<?xml version="1.0" encoding="UTF-8"?>
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<entry dataset="TrEMBL" created="2011-02-08" modified="2022-08-03" version="60" xmlns="http://uniprot.org/uniprot">
    <accession>E4UF15</accession>
    <name>E4UF15_9INFA</name>
    <protein>
        <recommendedName>
            <fullName evidence="25">Hemagglutinin</fullName>
        </recommendedName>
        <component>
            <recommendedName>
                <fullName evidence="25">Hemagglutinin HA1 chain</fullName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName evidence="25">Hemagglutinin HA2 chain</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name evidence="25 27" type="primary">HA</name>
    </gene>
    <organism evidence="27 28">
        <name type="scientific">Influenza A virus (A/northern shoveler/California/JN1447/2007(H7N2))</name>
        <dbReference type="NCBI Taxonomy" id="686561"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Negarnaviricota</taxon>
            <taxon>Polyploviricotina</taxon>
            <taxon>Insthoviricetes</taxon>
            <taxon>Articulavirales</taxon>
            <taxon>Orthomyxoviridae</taxon>
            <taxon>Alphainfluenzavirus</taxon>
        </lineage>
    </organism>
    <reference evidence="27 28" key="1">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <title>The NIAID Influenza Genome Sequencing Project.</title>
            <authorList>
                <person name="Spiro D."/>
                <person name="Halpin R."/>
                <person name="Boyne A."/>
                <person name="Bera J."/>
                <person name="Ghedin E."/>
                <person name="Dugan V."/>
                <person name="Hostetler J."/>
                <person name="Fedorova N."/>
                <person name="Hine E."/>
                <person name="Overton L."/>
                <person name="Kim M."/>
                <person name="Szczypinski B."/>
                <person name="Stockwell T."/>
                <person name="Sitz J."/>
                <person name="Katzel D."/>
                <person name="Li K."/>
                <person name="Axelrod N."/>
                <person name="Safford T."/>
                <person name="Amedeo P."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Wang S."/>
                <person name="Resnick A."/>
                <person name="Thovarai V."/>
                <person name="Cardona C."/>
                <person name="Boyce W."/>
                <person name="Anchell N."/>
                <person name="Dao N."/>
                <person name="Dao P."/>
                <person name="Lee G."/>
                <person name="Nelson J."/>
                <person name="Kelly T."/>
                <person name="Lin X."/>
                <person name="Wentworth D."/>
                <person name="Bao Y."/>
                <person name="Sanders R."/>
                <person name="Dernovoy D."/>
                <person name="Kiryutin B."/>
                <person name="Lipman D.J."/>
                <person name="Tatusova T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="27">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <reference evidence="27 28" key="2">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="The NIAID Influenza Genome Sequencing Consortium"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="27">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="25">Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization either through clathrin-dependent endocytosis or through clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.</text>
    </comment>
    <comment type="function">
        <text evidence="26">Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.</text>
    </comment>
    <comment type="subunit">
        <text evidence="25 26">Homotrimer of disulfide-linked HA1-HA2.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Apical cell membrane</location>
            <topology evidence="1">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell membrane</location>
            <topology evidence="2">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3 25">Host apical cell membrane</location>
            <topology evidence="3 25">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Membrane</location>
            <topology evidence="4">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="25">Virion membrane</location>
            <topology evidence="25">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <text evidence="25">Targeted to the apical plasma membrane in epithelial polarized cells through a signal present in the transmembrane domain. Associated with glycosphingolipid- and cholesterol-enriched detergent-resistant lipid rafts.</text>
    </comment>
    <comment type="PTM">
        <text evidence="25">In natural infection, inactive HA is matured into HA1 and HA2 outside the cell by one or more trypsin-like, arginine-specific endoprotease secreted by the bronchial epithelial cells. One identified protease that may be involved in this process is secreted in lungs by Clara cells.</text>
    </comment>
    <comment type="PTM">
        <text evidence="25">Palmitoylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5 25 26">Belongs to the influenza viruses hemagglutinin family.</text>
    </comment>
    <comment type="caution">
        <text evidence="25">Lacks conserved residue(s) required for the propagation of feature annotation.</text>
    </comment>
    <dbReference type="EMBL" id="CY076872">
        <property type="protein sequence ID" value="ADP95464.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000140696">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016324">
        <property type="term" value="C:apical plasma membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0020002">
        <property type="term" value="C:host cell plasma 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:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0075512">
        <property type="term" value="P:clathrin-dependent endocytosis of virus by 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>
    <dbReference type="GO" id="GO:0019064">
        <property type="term" value="P:fusion of virus membrane with host plasma membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046761">
        <property type="term" value="P:viral budding from plasma membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019062">
        <property type="term" value="P:virion attachment to host cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.209.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04072">
        <property type="entry name" value="INFV_HEMA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008980">
        <property type="entry name" value="Capsid_hemagglutn"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013828">
        <property type="entry name" value="Hemagglutn_HA1_a/b_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000149">
        <property type="entry name" value="Hemagglutn_influenz_A"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001364">
        <property type="entry name" value="Hemagglutn_influenz_A/B"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00509">
        <property type="entry name" value="Hemagglutinin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00330">
        <property type="entry name" value="HEMAGGLUTN1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00329">
        <property type="entry name" value="HEMAGGLUTN12"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF49818">
        <property type="entry name" value="SSF49818"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="22 25" id="KW-1167">Clathrin- and caveolin-independent endocytosis of virus by host</keyword>
    <keyword evidence="10 25" id="KW-1165">Clathrin-mediated endocytosis of virus by host</keyword>
    <keyword evidence="20 25" id="KW-1015">Disulfide bond</keyword>
    <keyword evidence="7 25" id="KW-1170">Fusion of virus membrane with host endosomal membrane</keyword>
    <keyword evidence="6 25" id="KW-1168">Fusion of virus membrane with host membrane</keyword>
    <keyword evidence="21 25" id="KW-0325">Glycoprotein</keyword>
    <keyword evidence="9 25 26" id="KW-0348">Hemagglutinin</keyword>
    <keyword evidence="8 25" id="KW-1032">Host cell membrane</keyword>
    <keyword evidence="15 25" id="KW-1043">Host membrane</keyword>
    <keyword evidence="11 25" id="KW-0945">Host-virus interaction</keyword>
    <keyword evidence="23 25" id="KW-0449">Lipoprotein</keyword>
    <keyword evidence="18 25" id="KW-0472">Membrane</keyword>
    <keyword evidence="19 25" id="KW-0564">Palmitate</keyword>
    <keyword evidence="28" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="25" id="KW-0732">Signal</keyword>
    <keyword evidence="25" id="KW-0812">Transmembrane</keyword>
    <keyword evidence="25" id="KW-1133">Transmembrane helix</keyword>
    <keyword evidence="13 25" id="KW-1161">Viral attachment to host cell</keyword>
    <keyword evidence="16 25 26" id="KW-0261">Viral envelope protein</keyword>
    <keyword evidence="12 25" id="KW-1162">Viral penetration into host cytoplasm</keyword>
    <keyword evidence="14 25" id="KW-0946">Virion</keyword>
    <keyword evidence="17 25" id="KW-1164">Virus endocytosis by host</keyword>
    <keyword evidence="24 25" id="KW-1160">Virus entry into host cell</keyword>
    <feature type="transmembrane region" description="Helical" evidence="25">
        <location>
            <begin position="524"/>
            <end position="549"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by host" evidence="25">
        <location>
            <begin position="339"/>
            <end position="340"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine; by host" evidence="25">
        <location>
            <position position="556"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine; by host" evidence="25">
        <location>
            <position position="559"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="25">
        <location>
            <begin position="72"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="25">
        <location>
            <begin position="290"/>
            <end position="314"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="25">
        <location>
            <begin position="483"/>
