Affinage

SYT11

Synaptotagmin-11 · UniProt Q9BT88

Length
431 aa
Mass
48.3 kDa
Annotated
2026-04-28
61 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Synaptotagmin-11 (SYT11) is a Ca²⁺-independent membrane-trafficking protein that functions as an inhibitory regulator of vesicle exocytosis and endocytosis across multiple cell types. In neurons, Syt11 resides on trafficking endosome-like vesicles distinct from synaptic vesicles, suppresses spontaneous neurotransmitter release by binding the SNARE protein vti1a via its C2A domain, and inhibits synaptic vesicle endocytosis through direct C2B-domain interaction with endophilin A1; it also recruits GABAB receptors and Cav2.2 channels to post-Golgi vesicles via KCTD16, stabilizing these signaling complexes at the plasma membrane (PMID:30808661, PMID:34599505, PMID:37474308, PMID:38698221). In microglia, Syt11 suppresses cytokine secretion and phagocytosis through vti1a/vti1b binding, and in astrocytes it regulates caveolae-mediated endocytosis via interaction with cavin1 and EHD2 (PMID:28686317, PMID:37924268, PMID:31908017). Syt11 is a short-lived protein degraded by parkin- and VHL-mediated ubiquitin–proteasome pathways and stabilized by palmitoylation at Cys39/Cys40, which also promotes pathological α-synuclein monomerization; accumulation of Syt11 due to parkin loss-of-function impairs dopamine release and causes dopaminergic neurodegeneration relevant to Parkinson's disease, while its early developmental loss in dopamine neurons produces schizophrenia-like social deficits through dopamine over-transmission (PMID:29311685, PMID:36787382, PMID:32976921, PMID:39632880).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2005 Medium

    Establishing that non-CpG methylation within the SYT11 promoter reduces Sp-family transcription factor binding and transcription revealed an epigenetic layer controlling SYT11 expression levels.

    Evidence Gel shift and reporter assays with artificially methylated promoter constructs

    PMID:15777718

    Open questions at the time
    • In vivo relevance of non-CpG methylation at endogenous SYT11 locus not demonstrated
    • No link to functional consequences of altered Syt11 protein levels
  2. 2007 Medium

    Identification that variable 33-bp repeat number in the SYT11 promoter modulates transcription via Sp1 binding, with a YY1-dependent 5′UTR SNP also affecting expression, connected SYT11 dosage variation to schizophrenia risk.

    Evidence Reporter assays, gel shift assays, and genetic association in schizophrenia cohorts

    PMID:17192956

    Open questions at the time
    • Functional consequence of altered Syt11 expression in neurons not tested
    • Genetic association not replicated in independent cohorts within this study
  3. 2012 Medium

    Demonstrating that Syt11 localizes to presynaptic vesicles and plasma membrane at both excitatory and inhibitory synapses, and is recruited by neuroligins, established its synaptic identity as a vesicle-associated protein.

    Evidence Immunogold electron microscopy, subcellular fractionation, neuroligin co-culture recruitment assay in neurons

    PMID:22960622

    Open questions at the time
    • Functional role at the synapse not addressed
    • Whether endogenous neuroligin-dependent recruitment is physiologically required was not tested
  4. 2014 Medium

    Discovery that the Syt11 C2A domain binds vti1a and the C2B domain binds RISC components (SND1, Ago2, FMRP) in β-cells hinted at dual trafficking and RNA-regulatory roles.

    Evidence Affinity purification/mass spectrometry, domain-specific pulldowns, direct binding assay in pancreatic β-cells

    PMID:24882364

    Open questions at the time
    • Functional consequences of RISC interaction not established
    • Whether Syt11-RISC binding occurs in neurons is unknown
  5. 2016 High

    Placing SYT11 downstream of an ATP13A2–MYCBP2–TSC2–mTORC1–TFEB signaling axis, and showing that SYT11 depletion causes lysosomal dysfunction and impaired autophagosome degradation, established SYT11 as a node linking PD-associated genes to lysosomal homeostasis.

    Evidence siRNA knockdown, ubiquitination assays, mTORC1/TFEB pathway analysis, lysosomal function assays

    PMID:27278822

    Open questions at the time
    • Direct mechanism by which Syt11 maintains lysosomal function not identified
    • Whether this pathway operates in dopaminergic neurons in vivo is unconfirmed
  6. 2017 High

    Demonstrating that Syt11 inhibits cytokine secretion and phagocytosis in microglia, localizing to the TGN and recycling endosomes and being recruited to phagosomes, expanded Syt11's role beyond neurons to innate immune regulation.

