ID POLG_EC11G Reviewed; 2195 AA. AC P29813; Q66785; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 03-MAY-2023, entry version 182. 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 11 (strain Gregory). OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; OC Picornavirales; Picornaviridae; Ensavirinae; Enterovirus; Enterovirus B. OX NCBI_TaxID=31705; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=7762294; DOI=10.1016/0168-1702(94)00104-k; RA Dahllund L., Nissinen L., Pulli T., Hyttinen V.P., Stanway G., Hyypiae T.; RT "The genome of echovirus 11."; RL Virus Res. 35:215-222(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 822-2195. RX PubMed=2170575; DOI=10.1099/0022-1317-71-9-2133; RA Auvinen P., Hyypiae T.; RT "Echoviruses include genetically distinct serotypes."; RL J. Gen. Virol. 71:2133-2139(1990). RN [3] RP INTERACTION WITH HOST CD55. RX PubMed=7517044; DOI=10.1073/pnas.91.13.6245; RA Bergelson J.M., Chan M., Solomon K.R., St John N.F., Lin H., Finberg R.W.; RT "Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored RT complement regulatory protein, is a receptor for several echoviruses."; RL Proc. Natl. Acad. Sci. U.S.A. 91:6245-6248(1994). RN [4] RP FUNCTION (CAPSID PROTEIN VP1), AND INTERACTION WITH HOST FCGRT (CAPSID RP PROTEIN VP1). RX PubMed=30808762; DOI=10.1073/pnas.1817341116; RA Morosky S., Wells A.I., Lemon K., Evans A.S., Schamus S., Bakkenist C.J., RA Coyne C.B.; RT "The neonatal Fc receptor is a pan-echovirus receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 116:3758-3763(2019). RN [5] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-859. RC STRAIN=Isolate clinical EV11-207; RX PubMed=12097583; DOI=10.1128/jvi.76.15.7694-7704.2002; RA Stuart A.D., McKee T.A., Williams P.A., Harley C., Shen S., Stuart D.I., RA Brown T.D., Lea S.M.; RT "Determination of the structure of a decay accelerating factor-binding RT clinical isolate of echovirus 11 allows mapping of mutants with altered RT receptor requirements for infection."; RL J. Virol. 76:7694-7704(2002). CC -!- FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo CC T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). 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 (By CC similarity). Capsid protein VP1 mainly forms the vertices of the capsid CC (By similarity). Capsid protein VP1 interacts with host cell receptor CC to provide virion attachment to target host cells (By similarity). This CC attachment induces virion internalization (By similarity). Tyrosine CC kinases are probably involved in the entry process (By similarity). CC After binding to its receptor, the capsid undergoes conformational CC changes (By similarity). Capsid protein VP1 N-terminus (that contains CC an amphipathic alpha-helix) and capsid protein VP4 are externalized (By CC similarity). Together, they shape a pore in the host membrane through CC which viral genome is translocated to host cell cytoplasm (By CC similarity). {ECO:0000250|UniProtKB:P03300}. CC -!- FUNCTION: [Capsid protein VP2]: Forms an icosahedral capsid of pseudo CC T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). 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 (By CC similarity). {ECO:0000250|UniProtKB:P03300}. CC -!- FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo CC T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). 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 (By CC similarity). {ECO:0000250|UniProtKB:P03300}. CC -!- FUNCTION: [Capsid protein VP4]: Lies on the inner surface of the capsid CC shell (By similarity). 