{"gene":"SYT5","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2019,"finding":"SYT5 localizes to Weibel-Palade bodies (WPBs) in human endothelial cells and acts as a Ca2+ sensor regulating Ca2+-dependent WPB exocytosis. shRNA knockdown of SYT5 reduced histamine-evoked WPB exocytosis and VWF-propeptide secretion; overexpression increased both. A Ca2+-binding defective mutant (Asp197Ser) mimicked SYT5 depletion, establishing Ca2+ binding as essential for function.","method":"shRNA knockdown, overexpression of SYT5-mEGFP/mCherry, Ca2+-binding defective mutant (Asp197Ser), live-cell exocytosis assays, Western blot, VWFpp secretion assay in HUVECs","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal gain- and loss-of-function with mutagenesis rescue, multiple orthogonal readouts (exocytosis rate, cargo secretion), single lab but rigorous controls","pmids":["30659119"],"is_preprint":false},{"year":2025,"finding":"SYT5 functions as the Ca2+ sensor for autophagosome-lysosome fusion, acting downstream of the MCOLN1/TRPML1-MCOLN3/TRPML3 heteromeric Ca2+ channel and PtdIns4P. Ca2+ released from autophagosomes via this channel is decoded by SYT5; binding of both Ca2+ and PtdIns4P to SYT5 is required for forming the fusion complex that drives autophagosome-lysosome fusion.","method":"Knockout and dominant-negative approaches for MCOLN1, MCOLN3, SYT5; Ca2+ imaging; PtdIns4P manipulation; autophagy flux assays (mRFP-GFP tandem LC3); co-immunoprecipitation; epistasis analysis","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 2 / Moderate — KO/DN epistasis plus co-IP, multiple orthogonal methods (Ca2+ imaging, flux assay, binding), single lab","pmids":["40413756"],"is_preprint":false},{"year":1997,"finding":"Human SYT5 (SYTV) encodes a 386-amino-acid protein that is 91% identical to rat Syt V, and its gene is located on chromosome 19q13.4 very close to SYTIII, with seven introns that can be alternatively spliced, establishing linked synaptotagmin genes.","method":"cDNA sequencing, genomic structure determination, PCR of somatic cell hybrids, DNA hybridization to chromosome 19 cosmid array","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct genomic and chromosomal mapping with multiple methods (PCR, hybridization), single lab; structural/localization finding","pmids":["9177789"],"is_preprint":false},{"year":2020,"finding":"Antibodies cross-reactive between Helicobacter pylori antigens and SYT5 (molecular mimicry) impair SYT5 function in SiMa neuroblastoma cells, as demonstrated by significant reduction of acetylcholine-dependent Ca2+ signals and vesicle recycling, mimicking the effect of SYT5-specific antibodies. This positions SYT5 as a functional Ca2+ sensor for vesicle recycling in neuroblastoma cells.","method":"Immunofluorescence, Western blot, multiprotein array, Ca2+ imaging, vesicle recycling assay in SiMa cells pretreated with anti-HPy antibodies or SYT5-specific antibodies","journal":"Journal of molecular neuroscience : MN","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — functional assays (Ca2+ imaging, vesicle recycling) with antibody perturbation, indirect approach, single lab with two orthogonal functional readouts","pmids":["32860155"],"is_preprint":false},{"year":2025,"finding":"In a neonatal rat HI brain injury model treated with BRT_002, proteomic analysis identified upregulation of Syt5, and protein-protein interaction analysis suggested Syt5 interacts with Fblim1 (which connects to Agrin, Zyxin, Vegfa, Vwf, and mitochondrial targets), implicating SYT5 in a network associated with brain repair.","method":"Proteomic analysis of brain tissue, bioinformatics protein-protein interaction analysis","journal":"Neurotherapeutics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — protein-protein interaction is bioinformatic inference only; proteomic upregulation without direct functional validation of SYT5 interactions","pmids":["40533307"],"is_preprint":false}],"current_model":"SYT5 (synaptotagmin 5) is a Ca2+-sensing membrane protein that functions in at least two distinct regulated secretion/fusion contexts: (1) it localizes to Weibel-Palade bodies in endothelial cells where Ca2+ binding through its C2 domains (requiring Asp197) drives Ca2+-dependent exocytosis of VWF; and (2) it acts downstream of the PtdIns4P-MCOLN1-MCOLN3 Ca2+ channel axis on autophagosomes, where binding of Ca2+ and PtdIns4P to SYT5 is required to form the fusion complex that mediates autophagosome-lysosome fusion."