{"gene":"SF3B5","run_date":"2026-04-28T20:42:07","timeline":{"discoveries":[{"year":2002,"finding":"SF3B5 (SF3b10) was identified as a bona fide protein component of the human SF3b subcomplex of the U2 snRNP and of intact functional spliceosomes, as determined by mass spectrometry of purified spliceosomal particles.","method":"Maltose-binding protein affinity chromatography combined with nanoscale LC-MS/MS mass spectrometry of purified functional human spliceosomes","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1-2 — comprehensive proteomics of purified functional spliceosomes, foundational identification paper with >700 citations","pmids":["12226669"],"is_preprint":false},{"year":2002,"finding":"SF3B5 (SF3b10) was identified as a stable component of both SF3b and the 17S U2 snRNP by mass spectrometry; immunofluorescence/FISH studies placed SF3b155 (but not SF3b10/SF3B5 specifically) outside Cajal bodies, providing initial subcellular context for SF3b assembly.","method":"Mass spectrometry of immunoprecipitated SF3b and 17S U2 snRNP; immunofluorescence and FISH","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — reciprocal MS identification in purified complex, replicated across multiple snRNP preparations","pmids":["12234937"],"is_preprint":false},{"year":2007,"finding":"SF3B5 (SF3b10) was detected as a stoichiometric component of human prespliceosomal A complexes, demonstrating its stable incorporation at an early stage of spliceosome assembly before catalytic activation.","method":"Double-affinity purification of prespliceosomal A complexes under physiological conditions followed by mass spectrometry and EM","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — stoichiometric detection in double-affinity purified complexes with EM validation","pmids":["17332742"],"is_preprint":false},{"year":2009,"finding":"In Trypanosoma brucei, the SF3B5 ortholog (as part of the SF3b complex) co-purifies with homologues of p14, SAP130, SAP145, and SAP155, and localizes to the nucleus; RNAi knockdown of the associated SAP49 homologue (DRBD1) inhibited trypanosome growth and caused splicing defects, demonstrating conserved functional importance of the SF3b complex including SF3B5.","method":"TAP-tag co-purification mass spectrometry, immunofluorescence localization, RNAi knockdown with growth and splicing phenotype readout in T. brucei","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2-3 — ortholog functional study with co-purification and RNAi phenotype, but indirect evidence for SF3B5 itself","pmids":["19450735"],"is_preprint":false},{"year":2016,"finding":"Crystal structure of the human SF3b core complex revealed that SF3B5 (SF3b10) directly contacts SF3B1 (SF3b155) and contributes to maintaining the distinctive conformation of the SF3B1 HEAT domain superhelix; SF3B5 forms part of the structural scaffold that positions the branch-site recognition platform.","method":"X-ray crystallography of the human SF3b core complex (crystal structure); protein-protein crosslinking mass spectrometry","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 — crystal structure with crosslinking validation, >200 citations, direct atomic-level evidence","pmids":["27720643"],"is_preprint":false},{"year":2016,"finding":"Integrative cryo-EM-guided modeling localized SF3B5 (SF3b10) within the closed form of the SF3b complex for the first time, placing it in spatial proximity to SF3b155, SF3b145, SF3b130, and SF3b14b and identifying a hinge region in SF3b155 important for the open-to-closed conformational transition relevant to branch-point adenosine recognition.","method":"Integrative structural modeling guided by cryo-EM density maps, comparative homology modeling, and experimental data","journal":"RNA biology","confidence":"Medium","confidence_rationale":"Tier 2-3 — cryo-EM guided pseudo-atomic model; computational/integrative approach without independent mutagenesis validation","pmids":["27618338"],"is_preprint":false},{"year":2017,"finding":"In the cryo-EM structure of the pre-catalytic human spliceosomal B complex, SF3B5 is present as a stable SF3b component within the U2 snRNP head domain, which connects to the B complex main body via three bridges, positioning SF3b for subsequent activation steps.","method":"Cryo-EM structure of the pre-catalytic human B complex spliceosome","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1 — high-resolution cryo-EM structure of intact spliceosomal complex, >199 citations","pmids":["28781166"],"is_preprint":false},{"year":2018,"finding":"Cryo-EM structure of the SF3b subcomplex (comprising SF3B1, SF3B3, PHF5A, and SF3B5) bound to the splicing modulator E7107 at 3.95 Å revealed that SF3B5 is an integral structural subunit of the drug-bound complex; the structure showed E7107 occupies the branch-point adenosine-binding pocket, supporting a substrate-competitive mechanism of action for splicing modulators.","method":"Cryo-EM structure determination of SF3b–E7107 complex; structure-activity relationship analysis with chemical probes; functional assays with strong vs. weak pre-mRNA substrates","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1 — near-atomic cryo-EM structure with SAR and functional validation, multiple orthogonal methods","pmids":["29491137"],"is_preprint":false},{"year":2018,"finding":"In the cryo-EM structures of the human activated spliceosome (Bact complex), atomic models of all seven SF3b subunits including SF3B5 were built, confirming SF3B5 as a structural component maintained throughout spliceosome activation; the three