{"gene":"UBR7","run_date":"2026-06-14T07:33:11","timeline":{"discoveries":[],"current_model":"Parse failed"},"narrative":{"mechanistic_narrative":"No mechanistic discoveries found in literature.","teleology":[],"mechanism_profile":null},"prefetch_data":{"uniprot":{"accession":"Q8N806","full_name":"Putative E3 ubiquitin-protein ligase UBR7","aliases":["N-recognin-7","RING-type E3 ubiquitin transferase UBR7"],"length_aa":425,"mass_kda":48.0,"function":"E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q8N806/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/UBR7","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/UBR7","total_profiled":1310},"omim":[{"mim_id":"619189","title":"LI-CAMPEAU SYNDROME; LICAS","url":"https://www.omim.org/entry/619189"},{"mim_id":"613816","title":"UBIQUITIN PROTEIN LIGASE E3 COMPONENT N-RECOGNIN 7; UBR7","url":"https://www.omim.org/entry/613816"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/UBR7"},"hgnc":{"alias_symbol":[],"prev_symbol":["C14orf130"]},"alphafold":{"accession":"Q8N806","domains":[{"cath_id":"-","chopping":"34-131","consensus_level":"high","plddt":94.0052,"start":34,"end":131},{"cath_id":"-","chopping":"142-203_286-336","consensus_level":"medium","plddt":92.6137,"start":142,"end":336},{"cath_id":"1.10.287","chopping":"355-417","consensus_level":"high","plddt":80.4275,"start":355,"end":417}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N806","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N806-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N806-F1-predicted_aligned_error_v6.png","plddt_mean":75.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=UBR7","jax_strain_url":"https://www.jax.org/strain/search?query=UBR7"},"sequence":{"accession":"Q8N806","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N806.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N806/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N806"}},"corpus_meta":[{"pmid":"31324801","id":"PMC_31324801","title":"TurboID-based proximity labeling reveals that UBR7 is a regulator of N NLR immune receptor-mediated immunity.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31324801","citation_count":212,"is_preprint":false},{"pmid":"32572277","id":"PMC_32572277","title":"Manumycin polyketides act as molecular glues between UBR7 and P53.","date":"2020","source":"Nature chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/32572277","citation_count":102,"is_preprint":false},{"pmid":"36419136","id":"PMC_36419136","title":"UBR7 inhibits HCC tumorigenesis by targeting Keap1/Nrf2/Bach1/HK2 and glycolysis.","date":"2022","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/36419136","citation_count":72,"is_preprint":false},{"pmid":"30923315","id":"PMC_30923315","title":"Atypical plant homeodomain of UBR7 functions as an H2BK120Ub ligase and breast tumor suppressor.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/30923315","citation_count":49,"is_preprint":false},{"pmid":"34786730","id":"PMC_34786730","title":"UBR7 acts as a histone chaperone for post-nucleosomal histone H3.","date":"2021","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/34786730","citation_count":24,"is_preprint":false},{"pmid":"24664117","id":"PMC_24664117","title":"Identification and characterization of RING-finger ubiquitin ligase UBR7 in mammalian spermatozoa.","date":"2014","source":"Cell and tissue research","url":"https://pubmed.ncbi.nlm.nih.gov/24664117","citation_count":22,"is_preprint":false},{"pmid":"33340455","id":"PMC_33340455","title":"UBR7 functions with UBR5 in the Notch signaling pathway and is involved in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism.","date":"2020","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/33340455","citation_count":19,"is_preprint":false},{"pmid":"33571115","id":"PMC_33571115","title":"NOTCH1-driven UBR7 stimulates nucleotide biosynthesis to promote T cell acute lymphoblastic leukemia.","date":"2021","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/33571115","citation_count":18,"is_preprint":false},{"pmid":"34739193","id":"PMC_34739193","title":"Molecular characterization of substrate-induced ubiquitin transfer by UBR7-PHD finger, a newly identified histone H2BK120 ubiquitin ligase.","date":"2021","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/34739193","citation_count":16,"is_preprint":false},{"pmid":"39424627","id":"PMC_39424627","title":"The interaction between UBR7 and PRMT5 drives PDAC resistance to gemcitabine by regulating glycolysis and immune microenvironment.","date":"2024","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/39424627","citation_count":13,"is_preprint":false},{"pmid":"38923455","id":"PMC_38923455","title":"UBR7 in concert with EZH2 inhibits the TGF-β signaling leading to extracellular matrix remodeling.","date":"2024","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/38923455","citation_count":11,"is_preprint":false},{"pmid":"37187513","id":"PMC_37187513","title":"The effects of the E3 ubiquitin-protein ligase UBR7 of Frankliniella occidentalis on the ability of insects to acquire and transmit TSWV.","date":"2023","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/37187513","citation_count":5,"is_preprint":false},{"pmid":"38382692","id":"PMC_38382692","title":"MiR-10b-5p Regulates Neuronal Autophagy and Apoptosis Induced by Spinal Cord Injury Through