P03311 (POLG_FMDVS) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Genome polyprotein Cleaved into the following 6 chains: Protein VP3 Alternative name(s): P1C Virion protein 3 Protein VP1 Alternative name(s): P1D Virion protein 1 Protein 2A Short name=P2A Alternative name(s): P52 Protein 2B Picornain 3C EC=3.4.22.28 Alternative name(s): Protease 3C Short name=P3C Protease P20B RNA-directed RNA polymerase 3D-POL Short name=P3D-POL EC=2.7.7.48 Alternative name(s): P56A
Organism	Foot-and-mouth disease virus (strain C1-Santa Pau) (Aphthovirus C) (FMDV)
Taxonomic identifier	12120 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Aphthovirus › Foot-and-mouth disease virus › Foot-and-mouth disease virus - type C
Virus host	Bos taurus (Bovine) [TaxID: 9913] Capra hircus (Goat) [TaxID: 9925] Cervidae (deer) [TaxID: 9850] Erinaceidae (hedgehogs) [TaxID: 9363] Loxodonta africana (African elephant) [TaxID: 9785] Ovis aries (Sheep) [TaxID: 9940] Rattus norvegicus (Rat) [TaxID: 10116] Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length	861 AA.
Sequence status	Fragments.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with host heparan sulfate and various integrins (alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta6, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis By similarity. Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease By similarity. RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals By similarity.
Catalytic activity	Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly. Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
Subunit structure	VP1 interacts (via RGD) with integrins heterodimers alphavbeta6, alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta8 By similarity.
Subcellular location	Protein VP3: Virion. Host cytoplasm Potential. Picornain 3C: Host cytoplasm Potential. RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity.
Post-translational modification	Specific enzymatic cleavages in vivo by the viral proteases yield a variety of precursors and mature proteins By similarity.
Sequence similarities	Belongs to the picornaviruses polyprotein family. Contains 1 peptidase C3 domain. Contains 1 RdRp catalytic domain.

Ontologies

Keywords
Biological process	Clathrin-mediated endocytosis of virus by host Host-virus interaction Ion transport Transport Viral RNA replication Viral attachment to host cell Viral penetration into host cytoplasm Virus endocytosis by host Virus entry into host cell
Cellular component	Host cytoplasm Host cytoplasmic vesicle Host membrane Membrane Virion
Ligand	Nucleotide-binding RNA-binding
Molecular function	Capsid protein Hydrolase Ion channel Nucleotidyltransferase Protease RNA-directed RNA polymerase Thiol protease Transferase Viral ion channel
Technical term	3D-structure
Gene Ontology (GO)
Biological_process	ion transport 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 attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via clathrin-mediated endocytosis Inferred from electronic annotation. Source: UniProtKB-KW viral genome replication Inferred from electronic annotation. Source: InterPro
Cellular_component	host cell cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW viral capsid Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW structural molecule 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 – 46

›46

Protein VP3

PRO_0000039886

Chain

47 – 252

206

Protein VP1 Potential

PRO_0000039887

Chain

253 – 270

18

Protein 2A Potential

PRO_0000039888

Chain

271 – ›332

›62

Protein 2B Potential

PRO_0000310979

Chain

‹333 – 391

›59

Picornain 3C Potential

PRO_0000039889

Chain

392 – 861

470

RNA-directed RNA polymerase 3D-POL Potential

PRO_0000039890

Regions

Domain

625 – 743

119

RdRp catalytic

Motif

186 – 188

3

Cell attachment site

Sites

Active site

341

1

For picornain 3C activity Potential

Site

46 – 47

2

Cleavage; by picornain 3C Potential

Site

252 – 253

2

Cleavage; by picornain 3C Potential

Site

270 – 271

2

Cleavage; by ribosomal skip Potential

Site

391 – 392

2

Cleavage; by picornain 3C Potential

Experimental info

Non-adjacent residues

332 – 333

2

Non-terminal residue

1

1

Secondary structure

1

.

.

.

.

.

.

.

861

Helix Strand Turn

Details...

