ID   POLG_FMDVT              Reviewed;        2327 AA.
AC   P15072; Q6PMY1; Q84755; Q84756; Q84757; Q84758;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   29-MAY-2013, sequence version 2.
DT   24-JAN-2024, entry version 173.
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 -/Germany/C1Oberbayen/1960 serotype
OS   C) (FMDV).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Picornavirales; Picornaviridae; Caphthovirinae; Aphthovirus;
OC   Foot-and-mouth disease virus.
OX   NCBI_TaxID=12121;
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].
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   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-1011.
RX   PubMed=6316275; DOI=10.1093/nar/11.22.7873;
RA   Beck E., Forss S., Strebel K., Cattaneo R., Feil G.;
RT   "Structure of the FMDV translation initiation site and of the structural
RT   proteins.";
RL   Nucleic Acids Res. 11:7873-7885(1983).
RN   [3]
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   [4] {ECO:0007744|PDB:1FMD}
RP   X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 287-504 AND 505-723.
RX   PubMed=8081743; DOI=10.1016/s0969-2126(00)00014-9;
RA   Lea S., Hernandez J., Blakemore W., Brocchi E., Curry S., Domingo E.,
RA   Fry E., Abu-Ghazaleh R., King A., Newman J.;
RT   "The structure and antigenicity of a type C foot-and-mouth disease virus.";
RL   Structure 2:123-139(1994).
RN   [5] {ECO:0007744|PDB:1EJO}
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 859-873.
RX   PubMed=10811933; DOI=10.1099/0022-1317-81-6-1495;
RA   Ochoa W.F., Kalko S.G., Mateu M.G., Gomes P., Andreu D., Domingo E.,
RA   Fita I., Verdaguer N.;
RT   "A multiply substituted G-H loop from foot-and-mouth disease virus in
RT   complex with a neutralizing antibody: a role for water molecules.";
RL   J. Gen. Virol. 81:1495-1505(2000).
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       {ECO:0000250|UniProtKB:P03305, ECO:0000250|UniProtKB:P03308}.
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. Cooperates with host DDX56 to inhibit IRF3
CC       nuclear translocation and subsequent type I interferon production.
CC       {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 + 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=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=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 (via R-G-D motif) with host ITGAV/ITGB6. Interacts with
CC       host MAVS; this interaction inhibits binding of host TRAF3 to MAVS,
CC       thereby suppressing interferon-mediated responses.
CC       {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:0000305}.
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=P15072-1; Sequence=Displayed;
CC       Name=Lb;
CC         IsoId=P15072-2; Sequence=VSP_018983;
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   -!- 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   -!- 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   -!- SIMILARITY: Belongs to the picornaviruses polyprotein family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Virus Particle ExploreR db; Note=Icosahedral capsid
CC       structure;
CC       URL="https://viperdb.scripps.edu/Info_Page.php?VDB=1fmd";
CC   -!- WEB RESOURCE: Name=Virus Particle ExploreR db; Note=Icosahedral capsid
CC       structure in complex with a fab fragment of a neutralizing antibody;
CC       URL="https://viperdb.scripps.edu/Info_Page.php?VDB=1qgc";
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DR   EMBL; AY593805; AAT01748.1; -; Genomic_RNA.
DR   EMBL; X00130; CAA24960.2; -; Genomic_RNA.
DR   PIR; A20288; GNNYC1.
DR   PDB; 1EJO; X-ray; 2.30 A; P=859-873.
DR   PDB; 1FMD; X-ray; 3.50 A; 2=287-504, 3=505-723.
DR   PDB; 1QGC; EM; 30.00 A; 2=287-504, 3=505-723.
DR   PDBsum; 1EJO; -.
DR   PDBsum; 1FMD; -.
DR   PDBsum; 1QGC; -.
DR   SMR; P15072; -.
DR   MEROPS; C03.008; -.
DR   MEROPS; C28.001; -.
DR   ABCD; P15072; 1 sequenced antibody.
DR   EvolutionaryTrace; P15072; -.
DR   Proteomes; UP000012671; Genome.
