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Protein

Protein X

Gene

X

Organism
Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979) (HBV-D)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity1 Publication

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Protein X
Alternative name(s):
HBx
Peptide X
pX
Gene namesi
Name:X
OrganismiHepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979) (HBV-D)
Taxonomic identifieri490133 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesHepadnaviridaeOrthohepadnavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Pan troglodytes (Chimpanzee) [TaxID: 9598]
Proteomesi
  • UP000007930 Componenti: Genome

Subcellular locationi

  • Host cytoplasm By similarity
  • Host nucleus By similarity
  • Host mitochondrion By similarity

  • Note: Mainly cytoplasmic as only a fraction is detected in the nucleus. In cytoplasm, a minor fraction associates with mitochondria or proteasomes.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host mitochondrion, Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi77 – 782RR → EE: No effect on interaction with human DDB1. 1 Publication
Mutagenesisi91 – 911K → E: No effect on interaction with human DDB1. 1 Publication
Mutagenesisi95 – 951K → E: No effect on interaction with human DDB1.
Mutagenesisi96 – 961R → E: Complete loss of interaction with human DDB1.
Mutagenesisi98 – 981L → F: Complete loss of interaction with human DDB1. 1 Publication
Mutagenesisi107 – 1071D → R: No effect on interaction with human DDB1. 1 Publication
Mutagenesisi113 – 1142KD → ER: No effect on interaction with human DDB1. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 154154Protein XPRO_0000222361Add
BLAST

Interactioni

Subunit structurei

May form homodimer. May interact with human CEBPA, CFLAR, CREB1, DDB1, E4F1, HBXIP, HSPD1/HSP60, NFKBIA, POLR2E and SMAD4 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
AKT1P317493EBI-7683985,EBI-296087From a different organism.
Akt1P317502EBI-7683985,EBI-298707From a different organism.

Protein-protein interaction databases

IntActiP03165. 4 interactions.
MINTiMINT-8306163.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni68 – 11750Mitochondrial targeting sequenceBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the orthohepadnavirus protein X family.Curated

Family and domain databases

InterProiIPR000236. Transactivation_prot_X.
[Graphical view]
PfamiPF00739. X. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P03165-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAARLCCQLD PARDVLCLRP VGAESRGRPF SGSLGTLSSP SPSAVPTDHG
60 70 80 90 100
AHLSLRGLPV CAFSSAGPCA LRFTSARRME TTVNAHQILP KVLHKRTLGL
110 120 130 140 150
SAMSTTDLEA YFKDCLFKDW EELGEEIRLK VFVLGGCRHK LVCAPAPCNF

FTSA
Length:154
Mass (Da):16,618
Last modified:April 1, 1990 - v2
Checksum:i29FD1CC9E09A34B5
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti26 – 261R → C in strain: Switzerland/Strubin/1999.
Natural varianti33 – 331S → P in strain: Switzerland/Strubin/1999.
Natural varianti36 – 361T → A in strain: Switzerland/Strubin/1999.
Natural varianti40 – 434PSPS → SSLP in strain: Switzerland/Strubin/1999.
Natural varianti46 – 461P → S in strain: Latvia.
Natural varianti47 – 482TD → AA in strain: Switzerland/Strubin/1999.
Natural varianti84 – 885NAHQI → KAQPF in strain: Latvia.
Natural varianti102 – 1021A → V in strain: Latvia.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01460 Genomic DNA. No translation available.
X02496 Genomic DNA. Translation: CAB41697.1.
PIRiA03719. QQVLD1.
A05237. QQVLBH.

Cross-referencesi

Web resourcesi

HepSEQ

Hepatitis virus B database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01460 Genomic DNA. No translation available.
X02496 Genomic DNA. Translation: CAB41697.1.
PIRiA03719. QQVLD1.
A05237. QQVLBH.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP03165. 4 interactions.
MINTiMINT-8306163.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

InterProiIPR000236. Transactivation_prot_X.
[Graphical view]
PfamiPF00739. X. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiX_HBVD3
AccessioniPrimary (citable) accession number: P03165
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 1, 1990
Last modified: May 11, 2016
This is version 75 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.Curated

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.