TBX3
Description
The TBX3 (T-box transcription factor 3) is a protein-coding gene located on chromosome 12.
TBX3 is a protein encoded by the TBX3 gene in humans. It belongs to the T-box gene family of transcription factors, all sharing a conserved DNA-binding domain called the T-box. TBX3 is part of the Tbx2 subfamily, which includes Tbx2, Tbx4, and Tbx5. The human TBX3 gene is located on chromosome 12 at position 12q23-24.1 and consists of 7 exons, encoding a 723 amino acid protein. Alternative splicing generates at least 4 distinct TBX3 isoforms, with TBX3 and TBX3+2a being the most prominent. TBX3+2a results from alternative splicing of the second intron, leading to the addition of the +2a exon and an extra 20 amino acids in the T-box DNA-binding domain. TBX3 has domains crucial for its transcription factor function: a DNA-binding domain (DBD), also known as the T-box, a nuclear localization signal, two repression domains (R2 and R1), and an activation domain (A). The T-box recognizes a palindromic DNA sequence known as the T-element or half-sites within this sequence. While the consensus T-element is T(G/C)ACACCT AGGTGTGAAATT, TBX3 can also bind variations of this sequence.
TBX3 acts as a transcriptional repressor involved in developmental processes, particularly in limb pattern formation, mammary gland development, and lung branching morphogenesis. It binds to the palindromic T site DNA sequence or its half-site, found in the regulatory regions of various genes. TBX3's role in mammary gland development includes induction of mammary placodes and maintenance of mammary buds. It participates in branching morphogenesis in both developing lungs and adult mammary glands, often acting redundantly with TBX2. TBX3, together with TBX2, maintains cell proliferation in the embryonic lung mesenchyme, possibly acting downstream of SHH, BMP, and TGFbeta signaling. In inner ear development, it modulates early stages, acting independently of, and redundantly with, TBX2 in different subregions. Notably, TBX3 negatively regulates PML function during cellular senescence.
TBX3 is also known as TBX3-ISO, UMS, XHL.
