{"gene":"UBL7","run_date":"2026-06-10T10:51:56","timeline":{"discoveries":[{"year":2006,"finding":"The UBA domain of human BMSC-UbP (UBL7) adopts a three-helix bundle with a hydrophobic patch (M-G-I motif in helix-1, loop-1, helix-3) that binds the conserved hydrophobic surface of ubiquitin (Leu8, Ile44, His68, Val70) via residues Met76, Ile78, and Leu99, with a dissociation constant of ~17 µM.","method":"Solution NMR structure determination, chemical shift perturbation mapping, mutagenesis, and HADDOCK-based complex modeling","journal":"Protein Science","confidence":"High","confidence_rationale":"Tier 1 / Moderate — NMR structure with mutagenesis validation and binding constant measurement, single lab but multiple orthogonal methods","pmids":["16731964"],"is_preprint":false},{"year":2003,"finding":"BMSC-UbP (UBL7) is a ubiquitin-like protein encoded by a 380-amino-acid ORF containing an N-terminal ubiquitin domain (UBQ) and a C-terminal ubiquitin-associated (UBA) domain, sharing homology with ubiquilin family members; its mRNA expression is modulated in a cell-type- and stimulus-specific manner (decreased in BMSC with PMA, increased in HL60 with LPS).","method":"cDNA library screening, sequence analysis, Northern blot/RT-PCR expression profiling","journal":"Immunology Letters","confidence":"Low","confidence_rationale":"Tier 3 / Weak — domain identification by sequence analysis and expression changes; no direct functional mechanistic experiment beyond cloning","pmids":["12644319"],"is_preprint":false},{"year":2023,"finding":"UBL7 enhances antiviral innate immunity by interacting with the E3 ubiquitin ligase TRIM21 and promoting TRIM21–MAVS association in a dose-dependent manner, thereby facilitating K27-linked polyubiquitination of MAVS and recruitment of TBK1 to potentiate IFN signaling. UBL7-deficient mice show increased viral susceptibility with attenuated antiviral immunity.","method":"Co-immunoprecipitation, knockout mouse model (viral infection phenotype), polyubiquitination assays, dose-dependent interaction assays, ISG induction analysis","journal":"Cell Reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, in vivo KO phenotype, ubiquitination assays, multiple orthogonal methods in single study","pmids":["36943869"],"is_preprint":false},{"year":2025,"finding":"UBL7 is required for spermiogenesis; it interacts with the VCP complex and proteasomes, shuttles substrates between them, and slows proteasomal degradation of ERAD substrates. Key protected spermatid factors identified by two-step immunoprecipitation include IFT140 (manchette), SPATA20 (head-tail coupling apparatus), and HK1/SLC2a3 (cytoplasmic droplets). UBL7 knockout mice display severe sperm head and tail malformations.","method":"Knockout mouse model, co-immunoprecipitation with VCP complex and proteasomes, two-step immunoprecipitation mass spectrometry substrate identification, protein degradation rate assays","journal":"Nature Communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — KO mouse with defined phenotype, reciprocal Co-IP, substrate identification by tandem IP-MS, degradation assays; single lab but multiple orthogonal methods","pmids":["40268954"],"is_preprint":false}],"current_model":"UBL7 is a UBL-UBA domain protein whose UBA domain directly binds ubiquitin (KD ~17 µM) via a conserved hydrophobic interface; it acts as an adaptor that (1) interacts with the VCP complex and proteasomes to protect specific substrates from excessive proteasomal degradation—essential for spermiogenesis—and (2) promotes K27-linked polyubiquitination of MAVS by facilitating TRIM21–MAVS interaction and TBK1 recruitment to amplify antiviral IFN signaling."},"narrative":{"mechanistic_narrative":"UBL7 is a ubiquilin-family ubiquitin-like protein that functions as a ubiquitin-binding adaptor coupling substrate recognition to two distinct cellular outcomes: protein quality control and antiviral signaling [PMID:16731964, PMID:36943869, PMID:40268954]. Its C-terminal UBA domain forms a three-helix bundle that directly engages the conserved hydrophobic surface of ubiquitin (Leu8, Ile44, Val70) through residues Met76, Ile78, and Leu99 with a dissociation constant of ~17 µM, providing the molecular basis for its adaptor activity [PMID:16731964]. In protein homeostasis, UBL7 associates with the VCP complex and the proteasome and shuttles substrates between them, slowing the proteasomal degradation of ERAD substrates; this activity is essential for spermiogenesis, where it protects spermatid factors including IFT140, SPATA20, and HK1/SLC2a3, and its loss in knockout mice causes severe sperm head and tail malformations [PMID:40268954]. In innate immunity, UBL7 interacts with the E3 ligase TRIM21 and promotes TRIM21–MAVS association to drive K27-linked polyubiquitination of MAVS and TBK1 recruitment, amplifying type I interferon signaling, with UBL7-deficient mice showing increased viral susceptibility [PMID:36943869].","teleology":[{"year":2003,"claim":"Establishing UBL7 as a ubiquilin-related protein with a defined UBQ-UBA domain architecture framed it as a candidate ubiquitin-system adaptor rather than an orphan ORF.","evidence":"cDNA cloning, sequence/domain analysis, and stimulus-dependent expression profiling in BMSC and HL60 cells","pmids":["12644319"],"confidence":"Low","gaps":["No direct functional or binding experiment beyond cloning and sequence homology","Expression changes not linked to any mechanism","Domain function inferred from homology, not tested"]},{"year":2006,"claim":"Resolving how the UBA domain recognizes ubiquitin answered whether UBL7 can physically read the ubiquitin signal, defining the structural and energetic basis of its adaptor activity.","evidence":"Solution NMR structure, chemical shift perturbation mapping, mutagenesis, and HADDOCK complex modeling with KD measurement","pmids":["16731964"],"confidence":"High","gaps":["Binding measured for mono-ubiquitin; chain-linkage preference of the UBA domain not determined","Does not connect ubiquitin binding to a cellular substrate or pathway","Role of the N-terminal UBQ domain not addressed"]},{"year":2023,"claim":"Identifying UBL7 as a TRIM21 partner that promotes MAVS K27-ubiquitination placed it within antiviral IFN signaling, showing it is not a generic degradation factor but a signaling amplifier.","evidence":"Reciprocal Co-IP, dose-dependent interaction assays, polyubiquitination assays, ISG induction, and viral-infection phenotype in knockout mice","pmids":["36943869"],"confidence":"High","gaps":["Whether the UBA domain's ubiquitin binding is required for the TRIM21–MAVS function not dissected","Mechanism by which UBL7 bridges TRIM21 to MAVS not structurally defined","Relationship between this signaling role and proteasomal functions unresolved"]},{"year":2025,"claim":"Demonstrating that UBL7 shuttles substrates between VCP and the proteasome to slow their degradation defined its role in protein quality control and explained its essentiality for spermiogenesis.","evidence":"Knockout mouse phenotyping, Co-IP with VCP and proteasome, two-step IP-MS substrate identification, and protein degradation rate assays","pmids":["40268954"],"confidence":"High","gaps":["Mechanism of substrate selection (IFT140, SPATA20, HK1/SLC2a3) not defined","How shuttling slows rather than promotes degradation mechanistically unclear","Connection to the UBA ubiquitin-binding interface not directly tested"]},{"year":null,"claim":"How a single ubiquitin-binding adaptor coordinates two seemingly opposing roles—protecting substrates from proteasomal degradation versus driving K27-ubiquitination in antiviral signaling—remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No unifying model linking the UBA/UBQ domains to both VCP-proteasome shuttling and TRIM21-MAVS signaling","Tissue- or context-specific partner switching not characterized","Structural basis of complex assembly with VCP, proteasome, or TRIM21 unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,3]}],"localization":[],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[2]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[3]}],"complexes":[],"partners":["TRIM21","MAVS","TBK1","VCP","IFT140","SPATA20","HK1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96S82","full_name":"Ubiquitin-like protein 7","aliases":["Bone marrow stromal cell ubiquitin-like protein","BMSC-UbP","Ubiquitin-like protein SB132"],"length_aa":380,"mass_kda":40.5,"function":"Interferon-stimulated protein that positively regulates RNA virus-triggered innate immune signaling. Mechanistically, promotes 'Lys-27'-linked polyubiquitination of MAVS through TRIM21 leading to enhanced the IFN signaling pathway","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q96S82/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/UBL7","classification":"Not Classified","n_dependent_lines":19,"n_total_lines":1208,"dependency_fraction":0.015728476821192054},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/UBL7","total_profiled":1310},"omim":[{"mim_id":"609748","title":"UBIQUITIN-LIKE 7; UBL7","url":"https://www.omim.org/entry/609748"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/UBL7"},"hgnc":{"alias_symbol":["BMSC-UbP","MGC14421"],"prev_symbol":[]},"alphafold":{"accession":"Q96S82","domains":[{"cath_id":"3.10.20.90","chopping":"8-92","consensus_level":"high","plddt":77.934,"start":8,"end":92},{"cath_id":"-","chopping":"107-199","consensus_level":"high","plddt":78.974,"start":107,"end":199},{"cath_id":"1.10.8,1.10.8","chopping":"336-376","consensus_level":"high","plddt":82.7993,"start":336,"end":376}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96S82","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96S82-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96S82-F1-predicted_aligned_error_v6.png","plddt_mean":66.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=UBL7","jax_strain_url":"https://www.jax.org/strain/search?query=UBL7"},"sequence":{"accession":"Q96S82","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96S82.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96S82/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96S82"}},"corpus_meta":[{"pmid":"16731964","id":"PMC_16731964","title":"Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin.","date":"2006","source":"Protein science : a publication of the Protein Society","url":"https://pubmed.ncbi.nlm.nih.gov/16731964","citation_count":48,"is_preprint":false},{"pmid":"32616055","id":"PMC_32616055","title":"Autoantibody signature in hepatocellular carcinoma using seromics.","date":"2020","source":"Journal of hematology & oncology","url":"https://pubmed.ncbi.nlm.nih.gov/32616055","citation_count":48,"is_preprint":false},{"pmid":"34836490","id":"PMC_34836490","title":"HYPK coordinates degradation of polyneddylated proteins by autophagy.","date":"2021","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/34836490","citation_count":21,"is_preprint":false},{"pmid":"36943869","id":"PMC_36943869","title":"UBL7 enhances antiviral innate immunity by promoting Lys27-linked polyubiquitination of MAVS.","date":"2023","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/36943869","citation_count":15,"is_preprint":false},{"pmid":"12644319","id":"PMC_12644319","title":"Cloning and identification of a novel ubiquitin-like protein, BMSC-UbP, from human bone marrow stromal cells.","date":"2003","source":"Immunology letters","url":"https://pubmed.ncbi.nlm.nih.gov/12644319","citation_count":15,"is_preprint":false},{"pmid":"26671595","id":"PMC_26671595","title":"t(15;21) translocations leading to the concurrent downregulation of RUNX1 and its transcription factor partner genes SIN3A and TCF12 in myeloid disorders.","date":"2015","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/26671595","citation_count":14,"is_preprint":false},{"pmid":"27018092","id":"PMC_27018092","title":"GNB2 is a mediator of lidocaine-induced apoptosis in rat pheochromocytoma PC12 cells.","date":"2016","source":"Neurotoxicology","url":"https://pubmed.ncbi.nlm.nih.gov/27018092","citation_count":11,"is_preprint":false},{"pmid":"35313638","id":"PMC_35313638","title":"Therapy-resistant and -sensitive lncRNAs, SNHG1 and UBL7-AS1 promote glioblastoma cell proliferation.","date":"2022","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/35313638","citation_count":8,"is_preprint":false},{"pmid":"40274920","id":"PMC_40274920","title":"Inferring past demography and genetic adaptation in Spain using the GCAT cohort.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40274920","citation_count":4,"is_preprint":false},{"pmid":"40268954","id":"PMC_40268954","title":"UBL7 is indispensable for spermiogenesis through protecting critical factors from excessive degradation by proteasomes.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/40268954","citation_count":2,"is_preprint":false},{"pmid":"36045665","id":"PMC_36045665","title":"Tetramethylpyrazine Inhibits the Proliferation and Invasion of Glioma Cells by Regulating the UBL7-AS1/miR-144-3p Pathway.","date":"2022","source":"Evidence-based complementary and alternative medicine : eCAM","url":"https://pubmed.ncbi.nlm.nih.gov/36045665","citation_count":2,"is_preprint":false},{"pmid":"41999721","id":"PMC_41999721","title":"Sex-specific autosomal susceptibility loci in systemic sclerosis: a genome-wide association study.","date":"2026","source":"The Lancet. Rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/41999721","citation_count":1,"is_preprint":false},{"pmid":"38125096","id":"PMC_38125096","title":"Retracted: Tetramethylpyrazine Inhibits the Proliferation and Invasion of Glioma Cells by Regulating the UBL7-AS1/miR-144-3p Pathway.","date":"2023","source":"Evidence-based complementary and alternative