Rap Guanine Nucleotide Exchange Factor 3 (RAPGEF3)

cAMP is a second messenger that induces a wide range of responses in different cell types, including activation of the RAS-related GTPase RAP1A.

Sequence analysis predicted that the 881-amino acid EPAC protein has a cAMP-binding site; a GEF homology domain; a RAS exchange motif, which may be important in GEF structure stabilization; and a DEP (dishevelled, egl10, pleckstrin) domain, which may be involved in membrane attachment. Northern blot analysis revealed ubiquitous expression of EPAC, with highest levels in kidney and heart. Binding analysis confirmed a direct interaction between EPAC and cAMP. Functional analysis showed that EPAC is a GEF for RAP1A that is directly regulated by cAMP.