Iron metabolism is essential for sustaining mammalian homeostasis. Iron uptake and distribution is a highly regulated process in mammalian cells that is monitored by two iron sensing proteins: IRP-1 and -2 (iron regulatory protein-1 and -2), also known as iron responsive element-binding protein-1 and -2 (IRE-BP-1 and -2) or aconitase 1 and 2. IRP-1 and IRP-2 are important soluble regulatory factors that mediate iron uptake and storage in mammalian cells. They are capable of either repressing translation or enhancing mRNA stability by associating with stem-loop motifs known as iron-responsive elements (IREs). IRPs respond to stress mediators, iron concentration and signaling factors, including nitrogen monoxide, cytokines and hydrogen peroxide.
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.
Subcellular Location:
Cytoplasm.
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.
Similarity:
Belongs to the aconitase/IPM isomerase family.
SWISS:
P48200
Gene ID:
3658
Database links:
Entrez Gene: 3658 Human
Entrez Gene: 475134 Dog
Entrez Gene: 6922 Mouse
Entrez Gene: 100153993 Pig
Entrez Gene: 64831 Rat
Omim: 147582 Human
SwissProt: P48200 Human
SwissProt: Q811J3 Mouse
SwissProt: B3VKQ2 Pig
SwissProt: Q62751 Rat
Unigene: 47231 Human
Unigene: 208991 Mouse
Unigene: 10132 Rat
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