| IED ID | IndEnz0002001867 |
| Enzyme Type ID | protease001867 |
| Protein Name |
Replicase polyprotein 1ab ORF1ab polyprotein Cleaved into: Nsp1 EC 3.4.22.- ; Nsp1-alpha papain-like cysteine proteinase EC 3.4.22.- PCP1-alpha ; Nsp1-beta papain-like cysteine proteinase EC 3.4.22.- PCP1-beta ; Nsp2 cysteine proteinase EC 3.4.19.12 EC 3.4.22.- CP2 CP ; Non-structural protein 3 Nsp3 ; 3C-like serine proteinase 3CLSP EC 3.4.21.- Nsp4 ; Non-structural protein 5-6-7 Nsp5-6-7 ; Non-structural protein 5 Nsp5 ; Non-structural protein 6 Nsp6 ; Non-structural protein 7-alpha Nsp7-alpha ; Non-structural protein 7-beta Nsp7-beta ; Non-structural protein 8 Nsp8 ; RNA-directed RNA polymerase Pol RdRp EC 2.7.7.48 Nsp9 ; Helicase Hel EC 3.6.4.12 EC 3.6.4.13 Nsp10 ; Uridylate-specific endoribonuclease nsp11 EC 4.6.1.- Non-structural protein 11 Nsp11 ; Non-structural protein 12 Nsp12 |
| Gene Name | rep 1a-1b |
| Organism | Porcine reproductive and respiratory syndrome virus (strain 16244B) (PRRSV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Arnidovirineae Arteriviridae unclassified Arteriviridae Porcine reproductive and respiratory syndrome virus (PRRSV) Porcine reproductive and respiratory syndrome virus (strain 16244B) (PRRSV) |
| Enzyme Sequence | MSGILDRCTCTPNARVFVAEGQVYCTRCLSARSLLPLNLQVSELGVLGLFYRPEEPLRWTLPRAFPTVECSPAGACWLSAIFPIARMTSGNLNFQQRMVRVAAEIYRAGQLTPAVLKALQVYERGCRWYPIVGPVPGVAVFANSLHVSDKPFPGATHVLTNLPLPQRPKPEDFCPFECAMATVYDIGHDAVMYVAEGKISWAPRGGDEVKFEAVPGELKLIANRLRTSFPPHHAVDMSKFAFTAPGCGVSMRVERQHGCLPADTVPEGNCWWSLFDLLPLEVQDKEIRHANQFGYQTKHGVSGKYLQRRLQVNGLRAVTDSNGPIVVQYFSVKESWIRHLKLAGEPSYSGFEDLLRIRVEPNTSPLANTEGKIFRFGSHKWYGAGKRARKARSCATATVAGRALSVRETRQAKEHEVAGADKAEHLKHYSPPAEGNCGWHCISAIANRMVNSIFETTLPERVRPPDDWATDDDLANAIQILRLPAALDRNGACTSAKYVLKLEGEHWTVTVTPGMSPSLLPLECVQGCCEHKGGLGSPDAIEVSGFDPACLDWLAEVMHLPSSAIPAALAEMSGDSDRSASPVTTVWTVSQFFARHSGGNHPDQVRLGKIISLCQVIEDCCCSQNKTNRVTPEEVAAKIDLYLRGATNLEECLARLEKARPPRVIDTSFDWDVVLPGVEAATQTNKLPQVNQCRALVPVVTQKSLDNNSVPLTAFSLANYYYRAQGDEVRHRERLTAVLSKLEEVVREEYGLMPTEPGPRPTLPRGLDELKDQMEEDLLRLANAQATSDMMAWAVEQVDLKTWVKNYPRWTPPPPPPKVQPRKTKPVKSLPERKPVPAPRRKVGPDCGSPVSLGGDVPNSWEDLAVSSPLDLPTPPEPATLSSELVIVSSPQCIFRPATPLSEPAPIPAPRGTVSRPVTPLSEPIPVPAPRRKFQQVKRLSSAAAVPLHQNEPLDLSASSQTEYEASPSAPPQSGGVLGVEGHEAEETLSEISDMSGNIKPASVSSSSSLSSVEITRPKYSAQAIIDSGGPCSGHLQGVKETCLSVMREACDATKLDDPATQEWLSRMWDRVDMLTWRNTSVCQAIRTLDGRLKFLPKMILETPPPYPCEFVMMPHTPAPSVGAESDLTIGSVATEDVPRILEKIENVGEMANQEPSAFSEDKPVDDQLVNDPRISSRRPDESTAAPSAGTGGAGSFTDLPSSDGADADGGGPFRTAKRKAERLFDQLSRQVFDLVSHLPVFFSRLFHPGGGYSTGDWGFAAFTLLCLFLCYSYPAFGIAPLLGVFSGTSRRVRMGVFGCWLAFAVGLFKPVSDPVGAACEFDSPECRNILLSFELLKPWDPVRSLVVGPVGLGLAILGRLLGGARCIWHFLLRLGIVADCILAGAYVLSQGRCKKCWGSCIRTAPNEVAFNVFPFTRATRSSLIDLCDRFCAPKGMDPIFLATGWRGCWAGRSPIEQPSEKPIAFAQLDEKKITARTVVAQPYDPNQAVKCLRVLQAGGAMVAEAVPKVVKVSAVPFRAPFFPTGVKVDPDCRVVVDPDTFTAALRSGYSTTNLVLGVGDFAQLNGLKIRQISKPSGGGPHLMAALHVACSMALHMLTGIYVTAVGSCGTGTNDPWCANPFAVPGYGPGSLCTSRLCISQHGLTLPLTALVAGFGIQEIALVVLIFVSIGGMAHRLSCKADMLCILLAIASYVWVPLTWLLCVFPCWLRCFSLHPLTILWLVFFLISVNMPSGILAMVLLVSLWLLGRYTNVAGLVTPYDIHHYTSGPRGVAALATAPDGTYLAAVRRAALTGRTMLFTPSQLGSLLEGAFRTRKPSLNTVNVIGSSMGSGGVFTIDGKVKCVTAAHVLTGNSARVSGVGFNQMLDFDVKGDFAIADCPNWQGAAPKAQFCADGWTGRAYWLTSSGVEPGVIGKGFAFCFTACGDSGSPVITEAGELVGVHTGSNKQGGGIVTRPSGQFCNVAPIKLSELSEFFAGPKVPLGDVKVGSHIIKDISEVPSDLCALLAAKPELEGGLSTVQLLCVFFLLWRMMGHAWTPLVAVSFFILNEVLPAVLVRSVFSFGMFVLSWLTPWSAQILMIRLLTAALNRNRWSLAFFSLGAVTGFVADLAATQGHPLQAVMNLSTYAFLPRMMVVTSPVPVITCGVVHLLAIILYLFKYRGLHQILVGDGVFSAAFFLRYFAEGKLREGVSQSCGMNHESLTGALAMRLNDEDLDFLMKWTDFKCFVSASNMRNAAGQFIEAAYAKALRVELAQLVQVDKVRGVLAKLEAFADTVAPQLSPGDIVVALGHTPVGSIFDLKVGSTKHTLQAIETRVLAGSKMTVARVVDPTPTPPPAPVPIPLPPKVLENGPNAWGDEDRLNKKKRRRMEALGIYVMGGKKYQKFWDKNSGDVFYEEVHNNTDEWECLRVGDPADFDPEKGTLCGHVTIENKAYHVYISPSGKKFLVPVNPENGRVQWEAAKLSMEQALGMMNVDGELTAKELEKLKRIIDKLQGLTKEQCLNCLLAASGLTRCGRGGLVVTETAVKIVKFHNRTFTLGPVNLKVASEVELKDAVEHNQHPVARPIDGGVVLLRSAVPSLIDVLISGADASPKLLAHHGPGNTGIDGTLWDFESEATKEEVALSAQIIQACDIRRGDAPKIGLPYKLYPVRGNPERVKGVLQNTRFGDIPYKTPSDTGSPVHAAACLTPNATPVTDGRSVLATTMPPGFELYVPTIPASVLDYLDSRPDCPKQLTEHGCEDAALKDLSKYDLSTQGFVLPGVLRLVRKYLFAHVGKCPPVHRPSTYPAKNSMAGINGNRFPTKDIQSVPEIDVLCAQAVRENWQTVTPCTLKKQYCGKKKTRTILGTNNFIALAHRAALSGVTQGFMKKAFNSPIALGKNKFKELQTSVLGRCLEADLASCDRSTPAIVRWFAANLLYELACAEEHLPSYVLNCCHDLLVTQSGAVTKRGGLSSGDPITSVSNTIYSLVIYAQHMVLSYFKSGHPHGLLFLQDQLKFEDMLKVQPLIVYSDDLVLYAESPTMPNYHWWVEHLNLMLGFQTDPKKTAITDSPSFLGCRIINGRQLVPNRDRILAALAYHMKASNVSEYYASAAAILMDSCACLEYDPEWFEELVVGIAQCARKDGYSFPGTPFFMSMWEKLRSNYEGKKSRVCGYCGAPAPYATACGLDVCIYHTHFHQHCPVTIWCGHPAGSGSCSECKSPVGKGTSPLDEVLEQVPYKPPRTVIMHVEQGLTPLDPGRYQTRRGLVSVRRGIRGNEVELPDGDYASTALLPTCKEINMVAVASNVLRSRFIIGPPGAGKTYWLLQQVQDGDVIYTPTHQTMLDMIRALGTCRFNVPAGTTLQFPVPSRTGPWVRILAGGWCPGKNSFLDEAAYCNHLDVLRLLSKTTLTCLGDFKQLHPVGFDSHCYVFDIMPQTQLKTIWRFGQNICDAIQPDYRDKLMSMVNTTRVTYVEKPVRYGQVLTPYHRDREDDAITIDSSQGATFDVVTLHLPTKDSLNRQRALVAITRARHAIFVYDPHRQLQGLFDLPAKGTPVNLAVHRDGQLIVLDRNNKECTVAQALGNGDKFRATDKRVVDSLRAICADLEGSSSPLPKVAHNLGFYFSPDLTQFAKLPVELAPHWPVVTTQNNEKWPDRLVASLRPIHKYSRACIGAGYMVGPSVFLGTPGVVSYYLTKFVKGEAQLLPETVFSTGRIEVDCREYLDDREREVAASLPHAFIGDVKGTTVGGCHHVTSRYLPRVLPKESVAVVGVSSPGKAAKALCTLTDVYLPDLEAYLHPETQSKCWKMMLDFKEVRLMVWRDKTAYFQLEGRYFTWYQLASYASYIRVPVNSTVYLDPCMGPALCNRRVVGSTHWGADLAVTPYDYGAKIILSSAYHGEMPPGYKILACAEFSLDDPVRYKHTWGFESDTAYLYEFTGNGEDWEDYNDAFRARQEGKIYKATATSLKFHFPPGPVIEPTLGLN |
| Enzyme Length | 3961 |
| Uniprot Accession Number | Q9YN02 |
| Absorption | |
| Active Site | ACT_SITE 76; /note=For Nsp1-alpha papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00872; ACT_SITE 146; /note=For Nsp1-alpha papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00872; ACT_SITE 270; /note=For Nsp1-beta papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00873; ACT_SITE 339; /note=For Nsp1-beta papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00873; ACT_SITE 437; /note=For Nsp2 cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00871; ACT_SITE 