POLG_EC06C
ID POLG_EC06C Reviewed; 2191 AA.
AC Q66474;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=P1;
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=P2;
DE Contains:
DE RecName: Full=Protease 2A;
DE Short=P2A;
DE EC=3.4.22.29 {ECO:0000250|UniProtKB:P03300};
DE AltName: Full=Picornain 2A;
DE AltName: Full=Protein 2A;
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 {ECO:0000250|UniProtKB:P03300};
DE Contains:
DE RecName: Full=P3;
DE Contains:
DE RecName: Full=Protein 3AB;
DE Contains:
DE RecName: Full=Protein 3A;
DE Short=P3A;
DE Contains:
DE RecName: Full=Viral protein genome-linked;
DE Short=VPg;
DE AltName: Full=Protein 3B;
DE Short=P3B;
DE Contains:
DE RecName: Full=Protein 3CD;
DE EC=3.4.22.28;
DE Contains:
DE RecName: Full=Protease 3C {ECO:0000255|PROSITE-ProRule:PRU01222};
DE EC=3.4.22.28 {ECO:0000255|PROSITE-ProRule:PRU01222};
DE AltName: Full=Picornain 3C {ECO:0000255|PROSITE-ProRule:PRU01222};
DE Short=P3C {ECO:0000255|PROSITE-ProRule:PRU01222};
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase {ECO:0000255|PROSITE-ProRule:PRU00539};
DE Short=RdRp;
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE AltName: Full=3D polymerase;
DE Short=3Dpol;
DE AltName: Full=Protein 3D;
DE Short=3D;
OS Echovirus 6 (strain Charles).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Picornaviridae; Enterovirus; Enterovirus B.
OX NCBI_TaxID=103913;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Righthand V.F., Gratsch T.E., Blackburn R.V.;
RT "The genome of echovirus 6.";
RL Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1526-2191.
RX PubMed=8184543; DOI=10.1006/viro.1994.1299;
RA Gratsch T.E., Righthand V.F.;
RT "Construction of a recombinant cDNA of echovirus 6 that established a
RT persistent in vitro infection.";
RL Virology 201:341-348(1994).
RN [3]
RP FUNCTION (CAPSID PROTEIN VP1), FUNCTION (CAPSID PROTEIN VP2), FUNCTION
RP (CAPSID PROTEIN VP3), FUNCTION (CAPSID PROTEIN VP4), SUBCELLULAR LOCATION
RP (CAPSID PROTEIN VP1), SUBCELLULAR LOCATION (CAPSID PROTEIN VP2),
RP SUBCELLULAR LOCATION (CAPSID PROTEIN VP3), SUBCELLULAR LOCATION (CAPSID
RP PROTEIN VP4), INTERACTION WITH CAPSID PROTEIN VP4 (CAPSID PROTEIN VP1),
RP INTERACTION WITH CAPSID PROTEIN VP1 (CAPSID PROTEIN VP2), INTERACTION WITH
RP CAPSID PROTEIN VP3 (CAPSID PROTEIN VP2), INTERACTION WITH CAPSID PROTEIN
RP VP1 (CAPSID PROTEIN VP3), INTERACTION WITH CAPSID PROTEIN VP1 (CAPSID
RP PROTEIN VP4), INTERACTION WITH CAPSID PROTEIN VP3 (CAPSID PROTEIN VP4),
RP INTERACTION WITH CAPSID PROTEIN VP4 (CAPSID PROTEIN VP3), INTERACTION WITH
RP CAPSID PROTEIN VP2 (CAPSID PROTEIN VP3), INTERACTION WITH HOST CD55 (CAPSID
RP PROTEIN VP1), INTERACTION WITH HOST FCGRT (CAPSID PROTEIN VP1), INTERACTION
RP WITH HOST CD55 (CAPSID PROTEIN VP2), INTERACTION WITH HOST FCGRT (CAPSID
RP PROTEIN VP2), AND INTERACTION WITH HOST FCGRT (CAPSID PROTEIN VP3).
