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<entry dataset="Swiss-Prot" created="1988-08-01" modified="2022-08-03" version="178" xmlns="http://uniprot.org/uniprot">
    <accession>P08617</accession>
    <accession>P06443</accession>
    <accession>P26580</accession>
    <accession>P26581</accession>
    <accession>P26582</accession>
    <accession>Q81082</accession>
    <accession>Q81094</accession>
    <accession>Q8V405</accession>
    <name>POLG_HAVHM</name>
    <protein>
        <recommendedName>
            <fullName>Genome polyprotein</fullName>
        </recommendedName>
        <component>
            <recommendedName>
                <fullName>Capsid protein VP0</fullName>
            </recommendedName>
            <alternativeName>
                <fullName>VP4-VP2</fullName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>Capsid protein VP4</fullName>
            </recommendedName>
            <alternativeName>
                <fullName>P1A</fullName>
            </alternativeName>
            <alternativeName>
                <fullName>Virion protein 4</fullName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>Capsid protein VP2</fullName>
            </recommendedName>
            <alternativeName>
                <fullName>P1B</fullName>
            </alternativeName>
            <alternativeName>
                <fullName>Virion protein 2</fullName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>Capsid protein VP3</fullName>
            </recommendedName>
            <alternativeName>
                <fullName>P1C</fullName>
            </alternativeName>
            <alternativeName>
                <fullName>Virion protein 3</fullName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protein VP1-2A</fullName>
            </recommendedName>
            <alternativeName>
                <fullName>VP1-pX</fullName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>Capsid protein VP1</fullName>
            </recommendedName>
            <alternativeName>
                <fullName>P1D</fullName>
            </alternativeName>
            <alternativeName>
                <fullName>Virion protein 1</fullName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>Assembly signal 2A</fullName>
            </recommendedName>
            <alternativeName>
                <fullName evidence="48">pX</fullName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protein 2BC</fullName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protein 2B</fullName>
                <shortName>P2B</shortName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protein 2C</fullName>
                <shortName>P2C</shortName>
                <ecNumber>3.6.1.15</ecNumber>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protein 3ABCD</fullName>
                <shortName>P3</shortName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protein 3ABC</fullName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protein 3AB</fullName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protein 3A</fullName>
                <shortName>P3A</shortName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName>Viral protein genome-linked</fullName>
                <shortName>VPg</shortName>
            </recommendedName>
            <alternativeName>
                <fullName>Protein 3B</fullName>
                <shortName>P3B</shortName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protein 3CD</fullName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName>Protease 3C</fullName>
                <shortName>P3C</shortName>
                <ecNumber evidence="19">3.4.22.28</ecNumber>
            </recommendedName>
            <alternativeName>
                <fullName>Picornain 3C</fullName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>RNA-directed RNA polymerase 3D-POL</fullName>
                <shortName>P3D-POL</shortName>
                <ecNumber evidence="35">2.7.7.48</ecNumber>
            </recommendedName>
        </component>
    </protein>
    <organism>
        <name type="scientific">Human hepatitis A virus genotype IB (isolate HM175)</name>
        <name type="common">HHAV</name>
        <name type="synonym">Human hepatitis A virus (isolate Human/Australia/HM175/1976)</name>
        <dbReference type="NCBI Taxonomy" id="12098"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Pisuviricota</taxon>
            <taxon>Pisoniviricetes</taxon>
            <taxon>Picornavirales</taxon>
            <taxon>Picornaviridae</taxon>
            <taxon>Hepatovirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Cercopithecus hamlyni</name>
        <name type="common">Owl-faced monkey</name>
        <name type="synonym">Hamlyn's monkey</name>
        <dbReference type="NCBI Taxonomy" id="9536"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Macaca</name>
        <name type="common">macaques</name>
        <dbReference type="NCBI Taxonomy" id="9539"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Pan troglodytes</name>
        <name type="common">Chimpanzee</name>
        <dbReference type="NCBI Taxonomy" id="9598"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1987" name="J. Virol." volume="61" first="50" last="59">
            <title>Complete nucleotide sequence of wild-type hepatitis A virus: comparison with different strains of hepatitis A virus and other picornaviruses.</title>
            <authorList>
                <person name="Cohen J.I."/>
                <person name="Ticehurst J.R."/>
                <person name="Purcell R.H."/>
                <person name="Buckler-White A."/>
                <person name="Baroudy B.M."/>
            </authorList>
            <dbReference type="PubMed" id="3023706"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
        <source>
            <strain>HM175/wt</strain>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1987" name="Proc. Natl. Acad. Sci. U.S.A." volume="84" first="2497" last="2501">
            <title>Complete nucleotide sequence of an attenuated hepatitis A virus: comparison with wild-type virus.</title>
            <authorList>
                <person name="Cohen J.I."/>
                <person name="Rosenblum B."/>
                <person name="Ticehurst J.R."/>
                <person name="Daemer R.J."/>
                <person name="Feinstone S.M."/>
                <person name="Purcell R.H."/>
            </authorList>
            <dbReference type="PubMed" id="3031686"/>
            <dbReference type="DOI" id="10.1073/pnas.84.8.2497"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
        <source>
            <strain>HM175/7 MK-5</strain>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1991" name="J. Virol." volume="65" first="2056" last="2065">
            <title>Antigenic and genetic variation in cytopathic hepatitis A virus variants arising during persistent infection: evidence for genetic recombination.</title>
            <authorList>
                <person name="Lemon S.M."/>
                <person name="Murphy P.C."/>
                <person name="Shields P.A."/>
                <person name="Ping L.H."/>
                <person name="Feinstone S.M."/>
                <person name="Cromeans T."/>
                <person name="Jansen R.W."/>
            </authorList>
            <dbReference type="PubMed" id="1705995"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
        <source>
            <strain>HM175/18f</strain>
            <strain>HM175/24a</strain>
            <strain>HM175/43c</strain>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1985" name="Proc. Natl. Acad. Sci. U.S.A." volume="82" first="2143" last="2147">
            <title>Sequence analysis of hepatitis A virus cDNA coding for capsid proteins and RNA polymerase.</title>
            <authorList>
                <person name="Baroudy B.M."/>
                <person name="Ticehurst J.R."/>
                <person name="Miele T.A."/>
                <person name="Maizel J.V.Jr."/>
                <person name="Purcell R.H."/>
                <person name="Feinstone S.M."/>
            </authorList>
            <dbReference type="PubMed" id="2984684"/>
            <dbReference type="DOI" id="10.1073/pnas.82.7.2143"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-854 AND 1724-2227</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1995" name="Virology" volume="213" first="213" last="222">
            <title>Identification and site-directed mutagenesis of the primary (2A/2B) cleavage site of the hepatitis A virus polyprotein: functional impact on the infectivity of HAV RNA transcripts.</title>
            <authorList>
                <person name="Martin A."/>
                <person name="Escriou N."/>
                <person name="Chao S.F."/>
                <person name="Girard M."/>
                <person name="Lemon S.M."/>
                <person name="Wychowski C."/>
            </authorList>
            <dbReference type="PubMed" id="7483265"/>
            <dbReference type="DOI" id="10.1006/viro.1995.1561"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 837-856</scope>
        <scope>MUTAGENESIS OF GLN-836</scope>
        <scope>PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN)</scope>
        <source>
