E3 ubiquitin 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.
Protein modification; protein ubiquitination.
Belongs to the TRIM/RBCC family. Contains 1 B box-type zinc finger. Contains 1 RING-type zinc finger.
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.
Endoplasmic reticulum membrane. Concentrates and colocalizes with p62/SQSTM1 and ZFYVE1 at the perinuclear endoplasmic reticulum.