ID   DPOL_HBVA4              Reviewed;         845 AA.
AC   P17100;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   10-JUN-2026, entry version 105.
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   Hepatitis B virus genotype A2 subtype adw2 (isolate Germany/991/1990)
OS   (HBV-A).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Blubervirales; Hepadnaviridae; Orthohepadnavirus;
OC   Orthohepadnavirus hominoidei; Hepatitis B virus.
OX   NCBI_TaxID=10410;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Koechel H.G., Schueler A., Lottmann S., Thomssen R.;
RL   Submitted (FEB-1990) to the EMBL/GenBank/DDBJ databases.
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; X51970; CAA36229.1; -; Genomic_DNA.
DR   PIR; S10382; JDVLKS.
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   FunFam; 3.30.70.270:FF:000009; Protein P; 1.
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; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR   InterPro; IPR000477; RT_dom.
DR   InterPro; IPR051320; Viral_Replic_Matur_Polypro.
DR   PANTHER; PTHR33064:SF29; PEPTIDASE A2 DOMAIN-CONTAINING PROTEIN-RELATED; 1.
DR   PANTHER; PTHR33064; POL PROTEIN; 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..845
FT                   /note="Protein P"
FT                   /id="PRO_0000222346"
FT   DOMAIN          359..602
FT                   /note="Reverse transcriptase"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   REGION          1..179
FT                   /note="Terminal protein domain (TP)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   REGION          180..348
FT                   /note="Spacer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   REGION          226..246
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          349..692
FT                   /note="Polymerase/reverse transcriptase domain (RT)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   BINDING         431
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   BINDING         553
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   BINDING         554
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT   SITE            65
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   845 AA;  94768 MW;  7E4CB51AC6DF70EA CRC64;
     MPLSYQHFRK LLLLDDGTEA GPLEEELPRL ADADLNRRVA EDLNLGNLNV SIPWTHKVGN
     FTGLYSSTAP IFNPEWQTPS FPKIHLQEDI INRCQQFVGP LTVNEKRRLK LIMPARFYPT
     HTKYLPLDKG IKPYYPDQVV NHYFQTRHYL HTLWKAGILY KRETTRSASF CGSPYSWEQE
     LQHGRLVIKT SQRHGDESFC SQPSGILSRS SVGPCIRSQL KQSRLGLQPH QGPLASSQPG
     RSGSIRARVH PSTRRCFGVE PSGSGHVDPS VNNSSSCLRQ SAVRKAAYSH LSTSKRQSSS
     GHAVEFHCLP PSSARPQSQG SVFSCWWLQF RNSKPCSEYC LSHLVNLRED RGPCDEHGEH
     HIRIPRTPAR VTGGVFLVDK NPHNTAESRL VVDFSQFSRG ITRVSWPKFA IPNLQSLTNL
     LSSNLSWLSL DVSAAFYHIP LHPAAMPHLL IGSSGLSRYV ARLSSNSRIN NNQYGTMQNL
     HDSCSRQLYV SLMLLYKTYG WKLHLYSHPI VLGFRKIPMG VGLSPFLLAQ FTSAICSVVR
     RAFPHCLAFS YMDDVVLGAK SVQHREFLYT AVTNFLLSLG IHLNPNKTKR WGYSLNFMGY
     VIGSWGTLPQ DHIVQKIKHC FRKLPVNRPI DWKVCQRIVG LLGFAAPFTQ CGYPALMPLY
     ACIQAKQAFT FSPTYKAFLS KQYMNLYPVA RQRPGLCQVF ADATPTGWGL AIGHQRMRGT
     FVAPLPIHTA ELLAACFARS RSGAKLIGTD NSVVLSRKYT SFPWLLGCAA NWILRGTSFV
     YVPSALNPAD DPSRGRLGLS RPLLRLPFQP TTGRTSLYAV SPSVPSHLPV RVHFASPLHV
     AWRPP
//