ID   RPOA_PRRSR              Reviewed;        3960 AA.
AC   Q9WJB2; Q80KX0; Q80KX1; Q9WJB3;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   12-APR-2005, sequence version 2.
DT   27-MAR-2024, entry version 141.
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.-;
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 VR-2332)
OS   (PRRSV).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Arnidovirineae; Arteriviridae; Variarterivirinae;
OC   Betaarterivirus; Ampobartevirus; Betaarterivirus suid 2.
OX   NCBI_TaxID=300559;
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9847330; DOI=10.1128/jvi.73.1.270-280.1999;
RA   Nelsen C.J., Murtaugh M.P., Faaberg K.S.;
RT   "Porcine reproductive and respiratory syndrome virus comparison: divergent
RT   evolution on two continents.";
RL   J. Virol. 73:270-280(1999).
RN   [2]
RP   SEQUENCE REVISION.
RA   Murtaugh M.P., Faaberg K.S., Nelsen C.J.;
RL   Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Infectious clone VR-2332;
RX   PubMed=12610145; DOI=10.1128/jvi.77.6.3702-3711.2003;
RA   Nielsen H.S., Liu G., Nielsen J., Oleksiewicz M.B., Botner A.,
RA   Storgaard T., Faaberg K.S.;
RT   "Generation of an infectious clone of VR-2332, a highly virulent North
RT   American-type isolate of porcine reproductive and respiratory syndrome
RT   virus.";
RL   J. Virol. 77:3702-3711(2003).
RN   [4]
RP   FUNCTION (NSP2 CYSTEINE PROTEINASE).
RX   PubMed=18078692; DOI=10.1016/j.chom.2007.09.014;
RA   Frias-Staheli N., Giannakopoulos N.V., Kikkert M., Taylor S.L., Bridgen A.,
RA   Paragas J., Richt J.A., Rowland R.R., Schmaljohn C.S., Lenschow D.J.,
RA   Snijder E.J., Garcia-Sastre A., Virgin H.W.;
RT   "Ovarian tumor domain-containing viral proteases evade ubiquitin- and
RT   ISG15-dependent innate immune responses.";
RL   Cell Host Microbe 2:404-416(2007).
RN   [5]
RP   FUNCTION (NSP1-ALPHA PAPAIN-LIKE CYSTEINE PROTEINASE), AND SUBCELLULAR
RP   LOCATION (NSP1-ALPHA PAPAIN-LIKE CYSTEINE PROTEINASE).
RX   PubMed=20850164; DOI=10.1016/j.virol.2010.08.025;
RA   Song C., Krell P., Yoo D.;
RT   "Nonstructural protein 1alpha subunit-based inhibition of NF-kappaB
RT   activation and suppression of interferon-beta production by porcine
RT   reproductive and respiratory syndrome virus.";
RL   Virology 407:268-280(2010).
RN   [6]
RP   FUNCTION (NSP1-ALPHA PAPAIN-LIKE CYSTEINE), FUNCTION (NSP1-BETA PAPAIN-LIKE
RP   CYSTEINE), PROTEOLYTIC PROCESSING (REPLICASE POLYPROTEIN 1AB), AND PROTEIN
RP   SEQUENCE OF 181-190 AND 384-393.
RC   STRAIN=Isolate SD23983;
RX   PubMed=20006994; DOI=10.1016/j.virol.2009.11.033;
RA   Chen Z., Lawson S., Sun Z., Zhou X., Guan X., Christopher-Hennings J.,
RA   Nelson E.A., Fang Y.;
RT   "Identification of two auto-cleavage products of nonstructural protein 1
RT   (nsp1) in porcine reproductive and respiratory syndrome virus infected
RT   cells: nsp1 function as interferon antagonist.";
RL   Virology 398:87-97(2010).
RN   [7]
RP   FUNCTION (NSP1-ALPHA PAPAIN-LIKE CYSTEINE), AND MUTAGENESIS OF CYS-76;
RP   HIS-146 AND CYS-270.
