POLG_FMDV1
ID POLG_FMDV1 Reviewed; 2332 AA.
AC P03306; Q64768; Q84750; Q84751; Q84752; Q84753; Q84754; Q84760; Q84761;
AC Q84762; Q84763; Q84764; Q84765; Q84766; Q84767; Q84768; Q84769; Q89824;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, 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 (strain A10-61) (Aphthovirus A) (FMDV).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Picornaviridae; Aphthovirus.
OX NCBI_TaxID=12112;
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=6324120; DOI=10.1093/nar/12.5.2461;
RA Carroll A.R., Rowlands D.J., Clarke B.E.;
RT "The complete nucleotide sequence of the RNA coding for the primary
RT translation product of foot and mouth disease virus.";
RL Nucleic Acids Res. 12:2461-2472(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 115-1048.
RX PubMed=6282711; DOI=10.1016/0378-1119(82)90068-3;
RA Boothroyd J.C., Harris T.J.R., Rowlands D.J., Lowe P.A.;
RT "The nucleotide sequence of cDNA coding for the structural proteins of
RT foot-and-mouth disease virus.";
RL Gene 17:153-161(1982).
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:2BHG}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1650-1855, AND ACTIVE SITE
RP (PROTEASE 3C).
RX PubMed=15654079; DOI=10.1074/jbc.m413254200;
RA Birtley J.R., Knox S.R., Jaulent A.M., Brick P., Leatherbarrow R.J.,
RA Curry S.;
RT "Crystal structure of foot-and-mouth disease virus 3C protease. New
RT insights into catalytic mechanism and cleavage specificity.";
RL J. Biol. Chem. 280:11520-11527(2005).
RN [5] {ECO:0007744|PDB:1ZBA, ECO:0007744|PDB:1ZBE}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 726-937; 287-504; 505-725 AND
RP 202-286.
RX PubMed=15958669; DOI=10.1099/vir.0.80730-0;
RA Fry E.E., Newman J.W., Curry S., Najjam S., Jackson T., Blakemore W.,
RA Lea S.M., Miller L., Burman A., King A.M., Stuart D.I.;
RT "Structure of Foot-and-mouth disease virus serotype A10 61 alone and
RT complexed with oligosaccharide receptor: receptor conservation in the face
RT of antigenic variation.";
RL J. Gen. Virol. 86:1909-1920(2005).
RN [6] {ECO:0007744|PDB:2J92}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1649-1855, AND MUTAGENESIS OF
RP CYS-1791.
RX PubMed=17065215; DOI=10.1128/jvi.01587-06;
RA Sweeney T.R., Roque-Rosell N., Birtley J.R., Leatherbarrow R.J., Curry S.;
RT "Structural and mutagenic analysis of foot-and-mouth disease virus 3C
RT protease reveals the role of the beta-ribbon in proteolysis.";
RL J. Virol. 81:115-124(2007).
RN [7] {ECO:0007744|PDB:2WV4, ECO:0007744|PDB:2WV5}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1650-1862 AND 931-940.
RX PubMed=19883658; DOI=10.1016/j.jmb.2009.10.048;
RA Zunszain P.A., Knox S.R., Sweeney T.R., Yang J., Roque-Rosell N.,
RA Belsham G.J., Leatherbarrow R.J., Curry S.;
RT "Insights into cleavage specificity from the crystal structure of foot-and-
RT mouth disease virus 3C protease complexed with a peptide substrate.";
RL J. Mol. Biol. 395:375-389(2010).
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 {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. {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 (via R-G-D motif) with host ITGAV/ITGB6.
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 Comment=Both isoforms are able to cleave the L/VP0 junction and the
CC host translation initiation factor EIF4G1.;
CC Name=Lab; Synonyms=P20a;
CC IsoId=P03306-1; Sequence=Displayed;
CC Name=Lb; Synonyms=P16;
CC IsoId=P03306-2; Sequence=VSP_018979;
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA25127.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X00429; CAA25127.1; ALT_FRAME; Genomic_RNA.
DR EMBL; V01130; CAA24361.1; -; Genomic_RNA.
DR PIR; A93508; GNNY2F.
DR PDB; 1ZBA; X-ray; 2.00 A; 1=726-937, 2=287-504, 3=505-725, 4=202-286.
DR PDB; 1ZBE; X-ray; 3.00 A; 1=726-937, 2=287-504, 3=505-725, 4=202-286.
DR PDB; 2BHG; X-ray; 1.90 A; A/B=1650-1855.
DR PDB; 2J92; X-ray; 2.20 A; A/B=1649-1855.
DR PDB; 2WV4; X-ray; 2.50 A; A/B=1650-1862, C/D=931-940.
DR PDB; 2WV5; X-ray; 2.70 A; A/B/C/D=1650-1862, E/F/G/H=936-940.
DR PDBsum; 1ZBA; -.
DR PDBsum; 1ZBE; -.
DR PDBsum; 2BHG; -.
DR PDBsum; 2J92; -.
DR PDBsum; 2WV4; -.
DR PDBsum; 2WV5; -.
DR SMR; P03306; -.
DR MEROPS; C03.008; -.
DR EvolutionaryTrace; P03306; -.
DR Proteomes; UP000008764; Genome.
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: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_0000039816"
FT CHAIN 1..201
FT /note="Leader protease"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039817"
FT CHAIN 202..504
FT /note="Capsid protein VP0"
FT /evidence="ECO:0000255"
FT /id="PRO_0000374073"
FT CHAIN 202..286
FT /note="Capsid protein VP4"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039820"
FT CHAIN 287..504
FT /note="Capsid protein VP2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039821"
FT CHAIN 505..725
FT /note="Capsid protein VP3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039822"
FT CHAIN 726..935
FT /note="Capsid protein VP1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039823"
FT CHAIN 936..953
FT /note="Protein 2A"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039824"
FT CHAIN 954..1107
FT /note="Protein 2B"
FT /evidence="ECO:0000255"
FT /id="PRO_0000310973"
FT CHAIN 1108..1425
FT /note="Protein 2C"
FT /evidence="ECO:0000255"
FT /id="PRO_0000310974"
FT CHAIN 1426..1578
FT /note="Protein 3A"
FT /evidence="ECO:0000255"
FT /id="PRO_0000310975"
FT CHAIN 1579..1601
FT /note="Protein 3B-1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039825"
FT CHAIN 1602..1625
FT /note="Protein 3B-2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039826"
FT CHAIN 1626..1649
FT /note="Protein 3B-3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039827"
FT CHAIN 1650..1862
FT /note="Protease 3C"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039828"
FT CHAIN 1863..2332
FT /note="RNA-directed RNA polymerase 3D-POL"
FT /evidence="ECO:0000255"
FT /id="PRO_0000039829"
FT TOPO_DOM 1..1480
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1481..1501
FT /evidence="ECO:0000255"
FT TOPO_DOM 1502..2332
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1..201
FT /note="Peptidase C28"
FT DOMAIN 1189..1353
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DOMAIN 1652..1848
FT /note="Peptidase C3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT DOMAIN 2096..2214
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..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1529..1588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 867..870
FT /note="Cell attachment site"
FT /evidence="ECO:0000269|PubMed:15958669"
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 1695
FT /note="For protease 3C activity; Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222,
FT ECO:0000269|PubMed:15654079"
FT ACT_SITE 1733
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222,
FT ECO:0000269|PubMed:15654079"
FT ACT_SITE 1812
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222,
FT ECO:0000269|PubMed:15654079"
FT ACT_SITE 2200
FT /note="For RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P12296"
FT BINDING 1217..1224
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 935..936
FT /note="Cleavage; by picornain 3C"
FT /evidence="ECO:0000255"
FT SITE 953..954
FT /note="Cleavage; by ribosomal skip"
FT /evidence="ECO:0000255"
FT SITE 1107..1108
FT /note="Cleavage; by picornain 3C"
FT /evidence="ECO:0000255"
FT SITE 1425..1426
FT /note="Cleavage; by picornain 3C"
FT /evidence="ECO:0000255"
FT SITE 1578..1579
FT /note="Cleavage; by picornain 3C"
FT /evidence="ECO:0000255"
FT SITE 1601..1602
FT /note="Cleavage; by picornain 3C"
FT /evidence="ECO:0000255"
FT SITE 1625..1626
FT /note="Cleavage; by picornain 3C"
FT /evidence="ECO:0000255"
FT SITE 1649..1650
FT /note="Cleavage; by picornain 3C"
FT /evidence="ECO:0000255"
FT SITE 1831
FT /note="Important for catalytic activity"
FT /evidence="ECO:0007744|PDB:2BHG"
FT SITE 1862..1863
FT /note="Cleavage; by picornain 3C"
FT /evidence="ECO:0000255"
FT MOD_RES 1581
FT /note="O-(5'-phospho-RNA)-tyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 1604
FT /note="O-(5'-phospho-RNA)-tyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 1628
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_018979"
FT MUTAGEN 1791
FT /note="C->S: Almost complete loss of picornain 3C
FT activity."
FT /evidence="ECO:0000269|PubMed:17065215"
FT CONFLICT 396
FT /note="S -> C (in Ref. 2; CAA24361)"
FT /evidence="ECO:0000305"
FT CONFLICT 632
FT /note="P -> L (in Ref. 2; CAA24361)"
FT /evidence="ECO:0000305"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 268..274
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 301..305
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 308..314
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 342..344
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 348..355
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 364..370
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 376..383
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 384..397
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 404..414
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 422..428
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 429..434
FT /evidence="ECO:0007829|PDB:1ZBA"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 440..446
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 450..455
FT /evidence="ECO:0007829|PDB:1ZBA"
FT TURN 457..459
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 463..474
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:1ZBE"
FT STRAND 483..499
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 548..554
FT /evidence="ECO:0007829|PDB:1ZBA"
FT TURN 562..564
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 565..569
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 572..574
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 577..583
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 588..590
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 594..599
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 602..607
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 609..615
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 622..630
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 632..636
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 641..644
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 647..653
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 659..664
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 669..671
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 673..676
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 688..698
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 703..710
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 715..719
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 730..732
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 740..743
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 753..755
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 757..761
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 763..767
FT /evidence="ECO:0007829|PDB:1ZBE"
FT STRAND 772..775
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 778..780
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 786..792
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 794..809
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 811..814
FT /evidence="ECO:0007829|PDB:1ZBA"
FT HELIX 820..824
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 828..831
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 838..842
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 847..853
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 890..892
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 894..911
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 921..923
FT /evidence="ECO:0007829|PDB:1ZBA"
FT STRAND 936..938
FT /evidence="ECO:0007829|PDB:2WV5"
FT HELIX 1657..1664
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1665..1672
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1675..1687
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1689..1693