    Evidence siRNA knockdown and overexpression in primary microglia, cytokine ELISA, phagocytosis assays, NF-κB activation assays

    PMID:28686317

    Open questions at the time
    • In vivo microglial phenotype of Syt11 loss not yet shown at this stage
    • Molecular mechanism linking Syt11 to NF-κB suppression not defined
  7. 2018 High

    Identifying Syt11 as a parkin substrate whose accumulation upon parkin deficiency impairs striatal dopamine release and causes dopaminergic neurodegeneration — reversible by SYT11 knockdown — directly linked Syt11 dosage to Parkinson's disease pathogenesis.

    Evidence Unilateral overexpression in SNpc, conditional KO, parkin-deficient mouse models, dopamine release measurements, motor behavior, immunoprecipitation

    PMID:29311685

    Open questions at the time
    • Specific ubiquitination sites on Syt11 by parkin not mapped
    • Whether Syt11 accumulation is sufficient for human PD pathology is unresolved
  8. 2019 High

    Revealing that Syt11 resides on trafficking endosomes (not canonical synaptic vesicles) that undergo slow activity-dependent exocytosis, and that conditional forebrain KO impairs synaptic plasticity and memory without affecting fast neurotransmitter release, redefined Syt11 as a plasticity regulator operating through a non-canonical vesicle population.

    Evidence Constitutive and conditional KO mice, live imaging, mass spectrometry interactome, electrophysiology, behavioral assays

    PMID:30808661

    Open questions at the time
    • Cargo of Syt11-positive endosomes not identified
    • Mechanism linking Syt11 vesicle cycling to long-term potentiation not resolved
  9. 2019 High

    Showing that Syt11 regulates caveolae-mediated endocytosis and osmotic stress response in astrocytes via direct interaction with cavin1 and EHD2 extended its trafficking-inhibitory function to a non-neuronal membrane domain.

    Evidence Syt11 KO astrocytes, live imaging, co-IP/pulldown, electron microscopy, osmotic stress assays

    PMID:31908017

    Open questions at the time
    • Whether Syt11-caveolae regulation occurs in neurons or other cell types is unknown
    • Structural basis of Syt11–cavin1/EHD2 interaction not determined
  10. 2020 Medium

    Quantifying Syt11 as a short-lived protein (t½ ~1.5 h in neurons, ~0.6 h in astrocytes) degraded by the ubiquitin–proteasome pathway in a parkin-dependent manner in neurons established that its abundance is tightly controlled by activity-dependent proteolysis.

    Evidence Cycloheximide chase, proteasome inhibitors, parkin overexpression/knockdown in neurons and astrocytes

    PMID:32976921

    Open questions at the time
    • Specific ubiquitin chain types and lysine residues on Syt11 not identified
    • Parkin-independent degradation mechanism in astrocytes not elucidated
  11. 2021 High

    Identifying vti1a as the direct C2A-domain binding partner through which Syt11 suppresses spontaneous neurotransmitter release — with genetic epistasis confirming vti1a as the principal target — resolved the molecular mechanism underlying Syt11's inhibitory role at the synapse.

    Evidence GST pulldown, co-IP, Syt11-KO neurons, mEPSC recordings, vti1a knockdown epistasis

    PMID:34599505

    Open questions at the time
    • Structural detail of the Syt11 C2A–vti1a interface is lacking
    • Whether this mechanism operates at inhibitory synapses was not tested
  12. 2022 Medium

    Discovery that Syt11 co-localizes with insulin granules and that its knockdown increases both basal and glucose-stimulated insulin secretion extended its inhibitory secretory function to pancreatic β-cells.

    Evidence siRNA knockdown in INS-1 832/13 cells, ELISA, patch-clamp, confocal colocalization

    PMID:35753051

    Open questions at the time
    • Mechanism by which Syt11 inhibits insulin secretion not determined
    • Single cell line study without in vivo validation
  13. 2022 Medium

    Identification of Syt11 as a scaffold bridging MKK7 and JNK1 to promote JNK/cJun signaling and EMT in gastric cancer revealed a non-canonical signaling scaffold function outside the nervous system.

