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.<ref name="entrez">{{cite web | title = Entrez gene: DOCK6 dedicator of cytokinesis 6|url= https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=57572&ordinalpos=2&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum}}</ref> 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.<ref name="Côté_2002">{{cite journal | vauthors = Côté JF, Vuori K | title = Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity | journal = J. Cell Sci. | volume = 115 | issue = Pt 24 | pages = 4901–13 |date=December 2002 | pmid = 12432077 | doi = 10.1242/jcs.00219| doi-access = free }}</ref> It has a similar domain arrangement to other DOCK proteins,<ref name="Meller_2005">{{cite journal | vauthors = Meller N, Merlot S, Guda C | title = CZH proteins: a new family of Rho-GEFs | journal = J. Cell Sci. | volume = 118 | issue = Pt 21 | pages = 4937–46|date=November 2005 | pmid = 16254241 | doi = 10.1242/jcs.02671| doi-access = free }}</ref> with a DHR1 domain known in other proteins to bind phospholipids,<ref name="Côté_2005">{{cite journal | vauthors = Côté JF, Motoyama AB, Bush JA, Vuori K | title = A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signaling| journal = Nat. Cell Biol. | volume = 7 | issue = 8 | pages = 797–807|date=August 2005 | pmid = 16025104 | doi = 10.1038/ncb1280| pmc = 1352170 }}</ref> and a DHR2 domain containing the GEF activity.<ref name="Côté_2006">{{cite book |vauthors=Côté JF, Vuori K |chapter=In Vitro Guanine Nucleotide Exchange Activity of DHR-2/DOCKER/CZH2 Domains |year=2006 |title=Regulators and Effectors of Small GTPases: Rho Family |series=Methods in Enzymology |volume=406 |pages=41–57 |doi=10.1016/S0076-6879(06)06004-6 |isbn=978-0-12-182811-0 |pmid=16472648}}</ref>

==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.<ref name="Miyamoto_2007">{{cite journal | vauthors = Miyamoto Y, Yamauchi J, Sanbe A, Tanoue A | title = Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth| journal = Exp. Cell Res. | volume = 313 | issue = 4 | pages = 791–804|date=February 2007 | pmid = 17196961 | doi = 10.1016/j.yexcr.2006.11.017}}</ref> 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== {{Reflist|2}}

==Further reading== {{refbegin | 2}} *{{cite journal | vauthors=Côté JF, Vuori K |title=GEF what? Dock180 and related proteins help Rac to polarize cells in new ways|journal=Trends Cell Biol. |volume=17 |issue=8|pages= 383–93|year= 2007 |pmid= 17765544 |doi=10.1016/j.tcb.2007.05.001 | pmc=2887429}} *{{cite journal | vauthors=Kwofie MA, Skowronski J |title=Specific recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 guanine nucleotide exchange factors|journal=J. Biol. Chem. |volume=283 |issue=6|pages= 3088–96|year= 2008 |pmid= 18056264 |doi=10.1074/jbc.M705170200|doi-access=free }} *{{cite journal | vauthors=Katoh H, Negishi M |title=RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo|journal=Nature |volume=424 |issue=6947|pages= 461–64|year= 2003 |pmid= 12879077 |doi=10.1038/nature01817|bibcode=2003Natur.424..461K |s2cid=4411133}} {{refend}}