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Gene Review

Fkbp5  -  FK506 binding protein 5

Mus musculus

Synonyms: 51 kDa FK506-binding protein, 51 kDa FKBP, D17Ertd592e, Dit1, FK506-binding protein 5, ...
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Disease relevance of Fkbp5

  • We previously showed that CsA toxicity is mediated by ROS generation as well as by inhibition of peptidyl-prolyl cis-trans isomerase (PPIase) activity of CypA in CsA-treated myoblasts [FASEB J. 16 (2002) 1633] [1].
  • Fractionation of differentiating murine teratocarcinoma F9 cells and extraction of the nuclear/microsomal pellets with ethidium bromide led to the purification and microsequencing of the protein mCyP-S1, a novel cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase (PPIase). mCyP-S1 is a new member of the cyclophilin class of proteins [2].

High impact information on Fkbp5

  • Having observed FKBP51 synthesis early during adipogenesis, we tested the effects of three immunosuppressive drugs--cyclosporin A, FK506, and rapamycin--on the terminal-differentiation process [3].
  • Increased levels of mRNAs for serum glucocorticoid-inducible kinase 1 (Sgk) and FK506-binding protein 51 (Fkbp5) were observed before and after onset of neurological symptoms, but plasma glucocorticoid was not significantly elevated in Mecp2-null mice [4].
  • Human FKBP51 mRNA is expressed in a wide range of tissues, and the protein has peptidylprolyl isomerase activity that is inhibited by FK506 but not cyclosporine [5].
  • Importantly, Western blot (immunoblot) analysis showed that unlike all other FKBPs characterized to date, FKBP51 expression was largely restricted to T cells [6].
  • Expression of two of these genes, the calcium-binding protein S100P and the FK-506-binding protein FKBP51, was decreased following androgen-deprivation, subsequently reexpressed in CWR22-R at levels comparable with CWR22, and elevated further upon treatment with androgens [7].

Biological context of Fkbp5


Anatomical context of Fkbp5

  • Identification of a new FKBP that can mediate calcineurin inhibition and is restricted in its expression to T cells suggests that new immunosuppressive drugs may be identified that, by virtue of their specific interaction with FKBP51, would be targeted in their site of action [6].
  • The expression of human FKBP51 increased the EC50 for dexamethasone in COS-7 cells by less than 3-fold, compared with control [8].
  • In this report, we have demonstrated that elevated FKBP51 is the unequivocal cause of glucocorticoid resistance in SML in the following ways: 1) FK506 increased GR binding in cytosol from SML in a concentration-dependent manner, an effect reproduced by rapamycin but not cyclosporin A [8].
  • 2) cytosol from COS-7 cells expressing squirrel monkey FKBP51 inhibited GR binding in cytosol from human lymphocytes by 74% [8].

Associations of Fkbp5 with chemical compounds

  • A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins [10].
  • However, the activity of a 3.4-kb fragment of the FKBP51 gene (FKBP5) promoter was only weakly increased by progestin and we show here that it is unresponsive to glucocorticoids and androgens [11].
  • Sodium salicylate induces the expression of the immunophilin FKBP51 and biglycan genes and inhibits p34cdc2 mRNA both in vitro and in vivo [9].
  • The circadian expression of Lpin1, FKBP51 and S-adenosyl methionine decarboxylase was also abolished in the ADX mice [12].

Other interactions of Fkbp5


  1. Transgenic mice overexpressing cyclophilin A are resistant to cyclosporin A-induced nephrotoxicity via peptidyl-prolyl cis-trans isomerase activity. Hong, F., Lee, J., Piao, Y.J., Jae, Y.K., Kim, Y.J., Oh, C., Seo, J.S., Yun, Y.S., Yang, C.W., Ha, J., Kim, S.S. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  2. Murine cyclophilin-S1: a variant peptidyl-prolyl isomerase with a putative signal sequence expressed in differentiating F9 cells. Schumacher, A., Schröter, H., Multhaup, G., Nordheim, A. Biochim. Biophys. Acta (1991) [Pubmed]
  3. Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells. Yeh, W.C., Bierer, B.E., McKnight, S.L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  4. Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett syndrome. Nuber, U.A., Kriaucionis, S., Roloff, T.C., Guy, J., Selfridge, J., Steinhoff, C., Schulz, R., Lipkowitz, B., Ropers, H.H., Holmes, M.C., Bird, A. Hum. Mol. Genet. (2005) [Pubmed]
  5. Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor. Nair, S.C., Rimerman, R.A., Toran, E.J., Chen, S., Prapapanich, V., Butts, R.N., Smith, D.F. Mol. Cell. Biol. (1997) [Pubmed]
  6. FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition. Baughman, G., Wiederrecht, G.J., Campbell, N.F., Martin, M.M., Bourgeois, S. Mol. Cell. Biol. (1995) [Pubmed]
  7. Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22-R1. Amler, L.C., Agus, D.B., LeDuc, C., Sapinoso, M.L., Fox, W.D., Kern, S., Lee, D., Wang, V., Leysens, M., Higgins, B., Martin, J., Gerald, W., Dracopoli, N., Cordon-Cardo, C., Scher, H.I., Hampton, G.M. Cancer Res. (2000) [Pubmed]
  8. Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding. Denny, W.B., Valentine, D.L., Reynolds, P.D., Smith, D.F., Scammell, J.G. Endocrinology (2000) [Pubmed]
  9. Sodium salicylate induces the expression of the immunophilin FKBP51 and biglycan genes and inhibits p34cdc2 mRNA both in vitro and in vivo. Silva, A.M., Reis, L.F. J. Biol. Chem. (2000) [Pubmed]
  10. A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. Davies, T.H., Ning, Y.M., Sánchez, E.R. J. Biol. Chem. (2002) [Pubmed]
  11. Intronic hormone response elements mediate regulation of FKBP5 by progestins and glucocorticoids. Hubler, T.R., Scammell, J.G. Cell Stress Chaperones (2004) [Pubmed]
  12. Genome-wide Expression Analysis Reveals 100 Adrenal Gland-dependent Circadian Genes in the Mouse Liver. Oishi, K., Amagai, N., Shirai, H., Kadota, K., Ohkura, N., Ishida, N. DNA Res. (2005) [Pubmed]
  13. FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506. Xu, X., Su, B., Barndt, R.J., Chen, H., Xin, H., Yan, G., Chen, L., Cheng, D., Heitman, J., Zhuang, Y., Fleischer, S., Shou, W. Transplantation (2002) [Pubmed]
  14. Regulation of gene expression by chronic morphine and morphine withdrawal in the locus ceruleus and ventral tegmental area. McClung, C.A., Nestler, E.J., Zachariou, V. J. Neurosci. (2005) [Pubmed]
  15. Gene expression profiling of glucocorticoid-inhibited osteoblasts. Leclerc, N., Luppen, C.A., Ho, V.V., Nagpal, S., Hacia, J.G., Smith, E., Frenkel, B. J. Mol. Endocrinol. (2004) [Pubmed]
  16. Gene expression profiles highlight adaptive brain mechanisms in corticotropin releasing factor overexpressing mice. Peeters, P.J., Fierens, F.L., van den Wyngaert, I., Goehlmann, H.W., Swagemakers, S.M., Kass, S.U., Langlois, X., Pullan, S., Stenzel-Poore, M.P., Steckler, T. Brain Res. Mol. Brain Res. (2004) [Pubmed]
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