Dock5

Dock5 (Dedicator of cytokinesis 5), also known as DOCK5, is a large (~180 kDa) protein 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.

DOCK5
Identifiers
Aliases	DOCK5, Dock5, dedicator of cytokinesis 5
External IDs	OMIM: 616904 MGI: 2652871 HomoloGene: 57016 GeneCards: DOCK5
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8p21.2 Start 25,184,689 bp[1] End 25,418,082 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 D1 Start 67,752,135 bp[2] End 67,933,442 bp[2]
Gene ontology Molecular function • guanyl-nucleotide exchange factor activity • GO:0001948 protein binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity Cellular component • cell membrane • membrane • cytoplasm • cytosol Biological process • small GTPase mediated signal transduction • negative regulation of vascular smooth muscle contraction • positive regulation of vascular associated smooth muscle cell migration • positive regulation of substrate adhesion-dependent cell spreading • positive regulation of epithelial cell migration • cell migration • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	80005	68813
Ensembl	ENSG00000147459	ENSMUSG00000044447
UniProt	Q9H7D0	B2RY04
RefSeq (mRNA)	NM_024940 NM_001322810	NM_177780
RefSeq (protein)	NP_001309739 NP_079216	NP_808448
Location (UCSC)	Chr 8: 25.18 – 25.42 Mb	Chr 14: 67.75 – 67.93 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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

1. GRCh38: Ensembl release 89: ENSG00000147459 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000044447 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: DOCK5 dedicator of cytokinesis 5".
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.
7. 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.
8. 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.
9. 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.
10. 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.