E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated E2 ligases, and transfers it to substrates promoting their degradation. Mediates the degradation of a broad range of substrates, including endoplasmic reticulum membrane proteins (ERQC), soluble nuclear proteins and soluble cytoplasmic proteins (CytoQC). Component of the doa10 ubiquitin ligase complex, which is part of the ERAD-C pathway responsible for the rapid degradation of membrane proteins with misfolded cytoplasmic domains. Also recognizes the N-terminally acetylated residue of proteins as degradation signal (degron). 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. The RING-CH-type zinc finger domain is required for E3 ligase activity. Belongs to the DOA10/MARCH6 family.