Six3 (also known as six homeobox-3), a vertebrate homolog of the Drosophila ‘sine oculis’ (so) gene, is a member of the evolutionarily conserved SIX family. The members of SIX family are found in diverse organisms including flatworms, fruit fly, medaka fish, chickens, frogs, zebrafish, mice and humans (Oliver et al., 1995). Members of the SIX gene family encode transcription factors characterized by the presence of evolutionarily conserved DNA-binding homeodomain and an upstream SIX domain, which may be involved both in determining DNA-binding specificity and in mediating protein-protein interactions (Fig. 1A). DNA-binding activity of so is mediated through the Prd class of homeobox nucleic acid recognition domain (HD). SIX proteins contain lysine residue at position fifty (K50), which assign SIX3 to an Orthodenticle sub-group within the Prd class. The site bound by SIX3 contains the traditional ATTA homeodomain core recognition sequence. Even though there are individual differences, the consensus binding sites for SIX proteins in flies and worms are TGATAC and GGGTATCA. The SIX domain which is the second interaction domain in the six3 protein, is 146 amino acids long, and lies just 50 and directly adjacent to the HD. This domain is involved in mediating protein-protein interactions.
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