{"gene":"SCFD1","run_date":"2026-06-10T07:46:29","timeline":{"discoveries":[{"year":1996,"finding":"Mammalian Sly1 (RA410/SCFD1) forms a native complex with syntaxin 5 in rat liver membranes, and overexpression of rSly1 neutralizes the dominant-negative effects of excess syntaxin 5 on ER-to-Golgi transport, establishing a positive regulatory role for SCFD1 in syntaxin 5-dependent early secretory pathway transport.","method":"Biochemical co-purification from rat liver membranes, dominant-negative rescue by transient overexpression in mammalian cells","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — native complex co-purification plus functional rescue in cells, single lab, two complementary methods","pmids":["8663406"],"is_preprint":false},{"year":1997,"finding":"RA410 (SCFD1), cloned from reoxygenated rat astrocytes, encodes a Sec1/Unc18-family vesicle transport protein that localizes predominantly to the plasma membrane fraction and, by immunoelectron microscopy, to large vesicles associated with the Golgi apparatus (but not the Golgi itself), consistent with a role in post-Golgi transport.","method":"Subcellular fractionation on sucrose gradients, immunoelectron microscopy, polyclonal antibody against synthetic peptide","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by two orthogonal methods (fractionation + immunoEM), single lab, no functional mutagenesis","pmids":["9195952"],"is_preprint":false},{"year":2002,"finding":"Sly1 binds to a short, evolutionarily conserved N-terminal peptide motif of the syntaxins Sed5p and Ufe1p (yeast) and syntaxins 5 and 18 (vertebrates); this binding site is upstream of the autonomously folded N-terminal domain of these syntaxins, defining a distinct peptide-based interaction mode for this SM protein that differs from the closed-conformation binding of Munc18 to syntaxin 1.","method":"Biochemical binding assays with purified proteins, peptide competition, domain mapping","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified proteins, replicated across yeast and vertebrate syntaxins, mechanistically defined interaction site","pmids":["11879635"],"is_preprint":false},{"year":2002,"finding":"Sly1p can bind simultaneously to the ER-to-Golgi core SNARE fusion complex assembled on syntaxin Sed5p; Sly1p-bound Sed5p supports assembly of the cognate SNARE complex without significantly altering kinetics, but prevents formation of several non-physiological SNARE complexes, demonstrating that this SM protein contributes to the specificity of SNARE pairing.","method":"In vitro SNARE complex assembly with purified yeast proteins, co-immunoprecipitation from yeast lysates","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstituted in vitro with purified proteins plus reciprocal co-IP from cell lysates, mechanistically informative with kinetic and specificity measurements","pmids":["11994317"],"is_preprint":false},{"year":2002,"finding":"In yeast, Sly1 binding to the t-SNARE Sed5 enhances trans-SNARE complex formation with the v-SNARE Bet1; a temperature-sensitive sly1 mutant with reduced Sed5 binding shows reduced presence in the Sed5-Bet1 complex, directly linking Sly1-Sed5 interaction to productive SNARE complex assembly.","method":"Co-immunoprecipitation, in vitro SNARE complex formation with recombinant proteins added to yeast lysate","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP plus in vitro reconstitution in lysate, single lab","pmids":["12186954"],"is_preprint":false},{"year":2003,"finding":"In zebrafish, the orthologue of yeast sly1 (SCFD1) is required for blastema formation and cell proliferation during caudal fin regeneration; a temperature-sensitive point mutation in sly1 blocks regeneration by reducing proliferation in the proximal blastema, demonstrating an essential in vivo role for this SM protein in cell proliferation during tissue regeneration.","method":"Positional cloning of temperature-sensitive zebrafish mutant (emmental), histology, BrdU proliferation assay, molecular analysis","journal":"Developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — positional cloning with temperature-sensitive allele plus cellular phenotyping, single lab, well-defined loss-of-function","pmids":["12798289"],"is_preprint":false},{"year":2003,"finding":"In yeast, the binding of Sly1 to the t-SNARE Sed5 cooperates with Sec18/NSF ATPase to promote disassembly of cis-SNARE complexes; a sly1(ts) mutant defective in Sed5 binding retards cis-SNARE disassembly, and the sly1(ts) and sec18-1 mutations show synthetic lethality.","method":"Genetic epistasis (synthetic lethality), temperature-sensitive yeast mutants, SNARE disassembly assay","journal":"Bioscience, biotechnology, and biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis plus biochemical disassembly assay, single lab","pmids":["12729020"],"is_preprint":false},{"year":2005,"finding":"The gain-of-function SLY1-20 allele in yeast does not bypass the requirement for vesicle tethering mediated by Uso1p; rather, an alternative Rab GTPase (Ypt6) substitutes for Ypt1p in tethering when SLY1-20 is expressed, and tethering/fusion remain sensitive to Rab GDI, indicating that SLY1-20 suppression still requires Rab-dependent tethering.","method":"Co-immunoprecipitation, cell-free tethering and fusion assays, Rab GDI sensitivity, genetic epistasis","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cell-free assays plus co-IP plus genetic epistasis, single lab, multiple orthogonal approaches","pmids":["15689495"],"is_preprint":false},{"year":2005,"finding":"RA410/Sly1 (SCFD1) overexpression in SH-SY5Y cells protects against MPP+- and 6-OHDA-induced cell death by suppressing caspase-2, -3, and -9 activation, and antisense knockdown of RA410/Sly1 accelerates ER disruption upon MPP+ treatment, demonstrating a cytoprotective role linked to ER integrity.","method":"Antisense and sense RNA stable transformants, cell viability assay, electron microscopy of ER morphology, caspase activation assays","journal":"Neurobiology of disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain- and loss-of-function with multiple mechanistic readouts (ER morphology, caspase activation), single lab","pmids":["15649705"],"is_preprint":false},{"year":2007,"finding":"Gain-of-function mutations in the SM protein Sly1 that bypass Ypt/Rab GTPase requirements for ER-to-Golgi vesicular transport all map to a short conserved alpha-helix (α-20); deletion of this helix also causes bypass suppression, identifying α-20 as the domain mediating Rab-regulated Sly1 function in membrane fusion.","method":"Mutagenesis screen, genetic complementation, domain deletion analysis in yeast","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — structure-guided mutagenesis with defined genetic phenotype, single lab","pmids":["18036347"],"is_preprint":false},{"year":2009,"finding":"The SM protein Sly1 (SCFD1) directly interacts with the Cog4 subunit of the conserved oligomeric Golgi (COG) tethering complex; Cog4 also independently interacts with Syntaxin 5 through a distinct binding site, and disruption of the Cog4-Sly1 interaction impairs SNARE pairing for intra-Golgi transport and markedly attenuates Golgi-to-ER retrograde transport.","method":"Co-immunoprecipitation, pulldown assays with purified proteins, siRNA knockdown, Golgi-to-ER retrograde transport assay","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding demonstrated with purified proteins, disruption-of-interaction experiment with functional transport readout, multiple orthogonal methods","pmids":["19536132"],"is_preprint":false},{"year":2014,"finding":"The yeast SM protein Sly1 binds to both the N-peptide and the closed conformation of the Qa-SNARE Sed5, and this dual engagement facilitates SNARE complex formation by loosening the closed conformation of Sed5, in contrast to Munc18 which locks syntaxin 1 in a closed state incompatible with SNARE assembly.","method":"Biochemical binding assays with purified proteins, fluorescence anisotropy, in vitro SNARE complex formation kinetics","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified proteins, multiple orthogonal binding assays, mechanistic comparison with controls","pmids":["25189771"],"is_preprint":false},{"year":2014,"finding":"SLY1 (SCFD1) is required for ER export of Procollagen VII but not Procollagen I; knockdown of SLY1 arrests Procollagen VII in the ER without affecting COPII recruitment, general secretion, or retrograde transport; among SLY1-interacting SNAREs, only Syntaxin 18 (not Syntaxin 17) is specifically required for Procollagen VII export, defining a TANGO1-SLY1-Syntaxin 18 pathway for bulky collagen export.","method":"siRNA knockdown, pulse-chase secretion assays, immunofluorescence colocalization, rescue experiments","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — siRNA knockdown with multiple cargo specificity controls, SNARE-selective requirement established, interaction with TANGO1 defined, consistent with independent zebrafish data","pmids":["24842878"],"is_preprint":false},{"year":2016,"finding":"Loss of scfd1 in zebrafish causes craniofacial defects due to failure of chondrogenesis; scfd1 mutation hinders ER-to-Golgi transport of ECM proteins and activates the unfolded protein response in chondrocytes; knockdown of either SCFD1 or STX18 (a SLY1-interacting t-SNARE) in mammalian chondrocytes severely impairs type II collagen transport, demonstrating a conserved SCFD1-STX18 pathway for large ECM protein secretion.","method":"Zebrafish forward mutagenesis screen, siRNA knockdown in mammalian chondrocytes, ER-to-Golgi transport assay, UPR activation markers","journal":"Developmental biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function in two species (zebrafish and mammalian cells) with defined cellular phenotype, consistent with independent SNARE selectivity data from eLife 2014","pmids":["27851892"],"is_preprint":false},{"year":2021,"finding":"mTORC1 phosphorylates VAMP8 to block autophagosome-lysosome fusion; dephosphorylated VAMP8 promotes recruitment of SCFD1 to autolysosomes; SCFD1 localizes to the autolysosome and is required for formation of the STX17-SNAP29-VAMP8 SNARE complex and for autophagosome-lysosome fusion; VAMP8 phosphorylation mimic or SCFD1 depletion blocks this fusion in vitro.","method":"mTORC1 kinase assay, phosphorylation site mutagenesis, siRNA knockdown, in vitro fusion assay, live-cell imaging, immunofluorescence co-localization, mouse liver overexpression","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro fusion reconstitution, mutagenesis of phosphorylation site, loss-of-function with defined molecular phenotype, multiple orthogonal methods across cell-free and cell-based systems","pmids":["34785650"],"is_preprint":false},{"year":2022,"finding":"SCFD1 is acetylated at residues K126 and K515 by the acetyltransferase KAT2B/PCAF, and deacetylated by SIRT4; acetylation of these residues inhibits autophagic flux by blocking STX17-SNAP29-VAMP8 SNARE complex formation; AMPK-mediated phosphorylation of SCFD1 disrupts SCFD1 interaction with KAT2B, keeping SCFD1 acetylation low during autophagy stimulation.","method":"Mass spectrometry identification of acetylation sites, acetyltransferase/deacetylase co-expression and knockdown, acetylation-mimetic and phospho-mimetic mutants, co-immunoprecipitation, autophagic flux assay","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 1 / Strong — site-specific PTM mapping by MS, writer/eraser identified, functional acetylation-mimic mutagenesis, cross-talk with phosphorylation mechanism established, multiple orthogonal methods","pmids":["35465820"],"is_preprint":false},{"year":2023,"finding":"Moderate silencing of Slh (Drosophila orthologue of SCFD1) causes climbing and flight motor defects in adult flies; severe knockdown causes larval mobility reduction, neuromuscular junction deficits, and lethality before metamorphosis; RNA-seq downstream of Slh ablation reveals downregulation of chaperone genes mediating protein folding.","method":"RNAi-mediated gene silencing in Drosophila, behavioral assays (climbing, flight), NMJ morphology analysis, RNA-seq transcriptomic profiling","journal":"Neurobiology of aging","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined neuromuscular phenotype and downstream transcriptomic mechanism, single lab","pmids":["36944290"],"is_preprint":false},{"year":2023,"finding":"Loss of scfd1 in zebrafish (nonsense mutation or CRISPR knockout) causes severe cardiac and craniofacial defects with ER stress; electron microscopy of scfd1-depleted cardiomyocytes shows reduced myofibril width, sarcomere density reduction, and Golgi fragmentation; qPCR confirms upregulation of ER stress response and apoptosis markers, linking scfd1 to ER/Golgi membrane transport in cardiomyocytes.","method":"Positional cloning, CRISPR/Cas9 knockout, electron microscopy, qPCR for ER stress markers, cardiac phenotype analysis","journal":"Journal of cardiovascular development and disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two independent zebrafish loss-of-function alleles with ultrastructural and molecular readouts, single lab","pmids":["37887855"],"is_preprint":false},{"year":2024,"finding":"Sly1 contains an ALPS (amphipathic lipid packing sensor)-like helix within a conserved regulatory loop that directly binds high-curvature membranes; this membrane binding both relieves Sly1 autoinhibition and allows Sly1 to tether incoming vesicles to the Qa-SNARE on the target organelle (close-range tethering); the SLY1-20 gain-of-function allele loses its bypass-tethering ability when this tethering activity is impaired, supporting a handoff model from long-range to Sly1-mediated close-range tethering.","method":"Chemically defined in vitro reconstitution of ER-Golgi fusion, genetic analyses with Sly1 loop mutants, liposome binding assay, gain-of-function allele analysis","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with chemically defined components, mutagenesis of ALPS helix, multiple mechanistic readouts, functionally validated tethering activity","pmids":["38478018"],"is_preprint":false},{"year":2024,"finding":"Sly1 promotes ER-Golgi SNARE-mediated membrane fusion through three parallel mechanisms: (i) opening the closed conformation of Qa-SNARE Sed5, (ii) close-range vesicle tethering via its regulatory loop, and (iii) nucleating productive trans-SNARE complexes; additionally, the autoinhibitory Habc domain of Sed5 has positive activities—required for correct Sed5 localization and directly promoting Sly1-dependent lipid mixing.","method":"Chemically defined in vitro fusion assays with SNARE and Sly1 mutants, 'split Sed5' in vitro and in vivo complementation, lipid mixing assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — chemically defined reconstitution with separation-of-function mutants for each proposed mechanism, in vitro and in vivo validation","pmids":["38478017"],"is_preprint":false},{"year":2024,"finding":"The T4SS effector EgeA of Anaplasma phagocytophilum directly binds SCFD1 (via its C-terminal half, confirmed by yeast two-hybrid), redirecting SCFD1 and its binding partner TANGO1 from ER-Golgi exit sites (ERES) to pathogen-occupied inclusions; knockdown of either TANGO1 or SCFD1 significantly reduces Anaplasma infection, demonstrating that SCFD1 function at ERES is exploited by the pathogen.","method":"Yeast two-hybrid (EgeA-C vs SCFD1), GFP-fusion localization, siRNA knockdown infection assay, pulldown for TANGO1 binding","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid plus loss-of-function infection assay, single lab, interaction confirmed by two methods","pmids":["39106308"],"is_preprint":false}],"current_model":"SCFD1 (Sly1) is a Sec1/Munc18-family SM protein that functions at multiple membrane fusion steps in the secretory and autophagic pathways: it binds the N-terminal peptide motif of ER/Golgi syntaxins (Syntaxin 5, 18, Sed5, Ufe1p), facilitates SNARE complex assembly and specificity by opening the closed conformation of Qa-SNAREs and nucleating trans-SNARE complexes, directly tethers vesicles at close range via an ALPS-like helix in its regulatory loop, links tethering to fusion by interacting with the COG tethering complex via Cog4, and is required in vivo for ER-to-Golgi transport of bulky cargo (collagens, ECM proteins) via a specific SCFD1-Syntaxin 18 pathway; additionally, SCFD1 localizes to autolysosomes where it is required for STX17-SNAP29-VAMP8 SNARE complex assembly and autophagosome-lysosome fusion, a process regulated by mTORC1-mediated phosphorylation of VAMP8 (controlling SCFD1 recruitment) and by KAT2B/SIRT4-mediated acetylation of SCFD1 itself at K126/K515 (controlled by AMPK phosphorylation of SCFD1)."},"narrative":{"mechanistic_narrative":"SCFD1 (Sly1/RA410) is a Sec1/Munc18-family SM protein that orchestrates SNARE-mediated membrane fusion in the early secretory pathway and in autophagy [PMID:8663406, PMID:11879635]. Unlike Munc18's closed-conformation clamp on syntaxin 1, SCFD1 engages ER/Golgi Qa-SNAREs (Syntaxin 5, Syntaxin 18, yeast Sed5 and Ufe1) through a short conserved N-terminal peptide motif while also binding the closed conformation, an interaction that loosens the closed state and licenses SNARE assembly [PMID:11879635, PMID:25189771]. Through this engagement it confers specificity on SNARE pairing by supporting cognate complex formation while preventing non-physiological complexes, and it enhances productive trans-SNARE assembly [PMID:11994317, PMID:12186954]. Mechanistic reconstitution resolves three parallel contributions to ER-Golgi fusion: opening the Qa-SNARE, nucleating trans-SNARE complexes, and close-range vesicle tethering via an ALPS-like amphipathic helix in a regulatory loop that binds high-curvature membranes and relieves SCFD1 autoinhibition, downstream of Rab-dependent long-range tethering [PMID:38478018, PMID:38478017, PMID:15689495]. SCFD1 couples tethering to fusion by directly binding the Cog4 subunit of the COG complex, an interaction required for intra-Golgi SNARE pairing and Golgi-to-ER retrograde transport [PMID:19536132]. In vivo, a SCFD1–Syntaxin 18 pathway is specifically required for ER export of bulky cargo such as procollagen VII and type II collagen, and its loss causes chondrogenesis, craniofacial, and cardiac defects with ER stress in zebrafish [PMID:24842878, PMID:27851892, PMID:37887855]. Independently, SCFD1 localizes to autolysosomes where it is required for STX17–SNAP29–VAMP8 SNARE complex assembly and autophagosome–lysosome fusion; this autophagic function is gated by mTORC1 phosphorylation of VAMP8 (controlling SCFD1 recruitment) and by KAT2B/SIRT4-mediated acetylation of SCFD1 at K126/K515, itself disrupted by AMPK phosphorylation of SCFD1 [PMID:34785650, PMID:35465820].","teleology":[{"year":1996,"claim":"Established that mammalian SCFD1 is a positive regulator of syntaxin 5-dependent ER-to-Golgi transport, placing the SM protein in the early secretory pathway.","evidence":"Native complex co-purification with syntaxin 5 from rat liver membranes and dominant-negative rescue in cells","pmids":["8663406"],"confidence":"Medium","gaps":["Binding mode to syntaxin 5 not defined","No reconstitution of the fusion step"]},{"year":1997,"claim":"Identified SCFD1 as a Sec1/Unc18-family protein and localized it to vesicles associated with the Golgi, framing it as a vesicle transport factor.","evidence":"Subcellular fractionation and immunoelectron microscopy with peptide antibody","pmids":["9195952"],"confidence":"Medium","gaps":["Localization without functional mutagenesis","Plasma membrane fraction signal unexplained mechanistically"]},{"year":2002,"claim":"Defined the distinctive binding mode of SCFD1: it recognizes a conserved N-terminal peptide motif of ER/Golgi syntaxins, mechanistically separating it from Munc18 closed-syntaxin binding, and showed it supports SNARE pairing specificity.","evidence":"In vitro binding and domain mapping with purified yeast and vertebrate syntaxins; in vitro SNARE assembly and co-IP","pmids":["11879635","11994317","12186954"],"confidence":"High","gaps":["How peptide binding mechanistically promotes assembly not yet resolved","Role of the syntaxin closed conformation not addressed"]},{"year":2003,"claim":"Connected SCFD1's syntaxin binding to upstream SNARE recycling and to an essential organismal proliferation requirement, broadening its functional importance.","evidence":"Yeast genetic epistasis with sec18/NSF plus disassembly assays; zebrafish temperature-sensitive mutant with proliferation phenotype","pmids":["12729020","12798289"],"confidence":"Medium","gaps":["Mechanistic link between Sed5 binding and cis-SNARE disassembly not defined","Whether fin regeneration defect is cell-autonomous secretory failure unclear"]},{"year":2005,"claim":"Showed SCFD1's fusion function operates downstream of, and still depends on, Rab-mediated tethering, and linked it to ER integrity and cytoprotection.","evidence":"Cell-free tethering/fusion assays with Rab GDI sensitivity and genetic epistasis; gain/loss-of-function in neuronal cells with ER morphology and caspase readouts","pmids":["15689495","15649705"],"confidence":"Medium","gaps":["Direct molecular handoff from Rab tethering to SCFD1 not shown","Cytoprotection mechanism downstream of ER integrity unresolved"]},{"year":2007,"claim":"Mapped the Rab-regulated function of SCFD1 to a short conserved alpha-helix (alpha-20), identifying the structural element that couples Rab signaling to fusion.","evidence":"Mutagenesis screen and domain deletion with genetic bypass phenotypes in yeast","pmids":["18036347"],"confidence":"Medium","gaps":["Biochemical activity of alpha-20 not defined at this stage","Membrane interaction not yet demonstrated"]},{"year":2009,"claim":"Linked SCFD1 tethering to fusion mechanistically by demonstrating a direct interaction with the Cog4 subunit of the COG tethering complex required for intra-Golgi SNARE pairing and retrograde transport.","evidence":"Purified-protein pulldowns, co-IP, siRNA, and Golgi-to-ER retrograde transport assay","pmids":["19536132"],"confidence":"High","gaps":["Structural basis of Cog4-SCFD1 interface not resolved","Whether COG binding competes with syntaxin engagement unknown"]},{"year":2014,"claim":"Resolved the mechanism of Qa-SNARE activation (dual N-peptide plus closed-conformation binding that loosens the closed state) and defined an in vivo SCFD1–Syntaxin 18 pathway dedicated to bulky collagen export.","evidence":"Fluorescence anisotropy and SNARE assembly kinetics with purified proteins; siRNA with cargo-specific pulse-chase secretion assays","pmids":["25189771","24842878"],"confidence":"High","gaps":["Why bulky cargo selectively requires this pathway not fully explained","Structural model of loosened Sed5 absent"]},{"year":2016,"claim":"Established the conserved physiological consequence of the SCFD1–STX18 pathway in ECM secretion, showing chondrocyte collagen transport failure and UPR activation across species.","evidence":"Zebrafish mutagenesis and mammalian chondrocyte siRNA with ER-to-Golgi transport and UPR markers","pmids":["27851892"],"confidence":"High","gaps":["Tissue specificity of cargo dependence not mechanistically resolved"]},{"year":2021,"claim":"Extended SCFD1 function beyond the secretory pathway to autophagy, showing it drives autophagosome-lysosome fusion via STX17-SNAP29-VAMP8 assembly under mTORC1 control of VAMP8 phosphorylation.","evidence":"mTORC1 kinase assay, phospho-site mutagenesis, in vitro fusion reconstitution, siRNA, imaging, mouse liver","pmids":["34785650"],"confidence":"High","gaps":["How dephospho-VAMP8 recruits SCFD1 at the molecular level not detailed","Relationship to its secretory role at the same locus unclear"]},{"year":2022,"claim":"Defined an acetylation/phosphorylation regulatory code on SCFD1 itself that gates its autophagic SNARE-assembly activity.","evidence":"MS site mapping, KAT2B/SIRT4 writer/eraser manipulation, acetyl- and phospho-mimetic mutants, autophagic flux assays","pmids":["35465820"],"confidence":"High","gaps":["Whether the same PTMs regulate secretory-pathway function untested","Structural impact of K126/K515 acetylation unknown"]},{"year":2024,"claim":"Provided the unified fusion mechanism: SCFD1 opens the Qa-SNARE, nucleates