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Showing STX1A — STX1 is a alias.

STX1A

Syntaxin-1A · UniProt Q16623

Length
288 aa
Mass
33.0 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STX1A (HPC-1/syntaxin 1A) is a membrane-anchored t-SNARE that governs regulated exocytosis at neuronal and neuroendocrine membranes, where it nucleates the core SNARE machinery together with SNAP-25/SNAP23 and VAMP2 (PMID:41123944). It localizes to the cytoplasmic face of presynaptic plasma membranes and synaptic vesicles, and is also found on dense-core secretory granules including chromaffin granules and insulin granules (PMID:8301329, PMID:7608144, PMID:8557645). Its C-terminal hydrophobic tail anchors the protein, directing trafficking from the ER to the plasma membrane via the exocytic pathway, and this membrane association is required for cleavage and inactivation by botulinum neurotoxin C1, a zinc-dependent metallo-endoprotease that thereby blocks transmitter release (PMID:7901002, PMID:9685720, PMID:12761168). STX1A interacts with the synaptic-vesicle release apparatus, assembling into a ternary complex with synaptotagmin and the N-type calcium channel (PMID:1334074), and its function is gated by Munc18-1 (STXBP1), which uses its central cavity both to chaperone monomeric STX1A and to activate SNARE-mediated membrane fusion (PMID:21900493). Genetic ablation in mice produces specific deficits in synaptic plasticity—impaired hippocampal LTP and fear memory—that trace to reduced dense-core-vesicle release of catecholamines and consequent loss of cAMP/PKA neuromodulation, and to reduced dopamine-induced oxytocin release underlying social behavior (PMID:16723534, PMID:22219298, PMID:27059771). Paradoxically, in several secretory systems STX1A acts as a brake on exocytosis: its overexpression suppresses stimulated insulin secretion while reducing its level enhances depolarization-evoked dopamine release and synaptic transmitter output (PMID:8557645, PMID:10101280, PMID:9427341). STX1A additionally binds tubulin and inhibits microtubule polymerization in vitro (PMID:15216893), and mediates lysosomal fusion with the plasma membrane through a SNAP23/SNAP25–VAMP2 SNARE complex that supports lysosomal exocytosis and the clearance of damaged lysosomes (PMID:41123944). Variants in STX1A are linked to autism, intellectual disability, and epilepsy, with a disease-associated R26Q variant reducing Ser14 phosphorylation by casein kinase 2 and STX1A–dopamine-transporter interaction (PMID:25774383).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 Medium

    Establishing how syntaxin 1A is physically coupled to the calcium-sensing release machinery answered where in the exocytic apparatus it acts.

    Evidence Co-immunoprecipitation from solubilized rat brain membranes showing a ternary complex with synaptotagmin and the N-type calcium channel

    PMID:1334074

    Open questions at the time
    • Stoichiometry and direct versus bridged interactions not resolved
    • Functional consequence of the ternary complex on Ca2+-triggered fusion not demonstrated
  2. 1993 High

    Pinpointing how botulinum neurotoxin C1 blocks neurotransmission identified syntaxin 1A as a direct proteolytic substrate and defined a requirement for membrane anchoring.

    Evidence In vitro proteolysis and proteoliposome reconstitution with TM-domain truncation mutants

    PMID:7901002

    Open questions at the time
    • Exact scissile bond/cleavage residues not defined in this entry
    • Link between cleavage and SNARE assembly failure not directly shown
  3. 1993 High

    Defining the subcellular topology of syntaxin 1A established it as a cytoplasmic-facing protein on presynaptic plasma membranes and synaptic vesicles.

    Evidence Cryoimmunogold electron microscopy with membrane-rupture topology validation on synaptosomes

    PMID:8301329

    Open questions at the time
    • Quantitative partitioning between plasma membrane and vesicles not established
    • Did not address non-neuronal localization
  4. 1996 High

    Testing whether syntaxin 1A is positive or negative for regulated secretion revealed a counterintuitive suppressive role in endocrine exocytosis.

    Evidence Overexpression in beta TC3 cells with insulin secretion assays, isoform comparison, and in vitro granule binding

    PMID:8557645 PMID:9070225

    Open questions at the time
    • Molecular basis of suppression (sequestration vs. dominant-negative SNARE) not defined
    • Overexpression may not reflect endogenous stoichiometry
  5. 1997 Medium

    Loss-of-function and dominant-negative perturbations at central synapses confirmed that syntaxin 1A restrains transmitter release rather than simply enabling it.

    Evidence Intracellular antibody dialysis and H3-domain peptide delivery at hippocampal/PC12 synapses with electrophysiological and release readouts

    PMID:10101280 PMID:11420120 PMID:9427341

    Open questions at the time
    • Reconciliation with the obligatory SNARE-fusion role not provided
    • Acute perturbation effects vs. chronic adaptation not separated
  6. 1998 High

    Mapping the membrane-targeting determinant explained how syntaxin 1A reaches the plasma membrane through the secretory pathway.

    Evidence Deletion/chimeric mutants in COS cells with N-glycosylation topology, fractionation, and immunofluorescence; later SCAM topology analysis

    PMID:12761168 PMID:9685720

    Open questions at the time
    • Trafficking machinery directing ER-to-PM transit not identified
    • Regulation of anchoring not addressed
  7. 1999 High

    Characterizing the tubulin interaction revealed a SNARE-independent cytoskeletal activity of syntaxin 1A.