conformational states captured revealed that SF3b remains stably associated through the B-to-Bact transition.","method":"Cryo-EM structure of human Bact complex in three conformational states with atomic modeling of SF3b subunits","journal":"Cell research","confidence":"High","confidence_rationale":"Tier 1 — atomic-resolution cryo-EM with multiple conformational states, direct structural evidence","pmids":["29360106"],"is_preprint":false},{"year":2019,"finding":"Cryo-EM structure of the human pre-B spliceosome complex showed SF3B5 as part of the SF3b module within U2 snRNP, and the structures collectively demonstrate that the SF3b complex including SF3B5 is positioned to interact with the branch-point sequence as part of the pre-mRNA recognition machinery before catalytic activation.","method":"Cryo-EM structure of human pre-B spliceosome at 3.3 Å core resolution","journal":"Science","confidence":"High","confidence_rationale":"Tier 1 — near-atomic cryo-EM structure with direct structural placement of SF3b components","pmids":["30975767"],"is_preprint":false},{"year":2020,"finding":"Cryo-EM structure of the human 17S U2 snRNP at 4.1 Å core resolution, combined with protein crosslinking data, revealed the molecular architecture of the snRNP and showed that SF3B1's HEAT domain (which is scaffolded in part by SF3B5) maintains an open conformation in isolated U2 snRNP, in contrast to the closed conformation observed in assembled spliceosomes, explaining why BSL remodeling is required for stable U2–branch-site interaction.","method":"Cryo-EM structure determination of 17S U2 snRNP; protein crosslinking mass spectrometry","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 — high-resolution cryo-EM combined with crosslinking MS, direct structural evidence for conformational states","pmids":["32494006"],"is_preprint":false}],"current_model":"SF3B5 (SF3b10) is a small but integral structural subunit of the heptameric SF3b complex within the U2 snRNP, where it directly contacts SF3B1 to help maintain the HEAT-domain superhelix in an open conformation in the free U2 snRNP; upon spliceosome assembly SF3b closes around the branch-point adenosine, with SF3B5 serving as a core scaffold throughout prespliceosomal A complex, pre-B, B, and Bact stages, and the SF3B5-containing SF3b pocket is the target of competitive splicing modulators such as E7107."},"narrative":{"teleology":[{"year":2002,"claim":"The discovery that SF3B5 is a bona fide subunit of both the SF3b subcomplex and intact spliceosomes established it as a previously unrecognized spliceosomal component, opening the question of its structural and functional role within the U2 snRNP.","evidence":"Mass spectrometry of affinity-purified human spliceosomes and immunoprecipitated SF3b/17S U2 snRNP","pmids":["12226669","12234937"],"confidence":"High","gaps":["No direct contacts with other SF3b subunits were mapped","No functional assay (e.g. depletion/reconstitution) was performed for SF3B5 specifically","Subcellular localization was inferred from the SF3b complex, not SF3B5 directly"]},{"year":2007,"claim":"Detection of SF3B5 in stoichiometric amounts within prespliceosomal A complexes demonstrated that the subunit is incorporated at the earliest stage of spliceosome assembly, before catalytic activation.","evidence":"Double-affinity purification of human A complexes under physiological conditions with MS and EM","pmids":["17332742"],"confidence":"High","gaps":["Whether SF3B5 makes direct contacts with pre-mRNA or other A-complex factors was unknown","No structure was available to explain how SF3B5 is positioned within the A complex"]},{"year":2016,"claim":"The crystal structure of the SF3b core complex resolved how SF3B5 directly contacts SF3B1's HEAT-domain superhelix and contributes to the scaffold that positions the branch-site recognition platform, answering the long-standing question of its structural role.","evidence":"X-ray crystallography of the human SF3b core complex with crosslinking MS validation; complementary cryo-EM-guided integrative modeling","pmids":["27720643","27618338"],"confidence":"High","gaps":["The open-versus-closed conformational dynamics of SF3B1 HEAT domain in the context of U2 snRNP were not yet resolved","Functional consequences of disrupting the SF3B5–SF3B1 interface were not tested by mutagenesis"]},{"year":2017,"claim":"Cryo-EM visualization of the pre-catalytic B complex placed SF3B5 within the U2 snRNP head domain connected to the spliceosome body, establishing its persistence beyond prespliceosomal stages.","evidence":"Cryo-EM structure of human pre-catalytic B complex spliceosome","pmids":["28781166"],"confidence":"High","gaps":["Whether SF3B5 makes stage-specific contacts that change between A and B complexes was unresolved","Resolution was insufficient to define SF3B5 side-chain interactions"]},{"year":2018,"claim":"Structures of the SF3b–E7107 complex and the activated Bact spliceosome together revealed that SF3B5 forms part of the drug-target pocket and remains stably associated through the B-to-Bact transition, linking the subunit to both pharmacological inhibition of splicing and the full activation pathway.","evidence":"Cryo-EM of SF3b–E7107 at 3.95 Å with SAR analysis; cryo-EM of human Bact in three conformational states with atomic modeling","pmids":["29491137","29360106"],"confidence":"High","gaps":["Whether SF3B5 depletion alone affects drug sensitivity was not tested","The exact contribution of SF3B5 to the open-to-closed conformational switch was not isolated from SF3B1 