Reviewed, UniProtKB/Swiss-Prot P03158 (DPOL_HBVA2)

Names and origin

Protein names

Recommended name:
    Protein P
Including the following 3 domains:
    1- Recommended name:
            DNA-directed DNA polymerase
              EC=2.7.7.7
    2- Recommended name:
            RNA-directed DNA polymerase
              EC=2.7.7.49
    3- Recommended name:
            Ribonuclease H
              EC=3.1.26.4

Gene names

Name:

P

Organism

Hepatitis B virus genotype A2 subtype adw (isolate Japan/Nishioka/1983) (HBV-A) [Complete proteome]

Taxonomic identifier

482134 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus

Virus host

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

Protein attributes

Sequence length	838 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 By similarity.
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 releive occlusion of the RNA-binding site by this domain. Inhibited by several reverse-transcriptase inhibitors: Lamivudine, Adefovir and Entecavir By similarity.
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 By similarity. 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 By similarity.
Miscellaneous	Hepadnaviral virions contain probably just one P protein molecule per particle By similarity.
Sequence similarities	Belongs to the hepadnaviridae P protein family. Contains 1 reverse transcriptase domain.

Ontologies

Keywords
Biological process	DNA replication
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
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 magnesium 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 – 838	838	Protein P		PRO_0000222339
Regions
	Domain	352 – 595	244	Reverse transcriptase
	Region	1 – 179	179	Terminal protein domain (TP) By similarity
	Region	180 – 341	162	Spacer By similarity
	Region	342 – 685	344	Polymerase/reverse transcriptase domain (RT) By similarity
	Region	686 – 838	153	RnaseH domain (RH) By similarity
Sites
	Metal binding	424	1	Magnesium; catalytic By similarity
	Metal binding	546	1	Magnesium; catalytic By similarity
	Metal binding	547	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)
	P03158-1 [UniParc]. Last modified March 18, 2008. Version 2. Checksum: B133A77F9C12E91C	FASTA	838	93,840
	10 20 30 40 50 60 MPLSYQHFRK LLLLDDGTEA GPLEEELPRL ADADLNRRVA 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 LQHSQRHGDE SFCSQPSGIP SRSSVGPCIR SQLNKSRLGL QPHQGPLASS QPGRSGSIRA 250 260 270 280 290 300 RAHPSTRRYF GVEPSGSGHI DHSVNNSSSC LHQSAVRKAA YSHLSTSKRQ SSSGHAVEFH 310 320 330 340 350 360 CLAPSSAGSQ SQGSVSSCWW LQFRNSKPCS EYCLSHLVNL REDWGPCDDH GEHHIRIPRT 370 380 390 400 410 420 PARVTGGVFL VDKNPHNTAE SRLVVDFSQF SRGITRVSWP KFAVPNLQSL TNLLSSNLSW 430 440 450 460 470 480 LSLDVSAAFY HIPLHPAAMP HLLIGSSGLS RYVARLSSNS RINNNQYGTM QNLHDSCSRQ 490 500 510 520 530 540 LFVSLMLLYK TYGWKLHLYS HPIVLGFRKI PMGVGLSPFL LAQFTSAICS VVRRAFPHCL 550 560 570 580 590 600 AFSYMDDVVL GAKSVQHRES LYTAVTNFLL SLGIHLNPNK TKRWGYSLNF MGYIIGSWGT 610 620 630 640 650 660 LPQDHIVQKI KHCFRKLPVN RPIDWKVCQR IVGLLGFAAP FTQCGYPALM PLYACIQAKQ 670 680 690 700 710 720 AFTFSPTYKA FLSKQYMNLY PVARQRPGLC QVFADATPTG WGLAIGHQRM RGTFVAPLPI 730 740 750 760 770 780 HTAELLAACF ARSRSGAKLI GTDNSVVLSR KYTSFPWLLG CTANWILRGT SFVYVPSALN 790 800 810 820 830 PADDPSRGRL GLSRPLLRLP FQPTTGRTSL YAVSPSVPSH LPVRVHFASP LHVAWRPP

References

[1]	"The complete nucleotide sequences of the cloned hepatitis B virus DNA; subtype adr and adw." Ono Y., Onda H., Sasada R., Igarashi K., Sugino Y., Nishioka K. Nucleic Acids Res. 11:1747-1757(1983) [PubMed: 6300776] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Hepatitis B virus replication." Beck J., Nassal M. World J. Gastroenterol. 13:48-64(2007) [PubMed: 17206754] [Abstract] Cited for: REVIEW.

Web resources

HepSEQ

Hepatitis virus B database

Cross-references

Sequence databases
EMBLGenBankDDBJ	V00866 Genomic DNA. No translation available.
3D structure databases
ModBase	Search...
Family and domain databases
InterPro	IPR000477. DNA_pol_RVTase. IPR001462. DNApol_viral_C. IPR000201. DNApol_viral_N. [Graphical view]
Pfam	PF00336. DNA_pol_viral_C. 1 hit. PF00242. DNA_pol_viral_N. 1 hit. PF00078. RVT_1. 2 hits. [Graphical view]
ProDom	PD000814. DNApol_viral_C. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS50878. RT_POL. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

DPOL_HBVA2

Accession

Primary (citable) accession number: P03158

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	March 18, 2008
Last modified:	June 16, 2009
This is version 54 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)