YWHAQ explained

14-3-3 protein theta is a protein that in humans is encoded by the YWHAQ gene.^[1]

Function

This gene product belongs to the 14-3-3 family of proteins that mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse and rat orthologs. This gene is upregulated in patients with amyotrophic lateral sclerosis. It contains in its 5' UTR a 6 bp tandem repeat sequence that is polymorphic; however, there is no correlation between the repeat number and the disease.^[2]

Interactions

YWHAQ has been shown to interact with:

• BAX,^[3]
• BAD,^{[4] [5]}
• C-Raf,^{[6] [7] [8]}
• CRTC2,^{[9] [10]}
• CBL^{[8] [11]}
• HDAC5,^[12]
• MEF2D,^[13]
• NRIP1,^[14]
• PFKFB2,^[15]
• PRKD1,^{[16] [17]}
• PRKCZ,^[7]
• TERT,^[18] and
• UCP3.^[19]

Further reading

• Kino T, Chrousos GP . Human immunodeficiency virus type-1 accessory protein Vpr: a causative agent of the AIDS-related insulin resistance/lipodystrophy syndrome? . Ann. N. Y. Acad. Sci. . 1024 . 153–67 . 2004 . 1 . 15265780 . 10.1196/annals.1321.013 . 2004NYASA1024..153K . 23655886 .
• Calinisan V, Gravem D, Chen RP, Brittin S, Mohandas N, Lecomte MC, Gascard P . New insights into potential functions for the protein 4.1 superfamily of proteins in kidney epithelium. . Front. Biosci. . 11 . 1646–66 . 2006 . 16368544 . 10.2741/1911 . 26325962 . free .
• Nielsen PJ . Primary structure of a human protein kinase regulator protein. . Biochim. Biophys. Acta . 1088 . 3 . 425–8 . 1991 . 2015305 . 10.1016/0167-4781(91)90136-a .
• Bonnefoy-Bérard N, Liu YC, von Willebrand M, Sung A, Elly C, Mustelin T, Yoshida H, Ishizaka K, Altman A . Inhibition of phosphatidylinositol 3-kinase activity by association with 14-3-3 proteins in T cells. . Proc. Natl. Acad. Sci. U.S.A. . 92 . 22 . 10142–6 . 1995 . 7479742 . 40752 . 10.1073/pnas.92.22.10142 . 1995PNAS...9210142B . free .
• Xiao B, Smerdon SJ, Jones DH, Dodson GG, Soneji Y, Aitken A, Gamblin SJ . Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways. . Nature . 376 . 6536 . 188–91 . 1995 . 7603573 . 10.1038/376188a0 . 1995Natur.376..188X . 4311234 .
• Leffers H, Madsen P, Rasmussen HH, Honoré B, Andersen AH, Walbum E, Vandekerckhove J, Celis JE . Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway. . J. Mol. Biol. . 231 . 4 . 982–98 . 1993 . 8515476 . 10.1006/jmbi.1993.1346 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction. . Anal. Biochem. . 236 . 1 . 107–13 . 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Liu YC, Elly C, Yoshida H, Bonnefoy-Berard N, Altman A . Activation-modulated association of 14-3-3 proteins with Cbl in T cells. . J. Biol. Chem. . 271 . 24 . 14591–5 . 1996 . 8663231 . 10.1074/jbc.271.24.14591 . free .
