{"gene":"ACOT8","run_date":"2026-06-09T22:02:39","timeline":{"discoveries":[{"year":2016,"finding":"ACOT8 regions Arg45-Phe55 and Arg86-Pro93 are required for interaction with HIV-1 Nef, and the K91S point mutation abrogates this interaction, indicating Lys91 plays a key role in Nef binding. When associated with ACOT8, Nef may be preserved from degradation.","method":"In silico structural modelling, co-immunoprecipitation, immunofluorescence, and ACOT8 deletion/point mutant analysis","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP with deletion mutants and point mutation validation, single lab, multiple orthogonal methods (co-IP + immunofluorescence + mutagenesis)","pmids":["26927806"],"is_preprint":false},{"year":2024,"finding":"TSC22D2 physically interacts with ACOT8 (identified by co-IP combined with mass spectrometry) and maintains ACOT8 protein stability; overexpression of TSC22D2 promotes ACOT8 expression and inhibits CRC cell proliferation and metastasis via an EMT mechanism.","method":"Co-immunoprecipitation combined with mass spectrometry, Western blot, CCK-8, colony formation, transwell assay, in vivo mouse model","journal":"OncoTargets and therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP/MS identification of interaction plus functional knockdown/overexpression with defined phenotypic readout, single lab","pmids":["38476309"],"is_preprint":false},{"year":2026,"finding":"ACOT8 modulates palmitate levels in renal tubular epithelial cells; elevated ACOT8 during ischemia-reperfusion injury leads to palmitate accumulation, which activates the cGAS-STING signaling pathway in macrophages, promoting M1 macrophage polarization and exacerbating renal inflammation. AAV9-mediated tubule-specific ACOT8 knockdown reduced palmitate accumulation, M1 macrophage infiltration, and improved renal function.","method":"In vivo AAV9 knockdown in mouse IRI model, single-cell RNA sequencing, lipidomics, in vitro experiments, multi-omics integration","journal":"International immunopharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo loss-of-function with defined pathway placement (cGAS-STING) and lipid metabolite readout, single lab, multiple orthogonal methods","pmids":["41905213"],"is_preprint":false}],"current_model":"ACOT8 is a peroxisomal acyl-CoA thioesterase that modulates fatty acid (particularly palmitate) levels in cells; it physically interacts with HIV-1 Nef via specific surface regions (Arg45-Phe55, Arg86-Pro93, key residue Lys91) potentially stabilizing Nef from degradation, is stabilized by TSC22D2 binding, and in renal tubular epithelial cells its activity promotes palmitate accumulation that activates the cGAS-STING pathway in macrophages to drive M1 polarization and inflammation."},"narrative":{"mechanistic_narrative":"ACOT8 is an acyl-CoA thioesterase that modulates cellular fatty acid levels, particularly palmitate, and through this metabolic activity influences inflammation and tumor cell behavior [PMID:41905213]. In renal tubular epithelial cells, elevated ACOT8 during ischemia-reperfusion injury drives palmitate accumulation that activates the cGAS-STING pathway in macrophages, promoting M1 polarization and renal inflammation; tubule-specific ACOT8 knockdown reduces palmitate accumulation, M1 infiltration, and improves renal function [PMID:41905213]. ACOT8 protein stability is supported by physical interaction with TSC22D2, and TSC22D2-driven ACOT8 expression restrains colorectal cancer proliferation and metastasis via an EMT-related mechanism [PMID:38476309]. ACOT8 also physically engages HIV-1 Nef through defined surface regions (Arg45-Phe55, Arg86-Pro93, with Lys91 as a key residue), an interaction that may preserve Nef from degradation [PMID:26927806]. Beyond these contexts, the enzymatic mechanism and structural basis of ACOT8 thioesterase activity have not been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Established that ACOT8 is a physical binding partner of HIV-1 Nef and mapped the specific surface determinants of that interaction, raising the possibility that ACOT8 stabilizes Nef.","evidence":"In silico structural modelling, reciprocal co-immunoprecipitation, immunofluorescence, and ACOT8 deletion/point mutant analysis","pmids":["26927806"],"confidence":"Medium","gaps":["Functional consequence of Nef stabilization for viral replication not