IRE1: a ser/thr protein kinase that possess endonuclease activity. Important in altering gene expression as a response to endoplasmic reticulum based stress signals. Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain, which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis. The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain. Ubiquitously expressed. High levels observed in pancreatic tissue. Functionally connected with insulin biosynthesis in pancreatic beta cells. Homodimer; disulfide-linked. Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges. Also binds HSPA5, a negative regulator of the unfolded protein response. This interaction may disrupt homodimerization and prevent activation of IRE1.
Protein type: Chaperone; EC 2.7.11.1; Endoplasmic reticulum; Apoptosis; Protein kinase, Other; Kinase, protein; Membrane protein, integral; Ribonuclease; Protein kinase, Ser/Thr (non-receptor); Other group; IRE family
Chromosomal Location of Human Ortholog: 17q24.2
Cellular Component: cytoplasm; endoplasmic reticulum; endoplasmic reticulum membrane; integral to endoplasmic reticulum membrane; mitochondrion; nuclear inner membrane
Molecular Function: ADP binding; ATP binding; endoribonuclease activity; enzyme binding; Hsp70 protein binding; Hsp90 protein binding; identical protein binding; magnesium ion binding; protein binding; protein homodimerization activity; protein serine/threonine kinase activity
Biological Process: activation of JNK activity; cell cycle arrest; endothelial cell proliferation; mRNA catabolic process; mRNA cleavage; positive regulation of RNA splicing; protein amino acid autophosphorylation; protein amino acid phosphorylation; regulation of macroautophagy; regulation of transcription, DNA-dependent; transcription, DNA-dependent; unfolded protein response, activation of signaling protein activity
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