ID   DPOL_WHV3               Reviewed;         884 AA.
AC   P12899;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   10-JUN-2026, entry version 107.
DE   RecName: Full=Protein P {ECO:0000255|HAMAP-Rule:MF_04073};
DE   Includes:
DE     RecName: Full=DNA-directed DNA polymerase {ECO:0000255|HAMAP-Rule:MF_04073};
DE              EC=2.7.7.7 {ECO:0000255|HAMAP-Rule:MF_04073};
DE   Includes:
DE     RecName: Full=RNA-directed DNA polymerase {ECO:0000255|HAMAP-Rule:MF_04073};
DE              EC=2.7.7.49 {ECO:0000255|HAMAP-Rule:MF_04073};
DE   Includes:
DE     RecName: Full=Ribonuclease H {ECO:0000255|HAMAP-Rule:MF_04073};
DE              EC=3.1.26.4 {ECO:0000255|HAMAP-Rule:MF_04073};
GN   Name=P {ECO:0000255|HAMAP-Rule:MF_04073};
OS   Woodchuck hepatitis B virus (isolate 59) (WHV).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Blubervirales; Hepadnaviridae; Orthohepadnavirus;
OC   Orthohepadnavirus marmotae; Woodchuck hepatitis virus.
OX   NCBI_TaxID=10431;
OH   NCBI_TaxID=9995; Marmota monax (Woodchuck).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3336938; DOI=10.1016/0042-6822(88)90389-3;
RA   Cohen J.I., Miller R.H., Rosenblum B., Denniston K., Gerin J.L.,
RA   Purcell R.H.;
RT   "Sequence comparison of woodchuck hepatitis virus replicative forms shows
RT   conservation of the genome.";
RL   Virology 162:12-20(1988).
RN   [2]
RP   REVIEW.
RX   PubMed=17206754; DOI=10.3748/wjg.v13.i1.48;
RA   Beck J., Nassal M.;
RT   "Hepatitis B virus replication.";
RL   World J. Gastroenterol. 13:48-64(2007).
CC   -!- FUNCTION: Multifunctional enzyme that converts the viral RNA genome
CC       into dsDNA in viral cytoplasmic capsids. This enzyme displays a DNA
CC       polymerase activity that can copy either DNA or RNA templates, and a
CC       ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-
CC       DNA heteroduplexes in a partially processive 3'- to 5'-endonucleasic
CC       mode. Neo-synthesized pregenomic RNA (pgRNA) are encapsidated together
CC       with the P protein, and reverse-transcribed inside the nucleocapsid.
CC       Initiation of reverse-transcription occurs first by binding the epsilon
CC       loop on the pgRNA genome, and is initiated by protein priming, thereby
CC       the 5'-end of (-)DNA is covalently linked to P protein. Partial (+)DNA
CC       is synthesized from the (-)DNA template and generates the relaxed
CC       circular DNA (RC-DNA) genome. After budding and infection, the RC-DNA
CC       migrates in the nucleus, and is converted into a plasmid-like
CC       covalently closed circular DNA (cccDNA). The activity of P protein does
CC       not seem to be necessary for cccDNA generation, and is presumably
CC       released from (+)DNA by host nuclear DNA repair machinery.
CC       {ECO:0000255|HAMAP-Rule:MF_04073}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) +
CC         diphosphate; Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-
CC         COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112;
CC         EC=2.7.7.7; Evidence={ECO:0000255|HAMAP-Rule:MF_04073};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) +
CC         diphosphate; Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-
CC         COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112;
CC         EC=2.7.7.49; Evidence={ECO:0000255|HAMAP-Rule:MF_04073};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_04073};
CC   -!- ACTIVITY REGULATION: Activated by host HSP70 and HSP40 in vitro to be
CC       able to bind the epsilon loop of the pgRNA. Because deletion of the
CC       RNase H region renders the protein partly chaperone-independent, the
CC       chaperones may be needed indirectly to relieve occlusion of the RNA-
CC       binding site by this domain. Inhibited by several reverse-transcriptase
CC       inhibitors: Lamivudine, Adefovir and Entecavir. {ECO:0000255|HAMAP-
CC       Rule:MF_04073}.
CC   -!- DOMAIN: Terminal protein domain (TP) is hepadnavirus-specific. Spacer
CC       domain is highly variable and separates the TP and RT domains.
CC       Polymerase/reverse-transcriptase domain (RT) and ribonuclease H domain
CC       (RH) are similar to retrovirus reverse transcriptase/RNase H.
CC       {ECO:0000255|HAMAP-Rule:MF_04073}.
CC   -!- DOMAIN: The polymerase/reverse transcriptase (RT) and ribonuclease H
CC       (RH) domains are structured in five subdomains: finger, palm, thumb,
CC       connection and RNase H. Within the palm subdomain, the 'primer grip'
CC       region is thought to be involved in the positioning of the primer
CC       terminus for accommodating the incoming nucleotide. The RH domain
CC       stabilizes the association of RT with primer-template.
