{"gene":"RPL35","run_date":"2026-04-28T20:42:06","timeline":{"discoveries":[{"year":1977,"finding":"RPL35 (L35) was isolated and purified as a component of the rat liver 60S ribosomal large subunit, with molecular weight estimated by SDS-PAGE and amino acid composition determined, establishing it as a bona fide structural ribosomal protein.","method":"Ion-exchange chromatography, gel filtration (Sephadex), SDS-PAGE, amino acid composition analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — direct biochemical isolation and characterization; foundational purification study","pmids":["863909"],"is_preprint":false},{"year":1990,"finding":"The primary structure of rat 60S ribosomal subunit protein L35 was determined: 122 amino acids (N-terminal Met cleaved post-translationally), molecular weight 14,412 Da. The protein is related to archaebacterial L33/L29E and E. coli L29, and the gene exists in 15–17 copies in the rat genome.","method":"cDNA sequencing, N-terminal amino acid sequencing, Southern blot hybridization","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 1 — direct protein sequencing confirmed by cDNA; primary structure established","pmids":["2322279"],"is_preprint":false},{"year":2008,"finding":"The eukaryote-specific C-terminal expansion segment (ES) of human RPL35 was functionally dissected: the first 25 amino acids of the 54-aa ES are essential for nuclear import of the protein, whereas the last 29 residues are dispensable for ribosome structure and translation but serve as a contact site for ribosomal docking to the endoplasmic reticulum.","method":"Deletion mutagenesis, in vivo recombinant ribosome analysis, nuclear import assays","journal":"Biochemistry and cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — direct mutagenesis with defined functional readouts; single lab study","pmids":["18523488"],"is_preprint":false},{"year":2010,"finding":"In Saccharomyces cerevisiae, L35 is required for processing of 27SB pre-rRNA to 7S pre-rRNA (cleavage at site C2 of ITS2). Depletion of L35 causes a deficit in 60S ribosomal subunits, half-mer polysomes, and blocks release of pre-60S particles from the nucleolus to the nucleoplasm. L35 assembles in the nucleolus and associates with early pre-60S ribosomal particles.","method":"Conditional depletion (tetO system), pulse-chase labeling, northern hybridization, primer extension, sucrose gradient sedimentation, fluorescence microscopy","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (pulse-chase, northern, primer extension, microscopy) in yeast ortholog; strong evidence","pmids":["20392820"],"is_preprint":false},{"year":2015,"finding":"RPL35 regulates translational elongation of β-casein (CSN2) in bovine mammary epithelial cells by directly interacting with eukaryotic elongation factor 2 (eEF2), placing eEF2 downstream of RPL35 in the methionine signaling pathway. RPL35 also controls CSN2 secretion by localizing it to the endoplasmic reticulum.","method":"Co-immunoprecipitation, co-localization microscopy, FRET, gene mutation analysis, overexpression and knockdown experiments","journal":"Archives of biochemistry and biophysics","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP and FRET for interaction; single lab with multiple methods","pmids":["26297660"],"is_preprint":false},{"year":2019,"finding":"The long noncoding RNA lncNB1 physically binds to RPL35 and enhances E2F1 protein synthesis, leading to DEPDC1B transcription, ERK phosphorylation, and N-Myc protein stabilization. Knockdown of RPL35 or lncNB1 abolishes clonogenic capacity and causes tumor regression in vivo, identifying RPL35 as a key factor for E2F1 translational upregulation in neuroblastoma.","method":"RNA pull-down, Co-immunoprecipitation, ribosome profiling, shRNA knockdown, xenograft mouse model","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (pulldown, Co-IP, in vivo rescue) with rigorous controls; single lab but comprehensive","pmids":["31690716"],"is_preprint":false},{"year":2021,"finding":"RPL35 knockdown in neuroblastoma cells decreases aerobic glycolysis and increases mitochondrial respiration, with mechanistic analysis showing that RPL35 positively regulates HIF1α expression (mRNA and protein) and acts through the RPL35/ERK/HIF1α signaling axis.","method":"shRNA knockdown, Seahorse metabolic flux assay, Western blot, qRT-PCR","journal":"American journal of cancer research","confidence":"Medium","confidence_rationale":"Tier 3 — KD with metabolic phenotype and pathway placement, single lab, single primary method per step","pmids":["34873488"],"is_preprint":false},{"year":2021,"finding":"RPL35 was identified as a direct binding partner of the Mycoplasma genitalium adhesin protein MgPa via far-Western blot and co-localization; this interaction promotes expression of translation-initiation proteins (EIF2, SRP68, SERBP1, RPL35A) and EGF/TGF-β, leading to enhanced urothelial cell proliferation.","method":"T7 phage display library screening, far-Western blot, co-localization, TMT proteomics, qRT-PCR, MTT proliferation assay","journal":"Pathogens","confidence":"Low","confidence_rationale":"Tier 3 — interaction validated by far-Western and co-localization; downstream pathway inferred from proteomics without direct mechanistic dissection","pmids":["34832605"],"is_preprint":false},{"year":2021,"finding":"RPL35 was identified as a candidate small-molecule binding target: molecular docking and NMR titration studies showed that the FDA-approved drugs atazanavir and artesunate bind to an overlapping cluster near the N-terminus of rpL35, accessible when RPL35 is integrated in the ribosome. This binding site was proposed to modulate translational readthrough at premature stop codons.","method":"Molecular docking, NMR chemical shift perturbation mapping","journal":"Skin pharmacology and physiology","confidence":"Low","confidence_rationale":"Tier 4 — computational docking plus NMR binding mapping; no functional readthrough assay performed","pmids":["33823521"],"is_preprint":false},{"year":2022,"finding":"DDX10 interacts with RPL35 in colorectal cancer cells, as identified by LC-MS/MS proteomics and confirmed by co-immunoprecipitation; DDX10 knockdown reduces CRC cell proliferation, migration and invasion, and both proteins are implicated in RNA splicing and E2F target pathways.","method":"LC-MS/MS interactome, Co-immunoprecipitation, shRNA knockdown, cell proliferation/migration assays","journal":"Cancer cell international","confidence":"Low","confidence_rationale":"Tier 3 — single Co-IP confirmation of MS hit; mechanistic link between DDX10-RPL35 interaction and downstream effects not directly established","pmids":["35109823"],"is_preprint":false},{"year":2024,"finding":"RPL35 knockdown in chondrocytes activates the Hedgehog (Hh)/Gli1 signaling pathway, induces cellular senescence, decreases anabolic markers, and increases catabolic markers. In vivo, adenovirus-mediated RPL35 overexpression in a mouse compression loading OA model protects articular cartilage from degeneration.","method":"RNA sequencing, adenovirus-mediated overexpression, destabilization of medial meniscus OA model, immunostaining, Western blot, cyclic strain loading of primary chondrocytes","journal":"Journal of orthopaedic translation","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo and in vitro models with pathway placement (Hh/Gli1); single lab but multiple complementary approaches","pmids":["38596341"],"is_preprint":false},{"year":2024,"finding":"EGR1 directly binds the TENT5A promoter and drives TENT5A expression; TENT5A then physically interacts with RPL35 (confirmed by Co-IP/GST pull-down with MS), participates in ribosome biogenesis, and negatively regulates the mTOR pathway to suppress HCC proliferation and metastasis.","method":"Chromatin immunoprecipitation, dual-luciferase reporter assay, Co-immunoprecipitation, GST pull-down, mass spectrometry","journal":"Cellular oncology","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP plus GST pull-down for TENT5A-RPL35 interaction; pathway consequence supported by loss/gain of function experiments","pmids":["39570560"],"is_preprint":false},{"year":2025,"finding":"GADD45GIP1 