{"gene":"SAP30BP","run_date":"2026-06-10T07:46:29","timeline":{"discoveries":[{"year":2004,"finding":"SAP30BP (HTRP) was cloned as an immediate-early gene product induced by HSV-1 binding in human embryo fibroblasts. Yeast two-hybrid, in vitro pull-down/Western blot, and in vivo immunoprecipitation experiments showed that SAP30BP directly interacts with SAP30, a component of the mSin3A co-repressor/HDAC complex, via SAP30BP's conserved domain. Fluorescent fusion-protein imaging confirmed nuclear localization of SAP30BP in HeLa cells.","method":"Yeast two-hybrid, pull-down/Western blot, co-immunoprecipitation, fluorescent fusion-protein localization","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus yeast two-hybrid and pull-down in a single study; single lab","pmids":["15496587"],"is_preprint":false},{"year":2010,"finding":"SAP30BP (HTRP) promotes HDAC activity and inhibits transcription of a viral promoter by interacting with SAP30 (mSin3A-associated protein). ChIP experiments demonstrated that SAP30BP increases histone H3 deacetylation at lysine 9 and lysine 14, and the interaction with SAP30 synergistically enhances transcriptional repression in a manner dependent on HDAC enzyme activity.","method":"Dual-luciferase reporter assay, real-time PCR, chromatin immunoprecipitation (ChIP)","journal":"Virologica Sinica","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus reporter assay and qPCR in single lab; two orthogonal methods","pmids":["21221920"],"is_preprint":false},{"year":2023,"finding":"SAP30BP forms a tight complex with CDK11 and cyclins L1/L2. Acute degradation of SAP30BP (mirroring CDK11 depletion) causes widespread defects in pre-mRNA splicing. In vitro and in vivo experiments showed that SAP30BP facilitates CDK11 kinase activity by ensuring the stability of cyclins L1/L2 and promoting their assembly with CDK11, identifying SAP30BP as a critical CDK11 activator. Additionally, a neural alternative exon in SAP30BP modulates interactions with RNA processing factors and regulates splicing of short (<100 nt) 'mini-introns' that control nuclear RNA levels.","method":"Acute protein degradation (degron system), in vitro kinase assay, co-immunoprecipitation, affinity purification-mass spectrometry (AP-MS)","journal":"The EMBO journal / Molecular cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro kinase assay plus acute degradation phenocopy and AP-MS, corroborated by independent AP-MS study in same year","pmids":["38059508","38065061"],"is_preprint":false},{"year":2025,"finding":"CDK11 T-loop threonine 595 (Thr595) phosphorylation is essential for formation of the active CDK11–cyclin L–SAP30BP complex. Mutational analysis showed that Thr595 is required for SAP30BP association, and CDK7 inhibition leads to sequential dephosphorylation of CDK11 Thr595 and SF3B1, implicating CDK7 in regulating the CDK11–SAP30BP complex upstream.","method":"Mutational analysis, SILAC-based phosphoproteomics, CDK7 inhibition experiments","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutational analysis plus phosphoproteomics in single study; single lab","pmids":["41428738"],"is_preprint":false},{"year":2026,"finding":"Cryo-EM structure of the CDK11–cyclin L2–SAP30BP complex at 2.3 Å resolution revealed that SAP30BP forms extensive interactions with cyclin L2 (stabilizing it) and makes critical contacts with the C-terminal kinase lobe of CDK11 that promote complex assembly. Biochemical experiments confirmed that cyclin L2 is destabilized in the absence of SAP30BP. A pseudo-substrate sequence near the CDK11 C-terminus was also identified and implicated in CDK11 auto-regulation. The complex promotes spliceosome activation (B-to-Bact transition) via SF3B1 phosphorylation.","method":"Cryo-EM (2.3 Å), biochemical stability assays, inhibitor binding analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution cryo-EM structure with biochemical validation of key structural findings in single rigorous study","pmids":["42034640"],"is_preprint":false},{"year":2025,"finding":"SAP30BP expression is elevated in hearts of diabetic cardiomyopathy (DCM) mice and high-glucose-treated cardiomyocytes. Mechanistically, SAP30BP inhibits transcription of MFN2 through HDAC1-mediated histone deacetylation, causing mitochondrial dynamic disruption that hinders mitochondrial translocation of ACSL4 and promotes mitochondria-associated ferroptosis. Knockdown of SAP30BP ameliorated ferroptosis, oxidative stress, and cardiac dysfunction in DCM.","method":"siRNA knockdown, RNA-seq, ChIP (HDAC1-mediated deacetylation), mitochondrial fractionation, cellular ferroptosis assays","journal":"European journal of pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown with RNA-seq and ChIP in single lab; multiple orthogonal methods","pmids":["40774404"],"is_preprint":false},{"year":2024,"finding":"BioID proximity mapping identified SAP30BP as an in vivo interactor of SAP18 within the SIN3 transcriptional repressor complex context, and complementary immunoprecipitation validated this interaction.","method":"BioID proximity labeling, mass spectrometry, co-immunoprecipitation","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single proximity-labeling study with complementary Co-IP; single lab, SAP30BP is a minor finding within a broader SAP18 interactome paper","pmids":["39522233"],"is_preprint":false}],"current_model":"SAP30BP is a nuclear protein that acts as a critical activator of CDK11 by stabilizing cyclin L1/L2 and promoting their assembly with CDK11, thereby enabling CDK11-dependent phosphorylation of SF3B1 and global pre-mRNA splicing (including short mini-introns); it also functions as a transcriptional co-repressor through direct interaction with SAP30 within the mSin3A–HDAC complex, promoting histone H3 deacetylation (H3K9 and H3K14) and gene silencing, with the cryo-EM structure of the CDK11–cyclin L2–SAP30BP ternary complex defining the molecular basis of SAP30BP's role in CDK11 activation and spliceosome B-to-Bact transition."},"narrative":{"mechanistic_narrative":"SAP30BP is a nuclear protein that bridges two distinct nuclear regulatory processes: pre-mRNA splicing through CDK11 activation and transcriptional silencing through the mSin3A–HDAC corepressor complex [PMID:15496587, PMID:38059508, PMID:38065061]. As a critical CDK11 activator, SAP30BP forms a tight complex with CDK11 and cyclins L1/L2, ensuring cyclin stability and promoting their assembly with the kinase; acute degradation of SAP30BP phenocopies CDK11 loss and causes widespread pre-mRNA splicing defects, including dysregulation of short (<100 nt) mini-introns [PMID:38059508, PMID:38065061]. The cryo-EM structure of the CDK11–cyclin L2–SAP30BP ternary complex shows that SAP30BP makes extensive contacts that stabilize cyclin L2 and critical contacts with the CDK11 C-terminal kinase lobe that drive complex assembly, enabling SF3B1 phosphorylation and the spliceosome B-to-Bact transition [PMID:42034640]. Formation of this active complex depends on CDK11 T-loop phosphorylation at Thr595, which is required for SAP30BP association and is controlled upstream by CDK7 [PMID:41428738]. Independently, SAP30BP acts as a transcriptional co-repressor by directly binding SAP30 within the mSin3A–HDAC complex, promoting histone H3 deacetylation at K9 and K14 in an HDAC-dependent manner to enforce gene silencing [PMID:15496587, PMID:21221920].","teleology":[{"year":2004,"claim":"Established SAP30BP as a nuclear protein physically linked to transcriptional repression machinery, answering where the uncharacterized HSV-1-induced gene product localizes and what it binds.","evidence":"Yeast two-hybrid, pull-down, reciprocal Co-IP, and fluorescent fusion localization in HeLa cells","pmids":["15496587"],"confidence":"Medium","gaps":["Did not define functional consequence of the SAP30 interaction on chromatin","No demonstration of HDAC recruitment or histone modification"]},{"year":2010,"claim":"Showed the SAP30BP–SAP30 interaction is functionally repressive, converting a binding observation into a chromatin-level silencing mechanism.","evidence":"Dual-luciferase reporter, qPCR, and ChIP for H3K9/K14 deacetylation","pmids":["21221920"],"confidence":"Medium","gaps":["Repression demonstrated on a viral promoter; cellular gene targets unclear","Did not establish whether SAP30BP is an obligate subunit of the complex"]},{"year":2023,"claim":"Identified an entirely separate molecular role: SAP30BP as a critical CDK11 activator required for global pre-mRNA splicing, answering how cyclin L1/L2–CDK11 assembly is achieved.","evidence":"Degron-based acute degradation phenocopy, in vitro kinase assay, AP-MS, corroborated by independent same-year AP-MS","pmids":["38059508","38065061"],"confidence":"High","gaps":["Structural basis of cyclin stabilization not yet resolved","Substrate scope of resulting CDK11 activity beyond splicing not defined"]},{"year":2025,"claim":"Placed the CDK11–SAP30BP complex in a regulatory cascade by showing CDK11 Thr595 phosphorylation gates SAP30BP association and that CDK7 acts upstream.","evidence":"Mutational analysis, SILAC phosphoproteomics, CDK7 inhibition","pmids":["41428738"],"confidence":"Medium","gaps":["Direct kinase responsible for Thr595 phosphorylation not formally proven","Single-lab study"]},{"year":2025,"claim":"Connected SAP30BP's repressor activity to disease physiology, showing it silences MFN2 via HDAC1 to drive mitochondrial ferroptosis in diabetic cardiomyopathy.","evidence":"siRNA knockdown, RNA-seq, ChIP, mitochondrial fractionation, ferroptosis assays in DCM mouse and high-glucose cardiomyocyte models","pmids":["40774404"],"confidence":"Medium","gaps":["Causal link in human disease not established","Whether splicing function contributes to the phenotype not addressed"]},{"year":2026,"claim":"Provided the atomic-resolution mechanism of CDK11 activation, defining how SAP30BP stabilizes cyclin L2 and promotes the assembly that drives spliceosome activation.","evidence":"2.3 Å cryo-EM of CDK11–cyclin L2–SAP30BP with biochemical stability assays and inhibitor binding analysis","pmids":["42034640"],"confidence":"High","gaps":["Function of the identified CDK11 pseudo-substrate sequence in vivo not fully resolved","Structure does not address the transcriptional co-repressor role"]},{"year":null,"claim":"How SAP30BP partitions between its splicing-activator and chromatin-repressor functions, and whether these are coordinated within a single regulatory program, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No study connects the CDK11/splicing and mSin3A/HDAC roles","Determinants of complex choice (e.g. the neural alternative exon) not mapped to either function"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,4]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,5]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[2,4]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,5]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[1,5]}],"complexes":["CDK11–cyclin L2–SAP30BP complex","mSin3A–HDAC corepressor complex"],"partners":["CDK11","CCNL1","CCNL2","SAP30","SAP18","SF3B1","HDAC1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UHR5","full_name":"SAP30-binding protein","aliases":["Transcriptional regulator protein HCNGP"],"length_aa":308,"mass_kda":33.9,"function":"Plays a role in transcriptional repression by promoting histone deacetylase activity, leading to deacetylation of histone H3 (PubMed:21221920). Acts as a regulator of pre-mRNA splicing by facilitating assembly of the cyclin-L-CDK11 cyclin-dependent protein kinase complex, thereby promoting phosphorylation of SF3B1 (PubMed:38059508). May be involved in the regulation of beta-2-microglobulin genes (By similarity) (Microbial infection) Involved in transcriptional repression of HHV-1 genes TK and gC","subcellular_location":"Nucleus; Nucleus speckle","url":"https://www.uniprot.org/uniprotkb/Q9UHR5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SAP30BP","classification":"Common Essential","n_dependent_lines":1204,"n_total_lines":1208,"dependency_fraction":0.9966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CDK11B","stoichiometry":10.0},{"gene":"CSNK2B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SAP30BP","total_profiled":1310},"omim":[{"mim_id":"610218","title":"SAP30-BINDING PROTEIN; SAP30BP","url":"https://www.omim.org/entry/610218"}],"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/SAP30BP"},"hgnc":{"alias_symbol":["HCNGP","HTRG","HTRP"],"prev_symbol":[]},"alphafold":{"accession":"Q9UHR5","domains":[{"cath_id":"-","chopping":"148-189","consensus_level":"medium","plddt":90.3564,"start":148,"end":189},{"cath_id":"1.20.5","chopping":"193-220","consensus_level":"medium","plddt":84.5921,"start":193,"end":220}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UHR5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UHR5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UHR5-F1-predicted_aligned_error_v6.png","plddt_mean":64.