P03159 (DPOL_HBVA3) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein P

Including the following 3 domains:

1. DNA-directed DNA polymerase
   EC=2.7.7.7
2. RNA-directed DNA polymerase
   EC=2.7.7.49
3. Ribonuclease H
   EC=3.1.26.4

Gene names

Name:

P

Organism

Hepatitis B virus genotype A2 subtype adw2 (strain Rutter 1979) (HBV-A) [Complete proteome]

Taxonomic identifier

480116 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus › Hepatitis B virus › Hepatitis B virus subtype adw › Hepatitis B virus subtype adw2

Virus host

Homo sapiens (Human) [TaxID: 9606]
Pan troglodytes (Chimpanzee) [TaxID: 9598]

Protein attributes

Sequence length	845 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Multifunctional enzyme that converts the viral RNA genome into dsDNA in viral cytoplasmic capsids. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3'- to 5'-endonucleasic mode. Neo-synthesized pregenomic RNA (pgRNA) are encapsidated together with the P protein, and reverse-transcribed inside the nucleocapsid. Initiation of reverse-transcription occurs first by binding the epsilon loop on the pgRNA genome, and is initiated by protein priming, thereby the 5'-end of (-)DNA is covalently linked to P protein. Partial (+)DNA is synthesized from the (-)DNA template and generates the relaxed circular DNA (RC-DNA) genome. After budding and infection, the RC-DNA migrates in the nucleus, and is converted into a plasmid-like covalently closed circular DNA (cccDNA). The activity of P protein does not seem to be necessary for cccDNA generation, and is presumably released from (+)DNA by host nuclear DNA repair machinery.
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). Endonucleolytic cleavage to 5'-phosphomonoester.
Enzyme regulation	Activated by host HSP70 and HSP40 in vitro to be able to bind the epsilon loop of the pgRNA. Because deletion of the RNase H region renders the protein partly chaperone-independent, the chaperones may be needed indirectly to relieve occlusion of the RNA-binding site by this domain By similarity. Inhibited by several reverse-transcriptase inhibitors: Lamivudine, Adefovir and Entecavir.
Domain	Terminal protein domain (TP) is hepadnavirus-specific. Spacer domain is highly variable and separates the TP and RT domains. Polymerase/reverse-transcriptase domain (RT) and ribonuclease H domain (RH) are similar to retrovirus reverse transcriptase/RNase H. The polymerase/reverse transcriptase (RT) and ribonuclease H (RH) domains are structured in five subdomains: finger, palm, thumb, connection and RNase H. Within the palm subdomain, the 'primer grip' region is thought to be involved in the positioning of the primer terminus for accommodating the incoming nucleotide. The RH domain stabilizes the association of RT with primer-template.
Miscellaneous	Hepadnaviral virions contain probably just one P protein molecule per particle.
Sequence similarities	Belongs to the hepadnaviridae P protein family. Contains 1 reverse transcriptase domain.

Ontologies

Keywords
Biological process	DNA replication Host-virus interaction Inhibition of host IFN-mediated response initiation by virus Inhibition of host TBK1-IKBKE-DDX3 complex by virus Inhibition of host innate immune response by virus Viral immunoevasion
Ligand	DNA-binding Magnesium Metal-binding
Molecular function	DNA-directed DNA polymerase Endonuclease Hydrolase Nuclease Nucleotidyltransferase RNA-directed DNA polymerase Transferase
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological_process	RNA-dependent DNA replication Inferred from electronic annotation. Source: InterPro nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC suppression by virus of host innate immune response Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host type I interferon production Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: InterPro RNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW ribonuclease H activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 845	845	Protein P		PRO_0000222333
Regions
	Domain	359 – 602	244	Reverse transcriptase
	Region	1 – 179	179	Terminal protein domain (TP)
	Region	180 – 348	169	Spacer
	Region	349 – 692	344	Polymerase/reverse transcriptase domain (RT)
	Region	693 – 845	153	RnaseH domain (RH)
Sites
	Metal binding	431	1	Magnesium; catalytic By similarity
	Metal binding	553	1	Magnesium; catalytic By similarity
	Metal binding	554	1	Magnesium; catalytic By similarity
	Site	65	1	Priming of reverse-transcription by covalently linking the first nucleotide of the (-)DNA By similarity

