Dedicator of cytokinesis protein 5
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.[5] 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.[6] 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,[7] and suppression of Dock5 expression with shRNA has been shown to inhibit survival and differentiation of osteoclast precursor cells.[8] In addition, a mutation in Dock5 has been associated with the rupture of murine lens cataracts.[9] In zebrafish Dock5 has been implicated in myoblast fusion.[10]
References
- GRCh38: Ensembl release 89: ENSG00000147459 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000044447 - 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: DOCK5 dedicator of cytokinesis 5".
- 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.
- Ha BG, Hong JM, Park JY (July 2008). "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. doi:10.1002/pmic.200701192. PMID 18600791. S2CID 5494045.
- Brazier H, Stephens S, Ory S (September 2006). "Expression profile of RhoGTPases and RhoGEFs during RANKL-stimulated osteoclastogenesis: identification of essential genes in osteoclasts" (PDF). J. Bone Miner. Res. 21 (9): 1387–98. doi:10.1359/jbmr.060613. PMID 16939397. S2CID 13138484.
- Omi N, Kiyokawa E, Matsuda M (May 2008). "Mutation of Dock5, a member of the guanine exchange factor Dock180 superfamily, in the rupture of lens cataract mouse" (PDF). Exp. Eye Res. 86 (5): 828–34. doi:10.1016/j.exer.2008.02.011. hdl:2433/124225. PMID 18396277.
- Moore CA, Parkin CA, Bidet Y, Ingham PW (September 2007). "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. doi:10.1242/dev.001214. PMID 17670792.
Further reading
- Meller N, Merlot S, Guda C (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, 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.
- Reif K, Cyster J (2002). "The CDM protein DOCK2 in lymphocyte migration". Trends Cell Biol. 12 (8): 368–73. doi:10.1016/S0962-8924(02)02330-9. PMID 12191913.
- Lu M, Ravichandran KS (2006). "Dock180-ELMO cooperation in Rac activation". Methods Enzymol. Methods in Enzymology. 406: 388–402. doi:10.1016/S0076-6879(06)06028-9. ISBN 9780121828110. PMID 16472672.