ID   RPOA_PRRSB              Reviewed;        3961 AA.
AC   Q8B912; Q8B911;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   10-AUG-2010, sequence version 3.
DT   27-MAR-2024, entry version 126.
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 HB-1) (PRRSV).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Arnidovirineae; Arteriviridae; Variarterivirinae;
OC   Betaarterivirus; Ampobartevirus; Betaarterivirus suid 2.
OX   NCBI_TaxID=300563;
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=15221535; DOI=10.1007/s00705-004-0292-0;
RA   Gao Z.Q., Guo X., Yang H.C.;
RT   "Genomic characterization of two Chinese isolates of porcine respiratory
RT   and reproductive syndrome virus.";
RL   Arch. Virol. 149:1341-1351(2004).
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       Cleaves the nsp2/nsp3 site in the viral polyprotein. Displays
CC       deubiquitinating activity that cleaves both ubiquitinated and ISGylated
CC       products and therefore inhibits ubiquitin and ISG15-dependent host
CC       innate immunity. Deubiquitinates also host NFKBIA, thereby interfering
CC       with NFKBIA degradation and impairing subsequent NF-kappa-B activation.
CC       {ECO:0000250|UniProtKB:A0MD28}.
CC   -!- FUNCTION: [Non-structural protein 3]: Plays a role in the inhibition of
CC       the immune response by interacting with host IFITM1. This interaction
CC       leads to the proteasomal degradation of the IFN-induced antiviral
CC       protein IFITM1. {ECO: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: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=Q8B912-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC         IsoId=Q8B912-2; Sequence=VSP_032891;
CC   -!- DOMAIN: The hydrophobic domains (HD) could mediate the membrane
CC       association of the replication complex and thereby alter the
CC       architecture of the host cell membrane. {ECO:0000250}.
CC   -!- DOMAIN: The OTU-like region is responsible for the deubiquitinating and
CC       deISGylation activities of Nsp2. {ECO:0000250}.
CC   -!- PTM: [Replicase polyprotein 1ab]: Specific enzymatic cleavages in vivo
CC       by its own proteases yield mature proteins. Nsp1 is autocleaved into
CC       two subunits, Nsp1-alpha and Nsp1-beta. There are two alternative
CC       pathways for processing. Either nsp4-5 is cleaved, which represents the
CC       major pathway or the nsp5-6 and nsp6-7 are processed, which represents
CC       the minor pathway. The major pathway occurs when nsp2 acts as a
CC       cofactor for nsp4. {ECO:0000250|UniProtKB:Q9WJB2}.
CC   -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1ab]: Produced by -1
CC       ribosomal frameshifting at the 1a-1b genes boundary.
CC   -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1a]: Produced by
CC       conventional translation. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the arteriviridae polyprotein family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAN73221.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AY150312; AAN73220.1; -; mRNA.
DR   EMBL; AY150312; AAN73221.1; ALT_INIT; mRNA.
DR   SMR; Q8B912; -.
DR   MEROPS; S32.002; -.
DR   ABCD; Q8B912; 8 sequenced antibodies.
