{"gene":"SF3B5","run_date":"2026-06-10T07:46:31","timeline":{"discoveries":[{"year":2016,"finding":"Crystal structure of the human SF3b core complex revealed that SF3B5 (SF3b10) makes multiple contacts with SF3B1 (SF3b155) and SF3b130, helping maintain the distinctive conformation of SF3b155's HEAT domain. SF3B5 is thus a structural component of the SF3b heptameric complex essential for pre-mRNA splicing.","method":"Crystal structure of human SF3b core complex; protein-protein crosslinking mass spectrometry","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with direct localization of SF3b10 contacts, supported by crosslinking data in a rigorous structural study","pmids":["27720643"],"is_preprint":false},{"year":2016,"finding":"Computational integrative modeling using cryo-EM density maps provided structural localization of SF3B5 (SF3b10) within the SF3b complex for the first time, and identified its position in the closed-form assembly scaffold that supports branch point adenosine recognition.","method":"Integrative structural modeling guided by cryo-EM density maps; comparative modeling","journal":"RNA biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — computational/integrative model guided by experimental cryo-EM data, single study, no mutagenesis validation","pmids":["27618338"],"is_preprint":false},{"year":2018,"finding":"Cryo-EM structure of the SF3b subcomplex (SF3B1, SF3B3, PHF5A, and SF3B5) bound to splicing modulator E7107 at 3.95 Å showed that SF3B5 is a structural component of the drug-bound SF3b complex; E7107 binds in the branch point adenosine-binding pocket and its binding is facilitated by the quaternary architecture including SF3B5.","method":"Cryo-EM structure at 3.95 Å resolution of SF3b subcomplex bound to E7107; functional assays with chemical probes","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure with functional validation using multiple chemical probes, SAR analysis, and resistance mutation data","pmids":["29491137"],"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, confirmed SF3B5 (SF3b10) as an integral structural subunit of the U2 snRNP complex, where SF3B1's HEAT domain maintains an open conformation through interactions with multiple SF3b subunits including SF3B5.","method":"Cryo-EM structure of human 17S U2 snRNP; protein crosslinking mass spectrometry","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution cryo-EM combined with orthogonal crosslinking data, published in Nature","pmids":["32494006"],"is_preprint":false},{"year":2009,"finding":"In Trypanosoma brucei, the SF3B5 (SF3b10) homologue (identified via SAP49/DRBD1 characterization) co-purifies as part of the SF3b-like complex including homologues of p14, SAP130, SAP145, and SAP155, demonstrating conserved complex membership across evolution.","method":"TAP-tag co-purification of DRBD1 and associated SF3b homologues; nuclear localization by imaging; RNAi growth inhibition assay","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — TAP purification in a distant organism (Trypanosoma), SF3b10 mentioned as complex member but not directly studied; single method","pmids":["19450735"],"is_preprint":false},{"year":2025,"finding":"In Candida albicans, the SF3B5 ortholog YSF3 (C1_11680C) is required for temperature-dependent fitness; loss-of-function screening identified YSF3 as essential for fungal survival at both low and high temperatures, implicating this splicing factor in thermal adaptation.","method":"Genome-wide functional genomics GRACE library screen under multiple temperature conditions; loss-of-function fitness assay","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genome-wide loss-of-function screen with defined fitness phenotype, but single study and no molecular mechanism dissected for YSF3 specifically","pmids":["41105619"],"is_preprint":false}],"current_model":"SF3B5 (SF3b10) is a structural subunit of the heptameric SF3b complex within the U2 snRNP, where it makes direct contacts with SF3B1's HEAT domain and SF3B130 to stabilize the open conformation of SF3B1 required for branch point adenosine recognition during pre-mRNA splicing, and is present in the drug-bound SF3b subcomplex targeted by splicing modulators such as E7107."},"narrative":{"mechanistic_narrative":"SF3B5 (SF3b10) is a small structural subunit of the heptameric SF3b complex within the U2 snRNP, where it contributes to the assembly architecture required for pre-mRNA splicing [PMID:27720643, PMID:32494006]. Crystallographic and crosslinking analysis of the human SF3b core showed that SF3B5 makes multiple direct contacts with SF3B1 (SF3b155) and SF3b130, helping maintain the distinctive conformation of the SF3B1 HEAT domain [PMID:27720643]; in the assembled 17S U2 snRNP, these contacts help hold the SF3B1 HEAT domain in the open conformation associated with branch point adenosine recognition [PMID:32494006]. SF3B5 is an integral component of the drug-bound SF3b subcomplex (SF3B1–SF3B3–PHF5A–SF3B5) whose quaternary architecture facilitates binding of the splicing modulator E7107 in the branch point adenosine pocket [PMID:29491137]. Its membership in an SF3b-like complex is evolutionarily conserved, with orthologs co-purifying with SF3b subunits in Trypanosoma and being required for