Affinage

STX3

Syntaxin-3 · UniProt Q13277

Length
289 aa
Mass
33.2 kDa
Annotated
2026-06-10
95 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 High

    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

    PMID:16598260

    Open questions at the time
    • Structural basis of fatty-acid activation not resolved
    • Whether this regulation operates in non-neuronal STX3 contexts untested
  2. 2008 High

    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

    PMID:18505797

    Open questions at the time
    • Direct fusion reconstitution not performed
    • Quantitative SNARE stoichiometry undefined
  3. 2010 High

    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

    PMID:20695848

    Open questions at the time
    • Order of N-peptide vs closed-conformation binding during fusion cycle unclear
  4. 2014 High

    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

    PMID:24726755

    Open questions at the time
    • Genotype–phenotype range across mutation types not fully mapped
  5. 2015 High

    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

    PMID:26553929

    Open questions at the time
    • How cargo identity is read out at the SNARE step unknown
    • Whether the cascade is universal across epithelial cargo classes untested
  6. 2017 High

    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

    PMID:28814500

    Open questions at the time
    • The ubiquitin ligase responsible not identified
    • Physiological triggers of STX3 ubiquitination unknown
  7. 2018 High

    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

    PMID:29475951

    Open questions at the time
    • Direct DNA-binding vs cofactor role of Stx3S unresolved
    • Signals controlling the splicing switch unknown
  8. 2018 High

    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

    PMID:29880488

    Open questions at the time
    • Regulatory inputs for Ca2+ vs cAMP-driven WPB fusion via STX3 not dissected
  9. 2018 High

    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

    PMID:30563839

    Open questions at the time
    • Molecular basis for compound vs single-vesicle selectivity unknown
  10. 2020 High

    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

    PMID:32778589

    Open questions at the time
    • Whether STX3 mediates fusion vs sorting at the connecting cilium unresolved
  11. 2020 Medium

    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

    PMID:33192329

    Open questions at the time
    • Single lab
    • Functional consequence of T14 phosphorylation on SNARE assembly not directly measured
  12. 2021 Medium

    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

    PMID:33288783

    Open questions at the time
    • No cellular functional consequence tested
    • Single lab in vitro only
  13. 2025 High

    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

    PMID:41033460

    Open questions at the time
    • Whether renal phenotype reflects the same cargo cascade as gut not directly tested
  14. 2026 High

