cyclophilin

Human genes encoding proteins containing the cyclophilin domain include:

• PPIA, PPIB, PPIC, PPID, PPIE, PPIF, PPIG, PPIH
• PPIL1, PPIL2, PPIL3, PPIL4, PPIAL4, PPIL6
• PPWD1

File: 1awv.jpg

Cyclophilin A (CYPA) also known as peptidylprolyl isomerase A (PPIA), which is found in the cytosol, has a beta barrel structure with two alpha helices and a beta-sheet. Other cyclophilins have similar structures to cyclophilin A. The cyclosporin-cyclophilin A complex inhibits a calcium/calmodulin-dependent phosphatase, calcineurin, the inhibition of which is thought to suppress organ rejection by halting the production of the pro-inflammatory molecules TNF alpha and interleukin 2.

Cyclophilin A is also known to be recruited by the Gag polyprotein during HIV-1 virus infection, and its incorporation into new virus particles is essential for HIV-1 infectivity.{{cite journal|pmid=7969495 | doi=10.1038/372363a0 | volume=372 | issue=6504 | title=Functional association of cyclophilin A with HIV-1 virions |date=24 November 1994 | journal=Nature | pages=363–365 | vauthors=Thali M, Bukovsky A, Kondo E| bibcode=1994Natur.372..363T | s2cid=4371206 |display-authors=etal}}

Cyclophilin D (PPIF, note that literature is confusing, the mitochondrial cyclophilin is encoded by the PPIF gene), which is located in the matrix of mitochondria, is only a modulatory, but may or may not be a structural component of the mitochondrial permeability transition pore.{{cite journal|pmid=15792954 | doi=10.1074/jbc.C500089200 | volume=280 | issue=19 | title=Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D |date=May 2005 | journal=J. Biol. Chem. | pages=18558–61 | vauthors=Basso E, Fante L, Fowlkes J, Petronilli V, Forte MA, Bernardi P| doi-access=free | hdl=11577/1474540 | hdl-access=free }}{{cite journal|pmid=21173147 | doi=10.1074/jbc.M110.196600 | pmc=3057831 | volume=286 | issue=8 | title=Complex contribution of cyclophilin D to Ca2+-induced permeability transition in brain mitochondria, with relation to the bioenergetic state |date=February 2011 | journal=J. Biol. Chem. | pages=6345–53 | vauthors=Doczi J, Turiák L, Vajda S|display-authors=etal| doi-access=free }} The pore opening raises the permeability of the mitochondrial inner membrane, allows influx of cytosolic molecules into the mitochondrial matrix, increases the matrix volume, and disrupts the mitochondrial outer membrane. As a result, the mitochondria fall into a functional disorder, so the opening of the pore plays an important role in cell death. Cyclophilin D is thought to regulate the opening of the pore because cyclosporin A, which binds to CyP-D, inhibits the pore opening.

However, mitochondria obtained from the cysts of Artemia franciscana, do not exhibit the mitochondrial permeability transition pore {{cite journal|pmid=15718386 | doi=10.1152/ajpregu.00844.2004 | volume=289 | issue=1 | title=Mitochondrial permeability transition in the crustacean Artemia franciscana: absence of a calcium-regulated pore in the face of profound calcium storage |date=July 2005 | journal=Am. J. Physiol. Regul. Integr. Comp. Physiol. | pages=R68–76 | vauthors=Menze MA, Hutchinson K, Laborde SM, Hand SC| s2cid=8352110 }}{{cite journal|pmid=21205213 | doi=10.1111/j.1742-4658.2010.08001.x | volume=278 | issue=5 | title=A distinct sequence in the adenine nucleotide translocase from Artemia franciscana embryos is associated with insensitivity to bongkrekate and atypical effects of adenine nucleotides on Ca2+ uptake and sequestration |date=March 2011 | journal=FEBS J. | pages=822–36 | vauthors=Konràd C, Kiss G, Töröcsik B|display-authors=etal| doi-access=free }}

Overexpression of Cyclophilin A has been linked to poor response to inflammatory diseases, the progression or metastasis of cancer, and aging.{{cite journal|title=Cyclophilin A: a key player for human disease|first1=P |last1=Nigro|first2=G |last2=Pompilio |first3=M C |last3=Capogrossi|journal=Cell Death and Disease|volume=4|date=2013|issue=10 |pages=e888 |doi=10.1038/cddis.2013.410 |pmid=24176846 |pmc=3920964 }}

Cyclophilin inhibitors, such as cyclosporin, are being developed to treat neurodegenerative diseases.[http://www.in-pharmatechnologist.com/Drug-Delivery/J-J-targets-degenerative-diseases-in-cyclophilin-inhibitor-partnership/ J&J targets degenerative diseases in cyclophilin inhibitor partnership. Dan Stanton. 08-Dec-2015] Cyclophilin inhibition may also be a therapy for liver diseases.{{cite journal|title=Cyclophilin inhibition as potential therapy for liver diseases|journal=Journal of Hepatology|volume=61|issue=5|date=November 2014|pages=1166–1174|doi=10.1016/j.jhep.2014.07.008|pmid=25048953|last1=Naoumov|first1=Nikolai V.|doi-access=free}}

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• {{MeshName|Cyclophilins}}

{{Immune receptors}}

{{Geometric isomerases}}

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Category:EC 5.2.1

Category:Isomerases