E3 ubiquitin-protein ligase that regulates cell proliferation (PubMed:19292867). Involved in apoptosis regulation (By similarity). Mediates ER stress-induced activation of JNK signaling pathway and apoptosis by promoting ERN1 activation and splicing of XBP1 mRNA (By similarity). Also involved in protein trafficking and localization (By similarity). 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. The mature protein is subjected to extensive proteolysis that leads to the shedding of the ectodomain into the lumen of vesicles and the release of the C-terminal fragment into the cytosol (PubMed:20230530). Not detected in early endosomes (PubMed:20230530). Treatment of the cells with either PMA or ionomycin stabilizes the full-length protein which relocalizes to recycling endosomes and to the inner nuclear membrane (PubMed:20230530). Expressed in the brain, heart, kidney, liver and spleen. Higher expression in adult tissues compared to the embryonic counterparts. The RING-type zinc finger domain is required for E3 ligase activity and for promoting ER stress-induced JNK activation and apoptosis. Autoubiquitinated. N-glycosylated and also modified with chondroitin sulfate.