{"gene":"RNF34","run_date":"2026-06-10T06:43:37","timeline":{"discoveries":[{"year":2019,"finding":"RNF34 binds to MAVS in the mitochondrial compartment after viral infection and catalyzes K27-/K29-linked ubiquitination of MAVS at Lys 297, 311, 348, and 362, serving as a recognition signal for NDP52-dependent autophagic degradation. RNF34 also initiates a K63- to K27-linked ubiquitination transition on MAVS primarily at Lys 311, facilitating autophagic degradation upon RIG-I stimulation and negatively regulating RLR-mediated antiviral immunity.","method":"Co-immunoprecipitation, ubiquitination assays with linkage-specific antibodies, site-directed mutagenesis of MAVS lysine residues, NDP52 interaction studies, autophagy flux assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods including mutagenesis of specific ubiquitination sites, identification of autophagy receptor, and functional immune signaling readouts in a single rigorous study","pmids":["31304625"],"is_preprint":false},{"year":2011,"finding":"RNF34 is a nuclear E3 ubiquitin ligase that interacts with and ubiquitinates PGC-1α to promote its proteasomal degradation via its C-terminal half, independently of the previously identified N-terminal phosphodegron motif. Knockdown of RNF34 in brown fat cells increases PGC-1α protein level, UCP1 expression, and oxygen consumption; cold exposure and β3-adrenergic signaling suppress RNF34 expression.","method":"Luciferase-based overexpression screen, co-immunoprecipitation, ubiquitination assay, RNF34 knockdown and overexpression with ligase-dead mutant control, oxygen consumption measurement","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — identified via functional screen, confirmed by Co-IP, ubiquitination assay, ligase-dead mutant, and multiple cellular functional readouts in a single study","pmids":["22064484"],"is_preprint":false},{"year":2014,"finding":"RNF34 interacts with the large intracellular loop of the GABAA receptor γ2 subunit and ubiquitinates it, promoting GABAAR degradation via both lysosomal and proteasomal pathways. Mutating several lysines in the γ2 intracellular loop to arginines renders the subunit resistant to RNF34-induced degradation. RNF34 overexpression in hippocampal neurons decreases γ2 GABAAR cluster density and GABAergic innervation, while RNF34 knockdown increases them.","method":"Yeast two-hybrid, in vitro pulldown, co-immunoprecipitation from brain extracts, co-transfection in HEK293 cells, ubiquitination assay, site-directed mutagenesis of γ2 lysines, leupeptin/MG132 inhibitor experiments, immunofluorescence of hippocampal neurons, electron microscopy immunocytochemistry, shRNA knockdown","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods including mutagenesis of ubiquitination sites, inhibitor pharmacology, neuronal overexpression and knockdown with cellular phenotype readouts","pmids":["25193658"],"is_preprint":false},{"year":2014,"finding":"RNF34 interacts with NOD1 and promotes its ubiquitination and degradation, negatively regulating NOD1-dependent NF-κB activation. RNF34 overexpression inhibits NOD1-dependent NF-κB activation, while RNF34 siRNA knockdown increases NF-κB activation upon NOD1 overexpression or ligand stimulation.","method":"Yeast two-hybrid screening, co-immunoprecipitation, GST pulldown, western blotting for NOD1 stability and ubiquitination, NF-κB reporter assay, siRNA knockdown","journal":"Cellular physiology and biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal binding assays (Y2H + Co-IP + GST pulldown) plus functional NF-κB reporter and knockdown, single lab","pmids":["25012219"],"is_preprint":false},{"year":2019,"finding":"RNF34 interacts with PGC-1α in neurons and targets it for ubiquitin-dependent proteasomal degradation, thereby potentiating mitochondrial dysfunction-mediated oxidative stress after intracerebral hemorrhage. RNF34 overexpression exacerbated ICH-induced decreases in PGC-1α, UCP2, and MnSOD expression.","method":"Co-immunoprecipitation, ubiquitination assay, RNF34 transgenic mouse model, measurement of ROS, mitochondrial ROS, ATP production, western blotting","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP and ubiquitination assay confirmed interaction and degradation, supported by transgenic mouse functional data, single lab","pmids":["31704983"],"is_preprint":false},{"year":2022,"finding":"RNF34 participates in peripheral quality control of CFTR by directly recognizing CFTR NBD1 and selectively promoting ubiquitination of unfolded proteins. RNF34 localizes to cytoplasm and endosomes. Simultaneous ablation of RNF34 and RFFL dramatically increases functional plasma membrane expression of ∆F508-CFTR and inhibits its degradation in post-Golgi compartments.","method":"In vitro ubiquitination assay with recombinant proteins, subcellular localization by fluorescence microscopy, RNF34 ablation (siRNA/knockout), CFTR-NLuc degradation assay, flow cytometry for PM density","journal":"Frontiers in molecular biosciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro direct recognition assay, localization, functional ablation with multiple readouts, single lab","pmids":["35355508"],"is_preprint":false},{"year":2021,"finding":"RNF34 interacts with