DPOL_HBVA9
ID DPOL_HBVA9 Reviewed; 845 AA.
AC Q4R1R9;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 68.
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 A3 (isolate Cameroon/CMR711/1994) (HBV-A).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=489459;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15958684; DOI=10.1099/vir.0.80922-0;
RA Kurbanov F., Tanaka Y., Fujiwara K., Sugauchi F., Mbanya D., Zekeng L.,
RA Ndembi N., Ngansop C., Kaptue L., Miura T., Ido E., Hayami M., Ichimura H.,
RA Mizokami M.;
RT "A new subtype (subgenotype) Ac (A3) of hepatitis B virus and recombination
RT between genotypes A and E in Cameroon.";
RL J. Gen. Virol. 86:2047-2056(2005).
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; AB194952; BAE00097.1; -; Genomic_DNA.
DR Proteomes; UP000007912; 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_0000323254"
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 186..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 288..318
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 COMPBIAS 231..245
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; 94770 MW; 330F137056D8E983 CRC64;
MPLSYQHFRK LLLLDDGTEV GPLEEELPRL ADEDLNRRVA EDLNLGNLNV SIPWTHKVGN
FTGLYSSTVP IFNQEWQTPS FPKIHLHEDI INRCQQFVGP LNVNEKRRLK LIMPARFYPN
STKYLPLDKG IKPYYPGHVV NHYFQARHYL HTLWKAGILY KRETTRSASF CGSPYSWEQE
LHHGRSVTKT SQRHGDESFC SQPSGILSRS SVGPCIRSQL KQPRLGLQPH QGPLATSQSG
RSGSIWARVH PSTRRSSGVE PSGSGHIDYS ASSSSSCLHQ SAVRKTAYSH LSTSKRQSSS
GHAVEFHKVP PNSARSQSQG PVFSCWWLQF RNSQPCSEYC LSHLVNLLED WGPCADHGEH
HIRIPRTPAR VTGGVFLVDK NPHNTAESRL VVDFSQFSRG STRVSWPKFA VPNLQSLTNL
LSSNLSWLSL DVSAAFYHIP LHPAAMPHLL IGSSGLSRYV ARLSSNSRIH NHQYGTLQNL
HDSCSRQLYV SLMLLYKTYG RKLHLYSHPI ILGFRKIPMG VGLSPFLLAQ FTSAICSVVR
RAFPHCLAFS YMDDVVLGAK SVQHLESLYT AVTNFLLSLG IHLNPNKTKR WGYSLNFMGY
IIGSWGSLPQ DHIVQKLKHC FRKLPVNRPI DWKVCQRIVG LLGFAAPFTQ CGYPALMPLY
ACIQARQAFT FSPTYKAFLS KQYMNLYPVA RQRPGLCQVF ADATPTGWGL AIGHQRMRGT
FVAPLPIHTA ELLAACFARS RSGATLIGTD NSVVLSRKYT SFPWLLGCTA NWILRGTSFV
YVPSALNPAD DPSRGRLGLY RPLLRLPYRP TTGRTSLYAV SPSVPSHLPD RVHFASPLHV
AWRPP