physically interacts with RPL35 (ranked second among 263 candidate interactors by IP/LC-MS/MS) and inhibits ubiquitin-mediated proteasomal degradation of RPL35. RPL35 knockdown activates the PERK/eIF2α ER stress pathway and reduces osteosarcoma cell viability; RPL35 overexpression rescues the phenotype caused by GADD45GIP1 knockdown.","method":"Immunoprecipitation with LC-MS/MS, Western blot, ubiquitination assay, PERK/eIF2α pathway analysis, rescue experiments","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2 — MS-identified interaction confirmed by IP; ubiquitination assay and epistatic rescue establish mechanistic hierarchy; single lab","pmids":["40604925"],"is_preprint":false},{"year":2025,"finding":"RPL35 functions as a host antiviral factor against FMDV by directly binding the viral structural protein VP2, recruiting the E3 ubiquitin ligase AMFR to mediate K48-linked polyubiquitination of VP2 at Lys217, leading to proteasomal degradation of VP2 and suppression of viral replication. FMDV counteracts this by inducing degradation of the nuclear transport protein KPNA3, blocking RPL35 nuclear translocation.","method":"Proteomic screen, Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (VP2 K217R), recombinant virus rescue, KPNA3 nuclear translocation assay","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods: Co-IP, ubiquitination assay, mutagenesis, recombinant virus validation; rigorous mechanistic dissection","pmids":["41065387"],"is_preprint":false}],"current_model":"RPL35 is a structural component of the 60S ribosomal large subunit whose eukaryote-specific C-terminal expansion segment mediates nuclear import and ER docking; beyond its ribosomal role it functions extra-ribosomally as a translational regulator (enhancing E2F1 and β-casein synthesis via eEF2 interaction when bound by lncNB1), promotes aerobic glycolysis through an ERK/HIF1α axis, protects chondrocytes from senescence via suppression of Hedgehog/Gli1 signaling, is stabilized by GADD45GIP1 to modulate PERK/eIF2α-dependent ER stress, participates in the EGR1/TENT5A/RPL35 tumor-suppressive axis regulating mTOR in hepatocellular carcinoma, and acts as an antiviral effector by recruiting the E3 ligase AMFR to drive K48-linked ubiquitination and degradation of the FMDV capsid protein VP2."},"narrative":{"teleology":[{"year":1977,"claim":"Establishing RPL35 as a bona fide structural component of the 60S large ribosomal subunit resolved its identity among the dozens of ribosomal proteins purified from rat liver.","evidence":"Ion-exchange chromatography, gel filtration, SDS-PAGE, and amino acid composition analysis of rat liver 60S subunit proteins","pmids":["863909"],"confidence":"High","gaps":["Post-translational modifications unknown","No functional data on ribosome assembly role"]},{"year":1990,"claim":"Determination of the full primary structure (122 aa, 14.4 kDa) and recognition of homology to archaeal L29E/bacterial L29 placed RPL35 within an evolutionarily conserved ribosomal protein family and revealed a multigene family in the rat genome.","evidence":"cDNA sequencing, N-terminal protein sequencing, Southern blot hybridization","pmids":["2322279"],"confidence":"High","gaps":["No structural model of RPL35 in the ribosome","No functional characterization of the eukaryote-specific extension"]},{"year":2008,"claim":"Functional dissection of the eukaryote-specific C-terminal expansion segment revealed dual roles: the proximal 25 residues are required for nuclear import while the distal 29 residues mediate ribosome–ER docking, establishing RPL35 as a key determinant of ribosome targeting.","evidence":"Deletion mutagenesis, in vivo recombinant ribosome analysis, and nuclear import assays in human cells","pmids":["18523488"],"confidence":"Medium","gaps":["Structural basis of ER docking contact not resolved","Import receptor identity not identified","Single-lab study"]},{"year":2010,"claim":"Demonstrating that L35 depletion in yeast blocks 27SB pre-rRNA cleavage at site C2 and traps pre-60S particles in the nucleolus established RPL35 as essential for a specific step in 60S ribosome biogenesis.","evidence":"Conditional depletion, pulse-chase labeling, northern blot, primer extension, sucrose gradients, fluorescence microscopy in S. cerevisiae","pmids":["20392820"],"confidence":"High","gaps":["Mechanism by which RPL35 promotes C2 cleavage not dissected","Human rRNA processing role not directly tested"]},{"year":2015,"claim":"Discovery that RPL35 directly binds eEF2 and controls β-casein translational elongation and ER-directed secretion in mammary cells provided the first evidence of an extra-ribosomal translational regulatory function for RPL35.","evidence":"Co-immunoprecipitation, FRET, co-localization, knockdown and overexpression in bovine mammary epithelial cells","pmids":["26297660"],"confidence":"Medium","gaps":["Whether RPL35-eEF2 interaction occurs on or off the ribosome unclear","Generalizability beyond β-casein not tested"]},{"year":2019,"claim":"Identification of lncNB1 as an RPL35-binding lncRNA that stimulates E2F1 protein synthesis, ERK signaling, and N-Myc stabilization in neuroblastoma linked RPL35 to oncogenic translational control and in vivo tumor growth.","evidence":"RNA pull-down, Co-IP, ribosome profiling, shRNA knockdown, xenograft mouse model","pmids":["31690716"],"confidence":"High","gaps":["Mechanism by which lncNB1-RPL35 complex selectively enhances E2F1 translation not elucidated","Specificity of lncNB1 for RPL35 versus other ribosomal proteins not fully addressed"]},{"year":2021,"claim":"Showing that RPL35 knockdown shifts neuroblastoma metabolism from aerobic glycolysis toward mitochondrial respiration through an ERK/HIF1α axis extended RPL35's oncogenic role to metabolic reprogramming.","evidence":"shRNA knockdown, Seahorse metabolic flux assay, Western blot, qRT-PCR in neuroblastoma cells","pmids":["34873488"],"confidence":"Medium","gaps":["Direct versus indirect regulation of HIF1α by RPL35 not distinguished","No rescue experiment with ERK activation reported"]},{"year":2024,"claim":"Demonstrating that RPL35 loss activates Hedgehog/Gli1 signaling and induces chondrocyte senescence, while RPL35 overexpression protects cartilage in a mouse OA model, revealed a tissue-protective extra-ribosomal role in joint homeostasis.","evidence":"RNA-seq, adenovirus overexpression, destabilization of medial meniscus OA model, immunostaining, cyclic strain loading of primary chondrocytes","pmids":["38596341"],"confidence":"Medium","gaps":["Direct molecular target linking RPL35 to Hh pathway suppression not identified","Whether effect is ribosome-dependent or independent not resolved"]},{"year":2024,"claim":"Placing RPL35 downstream of EGR1/TENT5A, where TENT5A physically binds RPL35 and negatively regulates mTOR signaling to suppress hepatocellular carcinoma, connected RPL35 to a tumor-suppressive transcriptional–translational axis.","evidence":"ChIP, dual-luciferase assay, Co-IP, GST pull-down with mass spectrometry in HCC cells","pmids":["39570560"],"confidence":"Medium","gaps":["How TENT5A-RPL35 interaction modulates mTOR not mechanistically resolved","Contribution of RPL35 poly(A) tail regulation not addressed"]},{"year":2025,"claim":"Discovery that GADD45GIP1 stabilizes RPL35 by blocking its ubiquitin-mediated proteasomal degradation, and that RPL35 loss activates PERK/eIF2α ER stress, established RPL35 protein stability as a regulatory node in ER stress signaling.","evidence":"IP/LC-MS/MS, ubiquitination assay, PERK/eIF2α pathway analysis, epistatic rescue experiments in osteosarcoma cells","pmids":["40604925"],"confidence":"Medium","gaps":["E3 ligase responsible for RPL35 ubiquitination not identified","Whether ER stress activation reflects ribosome depletion or a free RPL35 function unclear"]},{"year":2025,"claim":"RPL35 was shown to act as an innate antiviral effector by recruiting the E3 ligase AMFR to mediate K48-linked polyubiquitination and proteasomal degradation of FMDV VP2 at Lys217, with FMDV counteracting this by degrading KPNA3 to block RPL35 nuclear