p22phox in vascular smooth muscle cells and promotes its ubiquitin-mediated proteasomal degradation. Loss of RNF34 in smooth muscle cells increases p22phox protein stability, enhancing p22phox/p47phox and p22phox/NOX2 binding, NADPH oxidase complex formation, and ROS generation, leading to cerebrovascular remodeling and hypertension.","method":"Immunoprecipitation, ubiquitination assay, conditional (SMC-specific) RNF34 knockout mice, ROS measurement, NADPH oxidase activity assay, p22phox knockdown rescue experiment","journal":"Neurobiology of disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and ubiquitination assay, cell-type-specific KO mouse model with mechanistic rescue, single lab","pmids":["34015492"],"is_preprint":false},{"year":2021,"finding":"RNF34 is recruited to interact with TAX1BP1 and facilitates autophagic degradation of MAVS through K27-linked polyubiquitination. This interaction suppresses NLRP3 mitochondrial localization and inflammasome activation in cardiomyocytes under ischemic stress. Knockdown of RNF34 nullified TAX1BP1-mediated protection against MAVS mitochondrial accumulation and NLRP3 inflammasome activation.","method":"Co-immunoprecipitation, ubiquitination assay, siRNA knockdown of RNF34, adenoviral overexpression of TAX1BP1, mitochondrial membrane potential measurement","journal":"Science bulletin","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP and ubiquitination data, siRNA functional rescue, multiple cellular readouts; extends prior MAVS/RNF34 finding, single lab","pmids":["36654301"],"is_preprint":false},{"year":2018,"finding":"Drosophila RNF34 (dRNF34) ubiquitinates Drosophila PGC-1 (dPGC-1) and promotes its degradation. Muscle-specific knockdown of dRNF34 in vivo promotes mitochondrial biogenesis, improves locomotor performance, and counteracts high-fat-diet-induced triglyceride accumulation; these effects are reversed by co-knockdown of dPGC-1, establishing genetic epistasis.","method":"Immunoprecipitation and western blotting in HEK293T cells, in vivo RNAi using muscle-specific Gal4 driver, mitochondrial biogenesis assays, climbing/exercise assays, triglyceride measurement, epistasis by double knockdown","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis in Drosophila plus biochemical ubiquitination assay, single lab; ortholog evidence consistent with mammalian RNF34/PGC-1α axis","pmids":["30247505"],"is_preprint":false},{"year":2023,"finding":"RNF34 forms a 'ZRR' complex with ZFYVE21 (a Rab5 effector) and Rubicon on early endosomes. Within this complex, RNF34 ubiquitinates and degradatively removes Flightless I (FliI) — an inhibitory pseudosubstrate of caspase-1 — from the signaling endosome, thereby increasing endosome-associated caspase-1 available for activation and promoting NLRP3 inflammasome activity in endothelial cells.","method":"Proteomics/AP-MS of FACS-sorted inflammasomes, co-immunoprecipitation, endosomal fractionation, RNF34 functional studies in endothelial cells, in vivo mouse models (three models), human tissue validation","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — AP-MS complex identification, Co-IP, endosomal localization, functional ubiquitination of FliI, multiple in vivo mouse models and human tissue validation","pmids":["37225719"],"is_preprint":false}],"current_model":"RNF34 is a RING-domain E3 ubiquitin ligase that regulates innate immunity, mitochondrial homeostasis, and synaptic function by ubiquitinating multiple substrates: it catalyzes K27/K29-linked polyubiquitination of MAVS to direct it for NDP52-dependent selective autophagy, thereby dampening RLR antiviral signaling; it ubiquitinates PGC-1α via a C-terminal degron for proteasomal degradation to restrain thermogenesis and mitochondrial biogenesis; it ubiquitinates the GABAA receptor γ2 subunit to promote receptor degradation and limit GABAergic synapse density; it ubiquitinates NOD1 to suppress NF-κB activation; it ubiquitinates p22phox in vascular smooth muscle cells to limit NADPH oxidase-derived ROS; it participates in CFTR peripheral quality control by recognizing unfolded CFTR NBD1; and on endosomes it forms a ZFYVE21–Rubicon–RNF34 complex that ubiquitinates and removes the caspase-1 pseudosubstrate FliI to promote inflammasome activation."},"narrative":{"mechanistic_narrative":"RNF34 is a RING-domain E3 ubiquitin ligase that acts as a substrate-selective degradation factor across innate immune signaling, mitochondrial homeostasis, and synaptic regulation [PMID:31304625, PMID:22064484, PMID:25193658]. In antiviral immunity it binds mitochondrial MAVS after viral infection and catalyzes K27-/K29-linked polyubiquitination (with a K63-to-K27 linkage transition at Lys311), generating a recognition signal for NDP52-dependent selective autophagic degradation that dampens RLR-mediated signaling [PMID:31304625]; this MAVS-clearing activity is also recruited via TAX1BP1 to suppress NLRP3 inflammasome activation under ischemic stress [PMID:36654301]. In a distinct endosomal context, RNF34 assembles with ZFYVE21 and Rubicon into a 'ZRR' complex on early endosomes and ubiquitinates the caspase-1 pseudosubstrate Flightless I (FliI) for removal, thereby promoting NLRP3 inflammasome activity [PMID:37225719]. RNF34 