InterPro domain: IPR024936

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 represents the cyclophilin peptidyl-prolyl cis-trans isomerase family. The family includes RING-type E3 ubiquitin-protein ligase PPIL2, which is thought to be an inactive PPIase [ 6 ].

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. Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases. PLoS Biol. 8, e1000439