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. Note: This description may include information from UniProtKB.
Protein type: Protein kinase, Ser/Thr (non-receptor); Ribonuclease; Endoplasmic reticulum; Apoptosis; EC 126.96.36.199; Protein kinase, Other; Chaperone; Membrane protein, integral; Kinase, protein; Other group; IRE family
Cellular Component: endoplasmic reticulum membrane; mitochondrion; endoplasmic reticulum; cytoplasm; integral to endoplasmic reticulum membrane; nuclear inner membrane
Molecular Function: endoribonuclease activity; identical protein binding; protein serine/threonine kinase activity; protein binding; protein homodimerization activity; enzyme binding; magnesium ion binding; Hsp70 protein binding; Hsp90 protein binding; ADP binding; ATP binding
Biological Process: transcription, DNA-dependent; unfolded protein response; protein amino acid autophosphorylation; positive regulation of RNA splicing; protein amino acid phosphorylation; activation of JNK activity; cellular protein metabolic process; unfolded protein response, activation of signaling protein activity; regulation of transcription, DNA-dependent; endothelial cell proliferation; mRNA catabolic process; cell cycle arrest; regulation of macroautophagy; mRNA cleavage
LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.