ArfGAP1 is a 415 aa soluble protein that reversibly interacts with the Golgi apparatus (Cukierman et al. 1995). Originally isolated from rat liver cytosol (Makler et al. 1995), it is the founding member of the ArfGAP family of proteins, all characterized by a conserved catalytic domain containing a zinc finger model whose structure was solved by Goldberg (1999).
The substrate of ArfGAP1, Arf1, is a key regulator of the COPI system that mediates vesicular transport in the ER–Golgi shuttle. Upon GDP to GDP exchange, Arf1 associates with the Golgi membrane and recruits the heptameric COPI coat (coatomer), which in turn sorts cargo proteins and polymerizes to form the coat cage surrounding the vesicle. The subsequent hydrolysis of Arf-bound GTP is required for the release of coatomer from the membrane, a prerequisite for vesicle fusion. This reaction requires the action of a GAP. ArfGAP1 was the...