FKBP52

FKBP52, also known as FKBP4, is a human protein encoded by the FKBP4 gene. It is a member of the FKBP family of peptidyl-prolyl cis-trans isomerases (immunophilins) and is valued for its role as a 52-kDa protein involved in protein folding and complex assembly.

Protein structure and localization: FKBP52 contains an N-terminal FKBP-type PPIase domain and a C-terminal tetratricopeptide repeat (TPR) domain. The TPR domain mediates interactions with the heat shock protein 90 (Hsp90) chaperone complex, enabling FKBP52 to associate with hormone receptor complexes in the cytoplasm and nucleus.

Function and mechanisms: FKBP52 acts as a co-chaperone for Hsp90 in the maturation and activation of steroid hormone receptors, including glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. By stabilizing receptor–Hsp90 complexes and influencing receptor folding, trafficking, and signaling, FKBP52 modulates hormone sensitivity and response. It also participates in the dynein motor–dependent transport of receptor complexes to the nucleus, aiding their transcriptional activity.

Interactions and ligands: FKBP52 binds to Hsp90 and steroid receptors as part of the chaperone machinery. It can also bind immunosuppressant drugs such as FK506 (tacrolimus), reflecting its membership in the FKBP family and its PPIase activity.

Clinical and research notes: FKBP52 is widely expressed and studied for its involvement in hormone signaling and receptor regulation. Variations in FKBP4 expression or function have been explored in the context of hormone-responsive conditions and related cancers. It is distinct from the related co-chaperone FKBP51, though they share similar pathways.