Protein X
Function
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.
Post-translational modifications
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.
Sequence Similarities
Belongs to the orthohepadnavirus protein X family.
Cellular localization
- Host cytoplasm
- Host nucleus
- Host mitochondrion
- Mainly cytoplasmic as only a fraction is detected in the nucleus. In cytoplasm, a minor fraction associates with mitochondria or proteasomes.
Alternative names
Protein X, HBx, Peptide X, pX, X