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. Through their interaction with numerous signaling pathways, EPACs are implicated in insulin secretion, regulation of neurotransmitter release, cardiovascular function, inflammation, cancer, pain and infections.

Products
Background
Gene Data

Inhibitors

Cat. No. Product Name / Activity
4793 CE3F4
Noncompetitive Epac1 inhibitor
5969 (R)-CE3F4
Epac inhibitor; R-enantiomer of CE3F4 (Cat. No. 4793)
6320 ESI 05
Epac2 inhibitor
4773 ESI 09
Epac inhibitor
4844 HJC 0350
Selective Epac2 inhibitor

Activators

Cat. No. Product Name / Activity
1645 8-CPT-2Me-cAMP, sodium salt
Selective Epac activator
4853 8-pCPT-2-O-Me-cAMP-AM
Selective Epac activator; cell-permeable analog of 8CPT-2Me-cAMP (Cat. No. 1645)

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 :

EPAC Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
EPAC1 Human RAPGEF3 NM_006105 O95398
Mouse Rapgef3 NM_001177810 Q8VCC8
Rat Rapgef3 NM_021690 NP_067722
EPAC2 Human RAPGEF4 NM_007023 Q8WZA2
Mouse Rapgef4 XM_001060956 Q9EQZ6
Rat Rapgef4 NM_013199 XP_017447653