translocation.","evidence":"Proteomic screen, Co-IP, ubiquitination assay, site-directed mutagenesis (VP2 K217R), recombinant virus rescue, nuclear translocation assays","pmids":["41065387"],"confidence":"High","gaps":["Whether RPL35 antiviral activity extends to other picornaviruses not tested","Structural basis of RPL35-VP2-AMFR ternary complex unknown"]},{"year":null,"claim":"A unifying structural and mechanistic framework explaining how RPL35 partitions between ribosomal and extra-ribosomal functions—and how its free versus ribosome-bound pools are regulated—remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No quantitative model of free versus ribosome-incorporated RPL35 pools","No cryo-EM or crystallographic data specifically addressing extra-ribosomal RPL35 conformations","Relationship between RPL35 stability regulation and its diverse signaling outputs not integrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[5]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[4,5]}],"localization":[{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[3]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2,13]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[2,4]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[13]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1,3,4]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[3]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[3]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[5,6,10,11]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[5,6,11]}],"complexes":["60S ribosomal large subunit","80S ribosome"],"partners":["EEF2","AMFR","GADD45GIP1","TENT5A","DDX10","KPNA3"],"other_free_text":[]},"mechanistic_narrative":"RPL35 (uL29) is a core structural protein of the 60S ribosomal large subunit that functions in ribosome biogenesis, translational regulation, and several extra-ribosomal signaling pathways. Its eukaryote-specific C-terminal expansion segment mediates nuclear import and ribosome docking to the endoplasmic reticulum, and in yeast it is essential for 27SB-to-7S pre-rRNA processing and nucleolar release of pre-60S particles [PMID:20392820, PMID:18523488]. Beyond translation, RPL35 enhances E2F1 protein synthesis when engaged by the lncRNA lncNB1 and promotes aerobic glycolysis through an ERK/HIF1α axis in neuroblastoma [PMID:31690716, PMID:34873488], suppresses chondrocyte senescence by restraining Hedgehog/Gli1 signaling [PMID:38596341], modulates ER stress via the PERK/eIF2α pathway under stabilization by GADD45GIP1 [PMID:40604925], and acts as an antiviral effector that recruits the E3 ligase AMFR to drive K48-linked ubiquitination and proteasomal degradation of FMDV capsid protein VP2 [PMID:41065387]."},"prefetch_data":{"uniprot":{"accession":"P42766","full_name":"Large ribosomal subunit protein uL29","aliases":["60S ribosomal protein L35"],"length_aa":123,"mass_kda":14.6,"function":"Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547)","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/P42766/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/RPL35","classification":"Common Essential","n_dependent_lines":1207,"n_total_lines":1208,"dependency_fraction":0.9991721854304636},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000136942","cell_line_id":"CID000862","localizations":[{"compartment":"cytoplasmic","grade":3},{"compartment":"nucleolus_gc","grade":2}],"interactors":[{"gene":"EIF2S3","stoichiometry":10.0},{"gene":"METAP2","stoichiometry":10.0},{"gene":"RACK1","stoichiometry":10.0},{"gene":"RBM8A","stoichiometry":10.0},{"gene":"RPL11","stoichiometry":10.0},{"gene":"RPL19","stoichiometry":10.0},{"gene":"RPL15","stoichiometry":10.0},{"gene":"RPS10;RPS10-NUDT3","stoichiometry":10.0},{"gene":"SRP72","stoichiometry":10.0},{"gene":"RPL4","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID000862","total_profiled":1310},"omim":[{"mim_id":"621189","title":"LONG INTERGENIC NONCODING RNA 2525; LINC02525","url":"https://www.omim.org/entry/621189"},{"mim_id":"618315","title":"RIBOSOMAL PROTEIN L35; RPL35","url":"https://www.omim.org/entry/618315"},{"mim_id":"618312","title":"DIAMOND-BLACKFAN ANEMIA 19; DBA19","url":"https://www.omim.org/entry/618312"},{"mim_id":"617649","title":"UBIQUITIN-CONJUGATING ENZYME E2 O; UBE2O","url":"https://www.omim.org/entry/617649"},{"mim_id":"105650","title":"DIAMOND-BLACKFAN ANEMIA 1; DBA1","url":"https://www.omim.org/entry/105650"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Endoplasmic reticulum","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RPL35"},"hgnc":{"alias_symbol":["L35","uL29"],"prev_symbol":[]},"alphafold":{"accession":"P42766","domains":[{"cath_id":"1.10.287.310","chopping":"5-111","consensus_level":"high","plddt":94.9971,"start":5,"end":111}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P42766","model_url":"https://alphafold.ebi.ac.uk/files/AF-P42766-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P42766-F1-predicted_aligned_error_v6.png","plddt_mean":94.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPL35","jax_strain_url":"https://www.jax.org/strain/search?query=RPL35"},"sequence":{"accession":"P42766","fasta_url":"https://rest.uniprot.org/uniprotkb/P42766.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P42766/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P42766"}},"corpus_meta":[{"pmid":"10933704","id":"PMC_10933704","title":"Construction, phenotypic analysis, and immunogenicity of a UL5/UL29 double deletion mutant of herpes simplex virus 2.","date":"2000","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/10933704","citation_count":96,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31690716","id":"PMC_31690716","title":"The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31690716","citation_count":84,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1002715","id":"PMC_1002715","title":"Isolation of eukaryotic ribosomal proteins. 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Purification and characterization of 60 S ribosomal subunit proteins L3, L6, L7', L8, L10, L15, L17, L18, L19, L23', L25, L27', L28, L29, L31, L32, L34, L35, L36, L36', and L37'.","date":"1977","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/863909","citation_count":68,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20585571","id":"PMC_20585571","title":"Human cytomegalovirus UL29/28 protein interacts with components of the NuRD complex which promote accumulation of immediate-early RNA.","date":"2010","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/20585571","citation_count":64,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1453449","id":"PMC_1453449","title":"Messenger RNA secondary structure and translational coupling in the Escherichia coli operon encoding translation initiation factor IF3 and the ribosomal proteins, L35 and L20.","date":"1992","source":"Journal of molecular 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establishing it as a bona fide structural component of the large ribosomal subunit.\",\n      \"method\": \"Ion exchange chromatography, gel filtration, SDS-PAGE, amino acid analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct biochemical purification and characterization of the protein from the 60S subunit\",\n      \"pmids\": [\"863909\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1990,\n      \"finding\": \"The primary structure of rat RPL35 was determined: 122 amino acids (N-terminal Met removed post-translationally), MW 14,412 Da, with sequence relatedness to archaebacterial and prokaryotic ribosomal proteins, and evidence for 15–17 gene copies in the rat genome.\",\n      \"method\": \"cDNA sequencing, N-terminal protein sequencing, Southern blotting\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct sequencing and protein-level confirmation\",\n      \"pmids\": [\"2322279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The C-terminal eukaryotic expansion segment (ES) of human RPL35 contains a first 25-aa region essential for nuclear import, while the last 29 residues of the ES serve as a contact site for ribosomal docking to the endoplasmic reticulum but are not required for ribosome structural or translational functions.