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- and caveolin-independent endocytosis of virus by host;
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..2327
FT                   /note="Genome polyprotein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000039891"
FT   CHAIN           1..201
FT                   /note="Leader protease"
FT                   /id="PRO_0000039892"
FT   CHAIN           202..504
FT                   /note="Capsid protein VP0"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000374077"
FT   CHAIN           202..286
FT                   /note="Capsid protein VP4"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039895"
FT   CHAIN           287..504
FT                   /note="Capsid protein VP2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039896"
FT   CHAIN           505..723
FT                   /note="Capsid protein VP3"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039897"
FT   CHAIN           724..930
FT                   /note="Capsid protein VP1"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039898"
FT   CHAIN           931..948
FT                   /note="Protein 2A"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000039899"
FT   CHAIN           949..1102
FT                   /note="Protein 2B"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000310980"
FT   CHAIN           1103..1420
FT                   /note="Protein 2C"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000422519"
FT   CHAIN           1421..1573
FT                   /note="Protein 3A"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000422520"
FT   CHAIN           1574..1596
FT                   /note="Protein 3B-1"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000422521"
FT   CHAIN           1597..1620
FT                   /note="Protein 3B-2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000422522"
FT   CHAIN           1621..1644
FT                   /note="Protein 3B-3"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000422523"
FT   CHAIN           1645..1857
FT                   /note="Protease 3C"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000422524"
FT   CHAIN           1858..2327
FT                   /note="RNA-directed RNA polymerase 3D-POL"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000422525"
FT   TOPO_DOM        1..1475
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        1476..1496
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1497..2327
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1..201
FT                   /note="Peptidase C28"
FT   DOMAIN          1184..1348
FT                   /note="SF3 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   DOMAIN          1647..1843
FT                   /note="Peptidase C3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   DOMAIN          2091..2209
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          1524..1579
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           864..866
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        1690
FT                   /note="For protease 3C activity; Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        1728
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        1807
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        2195
FT                   /note="For RdRp activity"
FT                   /evidence="ECO:0000250|UniProtKB:P12296"
FT   BINDING         1212..1219
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            723..724
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            930..931
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            948..949
FT                   /note="Cleavage; by ribosomal skip"
FT                   /evidence="ECO:0000255"
FT   SITE            1102..1103
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1420..1421
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1573..1574
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1596..1597
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1620..1621
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1644..1645
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   SITE            1857..1858
FT                   /note="Cleavage; by picornain 3C"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1576
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1599
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1623
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                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..28
FT                   /note="Missing (in isoform Lb)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_018983"
FT   VARIANT         8
FT                   /note="I -> T"
FT   VARIANT         48
FT                   /note="H -> Q"
FT   VARIANT         307
FT                   /note="H -> Q"
FT   VARIANT         408..409
FT                   /note="LV -> QA"
FT   VARIANT         726
FT                   /note="A -> T"
FT   VARIANT         852
FT                   /note="A -> G"
FT   VARIANT         867
FT                   /note="S -> L"
FT   VARIANT         876
FT                   /note="R -> G"
FT   STRAND          291..293
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          302..305
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          308..311
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   HELIX           332..334