            <strain>HM175p35</strain>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1983" name="Proc. Natl. Acad. Sci. U.S.A." volume="80" first="5885" last="5889">
            <title>Molecular cloning and characterization of hepatitis A virus cDNA.</title>
            <authorList>
                <person name="Ticehurst J.R."/>
                <person name="Racaniello V.R."/>
                <person name="Baroudy B.M."/>
                <person name="Baltimore D."/>
                <person name="Purcell R.H."/>
                <person name="Feinstone S.M."/>
            </authorList>
            <dbReference type="PubMed" id="6310601"/>
            <dbReference type="DOI" id="10.1073/pnas.80.19.5885"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 2090-2227</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2002" name="J. Clin. Microbiol." volume="40" first="4148" last="4155">
            <title>Molecular characterization of hepatitis a virus isolates from a transcontinental shellfish-borne outbreak.</title>
            <authorList>
                <person name="Sanchez G."/>
                <person name="Pinto R.M."/>
                <person name="Vanaclocha H."/>
                <person name="Bosch A."/>
            </authorList>
            <dbReference type="PubMed" id="12409389"/>
            <dbReference type="DOI" id="10.1128/JCM.40.11.4148-4155.2002"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-819</scope>
        <source>
            <strain>Isolate Val8</strain>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1986" name="J. Virol." volume="60" first="124" last="130">
            <title>Detection of a genome-linked protein (VPg) of hepatitis A virus and its comparison with other picornaviral VPgs.</title>
            <authorList>
                <person name="Weitz M."/>
                <person name="Baroudy B.M."/>
                <person name="Maloy W.L."/>
                <person name="Ticehurst J.R."/>
                <person name="Purcell R.H."/>
            </authorList>
            <dbReference type="PubMed" id="3018280"/>
        </citation>
        <scope>IDENTIFICATION (VIRAL PROTEIN GENOME-LINKED)</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1991" name="J. Virol." volume="65" first="2595" last="2600">
            <title>Proteolytic activity of hepatitis A virus 3C protein.</title>
            <authorList>
                <person name="Jia X.-Y."/>
                <person name="Ehrenfeld E."/>
                <person name="Summers D.F."/>
            </authorList>
            <dbReference type="PubMed" id="1850033"/>
        </citation>
        <scope>PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN)</scope>
        <scope>FUNCTION (PROTEASE 3C)</scope>
        <scope>CATALYTIC ACTIVITY (PROTEASE 3C)</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1992" name="Virology" volume="186" first="609" last="618">
            <title>Hepatitis A virus polyprotein synthesis initiates from two alternative AUG codons.</title>
            <authorList>
                <person name="Tesar M."/>
                <person name="Harmon S.A."/>
                <person name="Summers D.F."/>
                <person name="Ehrenfeld E."/>
            </authorList>
            <dbReference type="PubMed" id="1310188"/>
            <dbReference type="DOI" id="10.1016/0042-6822(92)90027-M"/>
        </citation>
        <scope>IDENTIFICATION OF N-TERMINUS (GENOME POLYPROTEIN)</scope>
        <source>
            <strain>HM175/7</strain>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="1993" name="Virology" volume="194" first="616" last="626">
            <title>Analysis of a potential myristoylation site in hepatitis A virus capsid protein VP4.</title>
            <authorList>
                <person name="Tesar M."/>
                <person name="Jia X.-Y."/>
                <person name="Summers D.F."/>
                <person name="Ehrenfeld E."/>
            </authorList>
            <dbReference type="PubMed" id="8389076"/>
            <dbReference type="DOI" id="10.1006/viro.1993.1301"/>
        </citation>
        <scope>ABSENCE OF MYRISTOYLATION (PROTEIN VP4)</scope>
        <source>
            <strain>HM175/7</strain>
        </source>
    </reference>
    <reference key="12">
        <citation type="journal article" date="1993" name="Virology" volume="193" first="515" last="519">
            <title>Primary cleavage of the HAV capsid protein precursor in the middle of the proposed 2A coding region.</title>
            <authorList>
                <person name="Jia X.-Y."/>
                <person name="Summers D.F."/>
                <person name="Ehrenfeld E."/>
            </authorList>
            <dbReference type="PubMed" id="8382411"/>
            <dbReference type="DOI" id="10.1006/viro.1993.1157"/>
        </citation>
        <scope>PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN)</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="1994" name="Virology" volume="198" first="524" last="533">
            <title>Expression of hepatitis A virus precursor protein P3 in vivo and in vitro: polyprotein processing of the 3CD cleavage site.</title>
            <authorList>
                <person name="Tesar M."/>
                <person name="Pak I."/>
                <person name="Jia X.-Y."/>
                <person name="Richards O.C."/>
                <person name="Summers D.F."/>
                <person name="Ehrenfeld E."/>
            </authorList>
            <dbReference type="PubMed" id="8291234"/>
            <dbReference type="DOI" id="10.1006/viro.1994.1063"/>
        </citation>
        <scope>PROTEOLYTIC CLEAVAGE (CAPSID PROTEIN VP0)</scope>
        <scope>CATALYTIC ACTIVITY (RNA-DIRECTED RNA POLYMERASE 3D-POL)</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="1994" name="Virology" volume="198" first="275" last="281">
            <title>Proteinase 3C of hepatitis A virus (HAV) cleaves the HAV polyprotein P2-P3 at all sites including VP1/2A and 2A/2B.</title>
            <authorList>
                <person name="Schultheiss T."/>
                <person name="Kusov Y.Y."/>
                <person name="Gauss-Mueller V."/>
            </authorList>
            <dbReference type="PubMed" id="8259663"/>
        </citation>
        <scope>PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN)</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="1995" name="J. Virol." volume="69" first="1727" last="1733">
            <title>Cleavage specificity of purified recombinant hepatitis A virus 3C proteinase on natural substrates.</title>
            <authorList>
                <person name="Schultheiss T."/>
                <person name="Sommergruber W."/>
                <person name="Kusov Y."/>
                <person name="Gauss-Mueller V."/>
            </authorList>
            <dbReference type="PubMed" id="7853510"/>
        </citation>
        <scope>PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN)</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="1995" name="FEBS Lett." volume="367" first="5" last="11">
            <title>Mutations in the hydrophobic domain of poliovirus protein 3AB abrogate its permeabilizing activity.</title>
            <authorList>
                <person name="Lama J."/>
                <person name="Carrasco L."/>
            </authorList>
            <dbReference type="PubMed" id="7601283"/>
        </citation>
        <scope>FUNCTION (PROTEIN 3AB)</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="1997" name="J. Virol." volume="71" first="3288" last="3292">
            <title>Proteinase 3C-mediated processing of VP1-2A of two hepatitis A virus strains: in vivo evidence for cleavage at amino acid position 273/274 of VP1.</title>
            <authorList>
                <person name="Probst C."/>
                <person name="Jecht M."/>
                <person name="Gauss-Mueller V."/>
            </authorList>
            <dbReference type="PubMed" id="9060697"/>
        </citation>
        <scope>PROTEOLYTIC CLEAVAGE (CAPSID PROTEIN VP0)</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="1997" name="Virology" volume="237" first="66" last="77">
            <title>Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC.</title>
            <authorList>
                <person name="Teterina N.L."/>
                <person name="Bienz K."/>
                <person name="Egger D."/>
                <person name="Gorbalenya A.E."/>
                <person name="Ehrenfeld E."/>
            </authorList>
            <dbReference type="PubMed" id="9344908"/>
            <dbReference type="DOI" id="10.1006/viro.1997.8775"/>
        </citation>
        <scope>FUNCTION (PROTEIN 2C)</scope>
        <scope>FUNCTION (PROTEIN 2BC)</scope>
        <scope>FUNCTION (PROTEIN 2B)</scope>
        <source>
            <strain>HM175/24a</strain>
            <strain>HM175/wt</strain>
            <strain>HM175p35</strain>
        </source>
    </reference>
    <reference key="19">
        <citation type="journal article" date="1998" name="Biochem. Biophys. Res. Commun." volume="249" first="266" last="274">
            <title>Polypeptide 3AB of hepatitis A virus is a transmembrane protein.</title>
            <authorList>