RC   STRAIN=BJ-4;
RX   PubMed=21438756; DOI=10.1089/dna.2010.1188;
RA   Shi X., Zhang G., Wang L., Li X., Zhi Y., Wang F., Fan J., Deng R.;
RT   "The nonstructural protein 1 papain-like cysteine protease was necessary
RT   for porcine reproductive and respiratory syndrome virus nonstructural
RT   protein 1 to inhibit interferon-beta induction.";
RL   DNA Cell Biol. 30:355-362(2011).
RN   [8]
RP   FUNCTION (NSP1-BETA PAPAIN-LIKE CYSTEINE PROTEINASE).
RX   PubMed=23449802; DOI=10.1128/jvi.02643-12;
RA   Wang R., Nan Y., Yu Y., Zhang Y.J.;
RT   "Porcine reproductive and respiratory syndrome virus Nsp1beta inhibits
RT   interferon-activated JAK/STAT signal transduction by inducing karyopherin-
RT   alpha1 degradation.";
RL   J. Virol. 87:5219-5228(2013).
RN   [9]
RP   TOPOLOGY (NSP2 CYSTEINE PROTEINASE).
RX   PubMed=25768891; DOI=10.1016/j.virol.2015.01.028;
RA   Kappes M.A., Miller C.L., Faaberg K.S.;
RT   "Porcine reproductive and respiratory syndrome virus nonstructural protein
RT   2 (nsp2) topology and selective isoform integration in artificial
RT   membranes.";
RL   Virology 481:51-62(2015).
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 (PubMed:20850164, PubMed:20006994,
CC       PubMed:21438756). 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 (By similarity).
CC       {ECO:0000250|UniProtKB:Q04561, ECO:0000269|PubMed:20006994,
CC       ECO:0000269|PubMed:20850164, ECO:0000269|PubMed:21438756}.
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 (By similarity). Additionally, inhibits the
CC       interferon-activated JAK/STAT signal transduction by mediating the
CC       ubiquitination and subsequent proteasomal degradation of host KPNA1
CC       (PubMed:23449802). 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:Q04561,
CC       ECO:0000269|PubMed:20006994, ECO:0000269|PubMed:23449802}.
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 (PubMed:18078692). Deubiquitinates also host NFKBIA,
CC       thereby interfering with NFKBIA degradation and impairing subsequent
CC       NF-kappa-B activation (PubMed:18078692). {ECO:0000269|PubMed:18078692}.
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:0000250|UniProtKB:Q04561}.
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. Blocks host
CC       interferon beta induction and downstream signaling by cleaving
CC       mitochondrial MAVS, dislodging it from the mitochondria. Impairs host
CC       defense by cleaving host mRNA-decapping enzyme DCP1A to attenuate its
CC       antiviral activity. {ECO:0000250|UniProtKB:Q04561}.
CC   -!- FUNCTION: [Non-structural protein 5-6-7]: Plays a role in the initial
CC       induction of autophagosomes from host reticulum endoplasmic.
CC       {ECO:0000250|UniProtKB:Q04561}.
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:0000250|UniProtKB:Q04561}.
CC   -!- FUNCTION: [RNA-directed RNA polymerase]: Responsible for replication
CC       and transcription of the viral RNA genome.
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- FUNCTION: [Helicase nsp10]: Displays RNA and DNA duplex-unwinding
CC       activities with 5' to 3' polarity. {ECO:0000250|UniProtKB:Q04561}.
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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000250|UniProtKB:P19811, ECO:0000250|UniProtKB:Q04561}.
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         Evidence={ECO:0000250|UniProtKB:Q04561};
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         Evidence={ECO:0000250|UniProtKB:Q04561};
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; Evidence={ECO:0000250|UniProtKB:Q04561};
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       {ECO:0000250|UniProtKB:Q04561}.
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. Interacts with host G3BP1; this interaction
CC       probably plays a role in Nsp1-beta-mediated inhibition of host EIF2AK2.
CC       {ECO:0000250|UniProtKB:A6YQT5}.
CC   -!- SUBUNIT: [Nsp2 cysteine proteinase]: Interacts with host DDX18; this
CC       interaction redistributes host DDX18 to the cytoplasm.
