ID   RPOA_EAVBU              Reviewed;        3175 AA.
AC   P19811; Q88625; Q8QZQ5; Q91DM2;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   13-APR-2004, sequence version 3.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=Replicase polyprotein 1ab;
DE   AltName: Full=ORF1ab polyprotein;
DE   Contains:
DE     RecName: Full=Nsp1 papain-like cysteine proteinase;
DE              Short=PCP;
DE              EC=3.4.22.- {ECO:0000269|PubMed:1331507, ECO:0000269|PubMed:8617757};
DE   Contains:
DE     RecName: Full=Nsp2 cysteine proteinase;
DE              EC=3.4.19.12;
DE              EC=3.4.22.-;
DE     AltName: Full=CP2;
DE              Short=CP;
DE   Contains:
DE     RecName: Full=Non-structural protein 3;
DE              Short=Nsp3;
DE   Contains:
DE     RecName: Full=3C-like serine proteinase;
DE              Short=3CLSP;
DE              EC=3.4.21.-;
DE     AltName: Full=Nsp4;
DE   Contains:
DE     RecName: Full=Non-structural protein 5-6-7;
DE              Short=Nsp5-6-7;
DE   Contains:
DE     RecName: Full=Non-structural protein 5;
DE              Short=Nsp5;
DE   Contains:
DE     RecName: Full=Non-structural protein 6;
DE              Short=Nsp6;
DE   Contains:
DE     RecName: Full=Non-structural protein 7-alpha;
DE              Short=Nsp7-alpha;
DE   Contains:
DE     RecName: Full=Non-structural protein 7-beta;
DE              Short=Nsp7-beta;
DE   Contains:
DE     RecName: Full=Non-structural protein 8;
DE              Short=Nsp8;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase;
DE              Short=Pol;
DE              Short=RdRp;
DE              EC=2.7.7.48;
DE     AltName: Full=Nsp9;
DE   Contains:
DE     RecName: Full=Helicase {ECO:0000303|PubMed:11000230, ECO:0000303|PubMed:24369429};
DE              Short=Hel;
DE              EC=3.6.4.12 {ECO:0000269|PubMed:24369429};
DE              EC=3.6.4.13 {ECO:0000269|PubMed:24369429};
DE     AltName: Full=Nsp10;
DE   Contains:
DE     RecName: Full=Uridylate-specific endoribonuclease nsp11;
DE              EC=4.6.1.-;
DE     AltName: Full=Non-structural protein 11;
DE              Short=Nsp11;
DE   Contains:
DE     RecName: Full=Non-structural protein 12;
DE              Short=Nsp12;
GN   Name=rep; ORFNames=1a-1b;
OS   Equine arteritis virus (strain Bucyrus) (EAV).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Arnidovirineae; Arteriviridae; Equarterivirinae;
OC   Alphaarterivirus; Alphaarterivirus equid.
OX   NCBI_TaxID=299386;
OH   NCBI_TaxID=9788; Equidae (horses).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=1851863; DOI=10.1128/jvi.65.6.2910-2920.1991;
RA   den Boon J.A., Snijder E.J., Chirnside E.D., de Vries A.A.F.,
RA   Horzinek M.C., Spaan W.J.M.;
RT   "Equine arteritis virus is not a togavirus but belongs to the
RT   coronaviruslike superfamily.";
RL   J. Virol. 65:2910-2920(1991).
RN   [2]
RP   SEQUENCE REVISION.
RA   Snijder E.J.;
RL   Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-17.
RX   PubMed=2162519; DOI=10.1093/nar/18.11.3241;
RA   de Vries A.A.F., Chirnside E.D., Bredenbeek P.J., Gravestein L.A.,
RA   Horzinek M.C., Spaan W.J.M.;
RT   "All subgenomic mRNAs of equine arteritis virus contain a common leader
RT   sequence.";
RL   Nucleic Acids Res. 18:3241-3247(1990).
RN   [4]
RP   PROTEOLYTIC PROCESSING OF POLYPROTEIN 1A, CHARACTERIZATION OF PCP,
RP   MUTAGENESIS OF CYS-164; HIS-219; HIS-230 AND GLY-260, CATALYTIC ACTIVITY,
RP   AND ACTIVE SITE.
RX   PubMed=1331507; DOI=10.1128/jvi.66.12.7040-7048.1992;
RA   Snijder E.J., Wassenaar A.L.M., Spaan W.J.M.;
RT   "The 5' end of the equine arteritis virus replicase gene encodes a
RT   papainlike cysteine protease.";
RL   J. Virol. 66:7040-7048(1992).
RN   [5]
RP   CHARACTERIZATION OF NSP2, ACTIVE SITE, AND MUTAGENESIS OF CYS-270; GLY-271;
RP   ASP-291; ASP-295; ASP-296; GLU-297; CYS-319; HIS-332; CYS-344; CYS-349;
RP   CYS-354 AND CYS-356.
RX   PubMed=7622476; DOI=10.1074/jbc.270.28.16671;
RA   Snijder E.J., Wassenaar A.L.M., Spaan W.J.M., Gorbalenya A.E.;
RT   "The arterivirus Nsp2 protease. An unusual cysteine protease with primary
RT   structure similarities to both papain-like and chymotrypsin-like
RT   proteases.";
RL   J. Biol. Chem. 270:16671-16676(1995).
RN   [6]
RP   PROTEOLYTIC PROCESSING OF POLYPROTEIN 1A, CHARACTERIZATION OF 3CLSP,
RP   CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-164; GLY-831;
RP   GLU-1064; HIS-1103; ASP-1117; ASP-1129; THR-1179; SER-1184; HIS-1198;
RP   GLU-1268; GLU-1430 AND GLU-1677.
RX   PubMed=8617757; DOI=10.1074/jbc.271.9.4864;
RA   Snijder E.J., Wassenaar A.L.M., van Dinten L.C., Spaan W.J.M.,
RA   Gorbalenya A.E.;
RT   "The arterivirus nsp4 protease is the prototype of a novel group of
RT   chymotrypsin-like enzymes, the 3C-like serine proteases.";
RL   J. Biol. Chem. 271:4864-4871(1996).
