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    <accession>Q6R1L5</accession>
    <name>H9EJA2_CVHNL</name>
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            <fullName evidence="1">Envelope small membrane protein</fullName>
            <shortName evidence="1">E protein</shortName>
            <shortName evidence="1">sM protein</shortName>
        </recommendedName>
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    <gene>
        <name evidence="1 16" type="primary">E</name>
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    <organism evidence="16 70">
        <name type="scientific">Human coronavirus NL63</name>
        <name type="common">HCoV-NL63</name>
        <dbReference type="NCBI Taxonomy" id="277944"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Pisuviricota</taxon>
            <taxon>Pisoniviricetes</taxon>
            <taxon>Nidovirales</taxon>
            <taxon>Cornidovirineae</taxon>
            <taxon>Coronaviridae</taxon>
            <taxon>Orthocoronavirinae</taxon>
            <taxon>Alphacoronavirus</taxon>
            <taxon>Setracovirus</taxon>
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    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="6212" last="6216">
            <title>A previously undescribed coronavirus associated with respiratory disease in humans.</title>
            <authorList>
                <person name="Fouchier R.A."/>
                <person name="Hartwig N.G."/>
                <person name="Bestebroer T.M."/>
                <person name="Niemeyer B."/>
                <person name="De Jong J.C."/>
                <person name="Simon J.H."/>
                <person name="Osterhaus A.D."/>
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            <dbReference type="DOI" id="10.1073/pnas.0400762101"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <citation type="submission" date="2004-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Fouchier R.A.M."/>
                <person name="Bestebroer T.M."/>
                <person name="de Jong J.C."/>
                <person name="Niemeyer B."/>
                <person name="Simon J.H."/>
                <person name="Osterhaus A.D.M.E."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
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    <reference evidence="65 67 69" key="3">
        <citation type="journal article" date="2012" name="J. Gen. Virol." volume="93" first="2387" last="2398">
            <title>Genomic analysis of 16 Colorado human NL63 coronaviruses identifies a new genotype, high sequence diversity in the N-terminal domain of the spike gene and evidence of recombination.</title>
            <authorList>
                <person name="Dominguez S.R."/>
                <person name="Sims G.E."/>
                <person name="Wentworth D.E."/>
                <person name="Halpin R.A."/>
                <person name="Robinson C.C."/>
                <person name="Town C.D."/>
                <person name="Holmes K.V."/>
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            <dbReference type="DOI" id="10.1099/vir.0.044628-0"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <strain evidence="14">NL63/DEN/2005/1062</strain>
            <strain evidence="15">NL63/DEN/2005/1862</strain>
            <strain evidence="16">NL63/DEN/2005/1876</strain>
            <strain evidence="9">NL63/DEN/2005/193</strain>
            <strain evidence="10">NL63/DEN/2005/232</strain>
            <strain evidence="11">NL63/DEN/2005/235</strain>
            <strain evidence="12">NL63/DEN/2005/271</strain>
            <strain evidence="13">NL63/DEN/2005/347</strain>
            <strain evidence="7">NL63/DEN/2008/16</strain>
            <strain evidence="5">NL63/DEN/2009/14</strain>
            <strain evidence="6">NL63/DEN/2009/15</strain>
            <strain evidence="8">NL63/DEN/2009/20</strain>
            <strain evidence="4">NL63/DEN/2009/9</strain>
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    <reference evidence="17 64" key="4">
        <citation type="journal article" date="2012" name="J. Virol." volume="86" first="9546" last="9547">
            <title>Characterization and Complete Genome Sequence of Human Coronavirus NL63 Isolated in China.</title>
            <authorList>
                <person name="Geng H."/>
                <person name="Cui L."/>
                <person name="Xie Z."/>
                <person name="Lu R."/>
                <person name="Zhao L."/>
                <person name="Tan W."/>
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            <dbReference type="PubMed" id="22879617"/>
            <dbReference type="DOI" id="10.1128/JVI.01457-12"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="17">CBJ 037</strain>
        </source>
    </reference>
    <reference evidence="18 75" key="5">
        <citation type="submission" date="2012-08" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Geng H."/>
                <person name="Cui L."/>
                <person name="Xie Z."/>
                <person name="Lu R."/>
                <person name="Zhao L."/>
                <person name="Tan W."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="18">CBJ123</strain>
        </source>
    </reference>
    <reference evidence="19 66" key="6">
        <citation type="journal article" date="2013" name="Virol. J." volume="10" first="e213" last="e213">
            <title>Isolation and genetic characterization of human coronavirus NL63 in primary human renal proximal tubular epithelial cells obtained from a commercial supplier, and confirmation of its replication in two different types of human primary kidney cells.</title>
            <authorList>
                <person name="Lednicky J.A."/>
                <person name="Waltzek T.B."/>
                <person name="McGeehan E."/>
                <person name="Loeb J.C."/>
                <person name="Hamilton S.B."/>
                <person name="Luetke M.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="19">NL63/RPTEC/2004</strain>
        </source>
    </reference>
    <reference evidence="68 71 72" key="7">
        <citation type="submission" date="2013-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Town C.D."/>
                <person name="Halpin R.A."/>
                <person name="Ransier A."/>
                <person name="Fedorova N."/>
                <person name="Tsitrin T."/>
                <person name="Stockwell T."/>
                <person name="Amedeo P."/>
                <person name="Appalla L."/>
                <person name="Bishop B."/>
                <person name="Edworthy P."/>
                <person name="Gupta N."/>
                <person name="Hoover J."/>
                <person name="Katzel D."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Thovarai V."/>
                <person name="Wang S."/>
                <person name="Talbot H.K."/>
                <person name="Wentworth D.E."/>
                <person name="Williams J.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="28">NL63/human/USA/0111-25/2001</strain>
            <strain evidence="21">NL63/human/USA/012-31/2001</strain>
            <strain evidence="26">NL63/human/USA/838-9/1983</strain>
            <strain evidence="22">NL63/human/USA/8712-17/1987</strain>
            <strain evidence="30">NL63/human/USA/891-4/1989</strain>
            <strain evidence="24">NL63/human/USA/891-6/1989</strain>
            <strain evidence="27">NL63/human/USA/901-24/1990</strain>
            <strain evidence="25">NL63/human/USA/903-28/1990</strain>
            <strain evidence="20">NL63/human/USA/904-20/1990</strain>
            <strain evidence="29">NL63/human/USA/905-25/1990</strain>
            <strain evidence="23">NL63/human/USA/911-56/1991</strain>
        </source>
    </reference>
    <reference evidence="73" key="8">
        <citation type="submission" date="2015-07" db="EMBL/GenBank/DDBJ databases">
            <title>Human Coronavirus NL63 from the blood of a Haitian child with febrile illness.</title>
            <authorList>
                <person name="Lednicky J.A."/>
                <person name="Okech B.A."/>
                <person name="Morris J.G.Jr."/>
                <person name="Beau De Rochars V.M."/>
                <person name="White S.K."/>
                <person name="Elbadry M.A."/>
                <person name="Loeb J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference evidence="74" key="9">
        <citation type="submission" date="2015-08" db="EMBL/GenBank/DDBJ databases">
            <title>Human Coronavirus NL63 in a patient from Florida.</title>
            <authorList>
                <person name="Lednicky J.A."/>
                <person name="Morris J.G.Jr."/>
                <person name="Rand K.H."/>
                <person name="Loeb J.C."/>
                <person name="Okech B.A."/>
                <person name="Beau De Rochars V.M."/>
                <person name="Elbadry M.A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference evidence="31" key="10">
        <citation type="journal article" date="2016" name="Am. J. Trop. Med. Hyg." volume="0" first="0" last="0">
            <title>Isolation of Coronavirus NL63 from Blood from Children in Rural Haiti: Phylogenetic Similarities with Recent Isolates from Malaysia.</title>
            <authorList>
                <person name="Beau De Rochars V.M."/>
                <person name="Lednicky J."/>
                <person name="White S."/>
                <person name="Loeb J."/>
                <person name="Elbadry M.A."/>
                <person name="Telisma T."/>
                <person name="Chavannes S."/>
                <person name="Anilis M.G."/>
                <person name="Cella E."/>
                <person name="Ciccozzi M."/>
                <person name="Okech B.A."/>
                <person name="Salemi M."/>
                <person name="Morris J.G.Jr."/>
            </authorList>
            <dbReference type="PubMed" id="27799635"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="31">HCoV NL63/Haiti-1/2015</strain>
            <strain evidence="32">NL63/UF-1/2015</strain>
            <strain evidence="33">NL63/UF-2/2015</strain>
        </source>
    </reference>
    <reference evidence="33" key="11">
        <citation type="submission" date="2016-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Oliw E.H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="33">NL63/UF-2/2015</strain>
        </source>
    </reference>
    <reference evidence="34" key="12">
        <citation type="submission" date="2016-05" db="EMBL/GenBank/DDBJ databases">
            <title>Human coronavirus NL63 from a patient in Gainesville, Florida, in 2015.</title>
            <authorList>
                <person name="Lednicky J.A."/>
                <person name="Morris J.G.Jr."/>
                <person name="Rand K.H."/>
                <person name="White S.K."/>
                <person name="Loeb J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="34">NL63/UF-2/2015</strain>
        </source>
    </reference>
    <reference evidence="35" key="13">
        <citation type="journal article" date="2017" name="J. Infect. Dis." volume="216" first="203" last="209">
            <title>Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution.</title>
            <authorList>
                <person name="Ogimi C."/>
                <person name="Greninger A.L."/>
                <person name="Waghmare A.A."/>
                <person name="Kuypers J.M."/>
                <person name="Shean R.C."/>
