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<entry dataset="Swiss-Prot" created="1986-07-21" modified="2022-05-25" version="111" xmlns="http://uniprot.org/uniprot">
    <accession>P03138</accession>
    <name>HBSAG_HBVD3</name>
    <protein>
        <recommendedName>
            <fullName evidence="2">Large envelope protein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="2">L glycoprotein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="2">L-HBsAg</fullName>
            <shortName evidence="2">LHB</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="2">Large S protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="2">Large surface protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="2">Major surface antigen</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="2" type="primary">S</name>
    </gene>
    <organism>
        <name type="scientific">Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979)</name>
        <name type="common">HBV-D</name>
        <dbReference type="NCBI Taxonomy" id="490133"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Pararnavirae</taxon>
            <taxon>Artverviricota</taxon>
            <taxon>Revtraviricetes</taxon>
            <taxon>Blubervirales</taxon>
            <taxon>Hepadnaviridae</taxon>
            <taxon>Orthohepadnavirus</taxon>
            <taxon>hepatitis B virus genotype D</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Pan troglodytes</name>
        <name type="common">Chimpanzee</name>
        <dbReference type="NCBI Taxonomy" id="9598"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1979" name="Nature" volume="281" first="646" last="650">
            <title>Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli.</title>
            <authorList>
                <person name="Galibert F."/>
                <person name="Mandart E."/>
                <person name="Fitoussi F."/>
                <person name="Tiollais P."/>
                <person name="Charnay P."/>
            </authorList>
            <dbReference type="PubMed" id="399327"/>
            <dbReference type="DOI" id="10.1038/281646a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1985" name="FEBS Lett." volume="185" first="208" last="212">
            <title>Subtype ayw variant of hepatitis B virus. DNA primary structure analysis.</title>
            <authorList>
                <person name="Bichko V."/>
                <person name="Dreilina D."/>
                <person name="Pushko P.M."/>
                <person name="Pumpen P.P."/>
                <person name="Gren E."/>
            </authorList>
            <dbReference type="PubMed" id="3996597"/>
            <dbReference type="DOI" id="10.1016/0014-5793(85)80771-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <strain>Latvia</strain>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1984" name="Dokl. Akad. Nauk SSSR" volume="274" first="1250" last="1253">
            <title>Synthesis of the full amino acid sequence of the surface antigen of the hepatitis B virus in Escherichia coli.</title>
            <authorList>
                <person name="Kozlovskaia T.M."/>
                <person name="Pumpen P.P."/>
                <person name="Borisova G.P."/>
                <person name="Dishler A.V."/>
                <person name="Bychko V.V."/>
            </authorList>
            <dbReference type="PubMed" id="6373205"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <strain>Latvia</strain>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1987" name="J. Virol." volume="61" first="1672" last="1677">
            <title>The preS1 protein of hepatitis B virus is acylated at its amino terminus with myristic acid.</title>
            <authorList>
                <person name="Persing D.H."/>
                <person name="Varmus H.E."/>
                <person name="Ganem D."/>
            </authorList>
            <dbReference type="PubMed" id="3573147"/>
        </citation>
        <scope>MYRISTOYLATION AT GLY-2</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1995" name="EMBO J." volume="14" first="247" last="256">
            <title>Novel transmembrane topology of the hepatitis B virus envelope proteins.</title>
            <authorList>
                <person name="Prange R."/>
                <person name="Streeck R.E."/>
            </authorList>
            <dbReference type="PubMed" id="7835336"/>
        </citation>
        <scope>TRANSMEMBRANE TOPOLOGY</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1995" name="Virology" volume="213" first="292" last="299">
            <title>Myristylation of the hepatitis B virus large surface protein is essential for viral infectivity.</title>
            <authorList>
                <person name="Gripon P."/>
                <person name="Le Seyec J."/>
                <person name="Rumin S."/>
                <person name="Guguen-Guillouzo C."/>
            </authorList>
            <dbReference type="PubMed" id="7491754"/>
            <dbReference type="DOI" id="10.1006/viro.1995.0002"/>
        </citation>
        <scope>MUTAGENESIS OF GLY-2</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1998" name="J. Virol." volume="72" first="778" last="782">
            <title>Role for calnexin and N-linked glycosylation in the assembly and secretion of hepatitis B virus middle envelope protein particles.</title>
            <authorList>
                <person name="Werr M."/>
                <person name="Prange R."/>
            </authorList>
            <dbReference type="PubMed" id="9420286"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="11945" last="11957">
            <title>Analysis of the pre-S2 N- and O-linked glycans of the M surface protein from human hepatitis B virus.</title>
            <authorList>
                <person name="Schmitt S."/>
                <person name="Glebe D."/>
                <person name="Alving K."/>
                <person name="Tolle T.K."/>
                <person name="Linder M."/>
                <person name="Geyer H."/>
                <person name="Linder D."/>
                <person name="Peter-Katalinic J."/>
                <person name="Gerlich W.H."/>
                <person name="Geyer R."/>
            </authorList>
            <dbReference type="PubMed" id="10207016"/>
            <dbReference type="DOI" id="10.1074/jbc.274.17.11945"/>
        </citation>
        <scope>GLYCOSYLATION (ISOFORM M)</scope>
        <scope>ACETYLATION AT MET-1 (ISOFORM M)</scope>
        <source>
            <strain>Isolate clinical</strain>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2004" name="J. Gen. Virol." volume="85" first="2045" last="2053">
            <title>Structure of pre-S2 N- and O-linked glycans in surface proteins from different genotypes of hepatitis B virus.</title>
            <authorList>
                <person name="Schmitt S."/>
                <person name="Glebe D."/>
                <person name="Tolle T.K."/>
                <person name="Lochnit G."/>
                <person name="Linder D."/>
                <person name="Geyer R."/>
                <person name="Gerlich W.H."/>
            </authorList>
            <dbReference type="PubMed" id="15218190"/>
            <dbReference type="DOI" id="10.1099/vir.0.79932-0"/>
        </citation>
        <scope>GLYCOSYLATION AT THR-37 (ISOFORM M)</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2006" name="J. Virol." volume="80" first="11935" last="11945">
            <title>Analysis of the cytosolic domains of the hepatitis B virus envelope proteins for their function in viral particle assembly and infectivity.</title>
            <authorList>
                <person name="Blanchet M."/>
                <person name="Sureau C."/>
            </authorList>
            <dbReference type="PubMed" id="17020942"/>
            <dbReference type="DOI" id="10.1128/JVI.00621-06"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2006" name="Hepatology" volume="43" first="750" last="760">
            <title>Characterization of a hepatitis B and hepatitis delta virus receptor binding site.</title>
            <authorList>
                <person name="Engelke M."/>
                <person name="Mills K."/>
                <person name="Seitz S."/>
                <person name="Simon P."/>
                <person name="Gripon P."/>
                <person name="Schnolzer M."/>
                <person name="Urban S."/>
            </authorList>
            <dbReference type="PubMed" id="16557545"/>
            <dbReference type="DOI" id="10.1002/hep.21112"/>
        </citation>
        <scope>MUTAGENESIS OF LEU-11; GLY-12 AND 13-PHE-PHE-14</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2007" name="J. Virol." volume="81" first="5841" last="5849">
            <title>Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues.</title>
            <authorList>
                <person name="Blanchet M."/>
                <person name="Sureau C."/>
            </authorList>
            <dbReference type="PubMed" id="17376925"/>
            <dbReference type="DOI" id="10.1128/JVI.00096-07"/>
        </citation>
        <scope>MUTAGENESIS OF 11-LEU--PRO-15; 16-ASP--ASP-20; 21-PRO--ALA-25; 26-ASN--PRO-30; 31-ASP--ASN-35; 36-PRO--THR-40; 41-TRP--ASN-45; 46-LYS--GLY-50; 51-ALA--GLY-55; 56-PHE--HIS-60; 61-GLY--GLY-65; 66-TRP--ALA-70; 71-GLN--GLN-75; 76-THR--ASN-80; 81-PRO--SER-85; 86-THR--SER-90; 91-GLY--THR-95; 96-PRO--PRO-100; 101-LEU--HIS-105 AND 106-PRO--GLN-110</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="1996" name="Intervirology" volume="39" first="23" last="31">
            <title>Functions of the large hepatitis B virus surface protein in viral particle morphogenesis.</title>
            <authorList>
                <person name="Bruss V."/>
                <person name="Gerhardt E."/>
                <person name="Vieluf K."/>
                <person name="Wunderlich G."/>
            </authorList>
            <dbReference type="PubMed" id="8957666"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="1998" name="Adv. Exp. Med. Biol." volume="435" first="207" last="216">
            <title>Role of glycan processing in hepatitis B virus envelope protein trafficking.</title>
            <authorList>
                <person name="Block T.M."/>
                <person name="Lu X."/>
                <person name="Mehta A."/>
                <person name="Park J."/>
                <person name="Blumberg B.S."/>
                <person name="Dwek R."/>
            </authorList>
            <dbReference type="PubMed" id="9498079"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2004" name="Virus Res." volume="106" first="199" last="209">
            <title>Envelopment of the hepatitis B virus nucleocapsid.</title>
            <authorList>
                <person name="Bruss V."/>
            </authorList>
            <dbReference type="PubMed" id="15567498"/>
            <dbReference type="DOI" id="10.1016/j.virusres.2004.08.016"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2006" name="Cancer Sci." volume="97" first="683" last="688">
            <title>Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis.</title>
            <authorList>
                <person name="Wang H.C."/>
                <person name="Huang W."/>
                <person name="Lai M.D."/>
