SNAP-25

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Synaptosomal-associated protein, 25kDa
250px
PDB rendering based on 1jth.
Available structures
PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB
Identifiers
Symbols SNAP25 ; FLJ23079; RIC-4; RIC4; SEC9; SNAP; SNAP-25; bA416N4.2; dJ1068F16.2
External IDs OMIM: 600322 MGI98331 HomoloGene13311
RNA expression pattern
File:PBB GE SNAP25 202508 s at tn.png
File:PBB GE SNAP25 202507 s at tn.png
More reference expression data
Orthologs

| | bgcolor="#C3FDB8" | Human | bgcolor="#C3FDB8" | Mouse |-

    | bgcolor="#C3FDB8" | Entrez 
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| 6616
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| 20614

|-

     | bgcolor="#C3FDB8" | Ensembl
     | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| ENSG00000132639
     | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| ENSMUSG00000027273

|-

    | bgcolor="#C3FDB8" | Uniprot
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| P60880
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| P60879

|-

    | bgcolor="#C3FDB8" | Refseq
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd" | NM_003081 (mRNA)
NP_003072 (protein)
| bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd" |NM_011428 (mRNA)
NP_035558 (protein)

|-

    | bgcolor="#C3FDB8" | Location
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"|  Chr 20: 10.15 - 10.24 Mb 
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"|  Chr 2: 136.4 -  136.47 Mb 

|-

|-

    | bgcolor="#C3FDB8" | Pubmed search 
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| [1]
| bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| [2]
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

SNAP-25 (synaptosome-associated protein of 25,000 daltons) 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 [1] and interacts with the synaptotagmin C2B domain in Ca2+-independent fashion [2]. In glutamatergic synapses SNAP-25 decreases the Ca2+ responsiveness, while it is naturally absent in GABAergic synapses [3].

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 [4][5].

Botulinum toxins A, C and E cleave SNAP-25 [6] leading to paralysis in clinically developed botulism.

File:Exocytosis-machinery.jpg
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.


References

  1. Hodel A (1998). "SNAP-25". The International Journal of Biochemistry & Cell Biology. 30 (10): 1069–1073.
  2. Chapman ER (2002). "Synaptotagmin: A Ca2+ sensor that triggers exocytosis?". Nature Reviews Molecular Cell Biology. 3: 498–508. External link in |title= (help)
  3. Pozzi D, Verderio C, Patti L, Grumelli C, Inverardi F, Frassoni C, Bonanno G, Matteoli M (2004). "SNAP-25 modulation of calcium dynamics underlies differences in GABAergic and glutamatergic responsiveness to depolarization". Neuron. 41 (4): 599–610. External link in |title= (help)
  4. Brophy K, Hawi Z, Kirley A, Fitzgerald M, Gill M (2002). "Synaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity disorder (ADHD): evidence of linkage and association in the Irish population". Molecular Psychiatry. 7 (8): 913–917.
  5. Mill J, Curran S, Kent L, Gould A, Huckett L, Richards S, Taylor E, Asherson P (2002). "Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder". American Journal of Medical Genetics. 114 (3): 269–271.
  6. Aoki KR, Guyer B (2001). "Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions". European Journal of Neurology. 8: 21–29.

Further reading

  • Hanson PI, Otto H, Barton N, Jahn R (1995). "The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin". J. Biol. Chem. 270 (28): 16955–61. PMID 7622514.
  • Hata Y, Südhof TC (1995). "A novel ubiquitous form of Munc-18 interacts with multiple syntaxins. Use of the yeast two-hybrid system to study interactions between proteins involved in membrane traffic". J. Biol. Chem. 270 (22): 13022–8. PMID 7768895.
  • Chapman ER, An S, Barton N, Jahn R (1994). "SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils". J. Biol. Chem. 269 (44): 27427–32. PMID 7961655.
  • Zhao N, Hashida H, Takahashi N, Sakaki Y (1994). "Cloning and sequence analysis of the human SNAP25 cDNA". Gene. 145 (2): 313–4. PMID 8056350.
  • Bark IC, Wilson MC (1994). "Human cDNA clones encoding two different isoforms of the nerve terminal protein SNAP-25". Gene. 139 (2): 291–2. PMID 8112622.
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
  • Maglott DR, Feldblyum TV, Durkin AS, Nierman WC (1996). "Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p)". Mamm. Genome. 7 (5): 400–1. PMID 8661740.
  • Ravichandran V, Chawla A, Roche PA (1996). "Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues". J. Biol. Chem. 271 (23): 13300–3. PMID 8663154.
  • Rettig J, Sheng ZH, Kim DK; et al. (1996). "Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25". Proc. Natl. Acad. Sci. U.S.A. 93 (14): 7363–8. PMID 8692999.
  • Jagadish MN, Fernandez CS, Hewish DR; et al. (1996). "Insulin-responsive tissues contain the core complex protein SNAP-25 (synaptosomal-associated protein 25) A and B isoforms in addition to syntaxin 4 and synaptobrevins 1 and 2". Biochem. J. 317 ( Pt 3): 945–54. PMID 8760387.
  • Betz A, Okamoto M, Benseler F, Brose N (1997). "Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin". J. Biol. Chem. 272 (4): 2520–6. PMID 8999968.
  • Araki S, Tamori Y, Kawanishi M; et al. (1997). "Inhibition of the binding of SNAP-23 to syntaxin 4 by Munc18c". Biochem. Biophys. Res. Commun. 234 (1): 257–62. doi:10.1006/bbrc.1997.6560. PMID 9168999.
  • Lane SR, Liu Y (1997). "Characterization of the palmitoylation domain of SNAP-25". J. Neurochem. 69 (5): 1864–9. PMID 9349529.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K; et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. PMID 9373149.
  • Okamoto M, Südhof TC (1998). "Mints, Munc18-interacting proteins in synaptic vesicle exocytosis". J. Biol. Chem. 272 (50): 31459–64. PMID 9395480.
  • Low SH, Roche PA, Anderson HA; et al. (1998). "Targeting of SNAP-23 and SNAP-25 in polarized epithelial cells". J. Biol. Chem. 273 (6): 3422–30. PMID 9452464.
  • Poirier MA, Hao JC, Malkus PN; et al. (1998). "Protease resistance of syntaxin.SNAP-25.VAMP complexes. Implications for assembly and structure". J. Biol. Chem. 273 (18): 11370–7. PMID 9556632.
  • Prekeris R, Klumperman J, Chen YA, Scheller RH (1998). "Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes". J. Cell Biol. 143 (4): 957–71. PMID 9817754.
  • Gonelle-Gispert C, Halban PA, Niemann H; et al. (1999). "SNAP-25a and -25b isoforms are both expressed in insulin-secreting cells and can function in insulin secretion". Biochem. J. 339 ( Pt 1): 159–65. PMID 10085240.
  • Ilardi JM, Mochida S, Sheng ZH (1999). "Snapin: a SNARE-associated protein implicated in synaptic transmission". Nat. Neurosci. 2 (2): 119–24. doi:10.1038/5673. PMID 10195194.

External links


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