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<entry dataset="Swiss-Prot" created="2010-11-30" modified="2022-02-23" version="42" xmlns="http://uniprot.org/uniprot">
    <accession>P0C791</accession>
    <name>PB1F2_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Protein PB1-F2</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="1" type="primary">PB1</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Plays an important role in promoting lung pathology in both primary viral infection and secondary bacterial infection. Promotes alteration of mitochondrial morphology, dissipation of mitochondrial membrane potential, and cell death. Alternatively, inhibits the production of interferon in the infected cell at the level of host mitochondrial antiviral signaling MAVS. Its level of expression differs greatly depending on which cell type is infected, in a manner that is independent of the levels of expression of other viral proteins. Monocytic cells are more affected than epithelial cells. Seems to disable virus-infected monocytes or other host innate immune cells. During early stage of infection, predisposes the mitochondria to permeability transition through interaction with host SLC25A6/ANT3 and VDAC1. These proteins participate in the formation of the permeability transition pore complex (PTPC) responsible of the release of mitochondrial products that triggers apoptosis.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Oligomer. Interacts with human SLC25A6/ANT3 and VDAC1. Interacts with host MAVS.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Host mitochondrion inner membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host cytoplasm</location>
            <location evidence="1">Host cytosol</location>
        </subcellularLocation>
        <text evidence="1">Inner mitochondrial membrane in most cells types. Otherwise is detected in the nucleus and cytosol.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Is not encoded in all strains, and seems to be dispensable for replication.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the influenza viruses PB1-F2 family.</text>
    </comment>
    <dbReference type="EMBL" id="AF144301">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_473348.1">
        <property type="nucleotide sequence ID" value="NC_007358.1"/>
    </dbReference>
    <dbReference type="SMR" id="P0C791"/>
    <dbReference type="GeneID" id="3896424"/>
    <dbReference type="KEGG" id="vg:3896424"/>
    <dbReference type="Proteomes" id="UP000131152">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04064">
        <property type="entry name" value="INFV_PB1F2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR021045">
        <property type="entry name" value="Flu_proapoptotic_PB1-F2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF11986">
        <property type="entry name" value="PB1-F2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0053">Apoptosis</keyword>
    <keyword id="KW-1035">Host cytoplasm</keyword>
    <keyword id="KW-1043">Host membrane</keyword>
    <keyword id="KW-1045">Host mitochondrion</keyword>
    <keyword id="KW-1046">Host mitochondrion inner membrane</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-1090">Inhibition of host innate immune response by virus</keyword>
    <keyword id="KW-1097">Inhibition of host MAVS by virus</keyword>
    <keyword id="KW-1113">Inhibition of host RLR pathway by virus</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1119">Modulation of host cell apoptosis by virus</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0899">Viral immunoevasion</keyword>
    <feature type="chain" id="PRO_0000402432" description="Protein PB1-F2">
        <location>
            <begin position="1"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="region of interest" description="Mitochondrial targeting sequence" evidence="1">
        <location>
            <begin position="65"/>
            <end position="87"/>
        </location>
    </feature>
    <feature type="site" description="Low pathogenicity" evidence="1">
        <location>
            <position position="66"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04064"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <sequence length="90" mass="11002" checksum="5751602E64E03273" modified="2010-11-30" version="1">MEQEQDTPWTQSTEHINIQKRGNGQRTQRLEHPNSIRLMDHYLRIMSRVGMHKQIVYWKQWLSLKNPTQGSLKTRVLKRWKLFSKQEWIS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2012-10-03" modified="2020-12-02" version="31" xmlns="http://uniprot.org/uniprot">
    <accession>P0CK63</accession>
    <name>PAX_I96A0</name>
    <protein>
        <recommendedName>
            <fullName>Protein PA-X</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">PA</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">May play a role in the modulation of host immune response.</text>
    </comment>
    <comment type="alternative products">
        <event type="ribosomal frameshifting"/>
        <isoform>
            <id>P0CK63-1</id>
            <name>PA-X</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Q0U9-1</id>
            <name>PA</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the influenza viruses PA-X family.</text>
    </comment>
    <dbReference type="EMBL" id="AF144302">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_006495800.1">
        <molecule id="P0CK63-1"/>
        <property type="nucleotide sequence ID" value="NC_007359.1"/>
    </dbReference>
    <dbReference type="SMR" id="P0CK63"/>
    <dbReference type="GeneID" id="13229455"/>
    <dbReference type="KEGG" id="vg:13229455"/>
    <dbReference type="Proteomes" id="UP000131152">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.91.90">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001009">
        <property type="entry name" value="PA/PA-X"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038372">
        <property type="entry name" value="PA/PA-X_sf"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00603">
        <property type="entry name" value="Flu_PA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0688">Ribosomal frameshifting</keyword>
    <feature type="chain" id="PRO_0000419346" description="Protein PA-X">
        <location>
            <begin position="1"/>
            <end position="252"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000305" key="2"/>
    <sequence length="252" mass="29305" checksum="3069BED191CF1D9F" modified="2012-10-03" version="1">MEDFVRQCFNPMIVELAEKAMKEYGEDPKIETNKFAAICTHLEVCFMYSDFHFIDERGESTIIESGDPNALLKHRFEIIEGRDRTMAWTVVNSICNTTGVEKPKFLPDLYDYKENRFIEIGVTRREVHTYYLEKANKIKSEKTHIHIFSFTGEEMATKADYTLDEESRARIKTRLFTIRQEMASRGLWDSFVSPREAKRQLKKDLKSQGLCAGLPTKVSHLISPALKNLEPMWMDSNRTAALRASFLKCRKK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2017-06-07" modified="2020-10-07" version="13" xmlns="http://uniprot.org/uniprot">
    <accession>P0DOG5</accession>
    <name>PB2S1_I96A0</name>
    <protein>
        <recommendedName>
            <fullName>PB2-S1</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">PB2</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="2">May participate in the inhibition of type I interferon induction through inhibition of the host mitochondrial antiviral signaling protein MAVS. The knockout of PB2-S1 has no detectable effects on laboratory infected mice.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Host mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Host cytoplasm</location>
            <location evidence="2">Host cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P0DOG5-1</id>
            <name evidence="1">PB2-S1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Q0V1-1</id>
            <name>Polymerase basic protein 2</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <dbReference type="EMBL" id="AF144300">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="SMR" id="P0DOG5"/>
    <dbReference type="Proteomes" id="UP000131152">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001591">
        <property type="entry name" value="INV_PB2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00604">
        <property type="entry name" value="Flu_PB2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1035">Host cytoplasm</keyword>
    <keyword id="KW-1045">Host mitochondrion</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000440603" description="PB2-S1">
        <location>
            <begin position="1"/>
            <end position="508"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P03427"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P0DOG3"/>
        </source>
