InterPro domain: IPR044666

Cyclophilins exhibit peptidyl-prolyl cis-trans isomerase (PPIase) activity ( 5.2.1.8 ), accelerating protein folding by catalysing the cis-trans isomerisation of proline imidic peptide bonds in oligopeptides [ 1 , 2 ]. They also have protein chaperone-like functions [ 3 ] and are the major high-affinity binding proteins for the immunosuppressive drug cyclosporin A (CSA) in vertebrates [ 4 ].

Cyclophilins are found in all prokaryotes and eukaryotes, and have been structurally conserved throughout evolution, implying their importance in cellular function [ 4 ]. They share a common 109 amino acid cyclophilin-like domain (CLD) and additional domains unique to each member of the family. The CLD domain contains the PPIase activity, while the unique domains are important for selection of protein substrates and subcellular compartmentalisation [ 5 ].

This entry includes eukaryotic, bacterial and archeal proteins which exhibit a peptidylprolyl cis- trans isomerases activity (PPIase, Rotamase) and in addition bind the immunosuppressive drug cyclosporin (CsA). Immunosuppression in vertebrates is believed to be the result of the cyclophilin A-cyclosporin protein drug complex binding to and inhibiting the protein-phosphatase calcineurin [ 6 , 7 ]. This entry also includes proteins that do not have the peptidyl-prolyl cis-trans isomerase activity, such as CWC27 from humans [ 8 ].

1. Cyclophilins: a new family of proteins involved in intracellular folding. Trends Cell Biol. 2, 272-6
2. The mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cell. Biochemistry 29, 2205-12
3. The cyclophilins. Genome Biol. 6, 226
4. An overview of cyclophilins in human cancers. J. Int. Med. Res. 38, 1561-74
5. Emerging picture of host chaperone and cyclophilin roles in RNA virus replication. Virology 411, 374-82
6. Crystal structure implies that cyclophilin predominantly catalyzes the trans to cis isomerization. Biochemistry 35, 7356-61
7. X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal complex at 2.1 A resolution. J. Mol. Biol. 234, 1119-30
8. Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases. PLoS Biol. 8, e1000439