The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Abstract
Metal ions are essential cofactors for a wealth of biological processes, including oxidative phosphorylation, gene regulation and free-radical homeostasis. Failure to maintain appropriate levels of metal ions in humans is a feature of hereditary haemochromatosis, disorders of metal-ion deficiency, and certain neurodegenerative diseases. Despite their pivotal physiological roles, however, there is no molecular information on how metal ions are actively absorbed by mammalian cells. We have now identified a new metal-ion transporter in the rat, DCT1, which has an unusually broad substrate range that includes Fe2+, Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+ and Pb2+. DCT1 mediates active transport that is proton-coupled and depends on the cell membrane potential. It is a 561-amino-acid protein with 12 putative membrane-spanning domains and is ubiquitously expressed, most notably in the proximal duodenum. DCT1 is upregulated by dietary iron deficiency, and may represent a key mediator of intestinal iron absorption. DCT1 is a member of the 'natural-resistance-associated macrophage protein' (Nramp) family and thus its properties provide insight into how these proteins confer resistance to pathogens.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The uptake of ionic NHI in contrast, is a sequential process that is well characterized: Following the reduction of ferric iron by DCYTB (for duodenal cytochrome B) at the luminal surface of enterocytes (ENT), it is DMT1 (for divalent metal transporter-1) that imports iron into the cytoplasm (Gunshin et al., 1997;McKie et al., 2001).”
From Iron in infection and immunity (2020) · cites this paper as Gunshin et al., 1997
In the citing paper
“The freed ferric iron is then reduced to its bio-active ferrous form, Fe2+ by the ferrireductase STEAP3 (six-transmembrane epithelial antigen of prostate 3) and shuttled into the cytosol from the endosome by DMT1 (Fleming et al., 1997; Gunshin et al., 1997; Ohgami et al., 2005; Figure 1).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Gunshin et al., 1997
In the citing paper
“Iron absorption in the duodenum is controlled via the expression and transport activity of divalent metal transporter 1 (DMT1) on the luminal side of enterocytes [6] and by ferroportin (FPN1), the sole known iron exporter on the basal side, which transfers iron into the bloodstream [7].”
From Iron in immune cell function and host defense (2021) · cites this paper as [6]
In the citing paper
“Gunshin 13 and Hediger 15 showed that DMT1 is electrogenic, requiring proton cotransport to move Fe 2ϩ across the membrane.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [13]
In the citing paper
“In spite of these obstacles and entirely by chance, the first mammalian transmembrane iron transporter was discovered simultaneously in 2 laboratories, located within a city block of each other in Boston, using singularly modern techniques.12,13”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [13]
In the citing paper
“DMT1 may also serve as a physiologically significant portal of entry for other divalent metal cations including Mn 2ϩ , Co 2ϩ , Zn 2ϩ , Cu 2ϩ , and Pb 2ϩ , though its importance has only been definitively established for Fe 2ϩ in vivo.13”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [13]
In the citing paper
“DMT1 expression is dramatically induced in iron deficiency, 13 and possibly regulated at a posttranscriptional level by a 3Ј IRE present in the splice isoform expressed in intestine.57”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [13]
In the citing paper
“Recent evidence has implicated abnormal iron metabolism in the pathogenesis of neurodegeneration (120, 241).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [120]
Citations
Cites
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R., Ellis, M. C., Fullan, A., et al. (1996) · Nature Genetics · doi:10.1038/ng0896-399 · Cited by 3,664
Regulating the fate of mRNA: the control of cellular iron metabolism
Klausner, R. D., Rouault, T. A., & Harford, J. B. (1993) · Cell · doi:10.1016/0092-8674(93)90046-s · Cited by 1,210
Schaeren‐Wiemers, N., & Gerfin-Moser, A. (1993) · Histochemistry and Cell Biology · doi:10.1007/bf00267823 · Cited by 1,151
Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg
Vidal, S. M., Malo, D., Vogan, K., Skamene, E., & Gros, P. (1993) · Cell · doi:10.1016/0092-8674(93)90135-d · Cited by 1,104
Iron-Responsive Elements: Regulatory RNA Sequences That Control mRNA Levels and Translation
Casey, J. L., Hentze, M. W., Koeller, D. M., Caughman, S. W., Rouault, T. A., Klausner, R. D., & Harford, J. B. (1988) · Science · doi:10.1126/science.2452485 · Cited by 709
ZnT-3, a putative transporter of zinc into synaptic vesicles
Palmiter, R. D., Cole, T. B., Quaife, C. J., & Findley, S. D. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14934 · Cited by 708
Expression cloning and characterization of a renal electrogenic Na+ /HCO3− cotransporter
Romero, M. F., Hediger, M. A., Boulpaep, E. L., & Boron, W. F. (1997) · Nature · doi:10.1038/387409a0 · Cited by 423
Self-citationMolecular physiology of sodium-glucose cotransporters.