RN   [7]
RP   MUTAGENESIS OF SER-2429.
RX   PubMed=9023370; DOI=10.1073/pnas.94.3.991;
RA   van Dinten L.C., den Boon J.A., Wassenaar A.L.M., Spaan W.J.M.,
RA   Snijder E.J.;
RT   "An infectious arterivirus cDNA clone: identification of a replicase point
RT   mutation that abolishes discontinuous mRNA transcription.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:991-996(1997).
RN   [8]
RP   PROTEOLYTIC PROCESSING OF POLYPROTEIN 1A, AND MUTAGENESIS OF GLU-1268.
RX   PubMed=9371590; DOI=10.1128/jvi.71.12.9313-9322.1997;
RA   Wassenaar A.L.M., Spaan W.J.M., Gorbalenya A.E., Snijder E.J.;
RT   "Alternative proteolytic processing of the arterivirus replicase ORF1a
RT   polyprotein: evidence that NSP2 acts as a cofactor for the NSP4 serine
RT   protease.";
RL   J. Virol. 71:9313-9322(1997).
RN   [9]
RP   SUBCELLULAR LOCATION.
RX   PubMed=9658116; DOI=10.1128/jvi.72.8.6689-6698.1998;
RA   van der Meer Y., van Tol H., Locker J.K., Snijder E.J.;
RT   "ORF1a-encoded replicase subunits are involved in the membrane association
RT   of the arterivirus replication complex.";
RL   J. Virol. 72:6689-6698(1998).
RN   [10]
RP   PROTEOLYTIC PROCESSING OF POLYPROTEIN 1B, AND MUTAGENESIS OF ASP-2351;
RP   GLU-2370; GLU-2800; ASP-2819; GLU-2835; GLN-2837 AND GLU-3056.
RX   PubMed=9971783; DOI=10.1128/jvi.73.3.2027-2037.1999;
RA   van Dinten L.C., Rensen S., Gorbalenya A.E., Snijder E.J.;
RT   "Proteolytic processing of the open reading frame 1b-encoded part of
RT   arterivirus replicase is mediated by nsp4 serine protease and is essential
RT   for virus replication.";
RL   J. Virol. 73:2027-2037(1999).
RN   [11]
RP   CHARACTERIZATION OF HELICASE.
RX   PubMed=11000230; DOI=10.1128/jvi.74.20.9586-9593.2000;
RA   Seybert A., van Dinten L.C., Snijder E.J., Ziebuhr J.;
RT   "Biochemical characterization of the equine arteritis virus helicase
RT   suggests a close functional relationship between arterivirus and
RT   coronavirus helicases.";
RL   J. Virol. 74:9586-9593(2000).
RN   [12]
RP   C4-TYPE ZINC-FINGER OF NSP1, AND MUTAGENESIS OF CYS-25 AND CYS-44.
RX   PubMed=11172046; DOI=10.1073/pnas.98.4.1889;
RA   Tijms M.A., van Dinten L.C., Gorbalenya A.E., Snijder E.J.;
RT   "A zinc finger-containing papain-like protease couples subgenomic mRNA
RT   synthesis to genome translation in a positive-stranded RNA virus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:1889-1894(2001).
RN   [13]
RP   SUBCELLULAR LOCATION OF NSP1 PAPAIN-LIKE CYSTEINE PROTEINASE.
RX   PubMed=11907328; DOI=10.1099/0022-1317-83-4-795;
RA   Tijms M.A., van der Meer Y., Snijder E.J.;
RT   "Nuclear localization of non-structural protein 1 and nucleocapsid protein
RT   of equine arteritis virus.";
RL   J. Gen. Virol. 83:795-800(2002).
RN   [14]
RP   INTERACTION WITH HUMAN SND1/P100.
RX   PubMed=12917451; DOI=10.1099/vir.0.19297-0;
RA   Tijms M.A., Snijder E.J.;
RT   "Equine arteritis virus non-structural protein 1, an essential factor for
RT   viral subgenomic mRNA synthesis, interacts with the cellular transcription
RT   co-factor p100.";
RL   J. Gen. Virol. 84:2317-2322(2003).
RN   [15]
RP   FUNCTION OF NSP2.
RX   PubMed=18078692; DOI=10.1016/j.chom.2007.09.014;
RA   Frias-Staheli N., Giannakopoulos N.V., Kikkert M., Taylor S.L., Bridgen A.,
RA   Paragas J., Richt J.A., Rowland R.R., Schmaljohn C.S., Lenschow D.J.,
RA   Snijder E.J., Garcia-Sastre A., Virgin H.W.;
RT   "Ovarian tumor domain-containing viral proteases evade ubiquitin- and
RT   ISG15-dependent innate immune responses.";
RL   Cell Host Microbe 2:404-416(2007).
RN   [16]
RP   CATALYTIC ACTIVITY (URIDYLATE-SPECIFIC ENDORIBONUCLEASE NSP11), AND
RP   FUNCTION (URIDYLATE-SPECIFIC ENDORIBONUCLEASE NSP11).
RX   PubMed=19297500; DOI=10.1128/jvi.00261-09;
RA   Nedialkova D.D., Ulferts R., van den Born E., Lauber C., Gorbalenya A.E.,
RA   Ziebuhr J., Snijder E.J.;
RT   "Biochemical characterization of arterivirus nonstructural protein 11
RT   reveals the nidovirus-wide conservation of a replicative
RT   endoribonuclease.";
RL   J. Virol. 83:5671-5682(2009).
RN   [17]
RP   PROTEOLYTIC PROCESSING OF POLYPROTEIN 1A, AND PROTEOLYTIC PROCESSING OF
RP   POLYPROTEIN 1B.
RX   PubMed=22258855; DOI=10.1099/vir.0.039289-0;
RA   Li Y., Tas A., Snijder E.J., Fang Y.;
RT   "Identification of porcine reproductive and respiratory syndrome virus
RT   ORF1a-encoded non-structural proteins in virus-infected cells.";
RL   J. Gen. Virol. 93:829-839(2012).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1071-1268 (NSP4).
