DEP Domain

Structure:
No ImageThe DEP domain shown is from the mDvl1 protein and contains a core helix bundle of three a-helices (H1-H3). H1 and H2 are separated by a ß-hairpin “arm” (B1 and B2) and H3 is followed by two short ß-strands (B3 and B4). The triple a-helix architecture forms a hydrophobic core where key residues stabilize the structure through multiple hydrophobic interactions. It has been suggested that the H1 helix is the site of DEP domain interaction with other proteins. Structures to the mouse Epac2 and human  Pleckstrin DEP domains share this conserved core structure.

Structure Reference: Wong, H.C. et al. (2000) Nat. Struct. Bio 7(12), 1178-1184. PDB: 1FSH.



 


Domain binding and function:
The DEP domain is a protein module of ~90 amino acids that was first discovered in three proteins, Discheveled, EGL-10 and Pleckstrin hence the term “DEP”. Computational studies also suggest DEP domains can be found in Rho-family guanine nucleotide exchange factors as well as some GTPase-activating proteins. DEP domains have been implicated to mediate membrane localization. Furthermore, the DEP domain of a yeast regulator of G-protein signaling (RGS), Sst2, has recently been shown to interact with the unphosphorylated C-terminal tail of the yeast GPCR, Ste2, suggesting a role for DEP domains in selective targeting of RGS proteins to specific GPCRs.
Examples of Proteins: 
DEP domain proteins

Disheveled

EGL-10


Pleckstrin
Sst2


Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors: Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada