P03305 (POLG_FMDVO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Genome polyprotein Cleaved into the following 15 chains: Leader protease Short name=Lpro EC=3.4.22.46 Protein VP0 Alternative name(s): VP4-VP2 Protein VP4 Alternative name(s): P1A Virion protein 4 Protein VP2 Alternative name(s): P1B Virion protein 2 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 Short name=P2B Protein 2C Short name=P2C EC=3.6.1.15 Protein 3A Short name=P3A Protein 3B-1 Short name=P3B-1 Alternative name(s): Genome-linked protein VPg1 Protein 3B-2 Short name=P3B-2 Alternative name(s): Genome-linked protein VPg2 Protein 3B-3 Short name=P3B-3 Alternative name(s): Genome-linked protein VPg3 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 (isolate Bovine/Germany/O1Kaufbeuren/1966 serotype O) (FMDV) [Complete proteome]
Taxonomic identifier	73482 [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 O
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	2332 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	The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It also cleaves the host translation initiation factor EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription. Ref.5 Ref.6 Ref.8 Ref.10 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 (alphavbeta6, alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis. In strains adapted to cell culture, attachment to heparan sulfate can also be used and induces virion internalization through clathrin- and caveolin-independent endocytosis. Ref.5 Ref.6 Ref.8 Ref.10 VP0 precursor is a component of immature procapsids By similarity. Ref.5 Ref.6 Ref.8 Ref.10 Protein 2B affects membrane integrity and cause an increase in membrane permeability By similarity. Ref.5 Ref.6 Ref.8 Ref.10 Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities By similarity. Ref.5 Ref.6 Ref.8 Ref.10 Protein 3A, via its hydrophobic domain, serves as membrane anchor By similarity. Ref.5 Ref.6 Ref.8 Ref.10 Protein 3B-1, 3B-2 and 3B-3 are covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. They acts as a genome-linked replication primer By similarity. Ref.5 Ref.6 Ref.8 Ref.10 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. Ref.5 Ref.6 Ref.8 Ref.10 RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals By similarity. Ref.5 Ref.6 Ref.8 Ref.10
Catalytic activity	Autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-|-Gly bond, but then cleaves host cell initiation factor eIF-4G at bonds -Gly-|-Arg- and -Lys-|-Arg-. NTP + H2O = NDP + phosphate. 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.
Subcellular location	Protein VP2: Virion. Host cytoplasm Potential. Protein VP3: Virion. Host cytoplasm Potential. Protein VP1: Virion. Host cytoplasm Potential. Protein 2B: 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. Protein 2C: 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. Protein 3A: 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. Protein 3B-1: Virion Potential. Protein 3B-2: Virion Potential. Protein 3B-3: Virion 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. Polyprotein processing intermediates such as VP0 which is a VP4-VP2 precursor are produced. During virion maturation, non-infectious particles are rendered infectious following cleavage of VP0. This maturation cleavage is followed by a conformational change of the particle. The polyprotein seems to be cotranslationally cleaved at the 2A/2B junction by a ribosomal skip from one codon to the next without formation of a peptide bond. This process would release the L-P1-2A peptide from the translational complex By similarity. Ref.6 Ref.7 Ref.8 Myristoylation of VP4 is required during RNA encapsidation and formation of the mature virus particle By similarity. Protein 3B-1, 3B-2 and 3B-3 are uridylylated by the polymerase and are covalently linked to the 5'-end of genomic RNA. These uridylylated forms act as a nucleotide-peptide primer for the polymerase By similarity.
Miscellaneous	The capsid protein VP1 contains the main antigenic determinants of the virion; therefore, changes in its sequence must be responsible for the high antigenic variability of the virus.
Sequence similarities	Belongs to the picornaviruses polyprotein family. Contains 1 peptidase C28 domain. Contains 1 peptidase C3 domain. Contains 1 RdRp catalytic domain. Contains 1 SF3 helicase domain.

