| IED ID | IndEnz0002013884 |
| Enzyme Type ID | protease013884 |
| Protein Name |
Replicase polyprotein 1a pp1a ORF1a polyprotein Cleaved into: Non-structural protein 1 nsp1 p28 ; Non-structural protein 2 nsp2 p65 ; Non-structural protein 3 nsp3 EC 3.4.19.12 EC 3.4.22.69 PL1-PRO/PL2-PRO PL1/PL2 Papain-like proteinases 1/2 p210 ; Non-structural protein 4 nsp4 Peptide HD2 p44 ; 3C-like proteinase 3CL-PRO 3CLp EC 3.4.22.- M-PRO nsp5 p27 ; Non-structural protein 6 nsp6 ; Non-structural protein 7 nsp7 p10 ; Non-structural protein 8 nsp8 p22 ; Non-structural protein 9 nsp9 p12 ; Non-structural protein 10 nsp10 Growth factor-like peptide GFL p15 ; Non-structural protein 11 nsp11 |
| Gene Name | 1a |
| Organism | Murine coronavirus (strain A59) (MHV-A59) (Murine hepatitis virus) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Cornidovirineae Coronaviridae Orthocoronavirinae Betacoronavirus Embecovirus Murine coronavirus Murine hepatitis virus Murine coronavirus (strain A59) (MHV-A59) (Murine hepatitis virus) |
| Enzyme Sequence | MAKMGKYGLGFKWAPEFPWMLPNASEKLGNPERSEEDGFCPSAAQEPKVKGKTLVNHVRVNCSRLPALECCVQSAIIRDIFVDEDPQKVEASTMMALQFGSAVLVKPSKRLSIQAWTNLGVLPKTAAMGLFKRVCLCNTRECSCDAHVAFHLFTVQPDGVCLGNGRFIGWFVPVTAIPEYAKQWLQPWSILLRKGGNKGSVTSGHFRRAVTMPVYDFNVEDACEEVHLNPKGKYSCKAYALLKGYRGVKPILFVDQYGCDYTGCLAKGLEDYGDLTLSEMKELFPVWRDSLDSEVLVAWHVDRDPRAAMRLQTLATVRCIDYVGQPTEDVVDGDVVVREPAHLLAANAIVKRLPRLVETMLYTDSSVTEFCYKTKLCECGFITQFGYVDCCGDTCDFRGWVAGNMMDGFPCPGCTKNYMPWELEAQSSGVIPEGGVLFTQSTDTVNRESFKLYGHAVVPFGSAVYWSPCPGMWLPVIWSSVKSYSGLTYTGVVGCKAIVQETDAICRSLYMDYVQHKCGNLEQRAILGLDDVYHRQLLVNRGDYSLLLENVDLFVKRRAEFACKFATCGDGLVPLLLDGLVPRSYYLIKSGQAFTSMMVNFSHEVTDMCMDMALLFMHDVKVATKYVKKVTGKLAVRFKALGVAVVRKITEWFDLAVDIAASAAGWLCYQLVNGLFAVANGVITFVQEVPELVKNFVDKFKAFFKVLIDSMSVSILSGLTVVKTASNRVCLAGSKVYEVVQKSLSAYVMPVGCSEATCLVGEIEPAVFEDDVVDVVKAPLTYQGCCKPPTSFEKICIVDKLYMAKCGDQFYPVVVDNDTVGVLDQCWRFPCAGKKVEFNDKPKVRKIPSTRKIKITFALDATFDSVLSKACSEFEVDKDVTLDELLDVVLDAVESTLSPCKEHDVIGTKVCALLDRLAGDYVYLFDEGGDEVIAPRMYCSFSAPDDEDCVAADVVDADENQDDDAEDSAVLVADTQEEDGVAKGQVEADSEICVAHTGSQEELAEPDAVGSQTPIASAEETEVGEASDREGIAEAKATVCADAVDACPDQVEAFEIEKVEDSILDELQTELNAPADKTYEDVLAFDAVCSEALSAFYAVPSDETHFKVCGFYSPAIERTNCWLRSTLIVMQSLPLEFKDLEMQKLWLSYKAGYDQCFVDKLVKSVPKSIILPQGGYVADFAYFFLSQCSFKAYANWRCLECDMELKLQGLDAMFFYGDVVSHMCKCGNSMTLLSADIPYTLHFGVRDDKFCAFYTPRKVFRAACAVDVNDCHSMAVVEGKQIDGKVVTKFIGDKFDFMVGYGMTFSMSPFELAQLYGSCITPNVCFVKGDVIKVVRLVNAEVIVNPANGRMAHGAGVAGAIAEKAGSAFIKETSDMVKAQGVCQVGECYESAGGKLCKKVLNIVGPDARGHGKQCYSLLERAYQHINKCDNVVTTLISAGIFSVPTDVSLTYLLGVVTKNVILVSNNQDDFDVIEKCQVTSVAGTKALSLQLAKNLCRDVKFVTNACSSLFSESCFVSSYDVLQEVEALRHDIQLDDDARVFVQANMDCLPTDWRLVNKFDSVDGVRTIKYFECPGGIFVSSQGKKFGYVQNGSFKEASVSQIRALLANKVDVLCTVDGVNFRSCCVAEGEVFGKTLGSVFCDGINVTKVRCSAIYKGKVFFQYSDLSEADLVAVKDAFGFDEPQLLKYYTMLGMCKWPVVVCGNYFAFKQSNNNCYINVACLMLQHLSLKFPKWQWQEAWNEFRSGKPLRFVSLVLAKGSFKFNEPSDSIDFMRVVLREADLSGATCNLEFVCKCGVKQEQRKGVDAVMHFGTLDKGDLVRGYNIACTCGSKLVHCTQFNVPFLICSNTPEGRKLPDDVVAANIFTGGSVGHYTHVKCKPKYQLYDACNVNKVSEAKGNFTDCLYLKNLKQTFSSVLTTFYLDDVKCVEYKPDLSQYYCESGKYYTKPIIKAQFRTFEKVDGVYTNFKLVGHSIAEKLNAKLGFDCNSPFVEYKITEWPTATGDVVLASDDLYVSRYSSGCITFGKPVVWLGHEEASLKSLTYFNRPSVVCENKFNVLPVDVSEPTDKGPVPAAVLVTGVPGADASAGAGIAKEQKACASASVEDQVVTEVRQEPSVSAADVKEVKLNGVKKPVKVEGSVVVNDPTSETKVVKSLSIVDVYDMFLTGCKYVVWTANELSRLVNSPTVREYVKWGMGKIVTPAKLLLLRDEKQEFVAPKVVKAKAIACYCAVKWFLLYCFSWIKFNTDNKVIYTTEVASKLTFKLCCLAFKNALQTFNWSVVSRGFFLVATVFLLWFNFLYANVILSDFYLPNIGPLPTFVGQIVAWFKTTFGVSTICDFYQVTDLGYRSSFCNGSMVCELCFSGFDMLDNYDAINVVQHVVDRRLSFDYISLFKLVVELVIGYSLYTVCFYPLFVLIGMQLLTTWLPEFFMLETMHWSARLFVFVANMLPAFTLLRFYIVVTAMYKVYCLCRHVMYGCSKPGCLFCYKRNRSVRVKCSTVVGGSLRYYDVMANGGTGFCTKHQWNCLNCNSWKPGNTFITHEAAADLSKELKRPVNPTDSAYYSVTEVKQVGCSMRLFYERDGQRVYDDVNASLFVDMNGLLHSKVKGVPETHVVVVENEADKAGFLGAAVFYAQSLYRPMLMVEKKLITTANTGLSVSRTMFDLYVDSLLNVLDVDRKSLTSFVNAAHNSLKEGVQLEQVMDTFIGCARRKCAIDSDVETKSITKSVMSAVNAGVDFTDESCNNLVPTYVKSDTIVAADLGVLIQNNAKHVQANVAKAANVACIWSVDAFNQLSADLQHRLRKACSKTGLKIKLTYNKQEANVPILTTPFSLKGGAVFSRMLQWLFVANLICFIVLWALMPTYAVHKSDMQLPLYASFKVIDNGVLRDVSVTDACFANKFNQFDQWYESTFGLAYYRNSKACPVVVAVIDQDIGHTLFNVPTTVLRYGFHVLHFITHAFATDSVQCYTPHMQIPYDNFYASGCVLSSLCTMLAHADGTPHPYCYTGGVMHNASLYSSLAPHVRYNLASSNGYIRFPEVVSEGIVRVVRTRSMTYCRVGLCEEAEEGICFNFNRSWVLNNPYYRAMPGTFCGRNAFDLIHQVLGGLVRPIDFFALTASSVAGAILAIIVVLAFYYLIKLKRAFGDYTSVVVINVIVWCINFLMLFVFQVYPTLSCLYACFYFYTTLYFPSEISVVMHLQWLVMYGAIMPLWFCIIYVAVVVSNHALWLFSYCRKIGTEVRSDGTFEEMALTTFMITKESYCKLKNSVSDVAFNRYLSLYNKYRYFSGKMDTAAYREAACSQLAKAMETFNHNNGNDVLYQPPTASVTTSFLQSGIVKMVSPTSKVEPCIVSVTYGNMTLNGLWLDDKVYCPRHVICSSADMTDPDYPNLLCRVTSSDFCVMSGRMSLTVMSYQMQGCQLVLTVTLQNPNTPKYSFGVVKPGETFTVLAAYNGRPQGAFHVTLRSSHTIKGSFLCGSCGSVGYVLTGDSVRFVYMHQLELSTGCHTGTDFSGNFYGPYRDAQVVQLPVQDYTQTVNVVAWLYAAIFNRCNWFVQSDSCSLEEFNVWAMTNGFSSIKADLVLDALASMTGVTVEQVLAAIKRLHSGFQGKQILGSCVLEDETPSDVYQQLAGVKLQSKRTRVIKGTCCWILASTFLFCSIISAFVKWTMFMYVTTHMLGVTLCALCFVSFAMLLIKHKHLYLTMYIMPVLCTFYTNYLVVYKQSFRGLAYAWLSHFVPAVDYTYMDEVLYGVVLLVAMVFVTMRSINHDVFSIMFLVGRLVSLVSMWYFGANLEEEVLLFLTSLFGTYTWTTMLSLATAKVIAKWLAVNVLYFTDVPQIKLVLLSYLCIGYVCCCYWGILSLLNSIFRMPLGVYNYKISVQELRYMNANGLRPPRNSFEALMLNFKLLGIGGVPVIEVSQIQSRLTDVKCANVVLLNCLQHLHIASNSKLWQYCSTLHNEILATSDLSMAFDKLAQLLVVLFANPAAVDSKCLASIEEVSDDYVRDNTVLQALQSEFVNMASFVEYELAKKNLDEAKASGSANQQQIKQLEKACNIAKSAYERDRAVARKLERMADLALTNMYKEARINDKKSKVVSALQTMLFSMVRKLDNQALNSILDNAVKGCVPLNAIPSLTSNTLTIIVPDKQVFDQVVDNVYVTYAGNVWHIQFIQDADGAVKQLNEIDVNSTWPLVIAANRHNEVSTVVLQNNELMPQKLRTQVVNSGSDMNCNTPTQCYYNTTGTGKIVYAILSDCDGLKYTKIVKEDGNCVVLELDPPCKFSVQDVKGLKIKYLYFVKGCNTLARGWVVGTLSSTVRLQAGTATEYASNSAILSLCAFSVDPKKTYLDYIKQGGVPVTNCVKMLCDHAGTGMAITIKPEATTNQDSYGGASVCIYCRSRVEHPDVDGLCKLRGKFVQVPLGIKDPVSYVLTHDVCQVCGFWRDGSCSCVGTGSQFQSKDTNFLNGFGVQV |
| Enzyme Length | 4468 |
| Uniprot Accession Number | P0C6V0 |
| Absorption | |
| Active Site | ACT_SITE 1121; /note=For PL1-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1272; /note=For PL1-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1716; /note=For PL2-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1873; /note=For PL2-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 3374; /note=For 3CL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00772; ACT_SITE 3478; /note=For 3CL-PRO activity |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: 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; CATALYTIC ACTIVITY: 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; |
