Peptidyl-prolyl cis-trans isomerase B (PPIB)

Peptidyl-prolyl cis-trans isomerase B (PPIB), also known as Cyclophilin B, is a 21 kDa enzyme belonging to the cyclophilin family of peptidyl-prolyl isomerases. As a member of the PPIase family, PPIB catalyzes the cis-trans isomerization of proline imidic peptide bonds, a rate-limiting step in protein folding that is essential for proper protein maturation. The protein is primarily localized to the endoplasmic reticulum but is also secreted in notable levels in serum and breast milk, where it functions in both intracellular and extracellular contexts. Within cells, PPIB regulates transcriptional networks through Stat-mediated gene expression and interacts with the CD147 receptor at the cell surface to modulate signaling pathways controlling chemotaxis, cell adhesion, and apoptosis. PPIB is highly expressed in multiple cancer types—including breast, liver, colon, stomach, and pancreatic cancers—and contributes to viral replication in infections such as hepatitis C, AIDS, measles, and influenza. The protein binds the immunosuppressive drug cyclosporin A with high affinity, forming a complex that inhibits calcineurin and blocks T-cell activation. Given its involvement in protein folding, viral dynamics, cancer progression, and immune regulation, PPIB represents a multifunctional therapeutic target with potential applications in cancer immunotherapy, viral infection treatment, and immunosuppression, though its ubiquitous expression and fundamental cellular roles present challenges for selective therapeutic targeting.

Other names

Cyclophilin B (CypB)Peptidyl-prolyl cis-trans isomerase BPPIase BCYP-S1Rotamase BS-cyclophilinSCYLPCYPB

For cyclosporin A: Forms a complex with PPIB that inhibits calcineurin, blocking the signaling pathway for T-cell activation. Catalytic mechanism: Lowers the activation energy of the cis-trans isomerization transition and accelerates the isomerization process by stabilizing the conformational transition of proline peptide bonds. Post-translational modification-dependent signaling: Recognizes and catalyzes conformational changes in phosphorylated substrate proteins, regulating their activity, stability, and subcellular localization.