Copper-transporting ATPase (ATP7A/B)

Copper-transporting ATPases, specifically the alpha (ATP7A) and beta (ATP7B) isoforms, are critical P-type ATPases responsible for maintaining cellular copper homeostasis by transporting copper across membranes using energy from ATP hydrolysis (UniProt P35670, P35671). ATP7A is essential for copper absorption in the intestine and its delivery to the central nervous system, while ATP7B is primarily active in the liver, facilitating copper excretion into bile and its incorporation into ceruloplasmin (StatPearls, 2023). Mutations in these transporters lead to severe clinical conditions: ATP7A deficiency causes Menkes disease, a condition of systemic copper deficiency, and ATP7B deficiency leads to Wilson disease, characterized by toxic copper accumulation in the liver and brain (NIH, 2022). Beyond genetic disorders, these ATPases are implicated in cancer biology, where they contribute to resistance against platinum-based drugs like cisplatin by mediating their sequestration and efflux (PubMed PMID: 21543517). Clinical management involves copper chelators such as penicillamine and trientine to reduce copper burden, or zinc salts to inhibit absorption, while research into small-molecule inhibitors and gene therapy continues to evolve (AASLD, 2022).

Other names

ATP7AATP7BMenkes disease-associated proteinWilson disease-associated proteinP-type copper-transporting ATPaseCu2+-exporting ATPaseWNDMC1MNK

Therapeutic agents primarily function by chelating systemic copper to facilitate its urinary excretion (e.g., penicillamine, trientine) or by inducing intestinal metallothionein to sequester copper and prevent its absorption (e.g., zinc salts); additionally, these ATPases mediate the efflux of platinum-based chemotherapeutics, contributing to drug resistance.