SIX1 is a transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development []. It plays important roles in organogenesis and tumorigenesis [].
Members of the eye absent (EYA) family were originally characterised in fly eye development. EYA proteins are both transcriptional activators and tyrosine phosphatases [, ], and have been shown to dephosphorylate H2AX, promoting repair and cell survival in the response to DNA damage []. EYA proteins (EYA1-4) are normally expressed early in development [, ]. Their phosphatase activity regulates Six1-Dach-Eya transcriptional effects in precursor cell proliferation and survival in mammalian organogenesis [].EYA2 plays an important role in hypaxial muscle development together with Six1 and Dach2; in this it is functionally redundant with EYA1 []. EYA2 is a necessary co-factor for many of the metastasis promoting functions of Six1 [].
The SD domain is found N-terminal to the homeobox domain in the protein SIX1. As a transcription factor, SIX1 lacks intrinsic activation domains and thus needs to bind to the EYA family of co-factors in order to mediate transcriptional activation. The SD domain is necessary for this protein-protein interaction, binding to the C-terminal region of EYA (Eyes absent homologue proteins) [].
Members of the eye absent (EYA) family were originally characterised in fly eye development. EYA proteins are both transcriptional activators and tyrosine phosphatases [, ], and have been shown to dephosphorylate H2AX, promoting repair and cell survival in the response to DNA damage []. EYA proteins (EYA1-4) are normally expressed early in development [, ]. Their phosphatase activity regulates Six1-Dach-Eya transcriptional effects in precursor cell proliferation and survival in mammalian organogenesis [].EYA3 forms a complex with Six1 and Ski that regulates muscle terminal differentiation [].
