Q4R1R9 (DPOL_HBVA9) 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 A3 (isolate Cameroon/CMR711/1994) (HBV-A) [Complete proteome]

Taxonomic identifier

489459 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Hepadnaviridae › Orthohepadnavirus › Hepatitis B virus › HBV genotype A › HBV genotype A3

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 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 relieve 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 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_0000323254
Regions
	Domain	359 – 602	244	Reverse transcriptase
	Region	1 – 179	179	Terminal protein domain (TP) By similarity
	Region	180 – 348	169	Spacer By similarity
	Region	349 – 692	344	Polymerase/reverse transcriptase domain (RT) By similarity
	Region	693 – 845	153	RnaseH domain (RH) By similarity
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)
	Q4R1R9 [UniParc]. Last modified July 19, 2005. Version 1. Checksum: 330F137056D8E983	FASTA	845	94,770
	10 20 30 40 50 60 MPLSYQHFRK LLLLDDGTEV GPLEEELPRL ADEDLNRRVA EDLNLGNLNV SIPWTHKVGN 70 80 90 100 110 120 FTGLYSSTVP IFNQEWQTPS FPKIHLHEDI INRCQQFVGP LNVNEKRRLK LIMPARFYPN 130 140 150 160 170 180 STKYLPLDKG IKPYYPGHVV NHYFQARHYL HTLWKAGILY KRETTRSASF CGSPYSWEQE 190 200 210 220 230 240 LHHGRSVTKT SQRHGDESFC SQPSGILSRS SVGPCIRSQL KQPRLGLQPH QGPLATSQSG 250 260 270 280 290 300 RSGSIWARVH PSTRRSSGVE PSGSGHIDYS ASSSSSCLHQ SAVRKTAYSH LSTSKRQSSS 310 320 330 340 350 360 GHAVEFHKVP PNSARSQSQG PVFSCWWLQF RNSQPCSEYC LSHLVNLLED WGPCADHGEH 370 380 390 400 410 420 HIRIPRTPAR VTGGVFLVDK NPHNTAESRL VVDFSQFSRG STRVSWPKFA VPNLQSLTNL 430 440 450 460 470 480 LSSNLSWLSL DVSAAFYHIP LHPAAMPHLL IGSSGLSRYV ARLSSNSRIH NHQYGTLQNL 490 500 510 520 530 540 HDSCSRQLYV SLMLLYKTYG RKLHLYSHPI ILGFRKIPMG VGLSPFLLAQ FTSAICSVVR 550 560 570 580 590 600 RAFPHCLAFS YMDDVVLGAK SVQHLESLYT AVTNFLLSLG IHLNPNKTKR WGYSLNFMGY 610 620 630 640 650 660 IIGSWGSLPQ DHIVQKLKHC FRKLPVNRPI DWKVCQRIVG LLGFAAPFTQ CGYPALMPLY 670 680 690 700 710 720 ACIQARQAFT FSPTYKAFLS KQYMNLYPVA RQRPGLCQVF ADATPTGWGL AIGHQRMRGT 730 740 750 760 770 780 FVAPLPIHTA ELLAACFARS RSGATLIGTD NSVVLSRKYT SFPWLLGCTA NWILRGTSFV 790 800 810 820 830 840 YVPSALNPAD DPSRGRLGLY RPLLRLPYRP TTGRTSLYAV SPSVPSHLPD RVHFASPLHV AWRPP

References

[1]	"A new subtype (subgenotype) Ac (A3) of hepatitis B virus and recombination between genotypes A and E in Cameroon." Kurbanov F., Tanaka Y., Fujiwara K., Sugauchi F., Mbanya D., Zekeng L., Ndembi N., Ngansop C., Kaptue L., Miura T., Ido E., Hayami M., Ichimura H., Mizokami M. J. Gen. Virol. 86:2047-2056(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"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	AB194952 Genomic DNA. Translation: BAE00097.1.
3D structure databases
ProteinModelPortal	Q4R1R9.
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_HBVA9

Accession

Primary (citable) accession number: Q4R1R9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	July 19, 2005
Last modified:	October 3, 2012
This is version 33 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program