Gene Symbol: Capn2
Description: calpain 2
Alias: calpain-2 catalytic subunit, CANP 2, M-calpain, calcium-activated neutral proteinase 2, calpain 2, (m/II) large subunit, calpain II, calpain M-type, calpain-2 large subunit, millimolar-calpain
Species: rat
Products:     Capn2

Top Publications

  1. Tamada Y, Nakajima E, Nakajima T, Shearer T, Azuma M. Proteolysis of neuronal cytoskeletal proteins by calpain contributes to rat retinal cell death induced by hypoxia. Brain Res. 2005;1050:148-55 pubmed
    ..Calpain inhibitor SJA6017 may have potential for testing as a therapeutic agent against retinal pathologies such those caused by glaucoma, although future studies such as testing in in vivo animal models are required. ..
  2. Hosfield C, Elce J, Jia Z. Activation of calpain by Ca2+: roles of the large subunit N-terminal and domain III-IV linker peptides. J Mol Biol. 2004;343:1049-53 pubmed
    ..Differences in these interactions in mu-calpain and in calpain 3 are also consistent with their progressively lower K(d) values. ..
  3. Chang H, Zhang L, Xu P, Li Q, Sheng J, Wang Y, et al. Nuclear translocation of calpain-2 regulates propensity toward apoptosis in cardiomyocytes of tail-suspended rats. J Cell Biochem. 2011;112:571-80 pubmed publisher
    ..Larger intranuclear Ca(2+) further activates nuclear calpain-2 and hence induces cardiomyocyte apoptosis. ..
  4. Hood J, Logan B, Sinai A, Brooks W, Roszman T. Association of the calpain/calpastatin network with subcellular organelles. Biochem Biophys Res Commun. 2003;310:1200-12 pubmed
    ..Confocal microscopy reveals that calpain II colocalizes with the subcellular proteins calnexin and Rab6 in cells bound to laminin...
  5. Moldoveanu T, Gehring K, Green D. Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains. Nature. 2008;456:404-8 pubmed publisher
    ..Two regions target the penta-EF-hand domains of calpain and the third occupies the substrate-binding cleft, projecting a loop around the active site thiol to evade proteolysis. ..
  6. Sun M, Xu C. Neuroprotective mechanism of taurine due to up-regulating calpastatin and down-regulating calpain and caspase-3 during focal cerebral ischemia. Cell Mol Neurobiol. 2008;28:593-611 pubmed
  7. Li X, Li Y, Shan L, Shen E, Chen R, Peng T. Over-expression of calpastatin inhibits calpain activation and attenuates myocardial dysfunction during endotoxaemia. Cardiovasc Res. 2009;83:72-9 pubmed publisher
    ..The present study was to investigate the roles of calpain/calpastatin system in cardiomyocyte caspase-3 activation, TNF-alpha expression, and myocardial dysfunction during LPS stimulation...
  8. Huang C, Gurlo T, Haataja L, Costes S, Daval M, Ryazantsev S, et al. Calcium-activated calpain-2 is a mediator of beta cell dysfunction and apoptosis in type 2 diabetes. J Biol Chem. 2010;285:339-48 pubmed publisher
    ..Cleavage of alpha-spectrin, a marker of calpain hyperactivation, is increased in beta cells in T2DM. We conclude that overactivation of Ca(2+)-calpain pathways contributes to beta cell dysfunction and apoptosis in T2DM. ..
  9. Sultana T, Wahab Wahlgren A, Assmus M, Parvinen M, Weber G, Soder O. Expression and regulation of the prointerleukin-1alpha processing enzymes calpain I and II in the rat testis. Int J Androl. 2003;26:37-45 pubmed
    ..25-day-old rats, coinciding with important events of spermatogenesis and a gradual increase in IL-1alpha, while calpain II expression was constant...

More Information


  1. Morford L, Forrest K, Logan B, Overstreet L, Goebel J, Brooks W, et al. Calpain II colocalizes with detergent-insoluble rafts on human and Jurkat T-cells. Biochem Biophys Res Commun. 2002;295:540-6 pubmed
    ..In this study, we report the novel observation that calpain II, but not calpain I, associates with membrane lipid rafts on human peripheral blood T-cells and Jurkat cells...
