Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a DNA sequence on these target genes and is involved in processes like cell differentiation, cell migration and cell survival. Transactivates gene expression by binding a 5'-[CAT]A[CT][CT][CTG]GA[GAT]-3' motif present in the Trex site and from a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 site of the muscle-specific genes enhancer (PubMed:14966291). Acts cooperatively with EYA proteins to transactivate their target genes through interaction and nuclear translocation of EYA protein (PubMed:10490620). Acts synergistically with SIX1 to regulate target genes involved in formation of various organs, including muscle, kidney, gonad, ganglia, olfactory epithelium and cranial skeleton. Plays a role in several important steps of muscle development. Controls the genesis of hypaxial myogenic progenitors in the dermomyotome by transactivating PAX3 and the delamination and migration of the hypaxial precursors from the ventral lip to the limb buds through the transactivation of PAX3, MET and LBX1 (PubMed:15788460). Controls myoblast determination by transactivating MYF5, MYOD1 and MYF6 (PubMed:15788460, PubMed:17592144). Controls somitic differentiation in myocyte through MYOG transactivation (PubMed:15788460). Plays a role in synaptogenesis and sarcomere organization by participating in myofiber specialization during embryogenesis by activating fast muscle program in the primary myotome resulting in an up-regulation of fast muscle genes, including ATP2A1, MYL1 and TNNT3 (PubMed:19962975, PubMed:21884692). Simultaneously, is also able to activate inhibitors of slow muscle genes, such as SOX6, HRASLS, and HDAC4, thereby restricting the activation of the slow muscle genes (PubMed:21884692). During muscle regeneration, negatively regulates differentiation of muscle satellite cells through down-regulation of MYOG expression (PubMed:20696153). During kidney development regulates the early stages of metanephros development and ureteric bud formation through regulation of GDNF, SALL1, PAX8 and PAX2 expression (PubMed:17300925). Plays a role in gonad development by regulating both testis determination and size determination. In gonadal sex determination, transactivates ZFPM2 by binding a MEF3 consensus sequence, resulting in SRY up-regulation. In gonadal size determination, transactivates NR5A1 by binding a MEF3 consensus sequence resulting in gonadal precursor cell formation regulation (PubMed:23987514). During olfactory development mediates the specification and patterning of olfactory placode through fibroblast growth factor and BMP4 signaling pathways and also regulates epithelial cell proliferation during placode formation (PubMed:19027001). Promotes survival of sensory neurons during early trigeminal gangliogenesis (PubMed:16938278). In the developing dorsal root ganglia, up-regulates SLC12A2 transcription (PubMed:15955062). Regulates early thymus/parathyroid organogenesis through regulation of GCM2 and FOXN1 expression (PubMed:16530750). Forms gustatory papillae during development of the tongue (PubMed:21978088). Also plays a role during embryonic cranial skeleton morphogenesis (PubMed:20515681). Interacts with EYA3; acts cooperatively with EYA3 to transactivate target genes through interaction and nuclear translocation of EYA3 protein (PubMed:12215533, PubMed:10490620). Additional isoforms seem to exist. Mainly expressed in the skeletal muscle (isoform 1 and isoform 2 but not isoform 3), and weakly in the heart. Also found in the retina and the distal tube of kidney. Expressed in skeletal muscle, nasal epithelium, cochlea, parathyroid and salivary gland (PubMed:11313460). Expressed in muscle satellite cells of normal and regenerating muscles (PubMed:20696153). At 8.5 dpc expressed at the surface ectoderm outside the neural folds, somites, presomitic mesoderm. At 9.5 dpc expressed at the nasal and otic placodes, cranial ganglia, branchial arches, somites (dermamyotomes and sclerotomes). At 10.5-11.5 dpc expressed at the nasal pits, otic vesicles, cranial ganglia, dorsal root ganglia, branchial arches, somites, myotomes, limb mesenchyme, notochord, mesonephros. At 12.5-13.5 dpc expressed in skeletal muscles, mesenchyme in limbs and digits, nasal epithelium, inner ear (PubMed:11313460). Weakly expressed in the nephrogenic cord on 9.5 dpc and in the metanephric mesenchyme on 10.5 dpc (PubMed:17300925). At 11.5 dpc expressed in the epithelium of the lateral lingual swellings, and in the tongue epithelium, mesenchyme, and muscles at 12.5 dpc. In the fungiform papillae, expressed in the epithelium at 14-16.5 dpc. In the circumvallate and foliate papillae, expression is observed in the trench wall of these papillae at 15.5 dpc-P0 (PubMed:21978088). At 11.5 dpc mainly found in limbs, and somites, where is expressed in the dorsal root ganglion, myotomes, and ventral and dorsal dermomyotomal lips (PubMed:15788460). Expressed in a wide domain of the ectoderm in the presumptive olfactory region and in the thickened olfactory placode. Expressed in the peripheral precursors of the pit. At 12.5 dpc-14.5 dpc, expression become progressively restricted to the apical and basal progenitors.Also expressed strongly in the preplacodal region at 8.0 dpc and in the presumptive olfactory ectoderm at 9.0 dpc (PubMed:19027001). At 10.5 dpc expressed in the progenitors of the dermomyotome and in the myocytes (PubMed:19962975). Mice are viable and fertile; no gross morphological or histological abnormalities, or defects in hearing ability are detected in homozygous mice (PubMed:11313460). Double homozygous SIX1 and SIX4 knockout mice die soon after birth and show developmental defects in various organs (PubMed:15955062). Double homozygous SIX1 and SIX4 knockout mice causes severe defects in the trigeminal ganglia (PubMed:16938278). Double homozygous SIX1 and SIX4 knockout mice exhibit more severe kidney phenotypes than the SIX1 knockout mice. Double homozygous SIX1 and SIX4 knockout embryos show distinct morphological changes: fusion of the lateral lingual swellings is delayed, and the tongue is poorly developed. The primordia of fungiform papillae appears earlier, and the papillae rapidly increases in size; thus fusion of each papilla is evident. The circumvallate papillae show severe defects: invagination of the trenches starts asymmetrically, which results in longer and shorter trenches (PubMed:21978088). Double homozygous SIX1 and SIX4 knockout neonatal mice have a male-to-female sex-reversal phenotype in XY mutant gonads (PubMed:23987514). Double homozygous SIX1 and SIX4 knockout neonatal mice are characterized by severe craniofacial and rib defects, and general muscle hypoplasia (PubMed:15788460). Incomplete sequence. Incomplete sequence. Belongs to the SIX/Sine oculis homeobox family.