{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC11A2, which encodes the divalent metal transporter 1 (DMT1), is a proton‐coupled transmembrane protein primarily responsible for the cellular uptake of ferrous iron via both apical absorption in the duodenum and release of endosomal iron during the transferrin cycle. In addition, DMT1 mediates transport of several other divalent metals such as manganese, cobalt, cadmium, lead, and even certain forms of copper depending on the cellular context, though its affinity and capacity for these metals differ from that for Fe²⁺. Multiple study reports have shown that DMT1 exists as several isoforms generated by alternative transcription start sites and 3′ untranslated region splicing (with or without an iron‐responsive element), and while these isoforms have comparable transport efficiencies, their distinct N- and C-terminal sequences appear to govern tissue-specific targeting and regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its basic transport function, DMT1 expression and activity are tightly regulated by iron status, oxygen tension, and other metabolic cues. In iron deficiency, DMT1 mRNA and protein levels increase to enhance iron uptake, whereas high intracellular iron and modulators like calcium or hepcidin prompt membrane internalization and redistribution of DMT1. Retromer-mediated recycling and ubiquitination pathways further govern its intracellular trafficking, thereby fine-tuning cellular iron homeostasis. In various tissues—including intestinal epithelia, colorectal cancer cells, and other absorptive cell types—DMT1 regulation has been linked to transcriptional control by hypoxia-inducible factors and NF-κB signaling, as well as to posttranslational modifications that direct its localization between plasma membrane domains and intracellular compartments."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysfunction or mutations in SLC11A2 have been implicated in a spectrum of pathophysiological conditions ranging from anemia with paradoxical tissue iron overload to neurodegeneration. Elevated or aberrantly regulated DMT1 contributes to excessive iron deposition observed in the brains of Alzheimer’s and Parkinson’s disease patients, as well as in dopaminergic neurons where it may interact with α-synuclein or be subject to altered ubiquitin-mediated degradation. Moreover, DMT1’s role extends to various non-classical sites, participating in placental iron transfer, modulating metal uptake in airway and renal epithelia, and even influencing osteoblast autophagy and apoptotic responses in osteoporosis. Preclinical studies involving pharmacological inhibitors of DMT1 further underscore its potential as a therapeutic target for conditions such as iron overload disorders, Wilson’s disease, and amyotrophic lateral sclerosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "45"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Desmond I Bannon, Matthew E Portnoy, Luisa Olivi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Uptake of lead and iron by divalent metal transporter 1 in yeast and mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(02)00756-8"}], "href": "https://doi.org/10.1016/s0006-291x(02"}, {"type": "t", "text": "00756-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12127992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12127992"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nadia Hubert, Matthias W Hentze "}, {"type": "b", "children": [{"type": "t", "text": "Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.192423399"}], "href": "https://doi.org/10.1073/pnas.192423399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12209011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12209011"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Miguel Arredondo, Patricia Muñoz, Casilda V Mura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DMT1, a physiologically relevant apical Cu1+ transporter of intestinal cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00480.2002"}], "href": "https://doi.org/10.1152/ajpcell.00480.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12734107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12734107"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Haoxing Xu, Jie Jin, Louis J DeFelice, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A spontaneous, recurrent mutation in divalent metal transporter-1 exposes a calcium entry pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.0020050"}], "href": "https://doi.org/10.1371/journal.pbio.0020050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15024413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15024413"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Martha P Mims, Yongli Guan, Dagmar Pospisilova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-07-2966"}], "href": "https://doi.org/10.1182/blood-2004-07-2966"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15459009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15459009"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "E G Hoal, L A Lewis, S E Jamieson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLC11A1 (NRAMP1) but not SLC11A2 (NRAMP2) polymorphisms are associated with susceptibility to tuberculosis in a high-incidence community in South Africa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Tuberc Lung Dis (2004)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15636493"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15636493"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "W S Chong, P C Kwan, L Y Chan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of divalent metal transporter 1 (DMT1) isoforms in first trimester human placenta and embryonic tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dei246"}], "href": "https://doi.org/10.1093/humrep/dei246"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16123094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16123094"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Carole Beaumont, Jean Delaunay, Gilles Hetet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-10-4269"}], "href": "https://doi.org/10.1182/blood-2005-10-4269"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16439678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16439678"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Bryan Mackenzie, Hitomi Takanaga, Nadia Hubert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20061290"}], "href": "https://doi.org/10.1042/BJ20061290"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17109629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17109629"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Immacolata Andolfo, Luigia De Falco, Roberta Asci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of divalent metal transporter 1 (DMT1) non-IRE isoform by the microRNA Let-7d in erythroid cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Haematologica (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3324/haematol.2009.020685"}], "href": "https://doi.org/10.3324/haematol.2009.020685"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20410187"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20410187"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Anthony C Illing, Ali Shawki, Christopher L Cunningham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Substrate profile and metal-ion selectivity of human divalent metal-ion transporter-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.364208"}], "href": "https://doi.org/10.1074/jbc.M112.364208"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22736759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22736759"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Izumi Yanatori, Fumio Kishi "}, {"type": "b", "children": [{"type": "t", "text": "DMT1 and iron transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2018.07.020"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2018.07.