    Evidence Affinity chromatography, peptide competition mapping residues 89-106, cross-linking, and microtubule polymerization assays with binding-site deletion mutant

    PMID:15216893 PMID:9070277

    Open questions at the time
    • In vivo relevance of microtubule inhibition not established
    • Relationship to axonal sprouting suppression not directly tied
  8. 2006 High

    Genetic ablation in mice defined the in vivo phenotype, isolating a specific requirement for STX1A in synaptic plasticity rather than baseline transmission.

    Evidence STX1A knockout mice with hippocampal LTP recordings, fear conditioning, and SNARE immunoblot controls

    PMID:16723534

    Open questions at the time
    • Cellular locus of the plasticity defect not yet identified in this entry
    • Possible developmental compensation by STX1B not excluded
  9. 2011 High

    Dissecting Munc18-1 function clarified how STX1A is chaperoned as a monomer yet permits SNARE-driven fusion downstream.

    Evidence Munc18-1 mutagenesis, liposome fusion reconstitution, binding assays, and neuroendocrine secretion assays

    PMID:21900493

    Open questions at the time
    • Transition from Munc18-bound monomer to assembled SNARE complex in vivo not temporally resolved
    • Role of STX1A phosphorylation in this switch not tested
  10. 2012 High

    Pharmacological epistasis placed STX1A upstream of catecholaminergic neuromodulation, mechanistically explaining the LTP deficit through dense-core-vesicle release.

    Evidence STX1A KO LTP recordings with forskolin and catecholamine rescue plus HPLC catecholamine measurement

    PMID:22219298

    Open questions at the time
    • Whether STX1A acts in the catecholaminergic neurons themselves or postsynaptically not fully resolved
    • Selectivity for dense-core over synaptic-vesicle pools not mechanistically explained
  11. 2015 Medium

    Characterizing a disease variant connected STX1A phosphorylation and a transporter interaction to dopamine handling and behavior.

    Evidence Autism R26Q variant analysis with CK2 Ser14 kinase assay, STX1A/DAT co-IP, DAT reverse-transport assays, and animal models

    PMID:25774383

    Open questions at the time
    • Direct demonstration that Ser14 phosphorylation controls DAT binding under physiological conditions limited
    • Generalizability beyond the single variant unknown
  12. 2016 Medium

    Linking STX1A to oxytocin secretion explained its contribution to social behavior at the neuroendocrine level.

    Evidence STX1A KO with in vivo microdialysis of oxytocin and intracerebroventricular OXT behavioral rescue

    PMID:27059771

    Open questions at the time
    • Direct measurement of STX1A-dependent OXT vesicle fusion not shown
    • Circuit locus of the defect not pinpointed
  13. 2023 Medium

    Identifying SNAP23 as a competitive inhibitor of SNAP25 binding clarified a regulatory node controlling STX1A-dependent insulin exocytosis.

    Evidence SNAP23 gain/loss in INS-1 cells, co-IP with SNAP25/STX1A, domain mapping, and phospho-mutant insulin secretion assays

    PMID:37057886

    Open questions at the time
    • Whether this competition operates in primary beta cells in vivo not shown
    • Kinase responsible for SNAP23 Ser95 phosphorylation not identified
  14. 2025 High

    Discovering lysosomal STX1A extended its t-SNARE role beyond classical secretory vesicles to lysosomal exocytosis and damage clearance.

    Evidence GFP-STX1A overexpression, siRNA knockdown, TIRF imaging, SNARE co-IP, lysosome exocytosis/proteolytic assays, and LLOMe damage assays in HeLa cells

    PMID:41123944

    Open questions at the time
    • Whether lysosomal STX1A function operates in neurons/endocrine cells not tested
    • Regulation switching STX1A between plasma-membrane and lysosomal pools unknown
  15. 2025 Medium

    A reported mitochondrial localization tied STX1A to respiration and ferroptosis-mediated chemoresistance in cancer cells.

    Evidence STX1A knockdown with Seahorse respiration, oxidative stress and ferroptosis assays, and drug-resistance assays in gastric cancer cells

