Human p53 protein (Hp53) can be divided into five domains, each corresponding to specific functions:
I) The amino-terminus part 1-42 contains the acidic transactivation domain and the mdm2 protein binding site. It also contains the Highly Conserved Domain I (HCD I)
II) Region 40-92 contains series repeated proline residues that are conserved in the majority of p53. it also contains a second transactivation domain.
III) The central region (101-306) contains the DNA binding domain. It is the target of 90% of p53 mutations found in human cancers. It contains HCD II to V.
IV) The oligomerization domain (307-355, 4D) consists of a beta-strand, followed by an alpha-helix necessary for dimerization, as p53 is composed of a dimer of two dimers. A nuclear export signal (NES) is localized in this oligomerization domain.
V) The carboxy-terminus of p53 (356-393) contains 3 nuclear localization signals (NLS) and a non-specific DNA binding domain that binds to damaged DNA. This region is also involved in downregulation of DNA binding of the central domain.