FK506 binding proteins (FKBPs) are intracellular receptors for the immunosuppressive drug FK506. The FKBP/FK506 complex inhibits calcineurin, a calcium/calmodulin dependent Ser/Thr phosphatase that functions as a critical signaling molecule during T cell activation. FKBP38 functions as an anti-apoptotic molecule by modulating the intracellular distribution of Bcl-2 and Bcl-xL.
FK506 binding protein, 51 kDa molecular weight (FKBP51) is a peptidyl-prolyl isomerase that catalyzes the transition between cis- and trans- proline residues critical for proper folding of proteins. The macrolide immunosuppressants FK506 and Rapamycin are FKBP51 inhibitors. FKBP51 levels are induced by glucocorticoids. It associates with HSP90 complexes that are critical for the proper folding of steroid receptors. Single nucleotide polymorphisms in FKBP51 have been associated with major depression and hyper-responsiveness to antidepressants.