CAPN3

Summary

Gene Symbol: CAPN3
Description: calpain 3
Alias: CANP3, CANPL3, LGMD2, LGMD2A, nCL-1, p94, calpain-3, calpain p94, large [catalytic] subunit, calpain, large polypeptide L3, muscle-specific calcium-activated neutral protease 3 large subunit, new calpain 1
Species: human
Products:     CAPN3

Top Publications

  1. Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, et al. Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A. Cell. 1995;81:27-40 pubmed
    ..The autosomal recessive forms (LGMD2) constitute a genetically heterogeneous group with LGMD2A mapping to chromosome 15q15.1-q21.1...
  2. Guyon J, Kudryashova E, Potts A, Dalkilic I, Brosius M, Thompson T, et al. Calpain 3 cleaves filamin C and regulates its ability to interact with gamma- and delta-sarcoglycans. Muscle Nerve. 2003;28:472-83 pubmed
    b>Calpain 3 (C3) is the only muscle-specific member of the calcium-dependent protease family...
  3. Huang Y, de Morrée A, van Remoortere A, Bushby K, Frants R, den Dunnen J, et al. Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle. Hum Mol Genet. 2008;17:1855-66 pubmed publisher
    ..Two forms of limb-girdle muscular dystrophy, 2A and 2B, are caused by mutations in calpain 3 (CAPN3) and dysferlin (DYSF), respectively...
  4. Ono Y, Shimada H, Sorimachi H, Richard I, Saido T, Beckmann J, et al. Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A. J Biol Chem. 1998;273:17073-8 pubmed
    ..member of the calpain family, has been shown to be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A), a form of autosomal recessive and progressive neuromuscular disorder...
  5. Piluso G, Politano L, Aurino S, Fanin M, Ricci E, Ventriglia V, et al. Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes. J Med Genet. 2005;42:686-93 pubmed
    ..Mutations at the calpain 3 locus (CAPN3) cause LGMD type 2A. To obtain unbiased information on the consequences of CAPN3 mutations...
  6. Ruffini F, Tentori L, Dorio A, Arcelli D, D Amati G, D Atri S, et al. Platelet-derived growth factor C and calpain-3 are modulators of human melanoma cell invasiveness. Oncol Rep. 2013;30:2887-96 pubmed publisher
  7. De Tullio R, Stifanese R, Salamino F, Pontremoli S, Melloni E. Characterization of a new p94-like calpain form in human lymphocytes. Biochem J. 2003;375:689-96 pubmed
    ..The third, which shows peculiar activating and regulatory properties, is an alternatively spliced calpain 3 (p94) form...
  8. Beckmann J, Spencer M. Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance. Neuromuscul Disord. 2008;18:913-21 pubmed publisher
    b>Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases...
  9. Kramerova I, Kudryashova E, Ermolova N, Saenz A, Jaka O, Lopez de Munain A, et al. Impaired calcium calmodulin kinase signaling and muscle adaptation response in the absence of calpain 3. Hum Mol Genet. 2012;21:3193-204 pubmed publisher
    Mutations in the non-lysosomal, cysteine protease calpain 3 (CAPN3) result in the disease limb girdle muscular dystrophy type 2A (LGMD2A)...

More Information

Publications85

  1. Duno M, Sveen M, Schwartz M, Vissing J. cDNA analyses of CAPN3 enhance mutation detection and reveal a low prevalence of LGMD2A patients in Denmark. Eur J Hum Genet. 2008;16:935-40 pubmed publisher
    Calpainopathy or limb-girdle muscular dystrophy type 2A (LGMD2A) is generally recognized as the most prevalent form of recessive LGMD and is caused by mutations in the CAPN3 gene...
  2. Moretti D, Del Bello B, Cosci E, Biagioli M, Miracco C, Maellaro E. Novel variants of muscle calpain 3 identified in human melanoma cells: cisplatin-induced changes in vitro and differential expression in melanocytic lesions. Carcinogenesis. 2009;30:960-7 pubmed publisher
    ..Alterations of calpain 3 (p94), the muscle-specific isoform that contains three peculiar sequences (NS, IS1 and IS2), are strictly ..
