Английская Википедия:FKBP5

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Шаблон:Short description Шаблон:Infobox gene FK506 binding protein 5, also known as FKBP5, is a protein which in humans is encoded by the FKBP5 gene.[1]

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 (FK506) and sirolimus (rapamycin). It is thought to mediate calcineurin inhibition. It also interacts functionally with mature corticoid receptor hetero-complexes (i.e. progesterone-, glucocorticoid-, mineralocorticoid-receptor complexes) along with the 90 kDa heat shock protein and PTGES3 (P23 protein).[2]

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.[2]

Clinical significance

The FKBP5 gene has been found to have multiple polyadenylation sites[1] and is statistically associated with a higher rate of depressive disorders.[3]

Decreased methylation in the promoter of the FKBP5 gene has been observed in blood samples from patients with neurodegenerative diseases.[4]

FKBP51 Ligands

As a key player in several diseases like stress-related disorders, chronic pain, and obesity, FKBP51 is an attractive drug target. SAFit2 currently the most best characterized FKBP51 ligand, has shown promising effects in numerous animal models.[2] Macrocyclic FKBP51-selective ligands are non-immunosuppressive, engage FKBP51 in cells, and block the cellular effect of FKBP51.[5]

Interactions

FKBP5 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1.[6]

See also

  • FKBP4 - a functional antagonist to FKBP5 at corticoid receptors
  • FKBP3 - a DNA binding FKBP[7]

References

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Further reading

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