ID   POLG_EBHSG              Reviewed;        2334 AA.
AC   Q96725;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   24-JAN-2024, entry version 121.
DE   RecName: Full=Genome polyprotein;
DE   AltName: Full=p254;
DE   Contains:
DE     RecName: Full=Protein p16;
DE   Contains:
DE     RecName: Full=Protein p23;
DE   Contains:
DE     RecName: Full=NTPase;
DE              EC=3.6.1.15;
DE     AltName: Full=2C-like protein;
DE     AltName: Full=P2C;
DE     AltName: Full=p37;
DE   Contains:
DE     RecName: Full=Precursor p41;
DE   Contains:
DE     RecName: Full=Protein p29;
DE   Contains:
DE     RecName: Full=Protein p23/2;
DE   Contains:
DE     RecName: Full=Protein p18;
DE   Contains:
DE     RecName: Full=Viral genome-linked protein;
DE     AltName: Full=VPg;
DE     AltName: Full=p13;
DE   Contains:
DE     RecName: Full=3C-like protease;
DE              Short=3CLpro;
DE              EC=3.4.22.66;
DE     AltName: Full=Calicivirin;
DE     AltName: Full=Thiol protease P3C;
DE     AltName: Full=p15;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase;
DE              EC=2.7.7.48;
DE     AltName: Full=3Dpol;
DE     AltName: Full=p58;
DE   Contains:
DE     RecName: Full=Capsid protein VP60;
GN   ORFNames=ORF1;
OS   European brown hare syndrome virus (strain GD) (Ha/LV/EBHSV/GD/1989/FR)
OS   (EBHSV-GD).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Picornavirales; Caliciviridae; Lagovirus;
OC   European brown hare syndrome virus.
OX   NCBI_TaxID=316979;
OH   NCBI_TaxID=9983; Lepus europaeus (European hare).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=8760416; DOI=10.1099/0022-1317-77-8-1693;
RA   Le Gall G., Huguet S., Vende P., Vautherot J.-F., Rasschaert D.;
RT   "European brown hare syndrome virus: molecular cloning and sequencing of
RT   the genome.";
RL   J. Gen. Virol. 77:1693-1697(1996).
CC   -!- FUNCTION: NTPase presumably plays a role in replication. {ECO:0000250}.
CC   -!- FUNCTION: Viral genome-linked protein is covalently linked to the 5'-
CC       end of the positive-strand, negative-strand genomic RNAs and subgenomic
CC       RNA. Acts as a genome-linked replication primer. May recruit ribosome
CC       to viral RNA thereby promoting viral proteins translation (By
CC       similarity). {ECO:0000250}.
CC   -!- FUNCTION: 3C-like protease processes the polyprotein: 3CLpro-RdRp (p72)
CC       is first released by autocleavage, then all other proteins are cleaved.
CC       {ECO:0000250}.
CC   -!- FUNCTION: RNA-directed RNA polymerase replicates genomic and
CC       antigenomic RNA by recognizing replications specific signals.
CC       Transcribes also a subgenomic mRNA by initiating RNA synthesis
CC       internally on antigenomic RNA. This sgRNA codes for structural
CC       proteins. Catalyzes the covalent attachment VPg with viral RNAs (By
CC       similarity). {ECO:0000255|PROSITE-ProRule:PRU00539}.
CC   -!- FUNCTION: Capsid protein VP60 self assembles to form an icosahedral
CC       capsid with a T=3 symmetry, about 35 nm in diameter, and consisting of
CC       180 capsid proteins. A smaller form of capsid with a diameter of 23 nm
CC       might be capsid proteins assembled as icosahedron with T=1 symmetry.
CC       The capsid encapsulate VP2 proteins and genomic or subgenomic RNA.
CC       Attaches virion to target cells by binding histo-blood group antigens,
CC       inducing endocytosis of the viral particle. Acidification of the
CC       endosome induces conformational change of capsid protein thereby
CC       injecting virus genomic RNA into host cytoplasm (By similarity).
