DPOL_HBVA2
ID DPOL_HBVA2 Reviewed; 838 AA.
AC P03158;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 103.
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 adw (isolate Japan/Nishioka/1983)
OS (HBV-A).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=482134;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6300776; DOI=10.1093/nar/11.6.1747;
RA Ono Y., Onda H., Sasada R., Igarashi K., Sugino Y., Nishioka K.;
RT "The complete nucleotide sequences of the cloned hepatitis B virus DNA;
RT subtype adr and adw.";
RL Nucleic Acids Res. 11:1747-1757(1983).
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=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; V00866; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PRIDE; P03158; -.
DR Proteomes; UP000007906; 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..838
FT /note="Protein P"
FT /id="PRO_0000222339"
FT DOMAIN 352..595
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..341
FT /note="Spacer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT REGION 219..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 342..685
FT /note="Polymerase/reverse transcriptase domain (RT)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT COMPBIAS 219..236
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 424
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT BINDING 546
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04073"
FT BINDING 547
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 838 AA; 93840 MW; B133A77F9C12E91C CRC64;
MPLSYQHFRK LLLLDDGTEA GPLEEELPRL ADADLNRRVA EDLNLGNLNV SIPWTHKVGN
FTGLYSSTVP IFNPEWQTPS FPKIHLQEDI INRCQQFVGP LTVNEKRRLK LIMPARFYPT
HTKYLPLDKG IKPYYPDQVV NHYFQTRHYL HTLWKAGILY KRETTRSASF CGSPYSWEQE
LQHSQRHGDE SFCSQPSGIP SRSSVGPCIR SQLNKSRLGL QPHQGPLASS QPGRSGSIRA
RAHPSTRRYF GVEPSGSGHI DHSVNNSSSC LHQSAVRKAA YSHLSTSKRQ SSSGHAVEFH
CLAPSSAGSQ SQGSVSSCWW LQFRNSKPCS EYCLSHLVNL REDWGPCDDH GEHHIRIPRT
PARVTGGVFL VDKNPHNTAE SRLVVDFSQF SRGITRVSWP KFAVPNLQSL TNLLSSNLSW
LSLDVSAAFY HIPLHPAAMP HLLIGSSGLS RYVARLSSNS RINNNQYGTM QNLHDSCSRQ
LFVSLMLLYK TYGWKLHLYS HPIVLGFRKI PMGVGLSPFL LAQFTSAICS VVRRAFPHCL
AFSYMDDVVL GAKSVQHRES LYTAVTNFLL SLGIHLNPNK TKRWGYSLNF MGYIIGSWGT
LPQDHIVQKI KHCFRKLPVN RPIDWKVCQR IVGLLGFAAP FTQCGYPALM PLYACIQAKQ
AFTFSPTYKA FLSKQYMNLY PVARQRPGLC QVFADATPTG WGLAIGHQRM RGTFVAPLPI
HTAELLAACF ARSRSGAKLI GTDNSVVLSR KYTSFPWLLG CTANWILRGT SFVYVPSALN
PADDPSRGRL GLSRPLLRLP FQPTTGRTSL YAVSPSVPSH LPVRVHFASP LHVAWRPP
