{"gene":"GOLT1B","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2021,"finding":"GOLT1B promotes plasma membrane translocation of DVL2, which activates downstream Wnt/β-catenin signaling and increases nuclear β-catenin levels, thereby inducing epithelial-mesenchymal transition (EMT) in colorectal cancer cells.","method":"Overexpression/knockdown in CRC cell lines with subcellular fractionation/confocal imaging for membrane translocation, western blot for β-catenin pathway activation, in vivo xenograft model","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — multiple orthogonal methods (overexpression, KD, membrane fractionation, pathway readouts, in vivo), single lab","pmids":["34059062"],"is_preprint":false},{"year":2021,"finding":"GOLT1B interacts with PD-L2 and increases its cell surface membrane localization in colorectal cancer cells, leading to T cell apoptosis in co-culture assays.","method":"Co-immunoprecipitation/interaction assay, flow cytometry for membrane PD-L2 levels, co-culture with Jurkat T cells measuring apoptosis","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-IP for interaction plus functional T cell apoptosis readout, single lab, two orthogonal methods","pmids":["34059062"],"is_preprint":false},{"year":2021,"finding":"GOLT1B expression is induced during the unfolded protein response (ER stress), and its presence is essential for efficient hepatitis C virus (HCV) replication in hepatocytes, linking ER-Golgi trafficking to viral replication.","method":"RNAseq of laser-microdissected HCV-infected vs. uninfected hepatocytes, siRNA knockdown of GOLT1B with measurement of HCV replication levels, UPR induction assays","journal":"Pathogens (Basel, Switzerland)","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — single lab, gene expression plus functional KD with viral replication readout and UPR induction assay","pmids":["35055994"],"is_preprint":false},{"year":2020,"finding":"The C. elegans ortholog eas-1/GOLT1B is a conserved cis-Golgi membrane protein that negatively regulates glial cell growth by inhibiting the E3 ubiquitin ligase rnf-145/RNF145; at adult stage, eas-1-dependent shuttling of rnf-145 from cis-Golgi to trans-Golgi network releases inhibition of nuclear SREBP (sbp-1) activation, thereby controlling fatty acid synthesis and stopping glial growth.","method":"C. elegans genetics (loss-of-function mutants), epistasis analysis, fluorescent protein tagging with live imaging for subcellular localization (cis- vs trans-Golgi), fatty acid (EPA) supplementation rescue experiments","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (genetics, epistasis, live imaging, biochemical rescue), replicated across multiple alleles in a single rigorous study","pmids":["33370778"],"is_preprint":false},{"year":2025,"finding":"GOLT1B interacts with TANK-binding kinase 1 (TBK1) and activates the NF-κB signaling pathway in cervical squamous cell carcinoma cells, promoting cancer cell viability and migration.","method":"Co-immunoprecipitation for GOLT1B–TBK1 interaction, western blot for NF-κB pathway components, dual luciferase reporter assay for NF-κB transcriptional activity, in vitro functional assays (viability, migration), in vivo tumor model","journal":"Carcinogenesis","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — co-IP plus dual luciferase reporter plus functional assays, single lab, multiple orthogonal methods","pmids":["39113410"],"is_preprint":false}],"current_model":"GOLT1B is a cis-Golgi vesicle transport protein that regulates cell surface trafficking of specific cargo (DVL2, PD-L2) to activate Wnt/β-catenin and immune checkpoint signaling, interacts with TBK1 to modulate NF-κB activity, is required for efficient HCV replication through its ER-Golgi trafficking function, and (based on its C. elegans ortholog) controls cell growth by regulating RNF145/SREBP-mediated lipid synthesis through Golgi-compartment shuttling."},"narrative":{"mechanistic_narrative":"GOLT1B is a conserved cis-Golgi membrane protein that controls the trafficking and surface delivery of specific cargo to regulate signaling outputs governing cell growth, proliferation, and immune evasion [PMID:33370778, PMID:34059062]. Genetics in the C. elegans ortholog eas-1 establish its core mechanism: cis-Golgi GOLT1B drives shuttling of the E3 ubiquitin ligase RNF145 from the cis-Golgi to the trans-Golgi network, releasing inhibition of nuclear SREBP activation and thereby controlling fatty acid synthesis and arresting glial cell growth [PMID:33370778]. In human cancer cells GOLT1B promotes plasma-membrane translocation of DVL2 to activate Wnt/β-catenin signaling and drive epithelial-mesenchymal