\",\n      \"method\": \"In vivo recombinant ribosome analysis with deletion/truncation constructs, nuclear import assays\",\n      \"journal\": \"Biochemistry and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional dissection with defined domain-deletion constructs in vivo, single lab\",\n      \"pmids\": [\"18523488\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"In yeast (S. cerevisiae), depletion of ribosomal protein L35 causes a deficit in 60S ribosomal subunits, blocks 27SB→7S pre-rRNA processing (at ITS2 site C2), prevents release of pre-60S particles from the nucleolus, and causes a mild G1 cell-cycle delay; L35 was shown to assemble in the nucleolus and bind early pre-60S particles.\",\n      \"method\": \"Conditional depletion, pulse-chase, northern hybridization, primer extension, polysome analysis, flow cytometry, subcellular fractionation\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods establishing pathway position and processing step in a well-defined eukaryotic model\",\n      \"pmids\": [\"20392820\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"RPL35 regulates β-casein (CSN2) translational elongation in bovine mammary epithelial cells by interacting with eukaryotic translation elongation factor 2 (eEF2); it also controls CSN2 secretion by localizing it to the endoplasmic reticulum.\",\n      \"method\": \"Co-immunoprecipitation, colocalization, FRET, gene mutation, overexpression and RNAi knockdown\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Co-IP, FRET, mutagenesis) but single lab, bovine cell model\",\n      \"pmids\": [\"26297660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"lncNB1 binds directly to RPL35 to enhance E2F1 protein synthesis (translational upregulation), leading to DEPDC1B transcription, ERK phosphorylation, and N-Myc protein stabilization; knockdown of lncNB1 or RPL35 abolishes neuroblastoma clonogenic capacity and causes tumor regression in mice.\",\n      \"method\": \"RNA pulldown, Co-IP, ribosome fractionation, luciferase reporter, shRNA knockdown, xenograft mouse model\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods with in vivo validation; interaction directly demonstrated\",\n      \"pmids\": [\"31690716\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RPL35 knockdown in neuroblastoma cells decreases glycolysis and increases mitochondrial respiration, and reduces HIF1α expression (mRNA and protein) and ERK pathway activation, indicating RPL35 promotes aerobic glycolysis through an RPL35/ERK/HIF1α axis.\",\n      \"method\": \"siRNA knockdown, metabolic assays (glycolysis/mitochondrial respiration), Western blot, qRT-PCR\",\n      \"journal\": \"American journal of cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — defined pathway placement with cellular phenotype, but single lab and limited mechanistic depth\",\n      \"pmids\": [\"34873488\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The Mycoplasma genitalium adhesin MgPa directly interacts with human RPL35 (confirmed by far-Western blot and co-localization), and this interaction promotes expression of EIF2, SRP68, SERBP1, RPL35A, EGF, and TGF-β, thereby enhancing urothelial cell proliferation.\",\n      \"method\": \"T7 phage display library screen, far-Western blot, co-localization, TMT proteomics, qRT-PCR, MTT proliferation assay\",\n      \"journal\": \"Pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — interaction validated by far-Western and co-localization but indirect mechanistic link; single lab\",\n      \"pmids\": [\"34832605\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Atazanavir and artesunate were identified as small-molecule binders of human RPL35 via molecular docking and NMR titration, with binding mapped to a cluster near the N-terminus of RPL35 that is accessible when RPL35 is integrated into the ribosome; these compounds are candidate modulators of RPL35-mediated ribosomal readthrough at premature termination codons.\",\n      \"method\": \"Molecular docking, NMR chemical shift titration, chemical shift mapping onto 3D structure\",\n      \"journal\": \"Skin pharmacology and physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — NMR-based structural mapping of ligand binding sites on RPL35, single lab, no functional validation in cells\",\n      \"pmids\": [\"33823521\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX10 interacts with RPL35 (identified by LC-MS/MS and confirmed by Co-IP), and DDX10 knockdown reduces CRC cell proliferation, migration, and invasion; DDX10 is proposed to regulate RPL35 splicing.\",\n      \"method\": \"LC-MS/MS, Co-IP, qPCR, cell proliferation and invasion assays, xenograft\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — interaction confirmed by Co-IP but mechanism of splicing regulation not directly demonstrated\",\n      \"pmids\": [\"35109823\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RPL35 expression is reduced by excessive mechanical loading in mouse chondrocytes; RPL35 knockdown alone induces chondrocyte senescence and activates the Hedgehog (Hh)/Gli1 signaling pathway, increasing catabolic markers and decreasing anabolic markers; intra-articular overexpression of RPL35 protects against OA progression in vivo.\",\n      \"method\": \"RNA-seq, adenoviral overexpression, siRNA knockdown, immunostaining, Western blot, mouse OA models (DMM + compression loading), OARSI scoring\",\n      \"journal\": \"Journal of orthopaedic translation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — defined pathway (Hh/Gli1), multiple in vitro and in vivo methods, single lab\",\n      \"pmids\": [\"38596341\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TENT5A interacts with RPL35 (identified by Co-IP/GST pulldown + MS) and exerts a negative regulatory effect on the mTOR pathway through this interaction; TENT5A suppresses RPL35 protein stability, and the TENT5A/RPL35 axis is involved in ribosome biogenesis in hepatocellular carcinoma.\",\n      \"method\": \"Co-immunoprecipitation, GST pull-down, mass spectrometry, ChIP, dual-luciferase reporter, gain/loss-of-function experiments\",\n      \"journal\": \"Cellular oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — interaction directly demonstrated by reciprocal pulldown + MS; pathway placement established, single lab\",\n      \"pmids\": [\"39570560\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RPL35 directly interacts with FMDV structural protein VP2 and recruits the E3 ubiquitin ligase AMFR to mediate K48-linked polyubiquitination and proteasomal degradation of VP2; Lys217 of VP2 is the critical ubiquitination site; FMDV counters this by inducing degradation of KPNA3, which blocks RPL35 nuclear translocation.\",\n      \"method\": \"Co-IP, ubiquitination assays, site-directed mutagenesis (VP2-K217R), proteomic screen, recombinant mutant virus generation, nuclear translocation assays\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct interaction, enzymatic ubiquitination mechanism, mutagenesis validation, and viral rescue experiment; multiple orthogonal methods\",\n      \"pmids\": [\"41065387\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GADD45GIP1 interacts with RPL35 (identified by IP/LC-MS/MS, ranked second among interactors) and inhibits its ubiquitin-mediated degradation (elevated polyubiquitination upon GADD45GIP1 knockdown); RPL35 knockdown activates the PERK/eIF2α pathway and increases ER stress; RPL35 overexpression rescues cell viability loss from GADD45GIP1 knockdown in osteosarcoma.\",\n      \"method\": \"IP/LC-MS/MS, Co-IP, ubiquitination assays, siRNA knockdown, overexpression rescue, Western blot, in vivo xenograft\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — interaction and ubiquitination mechanism demonstrated, rescue experiment performed; single lab\",\n      \"pmids\": [\"40604925\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPL35 is a structural protein of the 60S ribosomal large subunit whose C-terminal eukaryotic expansion segment mediates nuclear import and ER docking; it is required for 27SB pre-rRNA processing and 60S subunit biogenesis, controls translational elongation via interaction with eEF2, can be bound by lncRNAs (e.g., lncNB1) to selectively enhance translation of specific mRNAs (e.g., E2F1), recruits the E3 ligase AMFR to ubiquitinate viral proteins, and is itself regulated by ubiquitin-mediated degradation controlled by GADD45GIP1, with additional non-ribosomal roles in the ERK/HIF1α metabolic axis and Hedgehog signaling in chondrocytes.