ID   POLG_FMDVA              Reviewed;        2333 AA.
AC   P03308; P03312; Q65038; Q65039; Q65040; Q65041; Q65042; Q65043; Q65044;
AC   Q65045; Q65046; Q65047; Q6PN34;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   29-MAY-2013, sequence version 2.
DT   24-JAN-2024, entry version 193.
DE   RecName: Full=Genome polyprotein;
DE   Contains:
DE     RecName: Full=Leader protease;
DE              Short=Lpro;
DE              EC=3.4.22.46;
DE   Contains:
DE     RecName: Full=Capsid protein VP0;
DE     AltName: Full=VP4-VP2;
DE   Contains:
DE     RecName: Full=Capsid protein VP4;
DE     AltName: Full=P1A;
DE     AltName: Full=Virion protein 4;
DE   Contains:
DE     RecName: Full=Capsid protein VP2;
DE     AltName: Full=P1B;
DE     AltName: Full=Virion protein 2;
DE   Contains:
DE     RecName: Full=Capsid protein VP3;
DE     AltName: Full=P1C;
DE     AltName: Full=Virion protein 3;
DE   Contains:
DE     RecName: Full=Capsid protein VP1;
DE     AltName: Full=P1D;
DE     AltName: Full=Virion protein 1;
DE   Contains:
DE     RecName: Full=Protein 2A;
DE              Short=P2A;
DE     AltName: Full=P52;
DE   Contains:
DE     RecName: Full=Protein 2B;
DE              Short=P2B;
DE   Contains:
DE     RecName: Full=Protein 2C;
DE              Short=P2C;
DE              EC=3.6.1.15;
DE   Contains:
DE     RecName: Full=Protein 3A;
DE              Short=P3A;
DE   Contains:
DE     RecName: Full=Protein 3B-1;
DE              Short=P3B-1;
DE     AltName: Full=Genome-linked protein VPg1;
DE   Contains:
DE     RecName: Full=Protein 3B-2;
DE              Short=P3B-2;
DE     AltName: Full=Genome-linked protein VPg2;
DE   Contains:
DE     RecName: Full=Protein 3B-3;
DE              Short=P3B-3;
DE     AltName: Full=Genome-linked protein VPg3;
DE   Contains:
DE     RecName: Full=Protease 3C;
DE              EC=3.4.22.28;
DE     AltName: Full=Picornain 3C;
DE              Short=P3C;
DE     AltName: Full=Protease P20B;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase 3D-POL;
DE              Short=P3D-POL;
DE              EC=2.7.7.48;
DE     AltName: Full=P56A;
OS   Foot-and-mouth disease virus (isolate Bovine/United
OS   Kingdom/A12Valle119/1932 serotype A) (FMDV).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Picornavirales; Picornaviridae; Caphthovirinae; Aphthovirus;
OC   Foot-and-mouth disease virus.
OX   NCBI_TaxID=12114;
OH   NCBI_TaxID=9913; Bos taurus (Bovine).
OH   NCBI_TaxID=9925; Capra hircus (Goat).
OH   NCBI_TaxID=9850; Cervidae (Deer).
OH   NCBI_TaxID=9363; Erinaceidae (hedgehogs).
OH   NCBI_TaxID=9785; Loxodonta africana (African elephant).
OH   NCBI_TaxID=9940; Ovis aries (Sheep).
OH   NCBI_TaxID=10116; Rattus norvegicus (Rat).
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=119ab variant;
RX   PubMed=2987518; DOI=10.1128/jvi.54.3.651-660.1985;
RA   Robertson B.H., Grubman M.J., Weddell G.N., Moore D.M., Welsh J.D.,
RA   Fischer T., Dowbenko D.J., Yansura D.G., Small B., Kleid D.G.;
RT   "Nucleotide and amino acid sequence coding for polypeptides of foot-and-
RT   mouth disease virus type A12.";
RL   J. Virol. 54:651-660(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=15858032; DOI=10.1128/jvi.79.10.6487-6504.2005;
RA   Carrillo C., Tulman E.R., Delhon G., Lu Z., Carreno A., Vagnozzi A.,
RA   Kutish G.F., Rock D.L.;
RT   "Comparative genomics of foot-and-mouth disease virus.";
RL   J. Virol. 79:6487-6504(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1863-2332.
