 14-3-3 Domain | | Class:Phospho-Ser binding | Structure:
 Crystal structures of the mammalian tau and epsilon isoforms of the 14-3-3 module show that each module is composed of nine anti-parallel alpha helices. Dimerization results in the formation of a negatively charged channel between the two monomers. This channel is lined with invariant residues that mediate interactions with a phosphoserine peptide target sequence. The figure shows the 14-3-3 x dimer complexed with phosphoserine peptide containing the 14-3-3 binding motif.
Structure Reference: PDB: 2B05. | Domain binding and function:
14-3-3 genes encode a ubiquitous family of highly conserved proteins of ~30 kDa acidic proteins found in eukaryotic lineages as diverse as fungi, plants and animals. Mammals encode seven closely related members (β, γ, ε, η, σ, τ, and ζ). Implicated in a wide variety of cellular processes such as apoptosis, stress response and cell cycle, their most notable function is to bind to phosphoserine/phosphothreonine motifs in a sequence-specific manner. The structure of 14-3-3 consists of a tertiary structure consisting of nine α-helices for each monomer, with the biologically functional dimer resembling a “U” shaped structure. 14-3-3 proteins have been linked to a number of diseases such as cancer, Cruezfeldt-Jacob disease, Alzheimers, and Miller-Dieker syndrome. | Examples of Proteins: | Binding partner |
| Function | Links
| | Cdc25 tyrosine phosphatase | | Cell cycle regulation | ELM | | BAD (Bcl-XL binding partner) | | Regulation of apotosis | SMART | | c-Raf Ser/Thr Kinase | | Regulation of kinase activity; Signal transduction | Pfam | | PKC Ser/Thr Kinase | | Signal transduction | GlobPlot | | MEKK1,2,3 Ser/Thr Kinase | | Signal transduction | |
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| Consensus Binding Sites
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| R-X-[Ar/S]-[+]-pS-[LEAM]-P or R-[S/Ar]-[+]-pS-[LEAM]-P
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| Where Ar=aromatic residue, [+]=basic residue and pS=phosphoserine
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| 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 |
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