钙蛋白酶3
（重定向自CAPN3）
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钙蛋白酶3（英语：Calpain-3）是一种蛋白质，在人类中由CAPN3基因编码。[1][2]
功能[编辑]
钙蛋白酶是细胞内的一种核心蛋白酶，通常由大、小两个亚基组成异源二聚体，不过其具体生理功能目前尚未完全明确。CAPN3基因编码的是钙蛋白酶大亚基家族中一个肌肉特异性成员，该成员能与肌联蛋白发生特异性结合。该基因的突变与2A型肢带型肌失养症密切相关。由于不同的启动子和可变剪接的存在，该基因拥有多种转录本变体，可编码不同的蛋白质亚型，其中部分变体在全身各组织中广泛表达。[3]
在黑素细胞中，CAPN3基因的表达可能受到小眼畸形相关转录因子（MITF）的调控。[4]
相互作用[编辑]
结构[编辑]
钙蛋白酶3由821个氨基酸残基组成，其全长结构可划分为四个功能结构域：[1]
- 结构域I（残基1至98）：该结构域较其他钙蛋白酶大亚基的结构域I长20至30个氨基酸残基，且序列差异显著（同源性<20%）。鉴于其氮端在钙蛋白酶1和2的激活中发挥着重要作用，其特异序列提示该激活过程（如果存在的话）可能具有不同的机制。
- 结构域II（残基99至400）：该结构域为半胱氨酸蛋白酶催化结构域，与其他钙蛋白酶的结构域II高度同源。此外，此结构域表明钙蛋白酶3可能具有蛋白水解活性。
- 结构域III（残基401至653）： 其确切的生理功能尚不完全明晰。
- 结构域IV（残基654至821）：该结构域包含四个EF手结构，表明钙蛋白酶3的结构域IV具有钙离子结合活性。
发现[编辑]
1989年，反町洋之等人在筛选人类骨骼肌cDNA文库时，发现了一种与常规μ型及m型钙蛋白酶仅具有部分同源性的全新蛋白酶，并将其暂命名为p94。后续研究表明，该蛋白属于钙蛋白酶家族的新成员，其编码序列在人类与大鼠间高度保守。[1]2013年，美国实验生物学学会联合会（FASEB）正式将p94重命名为钙蛋白酶3，尽管当时其特性尚未完全阐明。[7]
表达[编辑]
钙蛋白酶3仅在骨骼肌（包括舌）中广泛表达，而在其他器官如平滑肌（胃和肠）以及心肌中均未检测到。此外，钙蛋白酶3也可能广泛存在于哺乳动物中。[1]
参考文献[编辑]
- ^ 1.0 1.1 1.2 1.3 Sorimachi H, Imajoh-Ohmi S, Emori Y, Kawasaki H, Ohno S, Minami Y, Suzuki K. 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. December 1989, 264 (33): 20106–11. PMID 2555341. doi:10.1016/S0021-9258(19)47225-6 可免费查阅.
- ^ Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C. Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A. Cell. May 1995, 81 (1): 27–40. PMID 7720071. doi:10.1016/0092-8674(95)90368-2 可免费查阅.
- ^ Entrez Gene: CAPN3 calpain 3, (p94).
- ^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E. Novel MITF targets identified using a two-step DNA microarray strategy. Pigment Cell Melanoma Res. 2008, 21 (6): 665–76. PMID 19067971. doi:10.1111/j.1755-148X.2008.00505.x 可免费查阅.
- ^ Ono Y, Shimada H, Sorimachi H, Richard I, Saido TC, Beckmann JS, Ishiura S, Suzuki K. Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A. J. Biol. Chem. July 1998, 273 (27): 17073–8. PMID 9642272. doi:10.1074/jbc.273.27.17073 可免费查阅.
- ^ Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K. Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence. J. Biol. Chem. December 1995, 270 (52): 31158–62. PMID 8537379. doi:10.1074/jbc.270.52.31158 可免费查阅.
- ^ An eccentric calpain, CAPN3/p94/calpain-3. Biochimie. 2016-03-01, 122 [2026-05-27]. ISSN 0300-9084. doi:10.1016/j.biochi.2015.09.010 （en-US）.
引伸阅读[编辑]
- Sorimachi H, Ishiura S, Suzuki K. Structure and physiological function of calpains. Biochem. J. 1997, 328 (3): 721–32. PMC 1218978 可免费查阅. PMID 9396712. doi:10.1042/bj3280721.
