ID E5RD33_HBV Unreviewed; 843 AA. AC E5RD33; DT 08-FEB-2011, integrated into UniProtKB/TrEMBL. DT 08-FEB-2011, sequence version 1. DT 29-MAY-2024, entry version 59. 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:ADQ54009.1}; OS Hepatitis B virus (HBV). OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; OC Blubervirales; Hepadnaviridae; Orthohepadnavirus. OX NCBI_TaxID=10407 {ECO:0000313|EMBL:ADQ54009.1, ECO:0000313|Proteomes:UP000140217}; OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee). RN [1] {ECO:0000313|EMBL:ADQ54009.1, ECO:0000313|Proteomes:UP000140217} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=QHX-14 {ECO:0000313|EMBL:ADQ54009.1}; RX PubMed=21494570; DOI=10.1371/journal.pone.0018708; RA Zhou B., Xiao L., Wang Z., Chang E.T., Chen J., Hou J.; RT "Geographical and ethnic distribution of the HBV C/D recombinant on the RT Qinghai-Tibet Plateau."; RL PLoS ONE 6:E18708-E18708(2011). 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; HM750135; ADQ54009.1; -; Genomic_DNA. DR Proteomes; UP000140217; 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:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-KW. 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 218..273 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 290..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 218..236 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 255..273 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; 94458 MW; 9EB5AC7D44EDE80E CRC64; MPLSYQHFRK LLLLDDEAGP LEEELPRLAD EGLNRRVAKD LNLGNLNVSI PWTHKVGNFT GLYSSAVTVF NPDWQTPSFP HIHLQEDIIN RCQQYVGPLT VNEKRRLKLI MPARFYPNLT KYLPLDKGIK PYYPEHAVNH YFKTRHYLHT LWKAGILYKR ETTRSASFCG SPYSWEQELQ HGRLVFQTST RHGDESFCSQ SSGILSRSPV GPCVRSQLKQ SRLGLQPQQG SLARGKSGRS GSIRARVHPT TRRSFGVEPS GSGHIDNSAS STSSCLHQSA VRKTAYSHLS TSKRQSSSGH AVELHNIPPS SARSQSEGPI FSCWWLQFRN SKPCSDYCLT HIVNLLEDWG PCTEHGEHNI RIPRTPARVT GGVFLVDKNP HNTTESRLVV DFSQFSRGST HVSWPKFAVP NLQSLTNLLS SNLSWLSLDV SAAFYHIPLH PAAMPHLLVG SSGLPRYVAR LSSTSRNINH QHGTMQDLHD SCSRNLYVSL LLLYKTFGRK LHLYSHPIIL GFRKIPMGVG LSPFLLAQFT SAICSVVRRA FPHCLAFSYM DDVVLGAKSV QHLESLFTSI TNFLLSLGIH LNPNKTKRWG YSLNFMGYVI GSWGTLPQEH IVQKIKQCFR KLPVNRPIDW KVCQRIVGLL GFAAPFTQCG YPALMPLYAC IQSKQAFTFS PIYKAFLCQQ YLNLYPVARQ RSGLCQVFAD ATPTGWGLAI GHRRMRGTFV APLPIHTAEL LAACFARSRS GAKLIGTDNS VVLSRKYTSF PWLLGCAANW ILRGTSFVYV PSALNPADDP SRGRLGLYRP LLHLPFRPTT GRTSLYAVSP SVPSHLPDRV HFASPLHVAW RPP //