},"narrative":{"mechanistic_narrative":"SYT5 (synaptotagmin 5) is a Ca2+-sensing protein that couples Ca2+ signals to membrane fusion in multiple regulated secretion and organelle-fusion contexts [PMID:30659119, PMID:40413756]. In endothelial cells it localizes to Weibel-Palade bodies and acts as the Ca2+ sensor for histamine-evoked, Ca2+-dependent exocytosis of von Willebrand factor, with Ca2+ binding through residue Asp197 being essential — a Ca2+-binding-defective Asp197Ser mutant phenocopies SYT5 depletion [PMID:30659119]. SYT5 also serves as the Ca2+ sensor for autophagosome-lysosome fusion, operating downstream of the MCOLN1/MCOLN3 heteromeric Ca2+ channel and PtdIns4P; coincident binding of both Ca2+ and PtdIns4P to SYT5 is required to assemble the fusion complex that drives this step [PMID:40413756]. The human gene resides on chromosome 19q13.4 adjacent to SYT3 and is alternatively spliced [PMID:9177789]. Beyond these fusion roles, the molecular details of SYT5's fusion partners and structural mechanism have not been characterized in the available corpus.","teleology":[{"year":1997,"claim":"Established the human SYT5 gene's coding sequence, chromosomal location, and intron-exon organization, defining it as a member of a linked synaptotagmin gene cluster and providing the molecular foundation for functional study.","evidence":"cDNA sequencing, genomic structure determination, and chromosomal mapping by PCR and hybridization to chromosome 19 cosmids","pmids":["9177789"],"confidence":"Medium","gaps":["No functional or localization data for the protein","Significance of alternative splicing not resolved","No Ca2+-binding or fusion activity demonstrated"]},{"year":2019,"claim":"Resolved whether SYT5 acts as a functional Ca2+ sensor in regulated exocytosis by showing it controls Ca2+-dependent Weibel-Palade body exocytosis and VWF secretion in endothelial cells.","evidence":"shRNA knockdown, overexpression, Asp197Ser Ca2+-binding mutant, and live-cell exocytosis/VWFpp secretion assays in HUVECs","pmids":["30659119"],"confidence":"High","gaps":["Fusion machinery partners of SYT5 at the WPB not identified","Structural basis of Ca2+ sensing beyond Asp197 not defined","Single lab"]},{"year":2020,"claim":"Extended SYT5's Ca2+-sensor role to neuronal-type vesicle recycling and indicated it can be functionally impaired by cross-reactive antibodies, hinting at an autoimmune-mimicry vulnerability.","evidence":"Antibody perturbation (anti-H. pylori cross-reactive and SYT5-specific), Ca2+ imaging, and vesicle recycling assays in SiMa neuroblastoma cells","pmids":["32860155"],"confidence":"Medium","gaps":["Indirect antibody-based perturbation rather than genetic loss-of-function","Molecular epitope and mechanism of impairment undefined","Physiological relevance of the mimicry in vivo unknown"]},{"year":2025,"claim":"Defined SYT5 as the Ca2+ sensor for autophagosome-lysosome fusion, placing it in a discrete signaling axis where it decodes local Ca2+ and lipid cues to drive organelle fusion.","evidence":"KO and dominant-negative approaches for MCOLN1/MCOLN3/SYT5, Ca2+ imaging, PtdIns4P manipulation, mRFP-GFP-LC3 flux assays, co-IP, and epistasis analysis","pmids":["40413756"],"confidence":"High","gaps":["Identity of the SYT5-containing fusion complex components not fully defined","Structural basis of dual Ca2+/PtdIns4P binding not resolved","Single lab"]},{"year":2025,"claim":"Associated SYT5 upregulation with a brain-repair protein network following neonatal hypoxic-ischemic injury, raising a possible role in injury response.","evidence":"Proteomic profiling and bioinformatic protein-protein interaction analysis in a neonatal rat HI brain injury model","pmids":["40533307"],"confidence":"Low","gaps":["Interactions are bioinformatic inference, not experimentally validated","No direct functional role for SYT5 in brain repair demonstrated","Proteomic upregulation lacks mechanistic follow-up"]},{"year":null,"claim":"It remains unknown which SNARE or core fusion-machinery partners SYT5 engages at each membrane and what structural features confer its dual Ca2+/lipid coincidence detection.