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 th... See more...

Aliases for IREB2 Gene

Aliases for IREB2 Gene

  • Iron Responsive Element Binding Protein 2 2 3 5
  • IRP2 2 3 4
  • Iron-Responsive Element-Binding Protein 2 3 4
  • Iron Regulatory Protein 2 3 4
  • IRE-BP 2 3 4
  • EC 4.2.1.3 50
  • IRE-BP2 3
  • IRP2AD 3
  • NDCAMA 3
  • IREB2 5
  • ACO3 3

External Ids for IREB2 Gene

Previous GeneCards Identifiers for IREB2 Gene

  • GC15P074809
  • GC15P071820
  • GC15P076306
  • GC15P076446
  • GC15P076517
  • GC15P078730
  • GC15P055487

Summaries for IREB2 Gene

Entrez Gene Summary for IREB2 Gene

  • 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]

GeneCards Summary for IREB2 Gene

IREB2 (Iron Responsive Element Binding Protein 2) is a Protein Coding gene. Diseases associated with IREB2 include Neurodegeneration, Early-Onset, With Choreoathetoid Movements And Microcytic Anemia and Microcytic Anemia. Among its related pathways are Validated targets of C-MYC transcriptional activation and Iron metabolism in placenta. Gene Ontology (GO) annotations related to this gene include RNA binding and translation repressor activity. An important paralog of this gene is ACO1.

UniProtKB/Swiss-Prot Summary for IREB2 Gene

  • RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for IREB2 Gene

Genomics for IREB2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for IREB2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around IREB2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for IREB2

Top Transcription factor binding sites by QIAGEN in the IREB2 gene promoter:
  • AML1a
  • ATF-2
  • Bach1
  • Lmo2
  • p53
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • YY1

Genomic Locations for IREB2 Gene

Latest Assembly
chr15:78,437,431-78,501,453
(GRCh38/hg38)
Size:
64,023 bases
Orientation:
Plus strand

Previous Assembly
chr15:78,729,773-78,793,795
(GRCh37/hg19 by Entrez Gene)
Size:
64,023 bases
Orientation:
Plus strand

chr15:78,729,773-78,793,798
(GRCh37/hg19 by Ensembl)
Size:
64,026 bases
Orientation:
Plus strand

Genomic View for IREB2 Gene

Genes around IREB2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IREB2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IREB2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IREB2 Gene

Proteins for IREB2 Gene

  • Protein details for IREB2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P48200-IREB2_HUMAN
    Recommended name:
    Iron-responsive element-binding protein 2
    Protein Accession:
    P48200
    Secondary Accessions:
    • A0A0A6YY96
    • A8KAC7
    • E1CJT9
    • H0YKU0
    • Q13095
    • Q1HE21
    • Q59FQ7
    • Q8WVK6
    • Q9UF17

    Protein attributes for IREB2 Gene

    Size:
    963 amino acids
    Molecular mass:
    105059 Da
    Cofactor:
    Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
    Quaternary structure:
    • Interacts with RBCK1 isoform 1 and isoform 2 only in iron-rich conditions (PubMed:12629548). Interacts (when associated with the 4Fe-4S) with FBXL5 (PubMed:19762596, PubMed:19762597). Interacts with CIAO1 and CIAO2A (PubMed:23891004).
    SequenceCaution:
    • Sequence=AAA79926.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAD92640.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for IREB2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IREB2 Gene

Selected DME Specific Peptides for IREB2 Gene

P48200:
  • ANYLASP
  • TTDHISPAG
  • SIRVLLE
  • LGDSVTTDHISPA
  • GPKRPQD

Post-translational modifications for IREB2 Gene

  • Ubiquitinated and degraded by the proteasome in presence of high level of iron and oxygen. Ubiquitinated by a SCF complex containing FBXL5. Upon iron and oxygen depletion FBXL5 is degraded, preventing ubiquitination and allowing its RNA-binding activity.
  • Ubiquitination at Lys5, Lys34, Lys70, Lys72, Lys107, Lys136, Lys152, Lys216, Lys233, Lys404, Lys413, Lys449, Lys461, Lys471, Lys475, Lys611, Lys714, Lys769, Lys803, Lys807, Lys836, Lys847, Lys848, Lys860, Lys868, and Lys880
  • Modification sites at PhosphoSitePlus

Domains & Families for IREB2 Gene

Gene Families for IREB2 Gene

Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for IREB2 Gene

GenScript: Design optimal peptide antigens:
  • Iron-responsive element binding protein 2, isoform CRA_a (D3DW85_HUMAN)
  • Iron regulatory protein 2 (IREB2_HUMAN)
  • IREB2 protein (Q8WVK6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P48200

UniProtKB/Swiss-Prot:

IREB2_HUMAN :
  • Belongs to the aconitase/IPM isomerase family.
Family:
  • Belongs to the aconitase/IPM isomerase family.
genes like me logo Genes that share domains with IREB2: view

Function for IREB2 Gene

Molecular function for IREB2 Gene

UniProtKB/Swiss-Prot Function:
RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA.
GENATLAS Biochemistry:
iron responsive element binding protein 2,structurally related to aconitase

Enzyme Numbers (IUBMB) for IREB2 Gene

Phenotypes From GWAS Catalog for IREB2 Gene

Gene Ontology (GO) - Molecular Function for IREB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding TAS 9924025
GO:0003994 aconitate hydratase activity IBA 21873635
GO:0005515 protein binding IPI 19762596
GO:0030350 iron-responsive element binding IEA,TAS 9924025
GO:0030371 translation repressor activity IEA --
genes like me logo Genes that share ontologies with IREB2: view
genes like me logo Genes that share phenotypes with IREB2: view

Human Phenotype Ontology for IREB2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for IREB2 Gene

MGI Knock Outs for IREB2:

miRNA for IREB2 Gene

miRTarBase miRNAs that target IREB2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IREB2

No data available for Transcription Factor Targets and HOMER Transcription for IREB2 Gene

Localization for IREB2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IREB2 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for IREB2 gene
Compartment Confidence
cytosol 5
mitochondrion 4
nucleus 3
plasma membrane 2
extracellular 2
cytoskeleton 2
endosome 2
lysosome 2
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (2)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for IREB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,NAS 7983023
GO:0005739 mitochondrion IBA 21873635
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with IREB2: view

Pathways & Interactions for IREB2 Gene

genes like me logo Genes that share pathways with IREB2: view

Pathways by source for IREB2 Gene

1 Cell Signaling Technology pathway for IREB2 Gene

SIGNOR curated interactions for IREB2 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for IREB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006099 tricarboxylic acid cycle IBA 21873635
GO:0006101 citrate metabolic process IBA 21873635
GO:0006417 regulation of translation IEA --
GO:0006782 protoporphyrinogen IX biosynthetic process IEA --
GO:0006826 iron ion transport TAS 9924025
genes like me logo Genes that share ontologies with IREB2: view

Drugs & Compounds for IREB2 Gene

(16) Drugs for IREB2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Fe2+ Experimental Pharma 0

(9) Additional Compounds for IREB2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with IREB2: view

Transcripts for IREB2 Gene

mRNA/cDNA for IREB2 Gene

5 REFSEQ mRNAs :
18 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IREB2

Alternative Splicing Database (ASD) splice patterns (SP) for IREB2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23a · 23b ^
SP1: - - -
SP2: - -
SP3: -
SP4:
SP5: - -
SP6:
SP7:

ExUns: 24a · 24b ^ 25
SP1: -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:

Relevant External Links for IREB2 Gene

GeneLoc Exon Structure for
IREB2

Expression for IREB2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for IREB2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for IREB2 Gene

This gene is overexpressed in Cerebrospinal fluid (13.0), Plasma (7.3), and Esophagus (7.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for IREB2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for IREB2

SOURCE GeneReport for Unigene cluster for IREB2 Gene:

Hs.436031

Evidence on tissue expression from TISSUES for IREB2 Gene

  • Nervous system(4.8)
  • Intestine(3.1)
  • Liver(2.8)
  • Spleen(2.7)
  • Kidney(2.6)
  • Heart(2.5)
  • Lung(2.4)
  • Muscle(2.3)
  • Blood(2.3)
  • Bone marrow(2.2)
  • Skin(2.1)
genes like me logo Genes that share expression patterns with IREB2: view

Primer products for research

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for IREB2 Gene

Orthologs for IREB2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for IREB2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia IREB2 29 30
  • 99.83 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia IREB2 29 30
  • 94.39 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Ireb2 29 16 30
  • 91.36 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ireb2 29
  • 91.09 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 89 (a)
OneToMany
-- 30
  • 87 (a)
OneToMany
Dog
(Canis familiaris)
Mammalia IREB2 29 30
  • 88.47 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia IREB2 30
  • 64 (a)
OneToOne
Chicken
(Gallus gallus)
Aves IREB2 29 30
  • 77.55 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ireb2 29
  • 67.55 (n)
Zebrafish
(Danio rerio)
Actinopterygii ireb2 29 30
  • 62.47 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Irp-1B 30
  • 57 (a)
ManyToMany
Irp-1A 30
  • 56 (a)
ManyToMany
Worm
(Caenorhabditis elegans)
Secernentea aco-1 30
  • 55 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ACO2 30
  • 25 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.544 30
  • 56 (a)
OneToMany
Species where no ortholog for IREB2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for IREB2 Gene

