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Gene Review

Calm1  -  calmodulin 1

Mus musculus

Synonyms: AI256814, AI327027, AI461935, AL024000, CaM, ...
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Disease relevance of Calm1


Psychiatry related information on Calm1


High impact information on Calm1

  • Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has been implicated in the regulation of CRE-dependent transcription [8].
  • To explore the role of protein kinase A (PKA) in the late phase of long-term potentiation (L-LTP) and memory, we generated transgenic mice that express R(AB), an inhibitory form of the regulatory subunit of PKA, only in the hippocampus and other forebrain regions by using the promoter from the gene encoding Ca2+/ calmodulin protein kinase IIalpha [9].
  • MARCKS is a specific protein kinase C (PKC) substrate that binds both calmodulin and actin and is phosphorylated during phagocyte activation, neurosecretion, and growth factor-dependent mitogenesis [10].
  • Our data suggest the existence of a family of PKC substrates that are targeted to different subcellular locations and that function to integrate PKC and calcium/calmodulin-dependent signals in the control of the plastic actin cytoskeleton [10].
  • Calmodulin is implicated as the primary transducer of the calcium signal in pancreatic beta cells, where it is present at very high concentrations [11].

Chemical compound and disease context of Calm1


Biological context of Calm1


Anatomical context of Calm1

  • Calmodulin prevents activation of Ras by PKC in 3T3 fibroblasts [17].
  • We conclude that calmodulin may serve a vital regulatory function to direct the localization of Akt to the plasma membrane for its activation by PI-3 kinase [18].
  • These results imply that calcium/calmodulin may be a common regulator of Akt activation, irrespective of upstream receptor activator, mammalian species, and transformation status in mammary epithelial cells [18].
  • These results indicate that free histone H1 levels may specifically affect the ability of CaM to activate its target enzymes and suggests a novel level of control of CaM-dependent enzymes in eukaryotic cells [19].
  • CaM and CaMKII antagonists, using the newborn mouse calvaria in vivo model, cause a 50% decrease in osteoblast number (N.Ob-BS) and a 32% decrease in mineralization (BV/TV) [22].

Associations of Calm1 with chemical compounds


Physical interactions of Calm1

  • The murine Golli-MBP isoform J37 has also been shown to bind CaM in vitro, and an interaction site was predicted in the N-terminal Golli-specific portion of the protein [25].
  • Consequently, calmodulin binding is probably not required for the participation of AS160 in insulin-stimulated GLUT4 translocation [26].
  • Following basal autophosphorylation, the calmodulin-binding ability of CaMKII was also reduced, presumably accounting for the observed inactivation [27].
  • By using the yeast two-hybrid system, we found that calmodulin interacts with the COOH terminus of the NR1 subunit and inactivates the channels in a Ca2+-dependent manner [28].
  • Furthermore, the calmodulin-binding domain found in eukaryotic HSP70s is also the target for binding of Bag-1 - an enhancer of ADP/ATP exchange activity of Hsp70s [29].
  • Mutagenesis of CCTalpha Gln(243) not only resulted in loss of CaM binding but also led to complete calpain resistance in vitro and in vivo [30].

Enzymatic interactions of Calm1

  • Calmodulin-dependent protein kinases phosphorylate gp130 at the serine-based dileucine internalization motif [31].
  • We found that AMPA receptor (AMPAR) glutamate receptor 1 (GluR1) subunits are persistently dephosphorylated in slices maintained in vitro for up to 8 h. alpha calcium/calmodulin-dependent kinase II (alphaCamKII) was also strongly dephosphorylated during the first 3 h in vitro but thereafter recovered to near control levels [32].
  • Calcium/calmodulin-dependent protein kinase IV is cleaved by caspase-3 and calpain in SH-SY5Y human neuroblastoma cells undergoing apoptosis [33].
  • L-NG-Nitroarginine (NA) inhibited both the L-arginine oxidation and the L-arginine-independent NADPH oxidation reactions catalyzed by the calcium/calmodulin-dependent constitutive nitric oxide synthase (cNOS) from bovine brain [34].

Co-localisations of Calm1

  • No role has been assigned to the 66-, 44-, or 13-kDa proteins but the 50-kDa band comigrates with tubulin and the 18-kDa band comigrates with calmodulin [35].

