Gene Symbol: Ireb2
Description: iron responsive element binding protein 2
Alias: D9Ertd85e, Irp2, iron-responsive element-binding protein 2, IRE-BP 2, iron regulatory protein 2
Species: mouse
Products:     Ireb2

Top Publications

  1. Galy B, Holter S, Klopstock T, Ferring D, Becker L, Kaden S, et al. Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse. Nat Genet. 2006;38:967-9; discussion 969-70 pubmed
  2. LaVaute T, Smith S, Cooperman S, Iwai K, Land W, Meyron Holtz E, et al. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet. 2001;27:209-14 pubmed
    ..Here we generate mice with a targeted disruption of the gene encoding Irp2 (Ireb2). These mutant mice misregulate iron metabolism in the intestinal mucosa and the central nervous system...
  3. Meyron Holtz E, Ghosh M, Iwai K, LaVaute T, Brazzolotto X, Berger U, et al. Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J. 2004;23:386-95 pubmed
    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...
  4. Wilkinson N, Pantopoulos K. IRP1 regulates erythropoiesis and systemic iron homeostasis by controlling HIF2? mRNA translation. Blood. 2013;122:1658-68 pubmed publisher
    ..mechanism for translational regulation of its expression via iron regulatory proteins 1 and 2 (IRP1 and IRP2, respectively)...
  5. Moroishi T, Nishiyama M, Takeda Y, Iwai K, Nakayama K. The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. Cell Metab. 2011;14:339-51 pubmed publisher
    Iron-dependent degradation of iron-regulatory protein 2 (IRP2) is a key event for maintenance of an appropriate intracellular concentration of iron...
  6. Galy B, Ferring Appel D, Kaden S, Grone H, Hentze M. Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenum. Cell Metab. 2008;7:79-85 pubmed publisher
    ..Redundancy between IRP1 and IRP2 associated with embryonic lethality of doubly IRP-deficient mice has precluded the study of IRP function in vivo...
  7. Smith S, Cooperman S, Lavaute T, Tresser N, Ghosh M, Meyron Holtz E, et al. Severity of neurodegeneration correlates with compromise of iron metabolism in mice with iron regulatory protein deficiencies. Ann N Y Acad Sci. 2004;1012:65-83 pubmed
    In mammals, iron regulatory proteins 1 and 2 (IRP1 and IRP2) posttranscriptionally regulate expression of several iron metabolism proteins including ferritin and transferrin receptor...
  8. Galy B, Ferring D, Benesova M, Benes V, Hentze M. Targeted mutagenesis of the murine IRP1 and IRP2 genes reveals context-dependent RNA processing differences in vivo. RNA. 2004;10:1019-25 pubmed
    We report the targeted mutagenesis of the murine iron regulatory protein (IRP)-1 and IRP2 genes, respectively, with a classical gene trap construct...
  9. Crooks D, Ghosh M, Haller R, Tong W, Rouault T. Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery. Blood. 2010;115:860-9 pubmed publisher
    ..We investigated ferrochelatase expression in iron-deficient erythropoietic tissues of mice lacking iron regulatory protein 2, in iron-deficient murine erythroleukemia cells, and in human patients with ISCU myopathy...

More Information


  1. Ghosh M, Tong W, Zhang D, Ollivierre Wilson H, Singh A, Krishna M, et al. Tempol-mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IRP2 knockout mice. Proc Natl Acad Sci U S A. 2008;105:12028-33 pubmed publisher
    ..homologous cytosolic regulatory proteins, iron regulatory protein 1 (also known as IRP1 and Aco1) and iron regulatory protein 2 (also known as IRP2 and Ireb2), sense cytosolic iron levels and posttranscriptionally regulate iron ..
  2. Galy B, Ferring D, Minana B, Bell O, Janser H, Muckenthaler M, et al. Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2). Blood. 2005;106:2580-9 pubmed
    b>Iron regulatory protein 2 (IRP2)-deficient mice have been reported to suffer from late-onset neurodegeneration by an unknown mechanism...
  3. Grabill C, Silva A, Smith S, Koretsky A, Rouault T. MRI detection of ferritin iron overload and associated neuronal pathology in iron regulatory protein-2 knockout mice. Brain Res. 2003;971:95-106 pubmed
    Genetic ablation of iron regulatory protein 2 (IRP-2), a protein responsible for post-transcriptional regulation of expression of several iron metabolism proteins, predisposes IRP-2 -/- mice to develop adult onset neurodegenerative ..
