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FLASH GENE
Symbol STXBP1 contributors: mlm/pgu/m - updated : 02-11-2016
HGNC name syntaxin binding protein 1
HGNC id 11444
Corresponding disease
EIEE4 epileptic encephalopathy, early infantile, 4
Location 9q34.11      Physical location : 130.374.485 - 130.454.995
Synonym name
  • protein unc-18 homolog A
  • protein unc-18 homolog 1
  • neuronal SEC1
  • Synonym symbol(s) UNC18, UNC18-1, Munc18A, rbSec1, MUNC18-1, UNC18A, FLJ37475
    DNA
    TYPE functioning gene
    STRUCTURE 80.51 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    ANGPTL2 9q34 angiopoietin-like 2 DKFZp761J1523 9q34.13 hypothetical protein DKFZp761J1523 SLC2A8 9q34.1-q34.2 solute carrier family 2, (facilitated glucose transporter) member 8 ZNF79 9q34.1 zinc finger protein 79 (pT7) RPL12 9q34 ribosomal protein L12 LRSAM1 9q34.13 leucine rich repeat and sterile alpha motif containing 1 DKFZP434H0820 9q34.13 hypothetical protein DKFZp434H0820 STXBP1 9q34.1 syntaxin binding protein 1 LOC286207 9q34.13 hypothetical protein LOC286207 LOC138428 9q34.13 hypothetical protein LOC138428 TTC16 9q34.13 tetratricopeptide repeat domain 16 TOR2A 9q34.11 torsin family 2, member A SH2D3C 9q34.13 SH2 domain containing 3C CDK9 9q34.1 cyclin-dependent kinase 9 (CDC2-related kinase) FPGS 9cen-q34.11 folylpolyglutamate synthase ENG 9q34.1 endoglin (Osler-Rendu-Weber syndrome 1) AK1 9q34.12 adenylate kinase 1 ST6GALNAC6 9q34.13 adenylate kinase 1 SIAT7D 9q34.1 sialyltransferase 7D ((alpha-N-acetylneuraminyl-2,3-beta-galactosyl-1,3)-N-acetyl galactosaminide alpha-2,6-sialyltransferase) MGC46424 9q34.13 hypothetical protein MGC46424 LOC389790 9 similar to phosphatidylinositol phosphate kinase-like protein DPM2 9q34.13 dolichyl-phosphate mannosyltransferase polypeptide 2, regulatory subunit FLJ10232 9q34.13 hypothetical protein FLJ10232 DKFZp762G199 9q34.13 hypothetical protein DKFZp762G199 MCSC 9q34.13 mitochondrial Ca2+-dependent solute carrier PTGES2 9q34.13 prostaglandin E synthase 2 LOC389791 9 hypothetical gene supported by AK094537 LCN2 9q34 lipocalin 2 (oncogene 24p3) C9orf16 9q34.1 chromosome 9 open reading frame 16
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 splicing 3850 67.4 594 widely across cytosolic and synaptosomal compartments 2015 26628003
  • also called m-tymosin
  • M18S isoform
  • 20 splicing 3976 68.6 603 neural tissues, localized to the synaptosomal fraction, with a distribution matching lipid raft microdomains 2015 26628003
  • also called b-tymosin
  • additional exon
  • M18L isoform
  • lower M18L in inhibitory presynaptic terminals may be an early, independent contributor to cognitive decline
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal glandmedulla    Homo sapiens
     pancreas   moderately Homo sapiens
    Nervousbrainhindbraincerebellum predominantly
     nerve   highly
    Visualeyeretina  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion in the sperm
    at STAGE
    physiological period fetal
    Text moderately in umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a domain-1 controling vesicle docking and secretion by interacting with syntaxin-1 and chaperoning it to the plasma membrane
  • a domain 3a, playing a crucial role in priming of exocytosis, which is independent of its STX1A chaperoning activity and is downstream of dense-core vesicle docking
  • HOMOLOGY
    interspecies homolog to rattus Stxbp1 (100 pc)
    homolog to murine Stxbp1 (99.5 pc)
    homolog to C.Elegans Unc
    Homologene
    FAMILY
  • STXBP/UNC-18/sec1 family
  • CATEGORY chaperone/stress , signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • membrane-associated
  • highly enriched in axons
  • protein molecules move between membrane molecular depots distinct from vesicle docking sites
  • basic FUNCTION
  • soluble N ethylmaleimide-sensitive factor-attachment protein receptor, SNARE protein, involved in neurotransmission
  • regulates synaptic vesicle release, at least in part, by binding to syntaxin 1A (STX1A) as well as to the SNARE complex directly
  • expressed in an estrogen-dependent manner, plays an important role in the onset of female puberty via the regulation of glutamate release
  • participating in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins
  • involved in the regulation of SNARE complex-dependent membrane fusion events implicated in the ramification of axonal processes in neurons
