PAX Proteins

Abstract As in the case of the HOX proteins (described in Chapter 9), the PAX proteins represent a family of transcription factors whose members ap pear to play key roles in the development of both invertebrates and vertebrates (reviewed by Chalepakis et al., 1993; Strachan and Read, 1994; Stuart and Gruss, 1995). Nine PAX genes have been identified to date in mice and humans (Fig. 7.1). Unlike the HOX genes, which are clustered at four loci in the human and mouse genomes, mapping of the PAX genes revealed no clustering even though several of the genes have similar genomic structure and coding sequences. The proteins encoded by these genes have in common a unique 128- amino-acid DNA-binding domain, the paired domain. Although the paired domain contains three regions that are predicted to form a heli ces, there is no sequence similarity to the helix-turn-helix motif present in homeodomains. In addition to the paired domain, which is present in all nine PAX proteins, four of the proteins (PAX3, PAX4, PAX6, and PAX7) also contain a homeodomain that contributes to the affinity and specificity of DNA binding by these proteins. Curiously, three PAX proteins (PAX2, PAXS, and PAX8) contain truncated homeodomains of un known function. PAX 1 and PAX9 lack homeodomain-related sequences altogether and must therefore rely entirely on the paired domain for DNA-binding activity.