VAMP2

Vesicle-associated membrane protein 2 (synaptobrevin 2)
PDB rendering based on 1kil.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3FIE​, 3FII​, 3RK2​, 3RK3​, 3RL0​
Identifiers
Symbols	VAMP2 ; SYB2; VAMP-2
External IDs	OMIM: 185881 MGI: 1313277 HomoloGene: 7591 GeneCards: VAMP2 Gene
Gene ontology Molecular function • SNARE binding • SNAP receptor activity • protein binding • calmodulin binding • phospholipid binding • syntaxin-1 binding • syntaxin binding • protein self-association • calcium-dependent protein binding Cellular component • trans-Golgi network • cytosol • plasma membrane • integral component of plasma membrane • synaptic vesicle • voltage-gated potassium channel complex • membrane • cell junction • clathrin-coated vesicle • secretory granule • secretory granule membrane • synaptic vesicle membrane • SNARE complex • cytoplasmic vesicle • zymogen granule membrane • neuron projection • intracellular membrane-bounded organelle • neuron projection terminus • synapse • perinuclear region of cytoplasm • clathrin-sculpted glutamate transport vesicle membrane • clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane • synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex • synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex • synaptobrevin 2-SNAP-25-syntaxin-1a complex • extracellular exosome • clathrin-sculpted monoamine transport vesicle membrane Biological process • energy reserve metabolic process • protein complex assembly • exocytosis • post-Golgi vesicle-mediated transport • vesicle fusion • synaptic transmission • neurotransmitter secretion • response to glucose • glutamate secretion • protein transport • synaptic vesicle exocytosis • vesicle-mediated transport • calcium ion-dependent exocytosis • regulation of exocytosis • cellular response to insulin stimulus • Golgi to plasma membrane protein transport • eosinophil degranulation • neutrophil degranulation • natural killer cell degranulation • cellular protein metabolic process • small molecule metabolic process • regulation of insulin secretion • long-term synaptic potentiation • regulation of vesicle-mediated transport • membrane organization • membrane fusion • mucus secretion • positive regulation of intracellular protein transport • regulation of delayed rectifier potassium channel activity • regulation of histamine secretion by mast cell Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6844	22318
Ensembl	ENSG00000220205	ENSMUSG00000020894
UniProt	P63027	P63044
RefSeq (mRNA)	NM_014232	NM_009497
RefSeq (protein)	NP_055047	NP_033523
Location (UCSC)	Chr 17: 8.16 – 8.16 Mb	Chr 11: 69.09 – 69.09 Mb
PubMed search

Vesicle-associated membrane protein 2 is a protein that in humans is encoded by the VAMP2 gene.^[1][2]

Function

Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. VAMP2 is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. VAMP2 is thought to participate in neurotransmitter release at a step between docking and fusion. Mice lacking functional synaptobrevin2/VAMP2 gene cannot survive after birth, and have a dramatically reduced synaptic transmission, around 10% of control.^[3] The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and complexin. It also forms a distinct complex with synaptophysin.^[2]

Clinical significance

VAMP2 is a likely candidate gene for familial infantile myasthenia (FIMG) because of its map location and because it encodes a synaptic vesicle protein of the type that has been implicated in the pathogenesis of FIMG.

Interactions

VAMP2 has been shown to interact with:

• RABAC1,^[4]
• SNAP-25,^[5][6][7]
• SNAP23,^[8][9][10]
• STX1A,^{[6][7][11][12][13][14]} and
• STX4.^{[8][15][16][17]}

References

1. Archer BT, Ozçelik T, Jahn R, Francke U, Südhof TC (Oct 1990). "Structures and chromosomal localizations of two human genes encoding synaptobrevins 1 and 2". The Journal of Biological Chemistry 265 (28): 17267–73. PMID 1976629.
2. "Entrez Gene: VAMP2 vesicle-associated membrane protein 2 (synaptobrevin 2)".
3. Schoch S, Deák F, Königstorfer A, Mozhayeva M, Sara Y, Südhof TC, Kavalali ET (Nov 2001). "SNARE function analyzed in synaptobrevin/VAMP knockout mice". Science 294 (5544): 1117–22. doi:10.1126/science.1064335. PMID 11691998.
4. Martincic I, Peralta ME, Ngsee JK (Oct 1997). "Isolation and characterization of a dual prenylated Rab and VAMP2 receptor". The Journal of Biological Chemistry 272 (43): 26991–8. doi:10.1074/jbc.272.43.26991. PMID 9341137.
5. Li Y, Chin LS, Weigel C, Li L (Nov 2001). "Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis". The Journal of Biological Chemistry 276 (44): 40824–33. doi:10.1074/jbc.M106141200. PMID 11524423.
6. Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK (Mar 1997). "Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes". The Journal of Neuroscience 17 (5): 1596–603. PMID 9030619.
7. Chen X, Tomchick DR, Kovrigin E, Araç D, Machius M, Südhof TC, Rizo J (Jan 2002). "Three-dimensional structure of the complexin/SNARE complex". Neuron 33 (3): 397–409. doi:10.1016/s0896-6273(02)00583-4. PMID 11832227.
8. Paumet F, Le Mao J, Martin S, Galli T, David B, Blank U, Roa M (Jun 2000). "Soluble NSF attachment protein receptors (SNAREs) in RBL-2H3 mast cells: functional role of syntaxin 4 in exocytosis and identification of a vesicle-associated membrane protein 8-containing secretory compartment". Journal of Immunology 164 (11): 5850–7. doi:10.4049/jimmunol.164.11.5850. PMID 10820264.
9. Imai A, Nashida T, Yoshie S, Shimomura H (Aug 2003). "Intracellular localisation of SNARE proteins in rat parotid acinar cells: SNARE complexes on the apical plasma membrane". Archives of Oral Biology 48 (8): 597–604. doi:10.1016/s0003-9969(03)00116-x. PMID 12828989.
10. Kawanishi M, Tamori Y, Okazawa H, Araki S, Shinoda H, Kasuga M (Mar 2000). "Role of SNAP23 in insulin-induced translocation of GLUT4 in 3T3-L1 adipocytes. Mediation of complex formation between syntaxin4 and VAMP2". The Journal of Biological Chemistry 275 (11): 8240–7. doi:10.1074/jbc.275.11.8240. PMID 10713150.
11. Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J (Aug 1999). "A conformational switch in syntaxin during exocytosis: role of munc18". The EMBO Journal 18 (16): 4372–82. doi:10.1093/emboj/18.16.4372. PMC 1171512. PMID 10449403.
12. McMahon HT, Missler M, Li C, Südhof TC (Oct 1995). "Complexins: cytosolic proteins that regulate SNAP receptor function". Cell 83 (1): 111–9. doi:10.1016/0092-8674(95)90239-2. PMID 7553862.
13. Pérez-Brangulí F, Muhaisen A, Blasi J (Jun 2002). "Munc 18a binding to syntaxin 1A and 1B isoforms defines its localization at the plasma membrane and blocks SNARE assembly in a three-hybrid system assay". Molecular and Cellular Neurosciences 20 (2): 169–80. doi:10.1006/mcne.2002.1122. PMID 12093152.
14. Margittai M, Otto H, Jahn R (Mar 1999). "A stable interaction between syntaxin 1a and synaptobrevin 2 mediated by their transmembrane domains". FEBS Letters 446 (1): 40–4. doi:10.1016/s0014-5793(99)00028-9. PMID 10100611.
15. Mollinedo F, Martín-Martín B, Calafat J, Nabokina SM, Lazo PA (Jan 2003). "Role of vesicle-associated membrane protein-2, through Q-soluble N-ethylmaleimide-sensitive factor attachment protein receptor/R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor interaction, in the exocytosis of specific and tertiary granules of human neutrophils". Journal of Immunology 170 (2): 1034–42. doi:10.4049/jimmunol.170.2.1034. PMID 12517971.
16. Jagadish MN, Fernandez CS, Hewish DR, Macaulay SL, Gough KH, Grusovin J, Verkuylen A, Cosgrove L, Alafaci A, Frenkel MJ, Ward CW (Aug 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". The Biochemical Journal. 317 317 (3): 945–54. doi:10.1042/bj3170945. PMC 1217577. PMID 8760387.
17. Reed GL, Houng AK, Fitzgerald ML (Apr 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 93 (8): 2617–26. PMID 10194441.

