FKBP1A

FKBP1A, also known as FKBP12, is a member of the immunophilin protein family encoded by the FKBP1A gene. The protein is a small cytosolic peptidyl-prolyl cis-trans isomerase of about 108 amino acids and 12 kilodaltons. It binds immunosuppressive drugs tacrolimus (FK506) and rapamycin, enabling their biological effects.

Functionally, FKBP12 provides protein folding assistance via its PPIase activity and serves as a regulatory subunit in signaling complexes. It forms a complex with the immunosuppressant FK506 that inhibits calcineurin, blocking T-cell activation and cytokine production. It also binds rapamycin to form a complex that targets mTORC1, inhibiting cell growth and proliferation. In muscle and nervous tissue, FKBP12 associates with the ryanodine receptor calcium-release channels (RyR1 and RyR2), modulating intracellular calcium signaling and channel gating.

Expression of FKBP1A is widespread, with notable levels in skeletal and cardiac muscle, brain, and immune cells. FKBP12 participates in signaling through interactions with RyR calcium channels, the IP3 receptor complex in some cells, and with components of the mTOR pathway.

Clinical relevance is tied to its role as the target scaffold for major immunosuppressive drugs; FKBP12-drug complexes mediate inhibition of calcineurin and mTOR pathways, respectively. Alterations in FKBP1A expression or function can influence immune responses and calcium signaling, with potential implications for cardiac and muscle physiology.

See also: FKBP family; calcineurin; mTOR; RyR.