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R1A_BEV
ID   R1A_BEV                 Reviewed;        4569 AA.
AC   P0C6F3; P18458;
DT   10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT   10-JUN-2008, sequence version 1.
DT   03-AUG-2022, entry version 68.
DE   RecName: Full=Replicase polyprotein 1a;
DE            Short=pp1a;
DE   AltName: Full=ORF1a polyprotein;
DE   Contains:
DE     RecName: Full=Non-structural protein 1;
DE              Short=nsp1;
DE   Contains:
DE     RecName: Full=Non-structural protein 2;
DE              Short=nsp2;
DE   Contains:
DE     RecName: Full=3C-like serine proteinase;
DE              Short=3CLSP;
DE              EC=3.4.21.-;
DE     AltName: Full=M-PRO;
DE     AltName: Full=nsp3;
DE     AltName: Full=p27;
DE   Contains:
DE     RecName: Full=Non-structural protein 4;
DE              Short=nsp4;
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;
DE              Short=nsp7;
DE   Contains:
DE     RecName: Full=Non-structural protein 8;
DE              Short=nsp8;
DE   Contains:
DE     RecName: Full=Non-structural protein 9;
DE              Short=nsp9;
GN   ORFNames=1a;
OS   Berne virus (BEV).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Tornidovirineae; Tobaniviridae; Torovirinae; Torovirus;
OC   Renitovirus; Equine torovirus.
OX   NCBI_TaxID=11156;
OH   NCBI_TaxID=9796; Equus caballus (Horse).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA], CHARACTERIZATION OF 3C-LIKE PROTEINASE
RP   M-PRO, AND PROTEOLYTIC PROCESSING OF POLYPROTEIN.
RX   PubMed=16571831; DOI=10.1128/jvi.80.8.4157-4167.2006;
RA   Smits S.L., Snijder E.J., de Groot R.J.;
RT   "Characterization of a torovirus main proteinase.";
RL   J. Virol. 80:4157-4167(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-252.
RX   PubMed=1856694; DOI=10.1099/0022-1317-72-7-1635;
RA   Snijder E.J., den Boon J.A., Horzinek M.C., Spaan J.M.;
RT   "Characterization of defective interfering RNAs of Berne virus.";
RL   J. Gen. Virol. 72:1635-1643(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 4219-4569.
RC   STRAIN=Isolate P138/72;
RX   PubMed=2388833; DOI=10.1093/nar/18.15.4535;
RA   Snijder E.J., den Boon J.A., Bredenbeek P.J., Horzinek M.C., Rijnbrand R.,
RA   Spaan W.J.M.;
RT   "The carboxyl-terminal part of the putative Berne virus polymerase is
RT   expressed by ribosomal frameshifting and contains sequence motifs which
RT   indicate that toro- and coronaviruses are evolutionarily related.";
RL   Nucleic Acids Res. 18:4535-4542(1990).
CC   -!- FUNCTION: The 3C-like serine proteinase is responsible for the majority
CC       of cleavages.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 2]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=2;
CC       Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC         IsoId=P0C6F3-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC         IsoId=P0C6V7-1; 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   -!- PTM: Specific enzymatic cleavages in vivo by its own protease yield
CC       mature proteins. 3CL-PRO is autocatalytically processed (By
CC       similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1a]: Produced by
CC       conventional translation.
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DR   EMBL; DQ310701; ABC26008.1; -; Genomic_RNA.
DR   EMBL; X56016; CAA39493.1; -; Genomic_RNA.
DR   EMBL; X52374; CAA36600.1; -; Genomic_RNA.
DR   PIR; S11237; S11237.
DR   PIR; S11238; S11238.
DR   SMR; P0C6F3; -.
DR   MEROPS; S65.001; -.
DR   PRIDE; P0C6F3; -.
DR   Proteomes; UP000006571; Genome.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd21557; Macro_X_Nsp3-like; 1.
