ID   POLG_FCVC6              Reviewed;        1762 AA.
AC   P27407;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 3.
DT   24-JAN-2024, entry version 135.
DE   RecName: Full=Genome polyprotein;
DE   Contains:
DE     RecName: Full=Protein p5.6;
DE     AltName: Full=NS1;
DE   Contains:
DE     RecName: Full=Protein p32;
DE     AltName: Full=NS2;
DE   Contains:
DE     RecName: Full=NTPase;
DE              EC=3.6.1.15;
DE     AltName: Full=NS3;
DE     AltName: Full=p39;
DE   Contains:
DE     RecName: Full=Protein p30;
DE     AltName: Full=NS4;
DE   Contains:
DE     RecName: Full=Viral genome-linked protein;
DE     AltName: Full=NS5;
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;
DE     AltName: Full=NS6-7;
GN   ORFNames=ORF1;
OS   Feline calicivirus (strain CFI/68 FIV) (FCV).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Picornavirales; Caliciviridae; Vesivirus; Feline calicivirus.
OX   NCBI_TaxID=11979;
OH   NCBI_TaxID=9681; Felidae (cat family).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Neill J.D.;
RL   Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 479-1762.
RX   PubMed=2077782; DOI=10.1016/0168-1702(90)90061-f;
RA   Neill J.D.;
RT   "Nucleotide sequence of a region of the feline calicivirus genome which
RT   encodes picornavirus-like RNA-dependent RNA polymerase, cysteine protease
RT   and 2C polypeptides.";
RL   Virus Res. 17:145-160(1990).
CC   -!- FUNCTION: [NTPase]: NTPase presumably plays a role in replication.
CC       Despite having similarities with helicases, does not seem to display
CC       any helicase activity.
CC   -!- FUNCTION: [Viral genome-linked protein]: Viral genome-linked protein is
CC       covalently linked to the 5'-end of the positive-strand, negative-strand
CC       genomic RNAs and subgenomic RNA. Acts as a genome-linked replication
CC       primer. May recruit ribosome to viral RNA thereby promoting viral
CC       proteins translation. {ECO:0000250|UniProtKB:Q66914}.
CC   -!- FUNCTION: [Protease-polymerase p76]: The protease activity processes
CC       the polyprotein: Pro-Pol is first released by autocleavage, then all
CC       other proteins are cleaved (By similarity). Cleaves host translation
CC       initiation factor eIF4G1, eIF4G2 and PABP1 thereby inducing a shutdown
CC       of host protein synthesis (By similarity). This shutdown may not
CC       prevent viral mRNA from being translated since viral Vpg replaces the
CC       cap (By similarity). May cleave host polyadenylate-binding protein
CC       thereby inhibiting cellular translation (By similarity). Seems to act
CC       as a RNase and degrades host Pol II-driven mRNAs with the help of host
CC       XRN1 (By similarity). Inhibits the integrated stress response (ISR) in
CC       the infected cell by cleaving host G3BP1 and G3BP2 (By similarity).
CC       Stress granule formation is thus inhibited, which allows protein
CC       synthesis and viral replication (By similarity). The RNA-directed RNA
CC       polymerase activity 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. {ECO:0000250|UniProtKB:N0A3C0,
CC       ECO:0000250|UniProtKB:Q66914}.
CC   -!- CATALYTIC ACTIVITY: [NTPase]:
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: [Protease-polymerase p76]:
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: [Protease-polymerase p76]:
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 NTPase,
CC       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. {ECO:0000250|UniProtKB:Q66914}.
CC   -!- SUBUNIT: [Protease-polymerase p76]: Homooligomer. Interacts with Vpg,
CC       protein p32 and may interact with capsid protein VP1.
CC       {ECO:0000250|UniProtKB:Q66914}.
CC   -!- DOMAIN: [Protease-polymerase p76]: Protease-polymerase is composed of
CC       two domains displaying two different catalytic activity. These
CC       activities may act independently.
CC   -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield
CC       mature proteins. Pro-Pol is first autocatalytically cleaved, then
CC       processes the whole polyprotein. {ECO:0000250|UniProtKB:Q66914}.
CC   -!- PTM: [Viral genome-linked protein]: VPg is uridylylated by the
CC       polymerase and is covalently attached to the 5'-end of the
CC       polyadenylated genomic and subgenomic RNAs. This uridylylated form acts
CC       as a nucleotide-peptide primer for the polymerase.
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; U13992; AAC13992.1; -; Genomic_RNA.
DR   EMBL; M32296; AAA42927.1; -; Genomic_RNA.
DR   PIR; A43488; A43488.
DR   PIR; T09245; T09245.
DR   SMR; P27407; -.
DR   MEROPS; C24.002; -.
DR   Proteomes; UP000008667; Genome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
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:0039657; P:suppression by virus of host gene expression; 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   Gene3D; 1.10.260.110; -; 1.
DR   Gene3D; 1.20.960.20; -; 1.
DR   Gene3D; 3.30.70.270; -; 1.
DR   Gene3D; 6.10.140.320; -; 1.
DR   Gene3D; 6.10.250.3230; -; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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   InterPro; IPR049434; VPg.