trans-SNARE complexes, and tethers vesicles at close range via an ALPS-like helix that senses curvature and relieves autoinhibition, completing a tethering-to-fusion handoff model.","evidence":"Chemically defined in vitro ER-Golgi fusion reconstitution with separation-of-function and ALPS-helix mutants, liposome binding, split-Sed5 complementation","pmids":["38478018","38478017"],"confidence":"High","gaps":["Whether the ALPS-like tethering activity operates in the autophagic fusion context untested","Structural snapshot of the tethered intermediate absent"]},{"year":2024,"claim":"Showed SCFD1's ERES function is hijacked by a bacterial pathogen, identifying a direct effector interaction that redirects SCFD1 and TANGO1.","evidence":"Yeast two-hybrid, GFP-fusion localization, and siRNA infection assays with Anaplasma EgeA effector","pmids":["39106308"],"confidence":"Medium","gaps":["Y2H interaction not validated by reciprocal pulldown in mammalian cells","Mechanism by which EgeA binding relocalizes SCFD1 unresolved"]},{"year":null,"claim":"How SCFD1 is partitioned between its secretory (ER-Golgi/ERES) and autophagic (autolysosome) fusion roles, and whether its tethering and PTM-regulatory mechanisms are shared across both, remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of SCFD1 bound to closed Sed5/syntaxin","Spatial/temporal control switching SCFD1 between compartments unknown","No human disease mutation directly evaluated in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[3,11,19]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[18]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3,11,14]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1,10]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[12,13,17]},{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[14]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[1,18]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,10,12]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[10,18,19]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[14,15]},{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[12,13]}],"complexes":["STX17-SNAP29-VAMP8 SNARE complex","ER-Golgi (Sed5/Syntaxin 5) SNARE complex"],"partners":["STX5","STX18","SED5","UFE1","COG4","VAMP8","TANGO1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WVM8","full_name":"Sec1 family domain-containing protein 1","aliases":["SLY1 homolog","Sly1p","Syntaxin-binding protein 1-like 2"],"length_aa":642,"mass_kda":72.4,"function":"Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with COG4. Involved in vesicular transport between the endoplasmic reticulum and the Golgi (By similarity)","subcellular_location":"Cytoplasm; Endoplasmic reticulum membrane; Golgi apparatus, Golgi stack membrane","url":"https://www.uniprot.org/uniprotkb/Q8WVM8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SCFD1","classification":"Common Essential","n_dependent_lines":1202,"n_total_lines":1208,"dependency_fraction":0.9950331125827815},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000092108","cell_line_id":"CID000762","localizations":[{"compartment":"er","grade":3},{"compartment":"golgi","grade":3}],"interactors":[{"gene":"BET1L","stoichiometry":10.0},{"gene":"BNIP1","stoichiometry":10.0},{"gene":"GOLT1B","stoichiometry":10.0},{"gene":"GOSR1","stoichiometry":10.0},{"gene":"GOSR2","stoichiometry":10.0},{"gene":"STX5","stoichiometry":10.0},{"gene":"STX18","stoichiometry":10.0},{"gene":"NAPA","stoichiometry":4.0},{"gene":"USE1","stoichiometry":4.0},{"gene":"NSF","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/target/CID000762","total_profiled":1310},"omim":[{"mim_id":"618207","title":"SEC1 FAMILY DOMAIN-CONTAINING PROTEIN 1; SCFD1","url":"https://www.omim.org/entry/618207"},{"mim_id":"606976","title":"COMPONENT OF OLIGOMERIC GOLGI COMPLEX 4; COG4","url":"https://www.omim.org/entry/606976"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SCFD1"},"hgnc":{"alias_symbol":["RA410","KIAA0917","STXBP1L2","SLY1"],"prev_symbol":["C14orf163"]},"alphafold":{"accession":"Q8WVM8","domains":[{"cath_id":"3.40.50.2060","chopping":"14-151","consensus_level":"high","plddt":93.6651,"start":14,"end":151},{"cath_id":"3.40.50.1910","chopping":"154-265_545-639","consensus_level":"high","plddt":89.4555,"start":154,"end":639}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WVM8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WVM8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WVM8-F1-predicted_aligned_error_v6.png","plddt_mean":84.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SCFD1","jax_strain_url":"https://www.jax.org/strain/search?query=SCFD1"},"sequence":{"accession":"Q8WVM8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WVM8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WVM8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WVM8"}},"corpus_meta":[{"pmid":"11879635","id":"PMC_11879635","title":"Sly1 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England)","url":"https://pubmed.ncbi.nlm.nih.gov/11481671","citation_count":19,"is_preprint":false},{"pmid":"26306874","id":"PMC_26306874","title":"SLy1 regulates T-cell proliferation during Listeria monocytogenes infection in a Foxo1-dependent manner.","date":"2015","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/26306874","citation_count":18,"is_preprint":false},{"pmid":"19604361","id":"PMC_19604361","title":"The orphan adapter protein SLY1 as a novel anti-apoptotic protein required for thymocyte development.","date":"2009","source":"BMC immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19604361","citation_count":15,"is_preprint":false},{"pmid":"18950867","id":"PMC_18950867","title":"Reduced notch activity is associated with an impaired marginal zone B cell development and function in Sly1 mutant mice.","date":"2008","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18950867","citation_count":15,"is_preprint":false},{"pmid":"31267315","id":"PMC_31267315","title":"Does SCFD1 rs10139154 Polymorphism Decrease Alzheimer's Disease Risk?","date":"2019","source":"Journal of molecular neuroscience : MN","url":"https://pubmed.ncbi.nlm.nih.gov/31267315","citation_count":14,"is_preprint":false},{"pmid":"30631134","id":"PMC_30631134","title":"Structure of the SLy1 SAM homodimer reveals a new interface for SAM domain self-association.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30631134","citation_count":14,"is_preprint":false},{"pmid":"36944290","id":"PMC_36944290","title":"Loss of amyotrophic lateral sclerosis risk factor SCFD1 causes motor dysfunction in Drosophila.","date":"2023","source":"Neurobiology of aging","url":"https://pubmed.ncbi.nlm.nih.gov/36944290","citation_count":12,"is_preprint":false},{"pmid":"28123874","id":"PMC_28123874","title":"Deficiency of the adaptor protein SLy1 results in a natural killer cell ribosomopathy affecting tumor clearance.","date":"2016","source":"Oncoimmunology","url":"https://pubmed.ncbi.nlm.nih.gov/28123874","citation_count":9,"is_preprint":false},{"pmid":"37887855","id":"PMC_37887855","title":"Loss of Sec-1 Family Domain-Containing 1 (scfd1) Causes Severe Cardiac Defects and Endoplasmic Reticulum Stress in Zebrafish.","date":"2023","source":"Journal of cardiovascular development and disease","url":"https://pubmed.ncbi.nlm.nih.gov/37887855","citation_count":9,"is_preprint":false},{"pmid":"29260601","id":"PMC_29260601","title":"An association study between SCFD1 rs10139154 variant and amyotrophic lateral sclerosis in a Chinese cohort.","date":"2017","source":"Amyotrophic lateral sclerosis & frontotemporal degeneration","url":"https://pubmed.ncbi.nlm.nih.gov/29260601","citation_count":6,"is_preprint":false},{"pmid":"12729020","id":"PMC_12729020","title":"Cooperation of Sly1/SM-family protein and sec18/NSF of Saccharomyces cerevisiae in disassembly of cis-SNARE membrane-protein complexes.","date":"2003","source":"Bioscience, biotechnology, and biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12729020","citation_count":6,"is_preprint":false},{"pmid":"39106308","id":"PMC_39106308","title":"Anaplasma phagocytophilum effector EgeA