UniProt functional annotation for P03311



	UniProt functional annotation for P03311

UniProt code: P03311.

Organism: Foot-and-mouth disease virus (isolate -/Spain/S8c1SantaPau/1970 serotype C) (FMDV).

Taxonomy: Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; Picornavirales; Picornaviridae; Aphthovirus.

Function: [Leader protease]: Autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. Cleaves also the host translation initiation factors EIF4G1 and EIF4G3, in order to shutoff the capped cellular mRNA transcription. Plays a role in counteracting host innate antiviral response using diverse mechanisms. Possesses a deubiquitinase activity acting on both 'Lys'-48 and 'Lys'-63-linked polyubiquitin chains. In turn, inhibits the ubiquitination and subsequent activation of key signaling molecules of type I IFN response such as host DDX58, TBK1, TRAF3 and TRAF6. Inhibits host NF-kappa-B activity by inducing a decrease in RELA mRNA levels. Cleaves a peptide bond in the C-terminus of host ISG15, resulting in the damaging of this mofidier that can no longer be attached to target proteins. Cleaves also host G3BP1 and G3BP2 in order to inhibit cytoplasmic stress granules assembly. {ECO:0000250|UniProtKB:P03305, ECO:0000250|UniProtKB:P03308}.

Function: Capsid protein VP4: Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. Capsid protein VP4 is released, capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm. After genome has been released, the channel shrinks. {ECO:0000250|UniProtKB:P03300}.

Function: Capsid protein VP2: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP1 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome. {ECO:0000250|UniProtKB:P03305}.

Function: Capsid protein V1: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome. Mediates cell entry by attachment to an integrin receptor, usually host ITGAV/ITGB6, via a conserved arginine-glycine-aspartic acid (R-G-D) motif. {ECO:0000250|UniProtKB:P03305}.

Function: Capsid protein V3: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome. {ECO:0000250|UniProtKB:P03305}.

Function: [Protein 2A]: Mediates self-processing of the polyprotein by a translational effect termed 'ribosome skipping'. Mechanistically, 2A- mediated cleavage occurs between the C-terminal glycine and the proline of the downstream protein 2B. In the case of foot-and-mouth disease virus, the 2A oligopeptide is post-translationally 'trimmed' from the C-terminus of the upstream protein 1D by 3C proteinase. {ECO:0000250|UniProtKB:P03305}.

Function: [Protein 2B]: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication. {ECO:0000250|UniProtKB:P03305}.

Function: [Protein 2C]: Associates with and induces structural rearrangements of intracellular membranes. Triggers host autophagy by interacting with host BECN1 and thereby promotes viral replication. Participates in viral replication and interacts with host DHX9. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3. {ECO:0000250|UniProtKB:P03305}.

Function: [Protein 3A]: Plays important roles in virus replication, virulence and host range. {ECO:0000250|UniProtKB:P03305}.

Function: [Protein 3B-1]: Covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. Acts as a genome- linked replication primer. {ECO:0000250|UniProtKB:P03305}.

Function: [Protein 3B-2]: Covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. Acts as a genome- linked replication primer. {ECO:0000250|UniProtKB:P03305}.

Function: [Protein 3B-3]: Covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. Acts as a genome- linked replication primer. {ECO:0000250|UniProtKB:P03305}.

Function: [Protease 3C]: Cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, binds to viral RNA and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease. {ECO:0000250|UniProtKB:P03305}.

Function: RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated. {ECO:0000250|UniProtKB:P03305}.

Catalytic activity: Reaction=Autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-|-Gly bond, but then cleaves host cell initiation factor eIF-4G at bonds -Gly-|- Arg- and -Lys-|-Arg-.; EC=3.4.22.46;

Catalytic activity: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'- diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;

Catalytic activity: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA- COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};

Catalytic activity: Reaction=Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.; EC=3.4.22.28; Evidence={ECO:0000255|PROSITE-ProRule:PRU01222};

Subunit: [Leader protease]: Interacts with host ISG15. Capsid protein VP1: Interacts (via R-G-D motif) with host ITGAV/ITGB6. {ECO:0000250|UniProtKB:P03305}.

Subunit: [Protein 2B]: Forms homooligomers. {ECO:0000250|UniProtKB:P03305}.

Subunit: [Protein 2C]: Interacts with host VIM. Interacts with host BECN1. {ECO:0000250|UniProtKB:P03305}.

Subunit: [Protein 3A]: Interacts with host DCTN3. {ECO:0000250|UniProtKB:P03305}.

Subcellular location: [Capsid protein VP2]: Virion. Host cytoplasm {ECO:0000305}.

Subcellular location: [Capsid protein VP3]: Virion. Host cytoplasm {ECO:0000305}.

Subcellular location: [Capsid protein VP1]: Virion. Host cytoplasm {ECO:0000305}.

Subcellular location: [Protein 2B]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity). {ECO:0000250}.

Subcellular location: [Protein 2C]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity). {ECO:0000250}.

Subcellular location: [Protein 3A]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity). {ECO:0000250}.

Subcellular location: [Protein 3B-1]: Virion {ECO:0000305}.

Subcellular location: [Protein 3B-2]: Virion {ECO:0000305}.

Subcellular location: [Protein 3B-3]: Virion {ECO:0000305}.

Subcellular location: [Protease 3C]: Host cytoplasm {ECO:0000305}.

Subcellular location: [RNA-directed RNA polymerase 3D-POL]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity). {ECO:0000250}.

Ptm: Specific enzymatic cleavages in vivo by the viral proteases yield a variety of precursors and mature proteins. Polyprotein processing intermediates such as VP0 which is a VP4-VP2 precursor are produced. During virion maturation, non-infectious particles are rendered infectious following cleavage of VP0. This maturation cleavage is followed by a conformational change of the particle. The polyprotein seems to be cotranslationally cleaved at the 2A/2B junction by a ribosomal skip from one codon to the next without formation of a peptide bond. This process would release the L-P1-2A peptide from the translational complex (By similarity). {ECO:0000250}.

Ptm: Myristoylation of VP4 is required during RNA encapsidation and formation of the mature virus particle. {ECO:0000250}.

Ptm: Protein 3B-1, 3B-2 and 3B-3 are uridylylated by the polymerase and are covalently linked to the 5'-end of genomic RNA. These uridylylated forms act as a nucleotide-peptide primer for the polymerase (By similarity). {ECO:0000250}.

Miscellaneous: The capsid protein VP1 contains the main antigenic determinants of the virion; therefore, changes in its sequence must be responsible for the high antigenic variability of the virus. {ECO:0000250}.

Similarity: Belongs to the picornaviruses polyprotein family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Foot-and-mouth disease virus (isolate -/Spain/S8c1SantaPau/1970 serotype C) (FMDV).
Taxonomy:		Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; Picornavirales; Picornaviridae; Aphthovirus.



Function:		[Leader protease]: Autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. Cleaves also the host translation initiation factors EIF4G1 and EIF4G3, in order to shutoff the capped cellular mRNA transcription. Plays a role in counteracting host innate antiviral response using diverse mechanisms. Possesses a deubiquitinase activity acting on both 'Lys'-48 and 'Lys'-63-linked polyubiquitin chains. In turn, inhibits the ubiquitination and subsequent activation of key signaling molecules of type I IFN response such as host DDX58, TBK1, TRAF3 and TRAF6. Inhibits host NF-kappa-B activity by inducing a decrease in RELA mRNA levels. Cleaves a peptide bond in the C-terminus of host ISG15, resulting in the damaging of this mofidier that can no longer be attached to target proteins. Cleaves also host G3BP1 and G3BP2 in order to inhibit cytoplasmic stress granules assembly. {ECO:0000250\|UniProtKB:P03305, ECO:0000250\|UniProtKB:P03308}.



Function:		Capsid protein VP4: Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. Capsid protein VP4 is released, capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm. After genome has been released, the channel shrinks. {ECO:0000250\|UniProtKB:P03300}.



Function:		Capsid protein VP2: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP1 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome. {ECO:0000250\|UniProtKB:P03305}.



Function:		Capsid protein V1: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome. Mediates cell entry by attachment to an integrin receptor, usually host ITGAV/ITGB6, via a conserved arginine-glycine-aspartic acid (R-G-D) motif. {ECO:0000250\|UniProtKB:P03305}.



Function:		Capsid protein V3: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome. {ECO:0000250\|UniProtKB:P03305}.



Function:		[Protein 2A]: Mediates self-processing of the polyprotein by a translational effect termed 'ribosome skipping'. Mechanistically, 2A- mediated cleavage occurs between the C-terminal glycine and the proline of the downstream protein 2B. In the case of foot-and-mouth disease virus, the 2A oligopeptide is post-translationally 'trimmed' from the C-terminus of the upstream protein 1D by 3C proteinase. {ECO:0000250\|UniProtKB:P03305}.



Function:		[Protein 2B]: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication. {ECO:0000250\|UniProtKB:P03305}.