RX   PubMed=6305004; DOI=10.1016/s0042-6822(83)80017-8;
RA   Robertson B.H., Morgan D.O., Moore D.M., Grubman M.J., Card J., Fischer T.,
RA   Weddell G.N., Dowbenko D.J., Yansura D.G.;
RT   "Identification of amino acid and nucleotide sequence of the foot-and-mouth
RT   disease virus RNA polymerase.";
RL   Virology 126:614-623(1983).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 715-955.
RX   PubMed=6272395; DOI=10.1126/science.6272395;
RA   Kleid D.G., Yansura D.G., Small B., Dowbenko D.J., Moore D.M.,
RA   Grubman M.J., McKercher P.D., Morgan D.O., Robertson B.H., Bachrach H.L.;
RT   "Cloned viral protein vaccine for foot-and-mouth disease: responses in
RT   cattle and swine.";
RL   Science 214:1125-1129(1981).
RN   [5]
RP   ALTERNATIVE INITIATION.
RX   PubMed=3033601; DOI=10.1093/nar/15.8.3305;
RA   Sangar D.V., Newton S.E., Rowlands D.J., Clarke B.E.;
RT   "All foot and mouth disease virus serotypes initiate protein synthesis at
RT   two separate AUGs.";
RL   Nucleic Acids Res. 15:3305-3315(1987).
RN   [6]
RP   FUNCTION (LEADER PROTEASE), SUBCELLULAR LOCATION (PROTEIN VP1), AND
RP   MUTAGENESIS OF CYS-51.
RX   PubMed=30404792; DOI=10.1128/jvi.00922-18;
RA   Visser L.J., Medina G.N., Rabouw H.H., de Groot R.J., Langereis M.A.,
RA   de Los Santos T., van Kuppeveld F.J.M.;
RT   "Foot-and-Mouth Disease Virus Leader Protease Cleaves G3BP1 and G3BP2 and
RT   Inhibits Stress Granule Formation.";
RL   J. Virol. 93:0-0(2019).
CC   -!- FUNCTION: [Leader protease]: Autocatalytically cleaves itself from the
CC       polyprotein at the L/VP0 junction. Also cleaves the host translation
CC       initiation factors EIF4G1 and EIF4G3, in order to shut off the capped
CC       cellular mRNA transcription. Plays a role in counteracting host innate
CC       antiviral response using diverse mechanisms. Possesses a deubiquitinase
CC       activity acting on both 'Lys-48' and 'Lys-63'-linked polyubiquitin
CC       chains. In turn, inhibits the ubiquitination and subsequent activation
CC       of key signaling molecules of type I IFN response such as host RIGI,
CC       TBK1, TRAF3 and TRAF6. Inhibits host NF-kappa-B activity by inducing a
CC       decrease in RELA mRNA levels. Cleaves a peptide bond in the C-terminus
CC       of host ISG15, resulting in the damaging of this modifier that can no
CC       longer be attached to target proteins. Also cleaves host G3BP1 and
CC       G3BP2 in order to inhibit cytoplasmic stress granules assembly
CC       (PubMed:30404792). {ECO:0000250|UniProtKB:P03305,
CC       ECO:0000269|PubMed:30404792}.
CC   -!- FUNCTION: [Capsid protein VP4]: Lies on the inner surface of the capsid
CC       shell. After binding to the host receptor, the capsid undergoes
CC       conformational changes. Capsid protein VP4 is released, capsid protein
CC       VP1 N-terminus is externalized, and together, they shape a pore in the
CC       host membrane through which the viral genome is translocated into the
CC       host cell cytoplasm. After genome has been released, the channel
CC       shrinks. {ECO:0000250|UniProtKB:P03300}.