    </evidence>
    <sequence length="508" mass="57810" checksum="BB5FDC23FC7B5C25" modified="2017-06-07" version="1">MERIKELRDLMSQSRTREILTKTTVDHMAIIKKYTSGRQEKNPALRMKWMMAMKYPITADKRIMEMIPERNEQGQTLWSKTNDAGSDRVMVSPLAVTWWNRNGPTTSTVHYPKVYKTYFEKVERLKHGTFGPVHFRNQVKIRRRVDINPGHADLSAKEAQDVIMEVVFPNEVGARILTSESQLTITKEKKEELQDCKIAPLMVAYMLERELVRKTRFLPVAGGTSSVYIEVLHLTQGTCWEQMYTPGGEVRNDDVDQSLIIAARNIVRRATVSADPLASLLEMCHSTQIGGIRMVDILRQNPTEEQAVDICKAAMGLRISSSFSFGGFTFKRTNGSSVKKEEEVLTGNLQTLKIKVHEGYEEFTMVGRRATAILRKATRRLIQLIVSGRDEQSIAEAIIVAMVFSQEDCMIKAVRGDLNFVNRANQRLNPMHQLLRHFQKDAKVLFQNWGIEPIDNVMGMIGILPDMTPSAEMSLRGVRVSKMGVDEYSSTERVVQPHRSRAECSFLL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-03-18" modified="2022-02-23" version="98" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0L6</accession>
    <name>NS1_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Non-structural protein 1</fullName>
            <shortName evidence="1">NS1</shortName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">NS1A</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1" type="primary">NS</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">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="function">
        <text evidence="1">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="subunit">
        <text evidence="1">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="1">Host nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host cytoplasm</location>
        </subcellularLocation>
        <text evidence="1">In uninfected, transfected cells, NS1 is localized in the nucleus. Only in virus infected cells, the nuclear export signal is unveiled, presumably by a viral protein, and a fraction of NS1 is exported in the cytoplasm.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Q0L6-1</id>
            <name>NS1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Q0L7-1</id>
            <name>NEP</name>
            <name>NS2</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="1">The dsRNA-binding region is required for suppression of RNA silencing.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Upon interferon induction, ISGylated via host HERC5; this results in the impairment of NS1 interaction with RNA targets due to its inability to form homodimers and to interact with host EIF2AK2/PKR.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the influenza A viruses NS1 family.</text>
    </comment>
    <dbReference type="EMBL" id="AF144307">
        <property type="protein sequence ID" value="AAD51930.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_308673.1">
        <molecule id="Q9Q0L6-1"/>
        <property type="nucleotide sequence ID" value="NC_007364.1"/>
    </dbReference>
    <dbReference type="SMR" id="Q9Q0L6"/>
    <dbReference type="GeneID" id="8656648"/>
    <dbReference type="KEGG" id="vg:8656648"/>
    <dbReference type="Proteomes" id="UP000131152">
        <property type="component" value="Genome"/>
    </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 id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1262">Eukaryotic host gene expression shutoff by virus</keyword>
    <keyword id="KW-1035">Host cytoplasm</keyword>
    <keyword id="KW-1190">Host gene expression shutoff by virus</keyword>
    <keyword id="KW-1192">Host mRNA suppression by virus</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-1090">Inhibition of host innate immune response by virus</keyword>
    <keyword id="KW-1114">Inhibition of host interferon signaling pathway by virus</keyword>
    <keyword id="KW-1102">Inhibition of host PKR by virus</keyword>
    <keyword id="KW-1103">Inhibition of host pre-mRNA processing by virus</keyword>
    <keyword id="KW-1088">Inhibition of host RIG-I by virus</keyword>
    <keyword id="KW-1113">Inhibition of host RLR pathway by virus</keyword>
    <keyword id="KW-0922">Interferon antiviral system evasion</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0694">RNA-binding</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <keyword id="KW-0899">Viral immunoevasion</keyword>
    <feature type="chain" id="PRO_0000324282" description="Non-structural protein 1">
        <location>
            <begin position="1"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="region of interest" description="RNA-binding and homodimerization" evidence="1">
        <location>
            <begin position="1"/>
            <end position="73"/>
        </location>
    </feature>
    <feature type="region of interest" description="CPSF4-binding" evidence="1">
        <location>
            <begin position="180"/>
            <end position="215"/>
        </location>
    </feature>
    <feature type="region of interest" description="PABPN1-binding" evidence="1">
        <location>
            <begin position="223"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="1">
        <location>
            <begin position="34"/>
            <end position="38"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="1">
        <location>
            <begin position="137"/>
            <end position="146"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04066"/>
        </source>
    </evidence>
    <sequence length="230" mass="26095" checksum="C4174DF7B731D442" modified="2000-05-01" version="1">MDSNTITSFQVDCYLWHIRKLLSMRDMCDAPFDDRLRRDQKALKGRGSTLGLDLRVATMEGKKIVEDILKSETNENLKIAIASSPAPRYITDMSIEEMSREWYMLMPRQKITGGLMVKMDQAIMDKRIILKANFSVLFDQLETLVSLRAFTESGAIVAEIFPIPSVPGHFTEDVKNAIGILIGGLEWNDNSIRASENIQRFAWGIHDENGGPSLPPKQKRYMAKRVESEV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-03-18" modified="2022-08-03" version="91" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0L7</accession>
    <name>NEP_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Nuclear export protein</fullName>
            <shortName evidence="1">NEP</shortName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">Non-structural protein 2</fullName>
            <shortName evidence="1">NS2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1" type="primary">NS</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">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="subunit">
        <text evidence="1">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">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Q0L7-1</id>
            <name>NEP</name>
            <name>NS2</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Q0L6-1</id>
            <name>NS1</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the influenza viruses NEP family.</text>
    </comment>
    <dbReference type="EMBL" id="AF144307">
        <property type="protein sequence ID" value="AAD51931.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_308672.1">
        <molecule id="Q9Q0L7-1"/>
        <property type="nucleotide sequence ID" value="NC_007364.1"/>
    </dbReference>
    <dbReference type="SMR" id="Q9Q0L7"/>
    <dbReference type="GeneID" id="3654622"/>
    <dbReference type="KEGG" id="vg:3654622"/>
    <dbReference type="Proteomes" id="UP000131152">
        <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 id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-0946">Virion</keyword>
    <feature type="chain" id="PRO_0000324234" description="Nuclear export protein">
        <location>
            <begin position="1"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="1">
        <location>
            <begin position="12"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="1">
        <location>
            <begin position="85"/>
            <end position="94"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04067"/>
        </source>
    </evidence>
    <sequence length="121" mass="14331" checksum="2D54724D60302E89" modified="2000-05-01" version="1">MDSNTITSFQDILQRMSKMQLESSSVDLNGMITQFERLKIYRDSLGESMMRMGDLHSLQNRNATWRNELSQKFEEIRWLIAECRNILTKTENSFEQITFLQALQLLLEVESEIRTFSFQLI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-01-10" modified="2021-09-29" version="100" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0L8</accession>
    <name>M1_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Matrix protein 1</fullName>
            <shortName evidence="1">M1</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="1" type="primary">M</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE</scope>
    </reference>
    <comment type="function">
        <text evidence="1">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="function">
        <text evidence="1">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="subunit">
        <text evidence="1">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="1">Virion membrane</location>
