Affinage

SYT3

Synaptotagmin-3 · UniProt Q9BQG1

Round 2 corrected
Length
590 aa
Mass
63.3 kDa
Annotated
2026-04-28
62 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SYT3 encodes synaptotagmin-3, a Ca²⁺-sensing C2-domain membrane protein that operates in two molecularly distinct contexts: as a classical synaptotagmin in neurons and immune cells, and—through its extended synaptotagmin (E-Syt3) isoform—as an ER–plasma membrane tether and lipid transfer protein. In neurons, Syt3 localizes to postsynaptic endocytic zones where it drives Ca²⁺-dependent internalization of GluA2-containing AMPA receptors, a process required for long-term depression, LTP decay, and active forgetting; the same Syt3–GluA2 interaction is pathologically engaged after ischemia/reperfusion injury to remove surface GluA2 and promote Ca²⁺-permeable AMPA receptor formation (PMID:30545844, PMID:36892998). As E-Syt3, the protein tethers ER to PM via PI(4,5)P₂-dependent C2 domain binding and uses its SMP domain to transfer diacylglycerol and phosphatidylserine between bilayers, thereby maintaining PM lipid homeostasis and controlling cAMP-dependent epithelial ion transport through CFTR and NBCe1-B (PMID:23791178, PMID:27065097, PMID:40425857). Syt3 forms disulfide-linked homodimers and heterodimers with other synaptotagmins via conserved N-terminal cysteines, binds syntaxin and clathrin-AP2 in a Ca²⁺-dependent manner, and in non-neuronal settings participates in CXCR4 recycling in T cells and lipid droplet biogenesis in adipocytes (PMID:10531343, PMID:7791877, PMID:17179206, PMID:34693607).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 Medium

    Identification of Syt3 as a third synaptotagmin family member with the conserved five-domain architecture but distinct brain-region expression patterns established that individual neurons likely deploy specific synaptotagmin combinations.

    Evidence cDNA cloning, Northern blot, immunohistochemistry, and in situ hybridization in mouse brain and PC12 cells

    PMID:8058779

    Open questions at the time
    • No functional data; expression pattern alone does not reveal isoform-specific roles
  2. 1995 High

    Biochemical characterization revealed that Syt3's first C2 domain binds phospholipids and syntaxin in a Ca²⁺-dependent manner (EC₅₀ 3–6 µM), with a lower Ca²⁺ threshold for syntaxin binding than Syt1/2, and that all synaptotagmins bind clathrin-AP2 at nanomolar affinity—establishing Syt3 as a Ca²⁺ sensor with potential roles in both fusion and endocytosis.

    Evidence In vitro phospholipid-binding, syntaxin-binding, and clathrin-AP2 binding assays with purified recombinant domains

    PMID:7791877

    Open questions at the time
    • All data from in vitro assays; cellular context for syntaxin vs. AP2 engagement unknown
    • Functional consequence of lower Ca²⁺ threshold not tested in cells
  3. 1999 High

    Discovery that Syt3 forms disulfide-linked homodimers and heterodimers with Syt V/VI/X via conserved N-terminal cysteines (C10 essential) revealed an oligomerization mechanism that could diversify Ca²⁺-sensing complexes.

    Evidence Site-directed mutagenesis, co-immunoprecipitation, non-reducing SDS-PAGE of recombinant and native mouse brain protein

    PMID:10531343

    Open questions at the time
    • Functional significance of homo- vs. heterodimer pools in vivo unknown
    • Stoichiometry and dynamics of native complexes not resolved
  4. 2006 Medium

    SYT3 was identified as the sole synaptotagmin in T cells, localizing to multivesicular bodies where it controls CXCR4 recycling to the surface; its knockdown impaired chemokine-directed migration, broadening Syt3 function beyond neurons to immune cell trafficking.