CC   -!- FUNCTION: [Capsid protein VP2]: Forms an icosahedral capsid of pseudo
CC       T=3 symmetry with capsid proteins VP1 and VP3. The capsid is composed
CC       of 60 copies of each capsid protein organized in the form of twelve
CC       pentamers and encloses the viral positive strand RNA genome.
CC       {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo
CC       T=3 symmetry with capsid proteins VP2 and VP3. The capsid is composed
CC       of 60 copies of each capsid protein organized in the form of twelve
CC       pentamers and encloses the viral positive strand RNA genome. Mediates
CC       cell entry by attachment to an integrin receptor, usually host
CC       ITGAV/ITGB6. In addition, targets host MAVS to suppress type I IFN
CC       pathway. {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo
CC       T=3 symmetry with capsid proteins VP0 and VP3. The capsid is composed
CC       of 60 copies of each capsid protein organized in the form of twelve
CC       pentamers and encloses the viral positive strand RNA genome.
CC       {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Protein 2A]: Mediates self-processing of the polyprotein by
CC       a translational effect termed 'ribosome skipping'. Mechanistically, 2A-
CC       mediated cleavage occurs between the C-terminal glycine and the proline
CC       of the downstream protein 2B. In the case of foot-and-mouth disease
CC       virus, the 2A oligopeptide is post-translationally 'trimmed' from the
CC       C-terminus of the upstream protein 1D by 3C proteinase.
CC       {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Protein 2B]: Plays an essential role in the virus
CC       replication cycle by acting as a viroporin. Creates a pore in the host
CC       reticulum endoplasmic and as a consequence releases Ca2+ in the
CC       cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium
CC       may trigger membrane trafficking and transport of viral ER-associated
CC       proteins to viroplasms, sites of viral genome replication.
CC       {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Protein 2C]: Associates with and induces structural
CC       rearrangements of intracellular membranes. Triggers host autophagy by
CC       interacting with host BECN1 and thereby promotes viral replication.
CC       Participates in viral replication and interacts with host DHX9.
CC       Displays RNA-binding, nucleotide binding and NTPase activities. May
CC       play a role in virion morphogenesis and viral RNA encapsidation by
CC       interacting with the capsid protein VP3.
CC       {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Protein 3A]: Plays important roles in virus replication,
CC       virulence and host range. {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Protein 3B-1]: Covalently linked to the 5'-end of both the
CC       positive-strand and negative-strand genomic RNAs. Acts as a genome-
CC       linked replication primer. {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Protein 3B-2]: Covalently linked to the 5'-end of both the
CC       positive-strand and negative-strand genomic RNAs. Acts as a genome-
CC       linked replication primer. {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Protein 3B-3]: Covalently linked to the 5'-end of both the
CC       positive-strand and negative-strand genomic RNAs. Acts as a genome-
CC       linked replication primer. {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: [Protease 3C]: Cysteine protease that generates mature viral
CC       proteins from the precursor polyprotein. In addition to its proteolytic
CC       activity, binds to viral RNA and thus influences viral genome
CC       replication. RNA and substrate bind cooperatively to the protease.
CC       {ECO:0000250|UniProtKB:P03305}.
CC   -!- FUNCTION: RNA-directed RNA polymerase 3D-POL replicates genomic and
CC       antigenomic RNA by recognizing replications specific signals.
