POLG_HAVHM
ID POLG_HAVHM Reviewed; 2227 AA.
AC P08617; P06443; P26580; P26581; P26582; Q81082; Q81094; Q8V405;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Genome polyprotein;
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=Protein VP1-2A;
DE AltName: Full=VP1-pX;
DE Contains:
DE RecName: Full=Capsid protein VP1;
DE AltName: Full=P1D;
DE AltName: Full=Virion protein 1;
DE Contains:
DE RecName: Full=Assembly signal 2A;
DE AltName: Full=pX {ECO:0000303|PubMed:23542590};
DE Contains:
DE RecName: Full=Protein 2BC;
DE Contains:
DE RecName: Full=Protein 2B;
DE Short=P2B;
DE Contains:
DE RecName: Full=Protein 2C;
DE Short=P2C;
DE EC=3.6.1.15;
DE Contains:
DE RecName: Full=Protein 3ABCD;
DE Short=P3;
DE Contains:
DE RecName: Full=Protein 3ABC;
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 Contains:
DE RecName: Full=Protease 3C;
DE Short=P3C;
DE EC=3.4.22.28 {ECO:0000269|PubMed:1850033};
DE AltName: Full=Picornain 3C;
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase 3D-POL;
DE Short=P3D-POL;
DE EC=2.7.7.48 {ECO:0000269|PubMed:8291234};
OS Human hepatitis A virus genotype IB (isolate HM175) (HHAV) (Human hepatitis
OS A virus (isolate Human/Australia/HM175/1976)).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Picornaviridae; Hepatovirus.
OX NCBI_TaxID=12098;
OH NCBI_TaxID=9536; Cercopithecus hamlyni (Owl-faced monkey) (Hamlyn's monkey).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9539; Macaca (macaques).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=HM175/wt;
RX PubMed=3023706; DOI=10.1128/jvi.61.1.50-59.1987;
RA Cohen J.I., Ticehurst J.R., Purcell R.H., Buckler-White A., Baroudy B.M.;
RT "Complete nucleotide sequence of wild-type hepatitis A virus: comparison
RT with different strains of hepatitis A virus and other picornaviruses.";
RL J. Virol. 61:50-59(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=HM175/7 MK-5;
RX PubMed=3031686; DOI=10.1073/pnas.84.8.2497;
RA Cohen J.I., Rosenblum B., Ticehurst J.R., Daemer R.J., Feinstone S.M.,
RA Purcell R.H.;
RT "Complete nucleotide sequence of an attenuated hepatitis A virus:
RT comparison with wild-type virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:2497-2501(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=HM175/18f, HM175/24a, and HM175/43c;
RX PubMed=1705995; DOI=10.1128/jvi.65.4.2056-2065.1991;
RA Lemon S.M., Murphy P.C., Shields P.A., Ping L.H., Feinstone S.M.,
RA Cromeans T., Jansen R.W.;
RT "Antigenic and genetic variation in cytopathic hepatitis A virus variants
RT arising during persistent infection: evidence for genetic recombination.";
RL J. Virol. 65:2056-2065(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-854 AND 1724-2227.
RX PubMed=2984684; DOI=10.1073/pnas.82.7.2143;
RA Baroudy B.M., Ticehurst J.R., Miele T.A., Maizel J.V. Jr., Purcell R.H.,
RA Feinstone S.M.;
RT "Sequence analysis of hepatitis A virus cDNA coding for capsid proteins and
RT RNA polymerase.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:2143-2147(1985).
RN [5]
RP PROTEIN SEQUENCE OF 837-856, MUTAGENESIS OF GLN-836, AND PROTEOLYTIC
RP CLEAVAGE (GENOME POLYPROTEIN).
RC STRAIN=HM175p35;
RX PubMed=7483265; DOI=10.1006/viro.1995.1561;
RA Martin A., Escriou N., Chao S.-F., Girard M., Lemon S.M., Wychowski C.;
RT "Identification and site-directed mutagenesis of the primary (2A/2B)
RT cleavage site of the hepatitis A virus polyprotein: functional impact on
RT the infectivity of HAV RNA transcripts.";
RL Virology 213:213-222(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 2090-2227.
RX PubMed=6310601; DOI=10.1073/pnas.80.19.5885;
RA Ticehurst J.R., Racaniello V.R., Baroudy B.M., Baltimore D., Purcell R.H.,
RA Feinstone S.M.;
RT "Molecular cloning and characterization of hepatitis A virus cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:5885-5889(1983).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-819.
RC STRAIN=Isolate Val8;
RX PubMed=12409389; DOI=10.1128/jcm.40.11.4148-4155.2002;
RA Sanchez G., Pinto R.M., Vanaclocha H., Bosch A.;
RT "Molecular characterization of hepatitis a virus isolates from a
RT transcontinental shellfish-borne outbreak.";
RL J. Clin. Microbiol. 40:4148-4155(2002).
RN [8]
RP IDENTIFICATION (VIRAL PROTEIN GENOME-LINKED).
RX PubMed=3018280; DOI=10.1128/jvi.60.1.124-130.1986;
RA Weitz M., Baroudy B.M., Maloy W.L., Ticehurst J.R., Purcell R.H.;
RT "Detection of a genome-linked protein (VPg) of hepatitis A virus and its
RT comparison with other picornaviral VPgs.";
RL J. Virol. 60:124-130(1986).
RN [9]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN), FUNCTION (PROTEASE 3C), AND
RP CATALYTIC ACTIVITY (PROTEASE 3C).
RX PubMed=1850033; DOI=10.1128/jvi.65.5.2595-2600.1991;
RA Jia X.-Y., Ehrenfeld E., Summers D.F.;
RT "Proteolytic activity of hepatitis A virus 3C protein.";
RL J. Virol. 65:2595-2600(1991).
RN [10]
RP IDENTIFICATION OF N-TERMINUS (GENOME POLYPROTEIN).
RC STRAIN=HM175/7;
RX PubMed=1310188; DOI=10.1016/0042-6822(92)90027-m;
RA Tesar M., Harmon S.A., Summers D.F., Ehrenfeld E.;
RT "Hepatitis A virus polyprotein synthesis initiates from two alternative AUG
RT codons.";
RL Virology 186:609-618(1992).
RN [11]
RP ABSENCE OF MYRISTOYLATION (PROTEIN VP4).
RC STRAIN=HM175/7;
RX PubMed=8389076; DOI=10.1006/viro.1993.1301;
RA Tesar M., Jia X.-Y., Summers D.F., Ehrenfeld E.;
RT "Analysis of a potential myristoylation site in hepatitis A virus capsid
RT protein VP4.";
RL Virology 194:616-626(1993).
RN [12]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN).
RX PubMed=8382411; DOI=10.1006/viro.1993.1157;
RA Jia X.-Y., Summers D.F., Ehrenfeld E.;
RT "Primary cleavage of the HAV capsid protein precursor in the middle of the
RT proposed 2A coding region.";
RL Virology 193:515-519(1993).
RN [13]
RP PROTEOLYTIC CLEAVAGE (CAPSID PROTEIN VP0), AND CATALYTIC ACTIVITY
RP (RNA-DIRECTED RNA POLYMERASE 3D-POL).
RX PubMed=8291234; DOI=10.1006/viro.1994.1063;
RA Tesar M., Pak I., Jia X.-Y., Richards O.C., Summers D.F., Ehrenfeld E.;
RT "Expression of hepatitis A virus precursor protein P3 in vivo and in vitro:
RT polyprotein processing of the 3CD cleavage site.";
RL Virology 198:524-533(1994).
RN [14]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN).
RX PubMed=8259663; DOI=10.1006/viro.1994.1030;
RA Schultheiss T., Kusov Y.Y., Gauss-Mueller V.;
RT "Proteinase 3C of hepatitis A virus (HAV) cleaves the HAV polyprotein P2-P3
RT at all sites including VP1/2A and 2A/2B.";
RL Virology 198:275-281(1994).
RN [15]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN).
RX PubMed=7853510; DOI=10.1128/jvi.69.3.1727-1733.1995;
RA Schultheiss T., Sommergruber W., Kusov Y., Gauss-Mueller V.;
RT "Cleavage specificity of purified recombinant hepatitis A virus 3C
RT proteinase on natural substrates.";
RL J. Virol. 69:1727-1733(1995).
RN [16]
RP FUNCTION (PROTEIN 3AB).
RX PubMed=7601283; DOI=10.1016/0014-5793(95)00523-c;
RA Lama J., Carrasco L.;
RT "Mutations in the hydrophobic domain of poliovirus protein 3AB abrogate its
RT permeabilizing activity.";
RL FEBS Lett. 367:5-11(1995).
RN [17]
RP PROTEOLYTIC CLEAVAGE (CAPSID PROTEIN VP0).
RX PubMed=9060697; DOI=10.1128/jvi.71.4.3288-3292.1997;
RA Probst C., Jecht M., Gauss-Mueller V.;
RT "Proteinase 3C-mediated processing of VP1-2A of two hepatitis A virus
RT strains: in vivo evidence for cleavage at amino acid position 273/274 of
RT VP1.";
RL J. Virol. 71:3288-3292(1997).
RN [18]
RP FUNCTION (PROTEIN 2C), FUNCTION (PROTEIN 2BC), AND FUNCTION (PROTEIN 2B).
RC STRAIN=HM175/24a, HM175/wt, and HM175p35;
RX PubMed=9344908; DOI=10.1006/viro.1997.8775;
RA Teterina N.L., Bienz K., Egger D., Gorbalenya A.E., Ehrenfeld E.;
RT "Induction of intracellular membrane rearrangements by HAV proteins 2C and
RT 2BC.";
RL Virology 237:66-77(1997).
RN [19]
RP SUBUNIT (PROTEIN 3AB), FUNCTION (PROTEIN 3AB), TOPOLOGY (PROTEIN 3AB),
RP TOPOLOGY (PROTEIN 3A), AND FUNCTION (PROTEIN 3A).
RX PubMed=9705870; DOI=10.1006/bbrc.1998.9121;
RA Ciervo A., Beneduce F., Morace G.;
RT "Polypeptide 3AB of hepatitis A virus is a transmembrane protein.";
RL Biochem. Biophys. Res. Commun. 249:266-274(1998).
RN [20]
RP SUBCELLULAR LOCATION (PROTEIN 2C), RNA-BINDING (PROTEIN 2C), AND FUNCTION
RP (PROTEIN 2C).
RX PubMed=9645199; DOI=10.1007/s007050050343;
RA Kusov Y.Y., Probst C., Jecht M., Jost P.D., Gauss-Mueller V.;
RT "Membrane association and RNA binding of recombinant hepatitis A virus
RT protein 2C.";
RL Arch. Virol. 143:931-944(1998).
RN [21]
RP PROTEOLYTIC CLEAVAGE (CAPSID PROTEIN VP0).
RX PubMed=9733840; DOI=10.1128/jvi.72.10.8013-8020.1998;
RA Probst C., Jecht M., Gauss-Mueller V.;
RT "Processing of proteinase precursors and their effect on hepatitis A virus
RT particle formation.";
RL J. Virol. 72:8013-8020(1998).
RN [22]
RP FUNCTION (CAPSID PROTEIN VP1), FUNCTION (CAPSID PROTEIN VP2), AND FUNCTION
RP (CAPSID PROTEIN VP3).
RX PubMed=9658108; DOI=10.1128/jvi.72.8.6621-6628.1998;
RA Feigelstock D., Thompson P., Mattoo P., Zhang Y., Kaplan G.G.;
RT "The human homolog of HAVcr-1 codes for a hepatitis A virus cellular
RT receptor.";
RL J. Virol. 72:6621-6628(1998).
RN [23]
RP FUNCTION (PROTEIN 2B), FUNCTION (PROTEIN 2BC), SUBCELLULAR LOCATION
RP (PROTEIN 2B), AND SUBCELLULAR LOCATION (PROTEIN 2C).
RX PubMed=9875331; DOI=10.1006/viro.1998.9451;
RA Jecht M., Probst C., Gauss-Mueller V.;
RT "Membrane permeability induced by hepatitis A virus proteins 2B and 2BC and
RT proteolytic processing of HAV 2BC.";
RL Virology 252:218-227(1998).
RN [24]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN), AND FUNCTION (PROTEIN 3ABC).
RX PubMed=10559299; DOI=10.1128/jvi.73.12.9867-9878.1999;
RA Kusov Y., Gauss-Mueller V.;
RT "Improving proteolytic cleavage at the 3A/3B site of the hepatitis A virus
RT polyprotein impairs processing and particle formation, and the impairment
RT can be complemented in trans by 3AB and 3ABC.";
RL J. Virol. 73:9867-9878(1999).
RN [25]
RP FUNCTION (PROTEIN 3AB), INTERACTION WITH PROTEIN 3CD (PROTEIN 3AB),
RP INTERACTION WITH PROTEIN 3AB (PROTEIN 3CD), RNA-BINDING (PROTEIN 3AB),
RP FUNCTION (PROTEIN 3A), AND FUNCTION (PROTEIN 3CD).
RC STRAIN=HM175/7;
RX PubMed=10562502; DOI=10.1006/viro.1999.0017;
RA Beneduce F., Ciervo A., Kusov Y.Y., Gauss-Mueller V., Morace G.;
RT "Mapping of protein domains of hepatitis A virus 3AB essential for
RT interaction with 3CD and viral RNA.";
RL Virology 264:410-421(1999).
RN [26]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN), AND PROTEOLYTIC CLEAVAGE
RP (PROTEIN VP1-2A).
RC STRAIN=HM175p35, and HM175pE;
RX PubMed=10364353; DOI=10.1128/jvi.73.7.6015-6023.1999;
RA Graff J., Richards O.C., Swiderek K.M., Davis M.T., Rusnak F., Harmon S.A.,
RA Jia X.-Y., Summers D.F., Ehrenfeld E.;
RT "Hepatitis A virus capsid protein VP1 has a heterogeneous C terminus.";
RL J. Virol. 73:6015-6023(1999).
RN [27]
RP FUNCTION (PROTEIN VP1-2A), AND FUNCTION (PROTEIN VP4).
RX PubMed=9988685; DOI=10.1074/jbc.274.8.4527;
RA Probst C., Jecht M., Gauss-Mueller V.;
RT "Intrinsic signals for the assembly of hepatitis A virus particles. Role of
RT structural proteins VP4 and 2A.";
RL J. Biol. Chem. 274:4527-4531(1999).
RN [28]
RP FUNCTION (CAPSID PROTEIN VP1), FUNCTION (CAPSID PROTEIN VP2), AND FUNCTION
RP (CAPSID PROTEIN VP3).
RX PubMed=11134285; DOI=10.1128/jvi.75.2.717-725.2001;
RA Silberstein E., Dveksler G., Kaplan G.G.;
RT "Neutralization of hepatitis A virus (HAV) by an immunoadhesin containing
RT the cysteine-rich region of HAV cellular receptor-1.";
RL J. Virol. 75:717-725(2001).
RN [29]
RP FUNCTION (PROTEIN VP1-2A), AND DOMAIN (PROTEIN VP1-2A).
RC STRAIN=HM175/18f;
RX PubMed=12097562; DOI=10.1128/jvi.76.15.7495-7505.2002;
RA Cohen L., Benichou D., Martin A.;
RT "Analysis of deletion mutants indicates that the 2A polypeptide of
RT hepatitis A virus participates in virion morphogenesis.";
RL J. Virol. 76:7495-7505(2002).
RN [30]
RP SUBUNIT (PROTEIN VP1-2A), MUTAGENESIS OF ARG-769, DOMAIN (PROTEIN VP1-2A),
RP AND PROTEOLYTIC CLEAVAGE (CAPSID PROTEIN VP0).
RX PubMed=12782637; DOI=10.1074/jbc.m300454200;
RA Rachow A., Gauss-Mueller V., Probst C.;
RT "Homogenous hepatitis A virus particles. Proteolytic release of the
RT assembly signal 2A from procapsids by factor Xa.";
RL J. Biol. Chem. 278:29744-29751(2003).
RN [31]
RP MUTAGENESIS OF ALA-1052.
RX PubMed=12858403; DOI=10.1002/jmv.10457;
RA Graff J., Emerson S.U.;
RT "Importance of amino acid 216 in nonstructural protein 2B for replication
RT of hepatitis A virus in cell culture and in vivo.";
RL J. Med. Virol. 71:7-17(2003).
RN [32]
RP MUTAGENESIS OF CYS-1543 AND CYS-1691, DISULFIDE BOND (PROTEASE 3C), SUBUNIT
RP (PROTEASE 3C), AND RNA-BINDING (PROTEASE 3C).
RX PubMed=15361063; DOI=10.1042/bj20041153;
RA Peters H., Kusov Y.Y., Meyer S., Benie A.J., Baeuml E., Wolff M.,
RA Rademacher C., Peters T., Gauss-Mueller V.;
RT "Hepatitis A virus proteinase 3C binding to viral RNA: correlation with
RT substrate binding and enzyme dimerization.";
RL Biochem. J. 385:363-370(2005).
RN [33]
RP FUNCTION (PROTEIN 3ABC), SUBCELLULAR LOCATION (PROTEIN 3ABC), AND
RP INTERACTION WITH HUMAN MAVS (PROTEIN 3ABC).
RC STRAIN=HM175/18f;
RX PubMed=17438296; DOI=10.1073/pnas.0611506104;
RA Yang Y., Liang Y., Qu L., Chen Z., Yi M., Li K., Lemon S.M.;
RT "Disruption of innate immunity due to mitochondrial targeting of a
RT picornaviral protease precursor.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7253-7258(2007).
RN [34]
RP FUNCTION (PROTEASE 3C).
RX PubMed=17726047; DOI=10.1093/nar/gkm645;
RA Zhang B., Morace G., Gauss-Mueller V., Kusov Y.;
RT "Poly(A) binding protein, C-terminally truncated by the hepatitis A virus
RT proteinase 3C, inhibits viral translation.";
RL Nucleic Acids Res. 35:5975-5984(2007).
RN [35]
RP FUNCTION (PROTEIN 2B).
RX PubMed=18559929; DOI=10.1099/vir.0.83521-0;
RA Paulmann D., Magulski T., Schwarz R., Heitmann L., Flehmig B.,
RA Vallbracht A., Dotzauer A.;
RT "Hepatitis A virus protein 2B suppresses beta interferon (IFN) gene
RT transcription by interfering with IFN regulatory factor 3 activation.";
RL J. Gen. Virol. 89:1593-1604(2008).
RN [36]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN), MUTAGENESIS OF ARG-769, SUBUNIT
RP (PROTEIN VP1-2A), AND PROTEOLYTIC CLEAVAGE (PROTEIN VP1-2A).
RX PubMed=18823593; DOI=10.5483/bmbrep.2008.41.9.678;
RA Morace G., Kusov Y., Dzagurov G., Beneduce F., Gauss-Muller V.;
RT "The unique role of domain 2A of the hepatitis A virus precursor
RT polypeptide P1-2A in viral morphogenesis.";
RL BMB Rep. 41:678-683(2008).
RN [37]
RP FUNCTION (PROTEIN 2B), AND SUBCELLULAR LOCATION (PROTEIN 2B).
RX PubMed=18216106; DOI=10.1128/jvi.02076-07;
RA de Jong A.S., de Mattia F., Van Dommelen M.M., Lanke K., Melchers W.J.,
RA Willems P.H., van Kuppeveld F.J.;
RT "Functional analysis of picornavirus 2B proteins: effects on calcium
RT homeostasis and intracellular protein trafficking.";
RL J. Virol. 82:3782-3790(2008).
RN [38]
RP FUNCTION (PROTEIN 3CD), AND MUTAGENESIS OF CYS-1691.
RC STRAIN=HM175/18f;
RX PubMed=21931545; DOI=10.1371/journal.ppat.1002169;
RA Qu L., Feng Z., Yamane D., Liang Y., Lanford R.E., Li K., Lemon S.M.;
RT "Disruption of TLR3 signaling due to cleavage of TRIF by the hepatitis A
RT virus protease-polymerase processing intermediate, 3CD.";
RL PLoS Pathog. 7:E1002169-E1002169(2011).
RN [39]
RP DOMAIN LATE-BUDDING (GENOME POLYPROTEIN), DOMAIN LATE-BUDDING (CAPSID
RP PROTEIN VP2), AND MUTAGENESIS OF TYR-167 AND TYR-200.
RX PubMed=23542590; DOI=10.1038/nature12029;
RA Feng Z., Hensley L., McKnight K.L., Hu F., Madden V., Ping L., Jeong S.H.,
RA Walker C., Lanford R.E., Lemon S.M.;
RT "A pathogenic picornavirus acquires an envelope by hijacking cellular
RT membranes.";
RL Nature 496:367-371(2013).
RN [40]
RP INTERACTION WITH HOST ACBD3.
RX PubMed=23572552; DOI=10.1128/mbio.00098-13;
RA Greninger A.L., Knudsen G.M., Betegon M., Burlingame A.L., DeRisi J.L.;
RT "ACBD3 interaction with TBC1 domain 22 protein is differentially affected
RT by enteroviral and kobuviral 3A protein binding.";
RL MBio 4:E00098-E00098(2013).
RN [41]
RP FUNCTION (PROTEASE 3C).
RX PubMed=24920812; DOI=10.1128/jvi.00869-14;
RA Wang D., Fang L., Wei D., Zhang H., Luo R., Chen H., Li K., Xiao S.;
RT "Hepatitis A virus 3C protease cleaves NEMO to impair induction of beta
RT interferon.";
RL J. Virol. 88:10252-10258(2014).
RN [42]
RP FUNCTION (VIRAL PROTEIN GENOME-LINKED).
RX PubMed=25240314; DOI=10.1016/j.coviro.2014.09.003;
RA Sun Y., Guo Y., Lou Z.;
RT "Formation and working mechanism of the picornavirus VPg uridylylation
RT complex.";
RL Curr. Opin. Virol. 9:24-30(2014).
RN [43]
RP FUNCTION (PROTEIN 2B), SUBUNIT (PROTEIN 2B), DOMAIN (PROTEIN 2B), AND
RP SUBCELLULAR LOCATION (PROTEIN 2B).
RX PubMed=26515753; DOI=10.1038/srep15884;
RA Shukla A., Dey D., Banerjee K., Nain A., Banerjee M.;
RT "The C-terminal region of the non-structural protein 2B from Hepatitis A
RT Virus demonstrates lipid-specific viroporin-like activity.";
RL Sci. Rep. 5:15884-15884(2015).
RN [44]
RP REVIEW.
RX PubMed=26999188; DOI=10.3390/v8030082;
RA Sun D., Chen S., Cheng A., Wang M.;
RT "Roles of the picornaviral 3C proteinase in the viral life cycle and host
RT cells.";
RL Viruses 8:82-82(2016).
RN [45]
RP PROTEOLYTIC CLEAVAGE (PROTEIN VP1-2A), SUBCELLULAR LOCATION (CAPSID PROTEIN
RP VP1), SUBCELLULAR LOCATION (CAPSID PROTEIN VP2), AND SUBCELLULAR LOCATION
RP (CAPSID PROTEIN VP3).
RX PubMed=28490497; DOI=10.1073/pnas.1619519114;
RA McKnight K.L., Xie L., Gonzalez-Lopez O., Rivera-Serrano E.E., Chen X.,
RA Lemon S.M.;
RT "Protein composition of the hepatitis A virus quasi-envelope.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:6587-6592(2017).
RN [46]
RP FUNCTION (CAPSID PROTEIN VP1), FUNCTION (CAPSID PROTEIN VP2), AND FUNCTION
RP (CAPSID PROTEIN VP3).
RX PubMed=29437974; DOI=10.1128/jvi.02065-17;
RA Costafreda M.I., Kaplan G.;
RT "HAVCR1 (CD365) and its mouse ortholog are functional hepatitis A virus
RT (HAV) cellular receptors that mediate HAV infection.";
RL J. Virol. 92:0-0(2018).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736.
RX PubMed=8164744; DOI=10.1038/369072a0;
RA Allaire M., Chernaia M.M., Malcolm B.A., James M.N.;
RT "Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-
RT like serine proteinases.";
RL Nature 369:72-76(1994).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736, RNA-BINDING (PROTEASE
RP 3C), AND FUNCTION (PROTEASE 3C).
RX PubMed=9032381; DOI=10.1128/jvi.71.3.2436-2448.1997;
RA Bergmann E.M., Mosimann S.C., Chernaia M.M., Malcolm B.A., James M.N.G.;
RT "The refined crystal structure of the 3C gene product from hepatitis A
RT virus: specific proteinase activity and RNA recognition.";
RL J. Virol. 71:2436-2448(1997).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1520-1736 IN COMPLEX WITH THE
RP INHIBITOR IODOACETYL-VALYL-PHENYLALANYL-AMIDE.
RX PubMed=10603326; DOI=10.1006/viro.1999.9968;
RA Bergmann E.M., Cherney M.M., Mckendrick J., Frormann S., Luo C.,
RA Malcolm B.A., Vederas J.C., James M.N.G.;
RT "Crystal structure of an inhibitor complex of the 3C proteinase from
RT hepatitis A virus (HAV) and implications for the polyprotein processing in
RT HAV.";
RL Virology 265:153-163(1999).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1520-1731 IN COMPLEX WITH
RP PEPTIDE-BASED KETONE INHIBITORS.
RX PubMed=16860823; DOI=10.1016/j.jmb.2006.06.047;
RA Yin J., Cherney M.M., Bergmann E.M., Zhang J., Huitema C., Pettersson H.,
RA Eltis L.D., Vederas J.C., James M.N.G.;
RT "An episulfide cation (thiiranium ring) trapped in the active site of HAV
RT 3C proteinase inactivated by peptide-based ketone inhibitors.";
RL J. Mol. Biol. 361:673-686(2006).
RN [51] {ECO:0007744|PDB:4WZN}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 765-981, AND SUBUNIT (PROTEIN
RP 2B).
RX PubMed=25589659; DOI=10.1128/jvi.02881-14;
RA Vives-Adrian L., Garriga D., Buxaderas M., Fraga J., Pereira P.J.,
RA Macedo-Ribeiro S., Verdaguer N.;
RT "Structural basis for host membrane remodeling induced by protein 2B of
RT hepatitis A virus.";
RL J. Virol. 89:3648-3658(2015).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 24-245 AND 246-491, FUNCTION
RP (PROTEIN VP0), SUBCELLULAR LOCATION (PROTEIN VP4), INTERACTION WITH CAPSID
RP PROTEIN VP2 (CAPSID PROTEIN VP1), INTERACTION WITH CAPSID PROTEIN VP2
RP (CAPSID PROTEIN VP3), INTERACTION WITH CAPSID PROTEIN VP1 (CAPSID PROTEIN
RP VP2), INTERACTION WITH CAPSID PROTEIN VP1(CAPSID PROTEIN VP3), INTERACTION
RP WITH CAPSID PROTEIN VP3 (CAPSID PROTEIN VP1), INTERACTION WITH CAPSID
RP PROTEIN VP3 (CAPSID PROTEIN VP2), FUNCTION (CAPSID PROTEIN VP1), FUNCTION
RP (CAPSID PROTEIN VP2), FUNCTION (CAPSID PROTEIN VP3), SUBCELLULAR LOCATION
RP (CAPSID PROTEIN VP1), SUBCELLULAR LOCATION (CAPSID PROTEIN VP2), AND
RP SUBCELLULAR LOCATION (CAPSID PROTEIN VP3).
RC STRAIN=TZ84;
RX PubMed=25327248; DOI=10.1038/nature13806;
RA Wang X., Ren J., Gao Q., Hu Z., Sun Y., Li X., Rowlands D.J., Yin W.,
RA Wang J., Stuart D.I., Rao Z., Fry E.E.;
RT "Hepatitis A virus and the origins of picornaviruses.";
RL Nature 517:85-88(2015).
