ID   RPOA_PRRSL              Reviewed;        3855 AA.
AC   Q04561;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   10-AUG-2010, sequence version 3.
DT   27-MAR-2024, entry version 160.
DE   RecName: Full=Replicase polyprotein 1ab;
DE   AltName: Full=ORF1ab polyprotein;
DE   Contains:
DE     RecName: Full=Nsp1;
DE              EC=3.4.22.-;
DE   Contains:
DE     RecName: Full=Nsp1-alpha papain-like cysteine proteinase;
DE              EC=3.4.22.-;
DE     AltName: Full=PCP1-alpha;
DE   Contains:
DE     RecName: Full=Nsp1-beta papain-like cysteine proteinase;
DE              EC=3.4.22.-;
DE     AltName: Full=PCP1-beta;
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=Serine protease nsp4;
DE              Short=3CLSP;
DE              EC=3.4.21.- {ECO:0000269|PubMed:25008936};
DE     AltName: Full=3C-like serine proteinase;
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 nsp10;
DE              Short=Hel;
DE              EC=3.6.4.12;
DE              EC=3.6.4.13;
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   Porcine reproductive and respiratory syndrome virus (strain Lelystad)
OS   (PRRSV).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Arnidovirineae; Arteriviridae; Variarterivirinae;
OC   Betaarterivirus; Eurpobartevirus; Betaarterivirus suid 1.
OX   NCBI_TaxID=11049;
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=8517032; DOI=10.1006/viro.1993.1008;
RA   Meulenberg J.J.M., Hulst M.M., de Meijer E.J., Moonen P.L.J.M.,
RA   den Besten A., de Kluyver E.P., Wensvoort G., Moormann R.J.M.;
RT   "Lelystad virus, the causative agent of porcine epidemic abortion and
RT   respiratory syndrome (PEARS), is related to LDV and EAV.";
RL   Virology 192:62-72(1993).
RN   [2]
RP   SEQUENCE REVISION TO 3327.
RA   Kroese M.V., Moormann R.J.M.;
RL   Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 3323-3855.
RC   STRAIN=Isolate Boxmeer 10;
RX   PubMed=8438574; DOI=10.1006/viro.1993.1129;
RA   Conzelmann K.K., Visser N., van Woensel P., Thiel H.J.;
RT   "Molecular characterization of porcine reproductive and respiratory
RT   syndrome virus, a member of the arterivirus group.";
RL   Virology 193:329-339(1993).
RN   [4]
RP   ACTIVE SITES OF PCP1-ALPHA AND PCP1-BETA, AND MUTAGENESIS OF CYS-76;
RP   HIS-92; HIS-115; HIS-146; HIS-157; HIS-157; CYS-276 AND HIS-345.
RX   PubMed=7769711; DOI=10.1128/jvi.69.7.4500-4505.1995;
RA   den Boon J.A., Faaberg K.S., Meulenberg J.J.M., Wassenaar A.L.M.,
RA   Plagemann P.G.W., Gorbalenya A.E., Snijder E.J.;
RT   "Processing and evolution of the N-terminal region of the arterivirus
RT   replicase ORF1a protein: identification of two papainlike cysteine
RT   proteases.";
RL   J. Virol. 69:4500-4505(1995).
RN   [5]
RP   FUNCTION (HELICASE).
RX   PubMed=12127789; DOI=10.1006/viro.2002.1495;
RA   Bautista E.M., Faaberg K.S., Mickelson D., McGruder E.D.;
RT   "Functional properties of the predicted helicase of porcine reproductive
RT   and respiratory syndrome virus.";
RL   Virology 298:258-270(2002).
RN   [6]
RP   FUNCTION (SERINE PROTEASE NSP4), AND ACTIVE SITE (SERINE PROTEASE NSP4).
RC   STRAIN=JXA1;
RX   PubMed=19646449; DOI=10.1016/j.jmb.2009.07.062;
RA   Tian X., Lu G., Gao F., Peng H., Feng Y., Ma G., Bartlam M., Tian K.,
RA   Yan J., Hilgenfeld R., Gao G.F.;
RT   "Structure and cleavage specificity of the chymotrypsin-like serine
RT   protease (3CLSP/nsp4) of Porcine Reproductive and Respiratory Syndrome
RT   Virus (PRRSV).";
RL   J. Mol. Biol. 392:977-993(2009).
RN   [7]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 5-6-7), AND SUBCELLULAR LOCATION
RP   (NON-STRUCTURAL PROTEIN 5-6-7).
RX   PubMed=21799305; DOI=10.4161/auto.7.11.16642;
RA   Cottam E.M., Maier H.J., Manifava M., Vaux L.C., Chandra-Schoenfelder P.,
RA   Gerner W., Britton P., Ktistakis N.T., Wileman T.;
RT   "Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic
RT   reticulum via an omegasome intermediate.";
RL   Autophagy 7:1335-1347(2011).
RN   [8]
RP   FUNCTION (NSP1-ALPHA PAPAIN-LIKE CYSTEINE PROTEINASE), AND SUBCELLULAR
RP   LOCATION (NSP1-ALPHA PAPAIN-LIKE CYSTEINE PROTEINASE).
RC   STRAIN=PA8;
RX   PubMed=23287061; DOI=10.1016/j.virusres.2012.12.012;
RA   Han M., Du Y., Song C., Yoo D.;
RT   "Degradation of CREB-binding protein and modulation of type I interferon
RT   induction by the zinc finger motif of the porcine reproductive and
RT   respiratory syndrome virus nsp1alpha subunit.";
RL   Virus Res. 172:54-65(2013).
RN   [9]
RP   FUNCTION (SERINE PROTEASE NSP4).
RC   STRAIN=CH-1a;
RX   PubMed=23936003; DOI=10.1371/journal.pone.0069387;
RA   Ma Z., Wang Y., Zhao H., Xu A.T., Wang Y., Tang J., Feng W.H.;
RT   "Porcine reproductive and respiratory syndrome virus nonstructural protein
RT   4 induces apoptosis dependent on its 3C-like serine protease activity.";
RL   PLoS ONE 8:E69387-E69387(2013).
RN   [10]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 3), SUBCELLULAR LOCATION (NON-STRUCTURAL
RP   PROTEIN 3), AND INTERACTION WITH HOST IFITM1 (NON-STRUCTURAL PROTEIN 3).
RC   STRAIN=JXwn06;
RX   PubMed=25102331; DOI=10.1016/j.virusres.2014.07.025;
RA   Wang X., Li C., Zhou L., Zhang N., Wang X., Ge X., Guo X., Yang H.;
RT   "Porcine reproductive and respiratory syndrome virus counteracts the
RT   porcine intrinsic virus restriction factors-IFITM1 and Tetherin in MARC-145
RT   cells.";
RL   Virus Res. 191:92-100(2014).
RN   [11]
RP   FUNCTION (SERINE PROTEASE NSP4), ACTIVE SITE (SERINE PROTEASE NSP4), AND
RP   MUTAGENESIS OF HIS-1732; ASP-1757 AND SER-1810.
RX   PubMed=25008936; DOI=10.1128/jvi.01396-14;
RA   Huang C., Zhang Q., Guo X.K., Yu Z.B., Xu A.T., Tang J., Feng W.H.;
RT   "Porcine reproductive and respiratory syndrome virus nonstructural protein
RT   4 antagonizes beta interferon expression by targeting the NF-kappaB
RT   essential modulator.";
RL   J. Virol. 88:10934-10945(2014).
RN   [12]
RP   FUNCTION (RNA-DIRECTED RNA POLYMERASE), INTERACTION WITH HOST DDX5
RP   (RNA-DIRECTED RNA POLYMERASE), AND SUBCELLULAR LOCATION (RNA-DIRECTED RNA
RP   POLYMERASE).
RC   STRAIN=JXwn06;
RX   PubMed=25449571; DOI=10.1016/j.virusres.2014.10.021;
RA   Zhao S., Ge X., Wang X., Liu A., Guo X., Zhou L., Yu K., Yang H.;
RT   "The DEAD-box RNA helicase 5 positively regulates the replication of
RT   porcine reproductive and respiratory syndrome virus by interacting with
RT   viral Nsp9 in vitro.";
RL   Virus Res. 195:217-224(2015).
RN   [13]
RP   FUNCTION (URIDYLATE-SPECIFIC ENDORIBONUCLEASE NSP11).
RC   STRAIN=BJ-4;
RX   PubMed=26398903; DOI=10.1089/dna.2015.2929;
RA   Wang C., Shi X., Zhang X., Wang A., Wang L., Chen J., Deng R., Zhang G.;
RT   "The endoribonuclease activity essential for the nonstructural protein 11
RT   of porcine reproductive and respiratory syndrome virus to inhibit NLRP3
RT   inflammasome-Mediated IL-1beta induction.";
RL   DNA Cell Biol. 34:728-735(2015).
RN   [14]
RP   FUNCTION (SERINE PROTEASE NSP4).
RX   PubMed=27329948; DOI=10.1038/srep28497;
RA   Huang C., Du Y., Yu Z., Zhang Q., Liu Y., Tang J., Shi J., Feng W.H.;
RT   "Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Nsp4
RT   Cleaves VISA to Impair Antiviral Responses Mediated by RIG-I-like
RT   Receptors.";
RL   Sci. Rep. 6:28497-28497(2016).
RN   [15]
RP   FUNCTION (NSP1-BETA PAPAIN-LIKE CYSTEINE PROTEINASE), SUBCELLULAR LOCATION
RP   (NSP1-ALPHA PAPAIN-LIKE CYSTEINE PROTEINASE), AND SUBCELLULAR LOCATION
RP   (NSP1-BETA PAPAIN-LIKE CYSTEINE PROTEINASE).
RX   PubMed=28235682; DOI=10.1016/j.virol.2017.02.004;
RA   Han M., Ke H., Zhang Q., Yoo D.;
RT   "Nuclear imprisonment of host cellular mRNA by nsp1beta protein of porcine
RT   reproductive and respiratory syndrome virus.";
RL   Virology 505:42-55(2017).
RN   [16]
RP   FUNCTION (NSP1-ALPHA PAPAIN-LIKE CYSTEINE PROTEINASE), AND INTERACTION WITH
RP   HOST RNF31 (NSP1-ALPHA PAPAIN-LIKE CYSTEINE PROTEINASE).
RX   PubMed=27881655; DOI=10.1128/jvi.01911-16;
RA   Jing H., Fang L., Ding Z., Wang D., Hao W., Gao L., Ke W., Chen H.,
RA   Xiao S.;
RT   "Porcine Reproductive and Respiratory Syndrome Virus nsp1alpha Inhibits NF-
RT   kappaB Activation by Targeting the Linear Ubiquitin Chain Assembly
RT   Complex.";
RL   J. Virol. 91:0-0(2017).
RN   [17]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 5).
RX   PubMed=27881658; DOI=10.1128/jvi.02087-16;
RA   Yang L., Wang R., Ma Z., Xiao Y., Nan Y., Wang Y., Lin S., Zhang Y.J.;
RT   "Porcine Reproductive and Respiratory Syndrome Virus Antagonizes JAK/STAT3
RT   Signaling via nsp5, Which Induces STAT3 Degradation.";
RL   J. Virol. 91:0-0(2017).
RN   [18]
RP   INTERACTION WITH HOST DDX18 (NSP2 CYSTEINE PROTEINASE), INTERACTION WITH
RP   HOST DDX18 (HELICASE NSP10), SUBCELLULAR LOCATION (NSP2 CYSTEINE
RP   PROTEINASE), AND SUBCELLULAR LOCATION (HELICASE NSP10).
RX   PubMed=28648849; DOI=10.1016/j.virusres.2017.05.028;
RA   Jin H., Zhou L., Ge X., Zhang H., Zhang R., Wang C., Wang L., Zhang Z.,
RA   Yang H., Guo X.;
RT   "Cellular DEAD-box RNA helicase 18 (DDX18) Promotes the PRRSV Replication
RT   via Interaction with Virus nsp2 and nsp10.";
RL   Virus Res. 238:204-212(2017).
RN   [19]
RP   FUNCTION (URIDYLATE-SPECIFIC ENDORIBONUCLEASE NSP11), SUBCELLULAR LOCATION
RP   (URIDYLATE-SPECIFIC ENDORIBONUCLEASE NSP11), AND INTERACTION WITH HOST
RP   OTULIN (URIDYLATE-SPECIFIC ENDORIBONUCLEASE NSP11).
RX   PubMed=29444948; DOI=10.1128/jvi.00175-18;
RA   Su Y., Shi P., Zhang L., Lu D., Zhao C., Li R., Zhang L., Huang J.;
RT   "The Superimposed Deubiquitination Effect of OTULIN and Porcine
RT   Reproductive and Respiratory Syndrome Virus (PRRSV) Nsp11 Promotes
RT   Multiplication of PRRSV.";
RL   J. Virol. 92:0-0(2018).
RN   [20]
RP   FUNCTION (SERINE PROTEASE NSP4), AND MUTAGENESIS OF HIS-1732; ASP-1757 AND
RP   SER-1810.
RX   PubMed=30158128; DOI=10.4049/jimmunol.1701773;
RA   Tao R., Fang L., Bai D., Ke W., Zhou Y., Wang D., Xiao S.;
RT   "Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein
RT   4 Cleaves Porcine DCP1a To Attenuate Its Antiviral Activity.";
RL   J. Immunol. 201:2345-2353(2018).
RN   [21]
RP   INTERACTION WITH HOST LGALS3 (NON-STRUCTURAL PROTEIN 12), AND SUBCELLULAR
RP   LOCATION (NON-STRUCTURAL PROTEIN 12).
RX   PubMed=29920289; DOI=10.1016/j.virusres.2018.06.006;
RA   Li L., Zhou Y., Jiang Y., Gao F., Shan T., Zhao K., Zhang Y., Li L.,
RA   Tong G.;
RT   "Galectin-3 inhibits replication of porcine reproductive and respiratory
RT   syndrome virus by interacting with viral Nsp12 in vitro.";
RL   Virus Res. 253:87-91(2018).
CC   -!- FUNCTION: [Replicase polyprotein 1ab]: Contains the activities
CC       necessary for the transcription of negative stranded RNA, leader RNA,
CC       subgenomic mRNAs and progeny virion RNA as well as proteinases
CC       responsible for the cleavage of the polyprotein into functional
CC       products.
CC   -!- FUNCTION: [Nsp1-alpha papain-like cysteine proteinase]: Inhibits host
CC       IFN-beta production. Plays a role in the degradation of the host
CC       transcriptional activator CREBBP protein (PubMed:23287061). The
CC       degradation of host CREBBP which is a key component of the IFN
CC       enhanceosome is likely responsible for the inhibition of interferon
CC       mediated by Nsp1-alpha (PubMed:23287061). Participates also in the
CC       inhibition of host NF-kappa-B activation by counteracting LUBAC-
CC       dependent induction of NF-kappa-B (PubMed:27881655). Reduces host NEMO
CC       ubiquitination by blocking the interaction between the two LUBAC
CC       complex components RNF31 and SHARPIN (PubMed:27881655).
CC       {ECO:0000250|UniProtKB:Q9WJB2, ECO:0000269|PubMed:23287061,
CC       ECO:0000269|PubMed:27881655}.
CC   -!- FUNCTION: [Nsp1-beta papain-like cysteine proteinase]: Plays a role in
CC       blocking host mRNA nuclear export to the cytoplasm and subversion of
CC       host protein synthesis (PubMed:28235682). Additionally, inhibits the
CC       interferon-activated JAK/STAT signal transduction by mediating the
CC       ubiquitination and subsequent proteasomal degradation of host KPNA1 (By
CC       similarity). Repurposes the host antiviral stress granules into a
CC       proviral platform to counteract the EIF2AK2/PKR restriction, thereby
CC       regulating the host inflammatory response (By similarity).
CC       {ECO:0000250|UniProtKB:A6YQT5, ECO:0000250|UniProtKB:Q9WJB2,
CC       ECO:0000269|PubMed:28235682}.
CC   -!- FUNCTION: [Nsp2 cysteine proteinase]: Multifunctional protein that acts
CC       as a viral protease and as a viral antagonist of host immune response.
CC       Cleaves the nsp2/nsp3 site in the viral polyprotein. Displays
CC       deubiquitinating activity that cleaves both ubiquitinated and ISGylated
CC       products and therefore inhibits ubiquitin and ISG15-dependent host
CC       innate immunity. Deubiquitinates also host NFKBIA, thereby interfering
CC       with NFKBIA degradation and impairing subsequent NF-kappa-B activation.
CC       {ECO:0000250|UniProtKB:A0MD28}.
CC   -!- FUNCTION: [Non-structural protein 3]: Plays a role in the inhibition of
CC       the immune response by interacting with host IFITM1 (PubMed:25102331).
CC       This interaction leads to the proteasomal degradation of the IFN-
CC       induced antiviral protein IFITM1 (PubMed:25102331).
CC       {ECO:0000269|PubMed:25102331}.
CC   -!- FUNCTION: [Serine protease nsp4]: Cleaves the majority of cleavage
CC       sites present in the C-terminus of the polyprotein (PubMed:19646449).
CC       Triggers host apoptosis through caspase-3, -8, and -9 activations.
CC       Subverts host innate immune responses through its protease activity.
