{"gene":"UBE2J1","run_date":"2026-06-10T10:51:56","timeline":{"discoveries":[{"year":2002,"finding":"UBE2J1 (mammalian Ubc6 homologue) is localized to the cytoplasmic surface of the ER membrane via a C-terminal transmembrane domain, analogous to yeast Ubc6p. Overexpression of wild-type or dominant-negative alleles specifically affects ERAD of misfolded TCRα and mutant CFTR, establishing UBE2J1 as a functional E2 enzyme in mammalian ERAD.","method":"Dominant-negative allele overexpression, subcellular localization analysis, ERAD substrate degradation assays","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — dominant-negative approach plus localization, single lab with two orthogonal methods","pmids":["12082160"],"is_preprint":false},{"year":2000,"finding":"UBE2J1 (NCUBE1) encodes a noncanonical ubiquitin-conjugating enzyme with a conserved noncanonical active site and a C-terminal transmembrane domain, constituting a distinct UBC family related to yeast Ubc6 and predicted to localize to the ER.","method":"cDNA cloning, sequence analysis, differential display on chondrocytes","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/sequence analysis only, no direct functional assay","pmids":["10708578"],"is_preprint":false},{"year":2005,"finding":"UBE2J1 (Ubc6) binds the E3 ligase c-IAP1 and serves as its cognate E2 in vitro. Upon TNF-R2 engagement, UBE2J1 co-localizes with translocated TRAF2/c-IAP1 in a perinuclear ER-associated compartment, and a catalytically inactive UBE2J1 mutant inhibits TNF-α-induced TRAF2 ubiquitination and degradation.","method":"In vitro ubiquitination assay, confocal co-localization, catalytically inactive mutant overexpression","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro E2/E3 assay plus dominant-negative in vivo, single lab, two orthogonal methods","pmids":["15861135"],"is_preprint":false},{"year":2011,"finding":"UBE2J1 partners with the E3 ligase HRD1 (Synoviolin) in a complex that also includes Derlin 1 and p97 to ubiquitinate and dislocate misfolded MHC class I heavy chains (non-β2m-bound) for ERAD. HRD1 and UBE2J1 discriminate misfolded MHC I from properly assembled MHC I-β2m-peptide heterotrimers. HRD1 is also required for degradation of the HFE-C282Y hemochromatosis mutant.","method":"siRNA functional screen, co-immunoprecipitation, ubiquitination assay, dislocation assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — siRNA screen, reciprocal Co-IP, ubiquitination assay, and dislocation assay; multiple orthogonal methods in single rigorous study","pmids":["21245296"],"is_preprint":false},{"year":2013,"finding":"UBE2J1 is phosphorylated at Ser184 by MK2 (MAPKAP kinase-2) upon p38 MAPK-activating cytosolic stress and LPS stimulation. MK2 directly interacts with UBE2J1 (pulldown) and phosphorylates recombinant UBE2J1 in vitro; the S184A mutant is not phosphorylated. UBE2J1 Ser184 phosphorylation is abrogated in MK2/MK3-deficient cells. UBE2J1 contributes to MK2-dependent TNFα biosynthesis. However, the S184A mutant retains ubiquitinating activity toward TCRα, so phosphorylation at Ser184 does not regulate catalytic activity directly.","method":"Phosphoproteomics, in vitro kinase assay with recombinant proteins, pulldown assay, MK2/MK3 knockout cells, ubiquitination assay","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro kinase assay with mutagenesis, confirmed in knockout cells, phosphoproteomics; multiple orthogonal methods","pmids":["24020373"],"is_preprint":false},{"year":2014,"finding":"Ube2j1 knockout mice have reduced viability and male sterility due to a defect in late spermiogenesis (spermatid cytoplasm removal is incomplete), establishing a non-redundant physiological role for UBE2J1 in the ubiquitin-proteasome system during spermatogenesis.","method":"Ube2j1 knockout mouse model, ultrastructural analysis, fertility assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic knockout with defined cellular phenotype confirmed by ultrastructural analysis; clean loss-of-function model","pmids":["25320092"],"is_preprint":false},{"year":2017,"finding":"UBE2J1 phosphorylation at Ser184 (phospho-mimic S184D) is required for recovery from transient ER stress; the phospho-null S184A mutant cannot rescue cells. The E3 ligase c-IAP1 preferentially binds phosphorylated UBE2J1. Phosphorylated UBE2J1 is rapidly degraded by the proteasome during ER stress recovery.","method":"Ectopic expression of phospho-mimic and phospho-null mutants, co-immunoprecipitation, proteasome inhibitor treatment, cell viability assays","journal":"Journal of cell communication and signaling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — phospho-mutant rescue assay plus Co-IP, single lab, two orthogonal methods","pmids":["28321712"],"is_preprint":false},{"year":2018,"finding":"UBE2J1 negatively regulates type I interferon signaling by facilitating ubiquitination and degradation of transcription factor IRF3, thereby promoting RNA virus (Dengue) infection. Silencing UBE2J1 increases IFNβ production and impairs DENV infection; overexpression suppresses RIG-I-directed IFNβ promoter activation.","method":"RNAi screen, gene overexpression/knockdown, reporter assay, ubiquitination assay","journal":"Virology journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi plus overexpression plus reporter assay, single lab, multiple orthogonal methods","pmids":["30157886"],"is_preprint":false},{"year":2021,"finding":"UBE2J1 partners with the ER-anchored E3 ligase RNF26 as an E2/E3 pair localized in a perinuclear ER subdomain. The UBE2J1/RNF26 complex ubiquitylates SQSTM1/p62 on lysine 435, recruiting endosomal adaptors to immobilize endosomes/lysosomes in the perinuclear region, promoting EGFR trafficking to lysosomes and facilitating termination of EGF-induced AKT signaling.","method":"Co-immunoprecipitation, site-specific ubiquitylation mapping, live imaging, endosomal motility assays, EGFR/AKT signaling assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, site-specific ubiquitylation (K435), live imaging with functional readout, signaling assays; multiple orthogonal methods","pmids":["33472082"],"is_preprint":false},{"year":2022,"finding":"UBE2J1 forms an E2-E3 complex with TRIM25 and targets ribosomal protein RPS3 for ubiquitination and degradation at lysine 214. Degradation of RPS3 by UBE2J1/TRIM25 restrains NF-κB nuclear translocation and inactivates NF-κB signaling, suppressing colorectal cancer cell proliferation and metastasis.","method":"Co-immunoprecipitation, ubiquitination assay with K214 site mapping, NF-κB reporter, overexpression/knockdown in cell lines","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, site-specific ubiquitination assay, and signaling reporter; single lab, multiple orthogonal methods","pmids":["36567344"],"is_preprint":false},{"year":2023,"finding":"UBE2J1 is the critical E2 ubiquitin-conjugating enzyme responsible for androgen receptor (AR) ubiquitination and degradation. Loss of UBE2J1 disrupts AR ubiquitination, leading to AR protein accumulation and antiandrogen resistance in prostate cancer cells.","method":"UBE2J1 knockdown/knockout, ubiquitination assays, AR protein level and degradation assays, antiandrogen resistance assays","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with ubiquitination assay, single lab, two orthogonal methods","pmids":["38030789"],"is_preprint":false},{"year":2025,"finding":"The SEL1L-HRD1 ERAD complex requires direct SEL1L-HRD1 interaction for recruitment of UBE2J1. A knock-in L709P mutation in SEL1L that abolishes SEL1L-HRD1 binding impairs UBE2J1 recruitment, disrupts substrate ubiquitination, and causes accumulation and aggregation of misfolded ER proteins, resulting in neonatal lethality in mice.","method":"Knock-in mouse models (L709P, P699T, S658P mutations), biochemical interaction assays, ERAD substrate assays, protein aggregation analysis","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic knock-in mouse models with biochemical validation, preprint, single study","pmids":["bio_10.1101_2025.08.01.668162"],"is_preprint":true},{"year":2025,"finding":"UBE2J1 (UBC6) facilitates PRKN (Parkin)-mediated ubiquitination and degradation of AURKA, promoting AMPK phosphorylation at Thr172 in ovarian cancer cells. UBC6 interacts with PRKN as demonstrated by co-immunoprecipitation.","method":"Co-immunoprecipitation, ubiquitination assay, lentiviral knockdown, xenograft mouse model, AMPK phosphorylation assay","journal":"International immunopharmacology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP plus knockdown phenotype, single lab, limited mechanistic detail in abstract","pmids":["41237699"],"is_preprint":false}],"current_model":"UBE2J1 is an ER membrane-anchored E2 ubiquitin-conjugating enzyme that functions in ERAD by partnering with E3 ligases (principally HRD1 and RNF26) to ubiquitinate and dislocate misfolded ER substrates (including misfolded MHC class I, AR, and others) for proteasomal degradation; it is phosphorylated at Ser184 by MK2 downstream of p38 MAPK, which regulates its interaction with c-IAP1 and its stability, modulates ER stress recovery, and contributes to TNFα biosynthesis; it also acts outside classical ERAD to control endolysosomal positioning (via RNF26/SQSTM1-K435 ubiquitylation), innate immune suppression (via IRF3 ubiquitination), and spermiogenesis, underscoring its broad physiological roles as an ER-tethered ubiquitination hub."},"narrative":{"mechanistic_narrative":"UBE2J1 is an endoplasmic reticulum membrane-anchored E2 ubiquitin-conjugating enzyme that serves as a tethered ubiquitination hub for ER-associated degradation (ERAD) and related quality-control processes [PMID:12082160]. Anchored to the cytoplasmic face of the ER through a C-terminal transmembrane domain, it functions in the dislocation and proteasomal degradation of misfolded ER substrates, including misfolded TCRα, mutant CFTR, and non-β2m-bound MHC class I heavy chains [PMID:12082160, PMID:21245296]. In its principal ERAD role it acts as the cognate E2 for the SEL1L-HRD1 (Synoviolin) complex together with Derlin-1 and p97, with UBE2J1 recruitment dependent on direct SEL1L-HRD1 interaction; loss of this recruitment causes accumulation and aggregation of misfolded ER proteins [PMID:21245296, PMID:bio_10.1101_2025.08.01.668162]. UBE2J1 is phosphorylated at Ser184 by MK2 downstream of p38 MAPK, a modification that does not alter catalytic activity toward TCRα but governs preferential