GEFH1 is an ~110 kDa protein belonging to the Dbl family of proto-oncogenes. GEF-H1 can activate the small GTPase RhoA, but not Rac1 or Cdc42. Rho family GTPases are central regulators of epithelial tight junctions and the cytoskeleton. GEF-H1 can associate with different cytoskeletal structures, namely microtubules and the actin cytoskeleton. It has also been proposed to mediate crosstalk between the two types of filaments. Localization of GEF-H1 differs between cell types. In MRC-5 fibroblast cells, GEF-H1 localizes to stress fibers. In epithelial cells, GEF-H1 is associated with apical tight junctions and involved in regulating paracellular permeability of small hydrophilic tracers. Furthermore, its subcellular localization changes in mitotic cells, where endogenous GEF-H1 is concentrated at mitotic spindles. GEF-H1 is capable of binding to the F-actin binding junctional adaptor cingulin. Binding to cingulin inhibits GEF-H1 and results in the downregulation of RhoA and inhibition of G1/S phase transition. In low confluent cultured cells, the localization of GEF-H1 is predominantly cytoplasmic. With increasing density of the cells, free GEF-H1 is sequestered at the tight junctions by cingulin. GEF-H1 is part of the signaling pathway connecting epithelial polarity with the cell cycle, and as such involved in oncogenesis.Synonyms: GEF-H1, Guanine nucleotide exchange factor H1, KIAA0651, LFP40, Microtubule-regulated Rho-GEF, Proliferating cell nucleolar antigen p40, Rho guanine nucleotide exchange factor 2