ID   RPOA_PRRSS              Reviewed;        3838 AA.
AC   A0MD28; A0MD29; Q6U9W7; Q6U9W8;
DT   10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT   10-AUG-2010, sequence version 2.
DT   27-MAR-2024, entry version 81.
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;
OS   Porcine reproductive and respiratory syndrome virus (isolate Pig/United
OS   States/SD 01-08/2001) (PRRSV).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Arnidovirineae; Arteriviridae; Variarterivirinae;
OC   Betaarterivirus; Ampobartevirus; Betaarterivirus suid 2.
OX   NCBI_TaxID=857306;
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=15019241; DOI=10.1016/j.virusres.2003.12.026;
RA   Fang Y., Kim D.Y., Ropp S., Steen P., Christopher-Hennings J., Nelson E.A.,
RA   Rowland R.R.;
RT   "Heterogeneity in Nsp2 of European-like porcine reproductive and
RT   respiratory syndrome viruses isolated in the United States.";
RL   Virus Res. 100:229-235(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Infectious clone SD 01-08;
RX   PubMed=16971421; DOI=10.1128/jvi.01032-06;
RA   Fang Y., Rowland R.R., Roof M., Lunney J.K., Christopher-Hennings J.,
RA   Nelson E.A.;
RT   "A full-length cDNA infectious clone of North American type 1 porcine
RT   reproductive and respiratory syndrome virus: expression of green
RT   fluorescent protein in the Nsp2 region.";
RL   J. Virol. 80:11447-11455(2006).
RN   [3]
RP   FUNCTION (NSP2 CYSTEINE PROTEINASE), AND MUTAGENESIS OF CYS-429; ASP-458;
RP   SER-462; ASP-463; ASP-465 AND HIS-498.
RX   PubMed=20504922; DOI=10.1128/jvi.00217-10;
RA   Sun Z., Chen Z., Lawson S.R., Fang Y.;
RT   "The cysteine protease domain of porcine reproductive and respiratory
RT   syndrome virus nonstructural protein 2 possesses deubiquitinating and
RT   interferon antagonism functions.";
RL   J. Virol. 84:7832-7846(2010).
RN   [4]
RP   PROTEOLYTIC PROCESSING (REPLICASE POLYPROTEIN 1AB).
RX   PubMed=22258855; DOI=10.1099/vir.0.039289-0;
RA   Li Y., Tas A., Snijder E.J., Fang Y.;
RT   "Identification of porcine reproductive and respiratory syndrome virus
RT   ORF1a-encoded non-structural proteins in virus-infected cells.";
RL   J. Gen. Virol. 93:829-839(2012).
RN   [5]
RP   SUBCELLULAR LOCATION (NSP2 CYSTEINE PROTEINASE).
RX   PubMed=23043113; DOI=10.1073/pnas.1211145109;
RA   Fang Y., Treffers E.E., Li Y., Tas A., Sun Z., van der Meer Y., de Ru A.H.,
RA   van Veelen P.A., Atkins J.F., Snijder E.J., Firth A.E.;
RT   "Efficient -2 frameshifting by mammalian ribosomes to synthesize an
RT   additional arterivirus protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:E2920-E2928(2012).
RN   [6]
RP   FUNCTION (NSP2 CYSTEINE PROTEINASE).
RX   PubMed=22258253; DOI=10.1128/jvi.06466-11;
RA   Sun Z., Li Y., Ransburgh R., Snijder E.J., Fang Y.;
RT   "Nonstructural protein 2 of porcine reproductive and respiratory syndrome
RT   virus inhibits the antiviral function of interferon-stimulated gene 15.";
RL   J. Virol. 86:3839-3850(2012).
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:Q04561}.
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 (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:Q04561,
CC       ECO:0000250|UniProtKB:Q9WJB2}.
CC   -!- FUNCTION: [Nsp2 cysteine proteinase]: Multifunctional protein that acts
CC       as a viral protease and as a viral antagonist of host immune response
CC       (PubMed:20504922, PubMed:22258253). Cleaves the nsp2/nsp3 site in the
CC       viral polyprotein. Displays deubiquitinating activity that cleaves both
CC       ubiquitinated and ISGylated products and therefore inhibits ubiquitin
CC       and ISG15-dependent host innate immunity (PubMed:20504922,
CC       PubMed:22258253). Deubiquitinates also host NFKBIA, thereby interfering
CC       with NFKBIA degradation and impairing subsequent NF-kappa-B activation
CC       (PubMed:20504922). {ECO:0000269|PubMed:20504922,
CC       ECO:0000269|PubMed:22258253}.
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:0000250|UniProtKB:Q04561}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q04561}.
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:0000269|PubMed:23043113}. 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=3;
CC       Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC         IsoId=A0MD28-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC         IsoId=A0MD28-2; Sequence=VSP_039634;
CC       Name=Truncated polyprotein 1aTF;
CC         IsoId=P0DJY0-1; 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:0000269|PubMed:22258855}.
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=AAR37017.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AY375474; AAR37016.1; -; Genomic_RNA.
DR   EMBL; AY375474; AAR37017.1; ALT_INIT; Genomic_RNA.
DR   EMBL; DQ489311; ABF66340.1; -; Genomic_RNA.
DR   EMBL; DQ489311; ABF66341.1; -; Genomic_RNA.
DR   SMR; A0MD28; -.
DR   MEROPS; S32.002; -.
DR   Proteomes; UP000000937; 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: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   ATP-binding; Endonuclease; Helicase; Host cytoplasm;
KW   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..3838
FT                   /note="Replicase polyprotein 1ab"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000397084"
FT   CHAIN           1..385
FT                   /note="Nsp1"
FT                   /id="PRO_0000410830"
FT   CHAIN           1..180
FT                   /note="Nsp1-alpha papain-like cysteine proteinase"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000397085"
FT   CHAIN           181..385
FT                   /note="Nsp1-beta papain-like cysteine proteinase"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000397086"
FT   CHAIN           386..1446
FT                   /note="Nsp2 cysteine proteinase"
FT                   /id="PRO_0000397087"
FT   CHAIN           1447..1676
FT                   /note="Non-structural protein 3"
FT                   /id="PRO_0000397088"
FT   CHAIN           1677..1879
FT                   /note="Serine protease nsp4"
FT                   /id="PRO_0000397089"
FT   CHAIN           1880..2334
FT                   /note="Non-structural protein 5-6-7"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000397090"
FT   CHAIN           1880..2049
FT                   /note="Non-structural protein 5"
FT                   /id="PRO_0000423134"
FT   CHAIN           2050..2065
FT                   /note="Non-structural protein 6"
FT                   /id="PRO_0000423135"
FT   CHAIN           2066..2214
FT                   /note="Non-structural protein 7-alpha"
FT                   /id="PRO_0000423136"
FT   CHAIN           2215..2334
FT                   /note="Non-structural protein 7-beta"
FT                   /id="PRO_0000423137"
FT   CHAIN           2335..3020
FT                   /note="RNA-directed RNA polymerase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000397091"
FT   CHAIN           2335..2379
FT                   /note="Non-structural protein 8"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000397092"
FT   CHAIN           3021..3462
FT                   /note="Helicase nsp10"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000397093"
FT   CHAIN           3463..3686
FT                   /note="Uridylate-specific endoribonuclease nsp11"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000397094"
FT   CHAIN           3687..3838
FT                   /note="Non-structural protein 12"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000397095"
FT   TRANSMEM        1094..1114
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1117..1137
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1162..1182
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1211..1231
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1235..1255
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1450..1470
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1526..1546
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1556..1576
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1592..1612
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1875..1895
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1916..1936
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1960..1980
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2003..2023
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2029..2048
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          1677..1879
FT                   /note="Peptidase S32"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   DOMAIN          2364..2527
FT                   /note="NiRAN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01292"
FT   DOMAIN          2765..2899
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          3021..3084
FT                   /note="AV ZBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   DOMAIN          3134..3293
FT                   /note="(+)RNA virus helicase ATP-binding"
FT   DOMAIN          3294..3423
FT                   /note="(+)RNA virus helicase C-terminal"
FT   DOMAIN          3462..3559
FT                   /note="AV-Nsp11N/CoV-Nsp15M"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01306"
FT   DOMAIN          3561..3683
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                   /evidence="ECO:0000250"
