{"gene":"PCTP","run_date":"2026-04-29T11:37:58","timeline":{"discoveries":[{"year":2007,"finding":"PC-TP (StarD2) physically interacts with Them2 (thioesterase superfamily member 2) and the homeodomain transcription factor Pax3, identified by yeast two-hybrid screening and verified by pulldown assays and colocalization. The acyl-CoA thioesterase activity of purified recombinant Them2 is markedly enhanced by recombinant PC-TP, and PC-TP coactivates transcriptional activity of Pax3 in tissue culture.","method":"Yeast two-hybrid screening, pulldown assays, colocalization, in vitro enzymatic assay with recombinant proteins, transcriptional reporter assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods including in vitro reconstitution of enzymatic activity enhancement, pulldown verification, and functional reporter assay","pmids":["17704541"],"is_preprint":false},{"year":2008,"finding":"PC-TP catalyzes transfer of phosphatidylcholines between membranes in vitro; high-throughput screening identified six small-molecule inhibitors of this phosphatidylcholine transfer activity with IC50 values of 4.1–95.0 µM, establishing the in vitro enzymatic mechanism is druggable.","method":"Fluorescence quench in vitro transfer assay, high-throughput screening of 114,752 compounds","journal":"Analytical biochemistry","confidence":"High","confidence_rationale":"Tier 1 — direct in vitro enzymatic assay with quantified inhibition constants","pmids":["18762160"],"is_preprint":false},{"year":2008,"finding":"PC-TP deficiency (Pctp−/−) increases hepatic insulin sensitivity, reduces hepatic glucose production, gluconeogenesis, glycogenolysis, and promotes preferential fatty acid utilization, demonstrating a role for PC-TP in regulating hepatic energy substrate utilization and insulin signaling.","method":"Hyperinsulinemic-euglycemic clamp studies in Pctp−/− mice, indirect calorimetry, isotope tracer studies","journal":"FASEB journal","confidence":"High","confidence_rationale":"Tier 2 — clean KO with defined metabolic phenotype using multiple quantitative metabolic assays","pmids":["18347010"],"is_preprint":false},{"year":2009,"finding":"PC-TP limits mitochondrial fatty acid oxidation and regulates adaptive thermogenesis in brown adipose tissue (BAT); Pctp−/− mice have enlarged mitochondria in BAT, higher core body temperatures, and brown adipocytes lacking Pctp show higher oxygen consumption in response to norepinephrine.","method":"Pctp−/− mouse model, histology, oxygen consumption measurements in cultured brown adipocytes, adenovirus-mediated Pctp overexpression rescue","journal":"Journal of lipid research","confidence":"High","confidence_rationale":"Tier 2 — KO with defined cellular phenotype and rescue experiment","pmids":["19502644"],"is_preprint":false},{"year":2010,"finding":"PC-TP expression in cell culture controls the transcriptional activities of PPARα and HNF4α, and is itself regulated by PPARα; Pctp−/− mice fed fenofibrate exhibit altered lipid and glucose metabolism with differential expression of metabolic genes and their transcriptional regulators.","method":"Transcriptional reporter assays in cell culture, microarray profiling of Pctp−/− mouse livers, fenofibrate (PPARα ligand) treatment","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2–3 — reporter assay plus KO metabolic phenotype, single lab","pmids":["20045742"],"is_preprint":false},{"year":2013,"finding":"PC-TP selectively mediates PAR4- but not PAR1-mediated platelet activation; PC-TP inhibition or depletion blocks PAR4-induced platelet aggregation and calcium mobilization in human platelets and megakaryocytic cell lines. miR-376c inversely regulates PC-TP expression in megakaryocytes and is associated with PAR4 reactivity.","method":"PC-TP inhibitor treatment and siRNA depletion in human platelets and megakaryocytic cell lines, calcium mobilization assays, platelet aggregation assays, miR-376c functional studies","journal":"Nature medicine","confidence":"High","confidence_rationale":"Tier 2 — reciprocal pharmacological and genetic loss-of-function with specific functional readouts, large human cohort plus cell line validation","pmids":["24216752"],"is_preprint":false},{"year":2014,"finding":"Them2 and PC-TP interact to promote fatty acid oxidation and control glucose utilization in hepatocytes; under fasting conditions, Pctp−/− and Them2−/− hepatocytes each show decreased fatty acid oxidation and gluconeogenesis, and chemical inhibition of PC-TP fails to reproduce these changes in Them2−/− hepatocytes, demonstrating that PC-TP regulation of fatty acid oxidation is Them2-dependent.","method":"Primary hepatocyte cultures from Pctp−/− and Them2−/− mice, chemical inhibition of PC-TP, fatty acid oxidation assays, gluconeogenesis assays, glucose oxidation assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — genetic and pharmacological epistasis in primary cells with multiple biochemical readouts","pmids":["24732803"],"is_preprint":false},{"year":2017,"finding":"RUNX1 directly binds consensus sites in the PCTP promoter (~1 kb region) and transcriptionally regulates PCTP expression; RUNX1 overexpression increases and RUNX1 knockdown reduces PCTP expression in human erythroleukemia cells.","method":"DNA-protein binding studies, luciferase promoter reporter assays, RUNX1 overexpression and knockdown in HEL cells, patient platelet profiling","journal":"Circulation","confidence":"High","confidence_rationale":"Tier 2 — direct DNA binding, reporter assay, and bidirectional genetic manipulation with consistent