Recombinant human IRE1 (mutated R728A) protein (Active)

Supplementary info

This supplementary information is collated from multiple sources and compiled automatically.

Activity summary

The inositol-requiring enzyme 1 (IRE1) also known as ERN1 or IRE1 alpha is a critical endoplasmic reticulum (ER) stress sensor. It has a molecular weight of approximately 110 kDa. IRE1 is expressed in various cell types and tissues particularly in those subject to a high degree of protein synthesis such as the liver pancreas and secretory cells. This protein plays a dual role as both a RNase and a kinase which enables it to respond swiftly to misfolded proteins accumulating in the ER.

Biological function summary

IRE1 is an important regulator in the unfolded protein response (UPR) a cellular reaction to stress in the ER. It operates as part of a complex mechanism facilitating the splicing of X-box binding protein 1 (XBP1) mRNA which results in the production of a potent transcription factor. IRE1 activity helps in restoring normal function of the cell by upregulating genes involved in protein folding secretion and degradation. Its actions are important for maintaining cellular homeostasis during stressful conditions.

Pathways

IRE1 is an integral component of the UPR pathway which works to alleviate ER stress. It interacts closely with other UPR transducers such as activating transcription factor 6 (ATF6) and protein kinase RNA-like ER kinase (PERK). IRE1 connects with the XBP1 pathway facilitating adaptive responses that enhance protein-folding capacity lipid biosynthesis and ER-associated degradation. Altogether these pathways mediate cell survival or apoptosis depending on the severity of the stress.

Associated diseases and disorders

IRE1 has significant involvement in conditions like diabetes and cancer. In the context of diabetes improper UPR signaling due to chronic ER stress leads to insulin resistance and pancreatic beta-cell dysfunction. In cancer IRE1 modulates tumor microenvironment and promotes cancer cell survival under hypoxic conditions. The XBP1 pathway linked with IRE1 also plays a substantial role in these diseases by influencing cell proliferation and apoptosis. Understanding the mechanisms of IRE1 in these conditions might provide therapeutic insights.