binding to the E3 ligase c-IAP1, drives proteasomal turnover of UBE2J1, and is required for recovery from transient ER stress and for MK2-dependent TNFα biosynthesis [PMID:24020373, PMID:28321712]. Beyond classical ERAD, UBE2J1 pairs with distinct E3 ligases to act in trafficking and signaling: with RNF26 it ubiquitylates SQSTM1/p62 at K435 to immobilize endosomes/lysosomes perinuclearly and promote EGFR trafficking [PMID:33472082], and it controls degradation of the androgen receptor, where its loss confers antiandrogen resistance in prostate cancer [PMID:38030789]. A Ube2j1 knockout mouse is subviable and male-sterile owing to defective late spermiogenesis, establishing a non-redundant physiological requirement [PMID:25320092].","teleology":[{"year":2000,"claim":"Established UBE2J1 as a distinct, ER-predicted E2 enzyme family member with a noncanonical active site, defining the molecular class before any functional assay existed.","evidence":"cDNA cloning and sequence analysis from chondrocyte differential display","pmids":["10708578"],"confidence":"Low","gaps":["Computational/sequence inference only, no direct enzymatic or localization assay","ER localization predicted not demonstrated","No substrate or E3 partner identified"]},{"year":2002,"claim":"Showed UBE2J1 is a bona fide functional ERAD E2 anchored to the ER membrane, answering whether the predicted enzyme actually drives misfolded-protein degradation in mammalian cells.","evidence":"Dominant-negative overexpression, subcellular localization, and ERAD substrate (TCRα, mutant CFTR) degradation assays","pmids":["12082160"],"confidence":"Medium","gaps":["Cognate E3 ligase not identified","Mechanism of substrate selection unresolved","Dominant-negative approach without endogenous loss-of-function"]},{"year":2005,"claim":"Identified c-IAP1 as a UBE2J1 E3 partner and linked the enzyme to TNF-R2 signaling, extending its activity beyond housekeeping ERAD into receptor-coupled ubiquitination.","evidence":"In vitro ubiquitination, confocal co-localization, and catalytically inactive mutant in TNF-R2-engaged cells","pmids":["15861135"],"confidence":"Medium","gaps":["Endogenous requirement not tested with knockout","Relationship to ER-anchoring of this activity unclear"]},{"year":2011,"claim":"Defined the HRD1/Derlin-1/p97 complex as the major UBE2J1 ERAD machinery and showed it discriminates misfolded from properly assembled MHC class I, clarifying how quality control selects substrates.","evidence":"siRNA functional screen, reciprocal co-IP, ubiquitination and dislocation assays","pmids":["21245296"],"confidence":"High","gaps":["Structural basis of substrate discrimination not resolved","How UBE2J1 is recruited into the complex not yet defined"]},{"year":2013,"claim":"Identified MK2-mediated Ser184 phosphorylation as a stress-responsive regulatory input on UBE2J1 and showed it does not control catalytic activity directly, separating regulation from enzymatic function.","evidence":"Phosphoproteomics, in vitro kinase assay with S184A mutagenesis, MK2/MK3 knockout cells, ubiquitination assay","pmids":["24020373"],"confidence":"High","gaps":["Functional consequence of Ser184 phosphorylation left open at this stage","Mechanistic link to TNFα biosynthesis not detailed"]},{"year":2014,"claim":"Demonstrated a non-redundant in vivo role for UBE2J1 in spermiogenesis, moving beyond cell-based ERAD assays to organismal physiology.","evidence":"Ube2j1 knockout mouse with ultrastructural and fertility analysis","pmids":["25320092"],"confidence":"High","gaps":["Specific spermatid substrates not identified","E3 partner mediating the spermiogenesis function unknown"]},{"year":2017,"claim":"Resolved the function of Ser184 phosphorylation by showing it is required for ER stress recovery, drives c-IAP1 binding, and triggers UBE2J1's own proteasomal degradation, defining a self-limiting regulatory loop.","evidence":"Phospho-mimic/phospho-null rescue, co-IP, proteasome inhibition, viability assays","pmids":["28321712"],"confidence":"Medium","gaps":["E3 responsible for phospho-UBE2J1 turnover not pinpointed","Single-lab phospho-mutant approach"]},{"year":2018,"claim":"Extended UBE2J1 into innate immunity by showing it degrades IRF3 to dampen type I interferon and favor RNA virus replication, revealing a pro-viral immunoregulatory role.","evidence":"RNAi screen, overexpression/knockdown, IFNβ reporter, ubiquitination assay in Dengue infection","pmids":["30157886"],"confidence":"Medium","gaps":["Cognate E3 ligase for IRF3 ubiquitination not identified","Direct vs indirect action on IRF3 not fully separated"]},{"year":2021,"claim":"Defined the UBE2J1/RNF26 E2-E3 pair and its substrate SQSTM1 (K435), explaining how ER-anchored ubiquitination spatially organizes the endolysosomal system and terminates EGFR/AKT signaling.","evidence":"Reciprocal co-IP, site-specific ubiquitylation mapping, live imaging, endosomal motility and EGFR/AKT assays","pmids":["33472082"],"confidence":"High","gaps":["Relationship between RNF26 and HRD1 pathways not integrated","Regulation of the perinuclear subdomain assembly unresolved"]},{"year":2022,"claim":"Identified a UBE2J1/TRIM25 pair degrading RPS3 at K214 to restrain NF-κB, adding a tumor-suppressive