                <person name="Xie H."/>
                <person name="Leisenring W.M."/>
                <person name="Stevens-Ayers T.L."/>
                <person name="Jerome K.R."/>
                <person name="Englund J.A."/>
                <person name="Boeckh M."/>
            </authorList>
            <dbReference type="PubMed" id="28838146"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="37">N06-1144B</strain>
            <strain evidence="38">N07-185B</strain>
            <strain evidence="39">N07-196B</strain>
            <strain evidence="42">N07-262B</strain>
            <strain evidence="40">N07-324B_182X</strain>
            <strain evidence="41">N07-468B_176X</strain>
            <strain evidence="36">N07-64B</strain>
            <strain evidence="35">N07-6B</strain>
        </source>
    </reference>
    <reference evidence="43" key="14">
        <citation type="submission" date="2017-04" db="EMBL/GenBank/DDBJ databases">
            <title>Genome sequences of viral positives at UW Virology.</title>
            <authorList>
                <person name="Greninger A.L."/>
                <person name="Makhsous N."/>
                <person name="Kuypers J."/>
                <person name="Shean R.C."/>
                <person name="Jerome K.R."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="43">HCoV_NL63/Seattle/USA/SC2940/2015</strain>
        </source>
    </reference>
    <reference evidence="45" key="15">
        <citation type="journal article" date="2018" name="J. Infect. Dis." volume="217" first="1728" last="1739">
            <title>Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya.</title>
            <authorList>
                <person name="Kiyuka P.K."/>
                <person name="Agoti C.N."/>
                <person name="Munywoki P.K."/>
                <person name="Njeru R."/>
                <person name="Bett A."/>
                <person name="Otieno J.R."/>
                <person name="Otieno G.P."/>
                <person name="Kamau E."/>
                <person name="Clark T.G."/>
                <person name="van der Hoek L."/>
                <person name="Kellam P."/>
                <person name="Nokes D.J."/>
                <person name="Cotten M."/>
            </authorList>
            <dbReference type="PubMed" id="29741740"/>
            <dbReference type="DOI" id="10.1093/infdis/jiy098"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="49">Kilifi_HH_0511_01-Jun-2010</strain>
            <strain evidence="47">Kilifi_HH_0512_04-Jun-2010</strain>
            <strain evidence="51">Kilifi_HH_0522_21-May-2010</strain>
            <strain evidence="46">Kilifi_HH_1602_01-Jun-2010</strain>
            <strain evidence="48">Kilifi_HH_3807_11-May-2010</strain>
            <strain evidence="52">Kilifi_HH_3808_24-May-2010</strain>
            <strain evidence="53">Kilifi_HH_5401_20-May-2010</strain>
            <strain evidence="50">Kilifi_HH_5402_20-May-2010</strain>
            <strain evidence="45">Kilifi_HH_5709_19-May-2010</strain>
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    </reference>
    <reference evidence="44" key="16">
        <citation type="submission" date="2018-01" db="EMBL/GenBank/DDBJ databases">
            <title>The complete genome sequence of human coronavirus NL63 CN/0601/14 strain, first isolated from South Korea.</title>
            <authorList>
                <person name="Kim J.-M."/>
                <person name="Kim S.-T."/>
                <person name="Yang J.-S."/>
                <person name="Kim S.S."/>
                <person name="Cheong H.-M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="44">CN0601/14</strain>
        </source>
    </reference>
    <reference evidence="54" key="17">
        <citation type="submission" date="2019-06" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Kamau E."/>
                <person name="Luka M.M."/>
                <person name="de Laurent Z.R."/>
                <person name="Adema I."/>
                <person name="Agoti C.N."/>
                <person name="Nokes J.D."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="54">NL63_KLF_01_2018</strain>
        </source>
    </reference>
    <reference evidence="60" key="18">
        <citation type="submission" date="2019-08" db="EMBL/GenBank/DDBJ databases">
            <title>Genome sequences of clinical viruses from UW Virology.</title>
            <authorList>
                <person name="Lin M.J."/>
                <person name="Tait A."/>
                <person name="Greninger A.L."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="60">HCoV_NL63/Seattle/USA/SC0179/2018</strain>
            <strain evidence="61">HCoV_NL63/Seattle/USA/SC0768/2019</strain>
        </source>
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    <reference evidence="55" key="19">
        <citation type="journal article" date="2020" name="Microbiol. Resour. Announc." volume="9" first="e01597" last="19">
            <title>Complete Genome Sequences of Five Human Coronavirus NL63 Strains Causing Respiratory Illness in Hospitalized Children in China.</title>
            <authorList>
                <person name="Zhang L."/>
                <person name="Gan M."/>
                <person name="Zhang Z."/>
                <person name="Li X."/>
                <person name="Liu W."/>
                <person name="Zhu A."/>
                <person name="Sun J."/>
                <person name="Li F."/>
                <person name="Wang Y."/>
                <person name="Zhang F."/>
                <person name="Zhao J."/>
                <person name="Zhou R."/>
                <person name="Zhao J."/>
            </authorList>
            <dbReference type="PubMed" id="32079638"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="58">ChinaGD01</strain>
            <strain evidence="55">ChinaGD02</strain>
            <strain evidence="56">ChinaGD03</strain>
            <strain evidence="59">ChinaGD04</strain>
            <strain evidence="57">ChinaGD05</strain>
        </source>
    </reference>
    <reference evidence="62" key="20">
        <citation type="submission" date="2020-02" db="EMBL/GenBank/DDBJ databases">
            <title>Genome sequences of viral isolates from UW Virology.</title>
            <authorList>
                <person name="Addetia A."/>
                <person name="Greninger A.L."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="62">2019_0711</strain>
            <strain evidence="63">2019_1580</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in the induction of apoptosis.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homopentamer. Interacts with membrane protein M in the budding compartment of the host cell, which is located between endoplasmic reticulum and the Golgi complex. Interacts with Nucleoprotein.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Host Golgi apparatus membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <text evidence="1">The cytoplasmic tail functions as a Golgi complex-targeting signal.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the alphacoronaviruses E protein family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAS89769.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="molecule type" value="Genomic_RNA"/>
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        <source>
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        <source>
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    <evidence type="ECO:0000313" key="59">
        <source>
            <dbReference type="EMBL" id="QED88042.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="60">
        <source>
            <dbReference type="EMBL" id="QEG03733.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="61">
        <source>
            <dbReference type="EMBL" id="QEG03750.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="62">
        <source>
            <dbReference type="EMBL" id="QQY99323.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="63">
        <source>
            <dbReference type="EMBL" id="QQY99390.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="64">
        <source>
            <dbReference type="Proteomes" id="UP000098690"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="65">
        <source>
            <dbReference type="Proteomes" id="UP000100468"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="66">
        <source>
            <dbReference type="Proteomes" id="UP000103541"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="67">
        <source>
            <dbReference type="Proteomes" id="UP000105969"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="68">
        <source>
            <dbReference type="Proteomes" id="UP000106901"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="69">
        <source>
            <dbReference type="Proteomes" id="UP000108941"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="70">
        <source>
            <dbReference type="Proteomes" id="UP000110792"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="71">
        <source>
            <dbReference type="Proteomes" id="UP000136929"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="72">
        <source>
            <dbReference type="Proteomes" id="UP000140530"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="73">
        <source>
            <dbReference type="Proteomes" id="UP000141634"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="74">
        <source>
            <dbReference type="Proteomes" id="UP000145724"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="75">
        <source>
            <dbReference type="Proteomes" id="UP000158277"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="76">
        <source>
            <dbReference type="Proteomes" id="UP000161757"/>
        </source>
    </evidence>
    <sequence length="77" mass="9178" checksum="921B5332B22B3687" modified="2012-05-16" version="1">MFLRLIDDNGIVLNSILWLLVMIFFFVLAMTFIKLIQLCFTCHYFFSRTLYQPVYKIFLAYQDYMQIAPVPAEVLNV</sequence>
</entry>
<entry dataset="TrEMBL" created="2012-05-16" modified="2022-08-03" version="55" xmlns="http://uniprot.org/uniprot">
    <accession>H9EJA4</accession>
    <accession>Q6R1L3</accession>
    <name>H9EJA4_CVHNL</name>
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        <recommendedName>
            <fullName evidence="9">Nucleoprotein</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="19" type="primary">N</name>
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    <organism evidence="19 37">
        <name type="scientific">Human coronavirus NL63</name>
        <name type="common">HCoV-NL63</name>
        <dbReference type="NCBI Taxonomy" id="277944"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Pisuviricota</taxon>
            <taxon>Pisoniviricetes</taxon>
            <taxon>Nidovirales</taxon>
            <taxon>Cornidovirineae</taxon>
            <taxon>Coronaviridae</taxon>
            <taxon>Orthocoronavirinae</taxon>
            <taxon>Alphacoronavirus</taxon>
            <taxon>Setracovirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference evidence="14 41" key="1">
        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="6212" last="6216">
            <title>A previously undescribed coronavirus associated with respiratory disease in humans.</title>
            <authorList>
                <person name="Fouchier R.A."/>
                <person name="Hartwig N.G."/>
                <person name="Bestebroer T.M."/>
                <person name="Niemeyer B."/>
                <person name="De Jong J.C."/>
                <person name="Simon J.H."/>
                <person name="Osterhaus A.D."/>
            </authorList>
            <dbReference type="PubMed" id="15073334"/>
            <dbReference type="DOI" id="10.1073/pnas.0400762101"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference evidence="14" key="2">
        <citation type="submission" date="2004-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Fouchier R.A.M."/>
                <person name="Bestebroer T.M."/>
                <person name="de Jong J.C."/>
                <person name="Niemeyer B."/>
                <person name="Simon J.H."/>
                <person name="Osterhaus A.D.M.E."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
    </reference>
    <reference evidence="34 37 38" key="3">
        <citation type="journal article" date="2012" name="J. Gen. Virol." volume="93" first="2387" last="2398">
            <title>Genomic analysis of 16 Colorado human NL63 coronaviruses identifies a new genotype, high sequence diversity in the N-terminal domain of the spike gene and evidence of recombination.</title>
            <authorList>
                <person name="Dominguez S.R."/>
                <person name="Sims G.E."/>
                <person name="Wentworth D.E."/>
                <person name="Halpin R.A."/>
                <person name="Robinson C.C."/>
                <person name="Town C.D."/>
                <person name="Holmes K.V."/>
            </authorList>
            <dbReference type="PubMed" id="22837419"/>
            <dbReference type="DOI" id="10.1099/vir.0.044628-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="17">NL63/DEN/2005/1062</strain>
            <strain evidence="18">NL63/DEN/2005/1862</strain>
            <strain evidence="19">NL63/DEN/2005/1876</strain>
            <strain evidence="15">NL63/DEN/2005/193</strain>
            <strain evidence="16">NL63/DEN/2005/347</strain>
        </source>
    </reference>
    <reference evidence="20 35" key="4">
        <citation type="journal article" date="2013" name="Virol. J." volume="10" first="e213" last="e213">
            <title>Isolation and genetic characterization of human coronavirus NL63 in primary human renal proximal tubular epithelial cells obtained from a commercial supplier, and confirmation of its replication in two different types of human primary kidney cells.</title>
            <authorList>
                <person name="Lednicky J.A."/>
                <person name="Waltzek T.B."/>
                <person name="McGeehan E."/>
                <person name="Loeb J.C."/>
                <person name="Hamilton S.B."/>
                <person name="Luetke M.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="20">NL63/RPTEC/2004</strain>
        </source>
    </reference>
    <reference evidence="36 39 40" key="5">
        <citation type="submission" date="2013-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Town C.D."/>
                <person name="Halpin R.A."/>
                <person name="Ransier A."/>
                <person name="Fedorova N."/>
                <person name="Tsitrin T."/>
                <person name="Stockwell T."/>
                <person name="Amedeo P."/>
                <person name="Appalla L."/>
                <person name="Bishop B."/>
                <person name="Edworthy P."/>
                <person name="Gupta N."/>
                <person name="Hoover J."/>
                <person name="Katzel D."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Thovarai V."/>
                <person name="Wang S."/>
                <person name="Talbot H.K."/>
                <person name="Wentworth D.E."/>
                <person name="Williams J.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="27">NL63/human/USA/891-4/1989</strain>
            <strain evidence="23">NL63/human/USA/891-6/1989</strain>
            <strain evidence="25">NL63/human/USA/901-24/1990</strain>
            <strain evidence="24">NL63/human/USA/903-28/1990</strain>
            <strain evidence="21">NL63/human/USA/904-20/1990</strain>
            <strain evidence="26">NL63/human/USA/905-25/1990</strain>
            <strain evidence="22">NL63/human/USA/911-56/1991</strain>
        </source>
    </reference>
    <reference evidence="28" key="6">
        <citation type="journal article" date="2017" name="J. Infect. Dis." volume="216" first="203" last="209">
            <title>Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution.</title>
            <authorList>
                <person name="Ogimi C."/>
                <person name="Greninger A.L."/>
                <person name="Waghmare A.A."/>
                <person name="Kuypers J.M."/>
                <person name="Shean R.C."/>
                <person name="Xie H."/>
                <person name="Leisenring W.M."/>
                <person name="Stevens-Ayers T.L."/>
                <person name="Jerome K.R."/>
                <person name="Englund J.A."/>
                <person name="Boeckh M."/>
            </authorList>
            <dbReference type="PubMed" id="28838146"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="28">N07-196B</strain>
            <strain evidence="30">N07-262B</strain>
            <strain evidence="29">N07-468B_176X</strain>
        </source>
    </reference>
    <reference evidence="31" key="7">
        <citation type="submission" date="2017-03" db="EMBL/GenBank/DDBJ databases">
            <title>Partial sequencing and genotyping of twenty Human coronavirus NL63 (HCoV-NL63) circulated in Normandy from 2004 to 2016.</title>
            <authorList>
                <person name="Kin N."/>
                <person name="Miszczak F."/>
                <person name="Desvagues M."/>
                <person name="Diancourt L."/>
                <person name="Caro V."/>
                <person name="Vabret A."/>
                <person name="Le Gouil M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="32">NL63/FRA-EPI/Caen/2004/01</strain>
            <strain evidence="31">NL63/FRA-EPI/Caen/2004/02</strain>
        </source>
    </reference>
    <reference evidence="33" key="8">
        <citation type="submission" date="2019-09" db="EMBL/GenBank/DDBJ databases">
            <title>A target hybridization-based next-generation sequencing assay enhances surveillance of seasonal respiratory pathogens: a retrospective assessment.</title>
            <authorList>
                <person name="Janssens T.K.S."/>
                <person name="Zhan S.H."/>
                <person name="Overduin P."/>
                <person name="Alamouti S.M."/>
                <person name="Kwok B.S."/>
                <person name="Schmitz D."/>
                <person name="Qadir M.A."/>
                <person name="Meijer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
    </reference>
    <comment type="function">
        <text evidence="9">Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9">Virion</location>
        </subcellularLocation>
        <text evidence="9">Located inside the virion, complexed with the viral RNA. Probably associates with ER-derived membranes where it participates in viral RNA synthesis and virus budding.</text>
    </comment>
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        <property type="protein sequence ID" value="AAS89771.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="JQ765568">
        <property type="protein sequence ID" value="AFD98789.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="protein sequence ID" value="AFD98817.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AFD98824.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="protein sequence ID" value="AFD98831.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="protein sequence ID" value="AFD98838.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="protein sequence ID" value="AFV53152.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="protein sequence ID" value="AGT51328.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="protein sequence ID" value="AGT51356.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="protein sequence ID" value="AGT51363.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="protein sequence ID" value="AGT51377.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KF530113">
        <property type="protein sequence ID" value="AGT51391.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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    <dbReference type="EMBL" id="KF530114">
        <property type="protein sequence ID" value="AGT51398.1"/>
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        <property type="protein sequence ID" value="ARE29975.1"/>
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        <property type="protein sequence ID" value="ARE29987.1"/>
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        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="protein sequence ID" value="QHB49093.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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    <dbReference type="GeneID" id="2943504"/>
    <dbReference type="KEGG" id="vg:2943504"/>
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        <property type="component" value="Genome"/>
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        <property type="component" value="Genome"/>
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        <property type="entry name" value="COV_N_NTD"/>
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    </dbReference>
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    <keyword evidence="7" id="KW-0804">Transcription</keyword>
    <keyword evidence="5" id="KW-0805">Transcription regulation</keyword>
    <keyword evidence="6 9 10" id="KW-0543">Viral nucleoprotein</keyword>
    <keyword evidence="3 9 10" id="KW-0946">Virion</keyword>
    <feature type="domain" description="CoV N NTD" evidence="12">
        <location>
            <begin position="17"/>
            <end position="139"/>
        </location>
    </feature>
    <feature type="domain" description="CoV N CTD" evidence="13">
        <location>
            <begin position="223"/>
            <end position="337"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="11">
        <location>
            <begin position="140"/>
            <end position="183"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="11">
        <location>
            <begin position="196"/>
            <end position="244"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="11">
        <location>
            <begin position="196"/>
            <end position="218"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="11">
        <location>
            <begin position="228"/>
            <end position="242"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00022553"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00022765"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00022844"/>
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    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00022884"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00023015"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00023086"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="ARBA" id="ARBA00023163"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="ARBA" id="ARBA00023274"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="PIRNR" id="PIRNR003888"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="10">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="11">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="12">