UBR7.","date":"2024","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/38382692","citation_count":5,"is_preprint":false},{"pmid":"38938101","id":"PMC_38938101","title":"UBR7 E3 Ligase Suppresses Interferon-β Mediated Immune Signaling by Targeting Sp110 in Hepatitis B Virus-Induced Hepatocellular Carcinoma.","date":"2024","source":"ACS infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/38938101","citation_count":4,"is_preprint":false},{"pmid":"37478672","id":"PMC_37478672","title":"Establishment of a novel human induced pluripotent stem cell line (SIPDi001-A) with compound heterozygous mutations in the UBR7 gene from a Li-Campeau syndrome patient.","date":"2023","source":"Stem cell research","url":"https://pubmed.ncbi.nlm.nih.gov/37478672","citation_count":0,"is_preprint":false},{"pmid":"41558443","id":"PMC_41558443","title":"Silencing the ubiquitin-protein ligases gene (E3-UBR7) alters acquisition, replication, and transmission of groundnut bud necrosis virus by Thrips palmi.","date":"2026","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/41558443","citation_count":0,"is_preprint":false},{"pmid":"36757286","id":"PMC_36757286","title":"Eighth case of Li-Campeau syndrome in a Turkish patient caused by a novel pathogenic variant in UBR7 and expanding the phenotype.","date":"2023","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/36757286","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.07.23.666188","title":"Response of UBR-box E3 ubiquitin ligases and protein quality control pathways to perturbations in protein synthesis and skeletal muscle size","date":"2025-07-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.23.666188","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.07.07.602406","title":"Characterization of eight new  <i>Hydractinia</i>  i-cell markers reveals underlying heterogeneity in the adult pluripotent stem cell population","date":"2024-07-10","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.07.602406","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11634,"output_tokens":2936,"usd":0.039471,"stage1_stop_reason":"refusal"},"stage2":{"model":"","input_tokens":0,"output_tokens":0,"usd":0.0},"total_usd":0.039471,"stage1_batch_id":"msgbatch_015cW3C55o5xm8EPaM1UvcZR","stage2_batch_id":"msgbatch_018NDJHPntdYJzBohpB6hHKo","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"The PHD finger of UBR7 harbors E3 ubiquitin ligase activity toward monoubiquitination of histone H2B at lysine 120 (H2BK120Ub). Purified PHD finger or full-length UBR7 monoubiquitinated H2BK120 in vitro, and loss of UBR7 drastically reduced H2BK120Ub genome-wide binding sites in MCF10A cells.\",\n      \"method\": \"In vitro ubiquitination assay with purified PHD finger and full-length UBR7; genome-wide ChIP-seq of H2BK120Ub in UBR7 knockdown cells\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution of enzymatic activity with purified protein, complemented by genome-wide functional readout in cells\",\n      \"pmids\": [\"30923315\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"UBR7 loss reduced H2BK120Ub levels on cell adhesion genes including CDH4 and upregulated the Wnt/β-Catenin signaling pathway, establishing a mechanistic link between UBR7 histone ubiquitin ligase activity and breast cancer metastasis suppression.\",\n      \"method\": \"UBR7 knockdown/overexpression with invasion assays, EMT markers, tumor growth in vivo; CDH4 rescue experiments\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD/KO with defined cellular phenotypes and CDH4 rescue, single lab\",\n      \"pmids\": [\"30923315\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"UBR7 directly interacts with the TIR domain of the NLR immune receptor N (in Nicotiana tabacum). UBR7 downregulation increases N protein abundance and enhances TMV resistance, indicating UBR7 negatively regulates N protein levels. TMV-p50 effector disrupts the N-UBR7 interaction.\",\n      \"method\": \"TurboID proximity labeling, Co-IP/direct interaction assay, genetic knockdown with viral resistance phenotype\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity labeling plus direct interaction and genetic loss-of-function, but plant ortholog study\",\n      \"pmids\": [\"31324801\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Members of the manumycin polyketide family covalently target C374 of UBR7 in breast cancer cells, acting as molecular glues that induce a neo-interaction between UBR7 and the tumor suppressor TP53, leading to p53 transcriptional activation and cell death.\",\n      \"method\": \"Chemoproteomic platforms (activity-based protein profiling, chemoproteomics); covalent target identification; p53 transcriptional reporter assays\",\n      \"journal\": \"Nature chemical biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — chemoproteomic target identification with site-level resolution (C374), molecular glue mechanism validated by p53 activation, multiple orthogonal methods\",\n      \"pmids\": [\"32572277\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Genetic interaction analysis in C. elegans showed that ubr-7 and ubr-5 single and double mutants interact genetically with the Notch receptor gene glp-1, influencing development and embryo formation, placing UBR7 in the Notch signaling pathway.