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBUNIT: [Non-structural protein 3]: Interacts with host IFITM1.
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBUNIT: [RNA-directed RNA polymerase]: Interacts with host DDX5.
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBUNIT: [Helicase nsp10]: Interacts with host DDX18; this interaction
CC       redistributes host DDX18 to the cytoplasm.
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBUNIT: [Uridylate-specific endoribonuclease nsp11]: Interacts with
CC       host OTULIN. {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBUNIT: [Non-structural protein 12]: Interacts with host LGALS3.
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBCELLULAR LOCATION: [Nsp1]: Host nucleus
CC       {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBCELLULAR LOCATION: [Nsp1-alpha papain-like cysteine proteinase]:
CC       Host nucleus {ECO:0000269|PubMed:20850164}. Host cytoplasm
CC       {ECO:0000269|PubMed:20850164}.
CC   -!- SUBCELLULAR LOCATION: [Nsp1-beta papain-like cysteine proteinase]: Host
CC       nucleus {ECO:0000250|UniProtKB:A6YQT5}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:A6YQT5}. Note=Accumulates mainly in the host
CC       cytoplasm in early infection and then mostly in the host nucleus.
CC       {ECO:0000250|UniProtKB:A6YQT5}.
CC   -!- SUBCELLULAR LOCATION: [Nsp2 cysteine proteinase]: Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q04561}. Host membrane
CC       {ECO:0000250|UniProtKB:Q04561}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 5-6-7]: Host endoplasmic
CC       reticulum {ECO:0000250|UniProtKB:Q04561}. Host membrane
CC       {ECO:0000250|UniProtKB:Q04561}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBCELLULAR LOCATION: [Serine protease nsp4]: Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm, host perinuclear region
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBCELLULAR LOCATION: [Helicase nsp10]: Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm, host perinuclear region
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease nsp11]: Host
CC       cytoplasm {ECO:0000250|UniProtKB:Q04561}. Host nucleus
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 12]: Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q04561}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=2;
CC       Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC         IsoId=Q9WJB2-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC         IsoId=Q9WJB2-2; Sequence=VSP_032893;
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:0000269|PubMed:20006994}.
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=AAD12125.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAO13192.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; U87392; AAD12132.2; -; Genomic_RNA.
DR   EMBL; U87392; AAD12125.1; ALT_INIT; Genomic_RNA.
DR   EMBL; AY150564; AAO13191.1; -; Genomic_RNA.
DR   EMBL; AY150564; AAO13192.1; ALT_INIT; Genomic_RNA.
DR   SMR; Q9WJB2; -.
DR   MEROPS; S32.002; -.
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: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; 1.
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; IPR027417; P-loop_NTPase.
DR   InterPro; IPR032785; Pdase_C33_assoc.
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; PF19215; CoV_NSP15_C; 1.
DR   Pfam; PF14757; NSP2-B_epitope; 1.
DR   Pfam; PF14756; Pdase_C33_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; 2.
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   ATP-binding; Direct protein sequencing; 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   Ribosomal frameshifting; RNA-directed RNA polymerase; Serine protease;
KW   Thiol protease; Transferase; Transmembrane; Transmembrane helix;
KW   Viral immunoevasion; Viral RNA replication; Zinc; Zinc-finger.