CC       Targets the NF-kappa-B essential modulator NEMO and mediates its
CC       cleavage (PubMed:25008936). Blocks host interferon beta induction and
CC       downstream signaling by cleaving mitochondrial MAVS, dislodging it from
CC       the mitochondria (PubMed:27329948). Impairs host defense by cleaving
CC       host mRNA-decapping enzyme DCP1A to attenuate its antiviral activity
CC       (PubMed:30158128). {ECO:0000269|PubMed:19646449,
CC       ECO:0000269|PubMed:23936003, ECO:0000269|PubMed:25008936,
CC       ECO:0000269|PubMed:27329948, ECO:0000269|PubMed:30158128}.
CC   -!- FUNCTION: [Non-structural protein 5-6-7]: Plays a role in the initial
CC       induction of autophagosomes from host reticulum endoplasmic.
CC       {ECO:0000269|PubMed:21799305}.
CC   -!- FUNCTION: [Non-structural protein 5]: Plays a role in the inhibition of
CC       host STAT3 signaling pathway by inducing the degradation of STAT3.
CC       {ECO:0000269|PubMed:27881658}.
CC   -!- FUNCTION: [RNA-directed RNA polymerase]: Responsible for replication
CC       and transcription of the viral RNA genome.
CC       {ECO:0000269|PubMed:25449571}.
CC   -!- FUNCTION: [Helicase nsp10]: Displays RNA and DNA duplex-unwinding
CC       activities with 5' to 3' polarity. {ECO:0000269|PubMed:12127789}.
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, PKR (By
CC       similarity) and NLRP3 inflammasome (PubMed:26398903). Acts by degrading
CC       the 5'-polyuridines generated during replication of the poly(A) region
CC       of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in
CC       which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O
CC       transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P)
CC       (By similarity). If not degraded, poly(U) RNA would hybridize with
CC       poly(A) RNA tails and activate host dsRNA sensors (By similarity). Also
CC       plays a role in the inhibition of host type I interferon production by
CC       recruiting host OTULIN to promote removal of linear ubiquitination
CC       targeting host NEMO (PubMed:29444948). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000250|UniProtKB:P19811, ECO:0000269|PubMed:26398903,
CC       ECO:0000269|PubMed:29444948}.
CC   -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]:
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: [Helicase nsp10]:
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   -!- CATALYTIC ACTIVITY: [Helicase nsp10]:
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   -!- CATALYTIC ACTIVITY: [Nsp2 cysteine proteinase]:
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:0000250|UniProtKB:P19811};
CC   -!- SUBUNIT: Nsp1-alpha papain-like: Interacts with host RNF31
CC       (PubMed:27881655). {ECO:0000269|PubMed:27881655}.
CC   -!- SUBUNIT: [Nsp1-beta papain-like cysteine proteinase]: Interacts with
CC       host EIF2AK2; this interaction occurs in host stress granules and leads
CC       to EIF2AK2 inhibition (By similarity). Interacts with host G3BP1; this
CC       interaction probably plays a role in Nsp1-beta-mediated inhibition of
CC       host EIF2AK2 (By similarity). {ECO:0000250|UniProtKB:A6YQT5}.
CC   -!- SUBUNIT: [Nsp2 cysteine proteinase]: Interacts with host DDX18; this
CC       interaction redistributes host DDX18 to the cytoplasm
CC       (PubMed:28648849). {ECO:0000269|PubMed:28648849}.
CC   -!- SUBUNIT: [Non-structural protein 3]: Interacts with host IFITM1
CC       (PubMed:25102331). {ECO:0000269|PubMed:25102331}.
CC   -!- SUBUNIT: [RNA-directed RNA polymerase]: Interacts with host DDX5
CC       (PubMed:25449571). {ECO:0000269|PubMed:25449571}.
CC   -!- SUBUNIT: [Helicase nsp10]: Interacts with host DDX18; this interaction
CC       redistributes host DDX18 to the cytoplasm (PubMed:28648849).
CC       {ECO:0000269|PubMed:28648849}.
CC   -!- SUBUNIT: [Uridylate-specific endoribonuclease nsp11]: Interacts with
CC       host OTULIN (PubMed:29444948). {ECO:0000269|PubMed:29444948}.
CC   -!- SUBUNIT: [Non-structural protein 12]: Interacts with host LGALS3
CC       (PubMed:29920289). {ECO:0000269|PubMed:29920289}.
CC   -!- INTERACTION:
CC       PRO_0000036687; A0A068CA64: AIFM1; Xeno; NbExp=2; IntAct=EBI-11701979, EBI-11702079;
CC       PRO_0000036687; A5D9M6: BAG6; Xeno; NbExp=2; IntAct=EBI-11701979, EBI-11702016;
CC   -!- SUBCELLULAR LOCATION: [Nsp1]: Host nucleus
CC       {ECO:0000269|PubMed:23287061}. Host cytoplasm
CC       {ECO:0000269|PubMed:23287061}.
CC   -!- SUBCELLULAR LOCATION: [Nsp1-alpha papain-like cysteine proteinase]:
CC       Host nucleus {ECO:0000269|PubMed:23287061,
CC       ECO:0000269|PubMed:28235682}. Host cytoplasm
CC       {ECO:0000269|PubMed:23287061, ECO:0000269|PubMed:28235682}.
CC   -!- SUBCELLULAR LOCATION: [Nsp1-beta papain-like cysteine proteinase]: Host
CC       nucleus {ECO:0000269|PubMed:23287061, ECO:0000269|PubMed:28235682}.
CC       Host cytoplasm {ECO:0000250|UniProtKB:A6YQT5}. Note=Accumulates mainly
CC       in the host cytoplasm in early infection and then mostly in the host
CC       nucleus. {ECO:0000250|UniProtKB:A6YQT5}.
