title: Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments.
abstract: Copper is an essential trace element in prokaryotes and eukaryotes and is strictly regulated by biological mechanisms. Menkes and Wilson diseases are human disorders that arise from disruption of the normal process of copper export from the cytosol to the extracellular environment. Recently a gene for Wilson disease (WD)(also named the ATP7B gene) was cloned. This gene encodes a copper transporter of the P-type ATPase. We prepared monoclonal and polyclonal anti-(WD protein) antibodies and characterized the full-length WD protein as well as a shorter form that is produced by alternative splicing in the human brain. We found that the WD protein is localized mainly in the Golgi apparatus, whereas the shorter form is present in the cytosol. These results suggest that the alternative WD proteins act as key regulators of copper metabolism, perhaps by performing distinct roles in the intracellular transport and export of copper.
authors.affiliation: Department of Biochemistry, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita 010, Japan.
authors.forename: X L
authors.initials: XL
authors.lastname: Yang
authors.forename: N
authors.initials: N
authors.lastname: Miura
authors.forename: Y
authors.initials: Y
authors.lastname: Kawarada
authors.forename: K
authors.initials: K
authors.lastname: Terada
authors.forename: K
authors.initials: K
authors.lastname: Petrukhin
authors.forename: T
authors.initials: T
authors.lastname: Gilliam
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins; D002451:Cell Compartmentation; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases