Iron Responsive Element Binding Protein 2 (IREB2)

The second IREBP, represented by 'clone 10.1,' contained an inserted stretch of 73 amino acids between amino acids 37 and 38 of IREB1; the IREB2 gene product lacked a region homologous to the sequences between amino acids 436 and 470 of IREB1.Human IRP2 is 57% identical to human IRP1. IRP2 has a molecular mass of 105 kD, which is slightly larger than that of IRP1 due to a 73-amino acid insertion. IRP2-null cells misregulated iron metabolism when cultured in 3 to 6% oxygen, which is comparable to physiologic tissue concentrations, but not in 21% oxygen, a concentration that activated IRP1 and allowed it to substitute for IRP2. Thus, IRP2 dominates regulation of mammalian iron homeostasis because it alone registers iron concentrations and modulates its RNA-binding activity at physiologic oxygen tensions.