    PMID:40056239

    Open questions at the time
    • Mitochondrial localization is novel and not independently replicated
    • Mechanism by which a t-SNARE influences respiration not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single t-SNARE simultaneously functions as an obligatory fusion component and a suppressor of regulated exocytosis, and what governs its partitioning across plasma membrane, secretory granules, lysosomes, and reported mitochondria, remains unresolved.
  • No unified model reconciling facilitatory SNARE assembly with negative regulation of release
  • Trafficking/regulatory signals directing STX1A to distinct membranes not defined
  • Structural basis of disease-variant effects on STXBP1 binding and SNARE assembly not biochemically validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 3 GO:0005764 lysosome 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-162582 Signal Transduction 2
Partners
DATJNK2SNAP23SNAP25STXBP1SYT1TUBULINVAMP2
Complex memberships
SNARE complex (STX1A–SNAP25/SNAP23–VAMP2)STX1A–synaptotagmin–N-type calcium channel ternary complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Botulinum neurotoxin type C1 inhibits neurotransmitter release by directly cleaving HPC-1/syntaxin 1A via its light chain acting as a zinc-dependent metallo-endoprotease, generating a soluble fragment 2-4 kDa smaller than native protein; cleavage requires membrane association (transmembrane domain) of syntaxin 1A. In vitro proteolysis assay, in vitro translation with/without microsomes, proteoliposome reconstitution The EMBO journal High 7901002
1992 HPC-1/syntaxin 1A (p35) forms a ternary complex with synaptotagmin and the omega-conotoxin-sensitive N-type calcium channel (omega-CgTX receptor) in rat brain, as shown by co-immunoprecipitation with antibodies against each component. Co-immunoprecipitation from solubilized rat brain membranes The Journal of biological chemistry Medium 1334074
1993 HPC-1/syntaxin 1A localizes to the cytoplasmic face of presynaptic plasma membranes and synaptic vesicles in rat cerebellar neurons, as determined by cryoimmunogold electron microscopy; intact synaptosomes are not labeled, but ruptured membranes expose the cytoplasmic epitopes, establishing intracellular topology. Cryoimmunogold electron microscopy, pre-embedding protein A-gold technique on synaptosomes with membrane rupture Journal of neurocytology High 8301329
1995 Syntaxin 1A (HPC-1) is associated with chromaffin granules in adrenal medulla (not exclusively plasma membrane), suggesting it can function as a vesicle-SNARE receptor component in addition to its role as a target-SNARE on the plasma membrane. Subcellular fractionation, immunomorphological analysis of chromaffin cells The Journal of biological chemistry Medium 7608144
1996 Syntaxin 1A overexpression in pancreatic beta TC3 cells specifically suppresses glucose-stimulated and secretagogue-stimulated (PMA, forskolin) insulin release by ~50% via the regulatory exocytosis pathway, without affecting constitutive proinsulin secretion, glucose metabolism, or intracellular Ca2+; in vitro binding assays showed syntaxin 1A binds insulin secretory granules. Transient and stable transfection overexpression, insulin secretion assay, in vitro binding assay, metabolic labeling The Journal of biological chemistry High 8557645
1996 Suppression of HPC-1/syntaxin 1A function by antisense oligonucleotides (in cultured DRG neurons) or intra-axonal antibody injection (in chick retinal ganglion neurons) enhances axonal sprouting, indicating that axonal syntaxin 1A physiologically suppresses excess axon-collateral sprouting. Antisense oligonucleotide knockdown, intra-axonal antibody microinjection, neurite morphology analysis Brain research Medium 8973813
1995 Injection of HPC-1/syntaxin 1A (or syntaxin 1B) cRNA into amphibian embryonic cells causes morphological deformation of Golgi complexes, accumulation of vacuoles, and disappearance of extracellular matrix from the cell surface, demonstrating that syntaxin 1A disrupts intracellular membrane transport and inhibits constitutive secretion. cRNA microinjection into amphibian embryos, immunoelectron microscopy, immunoblotting Experimental cell research Medium 7589235
1997 Intracellular application of anti-HPC-1/syntaxin 1A antibody into presynaptic neurons enhances autaptic excitatory postsynaptic current amplitude in cultured rat hippocampal neurons, indicating syntaxin 1A suppresses transmitter release at central synapses; the increase was due to increased quantal content, not quantal size. Whole-cell patch-clamp with intracellular antibody dialysis at hippocampal autapses Neuroreport Medium 9427341
1997 HPC-1/syntaxin 1A binds directly to tubulin in vitro at residues 89–106 (a tubulin-binding motif), as shown by in vitro binding assay and competitive inhibition with synthetic peptides covering that region. In vitro binding assay (recombinant and brain-derived syntaxin 1A with tubulin), synthetic peptide competition Biochemical and biophysical research communications Medium 9070277
1997 HPC-1/syntaxin 1A in rat brain membranes is phosphorylated specifically on serine residues (not threonine or tyrosine), as detected by affinity purification and antiphosphoserine immunoblotting. Affinity column purification with isoform-specific monoclonal antibody 14D8, antiphosphoserine/threonine/tyrosine immunoblotting Journal of molecular neuroscience : MN Medium 9061612
1998 The C-terminal hydrophobic domain of HPC-1/syntaxin 1A functions as a membrane anchor directing localization first to the ER then to the plasma membrane via the exocytic pathway; truncation of this domain results in cytoplasmic mislocalization, and a chimeric protein with just the last 24 amino acids recapitulates transmembrane topology and exocytic pathway localization. Transient expression of deletion/chimeric mutants in COS cells, subcellular fractionation, N-glycosylation assay for ER topology, immunofluorescence Journal of biochemistry High 9685720
1999 Reduction of syntaxin 1A expression in PC12h cells (by stable antisense transfection) enhances depolarization-evoked dopamine release, with a strong inverse correlation between syntaxin 1A protein level and dopamine release, indicating syntaxin 1A suppresses exocytosis; Ca2+ influx was unaffected. Stable antisense transfection, dopamine release assay, intracellular Ca2+ measurement Journal of biochemistry Medium 10101280
1999 Syntaxin 1C, a soluble alternative splice variant of STX1A lacking the transmembrane domain, is expressed in human astroglioma cells and its expression is upregulated by PMA through a PKC-dependent signaling pathway. RT-PCR, immunoblotting, PKC inhibitor treatment FEBS letters Medium 12586365
2001 Intracellular delivery of the H3 domain of HPC-1/syntaxin 1A fused to HIV-1 Tat PTD suppresses transmitter release from PC12 cells, demonstrating that the H3 domain is functionally important for exocytosis regulation. Tat-fusion protein transduction into PC12 cells, transmitter release assay Biochimica et biophysica acta Medium 11420120
2002 Introduction of the H3 domain peptide of HPC-1/syntaxin 1A into presynaptic hippocampal neurons via patch electrode depresses inhibitory neurotransmitter release in a stimulation-frequency-dependent manner and slows recovery from vesicle depletion after tetanic stimulation, suggesting the H3 domain regulates refilling of the readily releasable pool. Paired whole-cell patch-clamp recording with intracellular peptide dialysis in hippocampal neuronal cultures Neuroscience letters Medium 12183029
2003 The C-terminal membrane-anchoring region of HPC-1/syntaxin 1A (23 amino acids) does not traverse the lipid bilayer as a classical transmembrane segment; the C-terminal tail (8 amino acids) is essential for plasma membrane anchoring. These conclusions were established using the substituted-cysteine-accessibility method (SCAM) and isoform-specific monoclonal antibodies combined with subcellular fractionation. Substituted-cysteine-accessibility method (SCAM), monoclonal antibody epitope accessibility, subcellular fractionation, immunocytochemistry of transmembrane mutants Journal of biochemistry High 12761168
2004 Syntaxin 1C (soluble splice variant of STX1A) overexpression or PMA-induced endogenous upregulation suppresses glucose uptake in astroglioma (T98G) cells by reducing GLUT-1 at the plasma membrane (Vmax decreased, Km unchanged), acting through inhibition of GLUT-1 intracellular trafficking rather than altering transporter kinetics. Overexpression, glucose uptake assay (2-deoxyglucose), immunofluorescence localization of GLUT-1, PMA stimulation The Journal of biological chemistry Medium 15037634
2006 STX1A knockout mice show impaired long-term potentiation (LTP) in hippocampal CA1 slices and deficits in conditioned fear memory consolidation and extinction, while basic synaptic transmission is normal; other SNARE proteins are unaffected, establishing a specific role for STX1A in synaptic plasticity. Targeted gene disruption (knockout mice), hippocampal slice LTP recordings, behavioral tests (Morris water maze, fear conditioning), immunoblotting The Journal of neuroscience High 16723534
1999 In vitro binding assays show that syntaxin 1A binds insulin secretory granules, and syntaxin 1A overexpression specifically inhibits the regulatory (stimulated) insulin release pathway in beta TC3 cells without affecting constitutive proinsulin secretion, glucose transport, or intracellular Ca2+ levels. In vitro granule binding assay, stable overexpression in beta TC3 cells, insulin secretion assay, 2-deoxyglucose uptake, fura-2 Ca2+ imaging Biochemical and biophysical research communications Medium 9070225
2007 STX1A knockout mice show enhanced mechanical allodynia and significantly greater excitatory synaptic transmission (increased evoked EPSC amplitude, increased aEPSC and mEPSC frequency) in spinal cord dorsal horn after peripheral nerve injury compared to wild-type mice, revealing a role for STX1A in modulating synaptic plasticity in nociceptive pathways. Partial sciatic nerve ligation, von Frey filament behavioral test, whole-cell patch-clamp recordings from spinal cord slices The European journal of neuroscience Medium 17953616
2011 Munc18-1 exerts dual functions through its central cavity: (1) chaperone activity via interaction with monomeric syntaxin 1A (STX1A), and (2) activation of SNARE-mediated membrane fusion via binding to assembled SNARE complexes. A novel Munc18-1 mutant with reduced STX1A interaction retains SNARE complex binding and promotes liposome fusion, while soluble STX1A H3 domain blocks Munc18-1 activation of liposome fusion by occupying the central cavity. Munc18-1 mutagenesis, liposome fusion reconstitution assay, pulldown/binding assays, secretion assay in neuroendocrine cells Molecular biology of the cell High 21900493
2012 LTP impairment in STX1A knockout mice results from reduced catecholamine (noradrenaline, dopamine) release from dense-core vesicles, leading to suppressed cAMP/PKA signaling; LTP is rescued by forskolin (adenylyl cyclase activator) or by exogenous noradrenaline/dopamine, and catecholamine depletion in wild-type mice reduces LTP, placing STX1A upstream of catecholaminergic neuromodulation of LTP. Hippocampal slice LTP recordings, HPLC catecholamine measurement, pharmacological rescue experiments (forskolin, noradrenaline, dopamine, catecholamine depletion), STX1A KO mice The Journal of neuroscience High 22219298
