P69714 (X_HBVA2) 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 adw (isolate Japan/Nishioka/1983) (HBV-A) [Complete proteome]

Taxonomic identifier

482134 [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	Inferred from homology

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 By similarity.
Subunit structure	May form homodimer. May interact with human CEBPA, CFLAR, CREB1, DDB1, E4F1, HBXIP, HSPD1/HSP60, NFKBIA, POLR2E and SMAD4 By similarity. Ref.4
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 By similarity.
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_0000222360
Regions
	Region	68 – 117	50	Mitochondrial targeting sequence By similarity
Experimental info
	Sequence conflict	80	1	E → A in CAA84789. Ref.2
	Sequence conflict	115	1	S → C in CAA84789. Ref.2
	Sequence conflict	130 – 131	2	KV → MI in CAA84789. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P69714 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 8B7BB32A4F02566A	FASTA	154	16,567
	10 20 30 40 50 60 MAARLYCQLD PSRDVLCLRP VGAESRGRPL SGPLGTLSSP SPSAVPADHG AHLSLRGLPV 70 80 90 100 110 120 CAFSSAGPCA LRFTSARCME TTVNAHQILP KVLHKRTLGL PAMSTTDLEA YFKDSVFKDW 130 140 150 EELGEEIRLK VFVLGGCRHK LVCAPAPCNF FTSA

References

[1]	"Characteristics of the X gene of hepatitis B virus." Lo S.J., Chien M.L., Lee Y.H.W. Virology 167:289-292(1988) [PubMed: 3188399] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The complete nucleotide sequences of the cloned hepatitis B virus DNA; subtype adr and adw." Ono Y., Onda H., Sasada R., Igarashi K., Sugino Y., Nishioka K. Nucleic Acids Res. 11:1747-1757(1983) [PubMed: 6300776] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	Plucienniczak A. Submitted (AUG-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Dimerization of hepatitis B viral X protein synthesized in a cell-free system." Lin M.H., Lo S.C. Biochem. Biophys. Res. Commun. 164:14-21(1989) [PubMed: 2803288] [Abstract] Cited for: HOMODIMERIZATION.
[5]	"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.
[6]	"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	M23692 Genomic DNA. Translation: AAA56820.1. V00866 Genomic DNA. No translation available. Z35717 Genomic DNA. Translation: CAA84789.1.
PIR	QQVLAW. A31289.
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_HBVA2

Accession

Primary (citable) accession number: P69714
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 32 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program