The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

SLC11A2  -  solute carrier family 11 (proton-coupled...

Homo sapiens

Synonyms: DCT1, DMT-1, DMT1, Divalent cation transporter 1, Divalent metal transporter 1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of SLC11A2


Psychiatry related information on SLC11A2


High impact information on SLC11A2

  • Iron uptake from the intestinal lumen through the apical surface of polarized duodenal enterocytes is mediated by the divalent metal transporter, DMTi [6].
  • DCT1 mediates active transport that is proton-coupled and depends on the cell membrane potential [7].
  • As selective iron chelation prevents NMDA neurotoxicity in cortical cultures, the NMDA-NO-Dexras1-PAP7-DMT1-iron uptake signaling cascade also appears to mediate NMDA neurotoxicity [8].
  • CONCLUSIONS: DMT1 and FP1 are centrally involved in iron uptake/transfer in the duodenum and in the adaptive changes of iron homeostasis to iron deficiency and overload [1].
  • INTERPRETATION: Increased NRAMP-2 mRNA expression in duodenal mucosa of patients with hereditary haemochromatosis may promote duodenal iron uptake and lead to iron overload [9].

Chemical compound and disease context of SLC11A2


Biological context of SLC11A2


Anatomical context of SLC11A2

  • Human NRAMP2/DMT1, which mediates iron transport across endosomal membranes, is localized to late endosomes and lysosomes in HEp-2 cells [16].
  • Iron treatment downregulates DMT1 and IREG1 mRNA expression in Caco-2 cells [17].
  • The aim of this study was to investigate the effects of iron treatment on DMT1 and IREG1 mRNA expression in Caco-2 cells, a human intestinal cell line [17].
  • This interaction may be critical in small-intestinal crypt cells which express HFE, where it may function to modulate their intrinsic iron status thereby programming iron absorption by DMT-1 in the mature enterocyte [18].
  • In undifferentiated Caco-2 cells, DMT-1 localized to a discrete late endosome compartment distinct from that occupied by HFE where, in addition to brush-border iron uptake, it may function to regulate the availability of iron delivery to intracellular iron pools [18].

Associations of SLC11A2 with chemical compounds

  • These results indicated that NRAMP2 is localized to the late endosomes and lysosomes, where NRAMP2 may function to transfer the endosomal free Fe(2+) into the cytoplasm in the transferrin cycle [16].
  • Ferrous iron uptake is facilitated by DMT-1 (Nramp-2, DCT-1) in a pathway shared with manganese [19].
  • One of these, 1303C-->A, occurs in the coding region of nramp2 and results in an amino acid change from leucine to isolecine [15].
  • Our data further indicates upregulation of DMT-1 and IREG-1 mRNA and protein in response to high levels of glucose [20].
  • Nuclear run-off analysis then demonstrated that the effects of iron and desferrioxamine on DMT1 and FPN1 mRNA expression are rather due to modulation of transcription of these genes [21].

Physical interactions of SLC11A2

  • Iron is released from transferrin as the result of the acidic pH in endosome and then is transported to the cytosol by DMT1 [22].
  • The membrane topology and transport properties of Nramp1HA and Nramp2HA were indistinguishable, suggesting that Nramp1 divalent-metal transport at the phagosomal membrane is mechanistically similar to that of Nramp2 at the membrane of acidified endosomes [23].

Co-localisations of SLC11A2


Regulatory relationships of SLC11A2


Other interactions of SLC11A2

  • To characterize better the potential mechanisms for iron transport into and within the brain, we have analyzed expression patterns of two factors: divalent metal transporter 1 (DMT1) and stimulator of Fe transport (SFT) [26].
  • Identification of the molecular interactions of HFE with DMT-1 and other key components of the iron transport pathway has implications for a mechanistic understanding of the pathophysiology of human iron storage diseases as well as the regulation of normal iron balance [18].
  • Our data show that expression levels of human DCT1 mRNA, and to a lesser extent IREG1 mRNA, are regulated in an iron-dependent manner, whereas mRNA of hephaestin is not affected [27].
  • In controls, we found inverse relationships between the DCT1 splice form containing an iron-responsive element (IRE) and blood hemoglobin, serum transferrin saturation, or ferritin [27].
  • The additional exons and introns account for much of the difference in length between nramp2 (> 36 kb) and nramp1 (12 kb) [15].