DR   Proteomes; UP000124990; 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; 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; 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   2: Evidence at transcript 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   Reference proteome; Ribosomal frameshifting; RNA-directed RNA polymerase;
KW   Serine protease; Thiol protease; Transferase; Transmembrane;
KW   Transmembrane helix; Viral immunoevasion; Viral RNA replication; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..3961
FT                   /note="Replicase polyprotein 1ab"
FT                   /id="PRO_0000036670"
FT   CHAIN           1..382
FT                   /note="Nsp1"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000410827"
FT   CHAIN           1..180
FT                   /note="Nsp1-alpha papain-like cysteine proteinase"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000036672"
FT   CHAIN           181..383
FT                   /note="Nsp1-beta papain-like cysteine proteinase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036673"
FT   CHAIN           384..1579
FT                   /note="Nsp2 cysteine proteinase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036674"
FT   CHAIN           1580..1809
FT                   /note="Non-structural protein 3"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036675"
FT   CHAIN           1810..2013
FT                   /note="Serine protease nsp4"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036676"
FT   CHAIN           2014..2458
FT                   /note="Non-structural protein 5-6-7"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036677"
FT   CHAIN           2014..2183
FT                   /note="Non-structural protein 5"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000423122"
FT   CHAIN           2184..2199
FT                   /note="Non-structural protein 6"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000423123"
FT   CHAIN           2200..2348
FT                   /note="Non-structural protein 7-alpha"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000423124"
FT   CHAIN           2349..2458
FT                   /note="Non-structural protein 7-beta"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000423125"
FT   CHAIN           2459..3144
FT                   /note="RNA-directed RNA polymerase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036678"
FT   CHAIN           2459..2503
FT                   /note="Non-structural protein 8"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036679"
FT   CHAIN           3145..3585
FT                   /note="Helicase nsp10"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036680"
FT   CHAIN           3586..3808
FT                   /note="Uridylate-specific endoribonuclease nsp11"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036681"
FT   CHAIN           3809..3961
FT                   /note="Non-structural protein 12"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036682"
FT   TRANSMEM        1266..1286
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1296..1316
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        1648..1668
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        2036..2056
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        2162..2182
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..2651
FT                   /note="NiRAN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01292"
FT   DOMAIN          2890..3024
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          3145..3208