                <person name="Su I.J."/>
            </authorList>
            <dbReference type="PubMed" id="16863502"/>
            <dbReference type="DOI" id="10.1111/j.1349-7006.2006.00235.x"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="2">The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches the virus to cell receptors and thereby initiating infection. This interaction determines the species specificity and liver tropism. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis. The large envelope protein also assures fusion between virion membrane and endosomal membrane. In its internal conformation the protein plays a role in virion morphogenesis and mediates the contact with the nucleocapsid like a matrix protein.</text>
    </comment>
    <comment type="function">
        <text evidence="2">The middle envelope protein plays an important role in the budding of the virion. It is involved in the induction of budding in a nucleocapsid independent way. In this process the majority of envelope proteins bud to form subviral lipoprotein particles of 22 nm of diameter that do not contain a nucleocapsid.</text>
    </comment>
    <comment type="subunit">
        <molecule>Isoform L</molecule>
        <text evidence="1">In its internal form (Li-HBsAg), interacts with the capsid protein and with the isoform S. Interacts with host chaperone CANX.</text>
    </comment>
    <comment type="subunit">
        <molecule>Isoform M</molecule>
        <text evidence="1">Associates with host chaperone CANX through its pre-S2 N glycan; this association may be essential for isoform M proper secretion.</text>
    </comment>
    <comment type="subunit">
        <molecule>Isoform S</molecule>
        <text evidence="1">Interacts with isoform L. Interacts with the antigens of satellite virus HDV (HDVAgs); this interaction is required for encapsidation of HDV genomic RNA.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Virion membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <event type="alternative initiation"/>
        <isoform>
            <id>P03138-1</id>
            <name>L</name>
            <name>Large envelope protein</name>
            <name>LHB</name>
            <name>L-HBsAg</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P03138-2</id>
            <name>M</name>
            <name>Middle envelope protein</name>
            <name>MHB</name>
            <name>M-HBsAg</name>
            <sequence type="described" ref="VSP_031405"/>
        </isoform>
        <isoform>
            <id>P03138-3</id>
            <name>S</name>
            <name>Small envelope protein</name>
            <name>SHB</name>
            <name>S-HBsAg</name>
            <sequence type="described" ref="VSP_031404"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="2">The large envelope protein is synthesized with the pre-S region at the cytosolic side of the endoplasmic reticulum and, hence will be within the virion after budding. Therefore the pre-S region is not N-glycosylated. Later a post-translational translocation of N-terminal pre-S and TM1 domains occur in about 50% of proteins at the virion surface. These molecules change their topology by an unknown mechanism, resulting in exposure of pre-S region at virion surface. For isoform M in contrast, the pre-S2 region is translocated cotranslationally to the endoplasmic reticulum lumen and is N-glycosylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2 4 5">Isoform M is N-terminally acetylated by host at a ratio of 90%, and N-glycosylated by host at the pre-S2 region.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Myristoylated.</text>
    </comment>
    <comment type="biotechnology">
        <text>Systematic vaccination of individuals at risk of exposure to the virus has been the main method of controlling the morbidity and mortality associated with hepatitis B. The first hepatitis B vaccine was manufactured by the purification and inactivation of HBsAg obtained from the plasma of chronic hepatitis B virus carriers. The vaccine is now produced by recombinant DNA techniques and expression of the S isoform in yeast cells. The pre-S region do not seem to induce strong enough antigenic response.</text>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the orthohepadnavirus major surface antigen family.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAA45496" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAA26324" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="V01460">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X02496">
        <property type="protein sequence ID" value="CAA26324.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M12393">
        <property type="protein sequence ID" value="AAA45496.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="PIR" id="A03703">
        <property type="entry name" value="SAVLAH"/>
    </dbReference>
    <dbReference type="ELM" id="P03138"/>
    <dbReference type="BindingDB" id="P03138"/>
    <dbReference type="ABCD" id="P03138">
        <property type="antibodies" value="4 sequenced antibodies"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P03138"/>
    <dbReference type="Proteomes" id="UP000007930">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016021">
        <property type="term" value="C:integral component of membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055036">
        <property type="term" value="C:virion membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0075513">
        <property type="term" value="P:caveolin-mediated endocytosis of virus by host cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039654">
        <property type="term" value="P:fusion of virus membrane with host endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019062">
        <property type="term" value="P:virion attachment to host cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04075">
        <property type="entry name" value="HBV_HBSAG"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000349">
        <property type="entry name" value="HBV_HBSAG"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00695">
        <property type="entry name" value="vMSA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0024">Alternative initiation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1166">Caveolin-mediated endocytosis of virus by host</keyword>
    <keyword id="KW-1170">Fusion of virus membrane with host endosomal membrane</keyword>
    <keyword id="KW-1168">Fusion of virus membrane with host membrane</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0519">Myristate</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</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="initiator methionine" description="Removed; by host" evidence="2">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000038107" description="Large envelope protein" evidence="2">
        <location>
            <begin position="2"/>
            <end position="389"/>
        </location>
    </feature>
    <feature type="topological domain" description="Intravirion; in internal conformation" evidence="2">
        <location>
            <begin position="2"/>
            <end position="242"/>
        </location>
    </feature>
    <feature type="topological domain" description="Virion surface; in external conformation" evidence="2">
        <location>
            <begin position="2"/>
            <end position="170"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=TM1; Note=In external conformation" evidence="2">
        <location>
            <begin position="171"/>
            <end position="191"/>
        </location>
    </feature>
    <feature type="topological domain" description="Intravirion; in external conformation" evidence="2">
        <location>
            <begin position="192"/>
            <end position="242"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=TM2" evidence="2">
        <location>
            <begin position="243"/>
            <end position="263"/>
        </location>
    </feature>
    <feature type="topological domain" description="Virion surface" evidence="2">
        <location>
            <begin position="264"/>
            <end position="337"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="338"/>
            <end position="358"/>
        </location>
    </feature>
    <feature type="topological domain" description="Intravirion" evidence="2">
        <location>
            <begin position="359"/>
            <end position="364"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=TM3" evidence="2">
        <location>
            <begin position="365"/>
            <end position="387"/>
        </location>
    </feature>
    <feature type="topological domain" description="Virion surface" evidence="2">
        <location>
            <begin position="388"/>
            <end position="389"/>
        </location>
    </feature>
    <feature type="region of interest" description="Pre-S" evidence="2">
        <location>
            <begin position="2"/>
            <end position="163"/>
        </location>
    </feature>
    <feature type="region of interest" description="Pre-S1" evidence="2">
        <location>
            <begin position="2"/>
            <end position="108"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="76"/>
            <end position="103"/>
        </location>
    </feature>
    <feature type="region of interest" description="Pre-S2" evidence="2">
        <location>
            <begin position="109"/>
            <end position="163"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="4">
        <location sequence="P03138-2">
            <position position="1"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="N-myristoyl glycine; by host" evidence="2">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; by host" evidence="2">
        <location>
            <position position="309"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (GalNAc...) threonine" evidence="5">
        <location sequence="P03138-2">
            <position position="37"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_031404" description="In isoform S." evidence="9">
        <location>
            <begin position="1"/>
            <end position="163"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_031405" description="In isoform M." evidence="9">
        <location>
            <begin position="1"/>
            <end position="108"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>L</original>
        <variation>I</variation>
        <location>
            <position position="150"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>MTT</original>
        <variation>TTP</variation>
        <location>
            <begin position="288"/>
            <end position="290"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of myristoylation. Complete loss of infectivity." evidence="8">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>LGFFP</original>
        <variation>KL</variation>
        <location>
            <begin position="11"/>
            <end position="15"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="6">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="11"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="6">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="12"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="6">
