DEP domain explained

Symbol:	DEP
Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)
Pfam:	PF00610
Interpro:	IPR000591
Cdd:	cd04371

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.^[1]
• 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.^{[2] [3]} 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.^[3]

Notes and References

1. Masuho . I. . Wakasugi-Masuho . H. . Posokhova . E. N. . Patton . J. R. . Martemyanov . K. A. . Type 5 G Protein Subunit (G 5) Controls the Interaction of Regulator of G Protein Signaling 9 (RGS9) with Membrane Anchors . 10.1074/jbc.M111.241513 . Journal of Biological Chemistry . 286 . 24 . 21806–21813 . 2011 . free . 21511947 . 3122235 .
2. Burchett SA . Regulators of G protein signaling: a bestiary of modular protein binding domains . J. Neurochem. . 75 . 4 . 1335–51 . October 2000 . 10987813 . 10.1046/j.1471-4159.2000.0751335.x.
3. Wong HC, Mao J, Nguyen JT, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J . Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway . Nat. Struct. Biol. . 7 . 12 . 1178–84 . December 2000 . 11101902 . 10.1038/82047 . 4381838 .