Izvorni kod stranice Kalcineurin

[[Datoteka:Protein PPP3CA PDB 1aui.png|thumb|Kristalografska struktura kalcineurinskog heterodimera formirana od katalitičke ([[PPP3CA]]) i regulatorne ([[PPP3R1]]) podjedinice.<ref name="pmid8524402">{{PDB|1AUI}}; {{cite journal | author = Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW | title = Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex | journal = Nature | volume = 378 | issue = 6557 | pages = 641–4 | year = 1995 | month = December | pmid = 8524402 | doi = 10.1038/378641a0 }}</ref>]]

'''Kalcineurin''' (CN) je [[Fosfataza|proteinska fosfataza]], takođe poznata kao [[protein]]ska [[fosfataza]] 3, i kalcijum-zavisna serin-treoninska fosfataza.<ref name="pmid15865209">{{cite journal | author = Liu L, Zhang J, Yuan J, Dang Y, Yang C, Chen X, Xu J, Yu L.  | title = Crystal Characterization of a human regulatory subunit of protein phosphatase 3 gene (PPP3RL) expressed specifically in testis | journal = Mol Biol Rep | volume = 32 | issue = 1 | pages = 41–45 | year = 2005 | month = March | pmid = 15865209 | doi=10.1007/s11033-004-4250-4}}</ref>. On aktivira [[T ćelija|T ćelije]] [[imunski sistem|imunskog sistema]], i može se blokirati lekovima. Kalcineurin aktivira nuklearni faktor aktiviranih T ćelija, citoplazmni ([[NFATC1|NFATc]]) [[transkripcioni faktor]], putem njegove [[defosforilacija|defosforilacije]]. Aktivirani NFATc se zatim translocira u jedro, gde povećava izražavanje [[interleukin 2|interleukina 2]] (IL-2), koji zatim stimuliše rast i diferencijaciju T ćelijskog responsa. Kalcineurin je biološki cilj klase lekova pod nazivom [[Imunosupresivi|kalcineurinski inhibitori]], koja obuhvata [[ciklosporin]], [[pimekrolimus]] i [[takrolimus]].

== Struktura ==
Kalcineurin je heterodimer od 61-kD kalmodulin-vezujuće katalitičke podjedinice, kalcineurina A i 19-kD Ca<sup>2+</sup>-vezujuće regulatorne podjedinice, kalcineurina B. Postoje tri [[izozim]]a katalitčke podjedinice, svaka od kojih je kodirana zasebnim genom ([[PPP3CA]], [[PPP3CB]], i [[PPP3CC]]) i dve regulatorne izoforme, takođe kodirane zasebnim genima ([[PPP3R1]], [[PPP3R2]]).

{|
|- valign="top"
|{{protein
| Name = Proteinska fosfataza 3, katalitička podjedinica, alfa izozim
| caption = 
| image = 
| width = 
| HGNCid = 9314
| Symbol = [[PPP3CA]]
| AltSymbols = CALN, CALNA
| EntrezGene = 5530
| OMIM = 114105
| RefSeq = NM_000944
| UniProt = Q08209 
| PDB = 
| ECnumber = 3.1.3.16
| Chromosome = 4
| Arm = q
| Band = 24
| LocusSupplementaryData = 
}}
|{{protein
| Name = Proteinska fosfataza 3, katalitička podjedinica, beta izozim
| caption = 
| image = 
| width = 
| HGNCid = 9315
| Symbol = [[PPP3CB]]
| AltSymbols = CALNB
| EntrezGene = 5532
| OMIM = 114106
| RefSeq = NM_021132
| UniProt = P16298
| PDB = 
| ECnumber = 3.1.3.16
| Chromosome = 10
| Arm = q
| Band = 22.2
| LocusSupplementaryData = 
}}
|{{protein
| Name = Proteinska fosfataza 3, katalitička podjedinica, gama izozim
| caption = 
| image = 
| width = 
| HGNCid = 9316
| Symbol = [[PPP3CC]]
| AltSymbols = 
| EntrezGene = 5533
| OMIM = 114107
| RefSeq = NM_005605
| UniProt = P48454
| PDB = 
| ECnumber = 3.1.3.16
| Chromosome = 8
| Arm = p
| Band = 21.3
| LocusSupplementaryData = 
}}
|}

