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.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Sequence Similarities

Belongs to the aconitase/IPM isomerase family.

Cellular localization

• Cytoplasm

Alternative names

Iron-responsive element-binding protein 2, IRE-BP 2, Iron regulatory protein 2, IRP2, IREB2

Database links

swissprot:P48200 swissprot:P21399 entrezGene:48 entrezGene:3658 omim:147582 omim:100880