POLG_FMDVA
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 03-AUG-2022, entry version 186.
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; Aphthovirus.
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. Cleaves also the host translation
CC initiation factors EIF4G1 and EIF4G3, in order to shutoff 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 DDX58,
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 mofidier that can no
CC longer be attached to target proteins. Cleaves also 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; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
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:ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0017111; F:nucleoside-triphosphatase activity; IEA:RHEA.
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-directed 5'-3' 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: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:0062030; P:negative regulation of stress granule assembly; IDA:UniProtKB.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0039690; P:positive stranded viral RNA replication; ISS:UniProtKB.
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:0018144; P:RNA-protein covalent cross-linking; IEA:UniProtKB-KW.
DR GO; GO:0039611; P:suppression by virus of host translation initiation factor activity; ISS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
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 CDD; cd00205; rhv_like; 3.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.60.120.20; -; 3.
DR Gene3D; 3.30.70.270; -; 2.
DR Gene3D; 4.10.90.10; -; 1.
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; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF56672; SSF56672; 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
