Predicted impact of TP53 mutations on p53 isoforms

In recent years, several isoforms of p53 have been described. A total of 10 isoforms are currently characterized that are produced by alternative splicing, use of alternative translation site or alternative promoter (reviewed in Marcel & Hainaut, 2008).

Most of these isoforms share a common DNA-binding domain with three different N-terminal domains (TA: entire transactivation domain; delta40: deleted from the first 39 residues; delta133: deleted from the first 132 residues) and/or three different C-terminal domains (alpha: entire oligomerisation domain; beta: 10 additional residues; gamma: 15 additional residues). By convention, TAp53alpha corresponds to the canonical p53 protein. In addition to these isoforms, deltap53 has been described that lacks residues from center of exon 7 to center of exon 9. See illustration below.

Current knowledge on the role and activities of these isoforms is still very limited. In the IARC TP53 Database, all annotations and data are in relation to the full-lenght protein (TA isoform). To introduce knowledge on p53 isoforms, we generated annotations on the predicted impact of TP53 gene mutations on the protein status of isoforms.

All mutations recorded in the database have thus been analyzed to predict their consequences on the status of each p53 protein isoform. These predictions are based on theoretical approaches taking into account the known protein sequences of each isoforms, the position of the mutation in these sequences and the type of mutation.

Annotations and rules used for the predictions:

  • WT = no amino acid change compared to the wild-type sequence
  • Altered = any change in the amino acid sequence
  • Not produced = any mutation affecting the start codon of the isoform
  • Unknown = uncertain prediction of mutation effect

    These annotations can be retrieved from the 'Mutation Validation' search option.




    From Bourdon et al., 2005.

    Reference sequences: