Cyclophilin G

Cyclophilin G (PPIG) is a nuclear member of the cyclophilin family that contains peptidyl-prolyl cis-trans isomerase (PPIase) activity and binds cyclosporin A, supporting protein folding and proline isomerization-dependent regulatory processes.^[1] PPIG is distinguished from canonical cyclophilins such as Cyclophilin A by its serine/arginine-rich (SR) domain and preferential nuclear localization, which links its catalytic activity to transcriptional and RNA-processing machinery rather than predominantly cytoplasmic protein-folding functions.^[1][2] Mechanistically, PPIG interacts with the phosphorylated C-terminal domain (CTD) of RNA polymerase II, positioning this cyclophilin within transcription-coupled regulatory pathways that coordinate gene expression and RNA maturation.^[1] PPIG also associates with nuclear matrix components and splicing-related factors, supporting a functional role in RNA-processing networks connected to active transcription.^[1][3] Compared with related cyclophilin isoforms that primarily regulate mitochondrial permeability, endoplasmic reticulum protein folding, or extracellular signaling, PPIG is characterized by its integration with nuclear transcriptional complexes and SR protein-associated processes.^[2][4] For experimental applications, PPIG retains the conserved cyclophilin property of cyclosporin A binding, making cyclophilin-directed inhibitors useful tools for investigating PPIase-dependent regulation and nuclear RNA-processing mechanisms.^[1][4]