Calpastatin

CAST
Identifiers
Aliases	CAST , BS-17, PLACK, calpastatin
External IDs	OMIM: 114090 MGI: 1098236 HomoloGene: 7658 GeneCards: CAST
Gene location (Human) Chr. Chromosome 5 (human) [1] Band 5q15 Start 96,525,267 bp [1] End 96,779,595 bp [1]
Gene location (Mouse) Chr. Chromosome 13 (mouse) [2] Band 13|13 C1 Start 74,840,487 bp [2] End 74,956,929 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon bronchial epithelial cell human penis synovial joint cavity of mouth urethra palpebral conjunctiva myocardium gums vagina Top expressed in spermatid seminiferous tubule lip esophagus triceps brachii muscle aorta myocardium of ventricle white adipose tissue sternocleidomastoid muscle belly cord More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase inhibitor activity cysteine-type endopeptidase inhibitor activity protein binding endopeptidase inhibitor activity RNA binding cadherin binding calcium-dependent cysteine-type endopeptidase inhibitor activity protease binding Cellular component endoplasmic reticulum membrane cytosol Biological process negative regulation of peptidase activity negative regulation of type B pancreatic cell apoptotic process inhibition of cysteine-type endopeptidase activity presynaptic active zone organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 831 12380 Ensembl ENSG00000153113 ENSMUSG00000021585 UniProt P20810 P51125 RefSeq (mRNA) NM_001042440 NM_001042441 NM_001042442 NM_001042443 NM_001042444 NM_001042445 NM_001042446 NM_001190442 NM_001284212 NM_001284213 NM_001750 NM_173060 NM_173061 NM_173062 NM_173063 NM_001330626 NM_001330627 NM_001330628 NM_001330629 NM_001330630 NM_001330631 NM_001330632 NM_001330633 NM_001330634 NM_001375317 NM_001301153 NM_001301155 NM_001301156 NM_001301157 NM_001301158 NM_001301160 NM_001301181 NM_009817 RefSeq (protein) NP_001035905 NP_001035906 NP_001035907 NP_001035908 NP_001035909 NP_001035910 NP_001035911 NP_001177371 NP_001271141 NP_001271142 NP_001317555 NP_001317556 NP_001317557 NP_001317558 NP_001317559 NP_001317560 NP_001317561 NP_001317562 NP_001317563 NP_001741 NP_775083 NP_001362246 NP_001288082 NP_001288084 NP_001288085 NP_001288086 NP_001288087 NP_001288089 NP_001288110 NP_033947 Location (UCSC) Chr 5: 96.53 – 96.78 Mb Chr 13: 74.84 – 74.96 Mb PubMed search [3] [4]
Wikidata
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Calpastatin is a protein that in humans is encoded by the CAST gene. ^{[5] [6] [7] [8]}

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.^{[ citation needed ]} 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. ^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000153113 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021585 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Ma H, Yang HQ, Takano E, Lee WJ, Hatanaka M, Maki M (Sep 1993). "Requirement of different subdomains of calpastatin for calpain inhibition and for binding to calmodulin-like domains". J Biochem. 113 (5): 591–9. doi:10.1093/oxfordjournals.jbchem.a124088. PMID   8340353.
6. Averna M, De Tullio R, Capini P, Salamino F, Pontremoli S, Melloni E (Dec 2003). "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. doi:10.1007/s00018-003-3288-0. PMID   14685690. S2CID   23794801.
7. Raynaud P, Jayat-Vignoles C, Laforet MP, Leveziel H, Amarger V (Apr 2005). "Four promoters direct expression of the calpastatin gene". Arch Biochem Biophys. 437 (1): 69–77. doi:10.1016/j.abb.2005.02.026. PMID   15820218.
8. "Entrez Gene: CAST calpastatin".

