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Gene Review

Capn1  -  calpain 1, (mu/I) large subunit

Rattus norvegicus

Synonyms: CANP 1, Calcium-activated neutral proteinase 1, Calpain mu-type, Calpain-1 catalytic subunit, Calpain-1 large subunit, ...
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Disease relevance of Capn1


Psychiatry related information on Capn1


High impact information on Capn1

  • The protease region is not affected by the endogenous inhibitor, calpastatin, and may contribute to calpain-mediated pathologies when the core is released by autoproteolysis [8].
  • Here we show that activation of the protease core of mu calpain requires cooperative binding of two Ca(2+) atoms at two non-EF-hand sites revealed in the 2.1 A crystal structure [8].
  • A Ca(2+) switch aligns the active site of calpain [8].
  • Conservation of the Ca(2+) binding residues defines an ancestral general mechanism of activation for most calpain isoforms, including some that lack EF-hand domains [8].
  • The putative protein revealed a potential calmodulin-binding site and six regions with amino acid compositions (PEST regions) common to proteins that are susceptible to calpain [9].

Chemical compound and disease context of Capn1


Biological context of Capn1


Anatomical context of Capn1

  • Force-[Ca2+] relations were compared before and 5 to 30 minutes after direct exposure of skinned trabeculae to calpain I (18 microgram/mL, 20 minutes at [Ca2+]=10.8 micromol/L), a Ca2+-activated protease that is present in myocardium [14].
  • Nerve growth factor-induced decrease in the calpain activity of PC12 cells [15].
  • Both the decrease in calpain activity and the growth of neurites are reversible upon the removal of nerve growth factor from the cultures [15].
  • Double labeling of calpain I and phosphorylated tau (AT8) in the same cells of spinal cord lesion further implicated pathogenesis of SCI [2].
  • Calpain expression varies among different rat and bovine central nervous system regions [16].

Associations of Capn1 with chemical compounds


Physical interactions of Capn1

  • Although calpastatin by complexing initially to calpain can prevent the association of this protease with subcellular organelles, it cannot dissociate calpains already bound to these subcellular fractions [19].
  • More importantly, calpain activation resulted in the disruption of GRIP binding to the GluR2 subunit of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors [20].

Enzymatic interactions of Capn1


Regulatory relationships of Capn1

  • Calpastatin-containing fractions from extracts of nerve growth factor-treated cells inhibit more calpain activity than do comparable fractions from control cells [15].
  • In conclusion, proteolysis of calpastatin by caspase 3 may regulate calpain activity during I/R injury [26].
  • The down-regulation of NMDAR current was blocked by bath application of selective calpain inhibitors [27].
  • Our results showed that calpain can down-regulate the caspase-9/caspase-3 cell death pathway during neurodegeneration due to chronic mitochondrial defects in vivo and that this effect may involve, at least in part, direct cleavage of the caspase-3 p20 subunit [28].
  • The data suggest that synaptobrevin, syntaxin, and SNAP-25 are subject to proteolytic modification by activated calpain in intact type II cells stimulated for secretion [29].