facilitates infection by hijacking TANGO1 and SCFD1 from ER-Golgi exit sites to pathogen-occupied inclusions.","date":"2024","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/39106308","citation_count":6,"is_preprint":false},{"pmid":"18036347","id":"PMC_18036347","title":"Mutations of the SM protein Sly1 resulting in bypass of GTPase requirement in vesicular transport are confined to a short helical region.","date":"2007","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/18036347","citation_count":6,"is_preprint":false},{"pmid":"38478018","id":"PMC_38478018","title":"SNARE chaperone Sly1 directly mediates close-range vesicle tethering.","date":"2024","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/38478018","citation_count":5,"is_preprint":false},{"pmid":"8647468","id":"PMC_8647468","title":"A mammalian homologue of SLY1, a yeast gene required for transport from endoplasmic reticulum to Golgi.","date":"1996","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/8647468","citation_count":5,"is_preprint":false},{"pmid":"35234271","id":"PMC_35234271","title":"Lack of an association between SCFD1 rs10139154 polymorphism and amyotrophic lateral sclerosis.","date":"2022","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/35234271","citation_count":4,"is_preprint":false},{"pmid":"39928872","id":"PMC_39928872","title":"Reenacting a mouse genetic evolutionary arms race in yeast reveals that SLXL1/SLX compete with SLY1/2 for binding to Spindlins.","date":"2025","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/39928872","citation_count":4,"is_preprint":false},{"pmid":"38478017","id":"PMC_38478017","title":"SM protein Sly1 and a SNARE Habc domain promote membrane fusion through multiple mechanisms.","date":"2024","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/38478017","citation_count":3,"is_preprint":false},{"pmid":"36401605","id":"PMC_36401605","title":"Knockout of SLy1 decreases double-negative thymocyte proliferation and protects mice from p53-induced tumor formation.","date":"2022","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36401605","citation_count":0,"is_preprint":false},{"pmid":"42010839","id":"PMC_42010839","title":"Structure-guided optimization of SLY1 expression and purification in Escherichia coli.","date":"2026","source":"Protein science : a publication of the Protein Society","url":"https://pubmed.ncbi.nlm.nih.gov/42010839","citation_count":0,"is_preprint":false},{"pmid":"39484540","id":"PMC_39484540","title":"Reenacting a mouse genetic evolutionary arms race in yeast reveals SLXL1/SLX compete with SLY1/2 for binding to Spindlins.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39484540","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.28.662167","title":"Spliformer-v2 predicts multi-tissue RNA splicing and reveals functional genomic links with neurodegenerative diseases","date":"2025-07-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.28.662167","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":20110,"output_tokens":6168,"usd":0.076425,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":14270,"output_tokens":4637,"usd":0.093637,"stage2_stop_reason":"end_turn"},"total_usd":0.170062,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully classify each paper before extracting discoveries.\n\n**Classification notes:**\n- Papers [1],[2],[5],[9],[11],[12],[13],[16],[17],[18],[20],[26],[28],[30],[31],[32],[33],[34],[37] = SCFD1/Sly1 (vesicle trafficking SM protein) ✓\n- Papers [3] = SlY1 from *Silene latifolia* (plant Y chromosome WD-repeat protein) — SYMBOL COLLISION, SKIP\n- Papers [8],[15],[39] = SLY1/SLEEPY1 from Arabidopsis (F-box protein in GA signaling) — SYMBOL COLLISION, SKIP\n- Papers [36],[40] = Mouse Y-linked Sly1/Sly2 spermatid proteins — SYMBOL COLLISION (different gene family), SKIP\n- Papers [4],[6],[7],[10] = SCFD1/SLY1 mammalian SM protein ✓\n- Papers [14],[21],[22],[23],[25],[27],[38] = SLy1 lymphocyte adapter protein (SH3 domain, X-chromosomal) — different gene, SKIP\n- Papers [19],[24],[29],[35] = GWAS/eQTL/association studies — EXCLUDE (no mechanism)\n- Paper [41] = computational/splicing prediction preprint — EXCLUDE\n- Paper [16] = RA410 (alias of SCFD1) from rat ✓\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1996,\n      \"finding\": \"Mammalian Sly1 (RA410/SCFD1) forms a native complex with syntaxin 5 in rat liver membranes, and overexpression of rSly1 neutralizes the dominant-negative effects of excess syntaxin 5 on ER-to-Golgi transport, establishing a positive regulatory role for SCFD1 in syntaxin 5-dependent early secretory pathway transport.\",\n      \"method\": \"Biochemical co-purification from rat liver membranes, dominant-negative rescue by transient overexpression in mammalian cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — native complex co-purification plus functional rescue in cells, single lab, two complementary methods\",\n      \"pmids\": [\"8663406\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"RA410 (SCFD1), cloned from reoxygenated rat astrocytes, encodes a Sec1/Unc18-family vesicle transport protein that localizes predominantly to the plasma membrane fraction and, by immunoelectron microscopy, to large vesicles associated with the Golgi apparatus (but not the Golgi itself), consistent with a role in post-Golgi transport.\",\n      \"method\": \"Subcellular fractionation on sucrose gradients, immunoelectron microscopy, polyclonal antibody against synthetic peptide\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by two orthogonal methods (fractionation + immunoEM), single lab, no functional mutagenesis\",\n      \"pmids\": [\"9195952\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Sly1 binds to a short, evolutionarily conserved N-terminal peptide motif of the syntaxins Sed5p and Ufe1p (yeast) and syntaxins 5 and 18 (vertebrates); this binding site is upstream of the autonomously folded N-terminal domain of these syntaxins, defining a distinct peptide-based interaction mode for this SM protein that differs from the closed-conformation binding of Munc18 to syntaxin 1.\",\n      \"method\": \"Biochemical binding assays with purified proteins, peptide competition, domain mapping\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified proteins, replicated across yeast and vertebrate syntaxins, mechanistically defined interaction site\",\n      \"pmids\": [\"11879635\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Sly1p can bind simultaneously to the ER-to-Golgi core SNARE fusion complex assembled on syntaxin Sed5p; Sly1p-bound Sed5p supports assembly of the cognate SNARE complex without significantly altering kinetics, but prevents formation of several non-physiological SNARE complexes, demonstrating that this SM protein contributes to the specificity of SNARE pairing.\",\n      \"method\": \"In vitro SNARE complex assembly with purified yeast proteins, co-immunoprecipitation from yeast lysates\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstituted in vitro with purified proteins plus reciprocal co-IP from cell lysates, mechanistically informative with kinetic and specificity measurements\",\n      \"pmids\": [\"11994317\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"In yeast, Sly1 binding to the t-SNARE Sed5 enhances trans-SNARE complex formation with the v-SNARE Bet1; a temperature-sensitive sly1 mutant with reduced Sed5 binding shows reduced presence in the Sed5-Bet1 complex, directly linking Sly1-Sed5 interaction to productive SNARE complex assembly.\",\n      \"method\": \"Co-immunoprecipitation, in vitro SNARE complex formation with recombinant proteins added to yeast lysate\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP plus in vitro reconstitution in lysate, single lab\",\n      \"pmids\": [\"12186954\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"In zebrafish, the orthologue of yeast sly1 (SCFD1) is required for blastema formation and cell proliferation during caudal fin regeneration; a temperature-sensitive point mutation in sly1 blocks regeneration by reducing proliferation in the proximal blastema, demonstrating an essential in vivo role for this SM protein in cell proliferation during tissue regeneration.