{|
|- valign="top"
|{{protein
| Name = Proteinska fosfataza 3, regulatorna podjedinica B, alfa
| caption = 
| image = 
| width = 
| HGNCid = 9317
| Symbol = [[PPP3R1]]
| AltSymbols = 
| EntrezGene = 5534
| OMIM = 601302
| RefSeq = NM_000945
| UniProt = P63098 
| PDB = 
| ECnumber = 3.1.3.16
| Chromosome = 2
| Arm = p
| Band = 14
| LocusSupplementaryData = 
}}
|{{protein
| Name = Proteinska fosfataza 3, regulatorna podjedinica B, beta
| caption = 
| image = 
| width = 
| HGNCid = 9318
| Symbol = [[PPP3R2]]
| AltSymbols = 
| EntrezGene = 5535
| OMIM = 613821
| RefSeq = NM_147180
| UniProt = Q96LZ3
| PDB = 
| ECnumber = 3.1.3.16
| Chromosome = 9
| Arm = q
| Band = 31
| LocusSupplementaryData = 
}}
|}

== Reference ==
{{reflist|2}}

== Literatura ==
{{refbegin|2}}
* {{Cite journal  | author=Crabtree GR |title=Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT |journal=Cell |volume=96 |issue= 5 |pages= 611–4 |year= 1999 |pmid= 10089876 |doi=  10.1016/S0092-8674(00)80571-1}}
* {{Cite journal  | author=Giri PR, Higuchi S, Kincaid RL |title=Chromosomal mapping of the human genes for the calmodulin-dependent protein phosphatase (calcineurin) catalytic subunit |journal=Biochem. Biophys. Res. Commun. |volume=181 |issue= 1 |pages= 252–8 |year= 1992 |pmid= 1659808 |doi=10.1016/S0006-291X(05)81410-X  }}
* {{Cite journal  | author=Kincaid RL, Giri PR, Higuchi S, ''et al.'' |title=Cloning and characterization of molecular isoforms of the catalytic subunit of calcineurin using nonisotopic methods |journal=J. Biol. Chem. |volume=265 |issue= 19 |pages= 11312–9 |year= 1990 |pmid= 2162844 |doi=  }}
* {{Cite journal  | author=Guerini D, Klee CB |title=Cloning of human calcineurin A: evidence for two isozymes and identification of a polyproline structural domain |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue= 23 |pages= 9183–7 |year= 1990 |pmid= 2556704 |doi=10.1073/pnas.86.23.9183  | pmc=298458  }}
* {{Cite journal  | author=Kincaid RL, Nightingale MS, Martin BM |title=Characterization of a cDNA clone encoding the calmodulin-binding domain of mouse brain calcineurin |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 23 |pages= 8983–7 |year= 1988 |pmid= 2848250 |doi=  10.1073/pnas.85.23.8983  | pmc=282646}}
* {{Cite journal  | author=Coghlan VM, Perrino BA, Howard M, ''et al.'' |title=Association of protein kinase A and protein phosphatase 2B with a common anchoring protein |journal=Science |volume=267 |issue= 5194 |pages= 108–11 |year= 1995 |pmid= 7528941 |doi=  10.1126/science.7528941}}
* {{Cite journal  | author=Griffith JP, Kim JL, Kim EE, ''et al.'' |title=X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex |journal=Cell |volume=82 |issue= 3 |pages= 507–22 |year= 1995 |pmid= 7543369 |doi=  10.1016/0092-8674(95)90439-5}}
* {{Cite journal  | author=Shibasaki F, McKeon F |title=Calcineurin functions in Ca(2+)-activated cell death in mammalian cells | url=https://archive.org/details/sim_journal-of-cell-biology_1995-11_131_3/page/735 |journal=J. Cell Biol. |volume=131 |issue= 3 |pages= 735–43 |year= 1995 |pmid= 7593193 |doi=  10.1083/jcb.131.3.735  | pmc=2120616}}
