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Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10 Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.
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