FK506-binding protein 51 (FKBP51)

FK506-binding protein 51 (FKBP51) is a large intracellular immunophilin encoded by the FKBP5 gene, best known for its peptidyl-prolyl cis-trans isomerase activity and as a co-chaperone in the Hsp90 complex[1][4][5]. It binds immunosuppressants such as tacrolimus (FK506) and rapamycin (sirolimus), mediating inhibition of calcineurin and mTOR signaling[1][2][5]. FKBP51 regulates the activity and hormone responsiveness of steroid hormone receptors (glucocorticoid, progesterone, androgen), and modulates signal transduction pathways relevant to stress, metabolism, and immunity[1][4][6]. It is implicated in pathologies such as stress disorders, chronic pain, metabolic diseases, several cancers, and tauopathies in neurodegeneration[3][4][6]. Drugs targeting FKBP51 are under investigation for treating depression, PTSD, and pain[4]. FKBP51 functions include molecular chaperoning, modulation of receptor complexes, and competitive binding to Hsp90[6]. The protein contains an active FK1 PPIase domain, a structurally similar FK2 domain, and a C-terminal tetratricopeptide repeat region critical for protein-protein interactions[1][5][6].

Other names

FKBP5FKBP-5FKBP 5151 kDa FK506-binding protein

Drugs such as tacrolimus and rapamycin bind FKBP51, forming complexes that inhibit calcineurin and mTOR signaling, affecting immune responses; Selective FKBP51 inhibitors (e.g., SAFit2) modulate stress hormone regulation and potentially reduce chronic pain or depression symptoms; Interference with chaperone activity to modulate steroid receptor function