results","pmids":["28676520"],"is_preprint":false},{"year":2017,"finding":"PC-TP promotes microvesicular steatosis and hepatocellular injury in MCD diet-induced steatohepatitis; Pctp−/− mice are protected from MCD diet-induced liver injury (reduced ALT/AST, decreased c-Jun activation), with a specific reduction in microvesicular lipid droplets, suggesting PC-TP mediates intermembrane PC transfer to stabilize pathogenic small lipid droplets independently of Them2.","method":"Pctp−/− mouse MCD diet model, histopathology, plasma enzyme assays, c-Jun activation, lipid droplet size quantification, mRNA/protein expression","journal":"American journal of physiology. Gastrointestinal and liver physiology","confidence":"Medium","confidence_rationale":"Tier 2 — KO with defined pathological phenotype and multiple biochemical readouts, single lab","pmids":["28385694"],"is_preprint":false},{"year":2021,"finding":"PC-TP contributes to human platelet activation by enhancing dense granule secretion (but not alpha granule secretion) downstream of multiple agonists (thrombin, PAR1AP, PAR4AP, convulxin, FcγRIIA); PC-TP inhibition reduces cytoplasmic Ca2+ increase and PKC activity downstream of thrombin.","method":"PC-TP inhibitor (compound A1) treatment of human platelets, dense/alpha granule secretion assays, calcium mobilization assays, PKC activity assays, aggregation assays with multiple agonists","journal":"Thrombosis research","confidence":"Medium","confidence_rationale":"Tier 2–3 — pharmacological inhibition with specific granule secretion and signaling readouts, single lab","pmids":["33770537"],"is_preprint":false},{"year":2023,"finding":"PC-TP directly interacts with PPARδ (but not PPARα or PPARγ) in a ligand-dependent manner to repress PPARδ-mediated transactivation; mutations in PC-TP residues implicated in PC binding and transfer reduce the PC-TP–PPARδ interaction and relieve repression. Methionine/choline reduction decreases, while serum starvation enhances, this interaction in hepatocytes.","method":"In-cell protein complementation screen, co-IP in Huh7 hepatocytes, PC-TP binding-site mutagenesis, PPARδ transactivation reporter assay, hepatocyte-specific Pctp knockdown mouse model","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1–2 — direct protein interaction confirmed by complementation and co-IP, functional repression validated by mutagenesis and reporter assay","pmids":["37173315"],"is_preprint":false},{"year":2024,"finding":"Molecular dynamics simulations of human STARD2/PC-TP reveal a ligand-dependent conformational change and a spontaneous PC lipid uptake mechanism involving metastable states stabilized by choline–tyrosine and choline–tryptophan cation-π interactions; free energy perturbation shows PC–tyrosine cation-π interactions contribute 1.8–2.5 kcal/mol to binding affinity of a metastable state.","method":"Microsecond-scale molecular dynamics simulations of apo and holo STARD2 with lipid bilayers, free energy perturbation calculations","journal":"The journal of physical chemistry letters","confidence":"Low","confidence_rationale":"Tier 4 — computational modeling only, no experimental validation of proposed mechanism","pmids":["39143857"],"is_preprint":false}],"current_model":"PC-TP (StarD2/PCTP) is a soluble START-domain phosphatidylcholine-binding protein that catalyzes intermembrane PC transfer in vitro and functions in vivo as a phosphatidylcholine sensor: it stimulates the long-chain acyl-CoA thioesterase activity of its binding partner Them2 to limit mitochondrial fatty acid oxidation and suppress hepatic insulin sensitivity, directly represses PPARδ transcriptional activity in a PC-ligand-dependent manner, and in platelets selectively mediates PAR4-dependent activation and dense granule secretion partly through Ca2+/PKC signaling, with its own expression controlled at the transcriptional level by RUNX1 and post-transcriptionally by miR-376c."},"narrative":{"teleology":[{"year":2007,"claim":"Identifying PC-TP's direct binding partners Them2 and Pax3 established that PC-TP is not merely a lipid shuttle but a protein–protein interaction hub that enhances Them2 thioesterase activity, linking lipid transfer to acyl-CoA metabolism.","evidence":"Yeast two-hybrid, pulldown, colocalization, and in vitro reconstitution of Them2 activity enhancement by recombinant PC-TP","pmids":["17704541"],"confidence":"High","gaps":["Structural basis of PC-TP–Them2 interaction not resolved","Whether PC binding by PC-TP is required for Them2 activation was not tested","Pax3 coactivation mechanism was not further dissected"]},{"year":2008,"claim":"Demonstrating that Pctp−/− mice have enhanced hepatic insulin sensitivity and altered substrate utilization revealed that PC-TP normally functions to limit insulin action and promote glucose output, positioning it as a metabolic regulator in vivo.","evidence":"Hyperinsulinemic-euglycemic clamp, indirect calorimetry, and isotope tracer studies in Pctp−/− mice","pmids":["18347010"],"confidence":"High","gaps":["Whether the metabolic phenotype is cell-autonomous to hepatocytes was not established","Signaling intermediates between PC-TP and insulin pathway not identified"]},{"year":2008,"claim":"An in vitro transfer assay confirmed PC-TP catalyzes intermembrane phosphatidylcholine transfer and identified small-molecule inhibitors, validating the enzymatic activity as a druggable target.","evidence":"Fluorescence quench transfer assay and high-throughput screen of ~115,000 compounds","pmids":["18762160"],"confidence":"High","gaps":["In