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<entry dataset="Swiss-Prot" created="2014-05-14" modified="2021-06-02" version="20" xmlns="http://uniprot.org/uniprot">
    <accession>D5SGZ8</accession>
    <name>AAP_AAV2S</name>
    <protein>
        <recommendedName>
            <fullName>Assembly activating protein AAP</fullName>
        </recommendedName>
    </protein>
    <organism>
        <name type="scientific">Adeno-associated virus 2 (isolate Srivastava/1982)</name>
        <name type="common">AAV-2</name>
        <dbReference type="NCBI Taxonomy" id="648242"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Quintoviricetes</taxon>
            <taxon>Piccovirales</taxon>
            <taxon>Parvoviridae</taxon>
            <taxon>Parvovirinae</taxon>
            <taxon>Dependoparvovirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Mammalia</name>
        <name type="common">mammals</name>
        <dbReference type="NCBI Taxonomy" id="40674"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1983" name="J. Virol." volume="45" first="555" last="564">
            <title>Nucleotide sequence and organization of the adeno-associated virus 2 genome.</title>
            <authorList>
                <person name="Srivastava A."/>
                <person name="Lusby E.W."/>
                <person name="Berns K.I."/>
            </authorList>
            <dbReference type="PubMed" id="6300419"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="J. Gen. Virol." volume="75" first="3385" last="3392">
            <title>Mutations in the carboxy terminus of adeno-associated virus 2 capsid proteins affect viral infectivity: lack of an RGD integrin-binding motif.</title>
            <authorList>
                <person name="Ruffing M."/>
                <person name="Heid H."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="7996133"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="1998-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Berns K.I."/>
                <person name="Bohenzky R.A."/>
                <person name="Cassinotti P."/>
                <person name="Colvin D."/>
                <person name="Donahue B.A."/>
                <person name="Dull T."/>
                <person name="Horer M."/>
                <person name="Kleinschmidt J.A."/>
                <person name="Ruffing M."/>
                <person name="Snyder R.O."/>
                <person name="Tratschin J.-D."/>
                <person name="Weitz M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2010" name="Proc. Natl. Acad. Sci. U.S.A." volume="107" first="10220" last="10225">
            <title>A viral assembly factor promotes AAV2 capsid formation in the nucleolus.</title>
            <authorList>
                <person name="Sonntag F."/>
                <person name="Schmidt K."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="20479244"/>
            <dbReference type="DOI" id="10.1073/pnas.1001673107"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Plays a role in capsid assembly. Promotes the transport of unassembled capsid proteins into the host nucleolus for capsid assembly.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Host nucleus</location>
            <location evidence="2">Host nucleolus</location>
        </subcellularLocation>
    </comment>
    <comment type="miscellaneous">
        <text>The protein AAP uses an unusual ACG start codon.</text>
    </comment>
    <dbReference type="EMBL" id="J01901">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF043303">
        <property type="protein sequence ID" value="ADH10168.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_004030758.1">
        <property type="nucleotide sequence ID" value="NC_001401.2"/>
    </dbReference>
    <dbReference type="DNASU" id="4192015"/>
    <dbReference type="GeneID" id="4192015"/>
    <dbReference type="Proteomes" id="UP000008469">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000180764">
        <property type="component" value="Genome"/>
    </dbReference>
    <proteinExistence type="predicted"/>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000428954" description="Assembly activating protein AAP">
        <location>
            <begin position="1"/>
            <end position="204"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="59"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="118"/>
            <end position="150"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="172"/>
            <end position="204"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="1">
        <location>
            <begin position="118"/>
            <end position="146"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="1">
        <location>
            <begin position="189"/>
            <end position="204"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="20479244"/>
        </source>
    </evidence>
    <sequence length="204" mass="22595" checksum="0404B03B5BFD8C31" modified="2010-07-13" version="1">METQTQYLTPSLSDSHQQPPLVWELIRWLQAVAHQWQTITRAPTEWVIPREIGIAIPHGWATESSPPAPEPGPCPPTTTTSTNKFPANQEPRTTITTLATAPLGGILTSTDSTATFHHVTGKDSSTTTGDSDPRDSTSSSLTFKSKRSRRMTVRRRLPITLPARFRCLLTRSTSSRTSSARRIKDASRRSQQTSSWCHSMDTSP</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2022-08-03" version="108" xmlns="http://uniprot.org/uniprot">
    <accession>P03132</accession>
    <accession>O56650</accession>
    <name>REP68_AAV2S</name>
    <protein>
        <recommendedName>
            <fullName>Protein Rep68</fullName>
            <ecNumber>3.6.4.12</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">Rep68</name>
    </gene>
    <organism>
        <name type="scientific">Adeno-associated virus 2 (isolate Srivastava/1982)</name>
        <name type="common">AAV-2</name>
        <dbReference type="NCBI Taxonomy" id="648242"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Quintoviricetes</taxon>
            <taxon>Piccovirales</taxon>
            <taxon>Parvoviridae</taxon>
            <taxon>Parvovirinae</taxon>
            <taxon>Dependoparvovirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Mammalia</name>
        <name type="common">mammals</name>
        <dbReference type="NCBI Taxonomy" id="40674"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1983" name="J. Virol." volume="45" first="555" last="564">
            <title>Nucleotide sequence and organization of the adeno-associated virus 2 genome.</title>
            <authorList>
                <person name="Srivastava A."/>
                <person name="Lusby E.W."/>
                <person name="Berns K.I."/>
            </authorList>
            <dbReference type="PubMed" id="6300419"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="J. Gen. Virol." volume="75" first="3385" last="3392">
            <title>Mutations in the carboxy terminus of adeno-associated virus 2 capsid proteins affect viral infectivity: lack of an RGD integrin-binding motif.</title>
            <authorList>
                <person name="Ruffing M."/>
                <person name="Heid H."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="7996133"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="1998-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Berns K.I."/>
                <person name="Bohenzky R.A."/>
                <person name="Cassinotti P."/>
                <person name="Colvin D."/>
