Dedicator of cytokinesis protein 6

Dedicator of cytokinesis protein 6 (Dock6), also known as Zir1 is a large (~200 kDa) protein encoded in the human by the DOCK6 gene, involved in intracellular signalling networks.[5] It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G-proteins.

DOCK6
Identifiers
AliasesDOCK6, AOS2, ZIR1, Dock6, dedicator of cytokinesis 6
External IDsOMIM: 614194 MGI: 1914789 HomoloGene: 83291 GeneCards: DOCK6
Orthologs
SpeciesHumanMouse
Entrez

57572

319899

Ensembl

ENSG00000130158

ENSMUSG00000032198

UniProt

Q96HP0

Q8VDR9

RefSeq (mRNA)

NM_020812
NM_001367830

NM_177030

RefSeq (protein)

NP_065863
NP_001354759

NP_796004

Location (UCSC)Chr 19: 11.2 – 11.26 MbChr 9: 21.71 – 21.76 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Discovery

Dock6 was identified as one of a family of proteins which share high sequence similarity with Dock180, the archetypal member of the DOCK family.[6] It has a similar domain arrangement to other DOCK proteins,[7] with a DHR1 domain known in other proteins to bind phospholipids,[8] and a DHR2 domain containing the GEF activity.[9]

Function

There is currently very little information about the cellular role of this protein. However, Dock6 has been reported to exhibit dual GEF specificity towards the small G proteins Rac1 and Cdc42.[10] It is the only DOCK family member reported to activate both of these G proteins. The same study also showed that transfection of the Dock6 DHR2 domain into N1E-115 neuroblastoma cells promoted Rac- and Cdc42-dependent neurite outgrowth, although the physiological significance of this has yet to be demonstrated.

References
  1. GRCh38: Ensembl release 89: ENSG00000130158 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000032198 - 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: DOCK6 dedicator of cytokinesis 6".
  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. Meller N, Merlot S, Guda C (November 2005). "CZH proteins: a new family of Rho-GEFs". J. Cell Sci. 118 (Pt 21): 4937–46. doi:10.1242/jcs.02671. PMID 16254241.
  8. Côté JF, Motoyama AB, Bush JA, Vuori K (August 2005). "A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signaling". Nat. Cell Biol. 7 (8): 797–807. doi:10.1038/ncb1280. PMC 1352170. PMID 16025104.
  9. Côté JF, Vuori K (2006). "In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains". Meth. Enzymol. Methods in Enzymology. 406: 41–57. doi:10.1016/S0076-6879(06)06004-6. ISBN 978-0-12-182811-0. PMID 16472648.
  10. Miyamoto Y, Yamauchi J, Sanbe A, Tanoue A (February 2007). "Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth". Exp. Cell Res. 313 (4): 791–804. doi:10.1016/j.yexcr.2006.11.017. PMID 17196961.

Further reading


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