Calcineurin
Calcineurin (CaN) is a
Structure
Calcineurin is a heterodimer of a 61-kD calmodulin-binding catalytic subunit, calcineurin A and a 19-kD Ca2+-binding regulatory subunit, calcineurin B. There are three isozymes of the catalytic subunit, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two isoforms of the regulatory, also encoded by separate genes (PPP3R1, PPP3R2).
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Mechanism of action
When an
Clinical relevance
Rheumatic diseases
Calcineurin inhibitors are prescribed for adult
Schizophrenia
Calcineurin is linked to receptors for several brain chemicals including
Diabetes
Calcineurin along with NFAT, may improve the function of diabetics'
Calcineurin/NFAT signaling is required for perinatal lung maturation and function.[10]
Organ transplantation
Calcineurin inhibitors such as tacrolimus are used to suppress the immune system in organ allotransplant recipients to prevent rejection of the transplanted tissue.[11]
Interactions
Calcineurin has been shown to
References
- S2CID 4337105.
- S2CID 43848098.
- PMID 10839803.
- ^ "Pharmacology and side effects of cyclosporine and tacrolimus". UpToDate. 2014-04-10.
- S2CID 18512241.
- PMID 12851457.
- S2CID 4397036.
- S2CID 21027866.
- PMID 17699434.
- PMID 16998587.
- ^ "Tacrolimus". New Zealand Formulary v81. 1 March 2019.
- PMID 10861295.
- PMID 9765270.
Further reading
- Cottrell JR, Levenson JM, Kim SH, Gibson HE, Richardson KA, Sivula M, Li B, Ashford CJ, Heindl KA, Babcock RJ, Rose DM, Hempel CM, Wiig KA, Laeng P, Levin ME, Ryan TA, Gerber DJ (July 2013). "Working memory impairment in calcineurin knock-out mice is associated with alterations in synaptic vesicle cycling and disruption of high-frequency synaptic and network activity in prefrontal cortex". J. Neurosci. 33 (27): 10938–49. PMID 23825400.
- Crabtree GR (1999). "Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT". Cell. 96 (5): 611–4. S2CID 8817053.
- Giri PR, Higuchi S, Kincaid RL (1991). "Chromosomal mapping of the human genes for the calmodulin-dependent protein phosphatase (calcineurin) catalytic subunit". Biochem. Biophys. Res. Commun. 181 (1): 252–8. PMID 1659808.
- Kincaid RL, Giri PR, Higuchi S, Tamura J, Dixon SC, Marietta CA, Amorese DA, Martin BM (1990). "Cloning and characterization of molecular isoforms of the catalytic subunit of calcineurin using nonisotopic methods". J. Biol. Chem. 265 (19): 11312–9. PMID 2162844.
- Guerini D, Klee CB (1989). "Cloning of human calcineurin A: evidence for two isozymes and identification of a polyproline structural domain". Proc. Natl. Acad. Sci. U.S.A. 86 (23): 9183–7. PMID 2556704.
- Kincaid RL, Nightingale MS, Martin BM (1988). "Characterization of a cDNA clone encoding the calmodulin-binding domain of mouse brain calcineurin". Proc. Natl. Acad. Sci. U.S.A. 85 (23): 8983–7. PMID 2848250.
- Coghlan VM, Perrino BA, Howard M, Langeberg LK, Hicks JB, Gallatin WM, Scott JD (1995). "Association of protein kinase A and protein phosphatase 2B with a common anchoring protein". Science. 267 (5194): 108–11. PMID 7528941.
- Griffith JP, Kim JL, Kim EE, Sintchak MD, Thomson JA, Fitzgibbon MJ, Fleming MA, Caron PR, Hsiao K, Navia MA (1995). "X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex". Cell. 82 (3): 507–22. S2CID 15502270.
- Shibasaki F, McKeon F (1995). "Calcineurin functions in Ca(2+)-activated cell death in mammalian cells". J. Cell Biol. 131 (3): 735–43. PMID 7593193.
- Muramatsu T, Kincaid RL (1993). "Molecular cloning of a full-length cDNA encoding the catalytic subunit of human calmodulin-dependent protein phosphatase (calcineurin A alpha)". Biochim. Biophys. Acta. 1178 (1): 117–20. PMID 8392375.
- Cameron AM, Steiner JP, Roskams AJ, Ali SM, Ronnett GV, Snyder SH (1995). "Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux". Cell. 83 (3): 463–72. S2CID 11594556.
- Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW (1995). "Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex". Nature. 378 (6557): 641–4. S2CID 4337105.
- Wang MG, Yi H, Guerini D, Klee CB, McBride OW (1996). "Calcineurin A alpha (PPP3CA), calcineurin A beta (PPP3CB) and calcineurin B (PPP3R1) are located on human chromosomes 4, 10q21-->q22 and 2p16-->p15 respectively". Cytogenet. Cell Genet. 72 (2–3): 236–41. PMID 8978785.
- Shibasaki F, Kondo E, Akagi T, McKeon F (1997). "Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2". Nature. 386 (6626): 728–31. S2CID 4277216.
- Kashishian A, Howard M, Loh C, Gallatin WM, Hoekstra MF, Lai Y (1998). "AKAP79 inhibits calcineurin through a site distinct from the immunophilin-binding region". J. Biol. Chem. 273 (42): 27412–9. PMID 9765270.
- Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC (1999). "Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD". Science. 284 (5412): 339–43. PMID 10195903.
- Fuentes JJ, Genescà L, Kingsbury TJ, Cunningham KW, Pérez-Riba M, Estivill X, de la Luna S (2000). "DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways". Hum. Mol. Genet. 9 (11): 1681–90. PMID 10861295.
- Hartley JL, Temple GF, Brasch MA (2000). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. PMID 11076863.
- Frey N, Richardson JA, Olson EN (2000). "Calsarcins, a novel family of sarcomeric calcineurin-binding proteins". Proc. Natl. Acad. Sci. U.S.A. 97 (26): 14632–7. PMID 11114196.
- Siddiq A, Miyazaki T, Takagishi Y, Kanou Y, Hayasaka S, Inouye M, Seo H, Murata Y (2001). "Expression of ZAKI-4 messenger ribonucleic acid in the brain during rat development and the effect of hypothyroidism". Endocrinology. 142 (5): 1752–9. PMID 11316738.
External links
- Calcineurin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)