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Gene Review

TFRC  -  transferrin receptor

Homo sapiens

Synonyms: CD71, T9, TFR, TFR1, TR, ...
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Disease relevance of TFRC


Psychiatry related information on TFRC


High impact information on TFRC


Chemical compound and disease context of TFRC


Biological context of TFRC

  • Iron regulatory proteins (IRPs) 1 and 2 post-transcriptionally control mammalian iron homeostasis by binding to iron-responsive elements (IREs), conserved RNA stem-loop structures located in the 5'- or 3'-untranslated regions of genes involved in iron metabolism (e.g. FTH1, FTL, and TFRC) [19].
  • This study analyzed the clinical effect of messenger RNA (mRNA) expression for PIK3CA (the gene that encodes phosphatidylinositol-3 kinase catalytic alpha-polypeptide) and TFRC (the gene that encodes the transferrin receptor), which map within chromosome 3q in ESCC [1].
  • Stratification of HFE genotype by TFRC genotype did not change the results [20].
  • NotI linking/jumping clones of human chromosome 3: mapping of the TFRC, RAB7 and HAUSP genes to regions rearranged in leukemia and deleted in solid tumors [21].
  • We investigated whether the cytoplasmic domain of 65 N-terminal amino acids or phosphorylated sites within this domain constitute a structure that is required for TR endocytosis [22].

Anatomical context of TFRC

  • It was strongly expressed by malignant epithelial cells; normal stromal and endothelial cells were not stained by anti-TFRC antibodies [2].
  • The expression of TFRC was negative in benign neuroendocrine tumours of the pancreas [2].
  • The TFRC gene was mapped to 3q29, close to the telomeric marker D3S2344, by linkage analysis, a panel of hybrid cell lines, GeneBridge 4 panel and FISH [21].
  • On a cell membrane containing both proteins, HFE would 'lie down' parallel to the membrane, such that the HFE helices that delineate the counterpart of the MHC peptide-binding groove make extensive contacts with helices in the TfR dimerization domain [23].
  • Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy [24].

Associations of TFRC with chemical compounds

  • To test this hypothesis, we modified the cytoplasmic serine residues or introduced a deletion of 36 amino acids by in vitro mutagenesis of a cDNA expression vector for human TR [22].
  • Consequently, little if any in TfR expression at the cell surface was measured during Baf treatment [25].
  • Transferrin receptor-dependent and -independent iron transport in gallium-resistant human lymphoid leukemic cells [26].
  • Thymidine incorporation was maximal early in the second week of culture and coincided with high transferrin receptor expression [27].
  • Exposure of cells grown in Fe or treated with DMSO to cycloheximide did not alter Tf receptor mRNA levels, thereby suggesting that receptor expression was not regulated by posttranscriptional processes dependent on protein synthesis [28].

Physical interactions of TFRC


Co-localisations of TFRC


Regulatory relationships of TFRC


Other interactions of TFRC

  • We also demonstrate that soluble TfR and HFE bind tightly at the basic pH of the cell surface, but not at the acidic pH of intracellular vesicles [13].
  • Metabolic labeling studies indicate that TfR2 protein levels are approximately 20-fold lower than TfR in these cells [42].
  • The increase in iron uptake is independent of DMT1 and TfR, suggesting an unknown transporter [43].
  • The region of recurrent increase is approximately 30 Mb in extent, ranging from EVI1 to TFRC [44].
  • RESULTS: Perl's staining showed increased iron in colorectal cancers, and there was a corresponding overexpression of components of the intracellular iron import machinery (DCYTB, DMT1, and TfR1) [45].