| DNA Binding | |
| EC Number | 3.4.19.12; 3.4.22.69; 3.4.22.- |
| Enzyme Function | FUNCTION: The papain-like proteinase 1 (PL1-PRO) and papain-like proteinase 2 (PL2-PRO) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3 (By similarity). {ECO:0000250}.; FUNCTION: [3C-like proteinase]: Responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). {ECO:0000255|PROSITE-ProRule:PRU00772}.; FUNCTION: Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter. {ECO:0000250}.; FUNCTION: Nsp9 is a ssRNA-binding protein. {ECO:0000250}.; FUNCTION: [Non-structural protein 1]: Binds to the 40S ribosomal subunit and inhibits host translation. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (By similarity). {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (6); Beta strand (6); Chain (12); Domain (15); Helix (4); Metal binding (8); Mutagenesis (9); Natural variant (2); Region (4); Sequence conflict (6); Site (10); Transmembrane (18); Zinc finger (4) |
| Keywords | 3D-structure;Activation of host autophagy by virus;Decay of host mRNAs by virus;Eukaryotic host gene expression shutoff by virus;Eukaryotic host translation shutoff by virus;Host cytoplasm;Host gene expression shutoff by virus;Host mRNA suppression by virus;Host membrane;Host-virus interaction;Hydrolase;Inhibition of host IRF3 by virus;Inhibition of host ISG15 by virus;Inhibition of host RLR pathway by virus;Inhibition of host innate immune response by virus;Inhibition of host interferon signaling pathway by virus;Membrane;Metal-binding;Modulation of host ubiquitin pathway by viral deubiquitinase;Modulation of host ubiquitin pathway by virus;Protease;RNA-binding;Reference proteome;Repeat;Ribosomal frameshifting;Thiol protease;Transmembrane;Transmembrane helix;Ubl conjugation pathway;Viral immunoevasion;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Non-structural protein 3]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; 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.; 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.; 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.; 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. |
| 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 | 2M0A; |
| Mapped Pubmed ID | 23302895; |
| Motif | |
| Gene Encoded By | |
| Mass | 496,341 |
| Kinetics | |
| Metal Binding | METAL 4391; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4394; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4400; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4407; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4433; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4436; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4444; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4446; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.22.B14; |