FK506-binding protein 12 F36V mutant domain (FKBP12(F36V))

The **FK506-binding protein 12 F36V mutant domain** (FKBP12(F36V)) is a genetically engineered variant of the human FKBP12 protein, in which the phenylalanine at position 36 is replaced by valine (F36V)[5][1]. This mutation creates a unique hydrophobic cavity in the protein's ligand-binding pocket, enabling high-affinity binding to designed synthetic “bumped” ligands (such as Shield-1 or analogues) that do not significantly interact with wild-type FKBP12[1][2][5][7]. FKBP12(F36V) is widely used in molecular and cell biology as a destabilizing domain (DD): when fused to another protein, the fusion protein is unstable and rapidly degraded unless cells are treated with the synthetic ligand, which stabilizes the domain (and thus, the entire fusion protein), allowing rapid, reversible, and tunable small-molecule control over protein abundance in living cells and organisms[1][2][5][6][7]. This domain serves as a valuable research tool for manipulating protein function, studying gene regulation, and dissecting biological signaling pathways but is not a therapeutic drug target itself.

Other names

FKBP12 F36VFKBP12(F36V) mutantdestabilizing domain (DD)engineered FKBP12 mutant domain

Synthetic ligand binding stabilizes the destabilized FKBP12(F36V) domain when fused to a target protein, allowing control over protein stability, abundance, and function in living cells[1][2][4][5].