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SAP30BP","jax_strain_url":"https://www.jax.org/strain/search?query=SAP30BP"},"sequence":{"accession":"Q9UHR5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UHR5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UHR5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UHR5"}},"corpus_meta":[{"pmid":"8663995","id":"PMC_8663995","title":"Cloning 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human embryo fibroblasts. Yeast two-hybrid, in vitro pull-down/Western blot, and in vivo immunoprecipitation experiments showed that SAP30BP directly interacts with SAP30, a component of the mSin3A co-repressor/HDAC complex, via SAP30BP's conserved domain. Fluorescent fusion-protein imaging confirmed nuclear localization of SAP30BP in HeLa cells.\",\n      \"method\": \"Yeast two-hybrid, pull-down/Western blot, co-immunoprecipitation, fluorescent fusion-protein localization\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus yeast two-hybrid and pull-down in a single study; single lab\",\n      \"pmids\": [\"15496587\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"SAP30BP (HTRP) promotes HDAC activity and inhibits transcription of a viral promoter by interacting with SAP30 (mSin3A-associated protein). ChIP experiments demonstrated that SAP30BP increases histone H3 deacetylation at lysine 9 and lysine 14, and the interaction with SAP30 synergistically enhances transcriptional repression in a manner dependent on HDAC enzyme activity.\",\n      \"method\": \"Dual-luciferase reporter assay, real-time PCR, chromatin immunoprecipitation (ChIP)\",\n      \"journal\": \"Virologica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus reporter assay and qPCR in single lab; two orthogonal methods\",\n      \"pmids\": [\"21221920\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SAP30BP forms a tight complex with CDK11 and cyclins L1/L2. Acute degradation of SAP30BP (mirroring CDK11 depletion) causes widespread defects in pre-mRNA splicing. In vitro and in vivo experiments showed that SAP30BP facilitates CDK11 kinase activity by ensuring the stability of cyclins L1/L2 and promoting their assembly with CDK11, identifying SAP30BP as a critical CDK11 activator. Additionally, a neural alternative exon in SAP30BP modulates interactions with RNA processing factors and regulates splicing of short (<100 nt) 'mini-introns' that control nuclear RNA levels.\",\n      \"method\": \"Acute protein degradation (degron system), in vitro kinase assay, co-immunoprecipitation, affinity purification-mass spectrometry (AP-MS)\",\n      \"journal\": \"The EMBO journal / Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro kinase assay plus acute degradation phenocopy and AP-MS, corroborated by independent AP-MS study in same year\",\n      \"pmids\": [\"38059508\", \"38065061\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CDK11 T-loop threonine 595 (Thr595) phosphorylation is essential for formation of the active CDK11–cyclin L–SAP30BP complex. Mutational analysis showed that Thr595 is required for SAP30BP association, and CDK7 inhibition leads to sequential dephosphorylation of CDK11 Thr595 and SF3B1, implicating CDK7 in regulating the CDK11–SAP30BP complex upstream.