506; /note=For Nsp2 cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00871; ACT_SITE 1848; /note=Charge relay system; for 3C-like serine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00826; ACT_SITE 1873; /note=Charge relay system; for 3C-like serine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00826; ACT_SITE 1927; /note=Charge relay system; for 3C-like serine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00826; ACT_SITE 3714; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303; ACT_SITE 3729; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303; ACT_SITE 3758; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: 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: 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: 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: 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: [Uridylate-specific endoribonuclease nsp11]: 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:P19811}; |
| DNA Binding | |
| EC Number | 3.4.22.-; 3.4.22.-; 3.4.22.-; 3.4.19.12; 3.4.22.-; 3.4.21.-; 2.7.7.48; 3.6.4.12; 3.6.4.13; 4.6.1.- |
| Enzyme Function | FUNCTION: The replicase polyprotein 1ab 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.; FUNCTION: Nsp1 is essential for viral subgenomic mRNA synthesis. {ECO:0000250}.; FUNCTION: Nsp1-alpha inhibits IFN-beta production. Counteracts the action of NF-kappaB by decreasing the phosphorylation of IkappaB-alpha, such that the degradation of IkappaB-alpha is suppressed. This leads to the blockage of NF-kappaB nuclear translocation and thus interference of NF-kappaB activation. Also seems to inhibit IRF3-dependent pathways (By similarity). {ECO:0000250}.; FUNCTION: Nsp2 cysteine proteinase which cleaves the nsp2/nsp3 site in the polyprotein. Also displays deubiquitinating and deISGylase activities. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent host innate immunity. Deubiquitinates host NFKBIA, thereby interfering with NFKBIA degradation and impairing subsequent NF-kappa-B activation (By similarity). {ECO:0000250}.; FUNCTION: The 3C-like serine proteinase chain is responsible for the majority of cleavages as it cleaves the C-terminus of the polyprotein. {ECO:0000250}.; FUNCTION: The helicase chain, which contains a zinc finger structure, displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. {ECO:0000250}.; FUNCTION: [Uridylate-specific endoribonuclease nsp11]: 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, ECO:0000250|UniProtKB:P19811}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 3298..3305; /note=ATP; /evidence=ECO:0000250 |
| Features | Active site (12); Alternative sequence (1); Beta strand (16); Chain (17); Compositional bias (5); Domain (11); Erroneous initiation (1); Helix (6); Metal binding (12); Nucleotide binding (1); Region (10); Site (13); Transmembrane (13); Turn (2); Zinc finger (1) |
