Copper-transporting ATPase 2 (ATP7B)

Molecular Classification

Transporter, P-type ATPase, Metal ion transporter

Other Names

ATPase copper transporting beta, ATP7B_HUMAN, ATPase, Cu++ transporting, beta polypeptide, Copper pump 2, PWD, WC1, Wilson disease-associated protein, WND

Disease Roles

Wilson disease (hereditary copper overload disorder)Other disorders involving copper metabolism dysregulationHepatic and neurological damage secondary to copper accumulation

Copper-transporting ATPase 2 Overview

Copper-transporting ATPase 2 (ATP7B) is a membrane-bound P-type ATPase enzyme, primarily expressed in the liver, responsible for the transport of copper ions out of cells and into bile for excretion, as well as supplying copper to cuproenzymes such as ceruloplasmin in the secretory pathway. ATP7B plays a crucial role in copper homeostasis in the human body; loss-of-function mutations in ATP7B result in Wilson disease, characterized by hepatic copper accumulation and systemic toxicity. This target is relevant for both diagnosis and pharmacological intervention in copper metabolic disorders.

Mechanism of Action

Chelation of copper for enhanced urinary excretion (trientine, penicillamine) Blockade of intestinal copper absorption (zinc)—not a direct ATP7B interaction, but relevant to Wilson disease therapy

Biological Functions

Copper ion transmembrane transport

Copper homeostasis

Protein maturation (via copper supply to ceruloplasmin and other enzymes)

Cellular response to copper ions

Removal of excess copper (detoxification)

Disease Associations

Wilson disease (hereditary copper overload disorder)

Other disorders involving copper metabolism dysregulation

Hepatic and neurological damage secondary to copper accumulation

Safety Considerations

Copper chelation therapy: risk of overtreatment (copper deficiency, anemia, neutropenia)
Hepatotoxicity and neurotoxicity due to incomplete/ineffective copper removal
Drug-specific adverse effects (e.g., penicillamine-induced hypersensitivity)

Interacting Drugs

Trientine

D-penicillamine

Zinc salts

Associated Biomarkers

Biomarker
Reduced ceruloplasmin in serum
Elevated liver copper concentrations
Increased urinary copper excretion