{"gene":"SEC14L1","run_date":"2026-06-10T07:46:30","timeline":{"discoveries":[{"year":2013,"finding":"SEC14L1 acts as a negative regulator of RIG-I-mediated antiviral signaling by directly interacting with the RIG-I CARD domain and competing with VISA/MAVS/IPS-1/Cardif for RIG-I-CARD binding, thereby preventing downstream IFN-β production. The PRELI-MSF1 and CRAL-TRIO domains (but not the GOLD domain) of SEC14L1 are required for this interaction and inhibitory function.","method":"Yeast two-hybrid screening, co-immunoprecipitation (endogenous and transfected), overexpression and knockdown (HEK293T and HT1080 cells), IFN-β promoter reporter assays, domain mapping, viral replication assays (Newcastle disease virus, Sendai virus)","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP (endogenous and overexpressed), domain mapping with deletion mutants, knockdown with functional readout (IFN-β production and viral replication), multiple orthogonal methods in a single focused study","pmids":["23843640"],"is_preprint":false},{"year":2006,"finding":"SEC14L1 interacts with the vesicular acetylcholine transporter (VAChT) via its GOLD domain, as determined by yeast two-hybrid and confirmed in mammalian cells by co-immunoprecipitation. SEC14L1 also co-immunoprecipitates with the high-affinity choline transporter (CHT1) but not with synaptophysin or synaptotagmin. Overexpression of VAChT or CHT1 recruits cytosolic SEC14L1 to large intracellular vesicle-like organelles. Overexpression of SEC14L1 modestly decreases high-affinity choline transport activity.","method":"Yeast two-hybrid screening of brain cDNA library, co-immunoprecipitation in mammalian cells, domain mapping (GOLD domain requirement), fluorescence localization in cultured cells, choline uptake assay","journal":"Neurochemistry international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and domain mapping with functional transport assay, single lab, multiple orthogonal methods","pmids":["17092608"],"is_preprint":false},{"year":1996,"finding":"SEC14L1 (then designated SEC14L) encodes a 715-amino-acid protein with partial homology to yeast SEC14 and to retinal-binding protein (RALBP) of the Japanese flying squid, suggesting a role in intracellular transport. The gene was mapped to human chromosome bands 17q25.1→q25.2 by fluorescence in situ hybridization and was expressed in all human tissues examined.","method":"cDNA cloning, sequence homology analysis, fluorescence in situ hybridization (FISH), Northern blot expression analysis","journal":"Cytogenetics and cell genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — FISH mapping confirmed, sequence homology-based functional inference replicated in subsequent papers; function inferred from homology not direct biochemical assay","pmids":["8697811"],"is_preprint":false},{"year":2001,"finding":"SEC14L1 contains 18 exons spanning ≥58 kb, produces two ubiquitously expressed transcripts (5.5 kb and 3.0 kb) via alternative splicing of exon 17 (which contains a VNTR), predicting proteins of 715 and 719 residues respectively. The protein contains a CRAL/TRIO domain homologous to alpha-tocopherol transfer protein (TTPA) and cellular retinaldehyde-binding protein (CRALBP), implicating SEC14L1 in retinoid/lipid binding.","method":"Genomic sequencing, exon mapping, RT-PCR for splice variant characterization, sequence homology analysis","journal":"Mammalian genome : official journal of the International Mammalian Genome Society","confidence":"Low","confidence_rationale":"Tier 3 / Weak — structural gene characterization with domain inference from homology; no direct biochemical functional validation of CRAL/TRIO lipid binding","pmids":["11707779"],"is_preprint":false}],"current_model":"SEC14L1 is a multi-domain cytosolic protein (containing PRELI-MSF1, CRAL-TRIO, and GOLD domains) that negatively regulates RIG-I-mediated innate antiviral signaling by binding the RIG-I CARD domain via its PRELI-MSF1 and CRAL-TRIO domains, competing with the adaptor MAVS/VISA for RIG-I interaction; it also interacts with cholinergic vesicular transporters (VAChT via its GOLD domain, and CHT1), modestly reducing choline transport activity and redistributing from cytosol to vesicular compartments upon transporter co-expression."