RAPGEF1

Rap guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the RAPGEF1 gene.[5][6]

RAPGEF1
Identifiers
Aliases	RAPGEF1, C3G, GRF2, Rap guanine nucleotide exchange factor 1
External IDs	OMIM: 600303 MGI: 104580 HomoloGene: 50501 GeneCards: RAPGEF1
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.13 Start 131,576,770 bp[1] End 131,740,074 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 B|2 20.32 cM Start 29,619,720 bp[2] End 29,740,978 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • SH3 domain binding • GO:0001948 protein binding • Rap guanyl-nucleotide exchange factor activity • guanyl-nucleotide exchange factor activity Cellular component • cytosol • endosome • early endosome • phagocytic vesicle membrane • perinuclear region of cytoplasm • cytoplasm • macromolecular complex Biological process • establishment of endothelial barrier • negative regulation of protein kinase B signaling • cellular response to nerve growth factor stimulus • regulation of cell junction assembly • activation of MAPKK activity • transmembrane receptor protein tyrosine kinase signaling pathway • small GTPase mediated signal transduction • Rap protein signal transduction • negative regulation of neural precursor cell proliferation • nerve growth factor signaling pathway • nervous system development • negative regulation of Ras protein signal transduction • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • blood vessel development • negative regulation of ERK1 and ERK2 cascade • platelet-derived growth factor receptor signaling pathway • negative regulation of canonical Wnt signaling pathway • cellular response to cAMP • signal transduction • positive regulation of neuron projection development • regulation of JNK cascade • positive regulation of ERK1 and ERK2 cascade • positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis • cell-cell adhesion • cytokine-mediated signaling pathway • positive regulation of Ras protein signal transduction • GO:0032861, GO:0032862, GO:0032856 activation of GTPase activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2889	107746
Ensembl	ENSG00000107263	ENSMUSG00000039844
UniProt	Q13905	n/a
RefSeq (mRNA)	NM_001304275 NM_005312 NM_198679 NM_001377935 NM_001377936 NM_001377937 NM_001377938	NM_001039086 NM_001039087 NM_054050 NM_001362702
RefSeq (protein)	NP_001291204 NP_005303 NP_941372 NP_001364864 NP_001364865 NP_001364866 NP_001364867	n/a
Location (UCSC)	Chr 9: 131.58 – 131.74 Mb	Chr 2: 29.62 – 29.74 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is a human guanine nucleotide releasing protein for Ras protein. It belongs to the adaptor-type Src homology (SH)2-containing molecules. Src homology 2 domains are globular protein modules present in a large variety of functionally distinct proteins. They mediate binding events that control the activity and localization of many proteins involved in the transmission of signals from the cell surface to the nucleus. The mRNAs of these proteins are expressed ubiquitously in human adult and fetal tissues. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined.[7]

Interactions

RAPGEF1 has been shown to interact with:

• BCAR1,[8]
• CRK,[6]
• CRKL[9][10][11][12][13][14][15]
• Grb2,[6][9] and
• HCK.[16]

References

1. GRCh38: Ensembl release 89: ENSG00000107263 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039844 - 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. Takai S, Tanaka M, Sugimura H, Yamada K, Naito Y, Kino I, Matsuda M (Nov 1994). "Mapping of the human C3G gene coding a guanine nucleotide releasing protein for Ras family to 9q34.3 by fluorescence in situ hybridization". Human Genetics. 94 (5): 549–50. doi:10.1007/bf00211024. PMID 7959692.
6. Tanaka S, Morishita T, Hashimoto Y, Hattori S, Nakamura S, Shibuya M, Matuoka K, Takenawa T, Kurata T, Nagashima K (Apr 1994). "C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins". Proceedings of the National Academy of Sciences of the United States of America. 91 (8): 3443–7. doi:10.1073/pnas.91.8.3443. PMC 43593. PMID 7512734.
7. "Entrez Gene: RAPGEF1 Rap guanine nucleotide exchange factor (GEF) 1".
8. Kirsch KH, Georgescu MM, Hanafusa H (Oct 1998). "Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G". The Journal of Biological Chemistry. 273 (40): 25673–9. doi:10.1074/jbc.273.40.25673. PMID 9748234.
9. Smit L, van der Horst G, Borst J (Apr 1996). "Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors". The Journal of Biological Chemistry. 271 (15): 8564–9. doi:10.1074/jbc.271.15.8564. PMID 8621483.
10. Kyono WT, de Jong R, Park RK, Liu Y, Heisterkamp N, Groffen J, Durden DL (Nov 1998). "Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI)". Journal of Immunology. 161 (10): 5555–63. PMID 9820532.
11. Grumbach IM, Mayer IA, Uddin S, Lekmine F, Majchrzak B, Yamauchi H, Fujita S, Druker B, Fish EN, Platanias LC (Feb 2001). "Engagement of the CrkL adaptor in interferon alpha signalling in BCR-ABL-expressing cells". British Journal of Haematology. 112 (2): 327–36. doi:10.1046/j.1365-2141.2001.02556.x. PMID 11167825.
12. Ahmad S, Alsayed YM, Druker BJ, Platanias LC (Nov 1997). "The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein". The Journal of Biological Chemistry. 272 (48): 29991–4. doi:10.1074/jbc.272.48.29991. PMID 9374471.
13. Chin H, Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N, Miura O (Oct 1997). "Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells". Biochemical and Biophysical Research Communications. 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. PMID 9344843.
14. Wu C, Lai CF, Mobley WC (Aug 2001). "Nerve growth factor activates persistent Rap1 signaling in endosomes". The Journal of Neuroscience. 21 (15): 5406–16. doi:10.1523/JNEUROSCI.21-15-05406.2001. PMID 11466412.
15. Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM (Apr 2000). "Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL". The Journal of Biological Chemistry. 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. PMID 10753869.
16. Shivakrupa R, Radha V, Sudhakar Ch, Swarup G (Dec 2003). "Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain". The Journal of Biological Chemistry. 278 (52): 52188–94. doi:10.1074/jbc.M310656200. PMID 14551197.

Further reading

• Pessin JE, Okada S (Mar 1999). "Insulin and EGF receptors integrate the Ras and Rap signaling pathways". Endocrine Journal. 46 Suppl: S11-6. doi:10.1507/endocrj.46.suppl_s11. PMID 12054111.
• Ehrhardt A, Ehrhardt GR, Guo X, Schrader JW (Oct 2002). "Ras and relatives--job sharing and networking keep an old family together". Experimental Hematology. 30 (10): 1089–106. doi:10.1016/S0301-472X(02)00904-9. PMID 12384139.
• Knudsen BS, Feller SM, Hanafusa H (Dec 1994). "Four proline-rich sequences of the guanine-nucleotide exchange factor C3G bind with unique specificity to the first Src homology 3 domain of Crk". The Journal of Biological Chemistry. 269 (52): 32781–7. PMID 7806500.
• Gotoh T, Hattori S, Nakamura S, Kitayama H, Noda M, Takai Y, Kaibuchi K, Matsui H, Hatase O, Takahashi H (Dec 1995). "Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G". Molecular and Cellular Biology. 15 (12): 6746–53. doi:10.1128/mcb.15.12.6746. PMC 230928. PMID 8524240.
• Smit L, van der Horst G, Borst J (Apr 1996). "Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors". The Journal of Biological Chemistry. 271 (15): 8564–9. doi:10.1074/jbc.271.15.8564. PMID 8621483.
• Matsuda M, Ota S, Tanimura R, Nakamura H, Matuoka K, Takenawa T, Nagashima K, Kurata T (Jun 1996). "Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins". The Journal of Biological Chemistry. 271 (24): 14468–72. doi:10.1074/jbc.271.24.14468. PMID 8662907.
• Uemura N, Salgia R, Li JL, Pisick E, Sattler M, Griffin JD (Mar 1997). "The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins". Leukemia. 11 (3): 376–85. doi:10.1038/sj.leu.2400590. PMID 9067577.
• Husson H, Mograbi B, Schmid-Antomarchi H, Fischer S, Rossi B (May 1997). "CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2". Oncogene. 14 (19): 2331–8. doi:10.1038/sj.onc.1201074. PMID 9178909.
• Chin H, Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N, Miura O (Oct 1997). "Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells". Biochemical and Biophysical Research Communications. 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. PMID 9344843.
• Ahmad S, Alsayed YM, Druker BJ, Platanias LC (Nov 1997). "The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein". The Journal of Biological Chemistry. 272 (48): 29991–4. doi:10.1074/jbc.272.48.29991. PMID 9374471.
• Guerrero C, Fernandez-Medarde A, Rojas JM, Font de Mora J, Esteban LM, Santos E (Feb 1998). "Transformation suppressor activity of C3G is independent of its CDC25-homology domain". Oncogene. 16 (5): 613–24. doi:10.1038/sj.onc.1201569. PMID 9482107.
• Ohashi Y, Tachibana K, Kamiguchi K, Fujita H, Morimoto C (Mar 1998). "T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its association of Crk and C3G". The Journal of Biological Chemistry. 273 (11): 6446–51. doi:10.1074/jbc.273.11.6446. PMID 9497377.
• Astier A, Manié SN, Law SF, Canty T, Haghayghi N, Druker BJ, Salgia R, Golemis EA, Freedman AS (Dec 1997). "Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: potential relevance to neoplastic lymphohematopoietic cells". Leukemia & Lymphoma. 28 (1–2): 65–72. doi:10.3109/10428199709058332. PMID 9498705.
• Yokote K, Hellman U, Ekman S, Saito Y, Rönnstrand L, Saito Y, Heldin CH, Mori S (Mar 1998). "Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins". Oncogene. 16 (10): 1229–39. doi:10.1038/sj.onc.1201641. PMID 9546424.
• Kirsch KH, Georgescu MM, Hanafusa H (Oct 1998). "Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G". The Journal of Biological Chemistry. 273 (40): 25673–9. doi:10.1074/jbc.273.40.25673. PMID 9748234.
• Ichiba T, Hashimoto Y, Nakaya M, Kuraishi Y, Tanaka S, Kurata T, Mochizuki N, Matsuda M (May 1999). "Activation of C3G guanine nucleotide exchange factor for Rap1 by phosphorylation of tyrosine 504". The Journal of Biological Chemistry. 274 (20): 14376–81. doi:10.1074/jbc.274.20.14376. PMID 10318861.
• Nosaka Y, Arai A, Miyasaka N, Miura O (Oct 1999). "CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3". The Journal of Biological Chemistry. 274 (42): 30154–62. doi:10.1074/jbc.274.42.30154. PMID 10514505.
• Uemura N, Griffin JD (Dec 1999). "The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration". The Journal of Biological Chemistry. 274 (53): 37525–32. doi:10.1074/jbc.274.53.37525. PMID 10608804.

External links

• RAPGEF1 Info with links in the Cell Migration Gateway