Further reading

• Murachi T (1989). "Intracellular regulatory system involving calpain and calpastatin". Biochem. Int. 18 (2): 263–94. PMID   2548504.
• Lee WJ, Ma H, Takano E, et al. (1992). "Molecular diversity in amino-terminal domains of human calpastatin by exon skipping". J. Biol. Chem. 267 (12): 8437–42. doi: 10.1016/S0021-9258(18)42463-5 . hdl: 2433/168719 . PMID   1569094.
• Adachi Y, Ishida-Takahashi A, Takahashi C, et al. (1991). "Phosphorylation and subcellular distribution of calpastatin in human hematopoietic system cells". J. Biol. Chem. 266 (6): 3968–72. doi: 10.1016/S0021-9258(19)67888-9 . PMID   1995645.
• Inazawa J, Nakagawa H, Misawa S, et al. (1991). "Assignment of the human calpastatin gene (CAST) to chromosome 5 at region q14----q22". Cytogenet. Cell Genet. 54 (3–4): 156–8. doi:10.1159/000132982. PMID   2265559.
• Uemori T, Shimojo T, Asada K, et al. (1990). "Characterization of a functional domain of human calpastatin". Biochem. Biophys. Res. Commun. 166 (3): 1485–93. doi:10.1016/0006-291X(90)91035-Q. PMID   2407243.
• Maki M, Bagci H, Hamaguchi K, et al. (1989). "Inhibition of calpain by a synthetic oligopeptide corresponding to an exon of the human calpastatin gene". J. Biol. Chem. 264 (32): 18866–9. doi: 10.1016/S0021-9258(19)47235-9 . PMID   2553724.
• Murachi T, Takano E, Maki M, et al. (1990). "Cloning and expression of the genes for calpains and calpastatins". Biochem. Soc. Symp. 55: 29–44. PMID   2559735.
• Asada K, Ishino Y, Shimada M, et al. (1991). "cDNA cloning of human calpastatin: sequence homology among human, pig, and rabbit calpastatins". J. Enzym. Inhib. 3 (1): 49–56. doi:10.3109/14756368909030363. PMID   2577276.
• Pontremoli S, Salamino F, Sparatore B, et al. (1989). "Characterization of the calpastatin defect in erythrocytes from patients with essential hypertension". Biochem. Biophys. Res. Commun. 157 (3): 867–74. doi:10.1016/S0006-291X(88)80955-0. PMID   2849943.
• Mimori T, Suganuma K, Tanami Y, et al. (1995). "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. Bibcode:1995PNAS...92.7267M. doi: 10.1073/pnas.92.16.7267 . PMC   41320 . PMID   7638179.
• Després N, Talbot G, Plouffe B, et al. (1995). "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. doi:10.1172/JCI117870. PMC   295733 . PMID   7706496.
• Wei SG, Wang LF, Miao SY, et al. (1995). "Expression of the calpastatin gene segment during spermiogenesis in human testis: an in situ hybridization study". Arch. Androl. 34 (1): 9–12. doi:10.3109/01485019508987826. PMID   7710300.
• Wang LF, Wei SG, Miao SY, et al. (1994). "Calpastatin gene in human testis". Biochem. Mol. Biol. Int. 33 (2): 245–51. PMID   7951045.
• Schwarz-Benmeir N, Glaser T, Barnoy S, Kosower NS (1995). "Calpastatin in erythrocytes of young and old individuals". Biochem. J. 304 (2): 365–70. doi:10.1042/bj3040365. PMC   1137502 . PMID   7998969.
• Fujitani K, Kambayashi J, Sakon M, et al. (1997). "Identification of mu-, m-calpains and calpastatin and capture of mu-calpain activation in endothelial cells". J. Cell. Biochem. 66 (2): 197–209. doi:10.1002/(SICI)1097-4644(19970801)66:2<197::AID-JCB7>3.0.CO;2-L. PMID   9213221. S2CID   85163404.
• Wang KK, Posmantur R, Nadimpalli R, et al. (1998). "Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis". Arch. Biochem. Biophys. 356 (2): 187–96. doi: 10.1006/abbi.1998.0748 . PMID   9705209. S2CID   11593624.
• Han Y, Weinman S, Boldogh I, et al. (1999). "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. doi: 10.1074/jbc.274.2.787 . PMID   9873017.
• Ishikawa H, Nakagawa Y, Shimizu K, et al. (2000). "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. doi:10.1006/bbrc.1999.1819. hdl: 2433/180881 . PMID   10600505.

External links

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