CypA

Cyclophilin A (CypA) is a small cytosolic enzyme that belongs to the cyclophilin family of peptidyl-prolyl cis-trans isomerases (PPIases). In humans it is encoded by the PPIA gene and comprises about 165 amino acids, giving a molecular weight of roughly 18–20 kDa. The enzyme catalyzes the cis–trans isomerization of proline residues in peptide bonds, aiding protein folding and conformational regulation. It is widely expressed and primarily localized to the cytosol, though it can be secreted by activated leukocytes under stress.

A defining feature of CypA is its high-affinity binding to the immunosuppressive drug cyclosporin A (CsA). The CypA–CsA complex inhibits the phosphatase activity of calcineurin, blocking NF-AT–mediated transcription and reducing interleukin-2 production and T-cell activation. This mechanism is central to the clinical use of CsA in preventing transplant rejection and in treating certain autoimmune diseases.

Beyond its enzymatic role, CypA participates in immune signaling and host-pathogen interactions. Extracellular CypA interacts with the CD147 (basigin) receptor and can promote chemotaxis and inflammatory responses. In virology, CypA binds to the HIV-1 capsid protein and modulates viral infectivity; inhibitors that disrupt this interaction can impact viral replication. The protein is also studied as a model PPIase to understand protein folding and as a potential target for therapies that modulate immune responses or viral infections.