ATP7B
Domain
Each HMA domain can bind a copper ion, they are tightly packed and closely interact with each other. Wild-type ATP7B can usually be loaded with an average 5.5 copper atoms per molecule.
Function
Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into the bile in response to copper overload.
Involvement in disease
Wilson disease
WD
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Isoform 1 may be proteolytically cleaved at the N-terminus to produce the WND/140 kDa form.
Sequence Similarities
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily.
Tissue Specificity
Most abundant in liver and kidney and also found in brain. Isoform 2 is expressed in brain but not in liver. The cleaved form WND/140 kDa is found in liver cell lines and other tissues.
Cellular localization
- Golgi apparatus
- trans-Golgi network membrane
- Multi-pass membrane protein
- Late endosome
- Predominantly found in the trans-Golgi network (TGN). Localized in the trans-Golgi network under low copper conditions, redistributes to cytoplasmic vesicles when cells are exposed to elevated copper levels, and then recycles back to the trans-Golgi network when copper is removed (PubMed:10942420).
- Isoform 1
- Golgi apparatus membrane
- Multi-pass membrane protein
- Isoform 2
- Cytoplasm
- WND/140 kDa
- Mitochondrion
Alternative names
PWD, WC1, WND, ATP7B, Copper-transporting ATPase 2, Copper pump 2, Wilson disease-associated protein