},"narrative":{"mechanistic_narrative":"SEC14L1 is a multi-domain cytosolic protein that functions as a negative regulator of RIG-I-mediated innate antiviral signaling [PMID:23843640]. It directly binds the RIG-I CARD domain through its PRELI-MSF1 and CRAL-TRIO domains and competes with the adaptor VISA/MAVS for RIG-I association, thereby dampening downstream IFN-β production and restraining the antiviral response to RNA virus infection [PMID:23843640]. Independently, SEC14L1 engages the cholinergic vesicular machinery: its GOLD domain mediates interaction with the vesicular acetylcholine transporter VAChT, and it co-precipitates with the high-affinity choline transporter CHT1; co-expression of these transporters recruits cytosolic SEC14L1 to vesicle-like organelles, and SEC14L1 overexpression modestly reduces high-affinity choline transport [PMID:17092608]. The protein's CRAL/TRIO domain shows homology to lipid/retinoid-binding proteins, but a direct lipid-transfer activity has not been demonstrated in the available corpus [PMID:8697811, PMID:11707779].","teleology":[{"year":1996,"claim":"Establishing the gene's existence and a candidate role: cloning revealed a SEC14-homologous protein, framing SEC14L1 as a putative intracellular transport factor before any biochemical function was known.","evidence":"cDNA cloning, sequence homology analysis, FISH mapping to 17q25, and Northern blot expression survey","pmids":["8697811"],"confidence":"Medium","gaps":["Function inferred from homology only, not from direct assay","No binding partner or substrate identified","No subcellular localization established"]},{"year":2001,"claim":"Defining the gene structure and domain content: identification of alternatively spliced transcripts and a CRAL/TRIO domain homologous to TTPA and CRALBP suggested a retinoid/lipid-binding capacity.","evidence":"Genomic sequencing, exon mapping, RT-PCR splice variant analysis, sequence homology","pmids":["11707779"],"confidence":"Low","gaps":["CRAL/TRIO lipid-binding activity inferred from homology, not biochemically validated","Functional significance of the exon 17 VNTR splice variation unknown"]},{"year":2006,"claim":"Linking SEC14L1 to cholinergic vesicular transport: it was shown to bind VAChT via its GOLD domain and to associate with CHT1, with transporter co-expression redistributing it to vesicles and reducing choline uptake.","evidence":"Yeast two-hybrid of brain cDNA library, reciprocal Co-IP in mammalian cells, GOLD-domain mapping, fluorescence localization, choline uptake assay","pmids":["17092608"],"confidence":"Medium","gaps":["Mechanism by which SEC14L1 reduces choline transport not defined","Physiological relevance in neurons not tested","Single-lab finding"]},{"year":2013,"claim":"Assigning a defined signaling function: SEC14L1 was shown to negatively regulate RIG-I antiviral signaling by binding the RIG-I CARD domain and competing with the adaptor VISA/MAVS, establishing a molecular mechanism for dampening IFN-β induction.","evidence":"Yeast two-hybrid, reciprocal endogenous and transfected Co-IP, domain mapping, knockdown/overexpression with IFN-β reporter and viral replication readouts (NDV, Sendai virus) in HEK293T and HT1080","pmids":["23843640"],"confidence":"High","gaps":["Structural basis of CARD competition not resolved","Whether lipid binding by CRAL-TRIO contributes to RIG-I regulation unknown","In vivo relevance in immune cells/animals not tested"]},{"year":null,"claim":"Whether the cholinergic transport role and the RIG-I regulatory role reflect a single unifying biochemical activity (e.g., lipid/cargo binding by its CRAL-TRIO/GOLD domains) remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No demonstrated lipid ligand for the CRAL-TRIO domain","No mechanistic link connecting transporter binding and innate immune signaling"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0]}],"complexes":[],"partners":["DDX58","VACHT","CHT1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q92503","full_name":"SEC14-like protein 1","aliases":[],"length_aa":715,"mass_kda":81.2,"function":"May play a role in innate immunity by inhibiting the antiviral RIG-I signaling pathway. In this pathway, functions as a negative regulator of RIGI, the cytoplasmic sensor of viral nucleic acids. Prevents the interaction of RIGI with MAVS/IPS1, an important step in signal propagation (PubMed:23843640). May also regulate the SLC18A3 and SLC5A7 cholinergic transporters (PubMed:17092608)","subcellular_location":"Cytoplasm; Golgi apparatus","url":"https://www.uniprot.org/uniprotkb/Q92503/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SEC14L1","classification":"Not Classified","n_dependent_lines":15,"n_total_lines":1208,"dependency_fraction":0.012417218543046357},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000129657","cell_line_id":"CID000282","localizations":[{"compartment":"cell_contact","grade":3},{"compartment":"membrane","grade":3},{"compartment":"cytoplasmic","grade":1},{"compartment":"nucleoplasm","grade":1}],"interactors":[{"gene":"PGAM1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000282","total_profiled":1310},"omim":[{"mim_id":"619412","title":"SEC14-LIKE LIPID-BINDING PROTEIN 5; SEC14L5","url":"https://www.omim.org/entry/619412"},{"mim_id":"604061","title":"SEPTIN 9; SEPTIN9","url":"https://www.omim.org/entry/604061"},{"mim_id":"601504","title":"SEC14-LIKE LIPID-BINDING