    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

    PMID:41932328

    Open questions at the time
    • Molecular SNARE partners at the postsynaptic membrane not identified
    • Link to AMPA-receptor trafficking not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • No unifying model of cargo selection at the STX3 fusion step
  • Crosstalk among regulatory modifications uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1 GO:0005768 endosome 1 GO:0005929 cilium 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 3
Partners
EZRPRPH2SEC22BSNAP23STXBP1STXBP2STXBP5VAMP8
Complex memberships
STX3/SNAP-23/VAMP8 SNARE complexSTX3/STX4/VTI1B/STX8/SEC22B secretory autolysosome SNARE complexSTX3/STXBP1/arrestin-4 light-regulated complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 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. In vitro screening assay using STX3 as target protein; direct binding/activation assay with fatty acids; neurite outgrowth functional readout Nature High 16598260
2014 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. Whole-exome sequencing of MVID patients; patient-derived organoid cultures; overexpression of truncated STX3 in Caco-2 cells Gastroenterology High 24726755
2015 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. Genome editing (CRISPR) to introduce Myo5B patient mutation in human epithelial cell line; Co-IP interaction studies; cargo trafficking assays The Journal of cell biology High 26553929
2008 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. Co-immunoprecipitation; protein knockdown (siRNA); apical surface biotinylation to measure AQP2 fusion Journal of cell science High 18505797
2013 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. siRNA knockdown; immunogold electron microscopy; co-immunoprecipitation; degranulation functional assays Journal of immunology High 24323579
2013 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. Crystal structure of Munc18-2 at 2.6 Å resolution; binding affinity measurements; mapping of disease-causing mutations to structure Proceedings of the National Academy of Sciences of the United States of America High 24194549
2010 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. In vitro binding/pull-down assays; mutagenesis of STX3 domains; constitutive exocytosis assay in mammalian cells The Biochemical journal High 20695848
2017 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. Monoubiquitination site mapping; live-cell antibody feeding endocytosis tracking in polarized MDCK cells; dominant-negative mutant analysis; HCMV virion excretion assay Molecular biology of the cell High 28814500
2018 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. Immunolocalization in human umbilical vein endothelial cells and patient-derived STX3-/- BOECs; VWF secretion assays; Co-IP of STX3 with VAMP8; ultrastructural analysis Arteriosclerosis, thrombosis, and vascular biology High 29880488
2018 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. Conditional knockout mice; electrophysiology; electron microscopy; passive systemic anaphylaxis in vivo model The Journal of biological chemistry High 30563839
2020 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. Photoreceptor-specific Stx3 conditional knockout mice; immunofluorescence localization; co-immunoprecipitation (PRPH2 C-terminal domain with STX3) Proceedings of the National Academy of Sciences of the United States of America High 32778589
2014 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. Co-immunoprecipitation; atomic force microscopy showing phosphorylation-induced ezrin unfolding; pharmacological inhibition of PKA; apical plasma membrane insertion assay The Journal of biological chemistry High 25301939
2018 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. 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 The Journal of biological chemistry High 29475951
2011 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. RNAi knockdown; immunogold labeling; RNAi-resistant construct rescue; ultrastructural analysis of assembly site Cellular microbiology Medium 21371234
2011 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. Blocking antibodies/siRNA inhibition of specific SNARE isoforms; chemokine release assay by ELISA following IgE receptor cross-linking Molecular immunology Medium 21981832
2014 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. siRNA knockdown; cytokine secretion profiling (CBA); MMP-9 exocytosis assay; subcellular localization by microscopy Journal of leukocyte biology Medium 25548252
2015 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. SNARE mRNA profiling; RNAi knockdown; IL-6 ELISA; confocal microscopy of STX3 subcellular translocation Frontiers in immunology Medium 25674084
2015 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. Immunofluorescence of patient biopsies; MYO5B depletion in 3D Caco-2 cyst model; electron microscopy Biology of the cell Medium 26526116