RX PubMed=31104841; DOI=10.1016/j.cell.2019.04.035;
RA Zhao X., Zhang G., Liu S., Chen X., Peng R., Dai L., Qu X., Li S., Song H.,
RA Gao Z., Yuan P., Liu Z., Li C., Shang Z., Li Y., Zhang M., Qi J., Wang H.,
RA Du N., Wu Y., Bi Y., Gao S., Shi Y., Yan J., Zhang Y., Xie Z., Wei W.,
RA Gao G.F.;
RT "Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for
RT Enterovirus B.";
RL Cell 177:1553-1565.E16(2019).
CC -!- FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo
CC T=3 symmetry with capsid proteins VP2 and VP3 (PubMed:31104841). The
CC capsid is 300 Angstroms in diameter, composed of 60 copies of each
CC capsid protein and enclosing the viral positive strand RNA genome
CC (PubMed:31104841). Capsid protein VP1 mainly forms the vertices of the
CC capsid (PubMed:31104841). Capsid protein VP1 interacts with host cell
CC receptor to provide virion attachment to target host cells (By
CC similarity). This attachment induces virion internalization (By
CC similarity). Tyrosine kinases are probably involved in the entry
CC process (By similarity). After binding to its receptor, the capsid
CC undergoes conformational changes (By similarity). Capsid protein VP1 N-
CC terminus (that contains an amphipathic alpha-helix) and capsid protein
CC VP4 are externalized (By similarity). Together, they shape a pore in
CC the host membrane through which viral genome is translocated to host
CC cell cytoplasm (By similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000269|PubMed:31104841}.
CC -!- FUNCTION: [Capsid protein VP2]: Forms an icosahedral capsid of pseudo
CC T=3 symmetry with capsid proteins VP2 and VP3 (PubMed:31104841). The
CC capsid is 300 Angstroms in diameter, composed of 60 copies of each
CC capsid protein and enclosing the viral positive strand RNA genome
CC (PubMed:31104841). {ECO:0000269|PubMed:31104841}.
CC -!- FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo
CC T=3 symmetry with capsid proteins VP2 and VP3 (PubMed:31104841). The
CC capsid is 300 Angstroms in diameter, composed of 60 copies of each
CC capsid protein and enclosing the viral positive strand RNA genome
CC (PubMed:31104841). {ECO:0000269|PubMed:31104841}.
CC -!- FUNCTION: [Capsid protein VP4]: Lies on the inner surface of the capsid
CC shell (PubMed:31104841). After binding to the host receptor, the capsid
CC undergoes conformational changes (By similarity). Capsid protein VP4 is
CC released, Capsid protein VP1 N-terminus is externalized, and together,
CC they shape a pore in the host membrane through which the viral genome
CC is translocated into the host cell cytoplasm (By similarity).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000269|PubMed:31104841}.
CC -!- FUNCTION: [Capsid protein VP0]: Component of immature procapsids, which
CC is cleaved into capsid proteins VP4 and VP2 after maturation (By
CC similarity). Allows the capsid to remain inactive before the maturation
CC step (By similarity). {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Protease 2A]: Cysteine protease that cleaves viral
CC polyprotein and specific host proteins (By similarity). It is
CC responsible for the autocatalytic cleavage between the P1 and P2
CC regions, which is the first cleavage occurring in the polyprotein (By
CC similarity). Cleaves also the host translation initiation factor
CC EIF4G1, in order to shut down the capped cellular mRNA translation (By
CC similarity). Inhibits the host nucleus-cytoplasm protein and RNA
CC trafficking by cleaving host members of the nuclear pores (By
CC similarity). Counteracts stress granule formation probably by
CC antagonizing its assembly or promoting its dissassembly (By
CC similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000250|UniProtKB:P03301}.
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:P03300}.
CC -!- FUNCTION: [Protein 2C]: Induces and associates with structural
CC rearrangements of intracellular membranes. Displays RNA-binding,
CC nucleotide binding and NTPase activities. May play a role in virion
CC morphogenesis and viral RNA encapsidation by interacting with the
CC capsid protein VP3. {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Protein 3AB]: Localizes the viral replication complex to the
CC surface of membranous vesicles. Together with protein 3CD binds the
CC Cis-Active RNA Element (CRE) which is involved in RNA synthesis
CC initiation. Acts as a cofactor to stimulate the activity of 3D
CC polymerase, maybe through a nucleid acid chaperone activity.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Protein 3A]: Localizes the viral replication complex to the
CC surface of membranous vesicles (By similarity). It inhibits host cell
CC endoplasmic reticulum-to-Golgi apparatus transport and causes the
CC disassembly of the Golgi complex, possibly through GBF1 interaction (By
CC similarity). This would result in depletion of MHC, trail receptors and
CC IFN receptors at the host cell surface (By similarity). Plays an
CC essential role in viral RNA replication by recruiting ACBD3 and PI4KB
CC at the viral replication sites, thereby allowing the formation of the
CC rearranged membranous structures where viral replication takes place
CC (By similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000250|UniProtKB:P03313}.