vivo efficacy of inhibitors not demonstrated","Selectivity of inhibitors for PC-TP over other START-domain proteins not fully characterized"]},{"year":2009,"claim":"Finding that Pctp−/− mice have enlarged BAT mitochondria and increased thermogenesis extended PC-TP's metabolic role beyond liver, showing it restrains mitochondrial fatty acid oxidation in brown adipose tissue.","evidence":"Pctp−/− mouse BAT histology, oxygen consumption in cultured brown adipocytes, adenoviral Pctp rescue","pmids":["19502644"],"confidence":"High","gaps":["Whether BAT phenotype is Them2-dependent was not tested","Mechanism linking PC-TP to mitochondrial morphology unknown"]},{"year":2013,"claim":"Showing that PC-TP selectively mediates PAR4- but not PAR1-dependent platelet activation, with miR-376c as a post-transcriptional regulator, revealed a receptor-specific platelet signaling role entirely distinct from its hepatic metabolic functions.","evidence":"PC-TP inhibitor and siRNA depletion in human platelets and megakaryocytic cell lines, calcium mobilization and aggregation assays, miR-376c functional studies","pmids":["24216752"],"confidence":"High","gaps":["Molecular mechanism of PAR4 selectivity over PAR1 not elucidated","Whether PC-TP lipid binding is required for platelet signaling not tested"]},{"year":2014,"claim":"Genetic and pharmacological epistasis experiments demonstrated that PC-TP's regulation of hepatic fatty acid oxidation is fully Them2-dependent, resolving whether PC-TP acts through its lipid transfer activity alone or through its protein partner.","evidence":"Primary hepatocyte cultures from Pctp−/− and Them2−/− mice, chemical PC-TP inhibition in Them2−/− cells, fatty acid oxidation and gluconeogenesis assays","pmids":["24732803"],"confidence":"High","gaps":["Whether PC-TP delivers PC to Them2 as a substrate or acts as an allosteric activator not distinguished","Stoichiometry and kinetics of the PC-TP–Them2 complex not characterized"]},{"year":2017,"claim":"Identification of RUNX1 as a direct transcriptional activator of PCTP connected the megakaryocyte lineage transcription factor to PC-TP-dependent platelet function and provided a mechanism for lineage-specific PCTP expression.","evidence":"DNA-protein binding studies, luciferase promoter reporter, RUNX1 overexpression/knockdown in HEL cells","pmids":["28676520"],"confidence":"High","gaps":["Whether RUNX1-driven PCTP expression is sufficient to modulate PAR4-dependent platelet reactivity in vivo not shown","Other transcription factors regulating PCTP in hepatocytes not identified"]},{"year":2017,"claim":"Showing that Pctp−/− mice are protected from MCD diet-induced microvesicular steatosis and liver injury, independently of Them2, suggested a Them2-independent role for PC-TP's lipid transfer activity in stabilizing small lipid droplets under steatohepatitic stress.","evidence":"Pctp−/− MCD diet model, histopathology, lipid droplet quantification, c-Jun activation measurement","pmids":["28385694"],"confidence":"Medium","gaps":["Them2-independence inferred indirectly; double-KO not performed","Direct evidence that PC transfer to lipid droplet membranes is the causative mechanism is lacking"]},{"year":2021,"claim":"Extending platelet studies showed PC-TP promotes dense (but not alpha) granule secretion downstream of multiple agonists via Ca²⁺ and PKC, broadening its platelet role beyond PAR4 selectivity to a general dense granule secretion pathway.","evidence":"Pharmacological PC-TP inhibition in human platelets, dense/alpha granule secretion assays, calcium and PKC activity measurements with multiple agonists","pmids":["33770537"],"confidence":"Medium","gaps":["Genetic confirmation (siRNA or KO platelets) for the broader agonist panel not provided","How PC-TP interfaces with Ca²⁺/PKC signaling machinery is unknown"]},{"year":2023,"claim":"Demonstrating that PC-TP directly binds PPARδ (but not PPARα or PPARγ) in a PC-ligand-dependent manner and represses its transactivation established PC-TP as a nuclear receptor corepressor whose regulatory activity depends on its lipid cargo.","evidence":"In-cell protein complementation, co-IP in hepatocytes, PC-binding-site mutagenesis, PPARδ reporter assay, hepatocyte-specific Pctp knockdown mice","pmids":["37173315"],"confidence":"High","gaps":["Whether PC-TP enters the nucleus or sequesters PPARδ in the cytoplasm is unresolved","Identity of endogenous PC species that regulate the PC-TP–PPARδ interaction not determined"]},{"year":null,"claim":"Major open questions include the structural basis of PC-TP's interactions with Them2 and PPARδ, whether its lipid-transfer and protein-interaction functions can be genetically separated in vivo, and the mechanism by which PC-TP selectively controls dense granule but not alpha granule secretion in platelets.","evidence":"","pmids":[],"confidence":"High","gaps":["No co-crystal structure of PC-TP with Them2 or PPARδ","Separation-of-function mutations distinguishing lipid transfer from protein interaction not generated in vivo","Platelet-specific conditional KO studies have not been performed"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[1,10,11]},{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[1,8]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,6,10]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,4,10]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,5,10]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[2,3,6]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[5,9]},{"term_id":"R-HSA-109582","term_label":"Hemostasis","supporting_discovery_ids":[5,9]}],"complexes":[],"partners":["ACOT13","PPARD","RUNX1","PAX3"],"other_free_text":[]},"mechanistic_narrative":"PC-TP (PCTP/StarD2) is a soluble START-domain lipid transfer protein that functions as a phosphatidylcholine sensor coupling membrane lipid status to metabolic and signaling outcomes. It catalyzes intermembrane phosphatidylcholine transfer in vitro and stimulates the long-chain acyl-CoA thioesterase activity of its physical partner Them2 in a Them2-dependent epistatic manner to promote hepatic fatty acid oxidation, gluconeogenesis, and suppress insulin sensitivity [PMID:17704541, PMID:24732803, PMID:18347010]. PC-TP directly binds and represses PPARδ transcriptional activity in a phosphatidylcholine-ligand-dependent fashion, with PC-binding-site mutations abolishing both the interaction and repression [PMID:37173315]. In platelets, PC-TP selectively mediates PAR4-dependent activation and dense granule secretion through Ca²⁺/PKC signaling, with its expression controlled transcriptionally by RUNX1 and post-transcriptionally by miR-376c [PMID:24216752, PMID:28676520, PMID:33770537]."},"prefetch_data":{"uniprot":{"accession":"Q9UKL6","full_name":"Phosphatidylcholine transfer protein","aliases":["START domain-containing protein 2","StARD2","StAR-related lipid transfer protein 2"],"length_aa":214,"mass_kda":24.8,"function":"Catalyzes the transfer of phosphatidylcholine between membranes. Binds a single lipid molecule","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9UKL6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PCTP","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PCTP","total_profiled":1310},"omim":[{"mim_id":"617382","title":"START DOMAIN-CONTAINING PROTEIN 10; STARD10","url":"https://www.omim.org/entry/617382"},{"mim_id":"616712","title":"START DOMAIN-CONTAINING PROTEIN 7; STARD7","url":"https://www.omim.org/entry/616712"},{"mim_id":"607049","title":"START DOMAIN-CONTAINING PROTEIN 4; STARD4","url":"https://www.omim.org/entry/607049"},{"mim_id":"606055","title":"PHOSPHATIDYLCHOLINE TRANSFER PROTEIN; PCTP","url":"https://www.omim.org/entry/606055"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Nucleoli","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"liver","ntpm":91.6}],"url":"https://www.proteinatlas.org/search/PCTP"},"hgnc":{"alias_symbol":["STARD2"],"prev_symbol":[]},"alphafold":{"accession":"Q9UKL6","domains":[{"cath_id":"3.30.530.20","chopping":"11-212","consensus_level":"high","plddt":94.9269,"start":11,"end":212}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UKL6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UKL6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UKL6-F1-predicted_aligned_error_v6.png","plddt_mean":93.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PCTP","jax_strain_url":"https://www.jax.org/strain/search?query=PCTP"},"sequence":{"accession":"Q9UKL6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UKL6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UKL6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UKL6"}},"corpus_meta":[{"pmid":"24216752","id":"PMC_24216752","title":"Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c.","date":"2013","source":"Nature medicine","url":"https://pubmed.ncbi.nlm.nih.gov/24216752","citation_count":179,"is_preprint":false},{"pmid":"17499021","id":"PMC_17499021","title":"Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2.","date":"2007","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/17499021","citation_count":86,"is_preprint":false},{"pmid":"17704541","id":"PMC_17704541","title":"Interacting proteins dictate function of the minimal START domain phosphatidylcholine transfer protein/StarD2.","date":"2007","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17704541","citation_count":58,"is_preprint":false},{"pmid":"20338778","id":"PMC_20338778","title":"PC-TP/StARD2: Of membranes and metabolism.","date":"2010","source":"Trends in endocrinology and metabolism: TEM","url":"https://pubmed.ncbi.nlm.nih.gov/20338778","citation_count":42,"is_preprint":false},{"pmid":"18347010","id":"PMC_18347010","title":"Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2.","date":"2008","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/18347010","citation_count":33,"is_preprint":false},{"pmid":"24732803","id":"PMC_24732803","title":"Thioesterase superfamily member 2 (Them2) and phosphatidylcholine transfer protein (PC-TP) interact to promote fatty acid oxidation and control glucose utilization.","date":"2014","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/24732803","citation_count":30,"is_preprint":false},{"pmid":"19502644","id":"PMC_19502644","title":"Mice lacking Pctp /StarD2 exhibit increased adaptive thermogenesis and enlarged mitochondria in brown adipose tissue.","date":"2009","source":"Journal of lipid research","url":"https://pubmed.ncbi.nlm.nih.gov/19502644","citation_count":27,"is_preprint":false},{"pmid":"28676520","id":"PMC_28676520","title":"Transcription Factor RUNX1 Regulates Platelet PCTP (Phosphatidylcholine Transfer Protein): Implications for Cardiovascular Events: Differential Effects of RUNX1 Variants.","date":"2017","source":"Circulation","url":"https://pubmed.ncbi.nlm.nih.gov/28676520","citation_count":19,"is_preprint":false},{"pmid":"20045742","id":"PMC_20045742","title":"Regulatory role for phosphatidylcholine transfer protein/StarD2 in the metabolic response to peroxisome proliferator activated receptor alpha (PPARalpha).","date":"2010","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/20045742","citation_count":16,"is_preprint":false},{"pmid":"10415339","id":"PMC_10415339","title":"Cloning and gene structure of rat phosphatidylcholine transfer protein, Pctp.","date":"1999","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/10415339","citation_count":14,"is_preprint":false},{"pmid":"28385694","id":"PMC_28385694","title":"Phosphatidylcholine transfer protein/StarD2 promotes microvesicular steatosis and liver injury in murine experimental steatohepatitis.","date":"2017","source":"American journal of physiology. Gastrointestinal and liver physiology","url":"https://pubmed.ncbi.nlm.nih.gov/28385694","citation_count":10,"is_preprint":false},{"pmid":"37173315","id":"PMC_37173315","title":"Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37173315","citation_count":9,"is_preprint":false},{"pmid":"18762160","id":"PMC_18762160","title":"Small-molecule inhibitors of phosphatidylcholine transfer protein/StarD2 identified by high-throughput screening.","date":"2008","source":"Analytical biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18762160","citation_count":9,"is_preprint":false},{"pmid":"16940277","id":"PMC_16940277","title":"Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E-deficient mice.","date":"2006","source":"Journal of lipid research","url":"https://pubmed.ncbi.nlm.nih.gov/16940277","citation_count":8,"is_preprint":false},{"pmid":"29148266","id":"PMC_29148266","title":"NAD+ -Dependent Dehydrogenase PctP and Pyridoxal 5'-Phosphate Dependent Aminotransferase PctC Catalyze the First Postglycosylation Modification of the Sugar Intermediate in Pactamycin Biosynthesis.","date":"2017","source":"Chembiochem : a European journal of chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/29148266","citation_count":8,"is_preprint":false},{"pmid":"28183446","id":"PMC_28183446","title":"Genetic ablation of phosphatidylcholine transfer protein/StarD2 in ob/ob mice improves glucose tolerance without increasing energy expenditure.","date":"2016","source":"Metabolism: clinical and experimental","url":"https://pubmed.ncbi.nlm.nih.gov/28183446","citation_count":6,"is_preprint":false},{"pmid":"39143857","id":"PMC_39143857","title":"Model Mechanism for Lipid Uptake by the Human STARD2/PC-TP Phosphatidylcholine Transfer Protein.","date":"2024","source":"The journal of physical chemistry letters","url":"https://pubmed.ncbi.nlm.nih.gov/39143857","citation_count":3,"is_preprint":false},{"pmid":"33770537","id":"PMC_33770537","title":"PCTP contributes to human platelet activation by enhancing dense granule secretion.","date":"2021","source":"Thrombosis research","url":"https://pubmed.ncbi.nlm.nih.gov/33770537","citation_count":2,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.06.18.599563","title":"RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events","date":"2024-06-21","source":"bioRxiv","url":"https://doi.org/10.1101/2024.06.18.599563","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10411,"output_tokens":2983,"usd":0.037989},"stage2":{"model":"claude-opus-4-6","input_tokens":6512,"output_tokens":2815,"usd":0.154402},"total_usd":0.192391,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"PC-TP (StarD2) physically interacts with Them2 (thioesterase superfamily member 2) and the homeodomain transcription factor Pax3, identified by yeast two-hybrid screening and verified by pulldown assays and colocalization. The acyl-CoA thioesterase activity of purified recombinant Them2 is markedly enhanced by recombinant PC-TP, and PC-TP coactivates transcriptional activity of Pax3 in tissue culture.\",\n      \"method\": \"Yeast two-hybrid screening, pulldown assays, colocalization, in vitro enzymatic assay with recombinant proteins, transcriptional reporter assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods including in vitro reconstitution of enzymatic activity enhancement, pulldown verification, and functional reporter assay\",\n      \"pmids\": [\"17704541\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"PC-TP catalyzes transfer of phosphatidylcholines between membranes in vitro; high-throughput screening identified six small-molecule inhibitors of this phosphatidylcholine transfer activity with IC50 values of 4.1–95.0 µM, establishing the in vitro enzymatic mechanism is druggable.\",\n      \"method\": \"Fluorescence quench in vitro transfer assay, high-throughput screening of 114,752 compounds\",\n      \"journal\": \"Analytical biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct in vitro enzymatic assay with quantified inhibition constants\",\n      \"pmids\": [\"18762160\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"PC-TP deficiency (Pctp−/−) increases hepatic insulin sensitivity, reduces hepatic glucose production, gluconeogenesis, glycogenolysis, and promotes preferential fatty acid utilization, demonstrating a role for PC-TP in regulating hepatic energy substrate utilization and insulin signaling.\",\n      \"method\": \"Hyperinsulinemic-euglycemic clamp studies in Pctp−/− mice, indirect calorimetry, isotope tracer studies\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined metabolic phenotype using multiple quantitative metabolic assays\",\n      \"pmids\": [\"18347010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"PC-TP limits mitochondrial fatty acid oxidation and regulates adaptive thermogenesis in brown adipose tissue (BAT); Pctp−/− mice have enlarged mitochondria in BAT, higher core body temperatures, and brown adipocytes lacking Pctp show higher oxygen consumption in response to norepinephrine.