FT                   /note="AV ZBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   DOMAIN          3265..3417
FT                   /note="(+)RNA virus helicase ATP-binding"
FT   DOMAIN          3418..3546
FT                   /note="(+)RNA virus helicase C-terminal"
FT   DOMAIN          3585..3681
FT                   /note="AV-Nsp11N/CoV-Nsp15M"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01306"
FT   DOMAIN          3683..3805
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          810..875
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          899..918
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1148..1191
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   COMPBIAS        825..840
FT                   /note="Basic and acidic 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        3714
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        3729
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   ACT_SITE        3758
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT   BINDING         3151
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3154
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3164
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3169
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3172
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3174
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3176
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3178
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3185
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3187
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3194
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3197
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT   BINDING         3293..3300
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            383..384
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250"
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            2503..2504
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            3144..3145
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250|UniProtKB:A0MD28"
FT   SITE            3585..3586
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250"
FT   SITE            3808..3809
FT                   /note="Cleavage; by 3CLSP"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         2504..3961
FT                   /note="Missing (in isoform Replicase polyprotein 1a)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_032891"
SQ   SEQUENCE   3961 AA;  433077 MW;  45D39828CC48EA77 CRC64;
     MSGILDRCTC TPNARVFVAE GQVYCTRCLS ARSLLPLNLQ VPELGVLGLF YRPEEPLRWT
     LPRAFPTVEC SPTGACWLSA IFPIARMTSG NLNFQQRMVR VAGEIYRAGQ LTPTVLKTIQ
     VYERGCRWYP IVGPVPGVGV YANSLHVSDK PFPGATHVLT NLPLPQRPKP EDFCPFECAM
     ADVYDIGRGA VMYVAGGKVS WAPRGGDEVK FEPVPKELKL VANRLHTSFP PHHVVDMSKF
     TFMTPGSGVS MRVEYQYGCL PADTVPEGNC WWRLFDLLPP EVQNKEIRHA NQFGYQTKHG
     VPGKYLQRRL QVNGLRAVTD THGPIVIQYF SVKESWIRHL KPVEEPSLPG FEDLLRIRVE
     PNTSPLAGKN EKIFRFGSHK WYGAGKRARK ARSGATTMVA HRASSAHETR QATKHEGAGA
     NKAEHLKLYS PPAEGNCGWH CISAIVNRMV NSNFETTLPE RVRPPDDWAT DEDLVNTIQI
     LRLPAALDRN GACGGAKYVL KLEGEHWTVS VNPGMSPSLL PLECVQGCCE HKGGLGSPDA
     VEVSGFDPAC LDRLLQVMHL PSSTIPAALA ELSDDSNRPV SPAAATWTVS QSYARHRGGN
     HHDQVCLGKI ISLCQVIEDC CCHQNKTNRA TPEEVAAKID QYLRGATSLE ECLAKLERVS
     PPGAADTSFD WNVVLPGVEA AHQTTEQLHV NPCRTLVPPV TQEPLGKDSV PLTAFSLSNC
     YYPAQGNEVR HRERLNSVLS KLEEVVLEEY GLMSTGLGPR PVLPSGLDEL KDQMEEDLLK
     LANTQATSEM MAWAAEQVDL KAWVKSYPRW TPPPPPPRVQ PRKTKSVKSL PEDKPVPAPR
     RKVRSGCGSP VLMGDNVPNG SEDLTVGGPL NFPTPSEPMT PMSEPVLTPA LQRVPKLMTP
