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Gene Review

Tfrc  -  transferrin receptor

Mus musculus

Synonyms: 2610028K12Rik, AI195355, AI426448, AU015758, CD71, ...
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Disease relevance of Tfrc


Psychiatry related information on Tfrc


High impact information on Tfrc

  • Furthermore, haploinsufficiency for Trfr results in impaired erythroid development and abnormal iron homeostasis [8].
  • Mice lacking Trfr have a more severe phenotype than hpx mice, affecting both erythropoiesis and neurologic development [8].
  • Transferrin receptor is necessary for development of erythrocytes and the nervous system [8].
  • We also correlated the frequency of coated pits with the level of TR expression in different transfected L cell lines [9].
  • These results indicate that the cytoplasmic domain plays an active role in sorting and endocytosis of TR by providing an assembly site for coated pit formation [9].

Chemical compound and disease context of Tfrc


Biological context of Tfrc

  • Transferrin receptor (TfR) facilitates cellular iron uptake by mediating endocytosis of its ligand, iron-loaded transferrin [15].
  • The high level of expression with our conjugate was confirmed using other tumor cells (M7609, TMK-1) whereas in normal diploid cells (HEL), which express low levels of Tf-R, expression was negligible [2].
  • These data suggest that the down-regulation in IL-12 mRNA by anti-TfR mAb may prevent the development of T helper cells, thereby promoting graft survival and altering cell-mediated immune responses [16].
  • The results suggest that the depletion of cellular non-heme iron due to the increase in heme synthesis maintains a high level of transferrin receptor expression in differentiating erythroid cells even after the cessation of cell division [17].
  • TfR expression increased in the course of induction, as judged by increased TfR mRNA synthesis, increased cytoplasmic TfR mRNA level, and by the increased number of cellular 125I-Tf binding sites [17].

Anatomical context of Tfrc

  • We conclude that a proportion of GLUT-4 is found in recycling endosomes in nonstimulated adipocytes together with cellubrevin and the transferrin receptor [18].
  • Conversely, T cells lacking TfR are arrested very early in their development, at the CD4-8-3- stage [15].
  • To elucidate the pathways by which nitric oxide (NO) influences macrophage iron metabolism, the uptake, release, and intracellular distribution of iron in the murine macrophage cell line J774 has been investigated, together with transferrin receptor (TfR) expression and iron-regulatory protein (IRP1 and IRP2) activity [19].
  • These results indicate that TfR is necessary for the normal maturation of thymocytes, but that B-cell development is less severely affected by the absence of TfR [15].
  • Transferrin receptor 1 is differentially required in lymphocyte development [15].

Associations of Tfrc with chemical compounds

  • Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor [20].
  • According to this view, a tumor-associated TF receptor is the functional unit responsible for the affinity of gallium for certain neoplasms [20].
  • Following direct acquisition of transferrin (Tf)-bound iron via the Tf receptor, iron uptake and release was equivalent in wild-type and mutant macrophages and was not influenced by interferon-gamma/lipopolysaccharide activation [21].
  • SA had no effect on TfR expression in Fw cells [17].
  • Comparison of the sequence with that of the human transferrin receptor shows a high degree of conservation of the sequences surrounding and penetrating the membrane, including cysteine residues that may be involved in interchain disulfide bonding and/or covalent attachment of lipid [22].

Physical interactions of Tfrc

  • Transferrin transports iron into cells via the transferrin receptor: thus, iron content of resident cells is low, of peptone- and FCS-elicited cells is intermediate, and of thioglycollate-elicited cells is high [23].

Co-localisations of Tfrc


Regulatory relationships of Tfrc

  • Mice with targeted deletion of IRP2 overexpress ferritin and express abnormally low TfR levels in multiple tissues [25].
  • MMTV-resistant human cells that expressed mouse transferrin receptor 1 became susceptible to MMTV infection, and treatment of mouse cells with a monoclonal antibody that down-regulated cell surface expression of the receptor blocked infection [26].
  • The function of HFE protein is unknown, but it is hypothesized that it acts in association with beta(2)-microglobulin and transferrin receptor 1 to regulate iron uptake from plasma transferrin by the duodenum, the proposed mechanism by which body iron levels are sensed [27].
  • Moreover, M-CSF regulated TfR and LDLR via the activation of distinct signaling pathways [28].
  • Flow-cytometric studies revealed that HRCs obtained from Epo-injected mice expressed the transferrin receptor on their surface membranes [29].