transition [PMID:34059062], and it binds and increases surface localization of the checkpoint ligand PD-L2 to induce T cell apoptosis [PMID:34059062]. GOLT1B also interacts with TBK1 to activate NF-κB-dependent transcription, enhancing cancer cell viability and migration [PMID:39113410]. Its ER-Golgi trafficking function is co-opted during the unfolded protein response, where GOLT1B is induced and is required for efficient hepatitis C virus replication [PMID:35055994].","teleology":[{"year":2020,"claim":"The fundamental molecular role of GOLT1B was unknown; ortholog genetics established it as a cis-Golgi protein that gates intra-Golgi shuttling of an E3 ligase to control SREBP-driven lipid synthesis and cell growth.","evidence":"C. elegans loss-of-function genetics, epistasis, live imaging of cis- vs trans-Golgi localization, and fatty acid supplementation rescue","pmids":["33370778"],"confidence":"High","gaps":["Whether the human GOLT1B–RNF145–SREBP axis operates identically in mammalian cells is not demonstrated in this study","Direct biochemical mechanism by which GOLT1B drives RNF145 shuttling is not resolved","No structural model of GOLT1B cargo engagement"]},{"year":2021,"claim":"Whether GOLT1B influences oncogenic signaling was unknown; it was shown to traffic DVL2 to the plasma membrane, activating Wnt/β-catenin and EMT, linking Golgi transport to colorectal cancer progression.","evidence":"Overexpression/knockdown in CRC cell lines with subcellular fractionation, confocal imaging, β-catenin pathway western blots, and xenograft model","pmids":["34059062"],"confidence":"Medium","gaps":["Whether GOLT1B directly binds DVL2 or acts indirectly is not established","Single lab; mechanism of cargo selectivity unknown"]},{"year":2021,"claim":"It was unknown whether GOLT1B contributes to tumor immune evasion; it was found to interact with PD-L2 and elevate its surface levels, driving T cell apoptosis.","evidence":"Co-immunoprecipitation, flow cytometry for membrane PD-L2, and Jurkat T cell co-culture apoptosis assay","pmids":["34059062"],"confidence":"Medium","gaps":["Co-IP without reciprocal validation or mapping of interaction interface","In vivo relevance to immune checkpoint suppression not tested"]},{"year":2022,"claim":"Whether GOLT1B participates in viral infection was unknown; its induction during ER stress and requirement for HCV replication tied its ER-Golgi trafficking role to the viral life cycle.","evidence":"RNAseq of laser-microdissected HCV-infected hepatocytes, siRNA knockdown with HCV replication readout, and UPR induction assays","pmids":["35055994"],"confidence":"Medium","gaps":["Specific trafficking step or viral cargo dependent on GOLT1B not identified","Mechanistic link between UPR induction and replication requirement unresolved"]},{"year":2025,"claim":"A further signaling input was unknown; GOLT1B was shown to interact with TBK1 and activate NF-κB transcription, promoting cervical carcinoma viability and migration.","evidence":"Co-IP for GOLT1B–TBK1 interaction, NF-κB dual luciferase reporter, functional viability/migration assays, and in vivo tumor model","pmids":["39113410"],"confidence":"Medium","gaps":["Whether GOLT1B regulates TBK1 kinase activity or simply scaffolds it is unknown","Single lab; interaction not independently confirmed"]},{"year":null,"claim":"How GOLT1B selects among its diverse reported cargo (DVL2, PD-L2, RNF145) and whether a single Golgi-shuttling mechanism underlies all its signaling roles remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unifying biochemical model connecting cargo trafficking to the multiple downstream pathways","No structural characterization of GOLT1B cargo recognition","Conservation of the RNF145/SREBP axis in human cells not demonstrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[0,1,3]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[3]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,3]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,4]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1]}],"complexes":[],"partners":["DVL2","PD-L2","TBK1","RNF145"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y3E0","full_name":"Vesicle transport protein GOT1B","aliases":["Germ cell tumor 2","Golgi transport 1 homolog B","Putative NF-kappa-B-activating protein 470","hGOT1a"],"length_aa":138,"mass_kda":15.4,"function":"May be involved in fusion of ER-derived transport vesicles with the Golgi complex","subcellular_location":"Golgi apparatus membrane","url":"https://www.uniprot.org/uniprotkb/Q9Y3E0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GOLT1B","classification":"Not