SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3)

SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3) is a protein encoded by the SRGAP3 gene on chromosome 3, primarily expressed in the central nervous system, especially in regions critical for higher cognitive functions such as the hippocampus and cortex[1][4]. It acts as a GTPase-activating protein (GAP) for RAC1, and potentially CDC42, thereby negatively regulating specific Rho family small GTPases involved in actin cytoskeleton remodeling and neuronal plasticity[1][2][6]. SRGAP3 is an intracellular effector in the Slit-Robo signaling pathway that governs neuronal migration and axonal branching, and its disruption has been linked to intellectual disability and abnormal neuronal development[1][2][3]. SRGAP3 is also referred to by alternative names such as MEGAP (Mental disorder-associated GAP) and ARHGAP14, and shares structural and functional similarities with other RhoGAP family proteins[1]. The protein contains key functional domains: an SH3 domain, a FES/CIP4 (FCH) domain, and the RhoGAP domain[1]. Loss or mutation of SRGAP3 can cause severe neurodevelopmental phenotypes due to impaired neuronal migration and synaptic assembly[1][2][5].

Other names

MEGAPARHGAP14KIAA0411KIAA1156WRPMental disorder-associated GAPRho GTPase-activating protein 14WAVE-associated Rac GTPase-activating proteinSLIT-ROBO Rho GTPase activating protein 3