        <original>FF</original>
        <variation>SS</variation>
        <location>
            <begin position="13"/>
            <end position="14"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity.">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>DHQLD</original>
        <variation>KL</variation>
        <location>
            <begin position="16"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>PAFRA</original>
        <variation>KL</variation>
        <location>
            <begin position="21"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>NTANP</original>
        <variation>KL</variation>
        <location>
            <begin position="26"/>
            <end position="30"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>DWDFN</original>
        <variation>KL</variation>
        <location>
            <begin position="31"/>
            <end position="35"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>PNKDT</original>
        <variation>KL</variation>
        <location>
            <begin position="36"/>
            <end position="40"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>WPDAN</original>
        <variation>KL</variation>
        <location>
            <begin position="41"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity.">
        <original>VGAG</original>
        <variation>L</variation>
        <location>
            <begin position="47"/>
            <end position="50"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>AFGLG</original>
        <variation>KL</variation>
        <location>
            <begin position="51"/>
            <end position="55"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>FTPPH</original>
        <variation>KL</variation>
        <location>
            <begin position="56"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>GGLLG</original>
        <variation>KL</variation>
        <location>
            <begin position="61"/>
            <end position="65"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>WSPQA</original>
        <variation>KL</variation>
        <location>
            <begin position="66"/>
            <end position="70"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of infectivity." evidence="7">
        <original>QGILQ</original>
        <variation>KL</variation>
        <location>
            <begin position="71"/>
            <end position="75"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on infectivity." evidence="7">
        <original>TLPAN</original>
        <variation>KL</variation>
        <location>
            <begin position="76"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on infectivity." evidence="7">
        <original>PPPAS</original>
        <variation>KL</variation>
        <location>
            <begin position="81"/>
            <end position="85"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on infectivity." evidence="7">
        <original>TNRQS</original>
        <variation>KL</variation>
        <location>
            <begin position="86"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on infectivity." evidence="7">
        <original>GRQPT</original>
        <variation>KL</variation>
        <location>
            <begin position="91"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on infectivity." evidence="7">
        <original>PLSPP</original>
        <variation>KL</variation>
        <location>
            <begin position="96"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on infectivity." evidence="7">
        <original>LRNTH</original>
        <variation>KL</variation>
        <location>
            <begin position="101"/>
            <end position="105"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on infectivity." evidence="7">
        <original>PQAMQ</original>
        <variation>KL</variation>
        <location>
            <begin position="106"/>
            <end position="110"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P03141"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04075"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10207016"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15218190"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16557545"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="17376925"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="7491754"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <sequence length="389" mass="42766" checksum="6DC9E682DA694F63" modified="2007-01-23" version="3">MGQNLSTSNPLGFFPDHQLDPAFRANTANPDWDFNPNKDTWPDANKVGAGAFGLGFTPPHGGLLGWSPQAQGILQTLPANPPPASTNRQSGRQPTPLSPPLRNTHPQAMQWNSTTFHQTLQDPRVRGLYFPAGGSSSGTVNPVLTTASPLSSIFSRIGDPALNMENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGTTVCLGQNSQSPTSNHSPTSCPPTCPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSSTTSTGPCRTCMTTAQGTSMYPSCCCTKPSDGNCTCIPIPSSWAFGKFLWEWASARFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYSILSPFLPLLPIFFCLWVYI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2022-08-03" version="119" xmlns="http://uniprot.org/uniprot">
    <accession>P03146</accession>
    <name>CAPSD_HBVD3</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Capsid protein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">Core antigen</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">Core protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">HBcAg</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">p21.5</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1" type="primary">C</name>
    </gene>
    <organism>
        <name type="scientific">Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979)</name>
        <name type="common">HBV-D</name>
        <dbReference type="NCBI Taxonomy" id="490133"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Pararnavirae</taxon>
            <taxon>Artverviricota</taxon>
            <taxon>Revtraviricetes</taxon>
            <taxon>Blubervirales</taxon>
            <taxon>Hepadnaviridae</taxon>
            <taxon>Orthohepadnavirus</taxon>
            <taxon>hepatitis B virus genotype D</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Pan troglodytes</name>
        <name type="common">Chimpanzee</name>
        <dbReference type="NCBI Taxonomy" id="9598"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1979" name="Nature" volume="281" first="646" last="650">
            <title>Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli.</title>
            <authorList>
                <person name="Galibert F."/>
                <person name="Mandart E."/>
                <person name="Fitoussi F."/>
                <person name="Tiollais P."/>
                <person name="Charnay P."/>
            </authorList>
            <dbReference type="PubMed" id="399327"/>
            <dbReference type="DOI" id="10.1038/281646a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1985" name="FEBS Lett." volume="185" first="208" last="212">
            <title>Subtype ayw variant of hepatitis B virus. DNA primary structure analysis.</title>
            <authorList>
                <person name="Bichko V."/>
                <person name="Dreilina D."/>
                <person name="Pushko P.M."/>
                <person name="Pumpen P.P."/>
                <person name="Gren E."/>
            </authorList>
            <dbReference type="PubMed" id="3996597"/>
            <dbReference type="DOI" id="10.1016/0014-5793(85)80771-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <strain>Latvia</strain>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1995" name="Structure" volume="3" first="1009" last="1019">
            <title>Evolutionary conservation in the hepatitis B virus core structure: comparison of human and duck cores.</title>
            <authorList>
                <person name="Kenney J.M."/>
                <person name="von Bonsdorff C.H."/>
                <person name="Nassal M."/>
                <person name="Fuller S.D."/>
            </authorList>
            <dbReference type="PubMed" id="8589996"/>
            <dbReference type="DOI" id="10.1016/S0969-2126(01)00237-4"/>
        </citation>
        <scope>CAPSID STRUCTURE</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1998" name="J. Virol." volume="72" first="3796" last="3803">
            <title>Phosphorylation of the core protein of hepatitis B virus by a 46-kilodalton serine kinase.</title>
            <authorList>
                <person name="Kau J.H."/>
                <person name="Ting L.P."/>
            </authorList>
            <dbReference type="PubMed" id="9557662"/>
        </citation>
        <scope>PHOSPHORYLATION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1999" name="J. Virol." volume="73" first="10122" last="10128">
            <title>Subtype-independent immature secretion and subtype-dependent replication deficiency of a highly frequent, naturally occurring mutation of human hepatitis B virus core antigen.</title>
            <authorList>
                <person name="Yuan T.T."/>
                <person name="Tai P.C."/>
                <person name="Shih C."/>
            </authorList>
            <dbReference type="PubMed" id="10559327"/>
        </citation>
        <scope>NATURALLY OCCURRING MUTATION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2002" name="J. Virol." volume="76" first="8124" last="8137">
            <title>Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein.</title>
            <authorList>
                <person name="Daub H."/>
                <person name="Blencke S."/>
                <person name="Habenberger P."/>
                <person name="Kurtenbach A."/>
                <person name="Dennenmoser J."/>
                <person name="Wissing J."/>
                <person name="Ullrich A."/>
                <person name="Cotten M."/>
            </authorList>
            <dbReference type="PubMed" id="12134018"/>
            <dbReference type="DOI" id="10.1128/JVI.76.16.8124-8137.2002"/>
        </citation>
        <scope>PHOSPHORYLATION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2005" name="J. Virol." volume="79" first="9810" last="9820">
            <title>Hepatitis B virus DNA replication is coordinated by core protein serine phosphorylation and HBx expression.</title>
            <authorList>
                <person name="Melegari M."/>
                <person name="Wolf S.K."/>
                <person name="Schneider R.J."/>
            </authorList>
            <dbReference type="PubMed" id="16014942"/>
            <dbReference type="DOI" id="10.1128/JVI.79.15.9810-9820.2005"/>
        </citation>
        <scope>PHOSPHORYLATION AT SER-155; SER-162 AND SER-170</scope>
        <scope>MUTAGENESIS OF SER-155; SER-162 AND SER-170</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="Virus Res." volume="106" first="199" last="209">
            <title>Envelopment of the hepatitis B virus nucleocapsid.</title>
            <authorList>
                <person name="Bruss V."/>
            </authorList>
            <dbReference type="PubMed" id="15567498"/>