\",\n      \"method\": \"Mutational analysis, SILAC-based phosphoproteomics, CDK7 inhibition experiments\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutational analysis plus phosphoproteomics in single study; single lab\",\n      \"pmids\": [\"41428738\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Cryo-EM structure of the CDK11–cyclin L2–SAP30BP complex at 2.3 Å resolution revealed that SAP30BP forms extensive interactions with cyclin L2 (stabilizing it) and makes critical contacts with the C-terminal kinase lobe of CDK11 that promote complex assembly. Biochemical experiments confirmed that cyclin L2 is destabilized in the absence of SAP30BP. A pseudo-substrate sequence near the CDK11 C-terminus was also identified and implicated in CDK11 auto-regulation. The complex promotes spliceosome activation (B-to-Bact transition) via SF3B1 phosphorylation.\",\n      \"method\": \"Cryo-EM (2.3 Å), biochemical stability assays, inhibitor binding analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution cryo-EM structure with biochemical validation of key structural findings in single rigorous study\",\n      \"pmids\": [\"42034640\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SAP30BP expression is elevated in hearts of diabetic cardiomyopathy (DCM) mice and high-glucose-treated cardiomyocytes. Mechanistically, SAP30BP inhibits transcription of MFN2 through HDAC1-mediated histone deacetylation, causing mitochondrial dynamic disruption that hinders mitochondrial translocation of ACSL4 and promotes mitochondria-associated ferroptosis. Knockdown of SAP30BP ameliorated ferroptosis, oxidative stress, and cardiac dysfunction in DCM.\",\n      \"method\": \"siRNA knockdown, RNA-seq, ChIP (HDAC1-mediated deacetylation), mitochondrial fractionation, cellular ferroptosis assays\",\n      \"journal\": \"European journal of pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown with RNA-seq and ChIP in single lab; multiple orthogonal methods\",\n      \"pmids\": [\"40774404\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"BioID proximity mapping identified SAP30BP as an in vivo interactor of SAP18 within the SIN3 transcriptional repressor complex context, and complementary immunoprecipitation validated this interaction.\",\n      \"method\": \"BioID proximity labeling, mass spectrometry, co-immunoprecipitation\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single proximity-labeling study with complementary Co-IP; single lab, SAP30BP is a minor finding within a broader SAP18 interactome paper\",\n      \"pmids\": [\"39522233\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SAP30BP is a nuclear protein that acts as a critical activator of CDK11 by stabilizing cyclin L1/L2 and promoting their assembly with CDK11, thereby enabling CDK11-dependent phosphorylation of SF3B1 and global pre-mRNA splicing (including short mini-introns); it also functions as a transcriptional co-repressor through direct interaction with SAP30 within the mSin3A–HDAC complex, promoting histone H3 deacetylation (H3K9 and H3K14) and gene silencing, with the cryo-EM structure of the CDK11–cyclin L2–SAP30BP ternary complex defining the molecular basis of SAP30BP's role in CDK11 activation and spliceosome B-to-Bact transition.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SAP30BP is a nuclear protein that bridges two distinct nuclear regulatory processes: pre-mRNA splicing through CDK11 activation and transcriptional silencing through the mSin3A–HDAC corepressor complex [#0, #2]. As a critical CDK11 activator, SAP30BP forms a tight complex with CDK11 and cyclins L1/L2, ensuring cyclin stability and promoting their assembly with the kinase; acute degradation of SAP30BP phenocopies CDK11 loss and causes widespread pre-mRNA splicing defects, including dysregulation of short (<100 nt) mini-introns [#2]. The cryo-EM structure of the CDK11–cyclin L2–SAP30BP ternary complex shows that SAP30BP makes extensive contacts that stabilize cyclin L2 and critical contacts with the CDK11 C-terminal kinase lobe that drive complex assembly, enabling SF3B1 phosphorylation and the spliceosome B-to-Bact transition [#4]. Formation of this active complex depends on CDK11 T-loop phosphorylation at Thr595, which is required for SAP30BP association and is controlled upstream by CDK7 [#3]. Independently, SAP30BP acts as a transcriptional co-repressor by directly binding SAP30 within the mSin3A–HDAC complex, promoting histone H3 deacetylation at K9 and K14 in an HDAC-dependent manner to enforce gene silencing [#0, #1].