    Evidence Phospho-kinase array, co-IP, xenograft and liver metastasis models, shRNA knockdown

    PMID:35768842

    Open questions at the time
    • Whether Syt11-MKK7-JNK1 scaffolding is direct (all three simultaneously bound) not confirmed by reconstitution
    • Relevance to non-cancer cell types not explored
  14. 2023 High

    Mapping the Syt11 C2B domain interaction with endophilin A1 and demonstrating that a blocking peptide and EndoA1 knockdown reverse the accelerated endocytosis of Syt11-KO neurons identified the molecular basis of Syt11's brake on synaptic vesicle recycling.

    Evidence GST pulldown, co-IP, Syt11-KO neurons, EndoA1 epistasis, peptide competition, calyx of Held electrophysiology

    PMID:37474308

    Open questions at the time
    • How Syt11 binding inhibits EndoA1's membrane-bending activity is structurally undefined
    • Whether the blocking peptide is therapeutically viable in vivo is untested
  15. 2023 High

    Demonstrating that palmitoylation at Cys39/40 stabilizes Syt11 on intracellular membranes and that the resulting increased Syt11 promotes α-synuclein monomerization uncovered a lipid-modification-dependent mechanism linking Syt11 accumulation to synucleinopathy.

    Evidence Acyl-RAC, site-directed mutagenesis of Cys39/40, biochemical fractionation, α-synuclein tetramer-to-monomer quantification in cortical neurons

    PMID:36787382

    Open questions at the time
    • Palmitoyl-transferase(s) responsible for Syt11 palmitoylation not identified
    • In vivo contribution of palmitoylation to PD pathology not tested
  16. 2023 High

    In vivo microglia-specific conditional KO of Syt11 confirmed its role as an immune brake: loss enhanced phagocytosis of α-synuclein fibrils and elevated cytokine production, with vti1a/vti1b identified as linker-domain binding partners mediating this suppression.

    Evidence Inducible microglia-specific cKO, LPS and α-synuclein PD model in vivo, co-IP, competitive peptide assay

    PMID:37924268

    Open questions at the time
    • How Syt11–vti1a/b interaction mechanistically suppresses NF-κB signaling is not resolved
    • Whether microglial Syt11 loss is neuroprotective or neurotoxic in long-term PD models is unknown
  17. 2024 High

    Showing that Syt11 bridges KCTD16, GABAB receptors, and Cav2.2 channels on post-Golgi vesicles and stabilizes them at the plasma membrane established a new role for Syt11 as a trafficking scaffold for presynaptic signaling complexes.

    Evidence Reciprocal co-IP, proximity ligation, Syt11 KO mouse electrophysiology, live imaging, biochemical fractionation

    PMID:38698221

    Open questions at the time
    • Whether other Syt family members compensate for Syt11 in GABAB trafficking is unknown
    • Structural basis of Syt11–KCTD16 interaction not determined
  18. 2024 High

    Stage-specific conditional KO demonstrated that Syt11 loss in dopamine neurons during early adolescence (but not adulthood) causes persistent schizophrenia-like social deficits via dopamine over-transmission, revealing a critical developmental window.

    Evidence Developmental stage-specific conditional KO in dopamine neurons, electrophysiology, dopamine measurements, behavioral assays, mPFC structural analysis

    PMID:39632880

    Open questions at the time
    • Molecular mechanism by which developmental dopamine excess permanently alters mPFC circuitry is unclear
    • Whether this maps onto human developmental schizophrenia trajectories is unresolved
  19. 2025 Medium

    Identification of VHL as a second E3 ligase that ubiquitinates and degrades Syt11, with downstream consequences for SPINK1 expression and gastric cancer cell growth, expanded the repertoire of Syt11 post-translational regulators beyond parkin.

    Evidence Co-IP, ubiquitination assay, MG132 rescue, cycloheximide chase, overexpression/knockdown in gastric cancer cells

    PMID:40576306

    Open questions at the time
    • Whether VHL-mediated Syt11 degradation occurs in neurons or only in cancer contexts is untested
    • Ubiquitination sites on Syt11 by VHL not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive functional characterization, the structural basis of Syt11's Ca²⁺-independent C2 domains, the identity of cargoes in Syt11-positive trafficking endosomes, and the palmitoyl-transferase(s) responsible for its stabilization remain unknown.
  • No crystal or cryo-EM structure of Syt11 C2 domains available
  • Cargo identity of Syt11-positive endosomal vesicles in neurons not defined
  • Palmitoyl-transferase(s) acting on Syt11 Cys39/40 not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7 GO:0060090 molecular adaptor activity 4
Localization
GO:0005794 Golgi apparatus 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-112316 Neuronal System 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 1
Partners
CACNA1BCAVIN1EHD2KCTD16PRKNSH3GL2VHLVTI1A

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Synaptotagmin-11 (Syt11) is a physiological substrate of parkin (E3 ubiquitin ligase). Overexpression of full-length, but not C2B-truncated, Syt11 in dopaminergic neurons of the substantia nigra pars compacta impairs striatal dopamine release by inhibiting endocytosis and vesicle pool replenishment, causing dopaminergic neuron degeneration. Parkin deficiency leads to Syt11 accumulation and PD-like neurotoxicity, which is reversed by SYT11 knockdown or knockout in dopaminergic neurons. In vivo unilateral overexpression, conditional knockout, parkin-deficient mouse models, dopamine release measurements, motor behavior assays, immunoprecipitation Nature communications High 29311685
2016 ATP13A2 depletion negatively regulates SYT11 at both transcriptional and post-translational levels. Decreased SYT11 transcription is controlled by MYCBP2-induced ubiquitination of TSC2, leading to mTORC1 activation and decreased TFEB-mediated transcription of SYT11. Increased SYT11 protein turnover is regulated by its ubiquitination and degradation. Decreased SYT11 levels induce lysosomal dysfunction and impaired autophagosome degradation. siRNA knockdown, transcriptional assays, ubiquitination assays, lysosomal function assays, mTORC1/TFEB pathway analysis Nature communications High 27278822
2019 Syt11 resides on abundant vesicles resembling trafficking endosomes (distinct from synaptic vesicles) in neurons. These vesicles recycle via the plasma membrane in an activity-dependent manner with slow, desynchronized exocytosis. Constitutive Syt11 knockout mice die shortly after birth. Conditional knockout in excitatory forebrain neurons impairs synaptic plasticity and memory without affecting fast neurotransmitter or peptide secretion, but reduces long-term synaptic potentiation. Conditional and constitutive knockout mice, live imaging, mass spectrometry (Syt11 interactome), electrophysiology, behavioral assays Genes & development High 30808661
2017 Syt11 inhibits cytokine secretion (IL-6, TNF-α) and phagocytosis in microglia. Syt11 localizes to the trans-Golgi network and recycling endosomes, and is recruited to phagosomes. Syt11 knockdown increases NF-κB activation and cytokine synthesis/secretion capacity, and enhances phagocytosis including of α-synuclein fibrils. Overexpression of Syt11 suppresses these functions. siRNA knockdown, overexpression rescue, immunofluorescence localization, cytokine ELISA, phagocytosis assays, NF-κB activation assays Glia High 28686317
2023 Syt11 is palmitoylated at Cys39 and Cys40 (adjacent to its transmembrane domain) in mouse and human brain tissue and cultured cortical neurons. This palmitoylation localizes Syt11 to digitonin-insoluble intracellular membranes and protects it from endolysosomal degradation. Palmitoylation-mediated increase in Syt11 abundance enhances α-synuclein binding to intracellular membranes, decreasing physiologic tetrameric α-synuclein and increasing aggregation-prone monomeric α-synuclein. A palmitoylation-deficient mutant does not replicate these effects. Palmitoylation assays (acyl-RAC), site-directed mutagenesis, biochemical fractionation, α-synuclein tetramer/monomer quantification in neurons, overexpression of WT vs palmitoylation-deficient mutant Science signaling High 36787382
