Homeobox protein TGIF1 is a protein that in humans is encoded by the TGIF1gene. Alternative splicing has been observed at this locus and eight variants, encoding four distinct isoforms, are described.
The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult.
Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. It has also been associated with risk of otitis media (inflammation of the middle ear)
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