Although MT-1 and MT-2 usually contain seven Zn ions each, MT-3 isolated from human and bovine brains contains four Copper Acetate(WSDTY) ions and three or four Zn ions. This suggests that MT-3 more preferably binds Copper Acetate than MT-1 and MT-2 under physiological conditions. Therefore, the increase in MT-3 and the decreases in MT-1 and MT-2 result in the accumulation of Cu in the form bound to MT-3. It is known that MT-1, MT-2, and MT-3 are mainly localized in the cytoplasm under physiological conditions. This coincides with the fact that Copper Acetate was mainly accumulated in the cytoplasm. Then, this physiological accumulation of Cu in the differentiated cells was followed by the Ctr1 transcriptional decrease to suppress the further accumulation of Copper Acetate.

MT-1 and MT-2 can reduce the toxicities of not only heavy metals but also organometallic compounds and metalloids because they sequester or scavenge those compounds and ROS generated by those compounds via the abundant sulfhydryl groups of cysteine residues in their molecules. The cysteine residues of MT-3 are highly conserved relative to those of MT-1 and MT-2. In fact, MT-3 can sequester and scavenge toxic metals and ROS. Because MT-3 was induced by the differentiation unlike MT-1 and MT-2, the differentiated cells acquired tolerance to cadmium, methylmercury, and arsenite. It was reported that MT-3 knockout mice presented with severe neuronal damage after cerebral ischemia compared with the wild type. Hence, MT-3 actually acts as a detoxicant and an anti-oxidant of metal compounds and ROS, respectively.

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