Ras GTPase-activating protein 4 (RASA4)

Ras GTPase-activating protein 4 (RASA4) is an enzyme encoded by the RASA4 gene and belongs to the GAP1 family of GTPase-activating proteins. RASA4 operates as a calcium-dependent suppressor of the Ras/mitogen-activated protein kinase pathway. In response to elevated intracellular calcium, RASA4 translocates to the plasma membrane, where it promotes the intrinsic GTPase activity of Ras, converting it from its active GTP-bound form to its inactive GDP-bound state. This action prevents Ras from propagating signals that regulate gene expression, cell growth, and cell differentiation. RASA4 participates in multiple biological processes, including calcium signaling, immune cell function, and negative regulation of pathological airway remodeling. Multiple isoforms exist due to transcript variants. While RASA4 is considered a relevant therapeutic target due to its regulatory role in oncogenic and pathological pathways, no drugs directly modulating RASA4 are in clinical use.

Other names

CAPRIGAPLCalcium-promoted Ras inactivatorRas p21 protein activator 4RasGAP-activating-like protein 2Ca²⁺-promoted Ras inactivatorKIAA0538

Drugs that inhibit or modulate the Ras pathway may exert effects by altering RASA4-mediated Ras inactivation, but no direct pharmacological modulators are described for RASA4 itself