The HaloTag protein is a modified version of a bacterial enzyme known as dehalogenase. This enzyme typically removes halogens from aliphatic hydrocarbon molecules using a nucleophilic aspartate residue. The natural form of the enzyme can regenerate its catalytic site to continue this process, however, the engineered HaloTag protein is designed to form a permanent covalent bond with its substrate. This irreversible bond enables the HaloTag protein to bond stably to any chloroalkane ligand used for labeling, making it highly useful for various downstream applications.