Homeobox protein SIX1

Definition:

Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development (By similarity). Plays an important role in the development of several organs, including kidney, muscle and inner ear (By similarity). Depending on context, functions as transcriptional repressor or activator (By similarity). Lacks an activation domain, and requires interaction with EYA family members for transcription activation. Mediates nuclear translocation of EYA1 and EYA2. Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the MYOG promoter and CIDEA enhancer. Regulates the expression of numerous genes, including MYC, CCND1 and EZR (By similarity). Acts as activator of the IGFBP5 promoter, probably coactivated by EYA2 (By similarity). Repression of precursor cell proliferation in myoblasts is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex (By similarity). During myogenesis, seems to act together with EYA2 and DACH2 (By similarity). Regulates the expression of CCNA1. Promotes brown adipocyte differentiation (By similarity).

References:

[1]. Ricardo D Coletta, et al. The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6478-83. [Content Brief]

[2]. Aaron N Patrick, et al. Biochemical and functional characterization of six SIX1 Branchio-oto-renal syndrome mutations. J Biol Chem. 2009 Jul 31;284(31):20781-90. [Content Brief]

[3]. Rainer G Ruf, et al. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8090-5. [Content Brief]

[4]. Reinhard Brunmeir, et al. Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators of Murine Brown Adipogenesis. PLoS Genet. 2016 Dec 6;12(12):e1006474. [Content Brief]

[5]. Aaron N Patrick, et al. Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome. Nat Struct Mol Biol. 2013 Apr;20(4):447-53. [Content Brief]

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