E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC6 and UBC7 E2 ligases, and transfers it to substrates promoting their degradation (PubMed:11641273, PubMed:16179952, PubMed:16437165, PubMed:16873066, PubMed:17051211, PubMed:18812321, PubMed:20110468). Mediates the degradation of a broad range of substrates, including endoplasmic reticulum membrane proteins (ERQC), soluble nuclear proteins and soluble cytoplasmic proteins (CytoQC) (PubMed:11641273, PubMed:16179952, PubMed:16437165, PubMed:16873066, PubMed:17051211, PubMed:18812321, PubMed:20110468). 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 (PubMed:16873066). ERAD-C substrates are ubiquitinated through DOA10 in conjunction with the E2 ubiquitin-conjugating enzymes UBC6 and UBC7-CUE1 (PubMed:11641273, PubMed:16179952, PubMed:16437165, PubMed:16873066, PubMed:17051211, PubMed:18812321, PubMed:20110468). Ubiquitinated substrates are then removed to the cytosol via the action of the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex and targeted to the proteasome (PubMed:11641273, PubMed:16179952, PubMed:16437165, PubMed:16873066, PubMed:17051211, PubMed:18812321, PubMed:20110468). Also recognizes the N-terminally acetylated residue of proteins as degradation signal (degron) (PubMed:20110468). N-terminally acetylated target proteins include MATALPHA2, TBF1, SLK19, YMR090W, HIS3, HSP104, UBP6 and ARO8 (PubMed:20110468). Catalyzes ubiquitination of mislocalized tail-anchored proteins that are extracted from the mitochondrion membrane by MSP1: following extraction, mistargeted proteins are transferred to the endoplasmic reticulum, where they are ubiquitinated by DOA10 and degraded by the proteasome (PubMed:31445887). 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. Component of the DOA10 ubiquitin ligase complex which contains E3 ligase SSM4/DOA10 and CDC48-binding protein UBX2/SEL1. The DOA10 complex interacts with the heterotrimeric CDC48-NPL4-UFD1 ATPase complex which is recruited by UBX2/SEL1 via its interaction with CDC48. Interacts with its associated ubiquitin conjugating enzymes UBC6 and UBC7 with its membrane anchor CUE1. Interacts with PEX29. The RING-CH-type zinc finger domain is required for E3 ligase activity. Belongs to the DOA10/MARCH6 family.