SNAP25

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Synaptosomal-associated protein, 25kDa
Protein SNAP25 PDB 1jth.png
PDB rendering based on 1jth.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SNAP25 ; RIC-4; RIC4; SEC9; SNAP; SNAP-25; bA416N4.2; dJ1068F16.2
External IDs OMIM600322 MGI98331 HomoloGene13311 GeneCards: SNAP25 Gene
RNA expression pattern
PBB GE SNAP25 202508 s at tn.png
PBB GE SNAP25 202507 s at tn.png
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 [1] [2]

Synaptosomal-associated protein 25 (SNAP-25) is a t-SNARE protein that is encoded by the SNAP25 gene in humans.[1] 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.[2]

Structure and function[edit]

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[3] and interacts with the synaptotagmin C2B domain in Ca2+-independent fashion.[4] In glutamatergic synapses SNAP-25 decreases the Ca2+ responsiveness, while it is naturally absent in GABAergic synapses.[5]

SNAP-25 family
PDB 1sfc EBI.jpg
Structure of a SNARE complex involved in synaptic exocytosis.
Identifiers
Symbol SNAP-25
Pfam PF00835
InterPro IPR000928
SCOP 1sfc
SUPERFAMILY 1sfc
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.[6]

Clinical significance[edit]

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[edit]

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[edit]

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[edit]

  1. ^ Maglott DR, Feldblyum TV, Durkin AS, Nierman WC (May 1996). "Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p)". Mamm. Genome 7 (5): 400–1. doi:10.1007/s003359900120. PMID 8661740. 
  2. ^ Sudhof TC, Rizo J (2002). "Snares and Munc18 in synaptic vesicle fusion". Nat Rev Neurosci 3 (8): 641–653. doi:10.1038/nrn898. PMID 12154365. 
  3. ^ Hodel A (October 1998). "SNAP-25". Int. J. Biochem. Cell Biol. 30 (10): 1069–73. doi:10.1016/S1357-2725(98)00079-X. PMID 9785471. 
  4. ^ Chapman ER (July 2002). "Synaptotagmin: a Ca(2+) sensor that triggers exocytosis?". Nat. Rev. Mol. Cell Biol. 3 (7): 498–508. doi:10.1038/nrm855. PMID 12094216. [dead link]
  5. ^ Verderio C, Pozzi D, Pravettoni E, Inverardi F, Schenk U, Coco S, Proux-Gillardeaux V, Galli T, Rossetto O, Frassoni C, Matteoli M (February 2004). "SNAP-25 modulation of calcium dynamics underlies differences in GABAergic and glutamatergic responsiveness to depolarization". Neuron 41 (4): 599–610. doi:10.1016/S0896-6273(04)00077-7. PMID 14980208. 
  6. ^ Georgiev, Danko D .; James F . Glazebrook (2007). "Subneuronal processing of information by solitary waves and stochastic processes". In Lyshevski, Sergey Edward. Nano and Molecular Electronics Handbook. Nano and Microengineering Series. CRC Press. pp. 17–1–17–41. ISBN 978-0-8493-8528-5. 
  7. ^ 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". Mol. Psychiatry 7 (8): 913–7. doi:10.1038/sj.mp.4001092. PMID 12232787. 
  8. ^ Mill J, Curran S, Kent L, Gould A, Huckett L, Richards S, Taylor E, Asherson P (April 2002). "Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder". Am. J. Med. Genet. 114 (3): 269–71. doi:10.1002/ajmg.10253. PMID 11920846. 
  9. ^ Terracciano A, Sanna S, Uda M, Deiana B, Usala G, Busonero F, Maschio A, Scally M, Patriciu N, Chen WM, Distel MA, Slagboom EP, Boomsma DI, Villafuerte S, Sliwerska E, Burmeister M, Amin N, Janssens AC, van Duijn CM, Schlessinger D, Abecasis GR, Costa PT (October 2008). "Genome-wide association scan for five major dimensions of personality". Mol. Psychiatry 15 (6): 647–56. doi:10.1038/mp.2008.113. PMC 2874623. PMID 18957941. 
  10. ^ Aoki KR, Guyer B (November 2001). "Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions". Eur. J. Neurol. 8 Suppl 5: 21–9. doi:10.1046/j.1468-1331.2001.00035.x. PMID 11851731. 
  11. ^ a b c d Hata, Y; Südhof T C (June 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. (UNITED STATES) 270 (22): 13022–8. doi:10.1074/jbc.270.22.13022. ISSN 0021-9258. PMID 7768895. 
  12. ^ a b c d Ravichandran, V; Chawla A, Roche P A (June 1996). "Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues". J. Biol. Chem. (UNITED STATES) 271 (23): 13300–3. doi:10.1074/jbc.271.23.13300. ISSN 0021-9258. PMID 8663154. 
  13. ^ Reed, G L; Houng A K, Fitzgerald M L (April 1999). "Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion". Blood (UNITED STATES) 93 (8): 2617–26. ISSN 0006-4971. PMID 10194441. 
  14. ^ a b c Steegmaier, M; Yang B, Yoo J S, Huang B, Shen M, Yu S, Luo Y, Scheller R H (Dec 1998). "Three novel proteins of the syntaxin/SNAP-25 family". J. Biol. Chem. (UNITED STATES) 273 (51): 34171–9. doi:10.1074/jbc.273.51.34171. ISSN 0021-9258. PMID 9852078. 
  15. ^ a b Stelzl, Ulrich; Worm Uwe, Lalowski Maciej, Haenig Christian, Brembeck Felix H, Goehler Heike, Stroedicke Martin, Zenkner Martina, Schoenherr Anke, Koeppen Susanne, Timm Jan, Mintzlaff Sascha, Abraham Claudia, Bock Nicole, Kietzmann Silvia, Goedde Astrid, Toksöz Engin, Droege Anja, Krobitsch Sylvia, Korn Bernhard, Birchmeier Walter, Lehrach Hans, Wanker Erich E (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell (United States) 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. ISSN 0092-8674. PMID 16169070. 
  16. ^ Dulubova, I; Sugita S, Hill S, Hosaka M, Fernandez I, Südhof T C, Rizo J (August 1999). "A conformational switch in syntaxin during exocytosis: role of munc18". EMBO J. (ENGLAND) 18 (16): 4372–82. doi:10.1093/emboj/18.16.4372. ISSN 0261-4189. PMC 1171512. PMID 10449403. 
  17. ^ McMahon, H T; Missler M, Li C, Südhof T C (October 1995). "Complexins: cytosolic proteins that regulate SNAP receptor function". Cell (UNITED STATES) 83 (1): 111–9. doi:10.1016/0092-8674(95)90239-2. ISSN 0092-8674. PMID 7553862. 
  18. ^ Gonelle-Gispert, C; Molinete M, Halban P A, Sadoul K (September 2000). "Membrane localization and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells". J. Cell. Sci. (ENGLAND) 113 (18): 3197–205. ISSN 0021-9533. PMID 10954418. 
  19. ^ a b Ilardi, J M; Mochida S, Sheng Z H (February 1999). "Snapin: a SNARE-associated protein implicated in synaptic transmission". Nat. Neurosci. (UNITED STATES) 2 (2): 119–24. doi:10.1038/5673. ISSN 1097-6256. PMID 10195194. 
  20. ^ a b c Li, Y; Chin L S, Weigel C, Li L (November 2001). "Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis". J. Biol. Chem. (United States) 276 (44): 40824–33. doi:10.1074/jbc.M106141200. ISSN 0021-9258. PMID 11524423. 
  21. ^ Chapman, E R; An S, Barton N, Jahn R (November 1994). "SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils". J. Biol. Chem. (UNITED STATES) 269 (44): 27427–32. ISSN 0021-9258. PMID 7961655. 
  22. ^ a b c Chen, Xiaocheng; Tomchick Diana R, Kovrigin Evguenii, Araç Demet, Machius Mischa, Südhof Thomas C, Rizo Josep (January 2002). "Three-dimensional structure of the complexin/SNARE complex". Neuron (United States) 33 (3): 397–409. doi:10.1016/S0896-6273(02)00583-4. ISSN 0896-6273. PMID 11832227. 
  23. ^ Diefenbach, Russell J; Diefenbach Eve, Douglas Mark W, Cunningham Anthony L (Dec 2002). "The heavy chain of conventional kinesin interacts with the SNARE proteins SNAP25 and SNAP23". Biochemistry (United States) 41 (50): 14906–15. doi:10.1021/bi026417u. ISSN 0006-2960. PMID 12475239. 
  24. ^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  25. ^ Hu, Kuang; Carroll Joe, Rickman Colin, Davletov Bazbek (November 2002). "Action of complexin on SNARE complex". J. Biol. Chem. (United States) 277 (44): 41652–6. doi:10.1074/jbc.M205044200. ISSN 0021-9258. PMID 12200427. 
  26. ^ Gerona, R R; Larsen E C, Kowalchyk J A, Martin T F (March 2000). "The C terminus of SNAP25 is essential for Ca(2+)-dependent binding of synaptotagmin to SNARE complexes". J. Biol. Chem. (UNITED STATES) 275 (9): 6328–36. doi:10.1074/jbc.275.9.6328. ISSN 0021-9258. PMID 10692432. 
  27. ^ Zhang, Xiaodong; Kim-Miller Mindy J, Fukuda Mitsunori, Kowalchyk Judith A, Martin Thomas F J (May 2002). "Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis". Neuron (United States) 34 (4): 599–611. doi:10.1016/S0896-6273(02)00671-2. ISSN 0896-6273. PMID 12062043. 
  28. ^ Hao, J C; Salem N, Peng X R, Kelly R B, Bennett M K (March 1997). "Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes". J. Neurosci. (UNITED STATES) 17 (5): 1596–603. ISSN 0270-6474. PMID 9030619. 
  29. ^ Okamoto, M; Schoch S, Südhof T C (June 1999). "EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis?". J. Biol. Chem. (UNITED STATES) 274 (26): 18446–54. doi:10.1074/jbc.274.26.18446. ISSN 0021-9258. PMID 10373452. 

Further reading[edit]

External links[edit]


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