Metal binding repeat 2 of the Wilson disease protein (ATP7B)
[ATP7B_HUMAN] Defects in ATP7B are the cause of Wilson disease (WD) [MIM:277900]. WD is an autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.                                                  
[ATP7B_HUMAN] Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.
Publication Abstract from PubMed
Human copper transporters ATP7B and ATP7A have been implicated in tumor resistance to cisplatin, a widely used anticancer drug. Cisplatin binds to the copper-binding sites in the N-terminal domain of ATP7B, and this binding may be an essential step of cisplatin detoxification involving copper ATPases. Here we demonstrate that cisplatin and a related platinum drug carboplatin produce the same adduct upon reaction with metal-binding repeat 2 (MBD2), where platinum is bound to the side chains of cysteine residues in the CxxC copper-binding motif. This suggests the same mechanism for detoxification of both drugs by ATP7B. Platinum can be also transferred to MBD2 from copper chaperone Atox1, which was previously shown to bind cisplatin. Binding of the free cisplatin and reaction with cisplatin-loaded Atox1 produce the same protein bound platinum intermediate. Transfer of platinum along the copper-transport pathways in the cell may serve as a mechanism of drug delivery to its target in the cell nucleus, and explain tumor cell resistance to cisplatin associated with overexpression of copper transporters ATP7B and ATP7A.
Copper chaperone Atox1 interacts with the metal-binding domain of Wilson disease protein in cisplatin detoxification.,Dolgova NV, Nokhrin S, Yu CH, George GN, Dmitriev OY Biochem J. 2013 Jun 11. PMID:23751120
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.