VAMP2

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.{{cite journal | vauthors = Schoch S, Deák F, Königstorfer A, Mozhayeva M, Sara Y, Südhof TC, Kavalali ET | title = SNARE function analyzed in synaptobrevin/VAMP knockout mice | journal = Science | volume = 294 | issue = 5544 | pages = 1117–22 | date = Nov 2001 | pmid = 11691998 | doi = 10.1126/science.1064335 | bibcode = 2001Sci...294.1117S | s2cid = 40321111 }} The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and complexin. It also forms a distinct complex with synaptophysin.

Heterozygous mutations in VAMP2 cause a neurodevelopmental disorder with hypotonia and autistic features (with or without hyperkinetic movements).{{cite journal | vauthors = Salpietro V, Malintan NT, Llano-Rivas I, et al. | title = Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment | journal = The American Journal of Human Genetics | volume = 104 | issue = 4 | pages = 721–730 | date = Apr 2019 | pmid = 30929742 | doi = 10.1016/j.ajhg.2019.02.016| pmc = 6451933 | doi-access = free }}{{cite journal | vauthors = Sunaga Y, Muramatsu K, Kosaki K, et al. | title = Variant in the neuronal vesicular SNARE VAMP2 (synaptobrevin-2): First report in Japan | journal = Brain and Development | date = Apr 2020 | volume = 42 | issue = 7 | pages = 529–533 | pmid = 32336483 | doi = 10.1016/j.braindev.2020.04.001 | s2cid = 216095891 }}{{cite web | title = OMIM entry: Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements| url = https://www.omim.org/entry/618760}}

VAMP2 has been shown to interact with:

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• RABAC1,{{cite journal | vauthors = Martincic I, Peralta ME, Ngsee JK | title = Isolation and characterization of a dual prenylated Rab and VAMP2 receptor | journal = The Journal of Biological Chemistry | volume = 272 | issue = 43 | pages = 26991–8 | date = Oct 1997 | pmid = 9341137 | doi = 10.1074/jbc.272.43.26991| doi-access = free }}
• SNAP-25,{{cite journal | vauthors = Li Y, Chin LS, Weigel C, Li L | title = Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis | journal = The Journal of Biological Chemistry | volume = 276 | issue = 44 | pages = 40824–33 | date = Nov 2001 | pmid = 11524423 | doi = 10.1074/jbc.M106141200 | doi-access = free }}{{cite journal | vauthors = Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK | title = Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes | journal = The Journal of Neuroscience | volume = 17 | issue = 5 | pages = 1596–603 | date = Mar 1997 | pmid = 9030619 | doi = 10.1523/JNEUROSCI.17-05-01596.1997 | pmc = 6573372}}{{cite journal | vauthors = Chen X, Tomchick DR, Kovrigin E, Araç D, Machius M, Südhof TC, Rizo J | title = Three-dimensional structure of the complexin/SNARE complex | journal = Neuron | volume = 33 | issue = 3 | pages = 397–409 | date = Jan 2002 | pmid = 11832227 | doi = 10.1016/s0896-6273(02)00583-4| s2cid = 17878965 | url = https://epublications.marquette.edu/cgi/viewcontent.cgi?article=1227&context=chem_fac | doi-access = free }}
• SNAP23,{{cite journal | vauthors = Imai A, Nashida T, Yoshie S, Shimomura H | title = Intracellular localisation of SNARE proteins in rat parotid acinar cells: SNARE complexes on the apical plasma membrane | journal = Archives of Oral Biology | volume = 48 | issue = 8 | pages = 597–604 | date = Aug 2003 | pmid = 12828989 | doi = 10.1016/s0003-9969(03)00116-x}}{{cite journal | vauthors = Kawanishi M, Tamori Y, Okazawa H, Araki S, Shinoda H, Kasuga M | title = Role of SNAP23 in insulin-induced translocation of GLUT4 in 3T3-L1 adipocytes. Mediation of complex formation between syntaxin4 and VAMP2 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 11 | pages = 8240–7 | date = Mar 2000 | pmid = 10713150 | doi = 10.1074/jbc.275.11.8240| doi-access = free }}
• STX1A,{{cite journal | vauthors = Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J | title = A conformational switch in syntaxin during exocytosis: role of munc18 | journal = The EMBO Journal | volume = 18 | issue = 16 | pages = 4372–82 | date = Aug 1999 | pmid = 10449403 | pmc = 1171512 | doi = 10.1093/emboj/18.16.4372 }}{{cite journal | vauthors = McMahon HT, Missler M, Li C, Südhof TC | title = Complexins: cytosolic proteins that regulate SNAP receptor function | journal = Cell | volume = 83 | issue = 1 | pages = 111–9 | date = Oct 1995 | pmid = 7553862 | doi = 10.1016/0092-8674(95)90239-2| s2cid = 675343 | doi-access = free }}{{cite journal | vauthors = Pérez-Brangulí F, Muhaisen A, Blasi J | title = 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 | journal = Molecular and Cellular Neurosciences | volume = 20 | issue = 2 | pages = 169–80 | date = Jun 2002 | pmid = 12093152 | doi = 10.1006/mcne.2002.1122| s2cid = 23927545 }}{{cite journal | vauthors = Margittai M, Otto H, Jahn R | title = A stable interaction between syntaxin 1a and synaptobrevin 2 mediated by their transmembrane domains | journal = FEBS Letters | volume = 446 | issue = 1 | pages = 40–4 | date = Mar 1999 | pmid = 10100611 | doi = 10.1016/s0014-5793(99)00028-9| s2cid = 9115709 | doi-access = free }} and
• STX4.{{cite journal | vauthors = Paumet F, Le Mao J, Martin S, Galli T, David B, Blank U, Roa M | title = 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 = Journal of Immunology | volume = 164 | issue = 11 | pages = 5850–7 | date = Jun 2000 | pmid = 10820264 | doi = 10.4049/jimmunol.164.11.5850| doi-access = free }}{{cite journal | vauthors = Mollinedo F, Martín-Martín B, Calafat J, Nabokina SM, Lazo PA | title = 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 = Journal of Immunology | volume = 170 | issue = 2 | pages = 1034–42 | date = Jan 2003 | pmid = 12517971 | doi = 10.4049/jimmunol.170.2.1034| doi-access = free }}{{cite journal | vauthors = Jagadish MN, Fernandez CS, Hewish DR, Macaulay SL, Gough KH, Grusovin J, Verkuylen A, Cosgrove L, Alafaci A, Frenkel MJ, Ward CW | title = 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 | journal = The Biochemical Journal | volume = 317 | issue = 3| pages = 945–54 | date = Aug 1996 | pmid = 8760387 | pmc = 1217577 | doi = 10.1042/bj3170945| series = 317 }}{{cite journal | vauthors = Reed GL, Houng AK, Fitzgerald ML | title = Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion | journal = Blood | volume = 93 | issue = 8 | pages = 2617–26 | date = Apr 1999 | pmid = 10194441 | doi = 10.1182/blood.V93.8.2617}}

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{{Reflist}}

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• {{cite journal | vauthors = Brumell JH, Volchuk A, Sengelov H, Borregaard N, Cieutat AM, Bainton DF, Grinstein S, Klip A | title = Subcellular distribution of docking/fusion proteins in neutrophils, secretory cells with multiple exocytic compartments | journal = Journal of Immunology | volume = 155 | issue = 12 | pages = 5750–9 | date = Dec 1995 | doi = 10.4049/jimmunol.155.12.5750 | pmid = 7499863 | s2cid = 32809167 }}
• {{cite journal | vauthors = Kutay U, Ahnert-Hilger G, Hartmann E, Wiedenmann B, Rapoport TA | title = Transport route for synaptobrevin via a novel pathway of insertion into the endoplasmic reticulum membrane | journal = The EMBO Journal | volume = 14 | issue = 2 | pages = 217–23 | date = Jan 1995 | pmid = 7835332 | pmc = 398073 | doi = 10.1002/j.1460-2075.1995.tb06994.x}}
• {{cite journal | vauthors = Chapman ER, An S, Barton N, Jahn R | title = SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils | journal = The Journal of Biological Chemistry | volume = 269 | issue = 44 | pages = 27427–32 | date = Nov 1994 | doi = 10.1016/S0021-9258(18)47003-2 | pmid = 7961655 | doi-access = free }}
• {{cite journal | vauthors = Hunt JM, Bommert K, Charlton MP, Kistner A, Habermann E, Augustine GJ, Betz H | title = A post-docking role for synaptobrevin in synaptic vesicle fusion | journal = Neuron | volume = 12 | issue = 6 | pages = 1269–79 | date = Jun 1994 | pmid = 8011337 | doi = 10.1016/0896-6273(94)90443-X | s2cid = 799315 }}
• {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
• {{cite journal | vauthors = Jagadish MN, Fernandez CS, Hewish DR, Macaulay SL, Gough KH, Grusovin J, Verkuylen A, Cosgrove L, Alafaci A, Frenkel MJ, Ward CW | title = 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 | journal = The Biochemical Journal | volume = 317 | issue = 3| pages = 945–54 | date = Aug 1996 | pmid = 8760387 | pmc = 1217577 | doi = 10.1042/bj3170945| series = 317 }}
• {{cite journal | vauthors = Mandon B, Chou CL, Nielsen S, Knepper MA | title = Syntaxin-4 is localized to the apical plasma membrane of rat renal collecting duct cells: possible role in aquaporin-2 trafficking | journal = The Journal of Clinical Investigation | volume = 98 | issue = 4 | pages = 906–13 | date = Aug 1996 | pmid = 8770861 | pmc = 507504 | doi = 10.1172/JCI118873 }}
• {{cite journal | vauthors = Timmers KI, Clark AE, Omatsu-Kanbe M, Whiteheart SW, Bennett MK, Holman GD, Cushman SW | title = Identification of SNAP receptors in rat adipose cell membrane fractions and in SNARE complexes co-immunoprecipitated with epitope-tagged N-ethylmaleimide-sensitive fusion protein | journal = The Biochemical Journal | volume = 320 | issue = 2| pages = 429–36 | date = Dec 1996 | pmid = 8973549 | pmc = 1217948 | doi = 10.1042/bj3200429| series = 320 }}
• {{cite journal | vauthors = Betz A, Okamoto M, Benseler F, Brose N | title = Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin | journal = The Journal of Biological Chemistry | volume = 272 | issue = 4 | pages = 2520–6 | date = Jan 1997 | pmid = 8999968 | doi = 10.1074/jbc.272.4.2520 | doi-access = free }}
• {{cite journal | vauthors = Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK | title = Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes | journal = The Journal of Neuroscience | volume = 17 | issue = 5 | pages = 1596–603 | date = Mar 1997 | pmid = 9030619 | doi = 10.1523/JNEUROSCI.17-05-01596.1997 | pmc = 6573372}}
• {{cite journal | vauthors = Martincic I, Peralta ME, Ngsee JK | title = Isolation and characterization of a dual prenylated Rab and VAMP2 receptor | journal = The Journal of Biological Chemistry | volume = 272 | issue = 43 | pages = 26991–8 | date = Oct 1997 | pmid = 9341137 | doi = 10.1074/jbc.272.43.26991 | doi-access = free }}
• {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
• {{cite journal | vauthors = Weir ML, Klip A, Trimble WS | title = 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 | journal = The Biochemical Journal | volume = 333 | issue = 2| pages = 247–51 | date = Jul 1998 | pmid = 9657962 | pmc = 1219579 | doi = 10.1042/bj3330247| series = 333 }}
• {{cite journal | vauthors = Isenmann S, Khew-Goodall Y, Gamble J, Vadas M, Wattenberg BW | title = A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal | journal = Molecular Biology of the Cell | volume = 9 | issue = 7 | pages = 1649–60 | date = Jul 1998 | pmid = 9658161 | pmc = 25402 | doi = 10.1091/mbc.9.7.1649 }}
• {{cite journal | vauthors = Prekeris R, Klumperman J, Chen YA, Scheller RH | title = Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes | journal = The Journal of Cell Biology | volume = 143 | issue = 4 | pages = 957–71 | date = Nov 1998 | pmid = 9817754 | pmc = 2132958 | doi = 10.1083/jcb.143.4.957 }}
• {{cite journal | vauthors = Nishimura Y, Hayashi M, Inada H, Tanaka T | title = Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins | journal = Biochemical and Biophysical Research Communications | volume = 254 | issue = 1 | pages = 21–6 | date = Jan 1999 | pmid = 9920726 | doi = 10.1006/bbrc.1998.9876 }}
• {{cite journal | vauthors = Valdez AC, Cabaniols JP, Brown MJ, Roche PA | title = Syntaxin 11 is associated with SNAP-23 on late endosomes and the trans-Golgi network | journal = Journal of Cell Science | volume = 112 | issue = 6| pages = 845–54 | date = Mar 1999 | pmid = 10036234 | series = 112 | doi = 10.1242/jcs.112.6.845 }}
• {{cite journal | vauthors = Margittai M, Otto H, Jahn R | title = A stable interaction between syntaxin 1a and synaptobrevin 2 mediated by their transmembrane domains | journal = FEBS Letters | volume = 446 | issue = 1 | pages = 40–4 | date = Mar 1999 | pmid = 10100611 | doi = 10.1016/S0014-5793(99)00028-9 | s2cid = 9115709 | doi-access = free }}
• {{cite journal | vauthors = Fasshauer D, Antonin W, Margittai M, Pabst S, Jahn R | title = Mixed and non-cognate SNARE complexes. Characterization of assembly and biophysical properties | journal = The Journal of Biological Chemistry | volume = 274 | issue = 22 | pages = 15440–6 | date = May 1999 | pmid = 10336434 | doi = 10.1074/jbc.274.22.15440 | doi-access = free }}

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{{Vesicular transport proteins}}