Reviewed, UniProtKB/Swiss-Prot P06275 (DPOL_WHV2)

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

Woodchuck hepatitis B virus (isolate 2) (WHV) [Complete proteome]

Taxonomic identifier

341946 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus

Virus host

Marmota monax (Woodchuck) [TaxID: 9995]

Protein attributes

Sequence length	883 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.
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 – 883	883	Protein P		PRO_0000222350
Regions
	Domain	397 – 638	242	Reverse transcriptase
	Region	1 – 181	181	Terminal protein domain (TP) By similarity
	Region	182 – 386	205	Spacer By similarity
	Region	387 – 728	342	Polymerase/reverse transcriptase domain (RT) By similarity
	Region	729 – 883	155	RnaseH domain (RH) By similarity
Sites
	Metal binding	469	1	Magnesium; catalytic By similarity
	Metal binding	589	1	Magnesium; catalytic By similarity
	Metal binding	590	1	Magnesium; catalytic By similarity
	Site	67	1	Priming of reverse-transcription by covalently linking the first nucleotide of the (-)DNA By similarity

Sequences

	Sequence		Length	Mass (Da)
	P06275-1 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 3506BB654AA891F7	FASTA	883	99,347
	10 20 30 40 50 60 MHPFSRLFRN IQSLEEEVQE LLGPPEDALP LLAGEDLNHR VADALNLHLP TADLQWVHKT 70 80 90 100 110 120 NAITGLYSNQ AAQFNPNWIQ PEFPELHLHN DLIQKLQQYF GPLTINEKRK LQLNFPARFF 130 140 150 160 170 180 PKATKYFPLI KGIKNHYPNF ALEHFFATAN YLWTLWEAGI LYLRKNQTTL TFKGKPYSWE 190 200 210 220 230 240 HRQLVQHNGQ QHKSHLQSRQ NSSMVACSGH LLHNHLSSES VSVSTRNLSN NISDKSQKST 250 260 270 280 290 300 RTGLCSYKQI QTDRLEHLAR ISCGSKIFIG QQGSSPKTLY KSISSNFRNQ TWAYNSSRNS 310 320 330 340 350 360 GHTTWFSSAS NSNKSRSREK AYSSNSTSKR YSPPLNYEKS DFSSPGVRRR ITRLDNNGTP 370 380 390 400 410 420 TQCLSRSFYN TKPCGSYCIH HIVSSLDDWG PCTVTGDVTI KSPRTPRRIT GGVFLVDKNP 430 440 450 460 470 480 NNSSESRLVV HFSQFSRGHT RVHWPKFAVP NLQTLANLLS TNLQWLSLDV SAAFYHIPIS 490 500 510 520 530 540 PAAVPHLLVG SPGLERFNTC LSSSTHNRNN SQLQTMHNLC TRHVYSSLLL LFKTYGRKLH 550 560 570 580 590 600 LLAHPFIMGF RKLPMGVGLS SSLLAQFTSA LASMVRRNFP HCVVFAYMDD LVLGARTSEH 610 620 630 640 650 660 LTAIYSHICS VFLDLGIHLN VNKTKWWGNH LHFMGYVITS SGVLPQDKHV KKISRYLLSV 670 680 690 700 710 720 PVNQPLDYKI SERLTGILNY VAPFTLCGYA ALMPLYHAIA SRMAFIFSSL YKSWLLSLYE 730 740 750 760 770 780 ELWPVVRQRG VVCTVFADAT PTGWGIATTC QLLSGTYAFP LPIATAELIA ACLARCWTGA 790 800 810 820 830 840 RLLGTDNSVV LSGKLTSFPW LLACVATWIL RGTSFCYVPS ALNPADLPSR GLLPALRPLP 850 860 870 880 RLRLRPQTTR ISLWAASPPV SPRAPVRVAW SSPVQTCEPW IPP

References

[1]	"Nucleotide sequence of a cloned woodchuck hepatitis virus genome: evolutional relationship between hepadnaviruses." Kodama K., Ogasawara N., Yoshikawa H., Murakami S. J. Virol. 56:978-986(1985) [PubMed: 3855246] [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.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M11082 Unassigned DNA. Translation: AAA19183.1.
PIR	JDVLC2. A00708.
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_WHV2

Accession

Primary (citable) accession number: P06275

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	June 16, 2009
This is version 49 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)