Alternative titles; symbols
HGNC Approved Gene Symbol: ERN2
Cytogenetic location: 16p12.2 Genomic coordinates (GRCh38) : 16:23,690,310-23,713,222 (from NCBI)
Various noxious circumstances lead to the accumulation of unfolded protein intermediates in the endoplasmic reticulum (ER) and trigger a stress response known as the unfolded protein response (UPR). In mammalian cells, the UPR induces transcription of genes encoding ER protein chaperones, such as BiP (138120). ER stress activates other pathways, including the expression of the CHOP (126337) transcription factor, and is also linked to the development of programmed cell death. In S. cerevisiae, the ER-associated transmembrane Ire1 (inositol-requiring-1)/Ern1 protein kinase is the UPR proximal sensor that monitors the status of unfolded protein inside the ER lumen. Wang et al. (1998) isolated cDNAs encoding a mouse Ire1 homolog, which they called mIre1 or Ern2. Like yeast Ire1, the predicted mouse Ern2 protein is a putative type I transmembrane protein and contains a C-terminal kinase/endonuclease effector domain. The C-terminal regions of Ire1 and Ern2 are 40% identical. When expressed in mammalian cells, Ern2 localized to the ER. Overexpression activated both BiP and CHOP expression, and also led to the development of programmed cell death. Wang et al. (1998) concluded that a single upstream component, Ern2, plays a role in multiple facets of the ER stress response in mammalian cells. Wang et al. (1998) identified a partial cDNA encoding human ERN2. They noted that ERN2 is distinct from ERN1 (604033), a second human Ire1 homolog.
By analysis of a radiation hybrid panel, Wang et al. (1998) mapped the ERN2 gene to mouse chromosome 7 and to human chromosome 16, in regions that show homology of synteny. The authors determined that the human ERN2 gene is located 55 bp from the PLK (602098) gene in a tail-to-tail configuration.
Wang, X.-Z., Harding, H. P., Zhang, Y., Jolicoeur, E. M., Kuroda, M., Ron, D. Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J. 17: 5708-5717, 1998. [PubMed: 9755171] [Full Text: https://doi.org/10.1093/emboj/17.19.5708]