  4. Sanchez M, Galy B, Schwanhaeusser B, Blake J, Bähr Ivacevic T, Benes V, et al. Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by iron regulatory proteins. Blood. 2011;118:e168-79 pubmed publisher
    ..To systematically define the IRE/IRP regulatory network on a transcriptome-wide scale, IRP1/IRE and IRP2/IRE messenger ribonucleoprotein complexes were immunoselected, and the mRNA composition was determined using ..
  5. Galy B, Ferring D, Hentze M. Generation of conditional alleles of the murine Iron Regulatory Protein (IRP)-1 and -2 genes. Genesis. 2005;43:181-8 pubmed
    Central aspects of cellular iron metabolism are controlled by IRP1 and IRP2, which are ubiquitously expressed in mouse organs and cells. Total and constitutive deficiency of both IRPs causes embryonic lethality in the mouse...
  6. Anderson S, Nizzi C, Chang Y, Deck K, Schmidt P, Galy B, et al. The IRP1-HIF-2? axis coordinates iron and oxygen sensing with erythropoiesis and iron absorption. Cell Metab. 2013;17:282-90 pubmed publisher
    ..HIF-2? messenger RNA (mRNA) is derepressed in kidneys of Irp1(-/-) mice but not in kidneys of Irp2(-/-) mice, leading to increased renal erythropoietin (Epo) mRNA and inappropriately elevated serum Epo levels...
  7. Galy B, Ferring Appel D, Sauer S, Kaden S, Lyoumi S, Puy H, et al. Iron regulatory proteins secure mitochondrial iron sufficiency and function. Cell Metab. 2010;12:194-201 pubmed publisher
    ..Mice lacking both IRP1 and IRP2 in their hepatocytes suffer from mitochondrial iron deficiency and dysfunction associated with alterations of the ..
  8. Cooperman S, Meyron Holtz E, Olivierre Wilson H, Ghosh M, McConnell J, Rouault T. Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. Blood. 2005;106:1084-91 pubmed
    ..Mice with targeted deletion of IRP2 overexpress ferritin and express abnormally low TfR levels in multiple tissues...
  9. Jeong S, Crooks D, Wilson Ollivierre H, Ghosh M, Sougrat R, Lee J, et al. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice. PLoS ONE. 2011;6:e25404 pubmed publisher
    Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis...
  10. Martelli A, Schmucker S, Reutenauer L, Mathieu J, Peyssonnaux C, Karim Z, et al. Iron regulatory protein 1 sustains mitochondrial iron loading and function in frataxin deficiency. Cell Metab. 2015;21:311-22 pubmed publisher
    ..Our results uncover an unexpected protective role of IRP1 in pathological conditions associated with altered Fe-S metabolism. ..
  11. Vendrell V, López Hernández I, Durán Alonso M, Feijoo Redondo A, Abello G, Gálvez H, et al. Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea. Development. 2015;142:2792-800 pubmed publisher
    ..Taken together, these data show that Otx2 acts downstream of N-myc and is essential for patterning and spatial restriction of the sensory domain of the mammalian cochlea. ..
  12. Cloonan S, Glass K, Laucho Contreras M, Bhashyam A, Cervo M, Pabón M, et al. Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice. Nat Med. 2016;22:163-74 pubmed publisher
    ..We have previously identified iron-responsive element-binding protein 2 (IRP2) as an important COPD susceptibility gene and have shown that IRP2 protein is increased in the lungs of individuals ..
  13. Nairz M, Ferring Appel D, Casarrubea D, Sonnweber T, Viatte L, Schroll A, et al. Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection. Cell Host Microbe. 2015;18:254-61 pubmed publisher
    ..This work reveals the importance of the IRPs in innate immunity. ..
  14. Magaki S, Mueller C, Yellon S, Fox J, Kim J, Snissarenko E, et al. Regional dissection and determination of loosely bound and non-heme iron in the developing mouse brain. Brain Res. 2007;1158:144-50 pubmed
    ..We examined 6, 12, and 24 week old wildtype C57BL/6 mice and mice with a targeted deletion of iron regulatory protein 2 (IRP2-/-) that have been reported to develop neurodegenerative symptoms in adulthood...
  15. Henderson B, Seiser C, Kuhn L. Characterization of a second RNA-binding protein in rodents with specificity for iron-responsive elements. J Biol Chem. 1993;268:27327-34 pubmed
    ..Our data support the existence of two distinct iron-regulated IRE-binding proteins in rodents. ..
