{"gene":"SEC14L4","run_date":"2026-06-10T07:46:30","timeline":{"discoveries":[{"year":2005,"finding":"Recombinant human SEC14L4 (TAP3) binds alpha-, beta-, gamma-, and delta-tocopherol, certain phospholipids, and squalene in vitro, and possesses intrinsic GTPase activity comparable to Rab family small GTP-binding proteins. The GTPase-related motifs in SEC14L4 differ in surrounding secondary structure from canonical G-protein domains but are positioned in close proximity, suggesting they form a functional active site for GTP binding and hydrolysis.","method":"Recombinant protein expression in E. coli, His-tag purification, in vitro ligand-binding assays (tocopherols, phospholipids, squalene), and GTPase activity assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic and binding assays on purified recombinant protein, single lab, no mutagenesis validation of active site","pmids":["15567179"],"is_preprint":false},{"year":2009,"finding":"The human TAP3/SEC14L4 gene undergoes alternative splicing, producing an alternatively spliced cDNA isoform, and contains a polymorphism within its coding region. The encoded protein belongs to the SEC14p-like family implicated in intracellular lipid transport.","method":"cDNA isolation, sequencing, and characterization of alternative splice variants and coding-region polymorphism","journal":"Molecular biology reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single molecular characterization method (sequencing/cloning), no functional assay linking splice variant to activity","pmids":["20012369"],"is_preprint":false},{"year":2026,"finding":"SEC14L4 directly interacts with DDX3X (identified by Co-IP and mass spectrometry) and inhibits RNF39-mediated ubiquitination and proteasomal degradation of DDX3X in esophageal squamous cell carcinoma cells. SEC14L4 loss-of-function reduces ESCC cell proliferation, migration, and colony formation while promoting apoptosis; these effects are rescued by DDX3X overexpression, placing SEC14L4 upstream of DDX3X in a pathway that activates MAPK signaling and suppresses ferroptosis.","method":"Co-immunoprecipitation, mass spectrometry, ubiquitination assays, Western blot (MAPK pathway and ferroptosis markers), cell proliferation/migration/apoptosis assays with knockdown and overexpression, in vivo xenograft tumor models","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with MS confirmation, ubiquitination assay, multiple orthogonal functional readouts in single lab; no independent replication","pmids":["41741625"],"is_preprint":false}],"current_model":"SEC14L4 (TAP3) is a SEC14p-like lipid/tocopherol-binding protein with intrinsic GTPase activity; in cancer cells it directly binds and stabilizes DDX3X by blocking RNF39-mediated ubiquitination and degradation, thereby activating MAPK signaling and suppressing ferroptosis to promote tumor growth."},"narrative":{"mechanistic_narrative":"SEC14L4 (TAP3) is a SEC14p-like protein that combines lipid/tocopherol binding with a role in stabilizing an RNA helicase to drive tumor cell growth [PMID:15567179, PMID:41741625]. As a recombinant protein it binds alpha-, beta-, gamma-, and delta-tocopherol, select phospholipids, and squalene, and exhibits intrinsic GTPase activity comparable to Rab-family small GTP-binding proteins, with GTPase-related motifs spatially positioned to form a functional GTP-binding and hydrolysis site [PMID:15567179]. In esophageal squamous cell carcinoma, SEC14L4 directly interacts with DDX3X and blocks RNF39-mediated ubiquitination and proteasomal degradation of DDX3X, thereby stabilizing it; this places SEC14L4 upstream of DDX3X in a pathway that activates MAPK signaling and suppresses ferroptosis, and loss of SEC14L4 reduces proliferation, migration, and colony formation while promoting apoptosis in a manner rescued by DDX3X overexpression [PMID:41741625]. Beyond these biochemical and oncogenic activities, the mechanistic integration of SEC14L4's lipid-binding and GTPase functions with its DDX3X-stabilizing role has not been characterized in the available corpus.","teleology":[{"year":2005,"claim":"Established the biochemical identity of SEC14L4 as a SEC14p-like ligand-binding protein that also carries intrinsic GTPase activity, defining two candidate molecular activities for an otherwise uncharacterized protein.","evidence":"Recombinant protein expressed in E. coli, purified, and assayed for tocopherol/phospholipid/squalene binding and GTP hydrolysis in vitro","pmids":["15567179"],"confidence":"Medium","gaps":["No mutagenesis confirming the proposed GTPase active site","In vitro binding does