Regulatory relationships of Calm1


Other interactions of Calm1

  • These results implicate calcium/calmodulin in the activation of Akt in these cells [18].
  • These data are consistent with the regulation of EGFR by calmodulin at several steps of the receptor signaling and trafficking pathways [40].
  • Reconstitution studies reveal that recombinant c-Raf kinase can associate directly with Cam in a Ca2+-dependent manner and this interaction is reduced in vitro by addition of W7 [23].
  • These findings suggested that membrane depolarization regulates the NPY gene transcription positively through the unique CaMRE by activation of CaM kinases following Ca entry through L-type Ca channels [41].
  • The results obtained confirmed the appropriate utilisation of simple residue substitutions to mimic the natural modifications, and demonstrated molecular mechanisms by which MBP-CaM interactions could be modulated in vivo [25].

Analytical, diagnostic and therapeutic context of Calm1


  1. Genes newly identified as regulated by glucocorticoids in murine thymocytes. Baughman, G., Harrigan, M.T., Campbell, N.F., Nurrish, S.J., Bourgeois, S. Mol. Endocrinol. (1991) [Pubmed]
  2. The role of calmodulin in the regulation of osteoclastogenesis. Zhang, L., Feng, X., McDonald, J.M. Endocrinology (2003) [Pubmed]
  3. Calmodulin kinase II inhibition protects against structural heart disease. Zhang, R., Khoo, M.S., Wu, Y., Yang, Y., Grueter, C.E., Ni, G., Price, E.E., Thiel, W., Guatimosim, S., Song, L.S., Madu, E.C., Shah, A.N., Vishnivetskaya, T.A., Atkinson, J.B., Gurevich, V.V., Salama, G., Lederer, W.J., Colbran, R.J., Anderson, M.E. Nat. Med. (2005) [Pubmed]
  4. Calsarcins, a novel family of sarcomeric calcineurin-binding proteins. Frey, N., Richardson, J.A., Olson, E.N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. Ventricular arrhythmias, increased cardiac calmodulin kinase II expression, and altered repolarization kinetics in ANP receptor deficient mice. Kirchhof, P., Fabritz, L., Kilić, A., Begrow, F., Breithardt, G., Kuhn, M. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  6. Derangements of hippocampal calcium/calmodulin-dependent protein kinase II in a mouse model for Angelman mental retardation syndrome. Weeber, E.J., Jiang, Y.H., Elgersma, Y., Varga, A.W., Carrasquillo, Y., Brown, S.E., Christian, J.M., Mirnikjoo, B., Silva, A., Beaudet, A.L., Sweatt, J.D. J. Neurosci. (2003) [Pubmed]
  7. The importance of calmodulin in the accessory olfactory bulb in the formation of an olfactory memory in mice. Nakazawa, H., Kaba, H., Higuchi, T., Inoue, S. Neuroscience (1995) [Pubmed]
  8. An important role of neural activity-dependent CaMKIV signaling in the consolidation of long-term memory. Kang, H., Sun, L.D., Atkins, C.M., Soderling, T.R., Wilson, M.A., Tonegawa, S. Cell (2001) [Pubmed]
  9. Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Abel, T., Nguyen, P.V., Barad, M., Deuel, T.A., Kandel, E.R., Bourtchouladze, R. Cell (1997) [Pubmed]
  10. MacMARCKS, a novel member of the MARCKS family of protein kinase C substrates. Li, J., Aderem, A. Cell (1992) [Pubmed]
  11. Calmodulin-induced early-onset diabetes in transgenic mice. Epstein, P.N., Overbeek, P.A., Means, A.R. Cell (1989) [Pubmed]
  12. Enhancement of sensitivity to adriamycin in resistant P388 leukemia by the calmodulin inhibitor trifluoperazine. Ganapathi, R., Grabowski, D. Cancer Res. (1983) [Pubmed]
  13. Enhancement of antineoplastic effects of cisplatin by calmodulin antagonists in nude mice bearing human ovarian carcinoma. Kikuchi, Y., Oomori, K., Kizawa, I., Hirata, J., Kita, T., Miyauchi, M., Kato, K. Cancer Res. (1987) [Pubmed]