Ontologies

Keywords
Biological process	Clathrin- and caveolin-independent endocytosis of virus by host Clathrin-mediated endocytosis of virus by host Host-virus interaction Ion transport Modulation of host chromatin by virus 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
Coding sequence diversity	Alternative initiation
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Capsid protein Helicase Hydrolase Ion channel Nucleotidyltransferase Protease RNA-directed RNA polymerase Thiol protease Transferase Viral ion channel
PTM	Covalent protein-RNA linkage Disulfide bond Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological_process	RNA-protein covalent cross-linking Inferred from electronic annotation. Source: UniProtKB-KW ion transport Inferred from electronic annotation. Source: UniProtKB-KW modulation by virus of host chromatin organization 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 viral protein processing Inferred from electronic annotation. Source: InterPro
Cellular_component	host cell cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell icosahedral viral capsid Inferred from electronic annotation. Source: InterPro membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW 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 structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform Lab (identifier: P03305-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Lb (identifier: P03305-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2332

2332

Genome polyprotein

PRO_0000039872

Chain

1 – 201

201

Leader protease

PRO_0000039873

Chain

202 – 504

303

Protein VP0 Potential

PRO_0000374076

Chain

202 – 286

85

Protein VP4 Potential

PRO_0000039876

Chain

287 – 504

218

Protein VP2 Potential

PRO_0000039877

Chain

505 – 724

220

Protein VP3 Potential

PRO_0000039878

Chain

725 – 935

211

Protein VP1

PRO_0000039879

Chain

936 – 953

18

Protein 2A Potential

PRO_0000039880

Chain

954 – 1107

154

Protein 2B Potential

PRO_0000310976

Chain

1108 – 1425

318

Protein 2C Potential

PRO_0000039881

Chain

1426 – 1578

153

Protein 3A Potential

PRO_0000039882

Chain

1579 – 1601

23

Protein 3B-1 Potential

PRO_0000039883

Chain

1602 – 1625

24

Protein 3B-2 Potential

PRO_0000310977

Chain

1626 – 1649

24

Protein 3B-3 Potential

PRO_0000310978

Chain

1650 – 1862

213

Picornain 3C Potential

PRO_0000039884

Chain

1863 – 2332

470

RNA-directed RNA polymerase 3D-POL Potential

PRO_0000039885

Regions

Topological domain

1 – 1480

1480

Cytoplasmic Potential

Intramembrane

1481 – 1501

21

Potential

Topological domain

1502 – 2332

831

Cytoplasmic Potential

Domain

1 – 201

201

Peptidase C28

Domain

1189 – 1353

165

SF3 helicase

Domain

1652 – 1836

185

Peptidase C3

Domain

2096 – 2214

119

RdRp catalytic

Nucleotide binding

1217 – 1224

8

ATP Potential

Motif

869 – 871

3

Cell attachment site By similarity

Sites

Active site

51

1

For leader protease activity

Active site

148

1

For leader protease activity

Active site

163

1

For leader protease activity

Active site

1695

1

For picornain 3C activity Potential

Active site

1722

1

For picornain 3C activity Potential

Active site

1812

1

For picornain 3C activity Potential

Site

201 – 202

2

Cleavage; by leader protease Potential

Site

286 – 287

2

Cleavage Potential

Site

504 – 505

2

Cleavage; by picornain 3C Potential

Site

724 – 725

2

Cleavage; by picornain 3C Potential

Site

935 – 936

2

Cleavage; by picornain 3C Potential

Site

953 – 954

2

Cleavage; by ribosomal skip Potential

Site

1107 – 1108

2

Cleavage; by picornain 3C Potential

Site

1425 – 1426

2

Cleavage; by picornain 3C Potential

Site

1578 – 1579

2

Cleavage; by picornain 3C Potential

Site

1601 – 1602

2

Cleavage; by picornain 3C Potential

Site

1625 – 1626

2

Cleavage; by picornain 3C Potential

Site

1649 – 1650

2

Cleavage; by picornain 3C Potential

Site

1862 – 1863

2

Cleavage; by picornain 3C Potential

Amino acid modifications

Modified residue

1581

1

O-(5'-phospho-RNA)-tyrosine By similarity

Modified residue

1604

1

O-(5'-phospho-RNA)-tyrosine By similarity

Modified residue

1628

1

O-(5'-phospho-RNA)-tyrosine By similarity

Lipidation

202

1

N-myristoyl glycine; by host

Disulfide bond

406 ↔ 858

Interchain (between VP2 and VP1 chains)

Disulfide bond

511

Interchain; in VP3 dimer

Natural variations

Alternative sequence

1 – 28

28

Missing in isoform Lb.

