IREB2

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]

Full Name

Iron Responsive Element Binding Protein 2

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.

Biological Process

Cellular iron ion homeostasisIEA:Ensembl
Citrate metabolic processManual Assertion Based On ExperimentIBA:GO_Central
Erythrocyte homeostasisIEA:Ensembl
Intestinal absorptionIEA:Ensembl
Iron ion homeostasisManual Assertion Based On ExperimentIMP:UniProtKB
Iron ion transportManual Assertion Based On ExperimentTAS:UniProtKB
Osteoclast differentiationIEA:Ensembl
Post-embryonic developmentIEA:Ensembl
Protoporphyrinogen IX biosynthetic processIEA:Ensembl
Tricarboxylic acid cycleManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Cytoplasm

Involvement in disease

Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia (NDCAMA):
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.

PTM

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.