SIX2: Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach. During kidney development, maintains cap mesenchyme multipotent nephron progenitor cells in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud and cooperates with WNT9B to promote renewing progenitor cells proliferation. Acts through its interaction with TCF7L2 and OSR1 in a canonical Wnt signaling independent manner preventing transcription of differentiation genes in cap mesenchyme such as WNT4. Also acts independently of OSR1 to activate expression of many cap mesenchyme genes, including itself, GDNF and OSR1. During craniofacial development plays a role in growth and elongation of the cranial base through regulation of chondrocyte differentiation. During stomach organogenesis, controls pyloric sphincter formation and mucosal growth through regulation of a gene network including NKX2-5, BMPR1B, BMP4, SOX9 and GREM1. During branchial arch development, acts to mediate HOXA2 control over the insulin-like growth factor pathway. Also may be involved in limb tendon and ligament development. Plays a role in cell proliferation and migration. {ECO:0000250|UniProtKB:Q62232, ECO:0000269|PubMed:22995329}. Belongs to the SIX/Sine oculis homeobox family. {ECO:0000305}. Interacts with TCF7L2; in a canonical Wnt signaling independent manner; prevents transcription of differentiation genes in cap mesenchyme. Interacts with OSR1; form a strong repressor complex with TCF7L2, TLE2 and TLE3 to prevent the activation of Wnt/beta-catenin target genes in the cap mesenchyme. Interacts with HOXA11, EYA1 and EYA3. {ECO:0000250|UniProtKB:Q62232}
Protein type: DNA-binding
Chromosomal Location of Human Ortholog: 2p21
Cellular Component: nucleoplasm; nuclear membrane; cytoplasm; plasma membrane; nucleus
Molecular Function: sequence-specific DNA binding; protein complex binding; transcription factor activity; transcription factor binding
Biological Process: anatomical structure morphogenesis; cell migration; embryonic cranial skeleton morphogenesis; middle ear morphogenesis; cell proliferation; embryonic digestive tract morphogenesis; protein import into nucleus; mesodermal cell fate specification; chondrocyte differentiation; positive regulation of transcription from RNA polymerase II promoter; regulation of chondrocyte differentiation; kidney development; regulation of ossification; anterior/posterior axis specification
Show more