                <person name="Donahue B.A."/>
                <person name="Dull T."/>
                <person name="Horer M."/>
                <person name="Kleinschmidt J.A."/>
                <person name="Ruffing M."/>
                <person name="Snyder R.O."/>
                <person name="Tratschin J.-D."/>
                <person name="Weitz M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1992" name="J. Virol." volume="66" first="317" last="324">
            <title>Colocalization of adeno-associated virus Rep and capsid proteins in the nuclei of infected cells.</title>
            <authorList>
                <person name="Hunter L.A."/>
                <person name="Samulski R.J."/>
            </authorList>
            <dbReference type="PubMed" id="1370086"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1999" name="J. Virol." volume="73" first="1580" last="1590">
            <title>Biochemical characterization of adeno-associated virus rep68 DNA helicase and ATPase activities.</title>
            <authorList>
                <person name="Zhou X."/>
                <person name="Zolotukhin I."/>
                <person name="Im D.S."/>
                <person name="Muzyczka N."/>
            </authorList>
            <dbReference type="PubMed" id="9882364"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1999" name="J. Virol." volume="73" first="260" last="269">
            <title>The adeno-associated virus type 2 regulatory proteins rep78 and rep68 interact with the transcriptional coactivator PC4.</title>
            <authorList>
                <person name="Weger S."/>
                <person name="Wendland M."/>
                <person name="Kleinschmidt J.A."/>
                <person name="Heilbronn R."/>
            </authorList>
            <dbReference type="PubMed" id="9847329"/>
        </citation>
        <scope>INTERACTION WITH HOST SUB1/PC4</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2002" name="J. Gen. Virol." volume="83" first="511" last="516">
            <title>Topors, a p53 and topoisomerase I binding protein, interacts with the adeno-associated virus (AAV-2) Rep78/68 proteins and enhances AAV-2 gene expression.</title>
            <authorList>
                <person name="Weger S."/>
                <person name="Hammer E."/>
                <person name="Heilbronn R."/>
            </authorList>
            <dbReference type="PubMed" id="11842245"/>
        </citation>
        <scope>INTERACTION WITH HOST TOPORS</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2007" name="Virology" volume="362" first="192" last="206">
            <title>Identification of a cytoplasmic interaction partner of the large regulatory proteins Rep78/Rep68 of adeno-associated virus type 2 (AAV-2).</title>
            <authorList>
                <person name="Weger S."/>
                <person name="Hammer E."/>
                <person name="Goetz A."/>
                <person name="Heilbronn R."/>
            </authorList>
            <dbReference type="PubMed" id="17239418"/>
            <dbReference type="DOI" id="10.1016/j.virol.2006.12.010"/>
        </citation>
        <scope>INTERACTION WITH KCTD5</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2003" name="Structure" volume="11" first="1025" last="1035">
            <title>Crystal structure of the SF3 helicase from adeno-associated virus type 2.</title>
            <authorList>
                <person name="James J.A."/>
                <person name="Escalante C.R."/>
                <person name="Yoon-Robarts M."/>
                <person name="Edwards T.A."/>
                <person name="Linden R.M."/>
                <person name="Aggarwal A.K."/>
            </authorList>
            <dbReference type="PubMed" id="12906833"/>
            <dbReference type="DOI" id="10.1016/S0969-2126(03)00152-7"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 225-490</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="12455" last="12460">
            <title>Structure of adeno-associated virus type 2 Rep40-ADP complex: insight into nucleotide recognition and catalysis by superfamily 3 helicases.</title>
            <authorList>
                <person name="James J.A."/>
                <person name="Aggarwal A.K."/>
                <person name="Linden R.M."/>
                <person name="Escalante C.R."/>
            </authorList>
            <dbReference type="PubMed" id="15310852"/>
            <dbReference type="DOI" id="10.1073/pnas.0403454101"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 225-490</scope>
    </reference>
    <comment type="function">
        <text evidence="6">Plays an essential role in the initiation of viral DNA synthesis. Binds specifically to an inverted terminal repeat element (ITR) on the 3' and 5' ends of the viral DNA, where it cleaves a site specifically to generate a priming site for initiation of the synthesis of a complementary strand. Also plays a role as transcriptional regulator, DNA helicase and as key factor in site-specific integration of the viral genome. Inhibits the host cell cycle G1/S and G2/M transitions. These arrests may provide essential cellular factors for viral DNA replication.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <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="3 4 5">Interacts with host TOPORS. Interacts with host KCTD5.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7387242">
            <id>P03132</id>
        </interactant>
        <interactant intactId="EBI-1779322">
            <id>P03120</id>
            <label>E2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7387242">
            <id>P03132</id>
        </interactant>
        <interactant intactId="EBI-1056857">
            <id>Q9NXV2</id>
            <label>KCTD5</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7387242">
            <id>P03132</id>
        </interactant>
        <interactant intactId="EBI-998260">
            <id>P53999</id>
            <label>SUB1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7387242">
            <id>P03132</id>
        </interactant>
        <interactant intactId="EBI-1996473">
            <id>Q9NS56</id>
            <label>TOPORS</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <dbReference type="EC" id="3.6.4.12"/>
    <dbReference type="EMBL" id="J01901">
        <property type="protein sequence ID" value="AAA42372.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF043303">
        <property type="protein sequence ID" value="AAC03774.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="PIR" id="A03694">
        <property type="entry name" value="UYAD1A"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_680422.1">
        <property type="nucleotide sequence ID" value="NC_001401.2"/>
    </dbReference>
    <dbReference type="PDB" id="1S9H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B/C=225-490"/>
    </dbReference>
    <dbReference type="PDB" id="1U0J">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=225-490"/>
    </dbReference>
    <dbReference type="PDB" id="4ZO0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B/C=1-206"/>
    </dbReference>
    <dbReference type="PDB" id="4ZQ9">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B/C=1-208"/>
    </dbReference>
    <dbReference type="PDB" id="5DCX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H/I/J/K=1-224"/>
    </dbReference>
