Genomes and Genes
Gene Symbol: Capn2
Description: calpain 2
Alias: AI326419, CALP80, Capa-2, Capa2, m-calpain, m-calpin, calpain-2 catalytic subunit, 80 kDa M-calpain subunit, CANP 2, calcium-activated neutral proteinase 2, calpain M-type, calpain-2 large subunit, cysteine proteinase, m-calpain 80 kDa large subunit, m-calpain large subunit, millimolar-calpain
- 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..by calpain has been shown in various cell types; however, no data are available concerning calpain 2 (capn2) localization in embryonic tissues...
- Benetti R, Copetti T, Dell Orso S, Melloni E, Brancolini C, Monte M, et al. The calpain system is involved in the constitutive regulation of beta-catenin signaling functions. J Biol Chem. 2005;280:22070-80 pubmed..In fact, in a context where the classical proteasome pathway is impaired, as in colon cancer cells, Gas2DN biological effects accounted for a significant reduction in proliferation and anchorage-independent growth of colon cancer. ..
- Shao H, Travers T, Camacho C, Wells A. The carboxyl tail of alpha-actinin-4 regulates its susceptibility to m-calpain and thus functions in cell migration and spreading. Int J Biochem Cell Biol. 2013;45:1051-63 pubmed publisher..These findings suggest that the C-terminal tail of alpha-actinin-4 is essential for its function in cell migration and adhesion to substratum. ..
- Kovacs L, Han W, Rafikov R, Bagi Z, Offermanns S, Saido T, et al. Activation of Calpain-2 by Mediators in Pulmonary Vascular Remodeling of Pulmonary Arterial Hypertension. Am J Respir Cell Mol Biol. 2016;54:384-93 pubmed publisher..PAH mediator-induced activation of calpain is caused by ERK1/2-dependent phosphorylation of calpain-2 at Ser50 and protein phosphatase 2A-dependent dephosphorylation of calpain-2 at Ser369 in pulmonary vascular remodeling of PAH. ..
- Subramanian V, Moorleghen J, Balakrishnan A, Howatt D, Chishti A, Uchida H. Calpain-2 compensation promotes angiotensin II-induced ascending and abdominal aortic aneurysms in calpain-1 deficient mice. PLoS ONE. 2013;8:e72214 pubmed publisher..Calpain-2 compensates for loss of calpain-1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation in mice. ..
- Westhoff M, Serrels B, Fincham V, Frame M, Carragher N. SRC-mediated phosphorylation of focal adhesion kinase couples actin and adhesion dynamics to survival signaling. Mol Cell Biol. 2004;24:8113-33 pubmed..This also highlights that dynamic regulation of actin and adhesions (which include the integrin matrix receptors) is critical to signaling output and biological responses. ..
- Bralic M, Stemberga V. Calpain expression in the brain cortex after traumatic brain injury. Coll Antropol. 2012;36:1319-23 pubmed..Our results indicate that prolonged calpain expression in resident brain cells (neurons, glial and endothelial cells) plays an important role in neuronal degeneration following TBI. ..
- Magnaghi Jaulin L, Marcilhac A, Rossel M, Jaulin C, Benyamin Y, Raynaud F. Calpain 2 is required for sister chromatid cohesion. Chromosoma. 2010;119:267-74 pubmed publisher..However, the specific functions of each calpain isoform remain unknown. Recent reports have shown that calpain 2 (Capn2) is essential for cell viability...
- Amini M, Ma C, Farazifard R, Zhu G, Zhang Y, Vanderluit J, et al. Conditional disruption of calpain in the CNS alters dendrite morphology, impairs LTP, and promotes neuronal survival following injury. J Neurosci. 2013;33:5773-84 pubmed publisher..These findings unequivocally establish two central roles of calpain-1/calpain-2 in CNS function in plasticity and neuronal death. ..
- Landrock D, Atshaves B, McIntosh A, Landrock K, Schroeder F, Kier A. Acyl-CoA binding protein gene ablation induces pre-implantation embryonic lethality in mice. Lipids. 2010;45:567-80 pubmed publisher..The fact that ACBP is the first known intracellular lipid binding protein whose deletion results in embryonic lethality suggests its vital importance in mammals. ..
