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Gene Review

Rcan1  -  regulator of calcineurin 1

Mus musculus

Synonyms: 2410048A02Rik, AA408855, ADAPT78, AI429645, AL024459, ...
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Disease relevance of Dscr1

  • Our observations of calcineurin-and Nfatc-deficient mice, Dscr1- and Dyrk1a-overexpressing mice, mouse models of Down's syndrome and human trisomy 21 are consistent with these predictions [1].
  • Paradoxically, however, cardiac hypertrophy in response to pressure overload or chronic adrenergic stimulation was blunted in MCIP1(-/-) mice [2].
  • Subcellular fractionation of insulinoma cells showed CSP1 (34/36 kDa) in granular fractions; the membrane and cytosol fractions contained predominantly CSP2 (27 kDa) [3].

Psychiatry related information on Dscr1

  • Finally, mcip1/2-null mice displayed a neurologic phenotype that was similar to calcineurin Abeta-null mice, such as increased locomotor activity and impaired working memory [4].

High impact information on Dscr1

  • To determine the function of the calcipressins, a family of putative calcineurin inhibitors, we assessed the calcineurin-dependent process of T cell activation in mice engineered to lack the gene encoding calcipressin 1 (Csp1) [5].
  • In the absence of Csp1, the apparent transactivation thresholds for all these genes were shifted because of enhanced calcineurin activity [5].
  • The threshold pattern of calcineurin-dependent gene expression is altered by loss of the endogenous inhibitor calcipressin [5].
  • This response is accompanied by transformation of specialized myofiber subtypes, and is blocked either by cyclosporin A, a specific chemical inhibitor of calcineurin, or by forced expression of the endogenous calcineurin inhibitory protein, myocyte-enriched calcineurin interacting protein 1 [6].
  • Amperometric measurements showed a significant decrease in insulin exocytosis in individual INS-1 cells after CSP1 overexpression [3].

Biological context of Dscr1

  • We also show that although Dscr1 is present in trisomy in the Ts65Dn mouse, the adult brain expression pattern is not significantly altered [7].
  • This lethal phenotype contrasted with, and was surprising in light of, mouse models of Down syndrome where multiple chromosome 21 genes including Dscr1 are overexpressed and survive to term [8].
  • In the absence of stress, MCIP1(-/-) animals exhibited no overt phenotype [2].
  • However, the lack of MCIP1 exacerbated the hypertrophic response to activated calcineurin expressed from a muscle-specific transgene, consistent with a role of MCIP1 as a negative regulator of calcineurin signaling [2].
  • Moreover, CD4(+) T cells from mcip1/2-null mice showed enhanced apoptosis that was further increased by loss of calcineurin Abeta [4].

Anatomical context of Dscr1


Associations of Dscr1 with chemical compounds


Other interactions of Dscr1

  • Contractile components unique to type 1 slow fibers were absent from skeletal muscle of adult Myo-Cre/Flox-MCIP1 mice, whereas oxidative capacity, myoglobin content, and mitochondrial abundance were unaltered [11].
  • The soleus muscles of Myo-Cre/Flox-MCIP1 mice fatigued more rapidly than the wild type as a consequence of the replacement of the slow myosin heavy chain MyHC-1 with a fast isoform, MyHC-2A [11].
  • When administered at a dose of higher than 200mg/kg body wt. daily for 7 days, CSP-1 produced a significant drop in blood glucose level in both STZ-induced diabetic rats and alloxan-induced diabetic mice [10].

Analytical, diagnostic and therapeutic context of Dscr1


  1. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Arron, J.R., Winslow, M.M., Polleri, A., Chang, C.P., Wu, H., Gao, X., Neilson, J.R., Chen, L., Heit, J.J., Kim, S.K., Yamasaki, N., Miyakawa, T., Francke, U., Graef, I.A., Crabtree, G.R. Nature (2006) [Pubmed]
  2. Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy. Vega, R.B., Rothermel, B.A., Weinheimer, C.J., Kovacs, A., Naseem, R.H., Bassel-Duby, R., Williams, R.S., Olson, E.N. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  3. Cysteine string protein (CSP) is an insulin secretory granule-associated protein regulating beta-cell exocytosis. Brown, H., Larsson, O., Bränström, R., Yang, S.N., Leibiger, B., Leibiger, I., Fried, G., Moede, T., Deeney, J.T., Brown, G.R., Jacobsson, G., Rhodes, C.J., Braun, J.E., Scheller, R.H., Corkey, B.E., Berggren, P.O., Meister, B. EMBO J. (1998) [Pubmed]
  4. Modulatory calcineurin-interacting proteins 1 and 2 function as calcineurin facilitators in vivo. Sanna, B., Brandt, E.B., Kaiser, R.A., Pfluger, P., Witt, S.A., Kimball, T.R., van Rooij, E., De Windt, L.J., Rothenberg, M.E., Tschop, M.H., Benoit, S.C., Molkentin, J.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. The threshold pattern of calcineurin-dependent gene expression is altered by loss of the endogenous inhibitor calcipressin. Ryeom, S., Greenwald, R.J., Sharpe, A.H., McKeon, F. Nat. Immunol. (2003) [Pubmed]
  6. Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway. Wu, H., Rothermel, B., Kanatous, S., Rosenberg, P., Naya, F.J., Shelton, J.M., Hutcheson, K.A., DiMaio, J.M., Olson, E.N., Bassel-Duby, R., Williams, R.S. EMBO J. (2001) [Pubmed]
  7. Dscr1, a novel endogenous inhibitor of calcineurin signaling, is expressed in the primitive ventricle of the heart and during neurogenesis. Casas, C., Martínez, S., Pritchard, M.A., Fuentes, J.J., Nadal, M., Guimerà, J., Arbonés, M., Flórez, J., Soriano, E., Estivill, X., Alcántara, S. Mech. Dev. (2001) [Pubmed]
  8. DSCR1 (ADAPT78) lethality: evidence for a protective effect of trisomy 21 genes? Kluetzman, K.S., Perez, A.V., Crawford, D.R. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  9. The synaptic vesicle protein, cysteine-string protein, is associated with the plasma membrane in 3T3-L1 adipocytes and interacts with syntaxin 4. Chamberlain, L.H., Graham, M.E., Kane, S., Jackson, J.L., Maier, V.H., Burgoyne, R.D., Gould, G.W. J. Cell. Sci. (2001) [Pubmed]
  10. Hypoglycemic activity of polysaccharide, with antioxidation, isolated from cultured Cordyceps mycelia. Li, S.P., Zhang, G.H., Zeng, Q., Huang, Z.G., Wang, Y.T., Dong, T.T., Tsim, K.W. Phytomedicine (2006) [Pubmed]
  11. Calcineurin is necessary for the maintenance but not embryonic development of slow muscle fibers. Oh, M., Rybkin, I.I., Copeland, V., Czubryt, M.P., Shelton, J.M., van Rooij, E., Richardson, J.A., Hill, J.A., De Windt, L.J., Bassel-Duby, R., Olson, E.N., Rothermel, B.A. Mol. Cell. Biol. (2005) [Pubmed]
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