fitness in Candida albicans [PMID:19450735, PMID:41105619]. Beyond its role as a conformational scaffold within SF3b, no independent catalytic or regulatory activity for SF3B5 has been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Establishing that the SF3B5 homologue is a conserved member of an SF3b-like complex addressed whether its complex association predates vertebrates.","evidence":"TAP-tag co-purification of the DRBD1/SF3b10 homologue with p14, SAP130, SAP145, and SAP155 in Trypanosoma brucei, with nuclear localization and RNAi growth assay","pmids":["19450735"],"confidence":"Low","gaps":["Single method (TAP purification) in a distant organism with SF3b10 not directly studied","No structural or molecular role defined for the homologue itself","No mapping of direct binding partners within the complex"]},{"year":2016,"claim":"Determining where SF3B5 sits in the SF3b complex answered whether it is a structural scaffold and which subunits it contacts.","evidence":"Crystal structure of the human SF3b core complex plus crosslinking mass spectrometry, with complementary integrative modeling guided by cryo-EM density","pmids":["27720643","27618338"],"confidence":"High","gaps":["No mutagenesis test of which SF3B5 contacts are functionally required","Conformational role inferred structurally rather than by functional perturbation","Does not define SF3B5 contribution to splicing catalysis directly"]},{"year":2018,"claim":"Resolving the drug-bound SF3b subcomplex established that SF3B5 is part of the architecture targeted by splicing modulators.","evidence":"Cryo-EM structure at 3.95 Å of the SF3B1–SF3B3–PHF5A–SF3B5 subcomplex bound to E7107, with chemical probe and resistance mutation analyses","pmids":["29491137"],"confidence":"High","gaps":["SF3B5 is a structural participant but no SF3B5 residue is shown to directly contact E7107","Functional consequence of SF3B5 perturbation on drug response not tested"]},{"year":2020,"claim":"Placing SF3B5 in the assembled 17S U2 snRNP confirmed its role in maintaining the open SF3B1 HEAT-domain conformation in the physiological particle.","evidence":"Cryo-EM structure of the human 17S U2 snRNP at 4.1 Å core resolution combined with protein crosslinking mass spectrometry","pmids":["32494006"],"confidence":"High","gaps":["Conformational role inferred from static structure","No dynamics of the open-to-closed transition resolved with respect to SF3B5"]},{"year":2025,"claim":"Loss-of-function screening tested whether the SF3B5 ortholog is required for organismal fitness, linking it to viability and thermal adaptation.","evidence":"Genome-wide GRACE library screen of YSF3 in Candida albicans across temperature conditions with a loss-of-function fitness assay","pmids":["41105619"],"confidence":"Medium","gaps":["No molecular mechanism dissected for YSF3 specifically","Single study","Connection between fitness phenotype and splicing function not directly demonstrated"]},{"year":null,"claim":"Whether SF3B5 contributes activity beyond a static conformational scaffold — and how its perturbation alters splice site selection — remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No functional perturbation of SF3B5 in human cells reported in the corpus","No defined effect of SF3B5 loss on specific splicing events","No regulatory or post-translational control of SF3B5 described"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,2,3]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3,4]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,3]}],"complexes":["SF3b complex","U2 snRNP"],"partners":["SF3B1","SF3B3","PHF5A"],"other_free_text":[]}},"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 Architecture of SF3b and Structural Consequences of Its Cancer-Related Mutations.","date":"2016","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/27720643","citation_count":211,"is_preprint":false},{"pmid":"29491137","id":"PMC_29491137","title":"The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action.","date":"2018","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/29491137","citation_count":100,"is_preprint":false},{"pmid":"32494006","id":"PMC_32494006","title":"Molecular architecture of the human 17S U2 snRNP.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32494006","citation_count":88,"is_preprint":false},{"pmid":"26936752","id":"PMC_26936752","title":"Approaches to Investigating Complex Genetic Traits in a Large-Scale Inbred Mouse Aging Study.","date":"2016","source":"Veterinary pathology","url":"https://pubmed.ncbi.nlm.nih.gov/26936752","citation_count":22,"is_preprint":false},{"pmid":"34938809","id":"PMC_34938809","title":"WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Nonalcoholic Fatty Liver Disease.","date":"2021","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/34938809","citation_count":22,"is_preprint":false},{"pmid":"36589261","id":"PMC_36589261","title":"Comprehensive transcriptomics and proteomics analysis of Carassius auratus gills in response to Aeromonas hydrophila.","date":"2022","source":"Fish and shellfish immunology reports","url":"https://pubmed.ncbi.nlm.nih.gov/36589261","citation_count":12,"is_preprint":false},{"pmid":"19450735","id":"PMC_19450735","title":"DRBD1 is the Trypanosoma brucei