- Mellgren R, Miyake K, Kramerova I, Spencer M, Bourg N, Bartoli M, et al. Calcium-dependent plasma membrane repair requires m- or mu-calpain, but not calpain-3, the proteasome, or caspases. Biochim Biophys Acta. 2009;1793:1886-93 pubmed publisher..Utilizing isozyme-selective siRNAs to decrease expression of Capn1 or Capn2, catalytic subunits of mu- and m-calpains, respectively, in a mouse embryonic fibroblast cell line, we now show ..
- Li Y, Li Y, Feng Q, Arnold M, Peng T. Calpain activation contributes to hyperglycaemia-induced apoptosis in cardiomyocytes. Cardiovasc Res. 2009;84:100-10 pubmed publisher..Our data suggest that calpain activation may be important in the development of diabetic cardiomyopathy and thus may represent a potential therapeutic target for diabetic heart diseases. ..
- 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...
- Sorimachi H, Ishiura S, Suzuki K. Structure and physiological function of calpains. Biochem J. 1997;328 ( Pt 3):721-32 pubmed..These findings indicate various important functional roles for intracellular proteases belonging to the calpain superfamily. ..
- Chen F, Qian L, Yang Z, Huang Y, Ngo S, Ruan N, et al. Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction. Neuron. 2007;55:247-60 pubmed..These results demonstrate that calpain participates in ACh-induced dispersion of AChR clusters, and rapsyn stabilizes AChR clusters by suppressing calpain activity. ..
- ElAli A, Doeppner T, Zechariah A, Hermann D. Increased blood-brain barrier permeability and brain edema after focal cerebral ischemia induced by hyperlipidemia: role of lipid peroxidation and calpain-1/2, matrix metalloproteinase-2/9, and RhoA overactivation. Stroke. 2011;42:3238-44 pubmed publisher..Hyperlipidemia is a highly prevalent risk factor for ischemic stroke. Its impact on brain injury and blood-brain barrier permeability, so far, has not been assessed in animal models of ischemic stroke...
- Wang Y, López D, Davey P, Cameron D, Nguyen K, Tran J, et al. Calpain-1 and calpain-2 play opposite roles in retinal ganglion cell degeneration induced by retinal ischemia/reperfusion injury. Neurobiol Dis. 2016;93:121-8 pubmed publisher..Our data indicate that calpain-1 and calpain-2 play opposite roles in high IOP-induced ischemic injury and that a selective calpain-2 inhibitor could prevent acute glaucoma-induced RGC death and blindness. ..
- Leloup L, Mazères G, Daury L, Cottin P, Brustis J. Involvement of calpains in growth factor-mediated migration. Int J Biochem Cell Biol. 2006;38:2049-63 pubmed..The increase in migration was totally inhibited by adding calpeptin, a calpain-specific inhibitor. These findings suggest that milli-calpain is involved in growth factor-mediated migration. ..
- Miyazaki T, Taketomi Y, Takimoto M, Lei X, Arita S, Kim Kaneyama J, et al. m-Calpain induction in vascular endothelial cells on human and mouse atheromas and its roles in VE-cadherin disorganization and atherosclerosis. Circulation. 2011;124:2522-32 pubmed publisher..Thus, a strategy to selectively inhibit m-calpain may be useful for the therapeutic treatment of patients with atherosclerosis. ..
- Glass J, Nash N, Dry I, Culver D, Levey A, Wesselingh S. Cloning of m-calpain 80 kD subunit from the axonal degeneration-resistant WLD(S) mouse mutant. J Neurosci Res. 1998;52:653-60 pubmed..These data suggest that a defect in m-calpain 80 kD subunit does not likely underlie the WLD(S) phenotype, but raise questions about other subunits of calpain and possibly other proteases. ..
- Scalia R, Gong Y, Berzins B, Freund B, Feather D, Landesberg G, et al. A novel role for calpain in the endothelial dysfunction induced by activation of angiotensin II type 1 receptor signaling. Circ Res. 2011;108:1102-11 pubmed publisher..Our results may have significant clinical implications in vascular disease. ..
- Nakajima T, Shearer T, Azuma M. Involvement of calpain 2 in ionomycin-induced cell death in cultured mouse lens epithelial cells. Curr Eye Res. 2011;36:930-6 pubmed publisher..Since calpain 2 is ubiquitously present in all animal lenses so far observed, the current results may predict the pathological consequences of calpain 2 activation in animal lenses including those of man. ..