Other interactions of Capn1


Analytical, diagnostic and therapeutic context of Capn1


  1. Dissociation and aggregation of calpain in the presence of calcium. Pal, G.P., Elce, J.S., Jia, Z. J. Biol. Chem. (2001) [Pubmed]
  2. Calpain inhibitor inhibits p35-p25-Cdk5 activation, decreases tau hyperphosphorylation, and improves neurological function after spinal cord hemisection in rats. Hung, K.S., Hwang, S.L., Liang, C.L., Chen, Y.J., Lee, T.H., Liu, J.K., Howng, S.L., Wang, C.H. J. Neuropathol. Exp. Neurol. (2005) [Pubmed]
  3. A calpain inhibitor attenuates cortical cytoskeletal protein loss after experimental traumatic brain injury in the rat. Posmantur, R., Kampfl, A., Siman, R., Liu, J., Zhao, X., Clifton, G.L., Hayes, R.L. Neuroscience (1997) [Pubmed]
  4. Calpain activity and expression are increased in splenic inflammatory cells associated with experimental allergic encephalomyelitis. Shields, D.C., Schaecher, K.E., Goust, J.M., Banik, N.L. J. Neuroimmunol. (1999) [Pubmed]
  5. beta-Amyloid (1-40)-induced apoptosis of cultured cortical neurones involves calpain-mediated cleavage of poly-ADP-ribose polymerase. Boland, B., Campbell, V. Neurobiol. Aging (2003) [Pubmed]
  6. Minocycline in phenotypic models of Huntington's disease. Bantubungi, K., Jacquard, C., Greco, A., Pintor, A., Chtarto, A., Tai, K., Galas, M.C., Tenenbaum, L., Déglon, N., Popoli, P., Minghetti, L., Brouillet, E., Brotchi, J., Levivier, M., Schiffmann, S.N., Blum, D. Neurobiol. Dis. (2005) [Pubmed]
  7. Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy. Medina, R., Wing, S.S., Goldberg, A.L. Biochem. J. (1995) [Pubmed]
  8. A Ca(2+) switch aligns the active site of calpain. Moldoveanu, T., Hosfield, C.M., Lim, D., Elce, J.S., Jia, Z., Davies, P.L. Cell (2002) [Pubmed]
  9. Molecular cloning and expression of a complementary DNA for inositol 1,4,5-trisphosphate 3-kinase. Choi, K.Y., Kim, H.K., Lee, S.Y., Moon, K.H., Sim, S.S., Kim, J.W., Chung, H.K., Rhee, S.G. Science (1990) [Pubmed]
  10. Transcriptional and translational regulation of calpain in the rat heart after myocardial infarction--effects of AT(1) and AT(2) receptor antagonists and ACE inhibitor. Sandmann, S., Yu, M., Unger, T. Br. J. Pharmacol. (2001) [Pubmed]
  11. Diverse stimuli induce calpain overexpression and apoptosis in C6 glioma cells. Ray, S.K., Wilford, G.G., Crosby, C.V., Hogan, E.L., Banik, N.L. Brain Res. (1999) [Pubmed]
  12. Characterization and regulation of lens-specific calpain Lp82. Fukiage, C., Nakajima, E., Ma, H., Azuma, M., Shearer, T.R. J. Biol. Chem. (2002) [Pubmed]
  13. Dysregulation of the calpain-calpastatin system plays a role in the development of cerulein-induced acute pancreatitis in the rat. Weber, H., Jonas, L., Hühns, S., Schuff-Werner, P. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  14. Intrinsic myofilament alterations underlying the decreased contractility of stunned myocardium. A consequence of Ca2+-dependent proteolysis? Gao, W.D., Liu, Y., Mellgren, R., Marban, E. Circ. Res. (1996) [Pubmed]
  15. Nerve growth factor-induced decrease in the calpain activity of PC12 cells. Oshima, M., Koizumi, S., Fujita, K., Guroff, G. J. Biol. Chem. (1989) [Pubmed]
  16. Calpain expression varies among different rat and bovine central nervous system regions. Shields, D.C., Ray, S.K., Gantt-Wilford, G., Banik, N.L. J. Neurosci. Res. (1998) [Pubmed]
  17. Oxidized lipoproteins inhibit surfactant phosphatidylcholine synthesis via calpain-mediated cleavage of CTP:phosphocholine cytidylyltransferase. Zhou, J., Ryan, A.J., Medh, J., Mallampalli, R.K. J. Biol. Chem. (2003) [Pubmed]