            <end position="487"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00004247"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00004251"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00004310"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00004479"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00006321"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00022506"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="ARBA" id="ARBA00022510"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="ARBA" id="ARBA00022511"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="ARBA" id="ARBA00022546"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="10">
        <source>
            <dbReference type="ARBA" id="ARBA00022570"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="11">
        <source>
            <dbReference type="ARBA" id="ARBA00022581"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="12">
        <source>
            <dbReference type="ARBA" id="ARBA00022595"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="13">
        <source>
            <dbReference type="ARBA" id="ARBA00022804"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="14">
        <source>
            <dbReference type="ARBA" id="ARBA00022844"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="15">
        <source>
            <dbReference type="ARBA" id="ARBA00022870"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="16">
        <source>
            <dbReference type="ARBA" id="ARBA00022879"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="17">
        <source>
            <dbReference type="ARBA" id="ARBA00022890"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="18">
        <source>
            <dbReference type="ARBA" id="ARBA00023136"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="19">
        <source>
            <dbReference type="ARBA" id="ARBA00023139"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="20">
        <source>
            <dbReference type="ARBA" id="ARBA00023157"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="21">
        <source>
            <dbReference type="ARBA" id="ARBA00023180"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="22">
        <source>
            <dbReference type="ARBA" id="ARBA00023261"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="23">
        <source>
            <dbReference type="ARBA" id="ARBA00023288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="24">
        <source>
            <dbReference type="ARBA" id="ARBA00023296"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="25">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04072"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="26">
        <source>
            <dbReference type="RuleBase" id="RU003324"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="27">
        <source>
            <dbReference type="EMBL" id="ADP95464.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="28">
        <source>
            <dbReference type="Proteomes" id="UP000140696"/>
        </source>
    </evidence>
    <sequence length="560" mass="62085" checksum="B9A7CB57088209A1" modified="2011-02-08" version="1"> </sequence>
</entry>
<entry dataset="TrEMBL" created="2011-02-08" modified="2022-08-03" version="40" xmlns="http://uniprot.org/uniprot">
    <accession>E4UF16</accession>
    <name>E4UF16_9INFA</name>
    <protein>
        <recommendedName>
            <fullName evidence="10 11">Matrix protein 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="10">Proton channel protein M2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="13" type="primary">M2</name>
        <name evidence="10" type="synonym">M</name>
    </gene>
    <organism evidence="13 14">
        <name type="scientific">Influenza A virus (A/northern shoveler/California/JN1447/2007(H7N2))</name>
        <dbReference type="NCBI Taxonomy" id="686561"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Negarnaviricota</taxon>
            <taxon>Polyploviricotina</taxon>
            <taxon>Insthoviricetes</taxon>
            <taxon>Articulavirales</taxon>
            <taxon>Orthomyxoviridae</taxon>
            <taxon>Alphainfluenzavirus</taxon>
        </lineage>
    </organism>
    <reference evidence="13 14" key="1">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <title>The NIAID Influenza Genome Sequencing Project.</title>
            <authorList>
                <person name="Spiro D."/>
                <person name="Halpin R."/>
                <person name="Boyne A."/>
                <person name="Bera J."/>
                <person name="Ghedin E."/>
                <person name="Dugan V."/>
                <person name="Hostetler J."/>
                <person name="Fedorova N."/>
                <person name="Hine E."/>
                <person name="Overton L."/>
                <person name="Kim M."/>
                <person name="Szczypinski B."/>
                <person name="Stockwell T."/>
                <person name="Sitz J."/>
                <person name="Katzel D."/>
                <person name="Li K."/>
                <person name="Axelrod N."/>
                <person name="Safford T."/>
                <person name="Amedeo P."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Wang S."/>
                <person name="Resnick A."/>
                <person name="Thovarai V."/>
                <person name="Cardona C."/>
                <person name="Boyce W."/>
                <person name="Anchell N."/>
                <person name="Dao N."/>
                <person name="Dao P."/>
                <person name="Lee G."/>
                <person name="Nelson J."/>
                <person name="Kelly T."/>
                <person name="Lin X."/>
                <person name="Wentworth D."/>
                <person name="Bao Y."/>
                <person name="Sanders R."/>
                <person name="Dernovoy D."/>
                <person name="Kiryutin B."/>
                <person name="Lipman D.J."/>
                <person name="Tatusova T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="13">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <reference evidence="13 14" key="2">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="The NIAID Influenza Genome Sequencing Consortium"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="13">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="10">Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="11">The M2 protein from most influenza A strains is inhibited by amantadine and rimantadine, resulting in viral uncoating incapacity. Emergence of amantadine-resistant variants is usually rapid.</text>
    </comment>
    <comment type="subunit">
        <text evidence="10 11">Homotetramer; composed of two disulfide-linked dimers held together by non-covalent interactions. May interact with matrix protein 1.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Virion membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Host apical cell membrane</location>
            <topology evidence="10">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <text evidence="10">Abundantly expressed at the apical plasma membrane in infected polarized epithelial cells, in close proximity to budding and assembled virions. Minor component of virions (only 16-20 molecules/virion).</text>
    </comment>
    <comment type="domain">
        <text evidence="10 11">Cytoplasmic tail plays an important role in virion assembly and morphogenesis.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="10">When the channel is activated, one or more imidazole moities of His-37 probably become bi-protonated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10 11">Belongs to the influenza viruses matrix protein M2 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="10">Lacks conserved residue(s) required for the propagation of feature annotation.</text>
    </comment>
    <dbReference type="EMBL" id="CY076873">
        <property type="protein sequence ID" value="ADP95466.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000140696">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0020002">
        <property type="term" value="C:host cell plasma 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:0044385">
        <property type="term" value="C:integral to membrane of host cell"/>
        <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:0005216">
        <property type="term" value="F:ion channel activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015078">
        <property type="term" value="F:proton transmembrane transporter activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039707">
        <property type="term" value="P:pore formation by virus in membrane of host cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051259">
        <property type="term" value="P:protein complex oligomerization"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039521">
        <property type="term" value="P:suppression by virus of host autophagy"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04069">
        <property type="entry name" value="INFV_M2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002089">
        <property type="entry name" value="Flu_M2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00599">
        <property type="entry name" value="Flu_M2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="10" id="KW-1015">Disulfide bond</keyword>
    <keyword evidence="10 11" id="KW-1032">Host cell membrane</keyword>
    <keyword evidence="10 11" id="KW-1043">Host membrane</keyword>
    <keyword evidence="10" id="KW-0945">Host-virus interaction</keyword>
    <keyword evidence="3 10 11" id="KW-0375">Hydrogen ion transport</keyword>
    <keyword evidence="10" id="KW-1083">Inhibition of host autophagy by virus</keyword>
    <keyword evidence="9 10 11" id="KW-0407">Ion channel</keyword>
    <keyword evidence="6 10 11" id="KW-0406">Ion transport</keyword>
    <keyword evidence="8 10" id="KW-0449">Lipoprotein</keyword>
    <keyword evidence="10 11 12" id="KW-0472">Membrane</keyword>
    <keyword evidence="7 10" id="KW-0564">Palmitate</keyword>
    <keyword evidence="2 10" id="KW-0597">Phosphoprotein</keyword>
    <keyword evidence="14" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="10 11" id="KW-0735">Signal-anchor</keyword>
    <keyword evidence="10 11 12" id="KW-0812">Transmembrane</keyword>
    <keyword evidence="10 11 12" id="KW-1133">Transmembrane helix</keyword>
    <keyword evidence="1 10 11" id="KW-0813">Transport</keyword>
    <keyword evidence="5 10" id="KW-1182">Viral ion channel</keyword>
    <keyword evidence="4 10 11" id="KW-0946">Virion</keyword>
