{"gene":"BLTP3B","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2010,"finding":"SHIP164 (UHRF1BP1L) was identified as a novel binding partner of the Habc domain of Syntaxin 6 by yeast two-hybrid/interaction screen, and is part of a large (~700 kDa) complex that interacts with components of the GARP (Golgi-associated retrograde protein) tethering complex. Depletion of GARP subunits or overexpression of Syntaxin 6 redistributes soluble SHIP164 to endosomal structures. Co-overexpression of Syntaxin 6 and SHIP164 produces excessive tubulation of endosomes and perturbs retrograde transport of CI-MPR and transferrin receptor, placing SHIP164 in the early/recycling endosomal sorting pathway.","method":"Yeast two-hybrid/interaction screen, co-immunoprecipitation, overexpression/knockdown with trafficking readouts (CI-MPR and transferrin receptor transport assays), immunofluorescence","journal":"Traffic","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — reciprocal interaction data, multiple functional readouts (endosome tubulation, cargo transport), single lab","pmids":["20163565"],"is_preprint":false},{"year":2022,"finding":"SHIP164 (UHRF1BP1L) shares structural and lipid transfer properties with VPS13-family proteins (chorein motif, bridge-like lipid transfer protein), localizes to a subpopulation of vesicle clusters in the early endocytic pathway containing CI-MPR, and is required for retrograde traffic of these organelles to the Golgi complex. Loss of SHIP164 disrupts this retrograde trafficking, indicating bulk lipid transfer to endocytic membranes plays a role in their trafficking.","method":"Structural predictions/sequence analysis confirming chorein motif; in vitro lipid transfer assays; immunofluorescence localization; loss-of-function (siRNA depletion) with CI-MPR retrograde trafficking readout","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro lipid transfer activity demonstrated, structural characterization of chorein motif, loss-of-function with defined trafficking phenotype, multiple orthogonal methods in single rigorous study","pmids":["35499567"],"is_preprint":false},{"year":2022,"finding":"Phylogenetic and structural analysis of the RBG (repeating beta groove) superfamily establishes that SHIP164 is one of five eukaryotic bridge-like lipid transfer protein families present since the last eukaryotic common ancestor. Unlike other RBG family members, the C-terminus of SHIP164 has a coiled-coil rather than amphipathic helices. Conserved exterior surface residues along the bridge suggest sites for partner interactions.","method":"Sequence analysis and AlphaFold structural prediction with phylogenetic analysis","journal":"Contact (Thousand Oaks (Ventura County, Calif.))","confidence":"Low","confidence_rationale":"Tier 4 / Moderate — computational/structural prediction analysis only, no direct experimental validation of lipid transfer or coiled-coil function","pmids":["36571082"],"is_preprint":false},{"year":2024,"finding":"SHIP164 forms a complex with the ATPase RhoBTB3 and the retromer subunit Vps26B at Golgi-early endosome (EE) contacts to promote formation of Rab14-positive EE buds. Vps26B acts as a novel Rab14 effector, and Rab14 activity regulates the association of SHIP164 with EEs. Depletion of SHIP164 results in enlarged Rab14+ EEs without buds, a phenotype rescued by wild-type SHIP164 but not by lipid transfer-defective SHIP164 mutants. Depletion of RhoBTB3 or Vps26B phenocopies SHIP164 depletion, establishing epistatic relationships within this complex.","method":"Co-immunoprecipitation (complex identification), siRNA knockdown with fluorescence microscopy readout (EE bud formation), rescue experiments with wild-type vs. lipid transfer-defective mutants, Rab14 effector assays","journal":"Cell discovery","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — complex identified by Co-IP, mutagenesis of lipid transfer function used in rescue, epistasis established by parallel depletions, multiple orthogonal methods","pmids":["38565878"],"is_preprint":false},{"year":2017,"finding":"RNAi-mediated knockdown of UHRF1BP1L (SHIP164) modulated mitochondrial dynamics in human neuronal cultures, identifying it as a functional candidate in a Parkinson's disease context.","method":"RNAi screen in human neuronal cell culture with mitochondrial dynamics readout","journal":"Genome biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single RNAi screen readout, no mechanistic pathway