Dock6

Dedicator of cytokinesis 6
Identifiers
Symbols	DOCK6; ZIR1
External IDs	MGI: 1914789 HomoloGene: 83291 GeneCards: DOCK6 Gene
Gene Ontology Molecular function • guanyl-nucleotide exchange factor activity • GTP binding • GTPase binding Cellular component • cytosol Biological process • blood coagulation Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	57572	319899
Ensembl	ENSG00000130158	ENSMUSG00000032198
UniProt	Q96HP0	Q8VDR9
RefSeq (mRNA)	NM_020812	NM_177030.3
RefSeq (protein)	NP_065863	NP_796004.2
Location (UCSC)	Chr 19: 11.31 – 11.37 Mb	Chr 9: 21.6 – 21.66 Mb
PubMed search	[1]	[2]

Dock6 (Dedicator of cytokinesis 6), also known as Zir1 is a large (~200 kDa) protein involved in intracellular signalling networks.^[1] 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.^[2] It has a similar domain arrangement to other DOCK proteins,^[3] with a DHR1 domain known in other proteins to bind phospholipids,^[4] and a DHR2 domain containing the GEF activity.^[5]

Function

There is currently very little information about the cellular role of this protein. Interestingly, however, Dock6 has been reported to exhibit dual GEF specificity towards the small G proteins Rac1 and Cdc42.^[6] 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. ^ "Entrez gene: DOCK6 dedicator of cytokinesis 6". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57572&ordinalpos=2&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum. 
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. ^ 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. 
4. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1352170. 
5. ^ Côté JF, Vuori K (2006). "In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains". Meth. Enzymol. 406: 41–57. doi:10.1016/S0076-6879(06)06004-6. PMID 16472648. 
6. ^ 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

• Côté JF, Vuori K (2007). "GEF what? Dock180 and related proteins help Rac to polarize cells in new ways". Trends Cell Biol. 17 (8): 383–93. doi:10.1016/j.tcb.2007.05.001. PMC 2887429. PMID 17765544. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2887429. 
• Kwofie MA, Skowronski J (2008). "Specific recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 guanine nucleotide exchange factors". J. Biol. Chem. 283 (6): 3088–96. doi:10.1074/jbc.M705170200. PMID 18056264. 
• Katoh H, Negishi M (2003). "RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo". Nature 424 (6947): 461–64. doi:10.1038/nature01817. PMID 12879077.