    <feature type="topological domain" description="Virion surface" evidence="10">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="12">
        <location>
            <begin position="26"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="topological domain" description="Intravirion" evidence="10">
        <location>
            <begin position="44"/>
            <end position="97"/>
        </location>
    </feature>
    <feature type="site" description="Essential for channel activity, possibly by being protonated during channel activation, and by forming the channel gate and the selective filter" evidence="10">
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="site" description="Seems to be involved in pH gating" evidence="10">
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by host" evidence="10">
        <location>
            <position position="64"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine; by host" evidence="10">
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (with Cys-17)" evidence="10">
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (with Cys-19)" evidence="10">
        <location>
            <position position="19"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00022448"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00022553"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00022781"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00022844"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00023039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00023065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="ARBA" id="ARBA00023139"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="ARBA" id="ARBA00023288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="ARBA" id="ARBA00023303"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="10">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04069"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="11">
        <source>
            <dbReference type="RuleBase" id="RU361247"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="12">
        <source>
            <dbReference type="SAM" id="Phobius"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="13">
        <source>
            <dbReference type="EMBL" id="ADP95466.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="14">
        <source>
            <dbReference type="Proteomes" id="UP000140696"/>
        </source>
    </evidence>
    <sequence length="97" mass="11112" checksum="01A78008EB920C0B" modified="2011-02-08" version="1">MSLLTEVATPTRSGWECRCSDSSDPIVIVASIIGILHLILWILDRLFFKCIYRRLKYGLKRGPSTEGIPESMREEYRQEQQNAVGVDDGHFVNIELE</sequence>
</entry>
<entry dataset="TrEMBL" created="2011-02-08" modified="2022-08-03" version="59" xmlns="http://uniprot.org/uniprot">
    <accession>E4UF17</accession>
    <name>E4UF17_9INFA</name>
    <protein>
        <recommendedName>
            <fullName evidence="8 9">Matrix protein 1</fullName>
            <shortName evidence="8 9">M1</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="11" type="primary">M1</name>
        <name evidence="8 9" type="synonym">M</name>
    </gene>
    <organism evidence="11 12">
        <name type="scientific">Influenza A virus (A/northern shoveler/California/JN1447/2007(H7N2))</name>
        <dbReference type="NCBI Taxonomy" id="686561"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Negarnaviricota</taxon>
            <taxon>Polyploviricotina</taxon>
            <taxon>Insthoviricetes</taxon>
            <taxon>Articulavirales</taxon>
            <taxon>Orthomyxoviridae</taxon>
            <taxon>Alphainfluenzavirus</taxon>
        </lineage>
    </organism>
    <reference evidence="11 12" key="1">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <title>The NIAID Influenza Genome Sequencing Project.</title>
            <authorList>
                <person name="Spiro D."/>
                <person name="Halpin R."/>
                <person name="Boyne A."/>
                <person name="Bera J."/>
                <person name="Ghedin E."/>
                <person name="Dugan V."/>
                <person name="Hostetler J."/>
                <person name="Fedorova N."/>
                <person name="Hine E."/>
                <person name="Overton L."/>
                <person name="Kim M."/>
                <person name="Szczypinski B."/>
                <person name="Stockwell T."/>
                <person name="Sitz J."/>
                <person name="Katzel D."/>
                <person name="Li K."/>
                <person name="Axelrod N."/>
                <person name="Safford T."/>
                <person name="Amedeo P."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Wang S."/>
                <person name="Resnick A."/>
                <person name="Thovarai V."/>
                <person name="Cardona C."/>
                <person name="Boyce W."/>
                <person name="Anchell N."/>
                <person name="Dao N."/>
                <person name="Dao P."/>
                <person name="Lee G."/>
                <person name="Nelson J."/>
                <person name="Kelly T."/>
                <person name="Lin X."/>
                <person name="Wentworth D."/>
                <person name="Bao Y."/>
                <person name="Sanders R."/>
                <person name="Dernovoy D."/>
                <person name="Kiryutin B."/>
                <person name="Lipman D.J."/>
                <person name="Tatusova T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="11">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <reference evidence="11 12" key="2">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="The NIAID Influenza Genome Sequencing Consortium"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="11">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="7 8 9">Determines the virion's shape: spherical or filamentous. Clinical isolates of influenza are characterized by the presence of significant proportion of filamentous virions, whereas after multiple passage on eggs or cell culture, virions have only spherical morphology. Filamentous virions are thought to be important to infect neighboring cells, and spherical virions more suited to spread through aerosol between hosts organisms.</text>
    </comment>
    <comment type="function">
        <text evidence="6 8 9">Plays critical roles in virus replication, from virus entry and uncoating to assembly and budding of the virus particle. M1 binding to ribonucleocapsids (RNPs) in nucleus seems to inhibit viral transcription. Interaction of viral NEP with M1-RNP is thought to promote nuclear export of the complex, which is targeted to the virion assembly site at the apical plasma membrane in polarized epithelial cells. Interactions with NA and HA may bring M1, a non-raft-associated protein, into lipid rafts. Forms a continuous shell on the inner side of the lipid bilayer in virion, where it binds the RNP. During virus entry into cell, the M2 ion channel acidifies the internal virion core, inducing M1 dissociation from the RNP. M1-free RNPs are transported to the nucleus, where viral transcription and replication can take place.</text>
    </comment>
    <comment type="subunit">
        <text evidence="8 9">Homodimer and homomultimer. Interacts with NEP. Binds ribonucleocapsid by both interacting with genomic RNA and NP protein. May interact with HA and NA. Cannot bind NP without genomic RNA.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8 9">Virion membrane</location>
            <topology evidence="8 9">Peripheral membrane protein</topology>
            <orientation evidence="8 9">Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8 9">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="miscellaneous">
        <text evidence="8 9">Most abundant protein in virion. When expressed alone can form virus-like particles in transfected cells.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8 9">Belongs to the influenza viruses Matrix protein M1 family.</text>
    </comment>
    <dbReference type="EMBL" id="CY076873">
        <property type="protein sequence ID" value="ADP95465.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000140696">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042025">
        <property type="term" value="C:host cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </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:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </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="GO" id="GO:0046761">
        <property type="term" value="P:viral budding from plasma membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.10.180">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.91.10">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04068">
        <property type="entry name" value="INFV_M1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036039">
        <property type="entry name" value="Flu_matrix_M1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013188">
        <property type="entry name" value="Flu_matrix_M1_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001561">
        <property type="entry name" value="Flu_matrix_M1_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015423">
        <property type="entry name" value="Flu_matrix_M1_N_sub1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015799">
        <property type="entry name" value="Flu_matrix_M1_N_sub2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037533">
        <property type="entry name" value="INFV_M1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00598">
        <property type="entry name" value="Flu_M1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08289">
        <property type="entry name" value="Flu_M1_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00759">
        <property type="entry name" value="Flu_M1_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48145">
        <property type="entry name" value="SSF48145"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="1 8 9" id="KW-1048">Host nucleus</keyword>
    <keyword evidence="4 8 9" id="KW-0472">Membrane</keyword>
    <keyword evidence="12" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="3 8 9" id="KW-0694">RNA-binding</keyword>
    <keyword evidence="5 8 9" id="KW-0468">Viral matrix protein</keyword>
    <keyword evidence="2 8 9" id="KW-0946">Virion</keyword>
    <feature type="domain" description="Flu_M1_C" evidence="10">
        <location>
            <begin position="158"/>