                <person name="Ciervo A."/>
                <person name="Beneduce F."/>
                <person name="Morace G."/>
            </authorList>
            <dbReference type="PubMed" id="9705870"/>
            <dbReference type="DOI" id="10.1006/bbrc.1998.9121"/>
        </citation>
        <scope>SUBUNIT (PROTEIN 3AB)</scope>
        <scope>FUNCTION (PROTEIN 3AB)</scope>
        <scope>TOPOLOGY (PROTEIN 3AB)</scope>
        <scope>TOPOLOGY (PROTEIN 3A)</scope>
        <scope>FUNCTION (PROTEIN 3A)</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="1998" name="Arch. Virol." volume="143" first="931" last="944">
            <title>Membrane association and RNA binding of recombinant hepatitis A virus protein 2C.</title>
            <authorList>
                <person name="Kusov Y.Y."/>
                <person name="Probst C."/>
                <person name="Jecht M."/>
                <person name="Jost P.D."/>
                <person name="Gauss-Mueller V."/>
            </authorList>
            <dbReference type="PubMed" id="9645199"/>
            <dbReference type="DOI" id="10.1007/s007050050343"/>
        </citation>
        <scope>SUBCELLULAR LOCATION (PROTEIN 2C)</scope>
        <scope>RNA-BINDING (PROTEIN 2C)</scope>
        <scope>FUNCTION (PROTEIN 2C)</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="1998" name="J. Virol." volume="72" first="8013" last="8020">
            <title>Processing of proteinase precursors and their effect on hepatitis A virus particle formation.</title>
            <authorList>
                <person name="Probst C."/>
                <person name="Jecht M."/>
                <person name="Gauss-Mueller V."/>
            </authorList>
            <dbReference type="PubMed" id="9733840"/>
        </citation>
        <scope>PROTEOLYTIC CLEAVAGE (CAPSID PROTEIN VP0)</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="1998" name="J. Virol." volume="72" first="6621" last="6628">
            <title>The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor.</title>
            <authorList>
                <person name="Feigelstock D."/>
                <person name="Thompson P."/>
                <person name="Mattoo P."/>
                <person name="Zhang Y."/>
                <person name="Kaplan G.G."/>
            </authorList>
            <dbReference type="PubMed" id="9658108"/>
        </citation>
        <scope>FUNCTION (CAPSID PROTEIN VP1)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP2)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP3)</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="1998" name="Virology" volume="252" first="218" last="227">
            <title>Membrane permeability induced by hepatitis A virus proteins 2B and 2BC and proteolytic processing of HAV 2BC.</title>
            <authorList>
                <person name="Jecht M."/>
                <person name="Probst C."/>
                <person name="Gauss-Mueller V."/>
            </authorList>
            <dbReference type="PubMed" id="9875331"/>
            <dbReference type="DOI" id="10.1006/viro.1998.9451"/>
        </citation>
        <scope>FUNCTION (PROTEIN 2B)</scope>
        <scope>FUNCTION (PROTEIN 2BC)</scope>
        <scope>SUBCELLULAR LOCATION (PROTEIN 2B)</scope>
        <scope>SUBCELLULAR LOCATION (PROTEIN 2C)</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="1999" name="J. Virol." volume="73" first="9867" last="9878">
            <title>Improving proteolytic cleavage at the 3A/3B site of the hepatitis A virus polyprotein impairs processing and particle formation, and the impairment can be complemented in trans by 3AB and 3ABC.</title>
            <authorList>
                <person name="Kusov Y."/>
                <person name="Gauss-Mueller V."/>
            </authorList>
            <dbReference type="PubMed" id="10559299"/>
        </citation>
        <scope>PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN)</scope>
        <scope>FUNCTION (PROTEIN 3ABC)</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="1999" name="Virology" volume="264" first="410" last="421">
            <title>Mapping of protein domains of hepatitis A virus 3AB essential for interaction with 3CD and viral RNA.</title>
            <authorList>
                <person name="Beneduce F."/>
                <person name="Ciervo A."/>
                <person name="Kusov Y.Y."/>
                <person name="Gauss-Mueller V."/>
                <person name="Morace G."/>
            </authorList>
            <dbReference type="PubMed" id="10562502"/>
            <dbReference type="DOI" id="10.1006/viro.1999.0017"/>
        </citation>
        <scope>FUNCTION (PROTEIN 3AB)</scope>
        <scope>INTERACTION WITH PROTEIN 3CD (PROTEIN 3AB)</scope>
        <scope>INTERACTION WITH PROTEIN 3AB (PROTEIN 3CD)</scope>
        <scope>RNA-BINDING (PROTEIN 3AB)</scope>
        <scope>FUNCTION (PROTEIN 3A)</scope>
        <scope>FUNCTION (PROTEIN 3CD)</scope>
        <source>
            <strain>HM175/7</strain>
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        <scope>PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN)</scope>
        <scope>PROTEOLYTIC CLEAVAGE (PROTEIN VP1-2A)</scope>
        <source>
            <strain>HM175p35</strain>
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        <scope>FUNCTION (PROTEIN VP1-2A)</scope>
        <scope>FUNCTION (PROTEIN VP4)</scope>
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        <scope>FUNCTION (CAPSID PROTEIN VP1)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP2)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP3)</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1520-1731 IN COMPLEX WITH PEPTIDE-BASED KETONE INHIBITORS</scope>
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        <scope>FUNCTION (PROTEIN VP1-2A)</scope>
        <scope>DOMAIN (PROTEIN VP1-2A)</scope>
        <source>
            <strain>HM175/18f</strain>
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        <scope>SUBUNIT (PROTEIN VP1-2A)</scope>
        <scope>MUTAGENESIS OF ARG-769</scope>
        <scope>DOMAIN (PROTEIN VP1-2A)</scope>
        <scope>PROTEOLYTIC CLEAVAGE (CAPSID PROTEIN VP0)</scope>
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        <scope>MUTAGENESIS OF CYS-1543 AND CYS-1691</scope>
        <scope>DISULFIDE BOND (PROTEASE 3C)</scope>
        <scope>SUBUNIT (PROTEASE 3C)</scope>
        <scope>RNA-BINDING (PROTEASE 3C)</scope>
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        <scope>FUNCTION (PROTEIN 3ABC)</scope>
        <scope>SUBCELLULAR LOCATION (PROTEIN 3ABC)</scope>
        <scope>INTERACTION WITH HUMAN MAVS (PROTEIN 3ABC)</scope>
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            <strain>HM175/18f</strain>
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        <scope>PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN)</scope>
        <scope>MUTAGENESIS OF ARG-769</scope>
        <scope>SUBUNIT (PROTEIN VP1-2A)</scope>
        <scope>PROTEOLYTIC CLEAVAGE (PROTEIN VP1-2A)</scope>
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        <scope>FUNCTION (PROTEIN 2B)</scope>
        <scope>SUBCELLULAR LOCATION (PROTEIN 2B)</scope>
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        <scope>FUNCTION (PROTEIN 3CD)</scope>
        <scope>MUTAGENESIS OF CYS-1691</scope>
        <source>
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        <scope>DOMAIN LATE-BUDDING (GENOME POLYPROTEIN)</scope>
        <scope>DOMAIN LATE-BUDDING (CAPSID PROTEIN VP2)</scope>
        <scope>MUTAGENESIS OF TYR-167 AND TYR-200</scope>
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            <dbReference type="PubMed" id="23572552"/>
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        <scope>INTERACTION WITH HOST ACBD3</scope>
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        <scope>FUNCTION (VIRAL PROTEIN GENOME-LINKED)</scope>
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        <scope>FUNCTION (PROTEIN 2B)</scope>
        <scope>SUBUNIT (PROTEIN 2B)</scope>
        <scope>DOMAIN (PROTEIN 2B)</scope>
        <scope>SUBCELLULAR LOCATION (PROTEIN 2B)</scope>
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        <scope>REVIEW</scope>
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        <scope>PROTEOLYTIC CLEAVAGE (PROTEIN VP1-2A)</scope>
        <scope>SUBCELLULAR LOCATION (CAPSID PROTEIN VP1)</scope>
        <scope>SUBCELLULAR LOCATION (CAPSID PROTEIN VP2)</scope>
        <scope>SUBCELLULAR LOCATION (CAPSID PROTEIN VP3)</scope>
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        <scope>FUNCTION (CAPSID PROTEIN VP1)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP2)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP3)</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736</scope>
        <scope>RNA-BINDING (PROTEASE 3C)</scope>
        <scope>FUNCTION (PROTEASE 3C)</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1520-1736 IN COMPLEX WITH THE INHIBITOR IODOACETYL-VALYL-PHENYLALANYL-AMIDE</scope>
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        <scope>FUNCTION (PROTEIN VP0)</scope>
        <scope>SUBCELLULAR LOCATION (PROTEIN VP4)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP2 (CAPSID PROTEIN VP1)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP2 (CAPSID PROTEIN VP3)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP1 (CAPSID PROTEIN VP2)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP1(CAPSID PROTEIN VP3)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP3 (CAPSID PROTEIN VP1)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP3 (CAPSID PROTEIN VP2)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP1)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP2)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP3)</scope>
        <scope>SUBCELLULAR LOCATION (CAPSID PROTEIN VP1)</scope>
        <scope>SUBCELLULAR LOCATION (CAPSID PROTEIN VP2)</scope>
        <scope>SUBCELLULAR LOCATION (CAPSID PROTEIN VP3)</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 765-981</scope>
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        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 492-769; 24-245 AND 246-491</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP2 (CAPSID PROTEIN VP1)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP2 (CAPSID PROTEIN VP3)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP1 (CAPSID PROTEIN VP2)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP1(CAPSID PROTEIN VP3)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP3 (CAPSID PROTEIN VP1)</scope>
        <scope>INTERACTION WITH CAPSID PROTEIN VP3 (CAPSID PROTEIN VP2)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP1)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP2)</scope>
        <scope>FUNCTION (CAPSID PROTEIN VP3)</scope>
        <scope>SUBCELLULAR LOCATION (CAPSID PROTEIN VP1)</scope>
        <scope>SUBCELLULAR LOCATION (CAPSID PROTEIN VP2)</scope>
        <scope>SUBCELLULAR LOCATION (CAPSID PROTEIN VP3)</scope>
    </reference>
    <comment type="function">
        <molecule>Capsid protein VP1</molecule>
        <text evidence="10 26 29 31 42">Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome (PubMed:25327248, PubMed:28074040). All these proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:25327248). Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms (PubMed:25327248). VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (PubMed:25327248). The naked capsid interacts with the host receptor HAVCR1 to provide virion attachment to and probably entry into the target cell (PubMed:9658108, PubMed:11134285, PubMed:29437974).</text>
    </comment>
    <comment type="function">
        <molecule>Capsid protein VP2</molecule>
        <text evidence="10 26 29 31 42">Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome (PubMed:25327248, PubMed:28074040). All these proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:25327248). Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms (PubMed:25327248). VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (PubMed:25327248). The naked capsid interacts with the host receptor HAVCR1 to provide virion attachment to and probably entry into the target cell (PubMed:9658108, PubMed:11134285, PubMed:29437974).</text>
    </comment>
    <comment type="function">
        <molecule>Capsid protein VP3</molecule>
        <text evidence="10 26 29 31 42">Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome (PubMed:25327248, PubMed:28074040). All these proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:25327248). Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms (PubMed:25327248). VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (PubMed:25327248). The naked capsid interacts with the host receptor HAVCR1 to provide virion attachment to and probably entry into the target cell (PubMed:9658108, PubMed:11134285, PubMed:29437974).</text>
    </comment>
    <comment type="function">
        <molecule>Capsid protein VP0</molecule>
        <text evidence="26">VP0 precursor is a component of the immature procapsids.</text>
    </comment>
    <comment type="function">
        <molecule>Capsid protein VP4</molecule>
        <text evidence="46">Plays a role in the assembly of the 12 pentamers into an icosahedral structure. Has not been detected in mature virions, supposedly owing to its small size.</text>
    </comment>
    <comment type="function">
        <molecule>Protein VP1-2A</molecule>
        <text evidence="11 46">Precursor component of immature procapsids that corresponds to an extended form of the structural protein VP1 (PubMed:9988685, PubMed:12097562). After maturation, possibly by the host Cathepsin L, the assembly signal 2A is cleaved to give rise to the mature VP1 protein (PubMed:9988685).</text>
    </comment>
    <comment type="function">
        <molecule>Protein 2B</molecule>
        <text evidence="18 20 28 40 45">Functions as a viroporin (PubMed:26515753). Affects membrane integrity and causes an increase in membrane permeability (PubMed:9875331). Involved in host intracellular membrane rearrangements probably to give rise to the viral factories (PubMed:9344908). Does not disrupt calcium homeostasis or glycoprotein trafficking (PubMed:18216106). Antagonizes the innate immune response of the host by suppressing IFN-beta synthesis, which it achieves by interfering with the DDX58/IFIH1 (RIG-I/MDA5) pathway (PubMed:18559929).</text>
    </comment>
    <comment type="function">
        <molecule>Protein 2BC</molecule>
        <text evidence="40 45">Affects membrane integrity and causes an increase in membrane permeability.</text>
    </comment>
    <comment type="function">
        <molecule>Protein 2C</molecule>
        <text evidence="40 41">Associates with and induces structural rearrangements of intracellular membranes (PubMed:9344908). Displays RNA-binding activity (PubMed:9645199).</text>
    </comment>
    <comment type="function">
        <molecule>Protein 3ABC</molecule>
        <text evidence="8 16">The precursor 3ABC is targeted to the mitochondrial membrane where protease 3C activity cleaves and inhibits the host antiviral protein MAVS, thereby disrupting activation of IRF3 through the IFIH1/MDA5 pathway (PubMed:17438296). In vivo, the protease activity of 3ABC precursor is more efficient in cleaving the 2BC precursor than that of protein 3C. The 3ABC precursor may therefore play a role in the proteolytic processing of the polyprotein (PubMed:10559299).</text>
    </comment>
    <comment type="function">
        <molecule>Protein 3AB</molecule>
        <text evidence="9 43">Interacts with the 3CD precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome (PubMed:10562502). Since the 3AB precursor contains the hydrophobic domain 3A, it probably anchors the whole viral replicase complex to intracellular membranes on which viral RNA synthesis occurs (PubMed:9705870).</text>
    </comment>
    <comment type="function">
        <molecule>Protein 3A</molecule>
        <text evidence="9 43">May serve as membrane anchor to the 3AB and 3ABC precursors via its hydrophobic domain (PubMed:9705870). May interact with RNA (PubMed:10562502).</text>
    </comment>
    <comment type="function">
        <molecule>Viral protein genome-linked</molecule>
        <text evidence="2 49">Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome.</text>
    </comment>
    <comment type="function">
        <molecule>Protease 3C</molecule>
        <text evidence="15 17 19 25 38">Cysteine protease that generates mature viral proteins from the precursor polyprotein (PubMed:1850033). In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication (PubMed:15361063). RNA and substrate bind cooperatively to the protease (PubMed:9032381). Cleaves IKBKG/NEMO to impair innate immune signaling (PubMed:24920812). Cleaves host PABPC1 which may participate in the switch of viral translation to RNA synthesis (PubMed:17726047).</text>
    </comment>
    <comment type="function">
        <molecule>Protein 3CD</molecule>
        <text evidence="9 22">Interacts with the 3AB precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome (PubMed:10562502). Disrupts TLR3 signaling by degrading the host adapter protein TICAM1/TRIF (PubMed:21931545).</text>
    </comment>
    <comment type="function">
        <text evidence="50">RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 35">
            <text>a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1)</text>
            <dbReference type="Rhea" id="RHEA:21248"/>
            <dbReference type="Rhea" id="RHEA-COMP:14527"/>
            <dbReference type="Rhea" id="RHEA-COMP:17342"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:61557"/>
            <dbReference type="ChEBI" id="CHEBI:140395"/>
            <dbReference type="EC" id="2.7.7.48"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate</text>
            <dbReference type="Rhea" id="RHEA:23680"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57930"/>
            <dbReference type="ChEBI" id="CHEBI:61557"/>
            <dbReference type="EC" id="3.6.1.15"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 19">
            <text>Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.</text>
            <dbReference type="EC" id="3.4.22.28"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <molecule>Protein 2B</molecule>
        <text evidence="27 28 50">Homodimer. Homomultimer; probably interacts with membranes in a multimeric form (PubMed:26515753). Seems to assemble into amyloid-like fibers (PubMed:25589659).</text>