RN [53] {ECO:0007744|PDB:5WTE, ECO:0007744|PDB:5WTF, ECO:0007744|PDB:5WTH}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 492-769; 24-245 AND
RP 246-491, INTERACTION WITH CAPSID PROTEIN VP2 (CAPSID PROTEIN VP1),
RP INTERACTION WITH CAPSID PROTEIN VP2 (CAPSID PROTEIN VP3), INTERACTION WITH
RP CAPSID PROTEIN VP1 (CAPSID PROTEIN VP2), INTERACTION WITH CAPSID PROTEIN
RP VP1(CAPSID PROTEIN VP3), INTERACTION WITH CAPSID PROTEIN VP3 (CAPSID
RP PROTEIN VP1), INTERACTION WITH CAPSID PROTEIN VP3 (CAPSID PROTEIN VP2),
RP FUNCTION (CAPSID PROTEIN VP1), FUNCTION (CAPSID PROTEIN VP2), FUNCTION
RP (CAPSID PROTEIN VP3), SUBCELLULAR LOCATION (CAPSID PROTEIN VP1),
RP SUBCELLULAR LOCATION (CAPSID PROTEIN VP2), AND SUBCELLULAR LOCATION (CAPSID
RP PROTEIN VP3).
RX PubMed=28074040; DOI=10.1073/pnas.1616502114;
RA Wang X., Zhu L., Dang M., Hu Z., Gao Q., Yuan S., Sun Y., Zhang B., Ren J.,
RA Kotecha A., Walter T.S., Wang J., Fry E.E., Stuart D.I., Rao Z.;
RT "Potent neutralization of hepatitis A virus reveals a receptor mimic
RT mechanism and the receptor recognition site.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:770-775(2017).
CC -!- FUNCTION: [Capsid protein VP1]: Capsid proteins VP1, VP2, and VP3 form
CC a closed capsid enclosing the viral positive strand RNA genome
CC (PubMed:25327248, PubMed:28074040). All these proteins contain a beta-
CC sheet structure called beta-barrel jelly roll (PubMed:25327248).
CC Together they form an icosahedral capsid (T=3) composed of 60 copies of
CC each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms
CC (PubMed:25327248). VP1 is situated at the 12 fivefold axes, whereas VP2
CC and VP3 are located at the quasi-sixfold axes (PubMed:25327248). The
CC naked capsid interacts with the host receptor HAVCR1 to provide virion
CC attachment to and probably entry into the target cell (PubMed:9658108,
CC PubMed:11134285, PubMed:29437974). {ECO:0000269|PubMed:11134285,
CC ECO:0000269|PubMed:25327248, ECO:0000269|PubMed:28074040,
CC ECO:0000269|PubMed:29437974, ECO:0000269|PubMed:9658108}.
CC -!- FUNCTION: [Capsid protein VP2]: Capsid proteins VP1, VP2, and VP3 form
CC a closed capsid enclosing the viral positive strand RNA genome
CC (PubMed:25327248, PubMed:28074040). All these proteins contain a beta-
CC sheet structure called beta-barrel jelly roll (PubMed:25327248).
CC Together they form an icosahedral capsid (T=3) composed of 60 copies of
CC each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms
CC (PubMed:25327248). VP1 is situated at the 12 fivefold axes, whereas VP2
CC and VP3 are located at the quasi-sixfold axes (PubMed:25327248). The
CC naked capsid interacts with the host receptor HAVCR1 to provide virion
CC attachment to and probably entry into the target cell (PubMed:9658108,
CC PubMed:11134285, PubMed:29437974). {ECO:0000269|PubMed:11134285,
CC ECO:0000269|PubMed:25327248, ECO:0000269|PubMed:28074040,
CC ECO:0000269|PubMed:29437974, ECO:0000269|PubMed:9658108}.
CC -!- FUNCTION: [Capsid protein VP3]: Capsid proteins VP1, VP2, and VP3 form
CC a closed capsid enclosing the viral positive strand RNA genome
CC (PubMed:25327248, PubMed:28074040). All these proteins contain a beta-
CC sheet structure called beta-barrel jelly roll (PubMed:25327248).
CC Together they form an icosahedral capsid (T=3) composed of 60 copies of
CC each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms
CC (PubMed:25327248). VP1 is situated at the 12 fivefold axes, whereas VP2
CC and VP3 are located at the quasi-sixfold axes (PubMed:25327248). The
CC naked capsid interacts with the host receptor HAVCR1 to provide virion
CC attachment to and probably entry into the target cell (PubMed:9658108,
CC PubMed:11134285, PubMed:29437974). {ECO:0000269|PubMed:11134285,
CC ECO:0000269|PubMed:25327248, ECO:0000269|PubMed:28074040,
CC ECO:0000269|PubMed:29437974, ECO:0000269|PubMed:9658108}.
CC -!- FUNCTION: [Capsid protein VP0]: VP0 precursor is a component of the
CC immature procapsids. {ECO:0000269|PubMed:25327248}.
CC -!- FUNCTION: [Capsid protein VP4]: Plays a role in the assembly of the 12
CC pentamers into an icosahedral structure. Has not been detected in
CC mature virions, supposedly owing to its small size.
CC {ECO:0000269|PubMed:9988685}.
CC -!- FUNCTION: [Protein VP1-2A]: Precursor component of immature procapsids
CC that corresponds to an extended form of the structural protein VP1
CC (PubMed:9988685, PubMed:12097562). After maturation, possibly by the
CC host Cathepsin L, the assembly signal 2A is cleaved to give rise to the
CC mature VP1 protein (PubMed:9988685). {ECO:0000269|PubMed:12097562,
CC ECO:0000269|PubMed:9988685}.
CC -!- FUNCTION: [Protein 2B]: Functions as a viroporin (PubMed:26515753).
CC Affects membrane integrity and causes an increase in membrane
CC permeability (PubMed:9875331). Involved in host intracellular membrane
CC rearrangements probably to give rise to the viral factories
CC (PubMed:9344908). Does not disrupt calcium homeostasis or glycoprotein
CC trafficking (PubMed:18216106). Antagonizes the innate immune response
CC of the host by suppressing IFN-beta synthesis, which it achieves by
CC interfering with the DDX58/IFIH1 (RIG-I/MDA5) pathway
CC (PubMed:18559929). {ECO:0000269|PubMed:18216106,
CC ECO:0000269|PubMed:18559929, ECO:0000269|PubMed:26515753,
CC ECO:0000269|PubMed:9344908, ECO:0000269|PubMed:9875331}.
CC -!- FUNCTION: [Protein 2BC]: Affects membrane integrity and causes an
CC increase in membrane permeability. {ECO:0000269|PubMed:9344908,
CC ECO:0000269|PubMed:9875331}.
CC -!- FUNCTION: [Protein 2C]: Associates with and induces structural
CC rearrangements of intracellular membranes (PubMed:9344908). Displays
CC RNA-binding activity (PubMed:9645199). {ECO:0000269|PubMed:9344908,
CC ECO:0000269|PubMed:9645199}.
CC -!- FUNCTION: [Protein 3ABC]: The precursor 3ABC is targeted to the
CC mitochondrial membrane where protease 3C activity cleaves and inhibits
CC the host antiviral protein MAVS, thereby disrupting activation of IRF3
CC through the IFIH1/MDA5 pathway (PubMed:17438296). In vivo, the protease
CC activity of 3ABC precursor is more efficient in cleaving the 2BC
CC precursor than that of protein 3C. The 3ABC precursor may therefore
CC play a role in the proteolytic processing of the polyprotein
CC (PubMed:10559299). {ECO:0000269|PubMed:10559299,
CC ECO:0000269|PubMed:17438296}.
CC -!- FUNCTION: [Protein 3AB]: Interacts with the 3CD precursor and with RNA
CC structures found at both the 5'- and 3'-termini of the viral genome
CC (PubMed:10562502). Since the 3AB precursor contains the hydrophobic
CC domain 3A, it probably anchors the whole viral replicase complex to
CC intracellular membranes on which viral RNA synthesis occurs
CC (PubMed:9705870). {ECO:0000269|PubMed:10562502,
CC ECO:0000269|PubMed:9705870}.
CC -!- FUNCTION: [Protein 3A]: May serve as membrane anchor to the 3AB and
CC 3ABC precursors via its hydrophobic domain (PubMed:9705870). May
CC interact with RNA (PubMed:10562502). {ECO:0000269|PubMed:10562502,
CC ECO:0000269|PubMed:9705870}.
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. The VPg-pUpU
CC is then used as primer on the genomic RNA poly(A) by the RNA-dependent
CC RNA polymerase to replicate the viral genome.
CC {ECO:0000250|UniProtKB:P03300, ECO:0000303|PubMed:25240314}.
CC -!- FUNCTION: [Protease 3C]: Cysteine protease that generates mature viral
CC proteins from the precursor polyprotein (PubMed:1850033). In addition
CC to its proteolytic activity, it binds to viral RNA, and thus influences
CC viral genome replication (PubMed:15361063). RNA and substrate bind
CC cooperatively to the protease (PubMed:9032381). Cleaves IKBKG/NEMO to
CC impair innate immune signaling (PubMed:24920812). Cleaves host PABPC1
CC which may participate in the switch of viral translation to RNA
CC synthesis (PubMed:17726047). {ECO:0000269|PubMed:15361063,
CC ECO:0000269|PubMed:17726047, ECO:0000269|PubMed:1850033,
CC ECO:0000269|PubMed:24920812, ECO:0000269|PubMed:9032381}.