2021 Syt11 inhibits spontaneous neurotransmitter release by directly interacting with vti1a (a non-canonical SNARE protein that maintains spontaneous release). The C2A domain of Syt11 binds vti1a with high affinity. Syt11-KO hippocampal neurons show increased miniature EPSC frequency; vti1a knockdown reverses this phenotype, identifying vti1a as the main target. GST pull-down, co-immunoprecipitation, affinity purification, Syt11 knockout neurons, electrophysiology (mEPSC recording), vti1a knockdown epistasis Journal of neurochemistry High 34599505
2023 Syt11 inhibits synaptic vesicle (SV) endocytosis through direct, Ca2+-independent binding to endophilin A1 (EndoA1) via the C2B domain of Syt11 and the N-terminus of EndoA1. Syt11-KO accelerates SV endocytosis and vesicle recycling. A peptide (aa 314-336) from Syt11 C2B blocks Syt11-EndoA1 binding in vitro and in vivo, inhibiting SV endocytosis. EndoA1 knockdown reverses the Syt11-KO phenotype, establishing EndoA1 as the main inhibitory target of Syt11 in SV endocytosis. GST pull-down, co-immunoprecipitation, Syt11-KO mouse neurons, EndoA1 knockdown epistasis, peptide competition assays, electrophysiology at calyx of Held, live imaging The Journal of neuroscience High 37474308
2024 Syt11 binds both the auxiliary GABAB receptor (GBR) subunit KCTD16 and Cav2.2 Ca2+ channels. Through these dual interactions, Syt11 recruits GBRs and Cav2.2 channels to post-Golgi vesicles, facilitating assembly of GBR/Cav2.2 signaling complexes. Syt11 also stabilizes GBRs and Cav2.2 at the neuronal plasma membrane by inhibiting constitutive internalization. Syt11-KO mice show deficits in presynaptic GBRs and Cav2.2, reduced neurotransmitter release, and decreased GBR-mediated presynaptic inhibition. Co-immunoprecipitation, proximity ligation, Syt11 KO mouse analysis, electrophysiology, live imaging, biochemical fractionation EMBO reports High 38698221
2019 Syt11 regulates caveolae-mediated endocytosis and caveolar response to mechanical stimuli in astrocytes. Syt11-KO accelerates caveolae-mediated endocytosis, reduces caveolar structures on the cell surface, and impairs caveolar disassembly and astrocyte swelling during hypoosmotic stimuli. Syt11 directly interacts with cavin1 and EHD2 (but not caveolin-1), and its absence increases turnover of cavin1 and EHD2 and compromises membrane integrity. Live imaging showed Syt11 leaves caveolar structures before cavin1 during hypoosmotic stress. Syt11 KO astrocytes, live imaging, co-immunoprecipitation/pulldown, electron microscopy, osmotic stress assays, endocytosis assays FASEB journal High 31908017
2023 Syt11 inhibits microglial immune responses in vivo. Inducible microglia-specific Syt11-cKO results in microglial activation and elevated cytokine mRNA. In a PD model, Syt11-cKO microglia show reduced migration to injection sites but enhanced phagocytosis of α-synuclein fibrils. Syt11 directly binds vti1a and vti1b via its linker domain; a competitive peptide derived from this domain induces cytokine secretion in WT microglia, phenocopying Syt11 KD. Inducible microglia-specific conditional KO, LPS and PD model in vivo, co-immunoprecipitation, peptide competition assay, cytokine measurements, phagocytosis assay Journal of neurochemistry High 37924268
2022 SYT11 functions as a scaffold protein in gastric cancer cells, binding both MKK7 and JNK1 to promote JNK1 phosphorylation. JNK activation leads to cJun activation and downstream expression of EMT-related genes (ANGPTL2, THBS4, Vimentin, JAM3). SYT11 knockdown reduces spheroid formation, tumor formation, and liver metastasis. Phospho-kinase array, co-immunoprecipitation, western blot, shRNA knockdown, mouse xenograft, liver metastasis model Journal of experimental & clinical cancer research Medium 35768842
2022 Impad1 interacts directly with Syt11 (a vesicle trafficking protein) to modulate Golgi apparatus morphology and vesicular trafficking. This interaction alters the extracellular matrix and tumor microenvironment to promote lung cancer invasion and metastasis. Inhibiting either Impad1 or Syt11 disrupts the cancer cell secretome and reverses invasive/metastatic phenotype. Co-immunoprecipitation/interaction assays, in vitro and in vivo shRNA screens, Golgi morphology imaging, secretome analysis, invasion and metastasis assays Cell reports Medium 36170810
2014 Syt11 interacts with components of the RNA-induced silencing complex (RISC) in pancreatic β-cells. The C2A domain of Syt11 interacts with the Q-SNARE Vti1a, while the C2B domain interacts with SND1, Ago2, and FMRP (RISC components). Binding of C2B to SND1 was shown to be direct via SND1's N-terminal tandem repeats. Affinity purification/mass spectrometry, co-immunoprecipitation, domain-specific pulldowns, direct binding assay FEBS letters Medium 24882364
