Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development (PubMed:12215533, PubMed:12668636, PubMed:12834866, PubMed:14628042, PubMed:14695375). Plays an important role in the development of several organs, including kidney, muscle and inner ear (PubMed:12668636, PubMed:12783782, PubMed:12834866, PubMed:14628042, PubMed:14695375). Depending on context, functions as transcriptional repressor or activator (PubMed:14628042). Lacks an activation domain, and requires interaction with EYA family members for transcription activation (By similarity). Mediates nuclear translocation of EYA1 and EYA2 (By similarity). Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the MYOG promoter and CIDEA enhancer (By similarity). Regulates the expression of numerous genes, including MYC, CCNA1, CCND1 and EZR (PubMed:16488997). Acts as activator of the IGFBP5 promoter, probably coactivated by EYA2 (PubMed:11978764). Repression of precursor cell proliferation in myoblasts is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex (PubMed:14628042). During myogenesis, seems to act together with EYA2 and DACH2. Regulates the expression of CCNA1 (By similarity). Promotes brown adipocyte differentiation (PubMed:27923061). Interacts with DACH1 (PubMed:14628042). Interacts with EYA1 (PubMed:15141091). Interacts with EYA2 (By similarity). Interacts with CDH1 (By similarity). Interacts with TBX18 (By similarity). Interacts with CEBPA (PubMed:27923061). Interacts with CEBPB (PubMed:27923061). Interacts with EBF2 (PubMed:27923061). Expressed in phalangeal tendons and in skeletal muscle and in head and body mesenchyme. First expressed at 8.2-8.5 dpc of embryo development in the anterior head mesoderm and developing pharyngeal pouches. Expression in the developing limb begins at 11 dpc and is more pronounced dorsally. It progresses into the developing phalanges at 13.5 dpc. In the developing inner ear detected in the otic placode and the surrounding surface ectoderm at 8.5 dpc. Expression became prominent at the invaginating otic pit and the nascent otic vesicle at 9.5 dpc. At 10.5 dpc, expression was limited to the ventral half of the otic vesicle. Subsequently, the expression became gradually restricted to the cochlear region at 11.5 dpc and 12.5 dpc. At later stages detected exclusively in the cochlea at 14.5 dpc, and the expression in the cochlear duct persisted in the neonate. In the developing kidney, is expressed in the uninduced metanephric mesenchyme at 10.5 dpc and in the induced mesenchyme around the ureteric bud at 11.5 dpc. At 17.5 dpc to P0, expression becomes restricted to a subpopulation of collecting tubule epithelial cells. Phosphorylated during interphase; becomes hyperphosphorylated during mitosis. Hyperphosphorylation impairs binding to promoter elements (By similarity). Ubiquitinated by the anaphase promoting complex (APC), leading to its proteasomal degradation. Perinatal lethality. Mice show failure in renal organogenesis, a severe reduction of most migratory hypaxial muscles including those of the forelimb, diaphragm and tongue, and severe rib-cage deformation. Besides, mice display craniofacial defects, including loss of inner ear structures. Pax2, Six2 and Sall1 expression is markedly reduced in the metanephric mesenchyme at 10.5 dpc during kidney development. Mice lacking both Six1 and Eya1 show defects in kidney development, complete absence of hypaxial muscle, severe reduction in epaxial muscle and a 5-10-fold by volume smaller pituarity than the wild-type gland. Belongs to the SIX/Sine oculis homeobox family.