CC -!- FUNCTION: [Viral protein genome-linked]: Acts as a primer for viral RNA
CC replication and remains covalently bound to viral genomic RNA. VPg is
CC uridylylated prior to priming replication into VPg-pUpU (By
CC similarity). The oriI viral genomic sequence may act as a template for
CC this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by
CC the RNA-dependent RNA polymerase to replicate the viral genome (By
CC similarity). Following genome release from the infecting virion in the
CC cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By
CC similarity). During the late stage of the replication cycle, host TDP2
CC is excluded from sites of viral RNA synthesis and encapsidation,
CC allowing for the generation of progeny virions (By similarity).
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Protein 3CD]: Involved in the viral replication complex and
CC viral polypeptide maturation. It exhibits protease activity with a
CC specificity and catalytic efficiency that is different from protease
CC 3C. Protein 3CD binds to the 5'UTR of the viral genome.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [RNA-directed RNA polymerase]: Replicates the viral genomic
CC RNA on the surface of intracellular membranes. May form linear arrays
CC of subunits that propagate along a strong head-to-tail interaction
CC called interface-I. Covalently attaches UMP to a tyrosine of VPg, which
CC is used to prime RNA synthesis. The positive stranded RNA genome is
CC first replicated at virus induced membranous vesicles, creating a dsRNA
CC genomic replication form. This dsRNA is then used as template to
CC synthesize positive stranded RNA genomes. ss(+)RNA genomes are either
CC translated, replicated or encapsidated. {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Protease 3C]: Major viral protease that mediates proteolytic
CC processing of the polyprotein (By similarity). Cleaves host EIF5B,
CC contributing to host translation shutoff (By similarity). Cleaves also
CC host PABPC1, contributing to host translation shutoff (By similarity).
CC Cleaves host NLRP1, triggers host N-glycine-mediated degradation of the
CC autoinhibitory NLRP1 N-terminal fragment (By similarity).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03303}.
CC -!- CATALYTIC ACTIVITY: [Protein 2C]:
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 Evidence={ECO:0000250|UniProtKB:P03300};
CC -!- CATALYTIC ACTIVITY: [Protease 2A]:
CC Reaction=Selective cleavage of Tyr-|-Gly bond in the picornavirus
CC polyprotein.; EC=3.4.22.29; Evidence={ECO:0000250|UniProtKB:P03300};
CC -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]:
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: [Protease 3C]:
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 -!- COFACTOR: [RNA-directed RNA polymerase]:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P03300};
CC Note=Binds 2 magnesium ions that constitute a dinuclear catalytic metal
CC center (By similarity). The magnesium ions are not prebound but only
CC present for catalysis (By similarity). Requires the presence of 3CDpro
CC or 3CPro (By similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000250|UniProtKB:P03313};
CC -!- ACTIVITY REGULATION: [RNA-directed RNA polymerase]: Replication or
CC transcription is subject to high level of random mutations by the
CC nucleotide analog ribavirin. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Capsid protein VP0]: Interacts with capsid protein VP1 and
CC capsid protein VP3 to form heterotrimeric protomers.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Capsid protein VP1]: Interacts with capsid protein VP0, and
CC capsid protein VP3 to form heterotrimeric protomers (By similarity).
CC Five protomers subsequently associate to form pentamers which serve as
CC building blocks for the capsid (By similarity). Interacts with capsid
CC protein VP2, capsid protein VP3 and capsid protein VP4 following
CC cleavage of capsid protein VP0 (PubMed:31104841). Interacts with host
CC CD55 and FCGRT; these interactions promote virus attachment to the host
CC cell and subsequent internalization (PubMed:31104841).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000269|PubMed:31104841}.