DR   Gene3D; 2.40.10.10; -; 2.
DR   Gene3D; 3.40.220.10; -; 1.
DR   InterPro; IPR002589; Macro_dom.
DR   InterPro; IPR043472; Macro_dom-like.
DR   InterPro; IPR044371; Macro_X_NSP3-like.
DR   InterPro; IPR039573; NS2A-like.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   Pfam; PF05213; Corona_NS2A; 1.
DR   Pfam; PF01661; Macro; 1.
DR   SMART; SM00506; A1pp; 1.
DR   SUPFAM; SSF50494; SSF50494; 1.
DR   SUPFAM; SSF52949; SSF52949; 1.
DR   SUPFAM; SSF54001; SSF54001; 1.
DR   PROSITE; PS51154; MACRO; 1.
PE   1: Evidence at protein level;
KW   Host membrane; Hydrolase; Membrane; Metal-binding; Protease;
KW   Reference proteome; Repeat; Ribosomal frameshifting; Thiol protease;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..4569
FT                   /note="Replicase polyprotein 1a"
FT                   /id="PRO_0000338016"
FT   CHAIN           1..2873
FT                   /note="Non-structural protein 1"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338017"
FT   CHAIN           2874..3251
FT                   /note="Non-structural protein 2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338018"
FT   CHAIN           3252..3543
FT                   /note="3C-like serine proteinase"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338020"
FT   CHAIN           3544..3802
FT                   /note="Non-structural protein 4"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338021"
FT   CHAIN           3803..3979
FT                   /note="Non-structural protein 5"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338022"
FT   CHAIN           3980..4161
FT                   /note="Non-structural protein 6"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338023"
FT   CHAIN           4162..4246
FT                   /note="Non-structural protein 7"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338024"
FT   CHAIN           4247..4399
FT                   /note="Non-structural protein 8"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338025"
FT   CHAIN           4400..4569
FT                   /note="Non-structural protein 9"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338026"
FT   TRANSMEM        2303..2323
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2330..2350
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2385..2405
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2535..2555
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2639..2659
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2664..2684
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2889..2909
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3057..3077