VSP_018982

Natural variant

780

1

I → V in strain: Isolate O1BFS.

Natural variant

808

1

G → R in strain: Isolate O1BFS.

Natural variant

861

1

N → S in strain: Isolate O1BFS.

Secondary structure

1

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2332

Helix Strand Turn

Details...

Beta strand

30 – 32

3

Beta strand

38 – 40

3

Beta strand

47 – 49

3

Helix

51 – 63

13

Helix

66 – 68

3

Helix

69 – 72

4

Beta strand

73 – 76

4

Helix

79 – 90

12

Helix

100 – 107

8

Helix

108 – 110

3

Beta strand

111 – 113

3

Beta strand

115 – 120

6

Beta strand

123 – 126

4

Beta strand

129 – 131

3

Helix

134 – 136

3

Beta strand

137 – 144

8

Turn

145 – 147

3

Beta strand

148 – 153

6

Beta strand

158 – 163

6

Beta strand

166 – 169

4

Helix

174 – 176

3

Beta strand

177 – 182

6

Turn

195 – 197

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Lab [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 4A83176F43447D68	FASTA	2,332	258,927
	10 20 30 40 50 60 MNTTDCFIAL VQAIREIKAL FLSRTTGKME LTLYNGEKKT FYSRPNNHDN CWLNAILQLF 70 80 90 100 110 120 RYVEEPFFDW VYSSPENLTL EAIKQLEDLT GLELHEGGPP ALVIWNIKHL LHTGIGTASR 130 140 150 160 170 180 PSEVCMVDGT DMCLADFHAG IFLKGQEHAV FACVTSNGWY AIDDEDFYPW TPDPSDVLVF 190 200 210 220 230 240 VPYDQEPLNG EWKAKVQRKL KGAGQSSPAT GSQNQSGNTG SIINNYYMQQ YQNSMDTQLG 250 260 270 280 290 300 DNAISGGSNE GSTDTTSTHT TNTQNNDWFS KLASSAFSGL FGALLADKKT EETTLLEDRI 310 320 330 340 350 360 LTTRNGHTTS TTQSSVGVTY GYATAEDFVS GPNTSGLETR VVQAERFFKT HLFDWVTSDS 370 380 390 400 410 420 FGRCHLLELP TDHKGVYGSL TDSYAYMRNG WDVEVTAVGN QFNGGCLLVA MVPELYSIQK 430 440 450 460 470 480 RELYQLTLFP HQFINPRTNM TAHITVPFVG VNRYDQYKVH KPWTLVVMVV APLTVNTEGA 490 500 510 520 530 540 PQIKVYANIA PTNVHVAGEF PSKEGIFPVA CSDGYGGLVT TDPKTADPVY GKVFNPPRNQ 550 560 570 580 590 600 LPGRFTNLLD VAEACPTFLR FEGGVPYVTT KTDSDRVLAQ FDMSLAAKQM SNTFLAGLAQ 610 620 630 640 650 660 YYTQYSGTIN LHFMFTGPTD AKARYMVAYA PPGMEPPKTP EAAAHCIHAE WDTGLNSKFT 670 680 690 700 710 720 FSIPYLSAAD YAYTASGVAE TTNVQGWVCL FQITHGKADG DALVVLASAG KDFELRLPVD 730 