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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.
Gene References into Functions
Five of these SNPs acted as cis-eQTLs, being associated with the transcription of IREB2 (rs2568494, rs16969968, rs11634351, rs6495309), PSMA4 (rs6495309) and ERCC1 (rs735482), out of 10,821 genes analyzed in lung. For these three genes, we obtained experimental evidence of differential allelic expression in lung tissue, pointing to the existence of in-cis genomic variants that regulate their transcription.PMID:28181565
Iron loading caused cell proliferation in cancer cell lines, which were less able to regulate IREB2 expression than primary bronchial epithelial cells (PBECs). Iron chelation resulted in a return of proliferation rates to baseline levels; knockdown of IREB2 had a similar effect. IRP2-positive tumours were larger and higher percentage staining related to poorer survival.PMID:28404645
The rs13180 (IREB2), rs16969968 (CHRNA5) and rs1051730 (CHRNA3) were significantly associated with Chronic obstructive pulmonary disease (COPD) in additive model [Padj =0.00001, odds ratio (OR)=0.64; Padj =0.0001, OR=1.41 and Padj =0.0001, OR=1.47]. The C-G haplotype by rs13180 and rs1051730 was a protective factor for COPD in our population (Padj =0.0005, OR=0.61).PMID:28474623
IRP2 expression was associated with mutations in BRAF.PMID:28281325
The current results revealed that there was significant association between IREB2 gene rs2568494 polymorphism with susceptibility to Chronic Obstructive Pulmonary Disease.PMID:26775557
This study confirms that the IREB2 variants contribute to an increased risk of lung cancer, whereas FAM13A predisposes to increased susceptibility to chronic obstructive pulmonary disease.PMID:26310313
IREB2 - candidate gene for Chronic Obstructive Pulmonary Disease identified by Genome-wide association studies.PMID:26527870
Irp2 expression is increased in airway epithelial cells exposed to cigarette smoke.PMID:26752519
IRP2 can regulate the expression of TfR and Fn by changing its own protein expression and thereby regulate iron metabolism.PMID:25117307
Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD.PMID:25101718
Haplotypes of IREB2 carrying major alleles of rs2568494 (G), rs2656069 (A), rs10851906 (A), rs965604 (C) and minor alleles of rs1964678 (T), rs12593229 (T) showed negative correlation with lung function amongst South Indian male smokers with COPD.PMID:24587150
IRE2 is located within genes previously associated with chronic obstructive pulmonary disease susceptibility.PMID:25006744
Ascorbate-induced up-regulation of cellular ferroportin levels was associated with increased levels of the iron regulatory protein IRP2, and the hypoxia-inducible factor HIF2alpha.PMID:24394537
dysregulation of IRP2 is an early nodal point underlying altered iron metabolism in breast cancer and may contribute to poor outcome of some patients with breast cancerPMID:24285726
IREB2 polymorphisms were associated with chronic obstructive pulmonary disease in non-smoking Chinese Han subjectsPMID:22914670
A replication of association between two SNPs previously associated with COPD (CHRNA3/5 and IREB2), as well as an association with COPD of one locus initially associated with lung function (ADCY2).PMID:22461431
Ggenetic polymorphisms of the iron regulatory protein 1 and 2 genes may be associated with development of age-related macular degeneration.PMID:22331484
The data showed that IREB2 and CHRNA3 are potential genetic modifiers of chronic obstructive pulmonary disease in individuals with severe alpha-1 antitrypsin deficiency and may be sex-specific in their impact.PMID:22356581
IRP2 may affect the expressions of transferrin receptor and ferritin in lung adenocarcinoma A549 cells by changing the amount of protein and regulating the iron metabolism.PMID:22093897
under physiological, iron-sufficient conditions, the steady-state level of IRP2 in HEK293A cells is regulated by the nonproteasomal pathway.PMID:21558272
an apparent pro-oncogenic activity of IRP2 depends on its specific 73 amino acids insert, providing further evidence for a link between IRPs and cancer biology.PMID:20405006
confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggested a new pathway in COPD pathogenesis invoking iron homeostasisPMID:21320324
variants in the IREB2 gene were only significantly associated with FEV.PMID:20656943
gene coding and flanking regions were sequenced and examined for mutations that might modulate the iron burden of individuals harboring the common mutant hemochromatosis HFE genotype or cause hemochromatosis independent of mutations in the HFE genePMID:11783942
Multiple, conserved iron-responsive elements in the 3'-untranslated region of transferrin receptor mRNA enhance binding of iron regulatory protein 2PMID:12200453
data suggest that the differential regulation of IRP1 and IRP2 during hypoxia may be important for cellular adaptation to low oxygen tension.PMID:12855587
2-oxoglutarate-dependent dioxygenase activity may be involved in the oxygen and iron regulation of IRP2 protein stabilityPMID:12888568
Mutations in the IRP2 gene are not a common cause of Parkinson Diseasse associated with SN iron accumulation.PMID:15057521
IRP2 degradation involving 2-oxoglutarate-dependent oxygenase does not require the E3 ubiquitin ligase activity of pVHLPMID:15777842
IRP2 exists as monomer in both the apo-IRP2 form and in the IRP2/iron regulatory element (IRE) complex.PMID:15938636
IRP2 is the major regulator of intracellular iron homeostasis in humans.PMID:16503547
Two mutations,rs2656070 and rs13180 showed statistically significant skewing of allelic and genotypic distributions between Alzheimer's disease patients and controlsPMID:16914832
Results describe thet effect of hypoxia on the binding and subcellular distribution of iron regulatory proteins 1 and 2.PMID:17200797
analysis of the iron regulatory protein systemPMID:17604281
Hypertransfusional (>8 transfusions/year) iron in liver biopsies correlated with increased expression (RNA) for iron regulatory proteins 1 and 2 (3-, 9- to 11-fold) and hepcidin RNA: (5- to 8-fold), while ferritin H and L RNA remained constant.PMID:17613866
it is unlikely that the iron-dependent degradation of IRP2 is mediated by haem binding to the intact 73aa-Domain, since the sequence resembling an HRM in the 73aa-Domain does not provide an axial ligand of the cofactor unless this domain is cleavedPMID:17760563
These data demonstrate that HOIL-1 is not required for iron-dependent degradation of IRP2 in HEK293 cells, and suggest that a HOIL-1 independent mechanism is used for IRP2 degradation in most cell types.PMID:17822790
reversible phosphorylation of IRP2 during G(2)/M has a role in modulating the iron-independent expression of ferritin and other IRE-containing mRNAs during the cell cycle.PMID:18574241
A role for lysosomes in the turnover of IRP2 is reported.PMID:18582596
iron-independent mechanism for regulating iron homeostasis through the redox regulation of IRP2 cysteines.PMID:19223469
IREB2 has a role as a COPD susceptibility genePMID:19800047