restrains mitochondrial biogenesis and thermogenesis by ubiquitinating PGC-1α through a C-terminal degron for proteasomal degradation, a function conserved from Drosophila and relevant to oxidative stress in neurons [PMID:22064484, PMID:30247505, PMID:31704983]. It additionally ubiquitinates the GABAA receptor γ2 subunit to drive receptor degradation and limit GABAergic synapse density [PMID:25193658], targets NOD1 to suppress NF-κB activation [PMID:25012219], degrades p22phox to limit NADPH oxidase-derived ROS in vascular smooth muscle [PMID:34015492], and recognizes unfolded CFTR NBD1 in peripheral quality control [PMID:35355508].","teleology":[{"year":2011,"claim":"Established RNF34 as a functional E3 ligase by identifying PGC-1α as a degradation substrate, defining a new C-terminal degradation route independent of the known N-terminal phosphodegron and linking RNF34 to thermogenic/mitochondrial control.","evidence":"Luciferase overexpression screen, Co-IP, ubiquitination assay with ligase-dead control, and oxygen consumption/UCP1 readouts in brown fat cells","pmids":["22064484"],"confidence":"High","gaps":["Ubiquitin linkage type on PGC-1α not defined","Specific PGC-1α lysine acceptor sites not mapped"]},{"year":2014,"claim":"Extended RNF34 substrate range into synaptic biology, showing it ubiquitinates the GABAA receptor γ2 subunit to control receptor turnover and synapse density.","evidence":"Yeast two-hybrid, Co-IP from brain, γ2 lysine-to-arginine mutagenesis, inhibitor pharmacology, and neuronal overexpression/knockdown with cluster-density readouts","pmids":["25193658"],"confidence":"High","gaps":["Dual lysosomal/proteasomal routing not mechanistically resolved","Linkage specificity not determined"]},{"year":2014,"claim":"Implicated RNF34 in innate immune signaling by showing it degrades NOD1 to suppress NF-κB activation.","evidence":"Yeast two-hybrid, Co-IP, GST pulldown, NF-κB reporter, and siRNA knockdown","pmids":["25012219"],"confidence":"Medium","gaps":["Single lab without reciprocal in vivo validation","Ubiquitin sites and linkage on NOD1 unmapped"]},{"year":2018,"claim":"Confirmed evolutionary conservation of the RNF34–PGC-1 axis and its physiological consequences for mitochondrial biogenesis and metabolism through genetic epistasis.","evidence":"Drosophila muscle-specific RNAi, biochemical ubiquitination in HEK293T, and double-knockdown epistasis with dPGC-1","pmids":["30247505"],"confidence":"Medium","gaps":["Ortholog evidence not directly extrapolated to mammalian tissues here","Single lab"]},{"year":2019,"claim":"Resolved how RNF34 negatively regulates antiviral signaling, defining specific K27-/K29-linked MAVS ubiquitination sites and a K63-to-K27 transition that routes MAVS to NDP52-dependent selective autophagy.","evidence":"Co-IP, linkage-specific ubiquitination assays, MAVS lysine mutagenesis, NDP52 interaction studies, and autophagy flux assays","pmids":["31304625"],"confidence":"High","gaps":["Trigger for the K63-to-K27 linkage switch unknown","Upstream signals controlling RNF34 recruitment to MAVS unresolved"]},{"year":2019,"claim":"Placed the RNF34–PGC-1α axis in a disease context, showing RNF34 potentiates mitochondrial dysfunction and oxidative stress after intracerebral hemorrhage.","evidence":"Co-IP, ubiquitination assay, RNF34 transgenic mouse, and ROS/ATP/MnSOD measurements","pmids":["31704983"],"confidence":"Medium","gaps":["Neuronal-specific regulation of RNF34 expression not defined","Single lab"]},{"year":2021,"claim":"Identified p22phox as an RNF34 substrate, linking RNF34 to control of NADPH oxidase assembly and vascular ROS, hypertension, and remodeling.","evidence":"Co-IP, ubiquitination assay, SMC-specific conditional knockout mice, NADPH oxidase activity, and p22phox knockdown rescue","pmids":["34015492"],"confidence":"Medium","gaps":["Ubiquitin sites on p22phox unmapped","Single lab"]},{"year":2021,"claim":"Connected RNF34's MAVS-clearing activity to inflammasome control, showing TAX1BP1-recruited RNF34 limits NLRP3 activation in ischemic cardiomyocytes.","evidence":"Co-IP, ubiquitination assay, RNF34 siRNA rescue, adenoviral TAX1BP1 overexpression, and mitochondrial membrane potential readouts","pmids":["36654301"],"confidence":"Medium","gaps":["Mechanism of TAX1BP1-dependent recruitment of RNF34 not detailed","Single lab"]},{"year":2022,"claim":"Revealed a quality-control role for RNF34, showing it directly recognizes unfolded CFTR NBD1 to drive peripheral degradation of mutant CFTR.","evidence":"In vitro ubiquitination with recombinant proteins, fluorescence localization, RNF34/RFFL ablation, and CFTR-NLuc degradation and PM density assays","pmids":["35355508"],"confidence":"Medium","gaps":["Functional redundancy with RFFL not fully separated","Structural basis of unfolded-NBD1 recognition unknown"]},{"year":2023,"claim":"Defined an inflammasome-promoting role on endosomes, placing RNF34 in a ZFYVE21–Rubicon–RNF34 complex that removes the caspase-1 pseudosubstrate FliI to enable NLRP3 activation.","evidence":"AP-MS of sorted inflammasomes, Co-IP, endosomal fractionation, endothelial functional studies, three in vivo mouse models, and human tissue validation","pmids":["37225719"],"confidence":"High","gaps":["Reconciliation