contributions"]},{"year":2019,"claim":"Near-atomic resolution structure of the human pre-B spliceosome confirmed SF3B5 is present at the earliest tri-snRNP engagement stage, completing the picture of SF3B5 occupancy across all major assembly intermediates (A → pre-B → B → Bact).","evidence":"Cryo-EM of human pre-B spliceosome at 3.3 Å core resolution","pmids":["30975767"],"confidence":"High","gaps":["Dynamics of SF3B5 release during the Bact-to-C transition were not captured","No kinetic or thermodynamic measurements of SF3B5 binding to SF3B1 in the context of assembly intermediates"]},{"year":2020,"claim":"The 17S U2 snRNP structure showed that SF3B1's HEAT domain—scaffolded by SF3B5—adopts an open conformation in the free snRNP, resolving why conformational remodeling is required for branch-site recognition and providing the structural basis for SF3B5's role in enabling this transition.","evidence":"Cryo-EM of human 17S U2 snRNP at 4.1 Å with protein crosslinking MS","pmids":["32494006"],"confidence":"High","gaps":["No mutagenesis or depletion/reconstitution experiment has isolated SF3B5's specific contribution to the open-to-closed transition","Whether SF3B5 has functions outside the canonical spliceosome cycle remains untested"]},{"year":null,"claim":"The direct functional consequence of SF3B5 loss on splicing activity in human cells has not been demonstrated by targeted depletion or mutagenesis, leaving the question of whether it is an essential or modulatory subunit unresolved at the biochemical level.","evidence":"","pmids":[],"confidence":"High","gaps":["No depletion/knockdown or reconstitution experiment for SF3B5 in a human system","No disease-causing mutations in SF3B5 have been reported","The precise energetic contribution of SF3B5 to SF3b complex stability is unmeasured"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[4,5,7,8,10]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,3]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[4,10]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,2,4,7,8,9,10]}],"complexes":["SF3b complex","U2 snRNP"],"partners":["SF3B1","SF3B3","PHF5A","SF3B2","SF3B4","SF3B6","SF3B14"],"other_free_text":[]},"mechanistic_narrative":"SF3B5 (SF3b10) is a constitutive structural subunit of the heptameric SF3b complex within the U2 snRNP, functioning as a core scaffold throughout the spliceosome assembly and activation cycle. Identified as a stoichiometric component of purified spliceosomes and the 17S U2 snRNP [PMID:12226669, PMID:12234937], SF3B5 directly contacts SF3B1 and helps maintain the HEAT-domain superhelix in an open conformation in the free U2 snRNP, which transitions to a closed state upon branch-point adenosine engagement during spliceosome assembly [PMID:27720643, PMID:32494006]. Structural studies across successive spliceosomal intermediates—prespliceosomal A, pre-B, B, and Bact complexes—confirm that SF3B5 remains stably integrated throughout these stages [PMID:17332742, PMID:30975767, PMID:28781166, PMID:29360106]. The SF3B5-containing SF3b pocket is the binding site for competitive splicing modulators such as E7107, which occupy the branch-point adenosine-binding pocket to inhibit splicing [PMID:29491137]."},"prefetch_data":{"uniprot":{"accession":"Q9BWJ5","full_name":"Splicing factor 3B subunit 5","aliases":["Pre-mRNA-splicing factor SF3b 10 kDa subunit"],"length_aa":86,"mass_kda":10.1,"function":"Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:12234937, PubMed:27720643, PubMed:28781166, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:12234937, PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3B4 is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA (PubMed:12234937, PubMed:27720643). Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9BWJ5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SF3B5","classification":"Common Essential","n_dependent_lines":1208,"n_total_lines":1208,"dependency_fraction":1.0},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000169976","cell_line_id":"CID001451","localizations":[{"compartment":"chromatin","grade":3}],"interactors":[{"gene":"SF3A1","stoichiometry":10.0},{"gene":"SF3A2","stoichiometry":10.0},{"gene":"SF3B1","stoichiometry":10.0},{"gene":"SF3B2","stoichiometry":10.0},{"gene":"SF3B3","stoichiometry":10.0},{"gene":"SNRPD2","stoichiometry":10.0},{"gene":"SF3B4","stoichiometry":10.0},{"gene":"SF3B6","stoichiometry":10.0},{"gene":"CCDC97","stoichiometry":10.0},{"gene":"SNRPA1","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID001451","total_profiled":1310},"omim":[{"mim_id":"617847","title":"SPLICING FACTOR 3B, SUBUNIT 5; SF3B5","url":"https://www.omim.org/entry/617847"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SF3B5"},"hgnc":{"alias_symbol":["SF3b10","MGC3133","Ysf3"],"prev_symbol":[]},"alphafold":{"accession":"Q9BWJ5","domains":[{"cath_id":"1.10.287","chopping":"26-77","consensus_level":"medium","plddt":97.0027,"start":26,"end":77}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BWJ5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BWJ5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BWJ5-F1-predicted_aligned_error_v6.png","plddt_mean":91.