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                   /evidence="ECO:0000250"
FT   REGION          418..505
FT                   /note="OTU-like"
FT   REGION          728..758
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1027..1064
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1132..1255
FT                   /note="HD1"
FT                   /evidence="ECO:0000250"
FT   REGION          1310..1334
FT                   /note="WCCH"
FT                   /evidence="ECO:0000250"
FT   REGION          1451..1612
FT                   /note="HD2"
FT                   /evidence="ECO:0000250"
FT   REGION          1902..2023
FT                   /note="HD3"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        740..754
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1044..1064
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   ACT_SITE        146
FT                   /note="For Nsp1-alpha papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00872"
FT   ACT_SITE        276
FT                   /note="For Nsp1-beta papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
FT   ACT_SITE        345
FT                   /note="For Nsp1-beta papain-like cysteine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
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        1715
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   ACT_SITE        1740
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   ACT_SITE        1793
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT   ACT_SITE        3592
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        3607
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        3636
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   BINDING         3027
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3030
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3040
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3045
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3048
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3050
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3052
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3054
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3061
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3063
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3070
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3073
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3168..3175
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            1446..1447
FT                   /note="Cleavage; by CP2"
FT                   /evidence="ECO:0000303|PubMed:22258855"
FT   SITE            1676..1677
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000269|PubMed:22258855"
FT   SITE            1879..1880
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000269|PubMed:22258855"
FT   SITE            2049..2050
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000269|PubMed:22258855"
FT   SITE            2065..2066
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000269|PubMed:22258855"
FT   SITE            2214..2215
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000269|PubMed:22258855"
FT   SITE            2334..2335
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000269|PubMed:22258855"
FT   SITE            2379..2380
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000269|PubMed:22258855"
FT   SITE            3020..3021
FT                   /note="Cleavage; by 3CLSP"
FT   SITE            3071
FT                   /note="Involved in mRNA transcription process"
FT                   /evidence="ECO:0000250"
FT   SITE            3462..3463
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250"
FT   SITE            3686..3687
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         2380..3838
FT                   /note="Missing (in isoform Replicase polyprotein 1a)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_039634"
FT   VARIANT         666
FT                   /note="R -> Q (in strain: Infectious clone SD 01-08)"
FT   VARIANT         1005
FT                   /note="R -> K (in strain: Infectious clone SD 01-08)"
FT   VARIANT         1012
FT                   /note="N -> S (in strain: Infectious clone SD 01-08)"
FT   VARIANT         3092
FT                   /note="P -> L (in strain: Infectious clone SD 01-08)"
FT   VARIANT         3682
FT                   /note="Y -> H (in strain: Infectious clone SD 01-08)"
FT   MUTAGEN         429
FT                   /note="C->A: Lethal."
FT                   /evidence="ECO:0000269|PubMed:20504922"
FT   MUTAGEN         458
FT                   /note="D->A: Slight reduction in the ability of Nsp2 to
FT                   impair NF-kappaB activation."
FT                   /evidence="ECO:0000269|PubMed:20504922"
FT   MUTAGEN         462
FT                   /note="S->A: Reduction in the ability of Nsp2 to impair
FT                   NF-kappaB activation."
FT                   /evidence="ECO:0000269|PubMed:20504922"
FT   MUTAGEN         463
FT                   /note="D->A: Lethal."
FT                   /evidence="ECO:0000269|PubMed:20504922"
FT   MUTAGEN         465
FT                   /note="D->A: Reduction in the ability of Nsp2 to impair
FT                   NF-kappaB activation."
FT                   /evidence="ECO:0000269|PubMed:20504922"
FT   MUTAGEN         498
FT                   /note="H->A: Lethal."
FT                   /evidence="ECO:0000269|PubMed:20504922"
SQ   SEQUENCE   3838 AA;  418948 MW;  07ADB34E6578FFC9 CRC64;
     MSGTFSRCMC TPAARVFWNA GQVFCTRCLS ARPLLSPELQ DTDLGVVGLF YKPKDKIHWK
     VPIGIPQVEC TPSGCCWLSA VFPLARMTSG NHNFLQRLVK VADVLYRDGC LAPRHLRELQ
     VYERGCSWYP ITGPVPGMGL FANSMHVSDQ PFPGATHVLT NSPLPQRACR QPFCPFEEAH
     SDVYRWKKFV IFTDSSPNGR FRMMWTPESD DSAALEVLPP ELERQVEILT RSFPAHHPIN
     LADWELTESP ENGFSFGTSH SCGHIVQNPN VFDGKCWLTC FLGQSAEVCY HEEHLANALG
     YQTKWGVHGK YLQRRLQVRG MRAVVDPDGP IHVEALSCSQ SWVRHLTLNN DVTPGFVRLT
     SIRIVSNTEP TAFRIFRFGA HKWYGAAGKR ARAKRATKSG KDSALAPKIA PPVPTCGITT
     YSPPTDGSCG WHVLAAIVNR MINGDFTSPL PQYNRPEDDW ASDYDLAQAI QCLQLPATVV
     RNRACPNAKY LIKLNGVHWE VEVRSGMAPR SLSRECVVGV CSEGCVAPPY PADGLPKRAL
     EALASAYRLP SDCVSSGIAD FLADPPPQEF WTLDKMLTSP SPERSGFSSL YKLLLEVVPQ
     KCGATEGAFV YAVERMLKDC PSPEQAMALL AKIKVPSSKA PSVSLDECFP AGVPADFEPA
     FQERPRSPGA AVALCSPDAK GFEGTASEEA QESGHKAVHA VPLAEGPNNE QVQVVAGEQL
     ELGGCGLAIG SAQSSSDSKR ENMHNSREDE PLDLSHPAPA ATTTLVGEQT PDNPGSDASA
     LPIAVRGFVP TGPILRHVEH CGTESGDSSS PLDLSFAQTL DQPLDLSLAA WPVKATASDP
     GWVRGRCEPV FLKPRKAFSD GDSALQFGEL SESSSVIEFD QTKDTLVADA PVDLTTSNEA
     LSAVDPSEFV ELRRPRHSAQ ALIDRGGPLA DVHAKIKNRV YEQCLQACEP GSRATPATRE
     WLDKMWDRVD MKTWRCTSQF QAGRILASLK FLPDMIQDTP PPVPRKNRAS DNAGLKQLVA
     RWDKKLSVTP PPKSAGLVLD QTVPPPTDIQ QEDATPSDGL SHASDFSSRV STSWSWKGLM
     LSGTRLAGSA GQRLMTWVFE VYSHLPAFIL TLFSPRGSMA PGDWLFAGVV LLALLLCRSY
     PILGCLPLLG VFSGSLRRVR LGVFGSWMAF AVFLFSTPSN PVGSSCDHDS PECHAELLAL
     EQRQLWEPVR GLVVGPSGLL CVILGKLLGG SRHLWHVILR LCMLTDLALS LVYVVSQGRC
     HKCWGKCIRT APAEVALNVF PFSRATRNSL TSLCDRFQTP KGVDPVHLAT GWRGCWRGES
     PIHQPHQKPI AYANLDEKKI SAQTVVAVPY DPSQAIKCLK VLQAGGAIVD QPTPEVVRVS
     EIPFSAPFFP KVPVNPDCRI VVDSDTFVAA VRCGYSTAQL VLGRGNFAKL NQTPLRDSAS
     TKTTGGASYT LAVAQVSVWT LVHFILGLWF TSPQVCGRGT ADPWCSNPFS YPAYGPGVVC
     SSRLCVSADG VTLPLFSAVA QLSGREVGIF ILVLVSLTAL AHRLALKADM LVVFSAFCAY
     AWPMSSWLIC FFPILLKWVT LHPLTMLWVH SFLVFCMPAA GILSLGITGL LWAVGRFTQV
     AGIITPYDIH QYTSGPRGAA AVATAPEGTY MAAVRRAALT GRTLIFTPSA VGSLLEGAFR
     THKPCLNTVN VVGSSLGSGG VFTIDGRKTV VTAAHVLNGD TARVTGDSYN RMHTFKTSGD
     YAWSHADDWQ GVAPVVKVAK GYRGRAYWQT STGVEPGVIG EGFAFCFTNC GDSGSPVISE
     SGDLIGIHTG SNKLGSGLVT TPEGETCAIK ETKLSDLSRH FAGPSVPLGD IKLSPAIVPD
