ArticleProceedings of the National Academy of Sciences of the United States of America2002
Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 1 of them a synthesis that pooled it.
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Who cites it
143 citing papers in PubMed, 1 synthesis or guideline pooled it, 430 citations in OpenAlex.
- A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.Communications biology · 2021Pooled it
- The DMT1 IVS4+44C>A polymorphism and the risk of iron deficiency anemia in children with celiac disease.PloS one · 2017Trial
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Disruption of iron metabolism resulting from Dmt1/Slc11a2 deficiency compromises Notch protein degradation and transcriptional activation.The FEBS journal · 2026Article
- Iron-endoplasmic reticulum-extracellular matrix axis regulates cancer cell invasion.bioRxiv : the preprint server for biology · 2026Article
- Non-transferrin-bound iron uptake by cardiomyocytes.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Acidosis, Iron Dyshomeostasis and Inflammatory Injury.International journal of molecular sciences · 2026Review
- Protein nanoparticle-based vaccine candidate produced inFrontiers in plant science · 2026Article
- α-lipoic acid attenuates duodenal non-heme iron absorption via microRNA-mediated regulation of divalent metal transporter 1 in iron overloaded rats.Molecular biology reports · 2025Article
- Lomitapide enhances cytotoxic effects of temozolomide in chemotherapy-resistant glioblastoma.JCI insight · 2025Article
- The solute carrier family 11 transporters: a bridge between iron homeostasis and tumor biology.Cell communication and signaling : CCS · 2025Review
- The Roles of DMT1 in Inflammatory and Degenerative Diseases.Molecular neurobiology · 2025Review
- Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes.PLoS computational biology · 2025Article
- Role of the human cytochrome b561 family in iron metabolism and tumors (Review).Oncology letters · 2025Review
- Evaluation of Different Polysaccharide-Iron Complex Preparations In Vitro and In Vivo.Pharmaceutics · 2025Article
- Supplementation with Zn-loaded montmorillonite enhanced Zn ion transport, trace element deposition, antioxidant capacity, and intestinal function in broilers.Frontiers in veterinary science · 2025Article
- Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells.Frontiers in molecular biosciences · 2025Article
- The role of mitochondria in iron overload-induced damage.Journal of translational medicine · 2024Review
- Unlocking ferroptosis in prostate cancer - the road to novel therapies and imaging markers.Nature reviews. Urology · 2024Review
- Ischemic Neuroprotection by Insulin with Down-Regulation of Divalent Metal Transporter 1 (DMT1) Expression and Ferrous Iron-Dependent Cell Death.Biomolecules · 2024Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Divalent metal transporter 1 (DMT1) mediates apical iron uptake into duodenal enterocytes and also transfers iron from the endosome into the cytosol after cellular uptake via the transferrin receptor. Hence, mutations in DMT1 cause systemic iron deficiency and anemia. DMT1 mRNA levels are increased in the duodenum of iron-deficient animals. This regulation has been observed for DMT1 mRNA harboring an iron-responsive element (IRE) in its 3' UTR, but not for a processing variant lacking a 3'UTR IRE, suggesting that the IRE regulates the expression of DMT1 mRNA in response to iron levels. Here, we show that iron regulation of DMT1 involves the expression of a previously unrecognized upstream 5' exon (exon 1A) of the human and murine DMT1 gene. The expression of this previously uncharacterized 5' exon is tissue-specific and particularly prevalent in the duodenum and kidney. It adds an in-frame AUG translation initiation codon extending the DMT1 ORF by a conserved sequence of 29-31 amino acids. In combination with the IRE- and non-IRE variants in the 3'UTR, our results reveal the existence of four DMT1 mRNA isoforms predicting the synthesis of four different DMT1 proteins. We show that two regulatory regions, the 5' promoter/exon 1A region and the IRE-containing terminal exon participate in iron regulation of DMT1 expression, which operate in a tissue-specific way. These results uncover an unexpected complexity of DMT1 expression and regulation, with implications for understanding the physiology, cell biology, and pathophysiology of mammalian iron metabolism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.