{"gene":"STX3","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2006,"finding":"STX3 (syntaxin 3) is a direct molecular target of omega-6 arachidonic acid and dietary omega-3 fatty acids (linolenic and docosahexaenoic acids), which activate STX3 to promote cell membrane expansion at neuronal growth cones, thereby stimulating neurite outgrowth.","method":"In vitro screening assay using STX3 as target protein; direct binding/activation assay with fatty acids; neurite outgrowth functional readout","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct in vitro biochemical assay identifying STX3 as the effector, coupled to functional neurite outgrowth phenotype; published in Nature with multiple orthogonal methods","pmids":["16598260"],"is_preprint":false},{"year":2014,"finding":"Loss-of-function (homozygous truncating) mutations in STX3 cause variant microvillus inclusion disease (MVID), demonstrating that STX3 is required as an apical SNARE receptor for membrane fusion of apical vesicles in enterocytes; patient-derived organoids and Caco-2 overexpression of truncated STX3 recapitulated MVID characteristics.","method":"Whole-exome sequencing of MVID patients; patient-derived organoid cultures; overexpression of truncated STX3 in Caco-2 cells","journal":"Gastroenterology","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function mutations in patients plus functional validation in organoids and cell lines with defined cellular phenotype","pmids":["24726755"],"is_preprint":false},{"year":2015,"finding":"Apical exocytosis of specific cargo (NHE3, CFTR, GLUT5) in polarized epithelial cells requires a sequential interaction cascade: Rab11 → Myo5B → Slp4a → Munc18-2 → Vamp7 → STX3. STX3 acts as the apical t-SNARE for selective cargo exocytosis, while brush border enzymes DPPIV and sucrase-isomaltase traffic independently of this pathway.","method":"Genome editing (CRISPR) to introduce Myo5B patient mutation in human epithelial cell line; Co-IP interaction studies; cargo trafficking assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genome-edited human cell line, multiple cargo tested, interaction cascade dissected with multiple orthogonal methods","pmids":["26553929"],"is_preprint":false},{"year":2008,"finding":"In renal collecting-duct principal cells, STX3 localizes to the apical plasma membrane and forms SNARE complexes with VAMP2, VAMP3, SNAP23, and Munc18b. Knockdown of STX3 strongly inhibits vasopressin-regulated AQP2 fusion at the apical membrane; Munc18b acts as a negative regulator of SNARE-complex formation in this pathway.","method":"Co-immunoprecipitation; protein knockdown (siRNA); apical surface biotinylation to measure AQP2 fusion","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP plus functional knockdown with quantitative surface biotinylation readout, multiple SNARE partners identified","pmids":["18505797"],"is_preprint":false},{"year":2013,"finding":"In mast cells, siRNA-mediated silencing of STX3 inhibits degranulation (membrane fusion step), while Munc18-2 silencing impairs secretory granule (SG) translocation; combined knockdown has additive inhibitory effect. Both proteins localize to granule surface and cytoskeletal clusters, and Munc18-2 (but not STX3) interacts with tubulin in resting cells.","method":"siRNA knockdown; immunogold electron microscopy; co-immunoprecipitation; degranulation functional assays","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — siRNA knockdown with defined phenotypic readout, immunogold localization, Co-IP, multiple orthogonal methods in single study","pmids":["24323579"],"is_preprint":false},{"year":2013,"finding":"Munc18-2 binds to the N-terminal peptide of STX11 with ~20-fold higher affinity than STX3 in vitro; upon IL-2 activation, increased STX3 levels allow Munc18-2 binding to STX3 when STX11 is absent, partially restoring cytotoxic function.","method":"Crystal structure of Munc18-2 at 2.6 Å resolution; binding affinity measurements; mapping of disease-causing mutations to structure","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus quantitative binding measurements, mechanistic explanation for disease compensation","pmids":["24194549"],"is_preprint":false},{"year":2010,"finding":"Munc18b interacts with both the N-terminal peptide and the closed-conformation C-terminus (Habc domain + linker + SNARE H3 motif) of STX3. Deletion of the Habc domain or mutations disrupting intramolecular Habc-H3 binding abolish Munc18b-STX3 interaction. Munc18b also binds VAMP8 and the assembled STX3/SNAP-23/VAMP8 core SNARE complex; overexpression of Munc18b increases constitutive exocytosis.","method":"In vitro binding/pull-down assays; mutagenesis of STX3 domains; constitutive exocytosis assay in mammalian cells","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with mutagenesis, multiple interaction interfaces mapped, functional exocytosis assay","pmids":["20695848"],"is_preprint":false},{"year":2017,"finding":"STX3 undergoes monoubiquitination in a conserved polybasic domain. Ubiquitinated STX3 at the basolateral plasma membrane is rapidly endocytosed, sorted to late endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A non-ubiquitinatable STX3-5R mutant fails to enter this pathway and acts as a dominant-negative inhibitor of GPRC5B cargo entry into ILVs/exosomes. HCMV exploits this STX3 exosomal pathway for virion excretion.","method":"Monoubiquitination site mapping; live-cell antibody feeding endocytosis tracking in polarized MDCK cells; dominant-negative mutant analysis; HCMV virion excretion assay","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct localization/endocytosis tracking, ubiquitination mapping, dominant-negative mutant with functional cargo and viral readout","pmids":["28814500"],"is_preprint":false},{"year":2018,"finding":"STX3 is localized to Weibel-Palade bodies (WPBs) in endothelial cells and is required for both basal and stimulated (Ca2+- and cAMP-mediated) VWF secretion. STX3 is absent in STX3-/- blood outgrowth endothelial cells (from MVID patient), resulting in defective WPB exocytosis. STX3 interacts with WPB-associated VAMP8. WPB formation and maturation are unaffected by STX3 loss.","method":"Immunolocalization in human umbilical vein endothelial cells and patient-derived STX3-/- BOECs; VWF secretion assays; Co-IP of STX3 with VAMP8; ultrastructural analysis","journal":"Arteriosclerosis, thrombosis, and vascular biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — patient-derived KO cells with defined secretion phenotype, Co-IP, orthogonal localization and functional assays","pmids":["29880488"],"is_preprint":false},{"year":2018,"finding":"STX3 (but not STX4) is required for mast cell regulated exocytosis; conditional Stx3 knockout mice show a specific inability to engage multigranular compound exocytosis, while single-vesicle fusion events are largely intact. STX3 is dispensable for constitutive cytokine secretion.","method":"Conditional knockout mice; electrophysiology; electron microscopy; passive systemic anaphylaxis in vivo model","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with multiple orthogonal readouts (electrophysiology, EM, in vivo anaphylaxis), distinguishes compound from single-vesicle exocytosis","pmids":["30563839"],"is_preprint":false},{"year":2020,"finding":"Photoreceptor-specific Stx3 knockout mice exhibit rapid photoreceptor degeneration. In the absence of STX3, outer segment (OS) proteins including peripherin 2 (PRPH2), ROM1, and rhodopsin are mislocalized along microtubules to the inner segment, cell body, and synaptic region. The PRPH2 C-terminal domain physically interacts with STX3 and other photoreceptor SNAREs.","method":"Photoreceptor-specific Stx3 conditional knockout mice; immunofluorescence localization; co-immunoprecipitation (PRPH2 C-terminal domain with STX3)","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with defined mislocalization phenotype plus direct Co-IP interaction, multiple OS proteins tested","pmids":["32778589"],"is_preprint":false},{"year":2014,"finding":"In gastric parietal cells, PKA-mediated phosphorylation of ezrin at Ser-66 induces a conformational change that enables ezrin association with STX3 (not other syntaxins), providing a spatial cue for H,K-ATPase trafficking to the apical plasma membrane. Inhibition of ezrin Ser-66 phosphorylation prevents ezrin-STX3 association and blocks H,K-ATPase insertion.","method":"Co-immunoprecipitation; atomic force microscopy showing phosphorylation-induced ezrin unfolding; pharmacological inhibition of PKA; apical plasma membrane insertion assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — multiple orthogonal methods including AFM structural analysis, Co-IP, and functional transport assay; phosphorylation mechanism rigorously dissected","pmids":["25301939"],"is_preprint":false},{"year":2018,"finding":"Alternative splicing of STX3 generates a soluble isoform (Stx3S) lacking the transmembrane anchor. Stx3S binds the nuclear import factor RanBP5, translocates to the nucleus, and physically and functionally interacts with transcription factors ETV4 and ATF2. Inhibition of endogenous Stx3S alters cancer-associated gene expression and promotes cell proliferation.","method":"Identification of splice isoform; Co-IP of Stx3S with RanBP5, ETV4, ATF2; nuclear localization by fractionation/imaging; siRNA knockdown with gene expression and proliferation readouts","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — novel isoform identified with Co-IP of multiple nuclear partners, functional knockdown with transcriptional and proliferation phenotype","pmids":["29475951"],"is_preprint":false},{"year":2011,"finding":"HCMV infection induces STX3 expression; STX3 localizes to the HCMV assembly site where it associates with virus-wrapping membranes. STX3 knockdown by RNAi reduces HCMV production and results in fewer mature virions with more viruses undergoing final envelopment; an RNAi-resistant STX3 construct rescues production. STX3 depletion also reduces lysosomal membrane glycoprotein expression.","method":"RNAi knockdown; immunogold labeling; RNAi-resistant construct rescue; ultrastructural analysis of assembly site","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi knockdown with rescue construct and ultrastructural readout, single lab","pmids":["21371234"],"is_preprint":false},{"year":2011,"finding":"STX3 and SNAP-23 are required for IgE receptor-mediated release of all chemokines (CXCL8, CCL2, CCL3, CCL4) from mature human mast cells, while blocking STX-2 or VAMP-3 does not affect chemokine release; STX4 and VAMP-8 selectively affect only CXCL8 release.","method":"Blocking antibodies/siRNA inhibition of specific SNARE isoforms; chemokine release assay by ELISA following IgE receptor cross-linking","journal":"Molecular immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional knockdown with multiple SNARE isoforms tested in parallel, single lab","pmids":["21981832"],"is_preprint":false},{"year":2014,"finding":"siRNA-mediated knockdown of STX3 in dHL-60 cells (neutrophil model) reduces maximal release of IL-1α, IL-1β, IL-12b, and CCL4 without altering other cytokine secretion, and inhibits MMP-9 exocytosis from gelatinase granules, where STX3 is partly localized.","method":"siRNA knockdown; cytokine secretion profiling (CBA); MMP-9 exocytosis assay; subcellular localization by microscopy","journal":"Journal of leukocyte biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA with defined cytokine secretion phenotype and granule localization, single lab","pmids":["25548252"],"is_preprint":false},{"year":2015,"finding":"In Toll-like receptor-activated dendritic cells, STX3 mRNA is upregulated by TLR4 and TLR7 (but not TLR2); RNAi knockdown of STX3 attenuates IL-6 secretion. STX3 translocates to the cell membrane only in DCs secreting IL-6 or MIP-1α.","method":"SNARE mRNA profiling; RNAi knockdown; IL-6 ELISA; confocal microscopy of STX3 subcellular translocation","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi with cytokine readout and direct localization imaging, single lab","pmids":["25674084"],"is_preprint":false},{"year":2015,"finding":"STX3 is mislocalized in MVID patient enterocytes bearing MYO5B or STX3 mutations, and loss of MYO5B in 3D Caco-2 cysts causes mislocalisation of apical polarity determinants (Cdc42, Par6B, PKCζ/ι, ezrin) and polarity inversion.","method":"Immunofluorescence of patient biopsies; MYO5B depletion in 3D Caco-2 cyst model; electron microscopy","journal":"Biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — patient tissue plus cell model with defined polarity phenotype, single lab","pmids":["26526116"],"is_preprint":false},{"year":2017,"finding":"Munc18-2 is required for Slp4a/STX3 interaction during fusion of cargo vesicles with the apical plasma membrane; loss of Munc18-2 selectively disrupts apical trafficking of NHE3 and GLUT5 but not DPPIV, establishing cargo selectivity in the STX3-dependent pathway.","method":"CRISPR/Cas9-generated Munc18-2 KO CaCo2 cells; Co-IP of Slp4a/STX3; cargo trafficking assays in patient biopsies, organoids, and genome-edited cells","journal":"JCI insight","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR KO model with Co-IP and cargo-selective trafficking phenotype validated in patient tissue, organoids, and cell line","pmids":["28724787"],"is_preprint":false},{"year":2018,"finding":"STX3 promotes breast cancer cell proliferation by binding PTEN and increasing PTEN ubiquitination and degradation, thereby activating the PI3K-Akt-mTOR signaling pathway; AKT inhibitors repress STX3-driven growth.","method":"Co-immunoprecipitation of STX3 with PTEN; ubiquitination assay; lentiviral knockdown and overexpression; in vitro and in vivo tumor growth assays","journal":"Biochimica et biophysica acta. Molecular basis of disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with PTEN, ubiquitination assay, functional rescue with AKT inhibitor, single lab","pmids":["29408595"],"is_preprint":false},{"year":2012,"finding":"In salivary glands of Sjögren's syndrome patients, STX3, STX4, SNAP-23, and VAMP8 relocalize from the apical to the basal region of acinar cells, and increased formation of SNARE complexes independent of secretory stimuli is detected, correlating with ectopic basolateral mucin secretion.","method":"Immunofluorescence localization; Western blotting; Co-IP for SNARE complex formation","journal":"Journal of autoimmunity","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — immunofluorescence and Co-IP with aberrant localization and function; disease tissue only, no experimental manipulation","pmids":["22285554"],"is_preprint":false},{"year":2015,"finding":"TGF-β1 stimulates SERT exocytosis to the apical surface of Caco-2 cells via PI3K activation; TGF-β1 increases the association of SERT with STX3, and STX3 promotes SERT insertion at the apical plasma membrane.","method":"Co-immunoprecipitation (SERT-STX3); surface biotinylation; brefeldin A inhibition; PI3K inhibitor; ex vivo Ussing chamber 5-HT uptake","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional surface biotinylation and pharmacological dissection, single lab","pmids":["25954931"],"is_preprint":false},{"year":2020,"finding":"In STX2-knockout pancreatic acini, increased apical and basolateral exocytosis requires formation of fusogenic SNARE complexes mediated by STX3 and STX4; STX2 normally blocks STX3- and STX4-mediated zymogen granule fusion with the plasma membrane.","method":"STX2-KO mice; live-cell exocytosis and Ca2+ imaging; SNARE complex formation assays by Co-IP; human pancreatic tissue analysis","journal":"Gastroenterology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO mice with live-cell imaging and SNARE complex biochemistry, human tissue validation, single lab","pmids":["29360461"],"is_preprint":false},{"year":2020,"finding":"The Habc domain of STX3 binds monomeric ubiquitin with low affinity and efficiently binds K63-linked (but not K48-linked) poly-ubiquitin chains within a narrow range of chain lengths; molecular modeling identifies conserved residues shared with the GAT domain of GGA proteins.","method":"In vitro ubiquitin-binding assays; molecular modeling","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro binding assay with linkage selectivity established, but single lab, no functional consequence tested in cells","pmids":["33288783"],"is_preprint":false},{"year":2015,"finding":"STX3 accumulates in the photoreceptor outer segment (OS) in Lztfl1/Bbs17 and Bbs1 mutant BBS mice; in normal photoreceptors STX3 is excluded from the OS. Loss of BBS proteins causes mislocalization of STX3 and Stxbp1/Munc18-1 into the OS, contributing to large vesicle formation and disruption of OS lamellar structure.","method":"Isolated OS proteomics; quantitative proteomics (>3-fold enrichment); immunofluorescence; ultrastructural analysis in BBS mouse models","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative proteomics plus ultrastructural analysis in two BBS mouse models, localization with functional consequence","pmids":["26216965"],"is_preprint":false},{"year":2019,"finding":"In CEP290 mutant mice, disruption of the C-terminal myosin-tail homology domain causes rapid accumulation of inner segment plasma membrane proteins, including STX3, SNAP25, and IMPG2, in the outer segment, indicating that CEP290 normally confines these inner segment proteins from entering the OS.","method":"Conditional Cep290 mutant mice; immunofluorescence localization of STX3 and other membrane proteins; comparison with endomembrane protein localization","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO mice with defined protein mislocalization phenotype, single lab","pmids":["31694913"],"is_preprint":false},{"year":2020,"finding":"Legionella deubiquitinase LotB deconjugates K63-linked ubiquitins from Sec22b on the Legionella-containing vacuole (LCV), stimulating dissociation of STX3 from Sec22b; this modulates non-canonical SNARE pairing dynamics at the LCV.","method":"Identification of Sec22b ubiquitination upon Legionella infection; LotB DUB activity assays; Co-IP of STX3-Sec22b; T4SS-dependent experiments","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — bacterial DUB activity assay with Co-IP showing STX3-Sec22b dissociation, T4SS dependency established","pmids":["32905772"],"is_preprint":false},{"year":2021,"finding":"STX3 interacts with the serotonin transporter (SERT) by co-immunoprecipitation; they colocalize in ER and Golgi in overexpressing cells, and in apical microvilli-like structures in polarized Caco-2 cells. STX3 overexpression reduces SERT plasma membrane expression (anchoring in ER/Golgi), while STX3 knockdown in Caco-2 cells marginally decreases serotonin uptake activity and alters SERT glycosylation state.","method":"Co-immunoprecipitation; immunocytochemistry; serotonin uptake assay; STX3 knockdown (siRNA); glycosylation state analysis","journal":"Journal of pharmacological sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional uptake assay and localization imaging, single lab","pmids":["33712280"],"is_preprint":false},{"year":2020,"finding":"In retinal ribbon synapses, STX3B (the retina-specific splice form of STX3) is phosphorylated at T14 by CaMKII in a light- and Ca2+-dependent manner. In rod photoreceptor terminals, pSTX3 is higher in dark-adapted (active) mice; in rod bipolar cell terminals, pSTX3 is higher in light-exposed mice. Pharmacological CaMKII inhibition suppresses both pSTX3 and evoked exocytosis measured by membrane capacitance.","method":"Quantitative immunofluorescence in dark- and light-adapted mice; isolated eyecup and isolated rod bipolar cell preparations with Ca2+ manipulation; staurosporine and CaMKII inhibitor (AIP) experiments; membrane capacitance measurements","journal":"Frontiers in cellular neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple experimental preparations with pharmacological manipulation, light-dependent in vivo phosphorylation correlated with exocytosis, single lab","pmids":["33192329"],"is_preprint":false},{"year":2022,"finding":"In neurons, the juxtamembrane domain (JMD) of STX1A regulates palmitoylation of its transmembrane domain (TMD), and loss of palmitoylation inhibits spontaneous vesicle fusion. Swapping STX1A's JMD into STX3A together with two TMD cysteines forces STX3A palmitoylation and dramatically enhances spontaneous vesicle fusion, showing that forced palmitoylation is sufficient to gain this function.","method":"Hippocampal neuron culture with site-directed mutagenesis of STX1A and chimeric STX3A constructs; electrophysiology (mEPSC recording)","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — mutagenesis with electrophysiological functional readout; mechanistic insight into STX3A palmitoylation, single lab","pmids":["35638903"],"is_preprint":false},{"year":2023,"finding":"L. pneumophila effector Lug15 (E3 ubiquitin ligase) ubiquitinates host Sec22b and mediates its recruitment to the LCV; Sec22b ubiquitination by Lug15 promotes non-canonical pairing of Sec22b with plasma membrane-derived syntaxins including STX3.","method":"Ubiquitin E3 ligase assay for Lug15; ubiquitination of Sec22b; Co-IP of Sec22b with STX3; LCV remodeling analysis","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical E3 ligase assay plus Co-IP showing STX3-Sec22b pairing, single lab","pmids":["37882795"],"is_preprint":false},{"year":2025,"finding":"STX3 is a component of a specialized SNARE complex (STX3/4, VTI1B, STX8 as Qabc-SNAREs and SEC22B as R-SNARE) that mediates fusion of PARK7-containing secretory autolysosomes with the plasma membrane for unconventional PARK7 secretion under oxidative stress.","method":"siRNA knockdown of STX3 and SNARE components; PARK7 secretion assay; autophagy flux analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown with functional secretion readout, SNARE complex identified, single lab","pmids":["40327696"],"is_preprint":false},{"year":2023,"finding":"STX3 localizes to Salmonella-containing vacuole (SCV) membranes; STX3 knockdown reduces bacterial proliferation and is restored by STX3 overexpression. STX3-SCV interaction requires SPI-2-encoded T3SS (ΔssaV abolishes it) but not SPI-1 T3SS, suggesting SPI-2 effectors recruit STX3 to facilitate SCV membrane acquisition for division.","method":"STX3 siRNA knockdown; STX3 overexpression rescue; live-cell imaging of Salmonella-infected cells; SPI-1 and SPI-2 T3SS mutant infections; in vivo mouse model","journal":"Traffic","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — knockdown, rescue, and genetic mutant bacteria with in vivo validation, single lab","pmids":["37114883"],"is_preprint":false},{"year":2023,"finding":"siRNA-mediated depletion of STX3 (along with RAB27A and VAMP3) reduces post-Golgi vesicle trafficking and sFLT1 secretion from endothelial cells, placing STX3 in the post-Golgi secretory pathway for sFLT1, distinct from STX6/ARF1/AP1 which act at the Golgi.","method":"siRNA knockdown of specific trafficking components; sFLT1 secretion assay; live imaging of temporally controlled sFLT1 release","journal":"Angiogenesis","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown with cargo-specific secretion assay, multiple SNAREs compared, single lab","pmids":["37695358"],"is_preprint":false},{"year":2025,"finding":"Cone-specific STX3 knockout mice exhibit early cone dysfunction followed by progressive rod impairment. In cones, STX3 loss selectively depletes STXBP1 and cone arrestin 4 at the connecting cilium. A light-dependent complex comprising STX3, STXBP1, and arrestin 4 is identified, with arrestin 4 preferentially associating with STX3 in dark-adapted retina and with STXBP1 in light-adapted retina.","method":"Cone-specific and rod-specific Stx3 conditional knockout mice; Co-IP of STX3-STXBP1-arrestin 4 complex; functional ERG analysis","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cell-type-specific KO mice with Co-IP of light-dependent complex and functional readout, single lab","pmids":["41220299"],"is_preprint":false},{"year":2025,"finding":"PTEC-specific Stx3 knockout (Stx3-cKO) mice develop Fanconi syndrome with increased urinary excretion of phosphorus, glucose, amino acids, and low-molecular-weight proteins. Brush border atrophy, vesicle transport stagnation (increased subapical Rab11 and VAMP8), mislocalization of transporters (NaPi-IIa, SGLT2, rBAT, megalin), and disrupted apical ezrin expression are observed. Both receptor-mediated and fluid-phase endocytosis are impaired.","method":"PTEC-specific Stx3 conditional knockout mice; electron microscopy; immunofluorescence localization; urine biochemistry; endocytosis assays; MVID patient urine analysis","journal":"Kidney international","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with multiple orthogonal readouts (EM, immunofluorescence, urine biochemistry, endocytosis), validated in human patient samples","pmids":["41033460"],"is_preprint":false},{"year":2026,"finding":"STX3 in hippocampal CA1 neurons is required for neural responses to novelty and for forming stable representations of rewarded locations, but dispensable for context and spatial representations inherited from upstream regions. CA1-specific Stx3 deletion combined with in vivo Ca2+ imaging demonstrates STX3's role in postsynaptic membrane fusion-dependent synaptic plasticity.","method":"CA1-specific Stx3 conditional knockout; in vivo population calcium imaging; novel environment and reward location behavioral paradigms","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with in vivo population imaging, defined behavioral phenotype distinguishing STX3-dependent vs independent computations","pmids":["41932328"],"is_preprint":false},{"year":2026,"finding":"ZNRF1 E3 ligase activity is required for STX3-Munc18-2 (Stxbp2) interaction in macrophages; ZNRF1 deficiency weakens this interaction, preventing FasL from reaching the macrophage surface despite normal lysosome-related organelle polarization. Stxbp2 knockdown reduces surface FasL; wild-type but not catalytically inactive ZNRF1 restores surface FasL, establishing a ZNRF1-Munc18-2-STX3 axis for FasL exocytosis.","method":"Myeloid-specific Znrf1 KO mice; Co-IP of Munc18-2-STX3; Stxbp2 knockdown; ZNRF1 rescue with catalytic mutant; surface FasL measurement; confocal imaging of LAMP1 organelles","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO mice with Co-IP and rescue experiments, functional FasL secretion readout, single lab","pmids":["41896526"],"is_preprint":false},{"year":2018,"finding":"Tomosyn-1 (STXBP5) acts as an inhibitor of mast cell degranulation; after FcεRI activation, PKCδ-dependent phosphorylation of tomosyn-1 causes it to dissociate from STX4 and associate with STX3, regulating the switch in STX partners during membrane fusion.","method":"Co-IP of tomosyn-1 with STX3 and STX4; PKCδ inhibitor experiments; phosphorylation mapping; degranulation assays","journal":"Science signaling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP demonstrating STX4→STX3 switch, PKCδ kinase identified, single lab","pmids":["29970602"],"is_preprint":false},{"year":2020,"finding":"Co-expression of STX3 with rat ENaC in Xenopus oocytes increases amiloride-sensitive whole-cell currents by ~50%, associated with increased ENaC surface expression. The stimulatory effect of STX3 on rENaC is independent of Rab11-mediated recycling endosome fusion and is not mediated by inhibiting channel retrieval.","method":"Xenopus oocyte expression system; electrophysiology (amiloride-sensitive current); FLAG-tagged ENaC surface expression assay; brefeldin A and dominant-negative Rab11 experiments","journal":"Pflugers Archiv : European journal of physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — heterologous expression system with electrophysiology and surface expression assay, pharmacological dissection, single lab","pmids":["32221667"],"is_preprint":false}],"current_model":"STX3 is a plasma membrane-localized SNARE protein that mediates selective apical vesicle-plasma membrane fusion in polarized epithelial cells (acting downstream of Rab11/Myo5B/Slp4a/Munc18-2/VAMP7), is directly activated by omega-3/6 fatty acids to promote membrane expansion at neuronal growth cones, undergoes monoubiquitination to control its endocytosis and exosomal cargo sorting, generates a soluble nuclear-targeted splice isoform (Stx3S) that regulates transcription, mediates compound exocytosis in mast cells, controls OS membrane protein trafficking in photoreceptors (interacting with PRPH2/ROM1/rhodopsin in a STXBP1/arrestin-4 light-regulated complex), supports postsynaptic membrane fusion-dependent synaptic plasticity in hippocampal CA1 neurons, and is regulated by phosphorylation (CaMKII-dependent T14 phosphorylation in retinal ribbon synapses) and by upstream factors including ezrin-PKA signaling and the ZNRF1-Munc18-2 axis; loss-of-function mutations cause variant microvillus inclusion disease and Fanconi syndrome-like renal tubular dysfunction."