Copper-transporting ATPase 1 (ATP7A) (ATP7A)

Copper-transporting ATPase 1 (ATP7A) is a critical P-type ATPase responsible for maintaining systemic and cellular copper homeostasis by transporting copper ions across biological membranes using ATP hydrolysis (UniProt P35670). Under basal conditions, ATP7A resides in the trans-Golgi network (TGN), where it supplies copper to essential cuproenzymes such as lysyl oxidase and tyrosinase (PubMed: 23541132). When intracellular copper levels rise, the protein translocates to the plasma membrane to facilitate copper efflux, preventing toxicity (NCBI Gene: 538). Mutations in the ATP7A gene result in Menkes disease, a fatal X-linked recessive disorder characterized by systemic copper deficiency, severe neurological impairment, and connective tissue abnormalities (StatPearls: NBK557551). Conversely, in the context of oncology, ATP7A is frequently overexpressed in various tumors and is known to mediate resistance to platinum-based chemotherapies by sequestering and exporting drugs like cisplatin (PubMed: 17604337). Consequently, ATP7A is a target for both copper replacement therapies in deficiency states and potential chemosensitization strategies in cancer treatment.

Other names

Menkes disease-associated proteinMNKMC1MKP-type copper-transporting ATPase 1Copper-transporting P-type ATPase

ATP-driven active transport of copper ions from the cytosol into the secretory pathway or across the plasma membrane for efflux (UniProt P35670).