Pumping iron: the strange partnership of the hemochromatosis protein, a class I MHC homolog, with the transferrin receptor

Traffic. 2001 Mar;2(3):167-74. doi: 10.1034/j.1600-0854.2001.020303.x.


People suffering from hereditary hemochromatosis (HH) can not regulate the uptake of iron properly and gradually accumulate iron in their body over their lifetime. The protein involved in HH, HFE, has been recently identified as a class I major histocompatibility complex (MHC) homolog. The wild-type HFE associates and co-traffics with the transferrin receptor (TfR). The mutation responsible for 83% of HH (C260Y) results in the failure of HFE to form a critical disulfide bond, bind beta2 microglobulin, bind TfR, and traffic to the cell surface. In non-polarized cells, the partnership of HFE and TfR results in decreased iron uptake into cells. The mechanism whereby a class I MHC homolog modifies the function of a membrane receptor and how this dynamic complex of molecules regulates iron transport across intestinal epithelial cells is the subject of this review.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • HLA Antigens / chemistry
  • HLA Antigens / genetics
  • HLA Antigens / metabolism*
  • Hemochromatosis / genetics
  • Hemochromatosis / metabolism*
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Histocompatibility Antigens Class I / physiology
  • Homeostasis
  • Humans
  • Iron / metabolism*
  • Membrane Proteins*
  • Models, Biological
  • Protein Structure, Secondary
  • Receptors, Transferrin / chemistry
  • Receptors, Transferrin / metabolism*
  • beta 2-Microglobulin / chemistry
  • beta 2-Microglobulin / metabolism


  • HFE protein, human
  • HLA Antigens
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Receptors, Transferrin
  • beta 2-Microglobulin
  • Iron