},"narrative":{"mechanistic_narrative":"STX3 is an apical/plasma-membrane t-SNARE that mediates selective vesicle–membrane fusion across diverse polarized secretory and trafficking contexts [PMID:26553929, PMID:18505797]. In epithelia it functions as the terminal apical t-SNARE of a Rab11→Myo5B→Slp4a→Munc18-2→Vamp7 cascade that delivers specific cargo (NHE3, CFTR, GLUT5) to the brush border, while bulk brush-border enzymes traffic independently [PMID:26553929, PMID:28724787]; loss-of-function STX3 mutations cause variant microvillus inclusion disease, and tubule-specific deletion produces Fanconi-syndrome-like renal dysfunction with transporter mislocalization and impaired endocytosis [PMID:24726755, PMID:41033460]. Its fusogenic activity is gated by Munc18 proteins that bind both the N-terminal peptide and the closed Habc–H3 conformation of STX3 and partner switching among VAMP and SNAP isoforms, supporting regulated secretion in mast cells (compound exocytosis), endothelial Weibel-Palade body/VWF release, and AQP2 insertion in collecting-duct cells [PMID:20695848, PMID:18505797, PMID:29880488, PMID:30563839]. STX3 is directly activated by omega-3/omega-6 fatty acids to drive growth-cone membrane expansion and neurite outgrowth [PMID:16598260], and supports postsynaptic, fusion-dependent synaptic plasticity in hippocampal CA1 neurons required for novelty responses and reward-location coding [PMID:41932328]. In photoreceptors STX3 confines outer-segment membrane proteins (PRPH2, ROM1, rhodopsin) and forms a light-regulated complex with STXBP1 and arrestin-4 at the connecting cilium [PMID:32778589, PMID:41220299]. STX3 activity is further controlled by monoubiquitination directing endocytosis and exosomal sorting [PMID:28814500], CaMKII-dependent T14 phosphorylation in retinal ribbon synapses [PMID:33192329], and ezrin–PKA signaling [PMID:25301939]; an alternatively spliced soluble isoform (Stx3S) enters the nucleus via RanBP5 and regulates transcription through ETV4 and ATF2 [PMID:29475951].","teleology":[{"year":2006,"claim":"Established the first direct biochemical effector role for STX3, showing it is activated by fatty acids to drive membrane expansion rather than acting only as a passive SNARE scaffold.","evidence":"In vitro binding/activation assay with arachidonic, linolenic and docosahexaenoic acids coupled to neurite outgrowth readout","pmids":["16598260"],"confidence":"High","gaps":["Structural basis of fatty-acid activation not resolved","Whether this regulation operates in non-neuronal STX3 contexts untested"]},{"year":2008,"claim":"Defined STX3 as an apical SNARE for regulated membrane insertion, identifying its core SNARE partners and a Munc18b regulatory brake.","evidence":"Co-IP and siRNA knockdown with apical surface biotinylation of AQP2 in renal collecting-duct cells","pmids":["18505797"],"confidence":"High","gaps":["Direct fusion reconstitution not performed","Quantitative SNARE stoichiometry undefined"]},{"year":2010,"claim":"Resolved how Munc18b engages STX3, mapping interaction to both N-peptide and closed Habc–H3 conformation and linking Munc18b levels to exocytosis output.","evidence":"In vitro pull-downs with STX3 domain mutagenesis and constitutive exocytosis assays","pmids":["20695848"],"confidence":"High","gaps":["Order of N-peptide vs closed-conformation binding during fusion cycle unclear"]},{"year":2014,"claim":"Connected STX3 to human disease, demonstrating that truncating mutations cause variant MVID through failed apical vesicle fusion in enterocytes.","evidence":"Whole-exome sequencing of patients, patient organoids, and truncated-STX3 overexpression in Caco-2","pmids":["24726755"],"confidence":"High","gaps":["Genotype–phenotype range across mutation types not fully mapped"]},{"year":2015,"claim":"Placed STX3 as the terminal t-SNARE of a defined cargo-selective apical trafficking cascade, explaining cargo specificity in epithelial polarity.","evidence":"CRISPR Myo5B mutant epithelial cells, Co-IP of the Rab11→Myo5B→Slp4a→Munc18-2→Vamp7→STX3 chain, and cargo trafficking assays","pmids":["26553929"],"confidence":"High","gaps":["How cargo identity is read out at the SNARE step unknown","Whether the cascade is universal across epithelial cargo classes untested"]},{"year":2017,"claim":"Showed that post-translational monoubiquitination routes STX3 itself into the endocytic/exosomal pathway and controls cargo entry into exosomes.","evidence":"Ubiquitination site mapping, live-cell endocytosis tracking, and dominant-negative STX3-5R analysis in polarized MDCK cells","pmids":["28814500"],"confidence":"High","gaps":["The ubiquitin ligase responsible not identified","Physiological triggers of STX3 ubiquitination unknown"]},{"year":2018,"claim":"Revealed a non-canonical nuclear function, identifying a soluble splice isoform that regulates transcription independent of membrane fusion.","evidence":"Splice isoform identification, Co-IP of Stx3S with RanBP5/ETV4/ATF2, and knockdown with transcriptional/proliferation readouts","pmids":["29475951"],"confidence":"High","gaps":["Direct DNA-binding vs cofactor role of Stx3S unresolved","Signals controlling the splicing switch unknown"]},{"year":2018,"claim":"Extended STX3's secretory role to endothelial hemostasis, showing it is required for VWF release from Weibel-Palade bodies.","evidence":"Patient-derived STX3-/- BOECs, VWF secretion assays, and Co-IP of STX3 with VAMP8","pmids":["29880488"],"confidence":"High","gaps":["Regulatory inputs for Ca2+ vs cAMP-driven WPB fusion via STX3 not dissected"]},{"year":2018,"claim":"Distinguished STX3's specific contribution to compound (multigranular) exocytosis from single-vesicle fusion in vivo.","evidence":"Conditional Stx3 knockout mice with electrophysiology, EM, and in vivo anaphylaxis","pmids":["30563839"],"confidence":"High","gaps":["Molecular basis for compound vs single-vesicle selectivity unknown"]},{"year":2020,"claim":"Established STX3 as essential for photoreceptor outer-segment protein delivery and survival, with direct binding to PRPH2.","evidence":"Photoreceptor-specific Stx3 knockout mice, immunofluorescence mislocalization, and Co-IP of PRPH2 C-terminus with STX3","pmids":["32778589"],"confidence":"High","gaps":["Whether STX3 mediates fusion vs sorting at the connecting cilium unresolved"]},{"year":2020,"claim":"Linked STX3 fusion activity to activity-dependent kinase regulation in ribbon synapses via CaMKII phosphorylation.","evidence":"Light/dark phosphorylation quantification, CaMKII inhibitor experiments, and membrane capacitance recordings","pmids":["33192329"],"confidence":"Medium","gaps":["Single lab","Functional consequence of T14 phosphorylation on SNARE assembly not directly measured"]},{"year":2021,"claim":"Characterized the ubiquitin-binding selectivity of STX3's Habc domain, providing a biochemical basis for ubiquitin-dependent regulation.","evidence":"In vitro ubiquitin-binding assays and molecular modeling","pmids":["33288783"],"confidence":"Medium","gaps":["No cellular functional consequence tested","Single lab in vitro only"]},{"year":2025,"claim":"Defined a renal physiological role, showing tubule STX3 maintains brush-border transport and endocytosis, with loss causing Fanconi-like syndrome.","evidence":"PTEC-specific Stx3 knockout mice with EM, transporter localization, urine biochemistry, endocytosis assays, and MVID patient urine","pmids":["41033460"],"confidence":"High","gaps":["Whether renal phenotype reflects the same cargo cascade as gut not directly tested"]},{"year":2026,"claim":"Demonstrated a postsynaptic, plasticity-related role for STX3 in defined hippocampal circuit computations.","evidence":"CA1-specific Stx3 conditional knockout with in vivo calcium imaging and behavioral paradigms","pmids":["41932328"],"confidence":"High","gaps":["Molecular SNARE partners at the postsynaptic membrane not identified","Link to AMPA-receptor trafficking not established"]},{"year":null,"claim":"How a single t-SNARE achieves its broad context-specific cargo and tissue selectivity—and how its regulatory layers (ubiquitination, phosphorylation, splicing, partner switching) are integrated in vivo—remains unresolved.","evidence":"No single study reconciles the regulatory and tissue-specific mechanisms","pmids":[],"confidence":"Medium","gaps":["No unifying model of cargo selection at the STX3 fusion step","Crosstalk among regulatory modifications uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[2,3,6,8]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[2,3]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[2,3,7,8]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[7]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[34]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[12]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[4,8]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[2,3,7,8,18]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[2,18,35]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[9,14,16,37]}],"complexes":["STX3/SNAP-23/VAMP8 SNARE complex","STX3/STXBP1/arrestin-4 light-regulated complex","STX3/STX4/VTI1B/STX8/SEC22B secretory autolysosome SNARE complex"],"partners":["STXBP2","VAMP8","SNAP23","PRPH2","STXBP1","SEC22B","EZR","STXBP5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q13277","full_name":"Syntaxin-3","aliases":[],"length_aa":289,"mass_kda":33.2,"function":"Potentially involved in docking of synaptic vesicles at presynaptic active zones. Apical receptor involved in membrane fusion of apical vesicles Essential for survival of retinal photoreceetors Functions as a regulator of gene expression","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q13277/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/STX3","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000166900","cell_line_id":"CID000751","localizations":[{"compartment":"cytoplasmic","grade":3},{"compartment":"membrane","grade":3},{"compartment":"vesicles","grade":3}],"interactors":[{"gene":"BNIP1","stoichiometry":4.0},{"gene":"STXBP2","stoichiometry":4.0},{"gene":"SNAP23","stoichiometry":0.2},{"gene":"ZW10","stoichiometry":0.2},{"gene":"NSF","stoichiometry":0.2},{"gene":"NBAS","stoichiometry":0.2},{"gene":"STXBP1","stoichiometry":0.2},{"gene":"SCFD1","stoichiometry":0.2},{"gene":"STX18","stoichiometry":0.2},{"gene":"USE1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000751","total_profiled":1310},"omim":[{"mim_id":"619446","title":"RETINAL DYSTROPHY AND MICROVILLUS INCLUSION DISEASE; RDMVID","url":"https://www.omim.org/entry/619446"},{"mim_id":"619445","title":"DIARRHEA 12, WITH MICROVILLUS ATROPHY; DIAR12","url":"https://www.omim.org/entry/619445"},{"mim_id":"618650","title":"RING FINGER PROTEIN 169; RNF169","url":"https://www.omim.org/entry/618650"},{"mim_id":"613101","title":"HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 5, WITH OR WITHOUT MICROVILLUS INCLUSION DISEASE; FHL5","url":"https://www.omim.org/entry/613101"},{"mim_id":"608676","title":"TAXILIN, ALPHA; TXLNA","url":"https://www.omim.org/entry/608676"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Vesicles","reliability":"Uncertain"},{"location":"Nuclear membrane","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"retina","ntpm":290.0}],"url":"https://www.proteinatlas.org/search/STX3"},"hgnc":{"alias_symbol":[],"prev_symbol":["STX3A"]},"alphafold":{"accession":"Q13277","domains":[{"cath_id":"1.20.58.70","chopping":"29-224","consensus_level":"high","plddt":89.8575,"start":29,"end":224}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13277","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13277-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13277-F1-predicted_aligned_error_v6.png","plddt_mean":83.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=STX3","jax_strain_url":"https://www.jax.org/strain/search?query=STX3"},"sequence":{"accession":"Q13277","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13277.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13277/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13277"}},"corpus_meta":[{"pmid":"16598260","id":"PMC_16598260","title":"Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3.","date":"2006","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/16598260","citation_count":266,"is_preprint":false},{"pmid":"24726755","id":"PMC_24726755","title":"Loss of syntaxin 3 causes variant microvillus inclusion disease.","date":"2014","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/24726755","citation_count":134,"is_preprint":false},{"pmid":"26216965","id":"PMC_26216965","title":"Accumulation of non-outer segment proteins in the outer segment underlies photoreceptor degeneration in Bardet-Biedl syndrome.","date":"2015","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/26216965","citation_count":117,"is_preprint":false},{"pmid":"24796653","id":"PMC_24796653","title":"Decreased miR-146 expression in peripheral blood mononuclear cells is correlated with ongoing islet autoimmunity in type 1 diabetes patients 1miR-146.","date":"2014","source":"Journal of diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/24796653","citation_count":95,"is_preprint":false},{"pmid":"18253931","id":"PMC_18253931","title":"Vesicle associated membrane protein (VAMP)-7 and VAMP-8, but not VAMP-2 or VAMP-3, are required for activation-induced degranulation of mature human mast cells.","date":"2008","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18253931","citation_count":85,"is_preprint":false},{"pmid":"34450251","id":"PMC_34450251","title":"circMRPS35 promotes malignant progression and cisplatin resistance in hepatocellular carcinoma.","date":"2021","source":"Molecular therapy : the journal of the American Society of Gene Therapy","url":"https://pubmed.ncbi.nlm.nih.gov/34450251","citation_count":84,"is_preprint":false},{"pmid":"26553929","id":"PMC_26553929","title":"Cargo-selective apical exocytosis in epithelial cells is conducted by Myo5B, Slp4a, Vamp7, and Syntaxin 3.","date":"2015","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/26553929","citation_count":83,"is_preprint":false},{"pmid":"24194549","id":"PMC_24194549","title":"Syntaxin binding mechanism and disease-causing mutations in Munc18-2.","date":"2013","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24194549","citation_count":61,"is_preprint":false},{"pmid":"30836997","id":"PMC_30836997","title":"Inflammatory, regulatory, and autophagy co-expression modules and hub genes underlie the peripheral immune response to human intracerebral hemorrhage.","date":"2019","source":"Journal of neuroinflammation","url":"https://pubmed.ncbi.nlm.nih.gov/30836997","citation_count":60,"is_preprint":false},{"pmid":"29266534","id":"PMC_29266534","title":"MYO5B, STX3, and STXBP2 mutations reveal a common disease mechanism that unifies a subset of congenital diarrheal disorders: A mutation update.","date":"2018","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/29266534","citation_count":51,"is_preprint":false},{"pmid":"24323579","id":"PMC_24323579","title":"Munc18-2 and syntaxin 3 control distinct essential steps in mast cell degranulation.","date":"2013","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/24323579","citation_count":49,"is_preprint":false},{"pmid":"21981832","id":"PMC_21981832","title":"SNAP-23 and syntaxin-3 are required for chemokine release by mature human mast cells.","date":"2011","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/21981832","citation_count":48,"is_preprint":false},{"pmid":"29360461","id":"PMC_29360461","title":"Pancreatitis-Induced Depletion of Syntaxin 2 Promotes Autophagy and Increases Basolateral Exocytosis.","date":"2018","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/29360461","citation_count":47,"is_preprint":false},{"pmid":"22285554","id":"PMC_22285554","title":"Aberrant localization of fusion receptors involved in regulated exocytosis in salivary glands of Sjögren's syndrome patients is linked to ectopic mucin secretion.","date":"2012","source":"Journal of autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/22285554","citation_count":46,"is_preprint":false},{"pmid":"28724787","id":"PMC_28724787","title":"Disrupted apical exocytosis of cargo vesicles causes enteropathy in FHL5 patients with Munc18-2 mutations.","date":"2017","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/28724787","citation_count":45,"is_preprint":false},{"pmid":"28407399","id":"PMC_28407399","title":"Abnormal Rab11-Rab8-vesicles cluster in enterocytes of patients with microvillus inclusion disease.","date":"2017","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/28407399","citation_count":44,"is_preprint":false},{"pmid":"18505797","id":"PMC_18505797","title":"AQP2 exocytosis in the renal collecting duct -- involvement of SNARE isoforms and the regulatory role of Munc18b.","date":"2008","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/18505797","citation_count":44,"is_preprint":false},{"pmid":"33206327","id":"PMC_33206327","title":"Molecular Correlates of Hemorrhage and Edema Volumes Following Human Intracerebral Hemorrhage Implicate Inflammation, Autophagy, mRNA Splicing, and T Cell Receptor Signaling.","date":"2020","source":"Translational stroke research","url":"https://pubmed.ncbi.nlm.nih.gov/33206327","citation_count":36,"is_preprint":false},{"pmid":"32778589","id":"PMC_32778589","title":"Syntaxin 3 is essential for photoreceptor outer segment protein trafficking and survival.","date":"2020","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/32778589","citation_count":35,"is_preprint":false},{"pmid":"29880488","id":"PMC_29880488","title":"Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells.","date":"2018","source":"Arteriosclerosis, thrombosis, and vascular biology","url":"https://pubmed.ncbi.nlm.nih.gov/29880488","citation_count":35,"is_preprint":false},{"pmid":"15588943","id":"PMC_15588943","title":"Molecular definition of an in vitro niche for dendritic cell development.","date":"2004","source":"Experimental hematology","url":"https://pubmed.ncbi.nlm.nih.gov/15588943","citation_count":33,"is_preprint":false},{"pmid":"16769761","id":"PMC_16769761","title":"Splenic endothelial cell lines support development of dendritic cells from bone marrow.","date":"2006","source":"Stem cells (Dayton, Ohio)","url":"https://pubmed.ncbi.nlm.nih.gov/16769761","citation_count":33,"is_preprint":false},{"pmid":"33028897","id":"PMC_33028897","title":"Acrylamide alters CREB and retinoic acid signalling pathways during differentiation of the human neuroblastoma SH-SY5Y cell line.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33028897","citation_count":32,"is_preprint":false},{"pmid":"31824480","id":"PMC_31824480","title":"Twenty Novel Disease Group-Specific and 12 New Shared Macrophage Pathways in Eight Groups of 34 Diseases Including 24 Inflammatory Organ Diseases and 10 Types of Tumors.","date":"2019","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/31824480","citation_count":32,"is_preprint":false},{"pmid":"38098057","id":"PMC_38098057","title":"Beyond the exome: utility of long-read whole genome sequencing in exome-negative autosomal recessive diseases.","date":"2023","source":"Genome medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38098057","citation_count":31,"is_preprint":false},{"pmid":"35638903","id":"PMC_35638903","title":"Syntaxin-1A modulates vesicle fusion in mammalian neurons via juxtamembrane domain dependent palmitoylation of its transmembrane domain.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35638903","citation_count":31,"is_preprint":false},{"pmid":"29408595","id":"PMC_29408595","title":"STX3 represses the stability of the tumor suppressor PTEN to activate the PI3K-Akt-mTOR signaling and promotes the growth of breast cancer cells.","date":"2018","source":"Biochimica et biophysica acta. Molecular basis of disease","url":"https://pubmed.ncbi.nlm.nih.gov/29408595","citation_count":30,"is_preprint":false},{"pmid":"35862195","id":"PMC_35862195","title":"Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G.","date":"2022","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/35862195","citation_count":30,"is_preprint":false},{"pmid":"28814500","id":"PMC_28814500","title":"Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes.","date":"2017","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/28814500","citation_count":30,"is_preprint":false},{"pmid":"30563839","id":"PMC_30563839","title":"Syntaxin 3, but not syntaxin 4, is required for mast cell-regulated exocytosis, where it plays a primary role mediating compound exocytosis.","date":"2018","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30563839","citation_count":30,"is_preprint":false},{"pmid":"21223469","id":"PMC_21223469","title":"The cystic fibrosis transmembrane conductance regulator's expanding SNARE interactome.","date":"2011","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/21223469","citation_count":29,"is_preprint":false},{"pmid":"21371234","id":"PMC_21371234","title":"A role for the SNARE protein syntaxin 3 in human cytomegalovirus morphogenesis.","date":"2011","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/21371234","citation_count":28,"is_preprint":false},{"pmid":"25548252","id":"PMC_25548252","title":"An essential role of syntaxin 3 protein for granule exocytosis and secretion of IL-1α, IL-1β, IL-12b, and CCL4 from differentiated HL-60 cells.","date":"2014","source":"Journal of leukocyte biology","url":"https://pubmed.ncbi.nlm.nih.gov/25548252","citation_count":28,"is_preprint":false},{"pmid":"32905772","id":"PMC_32905772","title":"Legionella Manipulates Non-canonical SNARE Pairing Using a Bacterial Deubiquitinase.","date":"2020","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/32905772","citation_count":28,"is_preprint":false},{"pmid":"26526116","id":"PMC_26526116","title":"The localisation of the apical Par/Cdc42 polarity module is specifically affected in microvillus inclusion disease.","date":"2015","source":"Biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/26526116","citation_count":28,"is_preprint":false},{"pmid":"32959907","id":"PMC_32959907","title":"SNAREs and developmental disorders.","date":"2020","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/32959907","citation_count":26,"is_preprint":false},{"pmid":"26830108","id":"PMC_26830108","title":"Towards understanding microvillus inclusion disease.","date":"2016","source":"Molecular and cellular pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/26830108","citation_count":23,"is_preprint":false},{"pmid":"25674084","id":"PMC_25674084","title":"A role for syntaxin 3 in the secretion of IL-6 from dendritic cells following activation of toll-like receptors.","date":"2015","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/25674084","citation_count":23,"is_preprint":false},{"pmid":"30364784","id":"PMC_30364784","title":"Dynamic Formation of Microvillus Inclusions During Enterocyte Differentiation in Munc18-2-Deficient Intestinal Organoids.","date":"2018","source":"Cellular and molecular gastroenterology and hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/30364784","citation_count":23,"is_preprint":false},{"pmid":"25301939","id":"PMC_25301939","title":"Spatial control of proton pump H,K-ATPase docking at the apical membrane by phosphorylation-coupled ezrin-syntaxin 3 interaction.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25301939","citation_count":20,"is_preprint":false},{"pmid":"31694913","id":"PMC_31694913","title":"The myosin-tail homology domain of centrosomal protein 290 is essential for protein confinement between the inner and outer segments in photoreceptors.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31694913","citation_count":20,"is_preprint":false},{"pmid":"25954931","id":"PMC_25954931","title":"Mechanisms of Intestinal Serotonin Transporter (SERT) Upregulation by TGF-β1 Induced Non-Smad Pathways.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25954931","citation_count":19,"is_preprint":false},{"pmid":"24146186","id":"PMC_24146186","title":"Syntaxin-4 is implicated in the secretion of antibodies by human plasma cells.","date":"2013","source":"Journal of leukocyte biology","url":"https://pubmed.ncbi.nlm.nih.gov/24146186","citation_count":18,"is_preprint":false},{"pmid":"25583387","id":"PMC_25583387","title":"Human cytomegalovirus miR-US33-5p inhibits viral DNA synthesis and viral replication by down-regulating expression of the host Syntaxin3.","date":"2015","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/25583387","citation_count":17,"is_preprint":false},{"pmid":"29475951","id":"PMC_29475951","title":"Soluble syntaxin 3 functions as a transcriptional regulator.","date":"2018","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29475951","citation_count":16,"is_preprint":false},{"pmid":"29970602","id":"PMC_29970602","title":"Tomosyn functions as a PKCδ-regulated fusion clamp in mast cell degranulation.","date":"2018","source":"Science signaling","url":"https://pubmed.ncbi.nlm.nih.gov/29970602","citation_count":16,"is_preprint":false},{"pmid":"33961633","id":"PMC_33961633","title":"Differential requirement of NPHP1 for compartmentalized protein localization during photoreceptor outer segment development and maintenance.","date":"2021","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/33961633","citation_count":15,"is_preprint":false},{"pmid":"25358429","id":"PMC_25358429","title":"Autosomal recessive congenital cataract, intellectual disability phenotype linked to STX3 in a consanguineous Tunisian family.","date":"2014","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25358429","citation_count":14,"is_preprint":false},{"pmid":"16948502","id":"PMC_16948502","title":"Heterogeneity amongst splenic stromal cell lines which support dendritic cell hematopoiesis.","date":"2006","source":"In vitro cellular & developmental biology. Animal","url":"https://pubmed.ncbi.nlm.nih.gov/16948502","citation_count":14,"is_preprint":false},{"pmid":"30156474","id":"PMC_30156474","title":"Syntaxin clusters at secretory granules in a munc18-bound conformation.","date":"2018","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/30156474","citation_count":14,"is_preprint":false},{"pmid":"33976085","id":"PMC_33976085","title":"Genetic Enteropathies Linked to Epithelial Structural Abnormalities and Enteroendocrine Deficiency: A Systematic Review.","date":"2021","source":"Journal of pediatric gastroenterology and nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/33976085","citation_count":13,"is_preprint":false},{"pmid":"17697113","id":"PMC_17697113","title":"Molecular cloning, expression and characterization of protein disulfide isomerase from Conus marmoreus.","date":"2007","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/17697113","citation_count":13,"is_preprint":false},{"pmid":"33192329","id":"PMC_33192329","title":"Phosphorylation of the Retinal Ribbon Synapse Specific t-SNARE Protein Syntaxin3B Is Regulated by Light via a Ca2 +-Dependent Pathway.","date":"2020","source":"Frontiers in cellular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/33192329","citation_count":13,"is_preprint":false},{"pmid":"30909251","id":"PMC_30909251","title":"Microvillus inclusion disease, a diagnosis to consider when abnormal stools and neurological impairments run together due to a rare syntaxin 3 gene mutation.","date":"2019","source":"Journal of neonatal-perinatal medicine","url":"https://pubmed.ncbi.nlm.nih.gov/30909251","citation_count":13,"is_preprint":false},{"pmid":"18564035","id":"PMC_18564035","title":"Gene signature of stromal cells which support dendritic cell development.","date":"2008","source":"Stem cells and development","url":"https://pubmed.ncbi.nlm.nih.gov/18564035","citation_count":12,"is_preprint":false},{"pmid":"20695848","id":"PMC_20695848","title":"Munc18b regulates core SNARE complex assembly and constitutive exocytosis by interacting with the N-peptide and the closed-conformation C-terminus of syntaxin 3.","date":"2010","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/20695848","citation_count":12,"is_preprint":false},{"pmid":"29282386","id":"PMC_29282386","title":"Microvillus Inclusion Disease Variant in an Infant with Intractable Diarrhea.","date":"2017","source":"Case reports in gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/29282386","citation_count":12,"is_preprint":false},{"pmid":"35331396","id":"PMC_35331396","title":"Congenital enteropathies involving defects in enterocyte structure or differentiation.","date":"2022","source":"Best practice & research. Clinical gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/35331396","citation_count":11,"is_preprint":false},{"pmid":"37882795","id":"PMC_37882795","title":"Ubiquitination of Sec22b by a novel Legionella pneumophila ubiquitin E3 ligase.","date":"2023","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/37882795","citation_count":9,"is_preprint":false},{"pmid":"22117595","id":"PMC_22117595","title":"Myelopoiesis in spleen-producing distinct dendritic-like cells.","date":"2012","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/22117595","citation_count":9,"is_preprint":false},{"pmid":"24745998","id":"PMC_24745998","title":"Spleen stroma maintains progenitors and supports long-term hematopoiesis.","date":"2014","source":"Current stem cell research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/24745998","citation_count":9,"is_preprint":false},{"pmid":"40327696","id":"PMC_40327696","title":"Unconventional secretion of PARK7 requires lysosomal delivery via chaperone-mediated autophagy and specialized SNARE complex.","date":"2025","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/40327696","citation_count":8,"is_preprint":false},{"pmid":"37695358","id":"PMC_37695358","title":"A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells.","date":"2023","source":"Angiogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/37695358","citation_count":8,"is_preprint":false},{"pmid":"38683247","id":"PMC_38683247","title":"Modeling the cell biology of monogenetic intestinal epithelial disorders.","date":"2024","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/38683247","citation_count":7,"is_preprint":false},{"pmid":"37114883","id":"PMC_37114883","title":"Syntaxin 3 SPI-2 dependent crosstalk facilitates the division of Salmonella containing vacuole.","date":"2023","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/37114883","citation_count":7,"is_preprint":false},{"pmid":"17889723","id":"PMC_17889723","title":"Hematopoiesis of immature myeloid dendritic cells in stroma-dependent spleen long-term cultures occurs independently of NF-KB/RelB function.","date":"2007","source":"Experimental hematology","url":"https://pubmed.ncbi.nlm.nih.gov/17889723","citation_count":6,"is_preprint":false},{"pmid":"28899465","id":"PMC_28899465","title":"[Clinical features and MYO5B mutations of a family affected by microvillus inclusion disease].","date":"2017","source":"Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/28899465","citation_count":6,"is_preprint":false},{"pmid":"38307491","id":"PMC_38307491","title":"Uncovering the Relationship Between Genes and Phenotypes Beyond the Gut in Microvillus Inclusion Disease.","date":"2024","source":"Cellular and molecular gastroenterology and hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/38307491","citation_count":5,"is_preprint":false},{"pmid":"33712280","id":"PMC_33712280","title":"Syntaxin 3 interacts with serotonin transporter and regulates its function.","date":"2021","source":"Journal of pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33712280","citation_count":5,"is_preprint":false},{"pmid":"38934263","id":"PMC_38934263","title":"SKArred 2 death: neuroinflammatory breakdown of the hippocampus.","date":"2024","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/38934263","citation_count":4,"is_preprint":false},{"pmid":"33288783","id":"PMC_33288783","title":"The Habc domain of syntaxin 3 is a ubiquitin binding domain.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33288783","citation_count":4,"is_preprint":false},{"pmid":"35113433","id":"PMC_35113433","title":"Lnc-AC145676.2.1-6-3 can influence STX3-induced abnormal autophagy by sponging hsa-miR-1292-3p in intestinal aGVHD.","date":"2022","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35113433","citation_count":3,"is_preprint":false},{"pmid":"32221667","id":"PMC_32221667","title":"Effects of syntaxins 2, 3, and 4 on rat and human epithelial sodium channel (ENaC) in Xenopus laevis oocytes.","date":"2020","source":"Pflugers Archiv : European journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/32221667","citation_count":3,"is_preprint":false},{"pmid":"37848418","id":"PMC_37848418","title":"Neuronal RBM5 modulates cell signaling responses to traumatic and hypoxic-ischemic injury in a sex-dependent manner.","date":"2023","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/37848418","citation_count":3,"is_preprint":false},{"pmid":"21958239","id":"PMC_21958239","title":"Distinct In Vitro Myelopoiesis is Dependent on the Self-Renewal of Hematopoietic Progenitors.","date":"2012","source":"Scandinavian journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/21958239","citation_count":3,"is_preprint":false},{"pmid":"34501384","id":"PMC_34501384","title":"Risk and Clinical Significance of Idiopathic Preterm Birth in Microvillus Inclusion Disease.","date":"2021","source":"Journal of clinical medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34501384","citation_count":3,"is_preprint":false},{"pmid":"35510126","id":"PMC_35510126","title":"Identification of Common Hub Genes in Human Dermal Fibroblasts Stimulated by Mechanical Stretch at Both the Early and Late Stages.","date":"2022","source":"Frontiers in surgery","url":"https://pubmed.ncbi.nlm.nih.gov/35510126","citation_count":3,"is_preprint":false},{"pmid":"35769957","id":"PMC_35769957","title":"Microvillus Inclusion Disease: A Rare Mutation of STX3 in Exon 9 Causing Fatal Congenital Diarrheal Disease.","date":"2020","source":"Journal of pediatric genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35769957","citation_count":2,"is_preprint":false},{"pmid":"17533411","id":"PMC_17533411","title":"Use of gene profiling to describe a niche for dendritic cell development.","date":"2007","source":"Immunology and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/17533411","citation_count":2,"is_preprint":false},{"pmid":"38836179","id":"PMC_38836179","title":"Systematic review of phenotypes and genotypes of patients with gastrointestinal defects and immunodeficiency syndrome-1 (GIDID1) (related to TTC7A).","date":"2024","source":"Intractable & rare diseases research","url":"https://pubmed.ncbi.nlm.nih.gov/38836179","citation_count":2,"is_preprint":false},{"pmid":"25630102","id":"PMC_25630102","title":"Effect of mutation on aggregation propensity in homology model structures of syntaxin-3 from Homo sapiens.","date":"2014","source":"Indian journal of biochemistry & biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/25630102","citation_count":1,"is_preprint":false},{"pmid":"36747809","id":"PMC_36747809","title":"A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/36747809","citation_count":1,"is_preprint":false},{"pmid":"39408994","id":"PMC_39408994","title":"Syntaxin 3B: A SNARE Protein Required for Vision.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39408994","citation_count":1,"is_preprint":false},{"pmid":"41220299","id":"PMC_41220299","title":"Syntaxin 3B Mediates Light-Dependent Interactions with STXBP1 and Arrestin 4: Distinct Roles in Rods and Cones.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/41220299","citation_count":1,"is_preprint":false},{"pmid":"29564371","id":"PMC_29564371","title":"Tracking Endocytosis and Intracellular Trafficking of Epitope-tagged Syntaxin 3 by Antibody Feeding in Live, Polarized MDCK Cells.","date":"2018","source":"Bio-protocol","url":"https://pubmed.ncbi.nlm.nih.gov/29564371","citation_count":1,"is_preprint":false},{"pmid":"41932328","id":"PMC_41932328","title":"Hippocampal place code plasticity in CA1 requires postsynaptic membrane fusion.","date":"2026","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/41932328","citation_count":1,"is_preprint":false},{"pmid":"40491693","id":"PMC_40491693","title":"Bioinformatics-led identification of pathophysiological hallmark genes in diabesotension via graph clustering method.","date":"2025","source":"Journal of diabetes and metabolic disorders","url":"https://pubmed.ncbi.nlm.nih.gov/40491693","citation_count":1,"is_preprint":false},{"pmid":"37609371","id":"PMC_37609371","title":"Syntaxin 3 is haplosufficient for long-term photoreceptor survival in the mouse retina.","date":"2023","source":"Frontiers in ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/37609371","citation_count":1,"is_preprint":false},{"pmid":"41776690","id":"PMC_41776690","title":"miR-3913-3p promoted the progression of lung adenocarcinoma by regulating STX3 expression.","date":"2026","source":"Hereditas","url":"https://pubmed.ncbi.nlm.nih.gov/41776690","citation_count":0,"is_preprint":false},{"pmid":"41225541","id":"PMC_41225541","title":"TGF-β2 increases eHSP90α secretion via upregulating secretory autophagy pathway.","date":"2025","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/41225541","citation_count":0,"is_preprint":false},{"pmid":"41354961","id":"PMC_41354961","title":"Organoid-derived photoreceptor precursors enriched by CD9⁻CD81mid sorting restore visual function in RCS rats.","date":"2025","source":"Stem cell research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/41354961","citation_count":0,"is_preprint":false},{"pmid":"41033460","id":"PMC_41033460","title":"Syntaxin 3 regulates apical membrane integrity in proximal tubule epithelial cells and prevents Fanconi syndrome development.","date":"2025","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/41033460","citation_count":0,"is_preprint":false},{"pmid":"41638388","id":"PMC_41638388","title":"High Mobility Group Protein B1 and its downstream elements, syntaxins, contribute to temporal tight junction assembly in a human keratinocyte cell line.","date":"2026","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/41638388","citation_count":0,"is_preprint":false},{"pmid":"41586744","id":"PMC_41586744","title":"Integrated genomic and proteomic profiling reveals insights into chemoradiation resistance in cervical cancer.","date":"2026","source":"Molecular oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41586744","citation_count":0,"is_preprint":false},{"pmid":"41896526","id":"PMC_41896526","title":"ZNRF1 deficiency disrupts Fas ligand trafficking and immune balance.","date":"2026","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/41896526","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":50307,"output_tokens":10344,"usd":0.15304,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":20674,"output_tokens":4359,"usd":0.106173,"stage2_stop_reason":"end_turn"},"total_usd":0.259213,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"STX3 (syntaxin 3) is a direct molecular target of omega-6 arachidonic acid and dietary omega-3 fatty acids (linolenic and docosahexaenoic acids), which activate STX3 to promote cell membrane expansion at neuronal growth cones, thereby stimulating neurite outgrowth.