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FLASH GENE

Symbol

SNAP25

contributors: mct - updated : 12-01-2017

HGNC name	synaptosomal-associated protein, 25kDa
HGNC id	11132

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003081 8 splicing 2053 NP_003072 23.3 206 - 2015 20519516 SNAP25-A variant 1 NM_130811 8 splicing 2053 NP_570824 - 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 NM_001322907 10 - 2357 NP_001309836 - 206 - 2015 20519516 NM_001322910 9 - 2254 NP_001309839 - 206 - 2015 20519516 NM_001322904 9 - 2199 NP_001309833 - 206 - 2015 20519516 NM_001322903 8 - 2229 NP_001309832 - 206 - 2015 20519516 NM_001322906 9 - 2156 NP_001309835 - 206 - 2015 20519516 NM_001322908 10 - 2280 NP_001309837 - 206 - 2015 20519516 NM_001322905 9 - 2162 NP_001309834 - 206 - 2015 20519516 NM_001322909 9 - 2147 NP_001309838 - 206 - 2015 20519516 NM_001322902 - - 2133 NP_001309831 - 206 - 2010 20519516

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine adrenal gland cortex     moderately Homo sapiens   pancreas       moderately Homo sapiens Hearing/Equilibrium ear       highly Nervous brain diencephalon hypothalamus   highly Homo sapiens   brain hindbrain cerebellum     Visual eye       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Homo sapiens Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	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

HOMOLOGY

intraspecies

homolog to SNAP23 (60 p100)

Homologene

FAMILY	SNAP-25 family
	soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNARE) protein family

CATEGORY

structural protein , receptor , transport

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,vesicle
text	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

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

exocytosis transport

PATHWAY

metabolism

signaling

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

INTERACTION

DNA

RNA

small molecule

protein	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

REGULATION

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

ASSOCIATED DISORDERS

corresponding disease(s)

CMS18

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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

Susceptibility

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
Marker	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

ANIMAL & CELL MODELS

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