\",\n      \"method\": \"Pctp−/− mouse model, histology, oxygen consumption measurements in cultured brown adipocytes, adenovirus-mediated Pctp overexpression rescue\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — KO with defined cellular phenotype and rescue experiment\",\n      \"pmids\": [\"19502644\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PC-TP expression in cell culture controls the transcriptional activities of PPARα and HNF4α, and is itself regulated by PPARα; Pctp−/− mice fed fenofibrate exhibit altered lipid and glucose metabolism with differential expression of metabolic genes and their transcriptional regulators.\",\n      \"method\": \"Transcriptional reporter assays in cell culture, microarray profiling of Pctp−/− mouse livers, fenofibrate (PPARα ligand) treatment\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — reporter assay plus KO metabolic phenotype, single lab\",\n      \"pmids\": [\"20045742\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PC-TP selectively mediates PAR4- but not PAR1-mediated platelet activation; PC-TP inhibition or depletion blocks PAR4-induced platelet aggregation and calcium mobilization in human platelets and megakaryocytic cell lines. miR-376c inversely regulates PC-TP expression in megakaryocytes and is associated with PAR4 reactivity.\",\n      \"method\": \"PC-TP inhibitor treatment and siRNA depletion in human platelets and megakaryocytic cell lines, calcium mobilization assays, platelet aggregation assays, miR-376c functional studies\",\n      \"journal\": \"Nature medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal pharmacological and genetic loss-of-function with specific functional readouts, large human cohort plus cell line validation\",\n      \"pmids\": [\"24216752\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Them2 and PC-TP interact to promote fatty acid oxidation and control glucose utilization in hepatocytes; under fasting conditions, Pctp−/− and Them2−/− hepatocytes each show decreased fatty acid oxidation and gluconeogenesis, and chemical inhibition of PC-TP fails to reproduce these changes in Them2−/− hepatocytes, demonstrating that PC-TP regulation of fatty acid oxidation is Them2-dependent.\",\n      \"method\": \"Primary hepatocyte cultures from Pctp−/− and Them2−/− mice, chemical inhibition of PC-TP, fatty acid oxidation assays, gluconeogenesis assays, glucose oxidation assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic and pharmacological epistasis in primary cells with multiple biochemical readouts\",\n      \"pmids\": [\"24732803\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RUNX1 directly binds consensus sites in the PCTP promoter (~1 kb region) and transcriptionally regulates PCTP expression; RUNX1 overexpression increases and RUNX1 knockdown reduces PCTP expression in human erythroleukemia cells.\",\n      \"method\": \"DNA-protein binding studies, luciferase promoter reporter assays, RUNX1 overexpression and knockdown in HEL cells, patient platelet profiling\",\n      \"journal\": \"Circulation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct DNA binding, reporter assay, and bidirectional genetic manipulation with consistent results\",\n      \"pmids\": [\"28676520\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PC-TP promotes microvesicular steatosis and hepatocellular injury in MCD diet-induced steatohepatitis; Pctp−/− mice are protected from MCD diet-induced liver injury (reduced ALT/AST, decreased c-Jun activation), with a specific reduction in microvesicular lipid droplets, suggesting PC-TP mediates intermembrane PC transfer to stabilize pathogenic small lipid droplets independently of Them2.\",\n      \"method\": \"Pctp−/− mouse MCD diet model, histopathology, plasma enzyme assays, c-Jun activation, lipid droplet size quantification, mRNA/protein expression\",\n      \"journal\": \"American journal of physiology. Gastrointestinal and liver physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KO with defined pathological phenotype and multiple biochemical readouts, single lab\",\n      \"pmids\": [\"28385694\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PC-TP contributes to human platelet activation by enhancing dense granule secretion (but not alpha granule secretion) downstream of multiple agonists (thrombin, PAR1AP, PAR4AP, convulxin, FcγRIIA); PC-TP inhibition reduces cytoplasmic Ca2+ increase and PKC activity downstream of thrombin.\",\n      \"method\": \"PC-TP inhibitor (compound A1) treatment of human platelets, dense/alpha granule secretion assays, calcium mobilization assays, PKC activity assays, aggregation assays with multiple agonists\",\n      \"journal\": \"Thrombosis research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — pharmacological inhibition with specific granule secretion and signaling readouts, single lab\",\n      \"pmids\": [\"33770537\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PC-TP directly interacts with PPARδ (but not PPARα or PPARγ) in a ligand-dependent manner to repress PPARδ-mediated transactivation; mutations in PC-TP residues implicated in PC binding and transfer reduce the PC-TP–PPARδ interaction and relieve repression. Methionine/choline reduction decreases, while serum starvation enhances, this interaction in hepatocytes.