{"gene":"YIPF2","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2016,"finding":"YIPF2 localizes primarily to the trans-Golgi region of the Golgi complex. It has a membrane topology with a long soluble N-terminal region oriented toward the cytosol, followed by 5 closely stacked transmembrane domains, and a C-terminus oriented toward the Golgi lumen. RNAi-mediated depletion of YIPF2 causes specific morphological changes to the Golgi apparatus, suggesting a role in regulating membrane dynamics in the endomembrane system.","method":"Immunofluorescence microscopy, RNA interference, membrane topology analysis","journal":"Histochemistry and cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immunofluorescence, RNAi loss-of-function with defined morphological phenotype, membrane topology characterization; single lab, multiple orthogonal methods","pmids":["27999994"],"is_preprint":false},{"year":2017,"finding":"YIPF1, YIPF2, and YIPF6 localize to the medial-/trans-Golgi and trans-Golgi network. YIPF6 forms stable complexes with YIPF1 and YIPF2, and knockdown of YIPF6 reduces YIPF1 and YIPF2 protein levels. Knockdown of YIPF1 and YIPF2 (but not YIPF6) markedly delays reassembly of the Golgi apparatus after brefeldin A washout, and also reduces intracellular glycan synthesis in HT-29 cells.","method":"Immunofluorescence staining, co-immunoprecipitation/complex formation analysis, RNAi knockdown, brefeldin A treatment/washout assay, glycan synthesis measurement","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (localization, complex formation, RNAi functional readouts), single lab","pmids":["28286305"],"is_preprint":false},{"year":2019,"finding":"YIPF2 is an ER-Golgi-resident transmembrane protein that acts as a Rab-GDF (GDI-displacement factor). It recruits and activates Rab5 and Rab22a GTPases to endomembrane structures. YIPF2 modulates endocytic recycling of CD147 through distinctive regulation of Rab5 and Rab22a, and mediates mature processing of CD147 via the ER-Golgi trafficking route, including its glycosylation. Decreased YIPF2 expression leads to increased CD147 cell-surface delivery and enhanced MMP secretion, promoting HCC malignant phenotypes.","method":"MAPPIT protein-protein interaction screen, confocal imaging, flow cytometry, biotin-labeled chase assays, GST-RBD pull-down (Rab GTPase activation), gelatin zymography, RNAi knockdown with phenotypic readouts","journal":"Cell death & disease","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (PPI screen, trafficking assays, Rab activation pulldown, functional knockdown with defined phenotype) in a single rigorous study establishing mechanism","pmids":["31189879"],"is_preprint":false},{"year":2020,"finding":"YIPF2 physically interacts with TNFRSF10B (DR5/TRAIL-R2) and RAB8. YIPF2 promotes recycling of TNFRSF10B to the plasma membrane and inhibits the physical interaction between TNFRSF10B and RAB8, thereby suppressing RAB8-mediated removal of TNFRSF10B from the plasma membrane to the cytoplasm. This maintains high cell-surface levels of TNFRSF10B and promotes chemotherapeutic agent-mediated apoptosis in NSCLC cells.","method":"Co-immunoprecipitation, flow cytometry (surface level measurement), RNAi knockdown, cell apoptosis assays","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP establishing physical interaction, functional knockdown with defined trafficking and apoptosis phenotype; single lab, multiple methods","pmids":["32303681"],"is_preprint":false},{"year":2024,"finding":"YIPF2 plays a critical role in maintaining genome stability. Depletion of YIPF2 hinders homologous recombination (HR) repair, triggering DNA damage response and cellular senescence. Overexpression of YIPF2 facilitates cellular recovery from chemotherapy-induced DNA damage or replicative senescence-associated DNA damage. Only an intact Golgi apparatus containing YIPF2 provides a protective effect on genome integrity.","method":"Whole-genome RNAi screen, HR repair assay, DNA damage response assays, overexpression/knockdown with senescence readouts","journal":"Cell & bioscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide RNAi screen with functional follow-up (HR repair assay, DNA damage response, senescence), single lab","pmids":["39238039"],"is_preprint":false},{"year":2024,"finding":"YIPF2 modulates the transfer of CD147 to the cell membrane in oligodendrocytes. hIAPP interferes with binding of MCT1 to CD147, and YIPF2 inhibition increases CD147 translocation to the membrane, optimizing MCT1-CD147 binding and ameliorating hIAPP-induced acidosis and demyelination in a diabetic encephalopathy model.","method":"Western blotting, co-immunoprecipitation, proteomic differential analysis of CD147-co-immunoprecipitated proteins, in vitro oligodendrocyte