homologue of the spliceosome-associated protein 49.","date":"2009","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19450735","citation_count":8,"is_preprint":false},{"pmid":"27618338","id":"PMC_27618338","title":"Structural and mechanistic insights into human splicing factor SF3b complex derived using an integrated approach guided by the cryo-EM density maps.","date":"2016","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/27618338","citation_count":7,"is_preprint":false},{"pmid":"32188628","id":"PMC_32188628","title":"Transcriptome complexity in intravascular NK/T-cell lymphoma.","date":"2020","source":"Journal of clinical pathology","url":"https://pubmed.ncbi.nlm.nih.gov/32188628","citation_count":4,"is_preprint":false},{"pmid":"41105619","id":"PMC_41105619","title":"Expansion of the functional genomics GRACE library reveals genes relevant for temperature-dependent fitness in Candida albicans.","date":"2025","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/41105619","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6943,"output_tokens":1482,"usd":0.02153,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8159,"output_tokens":2063,"usd":0.046185,"stage2_stop_reason":"end_turn"},"total_usd":0.067715,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structure of the human SF3b core complex revealed that SF3B5 (SF3b10) makes multiple contacts with SF3B1 (SF3b155) and SF3b130, helping maintain the distinctive conformation of SF3b155's HEAT domain. SF3B5 is thus a structural component of the SF3b heptameric complex essential for pre-mRNA splicing.\",\n      \"method\": \"Crystal structure of human SF3b core complex; protein-protein crosslinking mass spectrometry\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with direct localization of SF3b10 contacts, supported by crosslinking data in a rigorous structural study\",\n      \"pmids\": [\"27720643\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Computational integrative modeling using cryo-EM density maps provided structural localization of SF3B5 (SF3b10) within the SF3b complex for the first time, and identified its position in the closed-form assembly scaffold that supports branch point adenosine recognition.\",\n      \"method\": \"Integrative structural modeling guided by cryo-EM density maps; comparative modeling\",\n      \"journal\": \"RNA biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — computational/integrative model guided by experimental cryo-EM data, single study, no mutagenesis validation\",\n      \"pmids\": [\"27618338\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Cryo-EM structure of the SF3b subcomplex (SF3B1, SF3B3, PHF5A, and SF3B5) bound to splicing modulator E7107 at 3.95 Å showed that SF3B5 is a structural component of the drug-bound SF3b complex; E7107 binds in the branch point adenosine-binding pocket and its binding is facilitated by the quaternary architecture including SF3B5.\",\n      \"method\": \"Cryo-EM structure at 3.95 Å resolution of SF3b subcomplex bound to E7107; functional assays with chemical probes\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure with functional validation using multiple chemical probes, SAR analysis, and resistance mutation data\",\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 core resolution, combined with protein crosslinking data, confirmed SF3B5 (SF3b10) as an integral structural subunit of the U2 snRNP complex, where SF3B1's HEAT domain maintains an open conformation through interactions with multiple SF3b subunits including SF3B5.\",\n      \"method\": \"Cryo-EM structure of human 17S U2 snRNP; protein crosslinking mass spectrometry\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution cryo-EM combined with orthogonal crosslinking data, published in Nature\",\n      \"pmids\": [\"32494006\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"In Trypanosoma brucei, the SF3B5 (SF3b10) homologue (identified via SAP49/DRBD1 characterization) co-purifies as part of the SF3b-like complex including homologues of p14, SAP130, SAP145, and SAP155, demonstrating conserved complex membership across evolution.\",\n      \"method\": \"TAP-tag co-purification of DRBD1 and associated SF3b homologues; nuclear localization by imaging; RNAi growth inhibition assay\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — TAP purification in a distant organism (Trypanosoma), SF3b10 mentioned as complex member but not directly studied; single method\",\n      \"pmids\": [\"19450735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In Candida albicans, the SF3B5 ortholog YSF3 (C1_11680C) is required for temperature-dependent fitness; loss-of-function screening identified YSF3 as essential for fungal survival at both low and high temperatures, implicating this splicing factor in thermal adaptation.\",\n      \"method\": \"Genome-wide functional genomics GRACE library screen under multiple temperature conditions; loss-of-function fitness assay\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genome-wide loss-of-function screen with defined fitness phenotype, but single study and no molecular mechanism dissected for YSF3 specifically\",\n      \"pmids\": [\"41105619\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SF3B5 (SF3b10) is a structural subunit of the heptameric SF3b complex within the U2 snRNP, where it makes direct contacts with SF3B1's HEAT domain and SF3B130 to stabilize the open conformation of SF3B1 required for branch point adenosine recognition during pre-mRNA splicing, and is present in the drug-bound SF3b subcomplex targeted by splicing modulators such as E7107.