        <source>
            <dbReference type="PROSITE" id="PS51928"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="13">
        <source>
            <dbReference type="PROSITE" id="PS51929"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="14">
        <source>
            <dbReference type="EMBL" id="AAS89771.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="15">
        <source>
            <dbReference type="EMBL" id="AFD98789.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="16">
        <source>
            <dbReference type="EMBL" id="AFD98817.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="17">
        <source>
            <dbReference type="EMBL" id="AFD98824.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="18">
        <source>
            <dbReference type="EMBL" id="AFD98831.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="19">
        <source>
            <dbReference type="EMBL" id="AFD98838.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="20">
        <source>
            <dbReference type="EMBL" id="AFV53152.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="21">
        <source>
            <dbReference type="EMBL" id="AGT51328.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="22">
        <source>
            <dbReference type="EMBL" id="AGT51349.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="23">
        <source>
            <dbReference type="EMBL" id="AGT51356.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="24">
        <source>
            <dbReference type="EMBL" id="AGT51363.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="25">
        <source>
            <dbReference type="EMBL" id="AGT51377.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="26">
        <source>
            <dbReference type="EMBL" id="AGT51391.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="27">
        <source>
            <dbReference type="EMBL" id="AGT51398.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="28">
        <source>
            <dbReference type="EMBL" id="ARE29975.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="29">
        <source>
            <dbReference type="EMBL" id="ARE29987.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="30">
        <source>
            <dbReference type="EMBL" id="ARK08631.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="31">
        <source>
            <dbReference type="EMBL" id="AVL25611.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="32">
        <source>
            <dbReference type="EMBL" id="AVL25612.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="33">
        <source>
            <dbReference type="EMBL" id="QHB49093.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="34">
        <source>
            <dbReference type="Proteomes" id="UP000100468"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="35">
        <source>
            <dbReference type="Proteomes" id="UP000103541"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="36">
        <source>
            <dbReference type="Proteomes" id="UP000106901"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="37">
        <source>
            <dbReference type="Proteomes" id="UP000110792"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="38">
        <source>
            <dbReference type="Proteomes" id="UP000129674"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="39">
        <source>
            <dbReference type="Proteomes" id="UP000140530"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="40">
        <source>
            <dbReference type="Proteomes" id="UP000144638"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="41">
        <source>
            <dbReference type="Proteomes" id="UP000161757"/>
        </source>
    </evidence>
    <sequence length="377" mass="42252" checksum="704C71C0EF9CDB42" modified="2012-05-16" version="1">MASVNWADDRAARKKFPPPSFYMPLLVSSDKAPYRVIPRNLVPIGKGNKDEQIGYWNVQERWRMRRGQRVDLPPKVHFYYLGTGPHKDLKFRQRSDGVVWVAKEGAKTVNTSLGNRKRNQKPLEPKFSIALPPELSVVEFEDRSNNSSRASSRSSTRNNSRDSSRSTSRQQSRTRSDSNQSSSDLVAAVTLALKNLGFDNQSKSPSSSGTSTPKKPNKPLSQPRADKPSQLKKPRWKRVPTREENVIQCFGPRDFNHNMGDSDLVQNGVDAKGFPQLAELIPNQAALFFDSEVSTDEVGDNVQITYTYKMLVAKDNKNLPKFIEQISAFTKPSSIKEMQSQSSHVAQNTVLNASIPESKPLADDDSAIIEIVNEVLH</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-07-19" modified="2022-08-03" version="112" xmlns="http://uniprot.org/uniprot">
    <accession>Q6Q1S2</accession>
    <accession>Q5DIX7</accession>
    <accession>Q5DIX8</accession>
    <accession>Q5DIX9</accession>
    <accession>Q5DIY0</accession>
    <accession>Q6R1L7</accession>
    <name>SPIKE_CVHNL</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Spike glycoprotein</fullName>
            <shortName evidence="1">S glycoprotein</shortName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">E2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">Peplomer protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1" type="primary">S</name>
        <name type="ORF">2</name>
    </gene>
    <organism>
        <name type="scientific">Human coronavirus NL63</name>
        <name type="common">HCoV-NL63</name>
        <dbReference type="NCBI Taxonomy" id="277944"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Pisuviricota</taxon>
            <taxon>Pisoniviricetes</taxon>
            <taxon>Nidovirales</taxon>
            <taxon>Cornidovirineae</taxon>
            <taxon>Coronaviridae</taxon>
            <taxon>Orthocoronavirinae</taxon>
            <taxon>Alphacoronavirus</taxon>
            <taxon>Setracovirus</taxon>
        </lineage>
    </organism>
    <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="2004" name="Nat. Med." volume="10" first="368" last="373">
            <title>Identification of a new human coronavirus.</title>
            <authorList>
                <person name="Van Der Hoek L."/>
                <person name="Pyrc K."/>
                <person name="Jebbink M.F."/>
                <person name="Vermeulen-Oost W."/>
                <person name="Berkhout R.J."/>
                <person name="Wolthers K.C."/>
                <person name="Wertheim-Van Dillen P.M."/>
                <person name="Kaandorp J."/>
                <person name="Spaargaren J."/>
                <person name="Berkhout B."/>
            </authorList>
            <dbReference type="PubMed" id="15034574"/>
            <dbReference type="DOI" id="10.1038/nm1024"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="van der Hoek L."/>
                <person name="Pyrc K."/>
                <person name="Jebbink M.F."/>
                <person name="Vermeulen-Oost W."/>
                <person name="Berkhout R.J.M."/>
                <person name="Wolthers K.C."/>
                <person name="Wertheim-van Dillen P.M.E."/>
                <person name="Kaandorp J."/>
                <person name="Spaargaren J."/>
                <person name="Berkhout B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="6212" last="6216">
            <title>A previously undescribed coronavirus associated with respiratory disease in humans.</title>
            <authorList>
                <person name="Fouchier R.A."/>
                <person name="Hartwig N.G."/>
                <person name="Bestebroer T.M."/>
                <person name="Niemeyer B."/>
                <person name="De Jong J.C."/>
                <person name="Simon J.H."/>
                <person name="Osterhaus A.D."/>
            </authorList>
            <dbReference type="PubMed" id="15073334"/>
            <dbReference type="DOI" id="10.1073/pnas.0400762101"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
        <source>
            <strain>Isolate NL</strain>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2004-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Fouchier R.A.M."/>
                <person name="Bestebroer T.M."/>
                <person name="de Jong J.C."/>
                <person name="Niemeyer B."/>
                <person name="Simon J.H."/>
                <person name="Osterhaus A.D.M.E."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
        <source>
            <strain>Isolate NL</strain>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2004-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Moes E."/>
                <person name="Vijgen L."/>
                <person name="Keyaerts E."/>
                <person name="Zlateva K."/>
                <person name="Meurs M."/>
                <person name="Pyrc K."/>
                <person name="Berkhout B."/>
                <person name="van der Hoek L."/>
                <person name="Van Ranst M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-193</scope>
        <source>
            <strain>Isolate BE03-1153</strain>
            <strain>Isolate BE03-21596</strain>
            <strain>Isolate BE03-40001</strain>
            <strain>Isolate BE03-64880</strain>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2005" name="Proc. Natl. Acad. Sci. U.S.A." volume="102" first="7988" last="7993">
            <title>Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry.</title>
            <authorList>
                <person name="Hofmann H."/>
                <person name="Pyrc K."/>
                <person name="van der Hoek L."/>
                <person name="Geier M."/>
                <person name="Berkhout B."/>
                <person name="Poehlmann S."/>
            </authorList>
            <dbReference type="PubMed" id="15897467"/>
            <dbReference type="DOI" id="10.1073/pnas.0409465102"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH HUMAN ACE2</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2018" name="J. Virol." volume="92" first="0" last="0">
            <title>Entry of Human Coronavirus NL63 into the Cell.</title>
            <authorList>
                <person name="Milewska A."/>
                <person name="Nowak P."/>
                <person name="Owczarek K."/>
                <person name="Szczepanski A."/>
                <person name="Zarebski M."/>
                <person name="Hoang A."/>
                <person name="Berniak K."/>
                <person name="Wojarski J."/>
                <person name="Zeglen S."/>
                <person name="Baster Z."/>
                <person name="Rajfur Z."/>
                <person name="Pyrc K."/>
            </authorList>
            <dbReference type="PubMed" id="29142129"/>
            <dbReference type="DOI" id="10.1128/jvi.01933-17"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference evidence="8" key="8">
        <citation type="journal article" date="2006" name="Biochemistry" volume="45" first="15205" last="15215">
            <title>Core structure of S2 from the human coronavirus NL63 spike glycoprotein.</title>
            <authorList>
                <person name="Zheng Q."/>
                <person name="Deng Y."/>
                <person name="Liu J."/>
                <person name="van der Hoek L."/>
                <person name="Berkhout B."/>
                <person name="Lu M."/>
            </authorList>
            <dbReference type="PubMed" id="17176042"/>
            <dbReference type="DOI" id="10.1021/bi061686w"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 981-1038 AND 1242-1283</scope>
    </reference>
    <reference evidence="9" key="9">
        <citation type="journal article" date="2009" name="Proc. Natl. Acad. Sci. U.S.A." volume="106" first="19970" last="19974">
            <title>Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor.</title>
            <authorList>
                <person name="Wu K."/>
                <person name="Li W."/>
                <person name="Peng G."/>
                <person name="Li F."/>
            </authorList>
            <dbReference type="PubMed" id="19901337"/>
            <dbReference type="DOI" id="10.1073/pnas.0908837106"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.31 ANGSTROMS) OF 481-616</scope>
        <scope>GLYCOSYLATION AT ASN-486 AND ASN-512</scope>
        <scope>INTERACTION WITH HUMAN ACE2</scope>
        <scope>FUNCTION</scope>
        <scope>DISULFIDE BOND</scope>
    </reference>
    <reference evidence="10" key="10">
        <citation type="journal article" date="2016" name="Nat. Struct. Mol. Biol." volume="23" first="899" last="905">
            <title>Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy.</title>
            <authorList>
                <person name="Walls A.C."/>
                <person name="Tortorici M.A."/>
                <person name="Frenz B."/>
                <person name="Snijder J."/>
                <person name="Li W."/>
                <person name="Rey F.A."/>
                <person name="DiMaio F."/>
                <person name="Bosch B.J."/>
                <person name="Veesler D."/>
            </authorList>
            <dbReference type="PubMed" id="27617430"/>
            <dbReference type="DOI" id="10.1038/nsmb.3293"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 16-1291</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>GLYCOSYLATION AT ASN-35; ASN-52; ASN-98; ASN-155; ASN-187; ASN-193; ASN-240; ASN-276; ASN-301; ASN-330; ASN-354; ASN-358; ASN-403; ASN-426; ASN-486; ASN-506; ASN-512; ASN-626; ASN-645; ASN-666; ASN-699; ASN-723; ASN-749; ASN-762; ASN-768; ASN-1111; ASN-1196; ASN-1201; ASN-1218; ASN-1242; ASN-1247 AND ASN-1277</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 5 7">S1 region attaches the virion to the cell membrane by interacting with host ACE2, initiating the infection (PubMed:15897467, PubMed:29142129, PubMed:19901337). Binding to the receptor probably induces conformational changes in the S glycoprotein unmasking the fusion peptide and activating membranes fusion. S2 region belongs to the class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 4">Homotrimer. During virus morphogenesis, found in a complex with M proteins (By similarity). Interacts with host ACE2(PubMed:15897467).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-15814420">
            <id>Q6Q1S2</id>
        </interactant>
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
            <label>ACE2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Virion membrane</location>
            <topology evidence="1">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host endoplasmic reticulum-Golgi intermediate compartment membrane</location>
            <topology evidence="1">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <text evidence="1">Accumulates in the endoplasmic reticulum-Golgi intermediate compartment, where it participates in virus particle assembly.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The KxHxx motif seems to function as an ER retrieval signal.</text>
    </comment>
    <comment type="PTM">
        <text evidence="5 6">Glycosylated by host with heterogeneous N-linked glycans protruding from the trimer surface (PubMed:19901337, PubMed:27617430). Highly glycosylated by host, occluding many regions across the surface of the protein (PubMed:27617430).</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the alphacoronaviruses spike protein family.</text>
    </comment>
    <comment type="caution">
        <text evidence="1">In contrast to beta- and gammacoronaviruses, S glycoprotein is not cleaved into S1 and S2.</text>
    </comment>
    <dbReference type="EMBL" id="AY567487">
        <property type="protein sequence ID" value="AAS58177.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY518894">
        <property type="protein sequence ID" value="AAS89767.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY758297">
        <property type="protein sequence ID" value="AAW66968.1"/>
        <property type="status" value="ALT_TERM"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY758298">
        <property type="protein sequence ID" value="AAW66969.1"/>
        <property type="status" value="ALT_TERM"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY758300">
        <property type="protein sequence ID" value="AAW66970.1"/>
        <property type="status" value="ALT_TERM"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY758301">
        <property type="protein sequence ID" value="AAW66971.1"/>
        <property type="status" value="ALT_TERM"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_003767.1">
        <property type="nucleotide sequence ID" value="NC_005831.2"/>
    </dbReference>
    <dbReference type="PDB" id="2IEQ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.75 A"/>
        <property type="chains" value="A/B/C=981-1037, A/B/C=1242-1283"/>
    </dbReference>
    <dbReference type="PDB" id="3KBH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.31 A"/>
        <property type="chains" value="E/F/G/H=481-616"/>
    </dbReference>
    <dbReference type="PDB" id="5SZS">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A/B/C=16-1291"/>
    </dbReference>
    <dbReference type="PDB" id="7FC3">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.19 A"/>
        <property type="chains" value="E=481-611"/>
    </dbReference>
    <dbReference type="PDB" id="7KIP">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.39 A"/>
        <property type="chains" value="A/B/C=1-1356"/>
    </dbReference>
    <dbReference type="PDBsum" id="2IEQ"/>
    <dbReference type="PDBsum" id="3KBH"/>
    <dbReference type="PDBsum" id="5SZS"/>
    <dbReference type="PDBsum" id="7FC3"/>
    <dbReference type="PDBsum" id="7KIP"/>
    <dbReference type="SMR" id="Q6Q1S2"/>
    <dbReference type="DIP" id="DIP-49012N"/>
    <dbReference type="IntAct" id="Q6Q1S2">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="DNASU" id="2943499"/>
    <dbReference type="GeneID" id="2943499"/>
    <dbReference type="KEGG" id="vg:2943499"/>
    <dbReference type="SABIO-RK" id="Q6Q1S2"/>
    <dbReference type="EvolutionaryTrace" id="Q6Q1S2"/>
    <dbReference type="Proteomes" id="UP000008573">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000161757">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044173">
        <property type="term" value="C:host cell endoplasmic reticulum-Golgi intermediate compartment membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016021">
        <property type="term" value="C:integral component of membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019031">
        <property type="term" value="C:viral envelope"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055036">
        <property type="term" value="C:virion membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046789">
        <property type="term" value="F:host cell surface receptor binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0075509">
        <property type="term" value="P:endocytosis involved in viral entry into host cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039654">
        <property type="term" value="P:fusion of virus membrane with host endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
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    <feature type="sequence variant" description="In strain: Isolate NL.">
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    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference evidence="39 40" key="1">
        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="6212" last="6216">
            <title>A previously undescribed coronavirus associated with respiratory disease in humans.</title>
            <authorList>
                <person name="Fouchier R.A."/>
                <person name="Hartwig N.G."/>
                <person name="Bestebroer T.M."/>
                <person name="Niemeyer B."/>
                <person name="De Jong J.C."/>
                <person name="Simon J.H."/>
                <person name="Osterhaus A.D."/>
            </authorList>
            <dbReference type="PubMed" id="15073334"/>
            <dbReference type="DOI" id="10.1073/pnas.0400762101"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.</text>
    </comment>
    <comment type="function">
        <text evidence="3">Nsp9 is a ssRNA-binding protein.</text>
    </comment>
    <comment type="function">
        <text evidence="31">The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).</text>
            <dbReference type="EC" id="3.4.19.12"/>
        </reaction>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Host cytoplasm</location>
            <location evidence="6">Host perinuclear region</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5">Host membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the coronaviruses polyprotein 1ab family.</text>
    </comment>
    <dbReference type="EMBL" id="AY518894">
        <property type="protein sequence ID" value="AAS89766.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="MEROPS" id="C30.003"/>
    <dbReference type="Proteomes" id="UP000161757">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033644">
        <property type="term" value="C:host cell membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044220">
        <property type="term" value="C:host cell perinuclear region of cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016021">
        <property type="term" value="C:integral component of membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004843">
        <property type="term" value="F:cysteine-type deubiquitinase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004197">
        <property type="term" value="F:cysteine-type endopeptidase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008242">
        <property type="term" value="F:omega peptidase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016740">
        <property type="term" value="F:transferase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039520">
        <property type="term" value="P:induction by virus of host autophagy"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039648">
        <property type="term" value="P:modulation by virus of host protein ubiquitination"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039548">
        <property type="term" value="P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019079">
        <property type="term" value="P:viral genome replication"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019082">
        <property type="term" value="P:viral protein processing"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="CDD" id="cd21558">
        <property type="entry name" value="alphaCoV-Nsp6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd21665">
        <property type="entry name" value="alphaCoV_Nsp5_Mpro"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd21514">
        <property type="entry name" value="cv_alpha_Nsp2_HCoV-229E-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd21473">
        <property type="entry name" value="cv_Nsp4_TM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd21557">
        <property type="entry name" value="Macro_X_Nsp3-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd21466">
        <property type="entry name" value="Ubl2_cv_PLpro_N_Nsp3-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.150.420">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.1840.10">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.8.1190">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.8.370">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.30.1000">
        <property type="match status" value="1"/>
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        <property type="match status" value="2"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="A-CoV_nsp1_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043613">
        <property type="entry name" value="CoV_NSP2_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043611">
        <property type="entry name" value="CoV_NSP3_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR032505">
        <property type="entry name" value="CoV_NSP4_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043612">
        <property type="entry name" value="CoV_NSP4_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002589">
        <property type="entry name" value="Macro_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043472">
        <property type="entry name" value="Macro_dom-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR044371">
        <property type="entry name" value="Macro_X_NSP3-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036333">
        <property type="entry name" value="NSP10_sf_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR044385">
        <property type="entry name" value="NSP2_HCoV-229E-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043615">
        <property type="entry name" value="NSP2_N_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR044357">
        <property type="entry name" value="NSP3_Ubl1_dom_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR044353">
        <property type="entry name" value="Nsp3_Ubl2_dom_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038123">
        <property type="entry name" value="NSP4_C_sf_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR044309">
        <property type="entry name" value="NSP5_Mpro_alphaCoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR044369">
        <property type="entry name" value="NSP6_alphaCoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043610">
        <property type="entry name" value="NSP6_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014828">
        <property type="entry name" value="NSP7_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037204">
        <property type="entry name" value="NSP7_sf_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014829">
        <property type="entry name" value="NSP8_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037230">
        <property type="entry name" value="NSP8_sf_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014822">
        <property type="entry name" value="NSP9_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036499">
        <property type="entry name" value="NSP9_sf_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011050">
        <property type="entry name" value="Pectin_lyase_fold/virulence"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013016">
        <property type="entry name" value="Peptidase_C16_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008740">
        <property type="entry name" value="Peptidase_C30_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043477">
        <property type="entry name" value="Peptidase_C30_dom3_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009003">
        <property type="entry name" value="Peptidase_S1_PA"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043504">
        <property type="entry name" value="Peptidase_S1_PA_chymotrypsin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043178">
        <property type="entry name" value="PLpro_thumb_sf_CoV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018995">
        <property type="entry name" value="RNA_synth_NSP10_CoV"/>
    </dbReference>
    <dbReference type="Pfam" id="PF09401">
        <property type="entry name" value="CoV_NSP10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF19212">
        <property type="entry name" value="CoV_NSP2_C"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF19211">
        <property type="entry name" value="CoV_NSP2_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF19218">
        <property type="entry name" value="CoV_NSP3_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16348">
        <property type="entry name" value="CoV_NSP4_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF19217">
        <property type="entry name" value="CoV_NSP4_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF19213">
        <property type="entry name" value="CoV_NSP6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08716">
        <property type="entry name" value="CoV_NSP7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08717">
        <property type="entry name" value="CoV_NSP8"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08710">
        <property type="entry name" value="CoV_NSP9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08715">
        <property type="entry name" value="CoV_peptidase"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01661">
        <property type="entry name" value="Macro"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF05409">
        <property type="entry name" value="Peptidase_C30"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00506">
        <property type="entry name" value="A1pp"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF101816">
        <property type="entry name" value="SSF101816"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="SSF51126"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF52949">
        <property type="entry name" value="SSF52949"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51943">
        <property type="entry name" value="COV_NSP3A_UBL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51944">
        <property type="entry name" value="COV_NSP3D_UBL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51946">
        <property type="entry name" value="COV_NSP4C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51442">
        <property type="entry name" value="M_PRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51154">
        <property type="entry name" value="MACRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51124">
        <property type="entry name" value="PEPTIDASE_C16"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="27" id="KW-1072">Activation of host autophagy by virus</keyword>
    <keyword evidence="29" id="KW-1035">Host cytoplasm</keyword>
    <keyword evidence="22" id="KW-1043">Host membrane</keyword>
    <keyword evidence="9" id="KW-0945">Host-virus interaction</keyword>
    <keyword evidence="19" id="KW-0378">Hydrolase</keyword>
    <keyword evidence="10" id="KW-1090">Inhibition of host innate immune response by virus</keyword>
    <keyword evidence="25" id="KW-1092">Inhibition of host IRF3 by virus</keyword>
    <keyword evidence="8" id="KW-1113">Inhibition of host RLR pathway by virus</keyword>
    <keyword evidence="28 32" id="KW-0472">Membrane</keyword>
    <keyword evidence="14" id="KW-0479">Metal-binding</keyword>
    <keyword evidence="23" id="KW-1127">Modulation of host ubiquitin pathway by viral deubiquitinase</keyword>
    <keyword evidence="11" id="KW-1130">Modulation of host ubiquitin pathway by virus</keyword>
    <keyword evidence="12" id="KW-0645">Protease</keyword>
    <keyword evidence="40" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="15" id="KW-0677">Repeat</keyword>
    <keyword evidence="16" id="KW-0688">Ribosomal frameshifting</keyword>
    <keyword evidence="24" id="KW-0694">RNA-binding</keyword>
    <keyword evidence="20" id="KW-0788">Thiol protease</keyword>
    <keyword evidence="13 32" id="KW-0812">Transmembrane</keyword>
    <keyword evidence="26 32" id="KW-1133">Transmembrane helix</keyword>
    <keyword evidence="18" id="KW-0833">Ubl conjugation pathway</keyword>
    <keyword evidence="30" id="KW-0899">Viral immunoevasion</keyword>
    <keyword evidence="21" id="KW-0862">Zinc</keyword>
    <keyword evidence="17" id="KW-0863">Zinc-finger</keyword>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="1899"/>
            <end position="1918"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="1960"/>
            <end position="1983"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="2045"/>
            <end position="2062"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="2069"/>
            <end position="2087"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="2093"/>
            <end position="2113"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="2465"/>
            <end position="2483"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="2715"/>
            <end position="2740"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="2747"/>
            <end position="2764"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="2770"/>
            <end position="2788"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="2800"/>
            <end position="2824"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="3132"/>
            <end position="3154"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="3241"/>
            <end position="3264"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="3270"/>
            <end position="3291"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="3298"/>
            <end position="3324"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="3344"/>
            <end position="3360"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="3367"/>
            <end position="3385"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="3391"/>
            <end position="3414"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="32">
        <location>
            <begin position="3435"/>
            <end position="3457"/>
        </location>
    </feature>
    <feature type="domain" description="Ubiquitin-like" evidence="36">
        <location>
            <begin position="898"/>
            <end position="994"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase C16" evidence="33">
        <location>
            <begin position="1016"/>
            <end position="1270"/>
        </location>
    </feature>
    <feature type="domain" description="Macro" evidence="34">
        <location>
            <begin position="1248"/>
            <end position="1416"/>
        </location>
    </feature>
    <feature type="domain" description="Ubiquitin-like" evidence="37">
        <location>
            <begin position="1574"/>
            <end position="1628"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase C16" evidence="33">
        <location>
            <begin position="1635"/>
            <end position="1881"/>
        </location>
    </feature>
    <feature type="domain" description="Nsp4C" evidence="38">
        <location>
            <begin position="2839"/>
            <end position="2934"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase C30" evidence="35">
        <location>
            <begin position="2935"/>
            <end position="3237"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00000707"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00002928"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00003140"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00004141"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00004301"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00004407"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="ARBA" id="ARBA00008087"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="ARBA" id="ARBA00022482"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="ARBA" id="ARBA00022581"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="10">
        <source>
            <dbReference type="ARBA" id="ARBA00022632"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="11">
        <source>
            <dbReference type="ARBA" id="ARBA00022662"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="12">
        <source>
            <dbReference type="ARBA" id="ARBA00022670"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="13">
        <source>
            <dbReference type="ARBA" id="ARBA00022692"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="14">
        <source>
            <dbReference type="ARBA" id="ARBA00022723"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="15">
        <source>
            <dbReference type="ARBA" id="ARBA00022737"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="16">
        <source>
            <dbReference type="ARBA" id="ARBA00022758"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="17">
        <source>
            <dbReference type="ARBA" id="ARBA00022771"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="18">
        <source>
            <dbReference type="ARBA" id="ARBA00022786"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="19">
        <source>
            <dbReference type="ARBA" id="ARBA00022801"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="20">
        <source>
            <dbReference type="ARBA" id="ARBA00022807"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="21">
        <source>
            <dbReference type="ARBA" id="ARBA00022833"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="22">
        <source>
            <dbReference type="ARBA" id="ARBA00022870"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="23">
        <source>
            <dbReference type="ARBA" id="ARBA00022876"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="24">
        <source>
            <dbReference type="ARBA" id="ARBA00022884"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="25">
        <source>
            <dbReference type="ARBA" id="ARBA00022931"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="26">
        <source>
            <dbReference type="ARBA" id="ARBA00022989"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="27">
        <source>
            <dbReference type="ARBA" id="ARBA00023050"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="28">
        <source>
            <dbReference type="ARBA" id="ARBA00023136"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="29">
        <source>
            <dbReference type="ARBA" id="ARBA00023200"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="30">
        <source>
            <dbReference type="ARBA" id="ARBA00023280"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="31">
        <source>
            <dbReference type="ARBA" id="ARBA00025562"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="32">
        <source>
            <dbReference type="SAM" id="Phobius"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="33">
        <source>
            <dbReference type="PROSITE" id="PS51124"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="34">
        <source>
            <dbReference type="PROSITE" id="PS51154"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="35">
        <source>
            <dbReference type="PROSITE" id="PS51442"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="36">
        <source>
            <dbReference type="PROSITE" id="PS51943"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="37">
        <source>
            <dbReference type="PROSITE" id="PS51944"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="38">
        <source>
            <dbReference type="PROSITE" id="PS51946"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="39">
        <source>
            <dbReference type="EMBL" id="AAS89766.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="40">
        <source>
            <dbReference type="Proteomes" id="UP000161757"/>
        </source>
    </evidence>
    <sequence length="4055" mass="450874" checksum="E42D6F139536739C" modified="2004-07-05" version="1">MFYNQVTLAVASDSEISGFGFAIPSVAVRAYSEAAAQGFQACRFVAFGLQDCVTGINDDDYVIALTGTNQLCAKILLFSDRPLNLRGWLIFSNSNYVLQDFDVVFGHGAGSVVFVDKYMCGFDGKPVLPKNMWEFRDYFNDNTDSIVIGGVTYQLAWDVIRKDLSYEQQNVLAIESIHYLGTTGHTLKSGCKLINAKPPKYSSKVVLSGEWNAVYKAFGSPFITNGISLLDIIVKPVFFNAFVKCNCGSENWSVGAWDGYLSSCCGTPAKKLCVVPGNVVPGDVIITSTDAGCGVKYYAGLVVKHITNITGVSLWRVTAVHSDGMFVATSSYDALLHRNSLDPFCFDVNTLLSNQLRLAFLGASVTEDVKFAASTGVIDISAGMFGLYDDILTNNKPWFVRKASGLFDAIWDAFVAAIKLVPTTTGGLVRFVKSIASTVLTVSNGVIIMCADVPDAFQPVYRTFTQAICAAFDFSLDVFKIGDVKFKRLGDYVLTENALVRLTTEVVRGVRDARIKKAMFTKVVVGPTTEVKFSVIELATVNLRLVDCAPVVCPKGKIVVIAGQAFFYSGGFYRFMVDSTTVLNDPVFTGELFYTIKFSGFKLDGFNHQFVNASSATDAIIAVELLLSDFKTAVFVYTCVVDGCSVIVRRDATFATHVCFKDCYSIWEQFCIDNCGEPWFLTDYNAILQSNNPQCAIVQASESKVLLERFLPKCPEILLSIDDGHLWNLFVEKFNFVTDWLKTLKLTLTSNGLLGNCAKRFRRVLVKLLDVYNGFLETVCSVVHTAGVCIKYYAVNVPYVVISGFVSRVIRRERCDVTFPCVSCVTFFYEFLDTCFGVSKPNAIDVEHLELKETVFVEPKDGGQFFVSDDYLWYVVDDIYYPASCNGVLPVAFTKLAGGKISFSDDVIVHDVEPTHKVKLIFEFEDDVVTSLCKKSFGKSIIYTGDWEGLHEVLTSAMNVIGQHIKLPQFYIYDEEGGYDVSKPVMISQWPISDDSDGCVVEASTDFHQLESVREEVDIIEQPFGEVEHALSIRQPFSFSFRDELGVRVLDQSDNNCWISTTLIQLQLTKLLDDSIEMQLFKVGKVDSIVQKCYELSHLISGSLGDSGKLLSELLKDKYTCSITFEMSCDCGKKFDEQVGCLFWIMPYTKLFQKGECCICHKMQTYKLVSMKGTGVFVQDPAPIDIDAFPVRPICSSVYLGVKGSGHYQTNLYSFDKAIDGFGVFDIKNSSVNTVCFVDVDFHSVEIEAGEVKPFAVYKNVKFYLGDISHLVNCVSFDFVVNAANENLMHGGGVARAIDILTEGQLQSLSKDYISSNGPLKVGAGVMLECEKFNVFNVVGPRTGKHEHSLLVEAYNSILFENGIPLMPLLSCGIFGVRIENSLKALFSCDINKPLQVFVYSSNEEQAVLKFLDGLDLTPVIDDVDVVKPFRVEGNFSFFDCGVNALDGDIYLLFTNSILMLDKQGQLLDTKLNGILQQAVLDYLATVKTVPAGNLVKLVVESCTIYMCVVPSINDLSFDKNLGRCVRKLNRLKTCVIANVPAIDVLKKLLSSLTLTVKFVVESNVMDVNDCFKNDNVVLKITEDGINVKDVVVESSKSLGKQLGVVSDGVDSFEGVLPINTDTVLSVAPEVDWVAFYGFEKAALFASLDVKPYGYPNDFVGGFRVLGTTDNNCWVNATCIILQYLKPTFKSKGLNVLWNKFVTGDVGPFVSFIYFITMSSKGQKGDAEEALSKLSEYLISDSIVTLEQYSTCDICKSTVVEVKSAVVCASVLKDGCDVGFCPHRHKLRSRVKFVNGRVVITNVGEPIISQPSKLLNGIAYTTFSGSFDNGHYVVYDAANNAVYDGARLFASDLSTLAVTAIVVVGGCVTSNVPPIVSEKISVMDKLDTGAQKFFQFGDFVMNNIVLFLTWLLSMFSLLRTSIMKHDIKVIAKAPKRTGVILTRSFKYNIRSALFVVKQKWCVIVTLFKFLLLLYAIYALVFMIVQFSPFNSLLCGDIVSGYEKSTFNKDIYCGNSMVCKMCLFSYQEFNDLDHTSLVWKHIRDPILISLQPFVILVILLIFGNMYLRFGLLYFVAQFISTFGSFLGFHQKQWFLHFVPFDVLCNEFLATFIVCKIVLFVRHIIVGCNNADCVACSKSARLKRVPLQTIINGMHKSFYVNANGGTCFCNKHNFFCVNCDSFGPGNTFINGDIARELGNVVKTAVQPTAPAYVIIDKVDFVNGFYRLYSGDTFWRYDFDITESKYSCKEVLKNCNVLENFIVYNNSGSNITQIKNACVYFSQLLCEPIKLVNSELLSTLSVDFNGVLHKAYVDVLCNSFFKELTANMSMAECKATLGLTVSDDDFVSAVANAHRYDVLLSDLSFNNFFISYAKPEDKLSVYDIACCMRAGSKVVNHNVLIKESIPIVWGVKDFNTLSQEGKKYLVKTTKAKGLTFLLTFNDNQAITQVPATSIVAKQGAGFKRTYNFLWYVCLFVVALFIGVSFIDYTTTVTSFHGYDFKYIENGQLKVFEAPLHCVRNVFDNFNQWHEAKFGVVTTNSDKCPIVVGVSERINVVPGVPTNVYLVGKTLVFTLQAAFGNTGVCYDFDGVTTSDKCIFNSACTRLEGLGGDNVYCYNTDLIEGSKPYSILQPNAYYKYDVKNYVRFPEILARGFGLRTIRTLATRYCRVGECRDSHKGVCFGFDKWYVNDGRVDDGYICGDGLIDLLVNVLSIFSSSFSVVAMSGHMLFNFLFAAFITFLCFLVTKFKRVFGDLSYGVFTVVCATLINNISYVVTQNLFFMLLYAILYFVFTRTVRYAWIWHIAYIVAYFLLIPWWLLTWFSFAAFLELLPNVFKLKISTQLFEGDKFIGTFESAAAGTFVLDMRSYERLINTISPEKLKNYAASYNKYKYYSGSASEADYRCACYAHLAKAMLDYAKDHNDMLYSPPTISYNSTLQSGLKKMAQPSGCVERCVVRVCYGSTVLNGVWLGDTVTCPRHVIAPSTTVLIDYDHAYSTMRLHNFSVSHNGVFLGVVGVTMHGSVLRIKVSQSNVHTPKHVFKTLKPGASFNILACYEGIASGVFGVNLRTNFTIKGSFINGACGSPGYNVRNDGTVEFCYLHQIELGSGAHVGSDFTGSVYGNFDDQPSLQVESANLMLSDNVVAFLYAALLNGCRWWLRSTRVNVDGFNEWAMANGYTIVSSVECYSILAAKTGVSVEQLLASIQHLHEGFGGKNILGYSSLCDEFTLAEVVKQMYGVNLQSGKVIFGLKTMFLFSVFFTMFWAELFIYTNTIWINPVILTPIFCLLLFLSLVLTMFLKHKFLFLQVFLLPTVIATALYNCVLDYYIVKFLADHFNYNVSVLQMDVQGLVNVLVCLFVVFLHTWRFSKERFTHWFTYVCSLIAVAYTYFYSGDFLSLLVMFLCAISSDWYIGAIVFRLSRLIIFFSPESVFSVFGDVKLTLVVYLICGYLVCTYWGILYWFNRFFKCTMGVYDFKVSAAEFKYMVANGLHAPYGPFDALWLSFKLLGIGGDRCIKISTVQSKLTDLKCTNVVLLGCLSSMNIAANSSEWAYCVDLHNKINLCDDPEKAQGMLLALLAFFLSKHSDFGLDGLIDSYFDNSSTLQSVASSFVSMPSYIAYENARQAYEDAIANGSSSQLIKQLKRAMNIAKSEFDHEISVQKKINRMAEQAATQMYKEARSVNRKSKVISAMHSLLFGMLRRLDMSSVETVLNLARDGVVPLSVIPATSASKLTIVSPDLESYSKIVCDGSVHYAGVVWTLNDVKDNDGRPVHVKEITRENVETLTWPLILNCERVVKLQNNEIMPGKLKQKPMKAEGDGGVLGDGNALYNTEGGKTFMYAYISNKADLKFVKWEYEGGCNTIELDSPCRFMVETPNGPQVKYLYFVKNLNTLRRGAVLGFIGATIRLQAGKQTELAVNSGLLTACAFSVDPATTYLEAVKHGAKPVSNCIKMLSNGAGNGQAITTSVDANTNQDSYGGASICLYCRAHVPHPSMDGYCKFKGKCVQVPIGCLDPIRFCLENNVCNVCGCWLGHGCACDRTTIQSVDISYLNEQGVLVQLD</sequence>
</entry>
<entry dataset="TrEMBL" created="2004-07-05" modified="2022-08-03" version="140" xmlns="http://uniprot.org/uniprot">
    <accession>Q6R1L9</accession>
    <name>Q6R1L9_CVHNL</name>
    <protein>
        <recommendedName>
            <fullName evidence="15">Replicase polyprotein 1ab</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="56">ORF1ab polyprotein</fullName>
        </alternativeName>
    </protein>
    <organism evidence="69 70">
        <name type="scientific">Human coronavirus NL63</name>
        <name type="common">HCoV-NL63</name>
        <dbReference type="NCBI Taxonomy" id="277944"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Pisuviricota</taxon>
            <taxon>Pisoniviricetes</taxon>
            <taxon>Nidovirales</taxon>
            <taxon>Cornidovirineae</taxon>
            <taxon>Coronaviridae</taxon>
            <taxon>Orthocoronavirinae</taxon>
            <taxon>Alphacoronavirus</taxon>
            <taxon>Setracovirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference evidence="69 70" key="1">
        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="6212" last="6216">
            <title>A previously undescribed coronavirus associated with respiratory disease in humans.</title>
            <authorList>
                <person name="Fouchier R.A."/>
                <person name="Hartwig N.G."/>
                <person name="Bestebroer T.M."/>
                <person name="Niemeyer B."/>
                <person name="De Jong J.C."/>
                <person name="Simon J.H."/>
                <person name="Osterhaus A.D."/>
            </authorList>
            <dbReference type="PubMed" id="15073334"/>
            <dbReference type="DOI" id="10.1073/pnas.0400762101"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="5">Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.</text>
    </comment>
    <comment type="function">
        <text evidence="6">Nsp9 is a ssRNA-binding protein.</text>
    </comment>
    <comment type="function">
        <text evidence="53">Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (By similarity). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (By similarity). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors.</text>
    </comment>
    <comment type="function">
        <text evidence="7">The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction.</text>
    </comment>
    <comment type="function">
        <text evidence="54">The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3.</text>
    </comment>
    <comment type="function">
        <text evidence="8">The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>ATP + H2O = ADP + H(+) + phosphate</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="3.6.4.12"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>ATP + H2O = ADP + H(+) + phosphate</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="3.6.4.13"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).</text>
            <dbReference type="EC" id="3.4.19.12"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="51">
            <text>a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-adenosyl-L-homocysteine</text>
            <dbReference type="Rhea" id="RHEA:67020"/>
            <dbReference type="Rhea" id="RHEA-COMP:17167"/>
