| IED ID | IndEnz0002010722 |
| Enzyme Type ID | protease010722 |
| Protein Name |
Replicase polyprotein 1ab ORF1ab polyprotein Cleaved into: Nsp1 papain-like cysteine proteinase PCP EC 3.4.22.- ; 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 | Equine arteritis virus (strain Bucyrus) (EAV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Arnidovirineae Arteriviridae Equarterivirinae Alphaarterivirus Alphaarterivirus equid Equine arteritis virus (EAV) Equine arteritis virus (strain Bucyrus) (EAV) |
| Enzyme Sequence | MATFSATGFGGSFVRDWSLDLPDACEHGAGLCCEVDGSTLCAECFRGCEGMEQCPGLFMGLLKLASPVPVGHKFLIGWYRAAKVTGRYNFLELLQHPAFAQLRVVDARLAIEEASVFISTDHASAKRFPGARFALTPVYANAWVVSPAANSLIVTTDQEQDGFCWLKLLPPDRREAGLRLYYNHYREQRTGWLSKTGLRLWLGDLGLGINASSGGLKFHIMRGSPQRAWHITTRSCKLKSYYVCDISEADWSCLPAGNYGGYNPPGDGACGYRCLAFMNGATVVSAGCSSDLWCDDELAYRVFQLSPTFTVTIPGGRVCPNAKYAMICDKQHWRVKRAKGVGLCLDESCFRGICNCQRMSGPPPAPVSAAVLDHILEAATFGNVRVVTPEGQPRPVPAPRVRPSANSSGDVKDPAPVPPVPKPRTKLATPNPTQAPIPAPRTRLQGASTQEPLASAGVASDSAPKWRVAKTVYSSAERFRTELVQRARSVGDVLVQALPLKTPAVQRYTMTLKMMRSRFSWHCDVWYPLAVIACLLPIWPSLALLLSFAIGLIPSVGNNVVLTALLVSSANYVASMDHQCEGAACLALLEEEHYYRAVRWRPITGALSLVLNLLGQVGYVARSTFDAAYVPCTVFDLCSFAILYLCRNRCWRCFGRCVRVGPATHVLGSTGQRVSKLALIDLCDHFSKPTIDVVGMATGWSGCYTGTAAMERQCASTVDPHSFDQKKAGATVYLTPPVNSGSALQCLNVMWKRPIGSTVLGEQTGAVVTAVKSISFSPPCCVSTTLPTRPGVTVVDHALYNRLTASGVDPALLRVGQGDFLKLNPGFRLIGGWIYGICYFVLVVVSTFTCLPIKCGIGTRDPFCRRVFSVPVTKTQEHCHAGMCASAEGISLDSLGLTQLQSYWIAAVTSGLVILLVCHRLAISALDLLTLASPLVLLVFPWASVGLLLACSLAGAAVKIQLLATLFVNLFFPQATLVTMGYWACVAALAVYSLMGLRVKVNVPMCVTPAHFLLLARSAGQSREQMLRVSAAAPTNSLLGVARDCYVTGTTRLYIPKEGGMVFEGLFRSPKARGNVGFVAGSSYGTGSVWTRNNEVVVLTASHVVGRANMATLKIGDAMLTLTFKKNGDFAEAVTTQSELPGNWPQLHFAQPTTGPASWCTATGDEEGLLSGEVCLAWTTSGDSGSAVVQGDAVVGVHTGSNTSGVAYVTTPSGKLLGADTVTLSSLSKHFTGPLTSIPKDIPDNIIADVDAVPRSLAMLIDGLSNRESSLSGPQLLLIACFMWSYLNQPAYLPYVLGFFAANFFLPKSVGRPVVTGLLWLCCLFTPLSMRLCLFHLVCATVTGNVISLWFYITAAGTSYLSEMWFGGYPTMLFVPRFLVYQFPGWAIGTVLAVCSITMLAAALGHTLLLDVFSASGRFDRTFMMKYFLEGGVKESVTASVTRAYGKPITQESLTATLAALTDDDFQFLSDVLDCRAVRSAMNLRAALTSFQVAQYRNILNASLQVDRDAARSRRLMAKLADFAVEQEVTAGDRVVVIDGLDRMAHFKDDLVLVPLTTKVVGGSRCTICDVVKEEANDTPVKPMPSRRRRKGLPKGAQLEWDRHQEEKRNAGDDDFAVSNDYVKRVPKYWDPSDTRGTTVKIAGTTYQKVVDYSGNVHYVEHQEDLLDYVLGKGSYEGLDQDKVLDLTNMLKVDPTELSSKDKAKARQLAHLLLDLANPVEAVNQLNLRAPHIFPGDVGRRTFADSKDKGFVALHSRTMFLAARDFLFNIKFVCDEEFTKTPKDTLLGYVRACPGYWFIFRRTHRSLIDAYWDSMECVYALPTISDFDVSPGDVAVTGERWDFESPGGGRAKRLTADLVHAFQGFHGASYSYDDKVAAAVSGDPYRSDGVLYNTRWGNIPYSVPTNALEATACYRAGCEAVTDGTNVIATIGPFPEQQPIPDIPKSVLDNCADISCDAFIAPAAETALCGDLEKYNLSTQGFVLPSVFSMVRAYLKEEIGDAPPLYLPSTVPSKNSQAGINGAEFPTKSLQSYCLIDDMVSQSMKSNLQTATMATCKRQYCSKYKIRSILGTNNYIGLGLRACLSGVTAAFQKAGKDGSPIYLGKSKFDPIPAPDKYCLETDLESCDRSTPALVRWFATNLIFELAGQPELVHSYVLNCCHDLVVAGSVAFTKRGGLSSGDPITSISNTIYSLVLYTQHMLLCGLEGYFPEIAEKYLDGSLELRDMFKYVRVYIYSDDVVLTTPNQHYAASFDRWVPHLQALLGFKVDPKKTVNTSSPSFLGCRFKQVDGKCYLASLQDRVTRSLLYHIGAKNPSEYYEAAVSIFKDSIICCDEDWWTDLHRRISGAARTDGVEFPTIEMLTSFRTKQYESAVCTVCGAAPVAKSACGGWFCGNCVPYHAGHCHTTSLFANCGHDIMYRSTYCTMCEGSPKQMVPKVPHPILDHLLCHIDYGSKEELTLVVADGRTTSPPGRYKVGHKVVAVVADVGGNIVFGCGPGSHIAVPLQDTLKGVVVNKALKNAAASEYVEGPPGSGKTFHLVKDVLAVVGSATLVVPTHASMLDCINKLKQAGADPYFVVPKYTVLDFPRPGSGNITVRLPQVGTSEGETFVDEVAYFSPVDLARILTQGRVKGYGDLNQLGCVGPASVPRNLWLRHFVSLEPLRVCHRFGAAVCDLIKGIYPYYEPAPHTTKVVFVPNPDFEKGVVITAYHKDRGLGHRTIDSIQGCTFPVVTLRLPTPQSLTRPRAVVAVTRASQELYIYDPFDQLSGLLKFTKEAEAQDLIHGPPTACHLGQEIDLWSNEGLEYYKEVNLLYTHVPIKDGVIHSYPNCGPACGWEKQSNKISCLPRVAQNLGYHYSPDLPGFCPIPKELAEHWPVVSNDRYPNCLQITLQQVCELSKPCSAGYMVGQSVFVQTPGVTSYWLTEWVDGKARALPDSLFSSGRFETNSRAFLDEAEEKFAAAHPHACLGEINKSTVGGSHFIFSQYLPPLLPADAVALVGASLAGKAAKAACSVVDVYAPSFEPYLHPETLSRVYKIMIDFKPCRLMVWRNATFYVQEGVDAVTSALAAVSKLIKVPANEPVSFHVASGYRTNALVAPQAKISIGAYAAEWALSTEPPPAGYAIVRRYIVKRLLSSTEVFLCRRGVVSSTSVQTICALEGCKPLFNFLQIGSVIGPV |
| Enzyme Length | 3175 |
| Uniprot Accession Number | P19811 |
| Absorption | |
| Active Site | ACT_SITE 164; /note="For Nsp1 papain-like cysteine proteinase activity"; /evidence="ECO:0000269|PubMed:1331507, ECO:0000269|PubMed:8617757"; ACT_SITE 230; /note="For Nsp1 papain-like cysteine proteinase activity"; /evidence="ECO:0000269|PubMed:1331507"; ACT_SITE 270; /note="For Nsp2 cysteine proteinase activity"; /evidence="ECO:0000269|PubMed:7622476"; ACT_SITE 332; /note="For Nsp2 cysteine proteinase activity"; /evidence="ECO:0000269|PubMed:7622476"; ACT_SITE 1103; /note="Charge relay system; for 3C-like serine proteinase activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"; ACT_SITE 1129; /note="Charge relay system; for 3C-like serine proteinase activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"; ACT_SITE 1184; /note="Charge relay system; for 3C-like serine proteinase activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"; ACT_SITE 2963; /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"; ACT_SITE 2978; /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"; ACT_SITE 3007; /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; Evidence={ECO:0000269|PubMed:24369429}; 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; Evidence={ECO:0000269|PubMed:24369429}; 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:0000269|PubMed:19297500}; |
| DNA Binding | |
| EC Number | 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. {ECO:0000269|PubMed:18078692}.; FUNCTION: Nsp1 is essential for viral subgenomic mRNA synthesis. {ECO:0000269|PubMed:11172046}.; 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. {ECO:0000269|PubMed:18078692}.; FUNCTION: The 3C-like serine proteinase chain is responsible for the majority of cleavages as it cleaves the C-terminus of the polyprotein. {ECO:0000269|PubMed:18078692}.; FUNCTION: The helicase chain, which contains a zinc finger structure, displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. {ECO:0000269|PubMed:11000230, ECO:0000269|PubMed:24369429}.; 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) (PubMed:19297500). 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:0000269|PubMed:19297500}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 2528..2535; /note=ATP; /evidence=ECO:0000250 |