\",\n      \"method\": \"Positional cloning of temperature-sensitive zebrafish mutant (emmental), histology, BrdU proliferation assay, molecular analysis\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — positional cloning with temperature-sensitive allele plus cellular phenotyping, single lab, well-defined loss-of-function\",\n      \"pmids\": [\"12798289\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"In yeast, the binding of Sly1 to the t-SNARE Sed5 cooperates with Sec18/NSF ATPase to promote disassembly of cis-SNARE complexes; a sly1(ts) mutant defective in Sed5 binding retards cis-SNARE disassembly, and the sly1(ts) and sec18-1 mutations show synthetic lethality.\",\n      \"method\": \"Genetic epistasis (synthetic lethality), temperature-sensitive yeast mutants, SNARE disassembly assay\",\n      \"journal\": \"Bioscience, biotechnology, and biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis plus biochemical disassembly assay, single lab\",\n      \"pmids\": [\"12729020\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The gain-of-function SLY1-20 allele in yeast does not bypass the requirement for vesicle tethering mediated by Uso1p; rather, an alternative Rab GTPase (Ypt6) substitutes for Ypt1p in tethering when SLY1-20 is expressed, and tethering/fusion remain sensitive to Rab GDI, indicating that SLY1-20 suppression still requires Rab-dependent tethering.\",\n      \"method\": \"Co-immunoprecipitation, cell-free tethering and fusion assays, Rab GDI sensitivity, genetic epistasis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cell-free assays plus co-IP plus genetic epistasis, single lab, multiple orthogonal approaches\",\n      \"pmids\": [\"15689495\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"RA410/Sly1 (SCFD1) overexpression in SH-SY5Y cells protects against MPP+- and 6-OHDA-induced cell death by suppressing caspase-2, -3, and -9 activation, and antisense knockdown of RA410/Sly1 accelerates ER disruption upon MPP+ treatment, demonstrating a cytoprotective role linked to ER integrity.\",\n      \"method\": \"Antisense and sense RNA stable transformants, cell viability assay, electron microscopy of ER morphology, caspase activation assays\",\n      \"journal\": \"Neurobiology of disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain- and loss-of-function with multiple mechanistic readouts (ER morphology, caspase activation), single lab\",\n      \"pmids\": [\"15649705\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Gain-of-function mutations in the SM protein Sly1 that bypass Ypt/Rab GTPase requirements for ER-to-Golgi vesicular transport all map to a short conserved alpha-helix (α-20); deletion of this helix also causes bypass suppression, identifying α-20 as the domain mediating Rab-regulated Sly1 function in membrane fusion.\",\n      \"method\": \"Mutagenesis screen, genetic complementation, domain deletion analysis in yeast\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — structure-guided mutagenesis with defined genetic phenotype, single lab\",\n      \"pmids\": [\"18036347\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The SM protein Sly1 (SCFD1) directly interacts with the Cog4 subunit of the conserved oligomeric Golgi (COG) tethering complex; Cog4 also independently interacts with Syntaxin 5 through a distinct binding site, and disruption of the Cog4-Sly1 interaction impairs SNARE pairing for intra-Golgi transport and markedly attenuates Golgi-to-ER retrograde transport.\",\n      \"method\": \"Co-immunoprecipitation, pulldown assays with purified proteins, siRNA knockdown, Golgi-to-ER retrograde transport assay\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding demonstrated with purified proteins, disruption-of-interaction experiment with functional transport readout, multiple orthogonal methods\",\n      \"pmids\": [\"19536132\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The yeast SM protein Sly1 binds to both the N-peptide and the closed conformation of the Qa-SNARE Sed5, and this dual engagement facilitates SNARE complex formation by loosening the closed conformation of Sed5, in contrast to Munc18 which locks syntaxin 1 in a closed state incompatible with SNARE assembly.\",\n      \"method\": \"Biochemical binding assays with purified proteins, fluorescence anisotropy, in vitro SNARE complex formation kinetics\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified proteins, multiple orthogonal binding assays, mechanistic comparison with controls\",\n      \"pmids\": [\"25189771\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"SLY1 (SCFD1) is required for ER export of Procollagen VII but not Procollagen I; knockdown of SLY1 arrests Procollagen VII in the ER without affecting COPII recruitment, general secretion, or retrograde transport; among SLY1-interacting SNAREs, only Syntaxin 18 (not Syntaxin 17) is specifically required for Procollagen VII export, defining a TANGO1-SLY1-Syntaxin 18 pathway for bulky collagen export.\",\n      \"method\": \"siRNA knockdown, pulse-chase secretion assays, immunofluorescence colocalization, rescue experiments\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — siRNA knockdown with multiple cargo specificity controls, SNARE-selective requirement established, interaction with TANGO1 defined, consistent with independent zebrafish data\",\n      \"pmids\": [\"24842878\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Loss of scfd1 in zebrafish causes craniofacial defects due to failure of chondrogenesis; scfd1 mutation hinders ER-to-Golgi transport of ECM proteins and activates the unfolded protein response in chondrocytes; knockdown of either SCFD1 or STX18 (a SLY1-interacting t-SNARE) in mammalian chondrocytes severely impairs type II collagen transport, demonstrating a conserved SCFD1-STX18 pathway for large ECM protein secretion.\",\n      \"method\": \"Zebrafish forward mutagenesis screen, siRNA knockdown in mammalian chondrocytes, ER-to-Golgi transport assay, UPR activation markers\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function in two species (zebrafish and mammalian cells) with defined cellular phenotype, consistent with independent SNARE selectivity data from eLife 2014\",\n      \"pmids\": [\"27851892\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"mTORC1 phosphorylates VAMP8 to block autophagosome-lysosome fusion; dephosphorylated VAMP8 promotes recruitment of SCFD1 to autolysosomes; SCFD1 localizes to the autolysosome and is required for formation of the STX17-SNAP29-VAMP8 SNARE complex and for autophagosome-lysosome fusion; VAMP8 phosphorylation mimic or SCFD1 depletion blocks this fusion in vitro.\",\n      \"method\": \"mTORC1 kinase assay, phosphorylation site mutagenesis, siRNA knockdown, in vitro fusion assay, live-cell imaging, immunofluorescence co-localization, mouse liver overexpression\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro fusion reconstitution, mutagenesis of phosphorylation site, loss-of-function with defined molecular phenotype, multiple orthogonal methods across cell-free and cell-based systems\",\n      \"pmids\": [\"34785650\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SCFD1 is acetylated at residues K126 and K515 by the acetyltransferase KAT2B/PCAF, and deacetylated by SIRT4; acetylation of these residues inhibits autophagic flux by blocking STX17-SNAP29-VAMP8 SNARE complex formation; AMPK-mediated phosphorylation of SCFD1 disrupts SCFD1 interaction with KAT2B, keeping SCFD1 acetylation low during autophagy stimulation.