assays, in vivo DE mouse model with cognitive readouts","journal":"Neuroscience bulletin","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, proteomics, in vitro and in vivo functional assays with defined phenotypic readout; single lab, multiple orthogonal methods","pmids":["39078594"],"is_preprint":false}],"current_model":"YIPF2 is a multi-transmembrane ER-Golgi/trans-Golgi-resident protein that functions as a Rab-GDF (GDI-displacement factor), activating Rab5 and Rab22a GTPases to regulate endocytic recycling and ER-Golgi trafficking of cargo proteins (notably CD147 and TNFRSF10B); it is required for proper Golgi reassembly and glycan synthesis, interacts with YIPF6 for stable expression, modulates cell-surface levels of CD147 and TNFRSF10B by counteracting RAB8-mediated internalization, and also maintains genome integrity by supporting homologous recombination repair."},"narrative":{"mechanistic_narrative":"YIPF2 is a multi-transmembrane Golgi-resident protein that controls membrane dynamics in the endomembrane system and the surface delivery of specific cargo proteins [PMID:27999994, PMID:31189879]. It is anchored at the trans-Golgi region by five closely stacked transmembrane domains, with a cytosolic N-terminus and a lumenal C-terminus, and its depletion produces specific Golgi morphological changes [PMID:27999994]; together with YIPF1 and YIPF6 it forms a complex in the medial-/trans-Golgi, with YIPF6 required to maintain YIPF1 and YIPF2 protein levels, and loss of YIPF2 delays Golgi reassembly and reduces glycan synthesis [PMID:28286305]. Mechanistically, YIPF2 acts as a Rab-GDF (GDI-displacement factor) that recruits and activates Rab5 and Rab22a GTPases to endomembranes, thereby governing the endocytic recycling and ER-Golgi maturation/glycosylation of CD147; reduced YIPF2 increases CD147 surface delivery and MMP secretion [PMID:31189879]. YIPF2 also binds TNFRSF10B (DR5) and RAB8, blocking the TNFRSF10B-RAB8 interaction to prevent RAB8-mediated internalization and thus sustaining surface receptor levels and chemotherapy-induced apoptosis [PMID:32303681], and it likewise regulates CD147 translocation in oligodendrocytes to modulate MCT1-CD147 coupling [PMID:39078594]. Beyond trafficking, an intact YIPF2-containing Golgi supports homologous recombination repair, and YIPF2 loss impairs HR and triggers DNA damage response and senescence [PMID:39238039].","teleology":[{"year":2016,"claim":"Established where YIPF2 resides and how it is oriented in the membrane, providing the structural basis for a role in endomembrane dynamics.","evidence":"Immunofluorescence, RNAi depletion, and membrane topology analysis showing trans-Golgi localization, five transmembrane domains, and Golgi morphology defects","pmids":["27999994"],"confidence":"Medium","gaps":["Molecular partners and biochemical activity not defined","Mechanism linking depletion to Golgi morphology change unresolved"]},{"year":2017,"claim":"Showed YIPF2 operates within a YIPF1/YIPF2/YIPF6 complex and is functionally required for Golgi reassembly and glycan synthesis, framing it as a structural/regulatory component rather than an isolated protein.","evidence":"Co-immunoprecipitation, RNAi knockdown, brefeldin A washout reassembly assay, and glycan synthesis measurement in HT-29 cells","pmids":["28286305"],"confidence":"Medium","gaps":["Stoichiometry and architecture of the complex not resolved","Direct biochemical activity underlying reassembly defect not identified"]},{"year":2019,"claim":"Defined YIPF2's molecular activity as a Rab-GDF that activates Rab5 and Rab22a, connecting it mechanistically to endocytic recycling and ER-Golgi maturation of CD147.","evidence":"MAPPIT PPI screen, GST-RBD Rab activation pull-down, biotin chase trafficking assays, flow cytometry, zymography, and RNAi in HCC cells","pmids":["31189879"],"confidence":"High","gaps":["Structural basis of GDI displacement not determined","Whether additional Rab substrates exist beyond Rab5/Rab22a unknown"]},{"year":2020,"claim":"Extended YIPF2 cargo regulation to TNFRSF10B by showing it antagonizes RAB8-mediated receptor internalization to sustain surface levels and apoptotic signaling.","evidence":"Reciprocal co-IP, surface flow cytometry, RNAi knockdown, and apoptosis assays in NSCLC cells","pmids":["32303681"],"confidence":"Medium","gaps":["Direct vs indirect nature of YIPF2-RAB8 antagonism unclear","Whether this uses the same Rab-GDF activity as CD147 regulation not established"]},{"year":2024,"claim":"Revealed an unexpected role for YIPF2 in genome maintenance, linking an intact Golgi to homologous recombination repair.","evidence":"Whole-genome RNAi screen with HR repair assay, DNA damage response, and senescence readouts","pmids":["39238039"],"confidence":"Medium","gaps":["Mechanistic