Peptidyl-prolyl cis-trans isomerase FKBP3 (FKBP3)

Peptidyl-prolyl cis-trans isomerase FKBP3 (commonly known as FKBP25 or FKBP3) is a nuclear member of the immunophilin protein family characterized by peptidyl-prolyl cis-trans isomerase (PPIase) activity, which assists in protein folding by catalyzing the isomerization of proline residues within polypeptides[1][3]. FKBP3 binds immunosuppressive drugs FK506 (tacrolimus) and rapamycin (sirolimus), with higher affinity for rapamycin[3]. Unique among FKBPs, FKBP3 contains a C-terminal FKBP domain responsible for isomerase and drug-binding activity, as well as a central helix-loop-helix (HLH) or basic tilted helix bundle (BTHB) domain involved in nucleic acid binding[1][2]. FKBP3 participates in several cellular processes such as protein folding, regulation of cytokine signaling, chromatin modification (by directly interacting with histone deacetylases HDAC1/2 and transcription factors such as YY1), DNA/RNA binding, apoptosis modulation, and immunoregulation[1][2][3]. Its nuclear localization and interactions with chromatin and regulatory proteins associate FKBP3 with roles in transcriptional regulation and possibly in cancer biology, though direct disease links beyond immune modulation are still being established[3]. Drug binding to FKBP3 modulates its enzymatic and structural roles, making it (along with related FKBPs) a molecular player in immunosuppressive therapy[3][5].

Other names

FKBP25FKBP-25FKBP-325 kDa FK506-binding proteinFK506-binding protein 3Immunophilin FKBP25Rapamycin-selective 25 kDa immunophilinRotamasePPIase FKBP3

FK506 and rapamycin act as immunosuppressants by binding to FKBP3, altering its cis-trans isomerase activity; rapamycin in particular binds with higher affinity and may specifically inhibit its interaction with target proteins relevant to immune signaling[3][5]. Drug binding can disrupt or modulate FKBP3’s chaperone and regulatory functions, including its interactions with other nuclear proteins.