CC       {ECO:0000255|HAMAP-Rule:MF_04073}.
CC   -!- MISCELLANEOUS: Hepadnaviral virions contain probably just one P protein
CC       molecule per particle. {ECO:0000255|HAMAP-Rule:MF_04073}.
CC   -!- SIMILARITY: Belongs to the hepadnaviridae P protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04073}.
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DR   EMBL; M19183; AAA46763.1; -; Genomic_DNA.
DR   PIR; G29969; JDVL59.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0003964; F:RNA-directed DNA polymerase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniRule.
DR   GO; GO:0052170; P:symbiont-mediated suppression of host innate immune response; IEA:UniProtKB-UniRule.
DR   Gene3D; 3.30.70.270; -; 1.
DR   HAMAP; MF_04073; HBV_DPOL; 1.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR001462; DNApol_viral_C.
DR   InterPro; IPR000201; DNApol_viral_N.
DR   InterPro; IPR037531; HBV_DPOL.
DR   InterPro; IPR052055; Hepadnavirus_pol/RT.
DR   InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR   InterPro; IPR000477; RT_dom.
DR   PANTHER; PTHR33050; REVERSE TRANSCRIPTASE DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR33050:SF7; RIBONUCLEASE H; 1.
DR   Pfam; PF00336; DNA_pol_viral_C; 1.
DR   Pfam; PF00242; DNA_pol_viral_N; 1.
DR   Pfam; PF00078; RVT_1; 1.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   PROSITE; PS50878; RT_POL; 1.
PE   3: Inferred from homology;
KW   DNA replication; DNA-binding; DNA-directed DNA polymerase; Endonuclease;
KW   Host-virus interaction; Hydrolase;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host RLR pathway by virus; Magnesium; Metal-binding;
KW   Multifunctional enzyme; Nuclease; Nucleotidyltransferase;
KW   RNA-directed DNA polymerase; Transferase; Viral immunoevasion.
FT   CHAIN           1..884
FT                   /note="Protein P"
FT                   /id="PRO_0000222352"
FT   DOMAIN          398..639
FT                   /note="Reverse transcriptase"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   REGION          1..184
FT                   /note="Terminal protein domain (TP)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   REGION          185..387
FT                   /note="Spacer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   REGION          218..241
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          299..345
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          388..729
FT                   /note="Polymerase/reverse transcriptase domain (RT)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   COMPBIAS        222..241
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        323..332
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         470
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   BINDING         590
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   BINDING         591
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   SITE            68
FT                   /note="Priming of reverse-transcription by covalently
FT                   linking the first nucleotide of the (-)DNA"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
SQ   SEQUENCE   884 AA;  99400 MW;  8BAFF8DC6E7558D3 CRC64;
     MHPFSRLFRN IQSLGEEEVQ ELLGPPEDAL PLLAGEDLNH RVADALNLHL PTADLQWVHK
     TNAITGLYSN QAAQFNPHWI QPEFPELHLH NDLIQKLQQY FGPLTINEKR KLQLNFPARF
     FPKATKYFPL IKGIKNNYPN FALEHFFATA NYLWTLWEAG ILYLRKNQTT LTFKGKPYSW
     EHRQLVQHNG QQHKSHLQSR QNSSMVACSG HLLHNHLPSE PVSVSTRNLS NNISDKSQKS
     TRTGLCSYKQ VQTDRLEHLA RISCGSKITI GQQGSSPKTS YKSISSNFRN QTWAYNSSRN
     SGHTTWFSSA SNSNKSRSRE KAYSSNSTSQ RYSPPLNYEK SDFSSPGVRG RITRLDNNGT
     LPQCLWRSFY NTKPCGSYCI HHIVSSLDDW GPCTVTGDVT IKSPRTPRRI TGGVFLVDKN
     PNNSSESRLV VDFSQFSRGH TRVHWPKFAV PNLQTLANLL STNLQWLSLD VSAAFYHIPI
     SPAAVPHLLV GSPGLERFNT CMSSSTHNGN DSQLQTMHAL CTRHVYSSLL LLFKTYGRKL
     HLLAHPFIMG FRKLPMGVGL SPFLLAQFTS AIASMVRRNF PHCVVFAYMD DLVLGARTSE
     HLTAIYSHIC SVFLDLGIHL NVNKTKWWGN HLHFMGYVIT SSGVLPQDKH VKKLSRYLRS
     VPVNQPLDYK ICERLTGILN YVAPFTLCGY AALMPLYHAI ASRTAFIFSS LYKSWLLSLY
     EELWPVVRQR GVVCTVFADA TPTGWGIATT CQLLSGTFAF PLPIATAELI AACLARCWTG
     ARLLGTDNSV VLSGKLTSFP WLLACVANWI LRGTSFCYVP SALNPADLPS RGLLPVLRPL
     PRLRLRPQTS RISLWAASPP VSPRRPVRVA WSSPVQTCEP WIPP
//