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper and extract discoveries only from KEEP papers.\n\n**Classification summary:**\n\nKEEP (about RPL35 the ribosomal protein):\n- [2] lncNB1 interacts with RPL35 to enhance E2F1 synthesis\n- [3] Isolation/characterization of 60S ribosomal proteins including L35 (rat)\n- [4] Isolation/characterization of 60S ribosomal proteins including L35 (rat)\n- [7] Yeast L35 required for 27SB pre-rRNA processing (ortholog)\n- [13] RPL35 regulates β-casein translational elongation via eEF2 interaction\n- [14] DDX10 interacts with RPL35 (Co-IP confirmed)\n- [21] Human RPL35 expansion segment roles in nuclear entry, translation, ER docking\n- [22] RPL35 promotes aerobic glycolysis via ERK/HIF1α axis\n- [27] RPL35 downregulation promotes chondrocyte senescence via Hedgehog-Gli1\n- [28] Primary structure of rat L35 determined\n- [30] Drug targeting of rpL35 for readthrough therapy\n- [38] MgPa interacts with RPL35 to promote cell proliferation\n- [42] TENT5A interacts with RPL35, affects mTOR pathway\n- [44] GADD45GIP1 inhibits RPL35 ubiquitination; RPL35 knockdown activates PERK/eIF2α\n- [47] RPL35 recruits AMFR E3 ligase to ubiquitinate FMDV VP2\n- [48] Commentary on GADD45GIP1-RPL35 axis\n- [50] Porcine RPL35 cDNA sequencing\n\nEXCLUDE:\n- [1] HSV UL5/UL29 - viral genes, not RPL35\n- [5],[9],[23],[31],[32],[33],[34],[39],[40],[46] - UL29 viral gene papers\n- [6],[10],[11],[15],[19],[20],[36] - E. coli/B. subtilis L35 (prokaryotic, fundamentally different protein context - symbol collision)\n- [8] L35 = hemoglobin effector molecule (small molecule, not protein)\n- [12] L35 = residue position in VP5 protein\n- [16] L35 = lymphoblastoid cell line name\n- [17] Expression/mRNA stability correlation only\n- [18] MRPL35 (mitochondrial RPL35 paralog) - different gene\n- [24],[26] L35 hepatoma cell line - not the gene\n- [25] Spinach chloroplast L35 - plant, incompatible context\n- [29],[33] Herpesvirus genes\n- [35] L-35 = T cell antigen (antibody name)\n- [37] L35 = Lactobacillus strain name\n- [41] Babesia bovis bl35 - parasite, distant ortholog with minimal mechanistic info\n- [43] Amphioxus AmphiL35 - sequence/copy number only, no mechanism\n- [45] Yeast chromosome sequence - no mechanistic finding\n- [49] E. coli uL29 (different protein, prokaryotic)\n\nLarge-scale interactome papers (gene2pubmed): RPL35 appears as a detected protein but no specific RPL35 mechanism described - skip for discovery extraction.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1977,\n      \"finding\": \"RPL35 (L35) was isolated and purified as a component of the rat liver 60S ribosomal large subunit, with molecular weight estimated by SDS-PAGE and amino acid composition determined, establishing it as a bona fide structural ribosomal protein.\",\n      \"method\": \"Ion-exchange chromatography, gel filtration (Sephadex), SDS-PAGE, amino acid composition analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct biochemical isolation and characterization; foundational purification study\",\n      \"pmids\": [\"863909\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1990,\n      \"finding\": \"The primary structure of rat 60S ribosomal subunit protein L35 was determined: 122 amino acids (N-terminal Met cleaved post-translationally), molecular weight 14,412 Da. The protein is related to archaebacterial L33/L29E and E. coli L29, and the gene exists in 15–17 copies in the rat genome.\",\n      \"method\": \"cDNA sequencing, N-terminal amino acid sequencing, Southern blot hybridization\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct protein sequencing confirmed by cDNA; primary structure established\",\n      \"pmids\": [\"2322279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The eukaryote-specific C-terminal expansion segment (ES) of human RPL35 was functionally dissected: the first 25 amino acids of the 54-aa ES are essential for nuclear import of the protein, whereas the last 29 residues are dispensable for ribosome structure and translation but serve as a contact site for ribosomal docking to the endoplasmic reticulum.\",\n      \"method\": \"Deletion mutagenesis, in vivo recombinant ribosome analysis, nuclear import assays\",\n      \"journal\": \"Biochemistry and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct mutagenesis with defined functional readouts; single lab study\",\n      \"pmids\": [\"18523488\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"In Saccharomyces cerevisiae, L35 is required for processing of 27SB pre-rRNA to 7S pre-rRNA (cleavage at site C2 of ITS2). Depletion of L35 causes a deficit in 60S ribosomal subunits, half-mer polysomes, and blocks release of pre-60S particles from the nucleolus to the nucleoplasm. L35 assembles in the nucleolus and associates with early pre-60S ribosomal particles.\",\n      \"method\": \"Conditional depletion (tetO system), pulse-chase labeling, northern hybridization, primer extension, sucrose gradient sedimentation, fluorescence microscopy\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (pulse-chase, northern, primer extension, microscopy) in yeast ortholog; strong evidence\",\n      \"pmids\": [\"20392820\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"RPL35 regulates translational elongation of β-casein (CSN2) in bovine mammary epithelial cells by directly interacting with eukaryotic elongation factor 2 (eEF2), placing eEF2 downstream of RPL35 in the methionine signaling pathway. RPL35 also controls CSN2 secretion by localizing it to the endoplasmic reticulum.\",\n      \"method\": \"Co-immunoprecipitation, co-localization microscopy, FRET, gene mutation analysis, overexpression and knockdown experiments\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP and FRET for interaction; single lab with multiple methods\",\n      \"pmids\": [\"26297660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The long noncoding RNA lncNB1 physically binds to RPL35 and enhances E2F1 protein synthesis, leading to DEPDC1B transcription, ERK phosphorylation, and N-Myc protein stabilization. Knockdown of RPL35 or lncNB1 abolishes clonogenic capacity and causes tumor regression in vivo, identifying RPL35 as a key factor for E2F1 translational upregulation in neuroblastoma.\",\n      \"method\": \"RNA pull-down, Co-immunoprecipitation, ribosome profiling, shRNA knockdown, xenograft mouse model\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (pulldown, Co-IP, in vivo rescue) with rigorous controls; single lab but comprehensive\",\n      \"pmids\": [\"31690716\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RPL35 knockdown in neuroblastoma cells decreases aerobic glycolysis and increases mitochondrial respiration, with mechanistic analysis showing that RPL35 positively regulates HIF1α expression (mRNA and protein) and acts through the RPL35/ERK/HIF1α signaling axis.\",\n      \"method\": \"shRNA knockdown, Seahorse metabolic flux assay, Western blot, qRT-PCR\",\n      \"journal\": \"American journal of cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — KD with metabolic phenotype and pathway placement, single lab, single primary method per step\",\n      \"pmids\": [\"34873488\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RPL35 was identified as a direct binding partner of the Mycoplasma genitalium adhesin protein MgPa via far-Western blot and co-localization; this interaction promotes expression of translation-initiation proteins (EIF2, SRP68, SERBP1, RPL35A) and EGF/TGF-β, leading to enhanced urothelial cell proliferation.