| 1998 |
Syntaxin 13 (STX12) was identified as a novel SNARE protein localized to tubular early and recycling endosomes, colocalizing with transferrin receptor. Anti-syntaxin 13 antibody inhibited transferrin receptor recycling in permeabilized PC12 cells. Immunoprecipitation revealed STX12 forms a complex with βSNAP, VAMP2/3, and SNAP-25 that binds αSNAP and NSF and dissociates in the presence of ATP, establishing its role in endosomal membrane fusion during plasma membrane protein recycling. |
Confocal immunofluorescence, electron microscopy, immunoprecipitation, permeabilized-cell recycling assay |
The Journal of cell biology |
High |
9817754
|
| 1998 |
Syntaxin 13 (STX12) was characterized as one of seven novel mammalian SNARE proteins; it localizes to distinct endosomal membrane compartments and is enriched in brain, supporting a role in vesicular trafficking specificity through combinatorial SNARE complex formation. |
Subcellular fractionation, immunofluorescence colocalization with organelle markers, northern blot for tissue distribution |
The Journal of biological chemistry |
Medium |
9553086
|
| 1999 |
Syntaxin 13 (STX12) interacts directly with EEA1, a Rab5 effector present in high-molecular-weight oligomers that also contain NSF. This interaction is required to drive endosome fusion; dominant-negative EEA1 and synthetic FYVE-finger peptides that block EEA1–syntaxin 13 interaction inhibit fusion, suggesting that oligomeric EEA1/NSF complexes mediate local activation of syntaxin 13 upon membrane tethering to coordinate fusion pore assembly. |
Co-immunoprecipitation, in vitro endosome fusion assay, dominant-negative inhibition, synthetic peptide competition |
Cell |
High |
10458612
|
| 1999 |
Pallidin, the protein defective in pallid (platelet storage pool deficiency) mice, was identified as a direct binding partner of syntaxin 13 (STX12) via yeast two-hybrid screen and confirmed by co-immunoprecipitation. Pallidin and syntaxin 13 show overlapping subcellular distribution, placing STX12 in a vesicle-docking/fusion step required for organelle (lysosome-related organelle) biogenesis. |
Yeast two-hybrid, co-immunoprecipitation, immunofluorescence colocalization, positional cloning |
Nature genetics |
High |
10610180
|
| 2013 |
Drosophila syntaxin 13 (syx13) was identified as a strong genetic modifier of mutant CHMP2B (an ESCRT-III component causing frontotemporal dementia). In mammalian cells, knockdown of STX13 (STX12) or its binding partner Vti1a caused accumulation of LC3-positive phagophore puncta and blocked autophagic flux. STX13 was present on LC3-positive phagophores and on multilamellar structures induced by dysfunctional ESCRT-III, and its loss caused accumulation of Atg5-positive puncta, indicating STX12 participates in the maturation of phagophores into closed autophagosomes. |
Drosophila genetic modifier screen, siRNA knockdown in mammalian cells, LC3/Atg5 puncta assay, autophagic flux measurement, fluorescence microscopy |
Molecular cell |
High |
24095276
|
| 2014 |
STX12 (syntaxin 13) and SNAP23 mediate membrane trafficking required for invadopodia formation and tumor cell invasion. Inhibition of SNARE function impaired delivery of Src and EGFR to developing invadopodia, blocked β1-integrin-dependent Src activation and EGFR Tyr845 phosphorylation, and reduced matrix degradation. β1 integrin interaction with SNAP23 increased upon integrin inhibition, whereas the STX12–SNAP23 interaction was reduced, revealing β1-integrin regulation of STX12-dependent trafficking. |
Co-immunoprecipitation, SNARE inhibition (dominant-negative/antibody), invadopodia matrix degradation assay, cell invasion assay, phospho-immunoblot |
Journal of cell science |
High |
24496451
|
| 2015 |
STX13 (STX12), a recycling endosomal Qa-SNARE, is required for delivery of melanin-synthesizing enzymes TYR and TYRP1 from tubular recycling endosomes to maturing melanosomes. Depletion of STX13 reroutes melanosomal cargo to lysosomes. Deletion of its N-terminal regulatory domain increases SNARE activity in vivo and enhances melanosome cargo transport and pigmentation. STX13-dependent cargo transport requires the melanosomal R-SNARE VAMP7, and mutual dependency between STX13 and VAMP7 in regulating each other's localization was demonstrated. |
siRNA depletion, live-cell imaging, electron microscopy, domain-deletion mutagenesis, pigmentation assay, co-localization studies |
Journal of cell science |
High |
26208634
|
| 2019 |
STX12 (Ser139) is a specific substrate of SGK3 kinase at endosomes, identified by phosphoproteomic screens. SGK3 phosphorylation of STX12 at Ser139 was confirmed by in vitro kinase assay and shown to be poorly replicated by Akt due to an unfavorable n+1 residue. IGF1-stimulated SGK3 activation in HEK293 cells promoted phosphorylation of a significant fraction of endogenous STX12 in a manner blocked by SGK3 knockout or SGK inhibitor. SGK3 phosphorylation of STX12 enhanced interaction with the VAMP4/VTI1A/STX6-containing SNARE complex and promoted plasma membrane localization of STX12. |
Phosphoproteomic screen (genetic and pharmacological), in vitro kinase assay, Phos-tag gel, SGK3 knockout cells, SNARE complex co-immunoprecipitation, subcellular localization imaging |
The Biochemical journal |
High |
31665227
|
| 2020 |
STX12 was identified as a downstream transcriptional target of NFE2L1 in the ROS/STAT3/NFE2L1 retrograde mitochondrial signaling axis in hepatoma cells. Overexpression and depletion experiments showed STX12 acts as a key downstream effector of NFE2L1 in modulating hepatoma cell invasiveness, and co-expression of NFE2L1 and STX12 correlated with enrichment of EMT-related genes. |
cDNA microarray after NFE2L1 overexpression/depletion, ROS scavenger experiments, STAT3 inhibition, siRNA knockdown of STX12, invasion assay |
Cancers |
Medium |
32942643
|
| 2021 |
tSNARE1, a schizophrenia-risk protein, competes with STX12 for incorporation into an endosomal SNARE complex, suggesting STX12 is part of an early-endosomal SNARE complex that can be displaced by tSNARE1 acting as an inhibitory SNARE. This competition was demonstrated biochemically, and expression of tSNARE1 isoforms delayed trafficking of the dendritic endosomal cargo Nsg1 into late endosomal/lysosomal compartments, placing STX12 in early-to-late endosomal trafficking in neurons. |
Biochemical competition assay for SNARE complex incorporation, live-cell imaging of cargo trafficking in cortical neurons, subcellular localization |
The Journal of neuroscience |
Medium |
34642214
|
| 2022 |
STX12 (Stx12) physically associates with the VPS16B/VPS33B complex in megakaryocytes. Stx12-deficient megakaryocytes display reduced α-granule numbers and reduced overall levels of α-granule proteins, establishing Stx12 as a component of the platelet α-granule biogenesis machinery. CCDC22 (CCC complex) competes with Stx12 for binding to VPS16B/VPS33B, suggesting a hand-off mechanism coupling endosomal entry (Stx12-mediated fusion) with endosomal exit (CCC-mediated retrieval). |
Co-immunoprecipitation, siRNA/shRNA depletion, electron microscopy of α-granules, immunofluorescence quantification of granule cargo |
Blood |
High |
34905616
|
| 2023 |
F. nucleatum infection induces miR-31, which inhibits autophagic flux by targeting STX12, reducing STX12 protein levels in colorectal cancer cells. Reduced STX12 was associated with increased intracellular survival of F. nucleatum, establishing STX12 as a regulator of autophagic flux whose suppression promotes bacterial persistence. |
miR-31 overexpression/knockout, STX12 knockdown, autophagic flux assay, intracellular bacterial survival assay, luciferase reporter for miRNA targeting |
iScience |
Medium |
37216106
|
| 2024 |
IncE, a Chlamydia trachomatis inclusion membrane effector, binds STX12 (and STX7)-containing vesicles via a short linear motif (SLiM) that mimics an R-SNARE motif, recruiting these vesicles to the bacterial inclusion. This establishes STX12 as a host SNARE whose vesicles are hijacked by a bacterial effector through direct SLiM–SNARE interaction. |
Co-immunoprecipitation of IncE with STX7/STX12, vesicle recruitment imaging, SLiM mutagenesis, bacterial inclusion development assay |
Cell reports |
High |
39154341
|
| 2025 |
STX12 deficiency in mice causes depolarization of mitochondrial membrane potential, decreases mitochondrial complex subunit levels, and leads to mitochondrial DNA (mtDNA) release into the cytosol. In Stx12−/− mouse lungs, released mtDNA activates the cGAS-STING pathway and Type I interferon pathway, causing cytokine storm and neutrophil infiltration, contributing to perinatal lethality. This establishes a role for STX12 in maintaining mitochondrial membrane integrity and mtDNA stability. |