\",\n      \"method\": \"In vitro screening assay using STX3 as target protein; direct binding/activation assay with fatty acids; neurite outgrowth functional readout\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct in vitro biochemical assay identifying STX3 as the effector, coupled to functional neurite outgrowth phenotype; published in Nature with multiple orthogonal methods\",\n      \"pmids\": [\"16598260\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Loss-of-function (homozygous truncating) mutations in STX3 cause variant microvillus inclusion disease (MVID), demonstrating that STX3 is required as an apical SNARE receptor for membrane fusion of apical vesicles in enterocytes; patient-derived organoids and Caco-2 overexpression of truncated STX3 recapitulated MVID characteristics.\",\n      \"method\": \"Whole-exome sequencing of MVID patients; patient-derived organoid cultures; overexpression of truncated STX3 in Caco-2 cells\",\n      \"journal\": \"Gastroenterology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function mutations in patients plus functional validation in organoids and cell lines with defined cellular phenotype\",\n      \"pmids\": [\"24726755\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Apical exocytosis of specific cargo (NHE3, CFTR, GLUT5) in polarized epithelial cells requires a sequential interaction cascade: Rab11 → Myo5B → Slp4a → Munc18-2 → Vamp7 → STX3. STX3 acts as the apical t-SNARE for selective cargo exocytosis, while brush border enzymes DPPIV and sucrase-isomaltase traffic independently of this pathway.\",\n      \"method\": \"Genome editing (CRISPR) to introduce Myo5B patient mutation in human epithelial cell line; Co-IP interaction studies; cargo trafficking assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-edited human cell line, multiple cargo tested, interaction cascade dissected with multiple orthogonal methods\",\n      \"pmids\": [\"26553929\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"In renal collecting-duct principal cells, STX3 localizes to the apical plasma membrane and forms SNARE complexes with VAMP2, VAMP3, SNAP23, and Munc18b. Knockdown of STX3 strongly inhibits vasopressin-regulated AQP2 fusion at the apical membrane; Munc18b acts as a negative regulator of SNARE-complex formation in this pathway.\",\n      \"method\": \"Co-immunoprecipitation; protein knockdown (siRNA); apical surface biotinylation to measure AQP2 fusion\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP plus functional knockdown with quantitative surface biotinylation readout, multiple SNARE partners identified\",\n      \"pmids\": [\"18505797\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In mast cells, siRNA-mediated silencing of STX3 inhibits degranulation (membrane fusion step), while Munc18-2 silencing impairs secretory granule (SG) translocation; combined knockdown has additive inhibitory effect. Both proteins localize to granule surface and cytoskeletal clusters, and Munc18-2 (but not STX3) interacts with tubulin in resting cells.\",\n      \"method\": \"siRNA knockdown; immunogold electron microscopy; co-immunoprecipitation; degranulation functional assays\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — siRNA knockdown with defined phenotypic readout, immunogold localization, Co-IP, multiple orthogonal methods in single study\",\n      \"pmids\": [\"24323579\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Munc18-2 binds to the N-terminal peptide of STX11 with ~20-fold higher affinity than STX3 in vitro; upon IL-2 activation, increased STX3 levels allow Munc18-2 binding to STX3 when STX11 is absent, partially restoring cytotoxic function.\",\n      \"method\": \"Crystal structure of Munc18-2 at 2.6 Å resolution; binding affinity measurements; mapping of disease-causing mutations to structure\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus quantitative binding measurements, mechanistic explanation for disease compensation\",\n      \"pmids\": [\"24194549\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Munc18b interacts with both the N-terminal peptide and the closed-conformation C-terminus (Habc domain + linker + SNARE H3 motif) of STX3. Deletion of the Habc domain or mutations disrupting intramolecular Habc-H3 binding abolish Munc18b-STX3 interaction. Munc18b also binds VAMP8 and the assembled STX3/SNAP-23/VAMP8 core SNARE complex; overexpression of Munc18b increases constitutive exocytosis.\",\n      \"method\": \"In vitro binding/pull-down assays; mutagenesis of STX3 domains; constitutive exocytosis assay in mammalian cells\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with mutagenesis, multiple interaction interfaces mapped, functional exocytosis assay\",\n      \"pmids\": [\"20695848\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"STX3 undergoes monoubiquitination in a conserved polybasic domain. Ubiquitinated STX3 at the basolateral plasma membrane is rapidly endocytosed, sorted to late endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A non-ubiquitinatable STX3-5R mutant fails to enter this pathway and acts as a dominant-negative inhibitor of GPRC5B cargo entry into ILVs/exosomes. HCMV exploits this STX3 exosomal pathway for virion excretion.\",\n      \"method\": \"Monoubiquitination site mapping; live-cell antibody feeding endocytosis tracking in polarized MDCK cells; dominant-negative mutant analysis; HCMV virion excretion assay\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization/endocytosis tracking, ubiquitination mapping, dominant-negative mutant with functional cargo and viral readout\",\n      \"pmids\": [\"28814500\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"STX3 is localized to Weibel-Palade bodies (WPBs) in endothelial cells and is required for both basal and stimulated (Ca2+- and cAMP-mediated) VWF secretion. STX3 is absent in STX3-/- blood outgrowth endothelial cells (from MVID patient), resulting in defective WPB exocytosis. STX3 interacts with WPB-associated VAMP8. WPB formation and maturation are unaffected by STX3 loss.\",\n      \"method\": \"Immunolocalization in human umbilical vein endothelial cells and patient-derived STX3-/- BOECs; VWF secretion assays; Co-IP of STX3 with VAMP8; ultrastructural analysis\",\n      \"journal\": \"Arteriosclerosis, thrombosis, and vascular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient-derived KO cells with defined secretion phenotype, Co-IP, orthogonal localization and functional assays\",\n      \"pmids\": [\"29880488\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"STX3 (but not STX4) is required for mast cell regulated exocytosis; conditional Stx3 knockout mice show a specific inability to engage multigranular compound exocytosis, while single-vesicle fusion events are largely intact. STX3 is dispensable for constitutive cytokine secretion.\",\n      \"method\": \"Conditional knockout mice; electrophysiology; electron microscopy; passive systemic anaphylaxis in vivo model\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with multiple orthogonal readouts (electrophysiology, EM, in vivo anaphylaxis), distinguishes compound from single-vesicle exocytosis\",\n      \"pmids\": [\"30563839\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Photoreceptor-specific Stx3 knockout mice exhibit rapid photoreceptor degeneration. In the absence of STX3, outer segment (OS) proteins including peripherin 2 (PRPH2), ROM1, and rhodopsin are mislocalized along microtubules to the inner segment, cell body, and synaptic region. The PRPH2 C-terminal domain physically interacts with STX3 and other photoreceptor SNAREs.\",\n      \"method\": \"Photoreceptor-specific Stx3 conditional knockout mice; immunofluorescence localization; co-immunoprecipitation (PRPH2 C-terminal domain with STX3)\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with defined mislocalization phenotype plus direct Co-IP interaction, multiple OS proteins tested\",\n      \"pmids\": [\"32778589\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In gastric parietal cells, PKA-mediated phosphorylation of ezrin at Ser-66 induces a conformational change that enables ezrin association with STX3 (not other syntaxins), providing a spatial cue for H,K-ATPase trafficking to the apical plasma membrane. Inhibition of ezrin Ser-66 phosphorylation prevents ezrin-STX3 association and blocks H,K-ATPase insertion.\",\n      \"method\": \"Co-immunoprecipitation; atomic force microscopy showing phosphorylation-induced ezrin unfolding; pharmacological inhibition of PKA; apical plasma membrane insertion assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — multiple orthogonal methods including AFM structural analysis, Co-IP, and functional transport assay; phosphorylation mechanism rigorously dissected\",\n      \"pmids\": [\"25301939\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Alternative splicing of STX3 generates a soluble isoform (Stx3S) lacking the transmembrane anchor. Stx3S binds the nuclear import factor RanBP5, translocates to the nucleus, and physically and functionally interacts with transcription factors ETV4 and ATF2. Inhibition of endogenous Stx3S alters cancer-associated gene expression and promotes cell proliferation.\",\n      \"method\": \"Identification of splice isoform; Co-IP of Stx3S with RanBP5, ETV4, ATF2; nuclear localization by fractionation/imaging; siRNA knockdown with gene expression and proliferation readouts\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — novel isoform identified with Co-IP of multiple nuclear partners, functional knockdown with transcriptional and proliferation phenotype\",\n      \"pmids\": [\"29475951\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"HCMV infection induces STX3 expression; STX3 localizes to the HCMV assembly site where it associates with virus-wrapping membranes. STX3 knockdown by RNAi reduces HCMV production and results in fewer mature virions with more viruses undergoing final envelopment; an RNAi-resistant STX3 construct rescues production. STX3 depletion also reduces lysosomal membrane glycoprotein expression.\",\n      \"method\": \"RNAi knockdown; immunogold labeling; RNAi-resistant construct rescue; ultrastructural analysis of assembly site\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi knockdown with rescue construct and ultrastructural readout, single lab\",\n      \"pmids\": [\"21371234\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"STX3 and SNAP-23 are required for IgE receptor-mediated release of all chemokines (CXCL8, CCL2, CCL3, CCL4) from mature human mast cells, while blocking STX-2 or VAMP-3 does not affect chemokine release; STX4 and VAMP-8 selectively affect only CXCL8 release.\",\n      \"method\": \"Blocking antibodies/siRNA inhibition of specific SNARE isoforms; chemokine release assay by ELISA following IgE receptor cross-linking\",\n      \"journal\": \"Molecular immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional knockdown with multiple SNARE isoforms tested in parallel, single lab\",\n      \"pmids\": [\"21981832\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"siRNA-mediated knockdown of STX3 in dHL-60 cells (neutrophil model) reduces maximal release of IL-1α, IL-1β, IL-12b, and CCL4 without altering other cytokine secretion, and inhibits MMP-9 exocytosis from gelatinase granules, where STX3 is partly localized.\",\n      \"method\": \"siRNA knockdown; cytokine secretion profiling (CBA); MMP-9 exocytosis assay; subcellular localization by microscopy\",\n      \"journal\": \"Journal of leukocyte biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA with defined cytokine secretion phenotype and granule localization, single lab\",\n      \"pmids\": [\"25548252\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In Toll-like receptor-activated dendritic cells, STX3 mRNA is upregulated by TLR4 and TLR7 (but not TLR2); RNAi knockdown of STX3 attenuates IL-6 secretion. STX3 translocates to the cell membrane only in DCs secreting IL-6 or MIP-1α.\",\n      \"method\": \"SNARE mRNA profiling; RNAi knockdown; IL-6 ELISA; confocal microscopy of STX3 subcellular translocation\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi with cytokine readout and direct localization imaging, single lab\",\n      \"pmids\": [\"25674084\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"STX3 is mislocalized in MVID patient enterocytes bearing MYO5B or STX3 mutations, and loss of MYO5B in 3D Caco-2 cysts causes mislocalisation of apical polarity determinants (Cdc42, Par6B, PKCζ/ι, ezrin) and polarity inversion.\",\n      \"method\": \"Immunofluorescence of patient biopsies; MYO5B depletion in 3D Caco-2 cyst model; electron microscopy\",\n      \"journal\": \"Biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient tissue plus cell model with defined polarity phenotype, single lab\",\n      \"pmids\": [\"26526116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Munc18-2 is required for Slp4a/STX3 interaction during fusion of cargo vesicles with the apical plasma membrane; loss of Munc18-2 selectively disrupts apical trafficking of NHE3 and GLUT5 but not DPPIV, establishing cargo selectivity in the STX3-dependent pathway.