Cyclophilin E

Cyclophilin E (CypE/PPIE/Cyp33) is a nuclear cyclophilin with peptidyl-prolyl cis-trans isomerase activity and an N-terminal RNA-recognition motif, distinguishing it from many single-domain cyclophilin isoforms^[1]. Mechanistically, CypE links RNA binding to proline isomerization because human Cyp33 binds specifically to mRNA, and mRNA binding stimulates its PPIase activity^[2]. In spliceosome biology, proteomic and functional studies identify PPIE among human spliceosomal complexes, supporting its use as a target for pre-mRNA splicing research^[3][4]. In chromatin regulation, Cyp33 binds the MLL1 PHD3 region and connects H3K4 methylation readout to HDAC-mediated repression, making it relevant to epigenetic gene-expression models^[5][6]. In disease-related models, CypE negatively regulates influenza virus replication by impairing viral ribonucleoprotein complex formation, while CypE promotes osteoblast differentiation through Runx2 transcriptional activity^[7][8]. Compared with related cyclophilins, CypE is defined by its combined RRM and catalytic cyclophilin domain, whereas family-wide studies show that isoform-specific surfaces support selective ligand design^[9]. For experimental applications, subtype-selective CypE inhibitors exploit S2-pocket interactions and reversible covalent binding, enabling CypE-focused studies without broad pan-cyclophilin inhibition^[10].