<?xml version="1.0" encoding="UTF-8"?>
<uniprot xmlns="http://uniprot.org/uniprot"
 xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
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<entry dataset="Swiss-Prot" created="1996-10-01" modified="2022-02-23" version="81" xmlns="http://uniprot.org/uniprot">
    <accession>P50818</accession>
    <accession>Q80933</accession>
    <name>VL1_HPV50</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Major capsid protein L1</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="1" type="primary">L1</name>
    </gene>
    <organism>
        <name type="scientific">Human papillomavirus type 50</name>
        <dbReference type="NCBI Taxonomy" id="40539"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Papovaviricetes</taxon>
            <taxon>Zurhausenvirales</taxon>
            <taxon>Papillomaviridae</taxon>
            <taxon>Firstpapillomavirinae</taxon>
            <taxon>Gammapapillomavirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="submission" date="1995-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Delius H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1995" name="J. Virol." volume="69" first="3074" last="3083">
            <title>Analysis of genomic sequences of 95 papillomavirus types: uniting typing, phylogeny, and taxonomy.</title>
            <authorList>
                <person name="Chan S.-Y."/>
                <person name="Delius H."/>
                <person name="Halpern A.L."/>
                <person name="Bernard H.U."/>
            </authorList>
            <dbReference type="PubMed" id="7707535"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 380-475</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with L2 proteins. Binds to heparan sulfate proteoglycans on cell surface of basal layer keratinocytes to provide initial virion attachment. This binding mediates a conformational change in the virus capsid that facilitates efficient infection. The virion enters the host cell via endocytosis. During virus trafficking, L1 protein dissociates from the viral DNA and the genomic DNA is released to the host nucleus. The virion assembly takes place within the cell nucleus. Encapsulates the genomic DNA together with protein L2.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Self-assembles into homopentamers. The capsid has an icosahedral symmetry and consists of 72 capsomers, with each capsomer being a pentamer of L1. Interacts with the minor capsid protein L2; this interaction is necessary for viral genome encapsidation. Interacts with protein E2; this interaction enhances E2-dependent replication and transcription activation.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the papillomaviridae L1 protein family.</text>
    </comment>
    <dbReference type="EMBL" id="U31790">
        <property type="protein sequence ID" value="AAA79477.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U21870">
        <property type="protein sequence ID" value="AAA92832.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_043429.1">
        <property type="nucleotide sequence ID" value="NC_001691.1"/>
    </dbReference>
    <dbReference type="SMR" id="P50818"/>
    <dbReference type="GeneID" id="1403635"/>
    <dbReference type="KEGG" id="vg:1403635"/>
    <dbReference type="Proteomes" id="UP000168289">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.175.20">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04002">
        <property type="entry name" value="PPV_L1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002210">
        <property type="entry name" value="Capsid_L1_Papillomavir"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036973">
        <property type="entry name" value="Capsid_L1_sf_Papillomavir"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011222">
        <property type="entry name" value="dsDNA_vir_gr_I_capsid"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00500">
        <property type="entry name" value="Late_protein_L1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00865">
        <property type="entry name" value="HPVCAPSIDL1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF88648">
        <property type="entry name" value="SSF88648"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0167">Capsid protein</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0426">Late protein</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-1145">T=7 icosahedral capsid protein</keyword>
    <keyword id="KW-1161">Viral attachment to host cell</keyword>
    <keyword id="KW-1162">Viral penetration into host cytoplasm</keyword>
    <keyword id="KW-0946">Virion</keyword>
    <keyword id="KW-1164">Virus endocytosis by host</keyword>
    <keyword id="KW-1160">Virus entry into host cell</keyword>
    <feature type="chain" id="PRO_0000133533" description="Major capsid protein L1">
        <location>
            <begin position="1"/>
            <end position="515"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (with C-445)" evidence="1">
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (with C-174)" evidence="1">
        <location>
            <position position="445"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04002"/>
        </source>
    </evidence>
    <sequence length="515" mass="58426" checksum="0D79EA3A1A215BC0" modified="1998-07-15" version="2"> </sequence>
</entry>
<entry dataset="TrEMBL" created="1996-11-01" modified="2022-05-25" version="91" xmlns="http://uniprot.org/uniprot">
    <accession>Q80927</accession>
    <name>Q80927_HPV50</name>
    <protein>
        <recommendedName>
            <fullName evidence="3 4">Protein E6</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="3 5" type="primary">E6</name>
    </gene>
    <organism evidence="5 6">
        <name type="scientific">Human papillomavirus type 50</name>
        <dbReference type="NCBI Taxonomy" id="40539"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Papovaviricetes</taxon>
            <taxon>Zurhausenvirales</taxon>
            <taxon>Papillomaviridae</taxon>
            <taxon>Firstpapillomavirinae</taxon>
            <taxon>Gammapapillomavirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference evidence="5 6" key="1">
        <citation type="journal article" date="1989" name="J. Virol." volume="63" first="4910" last="4910">
            <title>Human papillomavirus (HPV) type 50, a type associated with epidermodysplasia verruciformis (EV) and only weakly related to other EV-specific HPVs.</title>
            <authorList>
                <person name="Favre M."/>
                <person name="Obalek S."/>
                <person name="Jablonska S."/>
                <person name="Orth G."/>
            </authorList>
            <dbReference type="PubMed" id="2552168"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="3">Plays a major role in the induction and maintenance of cellular transformation. E6 associates with host UBE3A/E6-AP ubiquitin-protein ligase and modulates its activity. Protects host keratinocytes from apoptosis by mediating the degradation of host BAK1. May also inhibit host immune response.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3">Forms homodimers. Interacts with ubiquitin-protein ligase UBE3A/E6-AP; this interaction stimulates UBE3A ubiquitin activity. Interacts with host BAK1.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3 4">Host cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3 4">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="1 3 4">Belongs to the papillomaviridae E6 protein family.</text>
    </comment>
    <comment type="caution">
        <text evidence="3">Lacks conserved residue(s) required for the propagation of feature annotation.</text>
    </comment>
    <dbReference type="EMBL" id="U31790">
        <property type="protein sequence ID" value="AAA79471.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_043423.1">
        <property type="nucleotide sequence ID" value="NC_001691.1"/>
    </dbReference>
    <dbReference type="SMR" id="Q80927"/>
    <dbReference type="GeneID" id="1403629"/>
    <dbReference type="KEGG" id="vg:1403629"/>
    <dbReference type="Proteomes" id="UP000168289">
        <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:0003677">
        <property type="term" value="F:DNA binding"/>
        <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:0039526">
        <property type="term" value="P:modulation by virus of host apoptotic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039649">
        <property type="term" value="P:modulation by virus of host ubiquitin-protein ligase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006355">
        <property type="term" value="P:regulation of transcription, DNA-templated"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039502">
        <property type="term" value="P:suppression by virus of host type I interferon-mediated signaling pathway"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-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="Gene3D" id="3.30.240.40">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04006">
        <property type="entry name" value="HPV_E6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001334">
        <property type="entry name" value="E6"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038575">
        <property type="entry name" value="E6_sf"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00518">
        <property type="entry name" value="E6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF161229">
        <property type="entry name" value="SSF161229"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="3 4" id="KW-0010">Activator</keyword>
    <keyword evidence="3 4" id="KW-0238">DNA-binding</keyword>
    <keyword evidence="3 4" id="KW-0244">Early protein</keyword>
    <keyword evidence="3" id="KW-1035">Host cytoplasm</keyword>
    <keyword evidence="3 4" id="KW-1048">Host nucleus</keyword>
    <keyword evidence="3" id="KW-0945">Host-virus interaction</keyword>
    <keyword evidence="3" id="KW-1090">Inhibition of host innate immune response by virus</keyword>
    <keyword evidence="3 4" id="KW-0479">Metal-binding</keyword>
    <keyword evidence="2 3" id="KW-1119">Modulation of host cell apoptosis by virus</keyword>
    <keyword evidence="6" id="KW-1185">Reference proteome</keyword>
    <keyword evidence="3 4" id="KW-0804">Transcription</keyword>
    <keyword evidence="3 4" id="KW-0805">Transcription regulation</keyword>
    <keyword evidence="3" id="KW-0899">Viral immunoevasion</keyword>
    <keyword evidence="3 4" id="KW-0862">Zinc</keyword>
    <keyword evidence="3 4" id="KW-0863">Zinc-finger</keyword>
    <feature type="zinc finger region" evidence="3">
        <location>
            <begin position="27"/>
            <end position="63"/>
        </location>
    </feature>
    <feature type="zinc finger region" evidence="3">
        <location>
            <begin position="100"/>
            <end position="136"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00006346"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00023323"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04006"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="RuleBase" id="RU363123"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="5">
        <source>
            <dbReference type="EMBL" id="AAA79471.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="6">
        <source>
            <dbReference type="Proteomes" id="UP000168289"/>
        </source>
    </evidence>
    <sequence length="141" mass="16410" checksum="6405CF758072B5B1" modified="1996-11-01" version="1">MEPQRAKNLVDYCKQQQISFFELELQCLFCKFVITLPDLASFHCKKLALVYRDGIAFAACAKCLRLSAIFENERYYTCSIKAYLLSDLIGRPLSEIAIRCENCMCLLDYIEKYDCICHGGYFHLVRGNWRGCCRNCYEHEG</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1998-07-15" modified="2022-08-03" version="86" xmlns="http://uniprot.org/uniprot">
    <accession>Q80928</accession>
    <name>VE7_HPV50</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Protein E7</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="1" type="primary">E7</name>
    </gene>
    <organism>
        <name type="scientific">Human papillomavirus type 50</name>
        <dbReference type="NCBI Taxonomy" id="40539"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Papovaviricetes</taxon>
            <taxon>Zurhausenvirales</taxon>
            <taxon>Papillomaviridae</taxon>
            <taxon>Firstpapillomavirinae</taxon>
            <taxon>Gammapapillomavirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="submission" date="1995-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Delius H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2002" name="Rev. Med. Virol." volume="12" first="81" last="92">
            <title>Interactions of SV40 large T antigen and other viral proteins with retinoblastoma tumour suppressor.</title>
            <authorList>
                <person name="Lee C."/>
                <person name="Cho Y."/>
            </authorList>
            <dbReference type="PubMed" id="11921304"/>
            <dbReference type="DOI" id="10.1002/rmv.340"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. E7 protein has both transforming and trans-activating activities. Induces the disassembly of the E2F1 transcription factor from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Interferes with host histone deacetylation mediated by HDAC1 and HDAC2, leading to transcription activation. Also plays a role in the inhibition of both antiviral and antiproliferative functions of host interferon alpha. Interaction with host TMEM173/STING impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homodimer. Homooligomer. Interacts with host RB1; this interaction induces dissociation of RB1-E2F1 complex thereby disrupting RB1 activity. Interacts with host EP300; this interaction represses EP300 transcriptional activity. Interacts with protein E2; this interaction inhibits E7 oncogenic activity. Interacts with host TMEM173/STING; this interaction impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Host cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
        <text evidence="1">Predominantly found in the host nucleus.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The E7 terminal domain is an intrinsically disordered domain, whose flexibility and conformational transitions confer target adaptability to the oncoprotein. It allows adaptation to a variety of protein targets and exposes the PEST degradation sequence that regulates its turnover in the cell.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Highly phosphorylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the papillomaviridae E7 protein family.</text>
    </comment>
    <dbReference type="EMBL" id="U31790">
        <property type="protein sequence ID" value="AAA79472.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_043424.1">
        <property type="nucleotide sequence ID" value="NC_001691.1"/>
    </dbReference>
    <dbReference type="SMR" id="Q80928"/>
    <dbReference type="GeneID" id="1403630"/>
    <dbReference type="KEGG" id="vg:1403630"/>
    <dbReference type="Proteomes" id="UP000168289">
        <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:0003677">
        <property type="term" value="F:DNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003700">
        <property type="term" value="F:DNA-binding transcription factor 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:0019904">
        <property type="term" value="F:protein domain specific binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039645">
        <property type="term" value="P:modulation by virus of host G1/S transition checkpoint"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039502">
        <property type="term" value="P:suppression by virus of host type I interferon-mediated signaling pathway"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-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="HAMAP" id="MF_04004">
        <property type="entry name" value="PPV_E7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000148">
        <property type="entry name" value="Papilloma_E7"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00527">
        <property type="entry name" value="E7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF003407">
        <property type="entry name" value="Papvi_E7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0010">Activator</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0244">Early protein</keyword>
    <keyword id="KW-1078">G1/S host cell cycle checkpoint dysregulation by virus</keyword>
    <keyword id="KW-1035">Host cytoplasm</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-0479">Metal-binding</keyword>
    <keyword id="KW-1121">Modulation of host cell cycle by virus</keyword>
    <keyword id="KW-0553">Oncogene</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <keyword id="KW-0899">Viral immunoevasion</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000133446" description="Protein E7">
        <location>
            <begin position="1"/>
            <end position="93"/>
        </location>
    </feature>
    <feature type="zinc finger region" evidence="1">
        <location>
            <begin position="47"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="region of interest" description="E7 terminal domain" evidence="1">
        <location>
            <begin position="1"/>
            <end position="39"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="1">
        <location>
            <begin position="65"/>
            <end position="73"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04004"/>
        </source>
    </evidence>
    <sequence length="93" mass="10516" checksum="65F1942EF3AAE9C8" modified="1996-11-01" version="1">MRGDKPTIPDIVLEELVLPVNLLSDESIETDDIAESERSPFKIDSTCKHCHCRVRLCCVATDAAIRVFECLLQSEFSFLCLKCSKELLRNGRT</sequence>
</entry>
<entry dataset="TrEMBL" created="1996-11-01" modified="2022-08-03" version="116" xmlns="http://uniprot.org/uniprot">
    <accession>Q80929</accession>
    <name>Q80929_HPV50</name>
    <protein>
        <recommendedName>
            <fullName evidence="9 10">Replication protein E1</fullName>
            <ecNumber evidence="9 10">3.6.4.12</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="9">ATP-dependent helicase E1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="9 13" type="primary">E1</name>
    </gene>
    <organism evidence="13 14">
        <name type="scientific">Human papillomavirus type 50</name>
        <dbReference type="NCBI Taxonomy" id="40539"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Papovaviricetes</taxon>
            <taxon>Zurhausenvirales</taxon>
            <taxon>Papillomaviridae</taxon>
            <taxon>Firstpapillomavirinae</taxon>
            <taxon>Gammapapillomavirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference evidence="13 14" key="1">
        <citation type="journal article" date="1989" name="J. Virol." volume="63" first="4910" last="4910">
            <title>Human papillomavirus (HPV) type 50, a type associated with epidermodysplasia verruciformis (EV) and only weakly related to other EV-specific HPVs.</title>
            <authorList>
                <person name="Favre M."/>
                <person name="Obalek S."/>
                <person name="Jablonska S."/>
                <person name="Orth G."/>
            </authorList>
            <dbReference type="PubMed" id="2552168"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="9">ATP-dependent DNA helicase required for initiation of viral DNA replication. It forms a complex with the viral E2 protein. The E1-E2 complex binds to the replication origin which contains binding sites for both proteins. During the initial step, a dimer of E1 interacts with a dimer of protein E2 leading to a complex that binds the viral origin of replication with high specificity. Then, a second dimer of E1 displaces the E2 dimer in an ATP-dependent manner to form the E1 tetramer. Following this, two E1 monomers are added to each half of the site, which results in the formation of two E1 trimers on the viral ori. Subsequently, two hexamers will be created. The double hexamer acts as a bi-directional helicase machinery and unwinds the viral DNA and then recruits the host DNA polymerase to start replication.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 10">
            <text>ATP + H2O = ADP + H(+) + phosphate</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="3.6.4.12"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="9">Can form hexamers. Interacts with E2 protein; this interaction increases E1 DNA binding specificity. Interacts with host DNA polymerase subunit POLA2. Interacts with host single stranded DNA-binding protein RPA1. Interacts with host TOP1; this interaction stimulates the enzymatic activity of TOP1.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="9">Phosphorylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9 10">Belongs to the papillomaviridae E1 protein family.</text>
    </comment>
    <comment type="caution">
        <text evidence="9">Lacks conserved residue(s) required for the propagation of feature annotation.</text>
