The first cyclophilin (Cyp/PPIases: EC 18.104.22.168) was isolated more than three decades ago as an intracellular receptor of the immunosuppressive drug cyclosporine A (CsA) from the bovine thymocyctes (Handschumacher et al. 1984). It was not until 1989, its PPIase activity was elucidated. Cyclophilins comprise a ubiquitous set of proteins which is present across diverse genera of organisms. The single domain cyclophilin has a single cyclophilin-like domain (CLD), whereas multidomain cyclophilins also possess additional domains such as tetratricopeptide repeat (TPR), RNA recognition motif (RRM), tryptophan aspartate domain (WD40), coiled-coil domain (CCD), and internal repeats domain (RPT). Cyclophilins are involved in a myriad of physiological cellular processes, such as protein trafficking and maturation, receptor complex stabilization, apoptosis, receptor...
KeywordsPPIase Activity PPIase Domain Extracellular Receptor Kinase Cyclophilin Inhibitor Abdominal Aortic Aneurysm Formation
- Allain F, Vanpouille C, Carpentier M, Slomianny MC, Durieux S, Spik G. Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix. Proc Natl Acad Sci U S A. 2002;99:2714–9.CrossRefPubMedPubMedCentralGoogle Scholar
- Austin C, Davis JB, Fliri HG, Ford RL, Steadman A. Prolyl Isomerases – Old Proteins as New Therapeutic Targets: Selcia Ltd, Essex, UK. 2015;1–12. https://www.selcia.com
- Chapman DC, Stocki P, DB W. Cyclophilin C participates in the US2-mediated degradation of major histocompatibility complex class I molecules. PLoS One. 2015; doi:10.1371/journal.pone.0145458.Google Scholar
- Davis TL, Walker JR, Campagna-Slater V, Finerty Jr PJ, Paramanathan R, Bernstein G, MacKenzie F, Tempel W, Ouyang H, Lee WH, Eisenmesser EZ, Dhe-Paganon S. Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases. PLoS Biol. 2010;8:e1000439.CrossRefPubMedPubMedCentralGoogle Scholar
- Seizer P, Ungern-Sternberg SN, Schönberger T, Borst O, Münzer P, Schmidt EM, Mack AF, Heinzmann D, Chatterjee M, Langer H, Malešević M, Lang F, Gawaz M, Fischer G, May AE. Extracellular cyclophilin A activates platelets via EMMPRIN (CD147) and PI3K/Akt signaling, which promotes platelet adhesion and thrombus formation in vitro and in vivo. Arterioscler Thromb Vasc Biol. 2015;35:655–63.CrossRefPubMedGoogle Scholar