\",\n      \"method\": \"T7 phage display library screening, far-Western blot, co-localization, TMT proteomics, qRT-PCR, MTT proliferation assay\",\n      \"journal\": \"Pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — interaction validated by far-Western and co-localization; downstream pathway inferred from proteomics without direct mechanistic dissection\",\n      \"pmids\": [\"34832605\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RPL35 was identified as a candidate small-molecule binding target: molecular docking and NMR titration studies showed that the FDA-approved drugs atazanavir and artesunate bind to an overlapping cluster near the N-terminus of rpL35, accessible when RPL35 is integrated in the ribosome. This binding site was proposed to modulate translational readthrough at premature stop codons.\",\n      \"method\": \"Molecular docking, NMR chemical shift perturbation mapping\",\n      \"journal\": \"Skin pharmacology and physiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 — computational docking plus NMR binding mapping; no functional readthrough assay performed\",\n      \"pmids\": [\"33823521\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX10 interacts with RPL35 in colorectal cancer cells, as identified by LC-MS/MS proteomics and confirmed by co-immunoprecipitation; DDX10 knockdown reduces CRC cell proliferation, migration and invasion, and both proteins are implicated in RNA splicing and E2F target pathways.\",\n      \"method\": \"LC-MS/MS interactome, Co-immunoprecipitation, shRNA knockdown, cell proliferation/migration assays\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP confirmation of MS hit; mechanistic link between DDX10-RPL35 interaction and downstream effects not directly established\",\n      \"pmids\": [\"35109823\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"RPL35 knockdown in chondrocytes activates the Hedgehog (Hh)/Gli1 signaling pathway, induces cellular senescence, decreases anabolic markers, and increases catabolic markers. In vivo, adenovirus-mediated RPL35 overexpression in a mouse compression loading OA model protects articular cartilage from degeneration.\",\n      \"method\": \"RNA sequencing, adenovirus-mediated overexpression, destabilization of medial meniscus OA model, immunostaining, Western blot, cyclic strain loading of primary chondrocytes\",\n      \"journal\": \"Journal of orthopaedic translation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo and in vitro models with pathway placement (Hh/Gli1); single lab but multiple complementary approaches\",\n      \"pmids\": [\"38596341\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"EGR1 directly binds the TENT5A promoter and drives TENT5A expression; TENT5A then physically interacts with RPL35 (confirmed by Co-IP/GST pull-down with MS), participates in ribosome biogenesis, and negatively regulates the mTOR pathway to suppress HCC proliferation and metastasis.\",\n      \"method\": \"Chromatin immunoprecipitation, dual-luciferase reporter assay, Co-immunoprecipitation, GST pull-down, mass spectrometry\",\n      \"journal\": \"Cellular oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus GST pull-down for TENT5A-RPL35 interaction; pathway consequence supported by loss/gain of function experiments\",\n      \"pmids\": [\"39570560\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GADD45GIP1 physically interacts with RPL35 (ranked second among 263 candidate interactors by IP/LC-MS/MS) and inhibits ubiquitin-mediated proteasomal degradation of RPL35. RPL35 knockdown activates the PERK/eIF2α ER stress pathway and reduces osteosarcoma cell viability; RPL35 overexpression rescues the phenotype caused by GADD45GIP1 knockdown.\",\n      \"method\": \"Immunoprecipitation with LC-MS/MS, Western blot, ubiquitination assay, PERK/eIF2α pathway analysis, rescue experiments\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — MS-identified interaction confirmed by IP; ubiquitination assay and epistatic rescue establish mechanistic hierarchy; single lab\",\n      \"pmids\": [\"40604925\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RPL35 functions as a host antiviral factor against FMDV by directly binding the viral structural protein VP2, recruiting the E3 ubiquitin ligase AMFR to mediate K48-linked polyubiquitination of VP2 at Lys217, leading to proteasomal degradation of VP2 and suppression of viral replication. FMDV counteracts this by inducing degradation of the nuclear transport protein KPNA3, blocking RPL35 nuclear translocation.\",\n      \"method\": \"Proteomic screen, Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (VP2 K217R), recombinant virus rescue, KPNA3 nuclear translocation assay\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods: Co-IP, ubiquitination assay, mutagenesis, recombinant virus validation; rigorous mechanistic dissection\",\n      \"pmids\": [\"41065387\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPL35 is a structural component of the 60S ribosomal large subunit whose eukaryote-specific C-terminal expansion segment mediates nuclear import and ER docking; beyond its ribosomal role it functions extra-ribosomally as a translational regulator (enhancing E2F1 and β-casein synthesis via eEF2 interaction when bound by lncNB1), promotes aerobic glycolysis through an ERK/HIF1α axis, protects chondrocytes from senescence via suppression of Hedgehog/Gli1 signaling, is stabilized by GADD45GIP1 to modulate PERK/eIF2α-dependent ER stress, participates in the EGR1/TENT5A/RPL35 tumor-suppressive axis regulating mTOR in hepatocellular carcinoma, and acts as an antiviral effector by recruiting the E3 ligase AMFR to drive K48-linked ubiquitination and degradation of the FMDV capsid protein VP2.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"RPL35 is a core structural component of the 60S ribosomal large subunit that functions in ribosome biogenesis, translational control, and extra-ribosomal signaling. Its C-terminal eukaryotic expansion segment contains separable domains for nuclear import and endoplasmic reticulum docking, and it assembles in the nucleolus where it is required for 27SB pre-rRNA processing and 60S subunit export [PMID:20392820, PMID:18523488]. Beyond canonical translation, RPL35 participates in selective mRNA translation—exemplified by lncNB1 binding RPL35 to enhance E2F1 synthesis and activate the ERK/N-Myc axis in neuroblastoma—and recruits the E3 ligase AMFR to ubiquitinate viral proteins for proteasomal degradation [PMID:31690716, PMID:41065387]. RPL35 protein stability is itself regulated by ubiquitin-mediated turnover controlled by GADD45GIP1, and its depletion triggers ER stress via PERK/eIF2α activation and promotes chondrocyte senescence through Hedgehog/Gli1 signaling [PMID:40604925, PMID:38596341].\",\n  \"teleology\": [\n    {\n      \"year\": 1977,\n      \"claim\": \"Establishing RPL35 as a bona fide 60S ribosomal subunit component resolved its identity among the large-subunit protein catalog and enabled subsequent functional studies.\",\n      \"evidence\": \"Biochemical purification from rat liver 60S subunits with SDS-PAGE and amino acid analysis\",\n      \"pmids\": [\"863909\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No functional data; purely compositional identification\", \"No information on assembly pathway or processing role\"]\n    },\n    {\n      \"year\": 1990,\n      \"claim\": \"Determining the full primary structure of RPL35 and its evolutionary conservation with archaeal ribosomal proteins placed it within a conserved ribosomal protein family and revealed multi-copy gene organization.\",\n      \"evidence\": \"cDNA sequencing, N-terminal protein sequencing, and Southern blot of rat genomic DNA\",\n      \"pmids\": [\"2322279\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No domain-function mapping\", \"Pseudogene versus functional gene copies not resolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Functional dissection of the eukaryotic expansion segment revealed that RPL35 carries separable signals for nuclear import and ER docking, establishing how a single ribosomal protein mediates two distinct subcellular targeting events.