Analytical, diagnostic and therapeutic context of TFRC


  1. PIK3CA and TFRC located in 3q are new prognostic factors in esophageal squamous cell carcinoma. Wada, S., Noguchi, T., Takeno, S., Kawahara, K. Ann. Surg. Oncol. (2006) [Pubmed]
  2. Transferrin receptor is a marker of malignant phenotype in human pancreatic cancer and in neuroendocrine carcinoma of the pancreas. Ryschich, E., Huszty, G., Knaebel, H.P., Hartel, M., Büchler, M.W., Schmidt, J. Eur. J. Cancer (2004) [Pubmed]
  3. Regulation of transferrin, transferrin receptor, and ferritin genes in human duodenum. Pietrangelo, A., Rocchi, E., Casalgrandi, G., Rigo, G., Ferrari, A., Perini, M., Ventura, E., Cairo, G. Gastroenterology (1992) [Pubmed]
  4. Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Connor, J.R., Wang, X.S., Patton, S.M., Menzies, S.L., Troncoso, J.C., Earley, C.J., Allen, R.P. Neurology (2004) [Pubmed]
  5. Transferrin receptors of rat and human brain and cerebral microvessels and their status in Alzheimer's disease. Kalaria, R.N., Sromek, S.M., Grahovac, I., Harik, S.I. Brain Res. (1992) [Pubmed]
  6. Plasma levels of soluble transferrin receptors and Clara cell protein (CC16) during bipolar mania and subsequent remission. Tsai, S.Y., Lee, H.C., Chen, C.C., Lee, C.H. Journal of psychiatric research. (2003) [Pubmed]
  7. Systemic iron metabolism and mortality from Parkinson's disease. Marder, K., Logroscino, G., Tang, M.X., Graziano, J., Cote, L., Louis, E., Alfaro, B., Mejia, H., Slavkovich, V., Mayeux, R. Neurology (1998) [Pubmed]
  8. Deoxyribonucleic acid binding and transcriptional silencing by a truncated c-erbA beta 1 thyroid hormone receptor identified in a severely retarded patient with resistance to thyroid hormone. Behr, M., Ramsden, D.B., Loos, U. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  9. TTP specifically regulates the internalization of the transferrin receptor. Tosoni, D., Puri, C., Confalonieri, S., Salcini, A.E., De Camilli, P., Tacchetti, C., Di Fiore, P.P. Cell (2005) [Pubmed]
  10. Structure of the human transferrin receptor-transferrin complex. Cheng, Y., Zak, O., Aisen, P., Harrison, S.C., Walz, T. Cell (2004) [Pubmed]
  11. Mysteries of the transferrin-transferrin receptor 1 interaction uncovered. Richardson, D.R. Cell (2004) [Pubmed]
  12. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Levy, J.E., Jin, O., Fujiwara, Y., Kuo, F., Andrews, N.C. Nat. Genet. (1999) [Pubmed]
  13. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Lebrón, J.A., Bennett, M.J., Vaughn, D.E., Chirino, A.J., Snow, P.M., Mintier, G.A., Feder, J.N., Bjorkman, P.J. Cell (1998) [Pubmed]
  14. Inhibition of uptake of transferrin-bound iron by human hepatoma cells by nontransferrin-bound iron. Trinder, D., Morgan, E. Hepatology (1997) [Pubmed]
  15. Reversal by transferrin of growth-inhibitory effect of suramin on hormone-refractory human prostate cancer cells. Donat, S.M., Powell, C.T., Israeli, R.S., Fair, W.R., Heston, W.D. J. Natl. Cancer Inst. (1995) [Pubmed]
  16. Regulation of expression of murine transferrin receptor 2. Kawabata, H., Germain, R.S., Ikezoe, T., Tong, X., Green, E.M., Gombart, A.F., Koeffler, H.P. Blood (2001) [Pubmed]
  17. Single-chain immunotoxins directed at the human transferrin receptor containing Pseudomonas exotoxin A or diphtheria toxin: anti-TFR(Fv)-PE40 and DT388-anti-TFR(Fv). Batra, J.K., Fitzgerald, D.J., Chaudhary, V.K., Pastan, I. Mol. Cell. Biol. (1991) [Pubmed]