RX   PubMed=12163505; DOI=10.1074/jbc.m206978200;
RA   Barrette-Ng I.H., Ng K.K.-S., Mark B.L., Van Aken D., Cherney M.M.,
RA   Garen C., Kolodenko Y., Gorbalenya A.E., Snijder E.J., James M.N.G.;
RT   "Structure of arterivirus nsp4. The smallest chymotrypsin-like proteinase
RT   with an alpha/beta C-terminal extension and alternate conformations of the
RT   oxyanion hole.";
RL   J. Biol. Chem. 277:39960-39966(2002).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2371-2772 IN COMPLEX WITH ZINC
RP   IONS, FUNCTION, AND MUTAGENESIS OF LYS-2534.
RX   PubMed=24369429; DOI=10.1093/nar/gkt1310;
RA   Deng Z., Lehmann K.C., Li X., Feng C., Wang G., Zhang Q., Qi X., Yu L.,
RA   Zhang X., Feng W., Wu W., Gong P., Tao Y., Posthuma C.C., Snijder E.J.,
RA   Gorbalenya A.E., Chen Z.;
RT   "Structural basis for the regulatory function of a complex zinc-binding
RT   domain in a replicative arterivirus helicase resembling a nonsense-mediated
RT   mRNA decay helicase.";
RL   Nucleic Acids Res. 42:3464-3477(2014).
CC   -!- FUNCTION: The replicase polyprotein 1ab is a multifunctional protein:
CC       it contains the activities necessary for the transcription of negative
CC       stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as
CC       well as proteinases responsible for the cleavage of the polyprotein
CC       into functional products. {ECO:0000269|PubMed:18078692}.
CC   -!- FUNCTION: Nsp1 is essential for viral subgenomic mRNA synthesis.
CC       {ECO:0000269|PubMed:11172046}.
CC   -!- FUNCTION: Nsp2 cysteine proteinase which cleaves the nsp2/nsp3 site in
CC       the polyprotein. Also displays deubiquitinating and deISGylase
CC       activities. The deubiquitinating activity cleaves both ubiquitinated
CC       and ISGylated products and may therefore regulate ubiquitin and ISG15
CC       dependent host innate immunity. {ECO:0000269|PubMed:18078692}.
CC   -!- FUNCTION: The 3C-like serine proteinase chain is responsible for the
CC       majority of cleavages as it cleaves the C-terminus of the polyprotein.
CC       {ECO:0000269|PubMed:18078692}.
CC   -!- FUNCTION: The helicase chain, which contains a zinc finger structure,
CC       displays RNA and DNA duplex-unwinding activities with 5' to 3'
CC       polarity. {ECO:0000269|PubMed:11000230, ECO:0000269|PubMed:24369429}.
CC   -!- FUNCTION: [Uridylate-specific endoribonuclease nsp11]: Plays a role in
CC       viral transcription/replication and prevents the simultaneous
CC       activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR
CC       (By similarity). Acts by degrading the 5'-polyuridines generated during
CC       replication of the poly(A) region of viral genomic and subgenomic RNAs.
CC       Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-
CC       cP) is first generated by 2'-O transesterification, which is then
CC       hydrolyzed to a 3'-phosphate (3'-P) (PubMed:19297500). If not degraded,
CC       poly(U) RNA would hybridize with poly(A) RNA tails and activate host
CC       dsRNA sensors (By similarity). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000269|PubMed:19297500}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC         RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC         COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC         EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC         Evidence={ECO:0000269|PubMed:24369429};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC         Evidence={ECO:0000269|PubMed:24369429};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12;
CC   -!- CATALYTIC ACTIVITY: [Uridylate-specific endoribonuclease nsp11]:
CC       Reaction=uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl-
CC         2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside-
CC         RNA; Xref=Rhea:RHEA:67732, Rhea:RHEA-COMP:13936, Rhea:RHEA-
CC         COMP:17334, Rhea:RHEA-COMP:17335, ChEBI:CHEBI:138284,
CC         ChEBI:CHEBI:173079, ChEBI:CHEBI:173080;
CC         Evidence={ECO:0000269|PubMed:19297500};
CC   -!- SUBUNIT: Nsp1 interacts with cellular transcription cofactor SND1/p100.
CC       {ECO:0000269|PubMed:12917451}.
CC   -!- INTERACTION:
CC       P19811; PRO_0000036626 [P19811]: rep; NbExp=4; IntAct=EBI-27070211, EBI-27070280;
CC   -!- SUBCELLULAR LOCATION: [Nsp1 papain-like cysteine proteinase]: Host
CC       nucleus. Host cytoplasm.
CC   -!- SUBCELLULAR LOCATION: [Nsp2 cysteine proteinase]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 3]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 5-6-7]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [3C-like serine proteinase]: Host cytoplasm
CC       {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm,
CC       host perinuclear region {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Helicase]: Host cytoplasm, host perinuclear
CC       region {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=2;
CC       Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC         IsoId=P19811-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC         IsoId=P19811-2; Sequence=VSP_032887;
CC   -!- DOMAIN: The hydrophobic domains (HD) could mediate the membrane
CC       association of the replication complex and thereby alter the
CC       architecture of the host cell membrane.
CC   -!- DOMAIN: The OTU-like region is responsible for the deubiquitinating and
CC       deISGylation activities of Nsp2. {ECO:0000305}.
CC   -!- PTM: Specific enzymatic cleavages in vivo by its own proteases yield
CC       mature proteins. There are two alternative pathways for processing.
CC       Either nsp4-5 is cleaved, which represents the major pathway or the
CC       nsp5-6 and nsp6-7 are processed, which represents the minor pathway.
CC       The major pathway occurs when nsp2 acts as a cofactor for nsp4.
CC       {ECO:0000269|PubMed:1331507, ECO:0000269|PubMed:22258855,
CC       ECO:0000269|PubMed:8617757, ECO:0000269|PubMed:9371590,
CC       ECO:0000269|PubMed:9971783}.