Beta strand

185 – 187

3

Helix

190 – 192

3

Beta strand

194 – 197

4

Sequences

	Sequence		Length	Mass (Da)
	P03311 [UniParc]. Last modified November 1, 1988. Version 1. Checksum: 507CD16E61C893D1	FASTA	861	95,556
	10 20 30 40 50 60 AETTCVQGWV CVYQITHGKA EPTRSSSRIX AGKDFELRLP VDARQQTTTT GESADPVTTT 70 80 90 100 110 120 VENYGGETQV QRRHHTDVAF VLDRFVKVTV SDNQHTLDVM QAHKDNIVGA LSRHTYYFSD 130 140 150 160 170 180 LEIAVTHTGK LTWVPNGAPV SALNNTTNPT AYHKGPVTRL ALPYTAPHRV LATAYTGTTT 190 200 210 220 230 240 YTASARGDLA HLTTTHARHL PTSFNFGAVK AETITELLVR MKRAELYCPR PILPIQPTGD 250 260 270 280 290 300 RHKQPLVAPA KQLLNFDLLK LAGDVESNLG PFFFSDVRSN FSKLVETINQ MQEDMSTKHE 310 320 330 340 350 360 PDFNRLVSAF EELASGVKAI RTGLDEAKPY KLKAATKVGY CGGAVLAKDG ADTFIVGTHS 370 380 390 400 410 420 AGGNGVGYCS CVSRSMLLKM KAHIDPEPHH EGLIVDTRDV EERVHVMRKT KLAPTVAHGV 430 440 450 460 470 480 FNPEFGPAAL SNKDPRLNEG VVLDEVIFSR HKGDTKMSAE DKALFRRCAA DYASRLHSVL 490 500 510 520 530 540 GTANAPLSIY EVIKGVDGLD AMEPDTAPSL PWALQGKRRG ALIDFENGTV GPEAEAALKL 550 560 570 580 590 600 MEKREYKFAC QTFLKDEIRP MEKVRAGKTR IVDVLPVEHI LYTRMMIGRF CAQMHSNNGP 610 620 630 640 650 660 QIGSAVGCNP DVDRQRSGTH LAQYRNVWDV DYSAFDANHC SDAMNIMFEE VFRTEFGFHP 670 680 690 700 710 720 NAEWILKTLV NTEYAYENKR ITVEGGMPSG CSATSIVNTI LNNIYVLYAL RRHYEGVELD 730 740 750 760 770 780 TYTMISYGDD IVVASDYDLD FEALKPHFKS LGQTITPADK SDKGFVLGHS ITDVTFLKRH 790 800 810 820 830 840 FHMDYGTGFY KPVMTSKTLE AILSFARRGT IQEKLISVAG LAVHSGPDEY RRFFEPFQGL 850 860 FEIPSYRSLY LRWVNAVCGR A

References

[1]	"Molecular cloning of cDNA from foot-and-mouth disease virus C1-Santa Pau (C-S8). Sequence of protein-VP1-coding segment." Villanueva N., Davila M., Ortin J., Domingo E. Gene 23:185-194(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-332.
[2]	"Sequence of the viral replicase gene from foot-and-mouth disease virus C1-Santa Pau (C-S8)." Martinez-Salas E., Ortin J., Domingo E. Gene 35:55-61(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 333-861.
[3]	"Structure of the complex of an Fab fragment of a neutralizing antibody with foot-and-mouth disease virus: positioning of a highly mobile antigenic loop." Hewat E.A., Verdaguer N., Fita I., Blakemore W., Brookes S., King A., Newman J., Domingo E., Mateu M.G., Stuart D.I. EMBO J. 16:1492-1500(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY ELECTRON MICROSCOPY (30.0 ANGSTROMS) OF 178-201.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M11027 Genomic RNA. Translation: AAA42654.1.

PIR

A03913.
A24031.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QGC	electron microscopy	30.00	5	178-201	[»]

ProteinModelPortal

P03311.

SMR

P03311. Positions 47-252, 302-385, 392-861.

ModBase

Search...

Protein family/group databases

MEROPS

C03.008.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR004080. FMDV_VP1_coat.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR001676. Picornavirus_capsid.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00548. Peptidase_C3. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 1 hit.
[Graphical view]

PRINTS

PR01542. FMDVP1COAT.

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P03311.

Entry information

Entry name

POLG_FMDVS

Accession

Primary (citable) accession number: P03311
Secondary accession number(s): Q84781, Q84782

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	November 1, 1988
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program