740 750 760 770 780 ARAETTSAGE SADPVTTTVE NYGGETQIQR RQHTDVSFIM DRFVKVTPQN QINILDLMQI 790 800 810 820 830 840 PSHTLVGALL RASTYYFSDL EIAVKHEGDL TWVPNGAPEK ALDNTTNPTA YHKAPLTRLA 850 860 870 880 890 900 LPYTAPHRVL ATVYNGECRY NRNAVPNLRG DLQVLAQKVA RTLPTSFNYG AIKATRVTEL 910 920 930 940 950 960 LYRMKRAETY CPRPLLAIHP TEARHKQKIV APVKQTLNFD LLKLAGDVES NPGPFFFSDV 970 980 990 1000 1010 1020 RSNFSKLVET INQMQEDMST KHGPDFNRLV SAFEELAIGV KAIRTGLDEA KPWYKLIKLL 1030 1040 1050 1060 1070 1080 SRLSCMAAVA ARSKDPVLVA IMLADTGLEI LDSTFVVKKI SDSLSSLFHV PAPVFSFGAP 1090 1100 1110 1120 1130 1140 VLLAGLVKVA SSFFRSTPED LERAEKQLKA RDINDIFAIL KNGEWLVKLI LAIRDWIKAW 1150 1160 1170 1180 1190 1200 IASEEKFVTM TDLVPGILEK QRDLNDPSKY KEAKEWLDNA RQACLKSGNV HIANLCKVVA 1210 1220 1230 1240 1250 1260 PAPSKSRPEP VVVCLRGKSG QGKSFLANVL AQAISTHFTG RIDSVWYCPP DPDHFDGYNQ 1270 1280 1290 1300 1310 1320 QTVVVMDDLG QNPDGKDFKY FAQMVSTTGF IPPMASLEDK GKPFNSKVII ATTNLYSGFT 1330 1340 1350 1360 1370 1380 PRTMVCPDAL NRRFHFDIDV SAKDGYKINS KLDIIKALED THANPVAMFQ YDCALLNGMA 1390 1400 1410 1420 1430 1440 VEMKRMQQDM FKPQPPLQNV YQLVQEVIDR VELHEKVSSH PIFKQISIPS QKSVLYFLIE 1450 1460 1470 1480 1490 1500 KGQHEAAIEF FEGMVHDSIK EELRPLIQQT SFVKRAFKRL KENFEIVALC LTLLANIVIM 1510 1520 1530 1540 1550 1560 IRETRKRQKM VDDAVNEYIE KANITTDDKT LDEAEKSPLE TSGASTVGFR ERTLPGQKAC 1570 1580 1590 1600 1610 1620 DDVNSEPAQP VEEQPQAEGP YAGPLERQKP LKVRAKLPQQ EGPYAGPMER QKPLKVKAKA 1630 1640 1650 1660 1670 1680 PVVKEGPYEG PVKKPVALKV KAKNLIVTES GAPPTDLQKM VMGNTKPVEL ILDGKTVAIC 1690 1700 1710 1720 1730 1740 CATGVFGTAY LVPRHLFAEK YDKIMVDGRA MTDSDYRVFE FEIKVKGQDM LSDAALMVLH 1750 1760 1770 1780 1790 1800 RGNRVRDITK HFRDTARMKK GTPVVGVINN ADVGRLIFSG EALTYKDIVV CMDGDTMPGL 1810 1820 1830 1840 1850 1860 FAYRAATKAG YCGGAVLAKD GADTFIVGTH SAGGNGVGYC SCVSRSMLLK MKAHIDPEPH 1870 1880 1890 1900 1910 1920 HEGLIVDTRD VEERVHVMRK TKLAPTVAHG VFNPEFGPAA LSNKDPRLNE GVVLDEVIFS 1930 1940 1950 1960 1970 1980 KHKGDTKMSE EDKALFRRCA ADYASRLHSV LGTANAPLSI YEAIKGVDGL DAMEPDTAPG 1990 2000 2010 2020 2030 2040 LPWALQGKRR GALIDFENGT VGPEVEAALK LMEKREYKFV CQTFLKDEIR