|Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)|
structural basis of the recognition of the dishevelled dep domain in the wnt signaling pathway
In molecular biology, the DEP domain (Dishevelled, Egl-10 and Pleckstrin domain) is a globular protein domain of about 80 amino acids that is found in over 50 proteins involved in G-protein signalling pathways. It was named after the three proteins it was initially found in:
- Dishevelled (Dsh and Dvl), which plays a key role in the transduction of the Wg/Wnt signal from the cell surface to the nucleus; it is a segment polarity protein required to establish coherent arrays of polarised cells and segments in embryos, and plays a role in wingless signalling.
- Egl-10, which regulates G-protein signalling in the central nervous system in RGS9.
- Pleckstrin, the major substrate of protein kinase C in platelets; Pleckstrin contains two PH domains flanking the DEP domain.
Mammalian regulators of G-protein signalling also contain these domains, and regulate signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving them into their inactive GDP-bound form. It has been proposed that the DEP domain could play a selective role in targeting DEP domain-containing proteins to specific subcellular membranous sites, perhaps even to specific G protein-coupled signaling pathways. Nuclear magnetic resonance spectroscopy has revealed that the DEP domain comprises a three-helix bundle, a beta-hairpin 'arm' composed of two beta-strands and two short beta-strands in the C-terminal region.
- Masuho, I.; Wakasugi-Masuho, H.; Posokhova, E. N.; Patton, J. R.; Martemyanov, K. A. (2011). "Type 5 G Protein Subunit (G 5) Controls the Interaction of Regulator of G Protein Signaling 9 (RGS9) with Membrane Anchors". Journal of Biological Chemistry. 286 (24): 21806–21813. doi:10.1074/jbc.M111.241513. PMC . PMID 21511947.
- Burchett SA (October 2000). "Regulators of G protein signaling: a bestiary of modular protein binding domains". J. Neurochem. 75 (4): 1335–51. doi:10.1046/j.1471-4159.2000.0751335.x. PMID 10987813.
- Wong HC, Mao J, Nguyen JT, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J (December 2000). "Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway". Nat. Struct. Biol. 7 (12): 1178–84. doi:10.1038/82047. PMID 11101902.