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Gene Review

Slc40a1  -  solute carrier family 40 (iron-regulated...

Mus musculus

Synonyms: Dusg, FPN1, Ferroportin-1, Fpn1, IREG1, ...
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Disease relevance of Slc40a1


High impact information on Slc40a1


Chemical compound and disease context of Slc40a1

  • Surprisingly, the expression of MTP in membranes of an intracellular compartment resulted in a cellular resistance or hypersensitivity to a range of drugs that included nucleoside and nucleobase analogs, antibiotics, anthracyclines, ionophores, and steroid hormones [8].
  • However, the cross-reactivity with BCG was regained in the MTP derivative that was formed by adding lysine to dipeptide containing methylalanine or valine [9].

Biological context of Slc40a1

  • The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis [10].
  • Previous reports concerning gene expression levels of the duodenal iron transporters DMT1 and IREG1 in HH patients and animal models are controversial, however, and in many cases only mRNA expression levels were investigated [1].
  • Disruption of ferroportin 1 regulation causes dynamic alterations in iron homeostasis and erythropoiesis in polycythaemia mice [11].
  • A 58 bp microdeletion in the Fpn1 promoter region alters transcription start sites and eliminates the iron responsive element (IRE) in the 5' untranslated region, resulting in increased duodenal and hepatic Fpn1 protein levels during early postnatal development [11].
  • Conversely, upon up-regulation of Hamp expression at 12 weeks of age, Fpn1 expression decreased, indicative of a Hamp-mediated homeostatic loop [3].

Anatomical context of Slc40a1


Associations of Slc40a1 with chemical compounds

  • Fpn1 increased in C57BL/6 mice, but not in the DBA/2 ones in parenteral iron loading [13].
  • The iron-induced induction of FPN1 mRNA was blocked by actinomycin D, suggesting that transcriptional control was responsible for this effect [14].
  • In this study, we use a lipopolysaccharide model of the acute inflammation in the mouse and demonstrate that MTP1 expression in RES cells of the spleen, liver, and bone marrow is down-regulated by inflammation [15].
  • CONCLUSIONS: Neuronal survival of iron accumulation associates with increased expression of the efflux transporter IREG1 [16].
  • Liver MTP-specific activity was significantly reduced in HCV-3 patients compared with those with other HCV genotypes (P = .004) and correlated with reduced serum cholesterol, apo B, and low-density lipoproteins [17].

Co-localisations of Slc40a1

  • We also show that GPI-Cp colocalizes on the astrocyte cell surface with the divalent metal transporter IREG1 and is physically associated with IREG1 [18].

Regulatory relationships of Slc40a1

  • In contrast, the iron permease Ireg1 localised to the basolateral membrane in both control and sla mice [19].

Other interactions of Slc40a1

  • Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency [12].
  • The function of hepcidin in regulating iron absorption is modeled through an inverse relationship between hepatocyte transferrin receptor 2 (TfR2) levels and the rate of iron export processes mediated by ferroportin (Fpn) [20].
  • The coordinated actions of GPI-Cp and IREG1 may be required for iron efflux from neural cells, and disruption of this balance could lead to iron accumulation in the central nervous system and neurodegeneration [18].
  • In conclusion, these results suggest that although Hfe is necessary for the establishment of hepcidin basal levels, it is dispensable for hepcidin regulation through both the iron-sensing and inflammatory pathways, and hepatic Fp1 regulation is largely independent of hepcidin and Hfe [21].
  • METHODS: Normal murine retinas were analyzed by immunohistochemistry to localize ferroportin, cytosolic ferritin, and mitochondrial ferritin, with double-labeling using cell-specific markers to identify cell types [22].

