Protein domains, posttranslational modification sites, and proteins that interact with human p53

The 393 amino acid human p53 polypeptide is represented schematically with postulated functional regions and domains indicated. Residues ~1-40 (TAD1) and 41-83 (TAD2) comprise independent tandem transactivation domains; residues ~61-94 represent a proline-rich (PRD), Src homology 3-like (SH3) domain which overlaps a poorly conserved segment (33-80) that lies mostly in TAD2. Residues 100-116 constitute a recently described N-terminal domain that is required for repressing basal p53 activity in some cell types. Residues ~102-292 contain the central, sequence-specific, DNA binding core region; residues 305-321 contains the primary bi-partite nuclear localization signal (NLS); residues 324-356 comprise the tetramerization domain (TET) which contains a nuclear export signal within residues 339-350; residues 363-393 (REG) negatively regulate DNA binding by the central core to consensus recognition sites in oligonucleotides and interact in a sequence-independent manner with single- and double-stranded nucleic acids but contribute positively to chromatin binding and transactivation in vivo. Posttranslational modification sites (P, phosphorylation; Ac, acetylation; G, glycosylation; Me, mono(1) or di-(2) methylation, N8, neddylation; Ub, ubiquitination; polyADP-R, poly-ADP-ribosylation) are indicated together with enzymes that can accomplish the modifications in vitro. The C-terminal six lysines (K370, K372, K373, K381, K382, and K386) are the primary site of ubiquitination by MDM2; whereas K291 and K292 can be ubiquitinated by MKRN1 and K320 is ubiquitinated by E4F1. K373, K372, and K373 are likely sites of attachment for the ubiquitin-like protein NEDD8, and Lys386 may be modified by conjugation with SUMO1, a ubiquitin-like peptide. Interaction regions for selected proteins are indicated below the polypeptide.

Updated from Anderson and Appella, in Handbook of Cell Signaling, Second Edition, Academic Press, 2009, and Meek and Anderson, Cold Spring Harbor Perspectives in Biology, The p53 Family, Cold Spring Harbor Press, 2009. This is figure 3 in the webpages of Carl W. Anderson.

Last Modified: December 12, 2012
Please forward all questions about this site to: Denise Monteleone

One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation for the State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.

Privacy and Security Notice  | Contact Web Services for help