POLG_FCVF4
ID POLG_FCVF4 Reviewed; 1763 AA.
AC P27408; Q66913;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Protein p5.6;
DE Contains:
DE RecName: Full=Protein p32;
DE Contains:
DE RecName: Full=NTPase;
DE EC=3.6.1.15;
DE AltName: Full=p39;
DE Contains:
DE RecName: Full=Protein p30;
DE Contains:
DE RecName: Full=Viral genome-linked protein;
DE AltName: Full=VPg;
DE AltName: Full=p13;
DE Contains:
DE RecName: Full=Protease-polymerase p76;
DE Short=Pro-Pol;
DE EC=2.7.7.48;
DE EC=3.4.22.66;
GN ORFNames=ORF1;
OS Feline calicivirus (strain Japanese F4) (FCV).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Caliciviridae; Vesivirus.
OX NCBI_TaxID=11980;
OH NCBI_TaxID=9681; Felidae (cat family).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7696398; DOI=10.1292/jvms.56.1093;
RA Oshikamo R., Tohya Y., Kawaguchi Y., Tomonaga K., Maeda K., Takeda N.,
RA Utagawa E., Kai C., Mikami T.;
RT "The molecular cloning and sequence of an open reading frame encoding for
RT non-structural proteins of feline calicivirus F4 strain isolated in
RT Japan.";
RL J. Vet. Med. Sci. 56:1093-1099(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1383-1763.
RX PubMed=1853578; DOI=10.1016/0042-6822(91)91016-a;
RA Tohya Y., Taniguchi Y., Takahashi E., Utagawa E., Takeda N., Miyamura K.,
RA Yamazaki S., Mikami T.;
RT "Sequence analysis of the 3'-end of feline calicivirus genome.";
RL Virology 183:810-814(1991).
RN [3]
RP ACTIVE SITES, AND MUTAGENESIS OF HIS-1079; HIS-1093; HIS-1099; HIS-1102;
RP HIS-1110; GLU-1121; ASP-1125; GLU-1131; ASP-1155; GLU-1164; CYS-1193 AND
RP HIS-1208.
RX PubMed=17459935; DOI=10.1128/jvi.02840-06;
RA Oka T., Yamamoto M., Yokoyama M., Ogawa S., Hansman G.S., Katayama K.,
RA Miyashita K., Takagi H., Tohya Y., Sato H., Takeda N.;
RT "Highly conserved configuration of catalytic amino acid residues among
RT calicivirus-encoded proteases.";
RL J. Virol. 81:6798-6806(2007).
CC -!- FUNCTION: NTPase presumably plays a role in replication. Despite having
CC similarities with helicases, does not seem to display any helicase
CC activity (By similarity). {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: Protease-polymerase p76 processes the polyprotein: Pro-Pol is
CC first released by autocleavage, then all other proteins are cleaved.
CC Cleaves host translation initiation factor eIF4G1, eIF4G2 and PABP1
CC thereby inducing a shutdown of host protein synthesis. This shutdown
CC may not prevent viral mRNA from being translated since viral Vpg
CC replaces the cap. May cleave host polyadenylate-binding protein thereby
CC inhibiting cellular translation. It is also an RNA-directed RNA
CC polymerase which replicates genomic and antigenomic viral RNA by
CC recognizing specific signals. Transcribes also a subgenomic mRNA by
CC initiating RNA synthesis internally on antigenomic RNA. This sgRNA
CC codes for structural proteins. Catalyzes the covalent attachment VPg
CC with viral RNAs (By similarity). {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: [Protein p32]: Homodimer (By similarity). Interacts with
CC NTPase, protein p30 and protease-polymerase p76 (By similarity).
CC {ECO:0000250|UniProtKB:Q66914}.
CC -!- SUBUNIT: [Viral genome-linked protein]: Interacts with capsid protein
CC VP1 and protease-polymerase p76 (By similarity).
CC {ECO:0000250|UniProtKB:Q66914}.
CC -!- SUBUNIT: [Protease-polymerase p76]: Homooligomer (By similarity).
CC Interacts with Vpg, protein p32 and may interact with capsid protein
CC VP1 (By similarity). {ECO:0000250|UniProtKB:Q66914}.
CC -!- DOMAIN: Protease-polymerase is composed of two domains displaying two
CC different catalytic activity. These activities may act independently
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. Pro-
CC Pol is first autocatalytically cleaved, then processes the whole
CC polyprotein.
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}.
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DR EMBL; D31836; BAA06622.2; -; Genomic_RNA.
DR EMBL; D90357; BAA14370.1; -; Genomic_RNA.
DR SMR; P27408; -.
DR MEROPS; C24.002; -.
DR PRIDE; P27408; -.
DR Proteomes; UP000008668; Genome.
DR Proteomes; UP000173772; Genome.
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:nucleoside-triphosphatase activity; IEA:RHEA.
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-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0018144; P:RNA-protein covalent cross-linking; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR Gene3D; 3.30.70.270; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
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; IPR001205; RNA-dir_pol_C.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR Pfam; PF03510; Peptidase_C24; 1.
DR Pfam; PF00680; RdRP_1; 1.
DR Pfam; PF00910; RNA_helicase; 1.
DR PRINTS; PR00916; 2CENDOPTASE.
DR PRINTS; PR00918; CALICVIRUSNS.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51894; CV_3CL_PRO; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR PROSITE; PS51218; SF3_HELICASE_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Covalent protein-RNA linkage;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus;
KW Host gene expression shutoff by virus; Host-virus interaction; Hydrolase;
KW Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein; Protease;
KW RNA-directed RNA polymerase; Thiol protease; Transferase;
KW Viral RNA replication.
FT CHAIN 1..1763
FT /note="Genome polyprotein"
FT /id="PRO_0000341991"
FT CHAIN 1..46
FT /note="Protein p5.6"
FT /id="PRO_0000341992"
FT CHAIN 47..331
FT /note="Protein p32"
FT /id="PRO_0000341993"
FT CHAIN 332..685
FT /note="NTPase"
FT /id="PRO_0000341994"
FT CHAIN 686..960
FT /note="Protein p30"
FT /id="PRO_0000341995"
FT CHAIN 961..1071
FT /note="Viral genome-linked protein"
FT /id="PRO_0000341996"
FT CHAIN 1072..1763
FT /note="Protease-polymerase p76"
FT /id="PRO_0000036899"
FT DOMAIN 458..614
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DOMAIN 1073..1229
FT /note="Peptidase C24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01242"
FT DOMAIN 1478..1603
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT ACT_SITE 1110
FT /note="For 3CLpro activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01242,
FT ECO:0000269|PubMed:17459935"
FT ACT_SITE 1131
FT /note="For 3CLpro activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01242,
FT ECO:0000269|PubMed:17459935"
FT ACT_SITE 1193
FT /note="For 3CLpro activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01242,
FT ECO:0000269|PubMed:17459935"
FT BINDING 484..491
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT SITE 46..47
FT /note="Cleavage; by Pro-Pol"
FT /evidence="ECO:0000250"
FT SITE 331..332
FT /note="Cleavage; by Pro-Pol"
FT /evidence="ECO:0000250"
FT SITE 685..686
FT /note="Cleavage; by Pro-Pol"
FT /evidence="ECO:0000250"
FT SITE 960..961
FT /note="Cleavage; by Pro-Pol"
FT /evidence="ECO:0000250"
FT SITE 1071..1072
FT /note="Cleavage; by Pro-Pol"
FT /evidence="ECO:0000250"
FT MOD_RES 984
FT /note="O-(5'-phospho-RNA)-tyrosine"
FT /evidence="ECO:0000250"
FT MUTAGEN 1079
FT /note="H->A: No effect on protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1093
FT /note="H->A: No effect on protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1099
FT /note="H->A: No effect on protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1102
FT /note="H->A: No effect on protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1110
FT /note="H->A: Complete loss of protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1121
FT /note="E->A: No effect on protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1125
FT /note="D->A: No effect on protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1131
FT /note="E->A: Complete loss of protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1155
FT /note="D->A: No effect on protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1164
FT /note="E->A: No effect on protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1193
FT /note="C->A: Complete loss of protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT MUTAGEN 1208
FT /note="H->A: Complete loss of protease activity in vitro."