    <dbReference type="PDB" id="6XB8">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A/B/C/D=1-206"/>
    </dbReference>
    <dbReference type="PDB" id="7JSE">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.60 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-536"/>
    </dbReference>
    <dbReference type="PDB" id="7JSF">
        <property type="method" value="EM"/>
        <property type="resolution" value="6.70 A"/>
        <property type="chains" value="A/B/C/D/E/F/G=2-536"/>
    </dbReference>
    <dbReference type="PDB" id="7JSG">
        <property type="method" value="EM"/>
        <property type="resolution" value="5.20 A"/>
        <property type="chains" value="A/B/C/D/E/F/G=2-536"/>
    </dbReference>
    <dbReference type="PDB" id="7JSH">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.40 A"/>
        <property type="chains" value="A/B/C/D/E/F/G=2-536"/>
    </dbReference>
    <dbReference type="PDB" id="7JSI">
        <property type="method" value="EM"/>
        <property type="resolution" value="5.01 A"/>
        <property type="chains" value="A/B/C/D/E/F=1-536"/>
    </dbReference>
    <dbReference type="PDBsum" id="1S9H"/>
    <dbReference type="PDBsum" id="1U0J"/>
    <dbReference type="PDBsum" id="4ZO0"/>
    <dbReference type="PDBsum" id="4ZQ9"/>
    <dbReference type="PDBsum" id="5DCX"/>
    <dbReference type="PDBsum" id="6XB8"/>
    <dbReference type="PDBsum" id="7JSE"/>
    <dbReference type="PDBsum" id="7JSF"/>
    <dbReference type="PDBsum" id="7JSG"/>
    <dbReference type="PDBsum" id="7JSH"/>
    <dbReference type="PDBsum" id="7JSI"/>
    <dbReference type="SMR" id="P03132"/>
    <dbReference type="IntAct" id="P03132">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="MINT" id="P03132"/>
    <dbReference type="DNASU" id="4192013"/>
    <dbReference type="GeneID" id="4192013"/>
    <dbReference type="KEGG" id="vg:4192013"/>
    <dbReference type="EvolutionaryTrace" id="P03132"/>
    <dbReference type="Proteomes" id="UP000008469">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000180764">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO: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:0003678">
        <property type="term" value="F:DNA helicase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO: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: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-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039665">
        <property type="term" value="P:permeabilization of host organelle membrane involved in viral entry into host cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039592">
        <property type="term" value="P:suppression by virus of G2/M transition of host mitotic cell cycle"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039693">
        <property type="term" value="P:viral DNA genome replication"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099008">
        <property type="term" value="P:viral entry via permeabilization of inner membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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<entry dataset="Swiss-Prot" created="1986-07-21" modified="2022-02-23" version="106" xmlns="http://uniprot.org/uniprot">
    <accession>P03135</accession>
    <accession>O56652</accession>
    <accession>O56653</accession>
    <accession>O92917</accession>
    <name>CAPSD_AAV2S</name>
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        <recommendedName>
            <fullName>Capsid protein VP1</fullName>
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        <name type="primary">VP1</name>
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    <organism>
        <name type="scientific">Adeno-associated virus 2 (isolate Srivastava/1982)</name>
        <name type="common">AAV-2</name>
        <dbReference type="NCBI Taxonomy" id="648242"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Quintoviricetes</taxon>
            <taxon>Piccovirales</taxon>
            <taxon>Parvoviridae</taxon>
            <taxon>Parvovirinae</taxon>
            <taxon>Dependoparvovirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Mammalia</name>
        <name type="common">mammals</name>
        <dbReference type="NCBI Taxonomy" id="40674"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1983" name="J. Virol." volume="45" first="555" last="564">
            <title>Nucleotide sequence and organization of the adeno-associated virus 2 genome.</title>
            <authorList>
                <person name="Srivastava A."/>
                <person name="Lusby E.W."/>
                <person name="Berns K.I."/>
            </authorList>
            <dbReference type="PubMed" id="6300419"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="J. Gen. Virol." volume="75" first="3385" last="3392">
            <title>Mutations in the carboxy terminus of adeno-associated virus 2 capsid proteins affect viral infectivity: lack of an RGD integrin-binding motif.</title>
            <authorList>
                <person name="Ruffing M."/>
                <person name="Heid H."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="7996133"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="1998-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Berns K.I."/>
                <person name="Bohenzky R.A."/>
                <person name="Cassinotti P."/>
                <person name="Colvin D."/>
                <person name="Donahue B.A."/>
                <person name="Dull T."/>
                <person name="Horer M."/>
                <person name="Kleinschmidt J.A."/>
                <person name="Ruffing M."/>
                <person name="Snyder R.O."/>
                <person name="Tratschin J.-D."/>
                <person name="Weitz M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1988" name="J. Virol." volume="62" first="2745" last="2754">
            <title>Synthesis of adeno-associated virus structural proteins requires both alternative mRNA splicing and alternative initiations from a single transcript.</title>
            <authorList>
                <person name="Becerra S.P."/>
                <person name="Koczot F."/>
                <person name="Fabisch P."/>
                <person name="Rose J.A."/>
            </authorList>
            <dbReference type="PubMed" id="2839699"/>
        </citation>
        <scope>ALTERNATIVE SPLICING</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1997" name="J. Virol." volume="71" first="1341" last="1352">
            <title>Subcellular compartmentalization of adeno-associated virus type 2 assembly.</title>
            <authorList>
                <person name="Wistuba A."/>
                <person name="Kern A."/>
                <person name="Weger S."/>
                <person name="Grimm D."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="8995658"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1998" name="J. Virol." volume="72" first="1438" last="1445">
            <title>Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions.</title>
            <authorList>
                <person name="Summerford C."/>
                <person name="Samulski R.J."/>
            </authorList>
            <dbReference type="PubMed" id="9445046"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2000" name="J. Virol." volume="74" first="2777" last="2785">
