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 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 by the complex into the cytosol for subsequent destruction. Required for INSIG1 ubiquitination. May be required for EIF3 complex ubiquitination. 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 VHL. Interacts with MHC class I and HM13. Component of SCAP-SREBP complex composed of SREBF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SREBF2 proteolytic processing. Interacts with SREBF2 (via C-terminal domain). Interacts with SCAP; the interaction inhibits the interaction of SCAP with SEC24B and hampering the ER to Golgi transport of the SCAP-SREBP complex. Interacts with SEC24B. Interacts with INSIG1 and INSIG2. Interacts with EIF3F and EIF3H; the interaction leads to protein translation inhibitions in a ubiquitination-dependent manner. Interacts with XBP1; the interaction induces ubiquitination and degradation of XBP1. Interacts with AUP1, AMFR and UBE2G2; interaction with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR/gp78, leading to sterol-induced ubiquitination of HMGCR and its subsequent proteasomal degradation. The RING-type zinc finger domain may be essential for ubiquitin ligase activity. Autoubiquitinated. Ubiquitination is induced by sterol and leads to ist degradation via the ubiquitin-proteasome pathway.