Model of the HFE protein

Hypothetical model of the HFE protein based upon its homology with MHC class I molecules. The HFE protein is a single polypeptide with three extracellular domains, which would be analogous to the α1, α2, and α3 domains of other MHC class I proteins. In contrast to other members of the MHC class I family, the α1 and α2 domains in the HFE protein are nonpolymorphic. β2-microglobulin is a separate protein and would interact with the HFE gene product in a noncovalent manner in the α3 homologous region. The HFE protein contains a membrane-spanning region and a short cytoplasmic tail. The approximate locations of C282Y (the major mutation in hereditary hemochromatosis) and H63D are indicated.