Stx12 knockout mouse model, zebrafish morpholino knockdown, mitochondrial membrane potential assay (JC-1), mitochondrial complex subunit immunoblot, mtDNA quantification, cGAS-STING pathway activation assays (immunoblot, cytokine ELISA), immunohistochemistry |
Cell communication and signaling |
Medium |
40200300
|
| 2025 |
Loss of STX12 in zebrafish and mice causes pericardial edema, cardiac malformations, and heart failure. Stx12-deficient cardiomyocytes show disrupted mitochondrial morphology, reduced iron and zinc levels, impaired ATP production, and prolonged repolarization due to decreased SERCA activity. Rapamycin rescues mitochondrial protein expression and SERCA activity via the TFEB-PGC1α and CAMKII-phospholamban pathways respectively, establishing STX12 as important for energy metabolism and metal homeostasis in cardiomyocytes. |
Zebrafish KO/KD, mouse cardiac-specific KO, mitochondrial morphology (EM), metal quantification (ICP-MS), ATP assay, calcium transient/SERCA activity assay, rapamycin rescue experiments, TFEB/PGC1α/phospholamban immunoblot |
Advanced science |
Medium |
40568929
|
| 2025 |
ELAPOR1, a tethering factor for proacrosomal vesicle (PAV) fusion during acrosome biogenesis, physically interacts with STX12. Conditional knockout of Stx12 in germ cells results in defective acrosome biogenesis similar to Elapor1-deficient mice, establishing STX12 as the SNARE fusion factor acting downstream of ELAPOR1 tethering during acrosome formation. |
Co-immunoprecipitation of ELAPOR1 and STX12, conditional germ-cell Stx12 KO, cryo-EM of ELAPOR1, acrosome morphology by electron microscopy, sperm fertility assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
40737321
|
| 2025 |
ATG9A vesicles fuse with the plasma membrane via the STX13 (STX12)–SNAP23–VAMP3 SNARE complex to mediate unconventional secretion of galectin-9 and related cargo. This is independent of classical autophagy. |
SNARE knockdown, co-immunoprecipitation, VAMP3/SNAP23/STX13 interaction assays, galectin secretion assay, vesicle fusion imaging |
Nature communications |
High |
40335523
|
| 2025 |
STX12 is identified as an interactor of ELAPOR1 and was confirmed as a substrate of UBE3B E3 ubiquitin ligase in neural stem cells; UBE3B interaction with STX12 was confirmed biochemically, suggesting STX12 protein levels at synapses may be regulated by ubiquitin-mediated degradation. |
Quantitative proteomics (ubiquitome), co-immunoprecipitation validation of UBE3B–STX12 interaction |
Autism research |
Low |
41844341
|
| 2025 |
siRNA-mediated knockdown of STX12 reduces MR1 antigen presentation of Mycobacterium tuberculosis-derived ligands to MAIT cells. STX12 blockade increases MR1 surface stabilization and total MR1 expression, indicating that STX12-dependent endosomal trafficking facilitates MR1 internalization and loading in the sorting endosome compartment. |
siRNA knockdown, MR1 antigen presentation assay (MAIT cell activation), MR1 surface flow cytometry, RFP-tagged construct colocalization |
bioRxivpreprint |
Medium |
41573916
|
| 2026 |
SF3A1 (Splicing Factor 3A1) promotes colorectal cancer cell survival by stabilizing STX12 mRNA. Knockdown of SF3A1 reduces STX12 mRNA levels; STX12 knockdown independently induces apoptosis in CRC cells but not in non-cancerous cells. RNA-immunoprecipitation confirmed SF3A1 binds STX12 mRNA, placing STX12 downstream of SF3A1-mediated RNA stabilization as an anti-apoptotic effector. |
SF3A1 siRNA KD, STX12 siRNA KD, RNA-immunoprecipitation (RIP), TUNEL/caspase-3/7/PARP apoptosis assays, xenograft model, transcriptome analysis |
International journal of molecular sciences |
Medium |
41683622
|
| 2026 |
GRIPAP1, a new α-granule biogenesis factor in megakaryocytes, localizes to endosome subdomains decorated by Rab4a and STX12. Fibrinogen and PF4 traffic through GRIPAP1-labeled compartments en route to α-granules, with GRIPAP1 binding GTP-loaded Rab4a for membrane recruitment, further defining STX12 as a marker and functional component of the Rab4a-positive endosomal subdomain involved in α-granule biogenesis. |
GRIPAP1 KO megakaryocytes, live-cell trafficking of fluorescent fibrinogen/PF4, co-localization with Rab4a and STX12, Rab4a-GTP pulldown, artificial mitochondria-targeting mislocalization assay |
The Journal of cell biology |
Medium |
41632639
|