Endoplasmic reticulum (ER) membrane anchored E3 ligase involved in the retrotranslocation and turnover of membrane and secretory proteins from the ER through a set of processes named ER-associated degradation (ERAD). This process acts on misfolded proteins as well as in the regulated degradation of correctly folded proteins. Enhances ionizing radiation-induced p53/TP53 stability and apoptosis via ubiquitinating MDM2 and AKT1 and decreasing AKT1 kinase activity through MDM2 and AKT1 proteasomal degradation. Regulates ER stress-induced autophagy, and may act as a tumor suppressor (PubMed:22178386). Also plays a role in innate immune response by stimulating NF-kappa-B activity in the TLR2 signaling pathway. Ubiquitinates TRAF6 via the 'Lys-29'-linked polyubiquitination chain resulting in NF-kappa-B activation (PubMed:28087809). Participates as well in T-cell receptor-mediated NF-kappa-B activation (PubMed:25088585). In the presence of TNF, modulates the IKK complex by regulating IKBKG/NEMO ubiquitination leading to the repression of NF-kappa-B (PubMed:25152375). 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 (via C-terminal domain) with VCP. Interacts with AKT1; the interaction ubiquitinates AKT1 and leads to its proteasomal degradation. Interacts with MDM2; the interaction ubiquitinates AKT1 and leads to its proteasomal degradation. Interacts with p62/SQSTM1. Interacts with TRAF6 (PubMed:28087809). Interacts with IKBKG/NEMO (PubMed:25152375). Concentrates and colocalizes with p62/SQSTM1 and ZFYVE1 at the perinuclear endoplasmic reticulum. The coiled-coil domain is required for the induction of autophagy during endoplasmic reticulum (ER) stress. The RING-type zinc finger is required for auto-polyubiquitination. The C-terminal domain transmembrane domain is indispensable for the localization to the ER. Auto-ubiquitinated; requires the RING-type zinc finger. Auto-polyubiquitination leads to proteasomal degradation. Located on chromosome 13 within the minimal deletion region for B-cell chronic lymphocytic leukemia. Belongs to the TRIM/RBCC family.