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FLASH GENE
Symbol SYT1 contributors: shn/npt/pgu - updated : 02-02-2014
HGNC name synaptotagmin I
HGNC id 11509
Location 12q21.2      Physical location : 79.257.772 - 79.845.787
Synonym symbol(s) SYT, SYTG1, P65, SVP65, DKFZp781D2042, FLJ37297, BRAMY2015503
DNA
TYPE functioning gene
STRUCTURE 588.02 kb     12 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map cen - D12S350 - D12S326 - SYT1 - D12S106 - D12S1708 - qter
Authors 4st Workshop chrom.12 (97)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
12 splicing 4841 - 422 neuron-specific 1995 7624059
11 splicing 4827 - 422 neuron-specific 1995 7624059
10 splicing 4427 - 422 neuron-specific 1995 7624059
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineneuroendocrinepituitary  moderately
Nervousbrainforebraincerebral cortexfrontalhighly
 brainlimbic systemhippocampus highly Mus musculus
 brainhindbraincerebellum highly Mus musculus
Reproductivefemale systembreastmammary gland moderately
Visualeyeretina    Mus musculus
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscular   moderately
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an intravesicular N terminal domain
  • a single transmembrane (TM) region
  • two protein kinase C-homologous repeats (Ca2+ binding domains C2), C2A and C2B domains(the binding of Ca(2+) to the C2A domain activates the exocytosis of secretory vesicles, while the binding of inositol polyphosphates (IP4-IP6) to the C2B domain inhibits this process )
  • a conserved WHXL motif in the C terminus
  • conjugated GlycoP , LipoP
    mono polymer homomer , heteromer , tetramer , complex
    HOMOLOGY
    interspecies ortholog to Syt1, Rattus norvegicus
    ortholog to Syt1, Mus musculus
    ortholog to SYT1, Pan troglodytes
    Homologene
    FAMILY
  • synaptotagmin family
  • CATEGORY structural protein , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus
    text
  • membrane of synaptic vesicle
  • chromaffin granules
  • basic FUNCTION
  • a calcium sensor on the synaptic vesicle surface
  • acting as a calcium regulator of neurotransmitter release at the central synapse to initiate signal transduction
  • Ca2+ sensor for fast synchronous neurotransmitter release in forebrain neurons and chromaffin cells
  • involved in exocytosis and endocytosis, selectively required for the fast synchronous component of exocytosis, but not for the delayed, asynchronous component
  • acting as a transcriptional coactivator with SNF/SWI complex characterized as a chromatin remodeling factor enhancing accessibility of the transcriptional machinery to DNA within a repressive chromatin structure
  • mediating FGF1 release
  • may have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse
  • Ca2+ sensor for fast neurotransmitter release, functioning by Ca2+-dependent phospholipid binding and/or by Ca2+-dependent soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex binding
  • Ca(2+)-binding motif of the C(2)B domain of synaptotagmin 1 essential for synaptic transmission
  • is necessary for the endocytosis of synaptic vesicles
  • triggers the fusion of docked vesicles by local Ca2+-dependent buckling of the plasma membrane together with the zippering of SNAREs
  • involved in neurite outgrowth, early neuronal cell development, neuropeptide signaling/synthesis and neuronal receptor
  • Syt1 controls both evoked and spontaneous release of neurotransmitter quanta at a synapse as a simultaneous Ca2+-dependent activator and clamp of exocytosis
  • modulates lipid acyl chain order in lipid bilayers by demixing phosphatidylserine
  • functions as a dual Ca(2+) sensor for both endo- and exocytosis, potentially coupling these two components of the vesicle cycle
  • importance of an asymmetric distribution of acidic lipids for synaptotagmin 1 function as a Ca2+ sensor
  • may be a Ca2+ sensors for spontaneous release
  • is necessary for the Ca++ dependence of clathrin-mediated endocytosis
  • synaptic vesicle membrane protein that serves as a multifunctional regulator during the exocytosis of neurotransmitter release
  • with SYT1, CPLX1 synchronizes and stimulates rapid fusion of accumulated docked vesicles in response to physiological Ca(2+) concentrations
  • in neurotransmission SYT1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS nervous system , exocytosis transport , endocytosis transport
    text Ca(2+) sensor in the process of vesicular trafficking and exocytosis
    PATHWAY
    metabolism
    signaling neurotransmission , signal transduction
    a component
  • multifunctional intrinsic membrane protein of synaptic vesicles of neurons and chromaffin granules
  • forming a complex with SV2B, syntaxin 1 and SNAP25
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+ (3 ions per subunit, via the C2 domain)
  • protein
  • transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha), TFAP2A
  • syntaxin 1A, STX1A
  • cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel, CACNA1A
  • S100 calcium binding protein A13, S100A13 (PMID :
  • Fibroblast growth factor 1, FGF1
  • regulating synaptic membrane exocytosis 1, RIMS1
  • zinc finger, DHHC-type containing 17, ZDHHC17 also known as HIP14
  • synaptic vesicle glycoprotein 2B, SV2B
  • intestinal epithelial SYT1 plays an important role in cAMP-stimulated endocytosis of apical SLC9A3 through cAMP-dependent phosphorylation of S605 that is required for NHE3 and SYT1 association
  • CPLX1, CPLX2 facilitate and inhibit neurotransmitter release through distinct domains, and their function was proposed to be coupled to the Ca(2+) sensor synaptotagmin-1 (SYT1)
  • interplay between STXBP5 and SYT1 underlies inhibitory control of Ca2+-dependent neurotransmitter release
  • binds SNARE complexes before Ca(2+) influx into presynaptic nerve terminals
  • SYT1 acts as an antagonist for STXBP1 in SNARE zippering and fusion pore opening
  • is a novel Ca(2+)-sensitive PSEN1 modulator that could regulate synaptic APP opening avenues for novel and selective synapse targeting therapeutic strategies
  • cell & other
  • acidic phospholipids via the first C2 domain
  • REGULATION
    repressed by
  • synaptic vesicle glycoprotein 2B, SV2B
  • ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with SSX1(C terminal region) in synovial sarcoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • deletions of Syt1 produce increases in spontaneous mini release in Drosophila neuromuscular junctions
  • introduction by homologous recombination the endogenous synaptotagmin I gene with a point mutation in mice led to a decrease of the Ca2+ sensitivity of neurotransmitter release twofold
  • in cultured cortical neurons stimulated at low frequency, deletion of synaptotagmin 1 blocks synchronous GABA and glutamate release without significantly increasing asynchronous release