            <title>Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors.</title>
            <authorList>
                <person name="Bartlett J.S."/>
                <person name="Wilcher R."/>
                <person name="Samulski R.J."/>
            </authorList>
            <dbReference type="PubMed" id="10684294"/>
            <dbReference type="DOI" id="10.1128/JVI.74.6.2777-2785.2000"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2002" name="J. Gen. Virol." volume="83" first="973" last="978">
            <title>The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity.</title>
            <authorList>
                <person name="Girod A."/>
                <person name="Wobus C.E."/>
                <person name="Zadori Z."/>
                <person name="Ried M."/>
                <person name="Leike K."/>
                <person name="Tijssen P."/>
                <person name="Kleinschmidt J.A."/>
                <person name="Hallek M."/>
            </authorList>
            <dbReference type="PubMed" id="11961250"/>
        </citation>
        <scope>FUNCTION OF VP1</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2006" name="J. Virol." volume="80" first="8961" last="8969">
            <title>Adeno-associated virus type 2 contains an integrin alpha5beta1 binding domain essential for viral cell entry.</title>
            <authorList>
                <person name="Asokan A."/>
                <person name="Hamra J.B."/>
                <person name="Govindasamy L."/>
                <person name="Agbandje-McKenna M."/>
                <person name="Samulski R.J."/>
            </authorList>
            <dbReference type="PubMed" id="16940508"/>
            <dbReference type="DOI" id="10.1128/JVI.00843-06"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2008" name="Methods Mol. Biol." volume="437" first="51" last="91">
            <title>The role of the adeno-associated virus capsid in gene transfer.</title>
            <authorList>
                <person name="Van Vliet K.M."/>
                <person name="Blouin V."/>
                <person name="Brument N."/>
                <person name="Agbandje-McKenna M."/>
                <person name="Snyder R.O."/>
            </authorList>
            <dbReference type="PubMed" id="18369962"/>
            <dbReference type="DOI" id="10.1007/978-1-59745-210-6_2"/>
        </citation>
        <scope>BIOTECHNOLOGY</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2002" name="Proc. Natl. Acad. Sci. U.S.A." volume="99" first="10405" last="10410">
            <title>The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy.</title>
            <authorList>
                <person name="Xie Q."/>
                <person name="Bu W."/>
                <person name="Bhatia S."/>
                <person name="Hare J."/>
                <person name="Somasundaram T."/>
                <person name="Azzi A."/>
                <person name="Chapman M.S."/>
            </authorList>
            <dbReference type="PubMed" id="12136130"/>
            <dbReference type="DOI" id="10.1073/pnas.162250899"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 217-735</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4 5 8">Capsid protein self-assembles to form an icosahedral capsid with a T=1 symmetry, about 22 nm in diameter, and consisting of 60 copies of three size variants of the capsid protein VP1, VP2 and VP3 which differ in their N-terminus. The capsid encapsulates the genomic ssDNA. Binds to host cell heparan sulfate and uses host ITGA5-ITGB1 as coreceptor on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis. Binding to the host receptor also induces capsid rearrangements leading to surface exposure of VP1 N-terminus, specifically its phospholipase A2-like region and putative nuclear localization signal(s). VP1 N-terminus might serve as a lipolytic enzyme to breach the endosomal membrane during entry into host cell and might contribute to virus transport to the nucleus.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Host nucleus</location>
            <location evidence="7">Host nucleolus</location>
        </subcellularLocation>
        <text>Capid proteins are first observed in the host nucleolus where capsid assembly may occur, and then are present over the whole nucleoplasm where encapsidation of the viral DNA takes place.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <event type="alternative initiation"/>
        <isoform>
            <id>P03135-1</id>
            <name>VP1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P03135-2</id>
            <name>VP2</name>
            <sequence type="described" ref="VSP_040829 VSP_040830"/>
        </isoform>
        <isoform>
            <id>P03135-3</id>
            <name>VP3</name>
            <sequence type="described" ref="VSP_040828"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text>The N-terminus of VP1 is sequestered within the mature capsid. It contains a phospholipase A2-like region and putative nuclear localization signals.</text>
    </comment>
    <comment type="biotechnology">
        <text evidence="10">AAV capsids serve as viral gene transfer vectors that have been shown to affect long-term gene expression and disease correction with low toxicity in animal models, and are well tolerated in human clinical trials.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="10">the ratio at which VP1, VP2 and VP3 proteins are synthesized in vivo is about 1:1:10, which is the same as in the mature virus particle.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform VP1</molecule>
        <text evidence="6">Produced by alternative splicing (2.6 kb mRNA).</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform VP2</molecule>
        <text evidence="6">Produced by alternative splicing (2.3 kb mRNA), with initiatory methionine encoded by an ACG codon.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform VP3</molecule>
        <text evidence="6">Produced by alternative initiation of the 2.3 kb mRNA.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the parvoviridae capsid protein family.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAA42376" version="1"/>
        </conflict>
    </comment>
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        <property type="status" value="ALT_FRAME"/>
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    <dbReference type="EMBL" id="AF043303">
        <property type="protein sequence ID" value="AAC03779.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF043303">
        <property type="protein sequence ID" value="AAC03780.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAC03778.1"/>
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<entry dataset="Swiss-Prot" created="2014-05-14" modified="2022-08-03" version="75" xmlns="http://uniprot.org/uniprot">
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            <fullName>Protein Rep78</fullName>
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            <taxon>Monodnaviria</taxon>
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            <taxon>Cossaviricota</taxon>
            <taxon>Quintoviricetes</taxon>
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            <taxon>Parvoviridae</taxon>
            <taxon>Parvovirinae</taxon>
            <taxon>Dependoparvovirus</taxon>