of RNF34's pro- versus anti-inflammasome roles across contexts unresolved","FliI ubiquitination sites not mapped"]},{"year":null,"claim":"How RNF34 selects among its diverse substrates and switches between distinct ubiquitin linkages and degradation fates (autophagic versus proteasomal versus lysosomal) in different subcellular compartments remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unifying model of substrate recruitment specificity","Determinants of linkage choice (K27/K29/K63/K48) per substrate undefined","Structural basis of RNF34 catalysis not characterized in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,1,2,5,9]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[5]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[5,9]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,3,7,9]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[0,7]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1,2,5]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[1,8]}],"complexes":["ZFYVE21-Rubicon-RNF34 (ZRR) complex"],"partners":["MAVS","PGC-1Α","GABRG2","NOD1","CYBA","CFTR","TAX1BP1","ZFYVE21"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q969K3","full_name":"E3 ubiquitin-protein ligase RNF34","aliases":["Caspase regulator CARP1","Caspases-8 and -10-associated RING finger protein 1","CARP-1","FYVE-RING finger protein Momo","Human RING finger homologous to inhibitor of apoptosis protein","hRFI","RING finger protein 34","RING finger protein RIFF","RING-type E3 ubiquitin transferase RNF34"],"length_aa":372,"mass_kda":41.6,"function":"E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis (PubMed:15069192). May mediate 'Lys-48'-linked polyubiquitination of RIPK1 and its subsequent proteasomal degradation thereby indirectly regulating the tumor necrosis factor-mediated signaling pathway (Ref.13). Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation (PubMed:17121812). Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN (PubMed:18382127). Mediates PPARGC1A proteasomal degradation probably through ubiquitination thereby indirectly regulating the metabolism of brown fat cells (PubMed:22064484). Possibly involved in innate immunity, through 'Lys-48'-linked polyubiquitination of NOD1 and its subsequent proteasomal degradation (PubMed:25012219)","subcellular_location":"Cell membrane; Endomembrane system; Nucleus; Nucleus speckle; Cytoplasm, cytosol","url":"https://www.uniprot.org/uniprotkb/Q969K3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RNF34","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HSPA4","stoichiometry":0.2},{"gene":"OST4","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/RNF34","total_profiled":1310},"omim":[{"mim_id":"608299","title":"RING FINGER PROTEIN 34; RNF34","url":"https://www.omim.org/entry/608299"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nuclear speckles","reliability":"Additional"},{"location":"Nuclear bodies","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RNF34"},"hgnc":{"alias_symbol":["RIFF","FLJ21786","RIF"],"prev_symbol":[]},"alphafold":{"accession":"Q969K3","domains":[{"cath_id":"1.10.720.140","chopping":"77-152","consensus_level":"high","plddt":94.0414,"start":77,"end":152},{"cath_id":"-","chopping":"256-316","consensus_level":"high","plddt":87.4618,"start":256,"end":316},{"cath_id":"3.30.40.10","chopping":"324-369","consensus_level":"high","plddt":94.7357,"start":324,"end":369}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q969K3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q969K3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q969K3-F1-predicted_aligned_error_v6.png","plddt_mean":71.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RNF34","jax_strain_url":"https://www.jax.org/strain/search?query=RNF34"},"sequence":{"accession":"Q969K3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q969K3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q969K3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q969K3"}},"corpus_meta":[{"pmid":"31304625","id":"PMC_31304625","title":"RNF34 functions in immunity and selective mitophagy by targeting MAVS for autophagic degradation.","date":"2019","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/31304625","citation_count":112,"is_preprint":false},{"pmid":"10627035","id":"PMC_10627035","title":"Intermediates of rifamycin polyketide synthase produced by an Amycolatopsis mediterranei mutant with inactivated rifF gene.","date":"1999","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/10627035","citation_count":47,"is_preprint":false},{"pmid":"22064484","id":"PMC_22064484","title":"RNF34 is a cold-regulated E3 ubiquitin ligase for PGC-1α and modulates brown fat cell metabolism.","date":"2011","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/22064484","citation_count":42,"is_preprint":false},{"pmid":"36654301","id":"PMC_36654301","title":"TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3-dependent manner.","date":"2021","source":"Science bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/36654301","citation_count":38,"is_preprint":false},{"pmid":"11812235","id":"PMC_11812235","title":"Expression and purification of the rifamycin amide synthase, RifF, an enzyme homologous to the prokaryotic arylamine N-acetyltransferases.","date":"2002","source":"Protein expression and purification","url":"https://pubmed.ncbi.nlm.nih.gov/11812235","citation_count":29,"is_preprint":false},{"pmid":"25193658","id":"PMC_25193658","title":"Ring finger protein 34 (RNF34) interacts with and promotes γ-aminobutyric acid type-A receptor degradation via ubiquitination of the γ2 subunit.