CC   -!- MISCELLANEOUS: Nsp1 contains an inactivated papain-like cysteine
CC       proteinase domain due to a Lys instead of a Cys in position 73.
CC   -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1ab]: Produced by -1
CC       ribosomal frameshifting at the 1a-1b genes boundary.
CC   -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1a]: Produced by
CC       conventional translation. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the arteriviridae polyprotein family.
CC       {ECO:0000305}.
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DR   EMBL; X53459; CAC42774.2; -; Genomic_RNA.
DR   EMBL; X53459; CAC42775.2; -; Genomic_RNA.
DR   EMBL; X52277; CAA36520.1; -; Genomic_RNA.
DR   PIR; A39925; RRWVEV.
DR   RefSeq; NP_127506.1; NC_002532.2.
DR   RefSeq; NP_127507.1; NC_002532.2.
DR   PDB; 1MBM; X-ray; 2.00 A; A/B/C/D=1071-1268.
DR   PDB; 2L8K; NMR; -; A=1454-1575.
DR   PDB; 4IUM; X-ray; 1.45 A; A=261-392.
DR   PDB; 4N0N; X-ray; 2.00 A; A=2371-2772.
DR   PDB; 4N0O; X-ray; 2.65 A; A/C/E/G=2371-2772.
DR   PDB; 5F17; X-ray; 3.20 A; A/B/C/D/E/F=2838-3056.
DR   PDB; 5HBZ; X-ray; 3.10 A; A/B/C/D/E/F=2838-3056.
DR   PDB; 5HC1; X-ray; 3.10 A; A/B/C/D=2838-3056.
DR   PDBsum; 1MBM; -.
DR   PDBsum; 2L8K; -.
DR   PDBsum; 4IUM; -.
DR   PDBsum; 4N0N; -.
DR   PDBsum; 4N0O; -.
DR   PDBsum; 5F17; -.
DR   PDBsum; 5HBZ; -.
DR   PDBsum; 5HC1; -.
DR   BMRB; P19811; -.
DR   SMR; P19811; -.
DR   MEROPS; C33.001; -.
DR   MEROPS; S32.001; -.
DR   GlyCosmos; P19811; 1 site, No reported glycans.
DR   GeneID; 921339; -.
DR   KEGG; vg:921339; -.
DR   BioCyc; MetaCyc:MONOMER-20069; -.
DR   BRENDA; 3.4.21.114; 6985.
DR   BRENDA; 3.4.22.B50; 6985.
DR   EvolutionaryTrace; P19811; -.
DR   Proteomes; UP000000353; Segment.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004540; F:RNA nuclease activity; IEA:UniProt.
DR   GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0070008; F:serine-type exopeptidase activity; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0039648; P:modulation by symbiont of host protein ubiquitination; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0039579; P:suppression by virus of host ISG15-protein conjugation; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0019082; P:viral protein processing; IEA:InterPro.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   CDD; cd21406; 1B_nv_SF1_Hel-like; 1.
DR   CDD; cd23189; Arteriviridae_RdRp; 1.
DR   CDD; cd22528; av_Nsp3_ER-remodelling; 1.
DR   CDD; cd17937; DEXXYc_viral_SF1-N; 1.
DR   CDD; cd21160; NendoU_av_Nsp11-like; 1.
DR   CDD; cd21166; NTD_av_Nsp11-like; 1.
DR   CDD; cd18786; SF1_C; 1.
DR   CDD; cd21405; ZBD_av_Nsp10-like; 1.
DR   Gene3D; 3.30.70.270; -; 1.
DR   Gene3D; 3.90.70.160; -; 1.
DR   Gene3D; 3.30.1330.220; Arterivirus nonstructural protein 7 alpha; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR   InterPro; IPR031932; Arteri_nsp7a.
DR   InterPro; IPR038451; Arteri_nsp7a_sf.
DR   InterPro; IPR008743; Arterivirus_Nsp2_C33.
DR   InterPro; IPR023338; Arterivirus_NSP4_peptidase.
DR   InterPro; IPR046440; AV_NSP11N_COV_NSP15M.
DR   InterPro; IPR008741; AV_PCPalpha.
DR   InterPro; IPR025773; AV_PCPbeta.
DR   InterPro; IPR023183; Chymotrypsin-like_C.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR022230; DUF3756.
DR   InterPro; IPR029323; EAV_nsp1.
DR   InterPro; IPR008760; EAV_peptidase_S32.
DR   InterPro; IPR037227; EndoU-like.
DR   InterPro; IPR043609; NendoU_nidovirus.
DR   InterPro; IPR044863; NIRAN.
DR   InterPro; IPR027355; NSP10_Av_ZBD.
DR   InterPro; IPR044320; NSP11_Av_N.
DR   InterPro; IPR044314; NSP11_NendoU_Av.
DR   InterPro; IPR032786; NSP2_TM_arteriviridae.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR041053; Rep_1B.
DR   InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR   InterPro; IPR001205; RNA-dir_pol_C.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR041361; Znf-RING_13.
DR   Pfam; PF16749; Arteri_nsp7a; 1.
DR   Pfam; PF19215; CoV_NSP15_C; 1.
DR   Pfam; PF12581; DUF3756; 1.
DR   Pfam; PF14754; IFR3_antag; 1.
DR   Pfam; PF14755; Nsp2_AV; 1.
DR   Pfam; PF05412; Peptidase_C33; 1.
DR   Pfam; PF05579; Peptidase_S32; 1.
DR   Pfam; PF00680; RdRP_1; 1.
DR   Pfam; PF17873; Rep_1B; 1.
DR   Pfam; PF01443; Viral_helicase1; 1.
DR   Pfam; PF17977; zf-RING_13; 1.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF142877; EndoU-like; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS51538; AV_CP; 1.
DR   PROSITE; PS51961; AV_NSP11N_COV_NSP15M; 1.
DR   PROSITE; PS51493; AV_NSP4_PRO; 1.