    Evidence Antisense knockdown, C2B domain overexpression, flow cytometry for surface CXCR4, chemotaxis assay, CXCR4 overexpression rescue in T cells

    PMID:17179206

    Open questions at the time
    • Antisense knockdown lacks specificity controls of modern siRNA/KO approaches
    • Direct physical interaction between Syt3 and CXCR4 not demonstrated
    • Whether the recycling role is C2 domain Ca²⁺-dependent was not tested
  5. 2007 Medium

    Characterization of E-Syt3 as an ER-resident protein whose C2C domain targets it to the PM established a distinct extended-synaptotagmin identity and began to separate E-Syt biology from classical synaptotagmin function.

    Evidence Myc-tagged domain deletion constructs, immunofluorescence microscopy in transfected cells

    PMID:17360437

    Open questions at the time
    • Overexpression system; endogenous localization not validated
    • Lipid-binding specificity of C2C domain not resolved
  6. 2010 High

    The crystal structure of Ca²⁺-bound Syt3 in complex with the SNARE complex showed that Ca²⁺-binding loops face away from the SNARE bundle, consistent with simultaneous membrane and SNARE engagement—providing a structural framework for Ca²⁺-triggered fusion.

    Evidence X-ray crystallography of Syt3–SNARE complex, comparison with smFRET-derived Syt1 models

    PMID:20173763

    Open questions at the time
    • Structure captured a static state; dynamics of membrane insertion not resolved
    • Functional relevance of the Syt3–SNARE interaction specifically (vs. Syt1) not tested in vivo
  7. 2013 High

    Demonstration that E-Syt2 and E-Syt3 constitutively tether ER to PM through PI(4,5)P₂-dependent C2 domain interactions, forming heteromeric complexes that confer Ca²⁺ regulation via E-Syt1, defined the molecular basis of E-Syt-mediated ER–PM contact sites.

    Evidence Co-immunoprecipitation, TIRF microscopy, PI(4,5)P₂ manipulation (pharmacological and genetic), Ca²⁺ imaging

    PMID:23791178

    Open questions at the time
    • Relative contributions of E-Syt2 vs. E-Syt3 to tethering not individually resolved
    • Downstream functional consequences of tethering loss not yet identified
  8. 2016 High

    Two studies established E-Syt3's lipid transfer function and organismal dispensability: the SMP domain transfers diacylglycerol from PM to ER to maintain lipid homeostasis after PLC activation, yet triple E-Syt knockout mice are viable due to compensatory upregulation of alternative ER–PM junction proteins (Orp5/8, STIM1, Orai1).

    Evidence In vitro lipid transfer assay, E-Syt triple-KO cells with DAG biosensor and rescue experiments; triple-KO mice with gene expression analysis

    PMID:27065097 PMID:27399837

    Open questions at the time
    • Individual contribution of E-Syt3 vs. E-Syt1/2 to lipid transfer not dissected
    • Physiological conditions that would reveal triple-KO phenotypes not identified
  9. 2018 High

    Syt3 was shown to be the postsynaptic Ca²⁺ sensor for AMPA receptor internalization: Syt3 knockout abolished GluA2 endocytosis, LTD, and LTP decay, and the TAT-GluA2-3Y peptide phenocopied and occluded the KO, establishing Syt3 as a molecular driver of forgetting.

    Evidence Syt3 KO mice, AMPA receptor internalization assay, LTD/LTP electrophysiology, TAT-GluA2-3Y peptide competition/occlusion, Morris water maze

    PMID:30545844

    Open questions at the time
    • Whether Syt3 interacts directly with the endocytic machinery (AP2/clathrin) at synapses was not shown
    • Upstream Ca²⁺ source (NMDAR vs. VGCC) driving Syt3 activation not resolved
  10. 2020 Medium

    E-Syt3 was linked to diet-induced obesity via POMC neuron-specific mechanisms: its ablation enhanced POMC-to-α-MSH processing and protected against metabolic dysfunction, revealing a role for ER–PM lipid transfer in hypothalamic energy balance.