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SF3B5 (SF3b10) is a small structural subunit of the heptameric SF3b complex within the U2 snRNP, where it contributes to the assembly architecture required for pre-mRNA splicing [#0, #3]. Crystallographic and crosslinking analysis of the human SF3b core showed that SF3B5 makes multiple direct contacts with SF3B1 (SF3b155) and SF3b130, helping maintain the distinctive conformation of the SF3B1 HEAT domain [#0]; in the assembled 17S U2 snRNP, these contacts help hold the SF3B1 HEAT domain in the open conformation associated with branch point adenosine recognition [#3]. SF3B5 is an integral component of the drug-bound SF3b subcomplex (SF3B1–SF3B3–PHF5A–SF3B5) whose quaternary architecture facilitates binding of the splicing modulator E7107 in the branch point adenosine pocket [#2]. Its membership in an SF3b-like complex is evolutionarily conserved, with orthologs co-purifying with SF3b subunits in Trypanosoma and being required for fitness in Candida albicans [#4, #5]. Beyond its role as a conformational scaffold within SF3b, no independent catalytic or regulatory activity for SF3B5 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing that the SF3B5 homologue is a conserved member of an SF3b-like complex addressed whether its complex association predates vertebrates.\",\n      \"evidence\": \"TAP-tag co-purification of the DRBD1/SF3b10 homologue with p14, SAP130, SAP145, and SAP155 in Trypanosoma brucei, with nuclear localization and RNAi growth assay\",\n      \"pmids\": [\"19450735\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single method (TAP purification) in a distant organism with SF3b10 not directly studied\", \"No structural or molecular role defined for the homologue itself\", \"No mapping of direct binding partners within the complex\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Determining where SF3B5 sits in the SF3b complex answered whether it is a structural scaffold and which subunits it contacts.\",\n      \"evidence\": \"Crystal structure of the human SF3b core complex plus crosslinking mass spectrometry, with complementary integrative modeling guided by cryo-EM density\",\n      \"pmids\": [\"27720643\", \"27618338\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No mutagenesis test of which SF3B5 contacts are functionally required\", \"Conformational role inferred structurally rather than by functional perturbation\", \"Does not define SF3B5 contribution to splicing catalysis directly\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Resolving the drug-bound SF3b subcomplex established that SF3B5 is part of the architecture targeted by splicing modulators.\",\n      \"evidence\": \"Cryo-EM structure at 3.95 Å of the SF3B1–SF3B3–PHF5A–SF3B5 subcomplex bound to E7107, with chemical probe and resistance mutation analyses\",\n      \"pmids\": [\"29491137\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"SF3B5 is a structural participant but no SF3B5 residue is shown to directly contact E7107\", \"Functional consequence of SF3B5 perturbation on drug response not tested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placing SF3B5 in the assembled 17S U2 snRNP confirmed its role in maintaining the open SF3B1 HEAT-domain conformation in the physiological particle.\",\n      \"evidence\": \"Cryo-EM structure of the human 17S U2 snRNP at 4.1 Å core resolution combined with protein crosslinking mass spectrometry\",\n      \"pmids\": [\"32494006\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Conformational role inferred from static structure\", \"No dynamics of the open-to-closed transition resolved with respect to SF3B5\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Loss-of-function screening tested whether the SF3B5 ortholog is required for organismal fitness, linking it to viability and thermal adaptation.\",\n      \"evidence\": \"Genome-wide GRACE library screen of YSF3 in Candida albicans across temperature conditions with a loss-of-function fitness assay\",\n      \"pmids\": [\"41105619\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular mechanism dissected for YSF3 specifically\", \"Single study\", \"Connection between fitness phenotype and splicing function not directly demonstrated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether SF3B5 contributes activity beyond a static conformational scaffold — and how its perturbation alters splice site selection — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No functional perturbation of SF3B5 in human cells reported in the corpus\", \"No defined effect of SF3B5 loss on specific splicing events\", \"No regulatory or post-translational control of SF3B5 described\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [\"SF3b complex\", \"U2 snRNP\"],\n    \"partners\": [\"SF3B1\", \"SF3B3\", \"PHF5A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}