GTPase-activating protein (GAP)

GTPase-activating proteins (GAPs) are a large and diverse family of regulatory enzymes that catalyze the hydrolysis of GTP to GDP on small GTPases, thereby inactivating them[4][10]. GAPs play a pivotal role in terminating intracellular signaling events mediated by GTPases, acting as critical off-switches that ensure proper timing and localization of processes such as cell growth, cycle progression, cytoskeletal rearrangement, vesicle trafficking, and immune activity[2][3][4][5][6][10]. Dysregulation or mutation of GAPs can result in prolonged signaling, contributing to cancer, neurodegeneration, and other disease states[2][5][6]. Specific GAP families (e.g., RasGAPs, RHOGAPs, RabGAPs) have dedicated roles related to their cognate small GTPase substrates[6][8]. Drugs and therapies impacting GAP-regulated pathways are under investigation but no direct selective inhibitors are yet in clinical use.

Other names

GTPase-accelerating proteinGAPRasGAP (specifically for Ras GTPase-activating proteins)RHOGAP (for Rho family GTPases)RabGAP (for Rab family)ArfGAP (for Arf family)

Negative regulation (inactivation) of small GTPases by accelerating GTP hydrolysis, turning the active GTP-bound form into the inactive GDP-bound form[4][6][7][10]. Modulating signal duration and intensity by controlling the off-switch of G protein activity.