Dept. of Biochemistry and Molecular Biology
Oregon Health & Science University
All organisms must implement a method of copper regulation in order to utilize yet protect the cell from cytotoxic effects. ATP7B, a P-type ATPase, is a copper transporter expressed in human cells that regulates the delivery of copper to proteins in the biosynthetic pathway and maintains the intracellular concentration of copper. Copper homeostasis is preserved through several mechanisms. The expression of a smaller protein product in the kidney, as opposed to full length ATP7B in the liver, leads to the different trafficking responses to elevated copper, no trafficking in the former and vesicular localization in the latter. Spatial control of ATP7B localization at the TGN, vesicles, or canalicular membrane is dependent on the copper status of the cell, controlling the ratio of intracellular copper to that destined for export. Phosphorylation of ATP7B in the serine rich region between MBD3 and 4 is also important in the regulation of ATP7B intracellular localization. The many mechanisms utilized by ATP7B for regulation of copper suggest there is a delicate balance between copper necessity and excess. In addition to direct regulation of copper homeostasis through ATP7B, other interacting proteins such as ceruloplasmin may play a role in copper maintenance.
School of Medicine
Bartee, Mee Y., "Characterization of the role of copper transporting ATPase, ATP7B (Wilsons disease protein), in copper homeostasis." (2008). Scholar Archive. 571.