link between Golgi/YIPF2 and HR machinery undefined","No molecular intermediary identified"]},{"year":2024,"claim":"Showed YIPF2 control of CD147 surface trafficking is physiologically relevant in oligodendrocytes, affecting MCT1-CD147 coupling in a disease model.","evidence":"Western blot, co-IP, proteomics, in vitro oligodendrocyte assays, and in vivo diabetic encephalopathy mouse model","pmids":["39078594"],"confidence":"Medium","gaps":["Whether the Rab-GDF activity drives this effect not directly tested","Generalizability beyond the hIAPP/diabetic context unknown"]},{"year":null,"claim":"How a single trans-Golgi Rab-GDF coordinates cargo-specific surface trafficking, Golgi reassembly, and genome stability through one or distinct molecular activities remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of YIPF2 or its Rab/cargo complexes","Unclear whether trafficking and DNA-repair roles share a common mechanism"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,3]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[2,3]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[2,3]}],"complexes":["YIPF1/YIPF2/YIPF6 complex"],"partners":["YIPF6","YIPF1","RAB5A","RAB22A","TNFRSF10B","RAB8A","CD147"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BWQ6","full_name":"Protein YIPF2","aliases":["YIP1 family member 2"],"length_aa":316,"mass_kda":35.2,"function":"","subcellular_location":"Golgi apparatus, cis-Golgi network membrane; Golgi apparatus, trans-Golgi network membrane; Late endosome membrane","url":"https://www.uniprot.org/uniprotkb/Q9BWQ6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/YIPF2","classification":"Not Classified","n_dependent_lines":35,"n_total_lines":1208,"dependency_fraction":0.028973509933774833},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/YIPF2","total_profiled":1310},"omim":[{"mim_id":"617522","title":"YIP1 DOMAIN FAMILY, MEMBER 2; YIPF2","url":"https://www.omim.org/entry/617522"},{"mim_id":"617521","title":"YIP1 DOMAIN FAMILY, MEMBER 1; YIPF1","url":"https://www.omim.org/entry/617521"},{"mim_id":"300996","title":"YIP1 DOMAIN FAMILY, MEMBER 6; YIPF6","url":"https://www.omim.org/entry/300996"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Mitochondria","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/YIPF2"},"hgnc":{"alias_symbol":["MGC3262","FinGER2","Yip5C","YIPFbeta3B"],"prev_symbol":[]},"alphafold":{"accession":"Q9BWQ6","domains":[{"cath_id":"-","chopping":"90-281","consensus_level":"high","plddt":88.2709,"start":90,"end":281}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BWQ6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BWQ6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BWQ6-F1-predicted_aligned_error_v6.png","plddt_mean":75.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=YIPF2","jax_strain_url":"https://www.jax.org/strain/search?query=YIPF2"},"sequence":{"accession":"Q9BWQ6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BWQ6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BWQ6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BWQ6"}},"corpus_meta":[{"pmid":"21670465","id":"PMC_21670465","title":"Mutations in 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It has a membrane topology with a long soluble N-terminal region oriented toward the cytosol, followed by 5 closely stacked transmembrane domains, and a C-terminus oriented toward the Golgi lumen. RNAi-mediated depletion of YIPF2 causes specific morphological changes to the Golgi apparatus, suggesting a role in regulating membrane dynamics in the endomembrane system.\",\n      \"method\": \"Immunofluorescence microscopy, RNA interference, membrane topology analysis\",\n      \"journal\": \"Histochemistry and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immunofluorescence, RNAi loss-of-function with defined morphological phenotype, membrane topology characterization; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"27999994\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"YIPF1, YIPF2, and YIPF6 localize to the medial-/trans-Golgi and trans-Golgi network. YIPF6 forms stable complexes with YIPF1 and YIPF2, and knockdown of YIPF6 reduces YIPF1 and YIPF2 protein levels. Knockdown of YIPF1 and YIPF2 (but not YIPF6) markedly delays reassembly of the Golgi apparatus after brefeldin A washout, and also reduces intracellular glycan synthesis in HT-29 cells.