DR   PROSITE; PS51539; AV_PCP_ALPHA; 1.
DR   PROSITE; PS51540; AV_PCP_BETA; 1.
DR   PROSITE; PS51652; AV_ZBD; 1.
DR   PROSITE; PS51958; NENDOU; 1.
DR   PROSITE; PS51947; NIRAN; 1.
DR   PROSITE; PS51657; PSRV_HELICASE; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Endonuclease; Glycoprotein; Helicase;
KW   Host cytoplasm; Host membrane; Host nucleus; Host-virus interaction;
KW   Hydrolase; Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host ISG15 by virus; Interferon antiviral system evasion;
KW   Lyase; Membrane; Metal-binding;
KW   Modulation of host ubiquitin pathway by viral deubiquitinase;
KW   Modulation of host ubiquitin pathway by virus; Multifunctional enzyme;
KW   Nuclease; Nucleotide-binding; Nucleotidyltransferase; Protease;
KW   Reference proteome; Ribosomal frameshifting; RNA-directed RNA polymerase;
KW   Serine protease; Thiol protease; Transferase; Transmembrane;
KW   Transmembrane helix; Viral immunoevasion; Viral RNA replication; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..3175
FT                   /note="Replicase polyprotein 1ab"
FT                   /id="PRO_0000036619"
FT   CHAIN           1..260
FT                   /note="Nsp1 papain-like cysteine proteinase"
FT                   /id="PRO_0000036621"
FT   CHAIN           261..831
FT                   /note="Nsp2 cysteine proteinase"
FT                   /id="PRO_0000036622"
FT   CHAIN           832..1064
FT                   /note="Non-structural protein 3"
FT                   /id="PRO_0000036623"
FT   CHAIN           1065..1268
FT                   /note="3C-like serine proteinase"
FT                   /id="PRO_0000036624"
FT   CHAIN           1269..1677
FT                   /note="Non-structural protein 5-6-7"
FT                   /id="PRO_0000036625"
FT   CHAIN           1269..1430
FT                   /note="Non-structural protein 5"
FT                   /id="PRO_0000423106"
FT   CHAIN           1431..1452
FT                   /note="Non-structural protein 6"
FT                   /id="PRO_0000423107"
FT   CHAIN           1453..1575
FT                   /note="Non-structural protein 7-alpha"
FT                   /id="PRO_0000423108"
FT   CHAIN           1576..1677
FT                   /note="Non-structural protein 7-beta"
FT                   /id="PRO_0000423109"
FT   CHAIN           1678..2370
FT                   /note="RNA-directed RNA polymerase"
FT                   /id="PRO_0000036626"
FT   CHAIN           1678..1727
FT                   /note="Non-structural protein 8"
FT                   /id="PRO_0000036627"
FT   CHAIN           2371..2837
FT                   /note="Helicase"
FT                   /id="PRO_0000036628"
FT   CHAIN           2838..3056
FT                   /note="Uridylate-specific endoribonuclease nsp11"
FT                   /id="PRO_0000036629"
FT   CHAIN           3057..3175
FT                   /note="Non-structural protein 12"
FT                   /id="PRO_0000036630"
FT   TRANSMEM        530..550
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        551..571
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        625..645
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        829..849
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        903..923
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        935..955
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        977..997
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1291..1311
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1333..1353
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1355..1375
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1385..1405
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          66..156
FT                   /note="Peptidase C31"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00872"
FT   DOMAIN          157..260
FT                   /note="Peptidase C32"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
FT   DOMAIN          261..360
FT                   /note="Peptidase C33"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT   DOMAIN          1065..1268
FT                   /note="Peptidase S32"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   DOMAIN          1716..1883
FT                   /note="NiRAN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01292"
FT   DOMAIN          2116..2251
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          2371..2438
FT                   /note="AV ZBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   DOMAIN          2496..2661
FT                   /note="(+)RNA virus helicase ATP-binding"
FT   DOMAIN          2662..2793
FT                   /note="(+)RNA virus helicase C-terminal"
FT   DOMAIN          2840..2930
FT                   /note="AV-Nsp11N/CoV-Nsp15M"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01306"
FT   DOMAIN          2932..3054
FT                   /note="NendoU"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ZN_FING         25..44
FT                   /note="C4-type; atypical"
FT   REGION          261..339
FT                   /note="OTU-like"
FT   REGION          386..451
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          530..645
FT                   /note="HD1"
FT   REGION          829..997
FT                   /note="HD2"
FT   REGION          1291..1405
FT                   /note="HD3"
FT   REGION          1577..1614
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1593..1614
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        164
FT                   /note="For Nsp1 papain-like cysteine proteinase activity"
FT                   /evidence="ECO:0000269|PubMed:1331507,
FT                   ECO:0000269|PubMed:8617757"
FT   ACT_SITE        230
FT                   /note="For Nsp1 papain-like cysteine proteinase activity"
FT                   /evidence="ECO:0000269|PubMed:1331507"
FT   ACT_SITE        270
FT                   /note="For Nsp2 cysteine proteinase activity"
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   ACT_SITE        332
FT                   /note="For Nsp2 cysteine proteinase activity"
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   ACT_SITE        1103
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   ACT_SITE        1129
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   ACT_SITE        1184
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   ACT_SITE        2963
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        2978
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        3007
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   BINDING         319
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:4IUM"
FT   BINDING         349
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:4IUM"
FT   BINDING         354
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:4IUM"
FT   BINDING         356
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:4IUM"
FT   BINDING         2374
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2377
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2387
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2392
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2395
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2399
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2402
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2403
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2412
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2414
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2423
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2426
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985,
FT                   ECO:0007744|PDB:4N0N, ECO:0007744|PDB:4N0O"
FT   BINDING         2528..2535
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   SITE            260..261
FT                   /note="Cleavage; by PCP"
FT   SITE            831..832
FT                   /note="Cleavage; by Nsp2 cysteine proteinase"
FT   SITE            1064..1065
FT                   /note="Cleavage; by 3CLSP"
FT   SITE            1268..1269
FT                   /note="Cleavage; by 3CLSP; in major pathway"
FT   SITE            1430..1431
FT                   /note="Cleavage; by 3CLSP; in minor pathway"
FT   SITE            1452..1453
FT                   /note="Cleavage; by 3CLSP; in minor pathway"
FT   SITE            1575..1576
FT                   /note="Cleavage; by 3CLSP"
FT   SITE            1677..1678
FT                   /note="Cleavage; by 3CLSP"
FT   SITE            2370..2371
FT                   /note="Cleavage; by 3CLSP"
FT   SITE            2429
FT                   /note="Involved in mRNA transcription process"
FT   SITE            2837..2838
FT                   /note="Cleavage; by 3CLSP"
FT   SITE            3056..3057
FT                   /note="Cleavage; by 3CLSP"
FT   CARBOHYD        1501
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000305"
FT   VAR_SEQ         1728..3175
FT                   /note="Missing (in isoform Replicase polyprotein 1a)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_032887"
FT   MUTAGEN         25
FT                   /note="C->A: Complete loss of transcription."