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of SYT5 C2 domains in the corpus","Direct fusion-machinery partners unidentified","Whether the WPB and autophagosome roles share mechanism is untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140299","term_label":"molecular sensor activity","supporting_discovery_ids":[0,1]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[1]}],"complexes":[],"partners":["MCOLN1","MCOLN3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O00445","full_name":"Synaptotagmin-5","aliases":["Synaptotagmin V","SytV"],"length_aa":386,"mass_kda":42.9,"function":"May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. Regulates the Ca(2+)-dependent secretion of norepinephrine in PC12 cells. Required for export from the endocytic recycling compartment to the cell surface (By similarity)","subcellular_location":"Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Recycling endosome membrane","url":"https://www.uniprot.org/uniprotkb/O00445/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SYT5","classification":"Not Classified","n_dependent_lines":37,"n_total_lines":1208,"dependency_fraction":0.030629139072847682},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SYT5","total_profiled":1310},"omim":[{"mim_id":"600782","title":"SYNAPTOTAGMIN 5; SYT5","url":"https://www.omim.org/entry/600782"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"brain","ntpm":106.0},{"tissue":"pituitary gland","ntpm":55.4}],"url":"https://www.proteinatlas.org/search/SYT5"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"O00445","domains":[{"cath_id":"2.60.40.150","chopping":"112-229","consensus_level":"high","plddt":91.7728,"start":112,"end":229},{"cath_id":"2.60.40.150","chopping":"243-374","consensus_level":"high","plddt":93.8549,"start":243,"end":374}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O00445","model_url":"https://alphafold.ebi.ac.uk/files/AF-O00445-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O00445-F1-predicted_aligned_error_v6.png","plddt_mean":83.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SYT5","jax_strain_url":"https://www.jax.org/strain/search?query=SYT5"},"sequence":{"accession":"O00445","fasta_url":"https://rest.uniprot.org/uniprotkb/O00445.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O00445/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O00445"}},"corpus_meta":[{"pmid":"31869440","id":"PMC_31869440","title":"Structural and functional relationships between plasmodesmata and plant endoplasmic reticulum-plasma membrane contact sites consisting of three synaptotagmins.","date":"2020","source":"The New phytologist","url":"https://pubmed.ncbi.nlm.nih.gov/31869440","citation_count":48,"is_preprint":false},{"pmid":"30867848","id":"PMC_30867848","title":"Genome-Wide Plasma Cell-Free DNA Methylation Profiling Identifies Potential Biomarkers for Lung Cancer.","date":"2019","source":"Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/30867848","citation_count":43,"is_preprint":false},{"pmid":"32820007","id":"PMC_32820007","title":"LCM-seq reveals unique transcriptional adaptation mechanisms of resistant neurons and identifies protective pathways in spinal muscular atrophy.","date":"2020","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/32820007","citation_count":36,"is_preprint":false},{"pmid":"32894758","id":"PMC_32894758","title":"Differential Effects of Voclosporin and Tacrolimus on 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medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33059718","citation_count":11,"is_preprint":false},{"pmid":"37889708","id":"PMC_37889708","title":"Genome-Wide Re-Sequencing Data Reveals the Population Structure and Selection Signatures of Tunchang Pigs in China.","date":"2023","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/37889708","citation_count":11,"is_preprint":false},{"pmid":"34468021","id":"PMC_34468021","title":"Expression and distribution of synaptotagmin family members in the zebrafish retina.","date":"2021","source":"The Journal of comparative neurology","url":"https://pubmed.ncbi.nlm.nih.gov/34468021","citation_count":10,"is_preprint":false},{"pmid":"9177789","id":"PMC_9177789","title":"Human synaptotagmin V (SYT5): sequence, genomic structure, and chromosomal 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2019,\n      \"finding\": \"SYT5 localizes to Weibel-Palade bodies (WPBs) in human endothelial cells and acts as a Ca2+ sensor regulating Ca2+-dependent WPB exocytosis. shRNA knockdown of SYT5 reduced histamine-evoked WPB exocytosis and VWF-propeptide secretion; overexpression increased both. A Ca2+-binding defective mutant (Asp197Ser) mimicked SYT5 depletion, establishing Ca2+ binding as essential for function.