iron regulatory protein 2


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

Top Publications

  1. Guo B, Yu Y, Leibold E. Iron regulates cytoplasmic levels of a novel iron-responsive element-binding protein without aconitase activity. J Biol Chem. 1994;269:24252-60 pubmed
    ..These data indicate that BP1 and BP2 are distinct proteins that have similar specificity for IRE binding and that function similarly in translation, but are regulated by iron via different mechanisms. ..
  2. Crooks D, Ghosh M, Braun Sommargren M, Rouault T, Smith D. Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007;85:1797-809 pubmed
    ..Mn treatment caused c-aconitase to be converted to iron regulatory protein 1 (IRP1) and increased the abundance of IRP2, leading to reduced H-ferritin expression, increased transferrin receptor expression, and increased uptake of ..
  3. Jiang X, Wang H, Shi W, Shen Z, Shen H, Li M. Hyperinsulinemia induces hepatic iron overload by increasing liver TFR1 via the PI3K/IRP2 pathway. J Mol Endocrinol. 2014;53:381-92 pubmed publisher
    ..common characteristic of DIOS, may stimulate liver transferrin receptor 1 (TFR1) expression via the PI3K/iron regulatory protein 2 (IRP2) pathway, leading to the occurrence of DIOS...
  4. 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
    ..Two distinct but highly homologous proteins, IRP1 and IRP2, bind IREs with high affinity when cells are depleted of iron, inhibiting translation of some transcripts, such as ..
  5. 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. ..
  6. 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...
  7. Coon K, Siegel A, Yee S, Dunckley T, Mueller C, Nagra R, et al. Preliminary demonstration of an allelic association of the IREB2 gene with Alzheimer's disease. J Alzheimers Dis. 2006;9:225-33 pubmed
    ..iron metabolism is mediated by two cytoplasmic RNA-binding proteins, the Iron Regulatory Proteins (IRP1 and IRP2), that function through post-transcriptional interactions with RNA stem loop structures called iron-responsive ..
  8. Lane D, Merlot A, Huang M, Bae D, Jansson P, Sahni S, et al. Cellular iron uptake, trafficking and metabolism: Key molecules and mechanisms and their roles in disease. Biochim Biophys Acta. 2015;1853:1130-44 pubmed publisher
    ..g., Friedreich's ataxia. Increased knowledge of the molecules and their mechanisms of action in iron processing pathways (e.g., ISC biogenesis) will shape the investigation of iron metabolism in human health and disease. ..
  9. 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...