CC -!- FUNCTION: [Protein 3CD]: Interacts with the 3AB precursor and with RNA
CC structures found at both the 5'- and 3'-termini of the viral genome
CC (PubMed:10562502). Disrupts TLR3 signaling by degrading the host
CC adapter protein TICAM1/TRIF (PubMed:21931545).
CC {ECO:0000269|PubMed:10562502, ECO:0000269|PubMed:21931545}.
CC -!- FUNCTION: RNA-directed RNA polymerase 3D-POL replicates genomic and
CC antigenomic RNA by recognizing replications specific signals.
CC {ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539,
CC ECO:0000269|PubMed:8291234};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=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 ECO:0000269|PubMed:1850033};
CC -!- SUBUNIT: [Protein 2B]: Homodimer. Homomultimer; probably interacts with
CC membranes in a multimeric form (PubMed:26515753). Seems to assemble
CC into amyloid-like fibers (PubMed:25589659).
CC {ECO:0000269|PubMed:25589659, ECO:0000269|PubMed:26515753,
CC ECO:0000305}.
CC -!- SUBUNIT: [Protein 3A]: Interacts with host ACBD3 (PubMed:23572552).
CC {ECO:0000269|PubMed:23572552}.
CC -!- SUBUNIT: [Protein 3AB]: Homodimer. Monomer (PubMed:9705870). Interacts
CC with protein 3CD (PubMed:10562502). {ECO:0000269|PubMed:10562502,
CC ECO:0000269|PubMed:9705870, ECO:0000305}.
CC -!- SUBUNIT: [Protein 3CD]: Interacts with protein 3AB (PubMed:10562502).
CC {ECO:0000269|PubMed:10562502}.
CC -!- SUBUNIT: [Protein 3ABC]: Interacts with human MAVS (PubMed:17438296).
CC {ECO:0000269|PubMed:17438296}.
CC -!- SUBUNIT: [Protease 3C]: Homodimer; disulfide-linked (PubMed:15361063).
CC {ECO:0000269|PubMed:15361063}.
CC -!- SUBUNIT: [Protein VP1-2A]: Homopentamer (PubMed:12782637). Homooligomer
CC (PubMed:18823593, PubMed:12782637). {ECO:0000269|PubMed:12782637,
CC ECO:0000269|PubMed:18823593}.
CC -!- SUBUNIT: [Capsid protein VP1]: Interacts with capsid protein VP2
CC (PubMed:25327248, PubMed:28074040). Interacts with capsid protein VP3
CC (PubMed:25327248, PubMed:28074040). {ECO:0000269|PubMed:25327248}.
CC -!- SUBUNIT: [Capsid protein VP2]: Interacts with capsid protein VP1
CC (PubMed:25327248, PubMed:28074040). Interacts with capsid protein VP3
CC (PubMed:25327248, PubMed:28074040). {ECO:0000269|PubMed:25327248}.
CC -!- SUBUNIT: [Capsid protein VP3]: Interacts with capsid protein VP1
CC (PubMed:25327248, PubMed:28074040). Interacts with capsid protein VP2
CC (PubMed:25327248, PubMed:28074040). {ECO:0000269|PubMed:25327248}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion
CC {ECO:0000269|PubMed:25327248, ECO:0000269|PubMed:28074040}. Host
CC endosome, host multivesicular body {ECO:0000269|PubMed:28490497}.
CC Note=The egress of newly formed virions occurs through an exosome-like
CC mechanism involving endosomal budding of viral capsids into
CC multivesicular bodies. {ECO:0000269|PubMed:28490497}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion
CC {ECO:0000269|PubMed:25327248, ECO:0000269|PubMed:28074040}. Host
CC endosome, host multivesicular body {ECO:0000269|PubMed:28490497}.
CC Note=The egress of newly formed virions occurs through an exosome-like
CC mechanism involving endosomal budding of viral capsids into
CC multivesicular bodies. {ECO:0000269|PubMed:28490497}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion
CC {ECO:0000269|PubMed:25327248, ECO:0000269|PubMed:28074040}. Host
CC endosome, host multivesicular body {ECO:0000269|PubMed:28490497}.
CC Note=The egress of newly formed virions occurs through an exosome-like
CC mechanism involving endosomal budding of viral capsids into
CC multivesicular bodies. {ECO:0000269|PubMed:28490497}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP4]: Virion
CC {ECO:0000269|PubMed:25327248}. Note=Present in the full mature virion
CC (PubMed:25327248). The egress of newly formed virions occurs through an
CC exosome-like mechanism involving endosomal budding of viral capsids
CC into multivesicular bodies (Probable). {ECO:0000269|PubMed:25327248,
CC ECO:0000305|PubMed:28490497}.
CC -!- SUBCELLULAR LOCATION: [Protein 2B]: Host membrane
CC {ECO:0000269|PubMed:18216106, ECO:0000269|PubMed:26515753,
CC ECO:0000269|PubMed:9875331}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9875331}. Note=Probably localizes to intracellular
CC membrane vesicles that are induced after virus infection as the site
CC for viral RNA replication. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Protein 2C]: Host membrane
CC {ECO:0000269|PubMed:9645199}; Single-pass membrane protein
CC {ECO:0000269|PubMed:9875331}. Note=Probably localizes to intracellular
CC membrane vesicles that are induced after virus infection as the site
CC for viral RNA replication. May associate with membranes through a N-
CC terminal amphipathic helix. {ECO:0000305|PubMed:9645199}.
CC -!- SUBCELLULAR LOCATION: [Protein 3ABC]: Host membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}. Host mitochondrion outer
CC membrane {ECO:0000269|PubMed:17438296}; Single-pass membrane protein
CC {ECO:0000305}. Note=Probably localizes to intracellular membrane
CC vesicles that are induced after virus infection as the site for viral
CC RNA replication. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Protein 3AB]: Host membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}. Note=Probably localizes to
CC intracellular membrane vesicles that are induced after virus infection
CC as the site for viral RNA replication. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Protein 3A]: Host membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}. Note=Probably localizes to
CC intracellular membrane vesicles that are induced after virus infection
CC as the site for viral RNA replication. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Viral protein genome-linked]: Virion
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase 3D-POL]: Host
CC cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Interacts with
CC membranes in a complex with viral protein 3AB. Probably localizes to
CC the surface of intracellular membrane vesicles that are induced after
CC virus infection as the site for viral RNA replication. These vesicles
CC are derived from the endoplasmic reticulum. {ECO:0000305}.
CC -!- DOMAIN: [Protein VP1-2A]: The assembly signal 2A region mediates
CC pentamerization of P1-2A. {ECO:0000269|PubMed:12097562,
CC ECO:0000269|PubMed:12782637}.
CC -!- DOMAIN: [Genome polyprotein]: Late-budding domains (L domains) are
CC short sequence motifs essential for viral particle budding (Probable).
CC They recruit proteins of the host ESCRT machinery (Endosomal Sorting
CC Complex Required for Transport) or ESCRT-associated proteins
CC (Probable). The genome polyprotein contains two L domains: a tandem of
CC (L)YPX(n)L domain which is known to bind the PDCD6IP/ALIX adaptater
CC protein (PubMed:23542590). {ECO:0000269|PubMed:23542590, ECO:0000305}.
CC -!- DOMAIN: [Capsid protein VP2]: Late-budding domains (L domains) are
CC short sequence motifs essential for viral particle budding (Probable).
CC They recruit proteins of the host ESCRT machinery (Endosomal Sorting
CC Complex Required for Transport) or ESCRT-associated proteins
CC (Probable). Capsid protein VP2 contains two L domains: a tandem of
CC (L)YPX(n)L domain which is known to bind the Alix adaptater protein
CC (PubMed:23542590). {ECO:0000269|PubMed:23542590, ECO:0000305}.
CC -!- DOMAIN: [Protein 2B]: The C-terminus displays a membrane-penetrating
CC ability. {ECO:0000269|PubMed:26515753}.
CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages by viral
CC protease in vivo yield a variety of precursors and mature proteins.
CC Polyprotein processing intermediates are produced, such as P1-2A which
CC is a functional precursor of the structural proteins, VP0 which is a
CC VP4-VP2 precursor, VP1-2A precursor, 3ABC precursor which is a stable
CC and catalytically active precursor of 3A, 3B and 3C proteins, 3AB and
CC 3CD precursors (PubMed:7483265, PubMed:1850033, PubMed:8382411,
CC PubMed:8291234, PubMed:9060697, PubMed:9733840, PubMed:8259663,
CC PubMed:7853510, PubMed:10559299). The assembly signal 2A is removed
CC from VP1-2A by a host protease, possibly host Cathepsin L
CC (PubMed:18823593). This cleavage occurs over a region of 3 amino-acids
CC probably generating VP1 proteins with heterogeneous C-termini
CC (PubMed:10364353). {ECO:0000269|PubMed:10364353,
CC ECO:0000269|PubMed:10559299, ECO:0000269|PubMed:1850033,
CC ECO:0000269|PubMed:18823593, ECO:0000269|PubMed:7483265,
CC ECO:0000269|PubMed:7853510, ECO:0000269|PubMed:8259663,
CC ECO:0000269|PubMed:8291234, ECO:0000269|PubMed:8382411,
CC ECO:0000269|PubMed:9060697, ECO:0000269|PubMed:9733840}.
