- Dock10
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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 bindingSources: 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 MbChr 1:
80.5 – 80.76 MbPubMed 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.
Contents
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
- ^ "Entrez Gene: DOCK10 dedicator of cytokinesis 10". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55619.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
Categories:- Human proteins
- Chromosome 2 gene stubs
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