CAPN10 explained

Calpain-10 is a protein that in humans is encoded by the CAPN10 gene.^{[1] [2]}

Overview

Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The typical calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. The heterodimer interface is predominantly found between domain IV and the small subunit, which is also a calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It therefore cannot heterodimerize with the small subunit. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM) and located within the NIDDM1 region. Multiple alternative transcript variants encoding different isoforms have been described for this gene.^[3]

Further reading

• Sorimachi H, Ishiura S, Suzuki K . Structure and physiological function of calpains. . Biochem. J. . 328 . 3. 721–32 . 1998 . 9396712 . 10.1042/bj3280721. 1218978 .
• Cox NJ . Linkage of calpain 10 to type 2 diabetes: the biological rationale . Diabetes . 53 . S19–25 . 2004 . 14749261 . 10.2337/diabetes.53.2007.s19. Hayes MG . Roe CA . 3 . Tsuchiya . T . Bell . GI . Suppl 1 . free.
• Turner MD, Cassell PG, Hitman GA . Calpain-10: from genome search to function . Diabetes Metab. Res. Rev. . 21 . 6 . 505–14 . 2006 . 16028216 . 10.1002/dmrr.578 . 39651682 . free .
• Horikawa Y . Calpain-10 (NIDDM1) as a Susceptibility Gene for Common Type 2 Diabetes . Endocr. J. . 53 . 5 . 567–76 . 2007 . 16873988 . 10.1507/endocrj.KR-70 . free .
• Nagase T . Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Res. . 8 . 2 . 85–95 . 2001 . 11347906 . 10.1093/dnares/8.2.85 . Nakayama M . Nakajima D . 3 . Kikuno . R . Ohara . O . free.
• Ma H . Characterization and expression of calpain 10. A novel ubiquitous calpain with nuclear localization . J. Biol. Chem. . 276 . 30 . 28525–31 . 2001 . 11375982 . 10.1074/jbc.M100603200 . Fukiage C . Kim YH . 3 . Duncan . MK . Reed . NA . Shih . M . Azuma . M . Shearer . TR . free .
• Evans JC . Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom . Am. J. Hum. Genet. . 69 . 3 . 544–52 . 2001 . 11481585 . 10.1086/323315 . 1235484 . Frayling TM . Cassell PG . 3 . Saker . Philip J. . Hitman . Graham A. . Walker . Mark . Levy . Jonathan C. . o’Rahilly . Stephen . Rao . Pamidighantam V. Subba .
• Tsai HJ . Type 2 diabetes and three calpain-10 gene polymorphisms in Samoans: no evidence of association . Am. J. Hum. Genet. . 69 . 6 . 1236–44 . 2002 . 11704924 . 10.1086/324646 . 1235535 . Sun G . Weeks DE . 3 . Kaushal . Ritesh . Wolujewicz . Michael . McGarvey . Stephen T. . Tufa . Joseph . Viali . Satupaitea . Deka . Ranjan .
• Woollard JR, Rothschild MF . Assignment of the porcine calpain-10 gene (CAPN10) to chromosome 15q23-26 . Anim. Genet. . 32 . 6 . 393 . 2002 . 11736815 . 10.1046/j.1365-2052.2001.0781d.x .
• Xiang K . [The impact of calpain-10 gene combined-SNP variation on type 2 diabetes mellitus and its related metabolic traits] . Zhonghua Yi Xue Yi Chuan Xue Za Zhi . 18 . 6 . 426–30 . 2002 . 11774208 . Fang Q . Zheng T . 3 . Jia . W . Wang . Y . Zhang . R . Li . J . Shen . K .
• Elbein SC . Role of calpain-10 gene variants in familial type 2 diabetes in Caucasians . J. Clin. Endocrinol. Metab. . 87 . 2 . 650–4 . 2002 . 11836299 . 10.1210/jcem.87.2.8210 . Chu W . Ren Q . 3 . Hemphill . C . Schay . J . Cox . NJ . Hanis . CL . Hasstedt . SJ . free .
• Daimon M . Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese . Diabetes Res. Clin. Pract. . 56 . 2 . 147–52 . 2002 . 11891023 . 10.1016/S0168-8227(01)00372-2 . Oizumi T . Saitoh T . 3 . Kameda . W . Yamaguchi . H . Ohnuma . H . Igarashi . M . Manaka . H . Kato . T .
• Fullerton SM . Geographic and haplotype structure of candidate type 2 diabetes susceptibility variants at the calpain-10 locus . Am. J. Hum. Genet. . 70 . 5 . 1096–106 . 2002 . 11891618 . 10.1086/339930 . 447588 . Bartoszewicz A . Ybazeta G . 3 . Horikawa . Yukio . Bell . Graeme I. . Kidd . Kenneth K. . Cox . Nancy J. . Hudson . Richard R. . Di Rienzo . Anna .
• Hoffstedt J . Polymorphism in the Calpain 10 gene influences glucose metabolism in human fat cells . Diabetologia . 45 . 2 . 276–82 . 2002 . 11935160 . 10.1007/s00125-001-0732-2 . Rydén M . Löfgren P . 3 . Orho-Melander . M. . Groop . L. . Arner . P. . free.
• Malecki MT . Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population . Eur. J. Endocrinol. . 146 . 5 . 695–9 . 2002 . 11980626 . 10.1530/eje.0.1460695 . Moczulski DK . Klupa T . 3 . Wanic . K . Cyganek . K . Frey . J . Sieradzki . J . free .
• Sun HX . Single nucleotide polymorphisms in CAPN10 gene of Chinese people and its correlation with type 2 diabetes mellitus in Han people of northern China . Biomed. Environ. Sci. . 15 . 1 . 75–82 . 2002 . 12046551 . Zhang KX . Du WN . 3 . Shi . JX . Jiang . ZW . Sun . H . Zuo . J . Huang . W . Chen . Z .
• Haddad L . Variation within the type 2 diabetes susceptibility gene calpain-10 and polycystic ovary syndrome . J. Clin. Endocrinol. Metab. . 87 . 6 . 2606–10 . 2002 . 12050223 . 10.1210/jcem.87.6.8608 . Evans JC . Gharani N . 3 . Robertson . C . Rush . K . Wiltshire . S . Frayling . TM . Wilkin . TJ . Demaine . A . free .

External links

• The MEROPS online database for peptidases and their inhibitors: C02.018

Notes and References

1. Horikawa Y, Oda N, Cox NJ, Li X, Orho-Melander M, Hara M, Hinokio Y, Lindner TH, Mashima H, Schwarz PE, del Bosque-Plata L, Horikawa Y, Oda Y, Yoshiuchi I, Colilla S, Polonsky KS, Wei S, Concannon P, Iwasaki N, Schulze J, Baier LJ, Bogardus C, Groop L, Boerwinkle E, Hanis CL, Bell GI . Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus . Nat Genet . 26 . 2 . 163–75 . Nov 2000 . 11017071 . 10.1038/79876 . 5940859 . 2019-09-19 . 2017-09-21 . https://web.archive.org/web/20170921222503/http://ir.library.osaka-u.ac.jp/dspace/bitstream/11094/44642/1/18152_%e8%a6%81%e6%97%a8.pdf . dead .
2. Baier LJ, Permana PA, Yang X, Pratley RE, Hanson RL, Shen GQ, Mott D, Knowler WC, Cox NJ, Horikawa Y, Oda N, Bell GI, Bogardus C . A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance . J Clin Invest . 106 . 7 . R69–73 . Oct 2000 . 11018080 . 387246 . 10.1172/JCI10665 .
3. Web site: Entrez Gene: CAPN10 calpain 10.