTRPNTWKKLVPLLSTVVVNTPNTYDVLAVDPLPVNNETSEEPISVKAPIPLYGLKATMVLNGTTYVPGNKGHLLCLKEFTLTDLQTFYVEGVQPFVLLKASHLSKVLGLRVSDSSLHVNHLSKGVVYAYAATRLTTRVTTSLLGGLVTRSVRKTADFVRSTNPGSKCVGLLCLFYQLFMRFWLLVKKPPIVKVSGIIAYNTGCGVTTCVLNYLRSRCGNISWSRLLKLLRYMLYIWFVWTCLTICGVWLSEPYAPSLVTRFKYFLGIVMPCDYVLVNETGTGWLHHLCMAGMDSLDYPALRMQQHRYGSPYNYTYILMLLEAFFAYLLYTPALPIVGILAVLHLIVLYLPIPLGNSWLVVFLYYIIRLVPFTSMLRMYIVIAFLWLCYKGFLHVRYGCNNVACLMCYKKNVAKRIECSTVVNGVKRMFYVNANGGTHFCTKHNWNCVSCDTYTVDSTFICRQVALDLSAQFKRPIIHTDEAYYEVTSVEVRNGYVYCYFESDGQRSYERFPMDAFTNVSKLHYSELKGAAPAFNVLVFDATNRIEENAVKTAAIYYAQLACKPILLVDKRMVGVVGDDATIARAMFEAYAQNYLLKYSIAMDKVKHLYSTALQQISSGMTVESVLKVFVGSTRAEAKDLESDVDTNDLVSCIRLCHQEGWEWTTDSWNNLVPTYIKQDTLSTLEVGQFMTANAKYVNANIAKGAAVNLIWRYADFIKLSESMRRQLKVAARKTGLNLLVTTSSLKADVPCMVTPFKIIGGHRRIVSWRRVLIHVFMLLVVLNPQWFTPWYIMRPIEYNVVDFKVIDNAVIRDITSADQCFANKFSAFENWYSNRYGSYVNSRGCPMVVGVVSDIVGSLVPGLPARFLRVGTTLLPLVNYGLGAVGSVCYTPHYAINYDVFDTSACVLAATCTLFSSASGERMPYCADAALIQNASRYDMLKPHVMYPFYEHSGYIRFPEVISAGVHIVRTMAMEYCKVGRCDVSEAGLCMSLQPRWVVNNAYFRQQSGVYCGTSAFDLFMNMLLPIFTPVGAVDITTSILMGALLAVVVSMSLYYLLRFRRAFGDYSGVIFTNILAFVLNVIVLCLEGPYPMLPSIYAMVFLYATCYFGSDIACMMHVSFLIMFAGVVPLWVTVLYIVVVLSRHILWFASLCTKRTVQVGDLAFHSFQDAALQTFMLDKEVFLRLKREISSDAYFKYLAMYNKYKYYSGPMDTAAYREAACSHLVMALEKYSNGGGDTIYQPPRCSVASAALQAGLTRMAHPSGLVEPCLVKVNYGSMTLNGIWLDNFVICPRHVMCSRDELANPDYPRLSMRAANYDFHVSQNGHNIRVIGHTMEGSLLKLTVDVNNPKTPAYSFIRVSTGQAMSLLACYDGLPTGVYTCTLRSNGTMRASFLCGSCGSPGFVMNGKEVQFCYLHQLELPNGTHTGTDFSGVFYGPFEDKQVPQLAAPDCTITVNVLAWLYAAVLSGENWFLTKSSISPAEFNNCAVKYMCQSVTSESLQVLQPLAAKTGISVERMLSALKVLLSAGFCGRTIMGSCSLEDEHTPYDIGRQMLGVKLQGKFQSMFRWTLQWFAIIFVLTILILLQLAQWTFVGALPFTLLLPLIGFVAVCVGFVSLLIKHKHTYLTVYLLPVAMVTAYYNFQYTPEGVQGYLLSLYNYVNPGRIDVIGTDLLTMLIISVACTLLSVRMVRTDAYSRIWYVCTAVGWLYNCWTGSADTVAISYLTFMVSVFTNYTGVACASLYAAQFMVWVLKFLDPTILLLYGRFRCVLVCYLLVGYLCTCYFGVFNLINRLFRCTLGNYEYVVSSQELRYMNSHGLLPPTNSWQALMLNIKLAGIGGIPIYRVSTIQSNMTDLKCTSVVLLSVLQQLRVESSSKLWALCVKLHNEILASNSPTEAFEAFVSLLSVLLSLPGAINLDELCSSILENNSVLQAVASEFSNLSSYVDYENAQKAYDTAVATGAPASTVNALKKAMNVAKSVLDKDVATTRKLERMSELAMTAMYKQARAEDRRSKVTAAMQTMLFNMIRRLDSDALSNILNNARNGVVPLGVIPRTAANKLLLVVPDFSVYTATITMPTLTYAGSAWDVMQVADADGKTVNATDITRENSVNLAWPLVVTAQRQQATSPVKLQNNELMPQTVKRMNVVAGVSQTACVTDAVAYYNATKEGRHVMAILADTDGLAFAKVEKSTGDGFVILELEPPCKFMVDTPKGPALKYLYFTKGLKNLCRGTVLGTLACTVRLHAGSATEVASNSSILSLCSFSVDPEATYKDYLDNGGSPIGNCVKMLTPHTGTGLAITAKPDANIDQESFGGASCCLYCRCHIEHPGASGVCKYKGKFVQIPLVGVNDPIGFCIRNVVCAVCNMWQGYGCPCSSLREINLQARDECFLNRVRGTSGVARLVPLGSGVQPDIVLRAFDICNTKVAGFGLHLKNNCCRYQELDADGTQLDSYFVVKRHTESNYLLEQRCYEKLKDCGVVARHDFFKFNIEGVMTPHVSRERLTKYTMADLVYSLRHFDNNNCDTLKEILVLRGCCTADYFDRKDWYDPVENPDIIRVYHNLGETVRKAVLSAVKMADSMVEQGLIGVLTLDNQDLNGQWYDFGDFIEGPAGAGVAVMDTYYSLAMPVYTMTNMLAAECHVDGDFSKPKRVWDICKYDYTQFKYSLFSKYFKYWDMQYHPNCVACADDRCILHCANFNILFSMVLPNTSFGPLVQKIYVDGVPFVVSTGYHYRELGVVMNQDIRQHAQRLSLRELLVYAADPAMHVAASNALADKRTVCMSVAAMTTGVTFQTVKPGQFNEDFYNFAVKCGFFKEGSTISFKHFFYAQDGNAAISDYDYYRYNLPTMCDIKQLLFSLEVVDKYFDCYDGGCLQASQVVVANYDKSAGFPFNKFGKARLYYESLSYADQDELFAYTKRNVLPTITQMNLKYAISAKNRARTVAGVSIASTMTNRQFHQKMLKSIAAARGASVVIGTTKFYGGWNRMLRTLCEGVENPHLMGWDYPKCDRAMPNLLRIFASLILARKHATCCNASERFYRLANECAQVLSEMVLCGGGFYVKPGGTSSGDSTTAYANSVFNICQAVSANLNTFLSIDGNKIYTTYVQELQRRLYLGIYRSNTVDNELVLDYYNYLRKHFSMMILSDDGVVCYNADYAQKGYVADIQGFKELLYFQNNVFMSESKCWVEPDITKGPHEFCSQHTMLVDMKGEQVYLPYPDPSRILGAGCFVDDLLKTDGTLMMERYVSLAIDAYPLTKHPDPEYQNVFWCYLQYIKKLHEELTGHLLDTYSVMLASDNASKYWEVEFYENMYMESATLQSVGTCVVCNSQTSLRCGGCIRRPFLCCKCCYDHVVSTTHKLVLSVTPYVCNNPSCDVADVTQLYLGGMSYYCRDHRPPISFPLCANGQVFGLYKNICTGSPDVADFNSLATCDWSNSKDYVLANTATERLKLFAAETLRATEENAKQAYASAVVKEVLSDRELVLSWETGKTRPPLNRNYVFTGFHITKNSKVQLGEYIFEKGDYGDVVNYRSSTTYKLQVGDYFVLTSHSVQPLSSPTLLPQERYTKLVGLYPAMNVPESFASNVVHYQRVGMSRYTTVQGPPGTGKSHLSIGLALYYPSAKIVYTACSHAAVDALCEKAHKNLPINRCSRIVPAKARVECFSKFKVNDVGAQYVFSTINALPETTADILVVDEVSMCTNYDLSMINARVRAKHIVYVGDPAQLPAPRTLLTKGTLAPEHFNSVCRLMVAVGPDIFLATCYRCPKEIVDTVSALVYDKKLKANKVTTGECYKCYYKGSVTHDSSSAINKPQLGLVKEFLIKNPKWQSAVFISPYNSQNSVARRMLGLQTQTVDSSQGSEFDYVIYCQTSDTAHALNVNRFNVAITRAKKGILCVMSDSTLYESLEFTPLDVNDYVKPKMQSEVTVGLFKDCAKAEPLGPAYAPTFVSVNDKFKLNESLCVHFDTTELQMPYNRLISKMGFKFDLNIPGYSKLFITREQAIREVRGWVGFDVEGAHACGPNIGTNLPLQIGFSTGVNFVVTPSGYIDTESGSRLANVVSKAPPGDQFKHLIPLMRKGEPWSVVRKRIVEMLCDTLDGVSDTVTFVTWAHGFELTTLHYFAKVGPERKCFMCPRRATLFSSVYGAYSCWSHHRHIGGADFVYNPFLVDVQQWGYVGNLQVNHDNVCDVHKGAHVASCDAIMTRCLAIHDCFCGEVNWDVEYPIIANELAINRACRSVQRVVLKAAVKALHIETIYDIGNPKAIKVYGVNVNNWNFYDTNPVVEGVKQLHYVYDVHRDQFKDGLAMFWNCNVDCYPHNALVCRFDTRVLSKLNLAGCNGGSLYVNQHAFHTDAFNKNAFVNLKPLPFFYYSDTACENATGVSTNYVSEVDYVPLKSNVCITRCNLGGAVCKKHADEYRNFLESYNTMVSAGFTLWVDKTFDVFNLWSTFVKLQSLENVAYNVLKSGHFTAVAGELPVAILNDRLYIKEDGADKLLFTNNTCLPTNVAFELWAKRSVNVVPEVKLLRNLGVTCTYNLVIWDYESNAPLVPNTVGICTYTDLTKLDDQVVLVDGRQLDAYSKFCQLKNAIYFSPSKPKCVCTRGPTHASINGVVVEAPDRGTAFWYAMRKDGAFVQPTDGYFTQSRTVDDFQPRTQLEIDFLDLEQSCFLDKYDLHDLGLEHIVYGQFDGTIGGLHLLIGAVRRKRTAHLVMETVLGTDTVTSYAVIDQPTASSKQVCSVVDIILDDFIALIKAQDRSVVSKVVQCCLDFKVFRFMLWCKGGKISTFYPQLQAKQDWKPGYSMPALYKVQNAVLEPCLLHNYGQAARLPSGTLMNVAKYTQLCQYLNTCSLAVPAKMRVMHFGAGSDKGVCPGTAVLKQWLPADAYLVDNDLCYCASDADSTYVGSCETFFSVNKWDFIFSDMYDARTKNTSGDNTSKEGFFTYLTGFIRSKLALGGSIAIKITEHSWSADLYAIMGHFNWWTCFCTSVNSSSSEAFLIGVNYIGVGALLDGWQMHANYVFWRNSTVMQLSSYSLYDLQRFPLRLKGTPVMSLKEDQLNELVLNLIRAGRLIVRDAVDIGVRGVACSGV |
| Enzyme Length | 6930 |
| Uniprot Accession Number | P0C6W5 |
| Absorption | |
| Active Site | ACT_SITE 1533; /note=For PL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1694; /note=For PL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 3144; /note=For 3CL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00772; ACT_SITE 3248; /note=For 3CL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00772; ACT_SITE 4992; /evidence=ECO:0000255|PROSITE-ProRule:PRU01293; ACT_SITE 4993; /evidence=ECO:0000255|PROSITE-ProRule:PRU01293; ACT_SITE 4994; /evidence=ECO:0000255|PROSITE-ProRule:PRU01293; ACT_SITE 5856; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; ACT_SITE 5858; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; ACT_SITE 5957; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; ACT_SITE 6037; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; ACT_SITE 6042; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; ACT_SITE 6523; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303; ACT_SITE 6537; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303; ACT_SITE 6576; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303; ACT_SITE 6679; /evidence=ECO:0000255|PROSITE-ProRule:PRU01300; ACT_SITE 6763; /evidence=ECO:0000255|PROSITE-ProRule:PRU01300; ACT_SITE 6803; /evidence=ECO:0000255|PROSITE-ProRule:PRU01300; ACT_SITE 6836; /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]: 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. {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:19264783}.; 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}.; 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 5447..5454; /note=ATP; /evidence=ECO:0000255 |