demonstrated","No direct measurement of ACOT8 thioesterase activity in the Nef-bound state","Interaction shown in a single lab without independent replication"]},{"year":2024,"claim":"Identified TSC22D2 as a physical partner that maintains ACOT8 protein stability, linking ACOT8 levels to suppression of colorectal cancer proliferation and metastasis.","evidence":"Co-IP/mass spectrometry interaction mapping with knockdown/overexpression functional assays and an in vivo mouse model","pmids":["38476309"],"confidence":"Medium","gaps":["Mechanism by which TSC22D2 stabilizes ACOT8 (e.g. blocking degradation) not defined","Whether ACOT8 thioesterase activity is required for the anti-EMT effect untested","Direct interaction not confirmed by reciprocal or in vitro binding"]},{"year":2026,"claim":"Placed ACOT8 in an inflammatory signaling axis by showing its activity drives palmitate accumulation that activates macrophage cGAS-STING and M1 polarization during renal ischemia-reperfusion injury.","evidence":"In vivo AAV9 tubule-specific knockdown in a mouse IRI model with single-cell RNA-seq, lipidomics, and in vitro experiments","pmids":["41905213"],"confidence":"Medium","gaps":["Direct enzymatic link between ACOT8 and palmitate generation not biochemically demonstrated","Mechanism of palmitate transfer from tubular cells to macrophages unclear","Generalizability beyond the IRI model not established"]},{"year":null,"claim":"The intrinsic biochemical substrate specificity, catalytic mechanism, and structural basis of ACOT8 thioesterase activity remain to be directly defined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No in vitro reconstitution of substrate range reported","No structural model of the active site","Unclear how ACOT8 activity is regulated across the distinct contexts (Nef, TSC22D2, IRI)"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[2]}],"localization":[],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[2]}],"complexes":[],"partners":["NEF","TSC22D2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O14734","full_name":"Acyl-coenzyme A thioesterase 8","aliases":["Choloyl-coenzyme A thioesterase","HIV-Nef-associated acyl-CoA thioesterase","Peroxisomal acyl-CoA thioesterase 2","PTE-2","Peroxisomal acyl-coenzyme A thioester hydrolase 1","PTE-1","Peroxisomal long-chain acyl-CoA thioesterase 1","Thioesterase II","hACTE-III","hACTEIII","hTE"],"length_aa":319,"mass_kda":35.9,"function":"Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:15194431, PubMed:9153233, PubMed:9299485). Displays no strong substrate specificity with respect to the carboxylic acid moiety of Acyl-CoAs (By similarity). Hydrolyzes medium length (C2 to C20) straight-chain, saturated and unsaturated acyl-CoAS but is inactive towards substrates with longer aliphatic chains (PubMed:9153233, PubMed:9299485). Moreover, it catalyzes the hydrolysis of CoA esters of bile acids, such as choloyl-CoA and chenodeoxycholoyl-CoA and competes with bile acid CoA:amino acid N-acyltransferase (BAAT) (By similarity). Is also able to hydrolyze CoA esters of dicarboxylic acids (By similarity). It is involved in the metabolic regulation of peroxisome proliferation (PubMed:15194431) (Microbial infection) May mediate Nef-induced down-regulation of CD4 cell-surface expression (PubMed:9153233)","subcellular_location":"Peroxisome matrix","url":"https://www.uniprot.org/uniprotkb/O14734/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ACOT8","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ACOT8","total_profiled":1310},"omim":[{"mim_id":"608123","title":"ACYL-CoA THIOESTERASE 8; ACOT8","url":"https://www.omim.org/entry/608123"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ACOT8"},"hgnc":{"alias_symbol":["hACTE-III","hTE","PTE-2","NAP1"],"prev_symbol":["PTE1"]},"alphafold":{"accession":"O14734","domains":[{"cath_id":"2.40.160.210","chopping":"27-131_149-313","consensus_level":"medium","plddt":92.2735,"start":27,"end":313}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O14734","model_url":"https://alphafold.ebi.ac.uk/files/AF-O14734-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O14734-F1-predicted_aligned_error_v6.png","plddt_mean":88.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ACOT8","jax_strain_url":"https://www.jax.org/strain/search?query=ACOT8"},"sequence":{"accession":"O14734","fasta_url":"https://rest.uniprot.org/uniprotkb/O14734.