Encyclopedia of Metalloproteins

2013 Edition
| Editors: Robert H. Kretsinger, Vladimir N. Uversky, Eugene A. Permyakov


  • Jagoree Roy
  • Martha S. Cyert
Reference work entry
DOI: https://doi.org/10.1007/978-1-4614-1533-6_54



Calcineurin: Calcineurin is a phosphatase that reverses the modification of proteins by kinase-mediated phosphorylation on either serine or threonine residues. Calcineurin requires Ca2+ and Ca2+-bound calmodulin for full activity. In different classification systems, calcineurin has also been labeled as PP2B or PP3.

Immunosuppressant: Drugs that inhibit the function of the immune system are termed immunosuppressants. Two commonly used immunosuppressants are cyclosporin A and FK506 (also called tacrolimus). Both of these immunosuppressants are also inhibitors of calcineurin.

Docking site: Docking sites, also termed docking motifs, are short linear sequences, 4–8 amino acids in length, which are contained within a substrate protein and mediate the...

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  1. Agbas A, Hui D, Wang X, Tek V, Zaidi A, Michaelis EK (2007) Activation of brain calcineurin (Cn) by Cu-Zn superoxide dismutase (SOD1) depends on direct SOD1-Cn protein interactions occurring in vitro and in vivo. Biochem J 405:51–59PubMedGoogle Scholar
  2. Aramburu J, Rao A, Klee CB (2000) Calcineurin: from structure to function. Curr Top Cell Regul 36:237–295CrossRefPubMedGoogle Scholar
  3. Cervantes-Chavez JA, Ali S, Bakkeren G (2011) Response to environmental stresses, cell-wall integrity, and virulence are orchestrated through the calcineurin pathway in Ustilago hordei. Mol Plant Microbe Interact 24:219–232CrossRefPubMedGoogle Scholar
  4. Cousin MA, Robinson PJ (2001) The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis. Trends Neurosci 24:659–665CrossRefPubMedGoogle Scholar
  5. Crabtree GR, Schreiber SL (2009) SnapShot: Ca2 + −calcineurin-NFAT signaling. Cell 138:210CrossRefPubMedGoogle Scholar
  6. Cyert MS (2003) Calcineurin signaling in Saccharomyces cerevisiae: how yeast go crazy in response to stress. Biochem Biophys Res Commun 311:1143–1150CrossRefPubMedGoogle Scholar
  7. Erdmann F, Weiwad M, Kilka S, Karanik M, Patzel M, Baumgrass R, Liebscher J, Fischer G (2010) The novel calcineurin inhibitor CN585 has potent immunosuppressive properties in stimulated human T cells. J Biol Chem 285:1888–1898CrossRefPubMedGoogle Scholar
  8. Ghosh MC, Wang X, Li S, Klee C (2003) Regulation of calcineurin by oxidative stress. Methods Enzymol 366:289–304CrossRefPubMedGoogle Scholar
  9. Heineke J, Molkentin JD (2006) Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol 7:589–600CrossRefPubMedGoogle Scholar
  10. Heineke J, Auger-Messier M, Correll RN, Xu J, Benard MJ, Yuan W, Drexler H, Parise LV, Molkentin JD (2010) CIB1 is a regulator of pathological cardiac hypertrophy. Nat Med 16:872–879CrossRefPubMedGoogle Scholar
  11. Heit JJ (2007) Calcineurin/NFAT signaling in the beta-cell: From diabetes to new therapeutics. Bioessays 29:1011–1021CrossRefPubMedGoogle Scholar
  12. Kahl CR, Means AR (2003) Regulation of cell cycle progression by calcium/calmodulin-dependent pathways. Endocr Rev 24:719–736CrossRefPubMedGoogle Scholar
  13. Katanosaka Y, Iwata Y, Kobayashi Y, Shibasaki F, Wakabayashi S, Shigekawa M (2005) Calcineurin inhibits Na+/Ca2+ exchange in phenylephrine-treated hypertrophic cardiomyocytes. J Biol Chem 280:5764–5772CrossRefPubMedGoogle Scholar