2012 Syt11 is expressed mainly in the brain and localizes to presynaptic neurotransmitter vesicles and plasma membrane (with some postsynaptic localization). Exogenously expressed Syt11 can form higher molecular weight complexes via its transmembrane domain. Syt11 is targeted to both dendrite and axon compartments, and is juxtaposed to postsynaptic markers in excitatory and inhibitory synapses. Both neuroligin-1 and neuroligin-2 recruit Syt11 in neuron co-culture. Immunocytochemistry, immunogold electron microscopy, subcellular fractionation, neuroligin recruitment assay, HEK293 expression Neuroscience Medium 22960622
2007 Transcriptional activity of the Syt11 gene is affected by the number of 33-bp repeats in its promoter region (containing an Sp1 binding site), with excessive expression associated with schizophrenia. A SNP in the 5'UTR region where YY1 can bind also affects transcriptional activity of Syt11. Reporter/transient transcription assays, gel mobility shift assay, genetic association American journal of medical genetics. Part B, Neuropsychiatric genetics Medium 17192956
2005 Non-CpG methylation in the promoter region of syt11 reduces the binding of an Sp family transcription factor, thereby reducing syt11 expression. Cytosine residues in the minus strand of the promoter are partially methylated, and artificial methylation of these sites reduces reporter gene expression. Gel mobility shift assay, transient transcription assay with artificially methylated promoter, sequence analysis Gene Medium 15777718
2020 Syt11 is a short-lived protein degraded primarily by the ubiquitin-proteasome pathway (UPP) in neurons (half-life ~1.49 h). Degradation is accelerated under sustained neuronal activity in a parkin-dependent manner. In astrocytes, Syt11 has a faster turnover (half-life ~0.58 h) partially via UPP, but is degraded via a parkin-independent mechanism under both isoosmotic and hypoosmotic conditions. Cycloheximide chase, proteasome inhibitors, parkin overexpression/knockdown, neuronal activity manipulation, western blot Neuroscience letters Medium 32976921
2024 Syt11 deficiency in dopamine neurons during early adolescence (but not in adults) leads to persistent social deficits and schizophrenia-like behaviors by mediating dopamine over-transmission. Dopamine neuron over-excitation before late adolescence induces persistent schizophrenia-associated behavioral deficits with structural and functional alterations in the mPFC. D2R-targeting interventions presynaptically or postsynaptically show therapeutic effects on social deficits. Conditional Syt11 knockout in dopamine neurons (developmental stage-specific), electrophysiology, dopamine measurements, behavioral assays, mPFC structural/functional analysis Nature communications High 39632880
2022 Syt11 and Syt13 co-localize with insulin in insulin granules in β-cells. Downregulation of Syt11 in INS-1 832/13 cells increases basal and glucose-induced insulin secretion (suggesting an inhibitory role), without affecting exocytosis amplitude or Ca2+ currents. Downregulation of Syt13 decreases insulin secretion and abolishes forskolin-enhanced secretion. siRNA knockdown, ELISA, patch-clamp electrophysiology, confocal microscopy colocalization Acta physiologica Medium 35753051
2025 VHL (an E3 ubiquitin ligase) binds SYT11 protein and promotes its proteasomal degradation by ubiquitination. VHL overexpression decreases SYT11 protein (not mRNA) and shortens its half-life; MG132 (proteasome inhibitor) reverses this. VHL-mediated SYT11 degradation downregulates SPINK1, which in turn inhibits gastric cancer cell growth and invasion. Co-immunoprecipitation, ubiquitination assay, MG132 rescue, cycloheximide chase, transcriptome sequencing, knockdown/overexpression functional assays Journal of cellular and molecular medicine Medium 40576306
2025 Compensatory upregulation of Syt11 in parkin knockout mice during the suckling stage (but not in adults) conceals PD-associated phenotypes. Parkin knockdown in adult SNpc impairs dopamine release and causes motor deficits. Overexpression of Syt11 alone induces PD-like motor and non-motor impairments, impaired dopamine release and reuptake. Parkin KO and KD mouse models, Syt11 overexpression in SNpc, dopamine release measurements, motor behavior assays, western blot Cell communication and signaling Medium 39901263

