E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130, PubMed:28827405). Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130, PubMed:28842558). Also promotes the degradation of normal but naturally short-lived proteins such as SGK. Protects cells from ER stress-induced apoptosis. Protects neurons from apoptosis induced by polyglutamine-expanded huntingtin (HTT) or unfolded GPR37 by promoting their degradation (PubMed:17141218). Sequesters p53/TP53 in the cytoplasm and promotes its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation and apoptosis (PubMed:17170702). Mediates the ubiquitination and subsequent degradation of cytoplasmic NFE2L1 (By similarity). During the early stage of B cell development, required for degradation of the pre-B cell receptor (pre-BCR) complex, hence supporting further differentiation into mature B cells (By similarity). 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. Homodimer (PubMed:16289116). Interacts with p53/TP53 (PubMed:17170702). Interacts with HTT (PubMed:17141218). Component of the HRD1 complex, which comprises at least SYNV1/HRD1, DERL1/2, FAM8A1, HERPUD1/HERP, OS9, SEL1L and UBE2J1 (PubMed:16289116, PubMed:16186509, PubMed:18264092, PubMed:26471130, PubMed:28827405). FAM8A1 is stabilized by interaction with SYNV1, which prevents its proteasomal degradation. OS9 and UBE2J1 recruitment to the complex may be mediated by SEL1L (PubMed:28827405). SYNV1 assembles with SEL1L and FAM8A1 through its transmembrane domains, but interaction with its cytoplasmic domain is required to confer stability to FAM8A1 and enhance recruitment of HERPUD1 (PubMed:28827405). The HRD1 complex also associates with VIMP and may transfer misfolded proteins from the endoplasmic reticulum to VCP (PubMed:16289116). May form a complex with ERLEC1; HSPA5; OS9 AND SEL1L (PubMed:18502753, PubMed:18264092). Interacts with VCP (PubMed:16289116, PubMed:16186510). Interacts with UBXN6 (PubMed:18656546). Interacts with BAG6 (PubMed:21636303). Interacts with NFE2L1 (By similarity). Interacts (via N-terminus) with components of the pre-B cell receptor, including IGLL1 and VPREB1 (By similarity). Interacts with CREB3L3; this interaction leads to CREB3L3 ubiquitination and proteasomal degradation (By similarity). Ubiquitously expressed, with highest levels in liver and kidney (at protein level). Up-regulated in synovial tissues from patients with rheumatoid arthritis (at protein level). By endoplasmic reticulum stress-inducing agents such as thapsigargin, tunicamycin or brefeldin A, but not by heat shock. The RING-type zinc finger is required for E3 ligase activity. Not N-glycosylated. Auto-ubiquitinated. In certain aggressive cases of activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL), plays a role in the degradation of misfolded N-terminal mutated PRDM1 proteins. Belongs to the HRD1 family.