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SF3B5","jax_strain_url":"https://www.jax.org/strain/search?query=SF3B5"},"sequence":{"accession":"Q9BWJ5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BWJ5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BWJ5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BWJ5"}},"corpus_meta":[{"pmid":"27720643","id":"PMC_27720643","title":"Molecular 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research","url":"https://pubmed.ncbi.nlm.nih.gov/29360106","citation_count":176,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23602568","id":"PMC_23602568","title":"The protein interaction landscape of the human CMGC kinase group.","date":"2013","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/23602568","citation_count":174,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32807901","id":"PMC_32807901","title":"UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination.","date":"2020","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/32807901","citation_count":168,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"30804502","id":"PMC_30804502","title":"H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids.","date":"2019","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/30804502","citation_count":162,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"17332742","id":"PMC_17332742","title":"Composition and three-dimensional EM structure of double affinity-purified, human prespliceosomal A complexes.","date":"2007","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/17332742","citation_count":161,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"30975767","id":"PMC_30975767","title":"Mechanism of 5' splice site transfer for human spliceosome activation.","date":"2019","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/30975767","citation_count":141,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6174,"output_tokens":1273,"usd":0.018808},"stage2":{"model":"claude-opus-4-6","input_tokens":4494,"output_tokens":1598,"usd":0.09363},"total_usd":0.295453,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":17980,"output_tokens":3347,"usd":0.052073},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":6204,"output_tokens":2251,"usd":0.130942}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structure of a human SF3b core complex revealed that SF3B5 (SF3b10) maintains the distinctive conformation of SF3b155's HEAT domain through multiple direct contacts with SF3b130, SF3b10, and SF3b14b. SF3b10 contributes to a composite RNA-binding platform together with p14 and U2AF65 within SF3b155's HEAT-repeat superhelix.\",\n      \"method\": \"Crystal structure of human SF3b core complex combined with protein-protein crosslinking mass spectrometry\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure with crosslinking-MS validation, high citation count indicating foundational work\",\n      \"pmids\": [\"27720643\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SF3B5 is a component of the SF3b subcomplex (SF3B1, SF3B3, PHF5A, and SF3B5) that participates in branch point adenosine recognition; cryo-EM structure showed the subcomplex bound to splicing modulator E7107 in the branch point adenosine-binding pocket, establishing that SF3B5 is part of the structural scaffold that positions the pre-mRNA branch point.\",\n      \"method\": \"Cryo-EM structure of SF3b subcomplex bound to E7107 at 3.95 Å resolution\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structure with functional validation via SAR and mutant analysis\",\n      \"pmids\": [\"29491137\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Cryo-EM structure of the human 17S U2 snRNP at 4.1 Å combined with protein crosslinking data placed SF3B5 (SF3b10) within the broader U2 snRNP architecture, confirming its role as part of the SF3b subcomplex that maintains SF3B1HEAT in an open conformation in the pre-assembled U2 snRNP, which must be remodeled for branch-site interaction.\",\n      \"method\": \"Cryo-EM of 17S U2 snRNP combined with protein crosslinking mass spectrometry\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — high-resolution cryo-EM structure with orthogonal crosslinking-MS, published in Nature\",\n      \"pmids\": [\"32494006\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Integrative structural modeling guided by cryo-EM density maps provided localization of SF3b10 (SF3B5) within the SF3b assembly for the first time, showing it contributes to the scaffold architecture that supports the closed-to-open conformational transition of SF3b155 pivotal for branch point adenosine recognition.\",\n      \"method\": \"Integrative structural modeling using cryo-EM density maps and comparative modeling\",\n      \"journal\": \"RNA biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 method but single lab, computational/modeling-guided approach without direct experimental mutagenesis validation\",\n      \"pmids\": [\"27618338\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"In Trypanosoma brucei, the SF3B5 homologue (SAP49/DRBD1 complex partner) co-purifies with homologues of p14, SAP130, SAP145, and SAP155 (components of the SF3b complex), establishing that the SF3b complex composition including the SF3B5-equivalent subunit is conserved in trypanosomes; RNAi knockdown of the SAP49 homologue inhibited growth and caused a splicing defect.\",\n      \"method\": \"TAP-tag co-purification and RNAi knockdown in Trypanosoma brucei\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single pulldown in a divergent organism (not a canonical ortholog context), indirect evidence for SF3B5 complex membership\",\n      \"pmids\": [\"19450735\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SF3B5 (SF3b10) is an integral structural subunit of the heptameric SF3b complex within the U2 snRNP, where it makes direct contacts with SF3B1/SF3b155 and SF3B130 to stabilize the HEAT-domain conformation required for branch point adenosine recognition during pre-mRNA splicing, and participates in the composite RNA-binding platform that positions the branch point sequence for the first transesterification step.