CC -!- SUBUNIT: [Capsid protein VP2]: Interacts with capsid protein VP1 and
CC capsid protein VP3 in the mature capsid (PubMed:31104841). Interacts
CC with host CD55 and FCGRT; these interactions promote virus attachment
CC to the host cell and subsequent internalization (PubMed:31104841).
CC {ECO:0000269|PubMed:31104841}.
CC -!- SUBUNIT: [Capsid protein VP3]: Interacts with capsid protein VP0 and
CC capsid protein VP1 to form heterotrimeric protomers (By similarity).
CC Five protomers subsequently associate to form pentamers which serve as
CC building blocks for the capsid (By similarity). Interacts with capsid
CC protein VP4 in the mature capsid (PubMed:31104841). Interacts with
CC protein 2C; this interaction may be important for virion morphogenesis
CC (By similarity). Interacts with host FCGRT; this interaction promotes
CC virus attachment to the host cell and subsequent internalization
CC (PubMed:31104841). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000269|PubMed:31104841}.
CC -!- SUBUNIT: [Capsid protein VP4]: Interacts with capsid protein VP1 and
CC capsid protein VP3. {ECO:0000269|PubMed:31104841}.
CC -!- SUBUNIT: [Protease 2A]: Homodimer. {ECO:0000250|UniProtKB:P04936}.
CC -!- SUBUNIT: [Protein 2C]: Homohexamer; forms a hexameric ring structure
CC with 6-fold symmetry characteristic of AAA+ ATPases (By similarity).
CC Interacts (via N-terminus) with host RTN3 (via reticulon domain); this
CC interaction is important for viral replication (By similarity).
CC Interacts with capsid protein VP3; this interaction may be important
CC for virion morphogenesis (By similarity).
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Protein 3AB]: Interacts with protein 3CD.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Protein 3A]: Homodimer (By similarity). Interacts with host
CC GBF1 (By similarity). Interacts (via GOLD domain) with host ACBD3 (via
CC GOLD domain); this interaction allows the formation of a viral protein
CC 3A/ACBD3 heterotetramer with a 2:2 stoichiometry, which will stimulate
CC the recruitment of host PI4KB in order to synthesize PI4P at the viral
CC RNA replication sites (By similarity). {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Viral protein genome-linked]: Interacts with RNA-directed RNA
CC polymerase. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Protein 3CD]: Interacts with protein 3AB and with RNA-
CC directed RNA polymerase. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase]: Interacts with Viral protein
CC genome-linked and with protein 3CD. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP0]: Virion. Host cytoplasm
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP4]: Virion
CC {ECO:0000269|PubMed:31104841}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion
CC {ECO:0000269|PubMed:31104841}. Host cytoplasm {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion
CC {ECO:0000269|PubMed:31104841}. Host cytoplasm {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion
CC {ECO:0000269|PubMed:31104841}. Host cytoplasm {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.
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.
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.
CC -!- SUBCELLULAR LOCATION: [Protein 3AB]: 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.
CC -!- SUBCELLULAR LOCATION: [Viral protein genome-linked]: Virion
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm
CC {ECO:0000250|UniProtKB:Q66478}.
CC -!- SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Protein 3CD]: Host nucleus
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P03300}. 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.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasmic
CC 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.
CC -!- DOMAIN: [Protein 2C]: The N-terminus has membrane-binding (By
CC similarity). The N-terminus also displays RNA-binding properties (By
CC similarity). The N-terminus is involved in oligomerization (By
CC similarity). The central part contains an ATPase domain and a
CC degenerate C4-type zinc-finger with only 3 cysteines (By similarity).
CC The C-terminus is involved in RNA-binding (By similarity). The extreme
CC C-terminus contains a region involved in oligomerization (By
CC similarity). {ECO:0000250|UniProtKB:B9VUU3,
CC ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo by the
CC viral proteases yield processing intermediates and the mature proteins.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Capsid protein VP0]: Myristoylation is required for the formation
CC of pentamers during virus assembly. Further assembly of 12 pentamers
CC and a molecule of genomic RNA generates the provirion.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Capsid protein VP0]: During virion maturation, immature virions
CC are rendered infectious following cleavage of VP0 into VP4 and VP2.