Sequences

	Sequence		Length	Mass (Da)
	P03159 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 68A09F4783463D98	FASTA	845	94,800
	10 20 30 40 50 60 MPLSYQHFRK LLLLDDGTEA GPLEEELPRL ADADLHRRVA EDLNLGNLNV SIPWTHKVGN 70 80 90 100 110 120 FTGLYSSTVP IFNPEWQTPS FPKIHLQEDI INRCQQFVGP LTVNEKRRLK LIMPARFYPT 130 140 150 160 170 180 HTKYLPLDKG IKPYYPDQVV NHYFQTRHYL HTLWKAGILY KRETTRSASF CGSPYSWEQE 190 200 210 220 230 240 LQHGRLVIKT SQRHGDESFC SQSSGILSRS SVGPCIRSQL KQSRLGLQPR QGRLASSQPS 250 260 270 280 290 300 RSGSIRAKAH PSTRRYFGVE PSGSGHIDHS VNNSSSCLHQ SAVRKAAYSH LSTSKRQSSS 310 320 330 340 350 360 GHAVEFHCLP PNSAGSQSQG SVSSCWWLQF RNSKPCSEYC LSHLVNLRED WGPCDEHGEH 370 380 390 400 410 420 HIRIPRTPAR VTGGVFLVDK NPHNTAESRL VVDFSQFSRG ISRVSWPKFA VPNLQSLTNL 430 440 450 460 470 480 LSSNLSWLSL DVSAAFYHIP LHPAAMPHLL IGSSGLSRYV ARLSSNSRIN NNQYGTMQNL 490 500 510 520 530 540 HDSCSRQLYV SLMLLYKTYG WKLHLYSHPI VLGFRKIPMG VGLSPFLLAQ FTSAICSVVR 550 560 570 580 590 600 RAFPHCLAFS YMDDVVLGAK SVQHRESLYT AVTNFLLSLG IHLNPNKTKR WGYSLNFMGY 610 620 630 640 650 660 IIGSWGTLPQ DHIVQKIKHC FRKLPVNRPI DWKVCQRIVG LLGFAAPFTQ CGYPALMPLY 670 680 690 700 710 720 ACIQAKQAFT FSPTYKAFLS KQYMNLYPVA RQRPGLCQVF ADATPTGWGL AIGHQRMRGT 730 740 750 760 770 780 FVAPLPIHTA ELLAACFARS RSGAKLIGTD NSVVLSRKYT SFPWLLGCTA NWILRGTSFV 790 800 810 820 830 840 YVPSALNPAD DPSRGRLGLS RPLLRLPFQP TTGRTSLYAV SPSVPSHLPV RVHFASPLHV AWRPP

References

[1]	"The nucleotide sequence of the hepatitis B viral genome and the identification of the major viral genes." Valenzuela P., Quiroga M., Zaldivar J., Gray P., Rutter W.J. (In) Field B.N., Jaenisch R., Fox C.F. (eds.); Animal virus genetics, pp.57-70, Academic Press, New York (1980) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen." Valenzuela P., Gray P., Quiroga M., Zaldivar J., Goodman H.M., Rutter W.J. Nature 280:815-819(1979) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 315-611.
[3]	"Profound suppression of hepatitis B virus replication with lamivudine." Lai C.L., Yuen M.F. J. Med. Virol. 61:367-373(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INHIBITION BY LAMIVUDINE.
[4]	"Adefovir dipivoxil in the treatment of chronic hepatitis B virus infection." Hadziyannis S.J., Papatheodoridis G.V. Expert Rev. Anti Infect. Ther. 2:475-483(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INHIBITION BY ADEFOVIR.
[5]	"Inhibition of hepatitis B virus polymerase by entecavir." Langley D.R., Walsh A.W., Baldick C.J., Eggers B.J., Rose R.E., Levine S.M., Kapur A.J., Colonno R.J., Tenney D.J. J. Virol. 81:3992-4001(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INHIBITION BY ENTECAVIR.
[6]	"Hepatitis B virus replication." Beck J., Nassal M. World J. Gastroenterol. 13:48-64(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.

Web resources

HepSEQ

Hepatitis virus B database

Cross-references

Sequence databases
EMBL GenBank DDBJ	J02205 Genomic RNA. No translation available. X02763 Genomic DNA. Translation: CAA26538.1.
PIR	JDVLVD. A94409.
3D structure databases
ProteinModelPortal	P03159.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR001462. DNApol_viral_C. IPR000201. DNApol_viral_N. IPR000477. RVT. [Graphical view]
Pfam	PF00336. DNA_pol_viral_C. 1 hit. PF00242. DNA_pol_viral_N. 1 hit. PF00078. RVT_1. 1 hit. [Graphical view]
PROSITE	PS50878. RT_POL. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

DPOL_HBVA3

Accession

Primary (citable) accession number: P03159

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	April 3, 2013
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program