Hephaestin

Hephaestin is a protein that in humans is encoded by the HEPH gene. It is named after Hephaestus, the Greek god of metalworking, due to its role in iron metabolism.

Function

Hephaestin is a multi-copper oxidase that is involved in the metabolism of iron. It is similar to ceruloplasmin, a protein that carries more than 95% of the total circulating copper in healthy human plasma. Hephaestin is believed to oxidize Fe2+ (ferrous) iron to Fe3+ (ferric), the form of iron that can bind to transferrin for transport to other cells. It is located on the basolateral surface of intestinal enterocytes and is likely involved in the transfer of iron from enterocytes to plasma.

Clinical significance

Mutations in the HEPH gene are associated with systemic iron overload, as seen in conditions such as hemochromatosis. In mice, a mutation in this gene results in the phenotype known as "sex-linked anemia," which leads to significant iron deficiency due to impaired iron export from enterocytes.

Structure

The HEPH gene is located on the X chromosome and spans approximately 120 kilobases. The protein product, hephaestin, is a transmembrane protein with six copper-binding sites, similar to other multi-copper oxidases.

See also

• Iron metabolism
• Ceruloplasmin
• Transferrin
• Enterocyte
• Hemochromatosis