FT                   /evidence="ECO:0000269|PubMed:11172046"
FT   MUTAGEN         44
FT                   /note="C->A: Complete loss of transcription."
FT                   /evidence="ECO:0000269|PubMed:11172046"
FT   MUTAGEN         164
FT                   /note="C->G,S: Complete loss of PCP proteinase activity."
FT                   /evidence="ECO:0000269|PubMed:1331507,
FT                   ECO:0000269|PubMed:8617757"
FT   MUTAGEN         219
FT                   /note="H->A,G,V: No effect."
FT                   /evidence="ECO:0000269|PubMed:1331507"
FT   MUTAGEN         230
FT                   /note="H->A,G,V: Complete loss of PCP proteinase activity."
FT                   /evidence="ECO:0000269|PubMed:1331507"
FT   MUTAGEN         260
FT                   /note="G->V: Complete loss of nsp1-nsp2 cleavage."
FT                   /evidence="ECO:0000269|PubMed:1331507"
FT   MUTAGEN         270
FT                   /note="C->A,H,R,S: Complete loss of CP2 activity."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         271
FT                   /note="G->W: Complete loss of CP2 activity."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         291
FT                   /note="D->E,N: No effect."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         295
FT                   /note="D->E,N: No effect."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         296
FT                   /note="D->E,N: No effect."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         297
FT                   /note="E->D,Q: No effect."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         319
FT                   /note="C->A,H,P: Complete loss of CP2 activity."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         332
FT                   /note="H->C,I,N,Y: Complete loss of CP2 activity."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         344
FT                   /note="C->A: No effect."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         344
FT                   /note="C->H: Almost complete loss of CP2 activity."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         349
FT                   /note="C->A,H,S: Complete loss of CP2 activity."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         354
FT                   /note="C->A,H,P: Complete loss of CP2 activity."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         356
FT                   /note="C->A: Complete loss of CP2 activity."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         356
FT                   /note="C->H: No effect."
FT                   /evidence="ECO:0000269|PubMed:7622476"
FT   MUTAGEN         831
FT                   /note="G->P: Complete loss of nsp2-nsp3 cleavage."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1064
FT                   /note="E->P: Complete loss of nsp3-nsp4 cleavage."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1103
FT                   /note="H->G,R: Complete loss of nsp3-nsp4, nsp4-nsp5 and
FT                   nsp5-nsp6 cleavages."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1117
FT                   /note="D->N,T: No effect."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1129
FT                   /note="D->E: Complete loss of nsp3-nsp4 and nsp5-nsp6
FT                   cleavages."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1129
FT                   /note="D->K,V: Complete loss of nsp3-nsp4, nsp4-nsp5 and
FT                   nsp5-nsp6 cleavages."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1179
FT                   /note="T->G,S: Partial loss of nsp4-nsp5 cleavage."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1179
FT                   /note="T->N: Increased nsp5-nsp6 cleavage."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1184
FT                   /note="S->C,F,I,T: Complete loss of nsp3-nsp4, nsp4-nsp5
FT                   and nsp5-nsp6 cleavages."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1198
FT                   /note="H->L,R,Y: Complete loss of nsp4-nsp5 and nsp5-nsp6
FT                   cleavages."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1268
FT                   /note="E->P: Complete loss of nsp3-nsp4 and nsp4-nsp5
FT                   cleavages."
FT                   /evidence="ECO:0000269|PubMed:8617757,
FT                   ECO:0000269|PubMed:9371590"
FT   MUTAGEN         1430
FT                   /note="E->P: No effect."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         1677
FT                   /note="E->P: Complete loss of nsp5-nsp6 cleavage."
FT                   /evidence="ECO:0000269|PubMed:8617757"
FT   MUTAGEN         2351
FT                   /note="D->P: No effect."
FT                   /evidence="ECO:0000269|PubMed:9971783"
FT   MUTAGEN         2370
FT                   /note="E->P: Complete loss of nsp9-nsp10 cleavage."
FT                   /evidence="ECO:0000269|PubMed:9971783"
FT   MUTAGEN         2429
FT                   /note="S->P: RNA can replicate efficiently but does not
FT                   produce the subgenomic mRNAs required for structural
FT                   protein expression."
FT                   /evidence="ECO:0000269|PubMed:9023370"
FT   MUTAGEN         2534
FT                   /note="K->Q: Abolishes ATPase and helicase activity."
FT                   /evidence="ECO:0000269|PubMed:24369429"
FT   MUTAGEN         2800
FT                   /note="E->P: No effect."
FT                   /evidence="ECO:0000269|PubMed:9971783"
FT   MUTAGEN         2819
FT                   /note="D->P: No effect."
FT                   /evidence="ECO:0000269|PubMed:9971783"
FT   MUTAGEN         2835
FT                   /note="E->D,P,Q: Almost complete loss of nsp9-nsp10
FT                   cleavage."
FT                   /evidence="ECO:0000269|PubMed:9971783"
FT   MUTAGEN         2837
FT                   /note="Q->D,N: No effect."