\",\n      \"method\": \"In-cell protein complementation screen, co-IP in Huh7 hepatocytes, PC-TP binding-site mutagenesis, PPARδ transactivation reporter assay, hepatocyte-specific Pctp knockdown mouse model\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct protein interaction confirmed by complementation and co-IP, functional repression validated by mutagenesis and reporter assay\",\n      \"pmids\": [\"37173315\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Molecular dynamics simulations of human STARD2/PC-TP reveal a ligand-dependent conformational change and a spontaneous PC lipid uptake mechanism involving metastable states stabilized by choline–tyrosine and choline–tryptophan cation-π interactions; free energy perturbation shows PC–tyrosine cation-π interactions contribute 1.8–2.5 kcal/mol to binding affinity of a metastable state.\",\n      \"method\": \"Microsecond-scale molecular dynamics simulations of apo and holo STARD2 with lipid bilayers, free energy perturbation calculations\",\n      \"journal\": \"The journal of physical chemistry letters\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 — computational modeling only, no experimental validation of proposed mechanism\",\n      \"pmids\": [\"39143857\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PC-TP (StarD2/PCTP) is a soluble START-domain phosphatidylcholine-binding protein that catalyzes intermembrane PC transfer in vitro and functions in vivo as a phosphatidylcholine sensor: it stimulates the long-chain acyl-CoA thioesterase activity of its binding partner Them2 to limit mitochondrial fatty acid oxidation and suppress hepatic insulin sensitivity, directly represses PPARδ transcriptional activity in a PC-ligand-dependent manner, and in platelets selectively mediates PAR4-dependent activation and dense granule secretion partly through Ca2+/PKC signaling, with its own expression controlled at the transcriptional level by RUNX1 and post-transcriptionally by miR-376c.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PC-TP (PCTP/StarD2) is a soluble START-domain lipid transfer protein that functions as a phosphatidylcholine sensor coupling membrane lipid status to metabolic and signaling outcomes. It catalyzes intermembrane phosphatidylcholine transfer in vitro and stimulates the long-chain acyl-CoA thioesterase activity of its physical partner Them2 in a Them2-dependent epistatic manner to promote hepatic fatty acid oxidation, gluconeogenesis, and suppress insulin sensitivity [PMID:17704541, PMID:24732803, PMID:18347010]. PC-TP directly binds and represses PPARδ transcriptional activity in a phosphatidylcholine-ligand-dependent fashion, with PC-binding-site mutations abolishing both the interaction and repression [PMID:37173315]. In platelets, PC-TP selectively mediates PAR4-dependent activation and dense granule secretion through Ca²⁺/PKC signaling, with its expression controlled transcriptionally by RUNX1 and post-transcriptionally by miR-376c [PMID:24216752, PMID:28676520, PMID:33770537].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Identifying PC-TP's direct binding partners Them2 and Pax3 established that PC-TP is not merely a lipid shuttle but a protein–protein interaction hub that enhances Them2 thioesterase activity, linking lipid transfer to acyl-CoA metabolism.\",\n      \"evidence\": \"Yeast two-hybrid, pulldown, colocalization, and in vitro reconstitution of Them2 activity enhancement by recombinant PC-TP\",\n      \"pmids\": [\"17704541\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of PC-TP–Them2 interaction not resolved\",\n        \"Whether PC binding by PC-TP is required for Them2 activation was not tested\",\n        \"Pax3 coactivation mechanism was not further dissected\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Demonstrating that Pctp−/− mice have enhanced hepatic insulin sensitivity and altered substrate utilization revealed that PC-TP normally functions to limit insulin action and promote glucose output, positioning it as a metabolic regulator in vivo.\",\n      \"evidence\": \"Hyperinsulinemic-euglycemic clamp, indirect calorimetry, and isotope tracer studies in Pctp−/− mice\",\n      \"pmids\": [\"18347010\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the metabolic phenotype is cell-autonomous to hepatocytes was not established\",\n        \"Signaling intermediates between PC-TP and insulin pathway not identified\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"An in vitro transfer assay confirmed PC-TP catalyzes intermembrane phosphatidylcholine transfer and identified small-molecule inhibitors, validating the enzymatic activity as a druggable target.\",\n      \"evidence\": \"Fluorescence quench transfer assay and high-throughput screen of ~115,000 compounds\",\n      \"pmids\": [\"18762160\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"In vivo efficacy of inhibitors not demonstrated\",\n        \"Selectivity of inhibitors for PC-TP over other START-domain proteins not fully characterized\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Finding that Pctp−/− mice have enlarged BAT mitochondria and increased thermogenesis extended PC-TP's metabolic role beyond liver, showing it restrains mitochondrial fatty acid oxidation in brown adipose tissue.\",\n      \"evidence\": \"Pctp−/− mouse BAT histology, oxygen consumption in cultured brown adipocytes, adenoviral Pctp rescue\",\n      \"pmids\": [\"19502644\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether BAT phenotype is Them2-dependent was not tested\",\n        \"Mechanism linking PC-TP to mitochondrial morphology unknown\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showing that PC-TP selectively mediates PAR4- but not PAR1-dependent platelet activation, with miR-376c as a post-transcriptional regulator, revealed a receptor-specific platelet signaling role entirely distinct from its hepatic metabolic functions.