EPAC

Exchange proteins directly activated by cAMP (EPAC) are intracellular sensors of cAMP and function as nucleotide exchange factors for the Rap subfamily of Ras GTPases (Rap GEFs). Two EPAC subtypes have been identified: Epac1, encoded by the RAPGEF3 gene, is ubiquitously expressed, while Epac2, encoded by the RAPGEF4, is particularly enriched in the nervous system and in endocrine tissues.

Both Epac1 and Epac2 are composed of two lobes joined by a central region. The N-terminal lobe is responsible for cAMP binding while the C-terminal lobe harbors guanine exchange factor (GEF) activity. In the absence of cAMP, EPACs exhibit an auto-inhibitory conformation where the N-terminal folds on top of the C-terminal and blocks the enzymatic active site. Upon cAMP binding a conformational change occurs that allows GEF activity to catalyze the dissociation of GDP from GTPases, and enable the binding of GTP.

EPACs can be found in signaling complexes associated with the plasma membrane, nuclear envelope and cytoskeleton, where they interact with a wide range of other proteins and pathways including calcium, MAPK, ERK, CaMKII, PI 3-K and mTOR signaling. EPAC signaling pathways have been implicated in insulin secretion, regulation of neurotransmitter release, cardiovascular function, inflammation, cancer, pain and infections.

External sources of pharmacological information for EPAC :

• IUPHAR Receptor Code

• BJP Guide

EPAC Gene Data