• Papin C, Denouel A, Calothy G, Eychène A . Identification of signalling proteins interacting with B-Raf in the yeast two-hybrid system. . Oncogene . 12 . 10 . 2213–21 . 1996 . 8668348 .
• Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ . Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L) . Cell . 87 . 4 . 619–28 . 1997 . 8929531 . 10.1016/S0092-8674(00)81382-3 . 860908 . free .
• Suzuki Y, Demoliere C, Kitamura D, Takeshita H, Deuschle U, Watanabe T . HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family tyrosine kinases. . J. Immunol. . 158 . 6 . 2736–44 . 1997 . 10.4049/jimmunol.158.6.2736 . 9058808 . 25584050 . free .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing. . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Dubois T, Rommel C, Howell S, Steinhussen U, Soneji Y, Morrice N, Moelling K, Aitken A . 14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction. . J. Biol. Chem. . 272 . 46 . 28882–8 . 1997 . 9360956 . 10.1074/jbc.272.46.28882 . free .
• Hsu SY, Kaipia A, Zhu L, Hsueh AJ . Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11. . Mol. Endocrinol. . 11 . 12 . 1858–67 . 1997 . 10.1210/mend.11.12.0023 . 9369453 . free .
• Brunati AM, Donella-Deana A, James P, Quadroni M, Contri A, Marin O, Pinna LA . Molecular features underlying the sequential phosphorylation of HS1 protein and its association with c-Fgr protein-tyrosine kinase. . J. Biol. Chem. . 274 . 11 . 7557–64 . 1999 . 10066823 . 10.1074/jbc.274.11.7557 . free .
• Hausser A, Storz P, Link G, Stoll H, Liu YC, Altman A, Pfizenmaier K, Johannes FJ . Protein kinase C mu is negatively regulated by 14-3-3 signal transduction proteins. . J. Biol. Chem. . 274 . 14 . 9258–64 . 1999 . 10092600 . 10.1074/jbc.274.14.9258 . free .
• Finlin BS, Andres DA . Phosphorylation-dependent association of the Ras-related GTP-binding protein Rem with 14-3-3 proteins. . Arch. Biochem. Biophys. . 368 . 2 . 401–12 . 1999 . 10441394 . 10.1006/abbi.1999.1316 .
• Chow CW, Davis RJ . Integration of calcium and cyclic AMP signaling pathways by 14-3-3. . Mol. Cell. Biol. . 20 . 2 . 702–12 . 2000 . 10611249 . 85175 . 10.1128/MCB.20.2.702-712.2000 .
• Mori H, Inoue M, Yano M, Wakabayashi H, Kido H . 14-3-3tau associates with a translational control factor FKBP12-rapamycin-associated protein in T-cells after stimulation by pervanadate. . FEBS Lett. . 467 . 1 . 61–4 . 2000 . 10664457 . 10.1016/S0014-5793(00)01126-1 . 12119302 . free .
• Mils V, Baldin V, Goubin F, Pinta I, Papin C, Waye M, Eychene A, Ducommun B . Specific interaction between 14-3-3 isoforms and the human CDC25B phosphatase. . Oncogene . 19 . 10 . 1257–65 . 2000 . 10713667 . 10.1038/sj.onc.1203419 . free .