  14. Fas binding to calmodulin regulates apoptosis in osteoclasts. Wu, X., Ahn, E.Y., McKenna, M.A., Yeo, H., McDonald, J.M. J. Biol. Chem. (2005) [Pubmed]
  15. Ca2+ x calmodulin prevents myristoylated alanine-rich kinase C substrate protein phosphorylation by protein kinase Cs in C6 rat glioma cells. Chakravarthy, B.R., Isaacs, R.J., Morley, P., Whitfield, J.F. J. Biol. Chem. (1995) [Pubmed]
  16. Effects of CGS 9343B (a putative calmodulin antagonist) on isolated skeletal muscle. Dissociation of signaling pathways for insulin-mediated activation of glycogen synthase and hexose transport. Shashkin, P., Koshkin, A., Langley, D., Ren, J.M., Westerblad, H., Katz, A. J. Biol. Chem. (1995) [Pubmed]
  17. Calmodulin prevents activation of Ras by PKC in 3T3 fibroblasts. Villalonga, P., López-Alcalá, C., Chiloeches, A., Gil, J., Marais, R., Bachs, O., Agell, N. J. Biol. Chem. (2002) [Pubmed]
  18. Calmodulin-mediated activation of Akt regulates survival of c-Myc-overexpressing mouse mammary carcinoma cells. Deb, T.B., Coticchia, C.M., Dickson, R.B. J. Biol. Chem. (2004) [Pubmed]
  19. Activation of calmodulin-dependent enzymes can be selectively inhibited by histone H1. Rasmussen, C., Garen, C. J. Biol. Chem. (1993) [Pubmed]
  20. Calmodulin-dependent protein kinase II triggers mouse egg activation and embryo development in the absence of Ca2+ oscillations. Knott, J.G., Gardner, A.J., Madgwick, S., Jones, K.T., Williams, C.J., Schultz, R.M. Dev. Biol. (2006) [Pubmed]
  21. Decreased calcium/calmodulin-dependent protein kinase II and protein kinase C activities mediate impairment of hippocampal long-term potentiation in the olfactory bulbectomized mice. Moriguchi, S., Han, F., Nakagawasai, O., Tadano, T., Fukunaga, K. J. Neurochem. (2006) [Pubmed]
  22. Calmodulin and calmodulin-dependent kinase IIalpha regulate osteoblast differentiation by controlling c-fos expression. Zayzafoon, M., Fulzele, K., McDonald, J.M. J. Biol. Chem. (2005) [Pubmed]
  23. Gonadotropin-releasing hormone induction of extracellular-signal regulated kinase is blocked by inhibition of calmodulin. Roberson, M.S., Bliss, S.P., Xie, J., Navratil, A.M., Farmerie, T.A., Wolfe, M.W., Clay, C.M. Mol. Endocrinol. (2005) [Pubmed]
  24. Suppression of dynamic Ca(2+) transient responses to pacing in ventricular myocytes from mice with genetic calmodulin kinase II inhibition. Wu, Y., Shintani, A., Grueter, C., Zhang, R., Hou, Y., Yang, J., Kranias, E.G., Colbran, R.J., Anderson, M.E. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  25. Electron paramagnetic resonance spectroscopy and molecular modelling of the interaction of myelin basic protein (MBP) with calmodulin (CaM)-diversity and conformational adaptability of MBP CaM-targets. Polverini, E., Boggs, J.M., Bates, I.R., Harauz, G., Cavatorta, P. J. Struct. Biol. (2004) [Pubmed]
  26. Calmodulin binds to the Rab GTPase activating protein required for insulin-stimulated GLUT4 translocation. Kane, S., Lienhard, G.E. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  27. Inactivation of Ca2+/calmodulin-dependent protein kinase II by basal autophosphorylation. Colbran, R.J. J. Biol. Chem. (1993) [Pubmed]
  28. Phosphorylation-dependent regulation of N-methyl-D-aspartate receptors by calmodulin. Hisatsune, C., Umemori, H., Inoue, T., Michikawa, T., Kohda, K., Mikoshiba, K., Yamamoto, T. J. Biol. Chem. (1997) [Pubmed]
  29. Identification of the divergent calmodulin binding motif in yeast Ssb1/Hsp75 protein and in other HSP70 family members. Heinen, R.C., Diniz-Mendes, L., Silva, J.T., Paschoalin, V.M. Braz. J. Med. Biol. Res. (2006) [Pubmed]