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}. 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 -!- 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 lacks polymerase activity. The 3C domain in the context CC of protein 3CD may have an RNA binding activity.Protein 3CD binds to CC the 5'UTR of the viral genome. {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 (By similarity). CC {ECO:0000250|UniProtKB:P03300}. CC -!- SUBUNIT: [Capsid protein VP2]: Interacts with capsid protein VP1 and CC capsid protein VP3 in the mature capsid. CC {ECO:0000250|UniProtKB:P03300}. 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 (By similarity). Interacts with CC protein 2C; this interaction may be important for virion morphogenesis CC (By similarity). {ECO:0000250|UniProtKB:P03300}. CC -!- SUBUNIT: [Capsid protein VP4]: Interacts with capsid protein VP1 and CC capsid protein VP3. {ECO:0000250|UniProtKB:P03300}. 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 -!- SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion CC {ECO:0000250|UniProtKB:P03300}. 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}. CC -!- WEB RESOURCE: Name=Virus Particle ExploreR db; Note=Icosahedral capsid CC structure; CC URL="https://viperdb.scripps.edu/Info_Page.php?VDB=1h8t"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X80059; CAA56365.1; -; Genomic_RNA. DR EMBL; D10582; BAA01439.1; -; Genomic_RNA. DR PIR; A36642; GNNYEC. DR PDB; 2C8I; EM; 14.00 A; A=570-857, B=79-328, C=332-569, D=2-69. DR PDBsum; 2C8I; -. DR SMR; P29813; -. DR DrugBank; DB08231; Myristic acid. DR MEROPS; C03.011; -. DR MEROPS; C03.020; -. DR MEROPS; N08.001; -. DR EvolutionaryTrace; P29813; -. DR Proteomes; UP000002684; 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: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:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW. DR GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0003724; F:RNA helicase activity; IEA:InterPro. DR GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro. DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW. DR GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro. 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:0039606; P:suppression by virus of host translation initiation; 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:0039694; P:viral RNA genome replication; IEA:InterPro. DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW. DR CDD; cd23213; Enterovirus_RdRp; 1. DR CDD; cd00205; rhv_like; 3. DR Gene3D; 1.20.960.20; -; 1. DR Gene3D; 2.60.120.20; -; 3. DR Gene3D; 3.30.70.270; -; 1. DR Gene3D; 4.10.80.10; Picornavirus coat protein VP4; 1. DR Gene3D; 6.10.20.20; Poliovirus 3A protein-like; 1. DR Gene3D; 4.10.880.10; Poliovirus 3D polymerase Domain 1 (Nucleotidyltransferase); 2. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 4. 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; SSF56672; DNA/RNA polymerases; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF88633; Positive stranded ssRNA viruses; 2. DR SUPFAM; SSF89043; Soluble domain of poliovirus core protein 3a; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 2. 