  18. Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC12 cells. Ray, S.K., Fidan, M., Nowak, M.W., Wilford, G.G., Hogan, E.L., Banik, N.L. Brain Res. (2000) [Pubmed]
  19. Hydrophobic association of calpains with subcellular organelles. Compartmentalization of calpains and the endogenous inhibitor calpastatin in tissues. Gopalakrishna, R., Barsky, S.H. J. Biol. Chem. (1986) [Pubmed]
  20. Proteolysis of glutamate receptor-interacting protein by calpain in rat brain: implications for synaptic plasticity. Lu, X., Wyszynski, M., Sheng, M., Baudry, M. J. Neurochem. (2001) [Pubmed]
  21. Calpain-dependent proteolytic cleavage of the p35 cyclin-dependent kinase 5 activator to p25. Kusakawa, G., Saito, T., Onuki, R., Ishiguro, K., Kishimoto, T., Hisanaga, S. J. Biol. Chem. (2000) [Pubmed]
  22. Myosin-Va proteolysis by Ca2+/calpain in depolarized nerve endings from rat brain. Casaletti, L., Tauhata, S.B., Moreira, J.E., Larson, R.E. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  23. Calpain and mitochondria in ischemia/reperfusion injury. Chen, M., Won, D.J., Krajewski, S., Gottlieb, R.A. J. Biol. Chem. (2002) [Pubmed]
  24. Neuronal nitric oxide synthase and calmodulin-dependent protein kinase IIalpha undergo neurotoxin-induced proteolysis. Hajimohammadreza, I., Raser, K.J., Nath, R., Nadimpalli, R., Scott, M., Wang, K.K. J. Neurochem. (1997) [Pubmed]
  25. Accumulation of non-erythroid alpha II-spectrin and calpain-cleaved alpha II-spectrin breakdown products in cerebrospinal fluid after traumatic brain injury in rats. Pike, B.R., Flint, J., Dutta, S., Johnson, E., Wang, K.K., Hayes, R.L. J. Neurochem. (2001) [Pubmed]
  26. Downregulation of the calpain inhibitor protein calpastatin by caspases during renal ischemia-reperfusion. Shi, Y., Melnikov, V.Y., Schrier, R.W., Edelstein, C.L. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  27. Regulation of N-methyl-D-aspartate receptors by calpain in cortical neurons. Wu, H.Y., Yuen, E.Y., Lu, Y.F., Matsushita, M., Matsui, H., Yan, Z., Tomizawa, K. J. Biol. Chem. (2005) [Pubmed]
  28. In vivo calpain/caspase cross-talk during 3-nitropropionic acid-induced striatal degeneration: implication of a calpain-mediated cleavage of active caspase-3. Bizat, N., Hermel, J.M., Humbert, S., Jacquard, C., Créminon, C., Escartin, C., Saudou, F., Krajewski, S., Hantraye, P., Brouillet, E. J. Biol. Chem. (2003) [Pubmed]
  29. Proteolysis of synaptobrevin, syntaxin, and SNAP-25 in alveolar epithelial type II cells. Zimmerman, U.J., Malek, S.K., Liu, L., Li, H.L. IUBMB Life (1999) [Pubmed]
  30. Proteolysis of neuronal cytoskeletal proteins by calpain contributes to rat retinal cell death induced by hypoxia. Tamada, Y., Nakajima, E., Nakajima, T., Shearer, T.R., Azuma, M. Brain Res. (2005) [Pubmed]
  31. Glutamate-induced apoptosis in neuronal cells is mediated via caspase-dependent and independent mechanisms involving calpain and caspase-3 proteases as well as apoptosis inducing factor (AIF) and this process is inhibited by equine estrogens. Zhang, Y., Bhavnani, B.R. BMC neuroscience [electronic resource]. (2006) [Pubmed]
  32. 3-[2-[4-(3-Chloro-2-methylphenylmethyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole Dihydro-chloride 3.5 Hydrate (DY-9760e) Is Neuroprotective in Rat Microsphere Embolism: Role of the Cross-Talk between Calpain and Caspase-3 through Calpastatin. Han, F., Shirasaki, Y., Fukunaga, K. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
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