signaling output in colorectal cancer.","evidence":"Co-IP, K214 site-mapped ubiquitination, NF-κB reporter, overexpression/knockdown","pmids":["36567344"],"confidence":"Medium","gaps":["In vivo relevance beyond cell lines limited","Whether ER anchoring is required for this activity untested"]},{"year":2023,"claim":"Established UBE2J1 as the critical E2 for androgen receptor ubiquitination and degradation, linking its loss to antiandrogen resistance in prostate cancer.","evidence":"Knockdown/knockout, ubiquitination assays, AR degradation and resistance assays","pmids":["38030789"],"confidence":"Medium","gaps":["Cognate E3 for AR not defined in this work","Single-lab loss-of-function evidence"]},{"year":2025,"claim":"Showed that UBE2J1 recruitment to the ERAD machinery requires direct SEL1L-HRD1 interaction, and that disrupting it causes lethal accumulation of misfolded ER proteins, mechanistically anchoring UBE2J1 to complex assembly.","evidence":"Knock-in mouse models (L709P, P699T, S658P), biochemical interaction and ERAD substrate/aggregation assays (preprint)","pmids":["bio_10.1101_2025.08.01.668162"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed","Direct UBE2J1-SEL1L/HRD1 contact residues not mapped"]},{"year":null,"claim":"How UBE2J1 is partitioned among its many E3 partners (HRD1, RNF26, c-IAP1, TRIM25, PRKN) and substrates across distinct subcellular contexts, and what determines partner/substrate selection, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of UBE2J1 in any of its E2-E3 complexes","Determinants of E3-partner choice unknown","Integration of stress-regulated phosphorylation with each pathway not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,3,8]},{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0,2,3]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0,3,8]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,3,11]},{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[4,6]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[8]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[8,9,10]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[7]}],"complexes":["SEL1L-HRD1 ERAD complex","UBE2J1/RNF26 E2-E3 complex"],"partners":["HRD1","SEL1L","RNF26","SQSTM1","C-IAP1","MK2","TRIM25","PRKN"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y385","full_name":"Ubiquitin-conjugating enzyme E2 J1","aliases":["E2 ubiquitin-conjugating enzyme J1","Non-canonical ubiquitin-conjugating enzyme 1","NCUBE-1","Yeast ubiquitin-conjugating enzyme UBC6 homolog E","HsUBC6e"],"length_aa":318,"mass_kda":35.2,"function":"Catalyzes the covalent attachment of ubiquitin to other proteins. Functions in the selective degradation of misfolded membrane proteins from the endoplasmic reticulum (ERAD) and is essential for cells to recover from ER stress (PubMed:28321712). Plays a role in MAPKAPK2-dependent translational control of TNF synthesis (PubMed:24020373). Also acts as a platform for perinuclear positioning of the endosomal system by mediating ubiquitination of SQSTM1 through interaction with the E3 ubiquitin-protein ligase RNF26 (PubMed:33472082). Plays a role in male fecundity through the interaction with the E3 ubiquitin-protein ligase RNF133 (PubMed:35831855) (Microbial infection) Promotes Dengue virus RNA replication by negatively regulating IFN-beta signaling and mediating 'Lys-48'-linked ubiquitination on IRF3 (PubMed:30157886)","subcellular_location":"Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/Q9Y385/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/UBE2J1","classification":"Not Classified","n_dependent_lines":14,"n_total_lines":1208,"dependency_fraction":0.011589403973509934},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/UBE2J1","total_profiled":1310},"omim":[{"mim_id":"620556","title":"RING FINGER PROTEIN 133; RNF133","url":"https://www.omim.org/entry/620556"},{"mim_id":"619756","title":"UBIQUITIN-CONJUGATING ENZYME E2 J2; UBE2J2","url":"https://www.omim.org/entry/619756"},{"mim_id":"616175","title":"UBIQUITIN-CONJUGATING ENZYME E2 J1; UBE2J1","url":"https://www.omim.org/entry/616175"},{"mim_id":"610304","title":"DER1-LIKE DOMAIN FAMILY, MEMBER 2; DERL2","url":"https://www.omim.org/entry/610304"},{"mim_id":"609677","title":"OS9 ENDOPLASMIC RETICULUM LECTIN; OS9","url":"https://www.omim.org/entry/609677"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/UBE2J1"},"hgnc":{"alias_symbol":["HSPC153","CGI-76","NCUBE1","UBC6"],"prev_symbol":[]},"alphafold":{"accession":"Q9Y385","domains":[{"cath_id":"3.10.110.10","chopping":"3-204","consensus_level":"high","plddt":89.5037,"start":3,"end":204}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y385","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y385-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y385-F1-predicted_aligned_error_v6.png","plddt_mean":77.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=UBE2J1","jax_strain_url":"https://www.jax.org/strain/search?query=UBE2J1"},"sequence":{"accession":"Q9Y385","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y385.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y385/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y385"}},"corpus_meta":[{"pmid":"21245296","id":"PMC_21245296","title":"HRD1 and UBE2J1 target misfolded MHC class I heavy chains for endoplasmic reticulum-associated degradation.","date":"2011","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/21245296","citation_count":120,"is_preprint":false},{"pmid":"12082160","id":"PMC_12082160","title":"A role for mammalian Ubc6 homologues in ER-associated protein degradation.","date":"2002","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/12082160","citation_count":97,"is_preprint":false},{"pmid":"15861135","id":"PMC_15861135","title":"TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination.","date":"2005","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/15861135","citation_count":88,"is_preprint":false},{"pmid":"36567344","id":"PMC_36567344","title":"UBE2J1 inhibits colorectal cancer progression by promoting ubiquitination and degradation of 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microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/38387235","citation_count":1,"is_preprint":false},{"pmid":"41237699","id":"PMC_41237699","title":"UBC6 mediated the inhibitory effect of quercetin on ovarian cancer through the PRKN-AURKA-AMPK axis.","date":"2025","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41237699","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.01.668162","title":"Functional integrity of the SEL1L-HRD1 complex is critical for ERAD and organismal viability","date":"2025-08-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.01.668162","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10727,"output_tokens":3538,"usd":0.042625,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10989,"output_tokens":4147,"usd":0.07931,"stage2_stop_reason":"end_turn"},"total_usd":0.121935,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"UBE2J1 (mammalian Ubc6 homologue) is localized to the cytoplasmic surface of the ER membrane via a C-terminal transmembrane domain, analogous to yeast Ubc6p. Overexpression of wild-type or dominant-negative alleles specifically affects ERAD of misfolded TCRα and mutant CFTR, establishing UBE2J1 as a functional E2 enzyme in mammalian ERAD.\",\n      \"method\": \"Dominant-negative allele overexpression, subcellular localization analysis, ERAD substrate degradation assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — dominant-negative approach plus localization, single lab with two orthogonal methods\",\n      \"pmids\": [\"12082160\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"UBE2J1 (NCUBE1) encodes a noncanonical ubiquitin-conjugating enzyme with a conserved noncanonical active site and a C-terminal transmembrane domain, constituting a distinct UBC family related to yeast Ubc6 and predicted to localize to the ER.\",\n      \"method\": \"cDNA cloning, sequence analysis, differential display on chondrocytes\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/sequence analysis only, no direct functional assay\",\n      \"pmids\": [\"10708578\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"UBE2J1 (Ubc6) binds the E3 ligase c-IAP1 and serves as its cognate E2 in vitro. Upon TNF-R2 engagement, UBE2J1 co-localizes with translocated TRAF2/c-IAP1 in a perinuclear ER-associated compartment, and a catalytically inactive UBE2J1 mutant inhibits TNF-α-induced TRAF2 ubiquitination and degradation.\",\n      \"method\": \"In vitro ubiquitination assay, confocal co-localization, catalytically inactive mutant overexpression\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro E2/E3 assay plus dominant-negative in vivo, single lab, two orthogonal methods\",\n      \"pmids\": [\"15861135\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"UBE2J1 partners with the E3 ligase HRD1 (Synoviolin) in a complex that also includes Derlin 1 and p97 to ubiquitinate and dislocate misfolded MHC class I heavy chains (non-β2m-bound) for ERAD. HRD1 and UBE2J1 discriminate misfolded MHC I from properly assembled MHC I-β2m-peptide heterotrimers. HRD1 is also required for degradation of the HFE-C282Y hemochromatosis mutant.\",\n      \"method\": \"siRNA functional screen, co-immunoprecipitation, ubiquitination assay, dislocation assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — siRNA screen, reciprocal Co-IP, ubiquitination assay, and dislocation assay; multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"21245296\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"UBE2J1 is phosphorylated at Ser184 by MK2 (MAPKAP kinase-2) upon p38 MAPK-activating cytosolic stress and LPS stimulation. MK2 directly interacts with UBE2J1 (pulldown) and phosphorylates recombinant UBE2J1 in vitro; the S184A mutant is not phosphorylated. UBE2J1 Ser184 phosphorylation is abrogated in MK2/MK3-deficient cells. UBE2J1 contributes to MK2-dependent TNFα biosynthesis. However, the S184A mutant retains ubiquitinating activity toward TCRα, so phosphorylation at Ser184 does not regulate catalytic activity directly.