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; Activation of host autophagy by virus; ATP-binding; KW Autocatalytic cleavage; Capsid protein; Covalent protein-RNA linkage; KW DNA replication; 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..2195 FT /note="Genome polyprotein" FT /id="PRO_0000426431" FT CHAIN 2..861 FT /note="P1" FT /id="PRO_0000426432" FT CHAIN 2..331 FT /note="Capsid protein VP0" FT /id="PRO_0000426433" FT CHAIN 2..69 FT /note="Capsid protein VP4" FT /id="PRO_0000426434" FT CHAIN 70..331 FT /note="Capsid protein VP2" FT /id="PRO_0000426435" FT CHAIN 332..569 FT /note="Capsid protein VP3" FT /id="PRO_0000426436" FT CHAIN 570..861 FT /note="Capsid protein VP1" FT /id="PRO_0000426437" FT CHAIN 862..1439 FT /note="P2" FT /id="PRO_0000426438" FT CHAIN 862..1011 FT /note="Protease 2A" FT /id="PRO_0000426439" FT CHAIN 1012..1110 FT /note="Protein 2B" FT /id="PRO_0000039708" FT CHAIN 1111..1439 FT /note="Protein 2C" FT /id="PRO_0000039709" FT CHAIN 1440..2195 FT /note="P3" FT /id="PRO_0000426440" FT CHAIN 1440..1550 FT /note="Protein 3AB" FT /id="PRO_0000426441" FT CHAIN 1440..1528 FT /note="Protein 3A" FT /id="PRO_0000039710" FT CHAIN 1529..1550 FT /note="Viral protein genome-linked" FT /id="PRO_0000426442" FT CHAIN 1551..2195 FT /note="Protein 3CD" FT /id="PRO_0000426443" FT CHAIN 1551..1733 FT /note="Protease 3C" FT /id="PRO_0000426444" FT CHAIN 1734..2195 FT /note="RNA-directed RNA polymerase" FT /id="PRO_0000426445" FT TOPO_DOM 2..1505 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT INTRAMEM 1506..1521 FT /evidence="ECO:0000255" FT TOPO_DOM 1522..2195 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 1215..1371 FT /note="SF3 helicase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551" FT DOMAIN 1551..1729 FT /note="Peptidase C3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222" FT DOMAIN 1960..2076 FT /note="RdRp catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539" FT ZN_FING 1379..1396 FT /note="C4-type; degenerate" FT /evidence="ECO:0000250|UniProtKB:B9VUU3" FT REGION 567..583 FT /note="Amphipathic alpha-helix" FT /evidence="ECO:0000255" FT REGION 1111..1249 FT /note="Oligomerization" FT /evidence="ECO:0000250|UniProtKB:P03300" FT REGION 1111..1183 FT /note="Membrane-binding" FT /evidence="ECO:0000250|UniProtKB:P03300" FT REGION 1132..1136 FT /note="RNA-binding" FT /evidence="ECO:0000250|UniProtKB:P03300" FT REGION 1423..1430 FT /note="RNA-binding" FT /evidence="ECO:0000250|UniProtKB:P03300" FT REGION 1434..1439 FT /note="Oligomerization" FT /evidence="ECO:0000250|UniProtKB:P03300" FT ACT_SITE 882 FT /note="For protease 2A activity" FT /evidence="ECO:0000250|UniProtKB:P03300" FT ACT_SITE 900 FT /note="For protease 2A activity" FT /evidence="ECO:0000250|UniProtKB:P03300" FT ACT_SITE 971 FT /note="For protease 2A activity" FT /evidence="ECO:0000250|UniProtKB:P03300" FT ACT_SITE 1590 FT /note="For protease 3C activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222" FT ACT_SITE 1621 FT /note="For protease 3C activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222" FT ACT_SITE 1697 FT /note="For protease 3C activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222" FT BINDING 917 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 919 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 977 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 979 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 1379 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:B9VUU3" FT BINDING 1391 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:B9VUU3" FT BINDING 1396 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:B9VUU3" FT BINDING 1966 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 1966 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 2062 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 2062 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 