\",\n      \"method\": \"Mass spectrometry identification of acetylation sites, acetyltransferase/deacetylase co-expression and knockdown, acetylation-mimetic and phospho-mimetic mutants, co-immunoprecipitation, autophagic flux assay\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — site-specific PTM mapping by MS, writer/eraser identified, functional acetylation-mimic mutagenesis, cross-talk with phosphorylation mechanism established, multiple orthogonal methods\",\n      \"pmids\": [\"35465820\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Moderate silencing of Slh (Drosophila orthologue of SCFD1) causes climbing and flight motor defects in adult flies; severe knockdown causes larval mobility reduction, neuromuscular junction deficits, and lethality before metamorphosis; RNA-seq downstream of Slh ablation reveals downregulation of chaperone genes mediating protein folding.\",\n      \"method\": \"RNAi-mediated gene silencing in Drosophila, behavioral assays (climbing, flight), NMJ morphology analysis, RNA-seq transcriptomic profiling\",\n      \"journal\": \"Neurobiology of aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined neuromuscular phenotype and downstream transcriptomic mechanism, single lab\",\n      \"pmids\": [\"36944290\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Loss of scfd1 in zebrafish (nonsense mutation or CRISPR knockout) causes severe cardiac and craniofacial defects with ER stress; electron microscopy of scfd1-depleted cardiomyocytes shows reduced myofibril width, sarcomere density reduction, and Golgi fragmentation; qPCR confirms upregulation of ER stress response and apoptosis markers, linking scfd1 to ER/Golgi membrane transport in cardiomyocytes.\",\n      \"method\": \"Positional cloning, CRISPR/Cas9 knockout, electron microscopy, qPCR for ER stress markers, cardiac phenotype analysis\",\n      \"journal\": \"Journal of cardiovascular development and disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two independent zebrafish loss-of-function alleles with ultrastructural and molecular readouts, single lab\",\n      \"pmids\": [\"37887855\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Sly1 contains an ALPS (amphipathic lipid packing sensor)-like helix within a conserved regulatory loop that directly binds high-curvature membranes; this membrane binding both relieves Sly1 autoinhibition and allows Sly1 to tether incoming vesicles to the Qa-SNARE on the target organelle (close-range tethering); the SLY1-20 gain-of-function allele loses its bypass-tethering ability when this tethering activity is impaired, supporting a handoff model from long-range to Sly1-mediated close-range tethering.\",\n      \"method\": \"Chemically defined in vitro reconstitution of ER-Golgi fusion, genetic analyses with Sly1 loop mutants, liposome binding assay, gain-of-function allele analysis\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with chemically defined components, mutagenesis of ALPS helix, multiple mechanistic readouts, functionally validated tethering activity\",\n      \"pmids\": [\"38478018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Sly1 promotes ER-Golgi SNARE-mediated membrane fusion through three parallel mechanisms: (i) opening the closed conformation of Qa-SNARE Sed5, (ii) close-range vesicle tethering via its regulatory loop, and (iii) nucleating productive trans-SNARE complexes; additionally, the autoinhibitory Habc domain of Sed5 has positive activities—required for correct Sed5 localization and directly promoting Sly1-dependent lipid mixing.\",\n      \"method\": \"Chemically defined in vitro fusion assays with SNARE and Sly1 mutants, 'split Sed5' in vitro and in vivo complementation, lipid mixing assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — chemically defined reconstitution with separation-of-function mutants for each proposed mechanism, in vitro and in vivo validation\",\n      \"pmids\": [\"38478017\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The T4SS effector EgeA of Anaplasma phagocytophilum directly binds SCFD1 (via its C-terminal half, confirmed by yeast two-hybrid), redirecting SCFD1 and its binding partner TANGO1 from ER-Golgi exit sites (ERES) to pathogen-occupied inclusions; knockdown of either TANGO1 or SCFD1 significantly reduces Anaplasma infection, demonstrating that SCFD1 function at ERES is exploited by the pathogen.\",\n      \"method\": \"Yeast two-hybrid (EgeA-C vs SCFD1), GFP-fusion localization, siRNA knockdown infection assay, pulldown for TANGO1 binding\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid plus loss-of-function infection assay, single lab, interaction confirmed by two methods\",\n      \"pmids\": [\"39106308\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SCFD1 (Sly1) is a Sec1/Munc18-family SM protein that functions at multiple membrane fusion steps in the secretory and autophagic pathways: it binds the N-terminal peptide motif of ER/Golgi syntaxins (Syntaxin 5, 18, Sed5, Ufe1p), facilitates SNARE complex assembly and specificity by opening the closed conformation of Qa-SNAREs and nucleating trans-SNARE complexes, directly tethers vesicles at close range via an ALPS-like helix in its regulatory loop, links tethering to fusion by interacting with the COG tethering complex via Cog4, and is required in vivo for ER-to-Golgi transport of bulky cargo (collagens, ECM proteins) via a specific SCFD1-Syntaxin 18 pathway; additionally, SCFD1 localizes to autolysosomes where it is required for STX17-SNAP29-VAMP8 SNARE complex assembly and autophagosome-lysosome fusion, a process regulated by mTORC1-mediated phosphorylation of VAMP8 (controlling SCFD1 recruitment) and by KAT2B/SIRT4-mediated acetylation of SCFD1 itself at K126/K515 (controlled by AMPK phosphorylation of SCFD1).\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SCFD1 (Sly1/RA410) is a Sec1/Munc18-family SM protein that orchestrates SNARE-mediated membrane fusion in the early secretory pathway and in autophagy [#0, #2]. Unlike Munc18's closed-conformation clamp on syntaxin 1, SCFD1 engages ER/Golgi Qa-SNAREs (Syntaxin 5, Syntaxin 18, yeast Sed5 and Ufe1) through a short conserved N-terminal peptide motif while also binding the closed conformation, an interaction that loosens the closed state and licenses SNARE assembly [#2, #11]. Through this engagement it confers specificity on SNARE pairing by supporting cognate complex formation while preventing non-physiological complexes, and it enhances productive trans-SNARE assembly [#3, #4]. Mechanistic reconstitution resolves three parallel contributions to ER-Golgi fusion: opening the Qa-SNARE, nucleating trans-SNARE complexes, and close-range vesicle tethering via an ALPS-like amphipathic helix in a regulatory loop that binds high-curvature membranes and relieves SCFD1 autoinhibition, downstream of Rab-dependent long-range tethering [#18, #19, #7]. SCFD1 couples tethering to fusion by directly binding the Cog4 subunit of the COG complex, an interaction required for intra-Golgi SNARE pairing and Golgi-to-ER retrograde transport [#10]. In vivo, a SCFD1–Syntaxin 18 pathway is specifically required for ER export of bulky cargo such as procollagen VII and type II collagen, and its loss causes chondrogenesis, craniofacial, and cardiac defects with ER stress in zebrafish [#12, #13, #17]. Independently, SCFD1 localizes to autolysosomes where it is required for STX17–SNAP29–VAMP8 SNARE complex assembly and autophagosome–lysosome fusion; this autophagic function is gated by mTORC1 phosphorylation of VAMP8 (controlling SCFD1 recruitment) and by KAT2B/SIRT4-mediated acetylation of SCFD1 at K126/K515, itself disrupted by AMPK phosphorylation of SCFD1 [#14, #15].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Established that mammalian SCFD1 is a positive regulator of syntaxin 5-dependent ER-to-Golgi transport, placing the SM protein in the early secretory pathway.\",\n      \"evidence\": \"Native complex co-purification with syntaxin 5 from rat liver membranes and dominant-negative rescue in cells\",\n      \"pmids\": [\"8663406\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding mode to syntaxin 5 not defined\", \"No reconstitution of the fusion step\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Identified SCFD1 as a Sec1/Unc18-family protein and localized it to vesicles associated with the Golgi, framing it as a vesicle transport factor.