  3. Kramerova I, Kudryashova E, Wu B, Ottenheijm C, Granzier H, Spencer M. Novel role of calpain-3 in the triad-associated protein complex regulating calcium release in skeletal muscle. Hum Mol Genet. 2008;17:3271-80 pubmed publisher
    Calpain-3 (CAPN3) is a non-lysosomal cysteine protease that is necessary for normal muscle function, as mutations in CAPN3 result in an autosomal recessive form of limb girdle muscular dystrophy type 2A...
  4. Fanin M, Nascimbeni A, Tasca E, Angelini C. How to tackle the diagnosis of limb-girdle muscular dystrophy 2A. Eur J Hum Genet. 2009;17:598-603 pubmed publisher
    ..We diagnosed a total of 94 LGMD2A patients, carrying 66 different mutations (six are newly identified)...
  5. de Morrée A, Lutje Hulsik D, Impagliazzo A, van Haagen H, de Galan P, van Remoortere A, et al. Calpain 3 is a rapid-action, unidirectional proteolytic switch central to muscle remodeling. PLoS ONE. 2010;5:e11940 pubmed publisher
    b>Calpain 3 (CAPN3) is a cysteine protease that when mutated causes Limb Girdle Muscular Dystrophy 2A. It is thereby the only described Calpain family member that genetically causes a disease...
  6. Nascimbeni A, Fanin M, Tasca E, Angelini C. Transcriptional and translational effects of intronic CAPN3 gene mutations. Hum Mutat. 2010;31:E1658-69 pubmed publisher
    Variants of unknown significance in the CAPN3 gene constitute a significant challenge for genetic counselling...
  7. Stuelsatz P, Pouzoulet F, Lamarre Y, Dargelos E, Poussard S, Leibovitch S, et al. Down-regulation of MyoD by calpain 3 promotes generation of reserve cells in C2C12 myoblasts. J Biol Chem. 2010;285:12670-83 pubmed publisher
    b>Calpain 3 is a calcium-dependent cysteine protease that is primarily expressed in skeletal muscle and is implicated in limb girdle muscular dystrophy type 2A...
  8. Diaz B, Moldoveanu T, Kuiper M, Campbell R, Davies P. Insertion sequence 1 of muscle-specific calpain, p94, acts as an internal propeptide. J Biol Chem. 2004;279:27656-66 pubmed
    The physiological role of the skeletal muscle-specific calpain 3, p94, is presently unknown, but defects in its gene cause limb girdle muscular dystrophy type 2A...
  9. Chrobáková T, Hermanova M, Kroupová I, Vondracek P, Maríková T, Mazanec R, et al. Mutations in Czech LGMD2A patients revealed by analysis of calpain3 mRNA and their phenotypic outcome. Neuromuscul Disord. 2004;14:659-65 pubmed
    ..or ability to interact with other muscular proteins) is manifested as limb girdle muscular dystrophy type 2A (LGMD2A, calpainopathy). These pathological changes in properties of calpain3 are caused by mutations in the calpain3 gene...
  10. Saenz A, Leturcq F, Cobo A, Poza J, Ferrer X, Otaegui D, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain. 2005;128:732-42 pubmed
    ..approximately 50% (238 out of 484) of the suspected calpainopathy cases referred for the molecular study of the calpain 3 (CAPN3) gene...
  11. Hayashi C, Ono Y, Doi N, Kitamura F, Tagami M, Mineki R, et al. Multiple molecular interactions implicate the connectin/titin N2A region as a modulating scaffold for p94/calpain 3 activity in skeletal muscle. J Biol Chem. 2008;283:14801-14 pubmed publisher
    p94/calpain 3 is a skeletal muscle-specific Ca(2+)-regulated cysteine protease (calpain), and genetic loss of p94 protease activity causes muscular dystrophy (calpainopathy)...
  12. Baghdiguian S, Martin M, Richard I, Pons F, Astier C, Bourg N, et al. Calpain 3 deficiency is associated with myonuclear apoptosis and profound perturbation of the IkappaB alpha/NF-kappaB pathway in limb-girdle muscular dystrophy type 2A. Nat Med. 1999;5:503-11 pubmed
  13. Saenz A, Ono Y, Sorimachi H, Goicoechea M, Leturcq F, Blázquez L, et al. Does the severity of the LGMD2A phenotype in compound heterozygotes depend on the combination of mutations?. Muscle Nerve. 2011;44:710-4 pubmed publisher
    Limb-girdle muscular dystrophy type 2A (LGMD2A) is caused by a deficiency of calpain-3/p94...