\",\n      \"evidence\": \"In vivo recombinant ribosome analysis with domain-deletion constructs and nuclear import assays in human cells\",\n      \"pmids\": [\"18523488\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Receptor identities for nuclear import and ER docking not defined\", \"Structural basis of ER contact not resolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Depletion studies in yeast pinpointed RPL35 as essential for 27SB→7S pre-rRNA processing at ITS2 site C2 and for nucleolar release of pre-60S particles, establishing its precise role in ribosome biogenesis.\",\n      \"evidence\": \"Conditional depletion, pulse-chase, northern hybridization, primer extension, polysome profiling, and flow cytometry in S. cerevisiae\",\n      \"pmids\": [\"20392820\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular contacts with pre-rRNA or assembly factors at the processing step not mapped\", \"Whether the G1 delay is a direct or checkpoint-mediated consequence unclear\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Demonstration that RPL35 interacts with eEF2 to regulate translational elongation of β-casein extended RPL35's role beyond ribosome structure to active translational control of specific mRNAs.\",\n      \"evidence\": \"Co-IP, FRET, mutagenesis, and RNAi in bovine mammary epithelial cells\",\n      \"pmids\": [\"26297660\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the RPL35-eEF2 interaction is direct or ribosome-mediated not distinguished\", \"Generalizability beyond β-casein not tested\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"The discovery that lncNB1 binds RPL35 to selectively enhance E2F1 translation, driving an ERK/N-Myc oncogenic axis in neuroblastoma, established RPL35 as a hub for lncRNA-directed selective translation with in vivo tumor relevance.\",\n      \"evidence\": \"RNA pulldown, ribosome fractionation, luciferase reporters, shRNA knockdown, and xenograft mouse models\",\n      \"pmids\": [\"31690716\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of lncNB1–RPL35 interaction unknown\", \"Whether other lncRNAs exploit RPL35 similarly not explored\", \"Whether RPL35 selectivity for E2F1 mRNA requires additional factors unclear\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Metabolic profiling upon RPL35 knockdown revealed that RPL35 promotes aerobic glycolysis through an ERK/HIF1α axis, linking a ribosomal protein to cancer metabolic reprogramming.\",\n      \"evidence\": \"siRNA knockdown, glycolysis and mitochondrial respiration assays, Western blot and qRT-PCR in neuroblastoma cells\",\n      \"pmids\": [\"34873488\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the metabolic effect is translation-dependent or an extra-ribosomal function not resolved\", \"Direct mechanism connecting RPL35 to ERK activation not identified\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"NMR-based mapping of small-molecule binding to an N-terminal cluster on RPL35 accessible within the assembled ribosome identified candidate pharmacological tools for modulating ribosomal readthrough.\",\n      \"evidence\": \"Molecular docking and NMR chemical shift titration with atazanavir and artesunate\",\n      \"pmids\": [\"33823521\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No cellular or functional validation of readthrough modulation\", \"Binding affinity and selectivity not quantified in competitive assays\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identification of RPL35 downregulation in mechanically loaded chondrocytes and its link to Hedgehog/Gli1-driven senescence and cartilage catabolism established a non-ribosomal role in osteoarthritis pathogenesis.\",\n      \"evidence\": \"RNA-seq, siRNA knockdown, adenoviral overexpression, immunostaining, and in vivo mouse OA models with OARSI scoring\",\n      \"pmids\": [\"38596341\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which RPL35 suppresses Hh/Gli1 signaling not defined\", \"Whether this is translation-dependent or a moonlighting function unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"TENT5A was shown to interact with RPL35 and suppress its stability, linking RPL35 to the mTOR pathway and ribosome biogenesis regulation in hepatocellular carcinoma.\",\n      \"evidence\": \"Co-IP, GST pull-down, mass spectrometry, ChIP, and gain/loss-of-function experiments\",\n      \"pmids\": [\"39570560\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ubiquitin ligase or degradation pathway mediating TENT5A-dependent RPL35 turnover not identified\", \"Whether TENT5A acts via its poly(A) polymerase activity on RPL35 mRNA or post-translationally unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"RPL35 was found to recruit the E3 ligase AMFR to ubiquitinate FMDV VP2 at K48-linked chains for proteasomal degradation, representing an innate antiviral mechanism; FMDV counteracts this by degrading KPNA3 to block RPL35 nuclear translocation.\",\n      \"evidence\": \"Co-IP, in vivo ubiquitination assays, site-directed mutagenesis (VP2-K217R), recombinant mutant virus, and nuclear translocation assays\",\n      \"pmids\": [\"41065387\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether RPL35 recruits AMFR to other viral or cellular substrates not examined\", \"Structural basis of the RPL35-AMFR-VP2 ternary complex unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"GADD45GIP1 was identified as a stabilizer of RPL35 protein by inhibiting its ubiquitin-mediated degradation; RPL35 loss triggers PERK/eIF2α-mediated ER stress, establishing RPL35 as a sensor point linking ribosome integrity to the unfolded protein response.\",\n      \"evidence\": \"IP/LC-MS/MS, Co-IP, ubiquitination assays, siRNA knockdown, overexpression rescue, and xenograft experiments in osteosarcoma\",\n      \"pmids\": [\"40604925\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The specific E3 ligase targeting RPL35 for degradation not identified\", \"Whether ER stress results from ribosome depletion or free RPL35 loss not distinguished\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Major open questions remain regarding the structural basis of RPL35's extra-ribosomal interactions, the identity of the E3 ligase controlling RPL35 turnover, and whether its roles in Hedgehog signaling and metabolic reprogramming are translation-dependent or represent moonlighting functions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No high-resolution structure of RPL35 in complex with lncNB1, AMFR, or eEF2\", \"E3 ligase mediating RPL35 degradation unknown\", \"Translation-dependent versus moonlighting distinction not experimentally resolved for non-ribosomal phenotypes\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2, 12]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [2, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [3, 11]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 6, 10]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [12]}\n    ],\n    \"complexes\": [\n      \"60S ribosomal large subunit\"\n    ],\n    \"partners\": [\n      \"eEF2\",\n      \"AMFR\",\n      \"GADD45GIP1\",\n      \"TENT5A\",\n      \"DDX10\",\n      \"KPNA3\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"RPL35 (uL29) is a core structural protein of the 60S ribosomal large subunit that functions in ribosome biogenesis, translational regulation, and several extra-ribosomal signaling pathways. Its eukaryote-specific C-terminal expansion segment mediates nuclear import and ribosome docking to the endoplasmic reticulum, and in yeast it is essential for 27SB-to-7S pre-rRNA processing and nucleolar release of pre-60S particles [PMID:20392820, PMID:18523488]. Beyond translation, RPL35 enhances E2F1 protein synthesis when engaged by the lncRNA lncNB1 and promotes aerobic glycolysis through an ERK/HIF1α axis in neuroblastoma [PMID:31690716, PMID:34873488], suppresses chondrocyte senescence by restraining Hedgehog/Gli1 signaling [PMID:38596341], modulates ER stress via the PERK/eIF2α pathway under stabilization by GADD45GIP1 [PMID:40604925], and acts as an antiviral effector that recruits the E3 ligase AMFR to drive K48-linked ubiquitination and proteasomal degradation of FMDV capsid protein VP2 [PMID:41065387].