PROSITE documentation PDOC00301

p53 family signature

The p53 tumor antigen [1,2,3,4,5] is a protein found in increased amounts in a wide variety of transformed cells. It is also detectable in many proliferating nontransformed cells, but it is undetectable or present at low levels in resting cells. It is frequently mutated or inactivated in many types of cancer. p53 seems to act as a tumor suppressor in some, but probably not all, tumor types. p53 is probably involved in cell cycle regulation, and may be a trans-activator that acts to negatively regulate cellular division by controlling a set of genes required for this process.

p53 is a phosphoprotein of about 390 amino acids which can be subdivided into four domains: a highly charged acidic region of about 75 to 80 residues, a hydrophobic proline-rich domain (position 80 to 150), a central region (from 150 to about 300), and a highly basic C-terminal region. The sequence of p53 is well conserved in vertebrate species; attempts to identify p53 in other eukaryotic philum has so far been unsuccessful.

The p53 protein belongs to a family [6] that also includes:

• p51 (p63 or Ket), a transcriptional activator.
• p73, a transcriptional activator that participates in the apoptotic response to DNA damage.

As a signature pattern for this family we selected a conserved stretch of 13 residues located in the central region of the protein. This region, known as domain IV in [3], is involved (along with an adjacent region) in the binding of the large T antigen of SV40. In man this region is the focus of a variety of point mutations in cancerous tumors.