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    <reference key="1">
        <citation type="journal article" date="1983" name="J. Virol." volume="45" first="555" last="564">
            <title>Nucleotide sequence and organization of the adeno-associated virus 2 genome.</title>
            <authorList>
                <person name="Srivastava A."/>
                <person name="Lusby E.W."/>
                <person name="Berns K.I."/>
            </authorList>
            <dbReference type="PubMed" id="6300419"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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    <reference key="2">
        <citation type="journal article" date="1994" name="J. Gen. Virol." volume="75" first="3385" last="3392">
            <title>Mutations in the carboxy terminus of adeno-associated virus 2 capsid proteins affect viral infectivity: lack of an RGD integrin-binding motif.</title>
            <authorList>
                <person name="Ruffing M."/>
                <person name="Heid H."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="7996133"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="1998-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Berns K.I."/>
                <person name="Bohenzky R.A."/>
                <person name="Cassinotti P."/>
                <person name="Colvin D."/>
                <person name="Donahue B.A."/>
                <person name="Dull T."/>
                <person name="Horer M."/>
                <person name="Kleinschmidt J.A."/>
                <person name="Ruffing M."/>
                <person name="Snyder R.O."/>
                <person name="Tratschin J.-D."/>
                <person name="Weitz M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1992" name="J. Virol." volume="66" first="317" last="324">
            <title>Colocalization of adeno-associated virus Rep and capsid proteins in the nuclei of infected cells.</title>
            <authorList>
                <person name="Hunter L.A."/>
                <person name="Samulski R.J."/>
            </authorList>
            <dbReference type="PubMed" id="1370086"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1997" name="J. Virol." volume="71" first="4461" last="4471">
            <title>The Rep78 gene product of adeno-associated virus (AAV) self-associates to form a hexameric complex in the presence of AAV ori sequences.</title>
            <authorList>
                <person name="Smith R.H."/>
                <person name="Spano A.J."/>
                <person name="Kotin R.M."/>
            </authorList>
            <dbReference type="PubMed" id="9151837"/>
        </citation>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1998" name="Mol. Cell. Biol." volume="18" first="5921" last="5929">
            <title>Inhibition of PrKX, a novel protein kinase, and the cyclic AMP-dependent protein kinase PKA by the regulatory proteins of adeno-associated virus type 2.</title>
            <authorList>
                <person name="Chiorini J.A."/>
                <person name="Zimmermann B."/>
                <person name="Yang L."/>
                <person name="Smith R.H."/>
                <person name="Ahearn A."/>
                <person name="Herberg F."/>
                <person name="Kotin R.M."/>
            </authorList>
            <dbReference type="PubMed" id="9742109"/>
        </citation>
        <scope>INTERACTION WITH HOST PRKX</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1998" name="Virology" volume="245" first="120" last="127">
            <title>The adeno-associated virus Rep78 major regulatory protein binds the cellular TATA-binding protein in vitro and in vivo.</title>
            <authorList>
                <person name="Hermonat P.L."/>
                <person name="Santin A.D."/>
                <person name="Batchu R.B."/>
                <person name="Zhan D."/>
            </authorList>
            <dbReference type="PubMed" id="9614873"/>
            <dbReference type="DOI" id="10.1006/viro.1998.9144"/>
        </citation>
        <scope>INTERACTION WITH HOST TBP</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1999" name="J. Virol." volume="73" first="260" last="269">
            <title>The adeno-associated virus type 2 regulatory proteins rep78 and rep68 interact with the transcriptional coactivator PC4.</title>
            <authorList>
                <person name="Weger S."/>
                <person name="Wendland M."/>
                <person name="Kleinschmidt J.A."/>
                <person name="Heilbronn R."/>
            </authorList>
            <dbReference type="PubMed" id="9847329"/>
        </citation>
        <scope>INTERACTION WITH HOST SUB1/PC4</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2000" name="EMBO J." volume="19" first="4351" last="4361">
            <title>Inhibition of S-phase progression by adeno-associated virus Rep78 protein is mediated by hypophosphorylated pRb.</title>
            <authorList>
                <person name="Saudan P."/>
                <person name="Vlach J."/>
                <person name="Beard P."/>
            </authorList>
            <dbReference type="PubMed" id="10944118"/>
            <dbReference type="DOI" id="10.1093/emboj/19.16.4351"/>
        </citation>
        <scope>FUNCTION IN HOST CELL CYCLE ARREST</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2002" name="J. Gen. Virol." volume="83" first="511" last="516">
            <title>Topors, a p53 and topoisomerase I binding protein, interacts with the adeno-associated virus (AAV-2) Rep78/68 proteins and enhances AAV-2 gene expression.</title>
            <authorList>
                <person name="Weger S."/>
                <person name="Hammer E."/>
                <person name="Heilbronn R."/>
            </authorList>
            <dbReference type="PubMed" id="11842245"/>
        </citation>
        <scope>INTERACTION WITH HOST TOPORS</scope>
    </reference>
    <comment type="function">
        <text evidence="3">Plays an essential role in the initiation of viral DNA synthesis. Binds specifically to an inverted terminal repeat element (ITR) on the 3' and 5' ends of the viral DNA, where it cleaves a site specifically to generate a priming site for initiation of the synthesis of a complementary strand. Also plays a role as transcriptional regulator, DNA helicase and as key factors in site-specific integration of the viral genome. Regulates host PKA activity by interacting with host PRKX as a mechanism of interfering with helper virus propagation and promoting its own replication. Inhibits the host cell cycle G1/S, S and G2/M transitions. These arrests may provide essential cellular factors for viral DNA replication.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 6 7 8 9">Hexamer when associated with the viral DNA ori sequence. Interacts with host PRKX. Interacts with host TOPORS. Interacts with host TBP AND SUB1/PC4; these interactions play important roles in transcriptional regulation.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <dbReference type="EMBL" id="J01901">
        <property type="protein sequence ID" value="AAA42374.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF043303">
        <property type="protein sequence ID" value="AAC03775.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="RefSeq" id="YP_680423.1">
        <property type="nucleotide sequence ID" value="NC_001401.2"/>
