Property Summary

NCBI Gene PubMed Count 63
PubMed Score 248.32
PubTator Score 101.25

Knowledge Summary


No data available


  Disease Sources (2)

Disease Target Count P-value
juvenile dermatomyositis 1189 6.31593241680348E-8
group 4 medulloblastoma 1875 0.00157388350159192
COPD 116 0.00985573281027846
ependymoma 2514 0.0159338770545838
Disease Target Count Z-score Confidence
Kidney disease 397 3.417 1.7
hemolytic-uremic syndrome 28 3.357 1.7


  Differential Expression (4)

Disease log2 FC p
ependymoma 1.400 0.016
juvenile dermatomyositis 1.007 0.000
group 4 medulloblastoma 1.100 0.002
COPD -1.100 0.010


Accession Q13905 Q5JUE4 Q68DL3 Q8IV73
Symbols C3G


  Ortholog (12)

Species Source
Chimp OMA EggNOG
Macaque OMA EggNOG Inparanoid
Mouse OMA EggNOG
Rat OMA EggNOG Inparanoid
Horse OMA EggNOG Inparanoid
Platypus OMA EggNOG Inparanoid
Chicken OMA EggNOG
Xenopus OMA EggNOG
Fruitfly EggNOG Inparanoid

Gene RIF (26)

25617801 C3G/RAP1 activity is involved in the metastatic spread of epithelial ovarian cancer.
22659131 C3G plays an important role in platelet clotting through a mechanism involving its GEF activity and suggest that it might be also involved in neutrophil development.
21876762 The possibility of cellular phospho-C3G (pC3G) being a substrate of the intracellular T-cell protein tyrosine phosphatase TC-PTP (PTPN2) using the human neuroblastoma cell line, was studied.
21628423 Lyn controls spatial activation of Rap1 by recruiting the CrkL-C3G protein complex to the leading edge
21399874 found somatic demethylation of a relaxed-criterion CpG island (CGI-B) located in the first intron of RAPGEF1 in 40% of colon cancers and 8% of gastric cancers relative to their matching normal tissues that were always methylated
21223981 C3G overexpression induces neurite-like extensions in MDA-MB-231 and BT549 breast carcinoma cells and not in a variety of other cancer cell lines examined.
21146886 Data demonstrated that the polymorphism in TP53 (rs1042522) was associated with type 2 diabetes, and that potential interaction of TP53 (rs1042522) and RAPGEF1 (rs11243444), or NRF1 (rs1882095) increased the risk of type 2 diabetes.
20581864 C3G as a novel target of c-Abl
20436929 significant positive correlation between layers II and IV of the dorso-lateral prefrontal cortex in the percentage of MR-GEF expressing neurons in individuals with bipolar disorder
20416077 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20190816 ALK activation of Rap1 via the Rap1-specific GEF C3Gmay contribute to cell proliferation and oncogenesis of neuroblastoma.
19324082 These results strongly suggest a dual regulatory role for C3G in chronic myeloid leukemia cells, modulating both apoptosis and survival via Rap-dependent and independent mechanisms.
19297053 Genetic polymorphisms in the RAPGEF1 gene and positive association between one polymorphism and type 2 diabetes in the Korean population.
19297053 Observational study of gene-disease association. (HuGE Navigator)
18832707 Rap1 and its exchange factor C3G in mediating Fc gammaR-dependent phagocytosis.
18809728 Results identify a mechanism by which the WAVE2 complex regulates T cell receptor signaling to Rap1 and integrin activation via Abl- and CrkL-C3G.
18660489 Observational study of gene-disease association. (HuGE Navigator)
18187620 Knockdown of Rap guanine nucleotide exchange factor 1 (RAPGEF1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells
17825818 C3G triggers PP2A activation and binding to MEK and ERK at the subcortical actin cytoskeleton, thus favouring ERK dephosphorylation.
16681758 Inactivation of Crk SH3 domain-binding guanine nucleotide-releasing factor is associated with cervical squamous cell carcinoma
15320955 Src family kinases or pervanadate treatment induces phosphorylation of C3G on Y504. Unlike C3G, which is mostly cytosolic, pY504C3G locates to the Golgi & subcortical actin cytoskeleton, providing evidence for a function for C3G at these compartments.
15138850 amplification and increased expression of the C3G gene may play some role in human lung carcinogenesis through derangement of the CRK-Rap1 signaling pathway
15077165 C3G interferes with at least two separate aspects of oncogenic transformation - cell cycle progression and loss of contact inhibition.
14551197 C3G and Hck interact physically and functionally in vivo to activate kinase-dependent and caspase-mediated apoptosis, which is independent of catalytic domain of C3G
12697763 Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells.

