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.

"Dock10" redirects here. For the British television facility, see Dock10 (television facility).
DOCK10
Identifiers
AliasesDOCK10, DRIP2, Nbla10300, ZIZ3, Dock10, dedicator of cytokinesis 10
External IDsOMIM: 611518 MGI: 2146320 HomoloGene: 45952 GeneCards: DOCK10
Orthologs
SpeciesHumanMouse
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
NP_001393483
NP_001393484

Location (UCSC)Chr 2: 224.77 – 225.04 MbChr 1: 80.48 – 80.74 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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. S2CID 36721405.
  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
  • Overview of all the structural information available in the PDB for UniProt: Q96BY6 (Dedicator of cytokinesis protein 10) at the PDBe-KB.
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