    </comment>
    <comment type="subunit">
        <molecule>Protein 3A</molecule>
        <text evidence="24">Interacts with host ACBD3 (PubMed:23572552).</text>
    </comment>
    <comment type="subunit">
        <molecule>Protein 3AB</molecule>
        <text evidence="9 43 50">Homodimer. Monomer (PubMed:9705870). Interacts with protein 3CD (PubMed:10562502).</text>
    </comment>
    <comment type="subunit">
        <molecule>Protein 3CD</molecule>
        <text evidence="9">Interacts with protein 3AB (PubMed:10562502).</text>
    </comment>
    <comment type="subunit">
        <molecule>Protein 3ABC</molecule>
        <text evidence="16">Interacts with human MAVS (PubMed:17438296).</text>
    </comment>
    <comment type="subunit">
        <molecule>Protease 3C</molecule>
        <text evidence="15">Homodimer; disulfide-linked (PubMed:15361063).</text>
    </comment>
    <comment type="subunit">
        <molecule>Protein VP1-2A</molecule>
        <text evidence="12 21">Homopentamer (PubMed:12782637). Homooligomer (PubMed:18823593, PubMed:12782637).</text>
    </comment>
    <comment type="subunit">
        <molecule>Capsid protein VP1</molecule>
        <text evidence="26">Interacts with capsid protein VP2 (PubMed:25327248, PubMed:28074040). Interacts with capsid protein VP3 (PubMed:25327248, PubMed:28074040).</text>
    </comment>
    <comment type="subunit">
        <molecule>Capsid protein VP2</molecule>
        <text evidence="26">Interacts with capsid protein VP1 (PubMed:25327248, PubMed:28074040). Interacts with capsid protein VP3 (PubMed:25327248, PubMed:28074040).</text>
    </comment>
    <comment type="subunit">
        <molecule>Capsid protein VP3</molecule>
        <text evidence="26">Interacts with capsid protein VP1 (PubMed:25327248, PubMed:28074040). Interacts with capsid protein VP2 (PubMed:25327248, PubMed:28074040).</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Capsid protein VP2</molecule>
        <subcellularLocation>
            <location evidence="26 29">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="30">Host endosome</location>
            <location evidence="30">Host multivesicular body</location>
        </subcellularLocation>
        <text evidence="30">The egress of newly formed virions occurs through an exosome-like mechanism involving endosomal budding of viral capsids into multivesicular bodies.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Capsid protein VP3</molecule>
        <subcellularLocation>
            <location evidence="26 29">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="30">Host endosome</location>
            <location evidence="30">Host multivesicular body</location>
        </subcellularLocation>
        <text evidence="30">The egress of newly formed virions occurs through an exosome-like mechanism involving endosomal budding of viral capsids into multivesicular bodies.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Capsid protein VP1</molecule>
        <subcellularLocation>
            <location evidence="26 29">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="30">Host endosome</location>
            <location evidence="30">Host multivesicular body</location>
        </subcellularLocation>
        <text evidence="30">The egress of newly formed virions occurs through an exosome-like mechanism involving endosomal budding of viral capsids into multivesicular bodies.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Capsid protein VP4</molecule>
        <subcellularLocation>
            <location evidence="26">Virion</location>
        </subcellularLocation>
        <text evidence="26 51">Present in the full mature virion (PubMed:25327248). The egress of newly formed virions occurs through an exosome-like mechanism involving endosomal budding of viral capsids into multivesicular bodies (Probable).</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Protein 2B</molecule>
        <subcellularLocation>
            <location evidence="18 28 45">Host membrane</location>
            <topology evidence="45">Peripheral membrane protein</topology>
        </subcellularLocation>
        <text evidence="50">Probably localizes to intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Protein 2C</molecule>
        <subcellularLocation>
            <location evidence="41">Host membrane</location>
            <topology evidence="45">Single-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="52">Probably localizes to intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. May associate with membranes through a N-terminal amphipathic helix.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Protein 3ABC</molecule>
        <subcellularLocation>
            <location evidence="50">Host membrane</location>
            <topology evidence="3">Single-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="16">Host mitochondrion outer membrane</location>
            <topology evidence="50">Single-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="50">Probably localizes to intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Protein 3AB</molecule>
        <subcellularLocation>
            <location evidence="50">Host membrane</location>
            <topology evidence="3">Single-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="50">Probably localizes to intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Protein 3A</molecule>
        <subcellularLocation>
            <location evidence="50">Host membrane</location>
            <topology evidence="3">Single-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="50">Probably localizes to intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Viral protein genome-linked</molecule>
        <subcellularLocation>
            <location evidence="50">Virion</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Protease 3C</molecule>
        <subcellularLocation>
            <location evidence="50">Host cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>RNA-directed RNA polymerase 3D-POL</molecule>
        <subcellularLocation>
            <location evidence="50">Host cytoplasmic vesicle membrane</location>
            <topology evidence="50">Peripheral membrane protein</topology>
            <orientation evidence="50">Cytoplasmic side</orientation>
        </subcellularLocation>
        <text evidence="50">Interacts with membranes in a complex with viral protein 3AB. Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.</text>
    </comment>
    <comment type="domain">
        <molecule>Protein VP1-2A</molecule>
        <text evidence="11 12">The assembly signal 2A region mediates pentamerization of P1-2A.</text>
    </comment>
    <comment type="domain">
        <molecule>Genome polyprotein</molecule>
        <text evidence="23 50">Late-budding domains (L domains) are short sequence motifs essential for viral particle budding (Probable). They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins (Probable). The genome polyprotein contains two L domains: a tandem of (L)YPX(n)L domain which is known to bind the PDCD6IP/ALIX adaptater protein (PubMed:23542590).</text>
    </comment>
    <comment type="domain">
        <molecule>Capsid protein VP2</molecule>
        <text evidence="23 50">Late-budding domains (L domains) are short sequence motifs essential for viral particle budding (Probable). They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins (Probable). Capsid protein VP2 contains two L domains: a tandem of (L)YPX(n)L domain which is known to bind the Alix adaptater protein (PubMed:23542590).</text>
    </comment>
    <comment type="domain">
        <molecule>Protein 2B</molecule>
        <text evidence="28">The C-terminus displays a membrane-penetrating ability.</text>
    </comment>
    <comment type="PTM">
        <molecule>Genome polyprotein</molecule>
        <text evidence="7 8 19 21 32 33 34 35 36 39 44">Specific enzymatic cleavages by viral protease in vivo yield a variety of precursors and mature proteins. Polyprotein processing intermediates are produced, such as P1-2A which is a functional precursor of the structural proteins, VP0 which is a VP4-VP2 precursor, VP1-2A precursor, 3ABC precursor which is a stable and catalytically active precursor of 3A, 3B and 3C proteins, 3AB and 3CD precursors (PubMed:7483265, PubMed:1850033, PubMed:8382411, PubMed:8291234, PubMed:9060697, PubMed:9733840, PubMed:8259663, PubMed:7853510, PubMed:10559299). The assembly signal 2A is removed from VP1-2A by a host protease, possibly host Cathepsin L (PubMed:18823593). This cleavage occurs over a region of 3 amino-acids probably generating VP1 proteins with heterogeneous C-termini (PubMed:10364353).</text>
    </comment>
    <comment type="PTM">
        <molecule>Capsid protein VP0</molecule>
        <text evidence="12 35 39 44">During virion maturation, immature virions are rendered infectious following cleavage of VP0 into VP4 and VP2. This maturation seems to be an autocatalytic event triggered by the presence of RNA in the capsid and is followed by a conformational change of the particle (PubMed:12782637, PubMed:8291234, PubMed:9060697, PubMed:9733840).</text>
    </comment>
    <comment type="PTM">
