Dedicator of cytokinesis protein 5 explained

Dedicator of cytokinesis protein 5 (Dock5) is a large (~180 kDa) protein encoded in the human by the DOCK5 gene, involved in intracellular signalling networks.^[1] It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G-proteins.^[2] Dock5 is predicted to activate the small G protein Rac.

Function

Dock5 shares significant sequence identity with Dock180, the archetypal member of the DOCK family. It is therefore predicted to partake in similar interactions although this has yet to be demonstrated. Indeed, the function and signalling properties of Dock5 are poorly understood thus far. Dock5 has been identified as a crucial signalling protein in osteoclasts,^[3] and suppression of Dock5 expression with shRNA has been shown to inhibit survival and differentiation of osteoclast precursor cells.^[4] In addition, a mutation in Dock5 has been associated with the rupture of murine lens cataracts.^[5] In zebrafish Dock5 has been implicated in myoblast fusion.^[6]

Further reading

• Meller N, Merlot S, Guda C . CZH proteins: a new family of Rho-GEFs . J. Cell Sci. . 118 . Pt 21 . 4937–46. 2005 . 16254241 . 10.1242/jcs.02671. free .
• Côté JF, Vuori K . GEF what? Dock180 and related proteins help Rac to polarize cells in new ways . Trends Cell Biol. . 17 . 8 . 383–93. 2007 . 17765544 . 10.1016/j.tcb.2007.05.001 . 2887429.
• Reif K, Cyster J . The CDM protein DOCK2 in lymphocyte migration . Trends Cell Biol. . 12 . 8 . 368–73. 2002 . 12191913 . 10.1016/S0962-8924(02)02330-9.
• Book: Lu M, Ravichandran KS . Dock180–ELMO Cooperation in Rac Activation . Regulators and Effectors of Small GTPases: Rho Family. 406 . 388–402. 2006 . 16472672 . 10.1016/S0076-6879(06)06028-9. Methods in Enzymology. 9780121828110.

Notes and References

1. Web site: Entrez Gene: DOCK5 dedicator of cytokinesis 5.
2. Côté JF, Vuori K . Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity . J. Cell Sci. . 115 . Pt 24 . 4901–13 . December 2002 . 12432077 . 10.1242/jcs.00219 . free .
3. Ha BG, Hong JM, Park JY . Proteomic profile of osteoclast membrane proteins: identification of Na+/H+ exchanger domain containing 2 and its role in osteoclast fusion . Proteomics . 8 . 13 . 2625–39. July 2008 . 18600791 . 10.1002/pmic.200701192. 5494045 .
4. Brazier H, Stephens S, Ory S . Expression profile of RhoGTPases and RhoGEFs during RANKL-stimulated osteoclastogenesis: identification of essential genes in osteoclasts . J. Bone Miner. Res. . 21 . 9 . 1387–98 . September 2006 . 16939397 . 10.1359/jbmr.060613. 13138484 . free .
5. Omi N, Kiyokawa E, Matsuda M . Mutation of Dock5, a member of the guanine exchange factor Dock180 superfamily, in the rupture of lens cataract mouse. Exp. Eye Res. . 86 . 5 . 828–34. May 2008 . 18396277 . 10.1016/j.exer.2008.02.011. 2433/124225. free .
6. Moore CA, Parkin CA, Bidet Y, Ingham PW. A role for the Myoblast city homologues Dock1 and Dock5 and the adaptor proteins Crk and Crk-like in zebrafish myoblast fusion. Development . 134 . 17 . 3145–53. September 2007 . 17670792 . 10.1242/dev.001214. free.