Rap guanine nucleotide exchange factor 3 (RAPGEF3)

Rap guanine nucleotide exchange factor 3 (RAPGEF3), also known as EPAC1, is a cytosolic enzyme that acts as a guanine nucleotide exchange factor specifically for the small GTPases Rap1 and Rap2, becoming activated by direct binding of cyclic adenosine monophosphate (cAMP). RAPGEF3 functions as a major cAMP sensor in human cells, mediating cAMP-induced, protein kinase A-independent signaling pathways. It plays critical roles in regulating actin cytoskeletal dynamics, endothelial barrier function, cellular adhesion, proliferation, stress responses, and other processes. RAPGEF3 is implicated in various pathological states, including cardiovascular disease, cancer, and neuroinflammation, and is considered a potential therapeutic target for related conditions. Small molecules that selectively modulate EPAC1 activity are being investigated for therapeutic intervention.

Other names

EPAC1Exchange protein directly activated by cAMP 1cAMP-GEFIexchange factor directly activated by cAMP 1cAMP-regulated guanine nucleotide exchange factor ICGEF1bcm910RAP1 guanine-nucleotide-exchange factor directly activated by cAMPHSU792759330170P05Rik

Direct modulation of intracellular cAMP signaling by allosterically activating or inhibiting RAPGEF3, leading to downstream regulation of Rap GTPase activity and integrin/cytoskeletal effects