SNAP25

Synaptosomal-associated protein, 25kDa
PDB rendering based on 1jth.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1KIL, 1XTG, 3DDA, 3DDB, 3RK2, 3RK3, 3RL0, 3ZUR
Identifiers
Symbols	SNAP25; RIC-4; RIC4; SEC9; SNAP; SNAP-25; bA416N4.2; dJ1068F16.2
External IDs	OMIM: 600322 MGI: 98331 HomoloGene: 13311 GeneCards: SNAP25 Gene
Gene Ontology Molecular function • SNARE binding • protein binding Cellular component • cytoplasm • trans-Golgi network • plasma membrane • membrane • cell junction • growth cone • BLOC-1 complex • SNARE complex • neuron projection • synapse • perinuclear region of cytoplasm • synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex Biological process • neurotransmitter uptake • energy reserve metabolic process • synaptic transmission • neurotransmitter secretion • glutamate secretion • synaptic vesicle docking involved in exocytosis • small molecule metabolic process • regulation of insulin secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6616	20614
Ensembl	ENSG00000132639	ENSMUSG00000027273
UniProt	P60880	P60879
RefSeq (mRNA)	NM_003081	NM_011428
RefSeq (protein)	NP_003072	NP_035558
Location (UCSC)	Chr 20: 10.2 – 10.29 Mb	Chr 2: 136.71 – 136.78 Mb
PubMed search
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Synaptosomal-associated protein 25 (SNAP-25) is a t-SNARE protein that is encoded by the SNAP25 gene in humans.^[2] SNAP-25 is a component of the trans-SNARE complex, which is proposed to account for the specificity of membrane fusion and to directly execute fusion by forming a tight complex that brings the synaptic vesicle and plasma membranes together.^[3]

Structure and function

SNAP-25 is a membrane bound protein anchored to the cytosolic face of membranes via palmitoyl side chains in the middle of the molecule. SNAP-25 is a Q-SNARE protein contributing two α-helices in the formation of the exocytotic fusion complex in neurons where it assembles with syntaxin-1 and synaptobrevin. SNAP-25 inhibits P/Q- and L-type voltage-gated calcium channels located presynaptically^[4] and interacts with the synaptotagmin C2B domain in Ca²⁺-independent fashion.^[5] In glutamatergic synapses SNAP-25 decreases the Ca²⁺ responsiveness, while it is naturally absent in GABAergic synapses.^[6]

SNAP-25 family Structure of a SNARE complex involved in synaptic exocytosis. Identifiers Symbol SNAP-25 Pfam PF00835 InterPro IPR000928 SCOP 1sfc SUPERFAMILY 1sfc Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Molecular machinery driving exocytosis in neuromediator release. The core SNARE complex is formed by four α-helices contributed by synaptobrevin, syntaxin and SNAP-25, synaptotagmin serves as a Ca2+ sensor and regulates intimately the SNARE zipping.[1]

Clinical significance

Consistent with the regulation of synaptic Ca²⁺ responsiveness, heterozygous deletion of the SNAP-25 gene in mice results in a hyperactive phenotype similar to attention deficit hyperactivity disorder (ADHD). In heterozygous mice, a decrease in hyperactivity is observed with dextroamphetamine (or Dexedrine), an active ingredient in the ADHD drug Adderall. Homozygous deletions of the SNAP-25 gene are lethal. Subsequent studies have suggested that at least some of the SNAP-25 gene mutations in humans might predispose to ADHD.^[7][8]

A genome wide association study pointed to the rs362584 polymorphism in the gene as possibly associated with the personality trait neuroticism.^[9] Botulinum toxins A, C and E cleave SNAP-25^[10] leading to paralysis in clinically developed botulism.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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Nicotine Activity on Dopaminergic Neurons edit

1. ↑ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602". 

Interactions

SNAP-25 has been shown to interact with STX4,^{[11][12][13][14]} STX2,^[11][12] Syntaxin 3,^[11][12][14] STX1A,^{[11][12][14][15][16][17][18][19][20][21][22]} KIF5B,^[23] TRIM9,^[20] STX11,^[15][24] CPLX1,^[22][25] SYT1,^[26][27] VAMP2,^[20][22][28] SNAPAP^[19] and ITSN1.^[29]

References

Further reading

External links

• SNAP25 Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

v t e PDB gallery 1jth: Crystal structure and biophysical properties of a complex between the N-terminal region of SNAP25 and the SNARE region of syntaxin 1a  1kil: Three-dimensional structure of the complexin/SNARE complex  1n7s: High Resolution Structure of a Truncated Neuronal SNARE Complex  1sfc: NEURONAL SYNAPTIC FUSION COMPLEX  1urq: CRYSTAL STRUCTURE OF NEURONAL Q-SNARES IN COMPLEX WITH R-SNARE MOTIF OF TOMOSYN  1xtg: Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25

This article incorporates text from the public domain Pfam and InterPro IPR000928