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FLASH GENE
Symbol STXBP5 contributors: mct - updated : 12-09-2015
HGNC name syntaxin binding protein 5 (tomosyn)
HGNC id 19665
Location 6q24.3      Physical location : 147.525.507 - 147.708.707
Synonym name
  • tomosyn 1
  • putative protein product of Nbla04300
  • lethal(2) giant larvae protein homolog 3
  • tomosyn-1
  • Synonym symbol(s) FLJ30922, LGL3, LLGL3, MGC141942, MGC141968, Nbla04300
    DNA
    TYPE functioning gene
    STRUCTURE 184.95 kb     28 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC391978 6 similar to ZNF131 protein EPM2A 6q24.3 epilepsy, progressive myoclonus type 2A, Lafora disease (laforin) FBXO30 6q24 F-box protein 30 SHPRH 6q24.2 SNF2 histone linker PHD RING helicase GRM1 6q24 glutamate receptor, metabotropic 1 RAB32 6q24.3 RAB32, member RAS oncogene family LOC389431 6 similar to hypothetical protein 9130014G24 STXBP5 6q24.3 syntaxin binding protein 5 (tomosyn) LOC391979 6 similar to yes-associated protein 2 LOC389432 6 similar to RIKEN cDNA E130306M17 gene SASH1 6q24.3 similar to RIKEN cDNA E130306M17 gene LOC340151 6q24.3 similar to laminin receptor 1 (ribosomal protein SA); P40-3, functional; P40-8, functional; laminin receptor 1 (67kD, ribosomal protein SA) UST 6q24.3-q25.1 uronyl-2-sulfotransferase MAP3K7IP2 6q25.1-q25.3 mitogen-activated protein kinase kinase kinase 7 interacting protein 2 LOC340152 6q24.3 similar to hypothetical protein D730019B10 PPIL4 6q24-q25 peptidylprolyl isomerase (cyclophilin)-like 4 C6orf72 6q24.3 chromosome 6 open reading frame 72 LOC389433 6 LOC389433 KATNA1 6q25.1 katanin p60 (ATPase-containing) subunit A 1 LATS1 6q24-q25.1 LATS, large tumor suppressor, homolog 1 (Drosophila) NUP43 6q24.3 nucleoporin 43kDa PCMT1 6q22.3-q24 protein-L-isoaspartate (D-aspartate) O-methyltransferase LRP11 6q24.3 low density lipoprotein receptor-related protein 11 RAET1E 6q25 retinoic acid early transcript 1E
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    28 - 6433 130 1151 - 1999 10066450
    26 - 6325 123 1115 - 1999 10066450
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly Homo sapiens
    Nervousbrainforebraincerebral cortexfrontal  Homo sapiens
     spinal cord     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiens
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal half with a WD-repeat motif, homologous to several beta-propeller -like protein, also having potent inhibitory activity toward Ca2+-dependent neurotransmitter release, although the molecular mechanism underlying this effect remains elusive
  • C-terminal domain homologous to the SNARE motif of synaptobrevin, a coil -coiled, VAMP-homology domain, acting as a SNARE domain that competes with VAMP2
  • HOMOLOGY
    interspecies homolog to rattus M-tomosyn
    homolog to Drosophila lethal(Z) giant larvae
    ortholog to yeast Sro7
    Homologene
    FAMILY
  • WD repeat L(2)GL family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • synapse and synaptosome
  • associates with synaptic vesicles through the N-terminal WD40 repeats
  • basic FUNCTION
  • involved in neurotransmitter release by stimulating SNARE complex formation
  • inhibiting the priming step and impairing the efficiency of vesicle pool refilling in a calcium-dependent manner
  • neural tissue-specific syntaxin-1-binding protein, which is capable of dissociating STXBP1 from syntaxin-1 to form a 10S tomosyn complex
  • involved in a post-docking event that prepares secretory granules for fusion and is necessary to sustain exocytosis of pancreatic beta-cells in response to insulin secretagogues
  • inhibits SNARE complex formation and neurotransmitter release by sequestering syntaxin-1 through its C-terminal vesicle-associated membrane protein (VAMP)-like domain (VLD)
  • negative regulator of neurotransmitter release, that inhibit SNARE complex formation by sequestering target SNAREs (VTI1A) upon interaction of its C-terminal VAMP-like domain with VTI1A
  • may be controling synaptic vesicle fusion positively by serving as a placeholder for VAMP2
  • negatively regulates Ca2+-dependent neurotransmitter release by sequestering target SNAREs through the C-terminal VAMP-like domain
  • multiple domains outside the R-SNARE of STXBP5 are critical to the efficacy of inhibition by tomosyn on exocytotic secretion
  • syntaxin-binding protein, known to inhibit vesicle priming and synaptic transmission via interference with the formation of SNARE complexes
  • roles for tomosyn1 in hippocampus-dependent spatial learning and memory
  • facilitates granule release from platelets, but it inhibits secretion from the Weibel-Palade bodies (WPBs) of endothelial cells
  • is required for normal arterial hemostasis, due to its contributions to platelet granule cargo packaging and secretion
  • inhibits endothelial exocytosis but promotes platelet secretion
  • STXBP5L and STXBP5 regulate docking and fusion of synaptic vesicles with the presynaptic membrane, a process of crucial importance for normal neurotransmission
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with SNAP-25, syntaxin, synaptotagmin
  • STXBP5–SNARE complex has been believed to be a dead-end complex to inhibit neurotransmitter release
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding partner of Syntaxin 1, and this interaction was shown to reduce Ca2+-dependent exocytosis mediated through Syntaxin 1
  • N-terminal WD40 repeats directly bind to syntaxin-1 and SNAP-25, thereby catalyzing oligomerization of the SNARE complex
  • SYT1 binding enhances the target SNARE-sequestering activity of STXBP5
  • interplay between STXBP5 and synaptotagmin-1 underlies inhibitory control of Ca2+-dependent neurotransmitter release
  • STXBP5 interacts with core secretion machinery complexes, such as syntaxin-11/SNAP23 heterodimers, and likely STXBP5 also interacts with the platelet cytoskeleton
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in a patient with autism, intellectual disability and seizures
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice lacking Stxbp5 had higher levels of vWF in the plasma, increased P-selectin translocation, and more platelet-endothelial interactions