HBx

For other uses, see HBX (disambiguation).
Protein X
Identifiers
OrganismHepatitis B virus genotype B2 (isolate Vietnam/9873/1997)
SymbolX
UniProtP0C685
Search for
StructuresSwiss-model
DomainsInterPro
Transactivation protein X
Identifiers
Symbol?
PfamPF00739
InterProIPR000236
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
The genome organisation of HBV; the genes overlap. ORF X, in yellow, encodes HBx.

HBx is a hepatitis B viral protein.[1][2] It is 154 amino acids long and interferes with transcription, signal transduction, cell cycle progress, protein degradation, apoptosis and chromosomal stability in the host. It forms a heterodimeric complex with its cellular target protein (HBX interacting protein: HBXIP), and this interaction dysregulates centrosome dynamics and mitotic spindle formation.[3] It interacts with DDB1 (Damaged DNA Binding Protein 1) redirecting the ubiquitin ligase activity of the CUL4-DDB1 E3 complexes, which are intimately involved in the intracellular regulation of DNA replication and repair, transcription and signal transduction.[4]

Although Protein X is normally absent in the Avihepadnavirus, a vestigial version has been identified in the duck hepatitis virus genome.[5]

Although it lacks significant sequence identity with any known vertebrate proteins, it seems likely that it evolved from a DNA glycosylase.[6]

Transgenic mice expressing the X protein in liver are more likely than the wild type to develop hepatocellular carcinoma. This is because the X protein promotes cell cycle progression while binding to and inhibiting tumor suppressor protein p53 from performing its role. Experimental observations also suggest that HBx protein increases TERT and telomerase activity, prolonging the lifespan of hepatocytes and contributing to malignant transformation.[7]

  1. ^ McClain SL, Clippinger AJ, Lizzano R, Bouchard MJ (November 2007). "Hepatitis B virus replication is associated with an HBx-dependent mitochondrion-regulated increase in cytosolic calcium levels". Journal of Virology. 81 (21): 12061–5. doi:10.1128/JVI.00740-07. PMC 2168786. PMID 17699583.
  2. ^ Bouchard MJ, Puro RJ, Wang L, Schneider RJ (July 2003). "Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in hepatitis B virus replication". Journal of Virology. 77 (14): 7713–9. doi:10.1128/JVI.77.14.7713-7719.2003. PMC 161925. PMID 12829810.
  3. ^ Wen Y, Golubkov VS, Strongin AY, Jiang W, Reed JC (February 2008). "Interaction of hepatitis B viral oncoprotein with cellular target HBXIP dysregulates centrosome dynamics and mitotic spindle formation". The Journal of Biological Chemistry. 283 (5): 2793–803. doi:10.1074/jbc.M708419200. PMID 18032378.
  4. ^ Li T, Robert EI, van Breugel PC, Strubin M, Zheng N (January 2010). "A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery". Nature Structural & Molecular Biology. 17 (1): 105–11. doi:10.1038/nsmb.1719. PMC 2823288. PMID 19966799.
  5. ^ Lin B, Anderson DA (2000). "A vestigial X open reading frame in duck hepatitis B virus". Intervirology. 43 (3): 185–90. doi:10.1159/000025037. PMID 11044813. S2CID 22542029.
  6. ^ van Hemert FJ, van de Klundert MA, Lukashov VV, Kootstra NA, Berkhout B, Zaaijer HL (2011). "Protein X of hepatitis B virus: origin and structure similarity with the central domain of DNA glycosylase". PLOS ONE. 6 (8): e23392. Bibcode:2011PLoSO...623392V. doi:10.1371/journal.pone.0023392. PMC 3153941. PMID 21850270.
  7. ^ Kew MC (January 2011). "Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma". Journal of Gastroenterology and Hepatology. 26 (Suppl 1): 144–52. doi:10.1111/j.1440-1746.2010.06546.x. PMID 21199526. S2CID 2456828.