Classified","n_dependent_lines":166,"n_total_lines":1208,"dependency_fraction":0.13741721854304637},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000111711","cell_line_id":"CID001654","localizations":[{"compartment":"golgi","grade":3},{"compartment":"er","grade":2},{"compartment":"vesicles","grade":2}],"interactors":[{"gene":"RTN3","stoichiometry":10.0},{"gene":"NSF","stoichiometry":10.0},{"gene":"SCFD1","stoichiometry":10.0},{"gene":"TMEM33","stoichiometry":4.0},{"gene":"BNIP1","stoichiometry":4.0},{"gene":"RABAC1","stoichiometry":0.2},{"gene":"ZW10","stoichiometry":0.2},{"gene":"PGRMC2","stoichiometry":0.2},{"gene":"BCAP31","stoichiometry":0.2},{"gene":"NBAS","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001654","total_profiled":1310},"omim":[{"mim_id":"620633","title":"GOLGI TRANSPORT 1A; GOLT1A","url":"https://www.omim.org/entry/620633"},{"mim_id":"615078","title":"GOLGI TRANSPORT 1B; GOLT1B","url":"https://www.omim.org/entry/615078"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GOLT1B"},"hgnc":{"alias_symbol":["CGI-141","YMR292W","GOT1"],"prev_symbol":[]},"alphafold":{"accession":"Q9Y3E0","domains":[{"cath_id":"1.10.287","chopping":"1-60","consensus_level":"medium","plddt":91.1885,"start":1,"end":60}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y3E0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y3E0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y3E0-F1-predicted_aligned_error_v6.png","plddt_mean":88.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GOLT1B","jax_strain_url":"https://www.jax.org/strain/search?query=GOLT1B"},"sequence":{"accession":"Q9Y3E0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y3E0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y3E0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y3E0"}},"corpus_meta":[{"pmid":"38130634","id":"PMC_38130634","title":"A pan-cancer analysis of the oncogenic role of Golgi transport 1B in human tumors.","date":"2023","source":"Journal of translational internal medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38130634","citation_count":27,"is_preprint":false},{"pmid":"34059062","id":"PMC_34059062","title":"Vesicle transporter GOLT1B mediates the cell membrane localization of DVL2 and PD-L2 and promotes colorectal cancer metastasis.","date":"2021","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/34059062","citation_count":16,"is_preprint":false},{"pmid":"38982223","id":"PMC_38982223","title":"Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis.","date":"2024","source":"Journal of molecular cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/38982223","citation_count":7,"is_preprint":false},{"pmid":"33370778","id":"PMC_33370778","title":"Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism.","date":"2020","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/33370778","citation_count":7,"is_preprint":false},{"pmid":"37995913","id":"PMC_37995913","title":"Comprehensive Genomic Analysis of Cemento-Ossifying Fibroma.","date":"2023","source":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","url":"https://pubmed.ncbi.nlm.nih.gov/37995913","citation_count":6,"is_preprint":false},{"pmid":"37679009","id":"PMC_37679009","title":"Mosaicism for a 12p12.1p12.2 microdeletion with a normal euploid cell line at amniocentesis in a pregnancy with a favorable outcome and postnatal decrease of the aneuploid cell line with microdeletion.","date":"2023","source":"Taiwanese journal of obstetrics & gynecology","url":"https://pubmed.ncbi.nlm.nih.gov/37679009","citation_count":5,"is_preprint":false},{"pmid":"35055994","id":"PMC_35055994","title":"GOLT1B Activation in Hepatitis C Virus-Infected Hepatocytes Links ER Trafficking and Viral Replication.","date":"2021","source":"Pathogens (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/35055994","citation_count":3,"is_preprint":false},{"pmid":"37460698","id":"PMC_37460698","title":"Important roles of Hif1a in maternal or adult BPA exposure induced pancreatic injuries.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/37460698","citation_count":3,"is_preprint":false},{"pmid":"40412277","id":"PMC_40412277","title":"LncRNA SNHG12 promotes EMT and metastasis of colorectal cancer via regulating TGF-β/Smad2/3 signaling pathway.","date":"2025","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40412277","citation_count":2,"is_preprint":false},{"pmid":"39113410","id":"PMC_39113410","title":"Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating the NF-kappaB signaling pathway via interaction with TANK-Binding Kinase 1.","date":"2025","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/39113410","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7988,"output_tokens":1324,"usd":0.021912,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8013,"output_tokens":2326,"usd":0.049107,"stage2_stop_reason":"end_turn"},"total_usd":0.071019,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"GOLT1B promotes plasma membrane translocation of DVL2, which activates downstream Wnt/β-catenin signaling and increases nuclear β-catenin levels, thereby inducing epithelial-mesenchymal transition (EMT) in colorectal cancer cells.\",\n      \"method\": \"Overexpression/knockdown in CRC cell lines with subcellular fractionation/confocal imaging for membrane translocation, western blot for β-catenin pathway activation, in vivo xenograft model\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — multiple orthogonal methods (overexpression, KD, membrane fractionation, pathway readouts, in vivo), single lab\",\n      \"pmids\": [\"34059062\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"GOLT1B interacts with PD-L2 and increases its cell surface membrane localization in colorectal cancer cells, leading to T cell apoptosis in co-culture assays.\",\n      \"method\": \"Co-immunoprecipitation/interaction assay, flow cytometry for membrane PD-L2 levels, co-culture with Jurkat T cells measuring apoptosis\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-IP for interaction plus functional T cell apoptosis readout, single lab, two orthogonal methods\",\n      \"pmids\": [\"34059062\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"GOLT1B expression is induced during the unfolded protein response (ER stress), and its presence is essential for efficient hepatitis C virus (HCV) replication in hepatocytes, linking ER-Golgi trafficking to viral replication.\",\n      \"method\": \"RNAseq of laser-microdissected HCV-infected vs. uninfected hepatocytes, siRNA knockdown of GOLT1B with measurement of HCV replication levels, UPR induction assays\",\n      \"journal\": \"Pathogens (Basel, Switzerland)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — single lab, gene expression plus functional KD with viral replication readout and UPR induction assay\",\n      \"pmids\": [\"35055994\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The C. elegans ortholog eas-1/GOLT1B is a conserved cis-Golgi membrane protein that negatively regulates glial cell growth by inhibiting the E3 ubiquitin ligase rnf-145/RNF145; at adult stage, eas-1-dependent shuttling of rnf-145 from cis-Golgi to trans-Golgi network releases inhibition of nuclear SREBP (sbp-1) activation, thereby controlling fatty acid synthesis and stopping glial growth.\",\n      \"method\": \"C. elegans genetics (loss-of-function mutants), epistasis analysis, fluorescent protein tagging with live imaging for subcellular localization (cis- vs trans-Golgi), fatty acid (EPA) supplementation rescue experiments\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (genetics, epistasis, live imaging, biochemical rescue), replicated across multiple alleles in a single rigorous study\",\n      \"pmids\": [\"33370778\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GOLT1B interacts with TANK-binding kinase 1 (TBK1) and activates the NF-κB signaling pathway in cervical squamous cell carcinoma cells, promoting cancer cell viability and migration.\",\n      \"method\": \"Co-immunoprecipitation for GOLT1B–TBK1 interaction, western blot for NF-κB pathway components, dual luciferase reporter assay for NF-κB transcriptional activity, in vitro functional assays (viability, migration), in vivo tumor model\",\n      \"journal\": \"Carcinogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — co-IP plus dual luciferase reporter plus functional assays, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"39113410\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GOLT1B is a cis-Golgi vesicle transport protein that regulates cell surface trafficking of specific cargo (DVL2, PD-L2) to activate Wnt/β-catenin and immune checkpoint signaling, interacts with TBK1 to modulate NF-κB activity, is required for efficient HCV replication through its ER-Golgi trafficking function, and (based on its C. elegans ortholog) controls cell growth by regulating RNF145/SREBP-mediated lipid synthesis through Golgi-compartment shuttling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GOLT1B is a conserved cis-Golgi membrane protein that controls the trafficking and surface delivery of specific cargo to regulate signaling outputs governing cell growth, proliferation, and immune evasion [#3, #0]. Genetics in the C. elegans ortholog eas-1 establish its core mechanism: cis-Golgi GOLT1B drives shuttling of the E3 ubiquitin ligase RNF145 from the cis-Golgi to the