\",\n      \"method\": \"Phosphoproteomics, in vitro kinase assay with recombinant proteins, pulldown assay, MK2/MK3 knockout cells, ubiquitination assay\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro kinase assay with mutagenesis, confirmed in knockout cells, phosphoproteomics; multiple orthogonal methods\",\n      \"pmids\": [\"24020373\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Ube2j1 knockout mice have reduced viability and male sterility due to a defect in late spermiogenesis (spermatid cytoplasm removal is incomplete), establishing a non-redundant physiological role for UBE2J1 in the ubiquitin-proteasome system during spermatogenesis.\",\n      \"method\": \"Ube2j1 knockout mouse model, ultrastructural analysis, fertility assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic knockout with defined cellular phenotype confirmed by ultrastructural analysis; clean loss-of-function model\",\n      \"pmids\": [\"25320092\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"UBE2J1 phosphorylation at Ser184 (phospho-mimic S184D) is required for recovery from transient ER stress; the phospho-null S184A mutant cannot rescue cells. The E3 ligase c-IAP1 preferentially binds phosphorylated UBE2J1. Phosphorylated UBE2J1 is rapidly degraded by the proteasome during ER stress recovery.\",\n      \"method\": \"Ectopic expression of phospho-mimic and phospho-null mutants, co-immunoprecipitation, proteasome inhibitor treatment, cell viability assays\",\n      \"journal\": \"Journal of cell communication and signaling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — phospho-mutant rescue assay plus Co-IP, single lab, two orthogonal methods\",\n      \"pmids\": [\"28321712\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"UBE2J1 negatively regulates type I interferon signaling by facilitating ubiquitination and degradation of transcription factor IRF3, thereby promoting RNA virus (Dengue) infection. Silencing UBE2J1 increases IFNβ production and impairs DENV infection; overexpression suppresses RIG-I-directed IFNβ promoter activation.\",\n      \"method\": \"RNAi screen, gene overexpression/knockdown, reporter assay, ubiquitination assay\",\n      \"journal\": \"Virology journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi plus overexpression plus reporter assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"30157886\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"UBE2J1 partners with the ER-anchored E3 ligase RNF26 as an E2/E3 pair localized in a perinuclear ER subdomain. The UBE2J1/RNF26 complex ubiquitylates SQSTM1/p62 on lysine 435, recruiting endosomal adaptors to immobilize endosomes/lysosomes in the perinuclear region, promoting EGFR trafficking to lysosomes and facilitating termination of EGF-induced AKT signaling.\",\n      \"method\": \"Co-immunoprecipitation, site-specific ubiquitylation mapping, live imaging, endosomal motility assays, EGFR/AKT signaling assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, site-specific ubiquitylation (K435), live imaging with functional readout, signaling assays; multiple orthogonal methods\",\n      \"pmids\": [\"33472082\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"UBE2J1 forms an E2-E3 complex with TRIM25 and targets ribosomal protein RPS3 for ubiquitination and degradation at lysine 214. Degradation of RPS3 by UBE2J1/TRIM25 restrains NF-κB nuclear translocation and inactivates NF-κB signaling, suppressing colorectal cancer cell proliferation and metastasis.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay with K214 site mapping, NF-κB reporter, overexpression/knockdown in cell lines\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, site-specific ubiquitination assay, and signaling reporter; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"36567344\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"UBE2J1 is the critical E2 ubiquitin-conjugating enzyme responsible for androgen receptor (AR) ubiquitination and degradation. Loss of UBE2J1 disrupts AR ubiquitination, leading to AR protein accumulation and antiandrogen resistance in prostate cancer cells.\",\n      \"method\": \"UBE2J1 knockdown/knockout, ubiquitination assays, AR protein level and degradation assays, antiandrogen resistance assays\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with ubiquitination assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"38030789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The SEL1L-HRD1 ERAD complex requires direct SEL1L-HRD1 interaction for recruitment of UBE2J1. A knock-in L709P mutation in SEL1L that abolishes SEL1L-HRD1 binding impairs UBE2J1 recruitment, disrupts substrate ubiquitination, and causes accumulation and aggregation of misfolded ER proteins, resulting in neonatal lethality in mice.\",\n      \"method\": \"Knock-in mouse models (L709P, P699T, S658P mutations), biochemical interaction assays, ERAD substrate assays, protein aggregation analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic knock-in mouse models with biochemical validation, preprint, single study\",\n      \"pmids\": [\"bio_10.1101_2025.08.01.668162\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"UBE2J1 (UBC6) facilitates PRKN (Parkin)-mediated ubiquitination and degradation of AURKA, promoting AMPK phosphorylation at Thr172 in ovarian cancer cells. UBC6 interacts with PRKN as demonstrated by co-immunoprecipitation.