Rho GTPase-activating protein 42 (ARHGAP42)

Rho GTPase-activating protein 42 (ARHGAP42) is an enzyme of the BAR-PH RhoGAP family, expressed predominantly in vascular smooth muscle cells, where it acts to inactivate RhoA by enhancing GTP hydrolysis. ARHGAP42 contains N-terminal BAR and PH domains, a central RhoGAP domain with selectivity for RhoA (and to a lesser extent Cdc42), and a C-terminal SH3 domain. It regulates cytoskeletal reorganization, focusing on cell adhesion sites and actin stress fibers. ARHGAP42 is activated by Src-mediated phosphorylation at tyrosine 376, which relieves autoinhibition by the BAR domain and promotes GAP activity. ARHGAP42 is critical for controlling vascular tone and blood pressure; genetic variants are associated with blood pressure regulation in humans[1][2][3][5][6]. Additionally, it serves as a rheostat linking blood volume or pressure status to contractility in smooth muscle cells, with implications for cardiovascular disease[6]. Currently, no approved drugs are known to target ARHGAP42 directly.

Other names

GRAF3TMEM133FLJ32810AD031Rho GTPase-activating protein 10-likeRho-type GTPase-activating protein 42transmembrane protein 133

Accelerates GTP hydrolysis by RhoA, leading to its inactivation and modulation of cytoskeletal dynamics and cell motility