CC This maturation seems to be an autocatalytic event triggered by the
CC presence of RNA in the capsid and it is followed by a conformational
CC change infectious virion. {ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Capsid protein VP4]: Myristoylation is required during RNA
CC encapsidation and formation of the mature virus particle.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Viral protein genome-linked]: VPg is uridylylated by the
CC polymerase into VPg-pUpU. This acts as a nucleotide-peptide primer for
CC the genomic RNA replication. {ECO:0000250|UniProtKB:P03300}.
CC -!- SIMILARITY: Belongs to the picornaviruses polyprotein family.
CC {ECO:0000305}.
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DR EMBL; U16283; AAA65044.1; -; Genomic_RNA.
DR SMR; Q66474; -.
DR MEROPS; C03.011; -.
DR MEROPS; N08.001; -.
DR PRIDE; Q66474; -.
DR Proteomes; UP000002693; Genome.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; 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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017111; F:nucleoside-triphosphatase activity; IEA:InterPro.
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:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; ISS:UniProtKB.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0044694; P:pore-mediated entry of viral genome into 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:0018144; P:RNA-protein covalent cross-linking; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR GO; GO:0039522; P:suppression by virus of host mRNA export from nucleus; ISS:UniProtKB.
DR GO; GO:0039611; P:suppression by virus of host translation initiation factor activity; ISS:UniProtKB.
DR GO; GO:0039540; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; 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; -; 4.
DR Gene3D; 2.60.120.20; -; 3.
DR Gene3D; 3.30.70.270; -; 1.
DR Gene3D; 4.10.80.10; -; 1.
DR Gene3D; 6.10.20.20; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR000605; Helicase_SF3_ssDNA/RNA_vir.
DR InterPro; IPR014759; Helicase_SF3_ssRNA_vir.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR014838; P3A.
DR InterPro; IPR036203; P3A_soluble_dom.
DR InterPro; IPR044067; PCV_3C_PRO.
DR InterPro; IPR000081; Peptidase_C3.
DR InterPro; IPR000199; Peptidase_C3A/C3B_picornavir.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR003138; Pico_P1A.
DR InterPro; IPR036988; Pico_P1A_sf.
DR InterPro; IPR002527; Pico_P2B.
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; PF08727; P3A; 1.
DR Pfam; PF00548; Peptidase_C3; 1.
DR Pfam; PF02226; Pico_P1A; 1.
DR Pfam; PF00947; Pico_P2A; 1.
DR Pfam; PF01552; Pico_P2B; 1.
DR Pfam; PF00680; RdRP_1; 1.
DR Pfam; PF00073; Rhv; 3.
DR Pfam; PF00910; RNA_helicase; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF50494; SSF50494; 2.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR SUPFAM; SSF89043; SSF89043; 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 Activation of host autophagy by virus; ATP-binding; Autocatalytic cleavage;
KW Capsid protein; Covalent protein-RNA linkage; DNA replication;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus; Helicase; Host cytoplasm;
KW Host cytoplasmic vesicle; Host gene expression shutoff by virus;
KW Host membrane; Host mRNA suppression by virus; Host nucleus;
KW Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host mRNA nuclear export by virus;
KW Inhibition of host RIG-I by virus; Inhibition of host RLR pathway by virus;
KW Ion channel; Ion transport; Lipoprotein; Magnesium; Membrane;