    Evidence Conditional KO (whole-body and POMC-specific), AAV overexpression in arcuate nucleus, metabolic phenotyping, PKC/AP-1 activity assays

    PMID:32747560

    Open questions at the time
    • Precise lipid species mediating the effect on POMC processing not identified
    • Single lab; independent replication lacking
  11. 2021 Medium

    Discovery that E-Syt3 undergoes proteasome-dependent C2C domain cleavage during adipocyte differentiation and localizes truncated E-Syt3 to a primordial ER cisterna for lipid droplet biogenesis revealed a non-canonical regulation of E-Syt3 function outside the ER–PM tethering context.

    Evidence Confocal and electron microscopy/tomography, proteasome inhibition, siRNA knockdown in differentiating adipocytes

    PMID:34693607

    Open questions at the time
    • Protease(s) responsible for cleavage not identified
    • Whether ER-PM tethering and lipid droplet roles are mutually exclusive not tested
    • Single lab
  12. 2023 High

    The Syt3–GluA2 internalization axis was shown to be pathologically co-opted during cerebral ischemia/reperfusion, where Syt3 upregulation drives GluA2 removal and Ca²⁺-permeable AMPAR formation; Syt3 KO or TAT-GluA2-3Y peptide conferred neuroprotection, nominating this interaction as a therapeutic target.

    Evidence Syt3 KO mice, MCAO model, surface biotinylation, co-IP of Syt3–GluA2, TAT-GluA2-3Y peptide, behavioral recovery assessment

    PMID:36892998

    Open questions at the time
    • Cell-type specificity of Syt3 upregulation in penumbra not resolved
    • Therapeutic window for peptide intervention not defined
  13. 2025 High

    E-Syt3 was shown to control epithelial ion transport by extracting phosphatidylserine from ER–PM junctions via its SMP domain, antagonizing ORP5; this dissociates cAMP signaling complexes and prevents CFTR and NBCe1-B activation, establishing E-Syt3 as a lipid-dependent regulator of epithelial secretion.

    Evidence siRNA knockdown, domain deletion mutants, PtdSer biosensor, electrophysiology (CFTR/NBCe1-B currents), in vitro lipid transfer, mouse gland secretion assays

    PMID:40425857

    Open questions at the time
    • Whether E-Syt3 transfers PtdSer to the same ER pool as DAG not established
    • Relative contribution of E-Syt3 vs. E-Syt2 in native epithelia not resolved
  14. 2025 Medium

    Syt3 KO exacerbated sevoflurane-induced neonatal cognitive impairment and neuroinflammation, while CRISPR-mediated Syt3 overexpression was protective, linking Syt3 to neuroprotection against anesthetic neurotoxicity beyond its role in forgetting.

    Evidence Syt3 KO mice, CRISPR activation overexpression, Western blot/ELISA for inflammatory markers, behavioral testing

    PMID:40890917

    Open questions at the time
    • Molecular mechanism connecting Syt3 to neuroinflammation not defined
    • Single lab; whether effect is GluA2-dependent or independent not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: (1) how classical Syt3 and E-Syt3 functions are coordinated in cells that express both, (2) the identity of the protease(s) cleaving E-Syt3 in adipocytes, (3) whether Syt3's presynaptic role as a GABAergic Ca²⁺ sensor generalizes beyond entopeduncular terminals, and (4) the upstream Ca²⁺ source and adaptor proteins linking Syt3 to the endocytic machinery at postsynaptic sites.
  • Presynaptic Ca²⁺-sensor role from single preprint only
  • No structural data for E-Syt3 full-length or SMP domain
  • Therapeutic applicability of Syt3–GluA2 disruption peptide not validated in clinical models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0140104 molecular carrier activity 2 GO:0140299 molecular sensor activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3 GO:0005768 endosome 1 GO:0005811 lipid droplet 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-112316 Neuronal System 3 R-HSA-1430728 Metabolism 3 R-HSA-382551 Transport of small molecules 1
Partners
CXCR4ESYT1ESYT2GRIA2STX1ASYT10SYT5SYT6
Complex memberships
E-Syt heteromeric complex (E-Syt1/2/3)Syt3 disulfide-linked homo/heterodimer

