PPIA

PPIA, or peptidyl-prolyl cis-trans isomerase A, commonly known as cyclophilin A (CyPA), is a cytosolic enzyme of the immunophilin family. The human PPIA protein consists of about 165 amino acids and has a molecular weight of approximately 18 kDa. It functions as a peptidyl-prolyl cis-trans isomerase, catalyzing the isomerization of peptide bonds at proline residues, which accelerates protein folding and can influence protein function. In addition to its intracellular chaperone-like role, PPIA can be secreted by cells in response to stress and acts as an extracellular signaling molecule, contributing to inflammatory responses via receptors such as CD147/Basigin.

PPIA binds the immunosuppressant cyclosporin A (CsA), and the PPIA-CsA complex inhibits the phosphatase calcineurin, thereby blocking T-cell activation and interleukin-2 production. This interaction underpins CsA’s immunosuppressive effects used in transplantation and autoimmune disease therapy. PPIA has also been reported to interact with viral components, notably the HIV-1 capsid, and can influence viral replication in certain contexts; cyclosporin A can inhibit this process by targeting PPIA.

In humans, PPIA is widely expressed and participates in diverse biological processes including signal transduction, inflammation, and cell migration. Aberrant PPIA expression or secretion has been associated with inflammatory disorders, cardiovascular disease, and cancer in various studies, though its precise roles remain under investigation. The gene is sometimes referred to simply as PPIA to indicate the encoded protein; its homologs include other cyclophilins such as PPIB and PPIL1.

See also: cyclophilin family, calcineurin, cyclosporin A, CD147/Basigin.