2017 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. CRISPR/Cas9-generated Munc18-2 KO CaCo2 cells; Co-IP of Slp4a/STX3; cargo trafficking assays in patient biopsies, organoids, and genome-edited cells JCI insight High 28724787
2018 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. Co-immunoprecipitation of STX3 with PTEN; ubiquitination assay; lentiviral knockdown and overexpression; in vitro and in vivo tumor growth assays Biochimica et biophysica acta. Molecular basis of disease Medium 29408595
2012 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. Immunofluorescence localization; Western blotting; Co-IP for SNARE complex formation Journal of autoimmunity Medium 22285554
2015 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. Co-immunoprecipitation (SERT-STX3); surface biotinylation; brefeldin A inhibition; PI3K inhibitor; ex vivo Ussing chamber 5-HT uptake PloS one Medium 25954931
2020 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. STX2-KO mice; live-cell exocytosis and Ca2+ imaging; SNARE complex formation assays by Co-IP; human pancreatic tissue analysis Gastroenterology Medium 29360461
2020 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. In vitro ubiquitin-binding assays; molecular modeling Scientific reports Medium 33288783
2015 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. Isolated OS proteomics; quantitative proteomics (>3-fold enrichment); immunofluorescence; ultrastructural analysis in BBS mouse models Proceedings of the National Academy of Sciences of the United States of America Medium 26216965
2019 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. Conditional Cep290 mutant mice; immunofluorescence localization of STX3 and other membrane proteins; comparison with endomembrane protein localization The Journal of biological chemistry Medium 31694913
2020 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. Identification of Sec22b ubiquitination upon Legionella infection; LotB DUB activity assays; Co-IP of STX3-Sec22b; T4SS-dependent experiments Cell reports Medium 32905772
2021 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. Co-immunoprecipitation; immunocytochemistry; serotonin uptake assay; STX3 knockdown (siRNA); glycosylation state analysis Journal of pharmacological sciences Medium 33712280
2020 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. 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 Frontiers in cellular neuroscience Medium 33192329
2022 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. Hippocampal neuron culture with site-directed mutagenesis of STX1A and chimeric STX3A constructs; electrophysiology (mEPSC recording) eLife Medium 35638903
2023 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. Ubiquitin E3 ligase assay for Lug15; ubiquitination of Sec22b; Co-IP of Sec22b with STX3; LCV remodeling analysis mBio Medium 37882795
2025 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. siRNA knockdown of STX3 and SNARE components; PARK7 secretion assay; autophagy flux analysis Proceedings of the National Academy of Sciences of the United States of America Medium 40327696
2023 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. 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 Traffic Medium 37114883
2023 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. siRNA knockdown of specific trafficking components; sFLT1 secretion assay; live imaging of temporally controlled sFLT1 release Angiogenesis Medium 37695358
2025 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. Cone-specific and rod-specific Stx3 conditional knockout mice; Co-IP of STX3-STXBP1-arrestin 4 complex; functional ERG analysis Advanced science Medium 41220299
2025 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. PTEC-specific Stx3 conditional knockout mice; electron microscopy; immunofluorescence localization; urine biochemistry; endocytosis assays; MVID patient urine analysis Kidney international High 41033460
2026 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. CA1-specific Stx3 conditional knockout; in vivo population calcium imaging; novel environment and reward location behavioral paradigms Neuron High 41932328
2026 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. 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 Cell death & disease Medium 41896526
2018 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. Co-IP of tomosyn-1 with STX3 and STX4; PKCδ inhibitor experiments; phosphorylation mapping; degranulation assays Science signaling Medium 29970602
2020 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. Xenopus oocyte expression system; electrophysiology (amiloride-sensitive current); FLAG-tagged ENaC surface expression assay; brefeldin A and dominant-negative Rab11 experiments Pflugers Archiv : European journal of physiology Medium 32221667

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3. Nature 266 16598260
2014 Loss of syntaxin 3 causes variant microvillus inclusion disease. Gastroenterology 134 24726755
2015 Accumulation of non-outer segment proteins in the outer segment underlies photoreceptor degeneration in Bardet-Biedl syndrome. Proceedings of the National Academy of Sciences of the United States of America 117 26216965
2014 Decreased miR-146 expression in peripheral blood mononuclear cells is correlated with ongoing islet autoimmunity in type 1 diabetes patients 1miR-146. Journal of diabetes 95 24796653
2008 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. European journal of immunology 85 18253931
2021 circMRPS35 promotes malignant progression and cisplatin resistance in hepatocellular carcinoma. Molecular therapy : the journal of the American Society of Gene Therapy 84 34450251
2015 Cargo-selective apical exocytosis in epithelial cells is conducted by Myo5B, Slp4a, Vamp7, and Syntaxin 3. The Journal of cell biology 83 26553929
2013 Syntaxin binding mechanism and disease-causing mutations in Munc18-2. Proceedings of the National Academy of Sciences of the United States of America 61 24194549
2019 Inflammatory, regulatory, and autophagy co-expression modules and hub genes underlie the peripheral immune response to human intracerebral hemorrhage. Journal of neuroinflammation 60 30836997
2018 MYO5B, STX3, and STXBP2 mutations reveal a common disease mechanism that unifies a subset of congenital diarrheal disorders: A mutation update. Human mutation 51 29266534
2013 Munc18-2 and syntaxin 3 control distinct essential steps in mast cell degranulation. Journal of immunology (Baltimore, Md. : 1950) 49 24323579
2011 SNAP-23 and syntaxin-3 are required for chemokine release by mature human mast cells. Molecular immunology 48 21981832
2018 Pancreatitis-Induced Depletion of Syntaxin 2 Promotes Autophagy and Increases Basolateral Exocytosis. Gastroenterology 47 29360461
2012 Aberrant localization of fusion receptors involved in regulated exocytosis in salivary glands of Sjögren's syndrome patients is linked to ectopic mucin secretion. Journal of autoimmunity 46 22285554
2017 Disrupted apical exocytosis of cargo vesicles causes enteropathy in FHL5 patients with Munc18-2 mutations. JCI insight 45 28724787
2017 Abnormal Rab11-Rab8-vesicles cluster in enterocytes of patients with microvillus inclusion disease. Traffic (Copenhagen, Denmark) 44 28407399
2008 AQP2 exocytosis in the renal collecting duct -- involvement of SNARE isoforms and the regulatory role of Munc18b. Journal of cell science 44 18505797
2020 Molecular Correlates of Hemorrhage and Edema Volumes Following Human Intracerebral Hemorrhage Implicate Inflammation, Autophagy, mRNA Splicing, and T Cell Receptor Signaling. Translational stroke research 36 33206327
2020 Syntaxin 3 is essential for photoreceptor outer segment protein trafficking and survival. Proceedings of the National Academy of Sciences of the United States of America 35 32778589
2018 Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells. Arteriosclerosis, thrombosis, and vascular biology 35 29880488
2006 Splenic endothelial cell lines support development of dendritic cells from bone marrow. Stem cells (Dayton, Ohio) 33 16769761
2004 Molecular definition of an in vitro niche for dendritic cell development. Experimental hematology 33 15588943
2020 Acrylamide alters CREB and retinoic acid signalling pathways during differentiation of the human neuroblastoma SH-SY5Y cell line. Scientific reports 32 33028897
2019 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. Frontiers in immunology 32 31824480
2023 Beyond the exome: utility of long-read whole genome sequencing in exome-negative autosomal recessive diseases. Genome medicine 31 38098057
2022 Syntaxin-1A modulates vesicle fusion in mammalian neurons via juxtamembrane domain dependent palmitoylation of its transmembrane domain. eLife 31 35638903
2022 Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G. JCI insight 30 35862195
2018 STX3 represses the stability of the tumor suppressor PTEN to activate the PI3K-Akt-mTOR signaling and promotes the growth of breast cancer cells. Biochimica et biophysica acta. Molecular basis of disease 30 29408595
2018 Syntaxin 3, but not syntaxin 4, is required for mast cell-regulated exocytosis, where it plays a primary role mediating compound exocytosis. The Journal of biological chemistry 30 30563839
2017 Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes. Molecular biology of the cell 30 28814500
2011 The cystic fibrosis transmembrane conductance regulator's expanding SNARE interactome. Traffic (Copenhagen, Denmark) 29 21223469
2020 Legionella Manipulates Non-canonical SNARE Pairing Using a Bacterial Deubiquitinase. Cell reports 28 32905772
2015 The localisation of the apical Par/Cdc42 polarity module is specifically affected in microvillus inclusion disease. Biology of the cell 28 26526116
2014 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. Journal of leukocyte biology 28 25548252
2011 A role for the SNARE protein syntaxin 3 in human cytomegalovirus morphogenesis. Cellular microbiology 28 21371234
2020 SNAREs and developmental disorders. Journal of cellular physiology 26 32959907
2018 Dynamic Formation of Microvillus Inclusions During Enterocyte Differentiation in Munc18-2-Deficient Intestinal Organoids. Cellular and molecular gastroenterology and hepatology 23 30364784
2016 Towards understanding microvillus inclusion disease. Molecular and cellular pediatrics 23 26830108
2015 A role for syntaxin 3 in the secretion of IL-6 from dendritic cells following activation of toll-like receptors. Frontiers in immunology 23 25674084
2019 The myosin-tail homology domain of centrosomal protein 290 is essential for protein confinement between the inner and outer segments in photoreceptors. The Journal of biological chemistry 20 31694913
2014 Spatial control of proton pump H,K-ATPase docking at the apical membrane by phosphorylation-coupled ezrin-syntaxin 3 interaction. The Journal of biological chemistry 20 25301939
2015 Mechanisms of Intestinal Serotonin Transporter (SERT) Upregulation by TGF-β1 Induced Non-Smad Pathways. PloS one 19 25954931
2013 Syntaxin-4 is implicated in the secretion of antibodies by human plasma cells. Journal of leukocyte biology 18 24146186
2015 Human cytomegalovirus miR-US33-5p inhibits viral DNA synthesis and viral replication by down-regulating expression of the host Syntaxin3. FEBS letters 17 25583387
2018 Soluble syntaxin 3 functions as a transcriptional regulator. The Journal of biological chemistry 16 29475951
2018 Tomosyn functions as a PKCδ-regulated fusion clamp in mast cell degranulation. Science signaling 16 29970602
2021 Differential requirement of NPHP1 for compartmentalized protein localization during photoreceptor outer segment development and maintenance. PloS one 15 33961633
2018 Syntaxin clusters at secretory granules in a munc18-bound conformation. Molecular biology of the cell 14 30156474
2014 Autosomal recessive congenital cataract, intellectual disability phenotype linked to STX3 in a consanguineous Tunisian family. Clinical genetics 14 25358429
2006 Heterogeneity amongst splenic stromal cell lines which support dendritic cell hematopoiesis. In vitro cellular & developmental biology. Animal 14 16948502
2021 Genetic Enteropathies Linked to Epithelial Structural Abnormalities and Enteroendocrine Deficiency: A Systematic Review. Journal of pediatric gastroenterology and nutrition 13 33976085
2020 Phosphorylation of the Retinal Ribbon Synapse Specific t-SNARE Protein Syntaxin3B Is Regulated by Light via a Ca2 +-Dependent Pathway. Frontiers in cellular neuroscience 13 33192329
2019 Microvillus inclusion disease, a diagnosis to consider when abnormal stools and neurological impairments run together due to a rare syntaxin 3 gene mutation. Journal of neonatal-perinatal medicine 13 30909251
2007 Molecular cloning, expression and characterization of protein disulfide isomerase from Conus marmoreus. The FEBS journal 13 17697113
2017 Microvillus Inclusion Disease Variant in an Infant with Intractable Diarrhea. Case reports in gastroenterology 12 29282386
2010 Munc18b regulates core SNARE complex assembly and constitutive exocytosis by interacting with the N-peptide and the closed-conformation C-terminus of syntaxin 3. The Biochemical journal 12 20695848
2008 Gene signature of stromal cells which support dendritic cell development. Stem cells and development 12 18564035
2022 Congenital enteropathies involving defects in enterocyte structure or differentiation. Best practice & research. Clinical gastroenterology 11 35331396
2023 Ubiquitination of Sec22b by a novel Legionella pneumophila ubiquitin E3 ligase. mBio 9 37882795
2014 Spleen stroma maintains progenitors and supports long-term hematopoiesis. Current stem cell research & therapy 9 24745998
2012 Myelopoiesis in spleen-producing distinct dendritic-like cells. Journal of cellular and molecular medicine 9 22117595
2025 Unconventional secretion of PARK7 requires lysosomal delivery via chaperone-mediated autophagy and specialized SNARE complex. Proceedings of the National Academy of Sciences of the United States of America 8 40327696
2023 A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells. Angiogenesis 8 37695358
2024 Modeling the cell biology of monogenetic intestinal epithelial disorders. The Journal of cell biology 7 38683247
2023 Syntaxin 3 SPI-2 dependent crosstalk facilitates the division of Salmonella containing vacuole. Traffic (Copenhagen, Denmark) 7 37114883
2017 [Clinical features and MYO5B mutations of a family affected by microvillus inclusion disease]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 6 28899465
2007 Hematopoiesis of immature myeloid dendritic cells in stroma-dependent spleen long-term cultures occurs independently of NF-KB/RelB function. Experimental hematology 6 17889723
2024 Uncovering the Relationship Between Genes and Phenotypes Beyond the Gut in Microvillus Inclusion Disease. Cellular and molecular gastroenterology and hepatology 5 38307491
2021 Syntaxin 3 interacts with serotonin transporter and regulates its function. Journal of pharmacological sciences 5 33712280
2024 SKArred 2 death: neuroinflammatory breakdown of the hippocampus. Autophagy 4 38934263
2020 The Habc domain of syntaxin 3 is a ubiquitin binding domain. Scientific reports 4 33288783
2023 Neuronal RBM5 modulates cell signaling responses to traumatic and hypoxic-ischemic injury in a sex-dependent manner. Cell death discovery 3 37848418
2022 Lnc-AC145676.2.1-6-3 can influence STX3-induced abnormal autophagy by sponging hsa-miR-1292-3p in intestinal aGVHD. European review for medical and pharmacological sciences 3 35113433
2022 Identification of Common Hub Genes in Human Dermal Fibroblasts Stimulated by Mechanical Stretch at Both the Early and Late Stages. Frontiers in surgery 3 35510126
2021 Risk and Clinical Significance of Idiopathic Preterm Birth in Microvillus Inclusion Disease. Journal of clinical medicine 3 34501384
2020 Effects of syntaxins 2, 3, and 4 on rat and human epithelial sodium channel (ENaC) in Xenopus laevis oocytes. Pflugers Archiv : European journal of physiology 3 32221667
2012 Distinct In Vitro Myelopoiesis is Dependent on the Self-Renewal of Hematopoietic Progenitors. Scandinavian journal of immunology 3 21958239
2024 Systematic review of phenotypes and genotypes of patients with gastrointestinal defects and immunodeficiency syndrome-1 (GIDID1) (related to TTC7A). Intractable & rare diseases research 2 38836179
2020 Microvillus Inclusion Disease: A Rare Mutation of STX3 in Exon 9 Causing Fatal Congenital Diarrheal Disease. Journal of pediatric genetics 2 35769957
2007 Use of gene profiling to describe a niche for dendritic cell development. Immunology and cell biology 2 17533411
2026 Hippocampal place code plasticity in CA1 requires postsynaptic membrane fusion. Neuron 1 41932328
2025 Bioinformatics-led identification of pathophysiological hallmark genes in diabesotension via graph clustering method. Journal of diabetes and metabolic disorders 1 40491693
2025 Syntaxin 3B Mediates Light-Dependent Interactions with STXBP1 and Arrestin 4: Distinct Roles in Rods and Cones. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41220299
2024 Syntaxin 3B: A SNARE Protein Required for Vision. International journal of molecular sciences 1 39408994
2023 A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells. bioRxiv : the preprint server for biology 1 36747809
2023 Syntaxin 3 is haplosufficient for long-term photoreceptor survival in the mouse retina. Frontiers in ophthalmology 1 37609371
2018 Tracking Endocytosis and Intracellular Trafficking of Epitope-tagged Syntaxin 3 by Antibody Feeding in Live, Polarized MDCK Cells. Bio-protocol 1 29564371
2014 Effect of mutation on aggregation propensity in homology model structures of syntaxin-3 from Homo sapiens. Indian journal of biochemistry & biophysics 1 25630102
2026 Integrated genomic and proteomic profiling reveals insights into chemoradiation resistance in cervical cancer. Molecular oncology 0 41586744
2026 High Mobility Group Protein B1 and its downstream elements, syntaxins, contribute to temporal tight junction assembly in a human keratinocyte cell line. Experimental cell research 0 41638388
2026 miR-3913-3p promoted the progression of lung adenocarcinoma by regulating STX3 expression. Hereditas 0 41776690
2026 ZNRF1 deficiency disrupts Fas ligand trafficking and immune balance. Cell death & disease 0 41896526
2025 Syntaxin 3 regulates apical membrane integrity in proximal tubule epithelial cells and prevents Fanconi syndrome development. Kidney international 0 41033460
2025 TGF-β2 increases eHSP90α secretion via upregulating secretory autophagy pathway. Cell communication and signaling : CCS 0 41225541
2025 Organoid-derived photoreceptor precursors enriched by CD9⁻CD81mid sorting restore visual function in RCS rats. Stem cell research & therapy 0 41354961

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