- Li J, Grynspan F, Berman S, Nixon R, Bursztajn S. Regional differences in gene expression for calcium activated neutral proteases (calpains) and their endogenous inhibitor calpastatin in mouse brain and spinal cord. J Neurobiol. 1996;30:177-91 pubmed
- 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. ..
- Zadran S, Qin Q, Bi X, Zadran H, Kim Y, Foy M, et al. 17-Beta-estradiol increases neuronal excitability through MAP kinase-induced calpain activation. Proc Natl Acad Sci U S A. 2009;106:21936-41 pubmed publisher..These effects could be responsible for E2-mediated increase in neuronal excitability and facilitation of cognitive processes. ..
- Norton R, Fredericks G, Huang Z, Fay J, Hoffmann F, Hoffmann P. Selenoprotein K regulation of palmitoylation and calpain cleavage of ASAP2 is required for efficient Fc?R-mediated phagocytosis. J Leukoc Biol. 2017;101:439-448 pubmed publisher..Overall, these findings identify ASAP2 as a new target of Selk-dependent palmitoylation and reveal a new mechanism regulating the efficiency of Fc?R-mediated phagocytosis. ..
- Hata S, Doi N, Kitamura F, Sorimachi H. Stomach-specific calpain, nCL-2/calpain 8, is active without calpain regulatory subunit and oligomerizes through C2-like domains. J Biol Chem. 2007;282:27847-56 pubmed
- Shao H, Chou J, Baty C, Burke N, Watkins S, Stolz D, et al. Spatial localization of m-calpain to the plasma membrane by phosphoinositide biphosphate binding during epidermal growth factor receptor-mediated activation. Mol Cell Biol. 2006;26:5481-96 pubmed..Growth factors activate m-calpain (calpain 2, CAPN2) via ERK/mitogen-activated protein kinases, but only when these kinases are localized to the plasma membrane...
- Franco S, Rodgers M, Perrin B, Han J, Bennin D, Critchley D, et al. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat Cell Biol. 2004;6:977-83 pubmed..Together, these findings identify calpain-mediated proteolysis of talin as a mechanism by which adhesion dynamics are regulated. ..
- Cui W, Ma J, Wang X, Yang W, Zhang J, Ji Q. Free fatty acid induces endoplasmic reticulum stress and apoptosis of ?-cells by Ca2+/calpain-2 pathways. PLoS ONE. 2013;8:e59921 pubmed publisher..Together, these results reveal pivotal roles for Ca(2+)/calpain-2 pathways in modulating FFA-induced ?-TC3 cell ERS and apoptosis. ..
- Piatkov K, Oh J, Liu Y, Varshavsky A. Calpain-generated natural protein fragments as short-lived substrates of the N-end rule pathway. Proc Natl Acad Sci U S A. 2014;111:E817-26 pubmed publisher..We suggest that this capability of the Arg/N-end rule pathway underlies a multitude of its previously known but mechanistically unclear functions. ..
- 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. ..
- Wang X, Ding Z, Lin J, Guo Z, Mehta J. LOX-1 in macrophage migration in response to ox-LDL and the involvement of calpains. Biochem Biophys Res Commun. 2015;467:135-9 pubmed publisher..These data indicate that LOX-1 is, at least in part, responsible for the inhibitory effect of ox-LDL on macrophage migration and this process involves calpain-1 and -2. ..
- Reed N, Castellini M, Ma H, Shearer T, Duncan M. Protein expression patterns for ubiquitous and tissue specific calpains in the developing mouse lens. Exp Eye Res. 2003;76:433-43 pubmed..These data support the hypothesis that Lp82 in rodent lens has an important role in crystallin proteolysis during normal lens maturation. In contrast, calpain 2, Lp85, and calpain 10 may have roles in cell signaling pathways. ..
- 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. ..
- Liu D, Yan Z, Minshall R, Schwartz D, Chen Y, Hu G. Activation of calpains mediates early lung neutrophilic inflammation in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2012;302:L370-9 pubmed publisher..Inhibition of calpain activation may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury. ..