CC       Covalently attaches UMP to a tyrosine of VPg, which is used to prime
CC       RNA synthesis. The positive stranded RNA genome is first replicated at
CC       virus induced membranous vesicles, creating a dsRNA genomic replication
CC       form. This dsRNA is then used as template to synthesize positive
CC       stranded RNA genomes. ss(+)RNA genomes are either translated,
CC       replicated or encapsidated. {ECO:0000250|UniProtKB:P03305}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Autocatalytically cleaves itself from the polyprotein of the
CC         foot-and-mouth disease virus by hydrolysis of a Lys-|-Gly bond, but
CC         then cleaves host cell initiation factor eIF-4G at bonds -Gly-|-
CC         Arg- and -Lys-|-Arg-.; EC=3.4.22.46;
CC   -!- CATALYTIC ACTIVITY:
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:
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:
CC       Reaction=Selective cleavage of Gln-|-Gly bond in the poliovirus
CC         polyprotein. In other picornavirus reactions Glu may be substituted
CC         for Gln, and Ser or Thr for Gly.; EC=3.4.22.28;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU01222};
CC   -!- SUBUNIT: [Leader protease]: Interacts with host ISG15. Capsid protein
CC       VP1: Interacts with host ITGAV/ITGB6. Interacts with host MAVS; this
CC       interaction inhibits binding of host TRAF3 to MAVS, thereby suppressing
CC       interferon-mediated responses. {ECO:0000250|UniProtKB:P03305}.
CC   -!- SUBUNIT: [Protein 2B]: Forms homooligomers.
CC       {ECO:0000250|UniProtKB:P03305}.
CC   -!- SUBUNIT: [Protein 2C]: Interacts with host VIM. Interacts with host
CC       BECN1. {ECO:0000250|UniProtKB:P03305}.
CC   -!- SUBUNIT: [Protein 3A]: Interacts with host DCTN3.
CC       {ECO:0000250|UniProtKB:P03305}.
CC   -!- SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion. Host cytoplasm
CC       {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion. Host cytoplasm
CC       {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion. Host cytoplasm
CC       {ECO:0000269|PubMed:30404792}.
CC   -!- SUBCELLULAR LOCATION: [Protein 2B]: Host cytoplasmic vesicle membrane
CC       {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic
CC       side {ECO:0000305}. Note=Probably localizes to the surface of
CC       intracellular membrane vesicles that are induced after virus infection
CC       as the site for viral RNA replication. These vesicles are derived from
CC       the endoplasmic reticulum (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Protein 2C]: Host cytoplasmic vesicle membrane
CC       {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic
CC       side {ECO:0000305}. Note=Probably localizes to the surface of
CC       intracellular membrane vesicles that are induced after virus infection
CC       as the site for viral RNA replication. These vesicles are derived from
CC       the endoplasmic reticulum (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane
CC       {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic
CC       side {ECO:0000305}. Note=Probably localizes to the surface of
CC       intracellular membrane vesicles that are induced after virus infection
CC       as the site for viral RNA replication. These vesicles are derived from
CC       the endoplasmic reticulum (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Protein 3B-1]: Virion {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Protein 3B-2]: Virion {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Protein 3B-3]: Virion {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase 3D-POL]: Host
CC       cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein
CC       {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes
CC       to the surface of intracellular membrane vesicles that are induced
CC       after virus infection as the site for viral RNA replication. These
CC       vesicles are derived from the endoplasmic reticulum (By similarity).
CC       {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=Lab;
CC         IsoId=P03308-1; Sequence=Displayed;
CC       Name=Lb;
CC         IsoId=P03308-2; Sequence=VSP_018980;
CC   -!- PTM: Specific enzymatic cleavages in vivo by the viral proteases yield
CC       a variety of precursors and mature proteins. Polyprotein processing
CC       intermediates such as VP0 which is a VP4-VP2 precursor are produced.
CC       During virion maturation, non-infectious particles are rendered
CC       infectious following cleavage of VP0. This maturation cleavage is
CC       followed by a conformational change of the particle. The polyprotein
CC       seems to be cotranslationally cleaved at the 2A/2B junction by a
CC       ribosomal skip from one codon to the next without formation of a
CC       peptide bond. This process would release the L-P1-2A peptide from the
CC       translational complex (By similarity). {ECO:0000250}.
CC   -!- PTM: Myristoylation of VP4 is required during RNA encapsidation and
CC       formation of the mature virus particle. {ECO:0000250}.