Notes and References

1. Malaspina A, Kaushik N, de Belleroche J . A 14-3-3 mRNA is up-regulated in amyotrophic lateral sclerosis spinal cord . J Neurochem . 75 . 6 . 2511–20 . November 2000 . 11080204 . 10.1046/j.1471-4159.2000.0752511.x . 2941793 . free .
2. Web site: Entrez Gene: YWHAQ tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide.
3. Nomura M, Shimizu S, Sugiyama T, Narita M, Ito T, Matsuda H, Tsujimoto Y . 14-3-3 Interacts directly with and negatively regulates pro-apoptotic Bax . J. Biol. Chem. . 278 . 3 . 2058–65 . January 2003 . 12426317 . 10.1074/jbc.M207880200 . free .
4. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC . Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function . Mol. Cell . 17 . 3 . 393–403 . February 2005 . 15694340 . 10.1016/j.molcel.2004.12.030 . free .
5. Hsu SY, Kaipia A, Zhu L, Hsueh AJ . Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11 . Mol. Endocrinol. . 11 . 12 . 1858–67 . November 1997 . 10.1210/mend.11.12.0023 . 9369453 . free .
6. Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, Sedivy JM, Kolch W . Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein . Mol. Cell. Biol. . 20 . 9 . 3079–85 . May 2000 . 10757792 . 85596 . 10.1128/MCB.20.9.3079-3085.2000.
7. Van Der Hoeven PC, Van Der Wal JC, Ruurs P, Van Dijk MC, Van Blitterswijk J . 14-3-3 isotypes facilitate coupling of protein kinase C-zeta to Raf-1: negative regulation by 14-3-3 phosphorylation . Biochem. J. . 345 . 2. 297–306 . January 2000 . 10620507 . 1220759 . 10.1042/0264-6021:3450297.
8. Liu YC, Elly C, Yoshida H, Bonnefoy-Berard N, Altman A . Activation-modulated association of 14-3-3 proteins with Cbl in T cells . J. Biol. Chem. . 271 . 24 . 14591–5 . June 1996 . 8663231 . 10.1074/jbc.271.24.14591. free .
9. Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR, Takemori H, Okamoto M, Montminy M . The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector . Cell . 119 . 1 . 61–74 . October 2004 . 15454081 . 10.1016/j.cell.2004.09.015 . 18616459 . free .
10. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1. 89 . 17353931 . 1847948 . 10.1038/msb4100134 . 2007.
11. Pedraza-Alva G, Sawasdikosol S, Liu YC, Mérida LB, Cruz-Muñoz ME, Oceguera-Yañez F, Burakoff SJ, Rosenstein Y . Regulation of Cbl molecular interactions by the co-receptor molecule CD43 in human T cells . J. Biol. Chem. . 276 . 1 . 729–37 . January 2001 . 11024037 . 10.1074/jbc.M008494200 . free .
12. Vega RB, Harrison BC, Meadows E, Roberts CR, Papst PJ, Olson EN, McKinsey TA . Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5 . Mol. Cell. Biol. . 24 . 19 . 8374–85 . October 2004 . 15367659 . 516754 . 10.1128/MCB.24.19.8374-8385.2004 .
13. Choi SJ, Park SY, Han TH . 14-3-3tau associates with and activates the MEF2D transcription factor during muscle cell differentiation . Nucleic Acids Res. . 29 . 13 . 2836–42 . July 2001 . 11433030 . 55772 . 10.1093/nar/29.13.2836.
14. Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA . Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140 . Mol. Endocrinol. . 15 . 4 . 501–11 . April 2001 . 11266503 . 10.1210/mend.15.4.0624 . free .
15. Pozuelo Rubio M, Peggie M, Wong BH, Morrice N, MacKintosh C . 14-3-3s regulate fructose-2,6-bisphosphate levels by binding to PKB-phosphorylated cardiac fructose-2,6-bisphosphate kinase/phosphatase . EMBO J. . 22 . 14 . 3514–23 . July 2003 . 12853467 . 165633 . 10.1093/emboj/cdg363 .
16. Storz P, Hausser A, Link G, Dedio J, Ghebrehiwet B, Pfizenmaier K, Johannes FJ . Protein kinase C [micro] is regulated by the multifunctional chaperon protein p32 . J. Biol. Chem. . 275 . 32 . 24601–7 . August 2000 . 10831594 . 10.1074/jbc.M002964200 . free .
17. Hausser A, Storz P, Link G, Stoll H, Liu YC, Altman A, Pfizenmaier K, Johannes FJ . Protein kinase C mu is negatively regulated by 14-3-3 signal transduction proteins . J. Biol. Chem. . 274 . 14 . 9258–64 . April 1999 . 10092600 . 10.1074/jbc.274.14.9258. free .
18. Seimiya H, Sawada H, Muramatsu Y, Shimizu M, Ohko K, Yamane K, Tsuruo T . Involvement of 14-3-3 proteins in nuclear localization of telomerase . EMBO J. . 19 . 11 . 2652–61 . June 2000 . 10835362 . 212742 . 10.1093/emboj/19.11.2652 .
19. Pierrat B, Ito M, Hinz W, Simonen M, Erdmann D, Chiesi M, Heim J . Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family . Eur. J. Biochem. . 267 . 9 . 2680–7 . May 2000 . 10785390 . 10.1046/j.1432-1327.2000.01285.x.