{"gene":"SAP130","run_date":"2026-06-10T07:46:29","timeline":{"discoveries":[{"year":2024,"finding":"SAP130 (Sin3A-associated protein 130) is sumoylated by SUMO1 at lysine residues K794, K878, and K932, both in vitro and in vivo. Mutation of these three SUMO-accepting lysines abolished SAP130 interaction with FAF1 but did not affect SAP130 association with Sin3A or its nuclear localization.","method":"In vitro sumoylation assay, in vivo sumoylation (transfection), site-directed mutagenesis (K→A mutations), co-immunoprecipitation","journal":"BMC molecular and cell biology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — in vitro and in vivo sumoylation with mutagenesis, single lab, no independent replication","pmids":["38172660"],"is_preprint":false},{"year":2024,"finding":"FAF1 interacts with sumoylated SAP130 (via FAF1's SIM motifs) and promotes SAP130 polyubiquitination and degradation in a sumoylation-dependent manner. FAF1 binding mitigates SAP130's transcriptional repressor activity and its cell proliferation-promoting function.","method":"Yeast two-hybrid screening (identification), co-immunoprecipitation, ubiquitination assay, transient transfection overexpression/knockdown, transcriptional reporter assay","journal":"BMC molecular and cell biology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Weak — reciprocal co-IP and functional assays in single lab, no independent replication","pmids":["38172660"],"is_preprint":false},{"year":2024,"finding":"SUMO1-modified SAP130 is less stable than unmodified SAP130; sumoylation-deficient SAP130 mutants showed enhanced transcriptional repression and attenuated promotion of cell growth, indicating that sumoylation negatively regulates SAP130's repressor function and stability.","method":"Site-directed mutagenesis (SUMO-site mutants), pulse-chase/protein stability assay, transcriptional reporter assay, cell proliferation assay","journal":"BMC molecular and cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — multiple functional readouts in single lab, no independent replication","pmids":["38172660"],"is_preprint":false},{"year":2023,"finding":"Zebrafish sap130a, ortholog of Sin3A-associated protein 130, is required for Second Heart Field (SHF) cell accretion to the growing ventricle and subsequent cardiomyocyte maturation; loss of sap130a results in smaller ventricle size and reduced cardiac output.","method":"Loss-of-function genetic mutant (sap130a knockout), confocal light sheet imaging of cardiac output, lineage tracing of SHF cells, transcriptome profiling","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with multiple orthogonal phenotypic readouts (imaging, lineage tracing, transcriptomics) in single lab; peer-reviewed and preprint versions concordant","pmids":["37711853","37034673"],"is_preprint":false},{"year":2023,"finding":"Genetic interaction between hdac1 and sap130a in zebrafish: double mutants show increased incidence of small ventricles, placing SAP130 functionally within the SIN3A/HDAC1 chromatin-modifying complex during cardiogenesis.","method":"Genetic epistasis (double mutant analysis), cardiac phenotype scoring","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic epistasis in zebrafish, single lab, functional readout tied to hdac1 interaction","pmids":["37711853"],"is_preprint":false}],"current_model":"SAP130 (Sin3A-associated protein 130) is a component of the SIN3A/HDAC chromatin-modifying complex that localizes to the nucleus; it is sumoylated at K794, K878, and K932, which regulates its interaction with FAF1 (leading to FAF1-dependent polyubiquitination and degradation of SAP130) and modulates its transcriptional repressor activity and cell proliferation function; in zebrafish, sap130a is required for Second Heart Field cell accretion and cardiomyocyte maturation during ventricular development through a mechanism that involves genetic interaction with hdac1."},"narrative":{"mechanistic_narrative":"SAP130 (Sin3A-associated protein 130) is a nuclear component of the SIN3A/HDAC chromatin-modifying complex that acts as a transcriptional repressor and promoter of cell proliferation [PMID:38172660]. Its activity and abundance are controlled by SUMO1 modification at K794, K878, and K932; sumoylation destabilizes the protein and dampens its repressor function [PMID:38172660]. Sumoylated SAP130 is recognized via the SIM motifs of FAF1, which drives its polyubiquitination and degradation and thereby mitigates SAP130-dependent transcriptional repression and proliferation; SUMO-site mutations abolish the FAF1 interaction without affecting Sin3A association or nuclear localization [PMID:38172660]. In zebrafish, sap130a is required for Second Heart Field cell accretion and cardiomyocyte maturation during ventricular development, and it interacts genetically with hdac1, anchoring its developmental role within the SIN3A/HDAC1 complex [PMID:37711853, PMID:37034673].","teleology":[{"year":2023,"claim":"Whether SAP130 has an essential developmental function in vivo was unresolved; loss-of-function in zebrafish established a specific requirement in cardiac morphogenesis.","evidence":"sap130a knockout with light-sheet imaging of cardiac output, SHF lineage tracing, and transcriptome profiling","pmids":["37711853","37034673"],"confidence":"Medium","gaps":["Does not define the direct transcriptional targets controlled by sap130a in the heart","Mammalian developmental requirement not addressed"]},{"year":2023,"claim":"It was unclear whether SAP130's developmental role operates through the SIN3A/HDAC complex; genetic epistasis placed it functionally with hdac1.","evidence":"hdac1/sap130a double-mutant analysis with cardiac phenotype scoring in zebrafish","pmids":["37711853"],"confidence":"Medium","gaps":["Genetic interaction does not establish a direct biochemical contact in the cardiac context","Other complex subunits not tested"]},{"year":2024,"claim":"How SAP130 stability and repressor activity are regulated was unknown; SUMO1 modification at three lysines was identified as a negative regulatory mark.","evidence":"In vitro and in vivo sumoylation assays with K→A mutagenesis, protein-stability/pulse-chase, and reporter assays","pmids":["38172660"],"confidence":"Medium","gaps":["Single lab, no independent replication","SUMO E3 ligase responsible not identified"]},{"year":2024,"claim":"The functional consequence of SAP130 sumoylation was undefined; FAF1 was shown to read the SUMO mark and target SAP130 for ubiquitin-dependent degradation.","evidence":"Yeast two-hybrid, reciprocal co-IP, ubiquitination assay, and reporter assays with SUMO-site and SIM-dependent readouts","pmids":["38172660"],"confidence":"Medium","gaps":["Single lab, no independent replication","E3 ubiquitin ligase mediating degradation not identified","Physiological context where FAF1 regulates SAP130 not established"]},{"year":null,"claim":"How SUMO-dependent FAF1 turnover of SAP130 connects to its developmental role in the SIN3A/HDAC1 complex remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No link drawn between the sumoylation/FAF1 axis and cardiac SHF function","Direct gene targets of the SAP130-containing complex not mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,2]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[1,4]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[3]}],"complexes":["SIN3A/HDAC complex"],"partners":["SIN3A","FAF1","HDAC1","SUMO1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15393","full_name":"Splicing factor 3B subunit 3","aliases":["Pre-mRNA-splicing factor SF3b 130 kDa subunit","SF3b130","STAF130","Spliceosome-associated protein 130","SAP 130"],"length_aa":1217,"mass_kda":135.6,"function":"Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:10490618, PubMed:10882114, 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, SF3B3 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). May also be involved in the assembly of the 'E' complex (PubMed:10882114). 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/Q15393/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SAP130","classification":"Not Classified","n_dependent_lines":373,"n_total_lines":1208,"dependency_fraction":0.3087748344370861},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HDAC1","stoichiometry":0.2},{"gene":"HDAC2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SAP130","total_profiled":1310},"omim":[{"mim_id":"609697","title":"SIN3A-ASSOCIATED PROTEIN, 130-KD; SAP130","url":"https://www.omim.org/entry/609697"},{"mim_id":"609696","title":"AT-RICH INTERACTION DOMAIN-CONTAINING PROTEIN 4B; ARID4B","url":"https://www.omim.org/entry/609696"},{"mim_id":"608250","title":"SDS3 HOMOLOG, SIN3A COREPRESSOR COMPLEX COMPONENT; SUDS3","url":"https://www.omim.org/entry/608250"},{"mim_id":"607776","title":"SIN3 TRANSCRIPTION REGULATOR FAMILY MEMBER A; SIN3A","url":"https://www.omim.org/entry/607776"},{"mim_id":"606576","title":"TAF3 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 140-KD; TAF3","url":"https://www.omim.org/entry/606576"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear speckles","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"testis","ntpm":44.2}],"url":"https://www.proteinatlas.org/search/SAP130"},"hgnc":{"alias_symbol":["FLJ12761"],"prev_symbol":[]},"alphafold":{"accession":"Q15393","domains":[{"cath_id":"2.130.10.10","chopping":"63-87_102-381","consensus_level":"medium","plddt":93.9313,"start":63,"end":381},{"cath_id":"1.10.150.910","chopping":"1132-1215","consensus_level":"high","plddt":93.1448,"start":1132,"end":1215}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15393","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15393-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15393-F1-predicted_aligned_error_v6.png","plddt_mean":92.