DPOL_WHV3
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 03-AUG-2022, entry version 93.
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.
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=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; M19183; AAA46763.1; -; Genomic_DNA.
DR PIR; G29969; JDVL59.
DR Proteomes; UP000007542; 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..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 219..241
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..340
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