2014 STX1B (not STX1A) is required for neuronal survival; STX1B knockout mice die before postnatal day 14 with impaired brain development. STX1B is required in glial cells for BDNF secretion: conditioned medium from STX1B-/- glia fails to support neuronal survival, BDNF localization in STX1B-/- glia is disrupted, and BDNF or NT-3 rescues STX1B-/- neuron survival, establishing a distinct role for STX1B versus STX1A. Targeted gene disruption (STX1B KO mice), conditioned medium assay, BDNF immunolocalization, neuronal survival counts, exogenous neurotrophin rescue Journal of neurochemistry High 24666284
2015 An autism-associated STX1A variant (R26Q) shows decreased phosphorylation at Ser14 by casein kinase 2 and reduced STX1A/DAT (dopamine transporter) interaction, both of which converge to inhibit reverse transport of dopamine and alter dopamine-associated behaviors. Autism patient variant characterization, biophysical/biochemical assays of DAT function, animal models, kinase assay for Ser14 phosphorylation by CK2, co-immunoprecipitation of STX1A/DAT EBioMedicine Medium 25774383
2016 Unusual social behavior in STX1A KO mice is caused by reduced dopamine-induced oxytocin (OXT) release in the CNS; in vivo microdialysis shows lower extracellular OXT in STX1A KO, intracerebroventricular OXT partially rescues social behavior, and dopamine-stimulated OXT release from amygdala is reduced. STX1A KO mice, social novelty preference test, intracerebroventricular OXT administration, in vivo microdialysis for OXT measurement Journal of neurochemistry Medium 27059771
1999 In vitro binding assays demonstrate that syntaxin 1A inhibits the regulatory (stimulated) insulin release pathway by interacting with vesicular proteins on secretory granules, without affecting glucose metabolism or intracellular Ca2+. In vitro granule binding assay, insulin secretion assay in stable overexpressing beta TC3 cells Biochemical and biophysical research communications Medium 9070225
1999 In vitro inhibition of microtubule polymerization by HPC-1/syntaxin 1A: affinity chromatography shows direct tubulin binding; synthetic peptides covering residues 89-106 competitively block binding; chemical cross-linking shows 1:1 stoichiometry (one syntaxin 1A molecule per tubulin monomer); light scattering and dark-field microscopy show decreased microtubule growth rate; a mutant lacking the tubulin-binding sequence (residues 1-97) does not suppress polymerization. Affinity column chromatography, synthetic peptide competition, chemical cross-linking (EDC), light scattering microtubule polymerization assay, dark-field microscopy Cell structure and function High 15216893
2019 JNK2 interacts with STX1A at presynaptic terminals, and this interaction is required for NMDA receptor-evoked glutamate release; a cell-permeable peptide (JGRi1) that disrupts the JNK2/STX1A interaction reduces NMDA-evoked glutamate release in vitro and ex vivo. Co-immunoprecipitation, cell-permeable interfering peptide, glutamate release assay in vitro and ex vivo, intraperitoneal administration with brain diffusion assay Scientific reports Medium 31073146
2022 De novo missense variants in STX1A (associated with epilepsy) are predicted in silico to weaken the inhibitory STX1A-STXBP1 (Munc18-1) interaction, while inframe single-amino-acid deletions (associated with intellectual disability/autism) are predicted to impair SNARE complex formation, suggesting two distinct pathogenic mechanisms. In silico structural modeling of STX1A missense and deletion variants; clinical cohort assembly (8 individuals with ultra-rare STX1A variants) European journal of human genetics : EJHG Low 36564538
2023 SNAP23 competitively inhibits insulin secretion by blocking SNAP25 binding to STX1A; full-length SNAP23 (requiring both N- and C-terminal SNARE binding domains) is needed for competition; SNAP23 serine 95 phosphorylation enhances the SNAP23-STX1A interaction and thereby further inhibits insulin secretion. SNAP23 overexpression/knockdown in INS-1 cells, insulin secretion assay, co-immunoprecipitation of SNAP23/SNAP25/STX1A, domain deletion analysis, phospho-mimetic/phospho-dead mutants Bioscience reports Medium 37057886
2025 STX1A localizes predominantly to lysosomes (and a cohort to the plasma membrane) in HeLa cells; STX1A knockdown causes accumulation of lysosomes beneath the cell surface with reduced lysosome exocytosis and proteolytic activity, while overexpression decreases lysosome number with peripheral dispersion; STX1A forms a SNARE complex with SNAP23 or SNAP25 (Qbc) and VAMP2 (R) to mediate lysosomal fusion with the plasma membrane. STX1A also localizes to LLOMe-induced damaged lysosomes and reduces their number by enhancing exocytosis. GFP-STX1A overexpression, siRNA knockdown, TIRF imaging, LAMP1 immunostaining, lysosome exocytosis assay, proteolytic activity assay, co-immunoprecipitation for SNARE complex, LLOMe-induced lysosome damage assay Molecular biology of the cell High 41123944
2025 STX1A is localized to mitochondria in gastric cancer cells; STX1A knockdown impairs mitochondrial respiration, increases oxidative stress, and induces ferroptosis; targeting STX1A or mitochondrial function reverses acquired 5-fluorouracil and cisplatin resistance by inducing ferroptosis. STX1A knockdown, mitochondrial respiration assay (Seahorse), oxidative stress measurement, cell viability/ferroptosis assay, drug resistance assay, subcellular fractionation/localization Human cell Medium 40056239

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin. The EMBO journal 463 7901002
1992 HPC-1 is associated with synaptotagmin and omega-conotoxin receptor. The Journal of biological chemistry 254 1334074
1992 Cloning and sequence analysis of cDNA for a neuronal cell membrane antigen, HPC-1. The Journal of biological chemistry 250 1587842
1999 Characterization of the baboon responses to Shiga-like toxin: descriptive study of a new primate model of toxic responses to Stx-1. The American journal of pathology 118 10233866
2006 Analysis of knock-out mice to determine the role of HPC-1/syntaxin 1A in expressing synaptic plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 107 16723534
1996 Expression and functional role of syntaxin 1/HPC-1 in pancreatic beta cells. Syntaxin 1A, but not 1B, plays a negative role in regulatory insulin release pathway. The Journal of biological chemistry 104 8557645
1994 Suppression of apoptosis in insect cells stably transfected with baculovirus p35: dominant interference by N-terminal sequences p35(1-76). Journal of virology 85 7966562
1995 Syntaxin 1 (HPC-1) is associated with chromaffin granules. The Journal of biological chemistry 80 7608144
1999 Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes. Journal of medical genetics 75 10874638
1999 Induction of cytokines in a human colon epithelial cell line by Shiga toxin 1 (Stx1) and Stx2 but not by non-toxic mutant Stx1 which lacks N-glycosidase activity. FEBS letters 69 9929007
1993 Immunoelectron microscopic localization of the HPC-1 antigen in rat cerebellum. Journal of neurocytology 69 8301329
2003 Multiplex real-time PCR method to identify Shiga toxin genes stx1 and stx2 and Escherichia coli O157:H7/H- serotype. Applied and environmental microbiology 67 14532101
2008 Genetic and expression analyses reveal elevated expression of syntaxin 1A ( STX1A) in high functioning autism. The international journal of neuropsychopharmacology 66 18593506
2015 Rare autism-associated variants implicate syntaxin 1 (STX1 R26Q) phosphorylation and the dopamine transporter (hDAT R51W) in dopamine neurotransmission and behaviors. EBioMedicine 60 25774383
2002 Shiga toxin-producing Escherichia coli infection and antibodies against Stx2 and Stx1 in household contacts of children with enteropathic hemolytic-uremic syndrome. Journal of clinical microbiology 58 11980959
2007 Prevalence of Shiga toxin-producing Escherichia coli stx1, stx2, eaeA, and rfbE genes and survival of E. coli O157:H7 in manure from organic and low-input conventional dairy farms. Applied and environmental microbiology 55 17277204
2001 Neutralization of Shiga toxins Stx1, Stx2c, and Stx2e by recombinant bacteria expressing mimics of globotriose and globotetraose. Infection and immunity 52 11179385
2005 Extended-spectrum beta-lactamase-producing Shiga toxin gene (Stx1)-positive Escherichia coli O26:H11: a new concern. Journal of clinical microbiology 48 15750063
1992 Neuron-specific antigen HPC-1 from bovine brain reveals strong homology to epimorphin, an essential factor involved in epithelial morphogenesis: identification of a novel protein family. Biochemical and biophysical research communications 45 1530610
2010 Human isolates of Aeromonas possess Shiga toxin genes (stx1 and stx2) highly similar to the most virulent gene variants of Escherichia coli. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 42 20219084
1993 Neuron specific expression of a membrane protein, HPC-1: tissue distribution, and cellular and subcellular localization of immunoreactivity and mRNA. Brain research. Molecular brain research 39 8361334
2014 HPC-1/syntaxin 1A and syntaxin 1B play distinct roles in neuronal survival. Journal of neurochemistry 35 24666284
2001 Activation of the caspase cascade during Stx1-induced apoptosis in Burkitt's lymphoma cells. Journal of cellular biochemistry 34 11180403
1998 Hemizygous deletion of the HPC-1/syntaxin 1A gene (STX1A) in patients with Williams syndrome. Cytogenetics and cell genetics 32 9763659
2014 New high-affinity monoclonal antibodies against Shiga toxin 1 facilitate the detection of hybrid Stx1/Stx2 in vivo. PloS one 31 24914553
2010 Intelligence in Williams Syndrome is related to STX1A, which encodes a component of the presynaptic SNARE complex. PloS one 31 20422020
1996 Enhancement of neurite-sprouting by suppression of HPC-1/syntaxin 1A activity in cultured vertebrate nerve cells. Brain research 31 8973813
2018 MiR-34a-5p mediates sevoflurane preconditioning induced inhibition of hypoxia/reoxygenation injury through STX1A in cardiomyocytes. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 29554593
2003 Genome analysis of a novel Shiga toxin 1 (Stx1)-converting phage which is closely related to Stx2-converting phages but not to other Stx1-converting phages. Journal of bacteriology 30 12813092
2006 The 13C4 monoclonal antibody that neutralizes Shiga toxin Type 1 (Stx1) recognizes three regions on the Stx1 B subunit and prevents Stx1 from binding to its eukaryotic receptor globotriaosylceramide. Infection and immunity 28 17030576
2012 Impairment of catecholamine systems during induction of long-term potentiation at hippocampal CA1 synapses in HPC-1/syntaxin 1A knock-out mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 22219298
2010 Replication study of Japanese cohorts supports the role of STX1A in autism susceptibility. Progress in neuro-psychopharmacology & biological psychiatry 27 21118708
2007 Search for genetic variants of the SYNTAXIN 1A (STX1A) gene: the -352 A>T variant in the STX1A promoter associates with impaired glucose metabolism in an Italian obese population. International journal of obesity (2005) 27 17912268
