Dock10

Dedicator of cytokinesis 10
Identifiers
Symbols DOCK10 ; DRIP2; Nbla10300; ZIZ3
External IDs OMIM: 611518 MGI: 2146320 HomoloGene: 45952 GeneCards: DOCK10 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 55619 210293
Ensembl ENSG00000135905 ENSMUSG00000038608
UniProt Q96BY6 Q8BZN6
RefSeq (mRNA) NM_001290263 NM_001285927
RefSeq (protein) NP_001277192 NP_001272856
Location (UCSC) Chr 2:
224.77 – 225.04 Mb		 Chr 1:
80.5 – 80.76 Mb
PubMed search

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) 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]

References

  1. ↑ "Entrez Gene: DOCK10 dedicator of cytokinesis 10".
  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. 1 2 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. 1 2 3 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.
  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


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