ARHGAP

ARHGAP is a gene family designation for Rho GTPase activating proteins, a diverse group of regulators that inactivate members of the Rho family of small GTPases. By accelerating the hydrolysis of GTP to GDP, ARHGAPs switch off signaling pathways that control the actin cytoskeleton, cell shape, adhesion, migration, and various aspects of cell cycle and gene expression. Through these actions, ARHGAPs influence processes such as development, immune responses, and tissue remodeling.

Most ARHGAP family members contain a conserved RhoGAP domain that provides catalytic activity. Many also harbor additional protein interaction domains, including SH3, PH, PDZ, CRIB, or BAR domains, which determine their localization and selectivity for specific GTPases and partners. The combination of domains gives each ARHGAP member unique regulatory properties and substrate preferences.

Regulation of ARHGAP activity is complex and can involve phosphorylation, lipid interactions at membranes, and binding to partner proteins. Subcellular localization—often to specific membrane surfaces or cytoskeletal structures—also modulates which Rho GTPases are targeted. Because different ARHGAPs can act on RhoA, Rac1, Cdc42, and related GTPases, they play context-dependent roles in signaling networks.

In humans, the ARHGAP family includes numerous genes such as ARHGAP1, ARHGAP5, ARHGAP35, ARHGAP11A, and ARHGAP21, among others. Dysregulation or mutation of ARHGAPs has been linked to developmental abnormalities, cancer progression and metastasis, and nervous system disorders, underscoring their importance as regulators of cytoskeletal dynamics and cellular behavior.