Rho GTPase-activating protein 21 (ARHGAP21)

Rho GTPase-activating protein 21 (ARHGAP21) is a multifunctional regulatory enzyme that acts as a GAP (GTPase-activating protein) for small Rho family GTPases, primarily CDC42 and RHOA. By accelerating the intrinsic GTPase activity of these proteins, ARHGAP21 shifts them from an active GTP-bound state to an inactive GDP-bound state, negatively regulating signaling pathways that control F-actin dynamics, the Arp2/3 complex, and cellular structure—particularly at the Golgi apparatus. ARHGAP21 is recruited to the Golgi by its interaction with ARF1, and its activity is essential for the maintenance of Golgi structure, vesicular trafficking, cell adhesion, migration, and has been implicated in insulin secretion. The protein has distinct domains including a PDZ domain, a pleckstrin homology (PH) domain, and a C-terminal RhoGAP domain, enabling complex regulatory interactions and localization. Dysfunction or altered regulation of ARHGAP21 has been linked to abnormal cell motility, adhesion, and possibly oncogenic processes.

Other names

ARHGAP21ARHGAP10KIAA1424Rho GTPase-activating protein 10Rho-type GTPase-activating protein 21

Drugs (or molecular modulators) that would interact with ARHGAP21 could modulate its GTPase-activating activity, likely affecting RHOA and CDC42 signaling, leading to changes in actin dynamics, cell migration, and Golgi function