  14. Hauerslev S, Sveen M, Duno M, Angelini C, Vissing J, Krag T. Calpain 3 is important for muscle regeneration: evidence from patients with limb girdle muscular dystrophies. BMC Musculoskelet Disord. 2012;13:43 pubmed publisher
    ..muscular dystrophy (LGMD) type 2A is caused by mutations in the CAPN3 gene and complete lack of functional calpain 3 leads to the most severe muscle wasting...
  15. Kawai H, Akaike M, Kunishige M, Inui T, Adachi K, Kimura C, et al. Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families. Muscle Nerve. 1998;21:1493-501 pubmed
    ..In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family...
  16. Dincer P, Leturcq F, Richard I, Piccolo F, Yalnizoglu D, de Toma C, et al. A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey. Ann Neurol. 1997;42:222-9 pubmed
    ..Five genes have already been identified: calpain-3 at LGMD2A (15q15), and four members of the sarcoglycan (SG) complex, alpha-SG at LGMD2D (17q21), beta-SG at LGMD2E (4q12), ..
  17. Fanin M, Nascimbeni A, Angelini C. Muscle atrophy in Limb Girdle Muscular Dystrophy 2A: a morphometric and molecular study. Neuropathol Appl Neurobiol. 2013;39:762-71 pubmed publisher
    ..that the ubiquitin-proteasome degradation pathway may have a crucial role in Limb Girdle Muscular Dystrophy 2A (LGMD2A)...
  18. Richard I, Brenguier L, Dincer P, Roudaut C, Bady B, Burgunder J, et al. Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins. Am J Hum Genet. 1997;60:1128-38 pubmed
    ..calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600)...
  19. Fardeau M, Hillaire D, Mignard C, Feingold N, Feingold J, Mignard D, et al. Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island. Brain. 1996;119 ( Pt 1):295-308 pubmed
    ..identified in a gene located in this region encoding for muscle-specific calcium activated neutral protease (CANP3)...
  20. Blazquez L, Azpitarte M, Saenz A, Goicoechea M, Otaegui D, Ferrer X, et al. Characterization of novel CAPN3 isoforms in white blood cells: an alternative approach for limb-girdle muscular dystrophy 2A diagnosis. Neurogenetics. 2008;9:173-82 pubmed publisher
    Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder caused by mutations in the CAPN3 gene...
  21. Krahn M, Pecheux C, Chapon F, Beroud C, Drouin Garraud V, Laforet P, et al. Transcriptional explorations of CAPN3 identify novel splicing mutations, a large-sized genomic deletion and evidence for messenger RNA decay. Clin Genet. 2007;72:582-92 pubmed
    Mutations in the gene encoding calpain-3 (CAPN3) cause autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A) and idiopathic eosinophilic myositis...
  22. Stehlikova K, Zapletalová E, Sedlackova J, Hermanova M, Vondracek P, Maríková T, et al. Quantitative analysis of CAPN3 transcripts in LGMD2A patients: involvement of nonsense-mediated mRNA decay. Neuromuscul Disord. 2007;17:143-7 pubmed
    Limb girdle muscular dystrophy type 2A (LGMD2A) is caused by single or small nucleotide changes widespread along the CAPN3 gene, which encodes the muscle-specific proteolytic enzyme calpain-3...
  23. Fanin M, Fulizio L, Nascimbeni A, Spinazzi M, Piluso G, Ventriglia V, et al. Molecular diagnosis in LGMD2A: mutation analysis or protein testing?. Hum Mutat. 2004;24:52-62 pubmed
    Limb girdle muscular dystrophy (LGMD) type 2A (LGMD2A) is caused by mutations in the CAPN3 gene encoding for calpain-3, a muscle specific protease...
  24. Baghdiguian S, Richard I, Martin M, Coopman P, Beckmann J, Mangeat P, et al. Pathophysiology of limb girdle muscular dystrophy type 2A: hypothesis and new insights into the IkappaBalpha/NF-kappaB survival pathway in skeletal muscle. J Mol Med (Berl). 2001;79:254-61 pubmed
    ..The gene responsible for LGMD2A has been identified and encodes calpain 3, a protease expressed mainly in skeletal muscle...
  25. Urtasun M, Saenz A, Roudaut C, Poza J, Urtizberea J, Cobo A, et al. Limb-girdle muscular dystrophy in Guipúzcoa (Basque Country, Spain). Brain. 1998;121 ( Pt 9):1735-47 pubmed
    ..Genetic studies demonstrated that 38 cases corresponded to the LGMD2A type, due to calpain-3 gene mutations...
  26. de Paula F, Vainzof M, Passos Bueno M, de Cássia M Pavanello R, Matioli S, V B Anderson L, et al. Clinical variability in calpainopathy: what makes the difference?. Eur J Hum Genet. 2002;10:825-32 pubmed
    ..b>LGMD2A, the most prevalent form of LGMD, is caused by mutations in the calpain-3 gene (CAPN-3)...
  27. Kawabata Y, Hata S, Ono Y, Ito Y, Suzuki K, Abe K, et al. Newly identified exons encoding novel variants of p94/calpain 3 are expressed ubiquitously and overlap the alpha-glucosidase C gene. FEBS Lett. 2003;555:623-30 pubmed
    There are two classes of an intracellular 'modulator protease', calpain: ubiquitous and tissue-specific. p94/calpain 3 is an example of the latter, predominantly expressed in muscle. A defect in the p94 gene causes muscular dystrophy...
  28. Shi Y, Ma K, Dai D. Sensitivity Enhancement in Si Nanophotonic Waveguides Used for Refractive Index Sensing. Sensors (Basel). 2016;16: pubmed publisher
    ..g., ~1.43) while the fabrication tolerance is very small (i.e., ∆w < ±5 nm). The comparative study shows that suspended Si nanowire is a good choice to achieve ultra-high waveguide sensitivity. ..
  29. DiFranco M, Kramerova I, Vergara J, SPENCER M. Attenuated Ca(2+) release in a mouse model of limb girdle muscular dystrophy 2A. Skelet Muscle. 2016;6:11 pubmed publisher
    Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase...
  30. Miller M, Bang M, Witt C, Labeit D, Trombitas C, Watanabe K, et al. The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules. J Mol Biol. 2003;333:951-64 pubmed
    ..Within the myofibril, MARPs, myopalladin, and the calpain protease p94 appear to be components of a titin N2A-based signaling complex...
  31. Hanisch F, Muller C, Grimm D, Xue L, Traufeller K, Merkenschlager A, et al. Frequency of calpain-3 c.550delA mutation in limb girdle muscular dystrophy type 2 and isolated hyperCKemia in German patients. Clin Neuropathol. 2007;26:157-63 pubmed
    ..The c.550delA mutation in the CAPN3 gene was frequently identified in LGMD2A patients from Eastern Europe and is considered a Slavic founder mutation. We screened for the c...
  32. Fadaee M, Kariminejad A, Fattahi Z, Nafissi S, Godarzi H, Beheshtian M, et al. Report of limb girdle muscular dystrophy type 2a in 6 Iranian patients, one with a novel deletion in CAPN3 gene. Neuromuscul Disord. 2016;26:277-82 pubmed publisher
    ..Many pathogenic mutations have been identified in calpain3, encoded by the CAPN3 gene, which leads to weakness of the pelvic and shoulder girdle muscles...
  33. Park H, Jang H, Lee J, Shin H, Cho S, Park K, et al. Clinical and Pathological Heterogeneity of Korean Patients with CAPN3 Mutations. Yonsei Med J. 2016;57:173-9 pubmed publisher
    ..patients from ten unrelated families were diagnosed with calpainopathy via direct or targeted sequencing of the CAPN3 gene. Clinical, mutational, and pathological spectra were then analyzed...
  34. Paco S, Ferrer I, Jou C, Cusi V, Corbera J, Torner F, et al. Muscle fiber atrophy and regeneration coexist in collagen VI-deficient human muscle: role of calpain-3 and nuclear factor-?B signaling. J Neuropathol Exp Neurol. 2012;71:894-906 pubmed
    ..Our results indicate that alterations in calpain-3 and nuclear factor-?B signaling pathways may contribute to muscle mass loss in UCMD muscle, whereas atrogin-1 and MURF1 are not likely to play a major role. ..