  16. Kim B, Jun Y, Jin J, Kim J, Kim N, Leibold E, et al. Alteration of iron regulatory proteins (IRP1 and IRP2) and ferritin in the brains of scrapie-infected mice. Neurosci Lett. 2007;422:158-63 pubmed
    ..These results suggest that alteration of iron metabolism contributes to development of neurodegeneration and that some protective mechanisms against iron-induced oxidative damage may occur during the pathogenesis of TSEs. ..
  17. Leichtmann Bardoogo Y, Cohen L, Weiss A, Marohn B, Schubert S, Meinhardt A, et al. Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload. Am J Physiol Endocrinol Metab. 2012;302:E1519-30 pubmed publisher
    ..proteins in testes of mice with iron overload and with genetic ablation of the iron regulators Hfe and iron regulatory protein 2. Iron accumulated mainly around seminiferous tubules, and only small amounts localized within the ..
  18. Ruiz J, Walker S, Anderson S, Eisenstein R, Bruick R. F-box and leucine-rich repeat protein 5 (FBXL5) is required for maintenance of cellular and systemic iron homeostasis. J Biol Chem. 2013;288:552-60 pubmed publisher
    ..of cellular iron homeostasis requires post-transcriptional regulation of iron metabolism genes by iron regulatory protein 2 (IRP2)...
  19. Schalinske K, Blemings K, Steffen D, Chen O, Eisenstein R. 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. Proc Natl Acad Sci U S A. 1997;94:10681-6 pubmed
    ..Two IRPs, IRP1 and IRP2, have been identified previously...
  20. Styś A, Galy B, Starzynski R, Smuda E, Drapier J, Lipinski P, et al. Iron regulatory protein 1 outcompetes iron regulatory protein 2 in regulating cellular iron homeostasis in response to nitric oxide. J Biol Chem. 2011;286:22846-54 pubmed publisher
    ..IRP1 is a bifunctional protein that mostly exists in a non-IRE-binding, [4Fe-4S] cluster aconitase form, whereas IRP2, which does not assemble an Fe-S cluster, spontaneously binds IREs...
  21. Zhang P, Land W, Lee S, Juliani J, Lefman J, Smith S, et al. Electron tomography of degenerating neurons in mice with abnormal regulation of iron metabolism. J Struct Biol. 2005;150:144-53 pubmed
    Previous studies have shown that IRP1(+/-) IRP2(-/-) knockout mice develop progressive neurodegenerative symptoms similar to those observed in human movement disorders such as Parkinson's disease...
  22. Chen M, Awe O, Chen Roetling J, Regan R. Iron regulatory protein-2 knockout increases perihematomal ferritin expression and cell viability after intracerebral hemorrhage. Brain Res. 2010;1337:95-103 pubmed publisher
    ..In order to assess the therapeutic potential of this approach after striatal ICH, the effect of IRP1 or IRP2 gene knockout on ferritin expression and injury was quantified...
  23. Salvatore M, Fisher B, Surgener S, Gerhardt G, Rouault T. Neurochemical investigations of dopamine neuronal systems in iron-regulatory protein 2 (IRP-2) knockout mice. Brain Res Mol Brain Res. 2005;139:341-7 pubmed
    ..Instead, these observations support that the IRP-2 -/- genotype may enable neurobiological events associated with aging. ..
  24. Yoon D, Pastore Y, Divoky V, Liu E, Mlodnicka A, Rainey K, et al. Hypoxia-inducible factor-1 deficiency results in dysregulated erythropoiesis signaling and iron homeostasis in mouse development. J Biol Chem. 2006;281:25703-11 pubmed
    ..These results identify a novel role for HIF-1 in the regulation of iron homeostasis and reveal unexpected regulatory differences in Epo/EpoR signaling in yolk sac and embryonic erythropoiesis. ..
  25. Hausmann A, Lee J, Pantopoulos K. Redox control of iron regulatory protein 2 stability. FEBS Lett. 2011;585:687-92 pubmed publisher
    b>Iron regulatory protein 2 (IRP2) is a critical switch for cellular and systemic iron homeostasis. In iron-deficient or hypoxic cells, IRP2 binds to mRNAs containing iron responsive elements (IREs) and regulates their expression...
  26. Meyron Holtz E, Ghosh M, Rouault T. Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science. 2004;306:2087-90 pubmed
    ..Although both IRPs can regulate expression of the same target genes, IRP2-/- mice significantly misregulate iron metabolism and develop neurodegeneration, whereas IRP1-/- mice are spared...
  27. Okazaki F, Matsunaga N, Okazaki H, Azuma H, Hamamura K, Tsuruta A, et al. Circadian Clock in a Mouse Colon Tumor Regulates Intracellular Iron Levels to Promote Tumor Progression. J Biol Chem. 2016;291:7017-28 pubmed publisher
    ..In this study, we identified a 24-h rhythm in iron regulatory protein 2 (IRP2) levels in colon-26 tumors implanted in mice...
