E3 ubiquitin-protein ligase that regulates cell proliferation. Involved in apoptosis regulation. Mediates ER stress-induced activation of JNK signaling pathway and apoptosis by promoting ERN1 activation and splicing of XBP1 mRNA. Also involved in protein trafficking and localization. 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. The RING-type zinc finger domain is required for E3 ligase activity and for promoting ER stress-induced JNK activation and apoptosis. Autoubiquitinated.