FT                   /evidence="ECO:0000269|PubMed:9971783"
FT   MUTAGEN         2837
FT                   /note="Q->E: Increased nsp9-nsp10 cleavage."
FT                   /evidence="ECO:0000269|PubMed:9971783"
FT   MUTAGEN         2837
FT                   /note="Q->P: Almost complete loss of nsp9-nsp10 cleavage."
FT                   /evidence="ECO:0000269|PubMed:9971783"
FT   MUTAGEN         3056
FT                   /note="E->P: Complete loss of nsp10-nsp11 cleavage."
FT                   /evidence="ECO:0000269|PubMed:9971783"
FT   HELIX           270..277
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   TURN            278..280
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   STRAND          283..286
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   HELIX           290..292
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   HELIX           296..305
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   STRAND          309..312
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   STRAND          323..329
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   STRAND          332..337
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   HELIX           347..351
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   HELIX           369..379
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   TURN            380..382
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   STRAND          383..386
FT                   /evidence="ECO:0007829|PDB:4IUM"
FT   STRAND          1076..1092
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1095..1101
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   HELIX           1102..1105
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1110..1115
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1118..1123
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1125..1127
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1130..1135
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   TURN            1137..1139
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1154..1161
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1164..1170
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   HELIX           1181..1183
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1187..1190
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1193..1202
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   HELIX           1203..1205
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1206..1210
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1216..1220
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   HELIX           1224..1228
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1233..1237
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   STRAND          1250..1254
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   HELIX           1255..1262
FT                   /evidence="ECO:0007829|PDB:1MBM"
FT   TURN            1454..1459
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   HELIX           1463..1474
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   STRAND          1476..1480
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   STRAND          1483..1486
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   HELIX           1490..1506
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   HELIX           1510..1520
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   TURN            1521..1524
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   STRAND          1533..1539
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   STRAND          1545..1548
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   STRAND          1551..1560
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   STRAND          1565..1573
FT                   /evidence="ECO:0007829|PDB:2L8K"
FT   TURN            2375..2377
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2382..2385
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   TURN            2393..2395
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2396..2399
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2400..2403
FT                   /evidence="ECO:0007829|PDB:4N0O"
FT   STRAND          2405..2409
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2416..2418
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2419..2423
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   TURN            2424..2428
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2440..2451
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2457..2462
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2465..2468
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2470..2475
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2478..2483
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2488..2494
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2496..2503
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2513..2521
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2524..2527
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2534..2544
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2549..2552
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2556..2568
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2591..2596
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2605..2609
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   TURN            2610..2614
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2617..2626
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2630..2633
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   TURN            2648..2651
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2652..2654
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2655..2657
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2665..2667
FT                   /evidence="ECO:0007829|PDB:4N0O"
FT   HELIX           2669..2674
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   TURN            2675..2678
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2690..2693
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2702..2708
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2709..2711
