14-3-3 protein
| 14-3-3 | |||||||||
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14-3-3 proteins are a family of conserved regulatory
Elevated amounts of 14-3-3 protein in cerebrospinal fluid are usually a sign of rapid neurodegeneration; a common indicator of Creutzfeldt–Jakob disease.[2]
Properties
Seven genes encode seven distinct 14-3-3 proteins in most mammals (See Human genes below) and 13-15 genes in many higher plants, though typically in fungi they are present only in pairs. Protists have at least one. Eukaryotes can tolerate the loss of a single 14-3-3 gene if multiple genes are expressed, but deletion of all 14-3-3s (as experimentally determined in yeast) results in death.[citation needed]
14-3-3 proteins are structurally similar to the
14-3-3 binds to peptides. There are common recognition motifs for 14-3-3 proteins that contain a phosphorylated serine or
| Canonical |
R[^DE]{0,2}[^DEPG]([ST])(([FWYLMV].)
|([^PRIKGN]P)
|([^PRIKGN].{2,4}[VILMFWYP]))
|
|---|---|
| C-terminal |
R[^DE]{0,2}[^DEPG]([ST])[^P]{0,1}$
|
| Non-phos (ATP) |
IR[^P][^P]N[^P][^P]WR[^P]W[YFH][ITML][^P]Y[IVL] |
| All entrys are in regular expression format. Newlines are added in "or" cases for readability. Phosphorylation sites are in bold.
The motif sites are way more diverse than the patterns here suggest. For an example with a modern recognizer using an artificial neural network, see the cited article.[5]
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Discovery and naming
14-3-3 proteins were initially found in brain tissue in 1967 and purified using
Function
14-3-3 proteins play an isoform-specific role in
Phosphorylation of
The eta (YWHAH) isoform is reported to be a biomarker (in synovial fluid) for rheumatoid arthritis.[9] In a systematic review, 14-3-3η has been described as a welcome addition to the rheumatology field. The authors indicate that the serum based 14-3-η marker is additive to the armamentarium of existing tools available to clinicians, and that there is adequate clinical evidence to support its clinical benefits in the management of patients diagnosed with rheumatoid arthritis (RA). [10]
14-3-3 proteins bind to and sequester the transcriptional coregulators YAP/TAZ to the cytoplasm, inhibiting their function.
14-3-3 regulating cell-signalling
Human genes
- YWHAB – "14-3-3 beta"
- 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"
- SFN or YWHAS – "14-3-3 sigma" (Stratifin)
The 14-3-3 proteins alpha and delta (YWHAA and YWHAD) are phosphorylated forms of YWHAB and YWHAZ, respectively.
In plants
The presence of large gene families of 14-3-3 proteins in the Viridiplantae kingdom reflects their essential role in plant physiology. A phylogenetic analysis of 27 plant species clustered the 14-3-3 proteins into four groups.
14-3-3 proteins activate the auto-inhibited plasma membrane P-type H+ ATPases. They bind the ATPases' C-terminus at a conserved threonine.[12]
References
Further reading
- Moore BW, Perez VJ (1967). FD Carlson (ed.). Physiological and Biochemical Aspects of Nervous Integration. Prentice-Hall, Inc., The Marine Biological Laboratory, Woods Hole, MA. pp. 343–359.
- Mhawech P (April 2005). "14-3-3 proteins--an update". Cell Research. 15 (4): 228–36. PMID 15857577.
- Steinacker P, Aitken A, Otto M (September 2011). "14-3-3 proteins in neurodegeneration". Seminars in Cell & Developmental Biology. 22 (7): 696–704. PMID 21920445.
External links
- Eukaryotic Linear Motif resource motif class LIG_14-3-3_1
- Eukaryotic Linear Motif resource motif class LIG_14-3-3_2
- Eukaryotic Linear Motif resource motif class LIG_14-3-3_3
- 14-3-3+Protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Three-dimensional structure of 14-3-3 Protein Theta (Human) complexed with a peptide in the PDB.
- Drosophila 14-3-3epsilon - The Interactive Fly
- Drosophila 14-3-3zeta - The Interactive Fly