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 SYT3 (Syt3) was identified as a third member of the synaptotagmin family in mouse brain, retaining the characteristic five-domain structure (transmembrane region plus two C2 domains) of other synaptotagmins but with only ~45% amino acid identity to Syt1/Syt2 in the C2 domain. Syt3 is expressed in many regions of the nervous system but not in extraneural tissues, and in PC12 cells it is coexpressed with Syt1 at higher abundance, suggesting individual neurons may express specific synaptotagmin combinations. cDNA cloning, Northern blot, immunohistochemistry, in situ hybridization Proceedings of the National Academy of Sciences of the United States of America Medium 8058779
1995 The first C2 domain of Syt III (but not the C2 domain of Syt IV, VI, or VIII) binds phospholipids in a Ca2+-dependent manner with EC50 = 3–6 µM, similar to Syt I and II. Syt III also binds syntaxin in a Ca2+-dependent manner, but with a lower Ca2+ concentration dependence (<10 µM) than Syt I, II, and V (>200 µM), and all synaptotagmins tested bind clathrin-AP2 with high affinity (Kd = 0.1–1.0 nM). In vitro phospholipid-binding assay, Ca2+-dependent syntaxin binding assay, clathrin-AP2 binding assay Nature High 7791877
1999 Syt III forms beta-mercaptoethanol-sensitive homodimers and heterodimers with Syt V, VI, and X via three conserved N-terminal cysteine residues (C10, C21, C33 in mouse Syt III). Site-directed mutagenesis showed that the first cysteine (C10) is essential for stable homodimer formation of Syt III, V, and VI, and for heterodimer formation among Syt III, V, VI, and X. Native Syt III from mouse brain also forms these disulfide-linked homodimers. Site-directed mutagenesis, co-immunoprecipitation, SDS-PAGE under reducing/non-reducing conditions, native brain protein analysis The Journal of biological chemistry High 10531343
2007 E-Syt3 (extended synaptotagmin-3) is an ER-resident transmembrane protein with three C-terminal C2 domains. Its C2C domain (the most C-terminal C2 domain) functions as a targeting motif directing E-Syt3 to the plasma membrane independently of its transmembrane region. E-Syt2 and E-Syt3 localize to the plasma membrane in transfected cells, unlike E-Syt1 which localizes to intracellular membranes. Transfection of myc-tagged constructs, immunofluorescence microscopy, domain deletion analysis Proceedings of the National Academy of Sciences of the United States of America Medium 17360437
2010 The crystal structure of Ca2+-bound Syt3 in complex with the SNARE complex was determined and revealed that the Ca2+-binding loops of Syt3 point away from the SNARE complex, suggesting they may interact with the same membrane. This loop arrangement is similar to that inferred from smFRET-derived models of the Syt1-SNARE complex, supporting a conserved mechanism by which synaptotagmin-SNARE interaction aids Ca2+-triggered fusion. X-ray crystallography (crystal structure of SNARE-induced Ca2+-bound Syt3), single-molecule FRET Nature structural & molecular biology High 20173763
2011 A lipid-binding screen using the C2AB fragment of Syt3 revealed Ca2+-independent lipid interactions mediated via a lysine-rich region of the C2B domain and Ca2+-dependent interactions via the Ca2+-binding loops, consistent with a conserved lipid-binding mechanism shared with Syt1. Lipid binding screen (protein-lipid overlay and liposome binding assays) with recombinant C2AB fragments, mass spectrometry Biochemistry Medium 21928778
2013 E-Syt2 and E-Syt3 function as ER-PM tethers through C2 domain-dependent interactions with the plasma membrane that require PI(4,5)P2. E-Syts form heteromeric complexes with each other, and through this heterodimerization, E-Syt1 (which also requires elevated cytosolic Ca2+) confers Ca2+ regulation to ER-PM contact formation. E-Syt-dependent contacts are functionally distinct from STIM1/Orai1-mediated contacts and are not required for store-operated Ca2+ entry. Co-immunoprecipitation, fluorescence microscopy, PI(4,5)P2 manipulation (pharmacological and genetic), Ca2+ imaging, TIRF microscopy Cell High 23791178