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    <dbReference type="PDB" id="5BYG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B/C/D=1-210"/>
    </dbReference>
    <dbReference type="PDBsum" id="5BYG"/>
    <dbReference type="SMR" id="Q89268"/>
    <dbReference type="IntAct" id="Q89268">
        <property type="interactions" value="3"/>
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    <dbReference type="DNASU" id="1489608"/>
    <dbReference type="GeneID" id="1489608"/>
    <dbReference type="KEGG" id="vg:1489608"/>
    <dbReference type="Proteomes" id="UP000008469">
        <property type="component" value="Genome"/>
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        <property type="term" value="C:host cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
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        <property type="project" value="UniProtKB-KW"/>
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        <property type="term" value="P:modulation by virus of host G1/S transition checkpoint"/>
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        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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        <property type="term" value="P:viral DNA genome replication"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR014015">
        <property type="entry name" value="Helicase_SF3_DNA-vir"/>
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    <dbReference type="InterPro" id="IPR027417">
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    </dbReference>
    <dbReference type="InterPro" id="IPR001257">
        <property type="entry name" value="Parvovirus_NS1_helicase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014835">
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        <property type="entry name" value="Parvo_NS1"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF08724">
        <property type="entry name" value="Rep_N"/>
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    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="SSF52540"/>
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    <dbReference type="PROSITE" id="PS51206">
        <property type="entry name" value="SF3_HELICASE_1"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0235">DNA replication</keyword>
    <keyword id="KW-1078">G1/S host cell cycle checkpoint dysregulation by virus</keyword>
    <keyword id="KW-1079">Host G2/M cell cycle arrest by virus</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-1121">Modulation of host cell cycle by virus</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000428953" description="Protein Rep78">
        <location>
            <begin position="1"/>
            <end position="621"/>
        </location>
    </feature>
    <feature type="domain" description="SF3 helicase" evidence="1">
        <location>
            <begin position="308"/>
            <end position="463"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="196"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="489"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="489"/>
            <end position="508"/>
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    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="334"/>
            <end position="341"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    </feature>
    <feature type="strand" evidence="10">
        <location>
            <begin position="4"/>
            <end position="11"/>
        </location>
    </feature>
    <feature type="turn" evidence="10">
        <location>
            <begin position="29"/>
            <end position="32"/>
        </location>
    </feature>
    <feature type="helix" evidence="10">
        <location>
            <begin position="45"/>
            <end position="47"/>
        </location>
    </feature>
    <feature type="helix" evidence="10">
        <location>
            <begin position="50"/>
            <end position="71"/>
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    </feature>
    <feature type="strand" evidence="10">
        <location>
            <begin position="78"/>
            <end position="84"/>
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    </feature>
    <feature type="strand" evidence="10">
        <location>
            <begin position="86"/>
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    </feature>
    <feature type="helix" evidence="10">
        <location>
            <begin position="102"/>
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    <feature type="turn" evidence="10">
        <location>
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    <feature type="strand" evidence="10">
        <location>
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    <feature type="strand" evidence="10">
        <location>
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    <feature type="helix" evidence="10">
        <location>
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    <feature type="turn" evidence="10">
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    <feature type="turn" evidence="10">
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    <feature type="strand" evidence="10">
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        <location>
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    <feature type="helix" evidence="10">
        <location>
            <begin position="182"/>
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    </feature>
    <feature type="helix" evidence="10">
        <location>
            <begin position="202"/>
            <end position="205"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00551"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
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        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11842245"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="1370086"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="9151837"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="9614873"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="9742109"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="9847329"/>
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    </evidence>
    <evidence type="ECO:0007829" key="10">
        <source>
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    </evidence>
    <sequence length="621" mass="70563" checksum="FBF4F1FEAF48FF2A" modified="1996-11-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2014-05-14" modified="2022-08-03" version="84" xmlns="http://uniprot.org/uniprot">
    <accession>Q89269</accession>
    <accession>Q77XY0</accession>
    <name>REP40_AAV2S</name>
    <protein>
        <recommendedName>
            <fullName>Protein Rep40</fullName>
            <ecNumber>3.6.4.12</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">Rep40</name>
    </gene>
    <organism>
        <name type="scientific">Adeno-associated virus 2 (isolate Srivastava/1982)</name>
        <name type="common">AAV-2</name>
        <dbReference type="NCBI Taxonomy" id="648242"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Quintoviricetes</taxon>
            <taxon>Piccovirales</taxon>
            <taxon>Parvoviridae</taxon>
            <taxon>Parvovirinae</taxon>