medicine : eCAM","url":"https://pubmed.ncbi.nlm.nih.gov/38125096","citation_count":0,"is_preprint":false},{"pmid":"39132510","id":"PMC_39132510","title":"An autoantibody profile identified by human genome-wide protein arrays in rheumatoid arthritis.","date":"2024","source":"MedComm","url":"https://pubmed.ncbi.nlm.nih.gov/39132510","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9854,"output_tokens":1199,"usd":0.023773,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7798,"output_tokens":2104,"usd":0.045795,"stage2_stop_reason":"end_turn"},"total_usd":0.069568,"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\": 2006,\n      \"finding\": \"The UBA domain of human BMSC-UbP (UBL7) adopts a three-helix bundle with a hydrophobic patch (M-G-I motif in helix-1, loop-1, helix-3) that binds the conserved hydrophobic surface of ubiquitin (Leu8, Ile44, His68, Val70) via residues Met76, Ile78, and Leu99, with a dissociation constant of ~17 µM.\",\n      \"method\": \"Solution NMR structure determination, chemical shift perturbation mapping, mutagenesis, and HADDOCK-based complex modeling\",\n      \"journal\": \"Protein Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR structure with mutagenesis validation and binding constant measurement, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"16731964\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"BMSC-UbP (UBL7) is a ubiquitin-like protein encoded by a 380-amino-acid ORF containing an N-terminal ubiquitin domain (UBQ) and a C-terminal ubiquitin-associated (UBA) domain, sharing homology with ubiquilin family members; its mRNA expression is modulated in a cell-type- and stimulus-specific manner (decreased in BMSC with PMA, increased in HL60 with LPS).\",\n      \"method\": \"cDNA library screening, sequence analysis, Northern blot/RT-PCR expression profiling\",\n      \"journal\": \"Immunology Letters\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — domain identification by sequence analysis and expression changes; no direct functional mechanistic experiment beyond cloning\",\n      \"pmids\": [\"12644319\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"UBL7 enhances antiviral innate immunity by interacting with the E3 ubiquitin ligase TRIM21 and promoting TRIM21–MAVS association in a dose-dependent manner, thereby facilitating K27-linked polyubiquitination of MAVS and recruitment of TBK1 to potentiate IFN signaling. UBL7-deficient mice show increased viral susceptibility with attenuated antiviral immunity.\",\n      \"method\": \"Co-immunoprecipitation, knockout mouse model (viral infection phenotype), polyubiquitination assays, dose-dependent interaction assays, ISG induction analysis\",\n      \"journal\": \"Cell Reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, in vivo KO phenotype, ubiquitination assays, multiple orthogonal methods in single study\",\n      \"pmids\": [\"36943869\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"UBL7 is required for spermiogenesis; it interacts with the VCP complex and proteasomes, shuttles substrates between them, and slows proteasomal degradation of ERAD substrates. Key protected spermatid factors identified by two-step immunoprecipitation include IFT140 (manchette), SPATA20 (head-tail coupling apparatus), and HK1/SLC2a3 (cytoplasmic droplets). UBL7 knockout mice display severe sperm head and tail malformations.\",\n      \"method\": \"Knockout mouse model, co-immunoprecipitation with VCP complex and proteasomes, two-step immunoprecipitation mass spectrometry substrate identification, protein degradation rate assays\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO mouse with defined phenotype, reciprocal Co-IP, substrate identification by tandem IP-MS, degradation assays; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"40268954\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"UBL7 is a UBL-UBA domain protein whose UBA domain directly binds ubiquitin (KD ~17 µM) via a conserved hydrophobic interface; it acts as an adaptor that (1) interacts with the VCP complex and proteasomes to protect specific substrates from excessive proteasomal degradation—essential for spermiogenesis—and (2) promotes K27-linked polyubiquitination of MAVS by facilitating TRIM21–MAVS interaction and TBK1 recruitment to amplify antiviral IFN signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"UBL7 is a ubiquilin-family ubiquitin-like protein that functions as a ubiquitin-binding adaptor coupling substrate recognition to two distinct cellular outcomes: protein quality control and antiviral signaling [#0, #2, #3]. Its C-terminal UBA domain forms a three-helix bundle that directly engages the conserved hydrophobic surface of ubiquitin (Leu8, Ile44, Val70) through residues Met76, Ile78, and Leu99 with a dissociation constant of ~17 \\u00b5M, providing the molecular basis for its adaptor activity [#0]. In protein homeostasis, UBL7 associates with the VCP complex and the proteasome and shuttles substrates between them, slowing the proteasomal degradation of ERAD substrates; this activity is essential for spermiogenesis, where it protects spermatid factors including IFT140, SPATA20, and HK1/SLC2a3, and its loss in knockout mice causes severe sperm head and tail malformations [#3]. In innate immunity, UBL7 interacts with the E3 ligase TRIM21 and promotes TRIM21\\u2013MAVS association to drive K27-linked polyubiquitination of MAVS and TBK1 recruitment, amplifying type I interferon signaling, with UBL7-deficient mice showing increased viral susceptibility [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing UBL7 as a ubiquilin-related protein with a defined UBQ-UBA domain architecture framed it as a candidate ubiquitin-system adaptor rather than an orphan ORF.\",\n      \"evidence\": \"cDNA cloning, sequence/domain analysis, and stimulus-dependent expression profiling in BMSC and HL60 cells\",\n      \"pmids\": [\"12644319\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct functional or binding experiment beyond cloning and sequence homology\",\n        \"Expression changes not linked to any mechanism\",\n        \"Domain function inferred from homology, not tested\"\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Resolving how the UBA domain recognizes ubiquitin answered whether UBL7 can physically read the ubiquitin signal, defining the structural and energetic basis of its adaptor activity.\",\n      \"evidence\": \"Solution NMR structure, chemical shift perturbation mapping, mutagenesis, and HADDOCK complex modeling with KD measurement\",\n      \"pmids\": [\"16731964\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Binding measured for mono-ubiquitin; chain-linkage preference of the UBA domain not determined\",\n        \"Does not connect ubiquitin binding to a cellular substrate or pathway\",\n        \"Role of the N-terminal UBQ domain not addressed\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying UBL7 as a TRIM21 partner that promotes MAVS K27-ubiquitination placed it within antiviral IFN signaling, showing it is not a generic degradation factor but a signaling amplifier.\",\n      \"evidence\": \"Reciprocal Co-IP, dose-dependent interaction assays, polyubiquitination assays, ISG induction, and viral-infection phenotype in knockout mice\",\n      \"pmids\": [\"36943869\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the UBA domain's ubiquitin binding is required for the TRIM21\\u2013MAVS function not dissected\",\n        \"Mechanism by which UBL7 bridges TRIM21 to MAVS not structurally defined\",\n        \"Relationship between this signaling role and proteasomal functions unresolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrating that UBL7 shuttles substrates between VCP and the proteasome to slow their degradation defined its role in protein quality control and explained its essentiality for spermiogenesis.\",\n      \"evidence\": \"Knockout mouse phenotyping, Co-IP with VCP and proteasome, two-step IP-MS substrate identification, and protein degradation rate assays\",\n      \"pmids\": [\"40268954\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism of substrate selection (IFT140, SPATA20, HK1/SLC2a3) not defined\",\n        \"How shuttling slows rather than promotes degradation mechanistically unclear\",\n        \"Connection to the UBA ubiquitin-binding interface not directly tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single ubiquitin-binding adaptor coordinates two seemingly opposing roles\\u2014protecting substrates from proteasomal degradation versus driving K27-ubiquitination in antiviral signaling\\u2014remains unresolved.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No unifying model linking the UBA/UBQ domains to both VCP-proteasome shuttling and TRIM21-MAVS signaling\",\n        \"Tissue- or context-specific partner switching not characterized\",\n        \"Structural basis of complex assembly with VCP, proteasome, or TRIM21 unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TRIM21\", \"MAVS\", \"TBK1\", \"VCP\", \"IFT140\", \"SPATA20\", \"HK1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":4,"faith_total":4,"faith_pct":100.0}}