FT   CHAIN           1..3960
FT                   /note="Replicase polyprotein 1ab"
FT                   /id="PRO_0000036696"
FT   CHAIN           1..382
FT                   /note="Nsp1"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000410829"
FT   CHAIN           1..180
FT                   /note="Nsp1-alpha papain-like cysteine proteinase"
FT                   /id="PRO_0000036698"
FT   CHAIN           181..383
FT                   /note="Nsp1-beta papain-like cysteine proteinase"
FT                   /id="PRO_0000036699"
FT   CHAIN           384..1579
FT                   /note="Nsp2 cysteine proteinase"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000036700"
FT   CHAIN           1580..1809
FT                   /note="Non-structural protein 3"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036701"
FT   CHAIN           1810..2013
FT                   /note="Serine protease nsp4"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036702"
FT   CHAIN           2014..2458
FT                   /note="Non-structural protein 5-6-7"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036703"
FT   CHAIN           2014..2183
FT                   /note="Non-structural protein 5"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000423130"
FT   CHAIN           2184..2199
FT                   /note="Non-structural protein 6"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000423131"
FT   CHAIN           2200..2348
FT                   /note="Non-structural protein 7-alpha"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000423132"
FT   CHAIN           2349..2458
FT                   /note="Non-structural protein 7-beta"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000423133"
FT   CHAIN           2459..3143
FT                   /note="RNA-directed RNA polymerase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036704"
FT   CHAIN           2459..2503
FT                   /note="Non-structural protein 8"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036705"
FT   CHAIN           3144..3584
FT                   /note="Helicase nsp10"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036706"
FT   CHAIN           3585..3807
FT                   /note="Uridylate-specific endoribonuclease nsp11"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036707"
FT   CHAIN           3808..3960
FT                   /note="Non-structural protein 12"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036708"
FT   TRANSMEM        1266..1286
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1296..1316
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1345..1365
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1368..1388
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1583..1603
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1650..1670
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1685..1705
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1719..1739
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2012..2032
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2060..2080
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2092..2112
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2137..2157
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2164..2184
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          69..180
FT                   /note="Peptidase C31"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00872"
FT   DOMAIN          263..383
FT                   /note="Peptidase C32"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
FT   DOMAIN          428..535
FT                   /note="Peptidase C33"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT   DOMAIN          1810..2013
FT                   /note="Peptidase S32"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   DOMAIN          2488..2650
