P63

From Proteopedia

Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights Function p63 is a tumor protein belonging to the p53 family. It is a multi-isoform protein required for epidermal development[1]. p63 domains structure is similar to that of p53 with an N-terminal transactivation domain (TAD) followed by proline-rich region, DNA-binding domain (DBD) and tetramerization domain. In addition, the p63 contains an additional C-terminal region with SAM (Sterile a-Motif) and transactivation inhibitory domains. The SAM domain is involved in protein-protein interactions. Disease Mutations in p63 result in cleft lip or palate syndromes, split hand/foot malformation or ectodermal dysplasia[2], [3]. Relevance One isoform of p63 is involved in skin development and stem/progenitor cell regulation[4]. Another isoform functions in apoptosis[5]. Structural highlights A-B dimer interactions with DNA. Water molecules are shown as red spheres. C-D dimer interactions with DNA. Zn coordination site.

spinqualitylabelsall models P63 DNA-binding domain complex with DNA and Zn+2 atoms (grey) (PDB code 3us0) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D Structures of P63

Updated on 21-August-2023

p63 DBD (153-384)

2rmn – hP63 - human - NMR

3qym, 3qyn, 3us0, 3us1, 3us2 – hP63 + DNA

7z71, 7z7e – hP63 + darpin

p63 tetramerization domain (397-455)

3zy0, 3zy1, 4a9z – hP63

2nb1 – hP63 + p73 tetramerization domain - NMR

7z73 – hP63 + darpin

p63 C terminal domain (501-575)

1rg6 – hP63 - NMR

p63 SAM domain (543-622)

2y9t – hP63 - NMR

2y9u – hP63 (mutant)

7z72 – hP63 + darpin

5n2o – P63 (mutant) - mouse

References

1. ↑ Parsa R, Yang A, McKeon F, Green H. Association of p63 with proliferative potential in normal and neoplastic human keratinocytes. J Invest Dermatol. 1999 Dec;113(6):1099-105. PMID:10594758 doi:http://dx.doi.org/10.1046/j.1523-1747.1999.00780.x
2. ↑ Leoyklang P, Siriwan P, Shotelersuk V. A mutation of the p63 gene in non-syndromic cleft lip. J Med Genet. 2006 Jun;43(6):e28. PMID:16740912 doi:43/6/e28
3. ↑ Tadini G, Santagada F, Brena M, Pezzani L, Nannini P. Ectodermal dysplasias: the p63 tail. G Ital Dermatol Venereol. 2013 Feb;148(1):53-8. PMID:23407076
4. ↑ Koster MI, Dai D, Roop DR. Conflicting roles for p63 in skin development and carcinogenesis. Cell Cycle. 2007 Feb 1;6(3):269-73. Epub 2007 Feb 3. PMID:17224652 doi:http://dx.doi.org/10.4161/cc.6.3.3792
5. ↑ Petre-Lazar B, Livera G, Moreno SG, Trautmann E, Duquenne C, Hanoux V, Habert R, Coffigny H. The role of p63 in germ cell apoptosis in the developing testis. J Cell Physiol. 2007 Jan;210(1):87-98. PMID:16998800 doi:http://dx.doi.org/10.1002/jcp.20829