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. 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 [ edit ]
Dock10 was identified via
bioinformatic approaches as one of a family of evolutionarily conserved proteins (the DOCK family) that share significant sequence homology. Dock10 is expressed in  peripheral blood leukocytes as well as in the  brain, spleen, lung and thymus.
Structure and Function [ edit ]
Dock10 shares the same domain arrangement as other members of the DOCK-D/Zizimin subfamily as well as a high level of sequence similarity.
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. The DHR2 domain of Dock10 appears to bind to the small G proteins  Cdc42, TC10 and TCL although these interactions are of low affinity. 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. 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.
References [ edit ]
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GRCh38: Ensembl release 89: ENSG00000135905 - Ensembl, May 2017
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GRCm38: Ensembl release 89: ENSMUSG00000038608 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: DOCK10 dedicator of cytokinesis 10".
Côté JF, Vuori K (December 2002). "Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity". J. Cell Sci. 115 (Pt 24): 4901–13. doi: . 10.1242/jcs.00219 PMID 12432077.
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Yelo E, Bernardo MV, Gimeno L, et al. (July 2008). "Dock10, a novel CZH protein selectively induced by interleukin-4 in human B lymphocytes". Mol. Immunol. 45 (12): 3411–18. doi: 10.1016/j.molimm.2008.04.003. PMID 18499258.
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Nishikimi A, Meller N, Uekawa N, et al. (February 2005). "Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes". FEBS Letters. 579 (5): 1039–46. doi: 10.1016/j.febslet.2005.01.006. PMID 15710388. S2CID 36721405.
Meller N, Westbrook MJ, Shannon JD, et al. (January 2008). "Function of the N-terminus of zizimin1: autoinhibition and membrane targeting". Biochem. J. 409 (2): 525–33. doi: 10.1042/BJ20071263. PMC . 2740492 PMID 17935486.
Fluge Ø, Bruland O, Akslen LA, et al. (February 2006). "Gene expression in poorly differentiated papillary thyroid carcinomas". Thyroid. 16 (2): 161–75. doi: 10.1089/thy.2006.16.161. PMID 16676402.
Further reading [ edit ]
External links [ edit ]
Overview of all the structural information available in the PDB for UniProt: (Dedicator of cytokinesis protein 10) at the Q96BY6 PDBe-KB.