PLEKVRAGKT 2050 2060 2070 2080 2090 2100 RIVDVLPVEH ILYTRMMIGR FCAQMHSNNG PQIGSAVGCN PDVDWQRFGT HFAQYRNVWD 2110 2120 2130 2140 2150 2160 VDYSAFDANH CSDAMNIMFE EVFRTEFGFH PNAEWILKTL VNTEHAYENK RITVGGGMPS 2170 2180 2190 2200 2210 2220 GCSATSIINT ILNNIYVLYA LRRHYEGVEL DTYTMISYGD DIVVASDYDL DFEALKPHFK 2230 2240 2250 2260 2270 2280 SLGQTITPAD KSDKGFVLGH SITDVTFLKR HFHMDYGTGF YKPVMASKTL EAILSFARRG 2290 2300 2310 2320 2330 TIQEKLISVA GLAVHSGPDE YRRLFEPFQG LFEIPSYRSL YLRWVNAVCG DA
	Isoform Lb [UniParc]. Checksum: 5372D197CC761349	FASTA	2,304	255,803
	10 20 30 40 50 60 MELTLYNGEK KTFYSRPNNH DNCWLNAILQ LFRYVEEPFF DWVYSSPENL TLEAIKQLED 70 80 90 100 110 120 LTGLELHEGG PPALVIWNIK HLLHTGIGTA SRPSEVCMVD GTDMCLADFH AGIFLKGQEH 130 140 150 160 170 180 AVFACVTSNG WYAIDDEDFY PWTPDPSDVL VFVPYDQEPL NGEWKAKVQR KLKGAGQSSP 190 200 210 220 230 240 ATGSQNQSGN TGSIINNYYM QQYQNSMDTQ LGDNAISGGS NEGSTDTTST HTTNTQNNDW 250 260 270 280 290 300 FSKLASSAFS GLFGALLADK KTEETTLLED RILTTRNGHT TSTTQSSVGV TYGYATAEDF 310 320 330 340 350 360 VSGPNTSGLE TRVVQAERFF KTHLFDWVTS DSFGRCHLLE LPTDHKGVYG SLTDSYAYMR 370 380 390 400 410 420 NGWDVEVTAV GNQFNGGCLL VAMVPELYSI QKRELYQLTL FPHQFINPRT NMTAHITVPF 430 440 450 460 470 480 VGVNRYDQYK VHKPWTLVVM VVAPLTVNTE GAPQIKVYAN IAPTNVHVAG EFPSKEGIFP 490 500 510 520 530 540 VACSDGYGGL VTTDPKTADP VYGKVFNPPR NQLPGRFTNL LDVAEACPTF LRFEGGVPYV 550 560 570 580 590 600 TTKTDSDRVL AQFDMSLAAK QMSNTFLAGL AQYYTQYSGT INLHFMFTGP TDAKARYMVA 610 620 630 640 650 660 YAPPGMEPPK TPEAAAHCIH AEWDTGLNSK FTFSIPYLSA ADYAYTASGV AETTNVQGWV 670 680 690 700 710 720 CLFQITHGKA DGDALVVLAS AGKDFELRLP VDARAETTSA GESADPVTTT VENYGGETQI 730 740 750 760 770 780 QRRQHTDVSF IMDRFVKVTP QNQINILDLM QIPSHTLVGA LLRASTYYFS DLEIAVKHEG 790 800 810 820 830 840 DLTWVPNGAP EKALDNTTNP TAYHKAPLTR LALPYTAPHR VLATVYNGEC RYNRNAVPNL 850 860 870 880 890 900 RGDLQVLAQK VARTLPTSFN YGAIKATRVT ELLYRMKRAE TYCPRPLLAI HPTEARHKQK 910 920 930 940 950 960 IVAPVKQTLN FDLLKLAGDV ESNPGPFFFS DVRSNFSKLV ETINQMQEDM STKHGPDFNR 970 980 990 1000 1010 1020 LVSAFEELAI GVKAIRTGLD EAKPWYKLIK LLSRLSCMAA VAARSKDPVL