Dedicator of cytokinesis protein 10 explained

Dedicator of cytokinesis protein 10 (Dock10), also known as Zizimin3, is a large (~240 kDa) protein involved in intracellular signalling networks that in humans is encoded by the DOCK10 gene.^[1] It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors, which function as activators of small G-proteins.

Discovery

Dock10 was identified via bioinformatic approaches as one of a family of evolutionarily conserved proteins (the DOCK family) that share significant sequence homology.^[2] Dock10 is expressed in peripheral blood leukocytes^[3] as well as in the brain, spleen, lung and thymus.^[4]

Structure and function

Dock10 shares the same domain arrangement as other members of the DOCK-D/Zizimin subfamily as well as a high level of sequence similarity.^[4] It contains a DHR2 domain that is involved in G protein binding and a DHR1 domain, which, in some DOCK family proteins, interacts with membrane phospholipids. Like other DOCK-D subfamily proteins Dock10 contains an N-terminal PH domain, which, in Dock9/Zizimin1, mediates recruitment to the plasma membrane.^[5] The DHR2 domain of Dock10 appears to bind to the small G proteins Cdc42, TC10 and TCL although these interactions are of low affinity.^[4] The physiological role of Dock10 is poorly characterised, however a study in lymphocytes has shown that Dock10 expression is upregulated in B-lymphocytes and Chronic Lymphocytic Leukemia (CLL) cells in response to the cytokine IL-4.^[3] This suggests that Dock10 may have a role in B-cell activation and proliferation. Another study identified Dock10 as a protein that was overexpressed in some aggressive papillary thyroid carcinomas.^[6]

Further reading

• Nishikimi A, Meller N, Uekawa N . Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes . FEBS Lett. . 579 . 5 . 1039–46 . 2005 . 15710388 . 10.1016/j.febslet.2005.01.006 . 2005FEBSL.579.1039N . 36721405 . etal.
• Meller N, Merlot S, Guda C. CZH proteins: a new family of Rho-GEFs . J. Cell Sci. . 118 . Pt 21 . 4937–46 . 2005 . 16254241 . 10.1242/jcs.02671 . free .
• Book: Côté JF, Vuori K. In Vitro Guanine Nucleotide Exchange Activity of DHR-2/DOCKER/CZH2 Domains . Regulators and Effectors of Small GTPases: Rho Family. 406 . 41–57 . 2006 . 16472648 . 10.1016/S0076-6879(06)06004-6 . Methods in Enzymology. 9780121828110.

Notes and References

1. Web site: Entrez Gene: DOCK10 dedicator of cytokinesis 10.
2. Côté JF, Vuori K. Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity. J. Cell Sci. . 115 . Pt 24 . 4901–13. December 2002 . 12432077 . 10.1242/jcs.00219. free.
3. Yelo E, Bernardo MV, Gimeno L. Dock10, a novel CZH protein selectively induced by interleukin-4 in human B lymphocytes. Mol. Immunol. . 45 . 12 . 3411–18. July 2008 . 18499258 . 10.1016/j.molimm.2008.04.003. etal.
4. Nishikimi A, Meller N, Uekawa N. Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes. FEBS Letters . 579 . 5 . 1039–46. February 2005 . 15710388 . 10.1016/j.febslet.2005.01.006. 2005FEBSL.579.1039N. 36721405. etal.
5. Meller N, Westbrook MJ, Shannon JD. Function of the N-terminus of zizimin1: autoinhibition and membrane targeting. Biochem. J. . 409 . 2 . 525–33. January 2008 . 17935486 . 10.1042/BJ20071263. 2740492 . etal.
6. Fluge Ø, Bruland O, Akslen LA. Gene expression in poorly differentiated papillary thyroid carcinomas. Thyroid . 16 . 2 . 161–75. February 2006 . 16676402 . 10.1089/thy.2006.16.161. etal.