P27408 (POLG_FCVF4) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Genome polyprotein

Cleaved into the following 6 chains:

1. Protein p5.6
2. Protein p32
3. NTPase
   EC=3.6.1.15
   Alternative name(s):
   p39
4. Protein p30
5. Viral genome-linked protein
   Alternative name(s):
   VPg
   p13
6. Protease-polymerase p76
   Short name=Pro-Pol
   EC=2.7.7.48
   EC=3.4.22.66

Gene names

ORF Names:

ORF1

Organism

Feline calicivirus (strain Japanese F4) (FCV) [Complete proteome]

Taxonomic identifier

11980 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Caliciviridae › Vesivirus › Feline calicivirus

Virus host

Felidae (cat family) [TaxID: 9681]

Protein attributes

Sequence length	1763 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity By similarity. Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation By similarity. Protease-polymerase p76 processes the polyprotein: Pro-Pol is first released by autocleavage, then all other proteins are cleaved. Cleaves host translation initiation factor eIF4G1 and eIF4G2 thereby inducing a shutdown of host protein synthesis. This shutdown may not prevent viral mRNA from being translated since viral Vpg replaces the cap. May cleave host polyadenylate-binding protein thereby inhibiting cellular translation. It is also a RNA-directed RNA polymerase which replicates genomic and antigenomic viral RNA by recognizing specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA encodes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs By similarity.
Catalytic activity	NTP + H2O = NDP + phosphate. Endopeptidase with a preference for cleavage when the P1 position is occupied by Glu-|-Xaa and the P1' position is occupied by Gly-|-Yaa. Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
Subunit structure	Protein p32: homodimer, interacts with NTPase, protein p30 and Pro-Pol. Viral genome-linked protein interacts with capsid protein and Pro-Pol. Protease-polymerase p76: Homooligomers, interacts with Vpg, protein p32 and may interact with capsid protein By similarity.
Domain	Protease-polymerase is composed of two domains displaying two different catalytic activity. These activities may act independently By similarity.
Post-translational modification	Specific enzymatic cleavages in vivo yield mature proteins. Pro-Pol is first autocatalytically cleaved, then processes the whole polyprotein. VPg is uridylylated by the polymerase and is covalently attached to the 5'-end of the polyadenylated genomic and subgenomic RNAs. This uridylylated form acts as a nucleotide-peptide primer for the polymerase By similarity.
Sequence similarities	Contains 1 peptidase C24 domain. Contains 1 RdRp catalytic domain. Contains 1 SF3 helicase domain.