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   SMART; SM00382; AAA; 1.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
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   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..1762
FT                   /note="Genome polyprotein"
FT                   /id="PRO_0000341990"
FT   CHAIN           1..46
FT                   /note="Protein p5.6"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036892"
FT   CHAIN           47..331
FT                   /note="Protein p32"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036893"
FT   CHAIN           332..684
FT                   /note="NTPase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036894"
FT   CHAIN           685..959
FT                   /note="Protein p30"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036895"
FT   CHAIN           960..1070
FT                   /note="Viral genome-linked protein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036896"
FT   CHAIN           1071..1762
FT                   /note="Protease-polymerase p76"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036897"
FT   DOMAIN          458..614
FT                   /note="SF3 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   DOMAIN          1072..1228
FT                   /note="Peptidase C24"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01242"
FT   DOMAIN          1477..1602
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   ACT_SITE        1109
FT                   /note="For 3CLpro activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01242"
FT   ACT_SITE        1130
FT                   /note="For 3CLpro activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01242"
FT   ACT_SITE        1192
FT                   /note="For 3CLpro activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01242"
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|UniProtKB:Q66914"
FT   SITE            331..332
FT                   /note="Cleavage; by Pro-Pol"
FT                   /evidence="ECO:0000250|UniProtKB:Q66914"
FT   SITE            684..685
FT                   /note="Cleavage; by Pro-Pol"
FT                   /evidence="ECO:0000250|UniProtKB:Q66914"
FT   SITE            959..960
FT                   /note="Cleavage; by Pro-Pol"
FT                   /evidence="ECO:0000250|UniProtKB:Q66914"
FT   SITE            1070..1071
FT                   /note="Cleavage; by Pro-Pol"
FT                   /evidence="ECO:0000250|UniProtKB:Q66914"
FT   MOD_RES         983
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P27409"
SQ   SEQUENCE   1762 AA;  195339 MW;  61C010202984AF40 CRC64;
     MSQTLSFVLK THNVRKDFVR SVKLTLARRR DLQYFYNKLS RSMRAEACPS CASYDVCPNC
     TSSDIPDDGS STELIPSWEE VTKTSTYSLL LSEDTSDELC PDDLANVAAH IRKAISTQSH
     PANSDMCKEQ LTSLLVMAEA MLPQRSRASI PLHQQHQAAR LEWREKFFSK PLDFLLERIG
     VSKDILQITA IWKIILEKAC YCKSYGEQWF TTAKQKLREM RSYESNTLKP LIGAFIDGLR
     FMTVDNPYPM GFLPKLIGLI KPLNLAMIID NHENTLSGWV ITLTAIMELY NITECTIDLM
     TSLITAFYDK IGKATKFYSH VKALFTGFRT EDVSNSFWYM AAAILCYLVT GLIPNNGRFL
     KIKCLLVRAT TLVSGIIATQ KLAAMFATWN SESIVNELSA RTVAISELNN PTTTSDTESV
     ERLLELAKIL HEEIKVHTLN PIMQSYNLIL RNLMSTLDGV ITCCNKRKAI ARKRQVPVCY
     ILTGPPGCGK TTAAQALAKK LSDQEPSVIN LDVDHHDTYT GNEVCIIDEF DSSDKVDYAN
     FVIGMVNSAP MVLNCDMLEN KGKLFTSKYI IMTSNSETPV KPSSKRAGAF YRRVTYHDVA
     TLVESHKRAR PGTAVPRSCY KKNFSHLSLA KRGAECWCKE YVLDPKGLQH QSTKAPPPTF
     LNIDSLAQTM KQDFALKNMA FEAEVGCSEH RYGFVCQQSE VETVRRLLNA IRMRLNATFT
     VCVGLEASNS VGCTAHVLTP DEPFNGKRFV VSRCNEASLS ALEGNCVQTA LGVCMSNKDL
     THLCHFIKGK IVNDSVRLDE LPANQHVVTV NSVFDLAWAL RRHSTLTGQF QAIRAAYDVL
     HVPDKVPAML RHWMDETSFS DEHVVTQFIT PGGVVILESC GGARIWALGN NVIRAGGVTA
     IPTGGCVRLM GLSAQTMPWS EILSELFSLL GKIWSSVKVS TLILTALSMY ASRFRPKTEA
     KGKTKSKIGP YRGRGVALTD DEYDEWKEHN AARKLDLSVE DFLMLRHRAA LGADDTDAVK
     FRSWWNSRSR LADDFEDVTV IGKGGVKHEK IRTNTLRAVD RGYDVSFAEE SGPGAKFHKN
     AIGSVTDVCG EHKGYCVHMG HGVYASVAHV VKGDSFFLGE RIFDLKTNGE FCCFRSTKIL
     PSAAPFFSGR PTRDPWGSPV ATDWKPKPYS TTSGKIVGCF ATTSTETHPG DCGLPYIDDN
     GRVTGLHTGS GGPKTPSAKL VVPYVHIDMK TKSVTAQKYD VTKPDISYKG LVCKQLDEIR
     IIPKGTRLHV SPAHLEDFEE CSHQPASLGS GDPRCPKSLT AIVVDSLKPY CVVVNGPPHD
     ILHRVQKMLI DHLSGFVPMN ISSDTSMLSA FHKLNHDTSC GPYLGGRKKD HMVNGEPDKA
     LLDLLSSKWK LATQGIALPH EYTIGLKDEL RPIEKVQEGK RRMIWGCDVG VATVCAAAFK
     GVSDAITANH QYGPIQVGIN MDSPSVEALF QRIKSARKVF AVDYSKWDST QSPRVSAASI
     DILRYFSDRT PIVDSATNTL KSPPIAVFNG VAVKVSSGLP SGMPLTSVIN SLNHCLYVGC
     AILQSLEARN VPVTWNLFST FDMMTYGDDG VYMFPTMYAS ISDQIFANLS AYGLKPTRVD
     KSVGSIEPID PNSVVFLKRT ITRTPQGIRG LLDRSSILRQ FYYIKGENTD NWKEPPKTID
     PMSRGQQLWN ACLYASQHGI DFYNKVYKLA EKAVEYEGLH LEPPSYSTAL EHYNSQFNGV
     EARTDQIDTS GMAALHCDVF EV
//