  35. Scientific Committee Of Consumer Safety Sccs -, Giménez Arnau A. Opinion of the Scientific Committee on Consumer safety (SCCS) - Opinion on the safety of the use of Methylisothiazolinone (MI) (P94), in cosmetic products (sensitisation only). Regul Toxicol Pharmacol. 2016;76:211-2 pubmed publisher
    ..The results of the recent Scandinavian study do not support safety of MI in rinse-off products at either 100 ppm or at 50 ppm for elicitation or induction. ..
  36. Sorbolini S, Marras G, Gaspa G, Dimauro C, Cellesi M, Valentini A, et al. Detection of selection signatures in Piemontese and Marchigiana cattle, two breeds with similar production aptitudes but different selection histories. Genet Sel Evol. 2015;47:52 pubmed publisher
    ..regions that harbour candidate genes that are known to affect productive traits in cattle such as DGAT1, ABCG2, CAPN3, MSTN and FTO...
  37. Hegde S, Kesterson R, Srivastava O. CRYβA3/A1-Crystallin Knockout Develops Nuclear Cataract and Causes Impaired Lysosomal Cargo Clearance and Calpain Activation. PLoS ONE. 2016;11:e0149027 pubmed publisher
    ..These defects are responsible for the development of nuclear cataract in KO lenses. ..
  38. Kumchantuek T, Nakata H, Sakulsak N, Yamamoto M, Iseki S. Expression and localization of calpain 3 in the submandibular gland of mice. Arch Oral Biol. 2016;70:9-15 pubmed publisher
    ..We herein revealed the expression and localization of calpain 3, the muscle-type calpain, in the submandibular gland (SMG) of mice...
  39. Todorova A, Georgieva B, Tournev I, Todorov T, Bogdanova N, Mitev V, et al. A large deletion and novel point mutations in the calpain 3 gene (CAPN3) in Bulgarian LGMD2A patients. Neurogenetics. 2007;8:225-9 pubmed
    Limb-girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the calpain 3 (CAPN3) gene...
  40. Kawauchi I, Jeremias J, Takeara P, de Souza D, Balieiro J, Pfrimer K, et al. Effect of dietary protein intake on the body composition and metabolic parameters of neutered dogs. J Nutr Sci. 2017;6:e40 pubmed publisher
    ..a diet containing 59·7 g protein/1000 kcal (4184 kJ) (P60) or a diet with 94·0 g protein/1000 kcal (4184 kJ) (P94) for 26 weeks after neutering to maintain their body weight prior to neutering...
  41. Muto Y, Morton J, Palmer D. Investigation of biochemical changes of the ovine calpain 3 exon-10 polymorphism. Mol Cell Probes. 2015;29:382-388 pubmed publisher
    b>Calpain 3 (CAPN3) is a tissue specific calpain, and its mRNA is the most expressed calpain isoform in skeletal muscles...
  42. Monies D, Alhindi H, Almuhaizea M, Abouelhoda M, Alazami A, Goljan E, et al. A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies. Hum Genomics. 2016;10:32 pubmed
    ..Mutations of DYSF were the most commonly identified cause of disease followed by that in CAPN3 and FKRP...
  43. Fanin M, Benedicenti F, Fritegotto C, Nascimbeni A, Peterle E, Stanzial F, et al. An intronic mutation causes severe LGMD2A in a large inbred family belonging to a genetic isolate in the Alps. Clin Genet. 2012;82:601-2 pubmed publisher
  44. Arranja A, Waton G, Schosseler F, Mendes E. Lack of a unique kinetic pathway in the growth and decay of Pluronic micelles. Soft Matter. 2016;12:769-78 pubmed publisher
    We report kinetic experiments on dilute brine solutions of P84, P94 and P104 Pluronic copolymer micelles...
