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A Novel Duodenal Iron-Regulated Transporter, IREG1, Implicated in the Basolateral Transfer of Iron to the Circulation
Open accessAbstract
Iron absorption by the duodenal mucosa is initiated by uptake of ferrous Fe(II) iron across the brush border membrane and culminates in transfer of the metal across the basolateral membrane to the portal vein circulation by an unknown mechanism. We describe here the isolation and characterization of a novel cDNA (Ireg1) encoding a duodenal protein that is localized to the basolateral membrane of polarized epithelial cells. Ireg1 mRNA and protein expression are increased under conditions of increased iron absorption, and the 5' UTR of the Ireg1 mRNA contains a functional iron-responsive element (IRE). IREG1 stimulates iron efflux following expression in Xenopus oocytes. We conclude that IREG1 represents the long-sought duodenal iron export protein and is upregulated in the iron overload disease, hereditary hemochromatosis.
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In the citing paper
“After export by FPN1, iron is reoxidized to its ferric form by membrane-anchored hephaestin or by circulating ceruloplasmin (McKie et al., 2000;Vulpe et al., 1999).”
From Iron in infection and immunity (2020) · cites this paper as McKie et al., 2000
In the citing paper
“The key iron exporter is ferroportin (FPN, also called SLC40A1) which exports Fe2+ iron (McKie et al., 2000).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as McKie et al., 2000
In the citing paper
“Cellular iron export – and, therefore, gastrointestinal absorption of iron – is uniquely mediated by the iron transporter ferroportin (FPN or SLC40A1). 21 , 22 , 23 , 24”
From The battle for iron in enteric infections (2020) · cites this paper as [24]
In the citing paper
“CYBRD1 was one of 2 iron transport-related molecules discovered by McKie through a very productive RNA subtraction approach.53,54”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [54]
In the citing paper
“The basolateral iron transporter, discovered simultaneously by 3 labs, is ferroportin (also called IREG1, MTP1, SLC39A1, and now SLC40A1).54,77,78”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [54]
In the citing paper
“Overexpression of ferritoid resulted in a shift in ferritin H distribution from cytoplasm to nucleus (201).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [201]
In the citing paper
“Ferritoid is a 30-kDa protein consisting of 270 amino acids specifically expressed in corneal epithelial cells (201).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [201]
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Metadata
- Authors
- McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., Hediger, M. A., Hentze, M. W., & Simpson, R. J.
- Affiliations
- King's College London (GB)
- Brigham and Women's Hospital (US)
- European Molecular Biology Laboratory (DE)
- Universitat de Barcelona (ES)
- Corresponding author
- McKie, Andrew T
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 5
- Issue
- 2
- Pages
- 299-309
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2143900678
- Cited by
- 1,422
- References
- 41
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 30 · 2023: 32 · 2022: 34 · 2021: 50 · 2020: 41 · 2019: 42 · 2018: 43 · 2017: 43 · 2016: 42 · 2015: 48 · 2014: 66 · 2013: 58 · 2012: 47
- FWCI
- 41.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- CYTED Ciencia y Tecnología para el Desarrollo
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- iron absorption, iron-responsive element, iron overload, hereditary hemochromatosis, iron efflux, duodenal epithelial cells, cDNA cloning, iron homeostasis
- MeSH terms
- Ferroportin, Amino Acid Sequence, Animals, Base Sequence, Biological Transport, Carrier Proteins, Cell Compartmentation, Cloning, Molecular, Duodenum, Ferric Compounds, Gene Expression Regulation, Intestinal Absorption, Intestinal Mucosa, Iron, Membrane Proteins, Models, Biological, Molecular Sequence Data, Portal Vein, RNA, Messenger, Sequence Homology, Nucleic Acid, Transferrin, Cell Polarity, Sequence Homology, Amino Acid, Response Elements, Cation Transport Proteins, Mice
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