CC   -!- SUBCELLULAR LOCATION: [Nsp2 cysteine proteinase]: Host cytoplasm
CC       {ECO:0000269|PubMed:28648849}. Host membrane {ECO:0000305}; Multi-pass
CC       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 endoplasmic
CC       reticulum {ECO:0000269|PubMed:21799305}. Host membrane {ECO:0000305};
CC       Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Serine protease nsp4]: Host cytoplasm
CC       {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm
CC       {ECO:0000269|PubMed:25449571}. Host cytoplasm, host perinuclear region
CC       {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Helicase nsp10]: Host cytoplasm
CC       {ECO:0000269|PubMed:28648849}. Host cytoplasm, host perinuclear region
CC       {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease nsp11]: Host
CC       cytoplasm {ECO:0000269|PubMed:29444948}. Host nucleus
CC       {ECO:0000269|PubMed:29444948}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 12]: Host cytoplasm
CC       {ECO:0000269|PubMed:29920289}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=3;
CC       Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC         IsoId=Q04561-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC         IsoId=Q04561-2; Sequence=VSP_032892;
CC       Name=Replicase polyprotein 1TF;
CC         IsoId=P0DJZ9-1; Sequence=External;
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. {ECO:0000250}.
CC   -!- DOMAIN: The OTU-like region is responsible for the deubiquitinating and
CC       deISGylation activities of Nsp2. {ECO:0000250}.
CC   -!- PTM: [Replicase polyprotein 1ab]: Specific enzymatic cleavages in vivo
CC       by its own proteases yield mature proteins. Nsp1 is autocleaved into
CC       two subunits, Nsp1-alpha and Nsp1-beta. There are two alternative
CC       pathways for processing. Either nsp4-5 is cleaved, which represents the
CC       major pathway or the nsp5-6 and nsp6-7 are processed, which represents
CC       the minor pathway. The major pathway occurs when nsp2 acts as a
CC       cofactor for nsp4. {ECO:0000250|UniProtKB:Q9WJB2}.
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA46273.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAA46274.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; M96262; AAA46273.2; ALT_INIT; Genomic_RNA.
DR   EMBL; M96262; AAA46274.1; ALT_INIT; Genomic_RNA.
DR   EMBL; L04493; AAA47101.1; -; Genomic_RNA.
DR   PIR; A36861; A36861.
DR   PIR; A45392; A45392.
DR   PIR; B36861; B36861.
DR   SMR; Q04561; -.
DR   IntAct; Q04561; 2.
DR   MEROPS; C32.001; -.
DR   MEROPS; S32.002; -.
DR   Proteomes; UP000006687; Genome.
DR   GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
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:0030291; F:protein serine/threonine kinase inhibitor 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:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0039563; P:disruption by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR   GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
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:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR   GO; GO:0039580; P:suppression by virus of host PKR signaling; 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; cd21410; 1B_av_Nsp10-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; 3.90.70.160; -; 1.
DR   Gene3D; 4.10.80.390; -; 1.
DR   Gene3D; 3.30.1330.220; Arterivirus nonstructural protein 7 alpha; 1.
DR   Gene3D; 2.30.31.30; Arterivirus nps1beta, nuclease domain; 1.
DR   Gene3D; 3.90.70.70; Arterivirus papain-like cysteine protease beta domain; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   Gene3D; 3.90.70.60; Porcine arterivirus-type cysteine proteinase alpha domain; 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; IPR038155; AV_PCPalpha_sf.
DR   InterPro; IPR025773; AV_PCPbeta.
DR   InterPro; IPR038154; AV_PCPbeta_sf.
DR   InterPro; IPR023183; Chymotrypsin-like_C.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR008760; EAV_peptidase_S32.
DR   InterPro; IPR037227; EndoU-like.
DR   InterPro; IPR043609; NendoU_nidovirus.
DR   InterPro; IPR044863; NIRAN.
DR   InterPro; IPR044348; NSP10_1B_Av.
DR   InterPro; IPR027355; NSP10_Av_ZBD.
DR   InterPro; IPR044320; NSP11_Av_N.
DR   InterPro; IPR044314; NSP11_NendoU_Av.
DR   InterPro; IPR032855; NSP2-B_epitope.
DR   InterPro; IPR032841; NSP2_assoc.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001205; RNA-dir_pol_C.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   Pfam; PF16749; Arteri_nsp7a; 1.
DR   Pfam; PF14757; NSP2-B_epitope; 1.
DR   Pfam; PF14758; NSP2_assoc; 1.
DR   Pfam; PF05410; Peptidase_C31; 1.
DR   Pfam; PF05411; Peptidase_C32; 1.
DR   Pfam; PF05412; Peptidase_C33; 1.
DR   Pfam; PF05579; Peptidase_S32; 1.
DR   Pfam; PF00680; RdRP_1; 1.