    </comment>
    <dbReference type="EC" id="3.6.4.12" evidence="9 10"/>
    <dbReference type="EMBL" id="U31790">
        <property type="protein sequence ID" value="AAA79473.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_043425.1">
        <property type="nucleotide sequence ID" value="NC_001691.1"/>
    </dbReference>
    <dbReference type="SMR" id="Q80929"/>
    <dbReference type="GeneID" id="1403631"/>
    <dbReference type="KEGG" id="vg:1403631"/>
    <dbReference type="Proteomes" id="UP000168289">
        <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:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="RHEA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003677">
        <property type="term" value="F:DNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003678">
        <property type="term" value="F:DNA helicase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006260">
        <property type="term" value="P:DNA replication"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.10.510">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04000">
        <property type="entry name" value="PPV_E1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001177">
        <property type="entry name" value="DNA_helicase_E1_C_Papillomavir"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014000">
        <property type="entry name" value="DNA_helicase_E1_N_Papillomavir"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014015">
        <property type="entry name" value="Helicase_SF3_DNA-vir"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016393">
        <property type="entry name" value="Rep_E1_papillomaV"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037102">
        <property type="entry name" value="Znf_lg_T-Ag_D1_dom_sf"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00519">
        <property type="entry name" value="PPV_E1_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00524">
        <property type="entry name" value="PPV_E1_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF003383">
        <property type="entry name" value="Rep_E1_papillomaV"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="SSF52540"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51206">
        <property type="entry name" value="SF3_HELICASE_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword evidence="7 9 10" id="KW-0067">ATP-binding</keyword>
    <keyword evidence="9 10" id="KW-0235">DNA replication</keyword>
    <keyword evidence="8 9 10" id="KW-0238">DNA-binding</keyword>
    <keyword evidence="1 9 10" id="KW-0244">Early protein</keyword>
    <keyword evidence="6 9 10" id="KW-0347">Helicase</keyword>
    <keyword evidence="3 9" id="KW-1048">Host nucleus</keyword>
    <keyword evidence="5 9 10" id="KW-0378">Hydrolase</keyword>
    <keyword evidence="4 9 10" id="KW-0547">Nucleotide-binding</keyword>
    <keyword evidence="2 9" id="KW-0597">Phosphoprotein</keyword>
    <keyword evidence="14" id="KW-1185">Reference proteome</keyword>
    <feature type="domain" description="SF3 helicase" evidence="12">
        <location>
            <begin position="387"/>
            <end position="551"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="11">
        <location>
            <begin position="576"/>
            <end position="599"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="9">
        <location>
            <begin position="79"/>
            <end position="81"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="9">
        <location>
            <begin position="93"/>
            <end position="102"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="11">
        <location>
            <begin position="583"/>
            <end position="599"/>
        </location>
    </feature>
    <feature type="binding site" evidence="9">
        <location>
            <begin position="427"/>
            <end position="434"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by host" evidence="9">
        <location>
            <position position="94"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="ARBA" id="ARBA00022518"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="ARBA" id="ARBA00022553"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="ARBA" id="ARBA00022562"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="ARBA" id="ARBA00022741"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="ARBA" id="ARBA00022801"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="ARBA" id="ARBA00022806"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="ARBA" id="ARBA00022840"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="ARBA" id="ARBA00023125"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04000"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="10">
        <source>
            <dbReference type="PIRNR" id="PIRNR003383"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="11">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000259" key="12">
        <source>
            <dbReference type="PROSITE" id="PS51206"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="13">
        <source>
            <dbReference type="EMBL" id="AAA79473.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="14">
        <source>