2016 E-Syt3 (along with E-Syt1 and E-Syt2) transfers glycerolipids between bilayers in vitro in a Ca2+-dependent manner requiring their SMP domain. Cells lacking all E-Syts show enhanced and sustained accumulation of plasma membrane diacylglycerol following PLC activation (PtdIns(4,5)P2 hydrolysis), demonstrating that E-Syts participate in homeostatic control of PM lipid composition by transferring diacylglycerol from the PM to the ER for metabolic recycling. In vitro lipid transfer assay, genome-edited E-Syt knockout cells, diacylglycerol imaging (DAG biosensor), rescue experiments with SMP-domain mutants Nature cell biology High 27065097
2016 Combined inactivation of all three E-Syt genes (E-Syt1, 2, and 3) in mice does not affect viability, fertility, or development under laboratory conditions, but induces compensatory upregulation of Orp5/8, Orai1, STIM1, and TMEM110 genes encoding other ER-PM junction proteins. Triple knockout mouse generation (insertion/deletion mutations), phenotypic analysis, gene expression analysis Cell cycle (Georgetown, Tex.) Medium 27399837
2017 RASSF4 regulates the ER-PM tethering function of E-Syt2 and E-Syt3 by controlling steady-state PM PI(4,5)P2 levels through ARF6-dependent regulation of type I PIP5Ks. RASSF4 knockdown reduces PM PI(4,5)P2, which is required for E-Syt2/3 localization at ER-PM junctions. siRNA knockdown, PI(4,5)P2 biosensor imaging, TIRF microscopy, RASSF4-ARF6 interaction analysis The Journal of cell biology Medium 28600435
2006 SYT3 is the only synaptotagmin expressed in T cells. SYT3 localizes predominantly to multivesicular bodies (not the plasma membrane) where it colocalizes with CXCR4. Knockdown of SYT3 by antisense mRNA or blockade by the isolated C2B domain (which impairs oligomerization) inhibits CXCR4 recycling back to the cell surface, reduces surface CXCR4 levels, and consequently inhibits CXCL12-induced T cell migration and actin polymerization. Overexpression of CXCR4 rescues migration, confirming the mechanism is through receptor recycling. Antisense mRNA knockdown, C2B domain overexpression, immunofluorescence microscopy, flow cytometry (surface CXCR4), chemotaxis assay, actin polymerization assay Journal of cell science Medium 17179206
2018 Syt3 localizes to postsynaptic endocytic zones in neurons and removes AMPA receptors (specifically GluA2-containing) from synaptic plasma membranes in a Ca2+-dependent manner in response to stimulation. Syt3 knockout abolishes AMPA receptor internalization, long-term depression (LTD), and decay of long-term potentiation (LTP). Disrupting the Syt3:GluA2 interaction using a TAT-GluA2-3Y peptide mimics the Syt3 KO phenotype (lack of LTP decay and lack of forgetting in spatial memory tasks), and these effects are occluded in the Syt3 KO, confirming direct mechanistic linkage. Syt3 knockout mice, immunofluorescence localization, AMPA receptor internalization assay, LTD and LTP electrophysiology, TAT-GluA2-3Y peptide competition, Morris water maze and spatial memory tasks Science (New York, N.Y.) High 30545844
2020 Hypothalamic E-Syt3 (extended synaptotagmin-3) contributes to diet-induced obesity. Whole-body or POMC neuron-specific ablation of E-Syt3 ameliorates diet-induced obesity, glucose intolerance, and dyslipidemia. Mechanistically, E-Syt3 ablation leads to increased processing of POMC to α-MSH, increased PKC and AP-1 activities, and enhanced expression of prohormone convertases. Conversely, E-Syt3 overexpression in the arcuate nucleus promotes food intake and impairs energy expenditure. Conditional KO (whole-body and POMC-neuron-specific), AAV-mediated overexpression, Western blot, ELISA, metabolic phenotyping, kinase activity assays Proceedings of the National Academy of Sciences of the United States of America Medium 32747560