            <dbReference type="DOI" id="10.1016/j.virusres.2004.08.016"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Self assembles to form an icosahedral capsid. Most capsids appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsids are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stuck in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse-transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genomes for transcription, or bud through the endoplasmic reticulum to provide new virions.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homodimerizes, then multimerizes. Interacts with cytosol exposed regions of viral L glycoprotein present in the reticulum-to-Golgi compartment. Interacts with human FLNB. Phosphorylated form interacts with host importin alpha; this interaction depends on the exposure of the NLS, which itself depends upon genome maturation and/or phosphorylation of the capsid protein. Interacts with host NUP153.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Virion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative initiation"/>
        <isoform>
            <id>P03146-1</id>
            <name>Capsid protein</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P0C573-1</id>
            <name>External core antigen</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylated by host SRPK1, SRPK2, and maybe protein kinase C or GAPDH. Phosphorylation is critical for pregenomic RNA packaging. Protein kinase C phosphorylation is stimulated by HBx protein and may play a role in transport of the viral genome to the nucleus at the late step during the viral replication cycle.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the orthohepadnavirus core antigen family.</text>
    </comment>
    <comment type="sequence caution">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAA24706" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="V01460">
        <property type="protein sequence ID" value="CAA24706.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X02496">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="YP_009173857.1">
        <property type="nucleotide sequence ID" value="NC_003977.2"/>
    </dbReference>
    <dbReference type="PDB" id="6HTX">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.66 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="6HU4">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.64 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="6HU7">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D/F/G/H=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7OCO">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7OCW">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7OD4">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7OD6">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7OD7">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7OD8">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7OEN">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7OEV">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7OEW">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7PZ9">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7PZI">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7PZK">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7PZL">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7PZM">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDB" id="7PZN">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A/B/C/D=1-183"/>
    </dbReference>
    <dbReference type="PDBsum" id="6HTX"/>
    <dbReference type="PDBsum" id="6HU4"/>
    <dbReference type="PDBsum" id="6HU7"/>
    <dbReference type="PDBsum" id="7OCO"/>
    <dbReference type="PDBsum" id="7OCW"/>
    <dbReference type="PDBsum" id="7OD4"/>
    <dbReference type="PDBsum" id="7OD6"/>
    <dbReference type="PDBsum" id="7OD7"/>
    <dbReference type="PDBsum" id="7OD8"/>
    <dbReference type="PDBsum" id="7OEN"/>
    <dbReference type="PDBsum" id="7OEV"/>
    <dbReference type="PDBsum" id="7OEW"/>
    <dbReference type="PDBsum" id="7PZ9"/>
    <dbReference type="PDBsum" id="7PZI"/>
    <dbReference type="PDBsum" id="7PZK"/>
    <dbReference type="PDBsum" id="7PZL"/>
    <dbReference type="PDBsum" id="7PZM"/>
    <dbReference type="PDBsum" id="7PZN"/>
    <dbReference type="BMRB" id="P03146"/>
    <dbReference type="SMR" id="P03146"/>
    <dbReference type="iPTMnet" id="P03146"/>
    <dbReference type="PRIDE" id="P03146"/>
    <dbReference type="GeneID" id="944568"/>
    <dbReference type="KEGG" id="vg:944568"/>
    <dbReference type="Proteomes" id="UP000007930">
        <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:0039619">
        <property type="term" value="C:T=4 icosahedral viral capsid"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </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:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005198">
        <property type="term" value="F:structural molecule activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0075521">
        <property type="term" value="P:microtubule-dependent intracellular transport of viral material towards nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046718">
        <property type="term" value="P:viral entry into host cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0075732">
        <property type="term" value="P:viral penetration into host nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.4090.10">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04076">
        <property type="entry name" value="HBV_HBEAG"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002006">
        <property type="entry name" value="Hepatitis_core"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036459">
        <property type="entry name" value="Viral_capsid_core_dom_sf_HBV"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00906">
        <property type="entry name" value="Hepatitis_core"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47852">
        <property type="entry name" value="SSF47852"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0024">Alternative initiation</keyword>
    <keyword id="KW-0167">Capsid protein</keyword>
    <keyword id="KW-1176">Cytoplasmic inwards viral transport</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-1035">Host cytoplasm</keyword>
    <keyword id="KW-0945">Host-virus interaction</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-0677">Repeat</keyword>
    <keyword id="KW-0694">RNA-binding</keyword>
    <keyword id="KW-1144">T=4 icosahedral capsid protein</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_0000222315" description="Capsid protein">
        <location>
            <begin position="1"/>
            <end position="183"/>
        </location>
    </feature>
    <feature type="repeat" description="1; half-length">
        <location>
            <begin position="155"/>
            <end position="161"/>
        </location>
    </feature>
    <feature type="repeat" description="2">
        <location>
            <begin position="162"/>
            <end position="169"/>
        </location>
    </feature>
    <feature type="repeat" description="3">
        <location>
            <begin position="170"/>
            <end position="177"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="136"/>
            <end position="183"/>
        </location>
    </feature>
    <feature type="region of interest" description="3 X 8 AA repeats of S-P-R-R-R-[PR]-S-Q">
        <location>
            <begin position="155"/>
            <end position="177"/>
        </location>
    </feature>
    <feature type="region of interest" description="RNA binding" evidence="1">
        <location>
            <begin position="177"/>
            <end position="183"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Bipartite nuclear localization signal" evidence="1">
        <location>
            <begin position="158"/>
            <end position="175"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="2">
        <location>
            <begin position="152"/>
            <end position="173"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by host" evidence="1 3">
        <location>
            <position position="155"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by host" evidence="1 3">
        <location>
            <position position="162"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by host" evidence="1 3">
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>A</original>
        <variation>I</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="sequence variant" description="Frequent mutation in chronic HBV carriers.">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of replication." evidence="3">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="155"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of pregenomic RNA encapsidation and replication." evidence="3">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="162"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Partial loss of replication." evidence="3">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="helix" evidence="4">
        <location>
            <begin position="7"/>
            <end position="9"/>
        </location>
    </feature>
    <feature type="helix" evidence="4">
        <location>
            <begin position="13"/>
            <end position="16"/>
        </location>
    </feature>
    <feature type="strand" evidence="5">
        <location>
            <begin position="17"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="helix" evidence="4">
        <location>
            <begin position="21"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="helix" evidence="4">
        <location>
            <begin position="27"/>
            <end position="42"/>
        </location>
    </feature>
    <feature type="strand" evidence="4">
        <location>
            <begin position="44"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="helix" evidence="4">
        <location>
            <begin position="50"/>
            <end position="75"/>
        </location>
    </feature>
    <feature type="helix" evidence="4">
        <location>
            <begin position="79"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="helix" evidence="4">
        <location>
            <begin position="92"/>
            <end position="109"/>
        </location>
    </feature>
    <feature type="helix" evidence="4">
        <location>
            <begin position="112"/>
            <end position="127"/>
        </location>
    </feature>
    <feature type="helix" evidence="4">
        <location>
            <begin position="130"/>
            <end position="132"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04076"/>
        </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="16014942"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="4">
        <source>
            <dbReference type="PDB" id="6HU4"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="5">
        <source>
            <dbReference type="PDB" id="7OD7"/>
        </source>
    </evidence>
    <sequence length="183" mass="21116" checksum="E0D9D9763F24E958" modified="1986-07-21" version="1">MDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMTLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQLLWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2022-08-03" version="111" xmlns="http://uniprot.org/uniprot">
    <accession>P03156</accession>
    <accession>P04484</accession>
    <name>DPOL_HBVD3</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Protein P</fullName>
        </recommendedName>
        <domain>
            <recommendedName>
                <fullName evidence="1">DNA-directed DNA polymerase</fullName>
                <ecNumber evidence="1">2.7.7.7</ecNumber>
            </recommendedName>
        </domain>
        <domain>
            <recommendedName>
                <fullName evidence="1">RNA-directed DNA polymerase</fullName>
                <ecNumber evidence="1">2.7.7.49</ecNumber>
            </recommendedName>
        </domain>
        <domain>
            <recommendedName>
                <fullName evidence="1">Ribonuclease H</fullName>
                <ecNumber evidence="1">3.1.26.4</ecNumber>
            </recommendedName>
        </domain>
    </protein>
    <gene>
        <name evidence="1" type="primary">P</name>
    </gene>
    <organism>
        <name type="scientific">Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979)</name>
        <name type="common">HBV-D</name>
        <dbReference type="NCBI Taxonomy" id="490133"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Pararnavirae</taxon>
            <taxon>Artverviricota</taxon>
            <taxon>Revtraviricetes</taxon>
            <taxon>Blubervirales</taxon>
            <taxon>Hepadnaviridae</taxon>
            <taxon>Orthohepadnavirus</taxon>
            <taxon>hepatitis B virus genotype D</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Pan troglodytes</name>
        <name type="common">Chimpanzee</name>
        <dbReference type="NCBI Taxonomy" id="9598"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1979" name="Nature" volume="281" first="646" last="650">
            <title>Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli.</title>
            <authorList>
                <person name="Galibert F."/>
                <person name="Mandart E."/>
                <person name="Fitoussi F."/>
                <person name="Tiollais P."/>
                <person name="Charnay P."/>
            </authorList>
            <dbReference type="PubMed" id="399327"/>
            <dbReference type="DOI" id="10.1038/281646a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1985" name="FEBS Lett." volume="185" first="208" last="212">
            <title>Subtype ayw variant of hepatitis B virus. DNA primary structure analysis.</title>
            <authorList>
                <person name="Bichko V."/>
                <person name="Dreilina D."/>
                <person name="Pushko P.M."/>
                <person name="Pumpen P.P."/>
                <person name="Gren E."/>
            </authorList>
            <dbReference type="PubMed" id="3996597"/>
            <dbReference type="DOI" id="10.1016/0014-5793(85)80771-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <strain>Latvia</strain>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2007" name="World J. Gastroenterol." volume="13" first="48" last="64">
            <title>Hepatitis B virus replication.</title>
            <authorList>
                <person name="Beck J."/>
                <person name="Nassal M."/>
            </authorList>
            <dbReference type="PubMed" id="17206754"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Multifunctional enzyme that converts the viral RNA genome into dsDNA in viral cytoplasmic capsids. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3'- to 5'-endonucleasic mode. Neo-synthesized pregenomic RNA (pgRNA) are encapsidated together with the P protein, and reverse-transcribed inside the nucleocapsid. Initiation of reverse-transcription occurs first by binding the epsilon loop on the pgRNA genome, and is initiated by protein priming, thereby the 5'-end of (-)DNA is covalently linked to P protein. Partial (+)DNA is synthesized from the (-)DNA template and generates the relaxed circular DNA (RC-DNA) genome. After budding and infection, the RC-DNA migrates in the nucleus, and is converted into a plasmid-like covalently closed circular DNA (cccDNA). The activity of P protein does not seem to be necessary for cccDNA generation, and is presumably released from (+)DNA by host nuclear DNA repair machinery.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1)</text>
            <dbReference type="Rhea" id="RHEA:22508"/>
            <dbReference type="Rhea" id="RHEA-COMP:17339"/>
            <dbReference type="Rhea" id="RHEA-COMP:17340"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:61560"/>
            <dbReference type="ChEBI" id="CHEBI:173112"/>
            <dbReference type="EC" id="2.7.7.7"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1)</text>
            <dbReference type="Rhea" id="RHEA:22508"/>
            <dbReference type="Rhea" id="RHEA-COMP:17339"/>
            <dbReference type="Rhea" id="RHEA-COMP:17340"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:61560"/>
            <dbReference type="ChEBI" id="CHEBI:173112"/>
            <dbReference type="EC" id="2.7.7.49"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>Endonucleolytic cleavage to 5'-phosphomonoester.</text>
            <dbReference type="EC" id="3.1.26.4"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="1">Activated by host HSP70 and HSP40 in vitro to be able to bind the epsilon loop of the pgRNA. Because deletion of the RNase H region renders the protein partly chaperone-independent, the chaperones may be needed indirectly to relieve occlusion of the RNA-binding site by this domain. Inhibited by several reverse-transcriptase inhibitors: Lamivudine, Adefovir and Entecavir.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">Terminal protein domain (TP) is hepadnavirus-specific. Spacer domain is highly variable and separates the TP and RT domains. Polymerase/reverse-transcriptase domain (RT) and ribonuclease H domain (RH) are similar to retrovirus reverse transcriptase/RNase H.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The polymerase/reverse transcriptase (RT) and ribonuclease H (RH) domains are structured in five subdomains: finger, palm, thumb, connection and RNase H. Within the palm subdomain, the 'primer grip' region is thought to be involved in the positioning of the primer terminus for accommodating the incoming nucleotide. The RH domain stabilizes the association of RT with primer-template.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="1">Hepadnaviral virions contain probably just one P protein molecule per particle.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the hepadnaviridae P protein family.</text>
    </comment>
    <dbReference type="EC" id="2.7.7.7" evidence="1"/>
    <dbReference type="EC" id="2.7.7.49" evidence="1"/>
    <dbReference type="EC" id="3.1.26.4" evidence="1"/>
    <dbReference type="EMBL" id="V01460">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X02496">
        <property type="protein sequence ID" value="CAB41700.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="PIR" id="A00702">
        <property type="entry name" value="JDVLVA"/>
    </dbReference>
    <dbReference type="PIR" id="A00703">
        <property type="entry name" value="JDVLVB"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000007930">
        <property type="component" value="Genome"/>
    </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:0003887">
        <property type="term" value="F:DNA-directed DNA polymerase 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:0003964">
        <property type="term" value="F:RNA-directed DNA polymerase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004523">
        <property type="term" value="F:RNA-DNA hybrid ribonuclease 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="GO" id="GO:0039503">
        <property type="term" value="P:suppression by virus of host innate immune response"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.70.270">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04073">
        <property type="entry name" value="HBV_DPOL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043502">
        <property type="entry name" value="DNA/RNA_pol_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001462">
        <property type="entry name" value="DNApol_viral_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000201">
        <property type="entry name" value="DNApol_viral_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037531">
        <property type="entry name" value="HBV_DPOL"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043128">
        <property type="entry name" value="Rev_trsase/Diguanyl_cyclase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000477">
        <property type="entry name" value="RT_dom"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00336">
        <property type="entry name" value="DNA_pol_viral_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00242">
        <property type="entry name" value="DNA_pol_viral_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00078">
        <property type="entry name" value="RVT_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56672">
        <property type="entry name" value="SSF56672"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50878">
        <property type="entry name" value="RT_POL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0235">DNA replication</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0239">DNA-directed DNA polymerase</keyword>
    <keyword id="KW-0255">Endonuclease</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1090">Inhibition of host innate immune response by virus</keyword>
    <keyword id="KW-1113">Inhibition of host RLR pathway by virus</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0511">Multifunctional enzyme</keyword>
    <keyword id="KW-0540">Nuclease</keyword>
    <keyword id="KW-0548">Nucleotidyltransferase</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0695">RNA-directed DNA polymerase</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0899">Viral immunoevasion</keyword>
    <feature type="chain" id="PRO_0000222344" description="Protein P">
        <location>
            <begin position="1"/>
            <end position="832"/>
        </location>
    </feature>
    <feature type="domain" description="Reverse transcriptase" evidence="1">
        <location>
            <begin position="346"/>
            <end position="589"/>
        </location>
    </feature>
    <feature type="region of interest" description="Terminal protein domain (TP)" evidence="1">
        <location>
            <begin position="1"/>
            <end position="177"/>
        </location>
    </feature>
    <feature type="region of interest" description="Spacer" evidence="1">
        <location>
            <begin position="178"/>
            <end position="335"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="186"/>
            <end position="225"/>
        </location>
    </feature>
    <feature type="region of interest" description="Polymerase/reverse transcriptase domain (RT)" evidence="1">
        <location>
            <begin position="336"/>
            <end position="679"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="418"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="540"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="541"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="site" description="Priming of reverse-transcription by covalently linking the first nucleotide of the (-)DNA" evidence="1">