FT /evidence="ECO:0000269|PubMed:17459935"
FT CONFLICT 1417
FT /note="V -> M (in Ref. 2; BAA14370)"
FT /evidence="ECO:0000305"
FT CONFLICT 1485..1487
FT /note="YSK -> FSN (in Ref. 2; BAA14370)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1763 AA; 194988 MW; 173626D6C862E46C CRC64;
MSQTLSFVLK THSVRKDFVH SVKVTLARRR DLQYLYNKLA RTMRAEACPS CSSYDVCPNC
TSSDIPDNGS STTSIPSWED VTKTSTYSLL LSEDTSDELC PDDLVNVAAH IRKALSTQAH
PANTEMCKEQ LTSLLVMAEA MLPQRSRASI PLHQQHQAAR LEWREKFFSK PLDFLLERIG
VSKDILQITA IWKIILEKAC YCKSYGEQWF CAAKQKLREM RTFESDTLKP LVGAFIDGLR
FMTVDNPNPM GFLPKLIGLV KPLNLAMIID NHENTLSGWV VTLTAIMELY NITECTIDVI
TSLVTGFYDK ISKATKFFSQ VKALFTGFRS EDVANSFWYM AAAILCYLIT GLIPNNGRFS
KIKACLSGAT TLVSGIIATQ KLAAMFATWN SESIVNELSA RTVAISELNN PTTTSDTDSV
ERLLELAKIL HEEIKVHTLN PIMQSYNPIL RNLMSTLDGV ITSCNKRKAI ARKRQVPVCY
ILTGPPGCGK TTAAQALAKK LSDQEPSVIN LDVDHHDTYT GNEVCIIDEF DSSDKVDYAN
FVIGMVNSAP MVLNCDMLEN KGKLFTSKYI IMTSNSETPV KPSSKRAGAF YRRVTIIDVT
NPLVESHKRA RPGTSVPRSC YKKNFSHLSL AKRGAECWCK EYVLDPKGLQ HQTIKAPPPT
FLNIDSLAQT MKQDFVLKNM AFEAEDGCSE HRYGFICQQS EVETVRRLLN AIRARLNATF
TVCVGPEASH SIGCTAHVLT PDEPFNGRRF IVSRCNEASL AALEGNCVQS ALGVCMSNKD
LTHLCHFIRG KIVNDSVRLD ELPANQHVVT VNSVFDLAWA LRRHLTLTGQ FQAIRAAYDV
LTVPDKVPAM LRHWMDETSF SDEHVVTQFV TPGGVVILES CGGARIWALG HNVIRAGGVT
ATPTGGCVRL VGLSAQTLPW SEIFRELFTL LGRIWSSIKV STLVLTALGM YASRFRPKSE
AKGKTKSKIG PYRGRGVALT DDEYDEWREH NANRKLDLSV EDFLMLRHRA ALGADDADAV
KFRSWWNSRT RPGDGFEDVT VIGKGGVKHE KIRTSTLRAV DRGYDVSFAE ESGPGTKFHK
NAIGSVTDVC GEHKGYCVHM GHGVYASVAH VVKGDSYFLG ERIFDVKTNG EFCCFRSTKI
LPSAAPFFSG KPTRDPWGSP VATEWKPKAY TTTSGKIVGC FATTSTETHP GDCGLPYIDD
NGRVTGLHTG SGGPKTPSAK LVVPYIHIDM KNKSVTPQKY DETKPNISYK GLVCKQLDEI
RIIPKGTRLH VSPAHVDDFE ECSHQPASLG SGDPRCPKSL TAIVVDSLKP YCDRVEGPPH
DVLHRVQKML IDHLSGFVPM NISSETSMLS AFHKLNHDTS CGPYLGGRKK DHMVNGEPDK
QLLDLLSSKW KLATQGIALP HEYTIGLKDE LRPIEKVQEG KRRMIWGCDV GVATVCAAAF
KGVSDAITAN HQYGPIQVGI NMDSPSVEVL YQRIKSAAKV FAVDYSKWDS TQSPRVSAAS
IDILRYFSDR SPIVDSAANT LKSPPIAIFN GVAVKVASGL PSGMPLTSVI NSLNHCMYVG
CAILQSLEAR QIPVTWNLFS SFDMMTYGDD GVYMFPTMFA SVSDQIFGNL SAYGLKPTRV
DKSVGAIESI DPESVVFLKR TITRTPNGIR GLLDRSSIIR QFFYIKGENS DDWKTPPKTI
DPTSRGQQLW NACLYASQHG VEFYNKVLKL AMRAVEYEGL HLKPPSYSSA LEHYNSQFNG
VEARSDQINM SDVTALHCDV FEV