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper first, then extract discoveries only from KEPT papers.\n\n**Classification:**\n\nRetrieved papers:\n1. PMID:27720643 — SF3b crystal structure, includes SF3B5 (SF3b10) — KEEP\n2. PMID:29491137 — Cryo-EM SF3b+E7107, includes SF3B5 — KEEP\n3. PMID:32494006 — 17S U2 snRNP cryo-EM, SF3B5 is part of SF3b — KEEP\n4. PMID:26936752 — Mouse aging GWAS, Sf3b5 mentioned as candidate gene only — EXCLUDE (no mechanistic finding)\n5. PMID:34938809 — WGCNA/NAFLD hub genes, SF3B5 listed as hub gene, no mechanism — EXCLUDE\n6. PMID:36589261 — Fish gill transcriptomics, sf3b5 mentioned as DEG — EXCLUDE\n7. PMID:19450735 — Trypanosoma brucei DRBD1/SAP49 homologue; SF3b complex in trypanosomes — KEEP (ortholog context, mechanistic)\n8. PMID:27618338 — Integrative modeling of SF3b, includes SF3b10 (SF3B5) localization — KEEP\n9. PMID:32188628 — NK/T-cell lymphoma transcriptomics, SF3B5 mutation mentioned — EXCLUDE (expression/mutation association, no mechanism)\n10. PMID:41105619 — Candida albicans YSF3 (splicing gene) — EXCLUDE (fungal symbol collision, not SF3B5 ortholog in mechanistic context)\n\nGene2pubmed curated papers (selecting those with mechanistic content about SF3B5/SF3b complex):\n- PMID:12226669 — Spliceosome proteomics, SF3B5 identified as component — KEEP\n- PMID:12234937 — SF3b and 17S U2 snRNP characterization — KEEP\n- PMID:17332742 — Prespliceosomal A complex, SF3b components — KEEP\n- PMID:28781166 — Pre-catalytic B complex cryo-EM, SF3b — KEEP\n- PMID:29360106 — Human Bact complex cryo-EM, SF3b — KEEP\n- PMID:30975767 — Pre-B spliceosome cryo-EM — KEEP\n- PMID:11564863 — STAGA/SAP130 interaction with SF3b — KEEP (SAP130 is SF3B3, contextual)\n- PMID:11256614 — Subcellular localization of novel proteins — KEEP if SF3B5 specifically localized\n- Others (BioPlex, HuRI, MGC, etc.) — EXCLUDE (no mechanistic finding specific to SF3B5)\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"SF3B5 (SF3b10) was identified as a bona fide protein component of the human SF3b subcomplex of the U2 snRNP and of intact functional spliceosomes, as determined by mass spectrometry of purified spliceosomal particles.\",\n      \"method\": \"Maltose-binding protein affinity chromatography combined with nanoscale LC-MS/MS mass spectrometry of purified functional human spliceosomes\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — comprehensive proteomics of purified functional spliceosomes, foundational identification paper with >700 citations\",\n      \"pmids\": [\"12226669\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"SF3B5 (SF3b10) was identified as a stable component of both SF3b and the 17S U2 snRNP by mass spectrometry; immunofluorescence/FISH studies placed SF3b155 (but not SF3b10/SF3B5 specifically) outside Cajal bodies, providing initial subcellular context for SF3b assembly.\",\n      \"method\": \"Mass spectrometry of immunoprecipitated SF3b and 17S U2 snRNP; immunofluorescence and FISH\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal MS identification in purified complex, replicated across multiple snRNP preparations\",\n      \"pmids\": [\"12234937\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"SF3B5 (SF3b10) was detected as a stoichiometric component of human prespliceosomal A complexes, demonstrating its stable incorporation at an early stage of spliceosome assembly before catalytic activation.\",\n      \"method\": \"Double-affinity purification of prespliceosomal A complexes under physiological conditions followed by mass spectrometry and EM\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — stoichiometric detection in double-affinity purified complexes with EM validation\",\n      \"pmids\": [\"17332742\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"In Trypanosoma brucei, the SF3B5 ortholog (as part of the SF3b complex) co-purifies with homologues of p14, SAP130, SAP145, and SAP155, and localizes to the nucleus; RNAi knockdown of the associated SAP49 homologue (DRBD1) inhibited trypanosome growth and caused splicing defects, demonstrating conserved functional importance of the SF3b complex including SF3B5.\",\n      \"method\": \"TAP-tag co-purification mass spectrometry, immunofluorescence localization, RNAi knockdown with growth and splicing phenotype readout in T. brucei\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — ortholog functional study with co-purification and RNAi phenotype, but indirect evidence for SF3B5 itself\",\n      \"pmids\": [\"19450735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structure of the human SF3b core complex revealed that SF3B5 (SF3b10) directly contacts SF3B1 (SF3b155) and contributes to maintaining the distinctive conformation of the SF3B1 HEAT domain superhelix; SF3B5 forms part of the structural scaffold that positions the branch-site recognition platform.\",\n      \"method\": \"X-ray crystallography of the human SF3b core complex (crystal structure); protein-protein crosslinking mass spectrometry\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure with crosslinking validation, >200 citations, direct atomic-level evidence\",\n      \"pmids\": [\"27720643\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Integrative cryo-EM-guided modeling localized SF3B5 (SF3b10) within the closed form of the SF3b complex for the first time, placing it in spatial proximity to SF3b155, SF3b145, SF3b130, and SF3b14b and identifying a hinge region in SF3b155 important for the open-to-closed conformational transition relevant to branch-point adenosine recognition.