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3106..3126
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3142..3162
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3556..3575
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3580..3602
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3611..3631
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3640..3660
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3663..3683
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3698..3718
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3723..3738
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1679..1860
FT                   /note="Macro"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   REGION          2158..2191
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2303..2683
FT                   /note="HD1"
FT   REGION          2889..3162
FT                   /note="HD2"
FT   REGION          3555..3738
FT                   /note="HD3"
FT   ACT_SITE        3304
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        3347
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        3416
FT                   /note="Charge relay system; for 3C-like serine proteinase
FT                   activity"
FT                   /evidence="ECO:0000255"
FT   SITE            2873..2874
FT                   /note="Cleavage; by 3C-like serine proteinase"
FT                   /evidence="ECO:0000255"
FT   SITE            3251..3252
FT                   /note="Cleavage; by 3C-like serine proteinase"
FT   SITE            3543..3544
FT                   /note="Cleavage; by 3C-like serine proteinase"
FT   SITE            3802..3803
FT                   /note="Cleavage; by 3C-like serine proteinase"
FT                   /evidence="ECO:0000255"
FT   SITE            3979..3980
FT                   /note="Cleavage; by 3C-like serine proteinase"
FT                   /evidence="ECO:0000255"
FT   SITE            4161..4162
FT                   /note="Cleavage; by 3C-like serine proteinase"
FT                   /evidence="ECO:0000255"
FT   SITE            4246..4247
FT                   /note="Cleavage; by 3C-like serine proteinase"
FT                   /evidence="ECO:0000255"
FT   SITE            4399..4400
FT                   /note="Cleavage; by 3C-like serine proteinase"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        251..252
FT                   /note="RR -> KK (in Ref. 2; CAA39493)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   4569 AA;  523793 MW;  753D2EA1FEF31AEA CRC64;
     MSTSSSILDI PSKMFRILKN NTRETEQHLS SSTLDLISKS QLLAQCFDTQ EIMASLSKTV
     RSILESQNLE HKSTLTPYNS SQSLQLLVMN TSCTQFKWTT GSTSSVKALL EKELCRGLVP
