Calpain-3

CAPN3
Identifiers
Aliases	CAPN3, CANP3, CANPL3, LGMD2, LGMD2A, nCL-1, p94, calpain 3, LGMDR1, LGMDD4
External IDs	OMIM: 114240; MGI: 107437; GeneCards: CAPN3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4OKH
Enzyme activity EC # BRENDA ExPASy KEGG MetaCyc 3.4.22.54 ↗ ↗ ↗ ↗
Gene location (Human) Chr. Chromosome 15 (human) Band 15q15.1 Start 42,359,498 bp End 42,412,949 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2 E5|2 60.31 cM Start 120,294,053 bp End 120,335,399 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in muscle of thigh skeletal muscle tissue C1 segment corpus callosum gastrocnemius muscle substantia nigra putamen hippocampus proper primary visual cortex caudate nucleus Top expressed in lens muscle of thigh muscle tissue skeletal muscle tissue quadriceps femoris muscle thymus zone of skin esophagus dentate gyrus of hippocampal formation granule cell hippocampus proper More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding cysteine-type peptidase activity sodium ion binding titin binding signal transducer activity metal ion binding calcium-dependent cysteine-type endopeptidase activity peptidase activity catalytic activity protein binding molecular adaptor activity structural constituent of muscle hydrolase activity ligase regulator activity Cellular component cytoplasm cytosol T-tubule plasma membrane intracellular anatomical structure myofibril Z discdkac nucleus protein-containing complex Biological process muscle structure development cellular response to calcium ion protein localization to membrane negative regulation of protein sumoylation positive regulation of satellite cell activation involved in skeletal muscle regeneration muscle cell cellular homeostasis muscle organ development self proteolysis negative regulation of apoptotic process positive regulation of release of sequestered calcium ion into cytosol proteolysis positive regulation of transcription, DNA-templated response to calcium ion negative regulation of skeletal muscle cell differentiation G1 to G0 transition involved in cell differentiation cellular response to salt stress myofibril assembly regulation of myoblast differentiation positive regulation of NF-kappaB transcription factor activity positive regulation of proteolysis regulation of catalytic activity negative regulation of transcription, DNA-templated sarcomere organization response to muscle activity regulation of I-kappaB kinase/NF-kappaB signaling apoptotic process signal transduction programmed cell death protein-containing complex assembly protein catabolic process protein destabilization calcium-dependent self proteolysis Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 825 12335 Ensembl ENSG00000092529 ENSMUSG00000079110 UniProt P20807 Q64691 RefSeq (mRNA) NM_000070 NM_024344 NM_173087 NM_173088 NM_173089 NM_173090 NM_212465 NM_001109761 NM_001177799 NM_007601 RefSeq (protein) NP_000061 NP_077320 NP_775110 NP_775111 NP_775112 NP_775113 NP_001103231 NP_001171270 NP_031627 Location (UCSC) Chr 15: 42.36 – 42.41 Mb Chr 2: 120.29 – 120.34 Mb PubMed search
Wikidata
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Calpain-3 is a protein that in humans is encoded by the CAPN3 gene.

Function

Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed.

In melanocytic cells CAPN3 gene expression may be regulated by MITF.

Interactions

CAPN3 has been shown to interact with Titin.