ENSEMBL:
Gene Tree for IREB2 (if available)
TreeFam:
Gene Tree for IREB2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for IREB2: view image
Alliance of Genome Resources:
Additional Orthologs for IREB2

Paralogs for IREB2 Gene

Paralogs for IREB2 Gene

(4) SIMAP similar genes for IREB2 Gene using alignment to 9 proteins:

  • IREB2_HUMAN
  • D3DW85_HUMAN
  • H0YKU0_HUMAN
  • H0YL48_HUMAN
  • H0YLE0_HUMAN
  • H0YMA8_HUMAN
  • H0YN46_HUMAN
  • H0YNL8_HUMAN
  • Q8WVK6_HUMAN
genes like me logo Genes that share paralogs with IREB2: view

Variants for IREB2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for IREB2 Gene

SNP ID Clinical significance and condition Chr 15 pos Variation AA Info Type
rs115506959 Benign: not provided 78,466,496(+) G/T
NM_004136.4(IREB2):c.629+7G>T
INTRON
rs1566982116 Likely Pathogenic: NEURODEGENERATION, EARLY-ONSET, WITH CHOREOATHETOSIS AND MICROCYTIC ANEMIA; Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia 78,476,233(+) G/T
NM_004136.4(IREB2):c.1069G>T (p.Gly357Ter)
NONSENSE,THREE_PRIME_UTR
rs1596009225 Uncertain Significance: NEURODEGENERATION, EARLY-ONSET, WITH CHOREOATHETOSIS AND MICROCYTIC ANEMIA; Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia 78,483,348(+) CCAT/C
NM_004136.4(IREB2):c.1329_1331del (p.Ser444del)
INFRAME_DELETION
rs1596016998 Uncertain Significance: NEURODEGENERATION, EARLY-ONSET, WITH CHOREOATHETOSIS AND MICROCYTIC ANEMIA; Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia 78,493,937(+) G/A
NM_004136.4(IREB2):c.2353G>A (p.Gly785Arg)
MISSENSE
rs35999247 Benign: not provided 78,471,845(+) A/G
NM_004136.4(IREB2):c.804A>G (p.Lys268=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for IREB2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for IREB2 Gene

Variant ID Type Subtype PubMed ID
esv3636983 CNV loss 21293372
nsv1116464 OTHER inversion 24896259
nsv833063 CNV loss 17160897

Variation tolerance for IREB2 Gene

Residual Variation Intolerance Score: 23.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.95; 36.14% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for IREB2 Gene

Human Gene Mutation Database (HGMD)
IREB2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IREB2
Leiden Open Variation Database (LOVD)
IREB2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IREB2 Gene

Disorders for IREB2 Gene

MalaCards: The human disease database

(28) MalaCards diseases for IREB2 Gene - From: OMI, CVR, GTR, COP, and GCD

Disorder Aliases PubMed IDs
neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia
  • ndcama
microcytic anemia
  • iron-refractory iron deficiency anemia
iron metabolism disease
  • disorder of iron metabolism
hemochromatosis, type 1
  • hfe1
anemia, sideroblastic, 1
  • sidba1
- elite association - COSMIC cancer census association via MalaCards
Search IREB2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

IREB2_HUMAN
  • Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia (NDCAMA) [MIM:618451]: An autosomal recessive disorder characterized by severe neurological and extra-neurological manifestations. Clinical features include early-onset global developmental delay, absent speech, dystonia, spasticity, choreoathetoid movement disorder, seizures, and microcytic hypochromic anaemia unresponsive to iron supplementation. {ECO:0000269 PubMed:30915432}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for IREB2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with IREB2: view

No data available for Genatlas for IREB2 Gene

Publications for IREB2 Gene

  1. Absence of iron-responsive element-binding protein 2 causes a novel neurodegenerative syndrome. (PMID: 30915432) Costain G … Yoon G (Brain : a journal of neurology 2019) 3 4 72
  2. An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. (PMID: 19762597) Salahudeen AA … Bruick RK (Science (New York, N.Y.) 2009) 3 4 22
  3. Control of iron homeostasis by an iron-regulated ubiquitin ligase. (PMID: 19762596) Vashisht AA … Wohlschlegel JA (Science (New York, N.Y.) 2009) 3 4 22
  4. Preliminary demonstration of an allelic association of the IREB2 gene with Alzheimer's disease. (PMID: 16914832) Coon KD … Kirsch WM (Journal of Alzheimer's disease : JAD 2006) 3 22 40
  5. Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2. (PMID: 12629548) Yamanaka K … Iwai K (Nature cell biology 2003) 3 4 22

Products for IREB2 Gene

Sources for IREB2 Gene