PROTEIN 1; SEC14L1","url":"https://www.omim.org/entry/601504"},{"mim_id":"162100","title":"AMYOTROPHY, HEREDITARY NEURALGIC; HNA","url":"https://www.omim.org/entry/162100"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SEC14L1"},"hgnc":{"alias_symbol":["PRELID4A"],"prev_symbol":["SEC14L"]},"alphafold":{"accession":"Q92503","domains":[{"cath_id":"3.30.530.20","chopping":"3-174","consensus_level":"high","plddt":89.6703,"start":3,"end":174},{"cath_id":"1.10.8.20","chopping":"238-309","consensus_level":"medium","plddt":88.2676,"start":238,"end":309},{"cath_id":"3.40.525.10","chopping":"312-505","consensus_level":"high","plddt":91.5739,"start":312,"end":505},{"cath_id":"2.60.120.680","chopping":"525-572_593-642_665-688","consensus_level":"medium","plddt":81.3877,"start":525,"end":688}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92503","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q92503-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q92503-F1-predicted_aligned_error_v6.png","plddt_mean":76.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SEC14L1","jax_strain_url":"https://www.jax.org/strain/search?query=SEC14L1"},"sequence":{"accession":"Q92503","fasta_url":"https://rest.uniprot.org/uniprotkb/Q92503.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q92503/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92503"}},"corpus_meta":[{"pmid":"16859891","id":"PMC_16859891","title":"Linkage disequilibrium mapping in domestic dog breeds narrows the progressive rod-cone degeneration interval and identifies ancestral disease-transmitting chromosome.","date":"2006","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/16859891","citation_count":58,"is_preprint":false},{"pmid":"23843640","id":"PMC_23843640","title":"Negative regulation of RIG-I-mediated innate antiviral signaling by SEC14L1.","date":"2013","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/23843640","citation_count":34,"is_preprint":false},{"pmid":"23676757","id":"PMC_23676757","title":"Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India.","date":"2013","source":"Genes and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/23676757","citation_count":33,"is_preprint":false},{"pmid":"8697811","id":"PMC_8697811","title":"Isolation and mapping of a human gene (SEC14L), partially homologous to yeast SEC14, that contains a variable number of tandem repeats (VNTR) site in its 3' untranslated region.","date":"1996","source":"Cytogenetics and cell genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8697811","citation_count":27,"is_preprint":false},{"pmid":"10191081","id":"PMC_10191081","title":"An integrated physical and gene map of human distal chromosome 17q24-proximal 17q25 encompassing multiple disease loci.","date":"1999","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/10191081","citation_count":25,"is_preprint":false},{"pmid":"17092608","id":"PMC_17092608","title":"SEC14-like protein 1 interacts with cholinergic transporters.","date":"2006","source":"Neurochemistry international","url":"https://pubmed.ncbi.nlm.nih.gov/17092608","citation_count":22,"is_preprint":false},{"pmid":"11707779","id":"PMC_11707779","title":"Genomic characterization of human SEC14L1 splice variants within a 17q25 candidate tumor suppressor gene region and identification of an unrelated embedded expressed sequence tag.","date":"2001","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/11707779","citation_count":21,"is_preprint":false},{"pmid":"37255567","id":"PMC_37255567","title":"Role of SEC14-like phosphatidylinositol transfer proteins in membrane identity and dynamics.","date":"2023","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/37255567","citation_count":20,"is_preprint":false},{"pmid":"32915352","id":"PMC_32915352","title":"Phylogenetic analysis of plant multi-domain SEC14-like phosphatidylinositol transfer proteins and structure-function properties of PATELLIN2.","date":"2020","source":"Plant molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/32915352","citation_count":17,"is_preprint":false},{"pmid":"25701228","id":"PMC_25701228","title":"Saccharomyces cerevisiae-like 1 overexpression is frequent in prostate cancer and has markedly different effects in Ets-related gene fusion-positive and fusion-negative cancers.","date":"2014","source":"Human pathology","url":"https://pubmed.ncbi.nlm.nih.gov/25701228","citation_count":9,"is_preprint":false},{"pmid":"24739497","id":"PMC_24739497","title":"Concordant or discordant results by the tuberculin skin test and the quantiFERON-TB test in children reflect immune biomarker profiles.","date":"2014","source":"Genes and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/24739497","citation_count":8,"is_preprint":false},{"pmid":"35581286","id":"PMC_35581286","title":"Identification of candidate genes associated