            <topology evidence="1">Peripheral membrane protein</topology>
            <orientation evidence="1">Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Q0L8-1</id>
            <name>M1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Q0L9-1</id>
            <name>M2</name>
            <sequence type="external"/>
        </isoform>
        <text>Only the first 9 residues are shared by the 2 isoforms.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="1">Most abundant protein in virion. When expressed alone can form virus-like particles in transfected cells.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the influenza viruses Matrix protein M1 family.</text>
    </comment>
    <dbReference type="EMBL" id="AF144306">
        <property type="protein sequence ID" value="AAD51928.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_308671.1">
        <molecule id="Q9Q0L8-1"/>
        <property type="nucleotide sequence ID" value="NC_007363.1"/>
    </dbReference>
    <dbReference type="SMR" id="Q9Q0L8"/>
    <dbReference type="GeneID" id="8656647"/>
    <dbReference type="KEGG" id="vg:8656647"/>
    <dbReference type="Proteomes" id="UP000131152">
        <property type="component" value="Genome"/>
    </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 id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0694">RNA-binding</keyword>
    <keyword id="KW-0468">Viral matrix protein</keyword>
    <keyword id="KW-0946">Virion</keyword>
    <feature type="chain" id="PRO_0000078856" description="Matrix protein 1">
        <location>
            <begin position="1"/>
            <end position="252"/>
        </location>
    </feature>
    <feature type="region of interest" description="Membrane-binding" evidence="1">
        <location>
            <begin position="1"/>
            <end position="164"/>
        </location>
    </feature>
    <feature type="region of interest" description="RNP-binding" evidence="1">
        <location>
            <begin position="165"/>
            <end position="252"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="1">
        <location>
            <begin position="101"/>
            <end position="105"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04068"/>
        </source>
    </evidence>
    <sequence length="252" mass="27853" checksum="2A482C994E664043" modified="2000-05-01" version="1">MSLLTEVETYVLSIVPSGPLKAEIAQRLEDVFAGKNTDLEALMEWLKTRPILSPLTKGILGFVFTLTVPSERGLQRRRFVQNALNGNGDPNNMDRAVKLYKKLKREITFHGAKEVALSYSTGALASCMGLIYNRMGTVTTEVAFGLVCATCEQIADSQHRSHRQMATTTNPLIRHENRMVLASTTAKAMEQMAGSSEQAAEAMEVASQARQMVQAMRTIGTHPSSSAGLKDNLLENLQAYQKRMGVQMQRFK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-12-06" modified="2021-06-02" version="96" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0L9</accession>
    <name>M2_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Matrix protein 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">Proton channel protein M2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1" type="primary">M</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Virus Res." volume="106" first="147" last="165">
            <title>Assembly and budding of influenza virus.</title>
            <authorList>
                <person name="Nayak D.P."/>
                <person name="Hui E.K."/>
                <person name="Barman S."/>
            </authorList>
            <dbReference type="PubMed" id="15567494"/>
            <dbReference type="DOI" id="10.1016/j.virusres.2004.08.012"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="FEBS Lett." volume="552" first="17" last="22">
            <title>Proton conduction through the M2 protein of the influenza A virus; a quantitative, mechanistic analysis of experimental data.</title>
            <authorList>
                <person name="Lear J.D."/>
            </authorList>
            <dbReference type="PubMed" id="12972146"/>
            <dbReference type="DOI" id="10.1016/S0014-5793(03)00778-6"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2003" name="FEBS Lett." volume="552" first="23" last="27">
            <title>Computational studies of proton transport through the M2 channel.</title>
            <authorList>
                <person name="Wu Y."/>
                <person name="Voth G.A."/>
            </authorList>
            <dbReference type="PubMed" id="12972147"/>
            <dbReference type="DOI" id="10.1016/S0014-5793(03)00779-8"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="1">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>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="1">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="1">Virion membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host apical cell membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <text evidence="1">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="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Q0L9-1</id>
            <name>M2</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Q0L8-1</id>
            <name>M1</name>
            <sequence type="external"/>
        </isoform>
        <text>Only the first 9 residues are shared by the 2 isoforms.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">Cytoplasmic tail plays an important role in virion assembly and morphogenesis.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="1">When the channel is activated, one or more imidazole moieties of His-37 probably become bi-protonated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the influenza viruses matrix protein M2 family.</text>
    </comment>
    <dbReference type="EMBL" id="AF144306">
        <property type="protein sequence ID" value="AAD51929.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_308670.1">
        <molecule id="Q9Q0L9-1"/>
        <property type="nucleotide sequence ID" value="NC_007363.1"/>
    </dbReference>
    <dbReference type="PDB" id="6BKK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=22-46"/>
    </dbReference>
    <dbReference type="PDB" id="6BKL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=22-46"/>
    </dbReference>
    <dbReference type="PDB" id="6BMZ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.63 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=22-46"/>
    </dbReference>
    <dbReference type="PDB" id="6BOC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.25 A"/>
        <property type="chains" value="A/B/C/D=22-46"/>
    </dbReference>
    <dbReference type="PDBsum" id="6BKK"/>
    <dbReference type="PDBsum" id="6BKL"/>
    <dbReference type="PDBsum" id="6BMZ"/>
    <dbReference type="PDBsum" id="6BOC"/>
    <dbReference type="SMR" id="Q9Q0L9"/>
    <dbReference type="GeneID" id="3654621"/>
    <dbReference type="KEGG" id="vg:3654621"/>
    <dbReference type="Proteomes" id="UP000131152">
        <property type="component" value="Genome"/>
    </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="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-1032">Host cell membrane</keyword>
    <keyword id="KW-1043">Host membrane</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0375">Hydrogen ion transport</keyword>
    <keyword id="KW-1083">Inhibition of host autophagy by virus</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0564">Palmitate</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-1182">Viral ion channel</keyword>
    <keyword id="KW-0946">Virion</keyword>
    <feature type="chain" id="PRO_0000078883" description="Matrix protein 2">
        <location>
            <begin position="1"/>
            <end position="97"/>
        </location>
    </feature>
    <feature type="topological domain" description="Virion surface" evidence="1">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type III membrane protein" evidence="1">
        <location>
            <begin position="23"/>
            <end position="43"/>
        </location>
    </feature>
    <feature type="topological domain" description="Intravirion" evidence="1">
        <location>
            <begin position="44"/>
            <end position="97"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="60"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="67"/>
            <end position="83"/>
        </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="1">
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="site" description="Seems to be involved in pH gating" evidence="1">
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by host" evidence="1">
        <location>
            <position position="64"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by host" evidence="1">
        <location>
            <position position="82"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine; by host" evidence="1">
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (with C-17)" evidence="1">
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (with C-19)" evidence="1">
        <location>
            <position position="19"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="25"/>
            <end position="45"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04069"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="3">
        <source>
            <dbReference type="PDB" id="6BKK"/>
        </source>
    </evidence>
    <sequence length="97" mass="11188" checksum="140254760161C7FA" modified="2000-05-01" version="1">MSLLTEVETPTKNEWECKCSDSSDPLVVAASIIGILHLILWILDRLFFKCIYRRLKYGLKRGPSTEGVPESMREEYRQEQQSAVDVDDGHFVNIELE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-06" modified="2021-06-02" version="121" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0U6</accession>
    <accession>Q9WNX2</accession>
    <name>HEMA_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Hemagglutinin</fullName>
        </recommendedName>
        <component>
            <recommendedName>
                <fullName evidence="1">Hemagglutinin HA1 chain</fullName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName evidence="1">Hemagglutinin HA2 chain</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name evidence="1" type="primary">HA</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1999" name="Zhongguo Nong Ye Ke Xue" volume="32" first="87" last="92">
            <title>Molecular analysis of hemagglutinin gene of a goose origin highly pathogenic avian influenza virus.</title>
            <authorList>
                <person name="Chen H."/>
                <person name="Yu K."/>
                <person name="Bu Z."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">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="subunit">
        <text evidence="1">Homotrimer of disulfide-linked HA1-HA2.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Virion membrane</location>
            <topology evidence="1">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host apical cell membrane</location>
            <topology evidence="1">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <text evidence="1">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="1">Palmitoylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">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="miscellaneous">
        <text>Major glycoprotein, comprises over 80% of the envelope proteins present in virus particle.</text>
    </comment>
    <comment type="miscellaneous">
        <text>The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However, HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="2">The influenza A genome consist of 8 RNA segments. Genetic variation of hemagglutinin and/or neuraminidase genes results in the emergence of new influenza strains. The mechanism of variation can be the result of point mutations or the result of genetic reassortment between segments of two different strains.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the influenza viruses hemagglutinin family.</text>
    </comment>
    <dbReference type="EMBL" id="AF144305">
        <property type="protein sequence ID" value="AAD51927.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF148678">
        <property type="protein sequence ID" value="AAD37782.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_308669.1">
        <property type="nucleotide sequence ID" value="NC_007362.1"/>
    </dbReference>
    <dbReference type="PDB" id="3S11">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/C/E=17-339"/>
    </dbReference>
    <dbReference type="PDB" id="4MHH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.56 A"/>
        <property type="chains" value="A/C/E=17-346"/>
    </dbReference>
    <dbReference type="PDB" id="4MHI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/C/E/G/I/K/M/O/Q=17-346, B/D/F/H/J/L/N/P/R=347-521"/>
    </dbReference>
    <dbReference type="PDB" id="4MHJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="6.98 A"/>
        <property type="chains" value="A/C/G/M/O/S=17-346, B/D/I/N/P/U=347-521"/>
    </dbReference>
    <dbReference type="PDBsum" id="3S11"/>
    <dbReference type="PDBsum" id="4MHH"/>
    <dbReference type="PDBsum" id="4MHI"/>
    <dbReference type="PDBsum" id="4MHJ"/>
    <dbReference type="SMR" id="Q9Q0U6"/>
    <dbReference type="UniLectin" id="Q9Q0U6"/>
    <dbReference type="ABCD" id="Q9Q0U6">
        <property type="antibodies" value="2 sequenced antibodies"/>
    </dbReference>
    <dbReference type="GeneID" id="3654620"/>
    <dbReference type="KEGG" id="vg:3654620"/>
    <dbReference type="Proteomes" id="UP000131152">
        <property type="component" value="Genome"/>
    </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">
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    <keyword id="KW-0348">Hemagglutinin</keyword>
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    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0564">Palmitate</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
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    <keyword id="KW-1160">Virus entry into host cell</keyword>
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    <sequence length="568" mass="64257" checksum="FBCD8D114879E52A" modified="2000-05-01" version="1" precursor="true">MEKIVLLLAIVSLVKSDQICIGYHANNSTEQVDTIMEKNVTVTHAQDILEKTHNGKLCDLNGVKPLILRDCSVAGWLLGNPMCDEFINVPEWSYIVEKASPANDLCYPGDFNDYEELKHLLSRTNHFEKIQIIPKSSWSNHDASSGVSSACPYHGRSSFFRNVVWLIKKNSAYPTIKRSYNNTNQEDLLVLWGIHHPNDAAEQTKLYQNPTTYISVGTSTLNQRLVPEIATRPKVNGQSGRMEFFWTILKPNDAINFESNGNFIAPEYAYKIVKKGDSAIMKSELEYGNCNTKCQTPMGAINSSMPFHNIHPLTIGECPKYVKSNRLVLATGLRNTPQRERRRKKRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGYAADKESTQKAIDGVTNKVNSIIDKMNTQFEAVGREFNNLERRIENLNKQMEDGFLDVWTYNAELLVLMENERTLDFHDSNVKNLYDKVRLQLRDNAKELGNGCFEFYHKCDNECMESVKNGTYDYPQYSEEARLNREEISGVKLESMGTYQILSIYSTVASSLALAIMVAGLSLWMCSNGSLQCRICI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-12-06" modified="2022-08-03" version="117" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0U7</accession>
    <name>NRAM_I96A0</name>
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        <recommendedName>
            <fullName evidence="1">Neuraminidase</fullName>
            <ecNumber evidence="1">3.2.1.18</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="1" type="primary">NA</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Virus Res." volume="106" first="147" last="165">
            <title>Assembly and budding of influenza virus.</title>
            <authorList>
                <person name="Nayak D.P."/>
                <person name="Hui E.K."/>
                <person name="Barman S."/>
            </authorList>
            <dbReference type="PubMed" id="15567494"/>
            <dbReference type="DOI" id="10.1016/j.virusres.2004.08.012"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2005" name="N. Engl. J. Med." volume="353" first="1363" last="1373">
            <title>Neuraminidase inhibitors for influenza.</title>
            <authorList>
                <person name="Moscona A."/>
            </authorList>
            <dbReference type="PubMed" id="16192481"/>
            <dbReference type="DOI" id="10.1056/NEJMra050740"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2005" name="Biol. Pharm. Bull." volume="28" first="399" last="408">
            <title>Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses.</title>
            <authorList>
                <person name="Suzuki Y."/>
            </authorList>
            <dbReference type="PubMed" id="15744059"/>
            <dbReference type="DOI" id="10.1248/bpb.28.399"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="1">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 moieties 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="1">
            <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">
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="1">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="1">Homotetramer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Virion membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host apical cell membrane</location>
            <topology evidence="1">Single-pass type II membrane protein</topology>
        </subcellularLocation>