Further reading

• Sorimachi H, Ishiura S, Suzuki K (1997). "Structure and physiological function of calpains". Biochem. J. 328 (3): 721–32. doi:10.1042/bj3280721. PMC 1218978. PMID 9396712.
• Kinbara K, Sorimachi H, Ishiura S, Suzuki K (1998). "Skeletal muscle-specific calpain, p49: structure and physiological function". Biochem. Pharmacol. 56 (4): 415–20. doi:10.1016/S0006-2952(98)00095-1. PMID 9763216.
• Sorimachi H, Ono Y, Suzuki K (2000). "Skeletal Muscle-Specific Calpain, p94, and Connectin/Titin: Their Physiological Functions and Relationship to Limb-Girdle Muscular Dystrophy Type 2A". Elastic Filaments of the Cell. Advances in Experimental Medicine and Biology. Vol. 481. pp. 383–95, discussion 395-7. doi:10.1007/978-1-4615-4267-4_23. ISBN 978-1-4613-6916-5. PMID 10987085.
• Baghdiguian S, Richard I, Martin M, Coopman P, Beckmann JS, Mangeat P, Lefranc G (2001). "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. 79 (5–6): 254–61. doi:10.1007/s001090100225. PMID 11485017. S2CID 286784.
• Canki-Klain N, Milic A, Kovac B, Trlaja A, Grgicevic D, Zurak N, Fardeau M, Leturcq F, Kaplan JC, Urtizberea JA, Politano L, Piluso G, Feingold J (2004). "Prevalence of the 550delA mutation in calpainopathy (LGMD 2A) in Croatia". Am. J. Med. Genet. A. 125A (2): 152–6. doi:10.1002/ajmg.a.20408. PMID 14981715. S2CID 21946737.
• Kramerova I, Beckmann JS, Spencer MJ (2007). "Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A)" (PDF). Biochim. Biophys. Acta. 1772 (2): 128–44. doi:10.1016/j.bbadis.2006.07.002. PMID 16934440. S2CID 35100606.
• Ohno S, Minoshima S, Kudoh J, Fukuyama R, Shimizu Y, Ohmi-Imajoh S, Shimizu N, Suzuki K (1990). "Four genes for the calpain family locate on four distinct human chromosomes". Cytogenet. Cell Genet. 53 (4): 225–9. doi:10.1159/000132937. PMID 2209092.
• Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K (1995). "Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence". J. Biol. Chem. 270 (52): 31158–62. doi:10.1074/jbc.270.52.31158. PMID 8537379.
• Fardeau M, Hillaire D, Mignard C, Feingold N, Feingold J, Mignard D, de Ubeda B, Collin H, Tome FM, Richard I, Beckmann J (1996). "Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island". Brain. 119 (1): 295–308. doi:10.1093/brain/119.1.295. PMID 8624690.
• Corasaniti MT, Navarra M, Catani MV, Melino G, Nisticò G, Finazzi-Agrò A (1996). "NMDA and HIV-1 coat protein, GP120, produce necrotic but not apoptotic cell death in human CHP100 neuroblastoma cultures via a mechanism involving calpain". Biochem. Biophys. Res. Commun. 229 (1): 299–304. doi:10.1006/bbrc.1996.1796. PMID 8954122.
• Richard I, Brenguier L, Dinçer P, Roudaut C, Bady B, Burgunder JM, Chemaly R, Garcia CA, Halaby G, Jackson CE, Kurnit DM, Lefranc G, Legum C, Loiselet J, Merlini L, Nivelon-Chevallier A, Ollagnon-Roman E, Restagno G, Topaloglu H, Beckmann JS (1997). "Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins". Am. J. Hum. Genet. 60 (5): 1128–38. PMC 1712426. PMID 9150160.
• Kinbara K, Sorimachi H, Ishiura S, Suzuki K (1997). "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. 342 (1): 99–107. doi:10.1006/abbi.1997.0108. PMID 9185618.
• Pratt VM, Jackson CE, Wallace DC, Gurley DS, Feit A, Feldman GL (1997). "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. 61 (1): 231–3. doi:10.1016/S0002-9297(07)64296-7. PMC 1715865. PMID 9246005.
• Dinçer P, Leturcq F, Richard I, Piccolo F, Yalnizoglu D, de Toma C, Akçören Z, Broux O, Deburgrave N, Brenguier L, Roudaut C, Urtizberea JA, Jung D, Tan E, Jeanpierre M, Campbell KP, Kaplan JC, Beckmann JS, Topaloglu H (1997). "A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey". Ann. Neurol. 42 (2): 222–9. doi:10.1002/ana.410420214. PMID 9266733. S2CID 28524591.
• Ono Y, Shimada H, Sorimachi H, Richard I, Saido TC, Beckmann JS, Ishiura S, Suzuki K (1998). "Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A". J. Biol. Chem. 273 (27): 17073–8. doi:10.1074/jbc.273.27.17073. PMID 9642272.
• Pénisson-Besnier I, Richard I, Dubas F, Beckmann JS, Fardeau M (1998). "Pseudometabolic expression and phenotypic variability of calpain deficiency in two siblings". Muscle Nerve. 21 (8): 1078–80. doi:10.1002/(SICI)1097-4598(199808)21:8<1078::AID-MUS15>3.0.CO;2-Q. PMID 9655129. S2CID 26307931.
• Urtasun M, Sáenz A, Roudaut C, Poza JJ, Urtizberea JA, Cobo AM, Richard I, García Bragado F, Leturcq F, Kaplan JC, Martí Massó JF, Beckmann JS, López de Munain A (1998). "Limb-girdle muscular dystrophy in Guipúzcoa (Basque Country, Spain)". Brain. 121 (9): 1735–47. doi:10.1093/brain/121.9.1735. PMID 9762961.
• Huang Y, de Morrée A, van Remoortere A, Bushby K, Frants RR, den Dunnen JT, van der Maarel SM (2008). "Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle". Hum. Mol. Genet. 17 (12): 1855–66. doi:10.1093/hmg/ddn081. PMC 2900895. PMID 18334579.

External links

• The MEROPS online database for peptidases and their inhibitors: C02.004 Archived 2008-04-11 at the Wayback Machine
• GeneReviews/NCBI/NIH/UW entry on Calpainopathy
• LOVD mutation database: CAPN3
• Human CAPN3 genome location and CAPN3 gene details page in the UCSC Genome Browser.