SIX4

This gene encodes a member of the homeobox family, subfamily SIX. The drosophila homolog is a nuclear homeoprotein required for eye development. Studies in mouse show that this gene product functions as a transcription factor, and may have a role in the differentiation or maturation of neuronal cells.

SIX homeobox 4

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 a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 site of the muscle-specific genes enhancer. Acts cooperatively with EYA proteins to transactivate their target genes through interaction and nuclear translocation of EYA protein. 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. Controls myoblast determination by transactivating MYF5, MYOD1 and MYF6. Controls somitic differentiation in myocyte through MYOG transactivation. 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. 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. During muscle regeneration, negatively regulates differentiation of muscle satellite cells through down-regulation of MYOG expression. During kidney development regulates the early stages of metanephros development and ureteric bud formation through regulation of GDNF, SALL1, PAX8 and PAX2 expression. 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. 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. Promotes survival of sensory neurons during early trigeminal gangliogenesis. In the developing dorsal root ganglia, up-regulates SLC12A2 transcription. Regulates early thymus/parathyroid organogenesis through regulation of GCM2 and FOXN1 expression. Forms gustatory papillae during development of the tongue. Also plays a role during embryonic cranial skeleton morphogenesis.

Biological Process anatomical structure morphogenesisManual Assertion Based On ExperimentTAS:ProtInc
Biological Process embryonic cranial skeleton morphogenesisIEA:Ensembl
Biological Process fungiform papilla morphogenesisISS:UniProtKB
Biological Process generation of neuronsISS:UniProtKB
Biological Process inner ear morphogenesisIEA:Ensembl
Biological Process male gonad developmentISS:UniProtKB
Biological Process male sex determinationISS:UniProtKB
Biological Process male sex differentiationISS:UniProtKB
Biological Process metanephric mesenchyme developmentISS:UniProtKB
Biological Process myoblast migrationIEA:Ensembl
Biological Process myotome developmentISS:UniProtKB
Biological Process negative regulation of apoptotic processISS:UniProtKB
Biological Process negative regulation of DNA-templated transcriptionISS:UniProtKB
Biological Process negative regulation of neuron apoptotic processISS:UniProtKB
Biological Process negative regulation of satellite cell differentiationISS:UniProtKB
Biological Process olfactory placode formationISS:UniProtKB
Biological Process pharyngeal system developmentISS:UniProtKB
Biological Process positive regulation of branching involved in ureteric bud morphogenesisISS:UniProtKB
Biological Process positive regulation of DNA-templated transcriptionISS:UniProtKB
Biological Process positive regulation of ureteric bud formationISS:UniProtKB
Biological Process protein localization to nucleusISS:UniProtKB
Biological Process regulation of branch elongation involved in ureteric bud branchingISS:UniProtKB
Biological Process regulation of epithelial cell proliferationISS:UniProtKB
Biological Process regulation of protein localizationIEA:Ensembl
Biological Process regulation of synaptic assembly at neuromuscular junctionIEA:Ensembl
Biological Process regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Biological Process sarcomere organizationISS:UniProtKB
Biological Process skeletal muscle fiber differentiationISS:UniProtKB
Biological Process skeletal muscle tissue developmentISS:UniProtKB
Biological Process thymus developmentIEA:Ensembl
Biological Process tongue developmentISS:UniProtKB
Biological Process trigeminal ganglion developmentISS:UniProtKB

Nucleus
Cytoplasm