Calpain-2 catalytic subunit explained

Calpain-2 catalytic subunit is a protein that in humans is encoded by the CAPN2 gene.^{[1] [2]}

Function

The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 2. Multiple heterogeneous transcriptional start sites in the 5' UTR have been reported.^[3]

Interactions

CAPN2 has been shown to interact with Bcl-2.^[4]

Further reading

• Suzuki K, Sorimachi H, Yoshizawa T, Kinbara K, Ishiura S . Calpain: novel family members, activation, and physiologic function . Biol. Chem. Hoppe-Seyler . 376 . 9 . 523–9 . 1995 . 8561910 . 10.1515/bchm3.1995.376.9.523.
• Cohen GM . Caspases: the executioners of apoptosis . Biochem. J. . 326 . Pt 1 . 1–16 . 1997 . 9337844 . 1218630 . 10.1042/bj3260001.
• Reverter D, Sorimachi H, Bode W . The structure of calcium-free human m-calpain: implications for calcium activation and function . Trends Cardiovasc. Med. . 11 . 6 . 222–9 . 2001 . 11673052 . 10.1016/S1050-1738(01)00112-8 .
• Kopp S . Reproducibility of response to a questionnaire on symptoms of masticatory dysfunction . Community Dent Oral Epidemiol . 4 . 5 . 205–9 . 1976 . 1067155 . 10.1111/j.1600-0528.1976.tb00985.x .
• Adachi Y, Kitahara-Ozawa A, Sugamura K, Lee WJ, Yodoi J, Maki M, Murachi T, Hatanaka M . Expression of calpain II gene in human hematopoietic system cells infected with human T-cell leukemia virus type I . J. Biol. Chem. . 267 . 27 . 19373–8 . 1992 . 10.1016/S0021-9258(18)41785-1 . 1527057 . free .
• 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. . 53 . 4 . 225–9 . 1990 . 2209092 . 10.1159/000132937 .
• Ishiguro H, Higashiyama S, Namikawa C, Kunimatsu M, Takano E, Tanaka K, Ohkubo I, Murachi T, Sasaki M . Interaction of human calpains I and II with high molecular weight and low molecular weight kininogens and their heavy chain: mechanism of interaction and the role of divalent cations . Biochemistry . 26 . 10 . 2863–70 . 1987 . 3038169 . 10.1021/bi00384a030 .
• Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES . The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32 . J. Biol. Chem. . 271 . 43 . 27099–106 . 1996 . 8900201 . 10.1074/jbc.271.43.27099 . free .
• 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. . 229 . 1 . 299–304 . 1996 . 8954122 . 10.1006/bbrc.1996.1796 .
• Fujitani K, Kambayashi J, Sakon M, Ohmi SI, Kawashima S, Yukawa M, Yano Y, Miyoshi H, Ikeda M, Shinoki N, Monden M . Identification of mu-, m-calpains and calpastatin and capture of mu-calpain activation in endothelial cells . J. Cell. Biochem. . 66 . 2 . 197–209 . 1997 . 9213221 . 10.1002/(SICI)1097-4644(19970801)66:2<197::AID-JCB7>3.0.CO;2-L . 85163404 .
• Rock MT, Brooks WH, Roszman TL . Calcium-dependent signaling pathways in T cells. Potential role of calpain, protein tyrosine phosphatase 1b, and p130Cas in integrin-mediated signaling events . J. Biol. Chem. . 272 . 52 . 33377–83 . 1997 . 9407132 . 10.1074/jbc.272.52.33377 . free .
• Ueyama H, Kumamoto T, Fujimoto S, Murakami T, Tsuda T . Expression of three calpain isoform genes in human skeletal muscles . J. Neurol. Sci. . 155 . 2 . 163–9 . 1998 . 9562261 . 10.1016/S0022-510X(97)00309-2 . 205898607 .
• Strobl S, Fernandez-Catalan C, Braun M, Huber R, Masumoto H, Nakagawa K, Irie A, Sorimachi H, Bourenkow G, Bartunik H, Suzuki K, Bode W . The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium . Proc. Natl. Acad. Sci. U.S.A. . 97 . 2 . 588–92 . 2000 . 10639123 . 15374 . 10.1073/pnas.97.2.588 . 2000PNAS...97..588S . free .
• Masumoto H, Nakagawa K, Irie S, Sorimachi H, Suzuki K, Bourenkov GP, Bartunik H, Fernandez-Catalan C, Bode W, Strobl S . Crystallization and preliminary X-ray analysis of recombinant full-length human m-calpain . Acta Crystallogr. D . 56 . Pt 1 . 73–5 . 2000 . 10666632 . 10.1107/S0907444999013748 . 2000AcCrD..56...73M .
• Chua BT, Guo K, Li P . Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases . J. Biol. Chem. . 275 . 7 . 5131–5 . 2000 . 10671558 . 10.1074/jbc.275.7.5131 . free .
• Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH . Neurotoxicity induces cleavage of p35 to p25 by calpain . Nature . 405 . 6784 . 360–4 . 2000 . 10830966 . 10.1038/35012636 . 2000Natur.405..360L . 205006589 .

External links

• The MEROPS online database for peptidases and their inhibitors: C02.002

Notes and References

1. Imajoh S, Aoki K, Ohno S, Emori Y, Kawasaki H, Sugihara H, Suzuki K . Molecular cloning of the cDNA for the large subunit of the high-Ca2+-requiring form of human Ca2+-activated neutral protease . Biochemistry . 27 . 21 . 8122–8 . 1988 . 2852952 . 10.1021/bi00421a022 .
2. Hata A, Ohno S, Akita Y, Suzuki K . Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit of calcium-dependent protease . J. Biol. Chem. . 264 . 11 . 6404–11 . May 1989 . 10.1016/S0021-9258(18)83364-6 . 2539381 . free .
3. Web site: Entrez Gene: CAPN2 calpain 2, (m/II) large subunit.
4. Gil-Parrado S, Fernández-Montalván A, Assfalg-Machleidt I, Popp O, Bestvater F, Holloschi A, Knoch TA, Auerswald EA, Welsh K, Reed JC, Fritz H, Fuentes-Prior P, Spiess E, Salvesen GS, Machleidt W . Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members . J. Biol. Chem. . 277 . 30 . 27217–26 . Jul 2002 . 12000759 . 10.1074/jbc.M202945200 . free .