ID E5RD33_HBV Unreviewed; 843 AA. AC E5RD33; DT 08-FEB-2011, integrated into UniProtKB/TrEMBL. DT 08-FEB-2011, sequence version 1. DT 31-JUL-2019, entry version 47. 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; 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 RT the Qinghai-Tibet Plateau."; RL PLoS ONE 6:E18708-E18708(2011). CC -!- FUNCTION: Multifunctional enzyme that converts the viral RNA CC genome into dsDNA in viral cytoplasmic capsids. This enzyme CC displays a DNA polymerase activity that can copy either DNA or RNA CC templates, and a ribonuclease H (RNase H) activity that cleaves CC the RNA strand of RNA-DNA heteroduplexes in a partially processive CC 3'- to 5'-endonucleasic mode. Neo-synthesized pregenomic RNA CC (pgRNA) are encapsidated together with the P protein, and reverse- CC transcribed inside the nucleocapsid. Initiation of reverse- CC transcription occurs first by binding the epsilon loop on the CC pgRNA genome, and is initiated by protein priming, thereby the 5'- CC end of (-)DNA is covalently linked to P protein. Partial (+)DNA is CC synthesized from the (-)DNA template and generates the relaxed CC circular DNA (RC-DNA) genome. After budding and infection, the RC- CC DNA migrates in the nucleus, and is converted into a plasmid-like CC covalently closed circular DNA (cccDNA). The activity of P protein CC does not seem to be necessary for cccDNA generation, and is CC presumably released from (+)DNA by host nuclear DNA repair CC machinery. {ECO:0000256|HAMAP-Rule:MF_04073, CC ECO:0000256|SAAS:SAAS00585225}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; CC EC=3.1.26.4; Evidence={ECO:0000256|HAMAP-Rule:MF_04073, CC ECO:0000256|SAAS:SAAS01126698}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA- CC COMP:11130, Rhea:RHEA-COMP:11131, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:61560, ChEBI:CHEBI:83828; EC=2.7.7.49; CC Evidence={ECO:0000256|HAMAP-Rule:MF_04073, CC ECO:0000256|SAAS:SAAS01126708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA- CC COMP:11130, Rhea:RHEA-COMP:11131, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:61560, ChEBI:CHEBI:83828; EC=2.7.7.7; CC Evidence={ECO:0000256|HAMAP-Rule:MF_04073, CC ECO:0000256|SAAS:SAAS01126713}; CC -!- ACTIVITY REGULATION: Activated by host HSP70 and HSP40 in vitro to CC be able to bind the epsilon loop of the pgRNA. Because deletion of CC the RNase H region renders the protein partly chaperone- CC independent, the chaperones may be needed indirectly to relieve CC occlusion of the RNA-binding site by this domain. Inhibited by CC several reverse-transcriptase inhibitors: Lamivudine, Adefovir and CC Entecavir. {ECO:0000256|HAMAP-Rule:MF_04073, CC ECO:0000256|SAAS:SAAS01070267}. CC -!- DOMAIN: Terminal protein domain (TP) is hepadnavirus-specific. CC Spacer domain is highly variable and separates the TP and RT CC domains. Polymerase/reverse-transcriptase domain (RT) and CC ribonuclease H domain (RH) are similar to retrovirus reverse CC transcriptase/RNase H. {ECO:0000256|HAMAP-Rule:MF_04073}. CC -!- DOMAIN: The polymerase/reverse transcriptase (RT) and ribonuclease CC H (RH) domains are structured in five subdomains: finger, palm, CC thumb, connection and RNase H. Within the palm subdomain, the CC 'primer grip' region is thought to be involved in the positioning CC of the primer terminus for accommodating the incoming nucleotide. CC The RH domain stabilizes the association of RT with primer- CC template. {ECO:0000256|HAMAP-Rule:MF_04073}. CC -!- MISCELLANEOUS: Hepadnaviral virions contain probably just one P CC protein molecule per particle. {ECO:0000256|HAMAP-Rule:MF_04073}. CC -!- SIMILARITY: Belongs to the hepadnaviridae P protein family. CC {ECO:0000256|HAMAP-Rule:MF_04073, ECO:0000256|SAAS:SAAS00585232}. 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:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-UniRule. DR HAMAP; MF_04073; HBV_DPOL; 1. DR InterPro; IPR001462; DNApol_viral_C. DR InterPro; IPR000201; DNApol_viral_N. DR InterPro; IPR037531; HBV_DPOL. 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 PROSITE; PS50878; RT_POL; 1. PE 3: Inferred from homology; KW Complete proteome {ECO:0000313|Proteomes:UP000140217}; KW DNA replication {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00141099}; KW DNA-binding {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00118800}; KW DNA-directed DNA polymerase {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00141145}; KW Endonuclease {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00141133}; KW Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00956452}; KW Hydrolase {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00477586}; KW Inhibition of host innate immune response by virus {ECO:0000256|HAMAP- KW Rule:MF_04073, ECO:0000256|SAAS:SAAS00956459}; KW Inhibition of host RLR pathway by virus {ECO:0000256|HAMAP- KW Rule:MF_04073, ECO:0000256|SAAS:SAAS00956460}; KW Magnesium {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00141073}; KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00141171}; KW Multifunctional enzyme {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00118716}; KW Nuclease {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00118722}; KW Nucleotidyltransferase {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00141162}; KW RNA-directed DNA polymerase {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00141129}; KW Transferase {ECO:0000256|HAMAP-Rule:MF_04073, KW ECO:0000256|SAAS:SAAS00141155}; KW Viral immunoevasion {ECO:0000256|HAMAP-Rule:MF_04073}. FT DOMAIN 357 600 Reverse transcriptase. FT {ECO:0000259|PROSITE:PS50878}. FT REGION 1 177 Terminal protein domain (TP). FT {ECO:0000256|HAMAP-Rule:MF_04073}. FT REGION 178 346 Spacer. {ECO:0000256|HAMAP-Rule: FT MF_04073}. FT REGION 218 273 Disordered. {ECO:0000256|SAM:MobiDB- FT lite}. FT REGION 290 314 Disordered. {ECO:0000256|SAM:MobiDB- FT lite}. FT REGION 347 690 Polymerase/reverse transcriptase domain FT (RT). {ECO:0000256|HAMAP-Rule:MF_04073}. FT COMPBIAS 218 236 Polar. {ECO:0000256|SAM:MobiDB-lite}. FT COMPBIAS 255 273 Polar. {ECO:0000256|SAM:MobiDB-lite}. FT METAL 429 429 Magnesium; catalytic. {ECO:0000256|HAMAP- FT Rule:MF_04073}. FT METAL 551 551 Magnesium; catalytic. {ECO:0000256|HAMAP- FT Rule:MF_04073}. FT METAL 552 552 Magnesium; catalytic. {ECO:0000256|HAMAP- FT Rule:MF_04073}. FT SITE 63 63 Priming of reverse-transcription by FT covalently linking the first nucleotide FT of the (-)DNA. {ECO:0000256|HAMAP-Rule: FT 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 //