\",\n      \"evidence\": \"PC-TP inhibitor and siRNA depletion in human platelets and megakaryocytic cell lines, calcium mobilization and aggregation assays, miR-376c functional studies\",\n      \"pmids\": [\"24216752\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism of PAR4 selectivity over PAR1 not elucidated\",\n        \"Whether PC-TP lipid binding is required for platelet signaling not tested\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Genetic and pharmacological epistasis experiments demonstrated that PC-TP's regulation of hepatic fatty acid oxidation is fully Them2-dependent, resolving whether PC-TP acts through its lipid transfer activity alone or through its protein partner.\",\n      \"evidence\": \"Primary hepatocyte cultures from Pctp−/− and Them2−/− mice, chemical PC-TP inhibition in Them2−/− cells, fatty acid oxidation and gluconeogenesis assays\",\n      \"pmids\": [\"24732803\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether PC-TP delivers PC to Them2 as a substrate or acts as an allosteric activator not distinguished\",\n        \"Stoichiometry and kinetics of the PC-TP–Them2 complex not characterized\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identification of RUNX1 as a direct transcriptional activator of PCTP connected the megakaryocyte lineage transcription factor to PC-TP-dependent platelet function and provided a mechanism for lineage-specific PCTP expression.\",\n      \"evidence\": \"DNA-protein binding studies, luciferase promoter reporter, RUNX1 overexpression/knockdown in HEL cells\",\n      \"pmids\": [\"28676520\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether RUNX1-driven PCTP expression is sufficient to modulate PAR4-dependent platelet reactivity in vivo not shown\",\n        \"Other transcription factors regulating PCTP in hepatocytes not identified\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Showing that Pctp−/− mice are protected from MCD diet-induced microvesicular steatosis and liver injury, independently of Them2, suggested a Them2-independent role for PC-TP's lipid transfer activity in stabilizing small lipid droplets under steatohepatitic stress.\",\n      \"evidence\": \"Pctp−/− MCD diet model, histopathology, lipid droplet quantification, c-Jun activation measurement\",\n      \"pmids\": [\"28385694\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Them2-independence inferred indirectly; double-KO not performed\",\n        \"Direct evidence that PC transfer to lipid droplet membranes is the causative mechanism is lacking\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extending platelet studies showed PC-TP promotes dense (but not alpha) granule secretion downstream of multiple agonists via Ca²⁺ and PKC, broadening its platelet role beyond PAR4 selectivity to a general dense granule secretion pathway.\",\n      \"evidence\": \"Pharmacological PC-TP inhibition in human platelets, dense/alpha granule secretion assays, calcium and PKC activity measurements with multiple agonists\",\n      \"pmids\": [\"33770537\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Genetic confirmation (siRNA or KO platelets) for the broader agonist panel not provided\",\n        \"How PC-TP interfaces with Ca²⁺/PKC signaling machinery is unknown\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrating that PC-TP directly binds PPARδ (but not PPARα or PPARγ) in a PC-ligand-dependent manner and represses its transactivation established PC-TP as a nuclear receptor corepressor whose regulatory activity depends on its lipid cargo.\",\n      \"evidence\": \"In-cell protein complementation, co-IP in hepatocytes, PC-binding-site mutagenesis, PPARδ reporter assay, hepatocyte-specific Pctp knockdown mice\",\n      \"pmids\": [\"37173315\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether PC-TP enters the nucleus or sequesters PPARδ in the cytoplasm is unresolved\",\n        \"Identity of endogenous PC species that regulate the PC-TP–PPARδ interaction not determined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Major open questions include the structural basis of PC-TP's interactions with Them2 and PPARδ, whether its lipid-transfer and protein-interaction functions can be genetically separated in vivo, and the mechanism by which PC-TP selectively controls dense granule but not alpha granule secretion in platelets.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No co-crystal structure of PC-TP with Them2 or PPARδ\",\n        \"Separation-of-function mutations distinguishing lipid transfer from protein interaction not generated in vivo\",\n        \"Platelet-specific conditional KO studies have not been performed\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [1, 10, 11]},\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [1, 8]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 6, 10]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 4, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 5, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [2, 3, 6]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 9]},\n      {\"term_id\": \"R-HSA-109582\", \"supporting_discovery_ids\": [5, 9]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ACOT13\", \"PPARD\", \"RUNX1\", \"PAX3\"],\n    \"other_free_text\": []\n  }\n}\n```"}