trans-Golgi network, releasing inhibition of nuclear SREBP activation and thereby controlling fatty acid synthesis and arresting glial cell growth [#3]. In human cancer cells GOLT1B promotes plasma-membrane translocation of DVL2 to activate Wnt/\\u03b2-catenin signaling and drive epithelial-mesenchymal transition [#0], and it binds and increases surface localization of the checkpoint ligand PD-L2 to induce T cell apoptosis [#1]. GOLT1B also interacts with TBK1 to activate NF-\\u03baB-dependent transcription, enhancing cancer cell viability and migration [#4]. Its ER-Golgi trafficking function is co-opted during the unfolded protein response, where GOLT1B is induced and is required for efficient hepatitis C virus replication [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"The fundamental molecular role of GOLT1B was unknown; ortholog genetics established it as a cis-Golgi protein that gates intra-Golgi shuttling of an E3 ligase to control SREBP-driven lipid synthesis and cell growth.\",\n      \"evidence\": \"C. elegans loss-of-function genetics, epistasis, live imaging of cis- vs trans-Golgi localization, and fatty acid supplementation rescue\",\n      \"pmids\": [\"33370778\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the human GOLT1B\\u2013RNF145\\u2013SREBP axis operates identically in mammalian cells is not demonstrated in this study\",\n        \"Direct biochemical mechanism by which GOLT1B drives RNF145 shuttling is not resolved\",\n        \"No structural model of GOLT1B cargo engagement\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether GOLT1B influences oncogenic signaling was unknown; it was shown to traffic DVL2 to the plasma membrane, activating Wnt/\\u03b2-catenin and EMT, linking Golgi transport to colorectal cancer progression.\",\n      \"evidence\": \"Overexpression/knockdown in CRC cell lines with subcellular fractionation, confocal imaging, \\u03b2-catenin pathway western blots, and xenograft model\",\n      \"pmids\": [\"34059062\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether GOLT1B directly binds DVL2 or acts indirectly is not established\",\n        \"Single lab; mechanism of cargo selectivity unknown\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"It was unknown whether GOLT1B contributes to tumor immune evasion; it was found to interact with PD-L2 and elevate its surface levels, driving T cell apoptosis.\",\n      \"evidence\": \"Co-immunoprecipitation, flow cytometry for membrane PD-L2, and Jurkat T cell co-culture apoptosis assay\",\n      \"pmids\": [\"34059062\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Co-IP without reciprocal validation or mapping of interaction interface\",\n        \"In vivo relevance to immune checkpoint suppression not tested\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Whether GOLT1B participates in viral infection was unknown; its induction during ER stress and requirement for HCV replication tied its ER-Golgi trafficking role to the viral life cycle.\",\n      \"evidence\": \"RNAseq of laser-microdissected HCV-infected hepatocytes, siRNA knockdown with HCV replication readout, and UPR induction assays\",\n      \"pmids\": [\"35055994\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific trafficking step or viral cargo dependent on GOLT1B not identified\",\n        \"Mechanistic link between UPR induction and replication requirement unresolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A further signaling input was unknown; GOLT1B was shown to interact with TBK1 and activate NF-\\u03baB transcription, promoting cervical carcinoma viability and migration.\",\n      \"evidence\": \"Co-IP for GOLT1B\\u2013TBK1 interaction, NF-\\u03baB dual luciferase reporter, functional viability/migration assays, and in vivo tumor model\",\n      \"pmids\": [\"39113410\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether GOLT1B regulates TBK1 kinase activity or simply scaffolds it is unknown\",\n        \"Single lab; interaction not independently confirmed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How GOLT1B selects among its diverse reported cargo (DVL2, PD-L2, RNF145) and whether a single Golgi-shuttling mechanism underlies all its signaling roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No unifying biochemical model connecting cargo trafficking to the multiple downstream pathways\",\n        \"No structural characterization of GOLT1B cargo recognition\",\n        \"Conservation of the RNF145/SREBP axis in human cells not demonstrated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"DVL2\", \"PD-L2\", \"TBK1\", \"RNF145\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}