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Symbol SNAP25 contributors: mct - updated : 12-01-2017
HGNC name synaptosomal-associated protein, 25kDa
HGNC id 11132
Corresponding disease
CMS18 myasthenic syndrome, congenital, 18
Location 20p12.2      Physical location : 10.199.476 - 10.288.065
Synonym name
  • resistance to inhibitors of cholinesterase 4 homolog
  • super protein
  • Synonym symbol(s) D20S140E, SNAP, FLJ23079, RIC-4, RIC4, SEC9, dJ1068F16.2, bA416N4.2, CMS18, RIC-4, SNAP-25, SUP
    TYPE functioning gene
    STRUCTURE 88.73 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • promoter contains functional SP1 response elements, and over-expression of SP1 increased SNAP25 gene expression and inhibition of SP1-mediated transcriptional activation reduced SNAP-25 gene expression
  • MAPPING cloned Y linked N status provisional
    Map pter - D20S175 - D20S162 - D20S505 - SNAP25 - D20S160 - D20S507 - JAG1 - D20S894 - D20S188 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 splicing 2053 23.3 206 - 2015 20519516
  • SNAP25-A variant 1
  • 8 splicing 2053 - 206 - 2015 20519516
  • SNAP25B
  • an alternate exon 5
  • DHHC15 promoted a statistically significant increase in membrane association of only SNAP25b
  • contains a minimal membrane targeting sequence that is located between AAs 85 and 120
  • 10 - 2357 - 206 - 2015 20519516
    9 - 2254 - 206 - 2015 20519516
    9 - 2199 - 206 - 2015 20519516
    8 - 2229 - 206 - 2015 20519516
    9 - 2156 - 206 - 2015 20519516
    10 - 2280 - 206 - 2015 20519516
    9 - 2162 - 206 - 2015 20519516
    9 - 2147 - 206 - 2015 20519516
    - - 2133 - 206 - 2010 20519516
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal glandcortex  moderately Homo sapiens
     pancreas   moderately Homo sapiens
    Hearing/Equilibriumear   highly
    Nervousbraindiencephalonhypothalamus highly Homo sapiens
    Visualeye   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • a central membrane targeting module including a palmitoylated cysteine cluster with four cysteines , and this cysteine-rich domain is designed to facilitate the dual function of this SNARE protein at the plasma membrane and endosomes
  • an additional five AA motif required for membrane anchoring
  • two T-SNARE coiled-coil homology domains
  • positively charged AAs at the SNAP25 C terminus promote tight SNARE complex zippering and are required for high release frequency and rapid release in individual fusion events
  • secondary structure two alpha helices contributing to the four helix bundle of the synaptic SNARE complex
    conjugated LipoP , MetalloP
    intraspecies homolog to SNAP23 (60 p100)
  • SNAP-25 family
  • soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNARE) protein family
  • CATEGORY structural protein , receptor , transport
    SUBCELLULAR LOCALIZATION     plasma membrane
  • fusion of plasma membrane to synaptic vesicles
  • pre-synaptic plasma membrane protein
  • axonally distributed
  • membrane association of all SNAP25/23 proteins is enhanced by Golgi-localized DHHC3, DHHC7, and DHHC17
  • peripheral membrane protein
  • basic FUNCTION
  • soluble N ethylmaleimide-sensitive factor-attachment protein receptor, SNARE protein
  • may play an important role in the synaptic function of specific neuronal systems
  • plays an important role in synaptic vesicle membrane docking and fusion, which is involved in the regulation of neurotransmitter release
  • involved in presynaptic neurotransmitter release
  • participates in synaptic vesicle exocytosis through the formation of a SNARE complex and also plays a pivotal role in modulating calcium homeostasis through negative regulation of voltage-gated calcium channels
  • heterogeneous distribution in brain may have important implications not only in relation to the function of the protein as a SNARE but also in the control of network excitability
  • having essential functions in presynaptic neurotransmitter release
  • play essential roles as SNARE proteins in membrane fusion events that occur at the plasma membrane
  • essential for synaptic vesicle release from presynaptic nerve terminals
  • regulates native voltage-gated calcium channels in glutamatergic neurons which could have important implications for neurological diseases associated with altered SNAP25 expression
  • peripheral membrane protein, and palmitoylation of a cluster of four cysteine residues mediates its stable association with the membrane
  • encodes a presynaptic protein with a role in regulation of neurotransmitter release
  • might represent the first description of an adaptively evolving gene with a role in cognition
  • dual role of VAMP1, SNAP25, STX1A in exo- and endocytosis suggests that SNARE proteins may be molecular substrates contributing to the exocytosis-endocytosis coupling, which maintains exocytosis in secretory cells