- Kinbara K, Sorimachi H, Ishiura S, Suzuki K. Skeletal muscle-specific calpain, p49: structure and physiological function. Biochem. Pharmacol. 1998, 56 (4): 415–20. PMID 9763216. doi:10.1016/S0006-2952(98)00095-1.
- 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. Elastic Filaments of the Cell. Advances in Experimental Medicine and Biology 481. 2000: 383–95; discussion 395–7. ISBN 978-1-4613-6916-5. PMID 10987085. doi:10.1007/978-1-4615-4267-4_23.
- Baghdiguian S, Richard I, Martin M, Coopman P, Beckmann JS, Mangeat P, Lefranc G. 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. 2001, 79 (5–6): 254–61. PMID 11485017. S2CID 286784. doi:10.1007/s001090100225.
- 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. Prevalence of the 550delA mutation in calpainopathy (LGMD 2A) in Croatia. Am. J. Med. Genet. A. 2004, 125A (2): 152–6. PMID 14981715. S2CID 21946737. doi:10.1002/ajmg.a.20408.
- Kramerova I, Beckmann JS, Spencer MJ. Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A) (PDF). Biochim. Biophys. Acta. 2007, 1772 (2): 128–44. PMID 16934440. S2CID 35100606. doi:10.1016/j.bbadis.2006.07.002.
- Ohno S, Minoshima S, Kudoh J, Fukuyama R, Shimizu Y, Ohmi-Imajoh S, Shimizu N, Suzuki K. Four genes for the calpain family locate on four distinct human chromosomes. Cytogenet. Cell Genet. 1990, 53 (4): 225–9. PMID 2209092. doi:10.1159/000132937.
- Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K. Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence. J. Biol. Chem. 1995, 270 (52): 31158–62. PMID 8537379. doi:10.1074/jbc.270.52.31158 可免费查阅.
- Fardeau M, Hillaire D, Mignard C, Feingold N, Feingold J, Mignard D, de Ubeda B, Collin H, Tome FM, Richard I, Beckmann J. Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island. Brain. 1996, 119 (1): 295–308. PMID 8624690. doi:10.1093/brain/119.1.295 可免费查阅.
- Corasaniti MT, Navarra M, Catani MV, Melino G, Nisticò G, Finazzi-Agrò A. 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. 1996, 229 (1): 299–304. PMID 8954122. doi:10.1006/bbrc.1996.1796.
- 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. Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins. Am. J. Hum. Genet. 1997, 60 (5): 1128–38. PMC 1712426 可免费查阅. PMID 9150160.
- 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 (1): 99–107. PMID 9185618. doi:10.1006/abbi.1997.0108.
- Pratt VM, Jackson CE, Wallace DC, Gurley DS, Feit A, Feldman GL. 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 (1): 231–3. PMC 1715865 可免费查阅. PMID 9246005. doi:10.1016/S0002-9297(07)64296-7.
- 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. A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey. Ann. Neurol. 1997, 42 (2): 222–9. PMID 9266733. S2CID 28524591. doi:10.1002/ana.410420214.
- Ono Y, Shimada H, Sorimachi H, Richard I, Saido TC, Beckmann JS, Ishiura S, Suzuki K. Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A. J. Biol. Chem. 1998, 273 (27): 17073–8. PMID 9642272. doi:10.1074/jbc.273.27.17073 可免费查阅.
- Pénisson-Besnier I, Richard I, Dubas F, Beckmann JS, Fardeau M. Pseudometabolic expression and phenotypic variability of calpain deficiency in two siblings. Muscle Nerve. 1998, 21 (8): 1078–80. PMID 9655129. S2CID 26307931. doi:10.1002/(SICI)1097-4598(199808)21:8<1078::AID-MUS15>3.0.CO;2-Q.
- 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. Limb-girdle muscular dystrophy in Guipúzcoa (Basque Country, Spain). Brain. 1998, 121 (9): 1735–47. PMID 9762961. doi:10.1093/brain/121.9.1735 可免费查阅.
- Huang Y, de Morrée A, van Remoortere A, Bushby K, Frants RR, den Dunnen JT, van der Maarel SM. Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle. Hum. Mol. Genet. 2008, 17 (12): 1855–66. PMC 2900895 可免费查阅. PMID 18334579. doi:10.1093/hmg/ddn081.
外部链接[编辑]
- The MEROPS online database for peptidases and their inhibitors: C02.004 互联网档案馆的存档，存档日期2008-04-11.
- 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.