Calpastatin Explained

Calpastatin is a protein that in humans is encoded by the CAST gene.^{[1] [2] [3] [4]}

The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N-terminal domain L and four repetitive calpain-inhibition domains (domains 1–4), and it is involved in the proteolysis of amyloid precursor protein. The calpain/calpastatin system is involved in numerous membrane fusion events, such as neural vesicle exocytosis and platelet and red-cell aggregation. The encoded protein is also thought to affect the expression levels of genes encoding structural or regulatory proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length natures of only some have been determined.^[4]

Further reading

• Murachi T . Intracellular regulatory system involving calpain and calpastatin. . Biochem. Int. . 18 . 2 . 263–94 . 1989 . 2548504 .
• Lee WJ, Ma H, Takano E . Molecular diversity in amino-terminal domains of human calpastatin by exon skipping. . J. Biol. Chem. . 267 . 12 . 8437–42 . 1992 . 10.1016/S0021-9258(18)42463-5 . 1569094 . etal. free . 2433/168719 . free .
• Adachi Y, Ishida-Takahashi A, Takahashi C . Phosphorylation and subcellular distribution of calpastatin in human hematopoietic system cells. . J. Biol. Chem. . 266 . 6 . 3968–72 . 1991 . 10.1016/S0021-9258(19)67888-9 . 1995645 . etal. free .
• Inazawa J, Nakagawa H, Misawa S . Assignment of the human calpastatin gene (CAST) to chromosome 5 at region q14----q22. . Cytogenet. Cell Genet. . 54 . 3–4 . 156–8 . 1991 . 2265559 . 10.1159/000132982 . etal.
• Uemori T, Shimojo T, Asada K . Characterization of a functional domain of human calpastatin. . Biochem. Biophys. Res. Commun. . 166 . 3 . 1485–93 . 1990 . 2407243 . 10.1016/0006-291X(90)91035-Q . etal.
• Maki M, Bagci H, Hamaguchi K . Inhibition of calpain by a synthetic oligopeptide corresponding to an exon of the human calpastatin gene. . J. Biol. Chem. . 264 . 32 . 18866–9 . 1989 . 10.1016/S0021-9258(19)47235-9 . 2553724 . etal. free .
• Murachi T, Takano E, Maki M . Cloning and expression of the genes for calpains and calpastatins. . Biochem. Soc. Symp. . 55 . 29–44 . 1990 . 2559735 . etal.
• Asada K, Ishino Y, Shimada M . cDNA cloning of human calpastatin: sequence homology among human, pig, and rabbit calpastatins. . J. Enzym. Inhib. . 3 . 1 . 49–56 . 1991 . 2577276 . 10.3109/14756368909030363 . etal.
• Pontremoli S, Salamino F, Sparatore B . Characterization of the calpastatin defect in erythrocytes from patients with essential hypertension. . Biochem. Biophys. Res. Commun. . 157 . 3 . 867–74 . 1989 . 2849943 . 10.1016/S0006-291X(88)80955-0 . etal.
• Mimori T, Suganuma K, Tanami Y . Autoantibodies to calpastatin (an endogenous inhibitor for calcium-dependent neutral protease, calpain) in systemic rheumatic diseases. . Proc. Natl. Acad. Sci. U.S.A. . 92 . 16 . 7267–71 . 1995 . 7638179 . 10.1073/pnas.92.16.7267 . 41320 . 1995PNAS...92.7267M . etal. free .
• Després N, Talbot G, Plouffe B . Detection and expression of a cDNA clone that encodes a polypeptide containing two inhibitory domains of human calpastatin and its recognition by rheumatoid arthritis sera. . J. Clin. Invest. . 95 . 4 . 1891–6 . 1995 . 7706496 . 10.1172/JCI117870 . 295733 . etal.
• Wei SG, Wang LF, Miao SY . Expression of the calpastatin gene segment during spermiogenesis in human testis: an in situ hybridization study. . Arch. Androl. . 34 . 1 . 9–12 . 1995 . 7710300 . 10.3109/01485019508987826 . etal.
• Wang LF, Wei SG, Miao SY . Calpastatin gene in human testis. . Biochem. Mol. Biol. Int. . 33 . 2 . 245–51 . 1994 . 7951045 . etal.
• Schwarz-Benmeir N, Glaser T, Barnoy S, Kosower NS . Calpastatin in erythrocytes of young and old individuals. . Biochem. J. . 304 . 2. 365–70 . 1995 . 7998969 . 10.1042/bj3040365. 1137502 .
• Fujitani K, Kambayashi J, Sakon 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 . etal.
• Wang KK, Posmantur R, Nadimpalli R . 11593624 . Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis. . Arch. Biochem. Biophys. . 356 . 2 . 187–96 . 1998 . 9705209 . 10.1006/abbi.1998.0748 . etal. free .
• Han Y, Weinman S, Boldogh I . Tumor necrosis factor-alpha-inducible IkappaBalpha proteolysis mediated by cytosolic m-calpain. A mechanism parallel to the ubiquitin-proteasome pathway for nuclear factor-kappab activation. . J. Biol. Chem. . 274 . 2 . 787–94 . 1999 . 9873017 . 10.1074/jbc.274.2.787 . etal. free .
• Ishikawa H, Nakagawa Y, Shimizu K . Inflammatory cytokines induced down-regulation of m-calpain mRNA expression in fibroblastic synoviocytes from patients with osteoarthritis and rheumatoid arthritis. . Biochem. Biophys. Res. Commun. . 266 . 2 . 341–6 . 2000 . 10600505 . 10.1006/bbrc.1999.1819 . etal. 2433/180881 . free .

External links

• The MEROPS online database for peptidases and their inhibitors: LI27.001

Notes and References

1. Ma H, Yang HQ, Takano E, Lee WJ, Hatanaka M, Maki M . Requirement of different subdomains of calpastatin for calpain inhibition and for binding to calmodulin-like domains . J Biochem . 113 . 5 . 591–9 . Sep 1993 . 8340353 . 10.1093/oxfordjournals.jbchem.a124088.
2. Averna M, De Tullio R, Capini P, Salamino F, Pontremoli S, Melloni E . Changes in calpastatin localization and expression during calpain activation: a new mechanism for the regulation of intracellular Ca(2+)-dependent proteolysis . Cell Mol Life Sci . 60 . 12 . 2669–78 . Dec 2003 . 14685690 . 10.1007/s00018-003-3288-0 . 23794801 . 11138551 .
3. Raynaud P, Jayat-Vignoles C, Laforet MP, Leveziel H, Amarger V . Four promoters direct expression of the calpastatin gene . Arch Biochem Biophys . 437 . 1 . 69–77 . Apr 2005 . 15820218 . 10.1016/j.abb.2005.02.026 .
4. Web site: Entrez Gene: CAST calpastatin.