E3 ubiquitin-protein ligase that regulates cell proliferation (PubMed:18794910, PubMed:23378536, PubMed:30595371). Involved in apoptosis regulation (PubMed:23378536, PubMed:30595371). Mediates ER stress-induced activation of JNK signaling pathway and apoptosis by promoting ERN1 activation and splicing of XBP1 mRNA (PubMed:23378536, PubMed:30595371). Also involved in protein trafficking and localization (PubMed:24387786). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with ERN1. Under certain conditions, relocalizes to recycling endosomes and to the inner nuclear membrane. Widely expressed (at protein level). In normal pancreas, expressed in islets, but not in ducts, nor in acini (at protein level). The RING-type zinc finger domain is required for E3 ligase activity and for promoting ER stress-induced JNK activation and apoptosis. Autoubiquitinated. The disease is caused by variants affecting the gene represented in this entry. Contaminating sequence. Potential poly-A sequence.