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SAP130","jax_strain_url":"https://www.jax.org/strain/search?query=SAP130"},"sequence":{"accession":"Q15393","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15393.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15393/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15393"}},"corpus_meta":[{"pmid":"34556635","id":"PMC_34556635","title":"SAP130 released by damaged tubule drives necroinflammation via miRNA-219c/Mincle signaling in acute kidney injury.","date":"2021","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/34556635","citation_count":35,"is_preprint":false},{"pmid":"18173839","id":"PMC_18173839","title":"Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome.","date":"2008","source":"BMC biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18173839","citation_count":34,"is_preprint":false},{"pmid":"38320352","id":"PMC_38320352","title":"SAP130 released by ferroptosis tubular epithelial cells promotes macrophage polarization via Mincle signaling in sepsis acute kidney injury.","date":"2024","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/38320352","citation_count":32,"is_preprint":false},{"pmid":"19368799","id":"PMC_19368799","title":"A mutation in teg-4, which encodes a protein homologous to the SAP130 pre-mRNA splicing factor, disrupts the balance between proliferation and differentiation in the C. elegans germ line.","date":"2009","source":"Mechanisms of development","url":"https://pubmed.ncbi.nlm.nih.gov/19368799","citation_count":27,"is_preprint":false},{"pmid":"11350031","id":"PMC_11350031","title":"Mutation in the prp12+ gene encoding a homolog of SAP130/SF3b130 causes differential inhibition of pre-mRNA splicing and arrest of cell-cycle progression in Schizosaccharomyces pombe.","date":"2001","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/11350031","citation_count":24,"is_preprint":false},{"pmid":"39163934","id":"PMC_39163934","title":"SAP130 mediates crosstalk between hepatocyte ferroptosis and M1 macrophage polarization in PFOS-induced hepatotoxicity.","date":"2024","source":"The Science of the total environment","url":"https://pubmed.ncbi.nlm.nih.gov/39163934","citation_count":17,"is_preprint":false},{"pmid":"23951410","id":"PMC_23951410","title":"Regulation of Cullin-RING ubiquitin ligase 1 by Spliceosome-associated protein 130 (SAP130).","date":"2013","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/23951410","citation_count":9,"is_preprint":false},{"pmid":"33800128","id":"PMC_33800128","title":"Ambiguity about Splicing Factor 3b Subunit 3 (SF3B3) and Sin3A Associated Protein 130 (SAP130).","date":"2021","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/33800128","citation_count":5,"is_preprint":false},{"pmid":"37711853","id":"PMC_37711853","title":"Sin3a associated protein 130 kDa, sap130, plays an evolutionary conserved role in zebrafish heart development.","date":"2023","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/37711853","citation_count":2,"is_preprint":false},{"pmid":"40773918","id":"PMC_40773918","title":"Sesamin attenuates liver inflammation caused by PFOS via regulating SAP130-mediated hepatocyte-macrophage crosstalk.","date":"2025","source":"Ecotoxicology and environmental safety","url":"https://pubmed.ncbi.nlm.nih.gov/40773918","citation_count":1,"is_preprint":false},{"pmid":"38172660","id":"PMC_38172660","title":"Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function.","date":"2024","source":"BMC molecular and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/38172660","citation_count":1,"is_preprint":false},{"pmid":"40792209","id":"PMC_40792209","title":"The SAP130/Mincle axis was involved in sevoflurane-induced neuronal death and microglial activation in juvenile mice.","date":"2025","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/40792209","citation_count":0,"is_preprint":false},{"pmid":"37034673","id":"PMC_37034673","title":"Sin3a Associated Protein 130kDa, sap130, plays an evolutionary conserved role in zebrafish heart development.