  45. Rey M, Davies P. The protease core of the muscle-specific calpain, p94, undergoes Ca2+-dependent intramolecular autolysis. FEBS Lett. 2002;532:401-6 pubmed
    Limb girdle muscular dystrophy type 2A is linked to a skeletal muscle-specific calpain isoform known as p94. Isolation of the intact 94-kDa enzyme has been difficult to achieve due to its rapid autolysis, and uncertainty has arisen over ..
  46. Charlton R, Henderson M, Richards J, Hudson J, Straub V, Bushby K, et al. Immunohistochemical analysis of calpain 3: advantages and limitations in diagnosing LGMD2A. Neuromuscul Disord. 2009;19:449-57 pubmed publisher
    ..exon 1) and Calp3-12A2 (exon 8), to label blots and sections of skeletal muscle from controls and patients with LGMD2A and other muscle diseases...
  47. Jaka O, Casas Fraile L, Azpitarte M, Aiastui A, Lopez de Munain A, Saenz A. FRZB and melusin, overexpressed in LGMD2A, regulate integrin ?1D isoform replacement altering myoblast fusion and the integrin-signalling pathway. Expert Rev Mol Med. 2017;19:e2 pubmed publisher
    Limb-girdle muscular dystrophy type 2A (LGMD2A) is characterised by muscle wasting and progressive degeneration of proximal muscles because of mutations in the CAPN3 gene...
  48. Wang Y, White M, Akay C, Chodroff R, Robinson J, Lindl K, et al. Activation of cyclin-dependent kinase 5 by calpains contributes to human immunodeficiency virus-induced neurotoxicity. J Neurochem. 2007;103:439-55 pubmed
    ..Taken together, our data suggest calpain activation of CDK5, a pathway activated in HIV-infected individuals, can mediate neuronal damage and death in a model of HIV-induced neurotoxicity. ..
  49. de Cid R, Ben Yaou R, Roudaut C, Charton K, Baulande S, Leturcq F, et al. A new titinopathy: Childhood-juvenile onset Emery-Dreifuss-like phenotype without cardiomyopathy. Neurology. 2015;85:2126-35 pubmed publisher
    To identify the genetic defects present in 3 families with muscular dystrophy, contractures, and calpain 3 deficiency...
  50. Chen Q, Müller J, Pang P, Laval S, Haslam S, Lochmüller H, et al. Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1). Biomolecules. 2015;5:2758-81 pubmed publisher
    ..CMS caused by mutations in DOK7, myopathy caused by mutations in MTND5, limb girdle muscular dystrophy type 2A (LGMD2A), and Pompe disease...
  51. Hadj Salem I, Kamoun F, Louhichi N, Rouis S, Mziou M, Fendri Kriaa N, et al. Mutations in LAMA2 and CAPN3 genes associated with genetic and phenotypic heterogeneities within a single consanguineous family involving both congenital and progressive muscular dystrophies. Biosci Rep. 2011;31:125-35 pubmed publisher
    ..Linkage analyses were compatible with the LGMD2A locus in one branch and the MDC1A (muscular dystrophy congenital type 1A) locus in the other branch...
  52. Kramerova I, Beckmann J, Spencer M. Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A). Biochim Biophys Acta. 2007;1772:128-44 pubmed
    Limb girdle muscular dystrophy type 2A results from mutations in the gene encoding the calpain 3 protease...
  53. Sorimachi H, Ono Y, Suzuki K. Skeletal muscle-specific calpain, p94, and connectin/titin: their physiological functions and relationship to limb-girdle muscular dystrophy type 2A. Adv Exp Med Biol. 2000;481:383-95; discussion 395-7 pubmed
    The skeletal muscle-specific calpain homologue, p94 (also called calpain 3), is essential for normal muscle function...
  54. Murphy R, Goodman C, McKenna M, Bennie J, Leikis M, Lamb G. Calpain-3 is autolyzed and hence activated in human skeletal muscle 24 h following a single bout of eccentric exercise. J Appl Physiol (1985). 2007;103:926-31 pubmed
    ..Eccentric exercise is the first physiological circumstance shown to result in calpain-3 activation in vivo. ..
