E3-ubiquitin ligase; acts as a negative regulator of cell proliferation through mechanisms involving G2/M arrest and cell death ( ). Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER) . Affects SREBP processing by hindering the SREBP-SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression (, ). Involved in the sterol-accelerated degradation of HMGCR (, ). This is achieved through binding of RNF139 to INSIG1 and/or INSIG2 at the ER membrane . In addition, interaction of RNF139 with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR, leading to ubiquitination of HMGCR . The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction (, ). Required for INSIG1 ubiquitination . May be required for EIF3 complex ubiquitination .
Subcellular locations: Endoplasmic reticulum membrane
Highly expressed in testis, placenta and adrenal gland. Moderate expression in heart, brain, liver, skeletal muscle and pancreas, and low expression in lung and kidney.