Antioxidant protein 1 copper chaperone (ATOX1)

Antioxidant protein 1 copper chaperone (ATOX1) is a small, highly conserved cytosolic protein that regulates intracellular copper distribution by delivering copper ions from the cytosol to ATPase transporters ATP7A and ATP7B in the secretory pathway. It ensures maturation and activity of several copper-dependent enzymes essential for neurotransmitter biosynthesis, iron metabolism (ceruloplasmin), neovascularization, wound healing, and blood pressure regulation. ATOX1 provides antioxidant protection both by direct sequestration of copper (limiting reactive oxygen species) and enhancing copper-dependent antioxidant enzymes. Beyond its chaperone function, ATOX1 has emerging roles as a transcription factor and regulator of inflammatory/angiogenic responses, particularly in cancer and cardiovascular disease contexts. The protein features a classic ferredoxin-like fold and a conserved MxCxxC motif that tightly coordinates copper(I), and may form adducts with drugs such as cisplatin. Loss or dysfunction of ATOX1 disrupts copper and redox homeostasis and can sensitize cells to oxidative damage or impair cellular proliferation and differentiation.

Other names

Copper transport protein ATOX1HAH1Metal transport protein ATX1ATX1 antioxidant protein 1 homologmetal transport protein ATX1

Drugs like cisplatin may bind to ATOX1's cysteine-rich copper-binding motif, potentially interfering with copper transport. Copper chelators alter the copper transfer process, impacting ATOX1-dependent copper homeostasis. LOX inhibitors reduce downstream angiogenesis that depends on ATOX1-facilitated copper delivery.