AA Sequence

EEALWELSLKIKPRNITRRKTDREEKT                                              1051 - 1077

Text Mined References (73)

PMID Year Title
26496610 2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
25617801 2015 The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis.
25218447 2014 Uncovering global SUMOylation signaling networks in a site-specific manner.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23033978 2012 Diagnostic exome sequencing in persons with severe intellectual disability.
22659131 2012 C3G transgenic mouse models with specific expression in platelets reveal a new role for C3G in platelet clotting through its GEF activity.
21876762 2011 TC-PTP dephosphorylates the guanine nucleotide exchange factor C3G (RapGEF1) and negatively regulates differentiation of human neuroblastoma cells.
21840392 2011 Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control.
21628423 2011 The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL-C3G complex and activating Rap1 at the leading edge.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21399874 2011 Frequent somatic demethylation of RAPGEF1/C3G intronic sequences in gastrointestinal and gynecological cancer.
21269460 2011 Initial characterization of the human central proteome.
21223981 2011 Cytoskeletal remodeling by C3G to induce neurite-like extensions and inhibit motility in highly invasive breast carcinoma cells.
21146886 2011 Association between polymorphisms in RAPGEF1, TP53, NRF1 and type 2 diabetes in Chinese Han population.
20936779 2010 A human MAP kinase interactome.
20581864 2010 F-actin-binding domain of c-Abl regulates localized phosphorylation of C3G: role of C3G in c-Abl-mediated cell death.
20436929 2010 Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder.
20416077 2010 Identification of type 2 diabetes-associated combination of SNPs using support vector machine.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20190816 2010 Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19380743 2009 Charting the molecular network of the drug target Bcr-Abl.
19324082 2009 C3G silencing enhances STI-571-induced apoptosis in CML cells through p38 MAPK activation, but it antagonizes STI-571 inhibitory effect on survival.
19297053 2009 RAPGEF1 gene variants associated with type 2 diabetes in the Korean population.
18832707 2008 Rap1 activation is required for Fc gamma receptor-dependent phagocytosis.
18809728 2008 The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1.
18660489 2008 Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17825818 2007 C3G mediated suppression of malignant transformation involves activation of PP2A phosphatases at the subcortical actin cytoskeleton.
17724123 2007 Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth.
17474147 2007 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening.
17456239 2007 Discovery of tissue-specific exons using comprehensive human exon microarrays.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16681758 Inactivation of Crk SH3 domain-binding guanine nucleotide-releasing factor (C3G) in cervical squamous cell carcinoma.
16443220 2006 Characterization of p87C3G, a novel, truncated C3G isoform that is overexpressed in chronic myeloid leukemia and interacts with Bcr-Abl.
16284401 2006 Identification of a switch in neurotrophin signaling by selective tyrosine phosphorylation.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15320955 2004 Phosphorylated guanine nucleotide exchange factor C3G, induced by pervanadate and Src family kinases localizes to the Golgi and subcortical actin cytoskeleton.
15164053 2004 DNA sequence and analysis of human chromosome 9.
15144186 2004 Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry.
15138850 2004 Amplification, up-regulation and over-expression of C3G (CRK SH3 domain-binding guanine nucleotide-releasing factor) in non-small cell lung cancers.
15077165 2004 C3G-mediated suppression of oncogene-induced focus formation in fibroblasts involves inhibition of ERK activation, cyclin A expression and alterations of anchorage-independent growth.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14551197 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.
12734187 2003 Src-CrkII-C3G-dependent activation of Rap1 switches growth hormone-stimulated p44/42 MAP kinase and JNK/SAPK activities.
12697763 2003 Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12384139 2002 Ras and relatives--job sharing and networking keep an old family together.
12054111 1999 Insulin and EGF receptors integrate the Ras and Rap signaling pathways.
11870224 2002 Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling.
11466412 2001 Nerve growth factor activates persistent Rap1 signaling in endosomes.
11309621 2001 Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10.
10608804 1999 The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration.
10548487 1999 nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein that interacts with synaptic scaffolding molecule (S-SCAM).
10514505 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.
10318861 1999 Activation of C3G guanine nucleotide exchange factor for Rap1 by phosphorylation of tyrosine 504.
9748234 1998 Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G.
9546424 1998 Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins.
9498705 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.
9497377 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.
9482107 1998 Transformation suppressor activity of C3G is independent of its CDC25-homology domain.
9374471 1997 The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein.
9344843 1997 Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells.
9178909 1997 CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2.
9069267 1997 Signal transduction by the neurotrophin receptors.
9067577 1997 The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins.
8662907 1996 Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins.
8621483 1996 Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors.
8524240 1995 Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G.
7959692 1994 Mapping of the human C3G gene coding a guanine nucleotide releasing protein for Ras family to 9q34.3 by fluorescence in situ hybridization.
7806500 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.
7512734 1994 C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins.