The human RAPGEF1/C3G gene is comprised of 24 exons, spanning 163 kb on chromosome 9q34.13.

Expression is ubiquitous, with some tissues like the heart, uterus and skeletal muscle showing higher expression.
Alternative spliced forms: Human RAPGEF1/C3G has two isoforms - isoform a and b which differ in the N-terminal (3 aa of Isoform a replaced by 21 aa in isoform b). Isoform-a has 6085 bps of transcript length whereas isoform-b has 6256 bps of transcript length.
An alternate isoform in rat has a 153bp insertion which is expressed only in testis and brain.
A truncated isoform is expressed in CML cells (K562) named p87C3G which has 4.5 kb of transcript length.

None.

This 140 kDa protein is a guanine nucleotide exchange factor for some members of Ras family GTPases.
Size: isoform a: 1077 amino acids; isoform b: 1095 amino acids.
Domains: C-terminal catalytic domain: homologous to CDC25, exchange factor activity.
Central protein interaction domain: contains poly-proline tracts, with the ability to bind to SH3 domains of various proteins.
N-terminal non-catalytic domain contains an E-cadherin binding domain.
Catalytic activity: Activates downstream GTPases like Ras family members Rap1, Rap2, R-Ras, TC21 and Rho family member TC-10.

Expression is ubiquitous. Higher levels of RAPGEF1/C3G are seen in differentiated human neuroblastoma cells compared to undifferentiated cells.
Interacting partners: p130Cas, Crk, Crk-L, Grb2, Hck, PDGF, Cas-L, Shc, Rap1, c-Abl, PP2A and E-cadherin.
Tyrosine phosphorylation: phosphorylated predominantly at Y504; phosphoryaltion also at other tyrosine residues. Kinases known to phosphorylate RAPGEF1/C3G are Hck, Src, c-Abl and Fyn. Rat and mouse isoforms show changes in sequence surrounding Y504.
Membrane anchoring: Constitutive association with Crk enables the complex to interact with phospho-tyrosine motifs upon stimulation of growth factor receptors in the cell membrane.
Actin cytoskeleton binding: Binds to actin cytoskeleton; phosphorylation at Y504 enhances F-actin binding.
Downstream effectors: Ras family members Rap1, Rap2, R-Ras, TC21, Rho family member TC-10.

Cytosolic.
Upon stimulation of growth factor receptors can be recruited to plasma membrane.
Upon phosphorylation by Src family kinases localizes to Golgi and sub-cortical cytoskeleton.
Also localizes to tips of filopodia and membranous ruffles.

- Suppression of transformation: In cells expressing various oncogenes C3G shows transformation-suppression activity independent of its catalytic domain. This function is mediated by inhibition of ERK phosphorylation and cyclin A expression.
- Cell survival and apoptosis: C3G expression protects against serum starvation induced cell death in neuroblastoma cells through induction of p21. Co-expression of Hck with C3G induced high level of apoptosis in many cell lines. C3G is phosphorylated at Y504 in cells undergoing apoptosis as a consequence of c-Abl expression. C3G is required for c-Abl induced apoptosis.
Upon serum deprivation, C3G induces survival in MEFs through inhibition of p38alpha MAPK activity, which mediates apoptosis. In response to oxidative stress, C3G behaves as a pro-apoptotic molecule, as its knockdown or knockout enhances survival through up-regulation of p38alpha activity, which plays an anti-apoptotic role under these conditions.
- Cell cycle arrest: C3G expression induced the cell cycle inhibitor p21 in human neuroblastoma cells.
- Filopodia formation: C3G is required for c-Abl-induced filopodia during cell spreading on fibronectin. C3G expression induces actin cytoskeletal reorganization and promotes filopodia formation independent of its catalytic activity.
- Neuronal differentiation: C3G is induced during neuronal differentiation and is required for differentiation of human neuroblastoma cells.
- Cell Proliferation: Expression of membrane targeted C3G in Drosophila leads to cell fate changes and overproliferation during development, mediated by the RAS-MAPK pathway and RAP1.
- Muscle integrity: C3G is an accessory component of the Drosophila musculature, essential for the proper localization of integrins at muscle-muscle and muscle-epidermis attachment sites and important for maintaining muscle integrity during larval stages.

Knockout phenotype:
- Knockout mice show embryonic lethality with C3G^-/- homozygous animals dying before embryonic day 7.5. Fibroblasts from knockout animals show impaired cell adhesion, delayed cell spreading and accelerated cell migration.
- Animals expressing hypomorphic allele of C3G show overproliferation of the cortical neuroepithelium, cortical neuron migration defects, and defects in blood vessel maturation.

C3G shares homology only in catalytic domain with other Ras family GTPases. It lacks multiple modular protein interaction domains seen in other family members.

Not known.