ATP7A

ATP7A

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Proposed structure of ATP7A

ATP7A is a copper-transporting P-type ATPase that plays a crucial role in the regulation of copper levels within the human body. It is encoded by the ATP7A gene, which is located on the X chromosome. This protein is essential for the proper functioning of various physiological processes, including the development of the nervous system, connective tissue, and the maintenance of skin and hair pigmentation.

Function

ATP7A is primarily involved in the transport of copper ions across cellular membranes. It facilitates the movement of copper from the cytosol into the Golgi apparatus, where copper is incorporated into copper-dependent enzymes. These enzymes are critical for numerous biological functions, such as oxidative phosphorylation, antioxidant defense, and the synthesis of neurotransmitters.

In addition to its role in copper transport, ATP7A is also involved in the export of excess copper from cells, thereby preventing copper toxicity. This export function is particularly important in the intestine, where ATP7A helps regulate the absorption of dietary copper.

Clinical Significance

Mutations in the ATP7A gene can lead to Menkes disease, a rare genetic disorder characterized by copper deficiency. Menkes disease is associated with severe developmental delays, connective tissue abnormalities, and neurological degeneration. The condition is typically fatal in early childhood if left untreated.

Another condition related to ATP7A dysfunction is occipital horn syndrome, a milder form of Menkes disease. This syndrome is characterized by connective tissue abnormalities, including the formation of bony projections on the occipital bone of the skull.

Structure

The ATP7A protein is composed of several distinct domains, including a transmembrane domain that spans the cellular membrane and a cytosolic domain that binds and hydrolyzes ATP. The transmembrane domain contains multiple copper-binding sites, which are essential for the protein's copper transport function.

The proposed structure of ATP7A, as depicted in the accompanying image, highlights the arrangement of these domains and the potential pathways for copper ion movement through the protein.

Related Pages

• Copper metabolism
• P-type ATPase
• Menkes disease
• Wilson's disease