  18. Effect of nitric oxide on expression of transferrin receptor and ferritin and on cellular iron metabolism in K562 human erythroleukemia cells. Oria, R., Sánchez, L., Houston, T., Hentze, M.W., Liew, F.Y., Brock, J.H. Blood (1995) [Pubmed]
  19. Iron regulation and the cell cycle: identification of an iron-responsive element in the 3'-untranslated region of human cell division cycle 14A mRNA by a refined microarray-based screening strategy. Sanchez, M., Galy, B., Dandekar, T., Bengert, P., Vainshtein, Y., Stolte, J., Muckenthaler, M.U., Hentze, M.W. J. Biol. Chem. (2006) [Pubmed]
  20. Hemochromatosis gene mutations and distal adenomatous colorectal polyps. McGlynn, K.A., Sakoda, L.C., Hu, Y., Schoen, R.E., Bresalier, R.S., Yeager, M., Chanock, S., Hayes, R.B., Buetow, K.H. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  21. NotI linking/jumping clones of human chromosome 3: mapping of the TFRC, RAB7 and HAUSP genes to regions rearranged in leukemia and deleted in solid tumors. Kashuba, V.I., Gizatullin, R.Z., Protopopov, A.I., Allikmets, R., Korolev, S., Li, J., Boldog, F., Tory, K., Zabarovska, V., Marcsek, Z., Sumegi, J., Klein, G., Zabarovsky, E.R., Kisselev, L. FEBS Lett. (1997) [Pubmed]
  22. Endocytosis of the transferrin receptor requires the cytoplasmic domain but not its phosphorylation site. Rothenberger, S., Iacopetta, B.J., Kühn, L.C. Cell (1987) [Pubmed]
  23. Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Bennett, M.J., Lebrón, J.A., Bjorkman, P.J. Nature (2000) [Pubmed]
  24. Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy. Moura, I.C., Centelles, M.N., Arcos-Fajardo, M., Malheiros, D.M., Collawn, J.F., Cooper, M.D., Monteiro, R.C. J. Exp. Med. (2001) [Pubmed]
  25. Transport from late endosomes to lysosomes, but not sorting of integral membrane proteins in endosomes, depends on the vacuolar proton pump. van Weert, A.W., Dunn, K.W., Gueze, H.J., Maxfield, F.R., Stoorvogel, W. J. Cell Biol. (1995) [Pubmed]
  26. Transferrin receptor-dependent and -independent iron transport in gallium-resistant human lymphoid leukemic cells. Chitambar, C.R., Wereley, J.P. Blood (1998) [Pubmed]
  27. Selective inhibition of the growth of human erythroid bursts by monoclonal antibodies against transferrin or the transferrin receptor. Shannon, K.M., Larrick, J.W., Fulcher, S.A., Burck, K.B., Pacely, J., Davis, J.C., Ring, D.B. Blood (1986) [Pubmed]
  28. Regulation of transferrin receptor expression in myeloid leukemia cells. Taetle, R., Ralph, S., Smedsrud, S., Trowbridge, I. Blood (1987) [Pubmed]
  29. Release of the soluble transferrin receptor is directly regulated by binding of its ligand ferritransferrin. Dassler, K., Zydek, M., Wandzik, K., Kaup, M., Fuchs, H. J. Biol. Chem. (2006) [Pubmed]
  30. Multiple, conserved iron-responsive elements in the 3'-untranslated region of transferrin receptor mRNA enhance binding of iron regulatory protein 2. Erlitzki, R., Long, J.C., Theil, E.C. J. Biol. Chem. (2002) [Pubmed]
  31. Differential expression and function of IgA receptors (CD89 and CD71) during maturation of dendritic cells. Pasquier, B., Lepelletier, Y., Baude, C., Hermine, O., Monteiro, R.C. J. Leukoc. Biol. (2004) [Pubmed]
