Rho guanine nucleotide exchange factor 5 (ARHGEF5)

Rho guanine nucleotide exchange factor 5 (ARHGEF5) is an enzyme that activates Rho family GTPases by stimulating the exchange of GDP for GTP, thereby switching them into an active state[1][5]. ARHGEF5 is part of the Dbl family of GEFs and plays a key role in regulating the actin cytoskeleton, microtubule stability, and cell motility through the RhoA-Rho pathway[1][3][5]. It is crucial for several cellular processes, including cell migration, invasion, and morphogenesis, and is essential for normal development of dendrites in neurons as well as the migration and maturation of muscle and immune cells[1][2]. ARHGEF5 is implicated in tumor malignancy, being required for Src-induced formation of invasive cellular structures (podosomes/invadopodia) particularly in mesenchymal-like cancer cells, and is upregulated during EMT—a process linked to increased metastasis[3]. Aberrant function or expression of ARHGEF5 is associated with cancer, neurodevelopmental defects, neuromuscular junction abnormalities, and immune cell trafficking disorders[1][2][3][5]. Note: There are currently no approved drugs directly targeting ARHGEF5, nor is it listed as a clinical biomarker; therapeutic potential remains an area of active research.

Other names

ARHGEF5TIMTIM1GEF5p60Ephexin-3Ephexin3Guanine nucleotide regulatory protein TIMOncogene TIMTransforming immortalized mammary oncogenep60 TIM

Activation of Rho GTPase signaling, especially RhoA (and to a lesser degree RHOB, RHOC, RHOG); Mediator of Src oncogenic signaling via phosphorylation; Induced by TGF-β/SMAD during epithelial-mesenchymal transition (EMT)