FT /evidence="ECO:0007829|PDB:2BHG"
FT HELIX 1694..1697
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1702..1706
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1709..1711
FT /evidence="ECO:0007829|PDB:2BHG"
FT HELIX 1713..1715
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1716..1719
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1722..1725
FT /evidence="ECO:0007829|PDB:2WV4"
FT STRAND 1726..1728
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1733..1742
FT /evidence="ECO:0007829|PDB:2BHG"
FT HELIX 1749..1751
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1752..1755
FT /evidence="ECO:0007829|PDB:2J92"
FT STRAND 1763..1770
FT /evidence="ECO:0007829|PDB:2BHG"
FT TURN 1771..1773
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1774..1784
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1800..1804
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1815..1820
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1823..1834
FT /evidence="ECO:0007829|PDB:2BHG"
FT STRAND 1837..1842
FT /evidence="ECO:0007829|PDB:2BHG"
FT HELIX 1845..1853
FT /evidence="ECO:0007829|PDB:2BHG"
SQ SEQUENCE 2332 AA; 259319 MW; FE8A553569F1A6DD CRC64;
MNTTNCFIAL VYLIREIKTL FRSRTKGKME FTLHNGEKKT FYSRPNNHDN CWLNTILQLF
RYVDEPFFDW VYNSPENLTL DAIKQLENFT GLELHEGGPP ALVIWNIKHL LQTGIGTASR
PSEVCMVDGT DMCLADFHAG IFMKGQEHAV FACVTSDGWY AIDDEDFYPW TPDPSDVLVF
VPYDQEPLNG DWKTQVQKKL KGAGQSSPAT GSQNQSGNTG SIINNYYMQQ YQNSMSTQLG
DNTISGGSNE GSTDTTSTHT TNTQNNDWFS KLASSAFTGL FGALLADKKT EETTLLEDRI
LTTRNGHTTS TTQSSVGVTY GYSTEEDHVA GPNTSGLETR VVQAERFFKK FLFDWTTDKP
FGYLTKLELP TDHHGVFGHL VDSYAYMRNG WDVEVSAVGN QFNGGCLLVA MVPEWKAFDT
REKYQLTLFP HQFISPRTNM TAHITVPYLG VNRYDQYKKH KPWTLVVMVL SPLTVSNTAA
PQIKVYANIA PTYVHVAGEL PSKEGIFPVA CADGYGGLVT TDPKTADPVY GKVYNPPKTN
YPGRFTNLLD VAEACPTFLR FDDGKPYVVT RADDTRLLAK FDVSLAAKHM SNTYLSGIAQ
YYTQYSGTIN LHFMFTGSTD SKARYMVAYI PPGVETPPDT PEEAAHCIHA EWDTGLNSKF
TFSIPYVSAA DYAYTASDTA ETTNVQGWVC VYQITHGKAE NDTLLVSASA GKDFELRLPI
DPRTQTTTTG ESADPVTTTV ENYGGDTQVQ RRHHTDVGFI MDRFVKINSL SPTHVIDLMQ
THKHGIVGAL LRAATYYFSD LEIVVRHDGN LTWVPNGAPE AALSNTSNPT AYNKAPFTRL
ALPYTAPHRV LATVYDGTNK YSASDSRSGD LGSIAARVAT QLPASFNYGA IQAQAIHELL
VRMKRAELYC PRPLLAIKVT SQDRYKQKII APAKQLLNFD LLKLAGDVES NLGPFFFADV
RSNFSKLVDT INQMQEDMST KHGPDFNRLV SAFEELATGV KAIRTGLDEA KPWYKLIKLL
SRLSCMAAVA ARSKDPVLVA IMLADTGLEI LDSTFVVKKS SDSLSSLFHV PAPAFSFGAP
VLLAGLVKVA SSFFRSTPED LERAEKQLKA RDINDIFAIL KNGEWLVKLI LAIRDWIKAW
IASEEKFVTM TDLVPGILEK QRDLNDPGKY KEAKEWLDNA RQACLKSGNV HIANLCKVVA
PAPSKSRPEP VVVCLRGKSG QGKSFLANVL AQAISTHFTG RIDSVWYCPP DPDHFDGYNQ
QTVVVMDDLG QNPDGKDFKY FAQMVSTTGF IPPMASLEDK GKPFNSKVII ATTNLYSGFT
PRTMVCPDAL NRRFHFDIDV SAKDGYKINN KLDIIKALED THTNPVAMFQ YDCALLNGMA
VEMKRLQQDM FKPQPPLQNV YQLVQEVIER VELHEKVSSH PIFKQISIPS QKSVLYFLIE
KGQHEAAIEF FEGMVHDSVK EELRPLIQQT SFVKRAFKRL KENFEIVALC LTLLANIVIM
IRETRKRQKM VDDAVNEYIE RANITTDDKT LDEAEKNPLE TSGASTVGFR ERSLTGQKVR
DDVSSEPAQP AEDQPQAEGP YSGPLERQKP LKVRAKLPQQ EGPYAGPMER QKPLKVKVKA
PVVKEGPYEG PVKKPVALKV KARNLIVTES GAPPTDLQKM VMGNTKPVEL NLDGKTVAIC
CATGVFGTAY LVPRHLFAEK YDKIMLDGRA MTDSDYRVFE FEIKVKGQDM LSDAALIVLH
RGNCVRDITK HFRDTARMKK GTPVVGVVNN ADVGRLIFSG EALTYKDIVV CMDGDTMPGL
FAYKAATRAG YCGGAVLAKD GADTFIVGTH SAGGNGVGYC SCVSRSMLQK MKAHVDPEPH
HEGLIVDTRD VEERVHVMRK TKLAPTVAYG VFNPEFGPAA LSNKDPRLNE GVVLDDVIFS
KHKGDAKMTE EDKALFRRCA ADYASRLHSV LGTANAPLSI YEAIKGVDGL DAMEPDTAPG
LPWALQGKRR GALIDFENGT VGPEVEAALK LMEKREYKFA CQTFLKDEIR PMEKVRAGKT
RIVDVLPVEH ILYTKMMIGR FCAQMHSNNG PQIGSAVGCN PDVDWQRFGT HFAQYRNVWD
VDYSAFDANH CSDAMNIMFE EVFRTDFGFH PNAEWILKTL VNTEHAYENK RITVEGGMPS
GCSATSIINT ILNNIYVLYA LRRHYEGVEL DTYTMISYGD DIVVASDYDL DFEALKPHFK
SLGQTITPAD KSDKGFVLGQ SITDVTFLKR HFHMDYGTGF YKPVMASKTL EAILSFARRG
TIQEKLISVA GLAVHSGPDE YRRLFEPFQG LFEIPSYRSL YLRWVNAVCG DA