placement, part of a large-scale screen not focused on this gene","pmids":["28137300"],"is_preprint":false},{"year":2024,"finding":"APEX2 proximity labeling of RAB14 identified SHIP164 (and its close ortholog UHRF1BP1) in the RAB14 proximal proteome, suggesting a functional relationship between RAB14 and SHIP164 consistent with SHIP164 operating at RAB14-positive endosomes.","method":"APEX2 proximity labeling proteomics","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proximity labeling only (no direct interaction confirmed), preprint, single method","pmids":["bio_10.1101_2024.11.05.621850"],"is_preprint":true}],"current_model":"SHIP164 (BLTP3B/UHRF1BP1L) is a bridge-like lipid transfer protein (chorein motif, RBG superfamily) that localizes to early endosomes where it forms a complex with RhoBTB3 and Vps26B at Golgi-endosome contact sites to mediate bulk lipid transfer, thereby driving Rab14-positive endosome bud formation and enabling retrograde trafficking of CI-MPR to the Golgi; it also physically interacts with Syntaxin 6 and the GARP tethering complex to regulate endosomal sorting."},"narrative":{"mechanistic_narrative":"BLTP3B (SHIP164/UHRF1BP1L) is a bridge-like lipid transfer protein of the RBG superfamily that mediates bulk lipid transfer at membrane contact sites to drive endosomal sorting and retrograde trafficking [PMID:35499567, PMID:38565878]. It contains a chorein motif characteristic of VPS13-family bridge-like lipid transfer proteins, possesses in vitro lipid transfer activity, and localizes to a subpopulation of CI-MPR-containing vesicle clusters in the early endocytic pathway, where its loss disrupts retrograde delivery of these organelles to the Golgi [PMID:35499567]. At Golgi–early endosome contacts, BLTP3B forms a complex with the ATPase RhoBTB3 and the retromer subunit Vps26B to promote formation of Rab14-positive endosome buds; depletion produces enlarged Rab14+ endosomes lacking buds, a defect rescued by wild-type but not lipid transfer-defective protein, establishing that its lipid transfer activity is required for bud formation [PMID:38565878]. BLTP3B also binds the Habc domain of Syntaxin 6 within a large complex that engages the GARP tethering complex, coupling it to endosomal tubulation and the retrograde transport of CI-MPR and transferrin receptor [PMID:20163565]. Beyond these contact-site sorting roles, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2010,"claim":"Established the first molecular context for BLTP3B by placing it in the endosomal retrograde sorting machinery via physical links to Syntaxin 6 and the GARP tethering complex.","evidence":"Yeast two-hybrid/interaction screen, co-IP, and overexpression/knockdown with CI-MPR and transferrin receptor transport readouts in human cells","pmids":["20163565"],"confidence":"Medium","gaps":["Did not define a molecular activity for the protein","Mechanism by which the Syntaxin 6/GARP complex recruits or activates BLTP3B unresolved","Single lab"]},{"year":2022,"claim":"Defined BLTP3B as a bridge-like lipid transfer protein, converting its sorting role into a biochemical mechanism by demonstrating chorein-motif structure and in vitro lipid transfer linked to CI-MPR retrograde traffic.","evidence":"Structural/sequence analysis of chorein motif, in vitro lipid transfer assays, immunofluorescence, and siRNA loss-of-function with CI-MPR retrograde trafficking readout","pmids":["35499567"],"confidence":"High","gaps":["Specific lipid species transferred in cells not defined","Contact sites bridged not directly imaged at this stage"]},{"year":2022,"claim":"Placed BLTP3B in the RBG superfamily phylogeny and predicted a distinctive C-terminal coiled-coil and surface residues for partner binding.","evidence":"Sequence analysis and AlphaFold structural prediction with phylogenetic analysis","pmids":["36571082"],"confidence":"Low","gaps":["Computational prediction only, no experimental validation of the coiled-coil or surface interaction sites","Functional role of C-terminal divergence untested"]},{"year":2024,"claim":"Resolved the contact-site machinery, showing BLTP3B acts in a RhoBTB3–Vps26B complex at Golgi–early endosome contacts to drive Rab14+ endosome bud formation in a lipid-transfer-dependent manner.","evidence":"Co-IP complex identification, siRNA knockdown with EE bud microscopy, rescue with wild-type vs lipid transfer-defective mutants, and Rab14 effector assays","pmids":["38565878"],"confidence":"High","gaps":["Stoichiometry