* {{Cite journal  | author=Muramatsu T, Kincaid RL |title=Molecular cloning of a full-length cDNA encoding the catalytic subunit of human calmodulin-dependent protein phosphatase (calcineurin A alpha) |journal=Biochim. Biophys. Acta |volume=1178 |issue= 1 |pages= 117–20 |year= 1993 |pmid= 8392375 |doi=10.1016/0167-4889(93)90117-8  }}
* {{Cite journal  | author=Cameron AM, Steiner JP, Roskams AJ, ''et al.'' |title=Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux |journal=Cell |volume=83 |issue= 3 |pages= 463–72 |year= 1996 |pmid= 8521476 |doi=10.1016/0092-8674(95)90124-8  }}
* {{Cite journal  | author=Kissinger CR, Parge HE, Knighton DR, ''et al.'' |title=Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex |journal=Nature |volume=378 |issue= 6557 |pages= 641–4 |year= 1996 |pmid= 8524402 |doi= 10.1038/378641a0 }}
* {{Cite journal  | author=Wang MG, Yi H, Guerini D, ''et al.'' |title=Calcineurin A alpha (PPP3CA), calcineurin A beta (PPP3CB) and calcineurin B (PPP3R1) are located on human chromosomes 4, 10q21→q22 and 2p16→p15 respectively |journal=Cytogenet. Cell Genet. |volume=72 |issue= 2–3 |pages= 236–41 |year= 1997 |pmid= 8978785 |doi=10.1159/000134198  }}
* {{Cite journal  | author=Shibasaki F, Kondo E, Akagi T, McKeon F |title=Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2 |journal=Nature |volume=386 |issue= 6626 |pages= 728–31 |year= 1997 |pmid= 9109491 |doi= 10.1038/386728a0 }}
* {{Cite journal  | author=Kashishian A, Howard M, Loh C, ''et al.'' |title=AKAP79 inhibits calcineurin through a site distinct from the immunophilin-binding region |journal=J. Biol. Chem. |volume=273 |issue= 42 |pages= 27412–9 |year= 1998 |pmid= 9765270 |doi=  10.1074/jbc.273.42.27412}}
* {{Cite journal  | author=Wang HG, Pathan N, Ethell IM, ''et al.'' |title=Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD |journal=Science |volume=284 |issue= 5412 |pages= 339–43 |year= 1999 |pmid= 10195903 |doi=  10.1126/science.284.5412.339}}
* {{Cite journal  | author=Fuentes JJ, Genescà L, Kingsbury TJ, ''et al.'' |title=DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways |journal=Hum. Mol. Genet. |volume=9 |issue= 11 |pages= 1681–90 |year= 2000 |pmid= 10861295 |doi=  10.1093/hmg/9.11.1681}}
* {{Cite journal  | author=Hartley JL, Temple GF, Brasch MA |title=DNA Cloning Using In Vitro Site-Specific Recombination |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi=10.1101/gr.143000  | pmc=310948  }}
* {{Cite journal  | author=Frey N, Richardson JA, Olson EN |title=Calsarcins, a novel family of sarcomeric calcineurin-binding proteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 26 |pages= 14632–7 |year= 2001 |pmid= 11114196 |doi= 10.1073/pnas.260501097  | pmc=18970 }}
* {{Cite journal  | author=Siddiq A, Miyazaki T, Takagishi Y, ''et al.'' |title=Expression of ZAKI-4 messenger ribonucleic acid in the brain during rat development and the effect of hypothyroidism |journal=Endocrinology |volume=142 |issue= 5 |pages= 1752–9 |year= 2001 |pmid= 11316738 |doi=  10.1210/en.142.5.1752}}
{{Refend}}

== Povezano ==
* [[Fosfoproteinska fosfataza]]

== Spoljašnje veze ==
* {{MeshName|Calcineurin}}
* {{EMedicineDictionary|Calcineurin}}
{{-}}
{{PDB Galerija|geneid=5530}}
{{Esteraze}}

{{Enzimi}}

[[Kategorija:Transdukcija signala]]
[[Kategorija:EC 3.1.3]]