with bacterial and viral infections in wild boars hunted in Tuscany (Italy).","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/35581286","citation_count":7,"is_preprint":false},{"pmid":"35283446","id":"PMC_35283446","title":"Evaluation of Saccharomyces cerevisiae -like 1 (SEC14L1) in Gynecologic Malignancies Shows Overexpression in Endometrial Serous Carcinoma.","date":"2022","source":"International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists","url":"https://pubmed.ncbi.nlm.nih.gov/35283446","citation_count":5,"is_preprint":false},{"pmid":"39061594","id":"PMC_39061594","title":"Transcriptomic Analysis Reveals the Effects of miR-122 Overexpression in the Liver of Qingyuan Partridge Chickens.","date":"2024","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/39061594","citation_count":2,"is_preprint":false},{"pmid":"38146067","id":"PMC_38146067","title":"Diffuse CNS cortical vein malformations with chromosome 17q microduplication: Possible link to SEC14L1.","date":"2023","source":"Journal of cerebrovascular and endovascular neurosurgery","url":"https://pubmed.ncbi.nlm.nih.gov/38146067","citation_count":1,"is_preprint":false},{"pmid":"39164264","id":"PMC_39164264","title":"Haplotype analysis identifies functional elements in 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The PRELI-MSF1 and CRAL-TRIO domains (but not the GOLD domain) of SEC14L1 are required for this interaction and inhibitory function.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation (endogenous and transfected), overexpression and knockdown (HEK293T and HT1080 cells), IFN-β promoter reporter assays, domain mapping, viral replication assays (Newcastle disease virus, Sendai virus)\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP (endogenous and overexpressed), domain mapping with deletion mutants, knockdown with functional readout (IFN-β production and viral replication), multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"23843640\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"SEC14L1 interacts with the vesicular acetylcholine transporter (VAChT) via its GOLD domain, as determined by yeast two-hybrid and confirmed in mammalian cells by co-immunoprecipitation. SEC14L1 also co-immunoprecipitates with the high-affinity choline transporter (CHT1) but not with synaptophysin or synaptotagmin. Overexpression of VAChT or CHT1 recruits cytosolic SEC14L1 to large intracellular vesicle-like organelles. Overexpression of SEC14L1 modestly decreases high-affinity choline transport activity.\",\n      \"method\": \"Yeast two-hybrid screening of brain cDNA library, co-immunoprecipitation in mammalian cells, domain mapping (GOLD domain requirement), fluorescence localization in cultured cells, choline uptake assay\",\n      \"journal\": \"Neurochemistry international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and domain mapping with functional transport assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"17092608\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"SEC14L1 (then designated SEC14L) encodes a 715-amino-acid protein with partial homology to yeast SEC14 and to retinal-binding protein (RALBP) of the Japanese flying squid, suggesting a role in intracellular transport. The gene was mapped to human chromosome bands 17q25.1→q25.2 by fluorescence in situ hybridization and was expressed in all human tissues examined.\",\n      \"method\": \"cDNA cloning, sequence homology analysis, fluorescence in situ hybridization (FISH), Northern blot expression analysis\",\n      \"journal\": \"Cytogenetics and cell genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — FISH mapping confirmed, sequence homology-based functional inference replicated in subsequent papers; function inferred from homology not direct biochemical assay\",\n      \"pmids\": [\"8697811\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"SEC14L1 contains 18 exons spanning ≥58 kb, produces two ubiquitously expressed transcripts (5.5 kb and 3.0 kb) via alternative splicing of exon 17 (which contains a VNTR), predicting proteins of 715 and 719 residues respectively. The protein contains a CRAL/TRIO domain homologous to alpha-tocopherol transfer protein (TTPA) and cellular retinaldehyde-binding protein (CRALBP), implicating SEC14L1 in retinoid/lipid binding.\",\n      \"method\": \"Genomic sequencing, exon mapping, RT-PCR for splice variant characterization, sequence homology analysis\",\n      \"journal\": \"Mammalian genome : official journal of the International Mammalian Genome Society\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — structural gene characterization with domain inference from homology; no direct biochemical functional validation of CRAL/TRIO lipid binding\",\n      \"pmids\": [\"11707779\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SEC14L1 is a multi-domain cytosolic protein (containing PRELI-MSF1, CRAL-TRIO, and GOLD domains) that negatively regulates RIG-I-mediated innate antiviral signaling by binding the RIG-I CARD domain via its PRELI-MSF1 and CRAL-TRIO domains, competing with the adaptor MAVS/VISA for RIG-I interaction; it also interacts with cholinergic vesicular transporters (VAChT via its GOLD domain, and CHT1), modestly reducing choline transport activity and redistributing from cytosol to vesicular compartments upon transporter co-expression.