2021 In differentiating adipocytes, E-Syt3 undergoes proteolytic cleavage of its C-terminal C2C domain by a proteasome-dependent multi-step mechanism. Truncated E-Syt3ΔC2C and endogenous E-Syt3 localize to a specialized ER cisterna (termed the 'primordial cisterna') that serves as the birth site of lipid droplets. Knockdown of E-Syt3 inhibits lipid droplet biogenesis in adipocytes. Confocal microscopy, live-cell time-lapse imaging, proteasome inhibition, siRNA knockdown, electron microscopy, 3D electron tomography Traffic (Copenhagen, Denmark) Medium 34693607
2023 Syt3 is upregulated in the penumbra after ischemia/reperfusion injury. Mechanistically, I/R injury augments Syt3-GluA2 interactions, decreases GluA2 surface expression, and promotes formation of Ca2+-permeable AMPA receptors (CP-AMPARs). Syt3 knockout mice are resistant to cerebral ischemia due to high surface GluA2 and low CP-AMPAR levels. Disrupting Syt3-GluA2 binding via TAT-GluA2-3Y peptide promotes recovery from neurological impairments. Syt3 KO mice, siRNA knockdown/overexpression, co-immunoprecipitation (Syt3-GluA2), surface biotinylation assay, TAT-GluA2-3Y peptide, MCAO model, behavioral testing Cell reports High 36892998
2025 E-Syt3 controls epithelial ion transport by transferring phosphatidylserine (PtdSer) away from ER/PM junction nanodomains, acting antagonistically to ORP5 (which supplies PtdSer). Removal of PtdSer from junctions by E-Syt3 dissociates the cAMP signaling complex, preventing CFTR chloride channel activation and blocking NBCe1-B activation by IRBIT. The C2C domain of E-Syt3 restricts its localization to ER/PM junctions, and lipid transfer activity requires the SMP domain. E-Syt3 depletion in mice improves chloride flux and fluid secretion in salivary glands and pancreatic ducts. SiRNA knockdown, domain deletion mutants, PtdSer biosensor, co-immunoprecipitation, electrophysiology (CFTR and NBCe1-B currents), mouse gland secretion assays, in vitro lipid transfer The EMBO journal High 40425857
2024 In zebrafish Mauthner cells, syt3 (ortholog of mammalian SYT3) negatively regulates axon regeneration after spinal cord injury, and this suppression depends on Ca2+ binding by Syt3. MicroRNA-2184 promotes axon regeneration by repressing syt3 expression. Pharmacological stimulation of the cAMP/PKA pathway suggests changes in the readily releasable pool may underlie the Syt3-dependent suppression of regeneration. Single M-cell miR-2184 overexpression/sponge silencing, syt3 knockdown/overexpression in zebrafish, Ca2+-binding mutant analysis, cAMP/PKA pathway pharmacology, axon regeneration imaging Journal of genetics and genomics Medium 38582297
2025 Syt3 knockout mice exposed to neonatal sevoflurane show exacerbated cognitive impairment, increased neuroinflammation (IL-1β, TNF-α, MCP-1), and increased anxiety-like behavior compared to WT mice. Conversely, CRISPR-mediated Syt3 overexpression in WT mice mitigates sevoflurane-induced cognitive deficits and neuroinflammation. Sevoflurane exposure itself reduces hippocampal Syt3 protein levels in WT mice. Syt3 KO mice, CRISPR activation overexpression, Western blot/ELISA for Syt3 and inflammatory markers, object location memory, novel object recognition, elevated plus maze ACS chemical neuroscience Medium 40890917
2026 In EPN neurons projecting to the lateral habenula, Syt3 is highly expressed and selectively co-localizes with VGAT (GABAergic vesicle marker) rather than VGLUT2, and antisense oligonucleotide knockdown of Syt3 increases mIPSC frequency (quantal GABA release probability) without affecting glutamate release, establishing Syt3 as the predominant Ca2+ sensor for GABAergic vesicle fusion at these dual-transmitter terminals. Confocal 3D reconstruction, antisense oligonucleotide knockdown, whole-cell patch-clamp electrophysiology (mEPSC and mIPSC recording) bioRxivpreprint Medium 41959127