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/37034673","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9486,"output_tokens":1835,"usd":0.027991,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7922,"output_tokens":1661,"usd":0.040567,"stage2_stop_reason":"end_turn"},"total_usd":0.068558,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully classify papers first, noting the important ambiguity identified in paper [8]: there are TWO different proteins called \"SAP130\":\n1. **Sin3A-associated protein 130** (SAP130, the query gene) — part of the SIN3A/HDAC complex\n2. **SF3B3/spliceosome-associated protein 130** — part of the SF3b RNA splicing complex, also called \"SAP130\" by some labs erroneously\n\nPaper [8] explicitly clarifies that papers [1], [3] (and similar) used reagents against SF3B3 while calling it SAP130. The Mincle ligand papers [1], [3], [6], [10], [12] refer to SF3B3 (spliceosome-associated protein 130), NOT the Sin3A-associated protein 130 (the query gene).\n\nThe query gene SAP130 = **Sin3A-associated protein 130** (part of HDAC/Sin3A complex).\n\nPapers to include:\n- [2] SAP130/SF3b-3 — WAIT: this paper calls SAP130 \"SF3b-3\" and treats it as a splicing/transcription complex component. Per paper [8], this is SF3B3, not the query SAP130. EXCLUDE.\n- [4] teg-4/SF3b-3 homolog — this is the splicing factor SF3B3 ortholog. EXCLUDE.\n- [5] prp12/SAP130/SF3b130 — splicing factor. EXCLUDE.\n- [7] SAP130/SF3b-3 regulating CRL — again refers to SF3B3. EXCLUDE.\n- [8] Clarification paper — relevant but meta.\n- [9] zebrafish sap130 / Sin3A-associated protein — this IS the query gene (Sin3A/HDAC complex). INCLUDE.\n- [11] Sumoylation of SAP130 — \"Sin3A-associated protein 130\" explicitly. INCLUDE.\n- [13] Preprint version of [9]. INCLUDE as same findings as [9].\n- [1], [3], [6], [10], [12] — these refer to SF3B3, not the query. EXCLUDE per paper [8].\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"SAP130 (Sin3A-associated protein 130) is sumoylated by SUMO1 at lysine residues K794, K878, and K932, both in vitro and in vivo. Mutation of these three SUMO-accepting lysines abolished SAP130 interaction with FAF1 but did not affect SAP130 association with Sin3A or its nuclear localization.\",\n      \"method\": \"In vitro sumoylation assay, in vivo sumoylation (transfection), site-directed mutagenesis (K→A mutations), co-immunoprecipitation\",\n      \"journal\": \"BMC molecular and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — in vitro and in vivo sumoylation with mutagenesis, single lab, no independent replication\",\n      \"pmids\": [\"38172660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"FAF1 interacts with sumoylated SAP130 (via FAF1's SIM motifs) and promotes SAP130 polyubiquitination and degradation in a sumoylation-dependent manner. FAF1 binding mitigates SAP130's transcriptional repressor activity and its cell proliferation-promoting function.\",\n      \"method\": \"Yeast two-hybrid screening (identification), co-immunoprecipitation, ubiquitination assay, transient transfection overexpression/knockdown, transcriptional reporter assay\",\n      \"journal\": \"BMC molecular and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — reciprocal co-IP and functional assays in single lab, no independent replication\",\n      \"pmids\": [\"38172660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SUMO1-modified SAP130 is less stable than unmodified SAP130; sumoylation-deficient SAP130 mutants showed enhanced transcriptional repression and attenuated promotion of cell growth, indicating that sumoylation negatively regulates SAP130's repressor function and stability.\",\n      \"method\": \"Site-directed mutagenesis (SUMO-site mutants), pulse-chase/protein stability assay, transcriptional reporter assay, cell proliferation assay\",\n      \"journal\": \"BMC molecular and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — multiple functional readouts in single lab, no independent replication\",\n      \"pmids\": [\"38172660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Zebrafish sap130a, ortholog of Sin3A-associated protein 130, is required for Second Heart Field (SHF) cell accretion to the growing ventricle and subsequent cardiomyocyte maturation; loss of sap130a results in smaller ventricle size and reduced cardiac output.\",\n      \"method\": \"Loss-of-function genetic mutant (sap130a knockout), confocal light sheet imaging of cardiac output, lineage tracing of SHF cells, transcriptome profiling\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with multiple orthogonal phenotypic readouts (imaging, lineage tracing, transcriptomics) in single lab; peer-reviewed and preprint versions concordant\",\n      \"pmids\": [\"37711853\", \"37034673\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Genetic interaction between hdac1 and sap130a in zebrafish: double mutants show increased incidence of small ventricles, placing SAP130 functionally within the SIN3A/HDAC1 chromatin-modifying complex during cardiogenesis.