| Features | Active site (10); Alternative sequence (1); Beta strand (65); Chain (15); Compositional bias (1); Domain (11); Glycosylation (1); Helix (32); Metal binding (16); Mutagenesis (44); Nucleotide binding (1); Region (6); Site (12); Transmembrane (11); Turn (13); Zinc finger (1) |
| Keywords | 3D-structure;ATP-binding;Endonuclease;Glycoprotein;Helicase;Host cytoplasm;Host membrane;Host nucleus;Host-virus interaction;Hydrolase;Inhibition of host ISG15 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;Reference proteome;Ribosomal frameshifting;Serine protease;Thiol protease;Transferase;Transmembrane;Transmembrane helix;Viral RNA replication;Viral immunoevasion;Zinc;Zinc-finger |
| Interact With | P19811 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Nsp1 papain-like cysteine proteinase]: Host nucleus. Host cytoplasm.; 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. 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. {ECO:0000269|PubMed:1331507, ECO:0000269|PubMed:22258855, ECO:0000269|PubMed:8617757, ECO:0000269|PubMed:9371590, ECO:0000269|PubMed:9971783}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (1); X-ray crystallography (7) |
| Cross Reference PDB | 1MBM; 2L8K; 4IUM; 4N0N; 4N0O; 5F17; 5HBZ; 5HC1; |
| Mapped Pubmed ID | 16439522; 17098961; 17626105; 21561912; 23401522; 24967365; 26041874; 27795409; |
| Motif | |
| Gene Encoded By | |
| Mass | 345,384 |
| Kinetics | |
| Metal Binding | METAL 319; /note="Zinc 1"; /evidence="ECO:0007744|PDB:4IUM"; METAL 349; /note="Zinc 1"; /evidence="ECO:0007744|PDB:4IUM"; METAL 354; /note="Zinc 1"; /evidence="ECO:0007744|PDB:4IUM"; METAL 356; /note="Zinc 1"; /evidence="ECO:0007744|PDB:4IUM"; METAL 2374; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2377; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2387; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2392; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2395; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2399; /note="Zinc 3; via tele nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2402; /note="Zinc 3; via pros nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2403; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2412; /note="Zinc 4"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2414; /note="Zinc 4; via pros nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2423; /note="Zinc 4"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"; METAL 2426; /note="Zinc 4"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00985, ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O" |
| Rhea ID | RHEA:21248; RHEA:13065; RHEA:67732 |
| Cross Reference Brenda | 3.4.21.114;3.4.22.B50; |