and assembly order of the BLTP3B–RhoBTB3–Vps26B complex not defined","How Rab14 activity controls BLTP3B endosome association mechanistically unknown"]},{"year":2024,"claim":"Independently corroborated the Rab14-endosome localization by detecting BLTP3B in the RAB14 proximal proteome.","evidence":"APEX2 proximity labeling proteomics (preprint)","pmids":["bio_10.1101_2024.11.05.621850"],"confidence":"Low","gaps":["Proximity labeling does not establish direct interaction","Preprint, single method"]},{"year":2017,"claim":"Implicated BLTP3B in mitochondrial dynamics in a Parkinson's disease neuronal context, raising an unresolved link between its endosomal function and organelle homeostasis.","evidence":"RNAi screen in human neuronal cell culture with mitochondrial dynamics readout","pmids":["28137300"],"confidence":"Low","gaps":["No mechanistic pathway connecting BLTP3B lipid transfer to mitochondrial dynamics","Part of a large-scale screen, not a focused study","Not independently validated"]},{"year":null,"claim":"The identity of the lipids transferred in vivo and the directionality of transfer across the Golgi–endosome bridge remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["Native lipid cargo and transfer direction not established","Connection between endosomal sorting role and reported mitochondrial phenotype unexplained"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[1,3]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[3]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1,3]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[1,3]}],"complexes":["GARP tethering complex (associated)","BLTP3B–RhoBTB3–Vps26B complex"],"partners":["STX6","RHOBTB3","VPS26B","RAB14"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A0JNW5","full_name":"Bridge-like lipid transfer protein family member 3B","aliases":["Syntaxin-6 Habc-interacting protein of 164 kDa","UHRF1-binding protein 1-like"],"length_aa":1464,"mass_kda":164.2,"function":"Tube-forming lipid transport protein which mediates the transfer of lipids between membranes at organelle contact sites (PubMed:35499567). Required for retrograde traffic of vesicle clusters in the early endocytic pathway to the Golgi complex (PubMed:20163565, PubMed:35499567)","subcellular_location":"Cytoplasm, cytosol; Early endosome","url":"https://www.uniprot.org/uniprotkb/A0JNW5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/BLTP3B","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":[{"gene":"DYNLL1","stoichiometry":0.2},{"gene":"DYNLL2","stoichiometry":0.2},{"gene":"MIF","stoichiometry":0.2},{"gene":"RAC1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/BLTP3B","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Nucleoplasm","reliability":"Uncertain"},{"location":"Vesicles","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/BLTP3B"},"hgnc":{"alias_symbol":["KIAA0701","SHIP164"],"prev_symbol":["UHRF1BP1L"]},"alphafold":{"accession":"A0JNW5","domains":[{"cath_id":"-","chopping":"2-105_114-271","consensus_level":"medium","plddt":86.6011,"start":2,"end":271},{"cath_id":"-","chopping":"347-409_454-550_571-586","consensus_level":"medium","plddt":92.1828,"start":347,"end":586}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A0JNW5","model_url":"https://alphafold.ebi.ac.uk/files/AF-A0JNW5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A0JNW5-F1-predicted_aligned_error_v6.png","plddt_mean":66.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=BLTP3B","jax_strain_url":"https://www.jax.org/strain/search?query=BLTP3B"},"sequence":{"accession":"A0JNW5","fasta_url":"https://rest.uniprot.org/uniprotkb/A0JNW5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A0JNW5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A0JNW5"}},"corpus_meta":[{"pmid":"28137300","id":"PMC_28137300","title":"Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.","date":"2017","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/28137300","citation_count":90,"is_preprint":false},{"pmid":"36571082","id":"PMC_36571082","title":"Sequence Analysis and Structural Predictions of Lipid Transfer Bridges in the Repeating Beta Groove (RBG) Superfamily Reveal Past and Present Domain Variations Affecting Form, Function and Interactions of VPS13, ATG2, SHIP164, Hobbit and Tweek.","date":"2022","source":"Contact (Thousand Oaks (Ventura County, Calif.))","url":"https://pubmed.ncbi.nlm.nih.gov/36571082","citation_count":50,"is_preprint":false},{"pmid":"35499567","id":"PMC_35499567","title":"SHIP164 