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate autophagy via a common pathway. Nature communications 159 27278822
2011 Genome-wide association study identifies candidate genes for Parkinson's disease in an Ashkenazi Jewish population. BMC medical genetics 137 21812969
1994 Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1. DNA research : an international journal for rapid publication of reports on genes and genomes 122 7584044
2021 Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease. Acta pharmaceutica Sinica. B 112 34729301
2012 Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes. Molecular and cellular endocrinology 107 22939844
2018 Synaptotagmin-11 is a critical mediator of parkin-linked neurotoxicity and Parkinson's disease-like pathology. Nature communications 85 29311685
2009 Differential mRNA expression patterns of the synaptotagmin gene family in the rodent brain. The Journal of comparative neurology 70 19030179
2019 Synaptotagmin-11 mediates a vesicle trafficking pathway that is essential for development and synaptic plasticity. Genes & development 58 30808661
2014 Mammalian Non-CpG Methylation: Stem Cells and Beyond. Biology 55 25393317
2008 A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 54 18937310
2017 The GBA variant E326K is associated with Parkinson's disease and explains a genome-wide association signal. Neuroscience letters 50 28830825
2021 Targeted sequencing of Parkinson's disease loci genes highlights SYT11, FGF20 and other associations. Brain : a journal of neurology 48 33349842
2017 Molecular Mechanisms for the Coupling of Endocytosis to Exocytosis in Neurons. Frontiers in molecular neuroscience 35 28348516
2017 Synaptotagmin-11 inhibits cytokine secretion and phagocytosis in microglia. Glia 35 28686317
2011 Genetics of Parkinson's disease and essential tremor. Current opinion in neurology 35 21734494
2007 Synaptotagmin XI as a candidate gene for susceptibility to schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 34 17192956
2016 Genome-wide assessment of Parkinson's disease in a Southern Spanish population. Neurobiology of aging 33 27393345
2023 Palmitoylation of the Parkinson's disease-associated protein synaptotagmin-11 links its turnover to α-synuclein homeostasis. Science signaling 31 36787382
2005 Effects of methylation of non-CpG sequence in the promoter region on the expression of human synaptotagmin XI (syt11). Gene 30 15777718
2017 MiR-335 overexpression impairs insulin secretion through defective priming of insulin vesicles. Physiological reports 27 29122960
2020 Schizophrenia-associated MicroRNA-Gene Interactions in the Dorsolateral Prefrontal Cortex. Genomics, proteomics & bioinformatics 26 32006661
2023 Novel Drug Targets for Atrial Fibrillation Identified Through Mendelian Randomization Analysis of the Blood Proteome. Cardiovascular drugs and therapy 25 37212950
2018 Detergent Insoluble Proteins and Inclusion Body-Like Structures Immunoreactive for PRKDC/DNA-PK/DNA-PKcs, FTL, NNT, and AIFM1 in the Amygdala of Cognitively Impaired Elderly Persons. Journal of neuropathology and experimental neurology 21 29186589
2018 Whole-transcriptomic Profile of SK-MEL-3 Melanoma Cells Treated with the Histone Deacetylase Inhibitor: Trichostatin A. Cancer genomics & proteomics 20 30194076
2014 Synaptotagmin 11 interacts with components of the RNA-induced silencing complex RISC in clonal pancreatic β-cells. FEBS letters 20 24882364
2010 Developmental expression of Synaptotagmin isoforms in single calyx of Held-generating neurons. Molecular and cellular neurosciences 19 20470891
2022 Synaptotagmin 11 scaffolds MKK7-JNK signaling process to promote stem-like molecular subtype gastric cancer oncogenesis. Journal of experimental & clinical cancer research : CR 17 35768842
2021 Identification and drug-induced reversion of molecular signatures of Alzheimer's disease onset and progression in AppNL-G-F, AppNL-F, and 3xTg-AD mouse models. Genome medicine 17 34702310
2022 The highly expressed calcium-insensitive synaptotagmin-11 and synaptotagmin-13 modulate insulin secretion. Acta physiologica (Oxford, England) 14 35753051
2019 Link synthetic lethality to drug sensitivity of cancer cells. Briefings in bioinformatics 12 29300844
2013 Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease. Gene 12 23916622
2024 Synaptotagmin-11 deficiency mediates schizophrenia-like behaviors in mice via dopamine over-transmission. Nature communications 11 39632880