        <text evidence="1">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="1">Intact N-terminus is essential for virion morphogenesis. Possesses 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="1">N-glycosylated.</text>
    </comment>
    <comment type="miscellaneous">
        <text>The influenza A genome consist of 8 RNA segments. Genetic variation of hemagglutinin and/or neuraminidase genes results in the emergence of new influenza strains. The mechanism of variation can be the result of point mutations or the result of genetic reassortment between segments of two different strains.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the glycosyl hydrolase 34 family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAD51926.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
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        <property type="nucleotide sequence ID" value="NC_007361.1"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.59 A"/>
        <property type="chains" value="C/F=449-457"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="C=233-241"/>
    </dbReference>
    <dbReference type="PDB" id="6KWN">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="C=449-457"/>
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    <dbReference type="PDB" id="6KWO">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="C=449-457"/>
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    <dbReference type="CAZy" id="GH34">
        <property type="family name" value="Glycoside Hydrolase Family 34"/>
    </dbReference>
    <dbReference type="GeneID" id="3654619"/>
    <dbReference type="KEGG" id="vg:3654619"/>
    <dbReference type="Proteomes" id="UP000131152">
        <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="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="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="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0106">Calcium</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0326">Glycosidase</keyword>
    <keyword id="KW-1032">Host cell membrane</keyword>
    <keyword id="KW-1043">Host membrane</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0946">Virion</keyword>
    <feature type="chain" id="PRO_0000078691" description="Neuraminidase">
        <location>
            <begin position="1"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="topological domain" description="Intravirion" evidence="1">
        <location>
            <begin position="1"/>
            <end position="6"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="7"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="topological domain" description="Virion surface" evidence="1">
        <location>
            <begin position="28"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="region of interest" description="Involved in apical transport and lipid raft association" evidence="1">
        <location>
            <begin position="11"/>
            <end position="33"/>
        </location>
    </feature>
    <feature type="region of interest" description="Hypervariable stalk region" evidence="1">
        <location>
            <begin position="36"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="region of interest" description="Head of neuraminidase" evidence="1">
        <location>
            <begin position="91"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor/acceptor" evidence="1">
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="active site" description="Nucleophile" evidence="1">
        <location>
            <position position="402"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="118"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="152"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="277"/>
            <end position="278"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="293"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="294"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="298"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="324"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="368"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; by host" evidence="1">
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; by host" evidence="1">
        <location>
            <position position="58"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; by host" evidence="1">
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; by host" evidence="1">
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; by host" evidence="1">
        <location>
            <position position="88"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; by host" evidence="1">
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; by host" evidence="1">
        <location>
            <position position="235"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="92"/>
            <end position="417"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="124"/>
            <end position="129"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="184"/>
            <end position="231"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="233"/>
            <end position="238"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="279"/>
            <end position="292"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="281"/>
            <end position="290"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="318"/>
            <end position="335"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="421"/>
            <end position="446"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04071"/>
        </source>
    </evidence>
    <sequence length="469" mass="51349" checksum="DA87FEF1540CAD99" modified="2000-05-01" version="1">MNPNQKIITIGSICMVVGIISLMLQIGNIISIWVSHSIQTGNQHQAEPCNQSIITYENNTWVNQTYVNISNTNFLTEKAVASVTLAGNSSLCPISGWAVHSKDNGIRIGSKGDVFVIREPFISCSHLECRTFFLTQGALLNDKHSNGTVKDRSPHRTLMSCPVGEAPSPYNSRFESVAWSASACHDGTSWLTIGISGPDNGAVAVLKYNGIITDTIKSWRNNILRTQESECACVNGSCFTVMTDGPSNGQASYKIFKMEKGKVVKSVELNAPNYHYEECSCYPDAGEITCVCRDNWHGSNRPWVSFNQNLEYQIGYICSGVFGDNPRPNDGTGSCGPVSPNGAYGVKGFSFKYGNGVWIGRTKSTNSRSGFEMIWDPNGWTGTDSSFSVKQDIVAITDWSGYSGSFVQHPELTGLDCIRPCFWVELIRGRPKESTIWTSGSSISFCGVNSDTVGWSWPDDAELPFTIDK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2010-11-30" modified="2022-02-23" version="99" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0U8</accession>
    <name>NCAP_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Nucleoprotein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">Nucleocapsid protein</fullName>
            <shortName evidence="1">Protein N</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1" type="primary">NP</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">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="1">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="1">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="1">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="1">Belongs to the influenza viruses nucleoprotein family.</text>
    </comment>
    <dbReference type="EMBL" id="AF144303">
        <property type="protein sequence ID" value="AAD51925.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_308667.1">
        <property type="nucleotide sequence ID" value="NC_007360.1"/>
    </dbReference>
    <dbReference type="PDB" id="4MJ6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.57 A"/>
        <property type="chains" value="C=188-198"/>
    </dbReference>
    <dbReference type="PDB" id="5GJX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.06 A"/>
        <property type="chains" value="C=55-63"/>
    </dbReference>
    <dbReference type="PDB" id="5GJY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.71 A"/>
        <property type="chains" value="C=189-197"/>
    </dbReference>
    <dbReference type="PDB" id="5NQ0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.10 A"/>
        <property type="chains" value="C=290-298"/>
    </dbReference>
    <dbReference type="PDB" id="5NQ1">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.14 A"/>
        <property type="chains" value="C/F=290-298"/>
    </dbReference>
    <dbReference type="PDB" id="5NQ2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.54 A"/>
        <property type="chains" value="C=217-225"/>
    </dbReference>
    <dbReference type="PDB" id="5SWS">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.86 A"/>
        <property type="chains" value="C=366-374"/>
    </dbReference>
    <dbReference type="PDB" id="5SWZ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.65 A"/>
        <property type="chains" value="C/H/M/R=366-374"/>
    </dbReference>
    <dbReference type="PDB" id="6J2A">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.40 A"/>
