DPOL_HBVD1
ID DPOL_HBVD1 Reviewed; 750 AA.
AC P03155;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Protein P;
DE Includes:
DE RecName: Full=DNA-directed DNA polymerase;
DE EC=2.7.7.7;
DE Includes:
DE RecName: Full=RNA-directed DNA polymerase;
DE EC=2.7.7.49;
DE Includes:
DE RecName: Full=Ribonuclease H;
DE EC=3.1.26.4;
DE Flags: Fragment;
GN Name=P;
OS Hepatitis B virus genotype D subtype adw (isolate United Kingdom/adyw/1979)
OS (HBV-D).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=10419;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=399329; DOI=10.1038/282575a0;
RA Pasek M., Goto T., Gilbert W., Zink B., Schaller H., McKay P.,
RA Leadbetter G., Murray K.;
RT "Hepatitis B virus genes and their expression in E. coli.";
RL Nature 282:575-579(1979).
RN [2]
RP FUNCTION.
RX PubMed=2854056; DOI=10.1002/j.1460-2075.1988.tb03315.x;
RA Bartenschlager R., Schaller H.;
RT "The amino-terminal domain of the hepadnaviral P-gene encodes the terminal
RT protein (genome-linked protein) believed to prime reverse transcription.";
RL EMBO J. 7:4185-4192(1988).
RN [3]
RP MUTAGENESIS OF 133-TYR-PRO-134; ASP-540; GLU-718; ALA-725 AND ASP-737.
RX PubMed=2153228; DOI=10.1128/jvi.64.2.613-620.1990;
RA Radziwill G., Tucker W., Schaller H.;
RT "Mutational analysis of the hepatitis B virus P gene product: domain
RT structure and RNase H activity.";
RL J. Virol. 64:613-620(1990).
RN [4]
RP FUNCTION.
RX PubMed=1380455; DOI=10.1002/j.1460-2075.1992.tb05420.x;
RA Bartenschlager R., Schaller H.;
RT "Hepadnaviral assembly is initiated by polymerase binding to the
RT encapsidation signal in the viral RNA genome.";
RL EMBO J. 11:3413-3420(1992).
RN [5]
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 (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:1380455,
CC ECO:0000269|PubMed:2854056}.
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|PROSITE-
CC ProRule:PRU00405};
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|PROSITE-
CC ProRule:PRU00405};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4;
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 (By similarity).
CC {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: Hepadnaviral virions contain probably just one P protein
CC molecule per particle. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the hepadnaviridae P protein family.
CC {ECO:0000305}.
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DR EMBL; J02202; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR PIR; A00701; JDVLVH.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003964; F:RNA-directed DNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; IEA:UniProtKB-EC.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR Gene3D; 3.30.70.270; -; 1.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR001462; DNApol_viral_C.
DR InterPro; IPR000201; DNApol_viral_N.
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 1: Evidence at protein level;
KW DNA replication; DNA-binding; DNA-directed DNA polymerase; Endonuclease;
KW Hydrolase; Magnesium; Metal-binding; Multifunctional enzyme; Nuclease;
KW Nucleotidyltransferase; RNA-directed DNA polymerase; Transferase.
FT CHAIN 1..>750
FT /note="Protein P"
FT /id="PRO_0000222345"
FT DOMAIN 346..589
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT REGION 1..177
FT /note="Terminal protein domain (TP)"
FT /evidence="ECO:0000250"
FT REGION 178..335
FT /note="Spacer"
FT /evidence="ECO:0000250"
FT REGION 186..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 279..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..679
FT /note="Polymerase/reverse transcriptase domain (RT)"
FT /evidence="ECO:0000250"
FT REGION 680..750
FT /note="RnaseH domain (RH)"
FT /evidence="ECO:0000250"
FT COMPBIAS 186..225
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 418
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 540
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 541
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT SITE 63
FT /note="Priming of reverse-transcription by covalently
FT linking the first nucleotide of the (-)DNA"
FT /evidence="ECO:0000250"
FT MUTAGEN 133..134
FT /note="YP->SA: 99% loss of polymerase activity."
FT /evidence="ECO:0000269|PubMed:2153228"
FT MUTAGEN 540
FT /note="D->H: Complete loss of polymerase activity."
FT /evidence="ECO:0000269|PubMed:2153228"
FT MUTAGEN 718
FT /note="E->H: 90% loss of polymerase activity."
FT /evidence="ECO:0000269|PubMed:2153228"
FT MUTAGEN 725
FT /note="A->D: Complete loss of polymerase activity."
FT /evidence="ECO:0000269|PubMed:2153228"
FT MUTAGEN 737
FT /note="D->V: 80% loss of polymerase activity."
FT /evidence="ECO:0000269|PubMed:2153228"
FT NON_TER 750
SQ SEQUENCE 750 AA; 84674 MW; 325F45EBC83EB07D CRC64;
MPLSYQRFRR LLLLDDEAGP LEEELPRLAD EDLNRRVAED LNLGNLNVSI PWTHKVGNFT
GLYSSTVPVF NPHWKPPSFP NIHLHQDIIK KCEQFVGPLT VNEKRRLKLI MPARFYPNFT
KYLPLDKGIK PYYPEHLVNH YFQTRHYLHT LWKAGVLYKR VSTHSASFCG SPYSWEQELQ
HGAESFHQQS SGILSRPPVG SSLQSKHQQS RLGLQSQQGH LARRQQGRSW SIRARVHPTA
RRPFGVEPSG SGHNANLASK SASCLYQSPV RTAAYPAVST SENHSSSGHA LELHNLPPNS
ARSQSERPVF PCWWLQFRDS KPCSDYYLSH IVNLLEDWGP CAEHGEHHIR IPRTPARVTG
GVFLVDKNPH NTAESRLVVD FSQFSRGNYR VSWPKFAVPN LQSLTNLLSS NLSWLSLDVS
AAFYHLPLHP AAMPHLLVGS SGLSRYVARL SSNSRIINHQ HGILQNLHDS CSRNLYVSLL
LLYKTFGWKL HLYSHPIILG FRKIPMGVGL SPFLLAQFTS AICSVVRRAF PHCLAFSYMD
DVVLGAKSVQ HLESLFTAVT NFLLSLGIHL NPNKTKRWGY SLNFMGYVIG CWGSLPQDHI
IHKIKECFRK LPVHRPIDWK VCQRIVGLLG FAAPFTQCGY PALMPLYACI QSKQAFTFSP
TYKAFLCKQY LNLYPVAEQR PGLCQVFADA TPTGWGLVMG HQRMRGTFLA PLPIHTAELL
AACFARSRSG ANILGTDNSV VLSRKYTSFP