More Information


  1. DeRuisseau K, Park Y, DeRuisseau L, Cowley P, Fazen C, Doyle R. Aging-related changes in the iron status of skeletal muscle. Exp Gerontol. 2013;48:1294-302 pubmed publisher
    ..TfR1), storage (ferritin), export (ferroportin; FPN), and regulation (iron regulatory protein-1 (IRP1) and -2 (IRP2)) of male F344xBN F1 rats (n=10/group) of various ages (8, 18, 28, 32, and 36 months) to further understand iron ..
  2. Guo B, Phillips J, Yu Y, Leibold E. Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J Biol Chem. 1995;270:21645-51 pubmed
    Iron regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that bind to specific structures, termed iron-responsive elements (IREs), that are located in the 5'- or 3'-untranslated regions of mRNAs that encode proteins involved in ..
  3. Zuo W, Xue Y, Liu Y. [Expression of iron regulatory protein-2 and ferritins in intestinal mucosa of rats with iron deficiency]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16:565-8 pubmed
    ..05). It is concluded that IRP(2) protein serves as an important regulator of iron metabolism in the human body, and regulates iron uptake from the intestine by controlling the expression of fn mRNA at the post transcriptional level. ..
  4. Zhang Y, Sun X, Xie C, Shu X, Oso A, Ruan Z, et al. Effects of ferrous carbamoyl glycine on iron state and absorption in an iron-deficient rat model. Genes Nutr. 2015;10:54 pubmed publisher
    ..between Fe-CGly and FeSO4 group showed that iron regulatory protein 1 (IRP1) and iron regulatory protein (IRP2) expressions were reduced (P < 0.05) in rats administered FeSO4 than in rats administered with Fe-Cgly...
  5. Samaniego F, Chin J, Iwai K, Rouault T, Klausner R. Molecular characterization of a second iron-responsive element binding protein, iron regulatory protein 2. Structure, function, and post-translational regulation. J Biol Chem. 1994;269:30904-10 pubmed
    ..This second gene product, which we call IRP2, is expressed in many tissues, but its mRNA abundance and tissue distribution are different from IRP1...
  6. Jiang S, Wang C, Lan L, Zhao D. Vitamin A deficiency aggravates iron deficiency by upregulating the expression of iron regulatory protein-2. Nutrition. 2012;28:281-7 pubmed publisher
    ..animal and in vitro experiments to investigate the effect of vitamin A deficiency on iron regulator protein-2 (IRP2)...
  7. Li Y, Yu P, Chang S, Wu Q, Yu P, Xie C, et al. Hypobaric Hypoxia Regulates Brain Iron Homeostasis in Rats. J Cell Biochem. 2017;118:1596-1605 pubmed publisher
    ..Further studies found that the iron regulatory protein 2 (IRP2) played a dominant regulatory role in the changes of iron hemostasis, whereas iron regulatory ..
  8. Guo B, Brown F, Phillips J, Yu Y, Leibold E. Characterization and expression of iron regulatory protein 2 (IRP2). Presence of multiple IRP2 transcripts regulated by intracellular iron levels. J Biol Chem. 1995;270:16529-35 pubmed
    Iron regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that bind to stem-loop structures, termed iron-responsive elements (IREs), present in either the 5'- or 3'-untranslated regions of specific mRNAs...
  9. Yang L, Wang C, Xiao F. [Effects of different zinc nutritional status on iron metabolism in rats]. Wei Sheng Yan Jiu. 2013;42:647-51 pubmed
    ..of different zinc nutritional status on iron metabolism and explore the potential role of iron regulator protein 2 (IRP2) under conditions of zinc deficiency...
  10. Rathnasamy G, Ling E, Kaur C. Iron and iron regulatory proteins in amoeboid microglial cells are linked to oligodendrocyte death in hypoxic neonatal rat periventricular white matter through production of proinflammatory cytokines and reactive oxygen/nitrogen species. J Neurosci. 2011;31:17982-95 pubmed publisher
    ..In response to hypoxia, the protein levels of IRP1, IRP2, and TfR in PWM and AMCs were significantly increased...
  11. 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 ..
  12. 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...
  13. Schumann K, Moret R, Künzle H, Kuhn L. Iron regulatory protein as an endogenous sensor of iron in rat intestinal mucosa. Possible implications for the regulation of iron absorption. Eur J Biochem. 1999;260:362-72 pubmed
    ..Our results are compatible with a role of IRPs in gearing the expression of intestinal iron transporters in the duodenal brushborder to the body's state of iron repletion. ..
  14. Wallander M, Zumbrennen K, Rodansky E, Romney S, Leibold E. Iron-independent phosphorylation of iron regulatory protein 2 regulates ferritin during the cell cycle. J Biol Chem. 2008;283:23589-98 pubmed publisher
    b>Iron regulatory protein 2 (IRP2) is a key iron sensor that post-transcriptionally regulates mammalian iron homeostasis by binding to iron-responsive elements (IREs) in mRNAs that encode proteins involved in iron metabolism (e.g...
  15. Siddappa A, Rao R, Wobken J, Leibold E, Connor J, Georgieff M. Developmental changes in the expression of iron regulatory proteins and iron transport proteins in the perinatal rat brain. J Neurosci Res. 2002;68:761-75 pubmed
