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

Ireb2  -  iron responsive element binding protein 2

Mus musculus

Synonyms: D9Ertd85e, IRE-BP 2, IRP2, Iron regulatory protein 2, Iron-responsive element-binding protein 2, ...
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 Ireb2


High impact information on Ireb2

  • Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse [5].
  • The two iron regulatory proteins IRP1 and IRP2 bind to transcripts of ferritin, transferrin receptor and other target genes to control the expression of iron metabolism proteins at the post-transcriptional level [6].
  • Moreover, treatment of RAW 264.7 cells with IFN-gamma and lipopolysaccharide caused IRP2 degradation and stimulated ferritin synthesis, changes that could be prevented by specific inhibitors of inducible nitric oxide synthase [7].
  • These observations indicate that NO+-mediated modulation of IRP2 plays an important role in controlling ferritin synthesis and iron metabolism in murine macrophages [7].
  • Third, the Ba/F3 family of cells express IRP2 mRNA at a level similar to other murine cell lines, but IRP1 mRNA is not detectable [8].

Biological context of Ireb2

  • We report that young adult Irp2-/- mice display signs of iron mismanagement within the central iron recycling pathway in the mammalian body, the liver-bone marrow-spleen axis, with altered body iron distribution and compromised hematopoiesis [9].
  • A reduction in transferrin receptor 1 (TfR1) mRNA levels in the bone marrow of Irp2-/- mice can plausibly explain the microcytosis by an intrinsic defect in erythropoiesis due to a failure to adequately protect TfR1 mRNA against degradation [9].
  • In comparison with wild-type littermates, Irp2-/- mice are mildly microcytic with reduced serum hemoglobin levels and hematocrit [9].
  • Our findings indicate that the small RNA-binding fraction of IRP1, which is insensitive to cellular iron status, contributes to basal mammalian iron homeostasis, whereas IRP2 is sensitive to iron status and can compensate for the loss of IRP1 by increasing its binding activity [6].
  • IRP2 downmodulation is associated with the upregulation of the ferritin L and H genes and decreased expression of the transferrin receptor 1 (TfR1) [10].

Anatomical context of Ireb2

  • However, in the central nervous system, evidence of abnormal iron metabolism in IRP2-/- mice precedes the development of adult-onset progressive neurodegeneration, characterized by widespread axonal degeneration and neuronal loss [2].
  • On histopathological examination we discovered relatively small vacuoles in these brain regions of IRP-2 -/- mice [4].
  • Here, we report that mice that are homozygous for a targeted deletion of IRP2 and heterozygous for a targeted deletion of IRP1 (IRP1+/- IRP2-/-) develop a much more severe form of neurodegeneration, characterized by widespread axonopathy and eventually by subtle vacuolization in several areas, particularly in the substantia nigra [11].
  • Essentially no staining for IRP2 was observed in the cerebellum in contrast to strong IRP1 immunoreactivity in Purkinje cells [12].
  • In both dorsal and ventral striatum of IRP-2 knockout mice, there was a 20-25% loss of TH protein and accompanied by a approximately 50% increase in serine 40 phosphorylation above wild-type levels [13].

Associations of Ireb2 with chemical compounds


Regulatory relationships of Ireb2

  • Mice with targeted deletion of IRP2 overexpress ferritin and express abnormally low TfR levels in multiple tissues [2].
  • Stimulation of J774 cells and primary macrophages with IFN-gamma/LPS activates the RNA binding affinities of iron regulatory protein-1 (IRP-1) and IRP-2 for iron-responsive elements, leading to translational repression of the iron storage protein ferritin [19].

Other interactions of Ireb2

  • We used mouse lines where a betaGeo gene trap construct was inserted into the second intron of the Irp1 and the Irp2 gene, generating hypomorphic alleles by interrupting the corresponding open reading frame near the amino-termini [20].
  • We postulate that IRP2 mutations or deletions may be a cause of refractory microcytic anemia and bone marrow iron depletion in patients with normal transferrin saturations, elevated serum ferritins, elevated red cell protoporphyrin IX levels, and adult-onset neurodegeneration [2].
  • Activation of IRP-1 and IRP-2 is caused by increased formation of nitric oxide (NO) via stimulation of the inducible NO synthase by IFN-gamma/LPS [19].


  1. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. LaVaute, T., Smith, S., Cooperman, S., Iwai, K., Land, W., Meyron-Holtz, E., Drake, S.K., Miller, G., Abu-Asab, M., Tsokos, M., Switzer, R., Grinberg, A., Love, P., Tresser, N., Rouault, T.A. Nat. Genet. (2001) [Pubmed]
  2. Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. Cooperman, S.S., Meyron-Holtz, E.G., Olivierre-Wilson, H., Ghosh, M.C., McConnell, J.P., Rouault, T.A. Blood (2005) [Pubmed]
  3. Rare causes of hereditary iron overload. Ponka, P. Semin. Hematol. (2002) [Pubmed]
  4. MRI detection of ferritin iron overload and associated neuronal pathology in iron regulatory protein-2 knockout mice. Grabill, C., Silva, A.C., Smith, S.S., Koretsky, A.P., Rouault, T.A. Brain Res. (2003) [Pubmed]
  5. Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse. Galy, B., Hölter, S.M., Klopstock, T., Ferring, D., Becker, L., Kaden, S., Wurst, W., Gröne, H.J., Hentze, M.W. Nat. Genet. (2006) [Pubmed]
  6. Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. Meyron-Holtz, E.G., Ghosh, M.C., Iwai, K., LaVaute, T., Brazzolotto, X., Berger, U.V., Land, W., Ollivierre-Wilson, H., Grinberg, A., Love, P., Rouault, T.A. EMBO J. (2004) [Pubmed]
  7. Nitrogen monoxide-mediated control of ferritin synthesis: implications for macrophage iron homeostasis. Kim, S., Ponka, P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Iron regulatory protein 1 is not required for the modulation of ferritin and transferrin receptor expression by iron in a murine pro-B lymphocyte cell line. Schalinske, K.L., Blemings, K.P., Steffen, D.W., Chen, O.S., Eisenstein, R.S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2). Galy, B., Ferring, D., Minana, B., Bell, O., Janser, H.G., Muckenthaler, M., Schümann, K., Hentze, M.W. Blood (2005) [Pubmed]
  10. IRP1-independent alterations of cardiac iron metabolism in doxorubicin-treated mice. Corna, G., Galy, B., Hentze, M.W., Cairo, G. J. Mol. Med. (2006) [Pubmed]
  11. Severity of neurodegeneration correlates with compromise of iron metabolism in mice with iron regulatory protein deficiencies. Smith, S.R., Cooperman, S., Lavaute, T., Tresser, N., Ghosh, M., Meyron-Holtz, E., Land, W., Ollivierre, H., Jortner, B., Switzer, R., Messing, A., Rouault, T.A. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  12. Immunolocalization of iron regulatory protein expression in the murine central nervous system. Leibold, E.A., Gahring, L.C., Rogers, S.W. Histochem. Cell Biol. (2001) [Pubmed]
  13. Neurochemical investigations of dopamine neuronal systems in iron-regulatory protein 2 (IRP-2) knockout mice. Salvatore, M.F., Fisher, B., Surgener, S.P., Gerhardt, G.A., Rouault, T. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  14. The nexus of iron and inflammation in hepcidin regulation: SMADs, STATs, and ECSIT. Milward, E., Johnstone, D., Trinder, D., Ramm, G., Olynyk, J. Hepatology (2007) [Pubmed]
  15. Nitrosative and oxidative modulation of iron regulatory proteins. Bouton, C. Cell. Mol. Life Sci. (1999) [Pubmed]
  16. Nitric oxide-mediated induction of ferritin synthesis in J774 macrophages by inflammatory cytokines: role of selective iron regulatory protein-2 downregulation. Recalcati, S., Taramelli, D., Conte, D., Cairo, G. Blood (1998) [Pubmed]
  17. Differential modulation of the RNA-binding proteins IRP-1 and IRP-2 in response to iron. IRP-2 inactivation requires translation of another protein. Henderson, B.R., Kühn, L.C. J. Biol. Chem. (1995) [Pubmed]
  18. Control of transferrin receptor expression via nitric oxide-mediated modulation of iron-regulatory protein 2. Kim, S., Ponka, P. J. Biol. Chem. (1999) [Pubmed]
  19. Pathways for the regulation of macrophage iron metabolism by the anti-inflammatory cytokines IL-4 and IL-13. Weiss, G., Bogdan, C., Hentze, M.W. J. Immunol. (1997) [Pubmed]
  20. Generation of conditional alleles of the murine Iron Regulatory Protein (IRP)-1 and -2 genes. Galy, B., Ferring, D., Hentze, M.W. Genesis (2005) [Pubmed]
WikiGenes - Universities