     LNDITPKSNY VELSLLTPSI LIGNETSTTT TLPEIPLDME QSIISCVENT LLKEVQALSG
     QESCQEYFLS ANYQSLIPPQ VLLNLMKMSS VVDLSPLTLP NTRLWLKLSP FHGGTSVSYA
     TQIKGYANCA RREEKCLKNR LTKKQKNQEK GSFDARSVIT LGGKMYRYKV VVLRCEDQSD
     NLSELQFEPQ VEYTMDMVPH CWKELVKKRL IRAKGTWDLS CVEDLDLDHV EVRGDSLLHR
     SSVVHDLTSI VDDTLQEKLF SRTWLRQSLK YSGNILQRLS SLFATEGLKK ITLVNSDITP
     VQVGDKWLNF VDFGKSTVFF VKTLNNIHLA MTRQRESCNY IHEKFGRVRW LGAKPEQGAI
     VKVFAWCLNK KEFKFRDNQL KQYVCRQGVI KHEPCEYLNV EVLDEFVALN NDLNCVQKIK
     TYLAAYFGLK KVKLTQKNFM TPLITKKQEL VFQPCNCPNH QFYVAQFDKH VTLGLGRKDG
     ILFAEQVPSY AIILAVGFGT VETQLVTHYY SEMRRVYHPL DFQSNTFVFD HQGVMLEDIS
     PADYNDVGEE DYQLEYSGGF DQPFQNYHSD DEDQAFPDFE DERHPDEENW ARPIISSGES
     SVVSSRPSSP LVYSSLVPVA SPFGYMNGIR VFDICLADDL DFLQIHGQCP CARCKGLYFY
     QPIRPRGFTI FENVVEFFSF VEKCEVFEEI GPFFKMIEYS MLYNEYNIFY GLGKKIYQSD
     LVLPVKHLDQ LWKRAQLDID VVSEFENFKN SLQNINNVVY IAPYFNDQGE WNDIFDGYEF
     NLNDNQFWFQ AKPVYDLVCY IYQGFFSDSR PLEKLYQKLC LDYHTSAMLH TQTHLKYCYV
     ALLHSERAFQ MSINLDSLDN EQLHFLATMG MGDASLVGPT YLSEYHSNFN WYSIMSKACH
     YVKLEQLVGL TYQEKRLMIL SRVQEFYEQQ HRGPIQLILS PLKVVNLPPI TCTEGYCYQP
     VTRLFDTCVM PDIMKKLSRK RTSVSDVFGI LADYFKRTLS YRCFKVHEFC GIERQQEFSD
     MTTLKLVTDW CQDTYYFYNE YATMTDVEPK VQVSSDYYLK IPSEVVEHIR QFLPHNVNVG
     LMNYVSSNCD FDQCKFEFCL SGKGYVLGNM FFNRCAIQYV KTNLFIVLFK SRPLLYITQE
     SIYLSDFNVL QAQCLTGEFC LDFEPVQGKT LFGVYFTNGQ RYGQQWETLP RFSLKPLNSP
     RKRVPTQPFE ELAEVCIFKQ KLKLTQLHND CSVTPRVCSI PQTITATFQP YYCLENFYGV
     KAPKVIVSGH LATHYVKLTH KISKCVLVTK LAVARAFYFT PTSMGSHYHL DPMEGISFGK
     RATVQFEPVG LIKDVNLLVY QFGSHVSIQF FPEAPCIVAD GHYPSKYSGV WLGYLPSVEE
     CKIAQVNHRV YVPTILRTSK SAPFHIIQNG DMGRGPITVT YHYAKNFDNK SLTPMFKMFQ
     QVFEKSKDDI FKAFNTMSLE QKKVLSHFCG EFDEAYTLQT MSDEISFESS AYPDVVACSL
     AYILGYEMCL TVKVNAKNEK LDIGSQCERV FVDYDVKKNE WTLSPEEGED SDDNLDLPFE
     QYYEFKIGQT NVVLVQDDFK SVFEFLKSEQ GVDYVVNPAN SQLKHGGGIA KVISCMCGPK
     LQAWSNNYIT KNKTVPVTKA IKSPGFQLGK KVNIIHAVGP RVSDGDVFQK LDQAWRSVFD
     LCEDQHTILT SMLSTGIFGC TVNDSFNTFL SNVARLDKSL VVFVVTNMVE QYNQAFAVIK
     MYQQYHGLPN FGNTCWFNAL YQLLKSFSEK EQCVNDLLNC FDDFYDCPTS QCVEWVCEQL
     GVQFGQQQDA VEMLMKVFDV FKCDVRVGFD CLSRLQQVNC GFCVEVPAQA VLMFSGKDQC
     GHWTAARKIV DKWYTFDDNH VVQKDPVWQN VVLVLRDRGI FRSADFERKP ARRRRVSHRV
     PRDTLSQDAI TYIEDLRFSS GTCLSRYFVE SVESFVSGDN VSEVSDEQTC VEVAIEESDG
     HVEQICQSSV DCVGMPESFQ FTFSMPLQTF VQECDQKCED DFSQEHVECD QQFEPVEQVG
     QGGQQDGQVD QQIKESEQVV EPSAPSGQES PQALLQQVVD EVVYQIEQVK CDQKQDQDSV
     QCDEIEEINS RGEQTVQQQL QPILGHDLNE NEGPTLSVGA GKLVRCRSLA VTESNLSTSN
     TIFVWSEVLT HQYIGFKTDL MGLTYNIKFK LICYVLFLWF GVLCCTSHNT PFYMRLCIYL
     VLLWLSLMIW NASQINVKTG WNELYVLKLL TSIKLPNIVK FRCELVQWFV LKCLFVSFYV