2022 miR-146a/KLF4 axis in epileptic mice: A novel regulator of synaptic plasticity involving STAT3 signaling. Brain research 11 35728661
2022 Impad1 and Syt11 work in an epistatic pathway that regulates EMT-mediated vesicular trafficking to drive lung cancer invasion and metastasis. Cell reports 10 36170810
2021 Synaptotagmin-11 inhibits spontaneous neurotransmission through vti1a. Journal of neurochemistry 10 34599505
2023 Tumor-associated macrophages respond to chemotherapy by detrimental transcriptional reprogramming and suppressing stabilin-1 mediated clearance of EGF. Frontiers in immunology 9 36960065
2019 Synaptotagmin-11 regulates the functions of caveolae and responds to mechanical stimuli in astrocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 31908017
2012 Developmental expression and subcellular distribution of synaptotagmin 11 in rat hippocampus. Neuroscience 9 22960622
2014 Association analysis of STK39, MCCC1/LAMP3 and sporadic PD in the Chinese Han population. Neuroscience letters 8 24631562
2022 Distribution of Copy Number Variation in SYT11 Gene and Its Association with Growth Conformation Traits in Chinese Cattle. Biology 6 35205089
2024 Synaptotagmin-11 facilitates assembly of a presynaptic signaling complex in post-Golgi cargo vesicles. EMBO reports 5 38698221
2023 Synaptotagmin-11 regulates immune functions of microglia in vivo. Journal of neurochemistry 5 37924268
2023 Synaptotagmin-11 Inhibits Synaptic Vesicle Endocytosis via Endophilin A1. The Journal of neuroscience : the official journal of the Society for Neuroscience 4 37474308
2025 In vitro and in vivo antidiabetic evaluation of new Coumarin and Chromone derivatives: Design, synthesis and molecular modeling. Bioorganic chemistry 3 40101577
2023 From Diagnosis to Treatment: A Comprehensive Review of Biomarkers and Therapeutic Advances in Parkinson's Disease. Annals of neurosciences 3 40017568
2020 Parkin-dependent and -independent degradation of synaptotagmin-11 in neurons and astrocytes. Neuroscience letters 3 32976921
2025 Inflammatory Gene Signature Identified by Machine Algorithms Reveals Novel Biomarkers of Coronary Artery Disease. Journal of inflammation research 2 39959641
2025 Comprehensive characterization of the RNA editing landscape in the human aging brains with Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association 2 40631452
2025 Plasma proteins and onset of atherosclerosis: integrating human plasma proteogenomics, transcriptomics and in vivo evidence. Journal of translational medicine 2 41254737
2024 Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation. World journal of diabetes 2 38766439
2025 Compensatory synaptotagmin-11 expression conceals parkinson's disease-like phenotypes in parkin knockout mice. Cell communication and signaling : CCS 1 39901263
2025 To reveal biomarkers related to macrophage and lactic acid metabolism in renal fibrosis and explore their mechanisms. Frontiers in immunology 1 40755781
2024 Role of SYT11 in human pan-cancer using comprehensive approaches. European journal of medical research 1 38890718
2020 The rs3129882/rs4248166 in HLA-DRA and rs34372695 in SYT11 are not associated with sporadic Parkinson's disease in Central Chinese population. The International journal of neuroscience 1 32253955
2026 The genetic architecture of Parkinson's disease in Mexico: a systematic review. Frontiers in aging neuroscience 0 41798285
2025 VHL-Mediated SYT11 Degradation Suppresses Gastric Cancer Cell Growth and Invasion Through Downregulation of SPINK1. Journal of cellular and molecular medicine 0 40576306
2025 Ca2+-Affinitive and Non-Ca2+-Affinitive Synaptotagmins in Human Pan-cancer. Neuromolecular medicine 0 40676322
2025 Protein regulatory network mediated by palmitoylation modifications in the pathological progression of Parkinson's disease: a narrative review. Frontiers in immunology 0 40703511
2025 Identification of breast cancer susceptibility genes via trans-ethnic Mendelian randomization and colocalization analyses. Medicine 0 41367007
2024 Use of mendelian randomization to assess the causal associations of circulating plasma proteins with 12-lead ECG parameters. International immunopharmacology 0 39486179
2021 De Novo 1q21.3q22 Duplication Revaluation in a "Cold" Complex Neuropsychiatric Case with Syndromic Intellectual Disability. Genes 0 33807234