is a chorein motif lipid transfer protein that controls endosome-Golgi membrane traffic.","date":"2022","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/35499567","citation_count":30,"is_preprint":false},{"pmid":"20163565","id":"PMC_20163565","title":"A novel syntaxin 6-interacting protein, SHIP164, regulates syntaxin 6-dependent sorting from early endosomes.","date":"2010","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/20163565","citation_count":29,"is_preprint":false},{"pmid":"23422819","id":"PMC_23422819","title":"Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2.","date":"2013","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/23422819","citation_count":28,"is_preprint":false},{"pmid":"38918974","id":"PMC_38918974","title":"Circular RNA hsa_circ_0005939 Regulates UHRF1BP1L Expression by Targeting miR-4693-3p to Promote Colorectal Cancer Progression.","date":"2024","source":"Protein and peptide letters","url":"https://pubmed.ncbi.nlm.nih.gov/38918974","citation_count":11,"is_preprint":false},{"pmid":"38565878","id":"PMC_38565878","title":"Biogenesis of Rab14-positive endosome buds at Golgi-endosome contacts by the RhoBTB3-SHIP164-Vps26B complex.","date":"2024","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/38565878","citation_count":5,"is_preprint":false},{"pmid":"39386594","id":"PMC_39386594","title":"BLTP3A is associated with membranes of the late endocytic pathway and is an effector of CASM.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39386594","citation_count":3,"is_preprint":false},{"pmid":"40040391","id":"PMC_40040391","title":"Single and multi-omic characterization of a porcine model of ethanol-induced hepatic fibrosis.","date":"2025","source":"Epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/40040391","citation_count":1,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.11.05.621850","title":"A Proximity MAP of RAB GTPases","date":"2024-11-06","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.05.621850","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7018,"output_tokens":1777,"usd":0.023855,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8640,"output_tokens":2393,"usd":0.051513,"stage2_stop_reason":"end_turn"},"total_usd":0.075368,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2010,\n      \"finding\": \"SHIP164 (UHRF1BP1L) was identified as a novel binding partner of the Habc domain of Syntaxin 6 by yeast two-hybrid/interaction screen, and is part of a large (~700 kDa) complex that interacts with components of the GARP (Golgi-associated retrograde protein) tethering complex. Depletion of GARP subunits or overexpression of Syntaxin 6 redistributes soluble SHIP164 to endosomal structures. Co-overexpression of Syntaxin 6 and SHIP164 produces excessive tubulation of endosomes and perturbs retrograde transport of CI-MPR and transferrin receptor, placing SHIP164 in the early/recycling endosomal sorting pathway.\",\n      \"method\": \"Yeast two-hybrid/interaction screen, co-immunoprecipitation, overexpression/knockdown with trafficking readouts (CI-MPR and transferrin receptor transport assays), immunofluorescence\",\n      \"journal\": \"Traffic\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — reciprocal interaction data, multiple functional readouts (endosome tubulation, cargo transport), single lab\",\n      \"pmids\": [\"20163565\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SHIP164 (UHRF1BP1L) shares structural and lipid transfer properties with VPS13-family proteins (chorein motif, bridge-like lipid transfer protein), localizes to a subpopulation of vesicle clusters in the early endocytic pathway containing CI-MPR, and is required for retrograde traffic of these organelles to the Golgi complex. Loss of SHIP164 disrupts this retrograde trafficking, indicating bulk lipid transfer to endocytic membranes plays a role in their trafficking.\",\n      \"method\": \"Structural predictions/sequence analysis confirming chorein motif; in vitro lipid transfer assays; immunofluorescence localization; loss-of-function (siRNA depletion) with CI-MPR retrograde trafficking readout\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro lipid transfer activity demonstrated, structural characterization of chorein motif, loss-of-function with defined trafficking phenotype, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"35499567\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Phylogenetic and structural analysis of the RBG (repeating beta groove) superfamily establishes that SHIP164 is one of five eukaryotic bridge-like lipid transfer protein families present since the last eukaryotic common ancestor. Unlike other RBG family members, the C-terminus of SHIP164 has a coiled-coil rather than amphipathic helices. Conserved exterior surface residues along the bridge suggest sites for partner interactions.\",\n      \"method\": \"Sequence analysis and AlphaFold structural prediction with phylogenetic analysis\",\n      \"journal\": \"Contact (Thousand Oaks (Ventura County, Calif.))\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Moderate — computational/structural prediction analysis only, no direct experimental validation of lipid transfer or coiled-coil function\",\n      \"pmids\": [\"36571082\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SHIP164 forms a complex with the ATPase RhoBTB3 and the retromer subunit Vps26B at Golgi-early endosome (EE) contacts to promote formation of Rab14-positive EE buds. Vps26B acts as a novel Rab14 effector, and Rab14 activity regulates the association of SHIP164 with EEs. Depletion of SHIP164 results in enlarged Rab14+ EEs without buds, a phenotype rescued by wild-type SHIP164 but not by lipid transfer-defective SHIP164 mutants. Depletion of RhoBTB3 or Vps26B phenocopies SHIP164 depletion, establishing epistatic relationships within this complex.\",\n      \"method\": \"Co-immunoprecipitation (complex identification), siRNA knockdown with fluorescence microscopy readout (EE bud formation), rescue experiments with wild-type vs. lipid transfer-defective mutants, Rab14 effector assays\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — complex identified by Co-IP, mutagenesis of lipid transfer function used in rescue, epistasis established by parallel depletions, multiple orthogonal methods\",\n      \"pmids\": [\"38565878\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RNAi-mediated knockdown of UHRF1BP1L (SHIP164) modulated mitochondrial dynamics in human neuronal cultures, identifying it as a functional candidate in a Parkinson's disease context.\",\n      \"method\": \"RNAi screen in human neuronal cell culture with mitochondrial dynamics readout\",\n      \"journal\": \"Genome biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single RNAi screen readout, no mechanistic pathway placement, part of a large-scale screen not focused on this gene\",\n      \"pmids\": [\"28137300\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"APEX2 proximity labeling of RAB14 identified SHIP164 (and its close ortholog UHRF1BP1) in the RAB14 proximal proteome, suggesting a functional relationship between RAB14 and SHIP164 consistent with SHIP164 operating at RAB14-positive endosomes.\",\n      \"method\": \"APEX2 proximity labeling proteomics\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proximity labeling only (no direct interaction confirmed), preprint, single method\",\n      \"pmids\": [\"bio_10.1101_2024.11.05.621850\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"SHIP164 (BLTP3B/UHRF1BP1L) is a bridge-like lipid transfer protein (chorein motif, RBG superfamily) that localizes to early endosomes where it forms a complex with RhoBTB3 and Vps26B at Golgi-endosome contact sites to mediate bulk lipid transfer, thereby driving Rab14-positive endosome bud formation and enabling retrograde trafficking of CI-MPR to the Golgi; it also physically interacts with Syntaxin 6 and the GARP tethering complex to regulate endosomal sorting.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"BLTP3B (SHIP164/UHRF1BP1L) is a bridge-like lipid transfer protein of the RBG superfamily that mediates bulk lipid transfer at membrane contact sites to drive endosomal sorting and retrograde trafficking [#1, #3]. It contains a chorein motif characteristic of VPS13-family bridge-like lipid transfer proteins, possesses in vitro lipid transfer activity, and localizes to a subpopulation of CI-MPR-containing vesicle clusters in the early endocytic pathway, where its loss disrupts retrograde delivery of these organelles to the Golgi [#1]. At Golgi–early endosome contacts, BLTP3B forms a complex with the ATPase RhoBTB3 and the retromer subunit Vps26B to promote formation of Rab14-positive endosome buds; depletion produces enlarged Rab14+ endosomes lacking buds, a defect rescued by wild-type but not lipid transfer-defective protein, establishing that its lipid transfer activity is required for bud formation [#3]. BLTP3B also binds the Habc domain of Syntaxin 6 within a large complex that engages the GARP tethering complex, coupling it to endosomal tubulation and the retrograde transport of CI-MPR and transferrin receptor [#0]. Beyond these contact-site sorting roles, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Established the first molecular context for BLTP3B by placing it in the endosomal retrograde sorting machinery via physical links to Syntaxin 6 and the GARP tethering complex.\",\n      \"evidence\": \"Yeast two-hybrid/interaction screen, co-IP, and overexpression/knockdown with CI-MPR and transferrin receptor transport readouts in human cells\",\n      \"pmids\": [\"20163565\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define a molecular activity for the protein\", \"Mechanism by which the Syntaxin 6/GARP complex recruits or activates BLTP3B unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defined BLTP3B as a bridge-like lipid transfer protein, converting its sorting role into a biochemical mechanism by demonstrating chorein-motif structure and in vitro lipid transfer linked to CI-MPR retrograde traffic.\",\n      \"evidence\": \"Structural/sequence analysis of chorein motif, in vitro lipid transfer assays, immunofluorescence, and siRNA loss-of-function with CI-MPR retrograde trafficking readout\",\n      \"pmids\": [\"35499567\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific lipid species transferred in cells not defined\", \"Contact sites bridged not directly imaged at this stage\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placed BLTP3B in the RBG superfamily phylogeny and predicted a distinctive C-terminal coiled-coil and surface residues for partner binding.\",\n      \"evidence\": \"Sequence analysis and AlphaFold structural prediction with phylogenetic analysis\",\n      \"pmids\": [\"36571082\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational prediction only, no experimental validation of the coiled-coil or surface interaction sites\", \"Functional role of C-terminal divergence untested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Resolved the contact-site machinery, showing BLTP3B acts in a RhoBTB3–Vps26B complex at Golgi–early endosome contacts to drive Rab14+ endosome bud formation in a lipid-transfer-dependent manner.\",\n      \"evidence\": \"Co-IP complex identification, siRNA knockdown with EE bud microscopy, rescue with wild-type vs lipid transfer-defective mutants, and Rab14 effector assays\",\n      \"pmids\": [\"38565878\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and assembly order of the BLTP3B–RhoBTB3–Vps26B complex not defined\", \"How Rab14 activity controls BLTP3B endosome association mechanistically unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Independently corroborated the Rab14-endosome localization by detecting BLTP3B in the RAB14 proximal proteome.\",\n      \"evidence\": \"APEX2 proximity labeling proteomics (preprint)\",\n      \"pmids\": [\"bio_10.1101_2024.11.05.621850\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Proximity labeling does not establish direct interaction\", \"Preprint, single method\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Implicated BLTP3B in mitochondrial dynamics in a Parkinson's disease neuronal context, raising an unresolved link between its endosomal function and organelle homeostasis.\",\n      \"evidence\": \"RNAi screen in human neuronal cell culture with mitochondrial dynamics readout\",\n      \"pmids\": [\"28137300\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No mechanistic pathway connecting BLTP3B lipid transfer to mitochondrial dynamics\", \"Part of a large-scale screen, not a focused study\", \"Not independently validated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The identity of the lipids transferred in vivo and the directionality of transfer across the Golgi–endosome bridge remain undefined.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Native lipid cargo and transfer direction not established\", \"Connection between endosomal sorting role and reported mitochondrial phenotype unexplained\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"complexes\": [\"GARP tethering complex (associated)\", \"BLTP3B–RhoBTB3–Vps26B complex\"],\n    \"partners\": [\"STX6\", \"RhoBTB3\", \"VPS26B\", \"RAB14\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}