        <property type="chains" value="C=44-52"/>
    </dbReference>
    <dbReference type="PDB" id="6PBH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.89 A"/>
        <property type="chains" value="C=145-156"/>
    </dbReference>
    <dbReference type="PDB" id="7JWI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.02 A"/>
        <property type="chains" value="C=366-374"/>
    </dbReference>
    <dbReference type="PDB" id="7JWJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.25 A"/>
        <property type="chains" value="C=366-374"/>
    </dbReference>
    <dbReference type="PDB" id="7NUI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="D=380-388"/>
    </dbReference>
    <dbReference type="PDBsum" id="4MJ6"/>
    <dbReference type="PDBsum" id="5GJX"/>
    <dbReference type="PDBsum" id="5GJY"/>
    <dbReference type="PDBsum" id="5NQ0"/>
    <dbReference type="PDBsum" id="5NQ1"/>
    <dbReference type="PDBsum" id="5NQ2"/>
    <dbReference type="PDBsum" id="5SWS"/>
    <dbReference type="PDBsum" id="5SWZ"/>
    <dbReference type="PDBsum" id="6J2A"/>
    <dbReference type="PDBsum" id="6PBH"/>
    <dbReference type="PDBsum" id="7JWI"/>
    <dbReference type="PDBsum" id="7JWJ"/>
    <dbReference type="PDBsum" id="7NUI"/>
    <dbReference type="SMR" id="Q9Q0U8"/>
    <dbReference type="GeneID" id="3654618"/>
    <dbReference type="KEGG" id="vg:3654618"/>
    <dbReference type="PRO" id="PR:Q9Q0U8"/>
    <dbReference type="Proteomes" id="UP000131152">
        <property type="component" value="Genome"/>
    </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="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0167">Capsid protein</keyword>
    <keyword id="KW-1139">Helical capsid protein</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0687">Ribonucleoprotein</keyword>
    <keyword id="KW-0694">RNA-binding</keyword>
    <keyword id="KW-0543">Viral nucleoprotein</keyword>
    <keyword id="KW-1163">Viral penetration into host nucleus</keyword>
    <keyword id="KW-0946">Virion</keyword>
    <keyword id="KW-1160">Virus entry into host cell</keyword>
    <feature type="chain" id="PRO_0000402424" description="Nucleoprotein">
        <location>
            <begin position="1"/>
            <end position="498"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Unconventional nuclear localization signal" evidence="1">
        <location>
            <begin position="1"/>
            <end position="18"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Bipartite nuclear localization signal" evidence="1">
        <location>
            <begin position="198"/>
            <end position="216"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04070"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <sequence length="498" mass="56258" checksum="323C73609C7C129E" modified="2000-05-01" version="1">MASQGTKRSYEQMETGGERQNATEIRASVGRMVGGIGRFYIQMCTELKLSDYEGRLIQNSITIERMVLSAFDERRNKYLEEHPSAGKDPKKTGGPIYRRRDGKWVRELILYDKEEIRRIWRQANNGEDATAGLTHMMIWHSNLNDATYQRTRALVRTGMDPRMCSLMQGSTLPRRSGAAGAAVKGVGTMVMELIRMIKRGINDRNFWRGENGRRTRIAYERMCNILKGKFQTAAQRAMMDQVRESRNPGNAEIEDLIFLARSALILRGSVAHKSCLPACVYGLAVASGYDFEREGYSLVGIDPFRLLQNSQVFSLIRPNENPAHKSQLVWMACHSAAFEDLRVSSFIRGTRVAPRGQLSTRGVQIASNENMETMDSSTLELRSRYWAIRTRSGGNTNQQRASAGQISVQPTFSVQRNLPFERATIMAAFTGNTEGRTSDMRTEIIRMMESSRPEDVSFQGRGVFELSDEKATNPIVPSFDMSNEGSYFFGDNAEEYDN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-06" modified="2022-08-03" version="95" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0U9</accession>
    <name>PA_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="2">Polymerase acidic protein</fullName>
            <ecNumber evidence="2">3.1.-.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="2">RNA-directed RNA polymerase subunit P2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="2" type="primary">PA</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2009" name="Nature" volume="458" first="909" last="913">
            <title>Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site.</title>
            <authorList>
                <person name="Yuan P."/>
                <person name="Bartlam M."/>
                <person name="Lou Z."/>
                <person name="Chen S."/>
                <person name="Zhou J."/>
                <person name="He X."/>
                <person name="Lv Z."/>
                <person name="Ge R."/>
                <person name="Li X."/>
                <person name="Deng T."/>
                <person name="Fodor E."/>
                <person name="Rao Z."/>
                <person name="Liu Y."/>
            </authorList>
            <dbReference type="PubMed" id="19194458"/>
            <dbReference type="DOI" id="10.1038/nature07720"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-256</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="2">Binds 2 manganese ions per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2">Influenza RNA polymerase is composed of three subunits: PB1, PB2 and PA. Interacts (via C-terminus) with PB1 (via N-terminus).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-15715136">
            <id>Q9Q0U9</id>
        </interactant>
        <interactant intactId="EBI-8290908">
            <id>Q9Q0V0</id>
            <label>PB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Host cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Host nucleus</location>
        </subcellularLocation>
        <text evidence="1 2">PB1 and PA are transported in the host nucleus as a complex.</text>
    </comment>
    <comment type="alternative products">
        <event type="ribosomal frameshifting"/>
        <isoform>
            <id>Q9Q0U9-1</id>
            <name>PA</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P0CK63-1</id>
            <name>PA-X</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="1 2">Phosphorylated on serines and threonines by host kinases, including human casein kinase II.</text>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the influenza viruses PA family.</text>
    </comment>
    <dbReference type="EC" id="3.1.-.-" evidence="2"/>
    <dbReference type="EMBL" id="AF144302">
        <property type="protein sequence ID" value="AAD51924.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_308666.1">
        <molecule id="Q9Q0U9-1"/>
        <property type="nucleotide sequence ID" value="NC_007359.1"/>
    </dbReference>
    <dbReference type="PDB" id="3EBJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B/C/D=1-256"/>
    </dbReference>
    <dbReference type="PDB" id="3HW3">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B/C/D=1-256"/>
    </dbReference>
    <dbReference type="PDB" id="3HW4">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B/C/D=1-256"/>
    </dbReference>
    <dbReference type="PDB" id="3HW5">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.81 A"/>
        <property type="chains" value="A/B/C/D=1-256"/>
    </dbReference>
    <dbReference type="PDB" id="3HW6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B/C/D=1-256"/>
    </dbReference>
    <dbReference type="PDBsum" id="3EBJ"/>
    <dbReference type="PDBsum" id="3HW3"/>
    <dbReference type="PDBsum" id="3HW4"/>
    <dbReference type="PDBsum" id="3HW5"/>
    <dbReference type="PDBsum" id="3HW6"/>
    <dbReference type="SMR" id="Q9Q0U9"/>
    <dbReference type="DIP" id="DIP-59837N"/>
    <dbReference type="IntAct" id="Q9Q0U9">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="MEROPS" id="S62.001"/>
    <dbReference type="PRIDE" id="Q9Q0U9"/>
    <dbReference type="GeneID" id="3654617"/>
    <dbReference type="KEGG" id="vg:3654617"/>
    <dbReference type="EvolutionaryTrace" id="Q9Q0U9"/>
    <dbReference type="Proteomes" id="UP000131152">
        <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:0004519">
        <property type="term" value="F:endonuclease activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <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-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="3.40.91.90">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04063">
        <property type="entry name" value="INFV_PA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037534">
        <property type="entry name" value="INFV_PA"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001009">
        <property type="entry name" value="PA/PA-X"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038372">
        <property type="entry name" value="PA/PA-X_sf"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00603">
        <property type="entry name" value="Flu_PA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-1157">Cap snatching</keyword>