            <end position="252"/>
        </location>
    </feature>
    <feature type="region of interest" description="Membrane-binding" evidence="8">
        <location>
            <begin position="1"/>
            <end position="164"/>
        </location>
    </feature>
    <feature type="region of interest" description="RNP-binding" evidence="8">
        <location>
            <begin position="165"/>
            <end position="252"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="8">
        <location>
            <begin position="101"/>
            <end position="105"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00022562"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00022844"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00022884"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00023136"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00023311"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00024859"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="ARBA" id="ARBA00025019"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="RuleBase" id="RU362105"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="10">
        <source>
            <dbReference type="SMART" id="SM00759"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="11">
        <source>
            <dbReference type="EMBL" id="ADP95465.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="12">
        <source>
            <dbReference type="Proteomes" id="UP000140696"/>
        </source>
    </evidence>
    <sequence length="252" mass="27866" checksum="8BCCEA0621CBCCFC" modified="2011-02-08" version="1">MSLLTEVATYVLSIVPSGPLKAEIAQRLEDVFAGKNTDLEALMEWLKTRPILSPLTKGILGFVFTLTVPSERGLQRRRFVQNALNGNGDPNNMDRAVKLYRKLKREITFHGAKEVALSYSTGALASCMGLIYNRMGTVTTEVAFGLVCATCEQIADSQHRSHRQMVTTTNPLIRHENRMVLASTTAKAMEQIAGSSEQAAEAMEVASQARQMVQAMRTIGTHPSSSAGLKDDLLENLQAYQKRMGMQMQRFK</sequence>
</entry>
<entry dataset="TrEMBL" created="2011-02-08" modified="2022-08-03" version="61" xmlns="http://uniprot.org/uniprot">
    <accession>E4UF18</accession>
    <name>E4UF18_9INFA</name>
    <protein>
        <recommendedName>
            <fullName evidence="16 17">Neuraminidase</fullName>
            <ecNumber evidence="16 17">3.2.1.18</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="16 17 19" type="primary">NA</name>
    </gene>
    <organism evidence="19 20">
        <name type="scientific">Influenza A virus (A/northern shoveler/California/JN1447/2007(H7N2))</name>
        <dbReference type="NCBI Taxonomy" id="686561"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Negarnaviricota</taxon>
            <taxon>Polyploviricotina</taxon>
            <taxon>Insthoviricetes</taxon>
            <taxon>Articulavirales</taxon>
            <taxon>Orthomyxoviridae</taxon>
            <taxon>Alphainfluenzavirus</taxon>
        </lineage>
    </organism>
    <reference evidence="19 20" key="1">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <title>The NIAID Influenza Genome Sequencing Project.</title>
            <authorList>
                <person name="Spiro D."/>
                <person name="Halpin R."/>
                <person name="Boyne A."/>
                <person name="Bera J."/>
                <person name="Ghedin E."/>
                <person name="Dugan V."/>
                <person name="Hostetler J."/>
                <person name="Fedorova N."/>
                <person name="Hine E."/>
                <person name="Overton L."/>
                <person name="Kim M."/>
                <person name="Szczypinski B."/>
                <person name="Stockwell T."/>
                <person name="Sitz J."/>
                <person name="Katzel D."/>
                <person name="Li K."/>
                <person name="Axelrod N."/>
                <person name="Safford T."/>
                <person name="Amedeo P."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Wang S."/>
                <person name="Resnick A."/>
                <person name="Thovarai V."/>
                <person name="Cardona C."/>
                <person name="Boyce W."/>
                <person name="Anchell N."/>
                <person name="Dao N."/>
                <person name="Dao P."/>
                <person name="Lee G."/>
                <person name="Nelson J."/>
                <person name="Kelly T."/>
                <person name="Lin X."/>
                <person name="Wentworth D."/>
                <person name="Bao Y."/>
                <person name="Sanders R."/>
                <person name="Dernovoy D."/>
                <person name="Kiryutin B."/>
                <person name="Lipman D.J."/>
                <person name="Tatusova T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="19">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <reference evidence="19 20" key="2">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="The NIAID Influenza Genome Sequencing Consortium"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="19">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="16">Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16 17">
            <text>Hydrolysis of alpha-(2-&gt;3)-, alpha-(2-&gt;6)-, alpha-(2-&gt;8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.</text>
            <dbReference type="EC" id="3.2.1.18"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1 16 17">
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="16">Inhibited by the neuraminidase inhibitors zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs interfere with the release of progeny virus from infected cells and are effective against all influenza strains. Resistance to neuraminidase inhibitors is quite rare.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 16 17">Homotetramer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Membrane</location>
            <topology evidence="2">Single-pass type II membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="16">Virion membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="16">Host apical cell membrane</location>
            <topology evidence="16">Single-pass type II membrane protein</topology>
        </subcellularLocation>
        <text evidence="16">Preferentially accumulates at the apical plasma membrane in infected polarized epithelial cells, which is the virus assembly site. Uses lipid rafts for cell surface transport and apical sorting. In the virion, forms a mushroom-shaped spike on the surface of the membrane.</text>
    </comment>
    <comment type="domain">
        <text evidence="16">Intact N-terminus is essential for virion morphogenesis. Possess two apical sorting signals, one in the ectodomain, which is likely to be a glycan, and the other in the transmembrane domain. The transmembrane domain also plays a role in lipid raft association.</text>
    </comment>
    <comment type="PTM">
        <text evidence="16 17">N-glycosylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="16 17">Belongs to the glycosyl hydrolase 34 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="16">Lacks conserved residue(s) required for the propagation of feature annotation.</text>
    </comment>
    <dbReference type="EC" id="3.2.1.18" evidence="16 17"/>
    <dbReference type="EMBL" id="CY076874">
        <property type="protein sequence ID" value="ADP95467.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="CAZy" id="GH34">
        <property type="family name" value="Glycoside Hydrolase Family 34"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000140696">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0020002">
        <property type="term" value="C:host cell plasma 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: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:0052794">
        <property type="term" value="F:exo-alpha-(2-&gt;3)-sialidase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052795">
        <property type="term" value="F:exo-alpha-(2-&gt;6)-sialidase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052796">
        <property type="term" value="F:exo-alpha-(2-&gt;8)-sialidase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005975">
        <property type="term" value="P:carbohydrate metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046761">
        <property type="term" value="P:viral budding from plasma membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="CDD" id="cd15483">
        <property type="entry name" value="Influenza_NA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04071">
        <property type="entry name" value="INFV_NRAM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001860">
        <property type="entry name" value="Glyco_hydro_34"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033654">
        <property type="entry name" value="Sialidase_Influenza_A/B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036278">
        <property type="entry name" value="Sialidase_sf"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00064">
        <property type="entry name" value="Neur"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50939">
        <property type="entry name" value="SSF50939"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="8 16 17" id="KW-0106">Calcium</keyword>
    <keyword evidence="16" id="KW-1015">Disulfide bond</keyword>
    <keyword evidence="14 16 17" id="KW-0325">Glycoprotein</keyword>
    <keyword evidence="15 16 17" id="KW-0326">Glycosidase</keyword>
    <keyword evidence="4 16 17" id="KW-1032">Host cell membrane</keyword>
    <keyword evidence="10 16 17" id="KW-1043">Host membrane</keyword>
    <keyword evidence="7 16 17" id="KW-0378">Hydrolase</keyword>
    <keyword evidence="13 16" id="KW-0472">Membrane</keyword>
    <keyword evidence="6 16 17" id="KW-0479">Metal-binding</keyword>
    <keyword evidence="20" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="11 16" id="KW-0735">Signal-anchor</keyword>
    <keyword evidence="5 16" id="KW-0812">Transmembrane</keyword>
    <keyword evidence="12 16" id="KW-1133">Transmembrane helix</keyword>
    <keyword evidence="9 16 17" id="KW-0946">Virion</keyword>
    <feature type="transmembrane region" description="Helical" evidence="16">
        <location>
            <begin position="12"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="region of interest" description="Involved in apical transport and lipid raft association" evidence="16">
        <location>
            <begin position="11"/>
            <end position="33"/>
        </location>
    </feature>