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30055235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30055235"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Andreas Rolfs, Herbert L Bonkovsky, James G Kohlroser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intestinal expression of genes involved in iron absorption in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00371.2001"}], "href": "https://doi.org/10.1152/ajpgi.00371.2001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11897618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11897618"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Marcia Simovich, Lucille N Hainsworth, P A Fields, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Localization of the iron transport proteins Mobilferrin and DMT-1 in the duodenum: the surprising role of mucin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hematol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajh.10383"}], "href": "https://doi.org/10.1002/ajh.10383"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12949888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12949888"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "R O Koch, H Zoller, I Theuri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distribution of DMT 1 within the human glandular system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histol Histopathol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14670/HH-18.1095"}], "href": "https://doi.org/10.14670/HH-18.1095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12973678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12973678"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Deborah M Johnson, Sachie Yamaji, Jason Tennant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of divalent metal transporter expression in human intestinal epithelial cells following exposure to non-haem iron."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2005.02.035"}], "href": "https://doi.org/10.1016/j.febslet.2005.02.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15792797"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15792797"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Susanne Ludwiczek, Igor Theurl, Martina U Muckenthaler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1542"}], "href": "https://doi.org/10.1038/nm1542"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17293870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17293870"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Zhu Li, Zhang Lai, Ke Ya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Correlation between the expression of divalent metal transporter 1 and the content of hypoxia-inducible factor-1 in hypoxic HepG2 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1582-4934.2007.00145.x"}], "href": "https://doi.org/10.1111/j.1582-4934.2007.00145.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18419598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18419598"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Marco T Núñez, Victoria Tapia, Alejandro Rojas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Iron supply determines apical/basolateral membrane distribution of intestinal iron transporters DMT1 and ferroportin 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00168.2009"}], "href": "https://doi.org/10.1152/ajpcell.00168.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20007457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20007457"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Ali Shawki, Bryan Mackenzie "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of calcium with the human divalent metal-ion transporter-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2010.02.025"}], "href": "https://doi.org/10.1016/j.bbrc.2010.02.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20152801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20152801"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Mitsuaki Tabuchi, Izumi Yanatori, Yasuhiro Kawai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retromer-mediated direct sorting is required for proper endosomal recycling of the mammalian iron transporter DMT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.060574"}], "href": "https://doi.org/10.1242/jcs.060574"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20164305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20164305"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Carole Brasse-Lagnel, Zoubida Karim, Philippe Letteron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intestinal DMT1 cotransporter is down-regulated by hepcidin via proteasome internalization and degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2010.12.037"}], "href": "https://doi.org/10.1053/j.gastro.2010.12.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21199652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21199652"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Vasuprada Iyengar, Raghu Pullakhandam, K Madhavan Nair "}, {"type": "b", "children": [{"type": "t", "text": "Coordinate expression and localization of iron and zinc transporters explain iron-zinc interactions during uptake in Caco-2 cells: implications for iron uptake at the enterocyte."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nutr Biochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jnutbio.2011.06.008"}], "href": "https://doi.org/10.1016/j.jnutbio.2011.06.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22137264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22137264"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Michael D Garrick, Lin Zhao, Jerome A Roth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Isoform specific regulation of divalent metal (ion) transporter (DMT1) by proteasomal degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biometals (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10534-012-9522-1"}], "href": "https://doi.org/10.1007/s10534-012-9522-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22310887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22310887"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Xiang Xue, Sadeesh K Ramakrishnan, Kevin Weisz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Iron Uptake via DMT1 Integrates Cell Cycle with JAK-STAT3 Signaling to Promote Colorectal Tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2016.07.015"}], "href": "https://doi.org/10.1016/j.cmet.2016.07.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27546461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27546461"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "María Lucas, David C Gershlick, Ander Vidaurrazaga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural Mechanism for Cargo Recognition by the Retromer Complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2016.10.056"}], "href": "https://doi.org/10.1016/j.cell.2016.10.056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27889239"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27889239"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Rosaria Ingrassia, Annamaria Lanzillotta, Ilenia Sarnico, et al. "}, {"type": "b", "children": [{"type": "t", "text": "1B/(-)IRE DMT1 expression during brain ischemia contributes to cell death mediated by NF-κB/RelA acetylation at Lys310."