    ..IRP and transport protein expression increased in parallel over time. IRP1, IRP2, and DMT-1 were partially expressed in the choroid plexus epithelial cells at PND 5 and 10, and fully expressed at ..
  16. Chen Q, Xiao D. Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus. Nitric Oxide. 2014;36:1-10 pubmed publisher
    ..blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS...
  17. Xu X, Persson H, Richardson D. Molecular pharmacology of the interaction of anthracyclines with iron. Mol Pharmacol. 2005;68:261-71 pubmed
    ..This review discusses the molecular interactions of anthracyclines with iron metabolism and the development of cardioprotective strategies such as iron chelators. ..
  18. Xiao F, Wang C, Yang L. [Effects of copper deficiency on iron metabolism in rats]. Wei Sheng Yan Jiu. 2013;42:652-5 pubmed
    ..05). Compared with that of the control group, the level of IRP2 mRNA in complete copper deficiency group was significantly increased (P < 0...
  19. Dornelles A, Garcia V, de Lima M, Vedana G, Alcalde L, Bogo M, et al. mRNA expression of proteins involved in iron homeostasis in brain regions is altered by age and by iron overloading in the neonatal period. Neurochem Res. 2010;35:564-71 pubmed publisher
    ..w. of Fe(2+)), at postnatal days 12-14. The expression of Transferrin Receptor (TfR), H-Ferritin, and IRP2 were analyzed by a semi-quantitative reverse transcriptase polymerase chain reaction assay in cortex, hippocampus ..
  20. Gammella E, Maccarinelli F, Buratti P, Recalcati S, Cairo G. The role of iron in anthracycline cardiotoxicity. Front Pharmacol. 2014;5:25 pubmed publisher
    ..This review discusses the pathogenic role of the disruption of iron homeostasis in Doxorubicin-mediated cardiotoxicity in the context of current and future pharmacologic approaches to cardioprotection. ..
  21. 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...
  22. Lan L, Wang C, Shi R, Wang K, Liu B, Jiang S. [Effect of all-trans retinoic acid deficiency on iron metabolism in rat primary hepatocyte]. Wei Sheng Yan Jiu. 2009;38:603-6 pubmed
    ..5, 1 and 50 micromol/L atRA and DMEM contained 10% fetal bovine serum. After 72h, IRP2 mRNA, TFR mRNA, Fnm RNA levels were measured by RT-PCR. VA deficiency can decrease the viability and function...
  23. Wang Z, Yang L, Ding Y, Chang Y, Cui H. Insights into the role of iron in immature rat model of hypoxic-ischemic brain injury. Exp Ther Med. 2016;12:1723-1731 pubmed
    ..Iron content and mRNA expression levels of iron regulatory protein 2 (IRP2) and transferrin receptor in the brain tissues were measured...
  24. 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. ..
  25. An L, Yue Y, Guo W, Miao Y, Mi W, Zhang H, et al. Surgical trauma induces iron accumulation and oxidative stress in a rodent model of postoperative cognitive dysfunction. Biol Trace Elem Res. 2013;151:277-83 pubmed publisher
    ..involved in the maintenance of brain iron homeostasis, including ferritin, transferrin receptor 1, and iron regulatory protein 2, were significantly different at postoperative days 1 and 3 in the hippocampus of splenectomized animals ..
  26. Irace C, Scorziello A, Maffettone C, Pignataro G, Matrone C, Adornetto A, et al. Divergent modulation of iron regulatory proteins and ferritin biosynthesis by hypoxia/reoxygenation in neurones and glial cells. J Neurochem. 2005;95:1321-31 pubmed
    ..Ferritin expression is regulated mainly at post-transcriptional level by iron regulatory proteins (IRP1 and IRP2) that bind specific RNA sequences (IREs) in the 5'untranslated region of ferritin mRNA...
  27. Davis M, Shawron K, Rendina E, Peterson S, Lucas E, Smith B, et al. Hypoxia inducible factor-2 ? is translationally repressed in response to dietary iron deficiency in Sprague-Dawley rats. J Nutr. 2011;141:1590-6 pubmed publisher
  28. Kwik Uribe C, Smith D. Temporal responses in the disruption of iron regulation by manganese. J Neurosci Res. 2006;83:1601-10 pubmed
  29. Beck G, Shinzawa K, Hayakawa H, Baba K, Yasuda T, Sumi Akamaru H, et al. Deficiency of Calcium-Independent Phospholipase A2 Beta Induces Brain Iron Accumulation through Upregulation of Divalent Metal Transporter 1. PLoS ONE. 2015;10:e0141629 pubmed publisher
    ..DMT1 and IRP2 were markedly upregulated in all examined brain regions of aged iPLA2β-KO mice compared to age-matched wild-type ..
  30. Huang E, Ong W, Go M, Connor J. Upregulation of iron regulatory proteins and divalent metal transporter-1 isoforms in the rat hippocampus after kainate induced neuronal injury. Exp Brain Res. 2006;170:376-86 pubmed
    Iron regulatory proteins (IRP1 and IRP2) bind to iron response elements (IRE) on specific mRNAs, to affect the translation of many proteins involved in iron metabolism...
  31. Thomson A, Rogers J, Leedman P. Thyrotropin-releasing hormone and epidermal growth factor regulate iron-regulatory protein binding in pituitary cells via protein kinase C-dependent and -independent signaling pathways. J Biol Chem. 2000;275:31609-15 pubmed
    Intracellular iron homeostasis is regulated, in part, by interactions between iron-regulatory proteins (IRP1 and IRP2) and iron-responsive elements (IREs) in ferritin and transferrin receptor mRNAs...
  32. 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 ..