Arf-GAP with Rho-GAP domain, ankyrin repeat and PH domain-containing protein 3 (ARAP3)

ARAP3 (Arf-GAP with Rho-GAP domain, ankyrin repeat and PH domain-containing protein 3) is a multi-domain signaling adapter and enzyme that integrates various signals to regulate small GTPases (notably RhoA and Arf6) through its dual GTPase-activating (GAP) domains[1][2][3]. It acts as a downstream effector of phosphoinositide 3-kinase (PI3K) and Rap1, requiring binding to phosphatidylinositol (3,4,5)-trisphosphate (PIP3) for membrane recruitment and activation[1][3]. ARAP3 coordinates actin cytoskeleton remodeling, cell shape, and adhesion, plays major roles in angiogenesis, cancer cell invasion, immune cell migration, and integrin-mediated signaling, and also participates in endocytosis and membrane trafficking[1][2][3]. Structurally, it comprises Arf-GAP, Rho-GAP, SAM (sterile alpha motif), ankyrin repeats, and multiple pleckstrin homology (PH) domains, enabling multifaceted regulatory functions[2][3][4]. No direct drugs or approved inhibitors currently target ARAP3, but its role suggests a potential therapeutic target in cancer, vascular, or immune diseases[1][2][3].

Other names

ARAP3CENTD3Cnt-d3FLJ21065DRAG1Centaurin-delta-3arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3Arf and Rho GAP adapter protein 3PtdIns(3,4,5)P3-binding proteincentaurin-delta-3phosphoinositide binding protein

Not established for approved drugs. Theoretical mechanisms may include inhibition of GAP activity, disruption of PI3K-Akt pathway signaling, and modulators of actin dynamics or integrin signaling.