331..332 FT /note="Cleavage; by protease 3C" FT /evidence="ECO:0000250|UniProtKB:P03301" FT SITE 861..862 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000250|UniProtKB:P03301" FT SITE 1011..1012 FT /note="Cleavage; by protease 3C" FT /evidence="ECO:0000250|UniProtKB:P03301" FT SITE 1110..1111 FT /note="Cleavage; by protease 3C" FT /evidence="ECO:0000250|UniProtKB:P03301" FT SITE 1135 FT /note="Involved in the interaction with host RTN3" FT /evidence="ECO:0000250|UniProtKB:Q66478" FT SITE 1439..1440 FT /note="Cleavage; by protease 3C" FT /evidence="ECO:0000250|UniProtKB:P03301" FT SITE 1528..1529 FT /note="Cleavage; by protease 3C" FT /evidence="ECO:0000250|UniProtKB:P03301" FT SITE 1550..1551 FT /note="Cleavage; by protease 3C" FT /evidence="ECO:0000250|UniProtKB:P03301" FT SITE 1733..1734 FT /note="Cleavage; by protease 3C" FT /evidence="ECO:0000250|UniProtKB:P03301" FT MOD_RES 1531 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" FT CONFLICT 823..827 FT /note="RLCQY -> SYANT (in Ref. 2; BAA01439)" FT /evidence="ECO:0000305" SQ SEQUENCE 2195 AA; 245407 MW; 1CFC5DF288831AF0 CRC64; MGAQVSTQKT GAHETGLNAS GSSIIHYTNI NYYKDAASNS ANRQEFSQDP GKFTEPVKDI MVKSLPALNS PSAEECGYSD RVRSITLGNS TITTQESANV VVGYGRWPEY LKDNEATAED QPTQPDVATC RFYTLESVTW ERDSPGWWWK FPDALKDMGL FGQNMYYHYL GRAGYTLHVQ CNASKFHQGC LLVVCVPEAE MGCSQVDGTV NEHGLSEGET AKKFSSTSTN GTNTVQTIVT NAGMGVGVGN LTIYPHQWIN LRTNNCATIV MPYINNVPMD NMFRHHNFTL MIIPFVPLDY SSDSSTYVPI TVTVAPMCAE YNGLRLSTSL QGLPVMNTPG SNQFLTSDDF QSPSAMPQFD VTPELNIPGE VQNLMEIAEV DSVVPVNNVE GKLDTMEVYR IPVQSGNHQS DQVFGFQVQP GLDSVFKHTL LGEILNYFAH WSGSIKLTFV FCGSAMATGK FLLAYAPPGA NAPKNRKDAM LGTHIIWDVG LQSSCVLCVP WISQTHYRLV QQDEYTSAGN VTCWYQTGIV VPAGTPTSCS IMCFVSACND FSVRLLKDTP FIEQTALLQG DVVEAVENAV ARVADTIGSG PSNSQAVPAL TAVETGHTSQ VTPSDTMQTR HVKNYHSRSE SSIENFLSRS ACVYMGGYHT TNTDQTKLFA SWTISARRMV QMRRKLEIFT YVRFDVEVTF VITSKQDQGS RLGQDMPPLT HQIMYIPPGG PIPKSVTDYA WQTSTNPSIF WTEGNAPPRM SIPFISIGNA YSNFYDGWSH FSQNGVYGYN TLNHMGQIYV RHVNGSSPLP MTSTVRMYFK PKHVKAWVPR PPRLCQYKNA STVNFTPTNV TDKRTSINYI PETVKPDLSN YGAFGYQSGA VYVVNYRVVN RHLATHTDWQ NCVWEDYNRD LLISTTTAHG CDVIARCRCS TGVYYCQSKG KHYPVNFEGP GLVEVQESEY YPKRYQSHVL LAAGFSEPGD CGGILRCEHG VIGIVTMGGE GVVGFADVRD LLWLEDDAME QGVKDYVEQL GNAFGSGFTN QICEQVNLLK ESLVGQDSIL EKSLKALVKI ISALVIVVRN HDDLITVTAT LALIGCTSSP WRWLKQKVSQ YYGIPMAERQ NNGWLKKFTE MTNSCKGMEW ISIKIQKFIE WLKVKILPEV REKHEFLNRL KQLPLLESQI ATIEQSAPSQ SDQEQLFSNV QYFAHYCRKY APLYASEAKR VFSLEKKMSN YIQFKSKCRI EPVCLLLHGS PGAGKSVATN LIGRSLAEKL NSSVYTLPPD PDHFDGYKQQ AVVIVDDLCQ NPDGKDVSLF CQMVSSVDFV PPMAALEEKG ILFTSLFVLA STNAGSINAP TVSDSRALAR RFHFDMNIEV ISMYSQNGKI NMPMSEKTCD EECCPVNFKR CCPLVCGKAI QFIDRRTQVR YSLDMLVTEM FREYNHRHSV GATLEALFQG PPIYREIKIS VAPETPPPPA IADLLKSVDS EAVREYCKEK GWLVPEVNST LQIEKHVSRA FICLQALTTF VSVAGIIYII YKLFAGFQGA YTGMPNQKPK VPTLRQAKVQ GPAFEFAVAM MKRNSSTVKT EYREFTMLGI YDRWAVLPRH AKPGPTILMN NQEVGVLDAK ELVDKDGTNL ELTLLKLNRN EKFRDIRGFL AKEEVEANQA VLAINTSKFP NMYIPVGQVT DYGFLNLGGT PTKRMLMSNF PTRAGQCGGV LMSTGKVLGI HVGGNGHQGF SAALLKHYFN DEQGEIEFIE SSKDAGFPII NTPSKTKLEP SVFHQVFEGD KEPAVLRNGD PRLKANFEEA IFSKYIGNVN THVDEYMLEA VDHYAGQLAT LDISTEPMRL EDAVYGTEGL EALDLTTSAG YPYVALGIKK RDILSRRTRD LTKLKECMDK YGLNLPMVTY VKDELRSADK VAKGKSRLIE ASSLNDSVAM RQTFGNLYRT FHLNPGIVTG SAVGCDPDLF WSKIPVMLDG HLIAFDYSGY DASLSPVWFA CLKLLLEKLG YTHKETNYID YLCNSHHLYR DKHYFERGGM PSGYSGTSMF NSMINNIIIR TLMLKVYKGI DLDQFRMIAY GDDVIASYPW PIDASLLAET GKGYGLIMTP ADKGECFNEV TWTNVTFLKR YFRADEQYPF LVHPVMPMKD IHESIRWTKD PKNTQDHVRS LCLLAWHNGE HEYEEFIRKI RSVPVGRCLT LPAFSTLRRK WLDSF //