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25193658","citation_count":28,"is_preprint":false},{"pmid":"31704983","id":"PMC_31704983","title":"RNF34 overexpression exacerbates neurological deficits and brain injury in a mouse model of intracerebral hemorrhage by potentiating mitochondrial dysfunction-mediated oxidative stress.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31704983","citation_count":24,"is_preprint":false},{"pmid":"25012219","id":"PMC_25012219","title":"The E3 ligase RNF34 is a novel negative regulator of the NOD1 pathway.","date":"2014","source":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/25012219","citation_count":20,"is_preprint":false},{"pmid":"35355508","id":"PMC_35355508","title":"The Ubiquitin Ligase RNF34 Participates in the Peripheral Quality Control of CFTR (RNF34 Role in CFTR PeriQC).","date":"2022","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/35355508","citation_count":15,"is_preprint":false},{"pmid":"34015492","id":"PMC_34015492","title":"RNF34 ablation promotes cerebrovascular remodeling and hypertension by increasing NADPH-derived ROS generation.","date":"2021","source":"Neurobiology of disease","url":"https://pubmed.ncbi.nlm.nih.gov/34015492","citation_count":11,"is_preprint":false},{"pmid":"30247505","id":"PMC_30247505","title":"RNF34 modulates the mitochondrial biogenesis and exercise capacity in muscle and lipid metabolism through ubiquitination of PGC-1 in Drosophila.","date":"2018","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/30247505","citation_count":10,"is_preprint":false},{"pmid":"37225719","id":"PMC_37225719","title":"A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37225719","citation_count":6,"is_preprint":false},{"pmid":"24769453","id":"PMC_24769453","title":"A new Riff: Rif1 eats its cake and has it too.","date":"2014","source":"EMBO 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pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/42030364","citation_count":0,"is_preprint":false},{"pmid":"41544989","id":"PMC_41544989","title":"IGF2BP stabilizes RNF34 mRNA to orchestrate apoptosis and host susceptibility to Vibrio splendidus in Apostichopus japonicus.","date":"2026","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/41544989","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.08.02.606416","title":"Computational enzyme design by catalytic motif scaffolding","date":"2024-08-03","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.02.606416","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11261,"output_tokens":3242,"usd":0.041207,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10717,"output_tokens":3724,"usd":0.073343,"stage2_stop_reason":"end_turn"},"total_usd":0.11455,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"RNF34 binds to MAVS in the mitochondrial compartment after viral infection and catalyzes K27-/K29-linked ubiquitination of MAVS at Lys 297, 311, 348, and 362, serving as a recognition signal for NDP52-dependent autophagic degradation. RNF34 also initiates a K63- to K27-linked ubiquitination transition on MAVS primarily at Lys 311, facilitating autophagic degradation upon RIG-I stimulation and negatively regulating RLR-mediated antiviral immunity.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays with linkage-specific antibodies, site-directed mutagenesis of MAVS lysine residues, NDP52 interaction studies, autophagy flux assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods including mutagenesis of specific ubiquitination sites, identification of autophagy receptor, and functional immune signaling readouts in a single rigorous study\",\n      \"pmids\": [\"31304625\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"RNF34 is a nuclear E3 ubiquitin ligase that interacts with and ubiquitinates PGC-1α to promote its proteasomal degradation via its C-terminal half, independently of the previously identified N-terminal phosphodegron motif. Knockdown of RNF34 in brown fat cells increases PGC-1α protein level, UCP1 expression, and oxygen consumption; cold exposure and β3-adrenergic signaling suppress RNF34 expression.\",\n      \"method\": \"Luciferase-based overexpression screen, co-immunoprecipitation, ubiquitination assay, RNF34 knockdown and overexpression with ligase-dead mutant control, oxygen consumption measurement\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — identified via functional screen, confirmed by Co-IP, ubiquitination assay, ligase-dead mutant, and multiple cellular functional readouts in a single study\",\n      \"pmids\": [\"22064484\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"RNF34 interacts with the large intracellular loop of the GABAA receptor γ2 subunit and ubiquitinates it, promoting GABAAR degradation via both lysosomal and proteasomal pathways. Mutating several lysines in the γ2 intracellular loop to arginines renders the subunit resistant to RNF34-induced degradation. RNF34 overexpression in hippocampal neurons decreases γ2 GABAAR cluster density and GABAergic innervation, while RNF34 knockdown increases them.