            <taxon>Dependoparvovirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Mammalia</name>
        <name type="common">mammals</name>
        <dbReference type="NCBI Taxonomy" id="40674"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1983" name="J. Virol." volume="45" first="555" last="564">
            <title>Nucleotide sequence and organization of the adeno-associated virus 2 genome.</title>
            <authorList>
                <person name="Srivastava A."/>
                <person name="Lusby E.W."/>
                <person name="Berns K.I."/>
            </authorList>
            <dbReference type="PubMed" id="6300419"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="J. Gen. Virol." volume="75" first="3385" last="3392">
            <title>Mutations in the carboxy terminus of adeno-associated virus 2 capsid proteins affect viral infectivity: lack of an RGD integrin-binding motif.</title>
            <authorList>
                <person name="Ruffing M."/>
                <person name="Heid H."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="7996133"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="1998-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Berns K.I."/>
                <person name="Bohenzky R.A."/>
                <person name="Cassinotti P."/>
                <person name="Colvin D."/>
                <person name="Donahue B.A."/>
                <person name="Dull T."/>
                <person name="Horer M."/>
                <person name="Kleinschmidt J.A."/>
                <person name="Ruffing M."/>
                <person name="Snyder R.O."/>
                <person name="Tratschin J.-D."/>
                <person name="Weitz M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1992" name="J. Virol." volume="66" first="317" last="324">
            <title>Colocalization of adeno-associated virus Rep and capsid proteins in the nuclei of infected cells.</title>
            <authorList>
                <person name="Hunter L.A."/>
                <person name="Samulski R.J."/>
            </authorList>
            <dbReference type="PubMed" id="1370086"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2001" name="EMBO J." volume="20" first="3282" last="3291">
            <title>DNA helicase-mediated packaging of adeno-associated virus type 2 genomes into preformed capsids.</title>
            <authorList>
                <person name="King J.A."/>
                <person name="Dubielzig R."/>
                <person name="Grimm D."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="11406604"/>
            <dbReference type="DOI" id="10.1093/emboj/20.12.3282"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="34011" last="34017">
            <title>A biochemical characterization of the adeno-associated virus Rep40 helicase.</title>
            <authorList>
                <person name="Collaco R.F."/>
                <person name="Kalman-Maltese V."/>
                <person name="Smith A.D."/>
                <person name="Dignam J.D."/>
                <person name="Trempe J.P."/>
            </authorList>
            <dbReference type="PubMed" id="12824181"/>
            <dbReference type="DOI" id="10.1074/jbc.M301537200"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2007" name="Biochemistry" volume="46" first="568" last="576">
            <title>Coupled ATP and DNA binding of adeno-associated virus Rep40 helicase.</title>
            <authorList>
                <person name="Dignam S.S."/>
                <person name="Collaco R.F."/>
                <person name="Bieszczad J."/>
                <person name="Needham P."/>
                <person name="Trempe J.P."/>
                <person name="Dignam J.D."/>
            </authorList>
            <dbReference type="PubMed" id="17209567"/>
            <dbReference type="DOI" id="10.1021/bi061762v"/>
        </citation>
        <scope>SUBUNIT</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4">Plays a critical role during packaging of viral DNA into empty capsids, where they are thought to be part of the packaging motor complex. The single stranded genomic DNA is packaged in a 3' to 5' direction and requires the association of viral DNA with Rep40.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <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"/>
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            <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="6">Homooligomer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <dbReference type="EC" id="3.6.4.12"/>
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        <property type="protein sequence ID" value="AAA42373.1"/>
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    <dbReference type="GO" id="GO:0003678">
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        <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="evidence at protein level"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0235">DNA replication</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000428951" description="Protein Rep40">
        <location>
            <begin position="1"/>
            <end position="312"/>
        </location>
    </feature>
    <feature type="domain" description="SF3 helicase" evidence="1">
        <location>
            <begin position="84"/>
            <end position="239"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="264"/>
            <end position="301"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="264"/>
            <end position="284"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="110"/>
            <end position="117"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00551"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="11406604"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="12824181"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="1370086"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="17209567"/>
        </source>
    </evidence>
    <sequence length="312" mass="34965" checksum="9465A291F2B044F0" modified="1996-11-01" version="1">MELVGWLVDKGITSEKQWIQEDQASYISFNAASNSRSQIKAALDNAGKIMSLTKTAPDYLVGQQPVEDISSNRIYKILELNGYDPQYAASVFLGWATKKFGKRNTIWLFGPATTGKTNIAEAIAHTVPFYGCVNWTNENFPFNDCVDKMVIWWEEGKMTAKVVESAKAILGGSKVRVDQKCKSSAQIDPTPVIVTSNTNMCAVIDGNSTTFEHQQPLQDRMFKFELTRRLDHDFGKVTKQEVKDFFRWAKDHVVEVEHEFYVKKGGAKKRPAPSDADISEPKRVRESVAQPSTSDAEASINYADRLARGHSL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2014-05-14" modified="2022-08-03" version="76" xmlns="http://uniprot.org/uniprot">
    <accession>Q89270</accession>
    <accession>Q77XX9</accession>
    <name>REP52_AAV2S</name>
    <protein>
        <recommendedName>
            <fullName>Protein Rep52</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">Rep52</name>
    </gene>
    <organism>
        <name type="scientific">Adeno-associated virus 2 (isolate Srivastava/1982)</name>
        <name type="common">AAV-2</name>
        <dbReference type="NCBI Taxonomy" id="648242"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Monodnaviria</taxon>
            <taxon>Shotokuvirae</taxon>
            <taxon>Cossaviricota</taxon>
            <taxon>Quintoviricetes</taxon>
            <taxon>Piccovirales</taxon>
            <taxon>Parvoviridae</taxon>
            <taxon>Parvovirinae</taxon>
            <taxon>Dependoparvovirus</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Mammalia</name>
