14-3-3 protein

14-3-3 proteins are a family of conserved regulatory molecules expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. More than 100 signaling proteins have been reported as 14-3-3 ligands.

The name 14-3-3 refers to the characteristic migration pattern of these proteins on electrophoretic gels.

Elevated amounts of 14-3-3 proteins are found in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

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Properties of 14-3-3 proteins

There are seven genes that encode 14-3-3s in most mammals and 13-15 genes in many higher plants, though typically in fungi they are present only in pairs. Protists, some algae, and other 'lower' forms of life have at least one. Eukaryotes can tolerate the loss of an 14-3-3 isoform if multiple isoforms are present, however deletion of all 14-3-3s (as experimentally determined in yeast) results in death.

14-3-3 proteins can be considered evolved members of the TetratricoPeptide Repeat superfamily, generally have 9 or 10 alpha helices, and usually form homo- and/or hetero-dimer interactions along their amino-termini helices. These proteins contain a number of known common modification domains, including regions for divalent cation interaction, phosphorylation & acetylation, and proteolytic cleavage, among others established and predicted.

There are common recognition motifs for 14-3-3 proteins that contain a phosphorylated serine or threonine residue; Mode 1 is R[SFYW]XpSXP & Mode 2 RX[SYFWTQAD]Xp(S/T)X[PLM] (where an 'x' can be several, but not all of the 20 amino acids and a lower case 'p' indicates the site of phosphorylation) but also binding to non-phosphorylated ligands has been reported. This interaction occurs along a so called binding groove or cleft that is amphipathic in nature. To date, the crystal structures of six classes of these proteins have been resolved and deposited in the public domain.

14-3-3 regulating cell-signalling

• Raf-1
• Bad - see Bcl-2
• Bax
• Cdc25

Genes

• YWHAA - "14-3-3 alpha"
• YWHAB - "14-3-3 beta"
• YWHAD - "14-3-3 delta"
• YWHAE - "14-3-3 epsilon"
• YWHAG - "14-3-3 gamma"
• YWHAH - "14-3-3 eta"
• YWHAQ - "14-3-3 tau"
• YWHAZ - "14-3-3 zeta"

References

• Mhawech P (2005). "14-3-3 proteins--an update". Cell Res. 15 (4): 228-36. doi:10.1038/sj.cr.7290291. PMID 15857577.