The DOI matches its Crossref record; 19 of the 20 references it cites were found in a registry or an index.
Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing.
Open accessAbstract
HFE and transferrin receptor 2 (TFR2) are membrane proteins integral to mammalian iron homeostasis and associated with human hereditary hemochromatosis. Here we demonstrate that HFE and TFR2 interact in cells, that this interaction is not abrogated by disease-associated mutations of HFE and TFR2, and that TFR2 competes with TFR1 for binding to HFE. We propose a new model for the mechanism of iron status sensing that results in the regulation of iron homeostasis.
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“Taking this into account, we have proposed a model in which TFR2 escorts HFE away from TFR1 when the serum iron level (reflected in the transferrin saturation) is elevated.149,150”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [150]
In the citing paper
“Like TFR1, TFR2 interacts with HFE to form a stable protein complex.150”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [150]
Citations
Cites
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803
Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004) · Cell · doi:10.1016/s0092-8674(04)00343-5 · Cited by 1,736
Self-citationNicolas, G., Chauvet, C., Viatte, L., Danan, J. L., Bigard, X., Devaux, I., Beaumont, C., Kahn, A., & Vaulont, S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215686 · Cited by 1,214
Molecular Cloning of Transferrin Receptor 2
Kawabata, H., Yang, R., Hirama, T., Vuong, P. T., Kawano, S., Gombart, A. F., & Koeffler, H. P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.20826 · Cited by 661
Weinstein, D. A., Roy, C. N., Fleming, M. D., Loda, M. F., Wolfsdorf, J. I., & Andrews, N. C. (2002) · Blood · doi:10.1182/blood-2002-04-1260 · Cited by 632
Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor
Bennett, M. J., Lebrón, J. A., & Björkman, P. J. (2000) · Nature · doi:10.1038/47417 · Cited by 343
Wu, J. C., Merlino, G. T., & Fausto, N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.2.674 · Cited by 317
The C282Y Mutation Causing Hereditary Hemochromatosis Does Not Produce a Null Allele
Levy, J. E., Montross, L. K., Cohen, D. E., Fleming, M. D., & Andrews, N. C. (1999) · Blood · doi:10.1182/blood.v94.1.9.413a43_9_11 · Cited by 259
West, A. P., Bennett, M. J., Sellers, V. M., Andrews, N. C., Enns, C. A., & Bjorkman, P. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000664200 · Cited by 257
Self-citationDiferric transferrin regulates transferrin receptor 2 protein stability
Johnson, M. B., & Enns, C. A. (2004) · Blood · doi:10.1182/blood-2004-06-2477 · Cited by 235
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- Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A. & Struhl, K. (eds) Current Protocols in Molecular Biology, pp. 9.1.1–9.1.11 and 12.1.1–12.1.6, Wiley-Interscience, New York
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Items 301–351 of 351
Regulation of hepcidin and hemojuvelin expression and their role in iron homeostasis
Salama, M. (2010) · UCL Discovery (University College London)
Mutations du gène HFE dans le cancer épithélial de l'ovaire
Medelci, S. (2008) · doi:10.71781/31650
Iron: Molecular Basis of Hemochromatosis
Schmidt, P. J. (2004) · Wiley eBooks · doi:10.1002/9781119951438.eibc2137
Ginzburg, Y. Z., & Rivella, S. (2012)
Iron transport and liver injury in mouse models of hereditary haemochromatosis
De Lima, R. (2013) · UWA Profiles and Research Repository (University of Western Australia)
Exercise induced hemolysis, inflammation and hepcidin activity in endurance trained runners
Peeling, P. (2009) · UWA Profiles and Research Repository (University of Western Australia)
Studies on the role of hephaestin and transferrin in iron transport
Hudson, D. M. (2008) · cIRcle (University of British Columbia) · doi:10.14288/1.0066537
“TfR2 is capable of binding and internalizing diferric Tf, in fact the cell surface stability of TfR2 is increased in the presence of diferric Tf (Goswami and Andrews, 2006).”
BackgroundМихайлова, С. В. (2008) · Mathematical Biology and Bioinformatics · doi:10.17537/2008.3.60
Research Update on Iron Metabolism and Its Regulation Mechanisms
Wang, L. (2008) · North American Journal of Medicine and Science · doi:10.7156/v1i1p015
“Interaction of diferric-transferrin complex (FeTF) with transferrin receptors on cell surface influences HFE’s association with transferrin receptor 1 and transferrin receptor 2 which will lead to a subsequent signal pathway that regulates hepcidin expression.(3,6) Hepcidin can bind to FPN, which is abundantly express…”
BackgroundHypoxia-Dependent Hepcidin Down-Regulation: In Vitro and In Vivo Studies
Ravasi, G. (2016) · BOA (University of Milano-Bicocca)
Evaluation of serum hepcidin in assessment of iron status in renal transplant patients
El-Khatib, M. M., Fawzy, M., Khashab, S., Ramzy, M. F., Elgayar, D. F., & Kamal, M. (2010) · African Journal of Nephrology · doi:10.21804/14-1-770
“Deficient production of hepcidin causes systemic iron overload, whereas hepcidin excess, caused by many factors including inflammatory mediators as IL-6 leads to the development of hypoferrinemia and anemia of chronic disease [9].”
BackgroundTandara, L. (2016) · Repozitorij Farmaceutsko-biokemijskog fakulteta (Sveučilišta u Zagrebu)
Metabolic and Genetic Liver Diseases: Hemochromatosis
Stotts, M. J., & Bacon, B. R. (2016) · Springer eBooks · doi:10.1007/978-3-319-30103-7_20
Transferrin Receptor 2 による鉄代謝シグナル : 赤血球造血における意義
川端, 浩. (2011) · 臨床血液 · doi:10.11406/rinketsu.52.399
Hemochromatosis and Iron Storage Disorders
Kowdley, K. V., & Handa, P. (2017) · Wiley eBooks · doi:10.1002/9781119251316.ch30
Multiple Modes of Hepcidin Regulation in Breast Cancer
Farra, N. (2017) · OpenCommons - UConn (University of Connecticut)
IN TRANSLATION Molecular Mechanisms of Hepcidin Regulation: Implications for the Anemia of CKD
Babitt, J. L., & Lin, H. Y.-F. (2010)
Physiological and pathological factors affecting the homeostasis of iron
Zeckei, J., & Obuchowicz, A. K. (2019) · Pediatria Polska · doi:10.5114/polp.2018.82655
“The TfR2-Tf complex, combined with the released HFE proteins from TfR1 receptors, leads to increased intracellular production of hepcidin.”
BackgroundInfluentialGenetic Variation of the HFE Gene and Associated Proteomes in Chronic Venous Leg Ulceration
Sydes, E. R. (1905) · Queensland University of Technology · doi:10.5204/thesis.eprints.127835
“Double Punch”: Hepatitis C in Patients with Genetic Defects of Iron Metabolism
Даниленко, Н. Г., Siniauskaya, M. G., Лукашик, С. П., Karpov, I., & Davydenko, O. G. (2019) · Cytology and Genetics · doi:10.3103/s0095452719050062
Nano‐sensing and nano‐therapy targeting central players in iron homeostasis
Wu, L., Li, Y., & Gu, N. (2020) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1667
Toth, E. L. (2019) · UA Campus Repository (The University of Arizona)
A vasanyagcsere szabályozása, hepcidinexpresszió fiziológiás és pathológiás körülmények között
Egyed, M. (2021) · Hematológia–Transzfuziológia · doi:10.1556/2068.2021.54.1.6
Sanyear, C., Chiawtada, B., Butthep, P., Svasti, S., Fucharoen, S., & Masaratana, P. (2021) · PeerJ · doi:10.7717/peerj.11367
Impact of the UPR on the expression of relevant genes for cellular iron metabolism
Oliveira, S. J. (2011)
Niederau, C. M. (2008) · Die Gastroenterologie · doi:10.1007/s11377-008-0146-5
Identification and analysis of genetic and chemical modulators of iron metabolism
Hawula, Z. J. (2021) · Queensland University of Technology · doi:10.5204/thesis.eprints.225904 · Cited by 1
State-of-the-Art Lecture II: Hereditary haemochromatosis: the genes and the disease
Pietrangelo, A. (2007) · Springer eBooks · doi:10.1007/978-1-4020-6393-0_7
Schuff‐Werner, P. (2010) · Springer eBooks · doi:10.1007/978-3-642-12765-6_9
Lackner, C., & Knisely, A. S. (2020) · Pathologie · doi:10.1007/978-3-642-04557-8_4
(2021) · PeerJ · doi:10.7287/peerj.11367v0.2/reviews/1
“Moreover, 82 transferrin-bound iron can induce hepcidin expression via HFE and transferrin receptor 2 (TFR2) 83 interaction (Goswami & Andrews, 2006; Gao et al., 2009).”
