Rho GTPase-activating protein 4 (ARHGAP4)

Rho GTPase-activating protein 4 (ARHGAP4) is an enzyme that enhances the intrinsic GTPase activity of Rho-family GTPases, thereby terminating their signaling and modulating downstream cellular functions. ARHGAP4 contains multiple domains: an N-terminal FCH (F-BAR) domain important for cell edge localization, a central GAP domain that stimulates GTP hydrolysis, and a C-terminal SH3 domain for protein-protein interactions. It is a key negative regulator of cell motility and axon outgrowth, acting by localizing to the leading edge of motile cells and axonal growth cones, regulating actin cytoskeleton dynamics, and modulating formation and turnover of focal adhesions. Suppression or knockdown of ARHGAP4 elicits mesenchymal characteristics, induces epithelial-mesenchymal transition, increases cell proliferation and migration, and promotes cell invasion—implicating ARHGAP4 in cancer progression and tissue remodeling. ARHGAP4 complexes with septin proteins (SEPT2, SEPT9), further influencing cytoskeletal reorganization. It is not currently a direct therapeutic target for approved drugs, though its functions suggest potential for future therapeutic intervention in cancer metastasis, wound healing, and neurological diseases.

Other names

ARHGAP4KIAA0131RGC1RHOGAP4C1p115RhoGAP4SrGAP4Rho-GAP hematopoietic protein C1Rho-type GTPase-activating protein 4

No clinical inhibitors/modulators documented; mechanism by which drugs would act is likely via inhibition or modulation of its GAP activity impacting Rho GTPase signaling