    <keyword id="KW-0255">Endonuclease</keyword>
    <keyword id="KW-1262">Eukaryotic host gene expression shutoff by virus</keyword>
    <keyword id="KW-1191">Eukaryotic host transcription shutoff by virus</keyword>
    <keyword id="KW-1035">Host cytoplasm</keyword>
    <keyword id="KW-1190">Host gene expression shutoff by virus</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1104">Inhibition of host RNA polymerase II by virus</keyword>
    <keyword id="KW-0464">Manganese</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0540">Nuclease</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0688">Ribosomal frameshifting</keyword>
    <feature type="chain" id="PRO_0000279246" description="Polymerase acidic protein">
        <location>
            <begin position="1"/>
            <end position="716"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal 1 (NLS1)" evidence="1 2">
        <location>
            <begin position="124"/>
            <end position="139"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal 2 (NLS2)" evidence="1 2">
        <location>
            <begin position="184"/>
            <end position="247"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="41"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="80"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="108"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="108"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="119"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="120"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="1"/>
            <end position="8"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="11"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="turn" evidence="3">
        <location>
            <begin position="28"/>
            <end position="30"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="32"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="strand" evidence="3">
        <location>
            <begin position="76"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="84"/>
            <end position="97"/>
        </location>
    </feature>
    <feature type="strand" evidence="3">
        <location>
            <begin position="108"/>
            <end position="111"/>
        </location>
    </feature>
    <feature type="turn" evidence="3">
        <location>
            <begin position="112"/>
            <end position="115"/>
        </location>
    </feature>
    <feature type="strand" evidence="3">
        <location>
            <begin position="116"/>
            <end position="125"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="127"/>
            <end position="138"/>
        </location>
    </feature>
    <feature type="strand" evidence="3">
        <location>
            <begin position="144"/>
            <end position="149"/>
        </location>
    </feature>
    <feature type="strand" evidence="3">
        <location>
            <begin position="154"/>
            <end position="156"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="157"/>
            <end position="159"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="165"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="188"/>
            <end position="193"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P03433"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04063"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="3">
        <source>
            <dbReference type="PDB" id="3HW5"/>
        </source>
    </evidence>
    <sequence length="716" mass="82673" checksum="C89CE96EB4BB71CB" modified="2000-05-01" version="1">MEDFVRQCFNPMIVELAEKAMKEYGEDPKIETNKFAAICTHLEVCFMYSDFHFIDERGESTIIESGDPNALLKHRFEIIEGRDRTMAWTVVNSICNTTGVEKPKFLPDLYDYKENRFIEIGVTRREVHTYYLEKANKIKSEKTHIHIFSFTGEEMATKADYTLDEESRARIKTRLFTIRQEMASRGLWDSFRQSERGEETVEERFEITGTMCRLADQSLPPNFSSLEKFRAYVDGFEPNGCIEGKLSQMSKEVNARIEPFLKTTPRPLRLPDGPPCSQRSKFLLMDALKLSIEDPSHEGEGIPLYDAIKCMKTFFGWKEPNIVKPHEKGINPNYLLAWKQVLAELQDIENEEKIPKTKNMRKTSQLKWALGENMAPEKVDFEDCKDVSDLRQYDSDEPKPRSLASWIQSEFNKACELTDSSWIELDEIGEDVAPIEHIASMRRNYFTAEVSHCRATEYIMKGVYINTALLNASCAAMDDFQLIPMISKCRTKEGRRKTNLYGFLIKGRSHLRNDTDVVNFVSMEFSLTDPRLEPHRWEKYCVLRIGDMLLRTEIGQVSRPMFLYVRTNGTSKIKMKWGMEMRRCPFQSLQQIESMIEAESSVKEKDMTKEFFENKSETWPIGESPKGVEEGSIGKVCRTLLAKSVFNSLYASPQLEGFSAESRKLLLIVQALRDNLEPGTFDLGGLYEAIEECLINDPWVLLNASWFNSFLTHALR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-06" modified="2022-02-23" version="93" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0V0</accession>
    <name>RDRP_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">RNA-directed RNA polymerase catalytic subunit</fullName>
            <ecNumber evidence="1">2.7.7.48</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">Polymerase basic protein 1</fullName>
            <shortName evidence="1">PB1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">RNA-directed RNA polymerase subunit P1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1" type="primary">PB1</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">RNA-dependent RNA polymerase which is responsible for replication and transcription of virus RNA segments. The transcription of viral mRNAs occurs by a unique mechanism called cap-snatching. 5' methylated caps of cellular mRNAs are cleaved after 10-13 nucleotides by PA. In turn, these short capped RNAs are used as primers by PB1 for transcription of viral mRNAs. During virus replication, PB1 initiates RNA synthesis and copy vRNA into complementary RNA (cRNA) which in turn serves as a template for the production of more vRNAs.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1)</text>
            <dbReference type="Rhea" id="RHEA:21248"/>
            <dbReference type="Rhea" id="RHEA-COMP:14527"/>
            <dbReference type="Rhea" id="RHEA-COMP:17342"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:61557"/>
            <dbReference type="ChEBI" id="CHEBI:140395"/>
            <dbReference type="EC" id="2.7.7.48"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="1">Influenza RNA polymerase is composed of three subunits: PB1, PB2 and PA. Interacts (via N-terminus) with PA (via C-terminus). Interacts (via C-terminus) with PB2 (via N-terminus); this interaction is essential for transcription initiation.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8290908">
            <id>Q9Q0V0</id>
        </interactant>
        <interactant intactId="EBI-15715136">
            <id>Q9Q0U9</id>
            <label>PA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8290908">
            <id>Q9Q0V0</id>
        </interactant>
        <interactant intactId="EBI-8290908">
            <id>Q9Q0V0</id>
            <label>PB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8290908">
            <id>Q9Q0V0</id>
        </interactant>
        <interactant intactId="EBI-8290926">
            <id>Q9Q0V1</id>
            <label>PB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylated by host PRKCA.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the influenza viruses polymerase PB1 family.</text>
    </comment>
    <dbReference type="EC" id="2.7.7.48" evidence="1"/>
    <dbReference type="EMBL" id="AF144301">
        <property type="protein sequence ID" value="AAD51923.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_308665.1">
        <property type="nucleotide sequence ID" value="NC_007358.1"/>
    </dbReference>
    <dbReference type="PDB" id="3J9B">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.30 A"/>
        <property type="chains" value="B/I=1-24"/>
    </dbReference>
    <dbReference type="PDBsum" id="3J9B"/>
    <dbReference type="SMR" id="Q9Q0V0"/>
    <dbReference type="DIP" id="DIP-59838N"/>
    <dbReference type="IntAct" id="Q9Q0V0">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="MINT" id="Q9Q0V0"/>
    <dbReference type="GeneID" id="3654616"/>
    <dbReference type="KEGG" id="vg:3654616"/>
    <dbReference type="Proteomes" id="UP000131152">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04065">
        <property type="entry name" value="INFV_RDRP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007099">
        <property type="entry name" value="RNA-dir_pol_NSvirus"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001407">
        <property type="entry name" value="RNA_pol_PB1_influenza"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00602">
        <property type="entry name" value="Flu_PB1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF000827">
        <property type="entry name" value="RdRPol_OMV"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50525">