CC   -!- PTM: Protein 3B-1, 3B-2 and 3B-3 are uridylylated by the polymerase and
CC       are covalently linked to the 5'-end of genomic RNA. These uridylylated
CC       forms act as a nucleotide-peptide primer for the polymerase (By
CC       similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: The capsid protein VP1 contains the main antigenic
CC       determinants of the virion; therefore, changes in its sequence must be
CC       responsible for the high antigenic variability of the virus.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the picornaviruses polyprotein family.
CC       {ECO:0000305}.
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DR   EMBL; M10975; AAA42593.1; -; Genomic_RNA.
DR   EMBL; AY593752; AAT01695.1; -; Genomic_RNA.
DR   EMBL; J02187; AAA42670.1; -; Genomic_RNA.
DR   PIR; A25794; GNNY4F.
DR   PDB; 1BCV; NMR; -; A=865-883.
DR   PDB; 7D3R; EM; 3.49 A; 4=202-286.
DR   PDBsum; 1BCV; -.
DR   PDBsum; 7D3R; -.
DR   SMR; P03308; -.
DR   MEROPS; C03.008; -.
DR   MEROPS; C28.001; -.
DR   TCDB; 1.A.85.1.4; the poliovirus 2b viroporin (2b viroporin) family.
DR   EvolutionaryTrace; P03308; -.
DR   Proteomes; UP000007707; Genome.
DR   Proteomes; UP000013587; Segment.
DR   GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0039618; C:T=pseudo3 icosahedral viral capsid; IEA:UniProtKB-KW.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
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:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR   GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0039520; P:induction by virus of host autophagy; ISS:UniProtKB.
DR   GO; GO:0039525; P:modulation by virus of host chromatin organization; IEA:UniProtKB-KW.
DR   GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR   GO; GO:0019082; P:viral protein processing; IEA:InterPro.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; IEA:UniProtKB-KW.
DR   CDD; cd23210; Aphthovirus_RdRp; 1.
DR   CDD; cd00205; rhv_like; 3.
DR   Gene3D; 1.20.960.20; -; 1.
DR   Gene3D; 2.60.120.20; -; 3.
DR   Gene3D; 3.30.70.270; -; 2.
DR   Gene3D; 4.10.90.10; Capsid protein VP4 superfamily, Picornavirus; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR015031; Capsid_VP4_Picornavir.
DR   InterPro; IPR037080; Capsid_VP4_sf_Picornavirus.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR004080; FMDV_VP1_coat.
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; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR044067; PCV_3C_PRO.
DR   InterPro; IPR008739; Peptidase_C28.
DR   InterPro; IPR000199; Peptidase_C3A/C3B_picornavir.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001676; Picornavirus_capsid.
DR   InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR   InterPro; IPR033703; Rhv-like.
DR   InterPro; IPR001205; RNA-dir_pol_C.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR029053; Viral_coat.
DR   Pfam; PF05408; Peptidase_C28; 1.
DR   Pfam; PF00548; Peptidase_C3; 1.
DR   Pfam; PF00680; RdRP_1; 1.
DR   Pfam; PF00073; Rhv; 3.
DR   Pfam; PF00910; RNA_helicase; 1.
DR   Pfam; PF08935; VP4_2; 1.
DR   PRINTS; PR00918; CALICVIRUSNS.
DR   PRINTS; PR01542; FMDVP1COAT.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF88633; Positive stranded ssRNA viruses; 2.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS51887; APHTHOVIRUS_LPRO; 1.
