Reviewed, UniProtKB/Swiss-Prot P12899 (DPOL_WHV3)

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 59) (WHV) [Complete proteome]

Taxonomic identifier

10431 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus

Virus host

Marmota monax (Woodchuck) [TaxID: 9995]

Protein attributes

Sequence length	884 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 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 – 884	884	Protein P		PRO_0000222352
Regions
	Domain	398 – 639	242	Reverse transcriptase
	Region	1 – 182	182	Terminal protein domain (TP) By similarity
	Region	183 – 387	205	Spacer By similarity
	Region	388 – 729	342	Polymerase/reverse transcriptase domain (RT) By similarity
	Region	730 – 884	155	RnaseH domain (RH) By similarity
Sites
	Metal binding	470	1	Magnesium; catalytic By similarity
	Metal binding	590	1	Magnesium; catalytic By similarity
	Metal binding	591	1	Magnesium; catalytic By similarity
	Site	68	1	Priming of reverse-transcription by covalently linking the first nucleotide of the (-)DNA By similarity

Sequences

	Sequence		Length	Mass (Da)
	P12899-1 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: 8BAFF8DC6E7558D3	FASTA	884	99,400
	10 20 30 40 50 60 MHPFSRLFRN IQSLGEEEVQ ELLGPPEDAL PLLAGEDLNH RVADALNLHL PTADLQWVHK 70 80 90 100 110 120 TNAITGLYSN QAAQFNPHWI QPEFPELHLH NDLIQKLQQY FGPLTINEKR KLQLNFPARF 130 140 150 160 170 180 FPKATKYFPL IKGIKNNYPN FALEHFFATA NYLWTLWEAG ILYLRKNQTT LTFKGKPYSW 190 200 210 220 230 240 EHRQLVQHNG QQHKSHLQSR QNSSMVACSG HLLHNHLPSE PVSVSTRNLS NNISDKSQKS 250 260 270 280 290 300 TRTGLCSYKQ VQTDRLEHLA RISCGSKITI GQQGSSPKTS YKSISSNFRN QTWAYNSSRN 310 320 330 340 350 360 SGHTTWFSSA SNSNKSRSRE KAYSSNSTSQ RYSPPLNYEK SDFSSPGVRG RITRLDNNGT 370 380 390 400 410 420 LPQCLWRSFY NTKPCGSYCI HHIVSSLDDW GPCTVTGDVT IKSPRTPRRI TGGVFLVDKN 430 440 450 460 470 480 PNNSSESRLV VDFSQFSRGH TRVHWPKFAV PNLQTLANLL STNLQWLSLD VSAAFYHIPI 490 500 510 520 530 540 SPAAVPHLLV GSPGLERFNT CMSSSTHNGN DSQLQTMHAL CTRHVYSSLL LLFKTYGRKL 550 560 570 580 590 600 HLLAHPFIMG FRKLPMGVGL SPFLLAQFTS AIASMVRRNF PHCVVFAYMD DLVLGARTSE 610 620 630 640 650 660 HLTAIYSHIC SVFLDLGIHL NVNKTKWWGN HLHFMGYVIT SSGVLPQDKH VKKLSRYLRS 670 680 690 700 710 720 VPVNQPLDYK ICERLTGILN YVAPFTLCGY AALMPLYHAI ASRTAFIFSS LYKSWLLSLY 730 740 750 760 770 780 EELWPVVRQR GVVCTVFADA TPTGWGIATT CQLLSGTFAF PLPIATAELI AACLARCWTG 790 800 810 820 830 840 ARLLGTDNSV VLSGKLTSFP WLLACVANWI LRGTSFCYVP SALNPADLPS RGLLPVLRPL 850 860 870 880 PRLRLRPQTS RISLWAASPP VSPRRPVRVA WSSPVQTCEP WIPP

References

[1]	"Sequence comparison of woodchuck hepatitis virus replicative forms shows conservation of the genome." Cohen J.I., Miller R.H., Rosenblum B., Denniston K., Gerin J.L., Purcell R.H. Virology 162:12-20(1988) [PubMed: 3336938] [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
EMBL GenBank DDBJ	M19183 Genomic DNA. Translation: AAA46763.1.
PIR	JDVL59. G29969.
3D structure databases
SMR	P12899. Positions 411-641, 413-702.
ModBase	Search...
Family and domain databases
InterPro	IPR001462. DNApol_viral_C. IPR000201. DNApol_viral_N. IPR000477. Reverse_transcriptase. [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_WHV3

Accession

Primary (citable) accession number: P12899

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	January 19, 2010
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)