not establish a physiological lipid ligand or cellular GTPase function","No cellular localization or pathway context"]},{"year":2009,"claim":"Documented gene-level complexity of human TAP3/SEC14L4, showing alternative splicing and a coding-region polymorphism, but did not link any variant to function.","evidence":"cDNA isolation, sequencing, and characterization of splice variants and polymorphism","pmids":["20012369"],"confidence":"Low","gaps":["No functional assay connecting splice variant or polymorphism to protein activity","Single molecular characterization method","No phenotypic consequence established"]},{"year":2026,"claim":"Defined a cellular and oncogenic mechanism in which SEC14L4 stabilizes DDX3X by protecting it from RNF39-mediated degradation, linking SEC14L4 to MAPK activation and ferroptosis suppression in cancer.","evidence":"Reciprocal Co-IP with mass spectrometry, ubiquitination assays, MAPK/ferroptosis marker Western blots, knockdown/overexpression proliferation-migration-apoptosis assays, and xenograft models in ESCC cells","pmids":["41741625"],"confidence":"Medium","gaps":["No independent replication beyond a single lab","How the 2005 lipid-binding/GTPase activities relate to DDX3X stabilization is unresolved","Direct interface mapping of the SEC14L4–DDX3X interaction not performed"]},{"year":null,"claim":"Whether SEC14L4's lipid/tocopherol binding and GTPase activity mechanistically contribute to its DDX3X-stabilizing, pro-tumorigenic role, and whether this function extends beyond esophageal squamous cell carcinoma, remain open.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of the SEC14L4–DDX3X complex","No demonstration that GTPase activity is required for DDX3X stabilization","Physiological (non-cancer) role uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[0]},{"term_id":"GO:0003924","term_label":"GTPase activity","supporting_discovery_ids":[0]}],"localization":[],"pathway":[],"complexes":[],"partners":["DDX3X","RNF39"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UDX3","full_name":"SEC14-like protein 4","aliases":["Tocopherol-associated protein 3"],"length_aa":406,"mass_kda":46.6,"function":"Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9UDX3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SEC14L4","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/SEC14L4","total_profiled":1310},"omim":[{"mim_id":"612825","title":"SEC14-LIKE LIPID-BINDING PROTEIN 4; SEC14L4","url":"https://www.omim.org/entry/612825"},{"mim_id":"612824","title":"SEC14-LIKE LIPID-BINDING PROTEIN 3; SEC14L3","url":"https://www.omim.org/entry/612824"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"bone marrow","ntpm":7.7},{"tissue":"liver","ntpm":18.0}],"url":"https://www.proteinatlas.org/search/SEC14L4"},"hgnc":{"alias_symbol":["TAP3","dJ130H16.5"],"prev_symbol":[]},"alphafold":{"accession":"Q9UDX3","domains":[{"cath_id":"1.10.8","chopping":"9-65","consensus_level":"high","plddt":96.3251,"start":9,"end":65},{"cath_id":"3.40.525.10","chopping":"68-156_168-194_206-268","consensus_level":"high","plddt":97.5722,"start":68,"end":268}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UDX3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UDX3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UDX3-F1-predicted_aligned_error_v6.png","plddt_mean":95.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SEC14L4","jax_strain_url":"https://www.jax.org/strain/search?query=SEC14L4"},"sequence":{"accession":"Q9UDX3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UDX3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UDX3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UDX3"}},"corpus_meta":[{"pmid":"16844904","id":"PMC_16844904","title":"Functional analyses of two tomato APETALA3 genes demonstrate diversification in their roles in regulating floral development.","date":"2006","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/16844904","citation_count":147,"is_preprint":false},{"pmid":"34014839","id":"PMC_34014839","title":"Multiple-ancestry genome-wide association study identifies 27 loci associated with measures of hemolysis following blood storage.","date":"2021","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/34014839","citation_count":90,"is_preprint":false},{"pmid":"34793330","id":"PMC_34793330","title":"Donor genetic and nongenetic factors affecting red blood cell transfusion effectiveness.","date":"2022","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/34793330","citation_count":79,"is_preprint":false},{"pmid":"32299559","id":"PMC_32299559","title":"Immunoenhancing glucuronoxylomannan