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 is followed by a conformational
CC change of the particle (PubMed:12782637, PubMed:8291234,
CC PubMed:9060697, PubMed:9733840). {ECO:0000269|PubMed:12782637,
CC ECO:0000269|PubMed:8291234, ECO:0000269|PubMed:9060697,
CC ECO:0000269|PubMed:9733840}.
CC -!- PTM: [Protein VP1-2A]: The assembly signal 2A is removed from VP1-2A by
CC a host protease, possibly host Cathepsin L in naked virions
CC (PubMed:18823593). This cleavage does not occur in enveloped virions
CC (PubMed:28490497). This cleavage occurs over a region of 3 amino-acids
CC probably generating VP1 proteins with heterogeneous C-termini
CC (PubMed:10364353). {ECO:0000269|PubMed:10364353,
CC ECO:0000269|PubMed:18823593, ECO:0000269|PubMed:28490497}.
CC -!- PTM: [Viral protein genome-linked]: VPg is uridylylated prior to
CC priming replication into VPg-pUpU. {ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Capsid protein VP4]: Unlike other picornaviruses, does not seem
CC to be myristoylated. {ECO:0000269|PubMed:8389076}.
CC -!- MISCELLANEOUS: The need for an intact eIF4G factor for the initiation
CC of translation of HAV results in an inability to shut off host protein
CC synthesis by a mechanism similar to that of other picornaviruses.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: During infection, enveloped virions (eHAV) are released
CC from cells (PubMed:23542590). These eHAV are cloaked in host-derived
CC membranes and resemble exosomes (PubMed:28490497). The membrane of eHAV
CC is devoid of viral proteins and thus prevents their neutralization by
CC antibodies (PubMed:23542590). eHAV budding is dependent on ESCRT-
CC associated proteins VPS4B and PDCD6IP/ALIX (PubMed:23542590). eHAV are
CC produced and released in the serum and plasma, but not in bile and
CC feces which only contain the naked, nonenveloped virions (Probable). It
CC is likely that eHAV also use HAVCR1 as a functional receptor to infect
CC cells, an evolutionary trait that may enhance HAV infectivity
CC (PubMed:29437974). {ECO:0000269|PubMed:23542590,
CC ECO:0000269|PubMed:28490497, ECO:0000269|PubMed:29437974,
CC ECO:0000303|PubMed:23542590, ECO:0000305}.
CC -!- MISCELLANEOUS: Wild-type HM175 (HM175/wt) comes from a sample isolated
CC from a patient in Australia in 1976 and subsequently passaged three
CC times in marmosets. HM175/7 is an attenuated strain derived from HM175
CC by 32 passages in African green monkey kidney cells. HM175/18f,
CC HM175/24a, and HM175/43c are cytopathic isolates derived from HM175 by
CC serial passages in FRhK-4 cells. {ECO:0000305}.
CC -!- MISCELLANEOUS: Mutations in proteins 2B and 2C seem to be essential for
CC strain HM175 adaptation to growth in cell culture.
CC -!- SIMILARITY: Belongs to the picornaviridae polyprotein family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-3 is the initiator. In
CC vitro, both are used, with a preference for Met-3.
CC {ECO:0000269|PubMed:1310188}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA45466.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M14707; AAA45465.1; -; Genomic_RNA.
DR EMBL; M14707; AAA45466.1; ALT_INIT; Genomic_RNA.
DR EMBL; M16632; AAA45471.1; -; Genomic_RNA.
DR EMBL; M59808; AAA45467.1; -; Genomic_RNA.
DR EMBL; M59809; AAA45469.1; -; Genomic_RNA.
DR EMBL; M59810; AAA45468.1; -; Genomic_RNA.
DR EMBL; M14114; AAA45475.1; -; Genomic_RNA.
DR EMBL; M14115; AAA45476.1; -; Genomic_RNA.
DR EMBL; K00386; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; AF396398; AAL66215.1; -; Genomic_RNA.
DR PIR; A03905; A03905.
DR PIR; A25981; GNNYHM.
DR PIR; A94149; GNNYMK.
DR PIR; JH0135; JH0135.
DR PIR; PQ0427; PQ0427.
DR PIR; PQ0428; PQ0428.
DR PIR; PQ0431; PQ0431.
DR RefSeq; NP_041007.1; NC_001489.1.
DR RefSeq; NP_041008.1; NC_001489.1.
DR PDB; 1HAV; X-ray; 2.00 A; A/B=1520-1736.
DR PDB; 1QA7; X-ray; 1.90 A; A/B/C/D=1520-1736.
DR PDB; 2H6M; X-ray; 1.40 A; A=1520-1731.
DR PDB; 2H9H; X-ray; 1.39 A; A=1520-1731.
DR PDB; 2HAL; X-ray; 1.35 A; A=1520-1731.
DR PDB; 4QPG; X-ray; 3.50 A; B=41-244, C=246-491.
DR PDB; 4QPI; X-ray; 3.01 A; B=24-245, C=246-491.
DR PDB; 4WZN; X-ray; 2.70 A; A/B=765-981.
DR PDB; 5WTE; EM; 3.40 A; A=492-769, B=24-245, C=246-491.
DR PDB; 5WTF; EM; 3.90 A; A=540-763, B=42-244, C=246-491.
DR PDB; 5WTH; EM; 4.20 A; A=492-769, B=24-245, C=246-491.
DR PDBsum; 1HAV; -.
DR PDBsum; 1QA7; -.
DR PDBsum; 2H6M; -.
DR PDBsum; 2H9H; -.
DR PDBsum; 2HAL; -.
DR PDBsum; 4QPG; -.
DR PDBsum; 4QPI; -.
DR PDBsum; 4WZN; -.
DR PDBsum; 5WTE; -.
DR PDBsum; 5WTF; -.
DR PDBsum; 5WTH; -.
DR BMRB; P08617; -.
DR SMR; P08617; -.
DR DrugBank; DB04634; N-BENZYLOXYCARBONYL-L-SERINE-BETALACTONE.
DR DrugBank; DB04029; Phenylalanylamide.
DR MEROPS; C03.005; -.
DR ABCD; P08617; 2 sequenced antibodies.
DR GeneID; 1493918; -.
DR GeneID; 1493919; -.
DR KEGG; vg:1493918; -.
DR KEGG; vg:1493919; -.
DR SABIO-RK; P08617; -.
DR EvolutionaryTrace; P08617; -.
DR Proteomes; UP000006724; Genome.
DR Proteomes; UP000096966; Genome.
DR Proteomes; UP000139151; Genome.
DR Proteomes; UP000155985; Genome.
DR Proteomes; UP000157977; Genome.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044193; C:host cell mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0072494; C:host multivesicular body; IEA:UniProtKB-SubCell.
DR GO; GO:0019030; C:icosahedral viral capsid; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0044385; C:integral to membrane of host cell; 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; IDA:UniProtKB.
DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0017111; F:nucleoside-triphosphatase activity; IEA:RHEA.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003724; F:RNA helicase activity; IEA:InterPro.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IDA:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0034140; P:negative regulation of toll-like receptor 3 signaling pathway; IDA:UniProtKB.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IDA: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:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR GO; GO:0019068; P:virion assembly; IDA:UniProtKB.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR CDD; cd00205; rhv_like; 2.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.60.120.20; -; 3.
DR Gene3D; 3.30.70.270; -; 1.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR004004; Helic/Pol/Pept_Calicivir-typ.
DR InterPro; IPR000605; Helicase_SF3_ssDNA/RNA_vir.
DR InterPro; IPR014759; Helicase_SF3_ssRNA_vir.
DR InterPro; IPR024354; Hepatitis_A_VP1-2A.
DR InterPro; IPR044067; PCV_3C_PRO.
DR InterPro; IPR000199; Peptidase_C3A/C3B_picornavir.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001676; Picornavirus_capsid.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR033703; Rhv-like.
DR InterPro; IPR001205; RNA-dir_pol_C.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR029053; Viral_coat.
DR Pfam; PF12944; HAV_VP; 1.
DR Pfam; PF00548; Peptidase_C3; 1.
DR Pfam; PF00680; RdRP_1; 1.
DR Pfam; PF00073; Rhv; 2.
DR Pfam; PF00910; RNA_helicase; 1.
DR PRINTS; PR00918; CALICVIRUSNS.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51874; PCV_3C_PRO; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR PROSITE; PS51218; SF3_HELICASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Capsid protein; Covalent protein-RNA linkage;
KW Direct protein sequencing; Disulfide bond; Helicase; Host cytoplasm;
KW Host cytoplasmic vesicle; Host endosome; Host membrane; Host mitochondrion;
KW Host mitochondrion outer membrane; Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW Interferon antiviral system evasion; Ion channel; Ion transport; Membrane;
KW Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein; Protease;
KW Reference proteome; RNA-binding; RNA-directed RNA polymerase;
KW T=pseudo3 icosahedral capsid protein; Thiol protease; Transferase;
KW Transmembrane; Transmembrane helix; Transport;
KW Viral attachment to host cell; Viral immunoevasion; Viral ion channel;
KW Viral RNA replication; Virion; Virus entry into host cell.
