E3 ubiquitin-protein ligase that regulates cell proliferation (PubMed:20015074). Involved in apoptosis regulation. Mediates ER stress-induced activation of JNK signaling pathway and apoptosis by promoting ERN1 activation and splicing of XBP1 mRNA (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. Under certain conditions, relocalizes to recycling endosomes and to the inner nuclear membrane. Widely expressed (at protein level). Lowest levels in the liver, moderate levels in the heart, intestine and spleen, and high levels in skeletal muscle, kidney, proventriculus and brain. Also expressed in inner ear after noise exposure. Expressed in skeletal muscle tissue during embryonic development and for 2 weeks after hatching; becomes undetectable 3 weeks after hatching (at protein level). By myostatin. The RING-type zinc finger domain is required for E3 ligase activity and for promoting ER stress-induced JNK activation and apoptosis.