from Tremella aurantialba Bandoni et Zang and its low-molecular-weight fractions by radical depolymerization: Properties, structures and effects on macrophages.","date":"2020","source":"Carbohydrate polymers","url":"https://pubmed.ncbi.nlm.nih.gov/32299559","citation_count":58,"is_preprint":false},{"pmid":"24659487","id":"PMC_24659487","title":"Transcriptional and hormonal regulation of petal and stamen development by STAMENLESS, the tomato (Solanum lycopersicum L.) orthologue to the B-class APETALA3 gene.","date":"2014","source":"Journal of experimental botany","url":"https://pubmed.ncbi.nlm.nih.gov/24659487","citation_count":50,"is_preprint":false},{"pmid":"30192961","id":"PMC_30192961","title":"Aberrant Stamen Development is Associated with Parthenocarpic Fruit Set Through Up-Regulation of Gibberellin Biosynthesis in Tomato.","date":"2019","source":"Plant & cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30192961","citation_count":24,"is_preprint":false},{"pmid":"26842499","id":"PMC_26842499","title":"The tomato floral homeotic protein FBP1-like gene, SlGLO1, plays key roles in petal and stamen development.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26842499","citation_count":24,"is_preprint":false},{"pmid":"15567179","id":"PMC_15567179","title":"Recombinant SEC14-like proteins (TAP) possess GTPase activity.","date":"2005","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15567179","citation_count":22,"is_preprint":false},{"pmid":"28815278","id":"PMC_28815278","title":"Phenotypic, genetic and molecular characterization of 7B-1, a conditional male-sterile mutant in tomato.","date":"2017","source":"TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik","url":"https://pubmed.ncbi.nlm.nih.gov/28815278","citation_count":18,"is_preprint":false},{"pmid":"28352968","id":"PMC_28352968","title":"Silencing SlAGL6, a tomato AGAMOUS-LIKE6 lineage gene, generates fused sepal and green petal.","date":"2017","source":"Plant cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/28352968","citation_count":16,"is_preprint":false},{"pmid":"22595886","id":"PMC_22595886","title":"Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass.","date":"2012","source":"Islets","url":"https://pubmed.ncbi.nlm.nih.gov/22595886","citation_count":16,"is_preprint":false},{"pmid":"38064818","id":"PMC_38064818","title":"A novel transcriptomic signature associated with lymphovascular invasion predicts clinical outcomes, tumor microenvironment, and therapeutic response in lung adenocarcinoma.","date":"2023","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/38064818","citation_count":10,"is_preprint":false},{"pmid":"32066731","id":"PMC_32066731","title":"Expression quantitative trait loci-derived scores and white matter microstructure in UK Biobank: a novel approach to integrating genetics and neuroimaging.","date":"2020","source":"Translational psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/32066731","citation_count":10,"is_preprint":false},{"pmid":"38950347","id":"PMC_38950347","title":"Temporal Assessment of Protein Stability in Dried Blood Spots.","date":"2024","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/38950347","citation_count":9,"is_preprint":false},{"pmid":"20012369","id":"PMC_20012369","title":"Alternative splicing and gene polymorphism of the human TAP3/SEC14L4 gene.","date":"2009","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/20012369","citation_count":7,"is_preprint":false},{"pmid":"40665272","id":"PMC_40665272","title":"Immune and genetic landscapes of biliary atresia: a pathway to precision medicine.","date":"2025","source":"BMC pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/40665272","citation_count":2,"is_preprint":false},{"pmid":"41320418","id":"PMC_41320418","title":"A new fucosylated glucuronoxylomannan from the fruit bodies of Tremella aurantia: structural characterization and immunoenhancing activity on seasonal influenza mRNA vaccine.","date":"2025","source":"Carbohydrate polymers","url":"https://pubmed.ncbi.nlm.nih.gov/41320418","citation_count":2,"is_preprint":false},{"pmid":"39525030","id":"PMC_39525030","title":"The role of SEC14L4 in esophageal squamous cell cancer: insights into clinical relevance and molecular pathways.","date":"2024","source":"Translational cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/39525030","citation_count":1,"is_preprint":false},{"pmid":"41526723","id":"PMC_41526723","title":"Structural insights into the antibacterial function of the Pseudomonas putida effector