DR   Pfam; PF01443; Viral_helicase1; 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   Activation of host autophagy by virus; ATP-binding; Endonuclease; Helicase;
KW   Host cytoplasm; Host endoplasmic reticulum; Host membrane; Host nucleus;
KW   Host-virus interaction; Hydrolase;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host ISG15 by virus; Inhibition of host NF-kappa-B by virus;
KW   Inhibition of host PKR by virus; Inhibition of host STAT1 by virus;
KW   Interferon antiviral system evasion; 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..3855
FT                   /note="Replicase polyprotein 1ab"
FT                   /id="PRO_0000036683"
FT   CHAIN           1..384
FT                   /note="Nsp1"
FT                   /id="PRO_0000410828"
FT   CHAIN           1..180
FT                   /note="Nsp1-alpha papain-like cysteine proteinase"
FT                   /id="PRO_0000036685"
FT   CHAIN           181..385
FT                   /note="Nsp1-beta papain-like cysteine proteinase"
FT                   /id="PRO_0000036686"
FT   CHAIN           386..1463
FT                   /note="Nsp2 cysteine proteinase"
FT                   /id="PRO_0000036687"
FT   CHAIN           1464..1693
FT                   /note="Non-structural protein 3"
FT                   /id="PRO_0000036688"
FT   CHAIN           1694..1896
FT                   /note="Serine protease nsp4"
FT                   /id="PRO_0000036689"
FT   CHAIN           1897..2351
FT                   /note="Non-structural protein 5-6-7"
FT                   /id="PRO_0000036690"
FT   CHAIN           1897..2066
FT                   /note="Non-structural protein 5"
FT                   /id="PRO_0000423126"
FT   CHAIN           2067..2082
FT                   /note="Non-structural protein 6"
FT                   /id="PRO_0000423127"
FT   CHAIN           2083..2231
FT                   /note="Non-structural protein 7-alpha"
FT                   /id="PRO_0000423128"
FT   CHAIN           2232..2351
FT                   /note="Non-structural protein 7-beta"
FT                   /id="PRO_0000423129"
FT   CHAIN           2352..3037
FT                   /note="RNA-directed RNA polymerase"
FT                   /id="PRO_0000036691"
FT   CHAIN           2352..2396
FT                   /note="Non-structural protein 8"
FT                   /id="PRO_0000036692"
FT   CHAIN           3038..3479
FT                   /note="Helicase nsp10"
FT                   /id="PRO_0000036693"
FT   CHAIN           3480..3703
FT                   /note="Uridylate-specific endoribonuclease nsp11"
FT                   /id="PRO_0000036694"
FT   CHAIN           3704..3855
FT                   /note="Non-structural protein 12"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036695"
FT   TRANSMEM        1134..1154
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1179..1199
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1252..1272
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1468..1488
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1521..1541
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1543..1563
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1573..1593
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1609..1629
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1919..1939
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1943..1963
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1977..1997
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2020..2040
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          69..180
FT                   /note="Peptidase C31"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00872"
FT   DOMAIN          269..385
FT                   /note="Peptidase C32"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
FT   DOMAIN          420..527
FT                   /note="Peptidase C33"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT   DOMAIN          1694..1896
FT                   /note="Peptidase S32"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   DOMAIN          2381..2544
FT                   /note="NiRAN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01292"
FT   DOMAIN          2783..2917
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          3038..3101
FT                   /note="AV ZBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   DOMAIN          3151..3310
FT                   /note="(+)RNA virus helicase ATP-binding"
FT   DOMAIN          3311..3440
FT                   /note="(+)RNA virus helicase C-terminal"
FT   DOMAIN          3479..3576
FT                   /note="AV-Nsp11N/CoV-Nsp15M"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01306"
FT   DOMAIN          3578..3700
FT                   /note="NendoU"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ZN_FING         8..28
FT                   /note="C4-type; atypical"
FT   REGION          69..182
FT                   /note="PCP1-alpha"
FT   REGION          203..204
FT                   /note="Important for host EIF2AK2 inhibition"
FT                   /evidence="ECO:0000250|UniProtKB:A6YQT5"
FT   REGION          269..384
FT                   /note="PCP1-beta"
FT   REGION          418..505
FT                   /note="OTU-like"
FT   REGION          752..797
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1047..1088
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1149..1272
FT                   /note="HD1"
FT   REGION          1327..1351
FT                   /note="WCCH"
FT   REGION          1468..1629
FT                   /note="HD2"
FT   REGION          1919..2040
FT                   /note="HD3"
FT   COMPBIAS        773..788
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        76
FT                   /note="For nsp1-alpha papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00872,
FT                   ECO:0000269|PubMed:7769711"
FT   ACT_SITE        146
FT                   /note="For nsp1-alpha papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00872,
FT                   ECO:0000269|PubMed:7769711"
FT   ACT_SITE        276
FT                   /note="For nsp1-beta papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00873,
FT                   ECO:0000269|PubMed:7769711"
FT   ACT_SITE        345
FT                   /note="For nsp1-beta papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00873,
FT                   ECO:0000269|PubMed:7769711"
FT   ACT_SITE        429
FT                   /note="For nsp2 cysteine proteinase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT   ACT_SITE        498
FT                   /note="For nsp2 cysteine proteinase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT   ACT_SITE        1732
FT                   /note="Charge relay system; for serine protease nsp4
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826,
FT                   ECO:0000269|PubMed:19646449, ECO:0000269|PubMed:25008936"
FT   ACT_SITE        1757
FT                   /note="Charge relay system; for serine protease nsp4
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826,
FT                   ECO:0000269|PubMed:19646449, ECO:0000269|PubMed:25008936"
FT   ACT_SITE        1810
FT                   /note="Charge relay system; for serine protease nsp4
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826,
FT                   ECO:0000269|PubMed:19646449, ECO:0000269|PubMed:25008936"
FT   ACT_SITE        3609
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        3624
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        3653
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   BINDING         3044
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3047
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3057
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3062
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3065
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3067
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3069
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3071
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3078
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3080
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3087
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3090
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3186..3193
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   SITE            180..181
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WJB2"
FT   SITE            385..386
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WJB2"
FT   SITE            1463..1464
FT                   /note="Cleavage; by CP2"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            1693..1694
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            1896..1897
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2066..2067
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2082..2083
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2231..2232
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2351..2352
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2396..2397
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            3037..3038
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            3088
FT                   /note="Involved in mRNA transcription process"
FT                   /evidence="ECO:0000250"
FT   SITE            3479..3480
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250"
FT   SITE            3703..3704
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         2397..3855
FT                   /note="Missing (in isoform Replicase polyprotein 1a)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_032892"
FT   MUTAGEN         76
FT                   /note="C->G,S: Complete loss of cleavage between nsp1-alpha
FT                   and nsp1-beta."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         92
FT                   /note="H->F,Y: No effect."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         115
FT                   /note="H->A: No effect."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         115
FT                   /note="H->Y: 50% loss of cleavage between nsp1-alpha and
FT                   nsp1-beta."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         146
FT                   /note="H->D,F,I,N,Y: Complete loss of cleavage between
FT                   nsp1-alpha and nsp1-beta."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         157
FT                   /note="H->D: 20% loss of cleavage between nsp1-alpha and
FT                   nsp1-beta."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         157
FT                   /note="H->I: 90% loss of cleavage between nsp1-alpha and
FT                   nsp1-beta."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         157
FT                   /note="H->N: 50% loss of cleavage between nsp1-alpha and
FT                   nsp1-beta."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         157
FT                   /note="H->Y: No effect."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         276
FT                   /note="C->I,L,R,S: Complete loss of cleavage between
FT                   nsp1-beta and nsp2."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         345
FT                   /note="H->D,Y: Complete loss of cleavage between nsp1-beta
FT                   and nsp2."
