Transferrin is the principal iron-binding protein in animal serum and is analogous in its iron-binding site and properties to lactoferrin1. Human transferrin is a single-chain glycoprotein of molecular weight near 80,000. The molecule is arranged in two lobes, each bearing a single metal-binding site.

Although similar in ligand structure2, 3, the sites are distinguishable in many of their properties 4, 5. Sequence homology between the lobes6 and internal homology in the organization of the transferrin gene7 establishes that the modern protein arose by duplication and fusion of a primitive gene specifying a single-sited transferrin precursor protein. Each lobe of the transferrin molecule contains a recognition site for the chick receptor, and that both lobes are required for binding to receptor8. The receptor-binding activity of human transferrin is essentially confined to the C-terminal lobe and is preserved in the C-fragment even in the absence of the N-fragment.