KW Metal-binding; Myristate; Nucleotide-binding; Nucleotidyltransferase;
KW Phosphoprotein; Pore-mediated penetration of viral genome into host cell;
KW Protease; Repeat; RNA-binding; RNA-directed RNA polymerase;
KW T=pseudo3 icosahedral capsid protein; Thiol protease; Transferase;
KW Transport; Viral attachment to host cell; Viral immunoevasion;
KW Viral ion channel; Viral penetration into host cytoplasm;
KW Viral RNA replication; Virion; Virus endocytosis by host;
KW Virus entry into host cell; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT CHAIN 2..2191
FT /note="Genome polyprotein"
FT /id="PRO_0000426386"
FT CHAIN 2..857
FT /note="P1"
FT /id="PRO_0000426387"
FT CHAIN 2..330
FT /note="Capsid protein VP0"
FT /id="PRO_0000426388"
FT CHAIN 2..69
FT /note="Capsid protein VP4"
FT /id="PRO_0000426389"
FT CHAIN 70..330
FT /note="Capsid protein VP2"
FT /id="PRO_0000426390"
FT CHAIN 331..568
FT /note="Capsid protein VP3"
FT /id="PRO_0000426391"
FT CHAIN 569..857
FT /note="Capsid protein VP1"
FT /id="PRO_0000426392"
FT CHAIN 858..1435
FT /note="P2"
FT /id="PRO_0000426393"
FT CHAIN 858..1007
FT /note="Protease 2A"
FT /id="PRO_0000426394"
FT CHAIN 1008..1106
FT /note="Protein 2B"
FT /id="PRO_0000039675"
FT CHAIN 1107..1435
FT /note="Protein 2C"
FT /id="PRO_0000039676"
FT CHAIN 1436..2191
FT /note="P3"
FT /id="PRO_0000426395"
FT CHAIN 1436..1546
FT /note="Protein 3AB"
FT /id="PRO_0000426396"
FT CHAIN 1436..1524
FT /note="Protein 3A"
FT /id="PRO_0000039677"
FT CHAIN 1525..1546
FT /note="Viral protein genome-linked"
FT /id="PRO_0000426397"
FT CHAIN 1547..2191
FT /note="Protein 3CD"
FT /id="PRO_0000426398"
FT CHAIN 1547..1729
FT /note="Protease 3C"
FT /id="PRO_0000426399"
FT CHAIN 1730..2191
FT /note="RNA-directed RNA polymerase"
FT /id="PRO_0000426400"
FT TOPO_DOM 2..1501
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1502..1517
FT /evidence="ECO:0000255"
FT TOPO_DOM 1518..2191
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1211..1367
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DOMAIN 1547..1725
FT /note="Peptidase C3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT DOMAIN 1956..2072
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT ZN_FING 1375..1392
FT /note="C4-type; degenerate"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT REGION 566..582
FT /note="Amphipathic alpha-helix"
FT /evidence="ECO:0000255"
FT REGION 1107..1245
FT /note="Oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1107..1179
FT /note="Membrane-binding"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1128..1132
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1419..1426
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1430..1435
FT /note="Oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 878
FT /note="For protease 2A activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 896
FT /note="For protease 2A activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 967
FT /note="For protease 2A activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 1586
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1617
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1693
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT BINDING 913
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT BINDING 915
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT BINDING 973
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT BINDING 975
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT BINDING 1375
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1392
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1962
