Reviewed, UniProtKB/Swiss-Prot P03155 (DPOL_HBVD1)

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 D subtype adw (isolate United Kingdom/adyw/1979) (HBV-D)

Taxonomic identifier

10419 [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	750 AA.
Sequence status	Fragment.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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	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 – ›750	›750	Protein P		PRO_0000222345
Regions
	Domain	346 – 589	244	Reverse transcriptase
	Region	1 – 177	177	Terminal protein domain (TP) By similarity
	Region	178 – 335	158	Spacer By similarity
	Region	336 – 679	344	Polymerase/reverse transcriptase domain (RT) By similarity
	Region	680 – 750	71	RnaseH domain (RH) By similarity
Sites
	Metal binding	418	1	Magnesium; catalytic By similarity
	Metal binding	540	1	Magnesium; catalytic By similarity
	Metal binding	541	1	Magnesium; catalytic By similarity
	Site	63	1	Priming of reverse-transcription by covalently linking the first nucleotide of the (-)DNA By similarity
Experimental info
	Mutagenesis	133 – 134	2	YP → SA: 99% loss of polymerase activity.
	Mutagenesis	540	1	D → H: Complete loss of polymerase activity. Ref.3
	Mutagenesis	718	1	E → H: 90% loss of polymerase activity. Ref.3
	Mutagenesis	725	1	A → D: Complete loss of polymerase activity. Ref.3
	Mutagenesis	737	1	D → V: 80% loss of polymerase activity. Ref.3
	Non-terminal residue	750	1

Sequences

	Sequence		Length	Mass (Da)
	P03155-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 325F45EBC83EB07D	FASTA	750	84,674
	10 20 30 40 50 60 MPLSYQRFRR LLLLDDEAGP LEEELPRLAD EDLNRRVAED LNLGNLNVSI PWTHKVGNFT 70 80 90 100 110 120 GLYSSTVPVF NPHWKPPSFP NIHLHQDIIK KCEQFVGPLT VNEKRRLKLI MPARFYPNFT 130 140 150 160 170 180 KYLPLDKGIK PYYPEHLVNH YFQTRHYLHT LWKAGVLYKR VSTHSASFCG SPYSWEQELQ 190 200 210 220 230 240 HGAESFHQQS SGILSRPPVG SSLQSKHQQS RLGLQSQQGH LARRQQGRSW SIRARVHPTA 250 260 270 280 290 300 RRPFGVEPSG SGHNANLASK SASCLYQSPV RTAAYPAVST SENHSSSGHA LELHNLPPNS 310 320 330 340 350 360 ARSQSERPVF PCWWLQFRDS KPCSDYYLSH IVNLLEDWGP CAEHGEHHIR IPRTPARVTG 370 380 390 400 410 420 GVFLVDKNPH NTAESRLVVD FSQFSRGNYR VSWPKFAVPN LQSLTNLLSS NLSWLSLDVS 430 440 450 460 470 480 AAFYHLPLHP AAMPHLLVGS SGLSRYVARL SSNSRIINHQ HGILQNLHDS CSRNLYVSLL 490 500 510 520 530 540 LLYKTFGWKL HLYSHPIILG FRKIPMGVGL SPFLLAQFTS AICSVVRRAF PHCLAFSYMD 550 560 570 580 590 600 DVVLGAKSVQ HLESLFTAVT NFLLSLGIHL NPNKTKRWGY SLNFMGYVIG CWGSLPQDHI 610 620 630 640 650 660 IHKIKECFRK LPVHRPIDWK VCQRIVGLLG FAAPFTQCGY PALMPLYACI QSKQAFTFSP 670 680 690 700 710 720 TYKAFLCKQY LNLYPVAEQR PGLCQVFADA TPTGWGLVMG HQRMRGTFLA PLPIHTAELL 730 740 750 AACFARSRSG ANILGTDNSV VLSRKYTSFP

References

[1]	"Hepatitis B virus genes and their expression in E. coli." Pasek M., Goto T., Gilbert W., Zink B., Schaller H., McKay P., Leadbetter G., Murray K. Nature 282:575-579(1979) [PubMed: 399329] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"The amino-terminal domain of the hepadnaviral P-gene encodes the terminal protein (genome-linked protein) believed to prime reverse transcription." Bartenschlager R., Schaller H. EMBO J. 7:4185-4192(1988) [PubMed: 2854056] [Abstract] Cited for: FUNCTION.
[3]	"Mutational analysis of the hepatitis B virus P gene product: domain structure and RNase H activity." Radziwill G., Tucker W., Schaller H. J. Virol. 64:613-620(1990) [PubMed: 2153228] [Abstract] Cited for: MUTAGENESIS OF 133-TYR-PRO-134; ASP-540; GLU-718; ALA-725 AND ASP-737.
[4]	"Hepadnaviral assembly is initiated by polymerase binding to the encapsidation signal in the viral RNA genome." Bartenschlager R., Schaller H. EMBO J. 11:3413-3420(1992) [PubMed: 1380455] [Abstract] Cited for: FUNCTION.
[5]	"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	J02202 Genomic RNA. No translation available.
PIR	JDVLVH. A00701.
3D structure databases
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. 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_HBVD1

Accession

Primary (citable) accession number: P03155

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	July 28, 2009
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)