P03165 (X_HBVD3) 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 D subtype ayw (isolate France/Tiollais/1979) (HBV-D) [Complete proteome]

Taxonomic identifier

490133 [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 By similarity. Ref.7
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 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_0000222361
Regions
	Region	68 – 117	50	Mitochondrial targeting sequence By similarity
Natural variations
	Natural variant	26	1	R → C in strain: Switzerland/Strubin/1999.
	Natural variant	33	1	S → P in strain: Switzerland/Strubin/1999.
	Natural variant	36	1	T → A in strain: Switzerland/Strubin/1999.
	Natural variant	40 – 43	4	PSPS → SSLP in strain: Switzerland/Strubin/1999.
	Natural variant	46	1	P → S in strain: Latvia.
	Natural variant	47 – 48	2	TD → AA in strain: Switzerland/Strubin/1999.
	Natural variant	84 – 88	5	NAHQI → KAQPF in strain: Latvia.
	Natural variant	102	1	A → V in strain: Latvia.
Experimental info
	Mutagenesis	77 – 78	2	RR → EE: No effect on interaction with human DDB1.
	Mutagenesis	91	1	K → E: No effect on interaction with human DDB1. Ref.4
	Mutagenesis	95	1	K → E: No effect on interaction with human DDB1.
	Mutagenesis	96	1	R → E: Complete loss of interaction with human DDB1.
	Mutagenesis	98	1	L → F: Complete loss of interaction with human DDB1. Ref.4
	Mutagenesis	107	1	D → R: No effect on interaction with human DDB1. Ref.4
	Mutagenesis	113 – 114	2	KD → ER: No effect on interaction with human DDB1.

Sequences

	Sequence		Length	Mass (Da)
	P03165 [UniParc]. Last modified April 1, 1990. Version 2. Checksum: 29FD1CC9E09A34B5	FASTA	154	16,618
	10 20 30 40 50 60 MAARLCCQLD PARDVLCLRP VGAESRGRPF SGSLGTLSSP SPSAVPTDHG AHLSLRGLPV 70 80 90 100 110 120 CAFSSAGPCA LRFTSARRME TTVNAHQILP KVLHKRTLGL SAMSTTDLEA YFKDCLFKDW 130 140 150 EELGEEIRLK VFVLGGCRHK LVCAPAPCNF FTSA

References

[1]	"Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli." Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P. Nature 281:646-650(1979) [PubMed: 399327] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Subtype ayw variant of hepatitis B virus. DNA primary structure analysis." Bichko V., Pushko P., Dreilina D., Pumpen P., Gren E.Y. FEBS Lett. 185:208-212(1985) [PubMed: 3996597] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Latvia.
[3]	"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: CHARACTERIZATION.
[4]	"Hepatitis B virus X protein interferes with cell viability through interaction with the p127-kDa UV-damaged DNA-binding protein." Lin-Marq N., Bontron S., Leupin O., Strubin M. Virology 287:266-274(2001) [PubMed: 11531405] [Abstract] Cited for: INTERACTION WITH HUMAN DDB1, MUTAGENESIS OF 77-ARG-ARG-78; LYS-91; 95-LYS-ARG-96; LEU-98; ASP-107 AND 113-LYS-ASP-114. Strain: Switzerland/Strubin/1999.
[5]	"Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2." Bontron S., Lin-Marq N., Strubin M. J. Biol. Chem. 277:38847-38854(2002) [PubMed: 12151405] [Abstract] Cited for: INTERACTION WITH HUMAN DDB1. Strain: Switzerland/Strubin/1999.
[6]	"Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities." Leupin O., Bontron S., Strubin M. J. Virol. 77:6274-6283(2003) [PubMed: 12743284] [Abstract] Cited for: INTERACTION WITH HUMAN DDB1. Strain: Switzerland/Strubin/1999.
[7]	"Hepatitis B virus X protein stimulates viral genome replication via a DDB1-dependent pathway distinct from that leading to cell death." Leupin O., Bontron S., Schaeffer C., Strubin M. J. Virol. 79:4238-4245(2005) [PubMed: 15767425] [Abstract] Cited for: FUNCTION. Strain: Switzerland/Strubin/1999.
[8]	"Interaction of the hepatitis B virus protein HBx with the human transcription regulatory protein p120E4F in vitro." Rui E., Moura P.R., Goncalves K.A., Rooney R.J., Kobarg J. Virus Res. 115:31-42(2006) [PubMed: 16112766] [Abstract] Cited for: INTERACTION WITH E4F1.
[9]	"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.
[10]	"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	V01460 Genomic DNA. No translation available. X02496 Genomic DNA. Translation: CAB41697.1.
PIR	QQVLD1. A03719. QQVLBH. A05237.
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_HBVD3

Accession

Primary (citable) accession number: P03165

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	April 1, 1990
Last modified:	December 14, 2011
This is version 59 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program