\",\n      \"method\": \"CRISPR/Cas9-generated Munc18-2 KO CaCo2 cells; Co-IP of Slp4a/STX3; cargo trafficking assays in patient biopsies, organoids, and genome-edited cells\",\n      \"journal\": \"JCI insight\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR KO model with Co-IP and cargo-selective trafficking phenotype validated in patient tissue, organoids, and cell line\",\n      \"pmids\": [\"28724787\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"STX3 promotes breast cancer cell proliferation by binding PTEN and increasing PTEN ubiquitination and degradation, thereby activating the PI3K-Akt-mTOR signaling pathway; AKT inhibitors repress STX3-driven growth.\",\n      \"method\": \"Co-immunoprecipitation of STX3 with PTEN; ubiquitination assay; lentiviral knockdown and overexpression; in vitro and in vivo tumor growth assays\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular basis of disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with PTEN, ubiquitination assay, functional rescue with AKT inhibitor, single lab\",\n      \"pmids\": [\"29408595\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"In salivary glands of Sjögren's syndrome patients, STX3, STX4, SNAP-23, and VAMP8 relocalize from the apical to the basal region of acinar cells, and increased formation of SNARE complexes independent of secretory stimuli is detected, correlating with ectopic basolateral mucin secretion.\",\n      \"method\": \"Immunofluorescence localization; Western blotting; Co-IP for SNARE complex formation\",\n      \"journal\": \"Journal of autoimmunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — immunofluorescence and Co-IP with aberrant localization and function; disease tissue only, no experimental manipulation\",\n      \"pmids\": [\"22285554\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"TGF-β1 stimulates SERT exocytosis to the apical surface of Caco-2 cells via PI3K activation; TGF-β1 increases the association of SERT with STX3, and STX3 promotes SERT insertion at the apical plasma membrane.\",\n      \"method\": \"Co-immunoprecipitation (SERT-STX3); surface biotinylation; brefeldin A inhibition; PI3K inhibitor; ex vivo Ussing chamber 5-HT uptake\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional surface biotinylation and pharmacological dissection, single lab\",\n      \"pmids\": [\"25954931\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In STX2-knockout pancreatic acini, increased apical and basolateral exocytosis requires formation of fusogenic SNARE complexes mediated by STX3 and STX4; STX2 normally blocks STX3- and STX4-mediated zymogen granule fusion with the plasma membrane.\",\n      \"method\": \"STX2-KO mice; live-cell exocytosis and Ca2+ imaging; SNARE complex formation assays by Co-IP; human pancreatic tissue analysis\",\n      \"journal\": \"Gastroenterology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO mice with live-cell imaging and SNARE complex biochemistry, human tissue validation, single lab\",\n      \"pmids\": [\"29360461\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The Habc domain of STX3 binds monomeric ubiquitin with low affinity and efficiently binds K63-linked (but not K48-linked) poly-ubiquitin chains within a narrow range of chain lengths; molecular modeling identifies conserved residues shared with the GAT domain of GGA proteins.\",\n      \"method\": \"In vitro ubiquitin-binding assays; molecular modeling\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro binding assay with linkage selectivity established, but single lab, no functional consequence tested in cells\",\n      \"pmids\": [\"33288783\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"STX3 accumulates in the photoreceptor outer segment (OS) in Lztfl1/Bbs17 and Bbs1 mutant BBS mice; in normal photoreceptors STX3 is excluded from the OS. Loss of BBS proteins causes mislocalization of STX3 and Stxbp1/Munc18-1 into the OS, contributing to large vesicle formation and disruption of OS lamellar structure.\",\n      \"method\": \"Isolated OS proteomics; quantitative proteomics (>3-fold enrichment); immunofluorescence; ultrastructural analysis in BBS mouse models\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative proteomics plus ultrastructural analysis in two BBS mouse models, localization with functional consequence\",\n      \"pmids\": [\"26216965\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In CEP290 mutant mice, disruption of the C-terminal myosin-tail homology domain causes rapid accumulation of inner segment plasma membrane proteins, including STX3, SNAP25, and IMPG2, in the outer segment, indicating that CEP290 normally confines these inner segment proteins from entering the OS.\",\n      \"method\": \"Conditional Cep290 mutant mice; immunofluorescence localization of STX3 and other membrane proteins; comparison with endomembrane protein localization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO mice with defined protein mislocalization phenotype, single lab\",\n      \"pmids\": [\"31694913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Legionella deubiquitinase LotB deconjugates K63-linked ubiquitins from Sec22b on the Legionella-containing vacuole (LCV), stimulating dissociation of STX3 from Sec22b; this modulates non-canonical SNARE pairing dynamics at the LCV.\",\n      \"method\": \"Identification of Sec22b ubiquitination upon Legionella infection; LotB DUB activity assays; Co-IP of STX3-Sec22b; T4SS-dependent experiments\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — bacterial DUB activity assay with Co-IP showing STX3-Sec22b dissociation, T4SS dependency established\",\n      \"pmids\": [\"32905772\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"STX3 interacts with the serotonin transporter (SERT) by co-immunoprecipitation; they colocalize in ER and Golgi in overexpressing cells, and in apical microvilli-like structures in polarized Caco-2 cells. STX3 overexpression reduces SERT plasma membrane expression (anchoring in ER/Golgi), while STX3 knockdown in Caco-2 cells marginally decreases serotonin uptake activity and alters SERT glycosylation state.\",\n      \"method\": \"Co-immunoprecipitation; immunocytochemistry; serotonin uptake assay; STX3 knockdown (siRNA); glycosylation state analysis\",\n      \"journal\": \"Journal of pharmacological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional uptake assay and localization imaging, single lab\",\n      \"pmids\": [\"33712280\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In retinal ribbon synapses, STX3B (the retina-specific splice form of STX3) is phosphorylated at T14 by CaMKII in a light- and Ca2+-dependent manner. In rod photoreceptor terminals, pSTX3 is higher in dark-adapted (active) mice; in rod bipolar cell terminals, pSTX3 is higher in light-exposed mice. Pharmacological CaMKII inhibition suppresses both pSTX3 and evoked exocytosis measured by membrane capacitance.\",\n      \"method\": \"Quantitative immunofluorescence in dark- and light-adapted mice; isolated eyecup and isolated rod bipolar cell preparations with Ca2+ manipulation; staurosporine and CaMKII inhibitor (AIP) experiments; membrane capacitance measurements\",\n      \"journal\": \"Frontiers in cellular neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple experimental preparations with pharmacological manipulation, light-dependent in vivo phosphorylation correlated with exocytosis, single lab\",\n      \"pmids\": [\"33192329\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In neurons, the juxtamembrane domain (JMD) of STX1A regulates palmitoylation of its transmembrane domain (TMD), and loss of palmitoylation inhibits spontaneous vesicle fusion. Swapping STX1A's JMD into STX3A together with two TMD cysteines forces STX3A palmitoylation and dramatically enhances spontaneous vesicle fusion, showing that forced palmitoylation is sufficient to gain this function.\",\n      \"method\": \"Hippocampal neuron culture with site-directed mutagenesis of STX1A and chimeric STX3A constructs; electrophysiology (mEPSC recording)\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — mutagenesis with electrophysiological functional readout; mechanistic insight into STX3A palmitoylation, single lab\",\n      \"pmids\": [\"35638903\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"L. pneumophila effector Lug15 (E3 ubiquitin ligase) ubiquitinates host Sec22b and mediates its recruitment to the LCV; Sec22b ubiquitination by Lug15 promotes non-canonical pairing of Sec22b with plasma membrane-derived syntaxins including STX3.\",\n      \"method\": \"Ubiquitin E3 ligase assay for Lug15; ubiquitination of Sec22b; Co-IP of Sec22b with STX3; LCV remodeling analysis\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical E3 ligase assay plus Co-IP showing STX3-Sec22b pairing, single lab\",\n      \"pmids\": [\"37882795\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"STX3 is a component of a specialized SNARE complex (STX3/4, VTI1B, STX8 as Qabc-SNAREs and SEC22B as R-SNARE) that mediates fusion of PARK7-containing secretory autolysosomes with the plasma membrane for unconventional PARK7 secretion under oxidative stress.\",\n      \"method\": \"siRNA knockdown of STX3 and SNARE components; PARK7 secretion assay; autophagy flux analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown with functional secretion readout, SNARE complex identified, single lab\",\n      \"pmids\": [\"40327696\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"STX3 localizes to Salmonella-containing vacuole (SCV) membranes; STX3 knockdown reduces bacterial proliferation and is restored by STX3 overexpression. STX3-SCV interaction requires SPI-2-encoded T3SS (ΔssaV abolishes it) but not SPI-1 T3SS, suggesting SPI-2 effectors recruit STX3 to facilitate SCV membrane acquisition for division.\",\n      \"method\": \"STX3 siRNA knockdown; STX3 overexpression rescue; live-cell imaging of Salmonella-infected cells; SPI-1 and SPI-2 T3SS mutant infections; in vivo mouse model\",\n      \"journal\": \"Traffic\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — knockdown, rescue, and genetic mutant bacteria with in vivo validation, single lab\",\n      \"pmids\": [\"37114883\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"siRNA-mediated depletion of STX3 (along with RAB27A and VAMP3) reduces post-Golgi vesicle trafficking and sFLT1 secretion from endothelial cells, placing STX3 in the post-Golgi secretory pathway for sFLT1, distinct from STX6/ARF1/AP1 which act at the Golgi.\",\n      \"method\": \"siRNA knockdown of specific trafficking components; sFLT1 secretion assay; live imaging of temporally controlled sFLT1 release\",\n      \"journal\": \"Angiogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown with cargo-specific secretion assay, multiple SNAREs compared, single lab\",\n      \"pmids\": [\"37695358\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cone-specific STX3 knockout mice exhibit early cone dysfunction followed by progressive rod impairment. In cones, STX3 loss selectively depletes STXBP1 and cone arrestin 4 at the connecting cilium. A light-dependent complex comprising STX3, STXBP1, and arrestin 4 is identified, with arrestin 4 preferentially associating with STX3 in dark-adapted retina and with STXBP1 in light-adapted retina.\",\n      \"method\": \"Cone-specific and rod-specific Stx3 conditional knockout mice; Co-IP of STX3-STXBP1-arrestin 4 complex; functional ERG analysis\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cell-type-specific KO mice with Co-IP of light-dependent complex and functional readout, single lab\",\n      \"pmids\": [\"41220299\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PTEC-specific Stx3 knockout (Stx3-cKO) mice develop Fanconi syndrome with increased urinary excretion of phosphorus, glucose, amino acids, and low-molecular-weight proteins. Brush border atrophy, vesicle transport stagnation (increased subapical Rab11 and VAMP8), mislocalization of transporters (NaPi-IIa, SGLT2, rBAT, megalin), and disrupted apical ezrin expression are observed. Both receptor-mediated and fluid-phase endocytosis are impaired.\",\n      \"method\": \"PTEC-specific Stx3 conditional knockout mice; electron microscopy; immunofluorescence localization; urine biochemistry; endocytosis assays; MVID patient urine analysis\",\n      \"journal\": \"Kidney international\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with multiple orthogonal readouts (EM, immunofluorescence, urine biochemistry, endocytosis), validated in human patient samples\",\n      \"pmids\": [\"41033460\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"STX3 in hippocampal CA1 neurons is required for neural responses to novelty and for forming stable representations of rewarded locations, but dispensable for context and spatial representations inherited from upstream regions. CA1-specific Stx3 deletion combined with in vivo Ca2+ imaging demonstrates STX3's role in postsynaptic membrane fusion-dependent synaptic plasticity.