        <name type="common">mammals</name>
        <dbReference type="NCBI Taxonomy" id="40674"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1983" name="J. Virol." volume="45" first="555" last="564">
            <title>Nucleotide sequence and organization of the adeno-associated virus 2 genome.</title>
            <authorList>
                <person name="Srivastava A."/>
                <person name="Lusby E.W."/>
                <person name="Berns K.I."/>
            </authorList>
            <dbReference type="PubMed" id="6300419"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="J. Gen. Virol." volume="75" first="3385" last="3392">
            <title>Mutations in the carboxy terminus of adeno-associated virus 2 capsid proteins affect viral infectivity: lack of an RGD integrin-binding motif.</title>
            <authorList>
                <person name="Ruffing M."/>
                <person name="Heid H."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="7996133"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="1998-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Berns K.I."/>
                <person name="Bohenzky R.A."/>
                <person name="Cassinotti P."/>
                <person name="Colvin D."/>
                <person name="Donahue B.A."/>
                <person name="Dull T."/>
                <person name="Horer M."/>
                <person name="Kleinschmidt J.A."/>
                <person name="Ruffing M."/>
                <person name="Snyder R.O."/>
                <person name="Tratschin J.-D."/>
                <person name="Weitz M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1992" name="J. Virol." volume="66" first="317" last="324">
            <title>Colocalization of adeno-associated virus Rep and capsid proteins in the nuclei of infected cells.</title>
            <authorList>
                <person name="Hunter L.A."/>
                <person name="Samulski R.J."/>
            </authorList>
            <dbReference type="PubMed" id="1370086"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1998" name="J. Virol." volume="72" first="4874" last="4881">
            <title>The Rep52 gene product of adeno-associated virus is a DNA helicase with 3'-to-5' polarity.</title>
            <authorList>
                <person name="Smith R.H."/>
                <person name="Kotin R.M."/>
            </authorList>
            <dbReference type="PubMed" id="9573254"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1998" name="Mol. Cell. Biol." volume="18" first="5921" last="5929">
            <title>Inhibition of PrKX, a novel protein kinase, and the cyclic AMP-dependent protein kinase PKA by the regulatory proteins of adeno-associated virus type 2.</title>
            <authorList>
                <person name="Chiorini J.A."/>
                <person name="Zimmermann B."/>
                <person name="Yang L."/>
                <person name="Smith R.H."/>
                <person name="Ahearn A."/>
                <person name="Herberg F."/>
                <person name="Kotin R.M."/>
            </authorList>
            <dbReference type="PubMed" id="9742109"/>
        </citation>
        <scope>INTERACTION WITH HOST PRKX</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2001" name="EMBO J." volume="20" first="3282" last="3291">
            <title>DNA helicase-mediated packaging of adeno-associated virus type 2 genomes into preformed capsids.</title>
            <authorList>
                <person name="King J.A."/>
                <person name="Dubielzig R."/>
                <person name="Grimm D."/>
                <person name="Kleinschmidt J.A."/>
            </authorList>
            <dbReference type="PubMed" id="11406604"/>
            <dbReference type="DOI" id="10.1093/emboj/20.12.3282"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="3 5">Plays a critical role during packaging of viral DNA into empty capsids, where they are thought to be part of the packaging motor complex. The single stranded genomic DNA is packaged in a 3' to 5' direction and requires the association between viral DNA and Rep40. Regulates host PKA activity by interacting with host PRKX as a mechanism to interfere with helper virus propagation and to promote its own replication.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6">Homooligomer. Interacts with host PRKX.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <dbReference type="EMBL" id="J01901">
        <property type="protein sequence ID" value="AAA42375.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF043303">
        <property type="protein sequence ID" value="AAC03777.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_680425.1">
        <property type="nucleotide sequence ID" value="NC_001401.2"/>
    </dbReference>
    <dbReference type="SMR" id="Q89270"/>
    <dbReference type="DNASU" id="1489607"/>
    <dbReference type="GeneID" id="1489607"/>
    <dbReference type="KEGG" id="vg:1489607"/>
    <dbReference type="Proteomes" id="UP000008469">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000180764">
        <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-KW"/>
    </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:0019079">
        <property type="term" value="P:viral genome replication"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="match status" value="1"/>
    </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="IPR001257">
        <property type="entry name" value="Parvovirus_NS1_helicase"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01057">
        <property type="entry name" value="Parvo_NS1"/>
        <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="evidence at protein level"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0235">DNA replication</keyword>
    <keyword id="KW-1048">Host nucleus</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000428952" description="Protein Rep52">
        <location>
            <begin position="1"/>
            <end position="397"/>
        </location>
    </feature>
    <feature type="domain" description="SF3 helicase" evidence="1">
        <location>
            <begin position="84"/>
            <end position="239"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="265"/>
            <end position="296"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="265"/>
            <end position="284"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="110"/>
            <end position="117"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00551"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="11406604"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="1370086"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="9573254"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="9742109"/>
        </source>
    </evidence>
    <sequence length="397" mass="44774" checksum="95763A5A51E408F7" modified="1996-11-01" version="1">MELVGWLVDKGITSEKQWIQEDQASYISFNAASNSRSQIKAALDNAGKIMSLTKTAPDYLVGQQPVEDISSNRIYKILELNGYDPQYAASVFLGWATKKFGKRNTIWLFGPATTGKTNIAEAIAHTVPFYGCVNWTNENFPFNDCVDKMVIWWEEGKMTAKVVESAKAILGGSKVRVDQKCKSSAQIDPTPVIVTSNTNMCAVIDGNSTTFEHQQPLQDRMFKFELTRRLDHDFGKVTKQEVKDFFRWAKDHVVEVEHEFYVKKGGAKKRPAPSDADISEPKRVRESVAQPSTSDAEASINYADRYQNKCSRHVGMNLMLFPCRQCERMNQNSNICFTHGQKDCLECFPVSESQPVSVVKKAYQKLCYIHHIMGKVPDACTACDLVNVDLDDCIFEQ</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>