            <dbReference type="Proteomes" id="UP000168289"/>
        </source>
    </evidence>
    <sequence length="599" mass="68862" checksum="EA8D2ED3E8C63D99" modified="1996-11-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1998-07-15" modified="2022-08-03" version="107" xmlns="http://uniprot.org/uniprot">
    <accession>Q80930</accession>
    <name>VE2_HPV50</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Regulatory protein E2</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="1" type="primary">E2</name>
    </gene>
    <organism>
        <name type="scientific">Human papillomavirus type 50</name>
        <dbReference type="NCBI Taxonomy" id="40539"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Papovaviricetes</taxon>
            <taxon>Zurhausenvirales</taxon>
            <taxon>Papillomaviridae</taxon>
            <taxon>Firstpapillomavirinae</taxon>
            <taxon>Gammapapillomavirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="submission" date="1995-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Delius H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Plays a role in the initiation of viral DNA replication. A dimer of E2 interacts with a dimer of E1 in order to improve specificity of E1 DNA binding activity. Once the complex recognizes and binds DNA at specific sites, the E2 dimer is removed from DNA. E2 also regulates viral transcription through binding to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory regions of the viral genome. Activates or represses transcription depending on E2RE's position with regards to proximal promoter elements including the TATA-box. Repression occurs by sterically hindering the assembly of the transcription initiation complex.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Binds DNA as homodimer. Interacts with protein E1; this interaction greatly increases E1 DNA-binding activity. Interacts with protein L1; this interaction enhances E2-dependent replication and transcription activation. Interacts with protein L2; this interaction inhibits E2 transcriptional activity but not DNA replication function E2. Interacts with protein E7; this interaction inhibits E7 oncogenic activity. Interacts with host TAF1; this interaction modulates E2-dependent transcriptional regulation. Interacts with host BRD4; this interaction mediates E2 transcriptional activation function. Additionally, the interaction with host BRD4 on mitotic chromosomes mediates tethering of the viral genome. Interacts with host TOPBP1; this interaction is required for optimal viral DNA replication.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the papillomaviridae E2 protein family.</text>
    </comment>
    <dbReference type="EMBL" id="U31790">
        <property type="protein sequence ID" value="AAA79474.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_043426.1">
        <property type="nucleotide sequence ID" value="NC_001691.1"/>
    </dbReference>
    <dbReference type="SMR" id="Q80930"/>
    <dbReference type="PRIDE" id="Q80930"/>
    <dbReference type="GeneID" id="1403632"/>
    <dbReference type="KEGG" id="vg:1403632"/>
    <dbReference type="Proteomes" id="UP000168289">
        <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:0003677">
        <property type="term" value="F:DNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003700">
        <property type="term" value="F:DNA-binding transcription factor activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000166">
        <property type="term" value="F:nucleotide binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006260">
        <property type="term" value="P:DNA replication"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006275">
        <property type="term" value="P:regulation of DNA replication"/>
        <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:0039693">
        <property type="term" value="P:viral DNA genome replication"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.287.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.170.200.10">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.70.330">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04001">
        <property type="entry name" value="PPV_E2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR035975">
        <property type="entry name" value="E2/EBNA1_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012677">
        <property type="entry name" value="Nucleotide-bd_a/b_plait_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000427">
        <property type="entry name" value="Papillomavirus_E2_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001866">
        <property type="entry name" value="Papillomavirus_E2_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033668">
        <property type="entry name" value="Reg_prot_E2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036050">
        <property type="entry name" value="Regulatory_protein_E2_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042503">
        <property type="entry name" value="Regulatory_protein_E2_N_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042504">
        <property type="entry name" value="Regulatory_protein_E2_N_2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00511">
