E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC1 and UBC7 E2 ligases, and transfers it to substrates promoting their degradation. Mediates the degradation of endoplasmic reticulum proteins (ERQC), also called ER-associated degradation (ERAD). Component of the HRD1 ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M pathways responsible for the rapid degradation of soluble lumenal and membrane proteins with misfolded lumenal domains (ERAD-L), or ER-membrane proteins with misfolded transmembrane domains (ERAD-M). In ERAD-L, facilitates retrotranslocation of misfolded proteins from the ER lumen through the ER membrane in conjunction with DER1 (PubMed:32327568). Both proteins have lateral gates facing each other which form a channel through the ER membrane and which distort the membrane region between the lateral gates, making it much thinner than a normal phospholipid bilayer (PubMed:32327568). Substrates insert into the membrane as a hairpin loop with one strand interacting with DER1 and the other with HRD1. ERAD-L substrates are ubiquitinated through HRD1 in conjunction with the E2 ubiquitin-conjugating enzymes UBC1 and UBC7-CUE1. Ubiquitinated substrates are then removed to the cytosol via the action of the CDC48-NPL4-UFD1 ATPase complex and targeted to the proteasome. ERAD-M substrates are processed by the same HRD1-HRD3 core complex, but only a subset of the other components is required for ERAD-M. 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. Monomer (PubMed:32327568). Has also been shown to form homodimers (PubMed:28682307). However, dimer assembly is likely to be non-physiological (PubMed:32327568). Forms homooligomers in a USA1-dependent manner (PubMed:20005842, PubMed:21074049). However, can function as a monomer in ERAD-L so the role of USA1-dependent oligomerization remains unclear (PubMed:32327568). Component of the HRD1 ubiquitin ligase complex which contains the E3 ligase HRD1, its cofactors HRD3, USA1 and DER1, substrate recruiting factor YOS9 and CDC48-binding protein UBX2 (PubMed:16873066). Within the complex, interacts directly with HRD3 and USA1 and indirectly with DER1 (PubMed:11018054, PubMed:16619026, PubMed:20005842, PubMed:21074049, PubMed:28682307). In ERAD-L, HRD3 and YOS9 jointly bind misfolded glycoproteins in the endoplasmic reticulum (ER) lumen (PubMed:32327568). Movement of ERAD-L substrates through the ER membrane is facilitated by HRD1 and DER1 which have lateral gates facing each other and which distort the membrane region between the lateral gates, making it much thinner than a normal phospholipid bilayer (PubMed:32327568). Substrates insert into the membrane as a hairpin loop with one strand interacting with DER1 and the other with HRD1 (PubMed:32327568). The HRD1 complex interacts with the heterotrimeric CDC48-NPL4-UFD1 ATPase complex which is recruited by UBX2 via its interaction with CDC48 and which moves ubiquitinated substrates to the cytosol for targeting to the proteasome (PubMed:16873066, PubMed:16619026). The HRD1 complex interacts with the ERAD substrates HMG1 and HMG2 (PubMed:11390656). Interacts with the associated E2 ubiquitin conjugating enzymes UBC1 and UBC7 with its membrane anchor CUE1 (PubMed:11146622). Impaired degradation of proteins with misfolded intramembrane or lumenal domains. Present with 2660 molecules/cell in log phase SD medium. Belongs to the HRD1 family.