  2. Kobeissy F, Liu M, Yang Z, Zhang Z, Zheng W, Glushakova O, et al. Degradation of βII-Spectrin Protein by Calpain-2 and Caspase-3 Under Neurotoxic and Traumatic Brain Injury Conditions. Mol Neurobiol. 2015;52:696-709 pubmed publisher
    ..This work extends on previous published work that discusses the interplay spectrin family (αII-spectrin and βII-spectrin) and their susceptibility to protease proteolysis and their implication to neuronal cell death mechanisms. ..
  3. Hosfield C, Elce J, Davies P, Jia Z. Crystal structure of calpain reveals the structural basis for Ca(2+)-dependent protease activity and a novel mode of enzyme activation. EMBO J. 1999;18:6880-9 pubmed
    ..This Ca(2+)-dependent activation mechanism is clearly distinct from those of classical proteases. ..
  4. Seinfeld J, Baudry N, Xu X, Bi X, Baudry M. Differential Activation of Calpain-1 and Calpain-2 following Kainate-Induced Seizure Activity in Rats and Mice. Eneuro. 2016;3: pubmed publisher
    ..In addition, calpain-1 knock-out mice exhibit increased long-term neurodegeneration in CA1, reinforcing the notion that calpain-1 activation is neuroprotective. ..
  5. Ozaki T, Yamashita T, Ishiguro S. Mitochondrial m-calpain plays a role in the release of truncated apoptosis-inducing factor from the mitochondria. Biochim Biophys Acta. 2009;1793:1848-59 pubmed publisher
    ..Our results demonstrated that mitochondrial m-calpain plays a role in the release of tAIF from mitochondria by cleaving VDAC, and tAIF is released through VDAC-Bax pores. ..
  6. Arthur J, Gauthier S, Elce J. Active site residues in m-calpain: identification by site-directed mutagenesis. FEBS Lett. 1995;368:397-400 pubmed
    ..Mutants Asn286Asp and Trp288Tyr had low activity, consistent with interaction of these residues with His262. ..
  7. Moldoveanu T, Hosfield C, Jia Z, Elce J, Davies P. Ca(2+)-induced structural changes in rat m-calpain revealed by partial proteolysis. Biochim Biophys Acta. 2001;1545:245-54 pubmed
    ..This result supports the hypothesis that Ca(2+) induces movement of domains I and II closer together to form the functional active site of calpain. ..
  8. Chung K, Park H, Jung S, Ha S, Yoo S, Woo H, et al. Calpain Determines the Propensity of Adult Hippocampal Neural Stem Cells to Autophagic Cell Death Following Insulin Withdrawal. Stem Cells. 2015;33:3052-64 pubmed publisher
    ..Our findings provide a novel insight into the complex mechanisms interconnecting autophagy and apoptosis and their roles in the regulation of NSC death. ..
  9. Enns D, Raastad T, Ugelstad I, Belcastro A. Calpain/calpastatin activities and substrate depletion patterns during hindlimb unweighting and reweighting in skeletal muscle. Eur J Appl Physiol. 2007;100:445-55 pubmed
    ..83, P < 0.001). The results suggest that calpain activation is an early event during unloading in skeletal muscle, and that the majority of the increase in calpain activity can be attributed to the micro-isoform. ..
  10. Zhang H, Chang L, Zhang H, Nie J, Zhang Z, Yang X, et al. Calpain-2/p35-p25/Cdk5 pathway is involved in the neuronal apoptosis induced by polybrominated diphenyl ether-153. Toxicol Lett. 2017;277:41-53 pubmed publisher
    ..Overall, the findings suggested that calpain-2/p35-p25/Cdk5 pathway was involved in BDE-153-induced neuronal apoptosis, which provides novel insight into the mechanisms of PBDE neurotoxicity. ..