\",\n      \"method\": \"Integrative structural modeling guided by cryo-EM density maps, comparative homology modeling, and experimental data\",\n      \"journal\": \"RNA biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — cryo-EM guided pseudo-atomic model; computational/integrative approach without independent mutagenesis validation\",\n      \"pmids\": [\"27618338\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In the cryo-EM structure of the pre-catalytic human spliceosomal B complex, SF3B5 is present as a stable SF3b component within the U2 snRNP head domain, which connects to the B complex main body via three bridges, positioning SF3b for subsequent activation steps.\",\n      \"method\": \"Cryo-EM structure of the pre-catalytic human B complex spliceosome\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — high-resolution cryo-EM structure of intact spliceosomal complex, >199 citations\",\n      \"pmids\": [\"28781166\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Cryo-EM structure of the SF3b subcomplex (comprising SF3B1, SF3B3, PHF5A, and SF3B5) bound to the splicing modulator E7107 at 3.95 Å revealed that SF3B5 is an integral structural subunit of the drug-bound complex; the structure showed E7107 occupies the branch-point adenosine-binding pocket, supporting a substrate-competitive mechanism of action for splicing modulators.\",\n      \"method\": \"Cryo-EM structure determination of SF3b–E7107 complex; structure-activity relationship analysis with chemical probes; functional assays with strong vs. weak pre-mRNA substrates\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — near-atomic cryo-EM structure with SAR and functional validation, multiple orthogonal methods\",\n      \"pmids\": [\"29491137\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In the cryo-EM structures of the human activated spliceosome (Bact complex), atomic models of all seven SF3b subunits including SF3B5 were built, confirming SF3B5 as a structural component maintained throughout spliceosome activation; the three conformational states captured revealed that SF3b remains stably associated through the B-to-Bact transition.\",\n      \"method\": \"Cryo-EM structure of human Bact complex in three conformational states with atomic modeling of SF3b subunits\",\n      \"journal\": \"Cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — atomic-resolution cryo-EM with multiple conformational states, direct structural evidence\",\n      \"pmids\": [\"29360106\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Cryo-EM structure of the human pre-B spliceosome complex showed SF3B5 as part of the SF3b module within U2 snRNP, and the structures collectively demonstrate that the SF3b complex including SF3B5 is positioned to interact with the branch-point sequence as part of the pre-mRNA recognition machinery before catalytic activation.\",\n      \"method\": \"Cryo-EM structure of human pre-B spliceosome at 3.3 Å core resolution\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — near-atomic cryo-EM structure with direct structural placement of SF3b components\",\n      \"pmids\": [\"30975767\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Cryo-EM structure of the human 17S U2 snRNP at 4.1 Å core resolution, combined with protein crosslinking data, revealed the molecular architecture of the snRNP and showed that SF3B1's HEAT domain (which is scaffolded in part by SF3B5) maintains an open conformation in isolated U2 snRNP, in contrast to the closed conformation observed in assembled spliceosomes, explaining why BSL remodeling is required for stable U2–branch-site interaction.\",\n      \"method\": \"Cryo-EM structure determination of 17S U2 snRNP; protein crosslinking mass spectrometry\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — high-resolution cryo-EM combined with crosslinking MS, direct structural evidence for conformational states\",\n      \"pmids\": [\"32494006\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SF3B5 (SF3b10) is a small but integral structural subunit of the heptameric SF3b complex within the U2 snRNP, where it directly contacts SF3B1 to help maintain the HEAT-domain superhelix in an open conformation in the free U2 snRNP; upon spliceosome assembly SF3b closes around the branch-point adenosine, with SF3B5 serving as a core scaffold throughout prespliceosomal A complex, pre-B, B, and Bact stages, and the SF3B5-containing SF3b pocket is the target of competitive splicing modulators such as E7107.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SF3B5 (SF3b10) is a constitutive subunit of the heptameric SF3b complex within the U2 snRNP, where it makes direct contacts with SF3B1 (SF3b155) and SF3B3 (SF3b130) to stabilize the distinctive conformation of SF3B1's HEAT-domain superhelix required for branch point adenosine recognition during pre-mRNA splicing [PMID:27720643, PMID:29491137]. Together with p14 and other SF3b subunits, SF3B5 contributes to a composite RNA-binding platform that positions the branch point sequence for catalysis, and it is part of the structural scaffold targeted by splicing modulators such as E7107 [PMID:29491137]. Within the pre-assembled 17S U2 snRNP, SF3B5 helps maintain SF3B1's HEAT domain in an open conformation that must be remodeled upon branch-site engagement [PMID:32494006]. The SF3b complex architecture including the SF3B5 subunit is evolutionarily conserved, as demonstrated by co-purification of an SF3B5 homologue with other SF3b components in Trypanosoma brucei [PMID:19450735].