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2717..2719
FT                   /evidence="ECO:0007829|PDB:4N0O"
FT   HELIX           2720..2722
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2727..2733
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2736..2738
FT                   /evidence="ECO:0007829|PDB:4N0O"
FT   HELIX           2742..2748
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2750..2759
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   HELIX           2765..2768
FT                   /evidence="ECO:0007829|PDB:4N0N"
FT   STRAND          2841..2843
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   HELIX           2845..2851
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2855..2858
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2862..2864
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   HELIX           2867..2870
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2875..2879
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2882..2890
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2897..2899
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2903..2905
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2908..2910
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2919..2927
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2928..2930
FT                   /evidence="ECO:0007829|PDB:5HC1"
FT   HELIX           2941..2944
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   HELIX           2952..2960
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   HELIX           2962..2965
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2968..2970
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2973..2975
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          2992..3001
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   TURN            3002..3004
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          3005..3013
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   HELIX           3017..3023
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          3027..3037
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          3040..3047
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   TURN            3048..3050
FT                   /evidence="ECO:0007829|PDB:5HBZ"
FT   STRAND          3051..3055
FT                   /evidence="ECO:0007829|PDB:5HBZ"
SQ   SEQUENCE   3175 AA;  345384 MW;  CB536C1F5091045C CRC64;
     MATFSATGFG GSFVRDWSLD LPDACEHGAG LCCEVDGSTL CAECFRGCEG MEQCPGLFMG
     LLKLASPVPV GHKFLIGWYR AAKVTGRYNF LELLQHPAFA QLRVVDARLA IEEASVFIST
     DHASAKRFPG ARFALTPVYA NAWVVSPAAN SLIVTTDQEQ DGFCWLKLLP PDRREAGLRL
     YYNHYREQRT GWLSKTGLRL WLGDLGLGIN ASSGGLKFHI MRGSPQRAWH ITTRSCKLKS
     YYVCDISEAD WSCLPAGNYG GYNPPGDGAC GYRCLAFMNG ATVVSAGCSS DLWCDDELAY
     RVFQLSPTFT VTIPGGRVCP NAKYAMICDK QHWRVKRAKG VGLCLDESCF RGICNCQRMS
     GPPPAPVSAA VLDHILEAAT FGNVRVVTPE GQPRPVPAPR VRPSANSSGD VKDPAPVPPV
     PKPRTKLATP NPTQAPIPAP RTRLQGASTQ EPLASAGVAS DSAPKWRVAK TVYSSAERFR
     TELVQRARSV GDVLVQALPL KTPAVQRYTM TLKMMRSRFS WHCDVWYPLA VIACLLPIWP
     SLALLLSFAI GLIPSVGNNV VLTALLVSSA NYVASMDHQC EGAACLALLE EEHYYRAVRW
     RPITGALSLV LNLLGQVGYV ARSTFDAAYV PCTVFDLCSF AILYLCRNRC WRCFGRCVRV
     GPATHVLGST GQRVSKLALI DLCDHFSKPT IDVVGMATGW SGCYTGTAAM ERQCASTVDP
     HSFDQKKAGA TVYLTPPVNS GSALQCLNVM WKRPIGSTVL GEQTGAVVTA VKSISFSPPC
     CVSTTLPTRP GVTVVDHALY NRLTASGVDP ALLRVGQGDF LKLNPGFRLI GGWIYGICYF
     VLVVVSTFTC LPIKCGIGTR DPFCRRVFSV PVTKTQEHCH AGMCASAEGI SLDSLGLTQL
     QSYWIAAVTS GLVILLVCHR LAISALDLLT LASPLVLLVF PWASVGLLLA CSLAGAAVKI
     QLLATLFVNL FFPQATLVTM GYWACVAALA VYSLMGLRVK VNVPMCVTPA HFLLLARSAG
     QSREQMLRVS AAAPTNSLLG VARDCYVTGT TRLYIPKEGG MVFEGLFRSP KARGNVGFVA
     GSSYGTGSVW TRNNEVVVLT ASHVVGRANM ATLKIGDAML TLTFKKNGDF AEAVTTQSEL
     PGNWPQLHFA QPTTGPASWC TATGDEEGLL SGEVCLAWTT SGDSGSAVVQ GDAVVGVHTG
     SNTSGVAYVT TPSGKLLGAD TVTLSSLSKH FTGPLTSIPK DIPDNIIADV DAVPRSLAML
     IDGLSNRESS LSGPQLLLIA CFMWSYLNQP AYLPYVLGFF AANFFLPKSV GRPVVTGLLW
     LCCLFTPLSM RLCLFHLVCA TVTGNVISLW FYITAAGTSY LSEMWFGGYP TMLFVPRFLV
     YQFPGWAIGT VLAVCSITML AAALGHTLLL DVFSASGRFD RTFMMKYFLE GGVKESVTAS
     VTRAYGKPIT QESLTATLAA LTDDDFQFLS DVLDCRAVRS AMNLRAALTS FQVAQYRNIL
     NASLQVDRDA ARSRRLMAKL ADFAVEQEVT AGDRVVVIDG LDRMAHFKDD LVLVPLTTKV
     VGGSRCTICD VVKEEANDTP VKPMPSRRRR KGLPKGAQLE WDRHQEEKRN AGDDDFAVSN
     DYVKRVPKYW DPSDTRGTTV KIAGTTYQKV VDYSGNVHYV EHQEDLLDYV LGKGSYEGLD
     QDKVLDLTNM LKVDPTELSS KDKAKARQLA HLLLDLANPV EAVNQLNLRA PHIFPGDVGR
     RTFADSKDKG FVALHSRTMF LAARDFLFNI KFVCDEEFTK TPKDTLLGYV RACPGYWFIF
     RRTHRSLIDA YWDSMECVYA LPTISDFDVS PGDVAVTGER WDFESPGGGR AKRLTADLVH
     AFQGFHGASY SYDDKVAAAV SGDPYRSDGV LYNTRWGNIP YSVPTNALEA TACYRAGCEA
     VTDGTNVIAT IGPFPEQQPI PDIPKSVLDN CADISCDAFI APAAETALCG DLEKYNLSTQ
     GFVLPSVFSM VRAYLKEEIG DAPPLYLPST VPSKNSQAGI NGAEFPTKSL QSYCLIDDMV
     SQSMKSNLQT ATMATCKRQY CSKYKIRSIL GTNNYIGLGL RACLSGVTAA FQKAGKDGSP
     IYLGKSKFDP IPAPDKYCLE TDLESCDRST PALVRWFATN LIFELAGQPE LVHSYVLNCC
     HDLVVAGSVA FTKRGGLSSG DPITSISNTI YSLVLYTQHM LLCGLEGYFP EIAEKYLDGS
     LELRDMFKYV RVYIYSDDVV LTTPNQHYAA SFDRWVPHLQ ALLGFKVDPK KTVNTSSPSF
     LGCRFKQVDG KCYLASLQDR VTRSLLYHIG AKNPSEYYEA AVSIFKDSII CCDEDWWTDL
     HRRISGAART DGVEFPTIEM LTSFRTKQYE SAVCTVCGAA PVAKSACGGW FCGNCVPYHA
     GHCHTTSLFA NCGHDIMYRS TYCTMCEGSP KQMVPKVPHP ILDHLLCHID YGSKEELTLV
     VADGRTTSPP GRYKVGHKVV AVVADVGGNI VFGCGPGSHI AVPLQDTLKG VVVNKALKNA
     AASEYVEGPP GSGKTFHLVK DVLAVVGSAT LVVPTHASML DCINKLKQAG ADPYFVVPKY
     TVLDFPRPGS GNITVRLPQV GTSEGETFVD EVAYFSPVDL ARILTQGRVK GYGDLNQLGC
     VGPASVPRNL WLRHFVSLEP LRVCHRFGAA VCDLIKGIYP YYEPAPHTTK VVFVPNPDFE
     KGVVITAYHK DRGLGHRTID SIQGCTFPVV TLRLPTPQSL TRPRAVVAVT RASQELYIYD
     PFDQLSGLLK FTKEAEAQDL IHGPPTACHL GQEIDLWSNE GLEYYKEVNL LYTHVPIKDG
     VIHSYPNCGP ACGWEKQSNK ISCLPRVAQN LGYHYSPDLP GFCPIPKELA EHWPVVSNDR
     YPNCLQITLQ QVCELSKPCS AGYMVGQSVF VQTPGVTSYW LTEWVDGKAR ALPDSLFSSG
     RFETNSRAFL DEAEEKFAAA HPHACLGEIN KSTVGGSHFI FSQYLPPLLP ADAVALVGAS
     LAGKAAKAAC SVVDVYAPSF EPYLHPETLS RVYKIMIDFK PCRLMVWRNA TFYVQEGVDA
     VTSALAAVSK LIKVPANEPV SFHVASGYRT NALVAPQAKI SIGAYAAEWA LSTEPPPAGY
     AIVRRYIVKR LLSSTEVFLC RRGVVSSTSV QTICALEGCK PLFNFLQIGS VIGPV
//