    <feature type="region of interest" description="Head of neuraminidase" evidence="16">
        <location>
            <begin position="91"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="region of interest" description="Substrate binding" evidence="16">
        <location>
            <begin position="276"/>
            <end position="277"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="18">
        <location>
            <begin position="326"/>
            <end position="349"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="18">
        <location>
            <begin position="326"/>
            <end position="342"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor/acceptor" evidence="16">
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="active site" description="Nucleophile" evidence="16">
        <location>
            <position position="406"/>
        </location>
    </feature>
    <feature type="binding site" evidence="16">
        <location>
            <position position="118"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="16">
        <location>
            <position position="152"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="16">
        <location>
            <position position="292"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="16">
        <location>
            <position position="293"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="16">
        <location>
            <position position="297"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="16">
        <location>
            <position position="324"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="16">
        <location>
            <position position="371"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="disulfide bond" evidence="16">
        <location>
            <begin position="92"/>
            <end position="417"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="16">
        <location>
            <begin position="124"/>
            <end position="129"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="16">
        <location>
            <begin position="183"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="16">
        <location>
            <begin position="232"/>
            <end position="237"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="16">
        <location>
            <begin position="278"/>
            <end position="291"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="16">
        <location>
            <begin position="280"/>
            <end position="289"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00001913"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00004606"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00011881"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00022511"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00022692"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00022723"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="ARBA" id="ARBA00022801"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="ARBA" id="ARBA00022837"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="ARBA" id="ARBA00022844"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="10">
        <source>
            <dbReference type="ARBA" id="ARBA00022870"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="11">
        <source>
            <dbReference type="ARBA" id="ARBA00022968"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="12">
        <source>
            <dbReference type="ARBA" id="ARBA00022989"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="13">
        <source>
            <dbReference type="ARBA" id="ARBA00023136"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="14">
        <source>
            <dbReference type="ARBA" id="ARBA00023180"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="15">
        <source>
            <dbReference type="ARBA" id="ARBA00023295"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="16">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04071"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="17">
        <source>
            <dbReference type="RuleBase" id="RU361252"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="18">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="19">
        <source>
            <dbReference type="EMBL" id="ADP95467.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="20">
        <source>
            <dbReference type="Proteomes" id="UP000140696"/>
        </source>
    </evidence>
    <sequence length="469" mass="51635" checksum="2859339C545C5360" modified="2011-02-08" version="1">MNPNQKIITIGSVSLTIATICFLMQIAILATTVTLHFKQNECRIPSNNQVVPCEPIIIERNITEIVYLNNTTIEKETCPGVPGYRNWSKPQCQITGFAPFSKDNSIRLSAGGDIWVTREPYVSCGPGKCYQFALGQGTTLNNKHSNGTIHDRIPHRTLLMSELGVPFHLGTKQVCIAWSSSSCHDGKAWLHVCVTGDDRNATASFIYDGMLVDSIGSWSQNILRTQESECVCINGTCAVVMTDGSASGRADTRILFIKEGKIVHISPLSGSAQHIEECSCYPRYPDVRCVCRDNWKGSNRPVIDINMADYSIDSSYVCSGLVGDTPRNDDSSSSSNCRDPNNERGSPGVKGWAFDNGNDVWMGRTISKDSRSGYETFRVIGGWTTANSKSQVNRQVIVDNNNWSGYSGVFSVEGKSCINRCFYVELIRGRPQETRVWWTSNSIVVFCGTSGTYGTGSWPDGANINFMPI</sequence>
</entry>
<entry dataset="TrEMBL" created="2011-02-08" modified="2022-08-03" version="52" xmlns="http://uniprot.org/uniprot">
    <accession>E4UF19</accession>
    <name>E4UF19_9INFA</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Nucleoprotein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="7">Nucleocapsid protein</fullName>
            <shortName evidence="7">Protein N</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="7 8 10" type="primary">NP</name>
    </gene>
    <organism evidence="10 11">
        <name type="scientific">Influenza A virus (A/northern shoveler/California/JN1447/2007(H7N2))</name>
        <dbReference type="NCBI Taxonomy" id="686561"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Negarnaviricota</taxon>
            <taxon>Polyploviricotina</taxon>
            <taxon>Insthoviricetes</taxon>
            <taxon>Articulavirales</taxon>
            <taxon>Orthomyxoviridae</taxon>
            <taxon>Alphainfluenzavirus</taxon>
        </lineage>
    </organism>
    <reference evidence="10 11" key="1">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <title>The NIAID Influenza Genome Sequencing Project.</title>
            <authorList>
                <person name="Spiro D."/>
                <person name="Halpin R."/>
                <person name="Boyne A."/>
                <person name="Bera J."/>
                <person name="Ghedin E."/>
                <person name="Dugan V."/>
                <person name="Hostetler J."/>
                <person name="Fedorova N."/>
                <person name="Hine E."/>
                <person name="Overton L."/>
                <person name="Kim M."/>
                <person name="Szczypinski B."/>
                <person name="Stockwell T."/>
                <person name="Sitz J."/>
                <person name="Katzel D."/>
                <person name="Li K."/>
                <person name="Axelrod N."/>
                <person name="Safford T."/>
                <person name="Amedeo P."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Wang S."/>
                <person name="Resnick A."/>
                <person name="Thovarai V."/>
                <person name="Cardona C."/>
                <person name="Boyce W."/>
                <person name="Anchell N."/>
                <person name="Dao N."/>
                <person name="Dao P."/>
                <person name="Lee G."/>
                <person name="Nelson J."/>
                <person name="Kelly T."/>
                <person name="Lin X."/>
                <person name="Wentworth D."/>
                <person name="Bao Y."/>
                <person name="Sanders R."/>
                <person name="Dernovoy D."/>
                <person name="Kiryutin B."/>
                <person name="Lipman D.J."/>
                <person name="Tatusova T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="10">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <reference evidence="10 11" key="2">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="The NIAID Influenza Genome Sequencing Consortium"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="10">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="7">Encapsidates the negative strand viral RNA, protecting it from nucleases. The encapsidated genomic RNA is termed the ribonucleoprotein (RNP) and serves as template for transcription and replication. The RNP needs to be localized in the host nucleus to start an infectious cycle, but is too large to diffuse through the nuclear pore complex. NP comprises at least 2 nuclear localization signals that are responsible for the active RNP import into the nucleus through cellular importin alpha/beta pathway. Later in the infection, nclear export of RNPs are mediated through viral proteins NEP interacting with M1 which binds nucleoproteins. It is possible that nucleoprotein binds directly host exportin-1/XPO1 and plays an active role in RNPs nuclear export. M1 interaction with RNP seems to hide nucleoprotein's nuclear localization signals. Soon after a virion infects a new cell, M1 dissociates from the RNP under acidification of the virion driven by M2 protein. Dissociation of M1 from RNP unmasks nucleoprotein's nuclear localization signals, targeting the RNP to the nucleus.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7">Homomultimerizes to form the nucleocapsid. May bind host exportin-1/XPO1. Binds to viral genomic RNA. Protein-RNA contacts are mediated by a combination of electrostatic interactions between positively charged residues and the phosphate backbone and planar interactions between aromatic side chains and bases.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7 8">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7 8">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="7">Late in virus-infected cells, may be cleaved from a 56-kDa protein to a 53-kDa protein by a cellular caspase. This cleavage might be a marker for the onset of apoptosis in infected cells or have a specific function in virus host interaction.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7 8">Belongs to the influenza viruses nucleoprotein family.</text>
    </comment>
    <dbReference type="EMBL" id="CY076875">
        <property type="protein sequence ID" value="ADP95468.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000140696">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019029">
