Calpain
Calpain | |||||||||||
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calpain-1 | |||||||||
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Identifiers | |||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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calpain-2 | |||||||||
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Identifiers | |||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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A calpain (
Discovery
The history of calpain's discovery originates in 1964, when calcium-dependent proteolytic activities caused by a "calcium-activated neutral protease" (CANP) were detected in
To date, these two isoforms remain the best characterised members of the calpain family. Structurally, these two
Cleavage specificity
No specific
Extended family
The Human Genome Project has revealed that more than a dozen other calpain
Gene | Protein | Aliases | Tissue expression | Disease linkage |
---|---|---|---|---|
CAPN1 |
Calpain 1 | Calpain-1 large subunit, Calpain mu-type | ubiquitous | |
CAPN2 |
Calpain 2 | Calpain-2 large subunit, Calpain m-type | ubiquitous | |
CAPN3 |
Calpain 3 | skeletal muscle retina and lens specific | Limb Girdle muscular dystrophy 2A | |
CAPN5 | Calpain 5 | ubiquitous (high in colon, small intestine and testis) | might be linked to necrosis, as it is an ortholog of the C. elegans necrosis gene tra-3 | |
CAPN6 |
Calpain 6 | CAPNX, Calpamodulin | ||
CAPN7 | Calpain 7 | palBH | ubiquitous | |
CAPN8 |
Calpain 8 | exclusive to stomach mucosa and the GI tract | might be linked to colon polyp formation | |
CAPN9 |
Calpain 9 | exclusive to stomach mucosa and the GI tract | might be linked to colon polyp formation | |
CAPN10 | Calpain 10 | susceptibility gene for type II diabetes | ||
CAPN11 | Calpain 11 | testis | ||
CAPN12 | Calpain 12 | ubiquitous but high in hair follicle | ||
CAPN13 | Calpain 13 | testis and lung | ||
CAPN14 | Calpain 14 | ubiquitous | ||
CAPN17 | Calpain 17 | Fish and amphibian-only | ||
SOLH | Calpain 15 | Sol H (homolog of the drosophila gene sol) | ||
CAPNS1 |
Calpain small subunit 1 | Calpain 4 | ||
CAPNS2 | Calpain small subunit 2 |
Function
Although the physiological role of calpains is still poorly understood, they have been shown to be active participants in processes such as
Enhanced calpain activity, regulated by CAPNS1, significantly contributes to platelet hyperreactivity under hypoxic environment.[10]
In the brain, while μ-calpain is mainly located in the
Clinical significance
Pathology
The structural and functional diversity of calpains in the cell is reflected in their involvement in the pathogenesis of a wide range of disorders. At least two well known genetic disorders and one form of cancer have been linked to tissue-specific calpains. When defective, the mammalian calpain 3 (also known as p94) is the gene product responsible for limb-girdle muscular dystrophy type 2A,
Therapeutic inhibitors
The exogenous regulation of calpain activity is therefore of interest for the development of therapeutics in a wide array of pathological states. As a few of the many examples supporting the therapeutic potential of calpain inhibition in ischemia, calpain inhibitor AK275 protected against focal ischemic brain damage in rats when administered after ischemia, and MDL28170 significantly reduced the size of damaged infarct tissue in a rat focal ischemia model. Also, calpain inhibitors are known to have neuroprotective effects: PD150606,[20] SJA6017,[21] ABT-705253,[22][23] and SNJ-1945.[24]
Calpain may be released in the brain for up to a month after a head injury, and may be responsible for a shrinkage of the brain sometimes found after such injuries.[25] However, calpain may also be involved in a "resculpting" process that helps repair damage after injury.[25]
See also
References
- ^ "the definition of calpain". Dictionary.com. Retrieved 23 April 2018.
- S2CID 4359635.
- S2CID 22674283.
- PMID 16216885.
- ^ Thompson V (2002-02-12). "Calpain Nomenclature". College of Agriculture and Life Sciences at the University of Arizona. Retrieved 2010-08-06.
- PMID 11516996.
- PMID 14749260.
- ^ PMID 23760237.
- S2CID 3538480.
- ^ PMID 24297866.
- ^ ISBN 978-0-471-36015-5.
- PMID 8905185.
- S2CID 17565219.
- PMID 9642272.
- S2CID 39292302.
- S2CID 21992464.
- S2CID 54228571.
- PMID 15140932.
- PMID 25068024.
- PMID 8692879.
- PMID 11721741.
- PMID 12773044.
- PMID 20233208.
- S2CID 29425598.
- ^ a b White V (1999-10-21). "– 'Biochemical Storm' Following Brain Trauma An Important Factor In Treatment, University of Florida Researcher Finds". University of Florida News. Archived from the original on 2011-06-23. Retrieved 2010-08-07.
Further reading
- Liu J, Liu MC, Wang KK (2008). "Calpain in the CNS: from synaptic function to neurotoxicity". Sci Signal. 1 (14): re1. S2CID 21992464.
- Suzuki K, Hata S, Kawabata Y, Sorimachi H (February 2004). "Structure, activation, and biology of calpain". Diabetes. 53. Suppl 1: S12–8. PMID 14749260.
- Yuen PW, Wang KW (1999). Calpains : Pharmacology and Toxicology of a Cellular Protease. Boca Raton: CRC Press. ISBN 978-1-56032-713-4.
External links
- Calpain at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- CaMPDB, Calpain for Modulatory Proteolysis Database
- The Calpain Family of Proteases. (2001). University of Arizona.
- Calpain Info with links in the Cell Migration Gateway
- Alzheimers and calpain protease, PMAP The Proteolysis Map-animation.