Cyclophilin 40: Proteins and Enzymes

Immunophilins are a family of soluble cytosolic receptors capable of binding to one of two major immunosuppressant agents: cyclosporin A (CsA) or FK506. Proteins that bind FK506 are termed FK506 Binding Proteins (FKBPs) and those that bind cyclosporin A are called cyclophilins (CyP). Both CyP:CsA and FKBP:FK506 complexes have been shown to inhibit calcineurin, a calcium and calmodulin dependent protein phosphatase which has been implicated as an important signaling enzyme in T-cell activation, providing a possible mechanism of immunosuppression by CsA and FK506. Immunophilins function as peptidyl prolyl cis-trans-isomerases (PPIase) whose activity is inhibited by their respective immunosuppressant compounds. As PPIase's, immunophilins accelerate folding of some proteins both in vivo and in vitro by catalyzing slow steps in the initial folding and rearrangement of proline containing proteins. CyP 40, a 40 kDa protein, shares significant homology with smaller CyPA (CyP 18) and FKBP59. CyP 40 exhibits the characteristic CsA binding and isomerase activity of CyP 18, though these activities appear to be less with CyP 40 than with Cyp 18. Like FKBP59, CyP 40 has been found in progesterone receptor complexes. CyP 40 is expressed at similar levels in many tissues.