  14. Kvajo M, McKellar H, Gogos JA (2010) Molecules, signaling, and schizophrenia. Curr Top Behav Neurosci 4:629–656CrossRefPubMedGoogle Scholar
  15. Lautermilch NJ, Spitzer NC (2000) Regulation of calcineurin by growth cone calcium waves controls neurite extension. J Neurosci 20:315–325PubMedGoogle Scholar
  16. Li H, Rao A, Hogan PG (2011) Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol 21:91–103CrossRefPubMedGoogle Scholar
  17. Liu JO (2003) Endogenous protein inhibitors of calcineurin. Biochem Biophys Res Commun 311:1103–1109CrossRefPubMedGoogle Scholar
  18. Mancini M, Toker A (2009) NFAT proteins: emerging roles in cancer progression. Nat Rev Cancer 9:810–820CrossRefPubMedGoogle Scholar
  19. Miyakawa T, Mizunuma M (2007) Physiological roles of calcineurin in Saccharomyces cerevisiae with special emphasis on its roles in G2/M cell-cycle regulation. Biosci Biotechnol Biochem 71:633–645CrossRefPubMedGoogle Scholar
  20. Mukherjee A, Soto C (2011) Role of calcineurin in neurodegeneration produced by misfolded proteins and endoplasmic reticulum stress. Curr Opin Cell Biol 23:223–230CrossRefPubMedGoogle Scholar
  21. Piña FJ, O’Donnell AF, Pagant S, Piao HL, Miller JP, Fields S, Miller EA, Cyert MS (2011) Hph1 and Hph2 are novel components of the Sec63/Sec62 posttranslational translocation complex that aid in vacuolar proton ATPase biogenesis. Eukaryot Cell 10:63–71CrossRefPubMedGoogle Scholar
  22. Roy J, Cyert MS (2009) Cracking the phosphatase code: docking interactions determine substrate specificity. Sci Signal 2:re9CrossRefPubMedGoogle Scholar
  23. Rusnak F, Mertz P (2000) Calcineurin: form and function. Physiol Rev 80:1483–1521PubMedGoogle Scholar
  24. Schiaffino S (2010) Fibre types in skeletal muscle: a personal account. Acta Physiol (Oxf) 199:451–463CrossRefGoogle Scholar
  25. Shi Y (2009) Serine/threonine phosphatases: mechanism through structure. Cell 139:468–484CrossRefPubMedGoogle Scholar
  26. Song HO, Ahnn J (2011) Calcineurin may regulate multiple endocytic processes in C. elegans. BMB Rep 44:96–101CrossRefPubMedGoogle Scholar
  27. Stie J, Fox D (2008) Calcineurin regulation in fungi and beyond. Eukaryot Cell 7:177–186CrossRefPubMedGoogle Scholar
  28. Takeo S, Hawley RS, Aigaki T (2010) Calcineurin and its regulation by Sra/RCAN is required for completion of meiosis in Drosophila. Dev Biol 344:957–967CrossRefPubMedGoogle Scholar
  29. Tandan S, Wang Y, Wang TT, Jiang N, Hall DD, Hell JW, Luo X, Rothermel BA, Hill JA (2009) Physical and functional interaction between calcineurin and the cardiac L-type Ca2+ channel. Circ Res 105:51–60CrossRefPubMedGoogle Scholar
  30. Wen Z, Han L, Bamburg JR, Shim S, Ming GL, Zheng JQ (2007) BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin. J Cell Biol 178:107–119CrossRefPubMedGoogle Scholar
  31. Wu X, Nguyen BC, Dziunycz P, Chang S, Brooks Y, Lefort K, Hofbauer GF, Dotto GP (2010) Opposing roles for calcineurin and ATF3 in squamous skin cancer. Nature 465:368–372CrossRefPubMedGoogle Scholar
  32. Zhang H, Zhao Q, Liu K, Zhang Z, Wang Y, Zheng X (2009) MgCRZ1, a transcription factor of Magnaporthe grisea, controls growth, development and is involved in full virulence. FEMS Microbiol Lett 293:160–169CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of BiologyStanford UniversityStanfordUSA