FKBP5
FK506 binding protein 5, also known as FKBP5, is a protein which in humans is encoded by the FKBP5 gene.
Function
The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants tacrolimus and sirolimus. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature corticoid receptor hetero-complexes along with the 90 kDa heat shock protein and PTGES3.As an Hsp90-associated co-chaperone that regulates the responsiveness of steroid hormone receptors, FKBP51 plays an important role in stress endocrinology and glucocorticoid signaling.
Structure
FKBP5 is part of the FKBP protein family and contains several functional domains. It includes an FKBP-type peptidyl-prolyl cis-trans isomerase domain, an FKBP-like domain, and a C-terminal region with three tetratricopeptide repeat motifs. The FK1 domain has PPIase activity, facilitating protein folding. In contrast, the FK2 domain, while structurally similar to FK1, lacks measurable PPIase activity. Instead, it is thought to play a role in protein-protein interactions, particularly in binding to progesterone receptor, suggesting a scaffolding function. The TPR motifs in the C-terminal region resemble those found in Hsp90 and contribute to molecular interactions.Clinical significance
The FKBP5 gene has been found to have multiple polyadenylation sites and is statistically associated with a higher rate of depressive disorders.Decreased methylation in the promoter of the FKBP5 gene has been observed in blood samples from patients with neurodegenerative diseases.