P69713 (X_HBVA3) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein X

Alternative name(s):
HBx
Peptide X
pX

Gene names

Name:

X

Organism

Hepatitis B virus genotype A2 subtype adw2 (strain Rutter 1979) (HBV-A) [Complete proteome]

Taxonomic identifier

480116 [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	154 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Multifunctional protein that may modulate protein degradation pathways, apoptosis, transcription, signal transduction, cell cycle progress, and genetic stability by directly or indirectly interacting with hosts factors. Does not seem to be essential for HBV infection. May be directly involved in development of cirrhosis and liver cancer (hepatocellular carcinoma). Most of cytosolic activities involve modulation of cytosolic calcium. The effect on apoptosis is controversial depending on the cell types in which the studies have been conducted. By binding to human DDB1, may affect cell viability and stimulate genome replication. May induce apoptosis by localizing in mitochondria and causing loss of mitochondrial membrane potential. May also modulate apoptosis by binding human CFLAR, a key regulator of the death-inducing signaling complex (DISC). Moderately stimulates transcription of many different viral and cellular transcription elements. Promoters and enhancers stimulated by HBx contain DNA binding sites for NF-kappa-B, AP-1, AP-2, c-EBP, ATF/CREB, or the calcium-activated factor NF-AT. May bind bZIP transcription factors like CREB1. Ref.9 Ref.14
Subunit structure	May form homodimer. May interact with human CEBPA, CFLAR, CREB1, DDB1, E4F1, HBXIP, HSPD1/HSP60, NFKBIA, POLR2E and SMAD4 By similarity.
Subcellular location	Host cytoplasm. Host nucleus. Host mitochondrion. Note: Mainly cytoplasmic as only a fraction is detected in the nucleus. In cytoplasm, a minor fraction associates with mitochondria or proteasomes. Ref.5 Ref.8 Ref.12 Ref.13
Post-translational modification	A fraction may be phosphorylated in insect cells and HepG2 cells, a human hepatoblastoma cell line. Phosphorylated in vitro by host protein kinase C or mitogen-activated protein kinase. N-acetylated in insect cells. Ref.3
Sequence similarities	Belongs to the orthohepadnavirus protein X family.
Caution	Transcriptional activities should be taken with a grain of salt. As of 2007, all studies demonstrating in vivo interaction between protein X and transcriptional components were performed with significant overexpression of both proteins and in the absence of viral infection.

Ontologies

Keywords
Biological process	Activation of host NF-kappa-B by virus Apoptosis Host G2/M cell cycle arrest by virus Host-virus interaction Modulation of host cell cycle by virus Transcription Transcription regulation
Cellular component	Host cytoplasm Host mitochondrion Host nucleus
Molecular function	Activator
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW viral genome replication Inferred from electronic annotation. Source: InterPro
Cellular component	host cell mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 154	154	Protein X		PRO_0000222359
Regions
	Region	68 – 117	50	Mitochondrial targeting sequence
Natural variations
	Natural variant	12	1	S → A in expression vector pCMVX.
	Natural variant	109	1	E → A in expression vector pCMVX.

Sequences

	Sequence		Length	Mass (Da)
	P69713 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 7F2AE32A4F025670	FASTA	154	16,583
	10 20 30 40 50 60 MAARLYCQLD PSRDVLCLRP VGAESRGRPL SGPLGTLSSP SPSAVPADHG AHLSLRGLPV 70 80 90 100 110 120 CAFSSAGPCA LRFTSARCME TTVNAHQILP KVLHKRTLGL PAMSTTDLEA YFKDCVFKDW 130 140 150 EELGEEIRLK VFVLGGCRHK LVCAPAPCNF FTSA