Analytical, diagnostic and therapeutic context of Slc40a1


  1. Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin. Herrmann, T., Muckenthaler, M., van der Hoeven, F., Brennan, K., Gehrke, S.G., Hubert, N., Sergi, C., Gröne, H.J., Kaiser, I., Gosch, I., Volkmann, M., Riedel, H.D., Hentze, M.W., Stewart, A.F., Stremmel, W. J. Mol. Med. (2004) [Pubmed]
  2. Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier. Wu, L.J., Leenders, A.G., Cooperman, S., Meyron-Holtz, E., Smith, S., Land, W., Tsai, R.Y., Berger, U.V., Sheng, Z.H., Rouault, T.A. Brain Res. (2004) [Pubmed]
  3. The molecular circuitry regulating the switch between iron deficiency and overload in mice. Mok, H., Mlodnicka, A.E., Hentze, M.W., Muckenthaler, M., Schumacher, A. J. Biol. Chem. (2006) [Pubmed]
  4. Expression of iron absorption genes in mouse large intestine. Takeuchi, K., Bjarnason, I., Laftah, A.H., Latunde-Dada, G.O., Simpson, R.J., McKie, A.T. Scand. J. Gastroenterol. (2005) [Pubmed]
  5. Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death. Ibdah, J.A., Paul, H., Zhao, Y., Binford, S., Salleng, K., Cline, M., Matern, D., Bennett, M.J., Rinaldo, P., Strauss, A.W. J. Clin. Invest. (2001) [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. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. 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. Mol. Cell (2000) [Pubmed]
  8. A mammalian lysosomal membrane protein confers multidrug resistance upon expression in Saccharomyces cerevisiae. Hogue, D.L., Kerby, L., Ling, V. J. Biol. Chem. (1999) [Pubmed]
  9. Cross-reactivity between haptenic muramyl di- or tripeptide derivatives and Mycobacterium bovis BCG: potential application for enhancing tumor immunity. Kosugi, A., Shima, J., Sano, H., Ogata, M., Kusama, T., Fujiwara, H., Hamaoka, T. Infect. Immun. (1986) [Pubmed]
  10. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Donovan, A., Lima, C.A., Pinkus, J.L., Pinkus, G.S., Zon, L.I., Robine, S., Andrews, N.C. Cell metabolism. (2005) [Pubmed]
  11. Disruption of ferroportin 1 regulation causes dynamic alterations in iron homeostasis and erythropoiesis in polycythaemia mice. Mok, H., Jelinek, J., Pai, S., Cattanach, B.M., Prchal, J.T., Youssoufian, H., Schumacher, A. Development (2004) [Pubmed]
  12. Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency. Chen, H., Su, T., Attieh, Z.K., Fox, T.C., McKie, A.T., Anderson, G.J., Vulpe, C.D. Blood (2003) [Pubmed]
  13. Hepatic expression of hemochromatosis genes in two mouse strains after phlebotomy and iron overload. Bondi, A., Valentino, P., Daraio, F., Porporato, P., Gramaglia, E., Carturan, S., Gottardi, E., Camaschella, C., Roetto, A. Haematologica (2005) [Pubmed]
  14. Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages. Knutson, M.D., Vafa, M.R., Haile, D.J., Wessling-Resnick, M. Blood (2003) [Pubmed]
  15. Regulation of reticuloendothelial iron transporter MTP1 (Slc11a3) by inflammation. Yang, F., Liu, X.B., Quinones, M., Melby, P.C., Ghio, A., Haile, D.J. J. Biol. Chem. (2002) [Pubmed]
  16. Iron homeostasis in neuronal cells: a role for IREG1. Aguirre, P., Mena, N., Tapia, V., Arredondo, M., Núñez, M.T. BMC neuroscience [electronic resource]. (2005) [Pubmed]
  17. Liver microsomal triglyceride transfer protein is involved in hepatitis C liver steatosis. Mirandola, S., Realdon, S., Iqbal, J., Gerotto, M., Dal Pero, F., Bortoletto, G., Marcolongo, M., Vario, A., Datz, C., Hussain, M.M., Alberti, A. Gastroenterology (2006) [Pubmed]
  18. Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system. Jeong, S.Y., David, S. J. Biol. Chem. (2003) [Pubmed]
  19. Mislocalisation of hephaestin, a multicopper ferroxidase involved in basolateral intestinal iron transport, in the sex linked anaemia mouse. Kuo, Y.M., Su, T., Chen, H., Attieh, Z., Syed, B.A., McKie, A.T., Anderson, G.J., Gitschier, J., Vulpe, C.D. Gut (2004) [Pubmed]
  20. A compartmental model of iron regulation in the mouse. Lao, B.J., Kamei, D.T. J. Theor. Biol. (2006) [Pubmed]
  21. Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation. Constante, M., Jiang, W., Wang, D., Raymond, V.A., Bilodeau, M., Santos, M.M. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  22. Immunolocalization and regulation of iron handling proteins ferritin and ferroportin in the retina. Hahn, P., Dentchev, T., Qian, Y., Rouault, T., Harris, Z.L., Dunaief, J.L. Mol. Vis. (2004) [Pubmed]
  23. Apical location of ferroportin 1 in airway epithelia and its role in iron detoxification in the lung. Yang, F., Haile, D.J., Wang, X., Dailey, L.A., Stonehuerner, J.G., Ghio, A.J. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) [Pubmed]
  24. Assignment of Slc11a3 to mouse chromosome 1 band 1B and SLC11A3 to human chromosome 2q32 by in situ hybridization. Haile, D.J. Cytogenet. Cell Genet. (2000) [Pubmed]
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