HaloTag protein (HaloTag) (HaloTag)

HaloTag is a 33 kDa engineered protein derivative of the bacterial haloalkane dehalogenase (DhaA) from Rhodococcus rhodochrous (Los et al., 2008). It is specifically designed to covalently and irreversibly bind to synthetic ligands containing a primary chloroalkane linker through a nucleophilic displacement of the chloride ion (Encell et al., 2012). This self-labeling technology is widely utilized in molecular biology for live-cell imaging, protein purification, and the study of protein-protein interactions (Promega). In the context of drug discovery, HaloTag is a critical component in the development of Halo-PROTACs, where it serves as a proxy for a protein of interest to evaluate degradation efficiency by E3 ligase recruitment (Buckley et al., 2015). Because it is of bacterial origin, its use in vivo is primarily restricted to research models due to potential immunogenicity in humans.

Other names

HaloTag7Modified haloalkane dehalogenaseDhaA variantHalo-tag

HaloTag is an engineered haloalkane dehalogenase that reacts with chloroalkane-functionalized ligands to form a highly stable, irreversible covalent bond via a nucleophilic displacement mechanism (Los et al., 2008; Promega).