\",\n      \"evidence\": \"Subcellular fractionation and immunoelectron microscopy with peptide antibody\",\n      \"pmids\": [\"9195952\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Localization without functional mutagenesis\", \"Plasma membrane fraction signal unexplained mechanistically\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Defined the distinctive binding mode of SCFD1: it recognizes a conserved N-terminal peptide motif of ER/Golgi syntaxins, mechanistically separating it from Munc18 closed-syntaxin binding, and showed it supports SNARE pairing specificity.\",\n      \"evidence\": \"In vitro binding and domain mapping with purified yeast and vertebrate syntaxins; in vitro SNARE assembly and co-IP\",\n      \"pmids\": [\"11879635\", \"11994317\", \"12186954\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How peptide binding mechanistically promotes assembly not yet resolved\", \"Role of the syntaxin closed conformation not addressed\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Connected SCFD1's syntaxin binding to upstream SNARE recycling and to an essential organismal proliferation requirement, broadening its functional importance.\",\n      \"evidence\": \"Yeast genetic epistasis with sec18/NSF plus disassembly assays; zebrafish temperature-sensitive mutant with proliferation phenotype\",\n      \"pmids\": [\"12729020\", \"12798289\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between Sed5 binding and cis-SNARE disassembly not defined\", \"Whether fin regeneration defect is cell-autonomous secretory failure unclear\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Showed SCFD1's fusion function operates downstream of, and still depends on, Rab-mediated tethering, and linked it to ER integrity and cytoprotection.\",\n      \"evidence\": \"Cell-free tethering/fusion assays with Rab GDI sensitivity and genetic epistasis; gain/loss-of-function in neuronal cells with ER morphology and caspase readouts\",\n      \"pmids\": [\"15689495\", \"15649705\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct molecular handoff from Rab tethering to SCFD1 not shown\", \"Cytoprotection mechanism downstream of ER integrity unresolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Mapped the Rab-regulated function of SCFD1 to a short conserved alpha-helix (alpha-20), identifying the structural element that couples Rab signaling to fusion.\",\n      \"evidence\": \"Mutagenesis screen and domain deletion with genetic bypass phenotypes in yeast\",\n      \"pmids\": [\"18036347\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Biochemical activity of alpha-20 not defined at this stage\", \"Membrane interaction not yet demonstrated\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Linked SCFD1 tethering to fusion mechanistically by demonstrating a direct interaction with the Cog4 subunit of the COG tethering complex required for intra-Golgi SNARE pairing and retrograde transport.\",\n      \"evidence\": \"Purified-protein pulldowns, co-IP, siRNA, and Golgi-to-ER retrograde transport assay\",\n      \"pmids\": [\"19536132\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of Cog4-SCFD1 interface not resolved\", \"Whether COG binding competes with syntaxin engagement unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Resolved the mechanism of Qa-SNARE activation (dual N-peptide plus closed-conformation binding that loosens the closed state) and defined an in vivo SCFD1–Syntaxin 18 pathway dedicated to bulky collagen export.\",\n      \"evidence\": \"Fluorescence anisotropy and SNARE assembly kinetics with purified proteins; siRNA with cargo-specific pulse-chase secretion assays\",\n      \"pmids\": [\"25189771\", \"24842878\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why bulky cargo selectively requires this pathway not fully explained\", \"Structural model of loosened Sed5 absent\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Established the conserved physiological consequence of the SCFD1–STX18 pathway in ECM secretion, showing chondrocyte collagen transport failure and UPR activation across species.\",\n      \"evidence\": \"Zebrafish mutagenesis and mammalian chondrocyte siRNA with ER-to-Golgi transport and UPR markers\",\n      \"pmids\": [\"27851892\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tissue specificity of cargo dependence not mechanistically resolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended SCFD1 function beyond the secretory pathway to autophagy, showing it drives autophagosome-lysosome fusion via STX17-SNAP29-VAMP8 assembly under mTORC1 control of VAMP8 phosphorylation.\",\n      \"evidence\": \"mTORC1 kinase assay, phospho-site mutagenesis, in vitro fusion reconstitution, siRNA, imaging, mouse liver\",\n      \"pmids\": [\"34785650\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How dephospho-VAMP8 recruits SCFD1 at the molecular level not detailed\", \"Relationship to its secretory role at the same locus unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defined an acetylation/phosphorylation regulatory code on SCFD1 itself that gates its autophagic SNARE-assembly activity.\",\n      \"evidence\": \"MS site mapping, KAT2B/SIRT4 writer/eraser manipulation, acetyl- and phospho-mimetic mutants, autophagic flux assays\",\n      \"pmids\": [\"35465820\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the same PTMs regulate secretory-pathway function untested\", \"Structural impact of K126/K515 acetylation unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided the unified fusion mechanism: SCFD1 opens the Qa-SNARE, nucleates trans-SNARE complexes, and tethers vesicles at close range via an ALPS-like helix that senses curvature and relieves autoinhibition, completing a tethering-to-fusion handoff model.\",\n      \"evidence\": \"Chemically defined in vitro ER-Golgi fusion reconstitution with separation-of-function and ALPS-helix mutants, liposome binding, split-Sed5 complementation\",\n      \"pmids\": [\"38478018\", \"38478017\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the ALPS-like tethering activity operates in the autophagic fusion context untested\", \"Structural snapshot of the tethered intermediate absent\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed SCFD1's ERES function is hijacked by a bacterial pathogen, identifying a direct effector interaction that redirects SCFD1 and TANGO1.\",\n      \"evidence\": \"Yeast two-hybrid, GFP-fusion localization, and siRNA infection assays with Anaplasma EgeA effector\",\n      \"pmids\": [\"39106308\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Y2H interaction not validated by reciprocal pulldown in mammalian cells\", \"Mechanism by which EgeA binding relocalizes SCFD1 unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SCFD1 is partitioned between its secretory (ER-Golgi/ERES) and autophagic (autolysosome) fusion roles, and whether its tethering and PTM-regulatory mechanisms are shared across both, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of SCFD1 bound to closed Sed5/syntaxin\", \"Spatial/temporal control switching SCFD1 between compartments unknown\", \"No human disease mutation directly evaluated in the corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [3, 11, 19]},\n      {\"term_id\": \"GO:0000149\", \"supporting_discovery_ids\": [2, 3, 14]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [18]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 11, 14]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1, 10]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [12, 13, 17]},\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [14]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [1, 18]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 10, 12]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [10, 18, 19]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [14, 15]},\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [12, 13]}\n    ],\n    \"complexes\": [\"STX17-SNAP29-VAMP8 SNARE complex\", \"ER-Golgi (Sed5/Syntaxin 5) SNARE complex\"],\n    \"partners\": [\"STX5\", \"STX18\", \"Sed5\", \"Ufe1\", \"COG4\", \"VAMP8\", \"TANGO1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}