\",\n      \"method\": \"Immunofluorescence staining, co-immunoprecipitation/complex formation analysis, RNAi knockdown, brefeldin A treatment/washout assay, glycan synthesis measurement\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (localization, complex formation, RNAi functional readouts), single lab\",\n      \"pmids\": [\"28286305\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"YIPF2 is an ER-Golgi-resident transmembrane protein that acts as a Rab-GDF (GDI-displacement factor). It recruits and activates Rab5 and Rab22a GTPases to endomembrane structures. YIPF2 modulates endocytic recycling of CD147 through distinctive regulation of Rab5 and Rab22a, and mediates mature processing of CD147 via the ER-Golgi trafficking route, including its glycosylation. Decreased YIPF2 expression leads to increased CD147 cell-surface delivery and enhanced MMP secretion, promoting HCC malignant phenotypes.\",\n      \"method\": \"MAPPIT protein-protein interaction screen, confocal imaging, flow cytometry, biotin-labeled chase assays, GST-RBD pull-down (Rab GTPase activation), gelatin zymography, RNAi knockdown with phenotypic readouts\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (PPI screen, trafficking assays, Rab activation pulldown, functional knockdown with defined phenotype) in a single rigorous study establishing mechanism\",\n      \"pmids\": [\"31189879\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"YIPF2 physically interacts with TNFRSF10B (DR5/TRAIL-R2) and RAB8. YIPF2 promotes recycling of TNFRSF10B to the plasma membrane and inhibits the physical interaction between TNFRSF10B and RAB8, thereby suppressing RAB8-mediated removal of TNFRSF10B from the plasma membrane to the cytoplasm. This maintains high cell-surface levels of TNFRSF10B and promotes chemotherapeutic agent-mediated apoptosis in NSCLC cells.\",\n      \"method\": \"Co-immunoprecipitation, flow cytometry (surface level measurement), RNAi knockdown, cell apoptosis assays\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP establishing physical interaction, functional knockdown with defined trafficking and apoptosis phenotype; single lab, multiple methods\",\n      \"pmids\": [\"32303681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"YIPF2 plays a critical role in maintaining genome stability. Depletion of YIPF2 hinders homologous recombination (HR) repair, triggering DNA damage response and cellular senescence. Overexpression of YIPF2 facilitates cellular recovery from chemotherapy-induced DNA damage or replicative senescence-associated DNA damage. Only an intact Golgi apparatus containing YIPF2 provides a protective effect on genome integrity.\",\n      \"method\": \"Whole-genome RNAi screen, HR repair assay, DNA damage response assays, overexpression/knockdown with senescence readouts\",\n      \"journal\": \"Cell & bioscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide RNAi screen with functional follow-up (HR repair assay, DNA damage response, senescence), single lab\",\n      \"pmids\": [\"39238039\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"YIPF2 modulates the transfer of CD147 to the cell membrane in oligodendrocytes. hIAPP interferes with binding of MCT1 to CD147, and YIPF2 inhibition increases CD147 translocation to the membrane, optimizing MCT1-CD147 binding and ameliorating hIAPP-induced acidosis and demyelination in a diabetic encephalopathy model.\",\n      \"method\": \"Western blotting, co-immunoprecipitation, proteomic differential analysis of CD147-co-immunoprecipitated proteins, in vitro oligodendrocyte assays, in vivo DE mouse model with cognitive readouts\",\n      \"journal\": \"Neuroscience bulletin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, proteomics, in vitro and in vivo functional assays with defined phenotypic readout; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"39078594\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"YIPF2 is a multi-transmembrane ER-Golgi/trans-Golgi-resident protein that functions as a Rab-GDF (GDI-displacement factor), activating Rab5 and Rab22a GTPases to regulate endocytic recycling and ER-Golgi trafficking of cargo proteins (notably CD147 and TNFRSF10B); it is required for proper Golgi reassembly and glycan synthesis, interacts with YIPF6 for stable expression, modulates cell-surface levels of CD147 and TNFRSF10B by counteracting RAB8-mediated internalization, and also maintains genome integrity by supporting homologous recombination repair.