        <property type="entry name" value="PPV_E2_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00508">
        <property type="entry name" value="PPV_E2_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51332">
        <property type="entry name" value="SSF51332"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54957">
        <property type="entry name" value="SSF54957"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0010">Activator</keyword>
    <keyword id="KW-0235">DNA replication</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0244">Early protein</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0678">Repressor</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <feature type="chain" id="PRO_0000133228" description="Regulatory protein E2">
        <location>
            <begin position="1"/>
            <end position="396"/>
        </location>
    </feature>
    <feature type="region of interest" description="Transactivation domain" evidence="1">
        <location>
            <begin position="1"/>
            <end position="208"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="206"/>
            <end position="292"/>
        </location>
    </feature>
    <feature type="region of interest" description="DNA-binding domain" evidence="1">
        <location>
            <begin position="312"/>
            <end position="396"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="2">
        <location>
            <begin position="222"/>
            <end position="254"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04001"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <sequence length="396" mass="45557" checksum="D481FE5C5CA81F02" modified="1996-11-01" version="1">MTQMETQETLSARFLAQQDIQLNLIEKDSKNLKDHIDYWESMRKEQVLAFYAKKENMSRLGLQPLPPAKVSEQKAKDAIRIQLLLQSLYKSDFGSEPWTLSECSLEMLNAPPRNCFKKQPFTVTVQFDNDPKNVYPYICYEYIYYQDDRDKWHKVKGLVDHNGLYFKEVTGDSVYFKLFQPDATVYGKSGQWTVIFKNKTIHSSVTSSSRSAFGPADEQPGPSTSYDKSQQERSGSGQPKALQDTEPPTSTSTVRLRRGRREREHHSYRHRKSQSELGADSAPTPEEVGRRSHTVAAHGLSRLRRLQEEARDPPVLIITGQQNNLKCWRYRFSQKYADLYECCSSAWKWLGPKSEGYRGDAKLLIAFKNPEQRLSFLNTVGLPKNTTYSMGHLDSL</sequence>
</entry>
<entry dataset="TrEMBL" created="1996-11-01" modified="2020-08-12" version="45" xmlns="http://uniprot.org/uniprot">
    <accession>Q80931</accession>
    <name>Q80931_HPV50</name>
    <protein>
        <submittedName>
            <fullName evidence="2">E4 protein</fullName>
        </submittedName>
    </protein>
    <gene>
        <name evidence="2" type="primary">E4</name>
    </gene>
    <organism evidence="2 3">
        <name type="scientific">Human papillomavirus type 50</name>
        <dbReference type="NCBI Taxonomy" id="40539"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Papovaviricetes</taxon>
            <taxon>Zurhausenvirales</taxon>
            <taxon>Papillomaviridae</taxon>
            <taxon>Firstpapillomavirinae</taxon>
            <taxon>Gammapapillomavirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference evidence="2 3" key="1">
        <citation type="journal article" date="1989" name="J. Virol." volume="63" first="4910" last="4910">
            <title>Human papillomavirus (HPV) type 50, a type associated with epidermodysplasia verruciformis (EV) and only weakly related to other EV-specific HPVs.</title>
            <authorList>
                <person name="Favre M."/>
                <person name="Obalek S."/>
                <person name="Jablonska S."/>
                <person name="Orth G."/>
            </authorList>
            <dbReference type="PubMed" id="2552168"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <dbReference type="EMBL" id="U31790">
        <property type="protein sequence ID" value="AAA79475.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_043427.1">
        <property type="nucleotide sequence ID" value="NC_001691.1"/>
    </dbReference>
    <dbReference type="GeneID" id="1403633"/>
    <dbReference type="KEGG" id="vg:1403633"/>
    <dbReference type="Proteomes" id="UP000168289">
        <property type="component" value="Genome"/>
    </dbReference>
    <proteinExistence type="predicted"/>
    <keyword evidence="3" id="KW-1185">Reference proteome</keyword>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="52"/>
            <end position="106"/>
        </location>
    </feature>
    <feature type="non-terminal residue" evidence="2">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="2">
        <source>
            <dbReference type="EMBL" id="AAA79475.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000313" key="3">
        <source>
            <dbReference type="Proteomes" id="UP000168289"/>
        </source>
    </evidence>
    <sequence length="146" mass="17153" checksum="F1119868035ECD68" modified="1996-11-01" version="1" fragment="single">LVIQYTLNSFNLMPLYMANLDNGLLYLKTKLFIPLSLAPQGVRLGLLTNSPGLPHRTTRANRKDLEAVNQKPYRTPNHPPRHQQYDFDEDDEKENTIPTDTESHNQNWEPTLRQLLKKWEEDLTQLQRMVCQDLDDYKRKLGIHQS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1998-07-15" modified="2020-08-12" version="70" xmlns="http://uniprot.org/uniprot">
    <accession>Q80932</accession>
    <name>VL2_HPV50</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Minor capsid protein L2</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="1" type="primary">L2</name>
    </gene>
    <organism>