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing that SF3b complex composition is evolutionarily conserved — co-purification in T. brucei demonstrated that an SF3B5-equivalent subunit associates with SF3B1, SF3B3, and p14 homologues, suggesting ancient conservation of SF3b architecture.\",\n      \"evidence\": \"TAP-tag co-purification and RNAi knockdown in Trypanosoma brucei\",\n      \"pmids\": [\"19450735\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single pulldown in a highly divergent organism; not independently confirmed in additional species\",\n        \"No direct functional assay of the SF3B5 homologue itself (knockdown targeted SAP49, not the SF3B5 orthologue)\",\n        \"No structural data on the trypanosome SF3b complex\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Resolving how SF3B5 is positioned within SF3b and what structural role it plays — crystal structure and integrative modeling revealed that SF3B5 maintains the distinctive HEAT-domain conformation of SF3B1 through multiple direct contacts with SF3B3, SF3B14b, and contributes to the composite RNA-binding platform for branch point recognition.\",\n      \"evidence\": \"Crystal structure of human SF3b core complex with crosslinking-MS (Molecular Cell) and integrative cryo-EM-guided modeling (RNA Biology)\",\n      \"pmids\": [\"27720643\", \"27618338\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No mutagenesis or depletion experiment to test the functional consequence of disrupting SF3B5–SF3B1 contacts\",\n        \"RNA-binding contribution of SF3B5 inferred from composite platform positioning but not directly measured\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Defining SF3B5 as part of the minimal scaffold that constitutes the branch point adenosine-binding pocket and the target site for splicing modulators — cryo-EM of the SF3B1/SF3B3/PHF5A/SF3B5 subcomplex bound to E7107 showed SF3B5 is integral to the pocket architecture.\",\n      \"evidence\": \"Cryo-EM at 3.95 Å of SF3b subcomplex bound to E7107 with SAR and mutant validation\",\n      \"pmids\": [\"29491137\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether SF3B5 directly contacts drug or branch-point RNA, or acts purely as a structural scaffold, is not resolved\",\n        \"No SF3B5-specific mutant tested for splicing modulator sensitivity\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placing SF3B5 within the fully assembled 17S U2 snRNP revealed that it helps maintain SF3B1's HEAT domain in an open conformation in the pre-engaged state, establishing that conformational remodeling of this scaffold is needed for branch-site interaction.\",\n      \"evidence\": \"Cryo-EM of human 17S U2 snRNP at 4.1 Å combined with crosslinking-MS\",\n      \"pmids\": [\"32494006\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The specific contribution of SF3B5 to the open-to-closed conformational switch has not been dissected by mutagenesis\",\n        \"Dynamics of SF3B5 during the pre-catalytic to catalytic spliceosome transition remain uncharacterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether SF3B5 directly contacts branch-point RNA, what happens to spliceosome assembly when SF3B5 is specifically depleted, and whether SF3B5 loss-of-function has consequences for splicing fidelity or specific transcript subsets in human cells.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No SF3B5-specific depletion or knockout study in mammalian cells\",\n        \"No direct RNA-binding assay for SF3B5 alone\",\n        \"No transcriptome-wide analysis of splicing changes upon SF3B5 perturbation\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\"SF3b complex\", \"U2 snRNP\"],\n    \"partners\": [\"SF3B1\", \"SF3B3\", \"PHF5A\", \"SF3B14b\"],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"SF3B5 (SF3b10) is a constitutive structural subunit of the heptameric SF3b complex within the U2 snRNP, functioning as a core scaffold throughout the spliceosome assembly and activation cycle. Identified as a stoichiometric component of purified spliceosomes and the 17S U2 snRNP [PMID:12226669, PMID:12234937], SF3B5 directly contacts SF3B1 and helps maintain the HEAT-domain superhelix in an open conformation in the free U2 snRNP, which transitions to a closed state upon branch-point adenosine engagement during spliceosome assembly [PMID:27720643, PMID:32494006]. Structural studies across successive spliceosomal intermediates—prespliceosomal A, pre-B, B, and Bact complexes—confirm that SF3B5 remains stably integrated throughout these stages [PMID:17332742, PMID:30975767, PMID:28781166, PMID:29360106]. The SF3B5-containing SF3b pocket is the binding site for competitive splicing modulators such as E7107, which occupy the branch-point adenosine-binding pocket to inhibit splicing [PMID:29491137].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"The discovery that SF3B5 is a bona fide subunit of both the SF3b subcomplex and intact spliceosomes established it as a previously unrecognized spliceosomal component, opening the question of its structural and functional role within the U2 snRNP.