     YDYVVKVCVS IFQMPQLRPF TWPFIKLGFV DTFLSHHILA FPEKVANQST LPTCGDKRYY
     VYVPSWCRAS FTSLVMRARE LTSTGRSKTL DNWHYQCCSK TAKPLSCFNV REFVFDQDCK
     HEAYGFLSSL CVYLLFYSGF LTFWLPLFCY YYVLFMCTFK NLPVDITKPI KWTVLQQVVN
     DVLSLVTKPL FGRPVCPPLT TYLTSTTADE AVKVSRSLLG RFCTPLGFQQ PVMNVENGVT
     VSNFGFFNPL MWPLFVVVLL DNRFIWFFNV LSYVMMPVFV IILFYFYLKK ICGCINFKGL
     SKCCTKHFNQ FSKPLVAAGV HGNRTNFTYQ PMQEHWCDRH SWYCPKEEHY MTPDMAVYIK
     NYYNLACAPT ADLVWCDYTK SAPTMTWSNF KYSSYKAKET VLCAPSSHAD SMLMAWYALL
     HNVRFTVNPN VVDLPPAVNT IYVSSDSEDS VQDKSQPDVK LRPKKPKGNF KKQSVAYFSR
     EPVDIWYYTT LVIVMGVLFM FMYSCLMVGQ YVVMPRDKFF GVNPTGYSYV NAPPYLHAAP
     PVLQNSDGMI LATQLKVPSI TYSVYRLLSG HLYFTKLIVS DNECTPPFGA ARLSNEFSCN
     GFTYVLPAHL RFFNRYVMLI HPDQLHMLPF EVEYGSHTRV CYTTGSNSVE CLPTFEIISP
     YVFVFIVVIF TVIFLILIRL YIVMYSYFKV FTYVVFKLLF VNIIMVLFVV CLPPLVPGVV
     FVLALWLCDS VMFLLYLAFL SLFILPWFYV LFFLFMVGGF VFWWMMRSAD VVHLTTDGLT
     FNGTFEQISK CVFPLNPLIV NRMLLDCQMS HSDLVEKSKL KTTEGKLANE MMKVFMTGET
     SYYQPSNFSF QSVFSKATSP FTLHARPPMP MFKLYVHFTG SCVGSTSTGT GFAIDDNTIV
     TAKHLFEYDD LKPTHVSVEI VTRSHSARSA SIIWKEPDVK GWTFKGENAY IQVENLKDFY
     IEDFKYLPFQ QIEKDFYKRM EPVTIYSVKY GSEFATQAWQ TVNGHFVCYN TEGGDSGAPL
     VCNGRIVGVH QGLCDNFKTT LASDFEGKMM TEVKGHHVDP PVYYKPIIIS AAYNKFVAGE
     DSSVGDGKNY HKFENEDFAC MCKELESVTF GDQLRRYCYN LPQFLEPLQY FHVPSFWQPF
     KKQSVSNNVS WVVEHLHFIF SIYFLICDFV AYWWLDDPFS VVLPLFFIVQ LLSTVFLKNV
     LFWTTSYLIT LAVTFYIHSE VAESMFLLGF LSDRVVNRMS LIIVVAIMCL FVVVRVVVNV
     KRAIFVFVVS VVLIFVHICL GIVQFNSFVN VVLFDVYAVF TALLTPQPVV AIIMLLLFDT
     KMLMSFAFIV IVLSFRVFKD YKFVKVLHNF CNFDFVLSQV SLFRYRHRNQ GNDPTHYEAL
     WLFLKELYYG IQDAKYEVFS PQAGSYNVKF LTDMTEQDQL EAVEQVQRRL QRFNIVQDKA
     SPRLVLYSKT IEFIKDQIQQ QRAVGANPFI ITTLTSNDIG LDNVEVHNPA NFKPEDLQAH
     MWFFSKSPVF IGQVPIPTNV QTAAVLDTTY NCQDLTADEK NNVAATLQIQ NAAITLSLFE
     KCTQFLESEL GEVPTLMWQA EDVADIKHLE SQIENLRKVL DGMQFGTTEY KATRKQLNIC
     QSQLDQAKAF ERKLAKFLEK VDQQQAITNE TAKQLSAFKN LVKQVYESYM SSLKVKVLEA
     NDASCLLTST DLPRKLVLMR PITGVDGIKI VEKANGCEIT AFGTTFNTGH GSNLAGLAYS
     TTQPLSAYPF IFNLEGIFKQ QANIGYKTVE CNMSSHNGSV LYKGKVVAVP SDDNPDFVVC
     GKGYKLDCGI NVLMIPSIVR YITLNLTDHL QKQSLKPRRR LQYRQQGVRL GGVNLGEHQA
     FSNELISTVG YTTWVSSTVC RDNTHKHPWF VQIPVNEKDP EWFMHNTQLK DNQWVVDLKP
     THWLVNADTG EQLFALSLTD EQALKAEAIL QKWSPITQDV ECWFKDLKGY YTVSGFQPLW
     PVCPVNICNV RLDPVFKPQS IVYADDPTHF LSLPVVNKNF LAAFYDLQEG FPGKKQVAPH
     ISLTMLKLSD EDIEKVEDIL DEMVLPNSWV TITNPHMMGK HYVCDVEGLD SLHDEVVSVL
     REHGIACDQK RLWKPHLTIG ELNDVSFDKF KDFAISCKLE DCDFVKLGAP KANARYEFIT
     TLPLGDLNC
 
 
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