DR   PROSITE; PS51874; PCV_3C_PRO; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR   PROSITE; PS51218; SF3_HELICASE_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative initiation; ATP-binding; Capsid protein;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Covalent protein-RNA linkage; Disulfide bond; Helicase; Host cytoplasm;
KW   Host cytoplasmic vesicle; Host membrane; Host-virus interaction; Hydrolase;
KW   Ion channel; Ion transport; Lipoprotein; Membrane;
KW   Modulation of host chromatin by virus; Myristate; Nucleotide-binding;
KW   Nucleotidyltransferase; Phosphoprotein; Protease; RNA-binding;
KW   RNA-directed RNA polymerase; T=pseudo3 icosahedral capsid protein;
KW   Thiol protease; Transferase; Translation regulation; Transport;
KW   Viral attachment to host cell; Viral ion channel;
KW   Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   CHAIN           1..2332
FT                   /note="Genome polyprotein"
FT                   /id="PRO_0000039833"
FT   CHAIN           1..201
FT                   /note="Leader protease"
FT                   /id="PRO_0000039834"
FT   CHAIN           202..504
FT                   /note="Capsid protein VP0"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000374074"
FT   CHAIN           202..286
FT                   /note="Capsid protein VP4"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039837"
FT   CHAIN           287..504
FT                   /note="Capsid protein VP2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039838"
FT   CHAIN           505..725
FT                   /note="Capsid protein VP3"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039839"
FT   CHAIN           726..936
FT                   /note="Capsid protein VP1"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039840"
FT   CHAIN           937..954
FT                   /note="Protein 2A"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039841"
FT   CHAIN           955..1108
FT                   /note="Protein 2B"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039842"
FT   CHAIN           1109..1426
FT                   /note="Protein 2C"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039843"
FT   CHAIN           1427..1579
FT                   /note="Protein 3A"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039844"
FT   CHAIN           1580..1602
FT                   /note="Protein 3B-1"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039845"
FT   CHAIN           1603..1626
FT                   /note="Protein 3B-2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039846"
FT   CHAIN           1627..1650
FT                   /note="Protein 3B-3"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039847"
FT   CHAIN           1651..1863
FT                   /note="Protease 3C"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039848"
FT   CHAIN           1864..2333
FT                   /note="RNA-directed RNA polymerase 3D-POL"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039849"
FT   TOPO_DOM        1..1481
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        1482..1502
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1503..2333
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1..201
FT                   /note="Peptidase C28"
FT   DOMAIN          1190..1354
FT                   /note="SF3 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   DOMAIN          1653..1849
FT                   /note="Peptidase C3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   DOMAIN          2097..2215
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          199..218
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          237..265
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1562..1589
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           869..871
FT                   /note="Cell attachment site"
FT   COMPBIAS        200..218
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        51