Other interactions of Tfrc

  • Coexpression of DMT1 and TfR in reticulocytes was also detected by double immunofluorescence and confocal microscopy [30].
  • Significantly, we found that c-Tf is efficiently processed and presented when the TfR is cross-linked, altering its normal cycling [31].
  • IRP2 downmodulation is associated with the upregulation of the ferritin L and H genes and decreased expression of the transferrin receptor 1 (TfR1) [32].
  • This data suggests that IFN gamma may enhance iron uptake during the early phase of macrophage activation, and in later phases, down-regulate TfR expression by inducing NO, thus contributing to intracellular oxidative stress reduction [33].
  • Finally, compound mutants lacking Hfe and the transferrin receptor accumulate more tissue iron than do mice lacking Hfe alone, consistent with the idea that interaction between these two proteins contributes to the control of normal iron absorption [34].

Analytical, diagnostic and therapeutic context of Tfrc


  1. Increased plasma transferrin, altered body iron distribution, and microcytic hypochromic anemia in ferrochelatase-deficient mice. Lyoumi, S., Abitbol, M., Andrieu, V., Henin, D., Robert, E., Schmitt, C., Gouya, L., de Verneuil, H., Deybach, J.C., Montagutelli, X., Beaumont, C., Puy, H. Blood (2007) [Pubmed]
  2. In vivo gene delivery to tumor cells by transferrin-streptavidin-DNA conjugate. Sato, Y., Yamauchi, N., Takahashi, M., Sasaki, K., Fukaura, J., Neda, H., Fujii, S., Hirayama, M., Itoh, Y., Koshita, Y., Kogawa, K., Kato, J., Sakamaki, S., Niitsu, Y. FASEB J. (2000) [Pubmed]
  3. Identification of the segments of the mouse transferrin receptor 1 required for mouse mammary tumor virus infection. Wang, E., Albritton, L., Ross, S.R. J. Biol. Chem. (2006) [Pubmed]
  4. The molecular circuitry regulating the switch between iron deficiency and overload in mice. Mok, H., Mlodnicka, A.E., Hentze, M.W., Muckenthaler, M., Schumacher, A. J. Biol. Chem. (2006) [Pubmed]
  5. In situ analysis of antigens on malignant and benign cells of the melanocyte lineage. Differential expression of two surface molecules, gp75 and p89. Holzmann, B., Johnson, J.P., Kaudewitz, P., Riethmüller, G. J. Exp. Med. (1985) [Pubmed]
  6. Ion channel blockers inhibit B cell activation at a precise stage of the G1 phase of the cell cycle. Possible involvement of K+ channels. Amigorena, S., Choquet, D., Teillaud, J.L., Korn, H., Fridman, W.H. J. Immunol. (1990) [Pubmed]
  7. Imaging brain amyloid of Alzheimer disease in vivo in transgenic mice with an Abeta peptide radiopharmaceutical. Lee, H.J., Zhang, Y., Zhu, C., Duff, K., Pardridge, W.M. J. Cereb. Blood Flow Metab. (2002) [Pubmed]
  8. 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]
  9. A role for the cytoplasmic domain in transferrin receptor sorting and coated pit formation during endocytosis. Iacopetta, B.J., Rothenberger, S., Kühn, L.C. Cell (1988) [Pubmed]
  10. Differential expression of a Mr approximately 90,000 cell surface transferrin receptor-related glycoprotein on murine B16 metastatic melanoma sublines selected for enhanced brain or ovary colonization. Nicolson, G.L., Inoue, T., Van Pelt, C.S., Cavanaugh, P.G. Cancer Res. (1990) [Pubmed]
  11. Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake. Kang, J.S., Cho, D., Kim, Y.I., Hahm, E., Kim, Y.S., Jin, S.N., Kim, H.N., Kim, D., Hur, D., Park, H., Hwang, Y.I., Lee, W.J. J. Cell. Physiol. (2005) [Pubmed]
  12. In vitro and in vivo effect of HPMA copolymer-bound doxorubicin targeted to transferrin receptor of B-cell lymphoma 38C13. Kovár, M., Strohalm, J., Ulbrich, K., Ríhová, B. Journal of drug targeting. (2002) [Pubmed]
  13. Effect of glycosylation inhibitors on the structure and function of the murine transferrin receptor. Ralton, J.E., Jackson, H.J., Zanoni, M., Gleeson, P.A. Eur. J. Biochem. (1989) [Pubmed]
  14. Cardiac dysfunction caused by myocardium-specific expression of a mutant thyroid hormone receptor. Pazos-Moura, C., Abel, E.D., Boers, M.E., Moura, E., Hampton, T.G., Wang, J., Morgan, J.P., Wondisford, F.E. Circ. Res. (2000) [Pubmed]
  15. Transferrin receptor 1 is differentially required in lymphocyte development. Ned, R.M., Swat, W., Andrews, N.C. Blood (2003) [Pubmed]
  16. Transferrin receptor in T cell activation and transplantation. Bayer, A.L., Baliga, P., Woodward, J.E. J. Leukoc. Biol. (1998) [Pubmed]
  17. Inhibition of heme synthesis decreases transferrin receptor expression in mouse erythroleukemia cells. Hradilek, A., Fuchs, O., Neuwirt, J. J. Cell. Physiol. (1992) [Pubmed]
  18. The glucose transporter (GLUT-4) and vesicle-associated membrane protein-2 (VAMP-2) are segregated from recycling endosomes in insulin-sensitive cells. Martin, S., Tellam, J., Livingstone, C., Slot, J.W., Gould, G.W., James, D.E. J. Cell Biol. (1996) [Pubmed]
  19. Regulation of iron metabolism in murine J774 macrophages: role of nitric oxide-dependent and -independent pathways following activation with gamma interferon and lipopolysaccharide. Mulero, V., Brock, J.H. Blood (1999) [Pubmed]
  20. Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor. Larson, S.M., Rasey, J.S., Allen, D.R., Nelson, N.J., Grunbaum, Z., Harp, G.D., Williams, D.L. J. Natl. Cancer Inst. (1980) [Pubmed]
  21. Solute carrier 11a1 (Slc11a1; formerly Nramp1) regulates metabolism and release of iron acquired by phagocytic, but not transferrin-receptor-mediated, iron uptake. Mulero, V., Searle, S., Blackwell, J.M., Brock, J.H. Biochem. J. (2002) [Pubmed]
  22. cDNA cloning of the murine transferrin receptor: sequence of trans-membrane and adjacent regions. Stearne, P.A., Pietersz, G.A., Goding, J.W. J. Immunol. (1985) [Pubmed]
  23. Role of transferrin, transferrin receptors, and iron in macrophage listericidal activity. Alford, C.E., King, T.E., Campbell, P.A. J. Exp. Med. (1991) [Pubmed]
  24. Tyrosine and serine protein kinase activities associated with ligand-induced internalized TCR/CD3 complexes. Luton, F., Legendre, V., Gorvel, J.P., Schmitt-Verhulst, A.M., Boyer, C. J. Immunol. (1997) [Pubmed]
  25. Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. Cooperman, S.S., Meyron-Holtz, E.G., Olivierre-Wilson, H., Ghosh, M.C., McConnell, J.P., Rouault, T.A. Blood (2005) [Pubmed]
  26. Mouse transferrin receptor 1 is the cell entry receptor for mouse mammary tumor virus. Ross, S.R., Schofield, J.J., Farr, C.J., Bucan, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  27. Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse. Trinder, D., Olynyk, J.K., Sly, W.S., Morgan, E.H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  28. Macrophage colony-stimulating factor differentially regulates low density lipoprotein and transferrin receptors. Du, L., Post, S.R. J. Lipid Res. (2004) [Pubmed]
  29. Characterization of haemolyser-resistant cells increased in the blood of erythropoietin-treated mice. Said, A.A., Yamaguchi, T., Uchida, E., Hayakawa, T. Br. J. Haematol. (1994) [Pubmed]
  30. Characterization of the iron transporter DMT1 (NRAMP2/DCT1) in red blood cells of normal and anemic mk/mk mice. Canonne-Hergaux, F., Zhang, A.S., Ponka, P., Gros, P. Blood (2001) [Pubmed]
  31. Antigen entry into early endosomes is insufficient for MHC class II processing. Niebling, W.L., Pierce, S.K. J. Immunol. (1993) [Pubmed]
  32. IRP1-independent alterations of cardiac iron metabolism in doxorubicin-treated mice. Corna, G., Galy, B., Hentze, M.W., Cairo, G. J. Mol. Med. (2006) [Pubmed]
  33. Modulation of transferrin synthesis, transferrin receptor expression, iNOS expression and NO production in mouse macrophages by cytokines, either alone or in combination. Ryu, S.Y., Jeong, K.S., Kang, B.N., Park, S.J., Yoon, W.K., Kim, S.H., Kim, T.H. Anticancer Res. (2000) [Pubmed]
  34. Genes that modify the hemochromatosis phenotype in mice. Levy, J.E., Montross, L.K., Andrews, N.C. J. Clin. Invest. (2000) [Pubmed]
  35. Targeted disruption of the hepatic transferrin receptor 2 gene in mice leads to iron overload. Wallace, D.F., Summerville, L., Subramaniam, V.N. Gastroenterology (2007) [Pubmed]
  36. Immunohistochemical localization of intraneuronal transferrin receptor immunoreactivity in the adult mouse central nervous system. Moos, T. J. Comp. Neurol. (1996) [Pubmed]
  37. Two compartments for insulin-stimulated exocytosis in 3T3-L1 adipocytes defined by endogenous ACRP30 and GLUT4. Bogan, J.S., Lodish, H.F. J. Cell Biol. (1999) [Pubmed]
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