RNF139

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..

Function from UniProtKB (Q8WU17), read 2026-09-23. CC BY 4.0.