RAPGEF2

Rap guanine nucleotide exchange factor (GEF) 2
Identifiers
Symbols	RAPGEF2 ; CNrasGEF; NRAPGEP; PDZ-GEF1; PDZGEF1; RA-GEF; RA-GEF-1; Rap-GEP; nRap GEP
External IDs	OMIM: 609530 MGI: 2659071 HomoloGene: 35477 GeneCards: RAPGEF2 Gene
Gene ontology Molecular function • signal transducer activity • Ras guanyl-nucleotide exchange factor activity • GTPase activator activity • calcium ion binding • protein binding • Rap guanyl-nucleotide exchange factor activity • diacylglycerol binding • PDZ domain binding • cAMP binding • cGMP binding • beta-1 adrenergic receptor binding • WW domain binding • phosphatidic acid binding Cellular component • cytoplasm • late endosome • cytosol • plasma membrane • integral component of plasma membrane • cell-cell junction • bicellular tight junction • membrane • apical plasma membrane • endocytic vesicle • neuron projection • neuronal cell body • protein complex • synapse • perinuclear region of cytoplasm Biological process • MAPK cascade • blood vessel development • neuron migration • G-protein coupled receptor signaling pathway • neuropeptide signaling pathway • small GTPase mediated signal transduction • negative regulation of cell proliferation • positive regulation of neuron projection development • cAMP-mediated signaling • ventricular system development • forebrain neuron development • microvillus assembly • neuron projection development • brain-derived neurotrophic factor receptor signaling pathway • positive regulation of protein binding • Rap protein signal transduction • intracellular signal transduction • nerve growth factor signaling pathway • positive regulation of GTPase activity • positive regulation of cAMP-mediated signaling • positive regulation of protein kinase activity • negative regulation of melanin biosynthetic process • regulation of synaptic plasticity • negative regulation of dendrite morphogenesis • establishment of endothelial barrier • positive regulation of ERK1 and ERK2 cascade • cellular response to cAMP • cellular response to cGMP • adenylate cyclase-activating adrenergic receptor signaling pathway • protein localization to plasma membrane • establishment of endothelial intestinal barrier • regulation of cell junction assembly • cellular response to nerve growth factor stimulus • positive regulation of cAMP-dependent protein kinase activity • positive regulation of dendritic cell apoptotic process • positive regulation of vasculogenesis • positive regulation of neuron migration Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9693	76089
Ensembl	ENSG00000109756	ENSMUSG00000062232
UniProt	Q9Y4G8	Q8CHG7
RefSeq (mRNA)	NM_014247	NM_001099624
RefSeq (protein)	NP_055062	NP_001093094
Location (UCSC)	Chr 4: 159.1 – 159.36 Mb	Chr 3: 79.06 – 79.29 Mb
PubMed search

Rap guanine nucleotide exchange factor 2 is a protein that in humans is encoded by the RAPGEF2 gene.^[1][2][3]

RAPGEF2 is a cyclic AMP binding protein.^[4][5]

Function

Members of the RAS subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF2, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation.^[2]

Interactions

RAPGEF2 has been shown to interact with RAP1A^[2] and RALGDS.^[6]

References

1. Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (September 1997). "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res 4 (2): 141–50. doi:10.1093/dnares/4.2.141. PMID 9205841.
2. Rebhun JF, Castro AF, Quilliam LA (November 2000). "Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction". J Biol Chem 275 (45): 34901–8. doi:10.1074/jbc.M005327200. PMID 10934204.
3. "Entrez Gene: RAPGEF2 Rap guanine nucleotide exchange factor (GEF) 2".
4. Pham N, Cheglakov I, Koch CA, de Hoog CL, Moran MF, Rotin D (May 2000). "The guanine nucleotide exchange factor CNrasGEF activates ras in response to cAMP and cGMP". Curr. Biol. 10 (9): 555–8. doi:10.1016/S0960-9822(00)00473-5. PMID 10801446.
5. Emery AC, Eiden MV, Mustafa T, Eiden LE (2013). "Rapgef2 Connects GPCR-Mediated cAMP Signals to ERK Activation in Neuronal and Endocrine Cells". Sci Signal 6 (281): ra51. doi:10.1126/scisignal.2003993. PMID 23800469.
6. Spaargaren M, Bischoff JR (December 1994). "Identification of the guanine nucleotide dissociation stimulator for Ral as a putative effector molecule of R-ras, H-ras, K-ras, and Rap". Proc. Natl. Acad. Sci. U.S.A. 91 (26): 12609–13. doi:10.1073/pnas.91.26.12609. PMC 45488. PMID 7809086.

Further reading

• Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Ohtsuka T, Hata Y, Ide N, et al. (1999). "nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein that interacts with synaptic scaffolding molecule (S-SCAM)". Biochem. Biophys. Res. Commun. 265 (1): 38–44. doi:10.1006/bbrc.1999.1619. PMID 10548487.
• Liao Y, Kariya K, Hu CD, et al. (2000). "RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a Ras/Rap1A-associating domain, is conserved between nematode and humans". J. Biol. Chem. 274 (53): 37815–20. doi:10.1074/jbc.274.53.37815. PMID 10608844.
• de Rooij J, Boenink NM, van Triest M, et al. (2000). "PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2". J. Biol. Chem. 274 (53): 38125–30. doi:10.1074/jbc.274.53.38125. PMID 10608883.
• Chikumi H, Fukuhara S, Gutkind JS (2002). "Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and LARG by tyrosine phosphorylation: evidence of a role for focal adhesion kinase". J. Biol. Chem. 277 (14): 12463–73. doi:10.1074/jbc.M108504200. PMID 11799111.
• Wistow G, Bernstein SL, Wyatt MK, et al. (2002). "Expressed sequence tag analysis of adult human lens for the NEIBank Project: over 2000 non-redundant transcripts, novel genes and splice variants". Mol. Vis. 8: 171–84. PMID 12107413.
• Aurandt J, Vikis HG, Gutkind JS, et al. (2002). "The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG". Proc. Natl. Acad. Sci. U.S.A. 99 (19): 12085–90. doi:10.1073/pnas.142433199. PMC 129402. PMID 12196628.
• 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.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Hisata S, Sakisaka T, Baba T, et al. (2007). "Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth". J. Cell Biol. 178 (5): 843–60. doi:10.1083/jcb.200610073. PMC 2064548. PMID 17724123.