  11. Luke C, Pak S, Askew Y, Naviglia T, Askew D, Nobar S, et al. An intracellular serpin regulates necrosis by inhibiting the induction and sequelae of lysosomal injury. Cell. 2007;130:1108-19 pubmed
    ..These findings suggest that multiple noxious stimuli converge upon a peptidase-driven, core stress response pathway that, in the absence of serpin regulation, triggers a lysosomal-dependent necrotic cell death routine. ..
  12. Zang Y, Chen S, Liao G, Zhu H, Wei X, Cui Y, et al. Calpain-2 contributes to neuropathic pain following motor nerve injury via up-regulating interleukin-6 in DRG neurons. Brain Behav Immun. 2015;44:37-47 pubmed publisher
    ..Taken together, the early increase of calpain-2 in L5-VRT rats might be responsible for the induction of allodynia via up-regulating IL-6 in DRG neurons. ..
  13. Miao Y, Dong L, Chen J, Hu X, Yang X, Wang Z. Involvement of calpain/p35-p25/Cdk5/NMDAR signaling pathway in glutamate-induced neurotoxicity in cultured rat retinal neurons. PLoS ONE. 2012;7:e42318 pubmed publisher
    ..All these results suggest that the activation of the calpain/p35-p25/Cdk5 signaling pathway may contribute to glutamate neurotoxicity in the retina by up-regulating p-NR2A(S1232) expression. ..
  14. Hernando V, Inserte J, Sartório C, Parra V, Poncelas Nozal M, Garcia Dorado D. Calpain translocation and activation as pharmacological targets during myocardial ischemia/reperfusion. J Mol Cell Cardiol. 2010;49:271-9 pubmed publisher
  15. Hanna R, Campbell R, Davies P. Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin. Nature. 2008;456:409-12 pubmed publisher
  16. Vermaelen M, Sirvent P, Raynaud F, Astier C, Mercier J, Lacampagne A, et al. Differential localization of autolyzed calpains 1 and 2 in slow and fast skeletal muscles in the early phase of atrophy. Am J Physiol Cell Physiol. 2007;292:C1723-31 pubmed
    ..Moreover, the activation of proteolytic pathways appears to differ in slow and fast muscles, and the proteolytic mechanisms involved in fast-type muscle atrophy remain unclear...
  17. Hosfield C, Moldoveanu T, Davies P, Elce J, Jia Z. Calpain mutants with increased Ca2+ sensitivity and implications for the role of the C(2)-like domain. J Biol Chem. 2001;276:7404-7 pubmed
  18. Sprague C, Fraley T, Jang H, Lal S, Greenwood J. Phosphoinositide binding to the substrate regulates susceptibility to proteolysis by calpain. J Biol Chem. 2008;283:9217-23 pubmed publisher
    ..In conclusion, phosphoinositide binding to the substrate is a potential mechanism for regulating susceptibility to proteolysis by calpain. ..
  19. Hanna R, Garcia Diaz B, Davies P. Calpastatin simultaneously binds four calpains with different kinetic constants. FEBS Lett. 2007;581:2894-8 pubmed
    ..Their K(d) values ranged from picomolar to nanomolar in the order CAST1>4>3>2. They have similar k(on) values but the k(off) values ranged over three orders of magnitude and can account for the differences in affinity. ..
  20. Zhang Z, Ottens A, Sadasivan S, Kobeissy F, Fang T, Hayes R, et al. Calpain-mediated collapsin response mediator protein-1, -2, and -4 proteolysis after neurotoxic and traumatic brain injury. J Neurotrauma. 2007;24:460-72 pubmed
    ..It is possible that the calpain-mediated truncation of CRMPs following TBI may be an inhibiting factor for post-injury neurite regeneration. ..
  21. Bevers M, Ingleton L, Che D, Cole J, Li L, Da T, et al. RNAi targeting micro-calpain increases neuron survival and preserves hippocampal function after global brain ischemia. Exp Neurol. 2010;224:170-7 pubmed publisher
    ..These findings represent the first in vivo evidence that reducing expression of an individual calpain isoform can decrease post-ischemic neuronal death and preserve hippocampal function. ..