     LDGSAPVPAP RRTVSRPMTP LSEPIFLSAP RHKFQQVEEA NPATTTLTHQ NEPLDLSASS
     QTEYEASPLA SSQNMSILEA GGQEAEEVLS EISDILNDTS PAPVSSSSSL SSVKITRPKY
     SAQAIIDSGG PCSGHLQKEK EACLSIMREA CDASKLSDPA TQEWLSRMWD RVDMLTWRNT
     SAYQAFRTLN GRFEFLPKMI LETPPPHPCG FVMLPHTPAP SVSAESDLTI GSVATEDVPR
     ILGKIGDTGE LLNQGPSAPF KGGPVCDQPA KNSRMSPRES DESIIAPPAD TGGAGSFTDL
     PSSDSVDANG GGPLRTVKTK AGRLLDQLSC QVFSLVSHLP VFFSHLFKSD SGYSPGDWGF
     AAFTLFCLFL CYSYPFFGFA PLLGVFSGSS RRVRMGVFGC WLAFAVGLFK PVSDPVGTAC
     EFDSPECRNV LHSFELLKPW DPVRSLVVGP VGLGLAILGR LLGGARYVWH FLLRFGIVAD
     CILAGAYVLS QGRCKKCWGS CVRTAPNEIA FNVFPFTRAT RSSLIDLCDR FCAPKGMDPI
     FLATVWRGCW TGRSPIEQPS EKPIAFAQLD EKRITARTVV AQPYDPNQAV KCLRVLQAGG
     AMVAEAVPKV VKVSAIPFRA PFFPAGVKVD PECRIVVDPD TFTTALRSGY STTNLVLGMG
     DFAQLNGLKI RQISKPSGGG SHLVAALHVA CSMALHMLAG VYVTAVGSCG TGTNDPWCTN
     PFAAPGYGPG SLCTSRLCIS QHGLTLPLTA LVAGFGLQEI ALVVLIFVSM GGMAHRLSCK
     ADMLCILLAI ASYVWVPLTW LLCVFPCWLR WFSLHPLTIL WLVFFLISVN IPSGILAVVL
     LVSLWLLGRY TNIAGLVTPY DIHHYTSGPR GVAALATAPD GTYLAAVRRA ALTGRTMLFT
     PSQLGSLLEG AFRTQKPSLN TVNVVGSSMG SGGVFTIDGK IKCVTAAHVL TGNSARVSGV
     GFNQMLDFDV KGDFAIADCP NWQGAAPKAQ FCEDGWTGRA YWLTSSGVEP GVIGNGFAFC
     FTACGDSGSP VITEAGELVG VHTGSNKQGG GIVTRPSGQF CNVTPIKLSE LSEFFAGPKV
     PLGDVKIGSH IIKDTCEVPS DLCALLAAKP ELEGGLSTVQ LLCVFFLLWR MMGHAWTPLV
     AVGFFILNEI LPAVLVRSVF SFGMFVLSWL TPWSAQVLMI RLLTAALNRN RLSLGFYSLG
     AVTSFVADLA VTQGHPLQVV MNLSTYAFLP RMMVVTSPVP VIACGVVHLL AIILYLFKYR
     CLHYVLVGDG VFSSAFFLRY FAEGKLREGV SQSCGMSHES LTGALAMRLT DEDLDFLTKW
     TDFKCFVSAS NMRNAAGQFI EAAYAKALRI ELAQLVQVDK VRGTLAKLEA FADTVAPQLS
     PGDIVVALGH TPVGSIFDLK VGSTKHTLQA IETRVLAGSK MTVARVVDPT PAPPPVPVPI
     PLPPKVLENG PNAWGDEDRL NKKKRRRMEA VGIFVMDGKK YQKFWDKNSG DVFYEEVHNS
     TDEWECLRAG DPADFDPETG VQCGHITIED RVYNVFTSPS GRKFLVPANP ENRRAQWEAA
     KLSVEQALGM MNVDGELTAK ELEKLKGIID KLQGLTKEQC LNCLLAASGL TRCGRGGLVV
     TETAVKIVKF HNRTFTLGPV NLKVASEVEL KDAVEHNQHP VARPVDGGVV LLRSAVPSLI
     DVLISGADAS PKLLARHGPG NTGIDGTLWD FEAEATKEEV ALSAQIIQAC DIRRGDAPEI
     GLPYKLYPVR GNPERVKGVL QNTRFGDIPY KTPSDTGSPV HAAACLTPNA TPVTDGRSVL
     ATTMPSGFEL YVPTIPASVL DYLDSRPDCP KQLTEHGCED AALRDLSKYD LVTQGFVLPG
     VLRLVRKYLF AHVGKCPPVH RPSTYPAKNS MAGINGNRFP TKDIQSVPEI DVLCAQAVRE
     NWQTVTPCTL KKQYCGKKKT RTILGTNNFI ALAHRAALSG VTQGFMKKAF NSPIALGKNK
     FKELQTPVLG RCLEADLASC DRSTPAIVRW FAANLLYELA CAEEHLPSYV LNCCHDLLVT
     QSGAVTKRGG LSSGDPITSV SNTIYSLVIY AQHMVLSYFK SGHPHGLLFL QDQLKFEDML
     KVQPLIVYSD DLVLYAESPS MPNYHWWVEH LNLMLGFQTD PKKTAITDSP TFLGCRIING
     RQLVPNRDRI LAALAYHMKA SNVSEYYASA AAILMDSCAC LEYDPEWFEE LVVGIAQCAR
     KDGYSFPGPP FFLSMWEKLR SNHEGKKSRM CGYCMAPAPY ATACGLDVCV YHTHFHQHCP
     VIIWCGHPAG SGSCGECEPP LGKGTSPLDE VLEQVPYKPP RTVIMHVEQG LTPLDPGRYQ
     TRRGLVSVRR GIRGNEVDLP DGDYASTALL PTCKEINMVA VAPNVLRSRF IIGPPGAGKT
     HWLLQQVQDG DVIYTPTHQT MLDMIRALGT CRFNVPAGTT LQFPAPSRTG PWVRILAGGW
     CPGKNSFLDE AAYCNHLDVL RLLSKTTLTC LGDFKQLHPV GFDSHCYVFD IMPQTQLKTI
     WRFGQNICDA IQPDYRDKLV SMVNTTRVTY VEKPVRYGQV LTPYHRDRED GAITIDSSQG
     ATFDVVTLHL PTKDSLNRQR ALVAITRARH AIFVYDPHRQ LQSMFDLPAK GTPVNLAVHR
     DEQLIVLDRN NKEITVAQAL GNGDKFRATD KRVVDSLRAI CADLEGSSSP LPKVAHNLGF
     YFSPDLTQFA KLPAELAPHW PVVTTQNNER WPDRLVASLR PIHKYSRACI GAGYMVGPSV
     FLGTPGVVSY YLTKFVRGEA QVLPETVFST GRIEVDCREY LDDREREVAE SLPHAFIGDV
     KGTTVGGCHH VTSKYLPRFL PKESVAVVGV SSPGEAAKAF CTLTDVYLPD LEAYLHPETQ
     SKCWKVMLDF KEVRLMVWKG KTAYFQLEGR HFTWYQLASY TSYIRVPVNS TVYLDPCMGP
     ALCNRRVVGS THWGADLAVT PYDYGAKIIL SSAYHGEMPP GYKILACAEF SLDDPVRYKH
     TWGFESDTAY LYEFTGNGED WEDYNGAFRA RQKGKIYKAT ATSMKFHFPP GPVIEPTLGL
     N
//