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT BINDING 1962
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT BINDING 2058
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT BINDING 2058
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT SITE 69..70
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT SITE 330..331
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 857..858
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1007..1008
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1106..1107
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1131
FT /note="Involved in the interaction with host RTN3"
FT /evidence="ECO:0000250|UniProtKB:Q66478"
FT SITE 1435..1436
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1524..1525
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1546..1547
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1729..1730
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT MOD_RES 1527
FT /note="O-(5'-phospho-RNA)-tyrosine"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03300"
SQ SEQUENCE 2191 AA; 245277 MW; 47E70448B05716DB CRC64;
MGAQVSTQKT GAHETGLSAS GNSIIHYTNI NYYKDAASNS ANRQDFTQDP GKFTEPVKDI
MAKTLPALNS PSAEECGYSD RVRSITLGNS TITTQESANV VVGYGVWPDY LKDDEATAED
QPTNPDVATC RFYTLDSVSW MKESQGWWWK FPDALRDMGL FGQNMQYHYL GRSGYTIHVQ
CNASKFHQGC LLVVCVPEAE MGAATVNEKI NREHLSNGEV ANTFTGTKSS NTNGVQQAVF
NAGMGVRVGN LTVFPHQWIN LRTNNCATIV MPYINSVPMD NMFRHYNFTL MIIPFAKLDY
AAGSSTYIPI TVTVAPMCAE YNGLRLAGHQ GLPVMSTPGS NQFLTSDDYQ SPTAMPQFDV
TPEMHIPGEV KNLMEIAEVD SVVPVNNVNE NVNSLEAYRI PVHSVTETGA QVFGFTLQPG
ADSVMERTLH GEILNYYANW SGSIKLTFMY CGSAMATGKF LLAYSPPGAG VPKNRKEAML
GTHMIWDIGL QSRCVLCVPW ISQTHYRFVS KDSYTDAGFI TCWYQTSIVV PAEVQNQSVI
LCFVSACNDF SVRLLRDSPF VTQTAFYQND VQNAVERSIV RVADTLPSGP SNSESIPALT
AAETGHTSQV VPSDTIQTRH VRNFHVRSES SVENFLSRSA CVYIVEYKTQ DTTPDKMYDS
WVINTRQVAQ LRRKLEFFTY VRFDVEVTFV ITSVQDDSTR QNTDTPVLTH QIMYVPPGGP
IPHAVDDYNW QTSTNPSVFW TEGNAPPRMS IPFMSVGNAY SNFYDGWSHF SQTGVYGFNT
LNNMGKLYFR HVNDRTISPI TSKVRIYFKP KHVKAWVPRP PRLCEYTHKD NVDYEPKGVT
TSRTSITITN SKHMETHGAF GQQSGAAYVG NYRVVNRHLA THTDWQNCVW EDYNRDLLVS
TTTAHGCDTI ARCHCTTGVY FCASRNKHHP VVFEGPGLVE VQESGYYPKR YQSHVLLAAG
LSEPGDCGGI LRCEHGVIGI VTMGGEGVVG FADVRDLLWL EDDAMEQGVK DYVEQLGNAF
GSGFTNQICE QVNLLKESLI GQDSILEKSL KALVKIISAL VIVVRNHDDL ITVTATLALI
GCTSSPWRWL KQKVSQYYGI SMAERQNNGW LKKFTEMTNA CKGMEWIAIK IQKFIEWLKV
KILPEVREKH EFLNRLKQLP LLESQIATIE QSAPSQSDQE QLFSNVQYFA HYCRKYAPLY
AAEAKRVFSL EKKMSNYIQF KSKCRIEPVC LLLHGSPGVG KSVATNLIGR SLAEKLNSSI
YSLPPDPDHF DGYKQQAVVI MDDLCQNPDG KDVSLFCQMV SSVDFVPPMA ALEEKGILFT
SPFVLASTNA GSINAPTVSD SRALARRFHF DMNIEVISMY NQNGKINMPM SVKTCDEECC
PVNFKKCCPL VCGKAIQFID RRTQVRYSLD MLVTEMFREY NHRHSVGATL EALFQGPPVY
REIKISVAPE IPPPPAIADL LKSVDSEAVR DYCKEKGWLV PEVNSTLQIE KHVSRAFICL
QALTTFVSVA GIIYIIYKLF AGFQGAYTGM PNQKPKVPTL RQAKVQGPAF EFAVAMMKRN
SSTVKTEYGE FTMLGIYDRW AVLPRHAKPG PTILMNDQEV GVVDAKELVD KDGTNLELTL
LKLNRNEKFR DIRGFLAKEE VEVNEAVLAI NTSKFPNMYI PVGQVTDYGF LNLGGTPTKR
MLMYNFPTRA GQCGGVLMST GKVLGIHVGG NGHQGFSAAL LKHYFNDEQG EIEFIESSKD
AGYPVINTPS RTKLEPSVFH QVFEGSKEPA VLRNGDPRLK ANFEEAIFSK YIGNVNTHVD
EYMLEAIDHY AGQLATLDIS TEPMKLEDAV YGTEGLEALD LTTSAGYPYV ALGIKKRDIL
SKKTRDLTKL KECMDKYGLN LPMVTYVKDE LRSAEKVAKG KSRLIEASSL NDSVAMRQTF
GNLYKAFHQN PGIVTGSAVG CDPDLFWSKI PVMLDGHLIA FDYSGYDASL SPVWFACLKL
LLEKLGYTHK ETNYIDYLCN SHHLYRDKHY FVRGGMPSGC SGTSIFNSMI NNIIIRTLML
KVYKGIDLDQ FRMIAYGDDV IASYPWPIDA SLLAEAGKDY GLIMTPADKG ECFNEVTWTN
VTFLKRYFRA DEQYPFLVHP VMPMKDIHES IRWTKDPKNT QDHVRSLCLL AWHNGEQEYE
EFIQKIRSVP VGRCLTLPAF STLRRKWLDS F
