Dedicator of cytokinesis protein 9 (DOCK9)

Dedicator of cytokinesis protein 9 (DOCK9) is a large intracellular guanine nucleotide exchange factor predominantly known as an activator of the small GTPase CDC42. It is a member of the DOCK-D (Zizimin) subfamily within the larger DOCK family of proteins, which regulate Rho GTPases and hence cytoskeletal dynamics and cell shape[2][3][4][1]. DOCK9 possesses a pleckstrin homology domain at its N-terminus for membrane localization and two core DHR1 and DHR2 domains. The DHR2 domain acts as the GEF that facilitates GDP release from CDC42, promoting its active GTP-bound state[1][2]. DOCK9 is widely expressed in tissues including brain, lung, placenta, uterus, kidney, and thyroid[3]. Functionally, it contributes to cell polarity, motility, and morphological changes such as filopodia and membrane ruffle formation[1][2][3]. Mutations and altered expression of DOCK9 have been linked to diseases such as keratoconus, certain cancers, and possibly bipolar disorder[1][2][4][5]. While there are no known drugs that directly target DOCK9, its regulatory role in cell structure and migration makes it a potential therapeutic target in oncology and other diseases characterized by aberrant cytoskeletal remodeling.

Other names

DOCK9ZIZ1ZIZIMIN1KIAA1058zizimin-1Cdc42 guanine nucleotide exchange factor zizimin-1

Inhibition or modulation of DOCK9 is expected to influence Rho GTPase signaling, reduce CDC42 activation, and alter cytoskeletal dynamics and cell migration[4].