\",\n      \"method\": \"Genetic epistasis (double mutant analysis), cardiac phenotype scoring\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic epistasis in zebrafish, single lab, functional readout tied to hdac1 interaction\",\n      \"pmids\": [\"37711853\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SAP130 (Sin3A-associated protein 130) is a component of the SIN3A/HDAC chromatin-modifying complex that localizes to the nucleus; it is sumoylated at K794, K878, and K932, which regulates its interaction with FAF1 (leading to FAF1-dependent polyubiquitination and degradation of SAP130) and modulates its transcriptional repressor activity and cell proliferation function; in zebrafish, sap130a is required for Second Heart Field cell accretion and cardiomyocyte maturation during ventricular development through a mechanism that involves genetic interaction with hdac1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SAP130 (Sin3A-associated protein 130) is a nuclear component of the SIN3A/HDAC chromatin-modifying complex that acts as a transcriptional repressor and promoter of cell proliferation [#1, #2]. Its activity and abundance are controlled by SUMO1 modification at K794, K878, and K932; sumoylation destabilizes the protein and dampens its repressor function [#0, #2]. Sumoylated SAP130 is recognized via the SIM motifs of FAF1, which drives its polyubiquitination and degradation and thereby mitigates SAP130-dependent transcriptional repression and proliferation; SUMO-site mutations abolish the FAF1 interaction without affecting Sin3A association or nuclear localization [#0, #1]. In zebrafish, sap130a is required for Second Heart Field cell accretion and cardiomyocyte maturation during ventricular development, and it interacts genetically with hdac1, anchoring its developmental role within the SIN3A/HDAC1 complex [#3, #4].\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether SAP130 has an essential developmental function in vivo was unresolved; loss-of-function in zebrafish established a specific requirement in cardiac morphogenesis.\",\n      \"evidence\": \"sap130a knockout with light-sheet imaging of cardiac output, SHF lineage tracing, and transcriptome profiling\",\n      \"pmids\": [\"37711853\", \"37034673\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not define the direct transcriptional targets controlled by sap130a in the heart\", \"Mammalian developmental requirement not addressed\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unclear whether SAP130's developmental role operates through the SIN3A/HDAC complex; genetic epistasis placed it functionally with hdac1.\",\n      \"evidence\": \"hdac1/sap130a double-mutant analysis with cardiac phenotype scoring in zebrafish\",\n      \"pmids\": [\"37711853\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Genetic interaction does not establish a direct biochemical contact in the cardiac context\", \"Other complex subunits not tested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"How SAP130 stability and repressor activity are regulated was unknown; SUMO1 modification at three lysines was identified as a negative regulatory mark.\",\n      \"evidence\": \"In vitro and in vivo sumoylation assays with K\\u2192A mutagenesis, protein-stability/pulse-chase, and reporter assays\",\n      \"pmids\": [\"38172660\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, no independent replication\", \"SUMO E3 ligase responsible not identified\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The functional consequence of SAP130 sumoylation was undefined; FAF1 was shown to read the SUMO mark and target SAP130 for ubiquitin-dependent degradation.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal co-IP, ubiquitination assay, and reporter assays with SUMO-site and SIM-dependent readouts\",\n      \"pmids\": [\"38172660\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, no independent replication\", \"E3 ubiquitin ligase mediating degradation not identified\", \"Physiological context where FAF1 regulates SAP130 not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SUMO-dependent FAF1 turnover of SAP130 connects to its developmental role in the SIN3A/HDAC1 complex remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No link drawn between the sumoylation/FAF1 axis and cardiac SHF function\", \"Direct gene targets of the SAP130-containing complex not mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\"SIN3A/HDAC complex\"],\n    \"partners\": [\"SIN3A\", \"FAF1\", \"HDAC1\", \"SUMO1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}