RPOA_PRRSR
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 03-AUG-2022, entry version 133.
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; unclassified Arteriviridae.
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 OF POLYPROTEIN, AND PROTEIN SEQUENCE OF
RP 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. {ECO:0000250|UniProtKB:Q04561}.
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 ECO:0000269|PubMed:20006994, ECO:0000269|PubMed:20850164,
CC 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. Additionally, inhibits the interferon-activated
CC JAK/STAT signal transduction by mediating the ubiquitination and
CC subsequent proteasomal degradation of host KPNA1.
CC {ECO:0000250|UniProtKB:Q04561, ECO:0000269|PubMed:20006994,
CC 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. Deubiquitinates also host NFKBIA, thereby interfering
CC with NFKBIA degradation and impairing subsequent NF-kappa-B activation.
CC {ECO:0000250|UniProtKB:A0MD28, 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, and PKR
CC (By similarity). Acts by degrading the 5'-polyuridines generated during
CC replication of the poly(A) region of viral genomic and subgenomic RNAs.
CC Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-
CC cP) is first generated by 2'-O transesterification, which is then
CC hydrolyzed to a 3'-phosphate (3'-P) (By similarity). If not degraded,
CC poly(U) RNA would hybridize with poly(A) RNA tails and activate host
CC dsRNA sensors (By similarity). {ECO:0000250|UniProtKB:P0C6X7,
CC ECO:0000250|UniProtKB:P19811}.
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:0000250|UniProtKB:Q04561};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC Evidence={ECO:0000250|UniProtKB:Q04561};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000250|UniProtKB:Q04561};
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; 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: [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:Q04561}.
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 3]: 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: 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. {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=AAD12125.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAO13192.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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: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: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: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:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; 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: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; -; 1.
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; 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; SSF142877; SSF142877; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
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 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 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 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 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 SITE 383..384
FT /note="Cleavage; by autolysis"
FT SITE 1579..1580
FT /note="Cleavage; by CP2"
FT /evidence="ECO:0000255"
FT SITE 1809..1810
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 2013..2014
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 2183..2184
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 2199..2200
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 2348..2349
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 2458..2459
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 3143..3144
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
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 VR-
FT 2332)"
FT VARIANT 1777
FT /note="T -> I (in strain: Isolate infectious clone VR-
FT 2332)"
FT VARIANT 2222
FT /note="D -> N (in strain: Isolate infectious clone VR-
FT 2332)"
FT VARIANT 3257
FT /note="G -> E (in strain: Isolate infectious clone VR-
FT 2332)"
FT VARIANT 3539
FT /note="C -> R (in strain: Isolate infectious clone VR-
FT 2332)"
FT VARIANT 3623
FT /note="S -> T (in strain: Isolate infectious clone VR-
FT 2332)"
FT VARIANT 3678
FT /note="G -> E (in strain: Isolate infectious clone VR-
FT 2332)"
FT VARIANT 3714
FT /note="G -> A (in strain: Isolate infectious clone VR-
FT 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