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O14734/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O14734"}},"corpus_meta":[{"pmid":"26927806","id":"PMC_26927806","title":"Molecular characterization of HIV-1 Nef and ACOT8 interaction: insights from in silico structural predictions and in vitro functional assays.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26927806","citation_count":9,"is_preprint":false},{"pmid":"20547355","id":"PMC_20547355","title":"Genetic replacement of tesB with PTE1 affects chain-length proportions of 3-hydroxyalkanoic acids produced through β-oxidation of oleic acid in Escherichia coli.","date":"2010","source":"Journal of bioscience and bioengineering","url":"https://pubmed.ncbi.nlm.nih.gov/20547355","citation_count":9,"is_preprint":false},{"pmid":"31179598","id":"PMC_31179598","title":"Physiological relevance of ACOT8-Nef interaction in HIV infection.","date":"2019","source":"Reviews in medical virology","url":"https://pubmed.ncbi.nlm.nih.gov/31179598","citation_count":7,"is_preprint":false},{"pmid":"38476309","id":"PMC_38476309","title":"TSC22D2 Regulates ACOT8 to Delay the Malignant Progression of Colorectal Cancer.","date":"2024","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/38476309","citation_count":6,"is_preprint":false},{"pmid":"25984768","id":"PMC_25984768","title":"Expression of synthetic human tropoelastin (hTE) protein in Nicotiana tabacum.","date":"2015","source":"GM crops & food","url":"https://pubmed.ncbi.nlm.nih.gov/25984768","citation_count":5,"is_preprint":false},{"pmid":"35886005","id":"PMC_35886005","title":"Identification and Characterization of PTE-2, a Stowaway-like MITE Activated in Transgenic Chinese Cabbage Lines.","date":"2022","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/35886005","citation_count":2,"is_preprint":false},{"pmid":"41009449","id":"PMC_41009449","title":"Switch from Ibalizumab to Lenacapavir in a Rescue Regimen for a Heavily Treatment-Experienced (HTE) Patient with Multidrug-Resistant (MDR) HIV-1 Infection.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41009449","citation_count":1,"is_preprint":false},{"pmid":"39280956","id":"PMC_39280956","title":"Herbal Tea Essences (HTE) Ameliorate HFD-Induced Obesity.","date":"2022","source":"Evidence-based complementary and alternative medicine : eCAM","url":"https://pubmed.ncbi.nlm.nih.gov/39280956","citation_count":0,"is_preprint":false},{"pmid":"41905213","id":"PMC_41905213","title":"ACOT8-mediated palmitate accumulation promotes M1 macrophage polarization in renal ischemia-reperfusion injury via activation of the cGAS-STING pathway.","date":"2026","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41905213","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.15.25338051","title":"Polygenic prediction of treatment efficacy with causal transfer learning","date":"2025-10-17","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.15.25338051","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.11.10.25339913","title":"Characterize Disease Progression Subphenotypes in Real World Populations with Overweight and Obesity using a Graph-based Neural Network Framework","date":"2025-11-13","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.10.25339913","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.10.23.684193","title":"High-throughput discovery of a [4+3] dearomative cycloaddition enables dual photochemical-photophysical perturbative probing of protein function","date":"2025-10-24","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.23.684193","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.06.09.25329205","title":"Part 1: Examining heterogeneity of treatment effects in transcranial direct current stimulation for knee osteoarthritis pain and symptoms","date":"2025-06-09","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.09.25329205","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.09.02.25334965","title":"Heterogeneity of effect of Intensive lifestyle intervention on cardiometabolic risk factors by sex hormones in diabetes","date":"2025-09-05","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.02.25334965","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.06.02.25328066","title":"Heterogeneity of Treatment Effects of Glucose-lowering Drug Classes for Type 2 Diabetes: LEGEND-T2DM Network Real-World Evidence","date":"2025-06-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.02.25328066","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.04.21.25326150","title":"Target Trial Emulation Applications in Hypertension Research: A Scoping Review","date":"2025-04-22","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.21.25326150","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.06.09.25329238","title":"Part 2: Predicting heterogeneity of treatment effects to transcranial direct current stimulation for knee osteoarthritis pain and symptoms","date":"2025-06-09","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.09.25329238","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.23.25320649","title":"The Heterogeneous Effect of High PEEP strategies on Survival in Acute Respiratory Distress Syndrome: preliminary results of a data-driven analysis of randomized trials","date":"2025-01-25","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.23.25320649","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.12.19.24319347","title":"Quantifying absolute treatment effect heterogeneity for time-to-event outcomes across different risk strata: divergence of conclusions with risk difference and restricted mean survival difference","date":"2024-12-22","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.19.24319347","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.12.06.627153","title":"Learning from and improving upon high-throughput screens for protein fitness with Generative AI - Application to BBB-crossing AAV design","date":"2024-12-11","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.06.627153","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.08.06.24311556","title":"Personalized Fluid Management in Patients with Sepsis and AKI: A Casual Machine Learning Approach","date":"2024-08-07","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.06.24311556","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":15027,"output_tokens":909,"usd":0.029358,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7372,"output_tokens":1598,"usd":0.038405,"stage2_stop_reason":"end_turn"},"total_usd":0.067763,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"ACOT8 regions Arg45-Phe55 and Arg86-Pro93 are required for interaction with HIV-1 Nef, and the K91S point mutation abrogates this interaction, indicating Lys91 plays a key role in Nef binding. When associated with ACOT8, Nef may be preserved from degradation.\",\n      \"method\": \"In silico structural modelling, co-immunoprecipitation, immunofluorescence, and ACOT8 deletion/point mutant analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP with deletion mutants and point mutation validation, single lab, multiple orthogonal methods (co-IP + immunofluorescence + mutagenesis)\",\n      \"pmids\": [\"26927806\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TSC22D2 physically interacts with ACOT8 (identified by co-IP combined with mass spectrometry) and maintains ACOT8 protein stability; overexpression of TSC22D2 promotes ACOT8 expression and inhibits CRC cell proliferation and metastasis via an EMT mechanism.\",\n      \"method\": \"Co-immunoprecipitation combined with mass spectrometry, Western blot, CCK-8, colony formation, transwell assay, in vivo mouse model\",\n      \"journal\": \"OncoTargets and therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP/MS identification of interaction plus functional knockdown/overexpression with defined phenotypic readout, single lab\",\n      \"pmids\": [\"38476309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ACOT8 modulates palmitate levels in renal tubular epithelial cells; elevated ACOT8 during ischemia-reperfusion injury leads to palmitate accumulation, which activates the cGAS-STING signaling pathway in macrophages, promoting M1 macrophage polarization and exacerbating renal inflammation. AAV9-mediated tubule-specific ACOT8 knockdown reduced palmitate accumulation, M1 macrophage infiltration, and improved renal function.