Transferrin receptor

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Transferrin receptor 1
Symbol TFRC
Alt. symbols CD71, TFR1
Entrez 7037
HUGO 11763
OMIM 190010
RefSeq NM_003234
UniProt P02786
Other data
Locus Chr. 3 q29
Transferrin receptor 2
Symbol TFR2
Alt. symbols HFE3, TFRC2
Entrez 7036
HUGO 11762
OMIM 604720
RefSeq NM_003227
UniProt Q9UP52
Other data
Locus Chr. 7 q22

Transferrin receptor (TfR) is a carrier protein for transferrin. It is needed for the import of iron into the cell and is regulated in response to intracellular iron concentration. It imports iron by internalizing the transferrin-iron complex through receptor-mediated endocytosis.[1] The existence of a receptor for transferrin iron uptake had been recognized over half a century back.[2] Earlier two transferrin receptors in humans, transferrin receptor 1 and transferrin receptor 2 had been characterized and until recently cellular iron uptake was believed to occur chiefly via these two well documented transferrin receptors. Both these receptors are transmembrane, glycoproteins. TfR1 is a high affinity ubiquitously expressed receptor while expression of TfR2 is restricted to certain cell types and is unaffected by intracellular iron concentrations. TfR2 binds to transferrin with a 25-30 fold lower affinity than TfR1.[3][4] Although TfR1 mediated iron uptake is the major pathway for iron acquisition by most cells and especially developing erythrocytes, several studies have indicated that the uptake mechanism varies depending upon the cell type. It is also reported that Tf uptake, independent of these TfR’s exists although the mechanisms are not well characterized.[5][6][7][8] The multifunctional glycolytic enzyme Glyceraldehyde 3-phosphate dehydrogenase (GAPDH,EC has been shown to utilize post translational modifications to exhibit higher order moonlighting behavior wherein it switches its function as a holo or apo transferrin receptor leading to either iron delivery or iron export respectively[9][10]

Translational regulation[edit]

Low iron concentrations promote increased levels of transferrin receptor, to increase iron intake into the cell. Thus, transferrin receptor maintains cellular iron homeostasis.

TfR production in the cell is regulated according to iron levels by iron-responsive element-binding proteins, IRP1 and IRP2. In the absence of iron, one of these proteins (generally IRP2) binds to the hairpin like structure (IRE) that is in the 3' UTR of the TfR mRNA. Once binding occurs, the mRNA is stabilized and degradation is inhibited.

See also[edit]


  1. ^ Qian ZM, Li H, Sun H, Ho K (December 2002). "Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway". Pharmacol. Rev. 54 (4): 561–87. doi:10.1124/pr.54.4.561. PMID 12429868. ; Figure 3: The cycle of transferrin and transferrin receptor 1-mediated cellular iron uptake.
  2. ^ Jandl JH, Inman JK, Simmons RL, Allen DW. Transfer of iron from serum iron-binding protein to human reticulocytes. J Clin Invest 1959;38(1, Part 1):161-85.
  3. ^ Kawabata H, Germain RS, Vuong PT, Nakamaki T, Said JW, Koeffler HP. Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo. J Biol Chem 2000;275(22):16618-25.
  4. ^ West AP, Jr., Bennett MJ, Sellers VM, Andrews NC, Enns CA, Bjorkman PJ. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J Biol Chem 2000;275(49):38135-8.
  5. ^ K. Gkouvatsos, G. Papanikolaou, K. Pantopoulos, Regulation of iron transport and the role of transferrin, Biochim. Biophys. Acta, 1820 (2012) 188-202.
  6. ^ D. Trinder, O. Zak, P. Aisen, Transferrin receptor-independent uptake of differic transferrin by human hepatoma cells with antisense inhibition of receptor expression, Hepatology, 23 (1996) 1512-1520.
  7. ^ R. Kozyraki, J. Fyfe, P.J. Verroust, C. Jacobsen, A. Dautry-Varsat, J. Gburek, T.E. Willnow, E.I. Christensen, S.K. Moestrup, Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia, Proceedings of the National Academy of Sciences, 98 (2001) 12491-12496.
  8. ^ J. Yang, D. Goetz, J.-Y. Li, W. Wang, K. Mori, D. Setlik, T. Du, H. Erdjument-Bromage, P. Tempst, R. Strong, J. Barasch, An Iron Delivery Pathway Mediated by a Lipocalin, Mol. Cell, 10 (2002) 1045-1056.
  9. ^ M. A. Sirover, Structural analysis of glyceraldehyde-3-phosphate dehydrogenase functional diversity The International Journal of Biochemistry & Cell Biology 57 (2014) 20–26.
  10. ^ V. M. Boradia, M. Raje and C.I. Raje, Protein moonlighting in iron metabolism: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Biochemical Society Transactions; 2014, 42(6): 1796-1801.

Further reading[edit]

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