References

[1]	"The nucleotide sequence of the hepatitis B viral genome and the identification of the major viral genes." Valenzuela P., Quiroga M., Zaldivar J., Gray P., Rutter W.J. (In) Field B.N., Jaenisch R., Fox C.F. (eds.); Animal virus genetics, pp.57-70, Academic Press, New York (1980) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The identification of hepatitis B virus X gene responsive elements reveals functional similarity of X and HTLV-I tax." Faktor O., Shaul Y. Oncogene 5:867-872(1990) [PubMed: 2359621] [Abstract] Cited for: PROMOTER STIMULATION.
[3]	"Phosphorylation and rapid turnover of hepatitis B virus X-protein expressed in HepG2 cells from a recombinant vaccinia virus." Schek N., Bartenschlager R., Kuhn C., Schaller H. Oncogene 6:1735-1744(1991) [PubMed: 1923499] [Abstract] Cited for: PHOSPHORYLATION IN HEPG2 CELLS.
[4]	"HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions." Maguire H.F., Hoeffler J.P., Siddiqui A. Science 252:842-844(1991) [PubMed: 1827531] [Abstract] Cited for: INTERACTION WITH HUMAN CREB1.
[5]	"The hepatitis B virus HBx protein is a dual specificity cytoplasmic activator of Ras and nuclear activator of transcription factors." Doria M., Klein N., Lucito R., Schneider R.J. EMBO J. 14:4747-4757(1995) [PubMed: 7588604] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"Isolation and molecular characterization of hepatitis B virus X-protein from a baculovirus expression system." Urban S., Hildt E., Eckerskorn C., Sirma H., Kekule A., Hofschneider P.H. Hepatology 26:1045-1053(1997) [PubMed: 9328333] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
[7]	"Hepatitis B virus pX targets TFIIB in transcription coactivation." Haviv I., Shamay M., Doitsh G., Shaul Y. Mol. Cell. Biol. 18:1562-1569(1998) [PubMed: 9488473] [Abstract] Cited for: INTERACTION WITH HUMAN CELL TRANSCRIPTION MACHINERY.
[8]	"Cytosol is the prime compartment of hepatitis B virus X protein where it colocalizes with the proteasome." Sirma H., Weil R., Rosmorduc O., Urban S., Israel A., Kremsdorf D., Brechot C. Oncogene 16:2051-2063(1998) [PubMed: 9572486] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell death." Takada S., Shirakata Y., Kaneniwa N., Koike K. Oncogene 18:6965-6973(1999) [PubMed: 10597295] [Abstract] Cited for: FUNCTION.
[10]	"Interaction of hepatitis B viral X protein and CCAAT/enhancer-binding protein alpha synergistically activates the hepatitis B viral enhancer II/pregenomic promoter." Choi B.H., Park G.T., Rho H.M. J. Biol. Chem. 274:2858-2865(1999) [PubMed: 9915821] [Abstract] Cited for: INTERACTION WITH HUMAN CEBPA.
[11]	"Direct association and nuclear import of the hepatitis B virus X protein with the NF-kappaB inhibitor IkappaBalpha." Weil R., Sirma H., Giannini C., Kremsdorf D., Bessia C., Dargemont C., Brechot C., Israel A. Mol. Cell. Biol. 19:6345-6354(1999) [PubMed: 10454581] [Abstract] Cited for: INTERACTION WITH HUMAN NFKBIA.
[12]	"Intracellular localization of the hepatitis B virus HBx protein." Henkler F., Hoare J., Waseem N., Goldin R.D., McGarvey M.J., Koshy R., King I.A. J. Gen. Virol. 82:871-882(2001) [PubMed: 11257193] [Abstract] Cited for: SUBCELLULAR LOCATION.
[13]	"Subcellular localisation of the X protein in HBV infected hepatocytes." Hoare J., Henkler F., Dowling J.J., Errington W., Goldin R.D., Fish D., McGarvey M.J. J. Med. Virol. 64:419-426(2001) [PubMed: 11468725] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"Hepatitis B virus X protein induces cell death by causing loss of mitochondrial membrane potential." Shirakata Y., Koike K. J. Biol. Chem. 278:22071-22078(2003) [PubMed: 12676947] [Abstract] Cited for: FUNCTION IN APOPTOSIS.
[15]	"Interaction of the hepatitis B virus X protein (HBx) with heat shock protein 60 enhances HBx-mediated apoptosis." Tanaka Y., Kanai F., Kawakami T., Tateishi K., Ijichi H., Kawabe T., Arakawa Y., Kawakami T., Nishimura T., Shirakata Y., Koike K., Omata M. Biochem. Biophys. Res. Commun. 318:461-469(2004) [PubMed: 15120623] [Abstract] Cited for: INTERACTION WITH HUMAN HSPD1/HSP60.
[16]	"The enigmatic X gene of hepatitis B virus." Bouchard M.J., Schneider R.J. J. Virol. 78:12725-12734(2004) [PubMed: 15542625] [Abstract] Cited for: REVIEW.
[17]	"Molecular functions and biological roles of hepatitis B virus x protein." Tang H., Oishi N., Kaneko S., Murakami S. Cancer Sci. 97:977-983(2006) [PubMed: 16984372] [Abstract] Cited for: REVIEW.

Web resources

HepSEQ

Hepatitis virus B database

Cross-references

Sequence databases
EMBL GenBank DDBJ	X02763 Genomic DNA. Translation: CAA26540.1.
PIR	QQVLAW. A31289. S47408.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR000236. Transactivation_prot_X. [Graphical view]
Pfam	PF00739. X. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

X_HBVA3

Accession

Primary (citable) accession number: P69713
Secondary accession number(s): P03166, P12935

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	December 14, 2011
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