RPOA_PRRSL
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 03-AUG-2022, entry version 153.
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. The degradation of host
CC CREBBP which is a key component of the IFN enhanceosome is likely
CC responsible for the inhibition of interferon mediated by Nsp1-alpha.
CC Participates also in the inhibition of host NF-kappa-B activation by
CC counteracting LUBAC-dependent induction of NF-kappa-B. Reduces host
CC NEMO ubiquitination by blocking the interaction between the two LUBAC
CC complex components RNF31 and SHARPIN. {ECO:0000250|UniProtKB:Q9WJB2,
CC ECO:0000269|PubMed:23287061, 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.
CC {ECO:0000250|UniProtKB:Q9WJB2, 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. This interaction
CC leads to the proteasomal degradation of the IFN-induced antiviral
CC protein IFITM1. {ECO:0000269|PubMed:25102331}.
CC -!- FUNCTION: [Serine protease nsp4]: Cleaves the majority of cleavage
CC sites present in the C-terminus of the polyprotein. Triggers host
CC apoptosis through caspase-3, -8, and -9 activations. Subverts host
CC innate immune responses through its protease activity. Targets the NF-
CC kappa-B essential modulator NEMO and mediates its cleavage
CC (PubMed:25008936). Blocks host interferon beta induction and downstream
CC signaling by cleaving mitochondrial MAVS, dislodging it from the
CC mitochondria (PubMed:27329948). Impairs host defense by cleaving host
CC 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:
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 -!- 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 -!- 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:0000250|UniProtKB:P19811};
CC -!- SUBUNIT: Nsp1-alpha papain-like: Interacts with host RNF31
CC (PubMed:27881655). {ECO:0000269|PubMed:27881655}.
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 -!- 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: Specific enzymatic cleavages in vivo by its own proteases yield
CC mature proteins. Nsp1 is autocleaved into two subunits, Nsp1-alpha and
CC Nsp1-beta. There are two alternative pathways for processing. Either
CC nsp4-5 is cleaved, which represents the major pathway or the nsp5-6 and
CC nsp6-7 are processed, which represents the minor pathway. The major
CC pathway occurs when nsp2 acts as cofactor for nsp4 (By similarity).
CC {ECO:0000250}.
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 PRIDE; Q04561; -.
DR Proteomes; UP000006687; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of 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:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
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:0003968; F:RNA-directed 5'-3' 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:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR GO; GO:0039648; P:modulation by virus 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:0039514; P:suppression by virus of host JAK-STAT cascade; IDA:UniProtKB.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039522; P:suppression by virus of host mRNA export from nucleus; IDA:UniProtKB.
DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IDA:UniProtKB.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
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; cd21160; NendoU_av_Nsp11-like; 1.
DR CDD; cd21166; NTD_av_Nsp11-like; 1.
DR CDD; cd21405; ZBD_av_Nsp10-like; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 3.30.1330.220; -; 1.
DR Gene3D; 3.30.40.20; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR Gene3D; 3.90.70.60; -; 1.
DR Gene3D; 3.90.70.70; -; 1.
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; 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; 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; SSF142877; SSF142877; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56672; SSF56672; 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 STAT1 by virus; 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 /evidence="ECO:0000250"
FT /id="PRO_0000410828"
FT CHAIN 1..180
FT /note="Nsp1-alpha papain-like cysteine proteinase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000036685"
FT CHAIN 181..385
FT /note="Nsp1-beta papain-like cysteine proteinase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000036686"
FT CHAIN 386..1463
FT /note="Nsp2 cysteine proteinase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000036687"
FT CHAIN 1464..1693
FT /note="Non-structural protein 3"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036688"
FT CHAIN 1694..1896
FT /note="Serine protease nsp4"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036689"
FT CHAIN 1897..2351
FT /note="Non-structural protein 5-6-7"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036690"
FT CHAIN 1897..2066
FT /note="Non-structural protein 5"
FT /evidence="ECO:0000250"
FT /id="PRO_0000423126"
FT CHAIN 2067..2082
FT /note="Non-structural protein 6"
FT /evidence="ECO:0000250"
FT /id="PRO_0000423127"
FT CHAIN 2083..2231
FT /note="Non-structural protein 7-alpha"
FT /evidence="ECO:0000250"
FT /id="PRO_0000423128"
FT CHAIN 2232..2351
FT /note="Non-structural protein 7-beta"
FT /evidence="ECO:0000250"
FT /id="PRO_0000423129"
FT CHAIN 2352..3037
FT /note="RNA-directed RNA polymerase"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036691"
FT CHAIN 2352..2396
FT /note="Non-structural protein 8"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036692"
FT CHAIN 3038..3479
FT /note="Helicase nsp10"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036693"
FT CHAIN 3480..3703
FT /note="Uridylate-specific endoribonuclease nsp11"
FT /evidence="ECO:0000250"
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 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:0000255"
FT SITE 385..386
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT SITE 1463..1464
FT /note="Cleavage; by CP2"
FT /evidence="ECO:0000255"
FT SITE 1693..1694
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 1896..1897
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 2066..2067
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 2082..2083
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 2231..2232
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 2351..2352
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 3037..3038
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
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 nsp1-
FT 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
