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FLASH GENE
Symbol IREB2 contributors: SGE/mct - updated : 21-08-2014
HGNC name iron-responsive element binding protein 2
HGNC id 6115
Location 15q25.1      Physical location : 78.730.517 - 78.793.798
Synonym name iron regulatory protein 2
Synonym symbol(s) ACO3, IRP2, IRP2AD, FLJ23381,
DNA
TYPE functioning gene
STRUCTURE 63.28 kb     22 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
FLJ14594 15q24.1 hypothetical protein FLJ14594 LOC342111 15q24.1 hypothetical gene supported by NM_001897 LOC388141 15 LOC388141 LOC390611 15 similar to hypothetical protein FLJ20452 KIAA1055 15q24.1 KIAA1055 protein LOC146013 15q24.1 similar to SH2 domain protein 2A (T cell-specific adapter protein) (TSAd) (VEGF receptor-associated protein) (SH2 domain containing adapter protein) KIP2 15q24.3 similar to SH2 domain protein 2A (T cell-specific adapter protein) (TSAd) (VEGF receptor-associated protein) (SH2 domain containing adapter protein) IDH3A 15q25.1-q25.2 isocitrate dehydrogenase 3 (NAD+) alpha BG1 15q24-q25 isocitrate dehydrogenase 3 (NAD+) alpha DNAJA4 15q24.1 DnaJ (Hsp40) homolog, subfamily A, member 4 REC14 15q24.1 recombination protein REC14 CRABP1 15q24 cellular retinoic acid binding protein 1 IREB2 15q24 iron-responsive element binding protein 2 LOC123688 15q24.1 similar to RIKEN cDNA C630028N24 gene PSMA4 15q24.1 proteasome (prosome, macropain) subunit, alpha type, 4 CHRNA5 15q24 cholinergic receptor, nicotinic, alpha polypeptide 5 CHRNA3 15q24 cholinergic receptor, nicotinic, alpha polypeptide 3 CHRNB4 15q24 cholinergic receptor, nicotinic, beta polypeptide 4 LOC390612 15 similar to ribosomal protein L18; 60S ribosomal protein L18 LOC388142 15 LOC388142 LOC390613 15 similar to Dynamin-1 (D100) (Dynamin, brain) (B-dynamin) ADAMTS7 15pter-qter a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 7 LOC390614 15 similar to cDNA sequence BC053073; G-protein coupled receptor SALPR; somatostatin and angiotensin-like peptide receptor LOC388143 15 similar to 60S ribosomal protein L21 MORF4L1 15q24 mortality factor 4 like 1 CTSH 15q24-q25 cathepsin H RASGRF1 15q24 Ras protein-specific guanine nucleotide-releasing factor 1
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
22 - 6367 105 963 - Wallander (2008)
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivemouthtongue  highly
 pharynx   highly
Lymphoid/Immunethymus   highly
Reproductivefemale systemuteruscervix  
 male systemtestis  highly
Urinarybladder   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow   
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 73AA-Domain (binding of haem to the 73aa-Domain that is unique in IREB2, but haem interacts with a cysteine residue only in truncated forms of the 73aa-Domain) (Dycke 2007)
  • HOMOLOGY
    intraspecies homolog to aconitase,structurally
    Homologene
    FAMILY
  • aconitase/IPM isomerase family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • central posttranscriptional regulator of cellular and systemic iron metabolism, undergoes proteasomal degradation in iron-replete cells
  • master regulator of cellular iron metabolism
  • binding to the transferrin receptor mRNA inhibiting the degradation of this otherwise rapidly degraded mRNA
  • RNA-binding protein that post-transcriptionally control the mRNA of proteins involved in storage, transport, and utilization of iron (Dycke 2007)
  • major role of ACO1, and IREB2 in cell biology: to ensure adequate iron supply to the mitochondrion for proper function of this critical organelle
  • controls the synthesis of many proteins involved in iron metabolism, and the level of IREB2 itself is regulated by varying the rate of its degradation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • FBXL5-IREB2 axis is integral to control of iron metabolism
  • a component
  • associating with SKP1-CUL1-FBXL5 ubiquitin ligase . protein and is iron-dependent ubiquitinated and degraded, depending on the stability and activity of FBXL5 (Vashisht 2009)
  • INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • binding 1 4Fe-4S cluster per subunit
  • protein
  • binds to iron-responsive elements (IREs) to regulate the translation and stability of mRNAs encoding several proteins involved in mammalian iron homeostasis (Zumbrennen 2008)
  • interacting with RBCK1 (Zumbrennen 2008)
  • FBXL5 targets IREB2 for proteasomal degradation under iron- and oxygen-replete conditions
  • FBXL5 regulates cellular and systemic iron homeostasis by facilitating IREB2 degradation
  • cell & other
    REGULATION
    repressed by increases in cellular iron, which stimulate the polyubiquitylation and proteasomal degradation of IREB2 (Zumbrennen 2008)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to chronic obstructive pulmonary disease (COPD)
    Variant & Polymorphism SNP
  • increasing the risk of chronic obstructive pulmonary disease (De Meo 2009)
  • association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS