ArfGAP with GTPase domain, ankyrin repeat and PH domain 1 (AGAP1)

AGAP1 is a cytoplasmic protein that functions as an ADP-ribosylation factor (Arf) GTPase-activating protein, integrating membrane trafficking and cytoskeletal regulation through its modular domains, which include a GTPase-like domain, ankyrin repeats, an ArfGAP domain, and a pleckstrin homology (PH) domain[1][3]. AGAP1 directly regulates the adaptor protein complex 3 (AP-3) on endosomes, promoting GTP hydrolysis by Arf1 (and to a lesser degree Arf5/Arf6) in a phosphoinositide-dependent manner[1][3]. Its role is especially critical in neurons, where it localizes to axons and dendritic spines, influencing endosomal recycling that controls dendritic spine morphology—a process relevant to neurodevelopmental disorders[1]. AGAP1 interacts with proteins like RhoA and is allosterically regulated by the binding of these partners, enhancing its specificity and catalytic efficiency toward Arf1[3]. Overexpression of AGAP1 alters the distribution of endosomal markers and cytoskeletal proteins, highlighting its role as a key node connecting membrane trafficking, signal transduction, and cytoskeletal remodeling[1][3]. There are currently no well-established drugs, biomarkers, or noted safety concerns directly associated with AGAP1 as a therapeutic target; its main significance lies in cellular regulation, not direct therapeutic modulation[1][3].

Other names

AGAP-1CENTG2KIAA1099CNT-G2GGAP1Centaurin-gamma-2GTP-binding and GTPase-activating protein 1