ERN1
ERN1 (endoplasmic reticulum to nucleus signalling 1, also known as IRE1 or IRE1P) is a transmembrane serine/threonine-protein kinase and endoribonuclease. It acts as a key sensor of unfolded proteins in the endoplasmic reticulum and initiates the unfolded protein response. Browse Assay Genie's current range of ERN1 research reagents below, or read on for the biology behind the target.
ERN1 is a key sensor of the endoplasmic reticulum (ER) unfolded protein response (UPR). In unstressed cells, its ER luminal domain is held in an inactive monomeric state by binding to the ER chaperone HSPA5/BiP. When misfolded proteins accumulate in the ER, HSPA5/BiP is released. The luminal domain can then homodimerise, which promotes autophosphorylation of the kinase domain and activates the endoribonuclease activity.
The endoribonuclease activity is specific for XBP1 mRNA, from which it excises 26 nucleotides. The spliced transcript encodes a transcriptional activator that up-regulates expression of UPR target genes. ERN1 also acts as an upstream signal for ER stress-induced, GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to the cell membrane, by modulating the expression and localisation of SEC16A. The UPR is conserved from yeast to mammals. It activates genes involved in degrading misfolded proteins, regulating protein synthesis and activating molecular chaperones.
The ERN1 gene encodes the transmembrane protein inositol-requiring enzyme 1, which contains two catalytic domains: a serine/threonine-protein kinase domain and an endoribonuclease domain. It belongs to the protein kinase superfamily and the Ser/Thr protein kinase family. HGNC places it in the endoribonucleases group and the endoplasmic reticulum to nucleus signalling family, and the mouse ortholog is Ern1. The previous name was ER to nucleus signalling 1. The ERN1 protein is a common subject in studies of ER stress and protein-folding homeostasis.
ERN1 senses misfolded proteins in the endoplasmic reticulum and triggers the UPR signalling pathway, making it central to ER stress research.
Its endoribonuclease activity removes 26 nucleotides from XBP1 mRNA, producing a transcriptional activator of UPR target genes.
Release of HSPA5/BiP from the luminal domain allows dimerisation and activation, a model for studying chaperone-controlled signalling.
ERN1 signals upstream of GORASP2-mediated unconventional CFTR trafficking to the cell membrane by modulating SEC16A expression and localisation.
ERN1 is a serine/threonine kinase and endoribonuclease that senses unfolded proteins in the endoplasmic reticulum. Once activated, it splices XBP1 mRNA, producing a transcription factor that up-regulates UPR target genes. It also acts upstream of unconventional CFTR trafficking to the cell membrane.
ERN1 stands for endoplasmic reticulum to nucleus signalling 1. Aliases are IRE1 and IRE1P, and the previous name was ER to nucleus signalling 1. UniProt lists the protein as serine/threonine-protein kinase/endoribonuclease IRE1, and NCBI describes it as inositol-requiring enzyme 1.
The UPR that ERN1 triggers is conserved from yeast to mammals. The mouse ortholog is Ern1. ERN2 is a related member of the endoplasmic reticulum to nucleus signalling family. Check the datasheet of any product for its validated reactivity.
Related members of the endoplasmic reticulum to nucleus signalling family with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O75460; product specifications from Assay Genie datasheets.