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

Summary

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

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_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
MiR-19a suppresses ferroptosis of colorectal cancer cells by targeting IREB2.
Title: MiR-19a suppresses ferroptosis of colorectal cancer cells by targeting IREB2.
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.
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.
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.
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.
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.
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.
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.
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	not available

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S275 (e-PCR)
- UniSTS:147992

RH77805 (e-PCR)
- UniSTS:14877

RH66624 (e-PCR)
- UniSTS:15144

RH44971 (e-PCR)
- UniSTS:1091

IREB2 (e-PCR)
- UniSTS:503115

SHGC-36650 (e-PCR)
- UniSTS:23906

D1S1423 (e-PCR)
- UniSTS:149619

IREB2__6476 (e-PCR)
- UniSTS:463999

SHGC-83059 (e-PCR)
- UniSTS:96150

RH65189 (e-PCR)
- UniSTS:91825

G43287 (e-PCR)
- UniSTS:94921

STS-R99019 (e-PCR)
- UniSTS:70354

A009V40 (e-PCR)
- UniSTS:40921

G32892 (e-PCR)
- UniSTS:117471

SHGC-172971 (e-PCR)
- UniSTS:183523

D15S908 (e-PCR)
- UniSTS:81658

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)

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
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
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
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
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]