鈣蛋白酶3
（重新導向自CAPN3）
Module:Infobox_gene第53行Lua錯誤：attempt to index field 'wikibase' (a nil value)
鈣蛋白酶3（英語：Calpain-3）是一種蛋白質，在人類中由CAPN3基因編碼。[1][2]
功能[編輯]
鈣蛋白酶是細胞內的一種核心蛋白酶，通常由大、小兩個亞基組成異源二聚體，不過其具體生理功能目前尚未完全明確。CAPN3基因編碼的是鈣蛋白酶大亞基家族中一個肌肉特異性成員，該成員能與肌聯蛋白發生特異性結合。該基因的突變與2A型肢帶型肌失養症密切相關。由於不同的啟動子和可變剪接的存在，該基因擁有多種轉錄本變體，可編碼不同的蛋白質亞型，其中部分變體在全身各組織中廣泛表達。[3]
在黑素細胞中，CAPN3基因的表達可能受到小眼畸形相關轉錄因子（MITF）的調控。[4]
相互作用[編輯]
結構[編輯]
鈣蛋白酶3由821個氨基酸殘基組成，其全長結構可劃分為四個功能結構域：[1]
- 結構域I（殘基1至98）：該結構域較其他鈣蛋白酶大亞基的結構域I長20至30個氨基酸殘基，且序列差異顯著（同源性<20%）。鑑於其氮端在鈣蛋白酶1和2的活化中發揮着重要作用，其特異序列提示該活化過程（如果存在的話）可能具有不同的機制。
- 結構域II（殘基99至400）：該結構域為半胱氨酸蛋白酶催化結構域，與其他鈣蛋白酶的結構域II高度同源。此外，此結構域表明鈣蛋白酶3可能具有蛋白水解活性。
- 結構域III（殘基401至653）： 其確切的生理功能尚不完全明晰。
- 結構域IV（殘基654至821）：該結構域包含四個EF手結構，表明鈣蛋白酶3的結構域IV具有鈣離子結合活性。
發現[編輯]
1989年，反町洋之等人在篩選人類骨骼肌cDNA文庫時，發現了一種與常規μ型及m型鈣蛋白酶僅具有部分同源性的全新蛋白酶，並將其暫命名為p94。後續研究表明，該蛋白屬於鈣蛋白酶家族的新成員，其編碼序列在人類與大鼠間高度保守。[1]2013年，美國實驗生物學學會聯合會（FASEB）正式將p94重命名為鈣蛋白酶3，儘管當時其特性尚未完全闡明。[7]
表達[編輯]
鈣蛋白酶3僅在骨骼肌（包括舌）中廣泛表達，而在其他器官如平滑肌（胃和腸）以及心肌中均未檢測到。此外，鈣蛋白酶3也可能廣泛存在於哺乳動物中。[1]
參考文獻[編輯]
- ^ 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 可免費查閱.
- ^ 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 可免費查閱.
- ^ 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 可免費查閱.
- ^ 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 可免費查閱.
- ^ 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 可免費查閱.
- ^ 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）.
引伸閱讀[編輯]
- Sorimachi H, Ishiura S, Suzuki K. Structure and physiological function of calpains. Biochem. J. 1997, 328 (3): 721–32. PMC 1218978 可免費查閱. 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 可免費查閱.
- 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 可免費查閱.
- 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 可免費查閱. 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 可免費查閱. 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 可免費查閱.
- 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 可免費查閱.
- 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 可免費查閱. PMID 18334579. doi:10.1093/hmg/ddn081.
外部連結[編輯]
- The MEROPS online database for peptidases and their inhibitors: C02.004 互聯網檔案館的存檔，存檔日期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.