FT                   /note="NiRAN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01292"
FT   DOMAIN          2889..3023
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          3144..3207
FT                   /note="AV ZBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   DOMAIN          3264..3416
FT                   /note="(+)RNA virus helicase ATP-binding"
FT   DOMAIN          3417..3545
FT                   /note="(+)RNA virus helicase C-terminal"
FT   DOMAIN          3584..3680
FT                   /note="AV-Nsp11N/CoV-Nsp15M"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01306"
FT   DOMAIN          3682..3804
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          199..200
FT                   /note="Important for host EIF2AK2 inhibition"
FT                   /evidence="ECO:0000250|UniProtKB:A6YQT5"
FT   REGION          263..382
FT                   /note="PCP1-beta"
FT   REGION          426..513
FT                   /note="OTU-like"
FT   REGION          809..882
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          899..979
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1156..1213
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1266..1388
FT                   /note="HD1"
FT   REGION          1583..1745
FT                   /note="HD2"
FT   REGION          2036..2157
FT                   /note="HD3"
FT   REGION          2329..2358
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        825..840
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        954..968
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1165..1179
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2329..2346
FT                   /note="Pro 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   ACT_SITE        146
FT                   /note="For Nsp1-alpha papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00872"
FT   ACT_SITE        270
FT                   /note="For Nsp1-beta papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
FT   ACT_SITE        339
FT                   /note="For Nsp1-beta papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
FT   ACT_SITE        437
FT                   /note="For Nsp2 cysteine proteinase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT   ACT_SITE        506
FT                   /note="For Nsp2 cysteine proteinase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT   ACT_SITE        1848
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   ACT_SITE        1873
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   ACT_SITE        1927
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   ACT_SITE        3713
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        3728
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        3757
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   BINDING         3150
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3153
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3163
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3168
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3171
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3173
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3175
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3177
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3184
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3186
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3193
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3196
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3292..3299
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:0000269|PubMed:20006994"
FT   SITE            383..384
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000269|PubMed:20006994"
FT   SITE            1579..1580
FT                   /note="Cleavage; by CP2"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            1809..1810