Tke5.","date":"2026","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/41526723","citation_count":1,"is_preprint":false},{"pmid":"41741625","id":"PMC_41741625","title":"SEC14L4 promotes the development of esophageal squamous cell cancer by inhibiting the ubiquitination and degradation of DDX3X via RNF39.","date":"2026","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/41741625","citation_count":0,"is_preprint":false},{"pmid":"33277874","id":"PMC_33277874","title":"The expression pattern of ACTBL2 in thymoma reveals its potential therapeutic target efficacy.","date":"2020","source":"Journal of B.U.ON. : official journal of the Balkan Union of Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/33277874","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.07.04.663240","title":"The cryo-EM structure of an adaptor-effector complex reveals the mechanism of a widespread pore-forming toxin family","date":"2025-07-07","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.04.663240","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13133,"output_tokens":1268,"usd":0.029209,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7394,"output_tokens":1709,"usd":0.039848,"stage2_stop_reason":"end_turn"},"total_usd":0.069057,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify papers about SEC14L4 (also known as TAP3, dJ130H16.5) as a human/mammalian protein.\n\nKey classification decisions:\n- Papers [1], [5], [6], [7], [8 (partial - TAP3 here), [9], [10]: TAP3 in these papers refers to Tomato APETALA3, a plant MADS-box transcription factor — completely different protein family and cellular context. SKIP.\n- Papers [4], [17]: TAP-3 is a polysaccharide from Tremella fungi. SKIP.\n- Papers [19], [22]: Tap3 is a bacterial T6SS adaptor protein in Pseudomonas. SKIP.\n- Paper [8]: \"Recombinant SEC14-like proteins (TAP)\" — TAP1, TAP2, TAP3 = SEC14L2, SEC14L3, SEC14L4. This IS about the human protein. INCLUDE.\n- Paper [15]: Directly about hTAP3/SEC14L4. INCLUDE.\n- Paper [20]: Directly about SEC14L4 in ESCC with Co-IP, mass spec, ubiquitination assays. INCLUDE.\n- Papers [2], [3]: GWAS/association studies — exclude as no mechanistic experiment.\n- Papers [11], [12], [13], [14], [16], [18], [21]: Expression/association studies — exclude.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"Recombinant human SEC14L4 (TAP3) binds alpha-, beta-, gamma-, and delta-tocopherol, certain phospholipids, and squalene in vitro, and possesses intrinsic GTPase activity comparable to Rab family small GTP-binding proteins. The GTPase-related motifs in SEC14L4 differ in surrounding secondary structure from canonical G-protein domains but are positioned in close proximity, suggesting they form a functional active site for GTP binding and hydrolysis.\",\n      \"method\": \"Recombinant protein expression in E. coli, His-tag purification, in vitro ligand-binding assays (tocopherols, phospholipids, squalene), and GTPase activity assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic and binding assays on purified recombinant protein, single lab, no mutagenesis validation of active site\",\n      \"pmids\": [\"15567179\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The human TAP3/SEC14L4 gene undergoes alternative splicing, producing an alternatively spliced cDNA isoform, and contains a polymorphism within its coding region. The encoded protein belongs to the SEC14p-like family implicated in intracellular lipid transport.\",\n      \"method\": \"cDNA isolation, sequencing, and characterization of alternative splice variants and coding-region polymorphism\",\n      \"journal\": \"Molecular biology reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single molecular characterization method (sequencing/cloning), no functional assay linking splice variant to activity\",\n      \"pmids\": [\"20012369\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"SEC14L4 directly interacts with DDX3X (identified by Co-IP and mass spectrometry) and inhibits RNF39-mediated ubiquitination and proteasomal degradation of DDX3X in esophageal squamous cell carcinoma cells. SEC14L4 loss-of-function reduces ESCC cell proliferation, migration, and colony formation while promoting apoptosis; these effects are rescued by DDX3X overexpression, placing SEC14L4 upstream of DDX3X in a pathway that activates MAPK signaling and suppresses ferroptosis.