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0038019"}], "href": "https://doi.org/10.1371/journal.pone.0038019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22666436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22666436"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Xinchao Wang, Andrew J Ghio, Funmei Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Iron uptake and Nramp2/DMT1/DCT1 in human bronchial epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00253.2001"}], "href": "https://doi.org/10.1152/ajplung.00253.2001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11943663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11943663"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Masato Okubo, Kyohei Yamada, Makoto Hosoyamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cadmium transport by human Nramp 2 expressed in Xenopus laevis oocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Appl Pharmacol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0041-008x(02)00078-9"}], "href": "https://doi.org/10.1016/s0041-008x(02"}, {"type": "t", "text": "00078-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12662899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12662899"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Mitchell Knutson, Sharon Menzies, James Connor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Developmental, regional, and cellular expression of SFT/UbcH5A and DMT1 mRNA in brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jnr.20113"}], "href": "https://doi.org/10.1002/jnr.20113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15139022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15139022"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Hua-Min Xu, Hong Jiang, Jun Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Over-expressed human divalent metal transporter 1 is involved in iron accumulation in MES23.5 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Int (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuint.2007.10.019"}], "href": "https://doi.org/10.1016/j.neuint.2007.10.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18082289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18082289"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Wei Zheng, Na Xin, Zhi-Hong Chi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Divalent metal transporter 1 is involved in amyloid precursor protein processing and Abeta generation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.09-135749"}], "href": "https://doi.org/10.1096/fj.09-135749"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19679638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19679638"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Zhong-Ming Qian, Xiao Mei Wu, Ming Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Divalent metal transporter 1 is a hypoxia-inducible gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.22485"}], "href": "https://doi.org/10.1002/jcp.22485"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20945371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20945371"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Hélène Blasco, Patrick Vourc'h, Yann Nadjar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between divalent metal transport 1 encoding gene (SLC11A2) and disease duration in amyotrophic lateral sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jns.2010.12.018"}], "href": "https://doi.org/10.1016/j.jns.2010.12.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21276595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21276595"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Qing He, Tingting Du, Xiaojun Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DMT1 polymorphism and risk of Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2011.07.001"}], "href": "https://doi.org/10.1016/j.neulet.2011.07.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21777657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21777657"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Mathieu F M Cellier "}, {"type": "b", "children": [{"type": "t", "text": "Nutritional immunity: homology modeling of Nramp metal import."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Exp Med Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-1-4614-0106-3_19"}], "href": "https://doi.org/10.1007/978-1-4614-0106-3_19"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21948377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21948377"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Alejandra Espinoza, Solange Le Blanc, Manuel Olivares, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Iron, copper, and zinc transport: inhibition of divalent metal transporter 1 (DMT1) and human copper transporter 1 (hCTR1) by shRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Trace Elem Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12011-011-9243-2"}], "href": "https://doi.org/10.1007/s12011-011-9243-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22068728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22068728"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Adam Przybyłkowski, Grażyna Gromadzka, Anna Członkowska "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms of metal transporter genes DMT1 and ATP7A in Wilson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Trace Elem Med Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jtemb.2013.08.002"}], "href": "https://doi.org/10.1016/j.jtemb.2013.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24120082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24120082"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Natascha A Wolff, Andrew J Ghio, Laura M Garrick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for mitochondrial localization of divalent metal transporter 1 (DMT1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.13-240564"}], "href": "https://doi.org/10.1096/fj.13-240564"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24448823"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24448823"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Jason Howitt, Amanda M Gysbers, Scott Ayton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased Ndfip1 in the substantia nigra of Parkinsonian brains is associated with elevated iron levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0087119"}], "href": "https://doi.org/10.1371/journal.pone.0087119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24475238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24475238"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "M Vázquez, D Vélez, V Devesa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Participation of divalent cation transporter DMT1 in the uptake of inorganic mercury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tox.2015.03.005"}], "href": "https://doi.org/10.1016/j.tox.2015.03.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25772431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25772431"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Chen Lin, Zhen Zhang, Tao Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Copper uptake by DMT1: a compensatory mechanism for CTR1 deficiency in human umbilical vein endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metallomics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1039/c5mt00097a"}], "href": "https://doi.org/10.1039/c5mt00097a"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26067577"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26067577"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Fei Liu, Wei-Lin Zhang, Hong-Zheng Meng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of DMT1 on autophagy and apoptosis in osteoblast."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Med Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijms.17860"}], "href": "https://doi.org/10.7150/ijms.17860"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28367088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28367088"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Jonai Pujol-Giménez, Matthias A Hediger, Gergely Gyimesi "}, {"type": "b", "children": [{"type": "t", "text": "A novel proton transfer mechanism in the SLC11 family of divalent metal ion transporters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-06446-y"}], "href": "https://doi.org/10.1038/s41598-017-06446-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28754960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28754960"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Mingxia Bi, Xixun Du, Qian Jiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "α-Synuclein Regulates Iron Homeostasis via Preventing Parkin-Mediated DMT1 Ubiquitylation in Parkinson's Disease Models."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "ACS Chem Neurosci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acschemneuro.0c00196"}], "href": "https://doi.org/10.1021/acschemneuro.0c00196"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32379419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32379419"}]}]}]}