Molecular evolution of the transferrin family and associated receptors

Biochim Biophys Acta. 2012 Mar;1820(3):244-55. doi: 10.1016/j.bbagen.2011.06.002. Epub 2011 Jun 15.


Background: In vertebrates, serum transferrins are essential iron transporters that have bind and release Fe(III) in response to receptor binding and changes in pH. Some family members such as lactoferrin and melanotransferrin can also bind iron while others have lost this ability and have gained other functions, e.g., inhibitor of carbonic anhydrase (mammals), saxiphilin (frogs) and otolith matrix protein 1 (fish).

Scope of review: This article provides an overview of the known transferrin family members and their associated receptors and interacting partners.

Major conclusions: The number of transferrin genes has proliferated as a result of multiple duplication events, and the resulting paralogs have developed a wide array of new functions. Some homologs in the most primitive metazoan groups resemble both serum and melanotransferrins, but the major yolk proteins show considerable divergence from the rest of the family. Among the transferrin receptors, the lack of TFR2 in birds and reptiles, and the lack of any TFR homologs among the insects draw attention to the differences in iron transport and regulation in those groups.

General significance: The transferrin family members are important because of their clinical significance, interesting biochemical properties, and evolutionary history. More work is needed to better understand the functions and evolution of the non-vertebrate family members. This article is part of a Special Issue entitled Molecular Mechanisms of Iron Transport and Disorders.

Publication types

  • Review

MeSH terms

  • Amphibian Proteins / genetics
  • Amphibian Proteins / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Conalbumin / genetics
  • Conalbumin / metabolism
  • Evolution, Molecular*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Ion Transport
  • Iron / metabolism*
  • Lactoferrin / genetics
  • Lactoferrin / metabolism
  • Metalloproteins / genetics
  • Metalloproteins / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Protein Binding / genetics
  • Receptors, Transferrin / genetics*
  • Transferrins / chemistry
  • Transferrins / genetics*
  • Transferrins / metabolism*


  • Amphibian Proteins
  • Carrier Proteins
  • GPI-Linked Proteins
  • Meltf protein, mouse
  • Metalloproteins
  • Neoplasm Proteins
  • Receptors, Transferrin
  • Transferrins
  • saxitoxin-binding protein, Rana catesbeiana
  • Conalbumin
  • Iron
  • Lactoferrin