DEF6 is a 631 amino acid protein that is widely expressed in T and B cells of the immune system. Localized to the nucleus, cytoplasm and cell membrane, DEF6 is a phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) that functions to activate Rho GTPases such as Rac 1, Cdc42 and Rho A. Via its ability to activate various Rho GTPases, DEF6 can regulate cell shape, movement and polarity and, through its interaction with T helper cells, DEF6 can also help mediate the immune response. DEF6 contains one PH (pleckstrin homology) domain which is required for binding to phosphatidylinositol 3,4,5-trisphosphate and subsequent recruitment to the plasma membrane.