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, lentiviral knockdown, xenograft mouse model, AMPK phosphorylation assay\",\n      \"journal\": \"International immunopharmacology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP plus knockdown phenotype, single lab, limited mechanistic detail in abstract\",\n      \"pmids\": [\"41237699\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"UBE2J1 is an ER membrane-anchored E2 ubiquitin-conjugating enzyme that functions in ERAD by partnering with E3 ligases (principally HRD1 and RNF26) to ubiquitinate and dislocate misfolded ER substrates (including misfolded MHC class I, AR, and others) for proteasomal degradation; it is phosphorylated at Ser184 by MK2 downstream of p38 MAPK, which regulates its interaction with c-IAP1 and its stability, modulates ER stress recovery, and contributes to TNFα biosynthesis; it also acts outside classical ERAD to control endolysosomal positioning (via RNF26/SQSTM1-K435 ubiquitylation), innate immune suppression (via IRF3 ubiquitination), and spermiogenesis, underscoring its broad physiological roles as an ER-tethered ubiquitination hub.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"UBE2J1 is an endoplasmic reticulum membrane-anchored E2 ubiquitin-conjugating enzyme that serves as a tethered ubiquitination hub for ER-associated degradation (ERAD) and related quality-control processes [#0]. Anchored to the cytoplasmic face of the ER through a C-terminal transmembrane domain, it functions in the dislocation and proteasomal degradation of misfolded ER substrates, including misfolded TCRα, mutant CFTR, and non-β2m-bound MHC class I heavy chains [#0, #3]. In its principal ERAD role it acts as the cognate E2 for the SEL1L-HRD1 (Synoviolin) complex together with Derlin-1 and p97, with UBE2J1 recruitment dependent on direct SEL1L-HRD1 interaction; loss of this recruitment causes accumulation and aggregation of misfolded ER proteins [#3, #11]. UBE2J1 is phosphorylated at Ser184 by MK2 downstream of p38 MAPK, a modification that does not alter catalytic activity toward TCRα but governs preferential binding to the E3 ligase c-IAP1, drives proteasomal turnover of UBE2J1, and is required for recovery from transient ER stress and for MK2-dependent TNFα biosynthesis [#4, #6]. Beyond classical ERAD, UBE2J1 pairs with distinct E3 ligases to act in trafficking and signaling: with RNF26 it ubiquitylates SQSTM1/p62 at K435 to immobilize endosomes/lysosomes perinuclearly and promote EGFR trafficking [#8], and it controls degradation of the androgen receptor, where its loss confers antiandrogen resistance in prostate cancer [#10]. A Ube2j1 knockout mouse is subviable and male-sterile owing to defective late spermiogenesis, establishing a non-redundant physiological requirement [#5].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established UBE2J1 as a distinct, ER-predicted E2 enzyme family member with a noncanonical active site, defining the molecular class before any functional assay existed.\",\n      \"evidence\": \"cDNA cloning and sequence analysis from chondrocyte differential display\",\n      \"pmids\": [\"10708578\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational/sequence inference only, no direct enzymatic or localization assay\", \"ER localization predicted not demonstrated\", \"No substrate or E3 partner identified\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Showed UBE2J1 is a bona fide functional ERAD E2 anchored to the ER membrane, answering whether the predicted enzyme actually drives misfolded-protein degradation in mammalian cells.\",\n      \"evidence\": \"Dominant-negative overexpression, subcellular localization, and ERAD substrate (TCRα, mutant CFTR) degradation assays\",\n      \"pmids\": [\"12082160\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cognate E3 ligase not identified\", \"Mechanism of substrate selection unresolved\", \"Dominant-negative approach without endogenous loss-of-function\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identified c-IAP1 as a UBE2J1 E3 partner and linked the enzyme to TNF-R2 signaling, extending its activity beyond housekeeping ERAD into receptor-coupled ubiquitination.\",\n      \"evidence\": \"In vitro ubiquitination, confocal co-localization, and catalytically inactive mutant in TNF-R2-engaged cells\",\n      \"pmids\": [\"15861135\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Endogenous requirement not tested with knockout\", \"Relationship to ER-anchoring of this activity unclear\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined the HRD1/Derlin-1/p97 complex as the major UBE2J1 ERAD machinery and showed it discriminates misfolded from properly assembled MHC class I, clarifying how quality control selects substrates.\",\n      \"evidence\": \"siRNA functional screen, reciprocal co-IP, ubiquitination and dislocation assays\",\n      \"pmids\": [\"21245296\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of substrate discrimination not resolved\", \"How UBE2J1 is recruited into the complex not yet defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identified MK2-mediated Ser184 phosphorylation as a stress-responsive regulatory input on UBE2J1 and showed it does not control catalytic activity directly, separating regulation from enzymatic function.