Menkes copper-translocating P-type ATPase (ATP7A): biochemical and cell biology properties, and role in Menkes disease.
The Menkes copper-translocating P-type ATPase (ATP7A; MNK) is a ubiquitous protein that regulates the absorption of copper in the gastrointestinal tract. Inside cells the protein has a dual function: it delivers copper to cuproenzymes in the Golgi compartment and effluxes excess copper. The latter property is achieved through copper-dependent vesicular trafficking of the Menkes protein to the plasma membrane of the cell. The trafficking mechanism and catalytic activity combine to facilitate absorption and intercellular transport of copper. The mechanism of catalysis and copper-dependent trafficking of the Menkes protein are the subjects of this review. Menkes disease, a systemic copper deficiency disorder, is caused by mutations in the gene encoding the Menkes protein. The effect of these mutations on the catalytic cycle and the cell biology of the Menkes protein, as well as predictions of the effect of particular mutant MNKs on observed Menkes disease symptoms will also be discussed.
Voskoboinik
Ilia
I
Department of Genetics, The University of Melbourne, Parkville, Victoria 3010, Australia.
Camakaris
James
J
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D010766:Phosphorylation; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins
D027682:Cation Transport Proteins; D011993:Recombinant Fusion Proteins; D003300:Copper; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases