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Protein X



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


Multifunctional protein that plays a role in silencing host antiviral defenses and promoting viral transcription. 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. May induce apoptosis by localizing in mitochondria and causing loss of mitochondrial membrane potential. May also modulate apoptosis by binding host CFLAR, a key regulator of the death-inducing signaling complex (DISC). Promotes viral transcription by using the host E3 ubiquitin ligase DDB1 to target the SMC5-SMC6 complex to proteasomal degradation. This host complex would otherwise bind to viral episomal DNA, and prevents its transcription. 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.UniRule annotation1 Publication

GO - Biological processi


Molecular functionActivator
Biological processActivation 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 XUniRule annotation
Alternative name(s):
HBxUniRule annotation
Peptide XUniRule annotation
pXUniRule annotation
Gene namesi
Name:XUniRule annotation
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]
  • UP000007930 Componenti: Genome

Subcellular locationi

  • Host cytoplasm UniRule annotation
  • Host nucleus UniRule annotation
  • Host mitochondrion UniRule annotation

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

GO - Cellular componenti

Keywords - Cellular componenti

Host cytoplasm, Host mitochondrion, Host nucleus

Pathology & Biotechi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi77 – 78RR → EE: No effect on interaction with human DDB1. 1 Publication2
Mutagenesisi91K → E: No effect on interaction with human DDB1. 1 Publication1
Mutagenesisi95K → E: No effect on interaction with human DDB1. 1
Mutagenesisi96R → E: Complete loss of interaction with human DDB1. 1
Mutagenesisi98L → F: Complete loss of interaction with human DDB1. 1 Publication1
Mutagenesisi107D → R: No effect on interaction with human DDB1. 1 Publication1
Mutagenesisi113 – 114KD → ER: No effect on interaction with human DDB1. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002223611 – 154Protein XAdd BLAST154

Post-translational modificationi

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.UniRule annotation


Subunit structurei

May form homodimer. May interact with host CEBPA, CFLAR, CREB1, DDB1, E4F1, HBXIP, HSPD1/HSP60, NFKBIA, POLR2E and SMAD4. Interacts with host SMC5-SMC6 complex and induces its degradation.UniRule annotation

Binary interactionsi

Show more details

Protein-protein interaction databases

IntActiP03165. 4 interactors.


3D structure databases


Family & Domainsi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni68 – 117Mitochondrial targeting sequenceUniRule annotationAdd BLAST50

Sequence similaritiesi

Belongs to the orthohepadnavirus protein X family.UniRule annotation

Phylogenomic databases


Family and domain databases

HAMAPiMF_04074. HBV_X. 1 hit.
InterProiView protein in InterPro
IPR000236. Transactivation_prot_X.
PfamiView protein in Pfam
PF00739. X. 1 hit.


Sequence statusi: Complete.

P03165-1 [UniParc]FASTAAdd to basket

« Hide

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60 70 80 90 100
110 120 130 140 150

Mass (Da):16,618
Last modified:April 1, 1990 - v2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti26R → C in strain: Switzerland/Strubin/1999. 1
Natural varianti33S → P in strain: Switzerland/Strubin/1999. 1
Natural varianti36T → A in strain: Switzerland/Strubin/1999. 1
Natural varianti40 – 43PSPS → SSLP in strain: Switzerland/Strubin/1999. 4
Natural varianti46P → S in strain: Latvia. 1
Natural varianti47 – 48TD → AA in strain: Switzerland/Strubin/1999. 2
Natural varianti84 – 88NAHQI → KAQPF in strain: Latvia. 5
Natural varianti102A → V in strain: Latvia. 1

Sequence databases

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

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.

Entry informationi

Entry nameiX_HBVD3
AccessioniPrimary (citable) accession number: P03165
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 1, 1990
Last modified: July 5, 2017
This is version 81 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program



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.

Keywords - Technical termi

Complete proteome, Reference proteome


  1. SIMILARITY comments
    Index of protein domains and families