Structure and functional roles of Epac2 (Rapgef4)

• Exchange protein directly activated by cAMP 2 (EPAC2) is encoded by Rapgef4 gene.
• Epac2 functions as a guanine-exchange factor regulated by cAMP.
• Epac2 has diverse roles in cellular functions of pancreatic islets, central nervous system and heart.
• Epac2 is a potential therapeutic target for treatment of type 2 diabetes.

Epac (exchange protein activated by cyclic-AMP) 2 is a direct target of 3′-5′-cyclic adenosine monophosphate (cAMP) and is involved in cAMP-mediated signal transduction through activation of the Ras-like small GTPase Rap. Crystallographic analyses revealed that activation of Epac2 by cAMP is accompanied by dynamic structural changes. Epac2 is expressed mainly in brain, neuroendocrine and endocrine tissues, and is involved in diverse cellular functions in the tissues. In this review, we summarize the structure and function of Epac2. We also discuss the physiological and pathophysiological roles of Epac2, and the possibility of Epac2 as a therapeutic target.