Further reading

• Brumell JH, Volchuk A, Sengelov H, Borregaard N, Cieutat AM, Bainton DF, Grinstein S, Klip A (Dec 1995). "Subcellular distribution of docking/fusion proteins in neutrophils, secretory cells with multiple exocytic compartments". Journal of Immunology 155 (12): 5750–9. PMID 7499863.
• Kutay U, Ahnert-Hilger G, Hartmann E, Wiedenmann B, Rapoport TA (Jan 1995). "Transport route for synaptobrevin via a novel pathway of insertion into the endoplasmic reticulum membrane". The EMBO Journal 14 (2): 217–23. PMC 398073. PMID 7835332.
• Chapman ER, An S, Barton N, Jahn R (Nov 1994). "SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils". The Journal of Biological Chemistry 269 (44): 27427–32. PMID 7961655.
• Hunt JM, Bommert K, Charlton MP, Kistner A, Habermann E, Augustine GJ, Betz H (Jun 1994). "A post-docking role for synaptobrevin in synaptic vesicle fusion". Neuron 12 (6): 1269–79. doi:10.1016/0896-6273(94)90443-X. PMID 8011337.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Jagadish MN, Fernandez CS, Hewish DR, Macaulay SL, Gough KH, Grusovin J, Verkuylen A, Cosgrove L, Alafaci A, Frenkel MJ, Ward CW (Aug 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". The Biochemical Journal. 317 317 (3): 945–54. doi:10.1042/bj3170945. PMC 1217577. PMID 8760387.
• Mandon B, Chou CL, Nielsen S, Knepper MA (Aug 1996). "Syntaxin-4 is localized to the apical plasma membrane of rat renal collecting duct cells: possible role in aquaporin-2 trafficking". The Journal of Clinical Investigation 98 (4): 906–13. doi:10.1172/JCI118873. PMC 507504. PMID 8770861.
• Timmers KI, Clark AE, Omatsu-Kanbe M, Whiteheart SW, Bennett MK, Holman GD, Cushman SW (Dec 1996). "Identification of SNAP receptors in rat adipose cell membrane fractions and in SNARE complexes co-immunoprecipitated with epitope-tagged N-ethylmaleimide-sensitive fusion protein". The Biochemical Journal. 320 320 (2): 429–36. doi:10.1042/bj3200429. PMC 1217948. PMID 8973549.
• Betz A, Okamoto M, Benseler F, Brose N (Jan 1997). "Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin". The Journal of Biological Chemistry 272 (4): 2520–6. doi:10.1074/jbc.272.4.2520. PMID 8999968.
• Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK (Mar 1997). "Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes". The Journal of Neuroscience 17 (5): 1596–603. PMID 9030619.
• Martincic I, Peralta ME, Ngsee JK (Oct 1997). "Isolation and characterization of a dual prenylated Rab and VAMP2 receptor". The Journal of Biological Chemistry 272 (43): 26991–8. doi:10.1074/jbc.272.43.26991. PMID 9341137.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Weir ML, Klip A, Trimble WS (Jul 1998). "Identification of a human homologue of the vesicle-associated membrane protein (VAMP)-associated protein of 33 kDa (VAP-33): a broadly expressed protein that binds to VAMP". The Biochemical Journal. 333 333 (2): 247–51. doi:10.1042/bj3330247. PMC 1219579. PMID 9657962.
• Isenmann S, Khew-Goodall Y, Gamble J, Vadas M, Wattenberg BW (Jul 1998). "A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal". Molecular Biology of the Cell 9 (7): 1649–60. doi:10.1091/mbc.9.7.1649. PMC 25402. PMID 9658161.
• Prekeris R, Klumperman J, Chen YA, Scheller RH (Nov 1998). "Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes". The Journal of Cell Biology 143 (4): 957–71. doi:10.1083/jcb.143.4.957. PMC 2132958. PMID 9817754.
• Nishimura Y, Hayashi M, Inada H, Tanaka T (Jan 1999). "Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins". Biochemical and Biophysical Research Communications 254 (1): 21–6. doi:10.1006/bbrc.1998.9876. PMID 9920726.
• Valdez AC, Cabaniols JP, Brown MJ, Roche PA (Mar 1999). "Syntaxin 11 is associated with SNAP-23 on late endosomes and the trans-Golgi network". Journal of Cell Science. 112 112 (6): 845–54. PMID 10036234.
• Margittai M, Otto H, Jahn R (Mar 1999). "A stable interaction between syntaxin 1a and synaptobrevin 2 mediated by their transmembrane domains". FEBS Letters 446 (1): 40–4. doi:10.1016/S0014-5793(99)00028-9. PMID 10100611.
• Fasshauer D, Antonin W, Margittai M, Pabst S, Jahn R (May 1999). "Mixed and non-cognate SNARE complexes. Characterization of assembly and biophysical properties". The Journal of Biological Chemistry 274 (22): 15440–6. doi:10.1074/jbc.274.22.15440. PMID 10336434.