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1995 Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins. Nature 552 7791877
2013 PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins. Cell 476 23791178
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. EMBO reports 281 11256614
2016 Control of plasma membrane lipid homeostasis by the extended synaptotagmins. Nature cell biology 207 27065097
2000 The C terminus of SNAP25 is essential for Ca(2+)-dependent binding of synaptotagmin to SNARE complexes. The Journal of biological chemistry 191 10692432
2010 Single-molecule FRET-derived model of the synaptotagmin 1-SNARE fusion complex. Nature structural & molecular biology 164 20173763
2007 E-Syts, a family of membranous Ca2+-sensor proteins with multiple C2 domains. Proceedings of the National Academy of Sciences of the United States of America 156 17360437
2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome research 151 11230166
1999 Conserved N-terminal cysteine motif is essential for homo- and heterodimer formation of synaptotagmins III, V, VI, and X. The Journal of biological chemistry 151 10531343
1996 Localization of synaptotagmin-binding domains on syntaxin. The Journal of neuroscience : the official journal of the Society for Neuroscience 141 8604041
2003 Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. Neuron 109 12526776
2018 Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting. Science (New York, N.Y.) 104 30545844
1994 A third synaptotagmin gene, Syt3, in the mouse. Proceedings of the National Academy of Sciences of the United States of America 88 8058779
2000 SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms. The Journal of biological chemistry 83 10734137
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2021 Synaptotagmins at the endoplasmic reticulum-plasma membrane contact sites maintain diacylglycerol homeostasis during abiotic stress. The Plant cell 61 33944955
2001 Genomic analysis of synaptotagmin genes. Genomics 58 11543631
2017 RASSF4 controls SOCE and ER-PM junctions through regulation of PI(4,5)P2. The Journal of cell biology 57 28600435
2022 NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia. Nature immunology 46 36138187
2004 From ORFeome to biology: a functional genomics pipeline. Genome research 38 15489336
2016 Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility. Cell cycle (Georgetown, Tex.) 34 27399837
2006 The LIFEdb database in 2006. Nucleic acids research 29 16381901
2020 SUMOylation of DDX39A Alters Binding and Export of Antiviral Transcripts to Control Innate Immunity. Journal of immunology (Baltimore, Md. : 1950) 27 32393512
2011 Post-translational modifications and lipid binding profile of insect cell-expressed full-length mammalian synaptotagmin 1. Biochemistry 27 21928778
2021 Identification of Biomarkers Related to CD8+ T Cell Infiltration With Gene Co-expression Network in Lung Squamous Cell Carcinoma. Frontiers in cell and developmental biology 23 33816462
2017 Extended Synaptotagmin 1 Interacts with Herpes Simplex Virus 1 Glycoprotein M and Negatively Modulates Virus-Induced Membrane Fusion. Journal of virology 22 29046455
2024 Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions. Neuron 20 39079530
2019 Synaptotagmins: Beyond Presynaptic Neurotransmitter Release. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 20 31046622
2010 Developmental expression of Synaptotagmin isoforms in single calyx of Held-generating neurons. Molecular and cellular neurosciences 19 20470891
