Dock10

Dedicator of cytokinesis 10
Identifiers
Symbols	DOCK10; DKFZp781A1532; DRIP2; Nbla10300; ZIZ3
External IDs	OMIM: 611518 MGI: 2146320 HomoloGene: 45952 GeneCards: DOCK10 Gene
Gene Ontology Molecular function • guanyl-nucleotide exchange factor activity • Rho guanyl-nucleotide exchange factor activity • GTP binding • Rho GTPase binding • GTPase binding Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	55619	210293
Ensembl	ENSG00000135905	ENSMUSG00000038608
UniProt	Q96BY6	n/a
RefSeq (mRNA)	NM_014689	NM_175291.3
RefSeq (protein)	NP_055504	NP_780500.2
Location (UCSC)	Chr 2: 225.63 – 225.91 Mb	Chr 1: 80.5 – 80.76 Mb
PubMed search	[1]	[2]

Dock10 (Dedicator of cytokinesis), also known as Zizimin3, is a large (~240 kDa) protein involved in intracellular signalling networks.^[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) which 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 which 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]

References

1. ^ "Entrez Gene: DOCK10 dedicator of cytokinesis 10". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55619. 
2. ^ 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. 
3. ^ ^{a b} 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. 
4. ^ ^{a b c} 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. 
5. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2740492. 
6. ^ 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

• Nishikimi A, Meller N, Uekawa N, et al. (2005). "Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes". FEBS Lett. 579 (5): 1039–46. doi:10.1016/j.febslet.2005.01.006. PMID 15710388. 
• Meller N, Merlot S, Guda C. (2005). "CZH proteins: a new family of Rho-GEFs". J. Cell Sci. 118 (Pt 21): 4937–46. doi:10.1242/jcs.02671. PMID 16254241. 
• Côté JF, Vuori K. (2006). "In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains". Methods Enzymol. 406: 41–57. doi:10.1016/S0076-6879(06)06004-6. PMID 16472648.