  • may play a role in determining the specificity of intracellular fusion reactions
  • controling multiple stages of exocytosis via both syntaxin-dependent and -independent protein interactions
  • plays a positive role in regulated insulin secretion from pancreatic beta cells
  • has a chaperone function in neurons, promoting anterograde transport of the plasma membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein Syntaxin-1
  • acts as a molecular chaperone for Syntaxin transport in neurons and the two modes of STXBP1 binding to Syntaxin are involved in different aspects of STXBP1 function
  • controls the accessibility of STX1A to its partners, a role that might be common to all SM proteins (Sec1/Munc18-like)
  • participates in the establishment of the membrane fusion pore, a step that is thought to occur after complete zipping of the SNARE complex
  • UNC13A, STXBP1 regulate early neurite outgrowth
  • acting at specific steps of intracellular membrane transport
  • required for the first phase of insulin secretion
  • indirectly promotes STX4-based granule docking and exocytosis to support the first phase of insulin secretion
  • key role for STXBP1 in first-phase exocytotic processes relevant to the maintenance of whole-body glucose homeostasis
  • has an essential role in acrosomal exocytosis
  • plays a key role in the dynamics of trans-SNARE complex assembly and/or stabilization, a process that is necessary for the docking of the outer acrosomal membrane to the plasma membrane and subsequent fusion pore opening
  • STXBP1 plays a dual role in transporting syntaxin-1A (STX1A) to the plasma membrane and regulating SNARE-mediated membrane fusion
  • promotes the zippering of trans-SNARE complexes and accelerates the kinetics of SNARE-dependent membrane fusion
  • cell death upon STXBP1, STX1A, or SNAP25 loss occurs via a degenerative pathway unrelated to the known synapse function of these proteins and involving early cis-Golgi abnormalities, distinct from apoptosis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS exocytosis transport , cellular trafficking transport
    text
  • Golgi to plasma membrane transport
  • vesicle docking during exocytosis
  • PATHWAY
    metabolism
    signaling neurotransmission
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with syntaxins 1, 2, and 3
  • binding to SYTL4 and STX1A
  • interact with SNARE proteins in vesicular fusion
  • STXBP1 and SYTL4 collaborate in the docking of insulin granules to the plasma membrane in an initial fusion-incompetent state, with STXBP1 subsequently playing a positive role in a later stage of insulin granule exocytosis
  • interacting with UNC13A (mediates the transition from the closed syntaxin-STXBP1 complex to the SNARE complex)
  • indirect role for STXBP1 in facilitating STX4-mediated granule pre-docking to support first-phase insulin exocytosis
  • STXBP1 is a central regulator of neurotransmitter release, interacting with STX1A and APBA1
  • DYRK1A interacts with and phosphorylates STXBP1 at the Thr(479) residue, linking STXBP1 and DYRK1A in synaptic vesicle trafficking and amyloid precursor protein processing
  • requirement of UNC13A for lipid mixing of STX1STXBP1 liposomes with synaptobrevin liposome
  • displaces SNAP25 from STX1
  • resulting STXBP1UNC13A-SNARE assembly underlies the primed state that enables fast membrane fusion through the action of synaptotagmin-1 and Ca2+
  • PTPRT could regulate the interaction of STXBP1 with STX1A, and as a result, the synaptic vesicle fusion appeared to be controlled through dephosphorylation of STXBP1
  • interact with PTPRT, and dephosphorylation of its tyrosine residue by PTPRT was attributed to its interaction with STX1A
  • RAB27A-SYTL4 complex on WPB (Weibel-Palade body) promotes exocytosis through an interaction with STXBP1, thereby controlling the release of vaso-active substances in the vasculature
  • SYT1 acts as an antagonist for STXBP1 in SNARE zippering and fusion pore opening
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EIEE4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    truncating/splacing mutation,
    constitutional     --over  
    in pancreatic islets enhances first-phase insulin release, the phase most commonly associated with early onset of islet dysfunction in the course of diabetes disease progression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Stxbp1 knock-out mice