\",\n      \"evidence\": \"Phosphoproteomics, in vitro kinase assay with S184A mutagenesis, MK2/MK3 knockout cells, ubiquitination assay\",\n      \"pmids\": [\"24020373\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of Ser184 phosphorylation left open at this stage\", \"Mechanistic link to TNFα biosynthesis not detailed\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrated a non-redundant in vivo role for UBE2J1 in spermiogenesis, moving beyond cell-based ERAD assays to organismal physiology.\",\n      \"evidence\": \"Ube2j1 knockout mouse with ultrastructural and fertility analysis\",\n      \"pmids\": [\"25320092\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific spermatid substrates not identified\", \"E3 partner mediating the spermiogenesis function unknown\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Resolved the function of Ser184 phosphorylation by showing it is required for ER stress recovery, drives c-IAP1 binding, and triggers UBE2J1's own proteasomal degradation, defining a self-limiting regulatory loop.\",\n      \"evidence\": \"Phospho-mimic/phospho-null rescue, co-IP, proteasome inhibition, viability assays\",\n      \"pmids\": [\"28321712\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"E3 responsible for phospho-UBE2J1 turnover not pinpointed\", \"Single-lab phospho-mutant approach\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended UBE2J1 into innate immunity by showing it degrades IRF3 to dampen type I interferon and favor RNA virus replication, revealing a pro-viral immunoregulatory role.\",\n      \"evidence\": \"RNAi screen, overexpression/knockdown, IFNβ reporter, ubiquitination assay in Dengue infection\",\n      \"pmids\": [\"30157886\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cognate E3 ligase for IRF3 ubiquitination not identified\", \"Direct vs indirect action on IRF3 not fully separated\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined the UBE2J1/RNF26 E2-E3 pair and its substrate SQSTM1 (K435), explaining how ER-anchored ubiquitination spatially organizes the endolysosomal system and terminates EGFR/AKT signaling.\",\n      \"evidence\": \"Reciprocal co-IP, site-specific ubiquitylation mapping, live imaging, endosomal motility and EGFR/AKT assays\",\n      \"pmids\": [\"33472082\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relationship between RNF26 and HRD1 pathways not integrated\", \"Regulation of the perinuclear subdomain assembly unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified a UBE2J1/TRIM25 pair degrading RPS3 at K214 to restrain NF-κB, adding a tumor-suppressive signaling output in colorectal cancer.\",\n      \"evidence\": \"Co-IP, K214 site-mapped ubiquitination, NF-κB reporter, overexpression/knockdown\",\n      \"pmids\": [\"36567344\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vivo relevance beyond cell lines limited\", \"Whether ER anchoring is required for this activity untested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established UBE2J1 as the critical E2 for androgen receptor ubiquitination and degradation, linking its loss to antiandrogen resistance in prostate cancer.\",\n      \"evidence\": \"Knockdown/knockout, ubiquitination assays, AR degradation and resistance assays\",\n      \"pmids\": [\"38030789\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cognate E3 for AR not defined in this work\", \"Single-lab loss-of-function evidence\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed that UBE2J1 recruitment to the ERAD machinery requires direct SEL1L-HRD1 interaction, and that disrupting it causes lethal accumulation of misfolded ER proteins, mechanistically anchoring UBE2J1 to complex assembly.\",\n      \"evidence\": \"Knock-in mouse models (L709P, P699T, S658P), biochemical interaction and ERAD substrate/aggregation assays (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.08.01.668162\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not peer-reviewed\", \"Direct UBE2J1-SEL1L/HRD1 contact residues not mapped\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How UBE2J1 is partitioned among its many E3 partners (HRD1, RNF26, c-IAP1, TRIM25, PRKN) and substrates across distinct subcellular contexts, and what determines partner/substrate selection, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of UBE2J1 in any of its E2-E3 complexes\", \"Determinants of E3-partner choice unknown\", \"Integration of stress-regulated phosphorylation with each pathway not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 3, 8]},\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0061631\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 3, 8]},\n      {\"term_id\": \"GO:0005789\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 3, 11]},\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [4, 6]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [8, 9, 10]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"complexes\": [\n      \"SEL1L-HRD1 ERAD complex\",\n      \"UBE2J1/RNF26 E2-E3 complex\"\n    ],\n    \"partners\": [\n      \"HRD1\",\n      \"SEL1L\",\n      \"RNF26\",\n      \"SQSTM1\",\n      \"c-IAP1\",\n      \"MK2\",\n      \"TRIM25\",\n      \"PRKN\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}