InterPro domain: IPR045133

Human IRE2 induces translational repression through 28S ribosomal RNA cleavage in response to ER stress [ 1 ]. However, mouse IRE2 does not have this function, instead, it plays a role in expression of the DDIT3 transcription factor, required for the unfolded-protein response, growth arrest and apoptosis [ 2 ].

This entry includes IRE1/2 and related proteins. Human IRE1 is a transmembrane protein kinase essential for the endoplasmic reticulum (ER) unfolded protein response (UPR) [ 3 , 4 , 4 , 5 , 6 , 7 ]. IRE1 is activated by autophosphorylation through its cytoplasmic kinase domain, and this leads to activation of the C-terminal ribonuclease domain, which splices Xbp1 mRNA generating an active Xbp1s transcriptional activator [ 8 ].

1. Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress. Nat. Cell Biol. 3, 158-64
2. Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J. 17, 5708-17
3. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107, 881-91
4. Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha. J Biol Chem 278, 17680-7
5. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 12, 1812-24
6. Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J 30, 894-905
7. A critical role of DDRGK1 in endoplasmic reticulum homoeostasis via regulation of IRE1α stability. Nat Commun 8, 14186