\",\n      \"method\": \"Yeast two-hybrid, in vitro pulldown, co-immunoprecipitation from brain extracts, co-transfection in HEK293 cells, ubiquitination assay, site-directed mutagenesis of γ2 lysines, leupeptin/MG132 inhibitor experiments, immunofluorescence of hippocampal neurons, electron microscopy immunocytochemistry, shRNA knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods including mutagenesis of ubiquitination sites, inhibitor pharmacology, neuronal overexpression and knockdown with cellular phenotype readouts\",\n      \"pmids\": [\"25193658\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"RNF34 interacts with NOD1 and promotes its ubiquitination and degradation, negatively regulating NOD1-dependent NF-κB activation. RNF34 overexpression inhibits NOD1-dependent NF-κB activation, while RNF34 siRNA knockdown increases NF-κB activation upon NOD1 overexpression or ligand stimulation.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation, GST pulldown, western blotting for NOD1 stability and ubiquitination, NF-κB reporter assay, siRNA knockdown\",\n      \"journal\": \"Cellular physiology and biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding assays (Y2H + Co-IP + GST pulldown) plus functional NF-κB reporter and knockdown, single lab\",\n      \"pmids\": [\"25012219\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"RNF34 interacts with PGC-1α in neurons and targets it for ubiquitin-dependent proteasomal degradation, thereby potentiating mitochondrial dysfunction-mediated oxidative stress after intracerebral hemorrhage. RNF34 overexpression exacerbated ICH-induced decreases in PGC-1α, UCP2, and MnSOD expression.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, RNF34 transgenic mouse model, measurement of ROS, mitochondrial ROS, ATP production, western blotting\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP and ubiquitination assay confirmed interaction and degradation, supported by transgenic mouse functional data, single lab\",\n      \"pmids\": [\"31704983\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RNF34 participates in peripheral quality control of CFTR by directly recognizing CFTR NBD1 and selectively promoting ubiquitination of unfolded proteins. RNF34 localizes to cytoplasm and endosomes. Simultaneous ablation of RNF34 and RFFL dramatically increases functional plasma membrane expression of ∆F508-CFTR and inhibits its degradation in post-Golgi compartments.\",\n      \"method\": \"In vitro ubiquitination assay with recombinant proteins, subcellular localization by fluorescence microscopy, RNF34 ablation (siRNA/knockout), CFTR-NLuc degradation assay, flow cytometry for PM density\",\n      \"journal\": \"Frontiers in molecular biosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro direct recognition assay, localization, functional ablation with multiple readouts, single lab\",\n      \"pmids\": [\"35355508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RNF34 interacts with p22phox in vascular smooth muscle cells and promotes its ubiquitin-mediated proteasomal degradation. Loss of RNF34 in smooth muscle cells increases p22phox protein stability, enhancing p22phox/p47phox and p22phox/NOX2 binding, NADPH oxidase complex formation, and ROS generation, leading to cerebrovascular remodeling and hypertension.\",\n      \"method\": \"Immunoprecipitation, ubiquitination assay, conditional (SMC-specific) RNF34 knockout mice, ROS measurement, NADPH oxidase activity assay, p22phox knockdown rescue experiment\",\n      \"journal\": \"Neurobiology of disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and ubiquitination assay, cell-type-specific KO mouse model with mechanistic rescue, single lab\",\n      \"pmids\": [\"34015492\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RNF34 is recruited to interact with TAX1BP1 and facilitates autophagic degradation of MAVS through K27-linked polyubiquitination. This interaction suppresses NLRP3 mitochondrial localization and inflammasome activation in cardiomyocytes under ischemic stress. Knockdown of RNF34 nullified TAX1BP1-mediated protection against MAVS mitochondrial accumulation and NLRP3 inflammasome activation.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, siRNA knockdown of RNF34, adenoviral overexpression of TAX1BP1, mitochondrial membrane potential measurement\",\n      \"journal\": \"Science bulletin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP and ubiquitination data, siRNA functional rescue, multiple cellular readouts; extends prior MAVS/RNF34 finding, single lab\",\n      \"pmids\": [\"36654301\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Drosophila RNF34 (dRNF34) ubiquitinates Drosophila PGC-1 (dPGC-1) and promotes its degradation. Muscle-specific knockdown of dRNF34 in vivo promotes mitochondrial biogenesis, improves locomotor performance, and counteracts high-fat-diet-induced triglyceride accumulation; these effects are reversed by co-knockdown of dPGC-1, establishing genetic epistasis.