FT                   /note="For leader protease activity"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        148
FT                   /note="For leader protease activity"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        163
FT                   /note="For leader protease activity"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        1696
FT                   /note="For protease 3C activity; Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        1734
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        1813
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        2200
FT                   /note="For RdRp activity"
FT                   /evidence="ECO:0000250|UniProtKB:P12296"
FT   BINDING         1218..1225
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   SITE            201..202
FT                   /note="Cleavage; by leader protease"
FT                   /evidence="ECO:0000255"
FT   SITE            286..287
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000255"
FT   SITE            504..505
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            725..726
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            936..937
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            954..955
FT                   /note="Cleavage; by ribosomal skip"
FT                   /evidence="ECO:0000255"
FT   SITE            1108..1109
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1426..1427
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1579..1580
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1602..1603
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1626..1627
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1650..1651
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1863..1864
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1582
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1605
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1629
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250"
FT   LIPID           202
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000250"
FT   DISULFID        511
FT                   /note="Interchain; in VP3 dimer"
FT   VAR_SEQ         1..28
FT                   /note="Missing (in isoform Lb)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_018980"
FT   VARIANT         122..124
FT                   /note="SEV -> AR (in 119ab variant)"
FT   VARIANT         131
FT                   /note="D -> N (in 119ab variant)"
FT   VARIANT         145
FT                   /note="G -> E (in 119ab variant)"
FT   VARIANT         357
FT                   /note="T -> P (in 119ab variant)"
FT   VARIANT         364..365
FT                   /note="LE -> RT (in 119ab variant)"
FT   VARIANT         417
FT                   /note="E -> T (in 119ab variant)"
FT   VARIANT         420
FT                   /note="K -> T (in 119ab variant)"
FT   VARIANT         423
FT                   /note="K -> E (in 119ab variant)"
FT   VARIANT         470
FT                   /note="V -> L (in 119ab variant)"
FT   VARIANT         504
FT                   /note="E -> V (in 119ab variant)"
FT   VARIANT         533
FT                   /note="V -> E (in 119ab variant)"
FT   VARIANT         538
FT                   /note="R -> K (in 119ab variant)"
FT   VARIANT         543
FT                   /note="G -> R (in 119ab variant)"
FT   VARIANT         701
FT                   /note="G -> D (in 119ab variant)"
FT   VARIANT         872
FT                   /note="S -> F (in 119ab variant)"
FT   VARIANT         954
FT                   /note="G -> R (in 119ab variant)"
FT   VARIANT         1034
FT                   /note="S -> T (in 119ab variant)"
FT   VARIANT         1095
FT                   /note="F -> L (in 119ab variant)"
FT   VARIANT         1151
FT                   /note="T -> M (in 119ab variant)"
FT   VARIANT         1156
FT                   /note="P -> L (in 119ab variant)"
