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

General

guanine nucleotide exchange factor (GDP/GTP dissociation stimulator, guanine nucleotide-releasing factor/protein, GNEF, GNDS, GDS) phosphoprotein

Properties

SIZE: entity length = 1011 aa MW = 116 kD COMPARTMENT: cytoplasm MOTIF: cAMP-binding site SITE: 43-166 DEP domain {216-291} cAMP-binding site SITE: 356-476 guanine nucleotide exchange domain NAME: guanine nucleotide exchange domain SITE: 496-634 Tyr phosphorylation site {Y681} guanine nucleotide exchange domain NAME: guanine nucleotide exchange domain SITE: 772-1009

Database Correlations

OMIM 606058 UniProt Q8WZA2 PFAM correlations Entrez Gene 11069 Kegg hsa:11069

References

UniProt :accession Q8WZA2