CC       {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC         diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
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:0000255|PROSITE-ProRule:PRU00539};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Endopeptidase with a preference for cleavage when the P1
CC         position is occupied by Glu-|-Xaa and the P1' position is occupied by
CC         Gly-|-Yaa.; EC=3.4.22.66; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU01242};
CC   -!- SUBUNIT: Binds to histo-blood group antigens at surface of target
CC       cells. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Capsid protein VP60]: Virion. Host cytoplasm
CC       {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative promoter usage; Named isoforms=2;
CC       Name=Genome polyprotein;
CC         IsoId=Q96725-1; Sequence=Displayed;
CC       Name=Subgenomic capsid protein VP60; Synonyms=VP1;
CC         IsoId=Q96725-2; Sequence=VSP_034377;
CC   -!- PTM: Specific enzymatic cleavages by its own cysteine protease yield
CC       mature proteins. The protease cleaves itself from the nascent
CC       polyprotein autocatalytically. Precursor p41 can be cleaved by viral
CC       3CLpro into protein p19 and VPg, or cleaved by host protease into
CC       protein p23/2 and protein p18 (By similarity). {ECO:0000250}.
CC   -!- PTM: VPg is uridylylated by the polymerase and is covalently attached
CC       to the 5'-end of the polyadenylated genomic and subgenomic RNAs. This
CC       uridylylated form acts as a nucleotide-peptide primer for the
CC       polymerase (By similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: Two different RNAs lead the expression of the capsid
CC       protein. One arises from the cleavage of the polyprotein translated
CC       from the genomic RNA and the other from the translation of a subgenomic
CC       RNA derived from the (-)RNA template. Capsid protein expressed from the
CC       subgenomic mRNA is produced in much larger amounts than the cleaved one
CC       (By similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: [Isoform Genome polyprotein]: Produced from the genomic
CC       RNA.
CC   -!- MISCELLANEOUS: [Isoform Subgenomic capsid protein VP60]: Produced from
CC       the subgenomic RNA. {ECO:0000305}.
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DR   EMBL; Z69620; CAA93445.1; -; Genomic_RNA.
DR   EMBL; Z32526; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   RefSeq; NP_068828.1; NC_002615.1.
DR   SMR; Q96725; -.
DR   MEROPS; C24.001; -.
DR   GeneID; 912265; -.
DR   KEGG; vg:912265; -.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:InterPro.
DR   GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   CDD; cd00009; AAA; 1.
DR   CDD; cd23192; Caliciviridae_RdRp; 1.
DR   CDD; cd00205; rhv_like; 1.
DR   Gene3D; 1.10.260.110; -; 1.
DR   Gene3D; 1.20.960.20; -; 1.
DR   Gene3D; 2.60.120.20; -; 1.
DR   Gene3D; 3.30.70.270; -; 1.
DR   Gene3D; 6.10.140.320; -; 1.
DR   Gene3D; 4.10.8.20; DNA/RNA polymerases; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR004005; Calicivirus_coat.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR004004; Helic/Pol/Pept_Calicivir-typ.
DR   InterPro; IPR000605; Helicase_SF3_ssDNA/RNA_vir.
DR   InterPro; IPR014759; Helicase_SF3_ssRNA_vir.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR000317; Peptidase_C24.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR   InterPro; IPR033703; Rhv-like.
DR   InterPro; IPR001205; RNA-dir_pol_C.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR029053; Viral_coat.
DR   InterPro; IPR049434; VPg.
DR   Pfam; PF00915; Calici_coat; 1.
DR   Pfam; PF03510; Peptidase_C24; 1.
DR   Pfam; PF00680; RdRP_1; 1.
DR   Pfam; PF00910; RNA_helicase; 1.
DR   Pfam; PF20915; VPg; 1.
DR   PRINTS; PR00916; 2CENDOPTASE.
DR   PRINTS; PR00918; CALICVIRUSNS.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF88633; Positive stranded ssRNA viruses; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS51894; CV_3CL_PRO; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR   PROSITE; PS51218; SF3_HELICASE_2; 1.
PE   3: Inferred from homology;
KW   Alternative promoter usage; ATP-binding; Capsid protein;
KW   Covalent protein-RNA linkage; Disulfide bond; Helicase; Host cytoplasm;
KW   Hydrolase; Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein;
KW   Protease; RNA-directed RNA polymerase; Thiol protease; Transferase;
KW   Viral RNA replication; Virion.