\",\n      \"method\": \"Immunoprecipitation and western blotting in HEK293T cells, in vivo RNAi using muscle-specific Gal4 driver, mitochondrial biogenesis assays, climbing/exercise assays, triglyceride measurement, epistasis by double knockdown\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis in Drosophila plus biochemical ubiquitination assay, single lab; ortholog evidence consistent with mammalian RNF34/PGC-1α axis\",\n      \"pmids\": [\"30247505\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RNF34 forms a 'ZRR' complex with ZFYVE21 (a Rab5 effector) and Rubicon on early endosomes. Within this complex, RNF34 ubiquitinates and degradatively removes Flightless I (FliI) — an inhibitory pseudosubstrate of caspase-1 — from the signaling endosome, thereby increasing endosome-associated caspase-1 available for activation and promoting NLRP3 inflammasome activity in endothelial cells.\",\n      \"method\": \"Proteomics/AP-MS of FACS-sorted inflammasomes, co-immunoprecipitation, endosomal fractionation, RNF34 functional studies in endothelial cells, in vivo mouse models (three models), human tissue validation\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — AP-MS complex identification, Co-IP, endosomal localization, functional ubiquitination of FliI, multiple in vivo mouse models and human tissue validation\",\n      \"pmids\": [\"37225719\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RNF34 is a RING-domain E3 ubiquitin ligase that regulates innate immunity, mitochondrial homeostasis, and synaptic function by ubiquitinating multiple substrates: it catalyzes K27/K29-linked polyubiquitination of MAVS to direct it for NDP52-dependent selective autophagy, thereby dampening RLR antiviral signaling; it ubiquitinates PGC-1α via a C-terminal degron for proteasomal degradation to restrain thermogenesis and mitochondrial biogenesis; it ubiquitinates the GABAA receptor γ2 subunit to promote receptor degradation and limit GABAergic synapse density; it ubiquitinates NOD1 to suppress NF-κB activation; it ubiquitinates p22phox in vascular smooth muscle cells to limit NADPH oxidase-derived ROS; it participates in CFTR peripheral quality control by recognizing unfolded CFTR NBD1; and on endosomes it forms a ZFYVE21–Rubicon–RNF34 complex that ubiquitinates and removes the caspase-1 pseudosubstrate FliI to promote inflammasome activation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RNF34 is a RING-domain E3 ubiquitin ligase that acts as a substrate-selective degradation factor across innate immune signaling, mitochondrial homeostasis, and synaptic regulation [#0, #1, #2]. In antiviral immunity it binds mitochondrial MAVS after viral infection and catalyzes K27-/K29-linked polyubiquitination (with a K63-to-K27 linkage transition at Lys311), generating a recognition signal for NDP52-dependent selective autophagic degradation that dampens RLR-mediated signaling [#0]; this MAVS-clearing activity is also recruited via TAX1BP1 to suppress NLRP3 inflammasome activation under ischemic stress [#7]. In a distinct endosomal context, RNF34 assembles with ZFYVE21 and Rubicon into a 'ZRR' complex on early endosomes and ubiquitinates the caspase-1 pseudosubstrate Flightless I (FliI) for removal, thereby promoting NLRP3 inflammasome activity [#9]. RNF34 restrains mitochondrial biogenesis and thermogenesis by ubiquitinating PGC-1\\u03b1 through a C-terminal degron for proteasomal degradation, a function conserved from Drosophila and relevant to oxidative stress in neurons [#1, #8, #4]. It additionally ubiquitinates the GABAA receptor \\u03b32 subunit to drive receptor degradation and limit GABAergic synapse density [#2], targets NOD1 to suppress NF-\\u03baB activation [#3], degrades p22phox to limit NADPH oxidase-derived ROS in vascular smooth muscle [#6], and recognizes unfolded CFTR NBD1 in peripheral quality control [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established RNF34 as a functional E3 ligase by identifying PGC-1\\u03b1 as a degradation substrate, defining a new C-terminal degradation route independent of the known N-terminal phosphodegron and linking RNF34 to thermogenic/mitochondrial control.\",\n      \"evidence\": \"Luciferase overexpression screen, Co-IP, ubiquitination assay with ligase-dead control, and oxygen consumption/UCP1 readouts in brown fat cells\",\n      \"pmids\": [\"22064484\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Ubiquitin linkage type on PGC-1\\u03b1 not defined\", \"Specific PGC-1\\u03b1 lysine acceptor sites not mapped\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Extended RNF34 substrate range into synaptic biology, showing it ubiquitinates the GABAA receptor \\u03b32 subunit to control receptor turnover and synapse density.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP from brain, \\u03b32 lysine-to-arginine mutagenesis, inhibitor pharmacology, and neuronal overexpression/knockdown with cluster-density readouts\",\n      \"pmids\": [\"25193658\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Dual lysosomal/proteasomal routing not mechanistically resolved\", \"Linkage specificity not determined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Implicated RNF34 in innate immune signaling by showing it degrades NOD1 to suppress NF-\\u03baB activation.