  • is involved in slow, clathrin-dependent endocytosis
  • essential role in enteric neurotransmission suggesting that SNAP25 is a marker for impaired synaptic plasticity in enteric neuropathies underlying intestinal motility disorders
  • is a Q-SNARE protein mediating exocytosis of neurosecretory vesicles including chromaffin granules
  • is required for the exocytosis of neurotransmitters during synaptic transmission by mediating synaptic vesicle fusion
  • is a key molecule in the soluble N-ethylmaleimide-sensitive factor attachment protein (SNARE) complex mediating fast Ca(2+)-triggered release of hormones and neurotransmitters
  • 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
  • is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder
    PHYSIOLOGICAL PROCESS exocytosis transport
    a component
  • constituent of a synaptic core (SNARE) complex with syntaxin and synaptosome associated proteins
  • SNARE component of the exocytotic apparatus involved in the release of neurotransmitter
  • fundamental component of the SNARE complex responsible for vesicle fusion
  • essential component of the synaptic vesicle fusion machinery
    small molecule
  • syntaxin 1A by the membrane targeting module, t-SNARES and synaptobrevin (VAMPx) after the fusion of synaptic vesicle to plasma membrane
  • RIMS1
  • interaction between EEA1 and SNAP25 dependent on the leucine zipper and a newly identified methyl-accepting domain of EEA1
  • present at the presynaptic plasma membrane and form a complex with syntaxin 1, an additional SNARE present at the plasma membrane, and the synaptic vesicle SNARE protein VAMP2
  • interaction between the cargo-binding domain of kinesin-1 heavy chain KIF5B and the membrane-associated SNARE proteins SNAP25 and SNAP23
  • SFXN5
  • bound to the same region in ZWINT as RAB3C
  • interacting with KIF1A, KIF1B, KIF1C (facilitates the transport of SNAP25 containing vesicles as a prerequisite to SNAP25 driven membrane fusion events
  • SNAP25 interacts with STXBP1, another SNARE synaptic protein
  • interacting with DHHC proteins which may be important in dynamic remodeling of SNAP25 palmitoylation
  • the overexpression of SNAP25 completely reversed the action of ADCY6
  • interaction of ADGRV1 and SNAP25 in organ of Corti and brain
  • NCOA6 inhibits likely regulated exocytosis through the interaction of its C2 domain with STX1A and SNAP25, potentially competing with other SNARE-binding, C2 domain-containing accessory proteins such as SYT1 and by directly inhibiting trans-SNARE complex formation
  • dual role of SNAP25 and VAMP1 in both exocytosis and slow endocytosis at conventional synapses
  • SNAP25 likely allows the organization of the molecular apparatus needed for spine formation by recruiting and stabilizing SRCIN1
  • SNAPIN, a SNAP25 interacting protein, interacts with LRRK2
  • FOXC1 regulates the expression of RAB3GAP1, RAB3GAP2 and SNAP25, three genes with central roles in both exocytosis and endocytosis, responsible for extracellular trafficking
  • cell & other
    Other palmitoylated in vivo for the binding to syntaxin
    synthesized as soluble protein and become membrane-associated via palmitoylation of its cysteine-rich domain
    dynamic palmitoylation acts as a mechanism to regulate the precise intracellular patterning of SNAP25
    phosphorylation is regulated in a stress-dependent manner through both central and peripheral mechanisms
    corresponding disease(s) CMS18
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    significant decrease in SNAP25 expression in Alzheimer disease (AD) across all the three brain regions in relation to the healthy elderly subjects, suggesting impairment in synaptic function, but no AD-associated differences in SNAP25 promoter DNA methylation were observed
    tumoral     --other  
    SH3BP5, LMO3, and SNAP25, were detected in diffuse large B-cell lymphoma
  • to attention deficit hyperactivity disorder 2 with preferential transmission of paternal alleles
  • to developmental and epileptic encephalopathy (DEE)
  • to early-onset bipolar disorder
  • Variant & Polymorphism SNP , repeat
  • SNPs (rs3746544, rs1051312) associated to attention deficit hyperactivity disorder
  • c.118A>G [p.Lys40Glu], c.127G>C [p.Gly43Arg] associated to DEE
  • promoter variant in SNAP25, rs6039769, is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex
  • Candidate gene
  • significantly higher levels of cerebrospinal fluid SNAP25 fragments in Alzheimer disease, even in the very early stages, and synaptic biomarkers may be important tools for early diagnosis, assessment of disease progression, and to monitor drug effects in treatment trials
  • Therapy target
  • Snap-25b-deficient mice fed with control diet developed hyperglycemia, liver steatosis, and adipocyte hypertrophy, conditions dramatically exacerbated when combined with the high-fat/high-sucrose diet