- Calle Y, Carragher N, Thrasher A, Jones G. Inhibition of calpain stabilises podosomes and impairs dendritic cell motility. J Cell Sci. 2006;119:2375-85 pubmed..In summary, our results provide evidence that calpain regulates podosome composition and turnover and that this process is required for efficient migration of dendritic cells. ..
- Zhang W, Guan D, Zhao R, Zhang J. [Expression of calpain 1 and calpain 2 during the skin incised wound healing in mice]. Fa Yi Xue Za Zhi. 2007;23:81-3 pubmed..The changes of calpain1 and calpain2 expressions appear to be bimodal after incised wound of skin in mice. ..
- Honda M, Masui F, Kanzawa N, Tsuchiya T, Toyo oka T. Specific knockdown of m-calpain blocks myogenesis with cDNA deduced from the corresponding RNAi. Am J Physiol Cell Physiol. 2008;294:C957-65 pubmed publisher..These results may indicate that m-calpain requiring millimolar Ca(2+) level for the full activation plays specific roles in myogenesis, independent of mu-calpain, and leave us challenging problems in the future. ..
- Undyala V, Dembo M, Cembrola K, Perrin B, Huttenlocher A, Elce J, et al. The calpain small subunit regulates cell-substrate mechanical interactions during fibroblast migration. J Cell Sci. 2008;121:3581-8 pubmed publisher..and calpain 2 (m-calpain), are heterodimers consisting of large catalytic subunits encoded by the Capn1 and Capn2 genes, respectively, and the small regulatory subunit encoded by Capn4...
- Choi H, Myung K. Vitamin Dâ‚ƒ regulation of body fat, cytokines, and calpain gene expression. J Sci Food Agric. 2012;92:632-7 pubmed..Vitamin Dâ‚ƒ amplified muscle u- and m-calpain protein content and suppressed muscle calpastatin protein content. These findings suggest that vitamin D3 can be used as a fat synthesizer and meat tenderizer in meat-producing animals. ..
- Elgheznawy A, Shi L, Hu J, Wittig I, Laban H, Pircher J, et al. Dicer cleavage by calpain determines platelet microRNA levels and function in diabetes. Circ Res. 2015;117:157-65 pubmed publisher..Thus, calpain inhibition may be one means of normalizing platelet miRNA processing as well as platelet function in diabetes mellitus. ..
- Chan K, Bennin D, Huttenlocher A. Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion kinase (FAK). J Biol Chem. 2010;285:11418-26 pubmed publisher..Expression of wild-type but not calpain-resistant FAK rescues talin dynamics in FAK-deficient cells. Taken together, our findings suggest a novel role for calpain proteolysis of FAK in regulating adhesion dynamics in motile cells. ..
- Ho W, Pikor L, Gao Y, Elliott B, Greer P. Calpain 2 regulates Akt-FoxO-p27(Kip1) protein signaling pathway in mammary carcinoma. J Biol Chem. 2012;287:15458-65 pubmed publisher..RNAi-mediated knockdown of the capn2 transcript was used to manipulate expression of the catalytic subunit of calpain 2 in the AC2M2 mouse mammary ..
- Santos D, Xavier J, Morgado A, Sola S, Rodrigues C. Distinct regulatory functions of calpain 1 and 2 during neural stem cell self-renewal and differentiation. PLoS ONE. 2012;7:e33468 pubmed publisher..Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation. ..
- Dear N, Matena K, Vingron M, Boehm T. A new subfamily of vertebrate calpains lacking a calmodulin-like domain: implications for calpain regulation and evolution. Genomics. 1997;45:175-84 pubmed..The discovery of these two new calpains highlights a hitherto unknown complexity of the calpain family with subclasses perhaps possessing different modes of regulation. ..
- Ohno S, Minoshima S, Kudoh J, Fukuyama R, Shimizu Y, Ohmi Imajoh S, et al. Four genes for the calpain family locate on four distinct human chromosomes. Cytogenet Cell Genet. 1990;53:225-9 pubmed..The genes for calpain L1 (CAPN1, large subunit of calpain I), L2 (CAPN2, large subunit of calpain II), L3 (CAPN3, a protein related to the large subunits), and S (CAPN4, a small subunit ..
- Wu Y, Liang S, Oda Y, Ohmori I, Nishiki T, Takei K, et al. Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation. EMBO J. 2007;26:2981-90 pubmed..These results suggest that calpain-dependent cleavage of amphiphysin I inhibits synaptic vesicle endocytosis during neural hyperexcitation and demonstrate a novel post-translational regulation of endocytosis. ..
- 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. ..
- Wan F, Letavernier E, Abid S, Houssaini A, Czibik G, Marcos E, et al. Extracellular Calpain/Calpastatin Balance Is Involved in the Progression of Pulmonary Hypertension. Am J Respir Cell Mol Biol. 2016;55:337-51 pubmed publisher..These results indicate that calpastatin limits PH severity via extracellular mechanisms. They suggest a new approach to the development of treatments for PH. ..
- Gomperts B, Gong Cooper X, Hackett B. Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells. J Cell Sci. 2004;117:1329-37 pubmed..In the absence of Foxj1, decreased calpastatin expression with decreased ezrin and EBP-50 results in an inability of basal bodies to anchor to the apical cytoskeleton and subsequent failure of axonemal formation. ..
- Wang Y, Briz V, Chishti A, Bi X, Baudry M. Distinct roles for ?-calpain and m-calpain in synaptic NMDAR-mediated neuroprotection and extrasynaptic NMDAR-mediated neurodegeneration. J Neurosci. 2013;33:18880-92 pubmed publisher..These results help to reconcile a number of contradictory results in the literature and have critical implications for the understanding and potential treatment of neurodegenerative diseases. ..
- Howatt D, Balakrishnan A, Moorleghen J, Muniappan L, Rateri D, Uchida H, et al. Leukocyte Calpain Deficiency Reduces Angiotensin II-Induced Inflammation and Atherosclerosis But Not Abdominal Aortic Aneurysms in Mice. Arterioscler Thromb Vasc Biol. 2016;36:835-45 pubmed publisher..The present study demonstrates a pivotal role for BM-derived calpains in mediating AngII-induced atherosclerosis by influencing macrophage function. ..
- Matsunaga T, Yamamoto G, Tachikawa T. Expression of typical calpains in mouse molar. Arch Oral Biol. 2009;54:885-92 pubmed publisher..Calpains have been detected in several studies during the embryonic and foetal stages. The aim of this study is to investigate the temporal transition of typical calpains and their inhibitor calpastatin during odontogenesis...
- Gokhin D, Tierney M, Sui Z, Sacco A, Fowler V. Calpain-mediated proteolysis of tropomodulin isoforms leads to thin filament elongation in dystrophic skeletal muscle. Mol Biol Cell. 2014;25:852-65 pubmed publisher..These results implicate Tmod proteolysis and resultant thin filament length misspecification as novel mechanisms that may contribute to DMD pathology, affecting muscles in a use- and disease severity-dependent manner. ..
- Spencer M, Tidball J. Calpain translocation during muscle fiber necrosis and regeneration in dystrophin-deficient mice. Exp Cell Res. 1996;226:264-72 pubmed..Furthermore, the stages of pathology at which calpain cleavage is least coincides with those stages when calpain is most concentrated at the cell membrane, suggesting that calpain is retained in an inactive form at the plasma membrane. ..
- Dargelos E, Dedieu S, Moyen C, Poussard S, Veschambre P, Brustis J, et al. Characterization of the calcium-dependent proteolytic system in a mouse muscle cell line. Mol Cell Biochem. 2002;231:147-54 pubmed..A comparison with other myogenic cells is presented. ..
- Li J, Nixon R, Messer A, Berman S, Bursztajn S. Altered gene expression for calpain/calpastatin system in motor neuron degeneration (Mnd) mutant mouse brain and spinal cord. Brain Res Mol Brain Res. 1998;53:174-86 pubmed..Such altered gene expression in specific cell types of brain and spinal cord suggests the involvement of the calpain/calpastatin system. ..
- Jeong S, Martchenko M, Cohen S. Calpain-dependent cytoskeletal rearrangement exploited for anthrax toxin endocytosis. Proc Natl Acad Sci U S A. 2013;110:E4007-15 pubmed publisher..Our results reveal a mechanism by which a bacterial toxin uses constitutively occurring calpain-mediated cytoskeletal rearrangement for internalization. ..