DPOL_HBVA3
ID DPOL_HBVA3 Reviewed; 845 AA.
AC P03159;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 101.
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 (strain Rutter 1979) (HBV-A).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=480116;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Valenzuela P., Quiroga M., Zaldivar J., Gray P., Rutter W.J.;
RT "The nucleotide sequence of the hepatitis B viral genome and the
RT identification of the major viral genes.";
RL (In) Field B.N., Jaenisch R., Fox C.F. (eds.);
RL Animal virus genetics, pp.57-70, Academic Press, New York (1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 315-611.
RX PubMed=471053; DOI=10.1038/280815a0;
RA Valenzuela P., Gray P., Quiroga M., Zaldivar J., Goodman H.M., Rutter W.J.;
RT "Nucleotide sequence of the gene coding for the major protein of hepatitis
RT B virus surface antigen.";
RL Nature 280:815-819(1979).
RN [3]
RP INHIBITION BY LAMIVUDINE.
RX PubMed=10861648;
RX DOI=10.1002/1096-9071(200007)61:3<367::aid-jmv15>3.0.co;2-a;
RA Lai C.L., Yuen M.F.;
RT "Profound suppression of hepatitis B virus replication with lamivudine.";
RL J. Med. Virol. 61:367-373(2000).
RN [4]
RP INHIBITION BY ADEFOVIR.
RX PubMed=15482214; DOI=10.1586/14787210.2.4.475;
RA Hadziyannis S.J., Papatheodoridis G.V.;
RT "Adefovir dipivoxil in the treatment of chronic hepatitis B virus
RT infection.";
RL Expert Rev. Anti Infect. Ther. 2:475-483(2004).
RN [5]
RP INHIBITION BY ENTECAVIR.
RX PubMed=17267485; DOI=10.1128/jvi.02395-06;
RA Langley D.R., Walsh A.W., Baldick C.J., Eggers B.J., Rose R.E.,
RA Levine S.M., Kapur A.J., Colonno R.J., Tenney D.J.;
RT "Inhibition of hepatitis B virus polymerase by entecavir.";
RL J. Virol. 81:3992-4001(2007).
RN [6]
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=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_04073};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|HAMAP-
CC 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; J02205; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; X02763; CAA26538.1; -; Genomic_DNA.
DR PIR; A94409; JDVLVD.
DR ChEMBL; CHEMBL3833482; -.
DR PRIDE; P03159; -.
DR Proteomes; UP000008766; Genome.
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:0039503; P:suppression by virus 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; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR000477; RT_dom.
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; SSF56672; 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_0000222333"
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..252
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 REGION 693..845
FT /note="RnaseH domain (RH)"
FT COMPBIAS 226..247
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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; 94800 MW; 68A09F4783463D98 CRC64;
MPLSYQHFRK LLLLDDGTEA GPLEEELPRL ADADLHRRVA EDLNLGNLNV SIPWTHKVGN
FTGLYSSTVP IFNPEWQTPS FPKIHLQEDI INRCQQFVGP LTVNEKRRLK LIMPARFYPT
HTKYLPLDKG IKPYYPDQVV NHYFQTRHYL HTLWKAGILY KRETTRSASF CGSPYSWEQE
LQHGRLVIKT SQRHGDESFC SQSSGILSRS SVGPCIRSQL KQSRLGLQPR QGRLASSQPS
RSGSIRAKAH PSTRRYFGVE PSGSGHIDHS VNNSSSCLHQ SAVRKAAYSH LSTSKRQSSS
GHAVEFHCLP PNSAGSQSQG SVSSCWWLQF RNSKPCSEYC LSHLVNLRED WGPCDEHGEH
HIRIPRTPAR VTGGVFLVDK NPHNTAESRL VVDFSQFSRG ISRVSWPKFA VPNLQSLTNL
LSSNLSWLSL DVSAAFYHIP LHPAAMPHLL IGSSGLSRYV ARLSSNSRIN NNQYGTMQNL
HDSCSRQLYV SLMLLYKTYG WKLHLYSHPI VLGFRKIPMG VGLSPFLLAQ FTSAICSVVR
RAFPHCLAFS YMDDVVLGAK SVQHRESLYT AVTNFLLSLG IHLNPNKTKR WGYSLNFMGY
IIGSWGTLPQ DHIVQKIKHC FRKLPVNRPI DWKVCQRIVG LLGFAAPFTQ CGYPALMPLY
ACIQAKQAFT FSPTYKAFLS KQYMNLYPVA RQRPGLCQVF ADATPTGWGL AIGHQRMRGT
FVAPLPIHTA ELLAACFARS RSGAKLIGTD NSVVLSRKYT SFPWLLGCTA NWILRGTSFV
YVPSALNPAD DPSRGRLGLS RPLLRLPFQP TTGRTSLYAV SPSVPSHLPV RVHFASPLHV
AWRPP