VAIMLADTGL 1030 1040 1050 1060 1070 1080 EILDSTFVVK KISDSLSSLF HVPAPVFSFG APVLLAGLVK VASSFFRSTP EDLERAEKQL 1090 1100 1110 1120 1130 1140 KARDINDIFA ILKNGEWLVK LILAIRDWIK AWIASEEKFV TMTDLVPGIL EKQRDLNDPS 1150 1160 1170 1180 1190 1200 KYKEAKEWLD NARQACLKSG NVHIANLCKV VAPAPSKSRP EPVVVCLRGK SGQGKSFLAN 1210 1220 1230 1240 1250 1260 VLAQAISTHF TGRIDSVWYC PPDPDHFDGY NQQTVVVMDD LGQNPDGKDF KYFAQMVSTT 1270 1280 1290 1300 1310 1320 GFIPPMASLE DKGKPFNSKV IIATTNLYSG FTPRTMVCPD ALNRRFHFDI DVSAKDGYKI 1330 1340 1350 1360 1370 1380 NSKLDIIKAL EDTHANPVAM FQYDCALLNG MAVEMKRMQQ DMFKPQPPLQ NVYQLVQEVI 1390 1400 1410 1420 1430 1440 DRVELHEKVS SHPIFKQISI PSQKSVLYFL IEKGQHEAAI EFFEGMVHDS IKEELRPLIQ 1450 1460 1470 1480 1490 1500 QTSFVKRAFK RLKENFEIVA LCLTLLANIV IMIRETRKRQ KMVDDAVNEY IEKANITTDD 1510 1520 1530 1540 1550 1560 KTLDEAEKSP LETSGASTVG FRERTLPGQK ACDDVNSEPA QPVEEQPQAE GPYAGPLERQ 1570 1580 1590 1600 1610 1620 KPLKVRAKLP QQEGPYAGPM ERQKPLKVKA KAPVVKEGPY EGPVKKPVAL KVKAKNLIVT 1630 1640 1650 1660 1670 1680 ESGAPPTDLQ KMVMGNTKPV ELILDGKTVA ICCATGVFGT AYLVPRHLFA EKYDKIMVDG 1690 1700 1710 1720 1730 1740 RAMTDSDYRV FEFEIKVKGQ DMLSDAALMV LHRGNRVRDI TKHFRDTARM KKGTPVVGVI 1750 1760 1770 1780 1790 1800 NNADVGRLIF SGEALTYKDI VVCMDGDTMP GLFAYRAATK AGYCGGAVLA KDGADTFIVG 1810 1820 1830 1840 1850 1860 THSAGGNGVG YCSCVSRSML LKMKAHIDPE PHHEGLIVDT RDVEERVHVM RKTKLAPTVA 1870 1880 1890 1900 1910 1920 HGVFNPEFGP AALSNKDPRL NEGVVLDEVI FSKHKGDTKM SEEDKALFRR CAADYASRLH 1930 1940 1950 1960 1970 1980 SVLGTANAPL SIYEAIKGVD GLDAMEPDTA PGLPWALQGK RRGALIDFEN GTVGPEVEAA 1990 2000 2010 2020 2030 2040 LKLMEKREYK FVCQTFLKDE IRPLEKVRAG KTRIVDVLPV EHILYTRMMI GRFCAQMHSN 2050 2060 2070 2080 2090 2100 NGPQIGSAVG CNPDVDWQRF GTHFAQYRNV WDVDYSAFDA NHCSDAMNIM FEEVFRTEFG 2110 2120 2130 2140 2150 2160 FHPNAEWILK TLVNTEHAYE NKRITVGGGM PSGCSATSII NTILNNIYVL YALRRHYEGV 2170 2180 2190 2200 2210 2220 ELDTYTMISY GDDIVVASDY DLDFEALKPH FKSLGQTITP ADKSDKGFVL GHSITDVTFL 2230 2240 2250 2260 2270 2280 KRHFHMDYGT GFYKPVMASK TLEAILSFAR RGTIQEKLIS VAGLAVHSGP DEYRRLFEPF 2290 2300 QGLFEIPSYR SLYLRWVNAV CGDA

References

[1]	"Nucleotide sequence and genome organization of foot-and-mouth disease virus." Forss S., Strebel K., Beck E., Schaller H. Nucleic Acids Res. 12:6587-6601(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Comparison of the amino acid sequence of the major immunogen from three serotypes of foot and mouth disease virus." Makoff A.J., Paynter C.A., Rowlands D.J., Boothroyd J.C. Nucleic Acids Res. 10:8285-8295(1982) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate O1BFS/Britain/1968.
[3]	"Foot-and-mouth disease virus leader proteinase: specificity at the P2 and P3 positions and comparison with other papain-like enzymes." Kuehnel E., Cencic R., Foeger N., Skern T. Biochemistry 43:11482-11490(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[4]	"All foot and mouth disease virus serotypes initiate protein synthesis at two separate AUGs." Sangar D.V., Newton S.E., Rowlands D.J., Clarke B.E. Nucleic Acids Res. 15:3305-3315(1987) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE INITIATION.
[5]	"The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities." Medina M., Domingo E., Brangwyn J.K., Belsham G.J. Virology 194:355-359(1993) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE LEADER PROTEASE.
[6]	"Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro." Glaser W., Skern T. FEBS Lett. 480:151-155(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE LEADER PROTEASE, CLEAVAGE OF HOST EIF4G1. Strain: Isolate O1k.
[7]	"Analysis of the aphthovirus 2A/2B polyprotein 'cleavage' mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal 'skip'." Donnelly M.L.L., Luke G., Mehrotra A., Li X., Hughes L.E., Gani D., Ryan M.D. J. Gen. Virol. 82:1013-1025(2001) [PubMed] [Europe PMC] [Abstract] Cited for: POLYPROTEIN PROCESSING.
[8]	"Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro." Gradi A., Foeger N., Strong R., Svitkin Y.V., Sonenberg N., Skern T., Belsham G.J. J. Virol. 78:3271-3278(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE LEADER PROTEASE, CLEAVAGE OF HOST EIF4G3.
[9]	"Factors required for the uridylylation of the foot-and-mouth disease virus 3B1, 3B2, and 3B3 peptides by the RNA-dependent RNA polymerase (3Dpol) in vitro." Nayak A., Goodfellow I.G., Belsham G.J. J. Virol. 79:7698-7706(2005) [PubMed] [Europe PMC] [Abstract] Cited for: COVALENT RNA-LINKAGE OF 3B PROTEINS, URIDYLYLATION.
[10]	"Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis." O'Donnell V., Larocco M., Baxt B. J. Virol. 82:9075-9085(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF CAPSID PROTEINS.
[11]	"Cellular receptors for foot and mouth disease virus." Ruiz-Saenz J., Goez Y., Tabares W., Lopez-Herrera A. Intervirology 52:201-212(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[12]	"The three-dimensional structure of foot-and-mouth disease virus at 2.9-A resolution." Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F. Nature 337:709-716(1989) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[13]	"Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition." Guarne A., Tormo J., Kirchweger R., Pfistermueller D., Fita I., Skern T. EMBO J. 17:7469-7479(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 29-201 OF MUTANT ALA-51.
[14]	"Structural and biochemical features distinguish the foot-and-mouth disease virus leader proteinase from other papain-like enzymes." Guarne A., Hampoelz B., Glaser W., Carpena X., Tormo J., Fita I., Skern T. J. Mol. Biol. 302:1227-1240(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 29-195 OF MUTANT ALA-51/SER-133.
+	Additional computationally mapped references.

Web resources

Virus Particle ExploreR db

Icosahedral capsid structure

Virus Particle ExploreR db

Icosahedral capsid structure

Virus Particle ExploreR db

Icosahedral capsid structure complexed with oligosaccharide receptor

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00871 Genomic RNA. Translation: CAA25416.1.
J02185 Genomic RNA. Translation: AAA42635.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QMY	X-ray	1.90	A/B/C	29-195	[»]
1QOL	X-ray	3.00	A/B/C/D/E/F/G/H	29-201	[»]
1QQP	X-ray	1.90	1	725-937	[»]
			2	287-504	[»]
			3	505-724	[»]
			4	202-286	[»]
2JQF	NMR	-	R/S	29-201	[»]
2JQG	NMR	-	R	29-195	[»]

ProteinModelPortal

P03305.

SMR

P03305. Positions 29-201, 216-286, 291-934, 1656-1856, 1863-2332.

ModBase

Search...

Protein family/group databases

MEROPS

C28.001.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

4.10.90.10. 1 hit.

InterPro

IPR015031. Capsid_VP4_Picornavir.
IPR004080. FMDV_VP1_coat.
IPR004004. Helic/Pol/Pept_Calicivir-typ.
IPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR027417. P-loop_NTPase.
IPR008739. Peptidase_C28.
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

PF05408. Peptidase_C28. 1 hit.
PF00548. Peptidase_C3. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 3 hits.
PF00910. RNA_helicase. 1 hit.
PF08935. VP4_2. 1 hit.
[Graphical view]

PRINTS

PR00918. CALICVIRUSNS.
PR01542. FMDVP1COAT.

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.
SSF52540. SSF52540. 1 hit.

PROSITE

PS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P03305.

Entry information

Entry name

POLG_FMDVO

Accession

Primary (citable) accession number: P03305

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 29, 2013
This is version 144 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program