\",\n      \"method\": \"In vivo AAV9 knockdown in mouse IRI model, single-cell RNA sequencing, lipidomics, in vitro experiments, multi-omics integration\",\n      \"journal\": \"International immunopharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo loss-of-function with defined pathway placement (cGAS-STING) and lipid metabolite readout, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"41905213\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ACOT8 is a peroxisomal acyl-CoA thioesterase that modulates fatty acid (particularly palmitate) levels in cells; it physically interacts with HIV-1 Nef via specific surface regions (Arg45-Phe55, Arg86-Pro93, key residue Lys91) potentially stabilizing Nef from degradation, is stabilized by TSC22D2 binding, and in renal tubular epithelial cells its activity promotes palmitate accumulation that activates the cGAS-STING pathway in macrophages to drive M1 polarization and inflammation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ACOT8 is an acyl-CoA thioesterase that modulates cellular fatty acid levels, particularly palmitate, and through this metabolic activity influences inflammation and tumor cell behavior [#2]. In renal tubular epithelial cells, elevated ACOT8 during ischemia-reperfusion injury drives palmitate accumulation that activates the cGAS-STING pathway in macrophages, promoting M1 polarization and renal inflammation; tubule-specific ACOT8 knockdown reduces palmitate accumulation, M1 infiltration, and improves renal function [#2]. ACOT8 protein stability is supported by physical interaction with TSC22D2, and TSC22D2-driven ACOT8 expression restrains colorectal cancer proliferation and metastasis via an EMT-related mechanism [#1]. ACOT8 also physically engages HIV-1 Nef through defined surface regions (Arg45-Phe55, Arg86-Pro93, with Lys91 as a key residue), an interaction that may preserve Nef from degradation [#0]. Beyond these contexts, the enzymatic mechanism and structural basis of ACOT8 thioesterase activity have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Established that ACOT8 is a physical binding partner of HIV-1 Nef and mapped the specific surface determinants of that interaction, raising the possibility that ACOT8 stabilizes Nef.\",\n      \"evidence\": \"In silico structural modelling, reciprocal co-immunoprecipitation, immunofluorescence, and ACOT8 deletion/point mutant analysis\",\n      \"pmids\": [\"26927806\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of Nef stabilization for viral replication not demonstrated\", \"No direct measurement of ACOT8 thioesterase activity in the Nef-bound state\", \"Interaction shown in a single lab without independent replication\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified TSC22D2 as a physical partner that maintains ACOT8 protein stability, linking ACOT8 levels to suppression of colorectal cancer proliferation and metastasis.\",\n      \"evidence\": \"Co-IP/mass spectrometry interaction mapping with knockdown/overexpression functional assays and an in vivo mouse model\",\n      \"pmids\": [\"38476309\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which TSC22D2 stabilizes ACOT8 (e.g. blocking degradation) not defined\", \"Whether ACOT8 thioesterase activity is required for the anti-EMT effect untested\", \"Direct interaction not confirmed by reciprocal or in vitro binding\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Placed ACOT8 in an inflammatory signaling axis by showing its activity drives palmitate accumulation that activates macrophage cGAS-STING and M1 polarization during renal ischemia-reperfusion injury.\",\n      \"evidence\": \"In vivo AAV9 tubule-specific knockdown in a mouse IRI model with single-cell RNA-seq, lipidomics, and in vitro experiments\",\n      \"pmids\": [\"41905213\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct enzymatic link between ACOT8 and palmitate generation not biochemically demonstrated\", \"Mechanism of palmitate transfer from tubular cells to macrophages unclear\", \"Generalizability beyond the IRI model not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic biochemical substrate specificity, catalytic mechanism, and structural basis of ACOT8 thioesterase activity remain to be directly defined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vitro reconstitution of substrate range reported\", \"No structural model of the active site\", \"Unclear how ACOT8 activity is regulated across the distinct contexts (Nef, TSC22D2, IRI)\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"NEF\", \"TSC22D2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":4,"faith_total":4,"faith_pct":100.0}}