Dedicator of cytokinesis protein 6

DOCK6
Identifiers
Aliases	DOCK6, AOS2, ZIR1, Dock6, dedicator of cytokinesis 6
External IDs	OMIM: 614194; MGI: 1914789; HomoloGene: 83291; GeneCards: DOCK6; OMA:DOCK6 - orthologs
Gene location (Human)
Chr.	Chromosome 19 (human)
End	11,262,524 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	21,763,931 bp
RNA expression pattern
	Top expressed in
	epithelium of colon; ; right lung; ; apex of heart; ; upper lobe of left lung; ; left lobe of thyroid gland; ; right lobe of thyroid gland; ; skin of leg; ; skin of abdomen; ; subcutaneous adipose tissue; ; gastric mucosa;
	Top expressed in
	interventricular septum; ; tail of embryo; ; lip; ; ascending aorta; ; left lung; ; semi-lunar valve; ; aortic valve; ; left lung lobe; ; internal carotid artery; ; muscle of thigh;
	More reference expression data
	n/a
Gene ontology
Molecular function	guanyl-nucleotide exchange factor activity;
Cellular component	perinuclear region of cytoplasm; cytoplasm; cytosol;
Biological process	small GTPase mediated signal transduction; blood coagulation;
	Sources:Amigo / QuickGO
Orthologs
	57572
	319899
	ENSG00000130158
	ENSMUSG00000032198
	Q96HP0
	Q8VDR9
	NM_020812; NM_001367830
	NM_177030
	NP_065863; NP_001354759
	NP_796004
	Wikidata
View/Edit Human	View/Edit Mouse

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.

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

GRCh38: Ensembl release 89: ENSG00000130158 – Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000032198 – Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez gene: DOCK6 dedicator of cytokinesis 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.
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.
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.
Côté JF, Vuori K (2006). "In Vitro Guanine Nucleotide Exchange Activity of DHR-2/DOCKER/CZH2 Domains". Regulators and Effectors of Small GTPases: Rho Family. Methods in Enzymology. Vol. 406. pp. 41–57. doi:10.1016/S0076-6879(06)06004-6. ISBN 978-0-12-182811-0. PMID 16472648.
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.

Discovery

Function

References

Further reading