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Established SAP30BP as a nuclear protein physically linked to transcriptional repression machinery, answering where the uncharacterized HSV-1-induced gene product localizes and what it binds.\",\n      \"evidence\": \"Yeast two-hybrid, pull-down, reciprocal Co-IP, and fluorescent fusion localization in HeLa cells\",\n      \"pmids\": [\"15496587\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define functional consequence of the SAP30 interaction on chromatin\", \"No demonstration of HDAC recruitment or histone modification\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Showed the SAP30BP–SAP30 interaction is functionally repressive, converting a binding observation into a chromatin-level silencing mechanism.\",\n      \"evidence\": \"Dual-luciferase reporter, qPCR, and ChIP for H3K9/K14 deacetylation\",\n      \"pmids\": [\"21221920\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Repression demonstrated on a viral promoter; cellular gene targets unclear\", \"Did not establish whether SAP30BP is an obligate subunit of the complex\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified an entirely separate molecular role: SAP30BP as a critical CDK11 activator required for global pre-mRNA splicing, answering how cyclin L1/L2–CDK11 assembly is achieved.\",\n      \"evidence\": \"Degron-based acute degradation phenocopy, in vitro kinase assay, AP-MS, corroborated by independent same-year AP-MS\",\n      \"pmids\": [\"38059508\", \"38065061\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of cyclin stabilization not yet resolved\", \"Substrate scope of resulting CDK11 activity beyond splicing not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed the CDK11–SAP30BP complex in a regulatory cascade by showing CDK11 Thr595 phosphorylation gates SAP30BP association and that CDK7 acts upstream.\",\n      \"evidence\": \"Mutational analysis, SILAC phosphoproteomics, CDK7 inhibition\",\n      \"pmids\": [\"41428738\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct kinase responsible for Thr595 phosphorylation not formally proven\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Connected SAP30BP's repressor activity to disease physiology, showing it silences MFN2 via HDAC1 to drive mitochondrial ferroptosis in diabetic cardiomyopathy.\",\n      \"evidence\": \"siRNA knockdown, RNA-seq, ChIP, mitochondrial fractionation, ferroptosis assays in DCM mouse and high-glucose cardiomyocyte models\",\n      \"pmids\": [\"40774404\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal link in human disease not established\", \"Whether splicing function contributes to the phenotype not addressed\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Provided the atomic-resolution mechanism of CDK11 activation, defining how SAP30BP stabilizes cyclin L2 and promotes the assembly that drives spliceosome activation.\",\n      \"evidence\": \"2.3 Å cryo-EM of CDK11–cyclin L2–SAP30BP with biochemical stability assays and inhibitor binding analysis\",\n      \"pmids\": [\"42034640\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Function of the identified CDK11 pseudo-substrate sequence in vivo not fully resolved\", \"Structure does not address the transcriptional co-repressor role\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SAP30BP partitions between its splicing-activator and chromatin-repressor functions, and whether these are coordinated within a single regulatory program, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No study connects the CDK11/splicing and mSin3A/HDAC roles\", \"Determinants of complex choice (e.g. the neural alternative exon) not mapped to either function\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [1, 5]}\n    ],\n    \"complexes\": [\"CDK11–cyclin L2–SAP30BP complex\", \"mSin3A–HDAC corepressor complex\"],\n    \"partners\": [\"CDK11\", \"CCNL1\", \"CCNL2\", \"SAP30\", \"SAP18\", \"SF3B1\", \"HDAC1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}