Twist-1: Proteins and Enzymes

Twist-1 (Twist-related protein 1; also H-Twist and bHLHa38) is a 25-27 kDa class B member of the bHLH transcription factor family of proteins. It is widely expressed in embryo, and select adult cells such as white adipocytes. In fat, Twist-1 induces fatty acid oxidation via PGC-1 alpha and CPT-1, and promotes MCP-1 and TNF-alpha secretion by adipocytes. In epithelium, Twist-1 dysregulation represses E-Cadherin and induces N-Cadherin expression, resulting in an epithelial-to-mesenchymal transition that can lead to cancer. Human Twist-1 is 202 amino acids (aa) in length. It contains a bHLH domain (aa 109-164) with an embedded DNA-binding motif. Twist-1 forms homodimers, and heterodimerizes with TCF3, HAND1 and HAND2. Two distinct mutations exist that may impact its dimerization pattern. There is one seven aa insertion after Ile135, and a second seven aa insertion after Pro139. A third unrelated variant shows a four Gly insert after Gly92. Full-length human Twist-1 shares 98% aa identity with mouse Twist-1.