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2013..2014
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2183..2184
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2199..2200
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2348..2349
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            2458..2459
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            3143..3144
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            3194
FT                   /note="Involved in mRNA transcription process"
FT                   /evidence="ECO:0000250"
FT   SITE            3584..3585
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250"
FT   SITE            3807..3808
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         2504..3960
FT                   /note="Missing (in isoform Replicase polyprotein 1a)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_032893"
FT   VARIANT         188
FT                   /note="H -> R (in strain: BJ-4)"
FT   VARIANT         386
FT                   /note="K -> R (in strain: BJ-4)"
FT   VARIANT         393
FT                   /note="S -> H (in strain: BJ-4)"
FT   VARIANT         1498
FT                   /note="S -> A (in strain: Isolate infectious clone
FT                   VR-2332)"
FT   VARIANT         1777
FT                   /note="T -> I (in strain: Isolate infectious clone
FT                   VR-2332)"
FT   VARIANT         2222
FT                   /note="D -> N (in strain: Isolate infectious clone
FT                   VR-2332)"
FT   VARIANT         3257
FT                   /note="G -> E (in strain: Isolate infectious clone
FT                   VR-2332)"
FT   VARIANT         3539
FT                   /note="C -> R (in strain: Isolate infectious clone
FT                   VR-2332)"
FT   VARIANT         3623
FT                   /note="S -> T (in strain: Isolate infectious clone
FT                   VR-2332)"
FT   VARIANT         3678
FT                   /note="G -> E (in strain: Isolate infectious clone
FT                   VR-2332)"
FT   VARIANT         3714
FT                   /note="G -> A (in strain: Isolate infectious clone
FT                   VR-2332)"
FT   MUTAGEN         76
FT                   /note="C->S: Complete loss of papain-like cysteine protease
FT                   activity of nsp1-alpha. Loss of inhibition of IFN-beta
FT                   production. Loss of inhibition of IRF-3 phosphorylation."
FT                   /evidence="ECO:0000269|PubMed:21438756"
FT   MUTAGEN         146
FT                   /note="H->D: Complete loss of papain-like cysteine protease
FT                   activity of nsp1-alpha."
FT                   /evidence="ECO:0000269|PubMed:21438756"
FT   MUTAGEN         270
FT                   /note="C->S: No effect on inhibition of IRF-3
FT                   phosphorylation."
FT                   /evidence="ECO:0000269|PubMed:21438756"
SQ   SEQUENCE   3960 AA;  432887 MW;  F219409DA3F3B73F CRC64;
     MSGILDRCTC TPNARVFMAE GQVYCTRCLS ARSLLPLNLQ VSELGVLGLF YRPEEPLRWT
     LPRAFPTVEC SPAGACWLSA IFPIARMTSG NLNFQQRMVR VAAELYRAGQ LTPAVLKALQ
     VYERGCRWYP IVGPVPGVAV FANSLHVSDK PFPGATHVLT NLPLPQRPKP EDFCPFECAM
     ATVYDIGHDA VMYVAERKVS WAPRGGDEVK FEAVPGELKL IANRLRTSFP PHHTVDMSKF
     AFTAPGCGVS MRVERQHGCL PADTVPEGNC WWSLFDLLPL EVQNKEIRHA NQFGYQTKHG
     VSGKYLQRRL QVNGLRAVTD LNGPIVVQYF SVKESWIRHL KLAGEPSYSG FEDLLRIRVE
     PNTSPLADKE EKIFRFGSHK WYGAGKRARK ARSCATATVA GRALSVRETR QAKEHEVAGA
     NKAEHLKHYS PPAEGNCGWH CISAIANRMV NSKFETTLPE RVRPPDDWAT DEDLVNAIQI
     LRLPAALDRN GACTSAKYVL KLEGEHWTVT VTPGMSPSLL PLECVQGCCG HKGGLGSPDA
     VEVSGFDPAC LDRLAEVMHL PSSAIPAALA EMSGDSDRSA SPVTTVWTVS QFFARHSGGN
     HPDQVRLGKI ISLCQVIEDC CCSQNKTNRV TPEEVAAKID LYLRGATNLE ECLARLEKAR
     PPRVIDTSFD WDVVLPGVEA ATQTIKLPQV NQCRALVPVV TQKSLDNNSV PLTAFSLANY
     YYRAQGDEVR HRERLTAVLS KLEKVVREEY GLMPTEPGPR PTLPRGLDEL KDQMEEDLLK
     LANAQTTSDM MAWAVEQVDL KTWVKNYPRW TPPPPPPKVQ PRKTKPVKSL PERKPVPAPR
     RKVGSDCGSP VSLGGDVPNS WEDLAVSSPF DLPTPPEPAT PSSELVIVSS PQCIFRPATP
     LSEPAPIPAP RGTVSRPVTP LSEPIPVPAP RRKFQQVKRL SSAAAIPPYQ DEPLDLSASS
     QTEYEASPPA PPQSGGVLGV EGHEAEETLS EISDMSGNIK PASVSSSSSL SSVRITRPKY
     SAQAIIDSGG PCSGHLQEVK ETCLSVMREA CDATKLDDPA TQEWLSRMWD RVDMLTWRNT
     SVYQAICTLD GRLKFLPKMI LETPPPYPCE FVMMPHTPAP SVGAESDLTI GSVATEDVPR
     ILEKIENVGE MANQGPLAFS EDKPVDDQLV NDPRISSRRP DESTSAPSAG TGGAGSFTDL
     PPSDGADADG GGPFRTVKRK AERLFDQLSR QVFDLVSHLP VFFSRLFYPG GGYSPGDWGF
     AAFTLLCLFL CYSYPAFGIA PLLGVFSGSS RRVRMGVFGC WLAFAVGLFK PVSDPVGAAC
     EFDSPECRNI LHSFELLKPW DPVRSLVVGP VGLGLAILGR LLGGARCIWH FLLRLGIVAD
     CILAGAYVLS QGRCKKCWGS CIRTAPNEVA FNVFPFTRAT RSSLIDLCDR FCAPKGMDPI
     FLATGWRGCW AGRSPIEQPS EKPIAFAQLD EKKITARTVV AQPYDPNQAV KCLRVLQSGG
     AMVAKAVPKV VKVSAVPFRA PFFPTGVKVD PDCRVVVDPD TFTAALRSGY STTNLVLGVG
     DFAQLNGLKI RQISKPSGGG PHLMAALHVA CSMALHMLAG IYVTAVGSCG TGTNDPWCAN
     PFAVPGYGPG SLCTSRLCIS QHGLTLPLTA LVAGFGIQEI ALVVLIFVSI GGMAHRLSCK
     ADMLCVLLAI ASYVWVPLTW LLCVFPCWLR CFSLHPLTIL WLVFFLISVN MPSGILAMVL
     LVSLWLLGRY TNVAGLVTPY DIHHYTSGPR GVAALATAPD GTYLAAVRRA ALTGRTMLFT
     PSQLGSLLEG AFRTRKPSLN TVNVIGSSMG SGGVFTIDGK VKCVTAAHVL TGNSARVSGV
     GFNQMLDFDV KGDFAIADCP NWQGAAPKTQ FCTDGWTGRA YWLTSSGVEP GVIGKGFAFC
     FTACGDSGSP VITEAGELVG VHTGSNKQGG GIVTRPSGQF CNVAPIKLSE LSEFFAGPKV
     PLGDVKVGSH IIKDISEVPS DLCALLAAKP ELEGGLSTVQ LLCVFFLLWR MMGHAWTPLV
     AVSFFILNEV LPAVLVRSVF SFGMFVLSWL TPWSAQVLMI RLLTAALNRN RWSLAFFSLG
     AVTGFVADLA ATQGHPLQAV MNLSTYAFLP RMMVVTSPVP VITCGVVHLL AIILYLFKYR
     GPHHILVGDG VFSAAFFLRY FAEGKLREGV SQSCGMNHES LTGALAMRLN DEDLDFLMKW
     TDFKCFVSAS NMRNAAGQFI EAAYAKALRV ELAQLVQVDK VRGTLAKLEA FADTVAPQLS
     PGDIVVALGH TPVGSIFDLK VGSTKHTLQA IETRVLAGSK MTVARVVDPT PTPPPAPVPI
     PLPPKVLENG PNAWGDEDRL NKKKRRRMEA LGIYVMGGKK YQKFWDKNSG DVFYEEVHNN
     TDEWECLRVG DPADFDPEKG TLCGHVTIEN KAYHVYTSPS GKKFLVPVNP ENGRVQWEAA
     KLSVEQALGM MNVDGELTAK ELEKLKRIID KLQGLTKEQC LNCLAASDLT RCGRGGLVVT
     ETAVKIVKFH NRTFTLGPVN LKVASEVELK DAVEHNQHPV ARPIDGGVVL LRSAVPSLID
     VLISGADASP KLLAHHGPGN TGIDGTLWDF ESEATKEEVA LSAQIIQACD IRRGDAPEIG
     LPYKLYPVRG NPERVKGVLQ NTRFGDIPYK TPSDTGSPVH AAACLTPNAT PVTDGRSVLA
     TTMPPGFELY VPTIPASVLD YLDSRPDCPK QLTEHGCEDA ALKDLSKYDL STQGFVLPGV
     LRLVRKYLFA HVGKCPPVHR PSTYPAKNSM AGINGNRFPT KDIQSVPEID VLCAQAVREN
     WQTVTPCTLK KQYCGKKKTR TILGTNNFIA LAHRAVLSGV TQGFMKKAFN SPIALGKNKF
     KELQTPVLGR CLEADLASCD RSTPAIVRWF AANLLYELAC AEEHLPSYVL NCCHDLLVTQ
     SGAVTKRGGL SSGDPITSVS NTIYSLVIYA QHMVLSYFKS GHPHGLLFLQ DQLKFEDMLK
     VQPLIVYSDD LVLYAESPTM PNYHWWVEHL NLMLGFQTDP KKTAITDSPS FLGCRIINGR
     QLVPNRDRIL AALAYHMKAS NVSEYYASAA AILMDSCACL EYDPEWFEEL VVGIAQCARK
     DGYSFPGTPF FMSMWEKLRS NYEGKKSRVC GYCGAPAPYA TACGLDVCIY HTHFHQHCPV
     TIWCGHPAGS GSCSECKSPV GKGTSPLDEV LEQVPYKPPR TVIMHVEQGL TPLDPGRYQT
     RRGLVSVRRG IRGNEVGLPD GDYASTALLP TCKEINMVAV ASNVLRSRFI IGPPGAGKTY
     WLLQQVQDGD VIYTPTHQTM LDMIRALGTC RFNVPAGTTL QFPVPSRTGP WVRILAGGWC
     PGKNSFLDEA AYCNHLDVLR LLSKTTLTCL GDFKQLHPVG FDSHCYVFDI MPQTQLKTIW
     RFGQNICDAI QPDYRDKLMS MVNTTRVTYV EKPVRYGQVL TPYHRDREDD AITIDSSQGA
     TFDVVTLHLP TKDSLNRQRA LVAITRARHA IFVYDPHRQL QGLFDLPAKG TPVNLAVHCD
     GQLIVLDRNN KECTVAQALG NGDKFRATDK RVVDSLRAIC ADLEGSSSPL PKVAHNLGFY
     FSPDLTQFAK LPVELAPHWP VVSTQNNEKW PDRLVASLRP IHKYSRACIG AGYMVGPSVF
     LGTPGVVSYY LTKFVKGGAQ VLPETVFSTG RIEVDCREYL DDREREVAAS LPHGFIGDVK
     GTTVGGCHHV TSRYLPRVLP KESVAVVGVS SPGKAAKALC TLTDVYLPDL EAYLHPETQS
     KCWKMMLDFK EVRLMVWKDK TAYFQLEGRY FTWYQLASYA SYIRVPVNST VYLDPCMGPA
     LCNRRVVGST HWGADLAVTP YDYGAKIILS SAYHGEMPPG YKILACAEFS LDDPVKYKHT
     WGFESDTAYL YEFTGNGEDW EDYNDAFRAR QEGKIYKATA TSLKFYFPPG PVIEPTLGLN
//