FT   CHAIN           1..2334
FT                   /note="Genome polyprotein"
FT                   /id="PRO_0000341986"
FT   CHAIN           1..138
FT                   /note="Protein p16"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036986"
FT   CHAIN           139..334
FT                   /note="Protein p23"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036987"
FT   CHAIN           335..711
FT                   /note="NTPase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036988"
FT   CHAIN           712..1108
FT                   /note="Precursor p41"
FT                   /id="PRO_0000341987"
FT   CHAIN           712..986
FT                   /note="Protein p29"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036989"
FT   CHAIN           712..929
FT                   /note="Protein p23/2"
FT                   /id="PRO_0000341988"
FT   CHAIN           930..1101
FT                   /note="Protein p18"
FT                   /id="PRO_0000341989"
FT   CHAIN           987..1101
FT                   /note="Viral genome-linked protein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036990"
FT   CHAIN           1102..1244
FT                   /note="3C-like protease"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036991"
FT   CHAIN           1245..1760
FT                   /note="RNA-directed RNA polymerase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036992"
FT   CHAIN           1761..2334
FT                   /note="Capsid protein VP60"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036994"
FT   DOMAIN          487..647
FT                   /note="SF3 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   DOMAIN          1102..1237
FT                   /note="Peptidase C24"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01242"
FT   DOMAIN          1488..1612
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          1760..1784
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1128
FT                   /note="For 3CLpro activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01242"
FT   ACT_SITE        1145
FT                   /note="For 3CLpro activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01242"
FT   ACT_SITE        1205
FT                   /note="For 3CLpro activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01242"
FT   SITE            138..139
FT                   /note="Cleavage; by 3CLpro"
FT                   /evidence="ECO:0000250"
FT   SITE            334..335
FT                   /note="Cleavage; by 3CLpro"
FT                   /evidence="ECO:0000250"
FT   SITE            711..712
FT                   /note="Cleavage; by 3CLpro"
FT                   /evidence="ECO:0000250"
FT   SITE            929..930
FT                   /note="Cleavage; by host"
FT                   /evidence="ECO:0000250"
FT   SITE            986..987
FT                   /note="Cleavage; by 3CLpro"
FT                   /evidence="ECO:0000250"
FT   SITE            1101..1102
FT                   /note="Cleavage; by 3CLpro"
FT                   /evidence="ECO:0000250"
FT   SITE            1244..1245
FT                   /note="Cleavage; by 3CLpro"
FT                   /evidence="ECO:0000250"
FT   SITE            1760..1761