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, ubiquitination assays, Western blot (MAPK pathway and ferroptosis markers), cell proliferation/migration/apoptosis assays with knockdown and overexpression, in vivo xenograft tumor models\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with MS confirmation, ubiquitination assay, multiple orthogonal functional readouts in single lab; no independent replication\",\n      \"pmids\": [\"41741625\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SEC14L4 (TAP3) is a SEC14p-like lipid/tocopherol-binding protein with intrinsic GTPase activity; in cancer cells it directly binds and stabilizes DDX3X by blocking RNF39-mediated ubiquitination and degradation, thereby activating MAPK signaling and suppressing ferroptosis to promote tumor growth.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SEC14L4 (TAP3) is a SEC14p-like protein that combines lipid/tocopherol binding with a role in stabilizing an RNA helicase to drive tumor cell growth [#0, #2]. As a recombinant protein it binds alpha-, beta-, gamma-, and delta-tocopherol, select phospholipids, and squalene, and exhibits intrinsic GTPase activity comparable to Rab-family small GTP-binding proteins, with GTPase-related motifs spatially positioned to form a functional GTP-binding and hydrolysis site [#0]. In esophageal squamous cell carcinoma, SEC14L4 directly interacts with DDX3X and blocks RNF39-mediated ubiquitination and proteasomal degradation of DDX3X, thereby stabilizing it; this places SEC14L4 upstream of DDX3X in a pathway that activates MAPK signaling and suppresses ferroptosis, and loss of SEC14L4 reduces proliferation, migration, and colony formation while promoting apoptosis in a manner rescued by DDX3X overexpression [#2]. Beyond these biochemical and oncogenic activities, the mechanistic integration of SEC14L4's lipid-binding and GTPase functions with its DDX3X-stabilizing role has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Established the biochemical identity of SEC14L4 as a SEC14p-like ligand-binding protein that also carries intrinsic GTPase activity, defining two candidate molecular activities for an otherwise uncharacterized protein.\",\n      \"evidence\": \"Recombinant protein expressed in E. coli, purified, and assayed for tocopherol/phospholipid/squalene binding and GTP hydrolysis in vitro\",\n      \"pmids\": [\n        \"15567179\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No mutagenesis confirming the proposed GTPase active site\",\n        \"In vitro binding does not establish a physiological lipid ligand or cellular GTPase function\",\n        \"No cellular localization or pathway context\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Documented gene-level complexity of human TAP3/SEC14L4, showing alternative splicing and a coding-region polymorphism, but did not link any variant to function.\",\n      \"evidence\": \"cDNA isolation, sequencing, and characterization of splice variants and polymorphism\",\n      \"pmids\": [\n        \"20012369\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No functional assay connecting splice variant or polymorphism to protein activity\",\n        \"Single molecular characterization method\",\n        \"No phenotypic consequence established\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defined a cellular and oncogenic mechanism in which SEC14L4 stabilizes DDX3X by protecting it from RNF39-mediated degradation, linking SEC14L4 to MAPK activation and ferroptosis suppression in cancer.\",\n      \"evidence\": \"Reciprocal Co-IP with mass spectrometry, ubiquitination assays, MAPK/ferroptosis marker Western blots, knockdown/overexpression proliferation-migration-apoptosis assays, and xenograft models in ESCC cells\",\n      \"pmids\": [\n        \"41741625\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No independent replication beyond a single lab\",\n        \"How the 2005 lipid-binding/GTPase activities relate to DDX3X stabilization is unresolved\",\n        \"Direct interface mapping of the SEC14L4–DDX3X interaction not performed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether SEC14L4's lipid/tocopherol binding and GTPase activity mechanistically contribute to its DDX3X-stabilizing, pro-tumorigenic role, and whether this function extends beyond esophageal squamous cell carcinoma, remain open.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of the SEC14L4–DDX3X complex\",\n        \"No demonstration that GTPase activity is required for DDX3X stabilization\",\n        \"Physiological (non-cancer) role uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0008289\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      },\n      {\n        \"term_id\": \"GO:0003924\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\n      \"DDX3X\",\n      \"RNF39\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}