RAPGEF4

Rap guanine nucleotide exchange factor (GEF) 4

PDB rendering based on 1o7f.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1o7f, 2byv

Identifiers

Symbols

RAPGEF4 ; 2; CAMP-GEFII; CGEF2; EPAC; EPAC 2; EPAC2; Nbla00496

External IDs

OMIM: 606058 MGI: 1917723 HomoloGene: 4451 IUPHAR: 1293 GeneCards: RAPGEF4 Gene

Gene ontology
Molecular function	• guanyl-nucleotide exchange factor activity • Ras guanyl-nucleotide exchange factor activity • protein binding • cAMP-dependent protein kinase regulator activity • Ras GTPase binding • cAMP binding
Cellular component	• cytosol • plasma membrane • cAMP-dependent protein kinase complex • membrane
Biological process	• energy reserve metabolic process • G-protein coupled receptor signaling pathway • small GTPase mediated signal transduction • blood coagulation • calcium ion-dependent exocytosis • regulation of exocytosis • cAMP-mediated signaling • insulin secretion • platelet activation • positive regulation of Ras GTPase activity • positive regulation of GTPase activity • small molecule metabolic process • regulation of protein kinase activity • regulation of insulin secretion
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 2:
173.6 – 173.92 Mb

Chr 2:
71.98 – 72.26 Mb

PubMed search

Rap guanine nucleotide exchange factor (GEF) 4 (RAPGEF4), also known as exchange protein directly activated by cAMP 2 (EPAC2), is a protein which in humans is encoded by the RAPGEF4 gene.^[1]^[2]^[3]

Interactions

RAPGEF4 has been shown to interact with RIMS2.^[4]^[5]

References

↑ "Entrez Gene: RAPGEF4 Rap guanine nucleotide exchange factor (GEF) 4".
↑ Kawasaki H, Springett GM, Mochizuki N, Toki S, Nakaya M, Matsuda M, Housman DE, Graybiel AM (December 1998). "A family of cAMP-binding proteins that directly activate Rap1". Science 282 (5397): 2275–9. doi:10.1126/science.282.5397.2275. PMID 9856955.
↑ de Rooij J, Rehmann H, van Triest M, Cool RH, Wittinghofer A, Bos JL (July 2000). "Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs". J. Biol. Chem. 275 (27): 20829–36. doi:10.1074/jbc.M001113200. PMID 10777494.
↑ Shibasaki, Tadao; Sunaga Yasuhiro; Fujimoto Kei; Kashima Yasushige; Seino Susumu (February 2004). "Interaction of ATP sensor, cAMP sensor, Ca2+ sensor, and voltage-dependent Ca2+ channel in insulin granule exocytosis". J. Biol. Chem. (United States) 279 (9): 7956–61. doi:10.1074/jbc.M309068200. ISSN 0021-9258. PMID 14660679.
↑ Kashima, Y; Miki T; Shibasaki T; Ozaki N; Miyazaki M; Yano H; Seino S (Dec 2001). "Critical role of cAMP-GEFII--Rim2 complex in incretin-potentiated insulin secretion". J. Biol. Chem. (United States) 276 (49): 46046–53. doi:10.1074/jbc.M108378200. ISSN 0021-9258. PMID 11598134.

Ehrhardt A, Ehrhardt GR, Guo X, Schrader JW (2002). "Ras and relatives--job sharing and networking keep an old family together.". Exp. Hematol. 30 (10): 1089–106. doi:10.1016/S0301-472X(02)00904-9. PMID 12384139.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Kawasaki H, Springett GM, Mochizuki N et al. (1999). "A family of cAMP-binding proteins that directly activate Rap1.". Science 282 (5397): 2275–9. doi:10.1126/science.282.5397.2275. PMID 9856955.
de Rooij J, Rehmann H, van Triest M et al. (2000). "Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs.". J. Biol. Chem. 275 (27): 20829–36. doi:10.1074/jbc.M001113200. PMID 10777494.
Ozaki N, Shibasaki T, Kashima Y et al. (2001). "cAMP-GEFII is a direct target of cAMP in regulated exocytosis.". Nat. Cell Biol. 2 (11): 805–11. doi:10.1038/35041046. PMID 11056535.
Coppola T, Magnin-Luthi S, Perret-Menoud V et al. (2001). "Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin.". J. Biol. Chem. 276 (35): 32756–62. doi:10.1074/jbc.M100929200. PMID 11438518.
Kashima Y, Miki T, Shibasaki T et al. (2002). "Critical role of cAMP-GEFII--Rim2 complex in incretin-potentiated insulin secretion.". J. Biol. Chem. 276 (49): 46046–53. doi:10.1074/jbc.M108378200. PMID 11598134.
Ueno H, Shibasaki T, Iwanaga T et al. (2002). "Characterization of the gene EPAC2: structure, chromosomal localization, tissue expression, and identification of the liver-specific isoform.". Genomics 78 (1–2): 91–8. doi:10.1006/geno.2001.6641. PMID 11707077.
Rehmann H, Prakash B, Wolf E et al. (2007). "Structure and regulation of the cAMP-binding domains of Epac2". Nat. Struct. Biol. 10 (1): 26–32. doi:10.1038/nsb878. PMID 12469113.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Bacchelli E, Blasi F, Biondolillo M et al. (2004). "Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene". Mol. Psychiatry 8 (11): 916–24. doi:10.1038/sj.mp.4001340. PMID 14593429.
Shibasaki T, Sunaga Y, Fujimoto K et al. (2004). "Interaction of ATP sensor, cAMP sensor, Ca2+ sensor, and voltage-dependent Ca2+ channel in insulin granule exocytosis". J. Biol. Chem. 279 (9): 7956–61. doi:10.1074/jbc.M309068200. PMID 14660679.
Magiera MM, Gupta M, Rundell CJ et al. (2005). "Exchange protein directly activated by cAMP (EPAC) interacts with the light chain (LC) 2 of MAP1A". Biochem. J. 382 (Pt 3): 803–10. doi:10.1042/BJ20040122. PMC 1133955. PMID 15202935.
Gerhard DS, Wagner L, Feingold EA et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Dupuy AG, L'Hoste S, Cherfils J et al. (2005). "Novel Rap1 dominant-negative mutants interfere selectively with C3G and Epac". Oncogene 24 (28): 4509–20. doi:10.1038/sj.onc.1208647. PMID 15856025.
Rual JF, Venkatesan K, Hao T et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
Lim J, Hao T, Shaw C et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
Ster J, De Bock F, Guérineau NC et al. (2007). "Exchange protein activated by cAMP (Epac) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons". Proc. Natl. Acad. Sci. U.S.A. 104 (7): 2519–24. doi:10.1073/pnas.0611031104. PMC 1892910. PMID 17284589.

PDB gallery

1o7f: CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2

2byv: STRUCTURE OF THE CAMP RESPONSIVE EXCHANGE FACTOR EPAC2 IN ITS AUTO-INHIBITED STATE

RAPGEF4

Interactions

References

Further reading