2015 A Four-Plex Real-Time PCR Assay, Based on rfbE, stx1, stx2, and eae Genes, for the Detection and Quantification of Shiga Toxin-Producing Escherichia coli O157 in Cattle Feces. Foodborne pathogens and disease 25 26317538
2005 Detection of Shiga toxin genes stx1, stx2, and the +93 uidA mutation of E. coli O157:H7/H-using SYBR Green I in a real-time multiplex PCR. Molecular and cellular probes 25 16271448
1997 Characterization of HPC-1 antigen, an isoform of syntaxin-1, with the isoform-specific monoclonal antibody, 14D8. Journal of molecular neuroscience : MN 24 9061612
2011 Dual roles of Munc18-1 rely on distinct binding modes of the central cavity with Stx1A and SNARE complex. Molecular biology of the cell 23 21900493
2010 HPC-1/syntaxin 1A gene knockout mice show abnormal behavior possibly related to a disruption in 5-HTergic systems. The European journal of neuroscience 23 20576034
2009 Risk factors for the occurrence of Escherichia coli virulence genes eae, stx1 and stx2 in wild bird populations. Epidemiology and infection 22 19327201
2016 Unusual social behavior in HPC-1/syntaxin1A knockout mice is caused by disruption of the oxytocinergic neural system. Journal of neurochemistry 21 27059771
1999 Expression analysis and protein localization of the human HPC-1/syntaxin 1A, a gene deleted in Williams syndrome. Genomics 21 10644452
2014 STX1A and Asperger syndrome: a replication study. Molecular autism 20 24548729
2003 Identification of the carboxyl-terminal membrane-anchoring region of HPC-1/syntaxin 1A with the substituted-cysteine-accessibility method and monoclonal antibodies. Journal of biochemistry 19 12761168
2001 Suppression of transmitter release by Tat HPC-1/syntaxin 1A fusion protein. Biochimica et biophysica acta 18 11420120
1999 Recruitment of renal tubular epithelial cells expressing verotoxin-1 (Stx1) receptors in HIV-1 transgenic mice with renal disease. Kidney international 18 9987079
1995 Rat HPC-1/syntaxin 1A and syntaxin 1B interrupt intracellular membrane transport and inhibit secretion of the extracellular matrix in embryonic cells of an amphibian. Experimental cell research 17 7589235
2020 Analysis of Genetic Variants in SCN1A, SCN2A, KCNK18, TRPA1 and STX1A as a Possible Marker of Migraine. Current genomics 16 33071616
2010 Detection of Escherichia coli O157 and Escherichia coli O157:H7 by the immunomagnetic separation technique and stx1 and stx2 genes by multiplex PCR in slaughtered cattle in Samsun Province, Turkey. Journal of veterinary science 16 21113101
2008 Production and characterization of rabbit polyclonal sera against Shiga toxins Stx1 and Stx2 for detection of Shiga toxin-producing Escherichia coli. Microbiology and immunology 16 18822082
2016 Stx1 prophage excision in Escherichia coli strain PA20 confers strong curli and biofilm formation by restoring native mlrA. FEMS microbiology letters 15 27190164
2017 A part of patients with autism spectrum disorder has haploidy of HPC-1/syntaxin1A gene that possibly causes behavioral disturbance as in experimentally gene ablated mice. Neuroscience letters 14 28235601
2012 Association analysis of STX1A gene variants in common forms of migraine. Cephalalgia : an international journal of headache 14 22250207
2008 No association between tagging SNPs of SNARE complex genes (STX1A, VAMP2 and SNAP25) and schizophrenia in a Japanese population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 14 18512733
1997 Mapping of the human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7 band q11.2. Genomics 14 9177791
2022 Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy. European journal of human genetics : EJHG 13 36564538
2008 Subtype analysis of stx1, stx2 and eae genes in Shiga toxin-producing Escherichia coli (STEC) and typical and atypical enteropathogenic E. coli (EPEC) from lambs in India. Veterinary journal (London, England : 1997) 13 18768338
2007 Enhancement of synaptic transmission and nociceptive behaviour in HPC-1/syntaxin 1A knockout mice following peripheral nerve injury. The European journal of neuroscience 13 17953616
2019 The selective disruption of presynaptic JNK2/STX1a interaction reduces NMDA receptor-dependent glutamate release. Scientific reports 12 31073146
2004 Activation of syntaxin 1C, an alternative splice variant of HPC-1/syntaxin 1A, by phorbol 12-myristate 13-acetate (PMA) suppresses glucose transport into astroglioma cells via the glucose transporter-1 (GLUT-1). The Journal of biological chemistry 12 15037634
1999 HPC-1/syntaxin 1A suppresses exocytosis of PC12 cells. Journal of biochemistry 12 10101280
2015 Extended-spectrum beta-lactamase-producing Shiga toxin gene (stx1)-positive Escherichia coli O91:H14 carrying blaCTX-M-15 on an IncI1-ST31 plasmid isolated from a human patient in Germany. International journal of medical microbiology : IJMM 11 25801683
2015 A simple method for expression and purification of Shiga toxin 1 (Stx1) with biological activities by using a single-promoter vector and native signal peptide. Biotechnology and applied biochemistry 11 26031547
2002 Reduction of neurotransmitter release by the exogenous H3 domain peptide of HPC-1/syntaxin 1A in cultured rat hippocampal neurons. Neuroscience letters 11 12183029
1997 Interaction of HPC-1/syntaxin 1A with the cytoskeletal protein, tubulin. Biochemical and biophysical research communications 11 9070277
1997 Enhancement of synaptic transmission by HPC-1 antibody in the cultured hippocampal neuron. Neuroreport 11 9427341
2020 Differentiation of stx1A gene for detection of Escherichia coli serotype O157: H7 and Shigella dysenteriae type 1 in food samples using high resolution melting curve analysis. Food science & nutrition 10 32724629
2019 STX1A gene variations contribute to the susceptibility of children attention-deficit/hyperactivity disorder: a case-control association study. European archives of psychiatry and clinical neuroscience 10 30976917