\",\n      \"method\": \"C. elegans single and double mutant epistasis analysis with glp-1 (Notch receptor) alleles\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis in C. elegans ortholog, single study\",\n      \"pmids\": [\"33340455\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"UBR7 is a histone H3.1 chaperone that binds post-nucleosomal H3K4me3 and H3K9me3 histones via its UBR box and PHD domains. UBR7 interacts with the non-nucleosomal histone chaperone NASP. Loss of UBR7 causes accumulation of NASP-bound post-nucleosomal histones and depletion of chromatin H3K4me3.\",\n      \"method\": \"Co-IP (UBR7-NASP and UBR7-histone H3 interactions); domain mapping (UBR box and PHD); chromatin fractionation; H3K4me3 ChIP in UBR7-depleted cells\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, domain mapping, functional chromatin phenotype upon KO, multiple orthogonal methods in one study\",\n      \"pmids\": [\"34786730\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"UBR7 interacts with phosphoribosyl pyrophosphate synthetases (PRPS1/2), the essential enzymes for nucleotide biosynthesis. UBR7 stabilizes PRPS catalytic subunits by mediating polyubiquitination-directed proteasomal degradation of PRPSAP (PRPS-associated protein), the negative regulator of PRPS. Loss of UBR7 causes nucleotide biosynthesis defects.\",\n      \"method\": \"Proteomic co-immunoprecipitation (MS-based interactome); ubiquitination assay for PRPSAP; nucleotide biosynthesis measurement upon UBR7 depletion\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — proteomic identification of interactors, ubiquitination assay for specific substrate (PRPSAP), functional nucleotide biosynthesis readout, multiple orthogonal methods\",\n      \"pmids\": [\"33571115\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"UBR7 is defined as a transcriptional target of NOTCH1, and is overexpressed in NOTCH1-driven T-ALL, linking NOTCH1 signaling to UBR7-mediated nucleotide metabolism.\",\n      \"method\": \"ChIP and transcriptional reporter analysis for NOTCH1 regulation of UBR7; expression analysis in T-ALL cell lines\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct transcriptional regulation established, single lab\",\n      \"pmids\": [\"33571115\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The PHD finger of UBR7 associates with E2 UbcH6 to catalyze ubiquitin transfer to histone H2B. The PHD finger forms a dimer, and this dimerization is essential for H2BK120 ubiquitination. Binding of substrate H2B to UBR7 induces a conformational change in the PHD finger that triggers ubiquitin transfer from UbcH6. The C-terminal tail residues 114–125 of H2B are sufficient for UBR7/UbcH6-mediated ubiquitin transfer.\",\n      \"method\": \"In vitro ubiquitination assay; thioester hydrolysis assay; mutagenesis of dimerization-critical residues; mass spectrometry confirmation of H2B ubiquitination site; domain-interaction mapping\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assays with mutagenesis, MS confirmation, mechanistic dissection of E2-E3-substrate interactions, single lab\",\n      \"pmids\": [\"34739193\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"UBR7 binds to the Keap1 promoter via H2BK120ub monoubiquitination, thereby upregulating Keap1 expression and suppressing the downstream Nrf2/Bach1/HK2 signaling axis, which inhibits glycolysis in HCC.\",\n      \"method\": \"ChIP-seq for H2BK120ub at Keap1 promoter; RNAi screening for epigenetic regulators of lactic acid; in vitro and in vivo tumor growth assays with UBR7 KO; pharmacological inhibition of glycolysis\",\n      \"journal\": \"Journal of experimental & clinical cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP evidence for H2BK120ub at specific promoter, pathway epistasis, functional rescue, single lab\",\n      \"pmids\": [\"36419136\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"UBR7 (identified by tandem mass spectrometry) is localized to the spermatid acrosomal cap and sperm acrosome. E3-type ubiquitin ligase activity was detected in sperm acrosomal fractions using the UBB+1 reporter substrate, and UBR7 remained with the ZP-bound acrosomal shroud following acrosomal exocytosis during fertilization.\",\n      \"method\": \"Tandem mass spectrometry identification from in vitro ubiquitination gel bands; immunofluorescence localization; Western blotting of sperm fractions\",\n      \"journal\": \"Cell and tissue research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS identification, immunofluorescence localization, in vitro ubiquitination activity in acrosomal fractions; localization tied to functional context of fertilization\",\n      \"pmids\": [\"24664117\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"UBR7 ubiquitinates the speckled family protein Sp110 at critical residues within its SAND domain. Sp110 ubiquitination promotes degradation and downregulates type I interferon response genes, facilitating HBV persistence. Silencing UBR7 induces IRF7 phosphorylation, augmenting IFN-β and downstream interferon-stimulated gene expression.\",\n      \"method\": \"Co-IP; ubiquitination assay with ubiquitination-defective Sp110 mutants; RNA-seq of UBR7/Sp110 knockdown; single-cell RNA-seq of patient samples; IRF7 phosphorylation assay\",\n      \"journal\": \"ACS infectious diseases\",\n      \"confidence\": \"Medium","stage2_raw":"","audit_flag":null,"evaluation":null}