\",\n      \"method\": \"shRNA knockdown, overexpression of SYT5-mEGFP/mCherry, Ca2+-binding defective mutant (Asp197Ser), live-cell exocytosis assays, Western blot, VWFpp secretion assay in HUVECs\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal gain- and loss-of-function with mutagenesis rescue, multiple orthogonal readouts (exocytosis rate, cargo secretion), single lab but rigorous controls\",\n      \"pmids\": [\"30659119\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SYT5 functions as the Ca2+ sensor for autophagosome-lysosome fusion, acting downstream of the MCOLN1/TRPML1-MCOLN3/TRPML3 heteromeric Ca2+ channel and PtdIns4P. Ca2+ released from autophagosomes via this channel is decoded by SYT5; binding of both Ca2+ and PtdIns4P to SYT5 is required for forming the fusion complex that drives autophagosome-lysosome fusion.\",\n      \"method\": \"Knockout and dominant-negative approaches for MCOLN1, MCOLN3, SYT5; Ca2+ imaging; PtdIns4P manipulation; autophagy flux assays (mRFP-GFP tandem LC3); co-immunoprecipitation; epistasis analysis\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO/DN epistasis plus co-IP, multiple orthogonal methods (Ca2+ imaging, flux assay, binding), single lab\",\n      \"pmids\": [\"40413756\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"Human SYT5 (SYTV) encodes a 386-amino-acid protein that is 91% identical to rat Syt V, and its gene is located on chromosome 19q13.4 very close to SYTIII, with seven introns that can be alternatively spliced, establishing linked synaptotagmin genes.\",\n      \"method\": \"cDNA sequencing, genomic structure determination, PCR of somatic cell hybrids, DNA hybridization to chromosome 19 cosmid array\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct genomic and chromosomal mapping with multiple methods (PCR, hybridization), single lab; structural/localization finding\",\n      \"pmids\": [\"9177789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Antibodies cross-reactive between Helicobacter pylori antigens and SYT5 (molecular mimicry) impair SYT5 function in SiMa neuroblastoma cells, as demonstrated by significant reduction of acetylcholine-dependent Ca2+ signals and vesicle recycling, mimicking the effect of SYT5-specific antibodies. This positions SYT5 as a functional Ca2+ sensor for vesicle recycling in neuroblastoma cells.\",\n      \"method\": \"Immunofluorescence, Western blot, multiprotein array, Ca2+ imaging, vesicle recycling assay in SiMa cells pretreated with anti-HPy antibodies or SYT5-specific antibodies\",\n      \"journal\": \"Journal of molecular neuroscience : MN\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — functional assays (Ca2+ imaging, vesicle recycling) with antibody perturbation, indirect approach, single lab with two orthogonal functional readouts\",\n      \"pmids\": [\"32860155\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In a neonatal rat HI brain injury model treated with BRT_002, proteomic analysis identified upregulation of Syt5, and protein-protein interaction analysis suggested Syt5 interacts with Fblim1 (which connects to Agrin, Zyxin, Vegfa, Vwf, and mitochondrial targets), implicating SYT5 in a network associated with brain repair.\",\n      \"method\": \"Proteomic analysis of brain tissue, bioinformatics protein-protein interaction analysis\",\n      \"journal\": \"Neurotherapeutics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — protein-protein interaction is bioinformatic inference only; proteomic upregulation without direct functional validation of SYT5 interactions\",\n      \"pmids\": [\"40533307\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SYT5 (synaptotagmin 5) is a Ca2+-sensing membrane protein that functions in at least two distinct regulated secretion/fusion contexts: (1) it localizes to Weibel-Palade bodies in endothelial cells where Ca2+ binding through its C2 domains (requiring Asp197) drives Ca2+-dependent exocytosis of VWF; and (2) it acts downstream of the PtdIns4P-MCOLN1-MCOLN3 Ca2+ channel axis on autophagosomes, where binding of Ca2+ and PtdIns4P to SYT5 is required to form the fusion complex that mediates autophagosome-lysosome fusion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SYT5 (synaptotagmin 5) is a Ca2+-sensing protein that couples Ca2+ signals to membrane fusion in multiple regulated secretion and organelle-fusion contexts [#0, #1]. In endothelial cells it localizes to Weibel-Palade bodies and acts as the Ca2+ sensor