Transferrin and Transferrin Receptors

Free iron is toxic by its ability to generate oxygen free radicals and cause damage to macromolecules. Iron in transported in the plasma bound to transferrin. Uptake of transferrin by the cell is mediated by transferrin receptors of which there are two types transferrin receptor 1 (TfR1) and transferrin receptor 2 (TfR2).


Transferrin (Tf) is an iron transport protein synthesised by the liver responsible for iron transport of iron. It is coded by the gene TF on 3q22.1 (OMIM 190000) There are 30 variants of Tf . Tf C is found in majority of individuals. Tf is synthesised in the liver as a single chain 80kDa in size. Each transferrin can bind two ferric atoms in a pH dependent manner. Alkaline pH promotes binding and acidic pH promotes release. Tf may exist as api-Tf, monoferric Tf and diferric Tf. Normally Monoferric Tf dominates. Diferric Tf dominates in iron overload.

Atrasnferrinaemia is characterised by hypochromic microcytic  anaemia with iron overload.

Transferrin Receptor

Two transferrin receptors have been identified TfR1 and TfR2. TfR1 is found in all cells  while TfR2 is found mainly in hepatocytes

Transferrin Receptor (TfR1) encoded by the TFRC gene on 3q29 (OMIM: 190010). It consists of two similar 760 amino acid peptide chains held together by a disulfide bone.  It binds transferrin in a pH dependent manner binding at physiological pH and releasing at acidic pH. On binding transferrin the the receptor is endocytosed. A V -type proton ATPase acidifies the endocytosed vesicles. Acidification weakens the binding of iron with transferrin releasing the iron in the vesicle.  The released ferric iron needs to be reduced to ferrous iron by  STEAP3. STEAP3 is an endosomal ferrireductase. Reduces iron is transported to the cytosol by DMT1.  TfR1 is recycled back to the surface where it is free to bind another transferrin.

Transferrin Receptor (TfR2) shares about 45% homology with TfR1. It had a lower affinity for transferrin and it’s role in transferrin uptake is not clear. It is involved in regulating hepcidin. Mutations of TfR2 are associated with haematochromatosis



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