        <property type="term" value="C:helical viral capsid"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042025">
        <property type="term" value="C:host cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019013">
        <property type="term" value="C:viral nucleocapsid"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </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-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005198">
        <property type="term" value="F:structural molecule activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046718">
        <property type="term" value="P:viral entry into host cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0075732">
        <property type="term" value="P:viral penetration into host nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04070">
        <property type="entry name" value="INFV_NCAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002141">
        <property type="entry name" value="Flu_NP"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00506">
        <property type="entry name" value="Flu_NP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="3 7 8" id="KW-0167">Capsid protein</keyword>
    <keyword evidence="1 7" id="KW-1139">Helical capsid protein</keyword>
    <keyword evidence="4 7 8" id="KW-1048">Host nucleus</keyword>
    <keyword evidence="7" id="KW-0945">Host-virus interaction</keyword>
    <keyword evidence="11" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="6 7" id="KW-0687">Ribonucleoprotein</keyword>
    <keyword evidence="5 7" id="KW-0694">RNA-binding</keyword>
    <keyword evidence="7 8 10" id="KW-0543">Viral nucleoprotein</keyword>
    <keyword evidence="2 7" id="KW-1163">Viral penetration into host nucleus</keyword>
    <keyword evidence="7 8" id="KW-0946">Virion</keyword>
    <keyword evidence="7" id="KW-1160">Virus entry into host cell</keyword>
    <feature type="region of interest" description="Disordered" evidence="9">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="9">
        <location>
            <begin position="79"/>
            <end position="98"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Unconventional nuclear localization signal" evidence="7">
        <location>
            <begin position="1"/>
            <end position="18"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Bipartite nuclear localization signal" evidence="7">
        <location>
            <begin position="198"/>
            <end position="216"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00022497"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00022524"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00022561"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00022562"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00022884"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00023274"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04070"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="RuleBase" id="RU361251"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="10">
        <source>
            <dbReference type="EMBL" id="ADP95468.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="11">
        <source>
            <dbReference type="Proteomes" id="UP000140696"/>
        </source>
    </evidence>
    <sequence length="498" mass="56299" checksum="0B0660795589F244" modified="2011-02-08" version="1">MASQGTKRSYEQMETGGERQNATEIRASVGRMVGGIGRFYIQMCTELKLSDYEGRLIQNSITIERMVLSAFDERRNKYLEEHPSAGKDPKKTGGPIYRRRDGKWMRELTLYDKEEIRRIWRQANNGEDATAGLTHLMIWHSNLNDATYQRTRALVRTGMDPRMCSLMQGSTLPRRSGAAGAAVKGVGTMVMELIRMIKRGINDRNFWRGENGRRTRIAYERMCNILKGKFQTAAQRAMMDQVRESRNPGNAEIEDLIFLARSALILRGSVAHKSCLPACVYGLAVASGYDFEREGYSLVGIDPFRLLQNSQVFSLIRPNENPAHKSQLVWMACHSAAFEDLRVSSFIRGTRVVPRGQLSTRGVQIASNENMETMDSSTLELRSRYWAIRTRSGGNTNQQRASAGQISVQPTFSVQRNLPFERATIMAAFTGNTEGRTSDMRTEIIRMMENARPEDVSFQGRGVFELSDEKATNPIVPSFDMSNEGSYFFGDNAEEYDN</sequence>
</entry>
<entry dataset="TrEMBL" created="2011-02-08" modified="2022-08-03" version="53" xmlns="http://uniprot.org/uniprot">
    <accession>E4UF20</accession>
    <name>E4UF20_9INFA</name>
    <protein>
        <recommendedName>
            <fullName evidence="6">Nuclear export protein</fullName>
            <shortName evidence="6">NEP</shortName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="6">Non-structural protein 2</fullName>
            <shortName evidence="6">NS2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="8" type="primary">NEP</name>
        <name evidence="6 7" type="synonym">NS</name>
    </gene>
    <organism evidence="8 9">
        <name type="scientific">Influenza A virus (A/northern shoveler/California/JN1447/2007(H7N2))</name>
        <dbReference type="NCBI Taxonomy" id="686561"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Negarnaviricota</taxon>
            <taxon>Polyploviricotina</taxon>
            <taxon>Insthoviricetes</taxon>
            <taxon>Articulavirales</taxon>
            <taxon>Orthomyxoviridae</taxon>
            <taxon>Alphainfluenzavirus</taxon>
        </lineage>
    </organism>
    <reference evidence="8 9" key="1">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <title>The NIAID Influenza Genome Sequencing Project.</title>
            <authorList>
                <person name="Spiro D."/>
                <person name="Halpin R."/>
                <person name="Boyne A."/>
                <person name="Bera J."/>
                <person name="Ghedin E."/>
                <person name="Dugan V."/>
                <person name="Hostetler J."/>
                <person name="Fedorova N."/>
                <person name="Hine E."/>
                <person name="Overton L."/>
                <person name="Kim M."/>
                <person name="Szczypinski B."/>
                <person name="Stockwell T."/>
                <person name="Sitz J."/>
                <person name="Katzel D."/>
                <person name="Li K."/>
                <person name="Axelrod N."/>
                <person name="Safford T."/>
                <person name="Amedeo P."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Wang S."/>
                <person name="Resnick A."/>
                <person name="Thovarai V."/>
                <person name="Cardona C."/>
                <person name="Boyce W."/>
                <person name="Anchell N."/>
                <person name="Dao N."/>
                <person name="Dao P."/>
                <person name="Lee G."/>
                <person name="Nelson J."/>
                <person name="Kelly T."/>
                <person name="Lin X."/>
                <person name="Wentworth D."/>
                <person name="Bao Y."/>
                <person name="Sanders R."/>
                <person name="Dernovoy D."/>
                <person name="Kiryutin B."/>
                <person name="Lipman D.J."/>
                <person name="Tatusova T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="8">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <reference evidence="8 9" key="2">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="The NIAID Influenza Genome Sequencing Consortium"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="8">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="6 7">Mediates the nuclear export of encapsidated genomic RNAs (ribonucleoproteins, RNPs). Acts as an adapter between viral RNPs complexes and the nuclear export machinery of the cell. Possesses no intrinsic RNA-binding activity, but includes a C-terminal M1-binding domain. This domain is believed to allow recognition of RNPs bound to the protein M1. Since protein M1 is not available in large quantities before late stages of infection, such an indirect recognition mechanism probably ensures that genomic RNPs are not exported from the host nucleus until sufficient quantities of viral mRNA and progeny genomic RNA have been synthesized. Furthermore, the RNPs enter the host cytoplasm only when associated with the M1 protein that is necessary to guide them to the plasma membrane. May down-regulate viral RNA synthesis when overproduced.</text>
    </comment>
    <comment type="function">
        <text evidence="4">Mediates the nuclear export of encapsidated genomic RNAs (ribonucleoproteins, RNPs). Acts as an adapter between viral RNPs complexes and the nuclear export machinery of the cell. Possesses no intrinsic RNA-binding activity, but includes a C-terminal M1-binding domain. This domain is believed to allow recognition of RNPs to which the M1 protein is bound. Because the M1 protein is not available in large quantities until the later stages of infection, such an indirect recognition mechanism probably ensures that genomic RNPs are not exported from the nucleus before sufficient quantities of viral mRNA and progeny genomic RNA have been synthesized. Furthermore, the RNPs enters the cytoplasm only when they have associated with the M1 protein that is necessary to guide them to the plasma membrane. May down-regulate viral RNA synthesis when overproduced.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7">Binds M1 protein. May interact with host nucleoporin RAB/HRB and exportin XPO1/CRM1.</text>
    </comment>
    <comment type="subunit">
        <text evidence="5">Binds M1 protein. May interact with human nucleoporin RAB/HRB and exportin XPO1/CRM1.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6">Interacts with protein M1. May interact with host nucleoporin RAB/HRB and exportin XPO1/CRM1.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6 7">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6 7">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="2 6 7">Belongs to the influenza viruses NEP family.</text>
    </comment>
    <dbReference type="EMBL" id="CY076876">
        <property type="protein sequence ID" value="ADP95470.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="SMR" id="E4UF20"/>
    <dbReference type="Proteomes" id="UP000140696">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042025">
        <property type="term" value="C:host cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044423">
        <property type="term" value="C:virion component"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039675">
        <property type="term" value="P:exit of virus from host cell nucleus through nuclear pore"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04067">
        <property type="entry name" value="INFV_NEP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000968">
        <property type="entry name" value="Flu_NS2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00601">
        <property type="entry name" value="Flu_NS2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="6 7" id="KW-1048">Host nucleus</keyword>
    <keyword evidence="6 7" id="KW-0945">Host-virus interaction</keyword>
    <keyword evidence="9" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="3 6 7" id="KW-0813">Transport</keyword>
    <keyword evidence="6 7" id="KW-0946">Virion</keyword>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="6">
        <location>
            <begin position="12"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="6">
        <location>
            <begin position="85"/>
            <end position="94"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00004123"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00010673"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00022448"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00024714"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00026037"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04067"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="RuleBase" id="RU362104"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="8">
        <source>
            <dbReference type="EMBL" id="ADP95470.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="9">
        <source>
            <dbReference type="Proteomes" id="UP000140696"/>
        </source>
    </evidence>
    <sequence length="121" mass="14338" checksum="F97DE09AE57377AF" modified="2011-02-08" version="1">MDSNTVSSFQDILMRMSKMQLGSSSEDLNGMITQFESLKLYRDSLGEAVMRMGDLHSLQSRNGKWREQLSQKFEEIRWLIEEVRHRLKITENSFEQITFMQALQLLLEVEQEIRTFSFQLI</sequence>
</entry>
<entry dataset="TrEMBL" created="2011-02-08" modified="2022-08-03" version="55" xmlns="http://uniprot.org/uniprot">
    <accession>E4UF21</accession>
    <name>E4UF21_9INFA</name>
    <protein>
        <recommendedName>
            <fullName evidence="17">Non-structural protein 1</fullName>
            <shortName evidence="17">NS1</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="19" type="primary">NS1</name>
        <name evidence="17" type="synonym">NS</name>
    </gene>
    <organism evidence="19 20">
        <name type="scientific">Influenza A virus (A/northern shoveler/California/JN1447/2007(H7N2))</name>
        <dbReference type="NCBI Taxonomy" id="686561"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Negarnaviricota</taxon>
            <taxon>Polyploviricotina</taxon>
            <taxon>Insthoviricetes</taxon>
            <taxon>Articulavirales</taxon>
            <taxon>Orthomyxoviridae</taxon>
            <taxon>Alphainfluenzavirus</taxon>
        </lineage>
    </organism>
    <reference evidence="19 20" key="1">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <title>The NIAID Influenza Genome Sequencing Project.</title>
            <authorList>
                <person name="Spiro D."/>
                <person name="Halpin R."/>
                <person name="Boyne A."/>
                <person name="Bera J."/>
                <person name="Ghedin E."/>
                <person name="Dugan V."/>
                <person name="Hostetler J."/>
                <person name="Fedorova N."/>
                <person name="Hine E."/>
                <person name="Overton L."/>
                <person name="Kim M."/>
                <person name="Szczypinski B."/>
                <person name="Stockwell T."/>
                <person name="Sitz J."/>
                <person name="Katzel D."/>
                <person name="Li K."/>
                <person name="Axelrod N."/>
                <person name="Safford T."/>
                <person name="Amedeo P."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Wang S."/>
                <person name="Resnick A."/>
                <person name="Thovarai V."/>
                <person name="Cardona C."/>
                <person name="Boyce W."/>
                <person name="Anchell N."/>
                <person name="Dao N."/>
                <person name="Dao P."/>
                <person name="Lee G."/>
                <person name="Nelson J."/>
                <person name="Kelly T."/>
                <person name="Lin X."/>
                <person name="Wentworth D."/>
                <person name="Bao Y."/>
                <person name="Sanders R."/>
                <person name="Dernovoy D."/>
                <person name="Kiryutin B."/>
                <person name="Lipman D.J."/>
                <person name="Tatusova T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="19">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <reference evidence="19 20" key="2">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="The NIAID Influenza Genome Sequencing Consortium"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="19">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="17">Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor/CPSF4 and the poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.</text>
    </comment>
    <comment type="function">
        <text evidence="17">Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA.</text>
    </comment>
    <comment type="subunit">
        <text evidence="17">Homodimer. Interacts with host TRIM25 (via coiled coil); this interaction specifically inhibits TRIM25 multimerization and TRIM25-mediated DDX58 CARD ubiquitination. Interacts with human EIF2AK2/PKR, CPSF4, IVNS1ABP and PABPN1.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="17">Host nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="17">Host cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="domain">
        <text evidence="17">The dsRNA-binding region is required for suppression of RNA silencing.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the influenza A viruses NS1 family.</text>
    </comment>
    <dbReference type="EMBL" id="CY076876">
        <property type="protein sequence ID" value="ADP95469.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000140696">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030430">
        <property type="term" value="C:host cell cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042025">
        <property type="term" value="C:host cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030291">
        <property type="term" value="F:protein serine/threonine kinase inhibitor activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </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:0039524">
        <property type="term" value="P:suppression by virus of host mRNA processing"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039580">
        <property type="term" value="P:suppression by virus of host PKR signaling"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039502">
        <property type="term" value="P:suppression by virus of host type I interferon-mediated signaling pathway"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039540">
        <property type="term" value="P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.420.330">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04066">
        <property type="entry name" value="INFV_NS1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004208">
        <property type="entry name" value="NS1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000256">
        <property type="entry name" value="NS1A"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038064">
        <property type="entry name" value="NS1A_effect_dom-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009068">
        <property type="entry name" value="S15_NS1_RNA-bd"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00600">
        <property type="entry name" value="Flu_NS1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF143021">
        <property type="entry name" value="SSF143021"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47060">
        <property type="entry name" value="SSF47060"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="14 17" id="KW-1262">Eukaryotic host gene expression shutoff by virus</keyword>
    <keyword evidence="13 17" id="KW-1035">Host cytoplasm</keyword>
    <keyword evidence="10 17" id="KW-1190">Host gene expression shutoff by virus</keyword>
    <keyword evidence="2 17" id="KW-1192">Host mRNA suppression by virus</keyword>
    <keyword evidence="3 17" id="KW-1048">Host nucleus</keyword>
    <keyword evidence="4 17" id="KW-0945">Host-virus interaction</keyword>
    <keyword evidence="5" id="KW-1090">Inhibition of host innate immune response by virus</keyword>
    <keyword evidence="6" id="KW-1114">Inhibition of host interferon signaling pathway by virus</keyword>
    <keyword evidence="11" id="KW-1102">Inhibition of host PKR by virus</keyword>
    <keyword evidence="7 17" id="KW-1103">Inhibition of host pre-mRNA processing by virus</keyword>
    <keyword evidence="12" id="KW-1088">Inhibition of host RIG-I by virus</keyword>
    <keyword evidence="1" id="KW-1113">Inhibition of host RLR pathway by virus</keyword>
    <keyword evidence="15 17" id="KW-0922">Interferon antiviral system evasion</keyword>
    <keyword evidence="20" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="9 17" id="KW-0694">RNA-binding</keyword>
    <keyword evidence="8" id="KW-0832">Ubl conjugation</keyword>
    <keyword evidence="16" id="KW-0899">Viral immunoevasion</keyword>
    <feature type="region of interest" description="Disordered" evidence="18">
        <location>
            <begin position="205"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="18">
        <location>
            <begin position="213"/>
            <end position="230"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00022482"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00022557"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00022562"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00022581"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00022632"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00022830"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="ARBA" id="ARBA00022834"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="ARBA" id="ARBA00022843"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="ARBA" id="ARBA00022884"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="10">
        <source>
            <dbReference type="ARBA" id="ARBA00022995"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="11">
        <source>
            <dbReference type="ARBA" id="ARBA00023041"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="12">
        <source>