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SEC14L1 is a multi-domain cytosolic protein that functions as a negative regulator of RIG-I-mediated innate antiviral signaling [#0]. It directly binds the RIG-I CARD domain through its PRELI-MSF1 and CRAL-TRIO domains and competes with the adaptor VISA/MAVS for RIG-I association, thereby dampening downstream IFN-\\u03b2 production and restraining the antiviral response to RNA virus infection [#0]. Independently, SEC14L1 engages the cholinergic vesicular machinery: its GOLD domain mediates interaction with the vesicular acetylcholine transporter VAChT, and it co-precipitates with the high-affinity choline transporter CHT1; co-expression of these transporters recruits cytosolic SEC14L1 to vesicle-like organelles, and SEC14L1 overexpression modestly reduces high-affinity choline transport [#1]. The protein's CRAL/TRIO domain shows homology to lipid/retinoid-binding proteins, but a direct lipid-transfer activity has not been demonstrated in the available corpus [#2, #3].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Establishing the gene's existence and a candidate role: cloning revealed a SEC14-homologous protein, framing SEC14L1 as a putative intracellular transport factor before any biochemical function was known.\",\n      \"evidence\": \"cDNA cloning, sequence homology analysis, FISH mapping to 17q25, and Northern blot expression survey\",\n      \"pmids\": [\"8697811\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Function inferred from homology only, not from direct assay\",\n        \"No binding partner or substrate identified\",\n        \"No subcellular localization established\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Defining the gene structure and domain content: identification of alternatively spliced transcripts and a CRAL/TRIO domain homologous to TTPA and CRALBP suggested a retinoid/lipid-binding capacity.\",\n      \"evidence\": \"Genomic sequencing, exon mapping, RT-PCR splice variant analysis, sequence homology\",\n      \"pmids\": [\"11707779\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"CRAL/TRIO lipid-binding activity inferred from homology, not biochemically validated\",\n        \"Functional significance of the exon 17 VNTR splice variation unknown\"\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Linking SEC14L1 to cholinergic vesicular transport: it was shown to bind VAChT via its GOLD domain and to associate with CHT1, with transporter co-expression redistributing it to vesicles and reducing choline uptake.\",\n      \"evidence\": \"Yeast two-hybrid of brain cDNA library, reciprocal Co-IP in mammalian cells, GOLD-domain mapping, fluorescence localization, choline uptake assay\",\n      \"pmids\": [\"17092608\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which SEC14L1 reduces choline transport not defined\",\n        \"Physiological relevance in neurons not tested\",\n        \"Single-lab finding\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Assigning a defined signaling function: SEC14L1 was shown to negatively regulate RIG-I antiviral signaling by binding the RIG-I CARD domain and competing with the adaptor VISA/MAVS, establishing a molecular mechanism for dampening IFN-\\u03b2 induction.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal endogenous and transfected Co-IP, domain mapping, knockdown/overexpression with IFN-\\u03b2 reporter and viral replication readouts (NDV, Sendai virus) in HEK293T and HT1080\",\n      \"pmids\": [\"23843640\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of CARD competition not resolved\",\n        \"Whether lipid binding by CRAL-TRIO contributes to RIG-I regulation unknown\",\n        \"In vivo relevance in immune cells/animals not tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the cholinergic transport role and the RIG-I regulatory role reflect a single unifying biochemical activity (e.g., lipid/cargo binding by its CRAL-TRIO/GOLD domains) remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No demonstrated lipid ligand for the CRAL-TRIO domain\",\n        \"No mechanistic link connecting transporter binding and innate immune signaling\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"DDX58\", \"VAChT\", \"CHT1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}