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    IREB2 iron responsive element binding protein 2 [ Homo sapiens (human) ]

    Gene ID: 3658, updated on 2-Nov-2024

    Summary

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    Official Symbol
    IREB2provided by HGNC
    Official Full Name
    iron responsive element binding protein 2provided by HGNC
    Primary source
    HGNC:HGNC:6115
    See related
    Ensembl:ENSG00000136381 MIM:147582; AllianceGenome:HGNC:6115
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ACO3; IRP2; IRP2AD; NDCAMA; IRE-BP2; IRE-BP 2
    Summary
    The protein encoded by this gene is an RNA-binding protein that acts to regulate iron levels in the cells by regulating the translation and stability of mRNAs that affect iron homeostasis under conditions when iron is depleted. When iron levels are low, this protein binds to iron-responsive elements (IRES), stem-loop structures located either in the 5' or 3' UTRs. Binding to the 5' UTR represses translation, while binding to the 3' UTR inhibits mRNA degradation. When iron is found in the cell, this protein is degraded in a F-box and leucine rich repeat protein 5-dependent manner. Variants in this gene have been associated with lung cancer and chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]
    Expression
    Ubiquitous expression in thyroid (RPKM 9.5), adrenal (RPKM 8.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See IREB2 in Genome Data Viewer
    Location:
    15q25.1
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (78437431..78501453)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (76300098..76364103)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (78729773..78793795)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene NANOG hESC enhancer GRCh37_chr15:78679989-78680490 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr15:78682970-78684169 Neighboring gene RWD domain containing 1 pseudogene 1 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr15:78687919-78688419 Neighboring gene uncharacterized LOC105370912 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9917 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9918 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6711 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:78759180-78759680 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:78759681-78760181 Neighboring gene hydroxylysine kinase Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9919 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:78833042-78833934 Neighboring gene proteasome 20S subunit alpha 4

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. [Regulating action of iron regulatory protein-2 in iron metabolism of lung cancer]. Cheng Z, et al. Zhonghua Yi Xue Za Zhi, 2011 Jul 26. PMID 22093897
    2. An iron-sulfur cluster plays a novel regulatory role in the iron-responsive element binding protein. Rouault TA, et al. Biometals, 1992 Autumn. PMID 1421965
    3. Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2. Iwai K, et al. EMBO J, 1995 Nov 1. PMID 7489724, Free PMC Article
    4. Polymorphisms in iron-responsive binding protein 2 and lack of association with sporadic Parkinson's disease. Lee PL, et al. Mov Disord, 2002 Nov. PMID 12465072
    5. Oxygen and iron regulation of iron regulatory protein 2. Hanson ES, et al. J Biol Chem, 2003 Oct 10. PMID 12888568

    See all (113) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. KLF14 regulates the growth of hepatocellular carcinoma cells via its modulation of iron homeostasis through the repression of iron-responsive element-binding protein 2.
      Title: KLF14 regulates the growth of hepatocellular carcinoma cells via its modulation of iron homeostasis through the repression of iron-responsive element-binding protein 2.
    2. MiR-19a suppresses ferroptosis of colorectal cancer cells by targeting IREB2.
      Title: MiR-19a suppresses ferroptosis of colorectal cancer cells by targeting IREB2.
    3. Iron Regulatory Protein 2 Exerts its Oncogenic Activities by Suppressing TAp63 Expression.
      Title: Iron Regulatory Protein 2 Exerts its Oncogenic Activities by Suppressing TAp63 Expression.
    4. IRP2-Hif1alpha/Hif2alpha signaling: a novel mechanism of metabolic switch from aerobic glycolysis to oxidative phosphorylation.
      Title: IRP2-Hif1α/Hif2α signaling: a novel mechanism of metabolic switch from aerobic glycolysis to oxidative phosphorylation.
    5. Mdm2 is a target and mediator of IRP2 in cell growth control.
      Title: Mdm2 is a target and mediator of IRP2 in cell growth control.
    6. This study has identified an iron-sulfur cluster within FBXL5, which promotes IRP2 polyubiquitination and degradation in response to both iron and oxygen concentrations.
      Title: FBXL5 Regulates IRP2 Stability in Iron Homeostasis via an Oxygen-Responsive [2Fe2S] Cluster.
    7. To better understand the mechanisms of zinc-induced iron absorption, we have studied the effect of zinc on iron uptake, iron transporter and iron regulatory protein (IRP 1 and 2) expression and the impact of the PI3K pathway in differentiated Caco-2 cells, an intestinal cell culture model. We found that zinc induces DMT1 protein and mRNA expression.
      Title: Zinc induces iron uptake and DMT1 expression in Caco-2 cells via a PI3K/IRP2 dependent mechanism.
    8. Ectopic expression of IRP2 suppressed cell growth in a mutant p53-dependent manner. Together, these data indicate that mutant p53 gain-of-function can be suppressed by IRP2 and Ferredoxin reductase deficiency, both of which may be explored to target tumors carrying mutant p53.
      Title: Iron regulatory protein 2 is a suppressor of mutant p53 in tumorigenesis.
    9. All four variants were significantly associated (P < 1.4 x 10(-6)) with blood DNA methylation of IREB2, CHRNA3 and PSMA4, of which two, including IREB2 and PSMA4, were also differentially methylated in Chronic obstructive pulmonary disease cases and controls
      Title: Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics.
    10. rs16969858 in IREB2 was significantly associated with COPD but in the univariate analysis only, and the multivariate analysis did not show any association.
      Title: Genetic variants in FAM13A and IREB2 are associated with the susceptibility to COPD in a Chinese rural population: a case-control study.
    Submit: New GeneRIF Correction See all GeneRIFs (53)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia
    MedGen: C5193104 OMIM: 618451 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.
    EBI GWAS Catalog
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS Catalog
    Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.
    EBI GWAS Catalog
    IREB2 and GALC are Associated with Pulmonary Artery Enlargement in Chronic Obstructive Pulmonary Disease.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog
    Variants in FAM13A are associated with chronic obstructive pulmonary disease.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ23381

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 4 iron, 4 sulfur cluster binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables RNA binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables aconitate hydratase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables iron-responsive element binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables iron-responsive element binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables iron-responsive element binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables mRNA regulatory element binding translation repressor activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in citrate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in erythrocyte homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intestinal absorption IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular iron ion homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in intracellular iron ion homeostasis TAS
    Traceable Author Statement
    more info
    		  
    involved_in mRNA stabilization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in multicellular organismal-level iron ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of translation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in osteoclast differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in post-embryonic development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protoporphyrinogen IX biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tricarboxylic acid cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    iron-responsive element-binding protein 2
    Names
    iron regulatory protein 2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001320941.2 → NP_001307870.2  iron-responsive element-binding protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC011270, AC027228, KF459563
      Conserved Domains (1) summary
      PTZ00092
      Location:3 → 711
      PTZ00092; aconitate hydratase-like protein; Provisional

    2. NM_001320942.2 → NP_001307871.2  iron-responsive element-binding protein 2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC011270, AC027228, KF459563
      Conserved Domains (1) summary
      PTZ00092
      Location:2 → 904
      PTZ00092; aconitate hydratase-like protein; Provisional

    3. NM_001320943.2 → NP_001307872.1  iron-responsive element-binding protein 2 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC011270, AC027228, BC017880
      Consensus CDS
      CCDS81912.1
      UniProtKB/Swiss-Prot
      P48200
      Related
      ENSP00000452938.1, ENST00000560440.5
      Conserved Domains (1) summary
      cl00285
      Location:84 → 342
      Aconitase; Aconitase catalytic domain; Aconitase catalyzes the reversible isomerization of citrate and isocitrate as part of the TCA cycle

    4. NM_001354994.2 → NP_001341923.2  iron-responsive element-binding protein 2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC011270, AC027228, KF459563
      Conserved Domains (1) summary
      PTZ00092
      Location:2 → 904
      PTZ00092; aconitate hydratase-like protein; Provisional

    5. NM_004136.4 → NP_004127.2  iron-responsive element-binding protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC011270, AC027228, KF459563
      Consensus CDS
      CCDS10302.1
      UniProtKB/Swiss-Prot
      A0A0A6YY96, A8KAC7, E1CJT9, H0YKU0, P48200, Q13095, Q1HE21, Q59FQ7, Q8WVK6, Q9UF17
      Related
      ENSP00000258886.8, ENST00000258886.13
      Conserved Domains (1) summary
      cl28376
      Location:10 → 961
      AcnA; Aconitase A [Energy production and conversion]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      78437431..78501453
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      76300098..76364103
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P48200.4 GenPept UniProtKB/Swiss-Prot:P48200

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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