BackgroundMendelian randomization study of micronutrients and development of CKD in a Korean population
Lee, J., Lee, S., Oh, K., & Park, S. K. (2025) · Nutrition Journal · doi:10.1186/s12937-025-01160-2
“Similarly, SNPs in genes regulating iron homeostasis, such as HFE and TF, could interact with high vitamin C intake to exacerbate oxidative damage through increased ROS production and iron overload in renal tissues [46, 47].”
Surcharges en fer rares d’origine génétique : caractérisation clinique, fonctionnelle, et biologique
Bardou‐Jacquet, E. (2013) · theses.fr (ABES) · doi:10.70675/99eb557fz5edcz4fdezbd26z84ca08eab5aa
Fer et autres métaux : interrelations métaboliques et rôle de l'hepcidine
Cavey, T. (2017) · theses.fr (ABES) · doi:10.70675/402f5b81z6d39z4031za866z25a316a87b2a
Etude du récepteur à la transferrine de type 2 dans l'érythropoïese.
Richard, C. (2019) · theses.fr (ABES) · doi:10.70675/c36ec54fz3a93z404cz8641z05a8f1db21d5
Le rôle de l'érythroferrone dans la régulation du métabolisme du fer
Sardo, U. (2020) · theses.fr (ABES) · doi:10.70675/d03e67aczc44bz4af9z8fa1zef080668f44f
Bories, G. F. P. (2011) · theses.fr (ABES) · doi:10.70675/81757398zf42fz45dcz8424z3f14e050bfb4
Iron dyshomeostasis in neuropsychiatric disorders
Cheng, M., Ma, J., Yang, Y., Cao, M., Zhang, E., Feng, B., Wang, Q., & Du, Z. J. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1771423
“In an environment rich in iron, Tf competes with HFE for TFR1, resulting in the separation of HFE and TFR1 and the binding of TFR2, thus activating the SMAD signaling pathway and inducing the expression of HAMP (30).”
The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression
Enns, C. A., Jue, S. F., Bethel, D., & Zhang, A.-S. (2026) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00167.2026
The role of Ncb5or in fatty acid metabolism and redox homeostasis
Xu, M. (2011) · KU ScholarWorks (The University of Kansas)
Sousa, F. F. D. (2012) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/9qa6-4j32
Metadata
- Authors
- Goswami, T., & Andrews, N. C.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Andrews, Nancy C.
- ORCID
- Andrews, Nancy C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 281
- Issue
- 39
- Pages
- 28494-28498
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1983970155
- Cited by
- 352
- References
- 20
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 4 · 2021: 15 · 2020: 13 · 2019: 12 · 2018: 12 · 2017: 18 · 2016: 16 · 2015: 16 · 2014: 18 · 2013: 31 · 2012: 17
- FWCI
- 19.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK53813, R01DK053813)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- hereditary hemochromatosis, HFE gene, transferrin receptor 2, transferrin receptor 1, protein-protein interaction, iron homeostasis, iron sensing, disease-associated mutations
- MeSH terms
- Hemochromatosis Protein, Animals, Hemochromatosis, Homeostasis, Humans, Iron, Membrane Proteins, Models, Biological, Mutation, Receptors, Transferrin, Histocompatibility Antigens Class I, Antigens, CD, Mice
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