rap guanine nucleotide exchange factor 4; exchange factor directly activated by cAMP 2; exchange protein directly activated by cAMP 2; EPAC 2; cAMP-regulated guanine nucleotide exchange factor II; cAMP-GEFII (RAPGEF4, CGEF2, EPAC2)

Function

• guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B & RAP2A small GTPases that is activated by binding cAMP
• seems not to activate RAB3
• role in cAMP-dependent exocytosis through interaction with RIMS2 (PKA-independent)
• interacts with RIMS1 & RIMS2
• part of a complex with RIMS2 & GTP-activated RAB3A (putative)

Structure

• the N-terminal nucleotide phosphate binding region cAMP 1 has a much lower affinity for cAMP as compared to cAMP 2
• the DEP domain is involved in membrane localization independent from regulation by cAMP (putative)
• contains 2 cyclic nucleotide-binding domains
• contains 1 DEP domain
• contains 1 N-terminal Ras-GEF domain
• contains 1 Ras-GEF domain

Compartment

• cytoplasm, membrane

Alternative splicing

named isoforms=3

Alternative promoter usage

• promoter analysis carried out in mouse

Expression

• predominantly expressed in brain & adrenal gland
• isoform 2 is expressed in liver
• isoform 1 is expressed in liver at very low levels

More general terms

• guanine nucleotide exchange factor
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=11069
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:11069
• OMIM: https://mirror.omim.org/entry/606058
• UniProt: http://www.uniprot.org/uniprot/Q8WZA2.html