  22. Chang H, Sheng J, Zhang L, Yue Z, Jiao B, Li J, et al. ROS-Induced Nuclear Translocation of Calpain-2 Facilitates Cardiomyocyte Apoptosis in Tail-Suspended Rats. J Cell Biochem. 2015;116:2258-69 pubmed publisher
    ..Therefore, calpain-2 may represent a potentially therapeutic target for prevention of oxidative stress-associated cardiomyocyte apoptosis. ..
  23. Heimann P, Kuschel T, Jockusch H. Elimination by necrosis, not apoptosis, of embryonic extraocular muscles in the muscular dysgenesis mutant of the mouse. Cell Tissue Res. 2004;315:243-7 pubmed
    ..MDG myotubes in situ are eliminated by necrosis, not apoptosis. ..
  24. Arnandis T, Ferrer Vicens I, García Trevijano E, Miralles V, Garcia C, Torres L, et al. Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization. Cell Death Differ. 2012;19:1536-48 pubmed publisher
    ..These results suggest that CAPNs are responsible for mitochondrial and lysosomal membrane permeabilization, supporting the idea that lysosomal-mediated cell death is a new hallmark of mammary gland involution. ..
  25. Chou J, Impens F, Gevaert K, Davies P. m-Calpain activation in vitro does not require autolysis or subunit dissociation. Biochim Biophys Acta. 2011;1814:864-72 pubmed publisher
    ..We propose a model for m-calpain activation that does not involve either autolysis or subunit dissociation. ..
  26. Ozaki T, Yamashita T, Ishiguro S. Ca²+-induced release of mitochondrial m-calpain from outer membrane with binding of calpain small subunit and Grp75. Arch Biochem Biophys. 2011;507:254-61 pubmed publisher
    ..Our results showed that the activating mechanism of mitochondrial OM-bound m-calpain and the release of mitochondrial m-calpain from the OM have important implications in facilitating apoptotic cell death. ..
  27. Raynaud F, Marcilhac A, Chebli K, Benyamin Y, Rossel M. Calpain 2 expression pattern and sub-cellular localization during mouse embryogenesis. Int J Dev Biol. 2008;52:383-8 pubmed publisher calpain has been shown in various cell types; however, no data are available concerning calpain 2 (capn2) localization in embryonic tissues...
  28. Dutt P, Croall D, Arthur J, Veyra T, Williams K, Elce J, et al. m-Calpain is required for preimplantation embryonic development in mice. BMC Dev Biol. 2006;6:3 pubmed
    ..These heterodimeric enzymes are composed of distinct catalytic subunits, encoded by Capn1 (mu-calpain) or Capn2 (m-calpain), and a common regulatory subunit encoded by Capn4...
  29. DeLuca C, Davies P, Samis J, Elce J. Molecular cloning and bacterial expression of cDNA for rat calpain II 80 kDa subunit. Biochim Biophys Acta. 1993;1216:81-93 pubmed
    The complete cDNA of 3.2 kb for rat calpain II large subunit has been constructed from library- and polymerase chain reaction-derived fragments, and sequenced...
  30. Joffroy S, Dourdin N, Delage J, Cottin P, Koenig J, Brustis J. M-calpain levels increase during fusion of myoblasts in the mutant muscular dysgenesis (mdg) mouse. Int J Dev Biol. 2000;44:421-8 pubmed
    ..Taking into account these observations, it is clear from our data that the muscular dysgenesis mouse provides a relevant model to study myoblast fusion and that m-calpain is involved in this process. ..
  31. Brule C, Dargelos E, Diallo R, Listrat A, Bechet D, Cottin P, et al. Proteomic study of calpain interacting proteins during skeletal muscle aging. Biochimie. 2010;92:1923-33 pubmed publisher
    ..Such interactions would suggest that calpains are implicated in many processes altered during aging including cytoskeletal disorganisation and mitochondrial dysfunction. ..
  32. Sheng J, Chang H, Yu Z. Nuclear Translocation of Calpain-2 Mediates Apoptosis of Hypertrophied Cardiomyocytes in Transverse Aortic Constriction Rat. J Cell Physiol. 2015;230:2743-54 pubmed publisher
    ..In conclusion, hypertrophied cardiomyocytes show increased susceptibility to apoptosis during Ang II stimulation via nuclear calpain-2 and CaMKIIδB pathway. ..
