P49303 (POLG_FMDVZ) Reviewed, UniProtKB/Swiss-Prot
Last modified May 29, 2013. Version 111. History...
Names and origin
|Protein names||Recommended name:|
Cleaved into the following 15 chains:
|Organism||Foot-and-mouth disease virus (isolate -/Azerbaijan/A22-550/1965 serotype A) (FMDV) [Complete proteome]|
|Taxonomic identifier||73481 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Aphthovirus ›|
|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]
|Sequence length||2336 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It cleaves the host translation initiation factors EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription By similarity.
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.
VP0 precursor is a component of immature procapsids By similarity.
Protein 2B affects membrane integrity and cause an increase in membrane permeability By similarity.
Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities By similarity.
Protein 3A, via its hydrophobic domain, serves as membrane anchor By similarity.
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.
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.
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).
VP1 interacts (via RGD) with integrins heterodimers alphavbeta6, alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta8 By similarity.
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.
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.
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.
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.
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 By similarity.
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.
|This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]|
|Isoform Lab (identifier: P49303-1) |
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: P49303-2) |
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 2336||2336||Genome polyprotein||PRO_0000039850|
|Chain||1 – 201||201||Leader protease||PRO_0000039851|
|Chain||202 – 504||303||Protein VP0 Potential||PRO_0000374075|
|Chain||202 – 286||85||Protein VP4 Potential||PRO_0000039854|
|Chain||287 – 504||218||Protein VP2 Potential||PRO_0000039855|
|Chain||505 – 725||221||Protein VP3 Potential||PRO_0000039856|
|Chain||726 – 936||211||Protein VP1 Potential||PRO_0000039857|
|Chain||937 – 954||18||Protein 2A Potential||PRO_0000039858|
|Chain||955 – 1108||154||Protein 2B Potential||PRO_0000039859|
|Chain||1109 – 1426||318||Protein 2C Potential||PRO_0000039860|
|Chain||1427 – 1579||153||Protein 3A Potential||PRO_0000039861|
|Chain||1580 – 1602||23||Protein 3B-1 Potential||PRO_0000039862|
|Chain||1603 – 1626||24||Protein 3B-2 Potential||PRO_0000039863|
|Chain||1627 – 1650||24||Protein 3B-3 Potential||PRO_0000039864|
|Chain||1651 – 1863||213||Picornain 3C Potential||PRO_0000039865|
|Chain||1864 – 2336||473||RNA-directed RNA polymerase 3D-POL Potential||PRO_0000039866|
|Topological domain||1 – 1481||1481||Cytoplasmic Potential|
|Intramembrane||1482 – 1502||21||Potential|
|Topological domain||1503 – 2336||834||Cytoplasmic Potential|
|Domain||1 – 201||201||Peptidase C28|
|Domain||1190 – 1354||165||SF3 helicase|
|Domain||1653 – 1837||185||Peptidase C3|
|Domain||2097 – 2215||119||RdRp catalytic|
|Nucleotide binding||1218 – 1225||8||ATP Potential|
|Motif||869 – 871||3||Cell attachment site|
|Active site||51||1||For leader protease activity By similarity|
|Active site||148||1||For leader protease activity By similarity|
|Active site||163||1||For leader protease activity By similarity|
|Active site||1696||1||For picornain 3C activity Potential|
|Active site||1723||1||For picornain 3C activity Potential|
|Active site||1813||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||725 – 726||2||Cleavage; by picornain 3C Potential|
|Site||936 – 937||2||Cleavage; by picornain 3C Potential|
|Site||954 – 955||2||Cleavage; by ribosomal skip Potential|
|Site||1108 – 1109||2||Cleavage; by picornain 3C Potential|
|Site||1426 – 1427||2||Cleavage; by picornain 3C Potential|
|Site||1579 – 1580||2||Cleavage; by picornain 3C Potential|
|Site||1602 – 1603||2||Cleavage; by picornain 3C Potential|
|Site||1626 – 1627||2||Cleavage; by picornain 3C Potential|
|Site||1650 – 1651||2||Cleavage; by picornain 3C Potential|
|Site||1863 – 1864||2||Cleavage; by picornain 3C Potential|
Amino acid modifications
|Modified residue||1582||1||O-(5'-phospho-RNA)-tyrosine By similarity|
|Modified residue||1605||1||O-(5'-phospho-RNA)-tyrosine By similarity|
|Modified residue||1629||1||O-(5'-phospho-RNA)-tyrosine By similarity|
|Lipidation||202||1||N-myristoyl glycine; by host By similarity|
|Disulfide bond||511||Interchain; in VP3 dimer|
|Alternative sequence||1 – 28||28||Missing in isoform Lb.||VSP_018981|
|Natural variant||726 – 728||3||TTS → NTT.|
|Natural variant||804||1||V → L.|
|Natural variant||859||1||G → S.|
|Natural variant||919||1||E → V.|
Helix Strand Turn
|Helix||229 – 232||4|
|Helix||269 – 274||6|
|||Sosnovtsev S.V., Onischenko A.M., Petrov N.A., Kalashnikova T.I., Mamaeva N.V., Drygin V.Y., Perevozchikova N.A., Vasilenko S.K.|
Submitted (AUG-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"The DNA-copy primary structure for the gene of the FMDV A-22 serotype VP1-protein."|
Onishchenko A.M., Petrov N.A., Blinov V.M., Vassilenko S.K., Sandakhchiev L.S., Burdov A.N., Ivanyushchenkov V.N., Perevozchikova N.A.
Bioorg. Khim. 12:416-419(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 702-955.
|+||Additional computationally mapped references.|
|X74812 Genomic RNA. Translation: CAA52812.1.|
M38362 Genomic RNA. Translation: AAA42664.1.
3D structure databases
|SMR||P49303. Positions 29-201, 216-286, 298-934, 1657-1857, 1864-2333. |
Protein family/group databases
Protocols and materials databases
Family and domain databases
|Gene3D||188.8.131.52. 1 hit. |
|InterPro||IPR015031. Capsid_VP4_Picornavir. |
|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.
|PRINTS||PR00918. CALICVIRUSNS. |
|SUPFAM||SSF50494. Pept_Ser_Cys. 1 hit. |
SSF52540. SSF52540. 1 hit.
|PROSITE||PS50507. RDRP_SSRNA_POS. 1 hit. |
PS51218. SF3_HELICASE_2. 1 hit.
|Accession||Primary (citable) accession number: P49303|
Secondary accession number(s): Q65094
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|