| Keywords | 3D-structure;ATP-binding;Endonuclease;Helicase;Host cytoplasm;Host membrane;Host nucleus;Host-virus interaction;Hydrolase;Inhibition of host ISG15 by virus;Inhibition of host NF-kappa-B by virus;Inhibition of host STAT1 by virus;Inhibition of host innate immune response by virus;Inhibition of host interferon signaling pathway by virus;Lyase;Membrane;Metal-binding;Modulation of host ubiquitin pathway by viral deubiquitinase;Modulation of host ubiquitin pathway by virus;Multifunctional enzyme;Nuclease;Nucleotide-binding;Nucleotidyltransferase;Protease;RNA-directed RNA polymerase;Ribosomal frameshifting;Serine protease;Thiol protease;Transferase;Transmembrane;Transmembrane helix;Viral RNA replication;Viral immunoevasion;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Nsp1]: Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Nsp1-alpha papain-like cysteine proteinase]: Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Nsp1-beta papain-like cysteine proteinase]: Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Nsp2 cysteine proteinase]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 3]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 5-6-7]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [3C-like serine proteinase]: Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm, host perinuclear region {ECO:0000305}.; SUBCELLULAR LOCATION: [Helicase]: Host cytoplasm, host perinuclear region {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | PTM: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. Nsp1 is autocleaved into two subunits, Nsp1-alpha and Nsp1-beta. There are two alternative pathways for processing. Either nsp4-5 is cleaved, which represents the major pathway or the nsp5-6 and nsp6-7 are processed, which represents the minor pathway. The major pathway occurs when nsp2 acts as cofactor for nsp4 (By similarity). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 5EYI; 5YLX; |
| Mapped Pubmed ID | 27795409; 31969884; |
| Motif | |
| Gene Encoded By | |
| Mass | 432,802 |
| Kinetics | |
| Metal Binding | METAL 3151; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3154; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3164; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3169; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3172; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3174; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3176; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3178; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3185; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3187; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3194; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 3197; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985 |
| Rhea ID | RHEA:21248; RHEA:13065; RHEA:67732 |
| Cross Reference Brenda |