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   TURN            342..344
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          348..355
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          364..372
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   HELIX           375..383
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          384..398
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          404..413
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   HELIX           421..423
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          429..434
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   TURN            436..438
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          440..446
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          450..455
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   HELIX           457..459
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          463..474
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   TURN            476..478
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          483..499
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   HELIX           548..554
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          561..563
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          571..574
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          576..581
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   TURN            587..591
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   HELIX           593..598
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          601..605
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          608..614
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          621..629
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          631..633
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   HELIX           639..642
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          645..651
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          659..662
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          667..669
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          671..674
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          686..696
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          701..708
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          713..717
FT                   /evidence="ECO:0007829|PDB:1FMD"
FT   STRAND          863..865
FT                   /evidence="ECO:0007829|PDB:1EJO"
SQ   SEQUENCE   2327 AA;  258119 MW;  A81AB150E79617DD CRC64;
     MNTTDCFIAV VNAIREIRAL FLPRTTGKME FTLHDGEKKV FYSRPNNHDN CWLNTILQLF
     RYVDEPFFDW VYNSPENLTL EAIKQLEELT GLELREGGPP ALVIWNIKHL LHTGIGTASR
     PSEVCMVDGT DMCLADFHAG IFMKGQEHAV FACVTSNGWY AIDDEDFYPW TPDPSDVLVF
     VPYDQEPLNE GWKANVQRKL KGAGQSSPAT GSQNQSGNTG SIINNYYMQQ YQNSMDTQLG
     DNAISGGSNE GSTDTTSTHT TNTQNNDWFS KLASSAFSGL FGALLADKKT EETTLLEDRI
     LTTRNGHTTS TTQSSVGVTF GYATAEDSTS GPNTSGLETR VHQAERFFKM ALFDWVPSQN
     FGHMHKVVLP HEPKGVYGGL VKSYAYMRNG WDVEVTAVGN QFNGGCLLVA LVPEMGDISD
     REKYQLTLYP HQFINPRTNM TAHITVPYVG VNRYDQYKQH RPWTLVVMVV APLTTNTAGA
     QQIKVYANIA PTNVHVAGEL PSKEGIFPVA CSDGYGNMVT TDPKTADPAY GKVYNPPRTA
     LPGRFTNYLD VAEACPTFLM FENVPYVSTR TDGQRLLAKF DVSLAAKHMS NTYLAGLAQY
     YTQYTGTINL HFMFTGPTDA KARYMVAYVP PGMDAPDNPE EAAHCIHAEW DTGLNSKFTF
     SIPYISAADY AYTASHEAET TCVQGWVCVY QITHGKADAD ALVVSASAGK DFELRLPVDA
     RQQTTATGES ADPVTTTVEN YGGETQVQRR HHTDVAFVLD RFVKVTVSGN QHTLDVMQAH
     KDNIVGALLR AATYYFSDLE IAVTHTGKLT WVPNGAPVSA LDNTTNPTAY HKGPLTRLAL
     PYTAPHRVLA TAYTGTTTYT ASTRGDSAHL TATRARHLPT SFNFGAVKAE TITELLVRMK
     RAELYCPRPI LPIQPTGDRH KQPLVAPAKQ LLNFDLLKLA GDVESNPGPF FFSDVRSNFS
     KLVETINQMQ EDMSTKHGPD FNRLVSAFEE LASGVKAIRT GLDEAKPWYK LIKLLSRLSC
     MAAVAARSKD PVLVAIMLAD TGLEILDSTF VVKKISDSLS SLFHVPAPAF SFGAPILLAG
     LVKVASSFFR STPEDLERAE KQLKARDIND IFAILKNGEW LVKLILAIRD WIKAWIASEE
     KFVTMTDLVP GILEKQRDLN DPSKYKDAKE WLDNTRQACL KSGNVHIANL CKVVAPAPSK
     SRPEPVVVCL RGKSGQGKSF LANVLAQAIS THLTGRTDSV WYCPPDPDHF DGYNQQTVVV
     MDDLGQNPDG KDFKYFAQMV STTGFIPPMA SLEDKGKPFS SKVIIATTNL YSGFTPKTMV
     CPDALNRRFH FDIDVSAKDG YKINNKLDII KALEDTHTNP VAMFQYDCAL LNGMAVEMKR
     LQQDMFKPQP PLQNVYQLVQ EVIERVELHE KVSSHPIFKQ ISIPSQKSVL YFLIEKGQHE
     AAIEFFEGMV HDSIKEELRP LIQQTSFVKR AFKRLKENFE IVALCLTLLA NIVIMIRETH
     KRQKMVDDAV NEYIEKANIT TDDKTLDEAE KNPLETSGAS TVGFRERTLP GQKARDDVNS
     EPAQPTEEQP QAEGPYAGPL ERQRPLKVRA KLPQQEGPYA GPMERQKPLK VKARAPVVKE
     GPYEGPVKKP VALKVKAKNL IVTESGAPPT DLQKMVMGNT KPVELILDGK TVAICCATGV
     FGTAYLVPRH LFAEKYDKIM LDGRALTDSD YRVFEFEIKV KGQDMLSDAA LMVLHRGNRV
     RDITKHFRDV ARMKKGTPVV GVINNADVGR LIFSGEALTY KDIVVCMDGD TMPGLFAYKA
     ATKAGYCGGA VLAKDGADTF IVGTHSAGGN GVGYCSCVSR SMLLKMKAHI DPEPHHEGLI
     VDTRDVEERV HVMRKTKLAP TVAHGVFNPE FGPAALSNKD PRLNEGVVLD EVIFSKHKGD
     TKMSEEDKAL FRRCAADYAS RLHSVLGTAN APLSIYEAIK GVDGLDAMEP DTAPGLPWAL
     QGKRRGALID FENGTVGPEV EAALKLMEKR EYKFACQTFL KDEIRPMEKV RAGKTRIVDV
     LPVEHILYTR MMIGRFCAQM HSNNGPQIGS AVGCNPDVDW QRFGTHFAQY RNVWDVDYSA
     FDANHCSDAM NIMFEEVFRT EFGFHPNAEW ILKTLVNTEH AYENKRITVE GGMPSGCSAT
     SIINTILNNI YVLYALRRHY EGVELDTYTM ISYGDDIVVA SDYDLDFEAL KPHFKSLGQT
     ITPADKSDKG FVLGHSITDV TFLKRHFHMD YGTGFYKPVM ASKTLEAILS FARRGTIQEK
     LISVAGLAVH SGPDEYRRLF EPFQGLFEIP SYRSLYLRWV NAVCGDA
//