  33. Silver K, Littlejohn A, Thomas L, Bawa B, Lillich J. Suppression of calpain expression by NSAIDs is associated with inhibition of cell migration in rat duodenum. Toxicology. 2017;383:1-12 pubmed publisher
    ..Our results are supportive of the hypothesis that suppression of calpain expression leading to slowing of cell migration is a potential mechanism through which NSAIDs cause GI toxicity. ..
  34. Graham Siegenthaler K, Gauthier S, Davies P, Elce J. Active recombinant rat calpain II. Bacterially produced large and small subunits associate both in vivo and in vitro. J Biol Chem. 1994;269:30457-60 pubmed
    ..Rat calpain II large subunit (80 kDa) was produced from a cDNA clone in E...
  35. Kaneko Y, Murphy C, Day M. Calpain 2 activity increases at the time of implantation in rat uterine luminal epithelial cells and administration of calpain inhibitor significantly reduces implantation sites. Histochem Cell Biol. 2014;141:423-30 pubmed publisher
    ..The present study suggests a role for calpain 2 in the disassembly of focal adhesions, which has been previously shown to play a key role in uterine receptivity for implantation. ..
  36. Alexa A, Bozoky Z, Farkas A, Tompa P, Friedrich P. Contribution of distinct structural elements to activation of calpain by Ca2+ ions. J Biol Chem. 2004;279:20118-26 pubmed
    ..A schematic model of this "extended transducer" mechanism is presented. ..
  37. Weber H, Jonas L, Hühns S, Schuff Werner P. Dysregulation of the calpain-calpastatin system plays a role in the development of cerulein-induced acute pancreatitis in the rat. Am J Physiol Gastrointest Liver Physiol. 2004;286:G932-41 pubmed
    ..05), histological score for eight parameters (P < 0.01), and actin filament alterations. Our findings support the hypothesis that dysregulation of the calpain-calpastatin system may play a role in the onset of acute pancreatitis. ..
  38. Weber H, Muller L, Jonas L, Schult C, Sparmann G, Schuff Werner P. Calpain mediates caspase-dependent apoptosis initiated by hydrogen peroxide in pancreatic acinar AR42J cells. Free Radic Res. 2013;47:432-46 pubmed publisher
    ..The findings also suggest that calpain may be involved in the execution phase of apoptosis. ..
  39. Wang C, Huang Y. Calpain 2 activated through N-methyl-D-aspartic acid receptor signaling cleaves CPEB3 and abrogates CPEB3-repressed translation in neurons. Mol Cell Biol. 2012;32:3321-32 pubmed publisher
    ..As a result, the calpain 2-cleaved CPEB3 fragment binds to RNA but fails to repress translation. Therefore, the cleavage of CPEB3 by NMDA-activated calpain 2 accounts for the activity-related translation of CPEB3-targeted RNAs. ..
  40. Xu P, Li Q, Sheng J, Chang H, Song Z, Yu Z. Passive stretch reduces calpain activity through nitric oxide pathway in unloaded soleus muscles. Mol Cell Biochem. 2012;367:113-24 pubmed publisher
    ..Therefore, stretch can resist in part atrophy of unloaded soleus muscles. ..
  41. Huang Z, Hoffmann F, Norton R, Hashimoto A, Hoffmann P. Selenoprotein K is a novel target of m-calpain, and cleavage is regulated by Toll-like receptor-induced calpastatin in macrophages. J Biol Chem. 2011;286:34830-8 pubmed publisher
    ..Overall, our findings identify SelK as a novel calpain target and reveal dynamic changes in the calpain/calpastatin system during TLR-induced activation of macrophages. ..
  42. Xu P, Song Z, Li Q, Zhang L, Wang Y, Yu Z. [Calpain mediates cardiac troponin I degradation in tail-suspended rats]. Sheng Li Xue Bao. 2010;62:415-20 pubmed
    ..01). These results suggest that an increase in calpain activity may enhance cTnI degradation in the myocardium of tail-suspended rats. ..