Rho GTPase-activating protein 15 (ARHGAP15)

Rho GTPase-activating protein 15 (ARHGAP15) is an enzyme that acts as a negative regulator of Rho family small GTPases, primarily inactivating RAC1 by stimulating its intrinsic GTPase activity, thereby promoting conversion to the inactive GDP-bound state[6]. ARHGAP15 is important for the regulation of actin cytoskeletal dynamics in both neuronal and immune cells. In the nervous system, it modulates neurite outgrowth, dendritic branching, synaptic formation, and migration of cortical interneurons, and its loss leads to hyperactivation of RAC1, altered interneuron development, and increased susceptibility to seizures and cognitive deficits[1][2][5]. In immune cells such as neutrophils and macrophages, ARHGAP15 limits RAC1-mediated chemotaxis and phagocytosis, affecting immune responses[2][4]. In multiple cancers, ARHGAP15 is considered a tumor suppressor, frequently downregulated in malignancy, and its restoration suppresses cell proliferation, migration, and invasion by acting on the PTEN/AKT/FOXO1 axis and other pathways[2]. Genetic variants of ARHGAP15 are linked to diseases such as diverticular disease and influence responses to infectious agents in livestock. At the molecular level, ARHGAP15's domains mediate interactions with both Rho GTPases and kinases such as PAK1 and PAK2, enabling it to fine-tune multiple signaling axes involved in cytoskeletal organization and cell function[3][5][6].

Other names

ARHGAP15BM-024BM-030BM-046BM046ArhGAP15rho GTPase-activating protein 15rho-type GTPase-activating protein 15

Promotes GTP hydrolysis on RAC1, inactivating RAC1-dependent pathways; Interacts with PAK1/PAK2 kinases, mediating mutual negative regulation.