\",\n      \"evidence\": \"Mass spectrometry of affinity-purified human spliceosomes and immunoprecipitated SF3b/17S U2 snRNP\",\n      \"pmids\": [\"12226669\", \"12234937\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No direct contacts with other SF3b subunits were mapped\",\n        \"No functional assay (e.g. depletion/reconstitution) was performed for SF3B5 specifically\",\n        \"Subcellular localization was inferred from the SF3b complex, not SF3B5 directly\"\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Detection of SF3B5 in stoichiometric amounts within prespliceosomal A complexes demonstrated that the subunit is incorporated at the earliest stage of spliceosome assembly, before catalytic activation.\",\n      \"evidence\": \"Double-affinity purification of human A complexes under physiological conditions with MS and EM\",\n      \"pmids\": [\"17332742\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether SF3B5 makes direct contacts with pre-mRNA or other A-complex factors was unknown\",\n        \"No structure was available to explain how SF3B5 is positioned within the A complex\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The crystal structure of the SF3b core complex resolved how SF3B5 directly contacts SF3B1's HEAT-domain superhelix and contributes to the scaffold that positions the branch-site recognition platform, answering the long-standing question of its structural role.\",\n      \"evidence\": \"X-ray crystallography of the human SF3b core complex with crosslinking MS validation; complementary cryo-EM-guided integrative modeling\",\n      \"pmids\": [\"27720643\", \"27618338\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The open-versus-closed conformational dynamics of SF3B1 HEAT domain in the context of U2 snRNP were not yet resolved\",\n        \"Functional consequences of disrupting the SF3B5–SF3B1 interface were not tested by mutagenesis\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Cryo-EM visualization of the pre-catalytic B complex placed SF3B5 within the U2 snRNP head domain connected to the spliceosome body, establishing its persistence beyond prespliceosomal stages.\",\n      \"evidence\": \"Cryo-EM structure of human pre-catalytic B complex spliceosome\",\n      \"pmids\": [\"28781166\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether SF3B5 makes stage-specific contacts that change between A and B complexes was unresolved\",\n        \"Resolution was insufficient to define SF3B5 side-chain interactions\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Structures of the SF3b–E7107 complex and the activated Bact spliceosome together revealed that SF3B5 forms part of the drug-target pocket and remains stably associated through the B-to-Bact transition, linking the subunit to both pharmacological inhibition of splicing and the full activation pathway.\",\n      \"evidence\": \"Cryo-EM of SF3b–E7107 at 3.95 Å with SAR analysis; cryo-EM of human Bact in three conformational states with atomic modeling\",\n      \"pmids\": [\"29491137\", \"29360106\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether SF3B5 depletion alone affects drug sensitivity was not tested\",\n        \"The exact contribution of SF3B5 to the open-to-closed conformational switch was not isolated from SF3B1 contributions\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Near-atomic resolution structure of the human pre-B spliceosome confirmed SF3B5 is present at the earliest tri-snRNP engagement stage, completing the picture of SF3B5 occupancy across all major assembly intermediates (A → pre-B → B → Bact).\",\n      \"evidence\": \"Cryo-EM of human pre-B spliceosome at 3.3 Å core resolution\",\n      \"pmids\": [\"30975767\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Dynamics of SF3B5 release during the Bact-to-C transition were not captured\",\n        \"No kinetic or thermodynamic measurements of SF3B5 binding to SF3B1 in the context of assembly intermediates\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The 17S U2 snRNP structure showed that SF3B1's HEAT domain—scaffolded by SF3B5—adopts an open conformation in the free snRNP, resolving why conformational remodeling is required for branch-site recognition and providing the structural basis for SF3B5's role in enabling this transition.\",\n      \"evidence\": \"Cryo-EM of human 17S U2 snRNP at 4.1 Å with protein crosslinking MS\",\n      \"pmids\": [\"32494006\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No mutagenesis or depletion/reconstitution experiment has isolated SF3B5's specific contribution to the open-to-closed transition\",\n        \"Whether SF3B5 has functions outside the canonical spliceosome cycle remains untested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct functional consequence of SF3B5 loss on splicing activity in human cells has not been demonstrated by targeted depletion or mutagenesis, leaving the question of whether it is an essential or modulatory subunit unresolved at the biochemical level.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No depletion/knockdown or reconstitution experiment for SF3B5 in a human system\",\n        \"No disease-causing mutations in SF3B5 have been reported\",\n        \"The precise energetic contribution of SF3B5 to SF3b complex stability is unmeasured\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [4, 5, 7, 8, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [4, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 2, 4, 7, 8, 9, 10]}\n    ],\n    \"complexes\": [\n      \"SF3b complex\",\n      \"U2 snRNP\"\n    ],\n    \"partners\": [\n      \"SF3B1\",\n      \"SF3B3\",\n      \"PHF5A\",\n      \"SF3B2\",\n      \"SF3B4\",\n      \"SF3B6\",\n      \"SF3B14\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}