            <dbReference type="ARBA" id="ARBA00023090"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="13">
        <source>
            <dbReference type="ARBA" id="ARBA00023200"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="14">
        <source>
            <dbReference type="ARBA" id="ARBA00023247"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="15">
        <source>
            <dbReference type="ARBA" id="ARBA00023258"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="16">
        <source>
            <dbReference type="ARBA" id="ARBA00023280"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="17">
        <source>
            <dbReference type="RuleBase" id="RU362113"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="18">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="19">
        <source>
            <dbReference type="EMBL" id="ADP95469.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="20">
        <source>
            <dbReference type="Proteomes" id="UP000140696"/>
        </source>
    </evidence>
    <sequence length="230" mass="26071" checksum="4514E86F929B5EC3" modified="2011-02-08" version="1">MDSNTVSSFQVDCFLWHVRKRFADQELGDAPFLDRLRRDQKSLRGRGSTLGLDIETATRAGKQIVERILEEESDEALKMTIASVPASRYLTDMTLEEMSRDWFMLMPKQKVAGSLCIRMDQAIMDKNITLKANFSVIFDRLETLILLRAFTEEGAIVGEISPLPSLPGHTDEDVKNAIGVLIGGLEWNDNTVRVSETLQRFAWRSSNEDGRPPLPPKQKRKMARTIESEV</sequence>
</entry>
<entry dataset="TrEMBL" created="2011-02-08" modified="2022-08-03" version="47" xmlns="http://uniprot.org/uniprot">
    <accession>E4UF22</accession>
    <name>E4UF22_9INFA</name>
    <protein>
        <recommendedName>
            <fullName evidence="4 12 13">Polymerase basic protein 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="12">RNA-directed RNA polymerase subunit P3</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="12 13 14" type="primary">PB2</name>
    </gene>
    <organism evidence="14 15">
        <name type="scientific">Influenza A virus (A/northern shoveler/California/JN1447/2007(H7N2))</name>
        <dbReference type="NCBI Taxonomy" id="686561"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Orthornavirae</taxon>
            <taxon>Negarnaviricota</taxon>
            <taxon>Polyploviricotina</taxon>
            <taxon>Insthoviricetes</taxon>
            <taxon>Articulavirales</taxon>
            <taxon>Orthomyxoviridae</taxon>
            <taxon>Alphainfluenzavirus</taxon>
        </lineage>
    </organism>
    <reference evidence="14 15" key="1">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <title>The NIAID Influenza Genome Sequencing Project.</title>
            <authorList>
                <person name="Spiro D."/>
                <person name="Halpin R."/>
                <person name="Boyne A."/>
                <person name="Bera J."/>
                <person name="Ghedin E."/>
                <person name="Dugan V."/>
                <person name="Hostetler J."/>
                <person name="Fedorova N."/>
                <person name="Hine E."/>
                <person name="Overton L."/>
                <person name="Kim M."/>
                <person name="Szczypinski B."/>
                <person name="Stockwell T."/>
                <person name="Sitz J."/>
                <person name="Katzel D."/>
                <person name="Li K."/>
                <person name="Axelrod N."/>
                <person name="Safford T."/>
                <person name="Amedeo P."/>
                <person name="Schobel S."/>
                <person name="Shrivastava S."/>
                <person name="Wang S."/>
                <person name="Resnick A."/>
                <person name="Thovarai V."/>
                <person name="Cardona C."/>
                <person name="Boyce W."/>
                <person name="Anchell N."/>
                <person name="Dao N."/>
                <person name="Dao P."/>
                <person name="Lee G."/>
                <person name="Nelson J."/>
                <person name="Kelly T."/>
                <person name="Lin X."/>
                <person name="Wentworth D."/>
                <person name="Bao Y."/>
                <person name="Sanders R."/>
                <person name="Dernovoy D."/>
                <person name="Kiryutin B."/>
                <person name="Lipman D.J."/>
                <person name="Tatusova T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="14">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <reference evidence="14 15" key="2">
        <citation type="submission" date="2010-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="The NIAID Influenza Genome Sequencing Consortium"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <source>
            <strain evidence="14">A/northern shoveler/California/JN1447/2007</strain>
        </source>
    </reference>
    <comment type="function">
        <text evidence="12">Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex.</text>
    </comment>
    <comment type="subunit">
        <text evidence="12">Influenza RNA polymerase is composed of three subunits: PB1, PB2 and PA. Interacts (via N-terminus) with PB1 (via C-terminus). Interacts with nucleoprotein NP (via N-terminus).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Host mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12 13">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12 13">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="3 12 13">Belongs to the influenza viruses PB2 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="12">Lacks conserved residue(s) required for the propagation of feature annotation.</text>
    </comment>
    <dbReference type="EMBL" id="CY076879">
        <property type="protein sequence ID" value="ADP95471.1"/>
        <property type="molecule type" value="Viral_cRNA"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000140696">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033650">
        <property type="term" value="C:host cell mitochondrion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042025">
        <property type="term" value="C:host cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044423">
        <property type="term" value="C:virion component"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </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-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003968">
        <property type="term" value="F:RNA-directed 5'-3' RNA polymerase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006370">
        <property type="term" value="P:7-methylguanosine mRNA capping"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0075526">
        <property type="term" value="P:cap snatching"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039523">
        <property type="term" value="P:suppression by virus of host mRNA transcription via inhibition of RNA polymerase II activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006351">
        <property type="term" value="P:transcription, DNA-templated"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039694">
        <property type="term" value="P:viral RNA genome replication"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.30.90">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04062">
        <property type="entry name" value="INV_PB2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001591">
        <property type="entry name" value="INV_PB2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037258">
        <property type="entry name" value="PDB2_C"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00604">
        <property type="entry name" value="Flu_PB2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF160453">
        <property type="entry name" value="SSF160453"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="7 12" id="KW-1157">Cap snatching</keyword>
    <keyword evidence="12" id="KW-1262">Eukaryotic host gene expression shutoff by virus</keyword>
    <keyword evidence="8 12" id="KW-1191">Eukaryotic host transcription shutoff by virus</keyword>
    <keyword evidence="12" id="KW-1190">Host gene expression shutoff by virus</keyword>
    <keyword evidence="5 12 13" id="KW-1048">Host nucleus</keyword>
    <keyword evidence="12" id="KW-0945">Host-virus interaction</keyword>
    <keyword evidence="10 12" id="KW-1104">Inhibition of host RNA polymerase II by virus</keyword>
    <keyword evidence="9 12 13" id="KW-0506">mRNA capping</keyword>
    <keyword evidence="6 12 13" id="KW-0507">mRNA processing</keyword>
    <keyword evidence="15" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="11 12" id="KW-1195">Viral transcription</keyword>
    <keyword evidence="12 13" id="KW-0946">Virion</keyword>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="12">
        <location>
            <begin position="736"/>
            <end position="739"/>
        </location>
    </feature>
    <feature type="site" description="Avian adaptation" evidence="12">
        <location>
            <position position="627"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00004173"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00004181"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00008660"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00014261"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00022562"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00022664"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="ARBA" id="ARBA00022715"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="ARBA" id="ARBA00022731"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="ARBA" id="ARBA00023042"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="10">
        <source>
            <dbReference type="ARBA" id="ARBA00023103"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="11">
        <source>
            <dbReference type="ARBA" id="ARBA00023314"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="12">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04062"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="13">
        <source>
            <dbReference type="RuleBase" id="RU361246"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="14">
        <source>
            <dbReference type="EMBL" id="ADP95471.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="15">
        <source>
            <dbReference type="Proteomes" id="UP000140696"/>
        </source>
    </evidence>
    <sequence length="759" mass="85906" checksum="D1B0F38C34B88501" modified="2011-02-08" version="1"> </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>