Hediger, M. A., & Rhoads, D. B. (1994) · Physiological Reviews · doi:10.1152/physrev.1994.74.4.993 · Cited by 417
Self-citationWilson disease and Menkes disease: new handles on heavy-metal transport
Bull, P. C., & Cox, D. W. (1994) · Trends in Genetics · doi:10.1016/0168-9525(94)90172-4 · Cited by 335
Supek, F., Supekova, L., Nelson, H., & Nelson, N. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.5105 · Cited by 325
Mager, S., Naeve, J., Quick, M. W., Labarca, C. G., Davidson, N., & Lester, H. A. (1993) · Neuron · doi:10.1016/0896-6273(93)90309-f · Cited by 324
Identification and characterization of a second mouse Nramp gene
Gruenheid, S., Cellier, M. F., Vidal, S. M., & Gros, P. (1995) · Genomics · doi:10.1016/0888-7543(95)80053-o · Cited by 287
Mechanisms of the Human Intestinal H+-coupled Oligopeptide Transporter hPEPT1
Mackenzie, B., Loo, D. D. F., Fei, Y.-J., Liu, W., Ganapathy, V., Leibach, F. H., & Wright, E. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.10.5430 · Cited by 157
Self-citationVidal, S. M., Gros, P., & Skamene, E. (1995) · Journal of Leukocyte Biology · doi:10.1002/jlb.58.4.382 · Cited by 153
Reduction of Fe(III) Is Required for Uptake of Nonheme Iron by Caco-2 Cells
Han, O., Failla, M. L., Hill, A. D., Morris, E. R., & Smith, J. C. (1995) · Journal of Nutrition · doi:10.1093/jn/125.5.1291 · Cited by 130
Mackenzie, B., Loo, D. D. F., Panayotova‐Heiermann, M., & Wright, E. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32678 · Cited by 127
Self-citationInvestigation of a role for reduction in ferric iron uptake by mouse duodenum
Raja, K. B., Simpson, R. J., & Peters, T. J. (1992) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(92)90129-y · Cited by 121
Relationships Between Na + /Glucose Cotransporter (SGLT1) Currents and Fluxes
Mackenzie, B., Loo, D. D. F., & Wright, E. M. (1998) · The Journal of Membrane Biology · doi:10.1007/s002329900347 · Cited by 117
Self-citationKinetics and Specificity of a H+/Amino Acid Transporter from Arabidopsis thaliana
Boorer, K. J., Frommer, W. B., Bush, D. R., Kreman, M., Loo, D. D. F., & Wright, E. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.4.2213 · Cited by 103
Boorer, K. J., Loo, D. D. F., & Wright, E. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32008-2 · Cited by 95
Molecular biology of iron and zinc uptake in eukaryotes
Eide, D. J. (1997) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(97)80036-1 · Cited by 91
Jordan, I., & Kaplan, J. (1994) · Biochemical Journal · doi:10.1042/bj3020875 · Cited by 88
Hereditary hemochromatosis: pathogenesis and clinical features of a common disease.
Nichols, G. M., & Bacon, B. R. (1989) · PubMed · Cited by 88
Biochemistry of Parkinson's disease with special reference to the dopaminergic systems
Hirsch, É. C. (1994) · Molecular Neurobiology · doi:10.1007/bf02816113 · Cited by 80
Nußberger, S., Steel, A., Trotti, D., Romero, M. F., Boron, W. F., & Hediger, M. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.12.7777 · Cited by 69
Self-citationMcEwan, G. T. A., Daniel, H., Fett, C., Burgess, M. N., & LUCAS, M. L. (1988) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1988.0045 · Cited by 69
Jauch, P., & Läuger, P. (1986) · The Journal of Membrane Biology · doi:10.1007/bf01871192 · Cited by 66
Iron speciation at physiological pH in media containing ascorbate and oxygen
Dorey, C., Cooper, C. E., Dickson, D. P. E., Gibson, J. F., Simpson, R. J., & Peters, T. J. (1993) · British Journal Of Nutrition · doi:10.1079/bjn19930113 · Cited by 43
Mobilferrin is an intermediate in iron transport between transferrin and hemoglobin in K562 cells.
Conrad, M. E., Umbreit, J. N., Moore, E., & Heiman, D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118933 · Cited by 23
Gunshin, H., Noguchi, T., & Naito, H. (1991) · Agricultural and Biological Chemistry · doi:10.1271/bbb1961.55.2813 · Cited by 17
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications
Stockwell, B. R. (2022) · Cell · doi:10.1016/j.cell.2022.06.003 · Cited by 3,211
Andrews, N. C. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912233412607 · Cited by 2,130
Two to tango: Regulation of Mammalian iron metabolism
Hentze, M. W., Muckenthaler, M. U., Galy, B., & Camaschella, C. (2010) · Cell · doi:10.1016/j.cell.2010.06.028 · Cited by 2,120
Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004) · Cell · doi:10.1016/s0092-8674(04)00343-5 · Cited by 1,736
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697
Metadata
- Authors
- Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., & Hediger, M. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Yale University (US)
- Corresponding author
- Gunshin, Hiromi
- Venue
- Nature
- Published
- 1997-07-31
- Volume
- 388
- Issue
- 6641
- Pages
- 482-488
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1568628619
- Cited by
- 3,166
- References
- 30
- Citations by year
- 2026: 47 · 2025: 70 · 2024: 60 · 2023: 69 · 2022: 85 · 2021: 82 · 2020: 94 · 2019: 100 · 2018: 98 · 2017: 102 · 2016: 82 · 2015: 98 · 2014: 129 · 2013: 92 · 2012: 129
- FWCI
- 68.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK009342)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
- Keywords
- metal transporters, intestinal iron absorption, Nramp family, dietary iron deficiency, proximal duodenum, metal homeostasis, membrane potential dependence
- MeSH terms
- Iron Deficiencies, Natural Resistance-associated Macrophage Protein 1, Solute Carrier Family 11, Member 2, Amino Acid Sequence, Animals, Carrier Proteins, Cations, Divalent, Cells, Cultured, Cloning, Molecular, Humans, Iron, Membrane Potentials, Membrane Proteins, Metals, Molecular Sequence Data, Oocytes, Organ Specificity, RNA, Messenger, Xenopus, Sequence Homology, Amino Acid, Cation Transport Proteins, Iron-Binding Proteins, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