        <molecule>Protein VP1-2A</molecule>
        <text evidence="7 21 30">The assembly signal 2A is removed from VP1-2A by a host protease, possibly host Cathepsin L in naked virions (PubMed:18823593). This cleavage does not occur in enveloped virions (PubMed:28490497). This cleavage occurs over a region of 3 amino-acids probably generating VP1 proteins with heterogeneous C-termini (PubMed:10364353).</text>
    </comment>
    <comment type="PTM">
        <molecule>Viral protein genome-linked</molecule>
        <text evidence="2">VPg is uridylylated prior to priming replication into VPg-pUpU.</text>
    </comment>
    <comment type="PTM">
        <molecule>Capsid protein VP4</molecule>
        <text evidence="37">Unlike other picornaviruses, does not seem to be myristoylated.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="50">The need for an intact eIF4G factor for the initiation of translation of HAV results in an inability to shut off host protein synthesis by a mechanism similar to that of other picornaviruses.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="23 30 31 48 50">During infection, enveloped virions (eHAV) are released from cells (PubMed:23542590). These eHAV are cloaked in host-derived membranes and resemble exosomes (PubMed:28490497). The membrane of eHAV is devoid of viral proteins and thus prevents their neutralization by antibodies (PubMed:23542590). eHAV budding is dependent on ESCRT-associated proteins VPS4B and PDCD6IP/ALIX (PubMed:23542590). eHAV are produced and released in the serum and plasma, but not in bile and feces which only contain the naked, nonenveloped virions (Probable). It is likely that eHAV also use HAVCR1 as a functional receptor to infect cells, an evolutionary trait that may enhance HAV infectivity (PubMed:29437974).</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="50">Wild-type HM175 (HM175/wt) comes from a sample isolated from a patient in Australia in 1976 and subsequently passaged three times in marmosets. HM175/7 is an attenuated strain derived from HM175 by 32 passages in African green monkey kidney cells. HM175/18f, HM175/24a, and HM175/43c are cytopathic isolates derived from HM175 by serial passages in FRhK-4 cells.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Mutations in proteins 2B and 2C seem to be essential for strain HM175 adaptation to growth in cell culture.</text>
    </comment>
    <comment type="similarity">
        <text evidence="50">Belongs to the picornaviridae polyprotein family.</text>
    </comment>
    <comment type="caution">
        <text evidence="14">It is uncertain whether Met-1 or Met-3 is the initiator. In vitro, both are used, with a preference for Met-3.</text>
    </comment>
    <comment type="sequence caution" evidence="50">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAA45466" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.6.1.15"/>
    <dbReference type="EC" id="3.4.22.28" evidence="19"/>
    <dbReference type="EC" id="2.7.7.48" evidence="35"/>
    <dbReference type="EMBL" id="M14707">
        <property type="protein sequence ID" value="AAA45465.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M14707">
        <property type="protein sequence ID" value="AAA45466.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M16632">
        <property type="protein sequence ID" value="AAA45471.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M59808">
        <property type="protein sequence ID" value="AAA45467.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M59809">
        <property type="protein sequence ID" value="AAA45469.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M59810">
        <property type="protein sequence ID" value="AAA45468.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M14114">
        <property type="protein sequence ID" value="AAA45475.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M14115">
        <property type="protein sequence ID" value="AAA45476.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="K00386">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF396398">
        <property type="protein sequence ID" value="AAL66215.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="PIR" id="A03905">
        <property type="entry name" value="A03905"/>
    </dbReference>
    <dbReference type="PIR" id="A25981">
        <property type="entry name" value="GNNYHM"/>
    </dbReference>
    <dbReference type="PIR" id="A94149">
        <property type="entry name" value="GNNYMK"/>
    </dbReference>
    <dbReference type="PIR" id="JH0135">
        <property type="entry name" value="JH0135"/>
    </dbReference>
    <dbReference type="PIR" id="PQ0427">
        <property type="entry name" value="PQ0427"/>
    </dbReference>
    <dbReference type="PIR" id="PQ0428">
        <property type="entry name" value="PQ0428"/>
    </dbReference>
    <dbReference type="PIR" id="PQ0431">
        <property type="entry name" value="PQ0431"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_041007.1">
        <property type="nucleotide sequence ID" value="NC_001489.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_041008.1">
        <property type="nucleotide sequence ID" value="NC_001489.1"/>
    </dbReference>
    <dbReference type="PDB" id="1HAV">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B=1520-1736"/>
    </dbReference>
    <dbReference type="PDB" id="1QA7">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B/C/D=1520-1736"/>
    </dbReference>
    <dbReference type="PDB" id="2H6M">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.40 A"/>
        <property type="chains" value="A=1520-1731"/>
    </dbReference>
    <dbReference type="PDB" id="2H9H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.39 A"/>
        <property type="chains" value="A=1520-1731"/>
    </dbReference>
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    <keyword id="KW-0694">RNA-binding</keyword>
    <keyword id="KW-0696">RNA-directed RNA polymerase</keyword>
    <keyword id="KW-1143">T=pseudo3 icosahedral capsid protein</keyword>
    <keyword id="KW-0788">Thiol protease</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-1161">Viral attachment to host cell</keyword>
    <keyword id="KW-0899">Viral immunoevasion</keyword>
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    <keyword id="KW-0693">Viral RNA replication</keyword>
    <keyword id="KW-0946">Virion</keyword>
    <keyword id="KW-1160">Virus entry into host cell</keyword>
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            <end position="2227"/>
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            <begin position="1"/>
            <end position="23"/>
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            <begin position="24"/>
            <end position="245"/>
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            <end position="491"/>
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            <end position="836"/>
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            <begin position="492"/>
            <end position="765"/>
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    <feature type="chain" id="PRO_0000039950" description="Assembly signal 2A">
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    <feature type="chain" id="PRO_0000308972" description="Protein 2BC">
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            <end position="1422"/>
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            <begin position="837"/>
            <end position="1087"/>
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            <begin position="1088"/>
            <end position="1422"/>
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    <feature type="chain" id="PRO_0000308973" description="Protein 3ABCD">
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            <begin position="1423"/>
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    <feature type="chain" id="PRO_0000308974" description="Protein 3ABC">
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            <begin position="1423"/>
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    <feature type="chain" id="PRO_0000308975" description="Protein 3AB">
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            <begin position="1423"/>
            <end position="1519"/>
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    <feature type="chain" id="PRO_0000039953" description="Protein 3A">
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            <begin position="1423"/>
            <end position="1496"/>
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    <feature type="chain" id="PRO_0000039954" description="Viral protein genome-linked">
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            <begin position="1497"/>
            <end position="1519"/>
        </location>
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    <feature type="chain" id="PRO_0000308976" description="Protein 3CD">
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            <begin position="1520"/>
            <end position="2227"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000039955" description="Protease 3C">
        <location>
            <begin position="1520"/>
            <end position="1738"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000039956" description="RNA-directed RNA polymerase 3D-POL">
        <location>
            <begin position="1739"/>
            <end position="2227"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="1011"/>
            <end position="1031"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3 43">
        <location>
            <begin position="1462"/>
            <end position="1482"/>
        </location>
    </feature>
    <feature type="domain" description="SF3 helicase" evidence="5">
        <location>
            <begin position="1204"/>
            <end position="1366"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase C3" evidence="6">
        <location>
            <begin position="1514"/>
            <end position="1728"/>
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    </feature>
    <feature type="domain" description="RdRp catalytic" evidence="4">
        <location>
            <begin position="1976"/>
            <end position="2097"/>
        </location>
    </feature>
    <feature type="region of interest" description="Involved in P1-2A pentamerization" evidence="11 12">
        <location>
            <begin position="766"/>
            <end position="836"/>
        </location>
    </feature>
    <feature type="region of interest" description="Membrane-penetrating ability" evidence="28">
        <location>
            <begin position="1043"/>
            <end position="1070"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="(L)YPX(n)L motif" evidence="23">
        <location>
            <begin position="167"/>
            <end position="171"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="(L)YPX(n)L motif" evidence="23">
        <location>
            <begin position="200"/>
            <end position="205"/>
        </location>
    </feature>
    <feature type="active site" description="For protease 3C activity" evidence="6">
        <location>
            <position position="1563"/>
        </location>
    </feature>
    <feature type="active site" description="For protease 3C activity" evidence="6">
        <location>
            <position position="1603"/>
        </location>
    </feature>
    <feature type="active site" description="For protease 3C activity" evidence="6">
        <location>
            <position position="1691"/>
        </location>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <begin position="1230"/>
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        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="site" description="Cleavage; by protease 3C" evidence="47">
        <location>
            <begin position="245"/>
            <end position="246"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by protease 3C" evidence="47">
        <location>
            <begin position="491"/>
            <end position="492"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; partial; by host" evidence="7 12">
        <location>
            <begin position="765"/>
            <end position="766"/>
        </location>
    </feature>
    <feature type="site" description="Important for VP1 folding and capsid assembly" evidence="12 21">
        <location>
            <position position="769"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by protease 3C" evidence="32 33">
        <location>
            <begin position="836"/>
            <end position="837"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by protease 3C" evidence="33">
        <location>
            <begin position="1087"/>
            <end position="1088"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by protease 3C" evidence="47">
        <location>
            <begin position="1422"/>
            <end position="1423"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by protease 3C" evidence="8">
        <location>
            <begin position="1496"/>
            <end position="1497"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by protease 3C" evidence="8">
        <location>
            <begin position="1519"/>
            <end position="1520"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by protease 3C" evidence="35">
        <location>
            <begin position="1738"/>
            <end position="1739"/>
        </location>
    </feature>
    <feature type="modified residue" description="O-(5'-phospho-RNA)-tyrosine" evidence="1">
        <location>
            <position position="1499"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain" evidence="15">
        <location>
            <position position="1543"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/24a and HM175/43c.">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="315"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f.">
        <original>T</original>
        <variation>K</variation>
        <location>
            <position position="336"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/24a.">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="638"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/24a and HM175/43c.">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="688"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f.">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="762"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7.">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="764"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/24a and HM175/43c.">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="767"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7.">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="821"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="838"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="849"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In 24.">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="941"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="993"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="1052"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7.">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="1062"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>AIY</original>
        <variation>GIC</variation>
        <location>
            <begin position="1109"/>
            <end position="1111"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7.">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="1118"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1151"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="1163"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="1180"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="1212"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="1229"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7.">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="1277"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="1407"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <location>
            <position position="1428"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="1480"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1487"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7.">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="1500"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="1507"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/43c.">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="1524"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f and HM175/24a.">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="1620"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/43c.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="1675"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="1805"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="1930"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: HM175/18f, HM175/24a and HM175/43c.">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="1962"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Severely decreases virus release but does not impair viral RNA replication." evidence="23">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="167"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Severely decreases virus release but does not impair viral RNA replication." evidence="23">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="200"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of viral particles assembly. Interferes with oligomerization of protein VP1-2A and maturation of procapsids." evidence="12 21">
        <original>R</original>
        <variation>M</variation>
        <location>
            <position position="769"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Partial loss of VP1-2A-2B cleavage." evidence="32">
        <original>Q</original>
        <variation>N</variation>
        <location>
            <position position="836"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of VP1-2A-2B cleavage." evidence="32">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="836"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="10-20 fold increase in virus yield." evidence="13">
        <original>A</original>
        <variation>I</variation>
        <variation>L</variation>