\",\n  \"teleology\": [\n    {\n      \"year\": 1977,\n      \"claim\": \"Establishing RPL35 as a bona fide structural component of the 60S large ribosomal subunit resolved its identity among the dozens of ribosomal proteins purified from rat liver.\",\n      \"evidence\": \"Ion-exchange chromatography, gel filtration, SDS-PAGE, and amino acid composition analysis of rat liver 60S subunit proteins\",\n      \"pmids\": [\"863909\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Post-translational modifications unknown\", \"No functional data on ribosome assembly role\"]\n    },\n    {\n      \"year\": 1990,\n      \"claim\": \"Determination of the full primary structure (122 aa, 14.4 kDa) and recognition of homology to archaeal L29E/bacterial L29 placed RPL35 within an evolutionarily conserved ribosomal protein family and revealed a multigene family in the rat genome.\",\n      \"evidence\": \"cDNA sequencing, N-terminal protein sequencing, Southern blot hybridization\",\n      \"pmids\": [\"2322279\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of RPL35 in the ribosome\", \"No functional characterization of the eukaryote-specific extension\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Functional dissection of the eukaryote-specific C-terminal expansion segment revealed dual roles: the proximal 25 residues are required for nuclear import while the distal 29 residues mediate ribosome–ER docking, establishing RPL35 as a key determinant of ribosome targeting.\",\n      \"evidence\": \"Deletion mutagenesis, in vivo recombinant ribosome analysis, and nuclear import assays in human cells\",\n      \"pmids\": [\"18523488\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of ER docking contact not resolved\", \"Import receptor identity not identified\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstrating that L35 depletion in yeast blocks 27SB pre-rRNA cleavage at site C2 and traps pre-60S particles in the nucleolus established RPL35 as essential for a specific step in 60S ribosome biogenesis.\",\n      \"evidence\": \"Conditional depletion, pulse-chase labeling, northern blot, primer extension, sucrose gradients, fluorescence microscopy in S. cerevisiae\",\n      \"pmids\": [\"20392820\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which RPL35 promotes C2 cleavage not dissected\", \"Human rRNA processing role not directly tested\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Discovery that RPL35 directly binds eEF2 and controls β-casein translational elongation and ER-directed secretion in mammary cells provided the first evidence of an extra-ribosomal translational regulatory function for RPL35.\",\n      \"evidence\": \"Co-immunoprecipitation, FRET, co-localization, knockdown and overexpression in bovine mammary epithelial cells\",\n      \"pmids\": [\"26297660\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether RPL35-eEF2 interaction occurs on or off the ribosome unclear\", \"Generalizability beyond β-casein not tested\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identification of lncNB1 as an RPL35-binding lncRNA that stimulates E2F1 protein synthesis, ERK signaling, and N-Myc stabilization in neuroblastoma linked RPL35 to oncogenic translational control and in vivo tumor growth.\",\n      \"evidence\": \"RNA pull-down, Co-IP, ribosome profiling, shRNA knockdown, xenograft mouse model\",\n      \"pmids\": [\"31690716\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which lncNB1-RPL35 complex selectively enhances E2F1 translation not elucidated\", \"Specificity of lncNB1 for RPL35 versus other ribosomal proteins not fully addressed\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Showing that RPL35 knockdown shifts neuroblastoma metabolism from aerobic glycolysis toward mitochondrial respiration through an ERK/HIF1α axis extended RPL35's oncogenic role to metabolic reprogramming.\",\n      \"evidence\": \"shRNA knockdown, Seahorse metabolic flux assay, Western blot, qRT-PCR in neuroblastoma cells\",\n      \"pmids\": [\"34873488\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect regulation of HIF1α by RPL35 not distinguished\", \"No rescue experiment with ERK activation reported\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrating that RPL35 loss activates Hedgehog/Gli1 signaling and induces chondrocyte senescence, while RPL35 overexpression protects cartilage in a mouse OA model, revealed a tissue-protective extra-ribosomal role in joint homeostasis.\",\n      \"evidence\": \"RNA-seq, adenovirus overexpression, destabilization of medial meniscus OA model, immunostaining, cyclic strain loading of primary chondrocytes\",\n      \"pmids\": [\"38596341\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct molecular target linking RPL35 to Hh pathway suppression not identified\", \"Whether effect is ribosome-dependent or independent not resolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Placing RPL35 downstream of EGR1/TENT5A, where TENT5A physically binds RPL35 and negatively regulates mTOR signaling to suppress hepatocellular carcinoma, connected RPL35 to a tumor-suppressive transcriptional–translational axis.\",\n      \"evidence\": \"ChIP, dual-luciferase assay, Co-IP, GST pull-down with mass spectrometry in HCC cells\",\n      \"pmids\": [\"39570560\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How TENT5A-RPL35 interaction modulates mTOR not mechanistically resolved\", \"Contribution of RPL35 poly(A) tail regulation not addressed\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Discovery that GADD45GIP1 stabilizes RPL35 by blocking its ubiquitin-mediated proteasomal degradation, and that RPL35 loss activates PERK/eIF2α ER stress, established RPL35 protein stability as a regulatory node in ER stress signaling.\",\n      \"evidence\": \"IP/LC-MS/MS, ubiquitination assay, PERK/eIF2α pathway analysis, epistatic rescue experiments in osteosarcoma cells\",\n      \"pmids\": [\"40604925\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"E3 ligase responsible for RPL35 ubiquitination not identified\", \"Whether ER stress activation reflects ribosome depletion or a free RPL35 function unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"RPL35 was shown to act as an innate antiviral effector by recruiting the E3 ligase AMFR to mediate K48-linked polyubiquitination and proteasomal degradation of FMDV VP2 at Lys217, with FMDV counteracting this by degrading KPNA3 to block RPL35 nuclear translocation.\",\n      \"evidence\": \"Proteomic screen, Co-IP, ubiquitination assay, site-directed mutagenesis (VP2 K217R), recombinant virus rescue, nuclear translocation assays\",\n      \"pmids\": [\"41065387\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether RPL35 antiviral activity extends to other picornaviruses not tested\", \"Structural basis of RPL35-VP2-AMFR ternary complex unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying structural and mechanistic framework explaining how RPL35 partitions between ribosomal and extra-ribosomal functions—and how its free versus ribosome-bound pools are regulated—remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No quantitative model of free versus ribosome-incorporated RPL35 pools\", \"No cryo-EM or crystallographic data specifically addressing extra-ribosomal RPL35 conformations\", \"Relationship between RPL35 stability regulation and its diverse signaling outputs not integrated\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [4, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2, 13]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [13]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1, 3, 4]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 6, 10, 11]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [5, 6, 11]}\n    ],\n    \"complexes\": [\n      \"60S ribosomal large subunit\",\n      \"80S ribosome\"\n    ],\n    \"partners\": [\n      \"EEF2\",\n      \"AMFR\",\n      \"GADD45GIP1\",\n      \"TENT5A\",\n      \"DDX10\",\n      \"KPNA3\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}