Gal80, the negative regulator of Gal4 appears to have evolved from a glucose-fructose oxidoreductase having lost its enzymatic activity. Similarly, TAFII150 seems to be derived from the aminopetidase N family of proteins and Spt16 from the aminopetidase P superfamily. Proteases, well capable of interaction with other proteins, seem to be a perfect starting material for shaping new factors having no enzymatic activity but retained their protein interaction capabilities.
Aravind, L., & Koonin, E. V. (2004). Eukaryotic transcription regulators derive from ancient enzymatic domains. Current Biology, 8(4), R111–R113. https://doi.org/10.1016/s0960-9822(98)70982-0