Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which plays a role in the activation of Rho GTPases RAC1, RhoA and CDC42 (PubMed:12648457, PubMed:12923183). Can regulate cell morphology in cooperation with activated RAC1 (PubMed:12648457, PubMed:12923183). Involved in immune homeostasis by ensuring proper trafficking and availability of T-cell regulator CTLA-4 at T-cell surface (By similarity). Plays a role in Th2 (T helper cells) development and/or activation, perhaps by interfering with ZAP70 signaling. Required for optimal T-cell effector function, lymphocyte homeostasis and the prevention of systemic autoimmunity (By similarity). Interacts with IRF4, activated RAC1 and F-actin. Both the phosphorylated and non-phosphorylated forms bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) (By similarity). Interacts with ZAP70. Interacts with RAB11A (By similarity). Recruited to the plasma membrane upon binding phosphatidylinositol 3,4,5-trisphosphate. Binds to actin filaments. Thymus. Up-regulated in differentiating Th2 cells and down-regulated in Th1 cells. The PH domain is essential for phosphatidylinositol 3,4,5-trisphosphate binding. Tyrosine-phosphorylated by tyrosine-protein kinase LCK in response to T-cell activation. Defects in Def6 results in spontaneous development of a lupus-like syndrome in aging female mice. It is characterized by the accumulation of effector/memory T-cells and IgG B-cells, profound hypergammaglobulinemia, autoantibody production, and glomerulonephritis.