Ontologies

Keywords
Biological process	Viral RNA replication
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase Nucleotidyltransferase Protease RNA-directed RNA polymerase Thiol protease Transferase
PTM	Covalent protein-RNA linkage Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological_process	RNA-protein covalent cross-linking Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro viral genome replication Inferred from electronic annotation. Source: InterPro
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: InterPro RNA helicase activity Inferred from electronic annotation. Source: InterPro RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1763	1763	Genome polyprotein		PRO_0000341991
	Chain	1 – 46	46	Protein p5.6		PRO_0000341992
	Chain	47 – 331	285	Protein p32		PRO_0000341993
	Chain	332 – 685	354	NTPase		PRO_0000341994
	Chain	686 – 960	275	Protein p30		PRO_0000341995
	Chain	961 – 1071	111	Viral genome-linked protein		PRO_0000341996
	Chain	1072 – 1763	692	Protease-polymerase p76		PRO_0000036899
Regions
	Domain	458 – 614	157	SF3 helicase
	Domain	1095 – 1199	105	Peptidase C24
	Domain	1478 – 1603	126	RdRp catalytic
	Nucleotide binding	484 – 491	8	ATP Potential
Sites
	Active site	1110	1	For protease activity
	Active site	1131	1	For protease activity
	Active site	1193	1	For protease activity
	Site	46 – 47	2	Cleavage; by Pro-Pol By similarity
	Site	331 – 332	2	Cleavage; by Pro-Pol By similarity
	Site	685 – 686	2	Cleavage; by Pro-Pol By similarity
	Site	960 – 961	2	Cleavage; by Pro-Pol By similarity
	Site	1071 – 1072	2	Cleavage; by Pro-Pol By similarity
Amino acid modifications
	Modified residue	984	1	O-(5'-phospho-RNA)-tyrosine By similarity
Experimental info
	Mutagenesis	1079	1	H → A: No effect on protease activity in vitro. Ref.3
	Mutagenesis	1093	1	H → A: No effect on protease activity in vitro. Ref.3
	Mutagenesis	1099	1	H → A: No effect on protease activity in vitro. Ref.3
	Mutagenesis	1102	1	H → A: No effect on protease activity in vitro. Ref.3
	Mutagenesis	1110	1	H → A: Complete loss of protease activity in vitro. Ref.3
	Mutagenesis	1121	1	E → A: No effect on protease activity in vitro. Ref.3
	Mutagenesis	1125	1	D → A: No effect on protease activity in vitro. Ref.3
	Mutagenesis	1131	1	E → A: Complete loss of protease activity in vitro. Ref.3
	Mutagenesis	1155	1	D → A: No effect on protease activity in vitro. Ref.3
	Mutagenesis	1164	1	E → A: No effect on protease activity in vitro. Ref.3
	Mutagenesis	1193	1	C → A: Complete loss of protease activity in vitro. Ref.3
	Mutagenesis	1208	1	H → A: Complete loss of protease activity in vitro. Ref.3
	Sequence conflict	1417	1	V → M in BAA14370. Ref.2
	Sequence conflict	1485 – 1487	3	YSK → FSN in BAA14370. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P27408 [UniParc]. Last modified July 1, 2008. Version 2. Checksum: 173626D6C862E46C	FASTA	1,763	194,988
	10 20 30 40 50 60 MSQTLSFVLK THSVRKDFVH SVKVTLARRR DLQYLYNKLA RTMRAEACPS CSSYDVCPNC 70 80 90 100 110 120 TSSDIPDNGS STTSIPSWED VTKTSTYSLL LSEDTSDELC PDDLVNVAAH IRKALSTQAH 130 140 150 160 170 180 PANTEMCKEQ LTSLLVMAEA MLPQRSRASI PLHQQHQAAR LEWREKFFSK PLDFLLERIG 190 200 210 220 230 240 VSKDILQITA IWKIILEKAC YCKSYGEQWF CAAKQKLREM RTFESDTLKP LVGAFIDGLR 250 260 270 280 290 300 FMTVDNPNPM GFLPKLIGLV KPLNLAMIID NHENTLSGWV VTLTAIMELY NITECTIDVI 310 320 330 340 350 360 TSLVTGFYDK ISKATKFFSQ VKALFTGFRS EDVANSFWYM AAAILCYLIT GLIPNNGRFS 370 380 390 400 410 420 KIKACLSGAT TLVSGIIATQ KLAAMFATWN SESIVNELSA RTVAISELNN PTTTSDTDSV 430 440 450 460 470 480 ERLLELAKIL HEEIKVHTLN PIMQSYNPIL RNLMSTLDGV ITSCNKRKAI ARKRQVPVCY 490 500 510 520 530 540 ILTGPPGCGK TTAAQALAKK LSDQEPSVIN LDVDHHDTYT GNEVCIIDEF DSSDKVDYAN 550 560 570 580 590 600 FVIGMVNSAP MVLNCDMLEN KGKLFTSKYI IMTSNSETPV KPSSKRAGAF YRRVTIIDVT 610 620 630 640 650 660 NPLVESHKRA RPGTSVPRSC YKKNFSHLSL AKRGAECWCK EYVLDPKGLQ HQTIKAPPPT 670 680 690 700 710 720 FLNIDSLAQT MKQDFVLKNM AFEAEDGCSE HRYGFICQQS EVETVRRLLN AIRARLNATF 730 740 750 760 770 780 TVCVGPEASH SIGCTAHVLT PDEPFNGRRF IVSRCNEASL AALEGNCVQS ALGVCMSNKD 790 800 810 820 830 840 LTHLCHFIRG KIVNDSVRLD ELPANQHVVT VNSVFDLAWA LRRHLTLTGQ FQAIRAAYDV 850 860 870 880 890 900 LTVPDKVPAM LRHWMDETSF SDEHVVTQFV TPGGVVILES CGGARIWALG HNVIRAGGVT 910 920 930 940 950 960 ATPTGGCVRL VGLSAQTLPW SEIFRELFTL LGRIWSSIKV STLVLTALGM YASRFRPKSE 970 980 990 1000 1010 1020 AKGKTKSKIG PYRGRGVALT DDEYDEWREH NANRKLDLSV EDFLMLRHRA ALGADDADAV 1030 1040 1050 1060 1070 1080 KFRSWWNSRT RPGDGFEDVT VIGKGGVKHE KIRTSTLRAV DRGYDVSFAE ESGPGTKFHK 1090 1100 1110 1120 1130 1140 NAIGSVTDVC GEHKGYCVHM GHGVYASVAH VVKGDSYFLG ERIFDVKTNG EFCCFRSTKI 1150 1160 1170 1180 1190 1200 LPSAAPFFSG KPTRDPWGSP VATEWKPKAY TTTSGKIVGC FATTSTETHP GDCGLPYIDD 1210 1220 1230 1240 1250 1260 NGRVTGLHTG SGGPKTPSAK LVVPYIHIDM KNKSVTPQKY DETKPNISYK GLVCKQLDEI 1270 1280 1290 1300 1310 1320 RIIPKGTRLH VSPAHVDDFE ECSHQPASLG SGDPRCPKSL TAIVVDSLKP YCDRVEGPPH 1330 1340 1350 1360 1370 1380 DVLHRVQKML IDHLSGFVPM NISSETSMLS AFHKLNHDTS CGPYLGGRKK DHMVNGEPDK 1390 1400 1410 1420 1430 1440 QLLDLLSSKW KLATQGIALP HEYTIGLKDE LRPIEKVQEG KRRMIWGCDV GVATVCAAAF 1450 1460 1470 1480 1490 1500 KGVSDAITAN HQYGPIQVGI NMDSPSVEVL YQRIKSAAKV FAVDYSKWDS TQSPRVSAAS 1510 1520 1530 1540 1550 1560 IDILRYFSDR SPIVDSAANT LKSPPIAIFN GVAVKVASGL PSGMPLTSVI NSLNHCMYVG 1570 1580 1590 1600 1610 1620 CAILQSLEAR QIPVTWNLFS SFDMMTYGDD GVYMFPTMFA SVSDQIFGNL SAYGLKPTRV 1630 1640 1650 1660 1670 1680 DKSVGAIESI DPESVVFLKR TITRTPNGIR GLLDRSSIIR QFFYIKGENS DDWKTPPKTI 1690 1700 1710 1720 1730 1740 DPTSRGQQLW NACLYASQHG VEFYNKVLKL AMRAVEYEGL HLKPPSYSSA LEHYNSQFNG 1750 1760 VEARSDQINM SDVTALHCDV FEV

References

[1]	"The molecular cloning and sequence of an open reading frame encoding for non-structural proteins of feline calicivirus F4 strain isolated in Japan." Oshikamo R., Tohya Y., Kawaguchi Y., Tomonaga K., Maeda K., Takeda N., Utagawa E., Kai C., Mikami T. J. Vet. Med. Sci. 56:1093-1099(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Sequence analysis of the 3'-end of feline calicivirus genome." Tohya Y., Taniguchi Y., Takahashi E., Utagawa E., Takeda N., Miyamura K., Yamazaki S., Mikami T. Virology 183:810-814(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1383-1763.
[3]	"Highly conserved configuration of catalytic amino acid residues among calicivirus-encoded proteases." Oka T., Yamamoto M., Yokoyama M., Ogawa S., Hansman G.S., Katayama K., Miyashita K., Takagi H., Tohya Y., Sato H., Takeda N. J. Virol. 81:6798-6806(2007) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF HIS-1079; HIS-1093; HIS-1099; HIS-1102; HIS-1110; GLU-1121; ASP-1125; GLU-1131; ASP-1155; GLU-1164; CYS-1193 AND HIS-1208.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D31836 Genomic RNA. Translation: BAA06622.2. D90357 Genomic RNA. Translation: BAA14370.1.
3D structure databases
ProteinModelPortal	P27408.
ModBase	Search...
Protein family/group databases
MEROPS	C24.002.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR003593. AAA+_ATPase. IPR004004. Helic/Pol/Pept_Calicivir-typ. IPR000605. Helicase_SF3_ssDNA/RNA_vir. IPR014759. Helicase_SF3_ssRNA_vir. IPR000317. Peptidase_C24. IPR001205. RNA-dir_pol_C. IPR007094. RNA-dir_pol_PSvirus. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF03510. Peptidase_C24. 1 hit. PF00680. RdRP_1. 1 hit. PF00910. RNA_helicase. 1 hit. [Graphical view]
PRINTS	PR00916. 2CENDOPTASE. PR00918. CALICVIRUSNS.
SMART	SM00382. AAA. 1 hit. [Graphical view]
SUPFAM	SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS50507. RDRP_SSRNA_POS. 1 hit. PS51218. SF3_HELICASE_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POLG_FCVF4

Accession

Primary (citable) accession number: P27408
Secondary accession number(s): Q66913

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	July 1, 2008
Last modified:	May 1, 2013
This is version 72 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program