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="118"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="136"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>F</original>
        <variation>I</variation>
        <location>
            <position position="236"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="240"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>TNF</original>
        <variation>RNV</variation>
        <location>
            <begin position="255"/>
            <end position="257"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="293"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>L</original>
        <variation>H</variation>
        <location>
            <position position="330"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="356"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>LNN</original>
        <variation>FNY</variation>
        <location>
            <begin position="457"/>
            <end position="459"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>PD</original>
        <variation>QN</variation>
        <location>
            <begin position="465"/>
            <end position="466"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>Y</original>
        <variation>S</variation>
        <location>
            <position position="470"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="583"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="598"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="613"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>SAP</original>
        <variation>LAR</variation>
        <location>
            <begin position="709"/>
            <end position="711"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>I</original>
        <variation>L</variation>
        <location>
            <position position="734"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>F</original>
        <variation>Y</variation>
        <location>
            <position position="749"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04073"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <sequence length="832" mass="93677" checksum="7AB3AAE58A57D0D6" modified="1986-07-21" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2022-05-25" version="45" xmlns="http://uniprot.org/uniprot">
    <accession>P03163</accession>
    <name>Y10K_HBVD3</name>
    <protein>
        <recommendedName>
            <fullName>Putative uncharacterized 10.4 kDa protein</fullName>
        </recommendedName>
    </protein>
    <organism>
        <name type="scientific">Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979)</name>
        <name type="common">HBV-D</name>
        <dbReference type="NCBI Taxonomy" id="490133"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Pararnavirae</taxon>
            <taxon>Artverviricota</taxon>
            <taxon>Revtraviricetes</taxon>
            <taxon>Blubervirales</taxon>
            <taxon>Hepadnaviridae</taxon>
            <taxon>Orthohepadnavirus</taxon>
            <taxon>hepatitis B virus genotype D</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Pan troglodytes</name>
        <name type="common">Chimpanzee</name>
        <dbReference type="NCBI Taxonomy" id="9598"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1979" name="Nature" volume="281" first="646" last="650">
            <title>Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli.</title>
            <authorList>
                <person name="Galibert F."/>
                <person name="Mandart E."/>
                <person name="Fitoussi F."/>
                <person name="Tiollais P."/>
                <person name="Charnay P."/>
            </authorList>
            <dbReference type="PubMed" id="399327"/>
            <dbReference type="DOI" id="10.1038/281646a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <comment type="caution">
        <text evidence="2">Product of a dubious gene prediction.</text>
    </comment>
    <dbReference type="EMBL" id="V01460">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="PIR" id="A03717">
        <property type="entry name" value="A03717"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000007930">
        <property type="component" value="Genome"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000222377" description="Putative uncharacterized 10.4 kDa protein">
        <location>
            <begin position="1"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1"/>
            <end position="73"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="1">
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="1">
        <location>
            <begin position="40"/>
            <end position="57"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="1">
        <location>
            <begin position="58"/>
            <end position="73"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="2"/>
    <sequence length="95" mass="10387" checksum="5AE920DA99EDE6F8" modified="1986-07-21" version="1">MRRAEVKRSAHGPADEKAQTGSPRKERCAPWSVGTADGEGDERVPSDPEKGRPQDSAPTGRKQRTSRAGSSWQHSLAAMETMYICGIGQQSYQSR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2022-05-25" version="45" xmlns="http://uniprot.org/uniprot">
    <accession>P03164</accession>
    <name>Y15K_HBVD3</name>
    <protein>
        <recommendedName>
            <fullName>Putative uncharacterized 15.3 kDa protein</fullName>
        </recommendedName>
    </protein>
    <organism>
        <name type="scientific">Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979)</name>
        <name type="common">HBV-D</name>
        <dbReference type="NCBI Taxonomy" id="490133"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Pararnavirae</taxon>
            <taxon>Artverviricota</taxon>
            <taxon>Revtraviricetes</taxon>
            <taxon>Blubervirales</taxon>
            <taxon>Hepadnaviridae</taxon>
            <taxon>Orthohepadnavirus</taxon>
            <taxon>hepatitis B virus genotype D</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Pan troglodytes</name>
        <name type="common">Chimpanzee</name>
        <dbReference type="NCBI Taxonomy" id="9598"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1979" name="Nature" volume="281" first="646" last="650">
            <title>Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli.</title>
            <authorList>
                <person name="Galibert F."/>
                <person name="Mandart E."/>
                <person name="Fitoussi F."/>
                <person name="Tiollais P."/>
                <person name="Charnay P."/>
            </authorList>
            <dbReference type="PubMed" id="399327"/>
            <dbReference type="DOI" id="10.1038/281646a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <comment type="caution">
        <text evidence="1">Product of a dubious gene prediction.</text>
    </comment>
    <dbReference type="EMBL" id="V01460">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="PIR" id="A03718">
        <property type="entry name" value="A03718"/>
    </dbReference>
    <dbReference type="SMR" id="P03164"/>
    <dbReference type="Proteomes" id="UP000007930">
        <property type="component" value="Genome"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000222376" description="Putative uncharacterized 15.3 kDa protein">
        <location>
            <begin position="1"/>
            <end position="133"/>
        </location>
    </feature>
    <evidence type="ECO:0000305" key="1"/>
    <sequence length="133" mass="15296" checksum="243740990BEFF67F" modified="1986-07-21" version="1">MDRQRSRKGSTHALMAHDQAPASGGCVSKHLAQTWPLPGNGVKVQVLFTQKGLVSWRESESLLRLNTCIQRHQRRITTLCKRGSKTQKTHNSLTYFPINRPVNRKFSKTFFDFLYDVFLWQGPITSNDITHKI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2022-05-25" version="99" xmlns="http://uniprot.org/uniprot">
    <accession>P03165</accession>
    <name>X_HBVD3</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Protein X</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">HBx</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">Peptide X</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">pX</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1" type="primary">X</name>
    </gene>
    <organism>
        <name type="scientific">Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979)</name>
        <name type="common">HBV-D</name>
        <dbReference type="NCBI Taxonomy" id="490133"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Pararnavirae</taxon>
            <taxon>Artverviricota</taxon>
            <taxon>Revtraviricetes</taxon>
            <taxon>Blubervirales</taxon>
            <taxon>Hepadnaviridae</taxon>
            <taxon>Orthohepadnavirus</taxon>
            <taxon>hepatitis B virus genotype D</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Pan troglodytes</name>
        <name type="common">Chimpanzee</name>
        <dbReference type="NCBI Taxonomy" id="9598"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1979" name="Nature" volume="281" first="646" last="650">
            <title>Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli.</title>
            <authorList>
                <person name="Galibert F."/>
                <person name="Mandart E."/>
                <person name="Fitoussi F."/>
                <person name="Tiollais P."/>
                <person name="Charnay P."/>
            </authorList>
            <dbReference type="PubMed" id="399327"/>
            <dbReference type="DOI" id="10.1038/281646a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1985" name="FEBS Lett." volume="185" first="208" last="212">
            <title>Subtype ayw variant of hepatitis B virus. DNA primary structure analysis.</title>
            <authorList>
                <person name="Bichko V."/>
                <person name="Dreilina D."/>
                <person name="Pushko P.M."/>
                <person name="Pumpen P.P."/>
                <person name="Gren E."/>
            </authorList>
            <dbReference type="PubMed" id="3996597"/>
            <dbReference type="DOI" id="10.1016/0014-5793(85)80771-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <strain>Latvia</strain>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1997" name="Hepatology" volume="26" first="1045" last="1053">
            <title>Isolation and molecular characterization of hepatitis B virus X-protein from a baculovirus expression system.</title>
            <authorList>
                <person name="Urban S."/>
                <person name="Hildt E."/>
                <person name="Eckerskorn C."/>
                <person name="Sirma H."/>
                <person name="Kekule A."/>
                <person name="Hofschneider P.H."/>
            </authorList>
            <dbReference type="PubMed" id="9328333"/>
            <dbReference type="DOI" id="10.1002/hep.510260437"/>
        </citation>
        <scope>CHARACTERIZATION</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2001" name="Virology" volume="287" first="266" last="274">
            <title>Hepatitis B virus X protein interferes with cell viability through interaction with the p127-kDa UV-damaged DNA-binding protein.</title>
            <authorList>
                <person name="Lin-Marq N."/>
                <person name="Bontron S."/>