FT   VARIANT         1356
FT                   /note="I -> V (in 119ab variant)"
FT   VARIANT         1800
FT                   /note="G -> S (in 119ab variant)"
FT   VARIANT         1846
FT                   /note="R -> K (in 119ab variant)"
FT   VARIANT         1861
FT                   /note="H -> Q (in 119ab variant)"
FT   VARIANT         1939
FT                   /note="R -> A (in 119ab variant)"
FT   VARIANT         2021
FT                   /note="A -> V (in 119ab variant)"
FT   VARIANT         2109
FT                   /note="A -> T (in 119ab variant)"
FT   VARIANT         2162
FT                   /note="G -> D (in 119ab variant)"
FT   VARIANT         2167
FT                   /note="S -> G (in 119ab variant)"
FT   MUTAGEN         51
FT                   /note="C->A: Complete loss of ability to inhibit host
FT                   stress granules assembly."
FT                   /evidence="ECO:0000269|PubMed:30404792"
FT   HELIX           229..232
FT                   /evidence="ECO:0007829|PDB:7D3R"
FT   HELIX           268..275
FT                   /evidence="ECO:0007829|PDB:7D3R"
SQ   SEQUENCE   2333 AA;  259162 MW;  3B61837F593073BD CRC64;
     MNTTNCFIAL VHAIREIRAF FLSRATGKME FTLYNGERKT FYSRPNNHDN CWLNTILQLF
     RYVDEPFFDW VYNSPENLTL AAIKQLEELT GLELHEGGPP ALVIWNIKHL LQTGIGTASR
     PSEVCMVDGT DMCLADFHAG IFLKGQEHAV FACVTSNGWY AIDDEDFYPW TPDPSDVLVF
     VPYDQEPLNG GWKANVQRKL KGAGQSSPAT GSQNQSGNTG SIINNYYMQQ YQNSMDTQLG
     DNAISGGSNE GSTDTTSTHT TNTQNNDWFS KLASSAFTGL FGALLADKKT EETTLLEDRI
     LTTRNGHTTS TTQSSVGVTY GYSTEEDHVA GPNTSGLETR VVQAERFFKK FLFDWTTDKP
     FGHLEKLELP TDHHGVFGHL VDSYAYMRNG WDVEVSAVGN QFNGGCLLVA MVPEWKEFDK
     REKYQLTLFP HQFISPRTNM TAHITVPYLG VNRYDQYKKH KPWTLVIMVV SPLTVSNTAA
     TQIKVYANIA PTYVHVAGEL PSKEGIFPVA CSDGYGGLVT TDPKTADPVY GKVYNPPRTN
     YPGRFTNLLD VAEACPTFLC FDDGKPYVVT RTDDTRLLAK FDVSLAAKHM SNTYLSGIAQ
     YYTQYSGTIN LHFMFTGSTD SKARYMVAYI PPGVETPPET PEGAAHCIHA EWDTGLNSKF
     TFSIPYVSAA DYAYTASDTA ETTNVQGWVC IYQITHGKAE GDTLVVSASA GKDFELRLPI
     DPRSQTTATG ESADPVTTTV ENYGGETQVQ RRHHTDVSFI MDRFVKIKSL NPTHVIDLMQ
     THQHGLVGAL LRAATYYFSD LEIVVRHDGN LTWVPNGAPE AALSNTGNPT AYNKAPFTRL
     ALPYTAPHRV LATVYNGTNK YSASGSGVRG DSGSLAPRVA RQLPASFNYG AIKAETIHEL
     LVRMKRAELY CPRPLLAIEV SSQDRHKQKI IAPGKQLLNF DLLKLAGDVE SNPGPFFFAD
     VRSNFSKLVD TINQMQEDMS TKHGPDFNRL VSAFEELATG VKAIRTGLDE AKPWYKLIKL
     LSRLSCMAAV AARSKDPVLV AIMLADTGLE ILDSTFVVKK ISDSLSSLFH VPAPVFSFGA
     PVLLAGLVKV ASSFFRSTPE DLERAEKQLK ARDINDIFAI LKNGEWLVKL ILAIRDWIKA
     WIASEEKFVT TTDLVPGILE KQRDLNDPSK YKEAKEWLDN ARQACLKSGN VHIANLCKVV
     APAPSKSRPE PVVVCLRGKS GQGKSFLANV LAQAISTHFT GRTDSVWYCP PDPDHFDGYN
     QQTVVVMDDL GQNPDGKDFK YFAQMVSTTG FIPPMASLED KGKPFNSKVI IATTNLYSGF
     TPRTMVCPDA LNRRFHFDID VSAKDGYKIN NKLDIIKALE DTHTNPVAMF QYDCALLNGM
     AVEMKRMQQD MFKPQPPLQN VYQLVQEVIE RVELHEKVSS HPIFKQISIP SQKSVLYFLI
     EKGQHEAAIE FFEGMVHDSI KEELRPLIQQ TSFVKRAFKR LKENFEIVAL CLTLLANIVI
     MIRETRKRQK MVDDAVNEYI EKANITTDDT TLDEAEKNPL ETSGASTVGF RERTLTGQRA
     CNDVNSEPAR PAEEQPQAEG PYTGPLERQR PLKVRAKLPQ QEGPYAGPLE RQKPLKVKAK
     APVVKEGPYE GPVKKPVALK VKAKNLIVTE SGAPPTDLQK MVMGNTKPVE LILDGKTVAI
     CCATGVFGTA YLVPRHLFAE KYDKIMLDGR AMTDSDYRVF EFEIKVKGQD MLSDAALMVL
     HRGNRVRDIT KHFRDTARMK KGTPVVGVVN NADVGRLIFS GEALTYKDIV VCMDGDTMPG
     LFAYKAATKA GYCGGAVLAK DGADTFIVGT HSAGGNGVGY CSCVSRSMLL RMKAHVDPEP
     HHEGLIVDTR DVEERVHVMR KTKLAPTVAH GVFNPEFGPA ALSNKDPRLN EGVVLDEVIF
     SKHKGDTKMS AEDKALFRRC AADYASRLHS VLGTANAPLS IYEAIKGVDG LDAMESDTAP
     GLPWAFQGKR RGALIDFENG TVGPEVEAAL KLMEKREYKF ACQTFLKDEI RPMEKVRAGK
     TRIVDVLPVE HILYTRMMIG RFCAQMHSNN GPQIGSAVGC NPDVDWQRFG THFAQYRNVW
     DVDYSAFDAN HCSDAMNIMF EEVFRTDFGF HPNAEWILKT LVNTEHAYEN KRITVEGGMP
     SGCSATSIIN TILNNIYVLY ALRRHYEGVE LDTYTMISYG DDIVVASDYD LDFEALKPHF
     KSLGQTITPA DKSDKGFVLG HSITDVTFLK RHFHIDYGTG FYKPVMASKT LEAILSFARR
     GTIQEKLTSV AGLAVHSGPD EYRRLFEPFQ GLFEIPSYRS LYLRWVNAVC GDA
//