Function:		[Protein 2C]: Associates with and induces structural rearrangements of intracellular membranes. Triggers host autophagy by interacting with host BECN1 and thereby promotes viral replication. Participates in viral replication and interacts with host DHX9. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3. {ECO:0000250\|UniProtKB:P03305}.



Function:		[Protein 3A]: Plays important roles in virus replication, virulence and host range. {ECO:0000250\|UniProtKB:P03305}.



Function:		[Protein 3B-1]: Covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. Acts as a genome- linked replication primer. {ECO:0000250\|UniProtKB:P03305}.



Function:		[Protein 3B-2]: Covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. Acts as a genome- linked replication primer. {ECO:0000250\|UniProtKB:P03305}.



Function:		[Protein 3B-3]: Covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. Acts as a genome- linked replication primer. {ECO:0000250\|UniProtKB:P03305}.



Function:		[Protease 3C]: Cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, binds to viral RNA and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease. {ECO:0000250\|UniProtKB:P03305}.



Function:		RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated. {ECO:0000250\|UniProtKB:P03305}.


Catalytic activity:		Reaction=Autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-\|-Gly bond, but then cleaves host cell initiation factor eIF-4G at bonds -Gly-\|- Arg- and -Lys-\|-Arg-.; EC=3.4.22.46;
Catalytic activity:		Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'- diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
Catalytic activity:		Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA- COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400; EC=2.7.7.48; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00539};
Catalytic activity:		Reaction=Selective cleavage of Gln-\|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.; EC=3.4.22.28; Evidence={ECO:0000255\|PROSITE-ProRule:PRU01222};
Subunit:		[Leader protease]: Interacts with host ISG15. Capsid protein VP1: Interacts (via R-G-D motif) with host ITGAV/ITGB6. {ECO:0000250\|UniProtKB:P03305}.
Subunit:		[Protein 2B]: Forms homooligomers. {ECO:0000250\|UniProtKB:P03305}.
Subunit:		[Protein 2C]: Interacts with host VIM. Interacts with host BECN1. {ECO:0000250\|UniProtKB:P03305}.
Subunit:		[Protein 3A]: Interacts with host DCTN3. {ECO:0000250\|UniProtKB:P03305}.
Subcellular location:		[Capsid protein VP2]: Virion. Host cytoplasm {ECO:0000305}.
Subcellular location:		[Capsid protein VP3]: Virion. Host cytoplasm {ECO:0000305}.
Subcellular location:		[Capsid protein VP1]: Virion. Host cytoplasm {ECO:0000305}.
Subcellular location:		[Protein 2B]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity). {ECO:0000250}.
Subcellular location:		[Protein 2C]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity). {ECO:0000250}.
Subcellular location:		[Protein 3A]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity). {ECO:0000250}.
Subcellular location:		[Protein 3B-1]: Virion {ECO:0000305}.
Subcellular location:		[Protein 3B-2]: Virion {ECO:0000305}.
Subcellular location:		[Protein 3B-3]: Virion {ECO:0000305}.
Subcellular location:		[Protease 3C]: Host cytoplasm {ECO:0000305}.
Subcellular location:		[RNA-directed RNA polymerase 3D-POL]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum (By similarity). {ECO:0000250}.
Ptm:		Specific enzymatic cleavages in vivo by the viral proteases yield a variety of precursors and mature proteins. Polyprotein processing intermediates such as VP0 which is a VP4-VP2 precursor are produced. During virion maturation, non-infectious particles are rendered infectious following cleavage of VP0. This maturation cleavage is followed by a conformational change of the particle. The polyprotein seems to be cotranslationally cleaved at the 2A/2B junction by a ribosomal skip from one codon to the next without formation of a peptide bond. This process would release the L-P1-2A peptide from the translational complex (By similarity). {ECO:0000250}.
Ptm:		Myristoylation of VP4 is required during RNA encapsidation and formation of the mature virus particle. {ECO:0000250}.
Ptm:		Protein 3B-1, 3B-2 and 3B-3 are uridylylated by the polymerase and are covalently linked to the 5'-end of genomic RNA. These uridylylated forms act as a nucleotide-peptide primer for the polymerase (By similarity). {ECO:0000250}.
Miscellaneous:		The capsid protein VP1 contains the main antigenic determinants of the virion; therefore, changes in its sequence must be responsible for the high antigenic variability of the virus. {ECO:0000250}.
Similarity:		Belongs to the picornaviruses polyprotein family. {ECO:0000305}.