2006 Synaptotagmin 3 deficiency in T cells impairs recycling of the chemokine receptor CXCR4 and thereby inhibits CXCL12 chemokine-induced migration. Journal of cell science 19 17179206
2020 Hypothalamic extended synaptotagmin-3 contributes to the development of dietary obesity and related metabolic disorders. Proceedings of the National Academy of Sciences of the United States of America 17 32747560
2024 Impaired neuronal macroautophagy in the prelimbic cortex contributes to comorbid anxiety-like behaviors in rats with chronic neuropathic pain. Autophagy 15 38522078
2023 Synaptotagmin-3 interactions with GluA2 mediate brain damage and impair functional recovery in stroke. Cell reports 15 36892998
2022 LukS-PV inhibits hepatocellular carcinoma cells migration by downregulating HDAC6 expression. BMC cancer 14 35676659
2019 Oral administration of heat-killed Lactobacillus brevis SBC8803 elevates the ratio of acyl/des-acyl ghrelin in blood and increases short-term food intake. Beneficial microbes 14 31190555
2013 SYT14L, especially its C2 domain, is involved in regulating melanocyte differentiation. Journal of dermatological science 14 23999003
2024 Cerebrovascular miRNAs Track Early Development of Alzheimer's Disease and Target Molecular Markers of Angiogenesis and Blood Flow Regulation. Journal of Alzheimer's disease : JAD 12 37458037
2023 Integrated GWAS and transcriptomic analysis reveal the candidate salt-responding genes regulating Na+/K+ balance in barley (Hordeum vulgare L.). Frontiers in plant science 7 36777542
1995 Synaptotagmin genes on mouse chromosomes 1, 7, and 10 and human chromosome 19. Mammalian genome : official journal of the International Mammalian Genome Society 5 7749232
2024 Using expression data to fine map QTL associated with fertility in dairy cattle. Genetics, selection, evolution : GSE 4 38844868
2022 Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4). Human molecular genetics 4 35640156
2021 The E-Syt3 cleavage and traffic uncovers the primordial cisterna, a new organelle that mothers the lipid droplets in the adipocyte. Traffic (Copenhagen, Denmark) 4 34693607
2012 PLXNC1 and RDH13 associated with bilateral convergent strabismus with exophthalmus in German Brown cattle. Molecular vision 3 22933835
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 Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions. The EMBO journal 1 40425857
2025 Synaptotagmin III Plays a Protective Role in Neonatal Multiple Sevoflurane Exposure-Induced Cognitive Deficits in Mice. ACS chemical neuroscience 1 40890917
2025 Insights Into the Antigenic Repertoire of Unclassified Synaptic Antibodies. Annals of clinical and translational neurology 1 41195642
2024 microRNA-2184 orchestrates Mauthner-cell axon regeneration in zebrafish via syt3 modulation. Journal of genetics and genomics = Yi chuan xue bao 1 38582297
2023 Neuronal Scaffold Protein ARMS Interacts with Synaptotagmin-4 C2AB through the Ankyrin Repeat Domain with an Unexpected Mode. International journal of molecular sciences 1 38069318
2026 Restricting Synaptotagmin-3 Internalization Mitigates Cerebral Ischemia/Reperfusion Injury by Curtailed Neuronal Apoptosis and Microglial Re-Programming. CNS neuroscience & therapeutics 0 41787472
2026 Tethers and Transporters: The Molecular Fingerprint of Plant ER-PM Contact Sites. Journal of experimental botany 0 41796074
2026 Synaptotagmin isoforms differentially regulate glutamate and GABA release in the lateral habenula. bioRxiv : the preprint server for biology 0 41959127
2025 Effects of Electroacupuncture on Syt3 and GluA2 in Rats With Limb Spasms After Intracerebral Hemorrhage. Brain and behavior 0 40021946