E3 ubiquitin protein ligase that is part of an apoptotic signaling pathway activated by endoplasmic reticulum stress. Stimulates the expression of proteins specific of the unfolded protein response (UPR), ubiquitinates BNIP1 and regulates its localization to the mitochondrion and induces calcium release from the endoplasmic reticulum that ultimately leads to cell apoptosis. Plays a role in the maintenance of intestinal homeostasis and clearance of enteric pathogens. Upon NOD2 stimulation, ubiquitinates the ER stress sensor activating transcription factor 6/ATF6 and promotes the unfolded protein response UPR. Participates in basal level of autophagy maintenance by regulating the ubiquitination of EPHB2. Upon stimulation by ligand EFNB1, ubiquitinates EPHB2 and further recruits MAP1LC3B for autophagy induction. Controls nutrient sensing by ubiquitinating Sestrin-2/SESN2, which is an intracellular sensor of cytosolic leucine and inhibitor of mTORC1 activity. 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 BNIP1. The RING-type domain is required for ubiquitination. Polyubiquitinated. 'Lys-29' autoubiquitination leads to proteasomal degradation.