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, GST pulldown, NF-\\u03baB reporter, and siRNA knockdown\",\n      \"pmids\": [\"25012219\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab without reciprocal in vivo validation\", \"Ubiquitin sites and linkage on NOD1 unmapped\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Confirmed evolutionary conservation of the RNF34\\u2013PGC-1 axis and its physiological consequences for mitochondrial biogenesis and metabolism through genetic epistasis.\",\n      \"evidence\": \"Drosophila muscle-specific RNAi, biochemical ubiquitination in HEK293T, and double-knockdown epistasis with dPGC-1\",\n      \"pmids\": [\"30247505\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ortholog evidence not directly extrapolated to mammalian tissues here\", \"Single lab\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Resolved how RNF34 negatively regulates antiviral signaling, defining specific K27-/K29-linked MAVS ubiquitination sites and a K63-to-K27 transition that routes MAVS to NDP52-dependent selective autophagy.\",\n      \"evidence\": \"Co-IP, linkage-specific ubiquitination assays, MAVS lysine mutagenesis, NDP52 interaction studies, and autophagy flux assays\",\n      \"pmids\": [\"31304625\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trigger for the K63-to-K27 linkage switch unknown\", \"Upstream signals controlling RNF34 recruitment to MAVS unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placed the RNF34\\u2013PGC-1\\u03b1 axis in a disease context, showing RNF34 potentiates mitochondrial dysfunction and oxidative stress after intracerebral hemorrhage.\",\n      \"evidence\": \"Co-IP, ubiquitination assay, RNF34 transgenic mouse, and ROS/ATP/MnSOD measurements\",\n      \"pmids\": [\"31704983\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Neuronal-specific regulation of RNF34 expression not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified p22phox as an RNF34 substrate, linking RNF34 to control of NADPH oxidase assembly and vascular ROS, hypertension, and remodeling.\",\n      \"evidence\": \"Co-IP, ubiquitination assay, SMC-specific conditional knockout mice, NADPH oxidase activity, and p22phox knockdown rescue\",\n      \"pmids\": [\"34015492\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ubiquitin sites on p22phox unmapped\", \"Single lab\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Connected RNF34's MAVS-clearing activity to inflammasome control, showing TAX1BP1-recruited RNF34 limits NLRP3 activation in ischemic cardiomyocytes.\",\n      \"evidence\": \"Co-IP, ubiquitination assay, RNF34 siRNA rescue, adenoviral TAX1BP1 overexpression, and mitochondrial membrane potential readouts\",\n      \"pmids\": [\"36654301\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of TAX1BP1-dependent recruitment of RNF34 not detailed\", \"Single lab\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Revealed a quality-control role for RNF34, showing it directly recognizes unfolded CFTR NBD1 to drive peripheral degradation of mutant CFTR.\",\n      \"evidence\": \"In vitro ubiquitination with recombinant proteins, fluorescence localization, RNF34/RFFL ablation, and CFTR-NLuc degradation and PM density assays\",\n      \"pmids\": [\"35355508\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional redundancy with RFFL not fully separated\", \"Structural basis of unfolded-NBD1 recognition unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined an inflammasome-promoting role on endosomes, placing RNF34 in a ZFYVE21\\u2013Rubicon\\u2013RNF34 complex that removes the caspase-1 pseudosubstrate FliI to enable NLRP3 activation.\",\n      \"evidence\": \"AP-MS of sorted inflammasomes, Co-IP, endosomal fractionation, endothelial functional studies, three in vivo mouse models, and human tissue validation\",\n      \"pmids\": [\"37225719\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Reconciliation of RNF34's pro- versus anti-inflammasome roles across contexts unresolved\", \"FliI ubiquitination sites not mapped\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RNF34 selects among its diverse substrates and switches between distinct ubiquitin linkages and degradation fates (autophagic versus proteasomal versus lysosomal) in different subcellular compartments remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unifying model of substrate recruitment specificity\", \"Determinants of linkage choice (K27/K29/K63/K48) per substrate undefined\", \"Structural basis of RNF34 catalysis not characterized in the corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 1, 2, 5, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [5, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 3, 7, 9]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1, 2, 5]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [1, 8]}\n    ],\n    \"complexes\": [\"ZFYVE21-Rubicon-RNF34 (ZRR) complex\"],\n    \"partners\": [\"MAVS\", \"PGC-1\\u03b1\", \"GABRG2\", \"NOD1\", \"CYBA\", \"CFTR\", \"TAX1BP1\", \"ZFYVE21\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}