  28. Viatte L, Grone H, Hentze M, Galy B. In vivo role(s) of the iron regulatory proteins (IRP) 1 and 2 in aseptic local inflammation. J Mol Med (Berl). 2009;87:913-21 pubmed publisher
    ..To explore the role of IRP1 and IRP2 in inflammation, IRP-deficient mice, i.e...
  29. Mueller C, Magaki S, Schrag M, Ghosh M, Kirsch W. Iron regulatory protein 2 is involved in brain copper homeostasis. J Alzheimers Dis. 2009;18:201-10 pubmed publisher
    ..we have therefore compared brain regional copper levels and AbetaPP expression in mice with a targeted deletion of IRP2-/-...
  30. Kerenyi M, Grebien F, Gehart H, Schifrer M, Artaker M, Kovacic B, et al. Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1. Blood. 2008;112:3878-88 pubmed publisher
    ..This reduction could be attributed to reduced transcription of TfR-1 mRNA and iron regulatory protein 2 (IRP-2), the major translational regulator of TfR-1 mRNA stability in erythroid cells...
  31. Ghosh M, Zhang D, Rouault T. Iron misregulation and neurodegenerative disease in mouse models that lack iron regulatory proteins. Neurobiol Dis. 2015;81:66-75 pubmed publisher
    Iron regulatory proteins 1 and 2 (IRP1 and IRP2) are two cytosolic proteins that maintain cellular iron homeostasis by binding to RNA stem loops known as iron responsive elements (IREs) that are found in the untranslated regions of target ..
  32. Regan R, Li Z, Chen M, Zhang X, Chen Roetling J. Iron regulatory proteins increase neuronal vulnerability to hydrogen peroxide. Biochem Biophys Res Commun. 2008;375:6-10 pubmed publisher
    Iron regulatory protein (IRP)-1 and IRP2 inhibit ferritin synthesis by binding to an iron responsive element in the 5'-untranslated region of its mRNA...
  33. Regan R, Chen M, Li Z, Zhang X, Benvenisti Zarom L, Chen Roetling J. Neurons lacking iron regulatory protein-2 are highly resistant to the toxicity of hemoglobin. Neurobiol Dis. 2008;31:242-9 pubmed publisher
    The effect of iron regulatory protein-2 (IRP2) on ferritin expression and neuronal vulnerability to hemoglobin was assessed in primary cortical cell cultures prepared from wild-type and IRP2 knockout mice...
  34. Patton S, Pinero D, Surguladze N, Beard J, Connor J. Subcellular localization of iron regulatory proteins to Golgi and ER membranes. J Cell Sci. 2005;118:4365-73 pubmed
    ..As a result of this study we propose a novel model for intracellular distribution of IRPs and identify differences between the two iron regulatory proteins. ..
  35. Hahn P, Dentchev T, Qian Y, Rouault T, Harris Z, Dunaief J. Immunolocalization and regulation of iron handling proteins ferritin and ferroportin in the retina. Mol Vis. 2004;10:598-607 pubmed
    ..Cytosolic ferritin accumulates in rod bipolar synaptic terminals, suggesting that ferritin may be involved in axonal iron transport. Mitochondrial ferritin increases with iron accumulation, suggesting a role in iron storage. ..
  36. Ishii K, Fumoto T, Iwai K, Takeshita S, Ito M, Shimohata N, et al. Coordination of PGC-1beta and iron uptake in mitochondrial biogenesis and osteoclast activation. Nat Med. 2009;15:259-66 pubmed publisher
    ..osteoclast development, transferrin receptor 1 (TfR1) expression was induced post-transcriptionally via iron regulatory protein 2. TfR1-mediated iron uptake promoted osteoclast differentiation and bone-resorbing activity, associated ..
  37. Zumbrennen Bullough K, Becker L, Garrett L, Holter S, Calzada Wack J, Mossbrugger I, et al. Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments. PLoS ONE. 2014;9:e98072 pubmed publisher
    b>Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism...
  38. Rathkolb B, Klempt M, Sabrautzki S, Michel D, Klaften M, Laufs J, et al. Screen for alterations of iron related parameters in N-ethyl-N-nitrosourea-treated mice identified mutant lines with increased plasma ferritin levels. Biometals. 2015;28:293-306 pubmed publisher
    ..For two of these lines the causative mutations were identified in the Fth1gene and the Ireb2 gene, respectively...