ID D0UE35_HBV Unreviewed; 843 AA.
AC D0UE35;
DT 15-DEC-2009, integrated into UniProtKB/TrEMBL.
DT 15-DEC-2009, sequence version 1.
DT 03-MAY-2023, entry version 58.
DE RecName: Full=Protein P {ECO:0000256|HAMAP-Rule:MF_04073};
DE Includes:
DE RecName: Full=DNA-directed DNA polymerase {ECO:0000256|HAMAP-Rule:MF_04073};
DE EC=2.7.7.7 {ECO:0000256|HAMAP-Rule:MF_04073};
DE Includes:
DE RecName: Full=RNA-directed DNA polymerase {ECO:0000256|HAMAP-Rule:MF_04073};
DE EC=2.7.7.49 {ECO:0000256|HAMAP-Rule:MF_04073};
DE Includes:
DE RecName: Full=Ribonuclease H {ECO:0000256|HAMAP-Rule:MF_04073};
DE EC=3.1.26.4 {ECO:0000256|HAMAP-Rule:MF_04073};
GN Name=P {ECO:0000256|HAMAP-Rule:MF_04073, ECO:0000313|EMBL:ACY07451.1};
OS Hepatitis B virus (HBV).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Blubervirales; Hepadnaviridae; Orthohepadnavirus.
OX NCBI_TaxID=10407 {ECO:0000313|EMBL:ACY07451.1, ECO:0000313|Proteomes:UP000156508};
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1] {ECO:0000313|EMBL:ACY07451.1, ECO:0000313|Proteomes:UP000156508}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=KOR33LC {ECO:0000313|EMBL:ACY07451.1};
RX PubMed=20513074; DOI=10.1002/jmv.21844;
RA Ahn S.H., Yuen L., Han K.H., Littlejohn M., Chang H.Y., Damerow H.,
RA Ayres A., Heo J., Locarnini S., Revill P.A.;
RT "Molecular and clinical characteristics of hepatitis B virus in Korea.";
RL J. Med. Virol. 82:1126-1134(2010).
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:0000256|HAMAP-Rule:MF_04073}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4;
CC Evidence={ECO:0000256|ARBA:ARBA00000077, ECO:0000256|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:0000256|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=2.7.7.7; Evidence={ECO:0000256|HAMAP-
CC 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:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_04073}.
CC -!- MISCELLANEOUS: Hepadnaviral virions contain probably just one P protein
CC molecule per particle. {ECO:0000256|HAMAP-Rule:MF_04073}.
CC -!- SIMILARITY: Belongs to the hepadnaviridae P protein family.
CC {ECO:0000256|ARBA:ARBA00007994, ECO:0000256|HAMAP-Rule:MF_04073}.
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DR EMBL; GQ475337; ACY07451.1; -; Genomic_DNA.
DR Proteomes; UP000156508; 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; DNA/RNA polymerases; 1.
DR PROSITE; PS50878; RT_POL; 1.
PE 3: Inferred from homology;
KW DNA replication {ECO:0000256|ARBA:ARBA00022705, ECO:0000256|HAMAP-
KW Rule:MF_04073}; DNA-binding {ECO:0000256|HAMAP-Rule:MF_04073};
KW DNA-directed DNA polymerase {ECO:0000256|ARBA:ARBA00022932,
KW ECO:0000256|HAMAP-Rule:MF_04073};
KW Endonuclease {ECO:0000256|ARBA:ARBA00022759, ECO:0000256|HAMAP-
KW Rule:MF_04073}; Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04073};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_04073};
KW Inhibition of host innate immune response by virus
KW {ECO:0000256|ARBA:ARBA00022632, ECO:0000256|HAMAP-Rule:MF_04073};
KW Inhibition of host RLR pathway by virus {ECO:0000256|ARBA:ARBA00022482,
KW ECO:0000256|HAMAP-Rule:MF_04073};
KW Magnesium {ECO:0000256|HAMAP-Rule:MF_04073};
KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_04073};
KW Multifunctional enzyme {ECO:0000256|HAMAP-Rule:MF_04073};
KW Nuclease {ECO:0000256|ARBA:ARBA00022722, ECO:0000256|HAMAP-Rule:MF_04073};
KW Nucleotidyltransferase {ECO:0000256|ARBA:ARBA00022695, ECO:0000256|HAMAP-
KW Rule:MF_04073};
KW RNA-directed DNA polymerase {ECO:0000256|ARBA:ARBA00022918,
KW ECO:0000256|HAMAP-Rule:MF_04073};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|HAMAP-
KW Rule:MF_04073};
KW Viral immunoevasion {ECO:0000256|ARBA:ARBA00023280, ECO:0000256|HAMAP-
KW Rule:MF_04073}.
FT DOMAIN 357..600
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000259|PROSITE:PS50878"
FT REGION 1..177
FT /note="Terminal protein domain (TP)"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_04073"
FT REGION 178..346
FT /note="Spacer"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_04073"
FT REGION 216..244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 250..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 347..690
FT /note="Polymerase/reverse transcriptase domain (RT)"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_04073"
FT COMPBIAS 216..236
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..269
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 429
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_04073"
FT BINDING 551
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_04073"
FT BINDING 552
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_04073"
FT SITE 63
FT /note="Priming of reverse-transcription by covalently
FT linking the first nucleotide of the (-)DNA"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_04073"
SQ SEQUENCE 843 AA; 94382 MW; CCAF3D6B2A609223 CRC64;
MPLSYQHFRK LLLLDDEAGP LEEELPRLAD EGLNRRVAED LNLGNLNVSI PWTHKVGNFT
GLYSSTVPVF NPEWQTPSFP NIHLQEDIIN RCQQYVGPLT VNEKRRLKLI MPARFYPNLT
KYLPLDKGIK PYYPEHAVNH YFKTRHYLHT LWKAGILYKR ETTRSASFCG SPYSWEQELQ
HGRLVFQTST RHGDESFCSQ SSGILSRSPV GPCVRSQLKQ SRLGLQPQQG SLARGKSGRS
GSIRARVHPT TRGSFGVEPS GSGHIDNSAS SASSCLHQSA VRKTAYSHLS SSKRQSSSGH
AVELHNIPPS SARSQSERPI FSCWWLQFRN SKPCSDYCLT HIVNLLEDWG PCTEHGEHNI
RIPRTPARVT GGVFLVDKNP HNTTESRLVV DFSQFSRGST HVSWPKFAVP NLQSLTNLLS
SNLSWLSLDV SAAFYHIPLH PAAMPHLLVG SSGLPRYVAR LSSTSRNINY QHGTMQDLHD
SCSRNLYVSL LLLYKTFGRK LHLYSHPIIL GFRKIPMGVG LSPFLLAQFT SAICSVVRRA
FPHCLAFSYM DDVVLGAKSV QHLESLFTSI TNFLLSLGIH LNPNKTKRWG YSLNFMGYVI
GSWGTLPQEH IVLKIKQCFR KLPVNRPIDW KVCQRIVGLL GFAAPFTQCG YPALMPLYAC
IQSKQAFTFS PTYKAFLCQQ YLHLYPVARQ RSGLCQVFAD ATPTGWGLAI GHRRMRGTFV
APLPIHTAEL LAACFARSRS GAKLIGTDNS VVLSRKYTSF PWLLGCAANW ILRGTSFVYV
PSALNPADDP SRGRLGLYRP LLHLPFLPTT GRTSLYAVSP SVPSHLPDRV HFASPLHVAW
KPP
//