        <variation>V</variation>
        <location>
            <position position="1052"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of protease 3C dimerization." evidence="15">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="1543"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of enzymatic activity. Complete loss of cleavage of host TICAM1." evidence="22">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="1691"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of proteolytic activity." evidence="15">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="1691"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; AAL66215." evidence="50" ref="7">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA45476." evidence="50" ref="4">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="1825"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA45476." evidence="50" ref="4">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="1850"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA45476." evidence="50" ref="4">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="1856"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="38"/>
            <end position="42"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="45"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="helix" evidence="59">
        <location>
            <begin position="76"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="84"/>
            <end position="92"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="100"/>
            <end position="104"/>
        </location>
    </feature>
    <feature type="helix" evidence="59">
        <location>
            <begin position="106"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="111"/>
            <end position="115"/>
        </location>
    </feature>
    <feature type="helix" evidence="59">
        <location>
            <begin position="118"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="124"/>
            <end position="137"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="143"/>
            <end position="154"/>
        </location>
    </feature>
    <feature type="helix" evidence="59">
        <location>
            <begin position="161"/>
            <end position="166"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="167"/>
            <end position="173"/>
        </location>
    </feature>
    <feature type="turn" evidence="59">
        <location>
            <begin position="174"/>
            <end position="176"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="177"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="189"/>
            <end position="197"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="202"/>
            <end position="215"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="217"/>
            <end position="219"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="221"/>
            <end position="239"/>
        </location>
    </feature>
    <feature type="helix" evidence="59">
        <location>
            <begin position="265"/>
            <end position="268"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="271"/>
            <end position="275"/>
        </location>
    </feature>
    <feature type="helix" evidence="59">
        <location>
            <begin position="276"/>
            <end position="278"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="286"/>
            <end position="288"/>
        </location>
    </feature>
    <feature type="helix" evidence="59">
        <location>
            <begin position="297"/>
            <end position="300"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="304"/>
            <end position="312"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="320"/>
            <end position="325"/>
        </location>
    </feature>
    <feature type="turn" evidence="59">
        <location>
            <begin position="336"/>
            <end position="339"/>
        </location>
    </feature>
    <feature type="helix" evidence="59">
        <location>
            <begin position="345"/>
            <end position="350"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="353"/>
            <end position="367"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="373"/>
            <end position="383"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="385"/>
            <end position="387"/>
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    <feature type="helix" evidence="59">
        <location>
            <begin position="394"/>
            <end position="397"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="400"/>
            <end position="406"/>
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    <feature type="strand" evidence="59">
        <location>
            <begin position="408"/>
            <end position="410"/>
        </location>
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    <feature type="strand" evidence="59">
        <location>
            <begin position="413"/>
            <end position="418"/>
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    <feature type="strand" evidence="59">
        <location>
            <begin position="423"/>
            <end position="428"/>
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    <feature type="helix" evidence="59">
        <location>
            <begin position="430"/>
            <end position="432"/>
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    <feature type="strand" evidence="59">
        <location>
            <begin position="433"/>
            <end position="435"/>
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    <feature type="strand" evidence="59">
        <location>
            <begin position="444"/>
            <end position="456"/>
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    <feature type="strand" evidence="59">
        <location>
            <begin position="459"/>
            <end position="461"/>
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    <feature type="strand" evidence="59">
        <location>
            <begin position="463"/>
            <end position="481"/>
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    <feature type="strand" evidence="61">
        <location>
            <begin position="532"/>
            <end position="534"/>
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    <feature type="helix" evidence="61">
        <location>
            <begin position="540"/>
            <end position="542"/>
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    <feature type="strand" evidence="61">
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            <end position="579"/>
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    <sequence length="2227" mass="251508" checksum="01E225E7AEB740A6" modified="1988-08-01" version="1">MNMSRQGIFQTVGSGLDHILSLADIEEEQMIQSVDRTAVTGASYFTSVDQSSVHTAEVGSHQVEPLRTSVDKPGSKKTQGEKFFLIHSADWLTTHALFHEVAKLDVVKLLYNEQFAVQGLLRYHTYARFGIEIQVQINPTPFQQGGLICAMVPGDQSYGSIASLTVYPHGLLNCNINNVVRIKVPFIYTRGAYHFKDPQYPVWELTIRVWSELNIGTGTSAYTSLNVLARFTDLELHGLTPLSTQMMRNEFRVSTTENVVNLSNYEDARAKMSFALDQEDWKSDPSQGGGIKITHFTTWTSIPTLAAQFPFNASDSVGQQIKVIPVDPYFFQMTNTNPDQKCITALASICQMFCFWRGDLVFDFQVFPTKYHSGRLLFCFVPGNELIDVSGITLKQATTAPCAVMDITGVQSTLRFRVPWISDTPYRVNRYTKSAHQKGEYTAIGKLIVYCYNRLTSPSNVASHVRVNVYLSAINLECFAPLYHAMDVTTQVGDDSGGFSTTVSTEQNVPDPQVGITTMKDLKGKANRGKMDVSGVQAPVGAITTIEDPVLAKKVPETFPELKPGESRHTSDHMSIYKFMGRSHFLCTFTFNSNNKEYTFPITLSSTSNPPHGLPSTLRWFFNLFQLYRGPLDLTIIITGATDVDGMAWFTPVGLAVDTPWVEKESALSIDYKTALGAVRFNTRRTGNIQIRLPWYSYLYAVSGALDGLGDKTDSTFGLVSIQIANYNHSDEYLSFSCYLSVTEQSEFYFPRAPLNSNAMLSTESMMSRIAAGDLESSVDDPRSEEDKRFESHIECRKPYKELRLEVGKQRLKYAQEELSNEVLPPPRKMKGLFSQAKISLFYTEEHEIMKFSWRGVTADTRALRRFGFSLAAGRSVWTLEMDAGVLTGRLIRLNDEKWTEMKDDKIVSLIEKFTSNKYWSKVNFPHGMLDLEEIAANSKDFPNMSETDLCFLLHWLNPKKINLADRMLGLSGVQEIKEQGVGLIAECRTFLDSIAGTLKSMMFGFHHSVTVEIINTVLCFVKSGILLYVIQQLNQDEHSHIIGLLRVMNYADIGCSVISCGKVFSKMLETVFNWQMDSRMMELRTQSFSNWLRDICSGITIFKNFKDAIYWLYTKLKDFYEVNYGKKKDILNILKDNQQKIEKAIEEADEFCILQIQDVEKFEQYQKGVDLIQKLRTVHSMAQVDPNLMVHLSPLRDCIARVHQKLKNLGSINQAMVTRCEPVVCYLYGKRGGGKSLTSIALATKICKHYGVEPEKNIYTKPVASDYWDGYSGQLVCIIDDIGQNTTDEDWSDFCQLVSGCPMRLNMASLEEKGRHFSSPFIIATSNWSNPSPKTVYVKEAIDRRLHFKVEVKPASFFKNPHNDMLNVNLAKTNDAIKDMSCVDLIMDGHNVSLMDLLSSLVMTVEIRKQNMTEFMELWSQGISDDDNDSAVAEFFQSFPSGEPSNSKLSGFFQSVTNHKWVAVGAAVGILGVLVGGWFVYKHFSRKEEEPIPAEGVYHGVTKPKQVIKLDADPVESQSTLEIAGLVRKNLVQFGVGEKNGCVRWVMNALGVKDDWLLVPSHAYKFEKDYEMMEFYFNRGGTYYSISAGNVVIQSLDVGFQDVVLMKVPTIPKFRDITQHFIKKGDVPRALNRLATLVTTVNGTPMLISEGPLKMEEKATYVHKKNDGTTVDLTVDQAWRGKGEGLPGMCGGALVSSNQSIQNAILGIHVAGGNSILVAKLVTQEMFQNIDKKIESQRIMKVEFTQCSMNVVSKTLFRKSPIYHHIDKTMINFPAAMPFSKAEIDPMAVMLSKYSLPIVEEPEDYKEASIFYQNKIVGKTQLVDDFLDLDMAITGAPGIDAINMDSSPGFPYVQEKLTKRDLIWLDENGLLLGVHPRLAQRILFNTVMMENCSDLDVVFTTCPKDELRPLEKVLESKTRAIDACPLDYSILCRMYWGPAISYFHLNPGFHTGVAIGIDPDRQWDELFKTMIRFGDVGLDLDFSAFDASLSPFMIREAGRIMSELSGTPSHFGTALINTIIYSKHLLYNCCYHVCGSMPSGSPCTALLNSIINNVNLYYVFSKIFGKSPVFFCQALKILCYGDDVLIVFSRDVQIDNLDLIGQKIVDEFKKLGMTATSADKNVPQLKPVSELTFLKRSFNLVEDRIRPAISEKTIWSLIAWQRSNAEFEQNLENAQWFAFMHGYEFYQKFYYFVQSCLEKEMIEYRLKSYDWWRMRFYDQCFICDLS</sequence>
</entry>
<copyright>
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms Distributed under the Creative Commons Attribution (CC BY 4.0) License
</copyright>
</uniprot>