        <name type="scientific">Human papillomavirus type 50</name>
        <dbReference type="NCBI Taxonomy" id="40539"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Papovaviricetes</taxon>
            <taxon>Zurhausenvirales</taxon>
            <taxon>Papillomaviridae</taxon>
            <taxon>Firstpapillomavirinae</taxon>
            <taxon>Gammapapillomavirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="submission" date="1995-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Delius H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Minor protein of the capsid that localizes along the inner surface of the virion, within the central cavities beneath the L1 pentamers. Plays a role in capsid stabilization through interaction with the major capsid protein L1. Once the virion enters the host cell, L2 escorts the genomic DNA into the nucleus by promoting escape from the endosomal compartments and traffic through the host Golgi network. Mechanistically, the C-terminus of L2 possesses a cell-penetrating peptide that protudes from the host endosome, interacts with host cytoplasmic retromer cargo and thereby mediates the capsid delivery to the host trans-Golgi network. Plays a role through its interaction with host dynein in the intracellular microtubule-dependent transport of viral capsid toward the nucleus. Mediates the viral genome import into the nucleus through binding to host importins. Once within the nucleus, L2 localizes viral genomes to host PML bodies in order to activate early gene expression for establishment of infection. Later on, promotes late gene expression by interacting with the viral E2 protein and by inhibiting its transcriptional activation functions. During virion assembly, encapsidates the genome by direct interaction with the viral DNA.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Interacts with major capsid protein L1. Interacts with E2; this interaction inhibits E2 transcriptional activity but not the DNA replication function E2. Interacts with host GADD45GIP1. Interacts with host HSPA8; this interaction is required for L2 nuclear translocation. Interacts with host importins KPNB2 and KPNB3. Forms a complex with importin alpha2-beta1 heterodimers via interaction with the importin alpha2 adapter. Interacts with host DYNLT1; this interaction is essential for virus intracellular transport during entry. Interacts (via C-terminus) with host retromer subunits VPS35 AND VPS29.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host early endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host Golgi apparatus</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="1">Highly phosphorylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the papillomaviridae L2 protein family.</text>
    </comment>
    <dbReference type="EMBL" id="U31790">
        <property type="protein sequence ID" value="AAA79476.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_043428.1">
        <property type="nucleotide sequence ID" value="NC_001691.1"/>
    </dbReference>
    <dbReference type="GeneID" id="1403634"/>
    <dbReference type="KEGG" id="vg:1403634"/>
    <dbReference type="Proteomes" id="UP000168289">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04003">
        <property type="entry name" value="PPV_L2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000784">
        <property type="entry name" value="Late_L2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00513">
        <property type="entry name" value="Late_protein_L2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0167">Capsid protein</keyword>
    <keyword id="KW-1176">Cytoplasmic inwards viral transport</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-1039">Host endosome</keyword>
    <keyword id="KW-1040">Host Golgi apparatus</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0426">Late protein</keyword>
    <keyword id="KW-1177">Microtubular inwards viral transport</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1185">Reference proteome</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_0000133616" description="Minor capsid protein L2">
        <location>
            <begin position="1"/>
            <end position="506"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="1">
        <location>
            <begin position="1"/>
            <end position="8"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="1">
        <location>
            <begin position="498"/>
            <end position="503"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="17"/>
            <end position="23"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04003"/>
        </source>
    </evidence>
    <sequence length="506" mass="55198" checksum="2B37C8139776E766" modified="1996-11-01" version="1">MLRRRKRASPTDLYRSCLQGGDCIPDVQNKFEGNTIADWLLKIFGGLVYFGNLGIGTGRGTGGTFGYRPFGAPGSGRPTQELPIARPNVVIDPLGPAPIVPVDPSAASIVPLVEGAPDVGFAAPDAGPAAGGTDIELYTITNSTTDVGAVGGGPTVTSNEEFEVAVIDAQPIAPYPKQLLYDSTIAATFETQINPFINPDINNVNVLVDPSFAGDTVGDYFYEEIPLERLDIQTFDILEPPTESTPTQLGNRFVSRARDLYSRFVAQQPISEPDFLSQPSRLVQFEYRNPAFDPDVSLYFERDLEGLRAAPLQEFADVVYLGRPRVSSTSEGTIRVSRLGTRAALTTRSGLSVGPQVHFYMDLSDIPPEDSIELHTLNVTPQTSTIVDDILATTTFDDPANSLFTQFNEDVLTDDVEHNFTESHLVIPATDEENDTAINIINLRNIPLTVGMNSGDISTTLSDYNILDASLIVKSNVSEQPLFVLDYSDYDLHPGLLPKRRRIDYF</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>