     VTSIPSDLAS LLASVPVMEG GLSTVQLLCV FFLLWRMMGH AWTPIVAVGF FLLNEILPAV
     LVRAVFSFAL FILAWATPWS AQVLMIRLLT ASLNRNKLSL AFYALGGVVG LAAEIGAFAG
     RLPELSQALS TYCFLPRVLA MASYVPIIII GGLHALGVIL WLFKYRCLHN MLVGDGSFSS
     AFFLRYFAEG NLRKGVSQSC GMSNESLTAA LACKLSQADL DFLSSLTNFK CFVSASNMKN
     AAGQYIEAAY AKALRQELAS LVQVDKMKGI LSKLEAFAET ATPSLDAGDV VVLLGQHPHG
     SILDINVGTE RKTVSVQETR SLGGSKFSVC TVVSNTPVDA LTGIPLQTPT PLFENGPRHR
     GEEDDLRVER MKKHCVSLGF HNINGKVYCK IWDKSTGDTF YTDDSRYTQD LAFQDRSADY
     RDRDYEGVQT APQQGFDPKS ETPIGTVVIG GITYNRYLIK GKEVLVPKPD NCLEAAKLSL
     EQALAGMGQT CDLTAAEVEK LRRIISQLQG LTTEQALNCL LAASGLTRCG RGGLVVTETA
     VKIVKYHSRT FTLGPLDLKV TSEAEVKKST EQGHAVVANL CSGVILMRPH PPSLVDVLLK
     PGLDTKPGIQ PGHGAGNMGV DGSTWDFETA PTKAELELSK QIIQACEVRR GDAPNLQLPY
     KLYPVRGDPE RHGGRLINTR FGDLSYKTPQ DTKSAIHAAC CLHPNGAPVS DGKSTLGTTL
     QHGFELYVPT VPYSVMEYLD SRPDTPFMCT KHGTSKAAAE DLQKYDLSTQ GFVLPGVLRL
     VRRFIFGHIG KAPPLFLPST YPAKNSMAGI NGQRFPTKDV QSIPEIDEMC ARAVKENWQT
     VTPCTLKKQY CSKPKTRTIL GTNNFIALAH RSALSGVTQA FMKKAWKSPI ALGKNKFKEL
     HCTVAGRCLE ADLASCDRST PAIVRWFVAN LLYELAGCEE YLPSYVLNCC HDLVATQDGA
     FTKRGGLSSG DPVTSVSNTV YSLIIYAQHM VLSALKMGHE IGLKFLEEQL KFEDLLEIQP
     MLVYSDDLVL YAERPTFPNY HWWVEHLDLM LGFRTDPKKT VITDKPSFLG CRIEAGRQLV
     PNRDRILAAL AYHMKAQNAS EYYASAAAIL MDSCACIDHD PEWYEDLICG IARCARQDGY
     SFPGPAFFMS MWEKLRSHNE GKKFRHCGIC DAKADHASAC GLDLCLFHSH FHQHCPVTLS
     CGHHAGSREC SQCQSPVGAG RSPLDAVLKQ IPYKPPRTVI MKVGNKTTAL DPGRYQSRRG
     LVAVKRGIAG NEVDLPDGDY QVVPLLPTCK DINMVKVACN VLLSKFIVGP PGSGKTTWLL
     SQVQDDDVIY TPTHQTMFDI VSALKVCRYS IPGASGLPFP PPARSGPWVR LVASGHVPGR
     TSYLDEAGYC NHLDILRLLS KTPLVCLGDL QQLHPVGFDS YCYVFDQMPQ KQLTTIYRFG
     PNICAAIQPC YREKLESKAR NTRVVFTTWP VAFGQVLTPY HKDRIGSAIT IDSSQGATFD
     IVTLHLPSPK SLNKSRALVA ITRARHGLFI YDPHNQLQEF FNLIPERTDC NLVFSRGDDL
     VVLSADNAVT TVAKALGTGP SRFRVSDPRC KSLLAACSAS LEGSCMPLPQ VAHNLGFYFS
     PDSPAFAPLP KELAPHWPVV THQNNRAWPD RLVASMRPID ARYSKPMVGA GYVVGPSTFL
     GTPGVVSYYL TLYIRGEPQA LPETLVSTGR IATDCREYLD AAEEEAAKEL PHAFIGDVKG
     TTVGGCHHIT SKYLPRTLPK DSVAVVGVSS PGRAAKAMCT LTDVYLPELR PYLQPETASK
     CWKLKLDFRD VRLMVWKGAT AYFQLEGLTW SALPDYARFI QLPKDAVVYI DPCIGPATAN
     RKVVRTTDWR ADLAVTPYDY GAQNILTTAW FEDLGPQWKI LGLQPFRRAF GFENTEDWAI
     LARRMSDGKD YTDYNWDCVR ERPHAIYGRA RDHTYHFAPG TELQVELGKP RLPPGREP
//