Peptidyl-prolyl cis-trans isomerase FKBP12 F36V-tagged fusion protein (FKBP12(F36V))

FKBP12 F36V-tagged fusion proteins are engineered protein constructs central to the degradation TAG (dTAG) system, a chemical biology platform used for the rapid and selective depletion of specific proteins. This system employs a mutant version of the human FKBP12 protein, where phenylalanine at position 36 is replaced by valine (F36V), creating a unique binding pocket that accommodates bulky synthetic ligands while avoiding cross-reactivity with endogenous wild-type FKBP12 [1]. These synthetic ligands, known as dTAG molecules, are heterobifunctional degraders (PROTACs) that bind specifically to the FKBP12 F36V tag and simultaneously recruit an E3 ubiquitin ligase, such as Cereblon (CRBN) or Von Hippel-Lindau (VHL) [1, 2]. The resulting ternary complex facilitates the polyubiquitination of the fusion protein, leading to its rapid degradation by the 26S proteasome [2]. This technology is primarily utilized in drug discovery and functional genomics to validate therapeutic targets by providing a means to pharmacologically control protein levels with high temporal precision [3]. While currently a research tool, the dTAG system represents a significant advancement in targeted protein degradation and offers a robust alternative to genetic knockdown or knockout methods [1].

Other names

dTAG systemFKBP12vFKBP12 F36VDegradation TAGFKBP12(F36V) fusion protein

The target functions as a docking site for heterobifunctional degraders (dTAG ligands). These ligands bridge the FKBP12 F36V-tagged protein and an E3 ubiquitin ligase (e.g., CRBN or VHL), inducing polyubiquitination and subsequent degradation of the fusion protein by the 26S proteasome [1, 2].