FT                   /evidence="ECO:0000269|PubMed:7769711"
FT   MUTAGEN         1732
FT                   /note="H->A: Complete loss of cleavage activity; when
FT                   associated with A-1757 and A-1810."
FT                   /evidence="ECO:0000269|PubMed:25008936"
FT   MUTAGEN         1732
FT                   /note="H->A: Complete loss of host DCP1A cleavage."
FT                   /evidence="ECO:0000269|PubMed:30158128"
FT   MUTAGEN         1757
FT                   /note="D->A: Complete loss of cleavage activity; when
FT                   associated with A-1732 and A-1810."
FT                   /evidence="ECO:0000269|PubMed:25008936"
FT   MUTAGEN         1757
FT                   /note="D->A: Complete loss of host DCP1A cleavage."
FT                   /evidence="ECO:0000269|PubMed:30158128"
FT   MUTAGEN         1810
FT                   /note="S->A: Complete loss of cleavage activity; when
FT                   associated with A-1732 and A-1757."
FT                   /evidence="ECO:0000269|PubMed:25008936"
FT   MUTAGEN         1810
FT                   /note="S->A: Complete loss of host DCP1A cleavage."
FT                   /evidence="ECO:0000269|PubMed:30158128"
FT   CONFLICT        3502
FT                   /note="T -> V (in Ref. 3; AAA47101)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        3740
FT                   /note="V -> I (in Ref. 3; AAA47101)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   3855 AA;  421332 MW;  421F613ED2E4858F CRC64;
     MSGTFSRCMC TPAARVFWNA GQVFCTRCLS ARSLLSPELQ DTDLGAVGLF YKPRDKLHWK
     VPIGIPQVEC TPSGCCWLSA VFPLARMTSG NHNFLQRLVK VADVLYRDGC LAPRHLRELQ
     VYERGCNWYP ITGPVPGMGL FANSMHVSDQ PFPGATHVLT NSPLPQQACR QPFCPFEEAH
     SSVYRWKKFV VFTDSSLNGR SRMMWTPESD DSAALEVLPP ELERQVEILI RSFPAHHPVD
     LADWELTESP ENGFSFNTSH SCGHLVQNPD VFDGKCWLSC FLGQSVEVRC HEEHLADAFG
     YQTKWGVHGK YLQRRLQVRG IRAVVDPDGP IHVEALSCPQ SWIRHLTLDD DVTPGFVRLT
     SLRIVPNTEP TTSRIFRFGA HKWYGAAGKR ARAKRAAKSE KDSAPTPKVA LPVPTCGITT
     YSPPTDGSCG WHVLAAIMNR MINGDFTSPL TQYNRPEDDW ASDYDLVQAI QCLRLPATVV
     RNRACPNAKY LIKLNGVHWE VEVRSGMAPR SLSRECVVGV CSEGCVAPPY PADGLPKRAL
     EALASAYRLP SDCVSSGIAD FLANPPPQEF WTLDKMLTSP SPERSGFSSL YKLLLEVVPQ
     KCGATEGAFI YAVERMLKDC PSSKQAMALL AKIKVPSSKA PSVSLDECFP TDVLADFEPA
     SQERPQSSGA AVVLCSPDAK EFEEAAPEEV QESGHKAVHS ALLAEGPNNE QVQVVAGEQL
     KLGGCGLAVG NAHEGALVSA GLINLVGGNL SPSDPMKENM LNSREDEPLD LSQPAPASTT
     TLVREQTPDN PGSDAGALPV TVREFVPTGP ILCHVEHCGT ESGDSSSPLD LSDAQTLDQP
     LNLSLAAWPV RATASDPGWV HGRREPVFVK PRNAFSDGDS ALQFGELSES SSVIEFDRTK
     DAPVVDAPVD LTTSNEALSV VDPFEFAELK RPRFSAQALI DRGGPLADVH AKIKNRVYEQ
     CLQACEPGSR ATPATREWLD KMWDRVDMKT WRCTSQFQAG RILASLKFLP DMIQDTPPPV
     PRKNRASDNA GLKQLVAQWD RKLSVTPPPK PVGPVLDQIV PPPTDIQQED VTPSDGPPHA
     PDFPSRVSTG GSWKGLMLSG TRLAGSISQR LMTWVFEVFS HLPAFMLTLF SPRGSMAPGD
     WLFAGVVLLA LLLCRSYPIL GCLPLLGVFS GSLRRVRLGV FGSWMAFAVF LFSTPSNPVG
     SSCDHDSPEC HAELLALEQR QLWEPVRGLV VGPSGLLCVI LGKLLGGSRY LWHVLLRLCM
     LADLALSLVY VVSQGRCHKC WGKCIRTAPA EVALNVFPFS RATRVSLVSL CDRFQTPKGV
