14-3-3 protein

Family of conserved regulatory molecules 14-3-3 14-3-3 File:2bq0 14-3-3.png Cartoon diagram of Human 14-3-3 protein beta PDB entry 2bq0 Structural basis for protein-protein interactions in the 14-3-3 protein family. Proc. Natl. Acad. Sci. U.S.A. 103 46 17237–17242 2006 17085597 1859916 10.1073/pnas.0605779103 Yang X. Lee W. H. Sobott F. Papagrigoriou E. Robinson C. V. Grossmann J. G. Sundstrom M. Doyle D. A. Elkins J. M. 2006PNAS..10317237Y free PF00244 IPR000308 14_3_3 PDOC00633 1a4o 14-3-3 proteins are a family of conserved regulatory molecules that are 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 200 signaling proteins have been reported as 14-3-3 ligands. Elevated amounts of 14-3-3 protein in cerebrospinal fluid are usually a sign of rapid neurodegeneration; a common indicator of Creutzfeldt–Jakob disease. Takahashi H, Iwata T, Kitagawa Y, Takahashi RH, Sato Y, Wakabayashi H, Takashima M, Kido H, Nagashima K, Kenney K, Gibbs CJ, Kurata T Increased levels of epsilon and gamma isoforms of 14-3-3 proteins in cerebrospinal fluid in patients with Creutzfeldt-Jakob disease Clinical and Diagnostic Laboratory Immunology 6 6 983–5 November 1999 10548598 95810 10.1128/CDLI.6.6.983-985.1999 thumb|right|Molecular structure of a 14-3-3 protein dimer bound to a peptide. 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.October 2016 14-3-3 proteins are structurally similar to the Tetratrico Peptide Repeat (TPR) superfamily, which 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. Bridges D, Moorhead GB 14-3-3 proteins: a number of functions for a numbered protein Science's STKE 2005 296 re10 August 2005 16091624 10.1126/stke.2962005re10 5795342 14-3-3 binds to peptides. There are common recognition motifs for 14-3-3 proteins that contain a phosphorylated serine or threonine residue, although binding to non-phosphorylated ligands has also 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.October 2016 14-3-3 recognition motifsELM search: "14-3-3" http://elm.eu.org/combined_search?query=14-3-3 Eukaryotic Linear Motif resource 16 May 2019 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. Madeira F, Tinti M, Murugesan G, Berrett E, Stafford M, Toth R, Cole C, MacKintosh C, Barton GJ 14-3-3-Pred: improved methods to predict 14-3-3-binding phosphopeptides Bioinformatics 31 14 2276–83 July 2015 25735772 4495292 10.1093/bioinformatics/btv133 Discovery and naming 14-3-3 proteins were initially found in brain tissue in 1967 and purified using chromatography and gel electrophoresis. In bovine brain samples, 14-3-3 proteins were located in the 14th fraction eluting from a DEAE-cellulose column and in position 3.3 on a starch electrophoresis gel. 14-3-3 proteins: a historic overview Semin Cancer Biol 50 6 993–1010 Aitken, A 2006 16678438 10.1023/A:1021261931561 41949194 Function 14-3-3 proteins play an isoform-specific role in class switch recombination. They are believed to interact with the protein activation-induced cytidine deaminase in mediating class switch recombination.Xu Z, Zan H, Pone EJ, Mai T, Casali P Immunoglobulin class-switch DNA recombination: induction, targeting and beyond Nat Rev Immunol 12 7 517–31 June 2012 22728528 3545482 10.1038/nri3216 Phosphorylation of Cdc25C by CDS1 and CHEK1 creates a binding site for the 14-3-3 family of phosphoserine binding proteins. Binding of 14-3-3 has little effect on Cdc25C activity, and it is believed that 14-3-3 regulates Cdc25C by sequestering it to the cytoplasm, thereby preventing the interactions with CycB-Cdk1 that are localized to the nucleus at the G2/M transition. Cann KL, Hicks GG Regulation of the cellular DNA double-strand break response Biochemistry and Cell Biology 85 6 663–74 December 2007 18059525 10.1139/O07-135 2007BCB....85..135C The eta isoform, YWHAH, is reported to be a biomarker (in synovial fluid) for rheumatoid arthritis.17611984 2007 Kilani R. T. Maksymowych W. P. Aitken A. Boire G. St-Pierre Y. Li Y. Ghahary A. Detection of high levels of 2 specific isoforms of 14-3-3 proteins in synovial fluid from patients with joint inflammation The Journal of Rheumatology 34 8 1650–1657 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 14-3-3η 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). Abdelhafiz D, Kilborn S, Bukhari M The role of 14-3-3 η as a biomarker in rheumatoid arthritis Rheumatology and Immunology Research. June 2021 2 2 87–90 10.2478/rir-2021-0012 36465971 9524784 238231522 free 14-3-3 proteins bind to and sequester the transcriptional coregulators YAP/TAZ to the cytoplasm, inhibiting their function.Callus Bernard A. Finch-Edmondson Megan L. Fletcher Sue Wilton Steve D. 2019 YAPping about and not forgetting TAZ FEBS Letters en 593 3 253–276 10.1002/1873-3468.13318 1873-3468 free 30570758 14-3-3 regulating cell-signalling Raf-1 Bad – see Bcl-2 Bax Cdc25 Akt SOS1 Saha M, Carriere A, Cheerathodi M, Zhang X, Lavoie G, Rush J, Roux PP, Ballif BA RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation The Biochemical Journal 447 1 159–66 October 2012 22827337 4198020 10.1042/BJ20120938 – see RSK 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 theta" 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.November 2024 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.November 2024 14-3-3 proteins activate the auto-inhibited plasma membrane P-type H+ ATPases. They bind the ATPases' C-terminus at a conserved threonine. Jahn TP, Schulz A, Taipalensuu J, Palmgren MG Post-translational modification of plant plasma membrane H(+)-ATPase as a requirement for functional complementation of a yeast transport mutant The Journal of Biological Chemistry 277 8 6353–8 February 2002 11744700 10.1074/jbc.M109637200 free References 30em Further reading Moore BW, Perez VJ Physiological and Biochemical Aspects of Nervous Integration. Prentice-Hall, Inc., The Marine Biological Laboratory, Woods Hole, MA FD Carlson 343–359 1967 Mhawech P 14-3-3 proteins--an update Cell Research 15 4 228–36 April 2005 15857577 10.1038/sj.cr.7290291 free 2005CelRe..15..228M Steinacker P, Aitken A, Otto M 14-3-3 proteins in neurodegeneration Seminars in Cell & Developmental Biology 22 7 696–704 September 2011 21920445 10.1016/j.semcdb.2011.08.005 External links LIG_14-3-3_1 LIG_14-3-3_2 LIG_14-3-3_3 14-3-3+Protein 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 Category:Programmed cell death Category:14-3-3 proteins