PROSITE documentation PDOC50952

KIX domain profile

Transcriptional activators are believed to stimulate gene expression via protein-protein interactions with the basal machinery. The cAMP-regulated transcription factor CREB has been shown to stimulate target gene expression, in part by associating with the coactivator paralogs p300 and CREB binding protein (CBP). CBP and P300 bind to the Ser-133-phosphorylated kinase-inducible domain (KID) (see <PDOC50953>) of CREB via a region of approximately 90 residues referred to as the KIX domain, which is highly conserved in CBP homologs from Caenorhabditis elegans and Drosophila melanogaster. In addition to CREB, the KIX domain of CBP also recognizes the transactivation domains of other nuclear factors, including Myb, Jun, cubitus interruptus, and HTLV-1 virally encoded Tax protein. Thus the KIX domain appears to be a common docking site on CBP for many transcriptional activators. The KIX domain is found in association with other domains, such as the bromodomain (see <PDOC00550>), the ZZ-type zinc finger (see <PDOC50135>), or the TAZ-type zinc finger (see <PDOC50134>) [1,2].

The KIX domain of CBP is composed of three mutually interacting α helices, designated α1, α2 and α3, and two short 3(10) helices G1 and G2, that together with the interconnecting loops define a compact structural domain with an extensive hydrophobic core (see <PDB:1KDX; A>). Helices α1 and α3 constitute the primary interacting surface for the phosphorylated KID domain (pKID), forming a hydrophobic patch on the protein surface that is large enough to accommodate up to 3 turns of an amphipathic α helix, designated αB, in pKID (see <PDB:1KDX>). A second α helix in pKID, referred to as αA, interacts with a different face of the α3 helix of KIX. The two helices of pKID are arranged at an angle of about 90 degree and essentially wrap around the α3 helix of KIX [1,2].

The profile we developed spans the entire KIX domain.