Cyclophilin [1] is the major high-affinity binding protein in vertebrates for the immunosuppressive drug cyclosporin A (CSA). It exhibits a peptidyl-prolyl cis-trans isomerase activity (EC 5.2.1.8) (PPIase or rotamase). PPIase is an enzyme that accelerates protein folding by catalyzing the cis-trans isomerization of proline imidic peptide bonds in oligopeptides [2]. It is probable that CSA mediates some of its effects via an inhibitory action on PPIase. Cyclophilin is a cytosolic protein which belongs to a family [3,4,5] that also includes the following isozymes:

• Cyclophilin B (or S-cyclophilin), a PPIase which is retained in an endoplasmic reticulum compartment.
• Cyclophilin C, a cytoplasmic PPiase.
• Mitochondrial matrix cyclophilin (cyp3).
• A PPIase which seems specific for the folding of rhodopsin and is an integral membrane protein anchored by a C-terminal transmembrane region. This protein was first characterized in Drosophila (gene ninaA).
• Bacterial periplasmic PPiase (gene ppiA).
• Bacterial cytosolic PPiase (gene ppiB).
• Natural-killer cell cyclophilin-related protein. This large protein (about 160 Kd) is a component of a putative tumor-recognition complex involved in the function of NK cells. It contains a cyclophilin-type PPiase domain.
• Mammalian nucleoporin Nup358 [6], a nuclear pore complex protein of 358 Kd that contains a C-terminal cyclophilin-type PPiase domain.
• Yeast hypothetical protein YJR032w.
• Fission yeast hypothetical protein SpAC21E11.05c.
• Caenorhabditis elegans hypothetical protein T27D1.1.

The sequences of the different forms of cyclophilin-type PPIases are well conserved. As a signature pattern, we selected a conserved region in the central part of these enzymes.