                <person name="Leupin O."/>
                <person name="Strubin M."/>
            </authorList>
            <dbReference type="PubMed" id="11531405"/>
            <dbReference type="DOI" id="10.1006/viro.2001.1036"/>
        </citation>
        <scope>INTERACTION WITH HUMAN DDB1</scope>
        <scope>MUTAGENESIS OF 77-ARG-ARG-78; LYS-91; 95-LYS-ARG-96; LEU-98; ASP-107 AND 113-LYS-ASP-114</scope>
        <source>
            <strain>Switzerland/Strubin/1999</strain>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2002" name="J. Biol. Chem." volume="277" first="38847" last="38854">
            <title>Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2.</title>
            <authorList>
                <person name="Bontron S."/>
                <person name="Lin-Marq N."/>
                <person name="Strubin M."/>
            </authorList>
            <dbReference type="PubMed" id="12151405"/>
            <dbReference type="DOI" id="10.1074/jbc.M205722200"/>
        </citation>
        <scope>INTERACTION WITH HUMAN DDB1</scope>
        <source>
            <strain>Switzerland/Strubin/1999</strain>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2003" name="J. Virol." volume="77" first="6274" last="6283">
            <title>Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities.</title>
            <authorList>
                <person name="Leupin O."/>
                <person name="Bontron S."/>
                <person name="Strubin M."/>
            </authorList>
            <dbReference type="PubMed" id="12743284"/>
            <dbReference type="DOI" id="10.1128/JVI.77.11.6274-6283.2003"/>
        </citation>
        <scope>INTERACTION WITH HUMAN DDB1</scope>
        <source>
            <strain>Switzerland/Strubin/1999</strain>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2005" name="J. Virol." volume="79" first="4238" last="4245">
            <title>Hepatitis B virus X protein stimulates viral genome replication via a DDB1-dependent pathway distinct from that leading to cell death.</title>
            <authorList>
                <person name="Leupin O."/>
                <person name="Bontron S."/>
                <person name="Schaeffer C."/>
                <person name="Strubin M."/>
            </authorList>
            <dbReference type="PubMed" id="15767425"/>
            <dbReference type="DOI" id="10.1128/JVI.79.7.4238-4245.2005"/>
        </citation>
        <scope>FUNCTION</scope>
        <source>
            <strain>Switzerland/Strubin/1999</strain>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2006" name="Virus Res." volume="115" first="31" last="42">
            <title>Interaction of the hepatitis B virus protein HBx with the human transcription regulatory protein p120E4F in vitro.</title>
            <authorList>
                <person name="Rui E."/>
                <person name="Moura P.R."/>
                <person name="Goncalves K.A."/>
                <person name="Rooney R.J."/>
                <person name="Kobarg J."/>
            </authorList>
            <dbReference type="PubMed" id="16112766"/>
            <dbReference type="DOI" id="10.1016/j.virusres.2005.07.003"/>
        </citation>
        <scope>INTERACTION WITH E4F1</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2004" name="J. Virol." volume="78" first="12725" last="12734">
            <title>The enigmatic X gene of hepatitis B virus.</title>
            <authorList>
                <person name="Bouchard M.J."/>
                <person name="Schneider R.J."/>
            </authorList>
            <dbReference type="PubMed" id="15542625"/>
            <dbReference type="DOI" id="10.1128/JVI.78.23.12725-12734.2004"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2006" name="Cancer Sci." volume="97" first="977" last="983">
            <title>Molecular functions and biological roles of hepatitis B virus x protein.</title>
            <authorList>
                <person name="Tang H."/>
                <person name="Oishi N."/>
                <person name="Kaneko S."/>
                <person name="Murakami S."/>
            </authorList>
            <dbReference type="PubMed" id="16984372"/>
            <dbReference type="DOI" id="10.1111/j.1349-7006.2006.00299.x"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3">Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. Does not seem to be essential for HBV infection. May be directly involved in development of cirrhosis and liver cancer (hepatocellular carcinoma). Most of cytosolic activities involve modulation of cytosolic calcium. The effect on apoptosis is controversial depending on the cell types in which the studies have been conducted. May induce apoptosis by localizing in mitochondria and causing loss of mitochondrial membrane potential. May also modulate apoptosis by binding host CFLAR, a key regulator of the death-inducing signaling complex (DISC). Promotes viral transcription by using the host E3 ubiquitin ligase DDB1 to target the SMC5-SMC6 complex to proteasomal degradation. This host complex would otherwise bind to viral episomal DNA, and prevents its transcription. Moderately stimulates transcription of many different viral and cellular transcription elements. Promoters and enhancers stimulated by HBx contain DNA binding sites for NF-kappa-B, AP-1, AP-2, c-EBP, ATF/CREB, or the calcium-activated factor NF-AT.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">May form homodimer. May interact with host CEBPA, CFLAR, CREB1, DDB1, E4F1, HBXIP, HSPD1/HSP60, NFKBIA, POLR2E and SMAD4. Interacts with host SMC5-SMC6 complex and induces its degradation.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7683985">
            <id>P03165</id>
        </interactant>
        <interactant intactId="EBI-296087">
            <id>P31749</id>
            <label>AKT1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7683985">
            <id>P03165</id>
        </interactant>
        <interactant intactId="EBI-298707">
            <id>P31750</id>
            <label>Akt1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Host cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host mitochondrion</location>
        </subcellularLocation>
        <text evidence="1">Mainly cytoplasmic as only a fraction is detected in the nucleus. In cytoplasm, a minor fraction associates with mitochondria or proteasomes.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">A fraction may be phosphorylated in insect cells and HepG2 cells, a human hepatoblastoma cell line. Phosphorylated in vitro by host protein kinase C or mitogen-activated protein kinase. N-acetylated in insect cells.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the orthohepadnavirus protein X family.</text>
    </comment>
    <comment type="caution">
        <text>Transcriptional activities should be taken with a grain of salt. As of 2007, all studies demonstrating in vivo interaction between protein X and transcriptional components were performed with significant overexpression of both proteins and in the absence of viral infection.</text>
    </comment>
    <dbReference type="EMBL" id="V01460">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X02496">
        <property type="protein sequence ID" value="CAB41697.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="PIR" id="A03719">
        <property type="entry name" value="QQVLD1"/>
    </dbReference>
    <dbReference type="PIR" id="A05237">
        <property type="entry name" value="QQVLBH"/>
    </dbReference>
    <dbReference type="SMR" id="P03165"/>
    <dbReference type="IntAct" id="P03165">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="MINT" id="P03165"/>
    <dbReference type="Proteomes" id="UP000007930">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033650">
        <property type="term" value="C:host cell mitochondrion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042025">
        <property type="term" value="C:host cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039652">
        <property type="term" value="P:induction by virus of host NF-kappaB cascade"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </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-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:0019079">
        <property type="term" value="P:viral genome replication"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04074">
        <property type="entry name" value="HBV_X"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000236">
        <property type="entry name" value="Transactivation_prot_X"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00739">
        <property type="entry name" value="X"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1074">Activation of host NF-kappa-B by virus</keyword>
    <keyword id="KW-0010">Activator</keyword>
    <keyword id="KW-0053">Apoptosis</keyword>
    <keyword id="KW-1035">Host cytoplasm</keyword>
    <keyword id="KW-1079">Host G2/M cell cycle arrest by virus</keyword>
    <keyword id="KW-1045">Host mitochondrion</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-1185">Reference proteome</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <feature type="chain" id="PRO_0000222361" description="Protein X">
        <location>
            <begin position="1"/>
            <end position="154"/>
        </location>
    </feature>
    <feature type="region of interest" description="Mitochondrial targeting sequence" evidence="1">
        <location>
            <begin position="68"/>
            <end position="117"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Switzerland/Strubin/1999.">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Switzerland/Strubin/1999.">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Switzerland/Strubin/1999.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Switzerland/Strubin/1999.">
        <original>PSPS</original>
        <variation>SSLP</variation>
        <location>
            <begin position="40"/>
            <end position="43"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Switzerland/Strubin/1999.">
        <original>TD</original>
        <variation>AA</variation>
        <location>
            <begin position="47"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>NAHQI</original>
        <variation>KAQPF</variation>
        <location>
            <begin position="84"/>
            <end position="88"/>
        </location>
    </feature>
    <feature type="sequence variant" description="In strain: Latvia.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="102"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with human DDB1." evidence="2">
        <original>RR</original>
        <variation>EE</variation>
        <location>
            <begin position="77"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with human DDB1." evidence="2">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="91"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with human DDB1.">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of interaction with human DDB1.">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of interaction with human DDB1." evidence="2">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with human DDB1." evidence="2">
        <original>D</original>
        <variation>R</variation>