FT CHAIN 1..2227
FT /note="Genome polyprotein"
FT /id="PRO_0000308969"
FT CHAIN 1..245
FT /note="Capsid protein VP0"
FT /id="PRO_0000308970"
FT CHAIN 1..23
FT /note="Capsid protein VP4"
FT /id="PRO_0000039946"
FT CHAIN 24..245
FT /note="Capsid protein VP2"
FT /id="PRO_0000039947"
FT CHAIN 246..491
FT /note="Capsid protein VP3"
FT /id="PRO_0000039948"
FT CHAIN 492..836
FT /note="Protein VP1-2A"
FT /id="PRO_0000308971"
FT CHAIN 492..765
FT /note="Capsid protein VP1"
FT /id="PRO_0000039949"
FT CHAIN 766..836
FT /note="Assembly signal 2A"
FT /id="PRO_0000039950"
FT CHAIN 837..1422
FT /note="Protein 2BC"
FT /id="PRO_0000308972"
FT CHAIN 837..1087
FT /note="Protein 2B"
FT /id="PRO_0000039951"
FT CHAIN 1088..1422
FT /note="Protein 2C"
FT /id="PRO_0000039952"
FT CHAIN 1423..2227
FT /note="Protein 3ABCD"
FT /id="PRO_0000308973"
FT CHAIN 1423..1738
FT /note="Protein 3ABC"
FT /id="PRO_0000308974"
FT CHAIN 1423..1519
FT /note="Protein 3AB"
FT /id="PRO_0000308975"
FT CHAIN 1423..1496
FT /note="Protein 3A"
FT /id="PRO_0000039953"
FT CHAIN 1497..1519
FT /note="Viral protein genome-linked"
FT /id="PRO_0000039954"
FT CHAIN 1520..2227
FT /note="Protein 3CD"
FT /id="PRO_0000308976"
FT CHAIN 1520..1738
FT /note="Protease 3C"
FT /id="PRO_0000039955"
FT CHAIN 1739..2227
FT /note="RNA-directed RNA polymerase 3D-POL"
FT /id="PRO_0000039956"
FT TRANSMEM 1011..1031
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1462..1482
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:9705870"
FT DOMAIN 1204..1366
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DOMAIN 1514..1728
FT /note="Peptidase C3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT DOMAIN 1976..2097
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 766..836
FT /note="Involved in P1-2A pentamerization"
FT /evidence="ECO:0000269|PubMed:12097562,
FT ECO:0000269|PubMed:12782637"
FT REGION 1043..1070
FT /note="Membrane-penetrating ability"
FT /evidence="ECO:0000269|PubMed:26515753"
FT MOTIF 167..171
FT /note="(L)YPX(n)L motif"
FT /evidence="ECO:0000269|PubMed:23542590"
FT MOTIF 200..205
FT /note="(L)YPX(n)L motif"
FT /evidence="ECO:0000269|PubMed:23542590"
FT ACT_SITE 1563
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1603
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1691
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT BINDING 1230..1237
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT SITE 245..246
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000303|PubMed:10559299"
FT SITE 491..492
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000303|PubMed:10559299"
FT SITE 765..766
FT /note="Cleavage; partial; by host"
FT /evidence="ECO:0000269|PubMed:10364353,
FT ECO:0000269|PubMed:12782637"
FT SITE 769
FT /note="Important for VP1 folding and capsid assembly"
FT /evidence="ECO:0000269|PubMed:12782637,
FT ECO:0000269|PubMed:18823593"
FT SITE 836..837
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000269|PubMed:7483265,
FT ECO:0000269|PubMed:7853510"
FT SITE 1087..1088
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000269|PubMed:7853510"
FT SITE 1422..1423
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000303|PubMed:10559299"
FT SITE 1496..1497
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000269|PubMed:10559299"
FT SITE 1519..1520
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000269|PubMed:10559299"
FT SITE 1738..1739
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000269|PubMed:8291234"
FT MOD_RES 1499
FT /note="O-(5'-phospho-RNA)-tyrosine"
FT /evidence="ECO:0000250"
FT DISULFID 1543
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:15361063"
FT VARIANT 77
FT /note="K -> R (in strain: HM175/7, HM175/18f, HM175/24a and
FT HM175/43c)"
FT VARIANT 315
FT /note="D -> A (in strain: HM175/24a and HM175/43c)"
FT VARIANT 336
FT /note="T -> K (in strain: HM175/18f)"
FT VARIANT 638
FT /note="I -> V (in strain: HM175/24a)"
FT VARIANT 688
FT /note="N -> S (in strain: HM175/24a and HM175/43c)"
FT VARIANT 762
FT /note="S -> P (in strain: HM175/18f)"
FT VARIANT 764
FT /note="E -> V (in strain: HM175/7)"
FT VARIANT 767
FT /note="M -> V (in strain: HM175/24a and HM175/43c)"
FT VARIANT 821
FT /note="N -> S (in strain: HM175/7)"
FT VARIANT 838
FT /note="K -> N (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 849
FT /note="I -> M (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 941
FT /note="D -> E (in 24)"
FT VARIANT 993
FT /note="D -> H (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 1052
FT /note="A -> V (in strain: HM175/7, HM175/18f, HM175/24a and
FT HM175/43c)"
FT VARIANT 1062
FT /note="G -> A (in strain: HM175/7)"
FT VARIANT 1109..1111
FT /note="AIY -> GIC (in strain: HM175/18f, HM175/24a and
FT HM175/43c)"
FT VARIANT 1118
FT /note="K -> M (in strain: HM175/7)"
FT VARIANT 1151
FT /note="E -> K (in strain: HM175/7, HM175/18f, HM175/24a and
FT HM175/43c)"
FT VARIANT 1163
FT /note="F -> S (in strain: HM175/7, HM175/18f, HM175/24a and
FT HM175/43c)"
FT VARIANT 1180
FT /note="H -> Y (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 1212
FT /note="S -> F (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 1229
FT /note="Y -> H (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 1277
FT /note="V -> I (in strain: HM175/7)"
FT VARIANT 1407
FT /note="E -> D (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 1428
FT /note="Missing (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 1480
FT /note="F -> V (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 1487
FT /note="R -> H (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 1500
FT /note="H -> Y (in strain: HM175/7)"
FT VARIANT 1507
FT /note="Q -> H (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT VARIANT 1524
FT /note="I -> V (in strain: HM175/43c)"
FT VARIANT 1620
FT /note="Q -> E (in strain: HM175/18f and HM175/24a)"
FT VARIANT 1675
FT /note="T -> A (in strain: HM175/43c)"
FT VARIANT 1805
FT /note="D -> G (in strain: HM175/7, HM175/18f, HM175/24a and
FT HM175/43c)"
FT VARIANT 1930
FT /note="S -> T (in strain: HM175/7, HM175/18f, HM175/24a and
FT HM175/43c)"
FT VARIANT 1962
FT /note="R -> K (in strain: HM175/18f, HM175/24a and HM175/
FT 43c)"
FT MUTAGEN 167
FT /note="Y->A: Severely decreases virus release but does not
FT impair viral RNA replication."
FT /evidence="ECO:0000269|PubMed:23542590"
FT MUTAGEN 200
FT /note="Y->A: Severely decreases virus release but does not
FT impair viral RNA replication."
FT /evidence="ECO:0000269|PubMed:23542590"
FT MUTAGEN 769
FT /note="R->M: Complete loss of viral particles assembly.
FT Interferes with oligomerization of protein VP1-2A and
FT maturation of procapsids."
FT /evidence="ECO:0000269|PubMed:12782637,
FT ECO:0000269|PubMed:18823593"
FT MUTAGEN 836
FT /note="Q->N: Partial loss of VP1-2A-2B cleavage."
FT /evidence="ECO:0000269|PubMed:7483265"
FT MUTAGEN 836
FT /note="Q->R: Complete loss of VP1-2A-2B cleavage."
FT /evidence="ECO:0000269|PubMed:7483265"
FT MUTAGEN 1052
FT /note="A->I,L,V: 10-20 fold increase in virus yield."
FT /evidence="ECO:0000269|PubMed:12858403"
FT MUTAGEN 1543
FT /note="C->S: Complete loss of protease 3C dimerization."
FT /evidence="ECO:0000269|PubMed:15361063"
FT MUTAGEN 1691
FT /note="C->A: Complete loss of enzymatic activity. Complete
FT loss of cleavage of host TICAM1."
FT /evidence="ECO:0000269|PubMed:21931545"
FT MUTAGEN 1691
FT /note="C->A: Complete loss of proteolytic activity."
FT /evidence="ECO:0000269|PubMed:15361063"
FT CONFLICT 67
FT /note="R -> K (in Ref. 7; AAL66215)"
FT /evidence="ECO:0000305"
FT CONFLICT 1825
FT /note="D -> V (in Ref. 4; AAA45476)"
FT /evidence="ECO:0000305"
FT CONFLICT 1850
FT /note="G -> R (in Ref. 4; AAA45476)"
FT /evidence="ECO:0000305"
FT CONFLICT 1856
FT /note="E -> G (in Ref. 4; AAA45476)"
FT /evidence="ECO:0000305"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 45..51
FT /evidence="ECO:0007829|PDB:4QPI"
FT HELIX 76..80
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 84..92
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:4QPI"
FT HELIX 106..110
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 111..115
FT /evidence="ECO:0007829|PDB:5WTE"
FT HELIX 118..121
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 124..137
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 143..154
FT /evidence="ECO:0007829|PDB:4QPI"
FT HELIX 161..166
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 167..173
FT /evidence="ECO:0007829|PDB:4QPI"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 177..184
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 189..197
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 202..215
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 221..239
FT /evidence="ECO:0007829|PDB:4QPI"
FT HELIX 265..268
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 271..275
FT /evidence="ECO:0007829|PDB:4QPI"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:4QPI"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:5WTE"
FT HELIX 297..300
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 304..312
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 320..325
FT /evidence="ECO:0007829|PDB:4QPI"
FT TURN 336..339
FT /evidence="ECO:0007829|PDB:4QPI"
FT HELIX 345..350
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 353..367
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 373..383
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 385..387
FT /evidence="ECO:0007829|PDB:5WTE"
FT HELIX 394..397
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 400..406
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 413..418
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 423..428
FT /evidence="ECO:0007829|PDB:4QPI"
FT HELIX 430..432
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 433..435
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 444..456
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 463..481
FT /evidence="ECO:0007829|PDB:4QPI"
FT STRAND 532..534
FT /evidence="ECO:0007829|PDB:5WTE"
FT HELIX 540..542
FT /evidence="ECO:0007829|PDB:5WTE"
FT TURN 549..553
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 568..571
FT /evidence="ECO:0007829|PDB:5WTE"
FT HELIX 576..579
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 584..591
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 593..603
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 606..608
FT /evidence="ECO:0007829|PDB:5WTE"
FT HELIX 616..621
FT /evidence="ECO:0007829|PDB:5WTE"
FT TURN 622..624
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 625..630
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 632..640
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 645..651
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 662..664
FT /evidence="ECO:0007829|PDB:5WTE"
FT HELIX 670..675
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 679..682
FT /evidence="ECO:0007829|PDB:5WTE"
FT TURN 683..685
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 687..693
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 698..700
FT /evidence="ECO:0007829|PDB:5WTE"
FT HELIX 708..714
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 716..725
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 734..742
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 747..751
FT /evidence="ECO:0007829|PDB:5WTE"
FT STRAND 840..846
FT /evidence="ECO:0007829|PDB:4WZN"
FT STRAND 850..853
FT /evidence="ECO:0007829|PDB:4WZN"
FT STRAND 856..859
FT /evidence="ECO:0007829|PDB:4WZN"
FT STRAND 861..872
FT /evidence="ECO:0007829|PDB:4WZN"
FT STRAND 878..883
FT /evidence="ECO:0007829|PDB:4WZN"
FT STRAND 886..893
FT /evidence="ECO:0007829|PDB:4WZN"
FT STRAND 900..902
FT /evidence="ECO:0007829|PDB:4WZN"
FT HELIX 905..914
FT /evidence="ECO:0007829|PDB:4WZN"
FT HELIX 932..938
FT /evidence="ECO:0007829|PDB:4WZN"
FT HELIX 947..957
FT /evidence="ECO:0007829|PDB:4WZN"
FT STRAND 960..963
FT /evidence="ECO:0007829|PDB:4WZN"
FT HELIX 964..968
FT /evidence="ECO:0007829|PDB:4WZN"
FT HELIX 1521..1531
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1532..1539
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1545..1555
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1557..1561
FT /evidence="ECO:0007829|PDB:2HAL"
FT HELIX 1562..1564
FT /evidence="ECO:0007829|PDB:2HAL"
FT TURN 1565..1567
FT /evidence="ECO:0007829|PDB:2HAL"
FT HELIX 1571..1573
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1574..1580
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1583..1588
FT /evidence="ECO:0007829|PDB:2HAL"
FT HELIX 1589..1591
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1592..1595
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1597..1600
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1603..1608
FT /evidence="ECO:0007829|PDB:2HAL"
FT HELIX 1619..1621
FT /evidence="ECO:0007829|PDB:2HAL"
FT HELIX 1625..1630
FT /evidence="ECO:0007829|PDB:2HAL"
FT TURN 1631..1633
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1636..1642
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1645..1651
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1655..1665
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1667..1669
FT /evidence="ECO:0007829|PDB:1HAV"
FT STRAND 1671..1683
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1694..1698
FT /evidence="ECO:0007829|PDB:2HAL"
FT HELIX 1700..1702
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1706..1714
FT /evidence="ECO:0007829|PDB:2HAL"
FT STRAND 1717..1722
FT /evidence="ECO:0007829|PDB:2HAL"
FT HELIX 1725..1730
FT /evidence="ECO:0007829|PDB:2HAL"
SQ SEQUENCE 2227 AA; 251508 MW; 01E225E7AEB740A6 CRC64;
MNMSRQGIFQ TVGSGLDHIL SLADIEEEQM IQSVDRTAVT GASYFTSVDQ SSVHTAEVGS
HQVEPLRTSV DKPGSKKTQG EKFFLIHSAD WLTTHALFHE VAKLDVVKLL YNEQFAVQGL
LRYHTYARFG IEIQVQINPT PFQQGGLICA MVPGDQSYGS IASLTVYPHG LLNCNINNVV
RIKVPFIYTR GAYHFKDPQY PVWELTIRVW SELNIGTGTS AYTSLNVLAR FTDLELHGLT
PLSTQMMRNE FRVSTTENVV NLSNYEDARA KMSFALDQED WKSDPSQGGG IKITHFTTWT
SIPTLAAQFP FNASDSVGQQ IKVIPVDPYF FQMTNTNPDQ KCITALASIC QMFCFWRGDL
VFDFQVFPTK YHSGRLLFCF VPGNELIDVS GITLKQATTA PCAVMDITGV QSTLRFRVPW
ISDTPYRVNR YTKSAHQKGE YTAIGKLIVY CYNRLTSPSN VASHVRVNVY LSAINLECFA
PLYHAMDVTT QVGDDSGGFS TTVSTEQNVP DPQVGITTMK DLKGKANRGK MDVSGVQAPV
GAITTIEDPV LAKKVPETFP ELKPGESRHT SDHMSIYKFM GRSHFLCTFT FNSNNKEYTF
PITLSSTSNP PHGLPSTLRW FFNLFQLYRG PLDLTIIITG ATDVDGMAWF TPVGLAVDTP
WVEKESALSI DYKTALGAVR FNTRRTGNIQ IRLPWYSYLY AVSGALDGLG DKTDSTFGLV
SIQIANYNHS DEYLSFSCYL SVTEQSEFYF PRAPLNSNAM LSTESMMSRI AAGDLESSVD
DPRSEEDKRF ESHIECRKPY KELRLEVGKQ RLKYAQEELS NEVLPPPRKM KGLFSQAKIS
LFYTEEHEIM KFSWRGVTAD TRALRRFGFS LAAGRSVWTL EMDAGVLTGR LIRLNDEKWT
EMKDDKIVSL IEKFTSNKYW SKVNFPHGML DLEEIAANSK DFPNMSETDL CFLLHWLNPK
KINLADRMLG LSGVQEIKEQ GVGLIAECRT FLDSIAGTLK SMMFGFHHSV TVEIINTVLC
FVKSGILLYV IQQLNQDEHS HIIGLLRVMN YADIGCSVIS CGKVFSKMLE TVFNWQMDSR
MMELRTQSFS NWLRDICSGI TIFKNFKDAI YWLYTKLKDF YEVNYGKKKD ILNILKDNQQ
KIEKAIEEAD EFCILQIQDV EKFEQYQKGV DLIQKLRTVH SMAQVDPNLM VHLSPLRDCI
ARVHQKLKNL GSINQAMVTR CEPVVCYLYG KRGGGKSLTS IALATKICKH YGVEPEKNIY
TKPVASDYWD GYSGQLVCII DDIGQNTTDE DWSDFCQLVS GCPMRLNMAS LEEKGRHFSS
PFIIATSNWS NPSPKTVYVK EAIDRRLHFK VEVKPASFFK NPHNDMLNVN LAKTNDAIKD
MSCVDLIMDG HNVSLMDLLS SLVMTVEIRK QNMTEFMELW SQGISDDDND SAVAEFFQSF
PSGEPSNSKL SGFFQSVTNH KWVAVGAAVG ILGVLVGGWF VYKHFSRKEE EPIPAEGVYH
GVTKPKQVIK LDADPVESQS TLEIAGLVRK NLVQFGVGEK NGCVRWVMNA LGVKDDWLLV
PSHAYKFEKD YEMMEFYFNR GGTYYSISAG NVVIQSLDVG FQDVVLMKVP TIPKFRDITQ
HFIKKGDVPR ALNRLATLVT TVNGTPMLIS EGPLKMEEKA TYVHKKNDGT TVDLTVDQAW
RGKGEGLPGM CGGALVSSNQ SIQNAILGIH VAGGNSILVA KLVTQEMFQN IDKKIESQRI
MKVEFTQCSM NVVSKTLFRK SPIYHHIDKT MINFPAAMPF SKAEIDPMAV MLSKYSLPIV
EEPEDYKEAS IFYQNKIVGK TQLVDDFLDL DMAITGAPGI DAINMDSSPG FPYVQEKLTK
RDLIWLDENG LLLGVHPRLA QRILFNTVMM ENCSDLDVVF TTCPKDELRP LEKVLESKTR
AIDACPLDYS ILCRMYWGPA ISYFHLNPGF HTGVAIGIDP DRQWDELFKT MIRFGDVGLD
LDFSAFDASL SPFMIREAGR IMSELSGTPS HFGTALINTI IYSKHLLYNC CYHVCGSMPS
GSPCTALLNS IINNVNLYYV FSKIFGKSPV FFCQALKILC YGDDVLIVFS RDVQIDNLDL
IGQKIVDEFK KLGMTATSAD KNVPQLKPVS ELTFLKRSFN LVEDRIRPAI SEKTIWSLIA
WQRSNAEFEQ NLENAQWFAF MHGYEFYQKF YYFVQSCLEK EMIEYRLKSY DWWRMRFYDQ
CFICDLS