            <dbReference type="Rhea" id="RHEA-COMP:17168"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57856"/>
            <dbReference type="ChEBI" id="CHEBI:59789"/>
            <dbReference type="ChEBI" id="CHEBI:156461"/>
            <dbReference type="ChEBI" id="CHEBI:167609"/>
            <dbReference type="EC" id="2.1.1.57"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="52">
            <text>uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl-2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside-RNA</text>
            <dbReference type="Rhea" id="RHEA:67732"/>
            <dbReference type="Rhea" id="RHEA-COMP:13936"/>
            <dbReference type="Rhea" id="RHEA-COMP:17334"/>
            <dbReference type="Rhea" id="RHEA-COMP:17335"/>
            <dbReference type="ChEBI" id="CHEBI:138284"/>
            <dbReference type="ChEBI" id="CHEBI:173079"/>
            <dbReference type="ChEBI" id="CHEBI:173080"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="4">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="55">3CL-PRO exists as monomer and homodimer. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer. Nsp9 is a dimer. Nsp10 forms a dodecamer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Endoplasmic reticulum-Golgi intermediate compartment</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12">Host cytoplasm</location>
            <location evidence="12">Host perinuclear region</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="13">Host endoplasmic reticulum-Golgi intermediate compartment</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Host membrane</location>
            <topology evidence="10">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Membrane</location>
            <topology evidence="9">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the coronaviruses polyprotein 1ab family.</text>
    </comment>
    <dbReference type="EMBL" id="AY518894">
        <property type="protein sequence ID" value="AAS89765.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="MEROPS" id="C30.003"/>
    <dbReference type="Proteomes" id="UP000161757">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005793">
        <property type="term" value="C:endoplasmic reticulum-Golgi intermediate compartment"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044172">
        <property type="term" value="C:host cell endoplasmic reticulum-Golgi intermediate compartment"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033644">
        <property type="term" value="C:host cell membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044220">
        <property type="term" value="C:host cell perinuclear region of cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016021">
        <property type="term" value="C:integral component of membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004843">
        <property type="term" value="F:cysteine-type deubiquitinase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004197">
        <property type="term" value="F:cysteine-type endopeptidase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003678">
        <property type="term" value="F:DNA helicase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004519">
        <property type="term" value="F:endonuclease activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004532">
        <property type="term" value="F:exoribonuclease activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProt"/>
    </dbReference>
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    <keyword evidence="39" id="KW-0067">ATP-binding</keyword>
    <keyword evidence="31" id="KW-0255">Endonuclease</keyword>
    <keyword evidence="38" id="KW-0269">Exonuclease</keyword>
    <keyword evidence="35" id="KW-0347">Helicase</keyword>
    <keyword evidence="48" id="KW-1035">Host cytoplasm</keyword>
    <keyword evidence="40" id="KW-1043">Host membrane</keyword>
    <keyword evidence="18" id="KW-0945">Host-virus interaction</keyword>
    <keyword evidence="34" id="KW-0378">Hydrolase</keyword>
    <keyword evidence="20" id="KW-1090">Inhibition of host innate immune response by virus</keyword>
    <keyword evidence="43" id="KW-1092">Inhibition of host IRF3 by virus</keyword>
    <keyword evidence="16" id="KW-1113">Inhibition of host RLR pathway by virus</keyword>
    <keyword evidence="49" id="KW-0456">Lyase</keyword>
    <keyword evidence="47 58" id="KW-0472">Membrane</keyword>
    <keyword evidence="27" id="KW-0479">Metal-binding</keyword>
    <keyword evidence="19" id="KW-0489">Methyltransferase</keyword>
    <keyword evidence="41" id="KW-1127">Modulation of host ubiquitin pathway by viral deubiquitinase</keyword>
    <keyword evidence="21" id="KW-1130">Modulation of host ubiquitin pathway by virus</keyword>
    <keyword evidence="26" id="KW-0540">Nuclease</keyword>
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                <person name="Gupta N."/>
                <person name="Hoover J."/>
                <person name="Katzel D."/>
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                <person name="Thovarai V."/>
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            <title>Human coronavirus NL63 from a patient in Gainesville, Florida, in 2015.</title>
            <authorList>
                <person name="Lednicky J.A."/>
                <person name="Morris J.G.Jr."/>
                <person name="Rand K.H."/>
                <person name="White S.K."/>
                <person name="Loeb J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
        <source>
            <strain evidence="8">NL63/UF-2/2015</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="2 3">Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 3">Homomultimer. Interacts with envelope E protein in the budding compartment of the host cell, which is located between endoplasmic reticulum and the Golgi complex. Forms a complex with HE and S proteins. Interacts with nucleocapsid N protein. This interaction probably participates in RNA packaging into the virus.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2 3">Host Golgi apparatus membrane</location>
            <topology evidence="2 3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2 3">Virion membrane</location>
            <topology evidence="2 3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="2">Largely embedded in the lipid bilayer.</text>
    </comment>
    <comment type="similarity">
        <text evidence="2 3">Belongs to the alphacoronaviruses M protein family.</text>
    </comment>
    <comment type="caution">
        <text evidence="2">Lacks conserved residue(s) required for the propagation of feature annotation.</text>
    </comment>
    <dbReference type="EMBL" id="AY518894">
        <property type="protein sequence ID" value="AAS89770.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KF530106">
        <property type="protein sequence ID" value="AGT51341.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KT381875">
        <property type="protein sequence ID" value="ALJ53434.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KU521535">
        <property type="protein sequence ID" value="ANU06087.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KX179500">
        <property type="protein sequence ID" value="APF29074.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000145724">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000146557">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000161757">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044178">
        <property type="term" value="C:host cell Golgi membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016021">
        <property type="term" value="C:integral component of membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019031">
        <property type="term" value="C:viral envelope"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055036">
        <property type="term" value="C:virion membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039660">
        <property type="term" value="F:structural constituent of virion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="CDD" id="cd21564">
        <property type="entry name" value="alphaCoV_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04201">
        <property type="entry name" value="ALPHA_CORONA_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042551">
        <property type="entry name" value="ALPHA_CORONA_M"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002574">
        <property type="entry name" value="M_CoV"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01635">
        <property type="entry name" value="CoV_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51927">
        <property type="entry name" value="COV_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="2" id="KW-0325">Glycoprotein</keyword>
    <keyword evidence="2 3" id="KW-1040">Host Golgi apparatus</keyword>
    <keyword evidence="2 3" id="KW-1043">Host membrane</keyword>
    <keyword evidence="2 3" id="KW-0472">Membrane</keyword>
    <keyword evidence="11" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="2 3" id="KW-0812">Transmembrane</keyword>
    <keyword evidence="2 3" id="KW-1133">Transmembrane helix</keyword>
    <keyword evidence="2 3" id="KW-0261">Viral envelope protein</keyword>
    <keyword evidence="1 2 3" id="KW-0468">Viral matrix protein</keyword>
    <keyword evidence="2 3" id="KW-0946">Virion</keyword>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="20"/>
            <end position="38"/>
        </location>
    </feature>
    <feature type="topological domain" description="Intravirion" evidence="2">
        <location>
            <begin position="33"/>
            <end position="41"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="50"/>
            <end position="71"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="77"/>
            <end position="97"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00023311"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04201"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="RuleBase" id="RU363118"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="4">
        <source>
            <dbReference type="EMBL" id="AAS89770.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="5">
        <source>
            <dbReference type="EMBL" id="AGT51341.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="6">
        <source>
            <dbReference type="EMBL" id="ALJ53434.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="7">
        <source>
            <dbReference type="EMBL" id="ANU06087.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="8">
        <source>
            <dbReference type="EMBL" id="APF29074.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="9">
        <source>
            <dbReference type="Proteomes" id="UP000145724"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="10">
        <source>
            <dbReference type="Proteomes" id="UP000146557"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="11">
        <source>
            <dbReference type="Proteomes" id="UP000161757"/>
        </source>
    </evidence>
    <sequence length="226" mass="25889" checksum="6552B9E8E5CEC15C" modified="2013-12-11" version="1">MSNSSVPLSEVYVHLRNWNFSWNLILTVFIVVLQYGHYKYSRLLYGLKMSVLWCLWPLVLALSIFDCFVNFNVDWVFFGFSILMSIITLCLWVMYFVNSFRLWRRVKTFWAFNPETNAIISLQVYGHNYYLPVMAAPTGVTLTLLSGVLLVDGHKIATRVQVGQLPKYVIVATPSTTIVCDRVGRSVNETSQTGWAFYVRAKHGDFSGVASQEGVLSEREKLLHLI</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>