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Calcium sensor that participates in triggering neurotransmitter release at the synapse. May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. Plays a role in dendrite formation by melanocytes.
基因功能參考文獻:
The present study replicates previously suggested association of the SYT1-rs2251214 SNP with ADHD in adults. PMID: 28130000
The MD simulations revealed that all peptides induced significant Syt1 rigidity by binding in the cleft of the C2A-C2B interface. The consequence of this binding event is the suppression of the protein motion associated with conformational change of Syt1 from the closed form to the open form. PMID: 29019108
Although both otoferlin and synaptotagmin bind membrane fusion SNARE proteins, only otoferlin interacts with the L-type calcium channel Cav1.3. PMID: 28696301
Circular oligomerization is an intrinsic property of SYT1. PMID: 28850328
that reduction in the synaptotagmin 1 level and presenilin 1-synaptotagmin 1 interactions in AD brain may present molecular underpinning of the pathogenic presenilin 1 conformation PMID: 28193235
findings show extended Synaptotagmi1 (E-Syt1), along with related E-Syt3, negatively modulates viral release into the extracellular milieu, cell-to-cell viral spread and viral entry, processes that implicate membrane fusion events; , these E-Syt proteins impacted formation of virus-induced syncytia; findings hint at the modulation of the viral fusion machinery by the E-Syt family of proteins PMID: 29046455
Using electron microscopy combined with targeted mutations, the authors show that under physiologically relevant conditions, both the Syt1 ring assembly and its rapid disruption by Ca(2+) involve the well-established functional surfaces on the C2B domain that are important for synaptic transmission. PMID: 27434670
This study found that the CSF levels of synaptotagmin-1 were consistently elevated in patients with dementia due to Alzheimer's disease. PMID: 27716408
SYT-SSX fusion is associated with synovial sarcoma. PMID: 27621063
the extended synaptotagmins (E-Syts), endoplasmic reticulum (ER) proteins that function as PtdIns(4,5)P2- and Ca(2+)-regulated tethers to the Pplasma membrane. PMID: 27065097
Data indicate that small protein sequence changes in the Ca(2+)-binding loops of the C2 domains may give rise to the difference in binding kinetics between Syt-1 and Syt-7 isoforms. PMID: 27997124
These findings identify Syt1 as a novel Ca(2+)-sensitive PS1 modulator that could regulate synaptic ABETA, opening avenues for novel and selective synapse targeting therapeutic strategies. PMID: 27036734
One-Step reverse transcriptase real time PCR for the detection SYT-SSX transcript is feasible as an aid in confirming the diagnosis of synovial sarcoma. PMID: 27126659
membrane tethering by E-Syt1 (ER to PM) and by synaptotagmin (secretory vesicles to PM) undergo a similar regulation by plasma membrane lipids and cytosolic Ca(2+). PMID: 26202220
A dominant negative de novo SYT1 missense variant(I368T)altered the kinetics of synaptic vesicle endocytosis and caused an early onset dyskinetic movement disorder, severe motor delay, and profound cognitive impairment. PMID: 25705886
Data suggest that calcium-dependent phosphatidylinositol 4,5-diphosphate- (PI(4,5)P2-) binding proteins (such as SYT1, PRKCA [protein kinase C alpha], and ANXA2 [annexin A2]) interactions with membrane microdomains are tightly regulated. [REVIEW] PMID: 25233429
Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements. PMID: 24505276
Hydrophobic interactions play a key role in Syt1 binding botulinum neurotoxin DC. PMID: 23932591
Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1. PMID: 24302762
synaptotagmin-1 is involved in a rapid vesicular Ca(2) sequestration through a Ca(2)/H antiport PMID: 23607712
PRIP inhibits regulated exocytosis through the interaction of its C2 domain with syntaxin 1 and SNAP-25, potentially competing with accessory proteins such as synaptotagmin I and by directly inhibiting trans-SNARE complex formation PMID: 23341457
Characterization of negative coupling interaction between the C2 domains of Syt I. PMID: 23071627
The mechanistic basis for C2A domain of synaptotagmin I's response to Ca(2+) and cellular function stems from marginal stability and ligand-induced redistributions of protein conformers. PMID: 22853901
The membrane dissociation of SYT7 C2A domain but not SYT1 C2A domain is slowed by Na(2)SO(4) and trehalose, solutes that enhance the hydrophobic effect. PMID: 22966849
Together with synaptotagmin 1, complexin synchronizes and stimulates rapid fusion of accumulated docked vesicles in response to physiological Ca(2+) concentrations. PMID: 22705946
The calcium binding site to the C2A domain of SYT1 has been identified; this SYT1 domain activates exocytosis of secretory vesicles during neurotransmitter release. PMID: 22475172
association between serum creatinine level and polymorphisms in the collagen type XXII alpha 1 (COL22A1) gene, on chromosome 8, and in the synaptotagmin-1 (SYT1) gene, on chromosome 12 PMID: 20222955
NMR characterization of copper and lipid interactions of the C2B domain of synaptotagmin I-relevance to the non-classical secretion of the human acidic fibroblast growth factor (hFGF-1). PMID: 19835837
intestinal epithelial Syt 1 plays an important role in cAMP-stimulated endocytosis of apical NHE3 through cAMP-dependent phosphorylation of S605 that is required for NHE3 and Syt 1 association PMID: 19926819
synaptotagmin-I expressing neuroblastoma cells require gangliosides for Botulinum neurotoxin A activity PMID: 12089155
both synaptotagmins I and II can interact with the syntaxin/synaptosomal-associated protein of 25 kDa (SNAP-25) dimer PMID: 14709554
Syt I mediates cAMP- and Ca(2+)-induced endocytosis of NHE3 through cargo recognition of NHE3 and subsequent recruitment of AP2-clathrin assembly required for membrane endocytosis. PMID: 17307723
The shared interface between C2A and C2B is stabilized by a network of interactions between residues on the C-terminal alpha-helix of the C2B domain and residues on loops 1-3 of the Ca2+-binding region of C2A. PMID: 17956130
These findings provide new information in the epileptogenesis of refractory epilepsy, and suggest that Synaptotagmin I might be involved in human refractory epilepsy. PMID: 18779938
mechanical stability of the C2A and C2B domains of human Syt1 PMID: 19186144
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A SYT1 rare mutation has been found in a child with a severe neuro-developmental disorder. The individual harboring this variant shows early onset dyskinetic movement disorder, severe motor delay and profound cognitive impairment, suggesting that SYT1 may play a role in the pathogenesis of this neuro-developmental disorder.