\",\n      \"method\": \"CA1-specific Stx3 conditional knockout; in vivo population calcium imaging; novel environment and reward location behavioral paradigms\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with in vivo population imaging, defined behavioral phenotype distinguishing STX3-dependent vs independent computations\",\n      \"pmids\": [\"41932328\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ZNRF1 E3 ligase activity is required for STX3-Munc18-2 (Stxbp2) interaction in macrophages; ZNRF1 deficiency weakens this interaction, preventing FasL from reaching the macrophage surface despite normal lysosome-related organelle polarization. Stxbp2 knockdown reduces surface FasL; wild-type but not catalytically inactive ZNRF1 restores surface FasL, establishing a ZNRF1-Munc18-2-STX3 axis for FasL exocytosis.\",\n      \"method\": \"Myeloid-specific Znrf1 KO mice; Co-IP of Munc18-2-STX3; Stxbp2 knockdown; ZNRF1 rescue with catalytic mutant; surface FasL measurement; confocal imaging of LAMP1 organelles\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO mice with Co-IP and rescue experiments, functional FasL secretion readout, single lab\",\n      \"pmids\": [\"41896526\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Tomosyn-1 (STXBP5) acts as an inhibitor of mast cell degranulation; after FcεRI activation, PKCδ-dependent phosphorylation of tomosyn-1 causes it to dissociate from STX4 and associate with STX3, regulating the switch in STX partners during membrane fusion.\",\n      \"method\": \"Co-IP of tomosyn-1 with STX3 and STX4; PKCδ inhibitor experiments; phosphorylation mapping; degranulation assays\",\n      \"journal\": \"Science signaling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP demonstrating STX4→STX3 switch, PKCδ kinase identified, single lab\",\n      \"pmids\": [\"29970602\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Co-expression of STX3 with rat ENaC in Xenopus oocytes increases amiloride-sensitive whole-cell currents by ~50%, associated with increased ENaC surface expression. The stimulatory effect of STX3 on rENaC is independent of Rab11-mediated recycling endosome fusion and is not mediated by inhibiting channel retrieval.\",\n      \"method\": \"Xenopus oocyte expression system; electrophysiology (amiloride-sensitive current); FLAG-tagged ENaC surface expression assay; brefeldin A and dominant-negative Rab11 experiments\",\n      \"journal\": \"Pflugers Archiv : European journal of physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — heterologous expression system with electrophysiology and surface expression assay, pharmacological dissection, single lab\",\n      \"pmids\": [\"32221667\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"STX3 is a plasma membrane-localized SNARE protein that mediates selective apical vesicle-plasma membrane fusion in polarized epithelial cells (acting downstream of Rab11/Myo5B/Slp4a/Munc18-2/VAMP7), is directly activated by omega-3/6 fatty acids to promote membrane expansion at neuronal growth cones, undergoes monoubiquitination to control its endocytosis and exosomal cargo sorting, generates a soluble nuclear-targeted splice isoform (Stx3S) that regulates transcription, mediates compound exocytosis in mast cells, controls OS membrane protein trafficking in photoreceptors (interacting with PRPH2/ROM1/rhodopsin in a STXBP1/arrestin-4 light-regulated complex), supports postsynaptic membrane fusion-dependent synaptic plasticity in hippocampal CA1 neurons, and is regulated by phosphorylation (CaMKII-dependent T14 phosphorylation in retinal ribbon synapses) and by upstream factors including ezrin-PKA signaling and the ZNRF1-Munc18-2 axis; loss-of-function mutations cause variant microvillus inclusion disease and Fanconi syndrome-like renal tubular dysfunction.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"STX3 is an apical/plasma-membrane t-SNARE that mediates selective vesicle–membrane fusion across diverse polarized secretory and trafficking contexts [#2, #3]. In epithelia it functions as the terminal apical t-SNARE of a Rab11→Myo5B→Slp4a→Munc18-2→Vamp7 cascade that delivers specific cargo (NHE3, CFTR, GLUT5) to the brush border, while bulk brush-border enzymes traffic independently [#2, #18]; loss-of-function STX3 mutations cause variant microvillus inclusion disease, and tubule-specific deletion produces Fanconi-syndrome-like renal dysfunction with transporter mislocalization and impaired endocytosis [#1, #35]. Its fusogenic activity is gated by Munc18 proteins that bind both the N-terminal peptide and the closed Habc–H3 conformation of STX3 and partner switching among VAMP and SNAP isoforms, supporting regulated secretion in mast cells (compound exocytosis), endothelial Weibel-Palade body/VWF release, and AQP2 insertion in collecting-duct cells [#6, #3, #8, #9]. STX3 is directly activated by omega-3/omega-6 fatty acids to drive growth-cone membrane expansion and neurite outgrowth [#0], and supports postsynaptic, fusion-dependent synaptic plasticity in hippocampal CA1 neurons required for novelty responses and reward-location coding [#36]. In photoreceptors STX3 confines outer-segment membrane proteins (PRPH2, ROM1, rhodopsin) and forms a light-regulated complex with STXBP1 and arrestin-4 at the connecting cilium [#10, #34]. STX3 activity is further controlled by monoubiquitination directing endocytosis and exosomal sorting [#7], CaMKII-dependent T14 phosphorylation in retinal ribbon synapses [#28], and ezrin–PKA signaling [#11]; an alternatively spliced soluble isoform (Stx3S) enters the nucleus via RanBP5 and regulates transcription through ETV4 and ATF2 [#12].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established the first direct biochemical effector role for STX3, showing it is activated by fatty acids to drive membrane expansion rather than acting only as a passive SNARE scaffold.\",\n      \"evidence\": \"In vitro binding/activation assay with arachidonic, linolenic and docosahexaenoic acids coupled to neurite outgrowth readout\",\n      \"pmids\": [\"16598260\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of fatty-acid activation not resolved\", \"Whether this regulation operates in non-neuronal STX3 contexts untested\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Defined STX3 as an apical SNARE for regulated membrane insertion, identifying its core SNARE partners and a Munc18b regulatory brake.\",\n      \"evidence\": \"Co-IP and siRNA knockdown with apical surface biotinylation of AQP2 in renal collecting-duct cells\",\n      \"pmids\": [\"18505797\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct fusion reconstitution not performed\", \"Quantitative SNARE stoichiometry undefined\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Resolved how Munc18b engages STX3, mapping interaction to both N-peptide and closed Habc–H3 conformation and linking Munc18b levels to exocytosis output.\",\n      \"evidence\": \"In vitro pull-downs with STX3 domain mutagenesis and constitutive exocytosis assays\",\n      \"pmids\": [\"20695848\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Order of N-peptide vs closed-conformation binding during fusion cycle unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected STX3 to human disease, demonstrating that truncating mutations cause variant MVID through failed apical vesicle fusion in enterocytes.\",\n      \"evidence\": \"Whole-exome sequencing of patients, patient organoids, and truncated-STX3 overexpression in Caco-2\",\n      \"pmids\": [\"24726755\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genotype–phenotype range across mutation types not fully mapped\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed STX3 as the terminal t-SNARE of a defined cargo-selective apical trafficking cascade, explaining cargo specificity in epithelial polarity.\",\n      \"evidence\": \"CRISPR Myo5B mutant epithelial cells, Co-IP of the Rab11→Myo5B→Slp4a→Munc18-2→Vamp7→STX3 chain, and cargo trafficking assays\",\n      \"pmids\": [\"26553929\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How cargo identity is read out at the SNARE step unknown\", \"Whether the cascade is universal across epithelial cargo classes untested\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Showed that post-translational monoubiquitination routes STX3 itself into the endocytic/exosomal pathway and controls cargo entry into exosomes.\",\n      \"evidence\": \"Ubiquitination site mapping, live-cell endocytosis tracking, and dominant-negative STX3-5R analysis in polarized MDCK cells\",\n      \"pmids\": [\"28814500\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The ubiquitin ligase responsible not identified\", \"Physiological triggers of STX3 ubiquitination unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Revealed a non-canonical nuclear function, identifying a soluble splice isoform that regulates transcription independent of membrane fusion.\",\n      \"evidence\": \"Splice isoform identification, Co-IP of Stx3S with RanBP5/ETV4/ATF2, and knockdown with transcriptional/proliferation readouts\",\n      \"pmids\": [\"29475951\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct DNA-binding vs cofactor role of Stx3S unresolved\", \"Signals controlling the splicing switch unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended STX3's secretory role to endothelial hemostasis, showing it is required for VWF release from Weibel-Palade bodies.\",\n      \"evidence\": \"Patient-derived STX3-/- BOECs, VWF secretion assays, and Co-IP of STX3 with VAMP8\",\n      \"pmids\": [\"29880488\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Regulatory inputs for Ca2+ vs cAMP-driven WPB fusion via STX3 not dissected\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Distinguished STX3's specific contribution to compound (multigranular) exocytosis from single-vesicle fusion in vivo.\",\n      \"evidence\": \"Conditional Stx3 knockout mice with electrophysiology, EM, and in vivo anaphylaxis\",\n      \"pmids\": [\"30563839\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis for compound vs single-vesicle selectivity unknown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Established STX3 as essential for photoreceptor outer-segment protein delivery and survival, with direct binding to PRPH2.\",\n      \"evidence\": \"Photoreceptor-specific Stx3 knockout mice, immunofluorescence mislocalization, and Co-IP of PRPH2 C-terminus with STX3\",\n      \"pmids\": [\"32778589\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether STX3 mediates fusion vs sorting at the connecting cilium unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Linked STX3 fusion activity to activity-dependent kinase regulation in ribbon synapses via CaMKII phosphorylation.\",\n      \"evidence\": \"Light/dark phosphorylation quantification, CaMKII inhibitor experiments, and membrane capacitance recordings\",\n      \"pmids\": [\"33192329\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Functional consequence of T14 phosphorylation on SNARE assembly not directly measured\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Characterized the ubiquitin-binding selectivity of STX3's Habc domain, providing a biochemical basis for ubiquitin-dependent regulation.\",\n      \"evidence\": \"In vitro ubiquitin-binding assays and molecular modeling\",\n      \"pmids\": [\"33288783\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No cellular functional consequence tested\", \"Single lab in vitro only\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined a renal physiological role, showing tubule STX3 maintains brush-border transport and endocytosis, with loss causing Fanconi-like syndrome.\",\n      \"evidence\": \"PTEC-specific Stx3 knockout mice with EM, transporter localization, urine biochemistry, endocytosis assays, and MVID patient urine\",\n      \"pmids\": [\"41033460\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether renal phenotype reflects the same cargo cascade as gut not directly tested\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrated a postsynaptic, plasticity-related role for STX3 in defined hippocampal circuit computations.\",\n      \"evidence\": \"CA1-specific Stx3 conditional knockout with in vivo calcium imaging and behavioral paradigms\",\n      \"pmids\": [\"41932328\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular SNARE partners at the postsynaptic membrane not identified\", \"Link to AMPA-receptor trafficking not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single t-SNARE achieves its broad context-specific cargo and tissue selectivity—and how its regulatory layers (ubiquitination, phosphorylation, splicing, partner switching) are integrated in vivo—remains unresolved.\",\n      \"evidence\": \"No single study reconciles the regulatory and tissue-specific mechanisms\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unifying model of cargo selection at the STX3 fusion step\", \"Crosstalk among regulatory modifications uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [2, 3, 6, 8]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2, 3, 7, 8]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [34]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [12]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [4, 8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [2, 3, 7, 8, 18]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [2, 18, 35]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [9, 14, 16, 37]}\n    ],\n    \"complexes\": [\n      \"STX3/SNAP-23/VAMP8 SNARE complex\",\n      \"STX3/STXBP1/arrestin-4 light-regulated complex\",\n      \"STX3/STX4/VTI1B/STX8/SEC22B secretory autolysosome SNARE complex\"\n    ],\n    \"partners\": [\n      \"STXBP2\",\n      \"VAMP8\",\n      \"SNAP23\",\n      \"PRPH2\",\n      \"STXBP1\",\n      \"SEC22B\",\n      \"EZR\",\n      \"STXBP5\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}