RAPGEF3 Gene - Rap Guanine Nucleotide Exchange Factor 3 | Function, Mutations & Diseases

RAPGEF3 (Rap guanine nucleotide exchange factor 3), also known as EPAC1, encodes a protein that acts as a guanine nucleotide exchange factor (GEF) for the small GTPase Rap1. It is directly activated by cyclic AMP (cAMP) and mediates cAMP-dependent signaling pathways independent of protein kinase A (PKA). The protein contains a cAMP-binding domain and a GEF domain, and is involved in diverse cellular processes including cell adhesion, exocytosis, proliferation, and differentiation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• cAMP/EPAC/Rap1 signaling pathway

• GPCR downstream signaling

• Integrin-mediated cell adhesion

The RAPGEF3 protein (EPAC1) is a 923-amino acid multi-domain protein that functions as a cAMP sensor and Rap1 activator. It contains an N-terminal regulatory region with a cAMP-binding domain (CBD) and a C-terminal catalytic region with a GEF domain. Upon cAMP binding, EPAC1 undergoes a conformational change that exposes the GEF domain, allowing it to catalyze the exchange of GDP for GTP on Rap1. EPAC1 is ubiquitously expressed with highest levels in brain, heart, and kidney. It plays critical roles in cell adhesion, exocytosis, and gene expression.