  55. Inashkina I, Jankevics E, Stavusis J, Vasiljeva I, Viksne K, Micule I, et al. Robust genotyping tool for autosomal recessive type of limb-girdle muscular dystrophies. BMC Musculoskelet Disord. 2016;17:200 pubmed publisher
    ..GoldenGate genotyping platform, Ion AmpliSeq Inherited Disease Panel and direct sequencing of mutations in calpain 3 (CAPN3), anoctamin 5 (ANO5) and fukutin related protein (FKRP) genes. Analysis revealed a homozygous CAPN3 c...
  56. Walder K, McMillan J, Lapsys N, Kriketos A, Trevaskis J, Civitarese A, et al. Calpain 3 gene expression in skeletal muscle is associated with body fat content and measures of insulin resistance. Int J Obes Relat Metab Disord. 2002;26:442-9 pubmed
    To investigate whether skeletal muscle gene expression of calpain 3 is related to obesity and insulin resistance...
  57. Han Y, Weinman S, Boldogh I, Walker R, Brasier A. Tumor necrosis factor-alpha-inducible IkappaBalpha proteolysis mediated by cytosolic m-calpain. A mechanism parallel to the ubiquitin-proteasome pathway for nuclear factor-kappab activation. J Biol Chem. 1999;274:787-94 pubmed
    ..Our results demonstrate that TNF-alpha activates cytosolic calpains, a parallel pathway that degrades IkappaBalpha and activates NF-kappaB activation independently of the ubiquitin-proteasome pathway. ..
  58. Sorimachi H, Imajoh Ohmi S, Emori Y, Kawasaki H, Ohno S, Minami Y, et al. Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types. Specific expression of the mRNA in skeletal muscle. J Biol Chem. 1989;264:20106-11 pubmed
    ..The encoded protein (designated "p94") consists of 821 amino acid residues (Mr 94,084) and shows significant sequence homology with both human mu-..
  59. Bartoli M, Roudaut C, Martin S, Fougerousse F, Suel L, Poupiot J, et al. Safety and efficacy of AAV-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2A. Mol Ther. 2006;13:250-9 pubmed
    ..2A, LGMD2A) is a recessive muscular disorder caused by deficiency in the calcium-dependent cysteine protease calpain 3. To date, no treatment exists for this disease...
  60. Ono Y, Torii F, Ojima K, Doi N, Yoshioka K, Kawabata Y, et al. Suppressed disassembly of autolyzing p94/CAPN3 by N2A connectin/titin in a genetic reporter system. J Biol Chem. 2006;281:18519-31 pubmed
    p94/calpain 3 is a skeletal muscle-specific member of the Ca(2+)-regulated cytosolic cysteine protease family, the calpains...
  61. Fanin M, Nascimbeni A, Angelini C. Screening of calpain-3 autolytic activity in LGMD muscle: a functional map of CAPN3 gene mutations. J Med Genet. 2007;44:38-43 pubmed
    ..However, in many patients with limb girdle muscular dystrophy type 2A (LGMD2A), the calpain-3 protein quantity is normal because loss-of-function mutations cause its enzymatic inactivation...
  62. Vissing J, Barresi R, Witting N, Van Ghelue M, Gammelgaard L, Bindoff L, et al. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy. Brain. 2016;139:2154-63 pubmed publisher
    ..Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation screening...
  63. Toral Ojeda I, Aldanondo G, Lasa Elgarresta J, Lasa Fernández H, Fernandez Torron R, Lopez de Munain A, et al. Calpain 3 deficiency affects SERCA expression and function in the skeletal muscle. Expert Rev Mol Med. 2016;18:e7 pubmed publisher
    Limb-girdle muscular dystrophy type 2A (LGMD2A) is a form of muscular dystrophy caused by mutations in calpain 3 (CAPN3)...
  64. Benayoun B, Baghdiguian S, Lajmanovich A, Bartoli M, Daniele N, Gicquel E, et al. NF-kappaB-dependent expression of the antiapoptotic factor c-FLIP is regulated by calpain 3, the protein involved in limb-girdle muscular dystrophy type 2A. FASEB J. 2008;22:1521-9 pubmed
    ..muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in the cysteine protease calpain 3 (CAPN3) that leads to selective muscle wasting...
  65. Federici C, Eshdat Y, Richard I, Bertin B, Guillaume J, Hattab M, et al. Purification and identification of two putative autolytic sites in human calpain 3 (p94) expressed in heterologous systems. Arch Biochem Biophys. 1999;363:237-45 pubmed
    Human muscle-specific calpain (CAPN3) was expressed in two heterologous systems: Sf9 insect cells and Escherichia coli cells...
