Dedicator of cytokinesis protein 10

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.[5] 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.

This article is about the protein. For the television facility based in Greater Manchester, United Kingdom, see Dock10 (television facility).

DOCK10
Identifiers
Aliases	DOCK10, DRIP2, Nbla10300, ZIZ3, Dock10, dedicator of cytokinesis 10
External IDs	OMIM: 611518 MGI: 2146320 HomoloGene: 45952 GeneCards: DOCK10
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q36.2 Start 224,765,090 bp[1] End 225,042,445 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 C5 Start 80,501,073 bp[2] End 80,758,527 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • guanyl-nucleotide exchange factor activity • molecular function Cellular component • extracellular exosome • membrane • cell nucleus • cytoplasm • cell projection • dendritic spine • nucleoplasm • cytosol • intracellular Biological process • small GTPase mediated signal transduction • regulation of cell migration • B cell homeostasis • marginal zone B cell differentiation • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • dendritic spine morphogenesis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	55619	210293
Ensembl	ENSG00000135905	ENSMUSG00000038608
UniProt	Q96BY6	Q8BZN6
RefSeq (mRNA)	NM_001290263 NM_014689 NM_017718 NM_001363762	NM_001285927 NM_175291
RefSeq (protein)	NP_001277192 NP_055504 NP_001350691	NP_001272856 NP_780500
Location (UCSC)	Chr 2: 224.77 – 225.04 Mb	Chr 1: 80.5 – 80.76 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Discovery

Dock10 was identified via bioinformatic approaches as one of a family of evolutionarily conserved proteins (the DOCK family) that share significant sequence homology.[6] Dock10 is expressed in peripheral blood leukocytes[7] as well as in the brain, spleen, lung and thymus.[8]

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.[8] 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.[9] The DHR2 domain of Dock10 appears to bind to the small G proteins Cdc42, TC10 and TCL although these interactions are of low affinity.[8] 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.[7] 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.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000135905 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000038608 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: DOCK10 dedicator of cytokinesis 10".
6. 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.
7. 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.
8. 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.
9. 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.
10. 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. Methods in Enzymology. 406: 41–57. doi:10.1016/S0076-6879(06)06004-6. ISBN 9780121828110. PMID 16472648.

External links

• Overview of all the structural information available in the PDB for UniProt: Q96BY6 (Dedicator of cytokinesis protein 10) at the PDBe-KB.