        <location>
            <position position="107"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with human DDB1." evidence="2">
        <original>KD</original>
        <variation>ER</variation>
        <location>
            <begin position="113"/>
            <end position="114"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04074"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="11531405"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="15767425"/>
        </source>
    </evidence>
    <sequence length="154" mass="16618" checksum="29FD1CC9E09A34B5" modified="1990-04-01" version="2">MAARLCCQLDPARDVLCLRPVGAESRGRPFSGSLGTLSSPSPSAVPTDHGAHLSLRGLPVCAFSSAGPCALRFTSARRMETTVNAHQILPKVLHKRTLGLSAMSTTDLEAYFKDCLFKDWEELGEEIRLKVFVLGGCRHKLVCAPAPCNFFTSA</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-03-18" modified="2022-08-03" version="57" xmlns="http://uniprot.org/uniprot">
    <accession>P0C573</accession>
    <name>HBEAG_HBVD3</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">External core antigen</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">HBeAg</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">Precore protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">p25</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1" type="primary">C</name>
    </gene>
    <organism>
        <name type="scientific">Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979)</name>
        <name type="common">HBV-D</name>
        <dbReference type="NCBI Taxonomy" id="490133"/>
        <lineage>
            <taxon>Viruses</taxon>
            <taxon>Riboviria</taxon>
            <taxon>Pararnavirae</taxon>
            <taxon>Artverviricota</taxon>
            <taxon>Revtraviricetes</taxon>
            <taxon>Blubervirales</taxon>
            <taxon>Hepadnaviridae</taxon>
            <taxon>Orthohepadnavirus</taxon>
            <taxon>hepatitis B virus genotype D</taxon>
        </lineage>
    </organism>
    <organismHost>
        <name type="scientific">Pan troglodytes</name>
        <name type="common">Chimpanzee</name>
        <dbReference type="NCBI Taxonomy" id="9598"/>
    </organismHost>
    <organismHost>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
    </organismHost>
    <reference key="1">
        <citation type="journal article" date="1979" name="Nature" volume="281" first="646" last="650">
            <title>Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli.</title>
            <authorList>
                <person name="Galibert F."/>
                <person name="Mandart E."/>
                <person name="Fitoussi F."/>
                <person name="Tiollais P."/>
                <person name="Charnay P."/>
            </authorList>
            <dbReference type="PubMed" id="399327"/>
            <dbReference type="DOI" id="10.1038/281646a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1985" name="FEBS Lett." volume="185" first="208" last="212">
            <title>Subtype ayw variant of hepatitis B virus. DNA primary structure analysis.</title>
            <authorList>
                <person name="Bichko V."/>
                <person name="Dreilina D."/>
                <person name="Pushko P.M."/>
                <person name="Pumpen P.P."/>
                <person name="Gren E."/>
            </authorList>
            <dbReference type="PubMed" id="3996597"/>
            <dbReference type="DOI" id="10.1016/0014-5793(85)80771-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <strain>Latvia</strain>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2007" name="J. Virol." volume="81" first="13218" last="13229">
            <title>A structural model for duck hepatitis B virus core protein derived by extensive mutagenesis.</title>
            <authorList>
                <person name="Nassal M."/>
                <person name="Leifer I."/>
                <person name="Wingert I."/>
                <person name="Dallmeier K."/>
                <person name="Prinz S."/>
                <person name="Vorreiter J."/>
            </authorList>
            <dbReference type="PubMed" id="17881438"/>
            <dbReference type="DOI" id="10.1128/JVI.00846-07"/>
        </citation>
        <scope>CLEAVAGE BY HOST FURIN</scope>
        <scope>MUTAGENESIS OF ARG-180; ARG-183; ARG-186; ARG-188; ARG-193; ARG-196; ARG-201 AND ARG-204</scope>
    </reference>
    <comment type="function">
        <text evidence="1">May regulate immune response to the intracellular capsid in acting as a T-cell tolerogen, by having an immunoregulatory effect which prevents destruction of infected cells by cytotoxic T-cells. This immune regulation may predispose to chronicity during perinatal infections and prevent severe liver injury during adult infections.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homodimerizes.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Secreted</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Host nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative initiation"/>
        <isoform>
            <id>P0C573-1</id>
            <name>External core antigen</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P03146-1</id>
            <name>Capsid protein</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Cleaved by host furin.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the orthohepadnavirus precore antigen family.</text>
    </comment>
    <dbReference type="EMBL" id="V01460">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X02496">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="SMR" id="P0C573"/>
    <dbReference type="ABCD" id="P0C573">
        <property type="antibodies" value="2 sequenced antibodies"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000007930">
        <property type="component" value="Genome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </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-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042025">
        <property type="term" value="C:host cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0039619">
        <property type="term" value="C:T=4 icosahedral viral capsid"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </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:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005198">
        <property type="term" value="F:structural molecule activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0075521">
        <property type="term" value="P:microtubule-dependent intracellular transport of viral material towards nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046718">
        <property type="term" value="P:viral entry into host cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="GO" id="GO:0075732">
        <property type="term" value="P:viral penetration into host nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniRule"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.4090.10">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_04076">
        <property type="entry name" value="HBV_HBEAG"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013195">
        <property type="entry name" value="Hepatitis_B_virus_capsid_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002006">
        <property type="entry name" value="Hepatitis_core"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036459">
        <property type="entry name" value="Viral_capsid_core_dom_sf_HBV"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08290">
        <property type="entry name" value="Hep_core_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00906">
        <property type="entry name" value="Hepatitis_core"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47852">
        <property type="entry name" value="SSF47852"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0024">Alternative initiation</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-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0899">Viral immunoevasion</keyword>
    <feature type="signal peptide" evidence="1">
        <location>
            <begin position="1"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000324724" description="External core antigen" evidence="1">
        <location>
            <begin position="20"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000324725">
        <location>
            <begin position="184"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="repeat" description="1; half-length">
        <location>
            <begin position="184"/>
            <end position="190"/>
        </location>
    </feature>
    <feature type="repeat" description="2">
        <location>
            <begin position="191"/>
            <end position="198"/>
        </location>
    </feature>
    <feature type="repeat" description="3">
        <location>
            <begin position="199"/>
            <end position="206"/>
        </location>
    </feature>
    <feature type="region of interest" description="HBEAG" evidence="1">
        <location>
            <begin position="25"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="165"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="region of interest" description="3 X 8 AA repeats of S-P-R-R-R-R-S-Q">
        <location>
            <begin position="184"/>
            <end position="206"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="2">
        <location>
            <begin position="181"/>
            <end position="202"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by host" evidence="1">
        <location>
            <begin position="183"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain" evidence="1">
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain" evidence="1">
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of cleavage." evidence="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="180"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of cleavage." evidence="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on cleavage." evidence="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="186"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on cleavage." evidence="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="188"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on cleavage." evidence="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="193"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on cleavage." evidence="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="196"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on cleavage." evidence="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="201"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on cleavage." evidence="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="204"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="HAMAP-Rule" id="MF_04076"/>
        </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="17881438"/>
        </source>
    </evidence>
    <sequence length="212" mass="24350" checksum="D3016A4E8B05A1B8" modified="2008-03-18" version="1" precursor="true">MQLFHLCLIISCSCPTVQASKLCLGWLWGMDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMTLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQLLWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC</sequence>
</entry>
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</uniprot>