  30. Calmodulin binds and stabilizes the regulatory enzyme, CTP: phosphocholine cytidylyltransferase. Chen, B.B., Mallampalli, R.K. J. Biol. Chem. (2007) [Pubmed]
  31. Calmodulin-dependent protein kinases phosphorylate gp130 at the serine-based dileucine internalization motif. Gibson, R.M., Laszlo, G.S., Nathanson, N.M. Biochim. Biophys. Acta (2005) [Pubmed]
  32. Phosphorylation of proteins involved in activity-dependent forms of synaptic plasticity is altered in hippocampal slices maintained in vitro. Ho, O.H., Delgado, J.Y., O'Dell, T.J. J. Neurochem. (2004) [Pubmed]
  33. Calcium/calmodulin-dependent protein kinase IV is cleaved by caspase-3 and calpain in SH-SY5Y human neuroblastoma cells undergoing apoptosis. McGinnis, K.M., Whitton, M.M., Gnegy, M.E., Wang, K.K. J. Biol. Chem. (1998) [Pubmed]
  34. Selective inhibition of constitutive nitric oxide synthase by L-NG-nitroarginine. Furfine, E.S., Harmon, M.F., Paith, J.E., Garvey, E.P. Biochemistry (1993) [Pubmed]
  35. The in vivo biosynthesis of embryonic proteins after maternal administration of phenytoin in the mouse. Hicks, H.E., Banes, A.J. Proc. Soc. Exp. Biol. Med. (1985) [Pubmed]
  36. Calmodulin antagonists inhibit insulin-stimulated GLUT4 (glucose transporter 4) translocation by preventing the formation of phosphatidylinositol 3,4,5-trisphosphate in 3T3L1 adipocytes. Yang, C., Watson, R.T., Elmendorf, J.S., Sacks, D.B., Pessin, J.E. Mol. Endocrinol. (2000) [Pubmed]
  37. Calmodulin inhibitor W13 induces sustained activation of ERK2 and expression of p21(cip1). Bosch, M., Gil, J., Bachs, O., Agell, N. J. Biol. Chem. (1998) [Pubmed]
  38. Induction of the expression of the interleukin-1 beta gene in mouse spleen by ionizing radiation. Ishihara, H., Tsuneoka, K., Dimchev, A.B., Shikita, M. Radiat. Res. (1993) [Pubmed]
  39. Cytoplasmic polyadenylation element binding protein-dependent protein synthesis is regulated by calcium/calmodulin-dependent protein kinase II. Atkins, C.M., Nozaki, N., Shigeri, Y., Soderling, T.R. J. Neurosci. (2004) [Pubmed]
  40. Calmodulin regulates intracellular trafficking of epidermal growth factor receptor and the MAPK signaling pathway. Tebar, F., Villalonga, P., Sorkina, T., Agell, N., Sorkin, A., Enrich, C. Mol. Biol. Cell (2002) [Pubmed]
  41. Ca2+/calmodulin-dependent transcriptional activation of neuropeptide Y gene induced by membrane depolarization: determination of Ca(2+)- and cyclic AMP/phorbol 12-myristate 13-acetate-responsive elements. Higuchi, H., Nakano, K., Kim, C.H., Li, B.S., Kuo, C.H., Taira, E., Miki, N. J. Neurochem. (1996) [Pubmed]
  42. Binding of calmodulin to the carboxy-terminal region of p21 induces nuclear accumulation via inhibition of protein kinase C-mediated phosphorylation of Ser153. Rodríguez-Vilarrupla, A., Jaumot, M., Abella, N., Canela, N., Brun, S., Díaz, C., Estanyol, J.M., Bachs, O., Agell, N. Mol. Cell. Biol. (2005) [Pubmed]
  43. Three different calmodulin-encoding cDNAs isolated by a modified 5'-RACE using degenerate oligodeoxyribonucleotides. Skinner, T.L., Kerns, R.T., Bender, P.K. Gene (1994) [Pubmed]
  44. Calmodulin binds to K-Ras, but not to H- or N-Ras, and modulates its downstream signaling. Villalonga, P., López-Alcalá, C., Bosch, M., Chiloeches, A., Rocamora, N., Gil, J., Marais, R., Marshall, C.J., Bachs, O., Agell, N. Mol. Cell. Biol. (2001) [Pubmed]
  45. Bradykinin B2 receptors activate Na+/H+ exchange in mIMCD-3 cells via Janus kinase 2 and Ca2+/calmodulin. Mukhin, Y.V., Vlasova, T., Jaffa, A.A., Collinsworth, G., Bell, J.L., Tholanikunnel, B.G., Pettus, T., Fitzgibbon, W., Ploth, D.W., Raymond, J.R., Garnovskaya, M.N. J. Biol. Chem. (2001) [Pubmed]
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