     DPVHLATGWR GCWRGESPIH QPHQKPIAYA NLDEKKMSAQ TVVAVPYDPS QAIKCLKVLQ
     AGGAIVDQPT PEVVRVSEIP FSAPFFPKVP VNPDCRVVVD SDTFVAAVRC GYSTAQLVLG
     RGNFAKLNQT PPRNSISTKT TGGASYTLAV AQVSAWTLVH FILGLWFTSP QVCGRGTADP
     WCSNPFSYPT YGPGVVCSSR LCVSADGVTL PLFSAVAQLS GREVGIFILV LVSLTALAHR
     MALKADMLVV FSAFCAYAWP MSSWLICFFP ILLKWVTLHP LTMLWVHSFL VFCLPAAGIL
     SLGITGLLWA IGRFTQVAGI ITPYDIHQYT SGPRGAAAVA TAPEGTYMAA VRRAALTGRT
     LIFTPSAVGS LLEGAFRTHK PCLNTVNVVG SSLGSGGVFT IDGRRTVVTA AHVLNGDTAR
     VTGDSYNRMH TFKTNGDYAW SHADDWQGVA PVVKVAKGYR GRAYWQTSTG VEPGIIGEGF
     AFCFTNCGDS GSPVISESGD LIGIHTGSNK LGSGLVTTPE GETCTIKETK LSDLSRHFAG
     PSVPLGDIKL SPAIIPDVTS IPSDLASLLA SVPVVEGGLS TVQLLCVFFL LWRMMGHAWT
     PIVAVGFFLL NEILPAVLVR AVFSFALFVL AWATPWSAQV LMIRLLTASL NRNKLSLAFY
     ALGGVVGLAA EIGTFAGRLS ELSQALSTYC FLPRVLAMTS CVPTIIIGGL HTLGVILWLF
     KYRCLHNMLV GDGSFSSAFF LRYFAEGNLR KGVSQSCGMN NESLTAALAC KLSQADLDFL
     SSLTNFKCFV SASNMKNAAG QYIEAAYAKA LRQELASLVQ IDKMKGVLSK LEAFAETATP
     SLDIGDVIVL LGQHPHGSIL DINVGTERKT VSVQETRSLG GSKFSVCTVV SNTPVDALTG
     IPLQTPTPLF ENGPRHRSEE DDLKVERMKK HCVSLGFHNI NGKVYCKIWD KSTGDTFYTD
     DSRYTQDHAF QDRSADYRDR DYEGVQTTPQ QGFDPKSETP VGTVVIGGIT YNRYLIKGKE
     VLVPKPDNCL EAAKLSLEQA LAGMGQTCDL TAAEVEKLKR IISQLQGLTT EQALNCLLAA
     SGLTRCGRGG LVVTETAVKI IKYHSRTFTL GPLDLKVTSE VEVKKSTEQG HAVVANLCSG
     VILMRPHPPS LVDVLLKPGL DTIPGIQPGH GAGNMGVDGS IWDFETAPTK AELELSKQII
     QACEVRRGDA PNLQLPYKLY PVRGDPERHK GRLINTRFGD LPYKTPQDTK SAIHAACCLH
     PNGAPVSDGK STLGTTLQHG FELYVPTVPY SVMEYLDSRP DTPFMCTKHG TSKAAAEDLQ
     KYDLSTQGFV LPGVLRLVRR FIFGHIGKAP PLFLPSTYPA KNSMAGINGQ RFPTKDVQSI
     PEIDEMCARA VKENWQTVTP CTLKKQYCSK PKTRTILGTN NFIALAHRSA LSGVTQAFMK
     KAWKSPIALG KNKFKELHCT VAGRCLEADL ASCDRSTPAI VRWFVANLLY ELAGCEEYLP
     SYVLNCCHDL VATQDGAFTK RGGLSSGDPV TSVSNTVYSL VIYAQHMVLS ALKMGHEIGL
     KFLEEQLKFE DLLEIQPMLV YSDDLVLYAE RPTFPNYHWW VEHLDLMLGF RTDPKKTVIT
     DKPSFLGCRI EAGRQLVPNR DRILAALAYH MKAQNASEYY ASAAAILMDS CACIDHDPEW
     YEDLICGIAR CARQDGYSFP GPAFFMSMWE KLRSHNEGKK FRHCGICDAK ADYASACGLD
     LCLFHSHFHQ HCPVTLSCGH HAGSKECSQC QSPVGAGRSP LDAVLKQIPY KPPRTVIMKV
     GNKTTALDPG RYQSRRGLVA VKRGIAGNEV DLSDGDYQVV PLLPTCKDIN MVKVACNVLL
     SKFIVGPPGS GKTTWLLSQV QDDDVIYTPT HQTMFDIVSA LKVCRYSIPG ASGLPFPPPA
     RSGPWVRLIA SGHVPGRVSY LDEAGYCNHL DILRLLSKTP LVCLGDLQQL HPVGFDSYCY
     VFDQMPQKQL TTIYRFGPNI CAAIQPCYRE KLESKARNTR VVFTTRPVAF GQVLTPYHKD
     RIGSAITIDS SQGATFDIVT LHLPSPKSLN KSRALVAITR ARHGLFIYDP HNQLQEFFNL
     TPERTDCNLV FSRGDELVVL NADNAVTTVA KALETGPSRF RVSDPRCKSL LAACSASLEG
     SCMPLPQVAH NLGFYFSPDS PTFAPLPKEL APHWPVVTHQ NNRAWPDRLV ASMRPIDARY
     SKPMVGAGYV VGPSTFLGTP GVVSYYLTLY IRGEPQALPE TLVSTGRIAT DCREYLDAAE
     EEAAKELPHA FIGDVKGTTV GGCHHITSKY LPRSLPKDSV AVVGVSSPGR AAKAVCTLTD
     VYLPELRPYL QPETASKCWK LKLDFRDVRL MVWKGATAYF QLEGLTWSAL PDYARFIQLP
     KDAVVYIDPC IGPATANRKV VRTTDWRADL AVTPYDYGAQ NILTTAWFED LGPQWKILGL
     QPFRRAFGFE NTEDWAILAR RMNDGKDYTD YNWNCVRERP HAIYGRARDH TYHFAPGTEL
     QVELGKPRLP PGQVP
//