  32. Trafficking of the human transferrin receptor in plant cells: effects of tyrphostin A23 and brefeldin A. Ortiz-Zapater, E., Soriano-Ortega, E., Marcote, M.J., Ortiz-Masi??, D., Aniento, F. Plant J. (2006) [Pubmed]
  33. Expression and localization of different forms of DMT1 in normal and tumor astroglial cells. Lis, A., Barone, T.A., Paradkar, P.N., Plunkett, R.J., Roth, J.A. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  34. CLIP-170 links endocytic vesicles to microtubules. Pierre, P., Scheel, J., Rickard, J.E., Kreis, T.E. Cell (1992) [Pubmed]
  35. Association of tissue factor pathway inhibitor with human umbilical vein endothelial cells. Hansen, J.B., Olsen, R., Webster, P. Blood (1997) [Pubmed]
  36. Hrs, a tyrosine kinase substrate with a conserved double zinc finger domain, is localized to the cytoplasmic surface of early endosomes. Komada, M., Masaki, R., Yamamoto, A., Kitamura, N. J. Biol. Chem. (1997) [Pubmed]
  37. Identification of a keratin-associated protein that localizes to a membrane compartment. Chou, C.F., Riopel, C.L., Omary, M.B. Biochem. J. (1994) [Pubmed]
  38. Transferrin receptor is negatively modulated by the hemochromatosis protein HFE: implications for cellular iron homeostasis. Salter-Cid, L., Brunmark, A., Li, Y., Leturcq, D., Peterson, P.A., Jackson, M.R., Yang, Y. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  39. Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo. Kawabata, H., Germain, R.S., Vuong, P.T., Nakamaki, T., Said, J.W., Koeffler, H.P. J. Biol. Chem. (2000) [Pubmed]
  40. Loss of the von Hippel Lindau tumor suppressor disrupts iron homeostasis in renal carcinoma cells. Alberghini, A., Recalcati, S., Tacchini, L., Santambrogio, P., Campanella, A., Cairo, G. J. Biol. Chem. (2005) [Pubmed]
  41. The acute-phase protein alpha 1-antitrypsin inhibits transferrin-receptor binding and proliferation of human skin fibroblasts. Graziadei, I., Kähler, C.M., Wiedermann, C.J., Vogel, W. Biochim. Biophys. Acta (1998) [Pubmed]
  42. Heterotypic interactions between transferrin receptor and transferrin receptor 2. Vogt, T.M., Blackwell, A.D., Giannetti, A.M., Bjorkman, P.J., Enns, C.A. Blood (2003) [Pubmed]
  43. Effects of iron regulatory protein regulation on iron homeostasis during hypoxia. Schneider, B.D., Leibold, E.A. Blood (2003) [Pubmed]
  44. Genomic copy number analysis of non-small cell lung cancer using array comparative genomic hybridization: implications of the phosphatidylinositol 3-kinase pathway. Massion, P.P., Kuo, W.L., Stokoe, D., Olshen, A.B., Treseler, P.A., Chin, K., Chen, C., Polikoff, D., Jain, A.N., Pinkel, D., Albertson, D.G., Jablons, D.M., Gray, J.W. Cancer Res. (2002) [Pubmed]
  45. Modulation of iron transport proteins in human colorectal carcinogenesis. Brookes, M.J., Hughes, S., Turner, F.E., Reynolds, G., Sharma, N., Ismail, T., Berx, G., McKie, A.T., Hotchin, N., Anderson, G.J., Iqbal, T., Tselepis, C. Gut (2006) [Pubmed]
  46. HFE gene mutations in susceptibility to childhood leukemia: HuGE review. Dorak, M.T., Burnett, A.K., Worwood, M. Genet. Med. (2005) [Pubmed]
  47. Transferrin synthesis by small cell lung cancer cells acts as an autocrine regulator of cellular proliferation. Vostrejs, M., Moran, P.L., Seligman, P.A. J. Clin. Invest. (1988) [Pubmed]
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