        <property type="entry name" value="RDRP_SSRNA_NEG_SEG"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-1262">Eukaryotic host gene expression shutoff by virus</keyword>
    <keyword id="KW-1191">Eukaryotic host transcription shutoff by virus</keyword>
    <keyword id="KW-1035">Host cytoplasm</keyword>
    <keyword id="KW-1190">Host gene expression shutoff by virus</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-1104">Inhibition of host RNA polymerase II by virus</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0548">Nucleotidyltransferase</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0696">RNA-directed RNA polymerase</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0693">Viral RNA replication</keyword>
    <keyword id="KW-1195">Viral transcription</keyword>
    <feature type="chain" id="PRO_0000279596" description="RNA-directed RNA polymerase catalytic subunit">
        <location>
            <begin position="1"/>
            <end position="757"/>
        </location>
    </feature>
    <feature type="domain" description="RdRp catalytic" evidence="1">
        <location>
            <begin position="286"/>
            <end position="483"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="50"/>
            <end position="82"/>
        </location>
    </feature>
    <feature type="region of interest" description="Promoter-binding site" evidence="1">
        <location>
            <begin position="249"/>
            <end position="256"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="1">
        <location>
            <begin position="187"/>
            <end position="195"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="1">
        <location>
            <begin position="203"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="2">
        <location>
            <begin position="50"/>
            <end position="65"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <sequence length="757" mass="86177" checksum="D3F07429E0421159" modified="2000-05-01" version="1">MDVNPTLLFLKVPAQNAISTTFPYTGDPPYSHGTGTGYTMDTVNRTHQYSEKGKWTTNTETGAPQLNPIDGPLPEDNEPSGYAQTDCVLEAMAFLEESHPGIFENSCLETMEVVQQTRVDKLTQGRQTYDWTLKRNQPAATALANTIEVFRSNGLTANESGRLIDFLKDVMESMDKGEMEIITHFQRKRRVRDNMTKKMVTQRTIGKKKQRLNKRSYLIRALTLNTMTKDAERGKLKRRAIATPGMQIRGFVYFVETLARSICEKLEQSGLPVGGNEKKAKLANVVRKMMTNSQDTELSFTITGDNTKWNENQNPRMFLAMITYITRNQPEWFRNVLSIAPIMFSNKMARLGKGYMFESKSMKLRTQIPAEMLASIDLKYFNESTRKKIEKIRPLLIDGTASLSPGMMMGMFNMLSTVLGVSILNLGQKRYTKTTYWWDGLQSSDDFALIVNAPNHEGIEAGVDRFYRTCKLVGINMTKKKSYINRTGTCEFTSFFYRYGFVANFSMELPSFGVSGINESADMSIGVTVIKNNMMDNDLGPATAQMALQLFIKDYRYPYRCHRGDTQIQTRRSFELKKLWEQTRSKAGLLVSDGGPNPYNIRNLHIPEAGLKWELMDEDYQGRLCNPLNPFVSHKEIESVNNAVVMPAHGPAKSMEYDAVATTHSWIPKRNRSILNTSQRGILEDEQMYQKCCNLFEKFFPSSSYRRPVGISSMVEAMVSRARIDARIDFESGRIKKEEFAEIMKICSTIEELGRQK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-06" modified="2022-08-03" version="104" xmlns="http://uniprot.org/uniprot">
    <accession>Q9Q0V1</accession>
    <name>PB2_I96A0</name>
    <protein>
        <recommendedName>
            <fullName evidence="2">Polymerase basic protein 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="2">RNA-directed RNA polymerase subunit P3</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="2" type="primary">PB2</name>
    </gene>
    <organism>
        <name type="scientific">Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd)</name>
        <dbReference type="NCBI Taxonomy" id="93838"/>
        <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>
    <organismHost>
        <name type="scientific">Aves</name>
        <name type="common">birds</name>
        <dbReference type="NCBI Taxonomy" id="8782"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Felis catus</name>
        <name type="common">Cat</name>
        <name type="synonym">Felis silvestris catus</name>
        <dbReference type="NCBI Taxonomy" id="9685"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera pardus</name>
        <name type="common">Leopard</name>
        <name type="synonym">Felis pardus</name>
        <dbReference type="NCBI Taxonomy" id="9691"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Panthera tigris</name>
        <name type="common">Tiger</name>
        <dbReference type="NCBI Taxonomy" id="9694"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Sus scrofa</name>
        <name type="common">Pig</name>
        <dbReference type="NCBI Taxonomy" id="9823"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1999" name="Virology" volume="261" first="15" last="19">
            <title>Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Subbarao K."/>
                <person name="Cox N.J."/>
                <person name="Guo Y."/>
            </authorList>
            <dbReference type="PubMed" id="10484749"/>
            <dbReference type="DOI" id="10.1006/viro.1999.9820"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC RNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="2">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="2">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="interaction">
        <interactant intactId="EBI-8290926">
            <id>Q9Q0V1</id>
        </interactant>
        <interactant intactId="EBI-8290908">
            <id>Q9Q0V0</id>
            <label>PB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Q0V1-1</id>
            <name>Polymerase basic protein 2</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P0DOG5-1</id>
            <name evidence="1">PB2-S1</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the influenza viruses PB2 family.</text>
    </comment>
    <dbReference type="EMBL" id="AF144300">
        <property type="protein sequence ID" value="AAD51922.1"/>
        <property type="molecule type" value="Genomic_RNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_308664.1">
        <molecule id="Q9Q0V1-1"/>
        <property type="nucleotide sequence ID" value="NC_007357.1"/>
    </dbReference>
    <dbReference type="SMR" id="Q9Q0V1"/>
    <dbReference type="IntAct" id="Q9Q0V1">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="MINT" id="Q9Q0V1"/>
    <dbReference type="GeneID" id="3654615"/>
    <dbReference type="KEGG" id="vg:3654615"/>
    <dbReference type="PRO" id="PR:Q9Q0V1"/>
    <dbReference type="Proteomes" id="UP000131152">
        <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: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="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1157">Cap snatching</keyword>
    <keyword id="KW-1262">Eukaryotic host gene expression shutoff by virus</keyword>
    <keyword id="KW-1191">Eukaryotic host transcription shutoff by virus</keyword>
    <keyword id="KW-1190">Host gene expression shutoff by virus</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-1104">Inhibition of host RNA polymerase II by virus</keyword>
    <keyword id="KW-0506">mRNA capping</keyword>
    <keyword id="KW-0507">mRNA processing</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-1195">Viral transcription</keyword>
    <keyword id="KW-0946">Virion</keyword>
    <feature type="chain" id="PRO_0000279631" description="Polymerase basic protein 2">
        <location>
            <begin position="1"/>
            <end position="759"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="2">
        <location>
            <begin position="736"/>
            <end position="739"/>
        </location>
    </feature>
    <feature type="site" description="Avian adaptation" evidence="2">
        <location>
            <position position="627"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P03427"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04062"/>
        </source>
    </evidence>
    <sequence length="759" mass="85972" checksum="F9C2D08303F2786D" modified="2000-05-01" version="1">MERIKELRDLMSQSRTREILTKTTVDHMAIIKKYTSGRQEKNPALRMKWMMAMKYPITADKRIMEMIPERNEQGQTLWSKTNDAGSDRVMVSPLAVTWWNRNGPTTSTVHYPKVYKTYFEKVERLKHGTFGPVHFRNQVKIRRRVDINPGHADLSAKEAQDVIMEVVFPNEVGARILTSESQLTITKEKKEELQDCKIAPLMVAYMLERELVRKTRFLPVAGGTSSVYIEVLHLTQGTCWEQMYTPGGEVRNDDVDQSLIIAARNIVRRATVSADPLASLLEMCHSTQIGGIRMVDILRQNPTEEQAVDICKAAMGLRISSSFSFGGFTFKRTNGSSVKKEEEVLTGNLQTLKIKVHEGYEEFTMVGRRATAILRKATRRLIQLIVSGRDEQSIAEAIIVAMVFSQEDCMIKAVRGDLNFVNRANQRLNPMHQLLRHFQKDAKVLFQNWGIEPIDNVMGMIGILPDMTPSAEMSLRGVRVSKMGVDEYSSTERVVVSIDRFLRVRDQQGNVLLSPEEVSETQGTEKLTITYSSSMMWEINGPESVLVNTYQWIIRNWETVKIQWSQDPTMLYNKMEFESFQSLVPKAARSQYSGFVRTLFQQMRDVLGTFDTVQIIKLLPFAAAPPEPSRMQFSSLTVNVRGSGMRILVRGNSPVFNYNKATKRLTVLGKDAGALTEDPDEGTAGVESAVLRGFLILGREDKRYGPALSINELSNLAKGEKANVLIMQGDVVLVMKRKRDFSILTDSQTATKRIRMAIN</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>