ADAM17

ADAM17

ADAM17, also known as tumor necrosis factor-α converting enzyme (TACE), is an enzyme that in humans is encoded by the ADAM17 gene. This enzyme belongs to the ADAM family, which is a group of peptidases known for their role in the shedding of membrane-anchored proteins. ADAM17 is particularly important in the regulation of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α).

Function

ADAM17 is a membrane protein that cleaves several membrane-bound cytokines, growth factors, receptors, and other proteins. Its most notable substrate is TNF-α, a cytokine involved in systemic inflammation and a member of a group of cytokines that stimulate the acute phase reaction. By cleaving the membrane-bound precursor of TNF-α, ADAM17 releases the soluble form of this cytokine, which is a key player in inflammatory processes.

Besides TNF-α, ADAM17 also acts on substrates like transforming growth factor-α (TGF-α), L-selectin, and amyloid precursor protein. Through the shedding of these molecules, ADAM17 regulates various biological processes including cell proliferation, adhesion, and migration.

Structure

ADAM17 is a type I transmembrane protein and consists of a prodomain that maintains the enzyme in an inactive state until it is removed, a metalloprotease domain that contains the catalytic site, a disintegrin domain, a cysteine-rich domain, and a cytoplasmic domain. The metalloprotease domain of ADAM17 contains a zinc-binding site essential for its proteolytic activity.

Clinical Significance

Given its role in shedding TNF-α and other regulatory molecules, ADAM17 has been implicated in various pathological conditions including cancer, rheumatoid arthritis, and Alzheimer's disease. Inhibitors of ADAM17 are being studied for their potential to treat these diseases by controlling the bioavailability of TNF-α and other growth factors.

Genetic Studies

Mutations in the ADAM17 gene have been associated with inflammatory diseases and certain cancers, highlighting the importance of regulated proteolysis in human health.

See Also

• Metalloproteinase
• Enzyme
• Cytokine
• Membrane protein

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