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"YIPF2 is a multi-transmembrane Golgi-resident protein that controls membrane dynamics in the endomembrane system and the surface delivery of specific cargo proteins [#0, #2]. It is anchored at the trans-Golgi region by five closely stacked transmembrane domains, with a cytosolic N-terminus and a lumenal C-terminus, and its depletion produces specific Golgi morphological changes [#0]; together with YIPF1 and YIPF6 it forms a complex in the medial-/trans-Golgi, with YIPF6 required to maintain YIPF1 and YIPF2 protein levels, and loss of YIPF2 delays Golgi reassembly and reduces glycan synthesis [#1]. Mechanistically, YIPF2 acts as a Rab-GDF (GDI-displacement factor) that recruits and activates Rab5 and Rab22a GTPases to endomembranes, thereby governing the endocytic recycling and ER-Golgi maturation/glycosylation of CD147; reduced YIPF2 increases CD147 surface delivery and MMP secretion [#2]. YIPF2 also binds TNFRSF10B (DR5) and RAB8, blocking the TNFRSF10B-RAB8 interaction to prevent RAB8-mediated internalization and thus sustaining surface receptor levels and chemotherapy-induced apoptosis [#3], and it likewise regulates CD147 translocation in oligodendrocytes to modulate MCT1-CD147 coupling [#5]. Beyond trafficking, an intact YIPF2-containing Golgi supports homologous recombination repair, and YIPF2 loss impairs HR and triggers DNA damage response and senescence [#4].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Established where YIPF2 resides and how it is oriented in the membrane, providing the structural basis for a role in endomembrane dynamics.\",\n      \"evidence\": \"Immunofluorescence, RNAi depletion, and membrane topology analysis showing trans-Golgi localization, five transmembrane domains, and Golgi morphology defects\",\n      \"pmids\": [\"27999994\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular partners and biochemical activity not defined\", \"Mechanism linking depletion to Golgi morphology change unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Showed YIPF2 operates within a YIPF1/YIPF2/YIPF6 complex and is functionally required for Golgi reassembly and glycan synthesis, framing it as a structural/regulatory component rather than an isolated protein.\",\n      \"evidence\": \"Co-immunoprecipitation, RNAi knockdown, brefeldin A washout reassembly assay, and glycan synthesis measurement in HT-29 cells\",\n      \"pmids\": [\"28286305\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stoichiometry and architecture of the complex not resolved\", \"Direct biochemical activity underlying reassembly defect not identified\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined YIPF2's molecular activity as a Rab-GDF that activates Rab5 and Rab22a, connecting it mechanistically to endocytic recycling and ER-Golgi maturation of CD147.\",\n      \"evidence\": \"MAPPIT PPI screen, GST-RBD Rab activation pull-down, biotin chase trafficking assays, flow cytometry, zymography, and RNAi in HCC cells\",\n      \"pmids\": [\"31189879\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of GDI displacement not determined\", \"Whether additional Rab substrates exist beyond Rab5/Rab22a unknown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended YIPF2 cargo regulation to TNFRSF10B by showing it antagonizes RAB8-mediated receptor internalization to sustain surface levels and apoptotic signaling.\",\n      \"evidence\": \"Reciprocal co-IP, surface flow cytometry, RNAi knockdown, and apoptosis assays in NSCLC cells\",\n      \"pmids\": [\"32303681\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect nature of YIPF2-RAB8 antagonism unclear\", \"Whether this uses the same Rab-GDF activity as CD147 regulation not established\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed an unexpected role for YIPF2 in genome maintenance, linking an intact Golgi to homologous recombination repair.\",\n      \"evidence\": \"Whole-genome RNAi screen with HR repair assay, DNA damage response, and senescence readouts\",\n      \"pmids\": [\"39238039\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between Golgi/YIPF2 and HR machinery undefined\", \"No molecular intermediary identified\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed YIPF2 control of CD147 surface trafficking is physiologically relevant in oligodendrocytes, affecting MCT1-CD147 coupling in a disease model.\",\n      \"evidence\": \"Western blot, co-IP, proteomics, in vitro oligodendrocyte assays, and in vivo diabetic encephalopathy mouse model\",\n      \"pmids\": [\"39078594\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the Rab-GDF activity drives this effect not directly tested\", \"Generalizability beyond the hIAPP/diabetic context unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single trans-Golgi Rab-GDF coordinates cargo-specific surface trafficking, Golgi reassembly, and genome stability through one or distinct molecular activities remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of YIPF2 or its Rab/cargo complexes\", \"Unclear whether trafficking and DNA-repair roles share a common mechanism\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [\"YIPF1/YIPF2/YIPF6 complex\"],\n    \"partners\": [\"YIPF6\", \"YIPF1\", \"RAB5A\", \"RAB22A\", \"TNFRSF10B\", \"RAB8A\", \"CD147\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":5,"faith_total":5,"faith_pct":100.0}}