2009 Antimicrobial resistance and virulence factors stx1, stx2, and eae in generic Escherichia coli isolates from calves in western Canadian cow-calf herds. Microbial drug resistance (Larchmont, N.Y.) 10 19216645
2002 Identification of Escherichia coli O157:H7 by multiplex PCR with primers specific to the hlyA, eaeA, stx1, stx2, fliC and rfb genes. Journal of the Formosan Medical Association = Taiwan yi zhi 10 12645196
2008 Transcription analysis of stx1, marA, and eaeA genes in Escherichia coli O157:H7 treated with sodium benzoate. Journal of food protection 9 18680949
2014 A novel transducible chimeric phage from Escherichia coli O157:H7 Sakai strain encoding Stx1 production. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 8 25445656
1998 Important roles of the C-terminal portion of HPC-1/syntaxin 1A in membrane anchoring and intracellular localization. Journal of biochemistry 8 9685720
1996 Localization of HPC-1/syntaxin 1 in developing rat cerebellar cortex. Cell structure and function 8 9078410
2011 Unusual retinal layer organization in HPC-1/syntaxin 1A knockout mice. Journal of molecular histology 7 21822613
1999 Reconstitution of active recombinant Shiga toxin (Stx)1 from recombinant Stx1-A and Stx1-B subunits independently produced by E. coli clones. FEMS microbiology letters 7 10483717
1993 Immunohistochemical demonstration of neuron specific antigen, HPC-1 in the enteric nervous system of the guinea-pig distal colon. Neuroscience letters 7 8247329
2025 STX1A regulates ferroptosis and chemoresistance in gastric cancer through mitochondrial function modulation. Human cell 6 40056239
2012 PCR-less DNA co-polymerization detection of Shiga like toxin 1 (stx1) in Escherichia coli O157:H7. Biosensors & bioelectronics 6 23261692
2005 Construction and use of an stx1 transcriptional fusion to gfp. FEMS microbiology letters 6 15796982
2002 Refinement of the genomic structure of STX1A and mutation analysis in nondeletion Williams syndrome patients. American journal of medical genetics 6 11977160
1997 Overexpressed syntaxin 1A/HPC-1 inhibits insulin secretion via a regulated pathway, but does not influence glucose metabolism and intracellular Ca2+ in insulinoma cell line beta TC3 cells. Biochemical and biophysical research communications 6 9070225
2003 Expression of syntaxin 1C, an alternative splice variant of HPC-1/syntaxin 1A, is enhanced by phorbol-ester stimulation in astroglioma: participation of the PKC signaling pathway. FEBS letters 5 12586365
2001 Altered immunoreactivity of HPC-1/syntaxin 1A in proliferated nerve fibers in the human aganglionic colon of Hirschsprung's disease. Journal of molecular neuroscience : MN 5 11345516
1999 Inhibition of microtubule assembly by HPC-1/syntaxin 1A, an exocytosis relating protein. Cell structure and function 5 15216893
1997 Transient decrease of HPC-1/syntaxin-1A mRNA in the rat hippocampus by kainic acid. Neuroscience research 5 9237272
1997 HPC-1/syntaxin-1A activity in the enteric nervous system of developing rat gastrointestinal tract. Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi 5 9403817
2023 SNAP23 decreases insulin secretion by competitively inhibiting the interaction between SNAP25 and STX1A. Bioscience reports 4 37057886
2018 Multiplex PCR for the simultaneous detection of the Enterobacterial gene wecA, the Shiga Toxin genes (stx1 and stx2) and the Intimin gene (eae). BMC research notes 3 29880035
2024 Development and Validation of the MAST ISOPLEX®VTEC Kit for Simultaneous Detection of Shiga Toxin/Verotoxin 1 and 2 (stx1/vt1 and stx2/vt2) with Inhibition Control (IC) in a Rapid Loop-Mediated Isothermal Amplification (LAMP) Multiplex Assay. International journal of molecular sciences 2 39337553
2023 Influence of temperature and pH on induction of Shiga toxin Stx1a in Escherichia coli. Frontiers in microbiology 2 37485504
2022 Validation of the 3M™ Molecular Detection Assay 2 - STEC Gene Screen (stx) for the Detection of Shiga Toxin Gene (stx1 and/or stx2) in Additional Matrixes: AOAC Performance Tested MethodSM 071903. Journal of AOAC International 2 35167674
2018 Structural Changes in Stx1 Engineering Monoclonal Antibody Improves Its Functionality as Diagnostic Tool for a Rapid Latex Agglutination Test. Antibodies (Basel, Switzerland) 2 31544861
2015 Different roles of the C-terminal end of Stx1A and Stx2A for AB5 complex integrity and retrograde transport of Stx in HeLa cells. Pathogens and disease 2 26443836
2008 [Molecular detection of shiga toxin-producing (stx1) Escherichia coli and rotavirus in stools of children with diarrhea]. Investigacion clinica 2 18846778
2023 Thermal Adaptation Alters Response to Thermal Stress and Expression of Virulent Genes (eae, stx1, stx2, and hlyA) in Pathogenic Escherichia coli Isolated from Pork. Current microbiology 1 37632548
2022 Validation of the 3M™ Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) for the Detection of Shiga Toxin Gene (stx1 and/or stx2) and Intimin Gene (eae): AOAC Performance Tested MethodSM 071902. Journal of AOAC International 1 35167682
2021 Frequency of k99, stx1, and stx2 Virulence Factors in Escherichia coli isolated from Diarrheic and Clinically Healthy Suckling Calves in Sistan and Baluchistan Province, Iran. Archives of Razi Institute 1 34223727
2018 Detection and Evaluation of Escherichia coli O157:H7 and Shiga-toxin Genes stx1, stx2 in Cattle Meat Samples. Clinical laboratory 1 30549994
2025 Occurrence of Multiple stx1 Genes and Rare Genomic Variation in stx1 Shiga Toxin-Producing Escherichia coli. Microorganisms 0 40431252
2025 STX1A localizes to the lysosome and controls its exocytosis. Molecular biology of the cell 0 41123944

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