Analytical, diagnostic and therapeutic context of SLC11A2

  • METHODS: DMT1, FP1 messenger RNA (mRNA), and protein expression were analyzed in duodenal biopsy specimens from patients by means of TaqMan real-time polymerase chain reaction, Western blotting technique, and immunohistochemistry [1].
  • The intracellular localization of endogenous NRAMP2 and recombinant green fluorescent protein (GFP)-NRAMP2 was examined by immunofluorescence staining and by native fluorescence of GFP, respectively [16].
  • DMT1 expression was significantly increased in HH patients who had undergone phlebotomy therapy (treated) and in patients with ID compared with controls [25].
  • DMT-1 protein expression was additionally assessed by immunohistochemistry [28].
  • DESIGN: A case-control study design was used to compare the frequencies of five polymorphisms in SLC11A1 and three in SLC11A2 between a group of bacteriologically confirmed TB patients and healthy community controls [29].


  1. Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload. Zoller, H., Koch, R.O., Theurl, I., Obrist, P., Pietrangelo, A., Montosi, G., Haile, D.J., Vogel, W., Weiss, G. Gastroenterology (2001) [Pubmed]
  2. Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis. Stuart, K.A., Anderson, G.J., Frazer, D.M., Murphy, T.L., Powell, L.W., Fletcher, L.M., Crawford, D.H. Hepatology (2004) [Pubmed]
  3. Modulation of iron transport proteins in human colorectal carcinogenesis. Brookes, M.J., Hughes, S., Turner, F.E., Reynolds, G., Sharma, N., Ismail, T., Berx, G., McKie, A.T., Hotchin, N., Anderson, G.J., Iqbal, T., Tselepis, C. Gut (2006) [Pubmed]
  4. Correlation between the expression of divalent metal transporter 1 and the content of hypoxia-inducible factor-1 in hypoxic HepG2 cells. Li, Z., Lai, Z., Ya, K., Fang, D., Ho, Y.W., Lei, Y., Ming, Q.Z. J. Cell. Mol. Med. (2008) [Pubmed]
  5. Candidate gene association study of solute carrier family 11a members 1 (SLC11A1) and 2 (SLC11A2) genes in Alzheimer's disease. Jamieson, S.E., White, J.K., Howson, J.M., Pask, R., Smith, A.N., Brayne, C., Evans, J.G., Xuereb, J., Cairns, N.J., Rubinsztein, D.C., Blackwell, J.M. Neurosci. Lett. (2005) [Pubmed]
  6. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S.J., Moynihan, J., Paw, B.H., Drejer, A., Barut, B., Zapata, A., Law, T.C., Brugnara, C., Lux, S.E., Pinkus, G.S., Pinkus, J.L., Kingsley, P.D., Palis, J., Fleming, M.D., Andrews, N.C., Zon, L.I. Nature (2000) [Pubmed]
  7. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Gunshin, H., Mackenzie, B., Berger, U.V., Gunshin, Y., Romero, M.F., Boron, W.F., Nussberger, S., Gollan, J.L., Hediger, M.A. Nature (1997) [Pubmed]
  8. NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexras1. Cheah, J.H., Kim, S.F., Hester, L.D., Clancy, K.W., Patterson, S.E., Papadopoulos, V., Snyder, S.H. Neuron (2006) [Pubmed]
  9. Duodenal metal-transporter (DMT-1, NRAMP-2) expression in patients with hereditary haemochromatosis. Zoller, H., Pietrangelo, A., Vogel, W., Weiss, G. Lancet (1999) [Pubmed]
  10. Divalent metal-ion transporter DMT1 mediates both H+ -coupled Fe2+ transport and uncoupled fluxes. Mackenzie, B., Ujwal, M.L., Chang, M.H., Romero, M.F., Hediger, M.A. Pflugers Arch. (2006) [Pubmed]
  11. Influence of parenteral iron preparations on non-transferrin bound iron uptake, the iron regulatory protein and the expression of ferritin and the divalent metal transporter DMT-1 in HepG2 human hepatoma cells. Scheiber-Mojdehkar, B., Sturm, B., Plank, L., Kryzer, I., Goldenberg, H. Biochem. Pharmacol. (2003) [Pubmed]
  12. Implication of distinct proteins in cadmium uptake and transport by intestinal cells HT-29. Lecoeur, S., Huynh-Delerme, C., Blais, A., Duché, A., Tomé, D., Kolf-Clauw, M. Cell Biol. Toxicol. (2002) [Pubmed]
  13. Phlebotomy increases cadmium uptake in hemochromatosis. Akesson, A., Stål, P., Vahter, M. Environ. Health Perspect. (2000) [Pubmed]
  14. Iron Imports. V. Transport of iron through the intestinal epithelium. Ma, Y., Yeh, M., Yeh, K.Y., Glass, J. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  15. The human Nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms. Lee, P.L., Gelbart, T., West, C., Halloran, C., Beutler, E. Blood Cells Mol. Dis. (1998) [Pubmed]
  16. Human NRAMP2/DMT1, which mediates iron transport across endosomal membranes, is localized to late endosomes and lysosomes in HEp-2 cells. Tabuchi, M., Yoshimori, T., Yamaguchi, K., Yoshida, T., Kishi, F. J. Biol. Chem. (2000) [Pubmed]
  17. Iron treatment downregulates DMT1 and IREG1 mRNA expression in Caco-2 cells. Martini, L.A., Tchack, L., Wood, R.J. J. Nutr. (2002) [Pubmed]
  18. Localization of iron transport and regulatory proteins in human cells. Griffiths, W.J., Kelly, A.L., Smith, S.J., Cox, T.M. QJM : monthly journal of the Association of Physicians. (2000) [Pubmed]
  19. Iron absorption and transport-an update. Conrad, M.E., Umbreit, J.N. Am. J. Hematol. (2000) [Pubmed]
  20. Glucose-induced regulation of novel iron transporters in vascular endothelial cell dysfunction. Khan, Z.A., Farhangkhoee, H., Barbin, Y.P., Adams, P.C., Chakrabarti, S. Free Radic. Res. (2005) [Pubmed]
  21. Mechanisms of iron mediated regulation of the duodenal iron transporters divalent metal transporter 1 and ferroportin 1. Zoller, H., Theurl, I., Koch, R., Kaser, A., Weiss, G. Blood Cells Mol. Dis. (2002) [Pubmed]
  22. Transferrin/transferrin receptor-mediated drug delivery. Li, H., Qian, Z.M. Medicinal research reviews. (2002) [Pubmed]
  23. Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Forbes, J.R., Gros, P. Blood (2003) [Pubmed]
  24. Expression and localization of different forms of DMT1 in normal and tumor astroglial cells. Lis, A., Barone, T.A., Paradkar, P.N., Plunkett, R.J., Roth, J.A. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  25. Increased DMT1 but not IREG1 or HFE mRNA following iron depletion therapy in hereditary haemochromatosis. Kelleher, T., Ryan, E., Barrett, S., Sweeney, M., Byrnes, V., O'Keane, C., Crowe, J. Gut (2004) [Pubmed]
  26. Developmental, regional, and cellular expression of SFT/UbcH5A and DMT1 mRNA in brain. Knutson, M., Menzies, S., Connor, J., Wessling-Resnick, M. J. Neurosci. Res. (2004) [Pubmed]
  27. Intestinal expression of genes involved in iron absorption in humans. Rolfs, A., Bonkovsky, H.L., Kohlroser, J.G., McNeal, K., Sharma, A., Berger, U.V., Hediger, M.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  28. Increased duodenal DMT-1 expression and unchanged HFE mRNA levels in HFE-associated hereditary hemochromatosis and iron deficiency. Byrnes, V., Barrett, S., Ryan, E., Kelleher, T., O'Keane, C., Coughlan, B., Crowe, J. Blood Cells Mol. Dis. (2002) [Pubmed]
  29. SLC11A1 (NRAMP1) but not SLC11A2 (NRAMP2) polymorphisms are associated with susceptibility to tuberculosis in a high-incidence community in South Africa. Hoal, E.G., Lewis, L.A., Jamieson, S.E., Tanzer, F., Rossouw, M., Victor, T., Hillerman, R., Beyers, N., Blackwell, J.M., Van Helden, P.D. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. (2004) [Pubmed]
WikiGenes - Universities