for histamine-evoked, Ca2+-dependent exocytosis of von Willebrand factor, with Ca2+ binding through residue Asp197 being essential — a Ca2+-binding-defective Asp197Ser mutant phenocopies SYT5 depletion [#0]. SYT5 also serves as the Ca2+ sensor for autophagosome-lysosome fusion, operating downstream of the MCOLN1/MCOLN3 heteromeric Ca2+ channel and PtdIns4P; coincident binding of both Ca2+ and PtdIns4P to SYT5 is required to assemble the fusion complex that drives this step [#1]. The human gene resides on chromosome 19q13.4 adjacent to SYT3 and is alternatively spliced [#2]. Beyond these fusion roles, the molecular details of SYT5's fusion partners and structural mechanism have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Established the human SYT5 gene's coding sequence, chromosomal location, and intron-exon organization, defining it as a member of a linked synaptotagmin gene cluster and providing the molecular foundation for functional study.\",\n      \"evidence\": \"cDNA sequencing, genomic structure determination, and chromosomal mapping by PCR and hybridization to chromosome 19 cosmids\",\n      \"pmids\": [\"9177789\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional or localization data for the protein\", \"Significance of alternative splicing not resolved\", \"No Ca2+-binding or fusion activity demonstrated\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Resolved whether SYT5 acts as a functional Ca2+ sensor in regulated exocytosis by showing it controls Ca2+-dependent Weibel-Palade body exocytosis and VWF secretion in endothelial cells.\",\n      \"evidence\": \"shRNA knockdown, overexpression, Asp197Ser Ca2+-binding mutant, and live-cell exocytosis/VWFpp secretion assays in HUVECs\",\n      \"pmids\": [\"30659119\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Fusion machinery partners of SYT5 at the WPB not identified\", \"Structural basis of Ca2+ sensing beyond Asp197 not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended SYT5's Ca2+-sensor role to neuronal-type vesicle recycling and indicated it can be functionally impaired by cross-reactive antibodies, hinting at an autoimmune-mimicry vulnerability.\",\n      \"evidence\": \"Antibody perturbation (anti-H. pylori cross-reactive and SYT5-specific), Ca2+ imaging, and vesicle recycling assays in SiMa neuroblastoma cells\",\n      \"pmids\": [\"32860155\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Indirect antibody-based perturbation rather than genetic loss-of-function\", \"Molecular epitope and mechanism of impairment undefined\", \"Physiological relevance of the mimicry in vivo unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined SYT5 as the Ca2+ sensor for autophagosome-lysosome fusion, placing it in a discrete signaling axis where it decodes local Ca2+ and lipid cues to drive organelle fusion.\",\n      \"evidence\": \"KO and dominant-negative approaches for MCOLN1/MCOLN3/SYT5, Ca2+ imaging, PtdIns4P manipulation, mRFP-GFP-LC3 flux assays, co-IP, and epistasis analysis\",\n      \"pmids\": [\"40413756\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the SYT5-containing fusion complex components not fully defined\", \"Structural basis of dual Ca2+/PtdIns4P binding not resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Associated SYT5 upregulation with a brain-repair protein network following neonatal hypoxic-ischemic injury, raising a possible role in injury response.\",\n      \"evidence\": \"Proteomic profiling and bioinformatic protein-protein interaction analysis in a neonatal rat HI brain injury model\",\n      \"pmids\": [\"40533307\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Interactions are bioinformatic inference, not experimentally validated\", \"No direct functional role for SYT5 in brain repair demonstrated\", \"Proteomic upregulation lacks mechanistic follow-up\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown which SNARE or core fusion-machinery partners SYT5 engages at each membrane and what structural features confer its dual Ca2+/lipid coincidence detection.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of SYT5 C2 domains in the corpus\", \"Direct fusion-machinery partners unidentified\", \"Whether the WPB and autophagosome roles share mechanism is untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140299\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MCOLN1\", \"MCOLN3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}