  66. Roudaut C, Le Roy F, Suel L, Poupiot J, Charton K, Bartoli M, et al. Restriction of calpain3 expression to the skeletal muscle prevents cardiac toxicity and corrects pathology in a murine model of limb-girdle muscular dystrophy. Circulation. 2013;128:1094-104 pubmed publisher
    Genetic defects in calpain3 (CAPN3) lead to limb-girdle muscular dystrophy type 2A, a disease of the skeletal muscle that affects predominantly the proximal limb muscles...
  67. Ankala A, Kohn J, Dastur R, Gaitonde P, Khadilkar S, Hegde M. Ancestral founder mutations in calpain-3 in the Indian Agarwal community: historical, clinical, and molecular perspective. Muscle Nerve. 2013;47:931-7 pubmed publisher
    ..We identified 2 founder mutations in CAPN3, a missense (c.2338G>C; p.D780H) and a splice-site (c...
  68. Pratt V, Jackson C, Wallace D, Gurley D, Feit A, Feldman G. DNA studies of limb-girdle muscular dystrophy type 2A in the Amish exclude a modifying mitochondrial gene and show no evidence for a modifying nuclear gene. Am J Hum Genet. 1997;61:231-3 pubmed
  69. Kinbara K, Sorimachi H, Ishiura S, Suzuki K. Muscle-specific calpain, p94, interacts with the extreme C-terminal region of connectin, a unique region flanked by two immunoglobulin C2 motifs. Arch Biochem Biophys. 1997;342:99-107 pubmed
    Using the yeast two-hybrid system, we have recently reported that skeletal muscle-specific calpain, p94, binds specifically to connectin (or titin), a gigantic muscle elastic protein...
  70. Mojbafan M, Tonekaboni S, Abiri M, Kianfar S, Sarhadi A, Nilipour Y, et al. Linkage Study Revealed Complex Haplotypes in a Multifamily due to Different Mutations in CAPN3 Gene in an Iranian Ethnic Group. J Mol Neurosci. 2016;59:392-6 pubmed publisher
    Calpainopathy is an autosomal recessive form of limb girdle muscular dystrophies which is caused by mutation in CAPN3 gene...
  71. Amato A. Adults with eosinophilic myositis and calpain-3 mutations. Neurology. 2008;70:730-1 pubmed publisher
  72. Krahn M, Goicoechea M, Hanisch F, Groen E, Bartoli M, Pecheux C, et al. Eosinophilic infiltration related to CAPN3 mutations: a pathophysiological component of primary calpainopathy?. Clin Genet. 2011;80:398-402 pubmed publisher
  73. Shirafuji T, Otsuka Y, Kobessho H, Minami N, Hayashi Y, Nishino I, et al. [Case of LGMD2A (calpainopathy) clinically presenting as Miyoshi distal myopathy]. Rinsho Shinkeigaku. 2008;48:651-5 pubmed
    ..Although the clinical features suggested Miyoshi's distal myopathy, gene analysis of calpain 3 revealed a c.802-9G > A mutation in intron 5 and a c.1319G > A (p.Arg440Gln) in exon 10...
  74. Nadaj Pakleza A, Dorobek M, Nestorowicz K, Ryniewicz B, Szmidt Sałkowska E, Kaminska A. Muscle pathology in 31 patients with calpain 3 gene mutations. Neurol Neurochir Pol. 2013;47:214-22 pubmed
    ..analysis, is not totally reliable, since up to 20% of molecularly confirmed LGMD2A show normal content of calpain 3 and a third of LGMD2A biopsies have normal calpain 3 proteo-lytic activity in the muscle...
  75. Sun S, Peng Y, Song H, Lin Z, He J. [Different splice of the calpain 3 gene in human skeletal muscle tissue and white blood cells]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010;27:272-5 pubmed publisher
    To investigate the splice variants of the calpain 3 gene existing in human skeletal muscle tissue and white blood cells, and to explore the feasibility of gene diagnosis using CAPN3 mRNA extracted from peripheral leukocytes...