RAPGEF2

RAPGEF2
Identifiers
Aliases	RAPGEF2, CNrasGEF, NRAPGEP, PDZ-GEF1, PDZGEF1, RA-GEF, RA-GEF-1, Rap-GEP, nRap GEP, Rap guanine nucleotide exchange factor 2, RAGEF
External IDs	OMIM: 609530; MGI: 2659071; HomoloGene: 35477; GeneCards: RAPGEF2; OMA:RAPGEF2 - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q32.1 Start 159,103,013 bp[1] End 159,360,174 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 E3 Start 78,969,823 bp[2] End 79,193,824 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 middle temporal gyrus endothelial cell frontal pole postcentral gyrus orbitofrontal cortex tibia Brodmann area 10 Brodmann area 46 entorhinal cortex Top expressed in olfactory tubercle subdivision of hippocampus Region I of hippocampus proper subiculum piriform cortex lateral septal nucleus Temporal Lobe primary motor cortex Amygdala anterior amygdaloid area More reference expression data BioGPS n/a
Gene ontology Molecular function calcium ion binding protein binding diacylglycerol binding signal transducer activity guanyl-nucleotide exchange factor activity WW domain binding phosphatidic acid binding PDZ domain binding cAMP binding cGMP binding beta-1 adrenergic receptor binding GTPase activator activity Cellular component cell-cell junction endocytic vesicle synapse integral component of plasma membrane apical plasma membrane bicellular tight junction endosome cell junction neuron projection soma cytoplasm cytosol late endosome membrane plasma membrane perinuclear region of cytoplasm protein-containing complex intracellular anatomical structure Biological process positive regulation of ERK1 and ERK2 cascade brain-derived neurotrophic factor receptor signaling pathway cellular response to cGMP ventricular system development positive regulation of protein binding forebrain neuron development regulation of cell junction assembly protein localization to plasma membrane positive regulation of neuron projection development adenylate cyclase-activating adrenergic receptor signaling pathway nervous system development neuron migration neuropeptide signaling pathway multicellular organism development G protein-coupled receptor signaling pathway negative regulation of melanin biosynthetic process cellular response to nerve growth factor stimulus cell differentiation positive regulation of cAMP-mediated signaling intracellular signal transduction cellular response to cAMP nerve growth factor signaling pathway regulation of cell population proliferation Rap protein signal transduction small GTPase mediated signal transduction negative regulation of cell population proliferation blood vessel development positive regulation of dendritic cell apoptotic process positive regulation of vasculogenesis microvillus assembly negative regulation of dendrite morphogenesis regulation of synaptic plasticity neuron projection development establishment of endothelial intestinal barrier positive regulation of cAMP-dependent protein kinase activity positive regulation of neuron migration positive regulation of protein kinase activity establishment of endothelial barrier signal transduction MAPK cascade positive regulation of GTPase activity cAMP-mediated signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9693 76089 Ensembl ENSG00000109756 ENSMUSG00000062232 UniProt Q9Y4G8 Q8CHG7 RefSeq (mRNA) NM_014247 NM_001351724 NM_001351725 NM_001351726 NM_001351727 NM_001351728 NM_001394067 NM_001099624 NM_001310536 RefSeq (protein) NP_055062 NP_001338653 NP_001338654 NP_001338655 NP_001338656 NP_001338657 NP_001093094 NP_001297465 Location (UCSC) Chr 4: 159.1 – 159.36 Mb Chr 3: 78.97 – 79.19 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Rap guanine nucleotide exchange factor 2 is a protein that in humans is encoded by the RAPGEF2 gene.[5][6][7]

RAPGEF2 is a cyclic AMP binding protein.[8][9]

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.[6]

Interactions

RAPGEF2 has been shown to interact with RAP1A[6] and RALGDS.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000109756 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000062232 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: RAPGEF2 Rap guanine nucleotide exchange factor (GEF) 2".
8. 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. Bibcode:2000CBio...10..555P. doi:10.1016/S0960-9822(00)00473-5. PMID 10801446. S2CID 16896523.
9. 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. PMC 3932028. PMID 23800469.
10. 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. Bibcode:1994PNAS...9112609S. 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. Bibcode:2002PNAS...9912085A. 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. Bibcode:2002PNAS...9916899M. 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.