| Features | Active site (19); Beta strand (7); Chain (15); Domain (27); Helix (2); Metal binding (32); Nucleotide binding (1); Region (6); Site (14); Transmembrane (20); 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;Reference proteome;Repeat;Ribosomal frameshifting;Thiol protease;Transferase;Transmembrane;Transmembrane helix;Ubl conjugation pathway;Viral RNA replication;Viral immunoevasion;Zinc;Zinc-finger |
| Interact With | |
| 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 | NMR spectroscopy (1) |
| Cross Reference PDB | 5UTV; |
| Mapped Pubmed ID | 28580734; |
| Motif | |
| Gene Encoded By | |
| Mass | 769,729 |
| Kinetics | |
| Metal Binding | METAL 4168; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4171; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4177; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4184; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4211; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4214; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4222; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4224; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 5170; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5173; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5181; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5184; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5191; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5194; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5198; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5204; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5215; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5220; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5237; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5240; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00986; METAL 5973; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 5976; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 5992; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 5995; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6026; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6030; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6033; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6048; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU01298; METAL 6218; /note=Zinc 8; /evidence=ECO:0000255|PROSITE-ProRule:PRU01299; METAL 6242; /note=Zinc 8; /evidence=ECO:0000255|PROSITE-ProRule:PRU01299; METAL 6253; /note=Zinc 8; /evidence=ECO:0000255|PROSITE-ProRule:PRU01299; METAL 6256; /note=Zinc 8; /evidence=ECO:0000255|PROSITE-ProRule:PRU01299 |
| Rhea ID | RHEA:21248; RHEA:13065; RHEA:67020; RHEA:67732 |
| Cross Reference Brenda |