FT                   /note="Cleavage; by 3CLpro"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1007
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250"
FT   DISULFID        1577..1584
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..1758
FT                   /note="Missing (in isoform Subgenomic capsid protein VP60)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_034377"
SQ   SEQUENCE   2334 AA;  255925 MW;  3865CFA2457C0FB6 CRC64;
     MAVASRPCGV ATSVLPAKKP LSFFTDLVGK TPPRCIRAPH TLAWPVFADL DNEEESPEIC
     RKCGKYANGF GVFDLTDLGD VCLCSIRPQR HVGGPCCLCN KQYIRACGRY CARVLKHYKA
     FNKVIPCLHS RQVKPVFEGE VEDLFVELGA PTRMNFTEAE LASQGASIMD RFVDLVEPCL
     STEDSNFLDN ICSDASIRKR LEDEYDVDMI AAARARKDFA KTLKLALQDR ERKPDKWYSK
     LGCITTKGRQ WAKKVVHGAK KLSDPLKTLA AILLVALHNC VAVDTTTMLS HFKPVNLLAI
     LLDWTNDLPG FLTTLIRFME LYGVVQSTVN LVVDAIKSFW DRVMCATERC CDLLKRLFDK
     FEDSVPTGPT AGCLIFMSFV FSVIVGYLPN NSVISTFMKG AGKLTTFAGV IGAIRTLWIT
     INQHMVAKDI TSIQEKVMAV VKMANEAATL NQLEIVSVLC SELESTLTNR CTLPSYNQHM
     GVLNAAQKVV ADIHTLVLGK INMTKQRPQP VAVVFKGAPG IGKTYLVHRL AKDLGCPHPS
     NINFGLDHFD SYTGEDVAIA DEFNTSGDER WVELFIQMVN TNPCPLNCDK VENKNKVFSS
     KYLLCTTNSS MVLNATHPRA TAFYRRVIIV DVRNKAVEGW QSTRHGSKPG KHCYTKDMSH
     LTFQVYPHNM PAPGFVFVGE KLVKSQVAPR ELKYNELLDM IKNEHPDANF EGATKHEFVY
     PDVQYEQALL MWKQYFLMYG CTARLAKVFV DDIPYNQVHV ARKSDPRSPG AVHHECELKY
     IWRMVPHFAL GCVNMTNQLG TDLTQSQLDR ITCGVEGITV TTVDNILPFH SQNTLINPSF
     LKLIWALRRH LRGLRGITQV ATFIWKVMCN PVCAYDTLIR TLTGAATFSE DPVTTTIVCP
     NCTIQIHTCG GLLVRYSGDP APVASDNVDR GNQGIDCLTN PNLIAGFSWR QIADLFSTVM
     TSLCNNHLVN LATMAAIGAV ATKALQGVKG KTKRGRGARI NLGNDEYDEW QQMRREFNNA
     HDMTAEEFLE LRNRAAMGSD DADAIKFRSW WTNRQLRQDE AHVTVVGKGG VRNEVIRTRV
     RNAPKGPRTL DDGGFYDNDY EGLPGYLRFN GSGWMIHIGN GMYLSNTHTA RSSCSEIVTC
     SPTTDLCLVK AEPIRSVAQI AEGTPVRDWK RASITTYGLK KTFSDSTKID VLAYDGPTQT
     THGDCGLPLF DEAGKVVAIH TGKLLGFSKM CTLIDCTITK GVYENTDLFC GDPIDYRGLV
     AFRVAGVEPR PPVSGTRYAK VPGVPEEYHT GYRPANLGRG DPDSHCTLMN IAVKNLQVYQ
     QEPKLTKVDT FIERAAADVL GFLRFLTKGE RQMNLNFSAA FNVLDLSTSC GPFVPGKKID
     HVKDGKLDEV LSKHLYKCWS VANSGKALHH VYACGLKDEL RPLDKVKEGK KRLLWGCNVG
     VALCAAAVFH NLCFKLKTVA RFGPIAVGID MTSRDVDVMI TQLTSKAGDF LCLDYSKWDS
     TMSPCVVRLA IDILADCCEQ TELTKSVVLT LKSLPMTVLD AMIVPTKRGL PSGMPFTSVI
     NSICHWLLWS AAVYKACDEI GLFCSNLYED APFFVYGDDG VYAMTPMMVS LLPAILDNLR
     DYGLSPTAAD KTEFIDVCPL KDISFLKRKF VMSELGWLSQ LDRSSILRQL EWTKTAKRHM
     CIEECSELDK DERGVQLEEL QIHAAAHGEE FFELVKKELR RQQAFTRFSV FDYQTARKTL
     GDRKRIVSVV PDDSFVNVME GKPRADAPGT ATTASVPGTT TDGMDPGVVA STDVVTADNV
     AASVATAGIG GPPQQASPQE SWRVNFFYND VFTWSVTDAP GSILYTVQHS PQNNPFTQVL
     SQMYAGWAGG MQFRFIVAGS GIFGGRLVCA IIPPGIQIQP GLEVRQFPHV VIDARSLEPV
     TITMPDLRPE MYHPTGNPGL VPTLVVSVYN NLINPFGGTT SAIQVTVETR PSEDFEFVLI
     RAPSSKTVDS VNPSWLLTTP VLTGAGSDNR WGAPIVGLQP VPGGFSTSNR HWNMNGETYG
     WSSPRFDDID HPSGNVSYPS GSATNTIETW YANAGTATTN PISNIAPDGF PDMGAIPFSG
     TTIPTGAWVG FGQVWNASNG TPYVGTVQAY ELGFANGAPS SIRPVTTTTG AQLVAKSIYG
     VAIAQNQTSA GIIFLSKGMV STPGVAATTY TPQPSAIVTT PGTPVAAPIG KNTPIMFSAV
     VRRTGDVNAG PGSANGTQYG VGSQPLSVTL GLSLTNYSSA LQPGQFFVWQ LNFASGFMEV
     GMNTDGYFYA GTGAYSGMID LTDLIDVRPV GVRPNTSTLV FNLAGVATTG YSYV
//