VAMP2

Vesicle-associated membrane protein 2 (VAMP2) is a protein that in humans is encoded by the VAMP2 gene.^[5][6]

VAMP2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3FIE, 3FII, 3RK2, 3RK3, 3RL0
Identifiers
Aliases	VAMP2, SYB2, VAMP-2, vesicle associated membrane protein 2, NEDHAHM
External IDs	OMIM: 185881; MGI: 1313277; HomoloGene: 7591; GeneCards: VAMP2; OMA:VAMP2 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p13.1 Start 8,159,149 bp[1] End 8,163,546 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B3 Start 68,979,316 bp[2] End 68,983,210 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 10 frontal pole paraflocculus of cerebellum right frontal lobe right hemisphere of cerebellum cingulate gyrus anterior cingulate cortex amygdala nucleus accumbens anterior pituitary Top expressed in perirhinal cortex entorhinal cortex superior frontal gyrus primary visual cortex dentate gyrus of hippocampal formation granule cell neural layer of retina CA3 field cerebellar cortex prefrontal cortex subiculum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function SNAP receptor activity protein self-association protein binding syntaxin-1 binding SNARE binding calmodulin binding syntaxin binding phospholipid binding calcium-dependent protein binding Cellular component integral component of membrane cytosol clathrin-sculpted monoamine transport vesicle membrane membrane secretory granule membrane plasma membrane clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane synapse integral component of plasma membrane synaptic vesicle membrane zymogen granule membrane cell junction neuron projection cytoplasmic vesicle clathrin-coated vesicle clathrin-sculpted glutamate transport vesicle membrane secretory granule intracellular membrane-bounded organelle synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex synaptobrevin 2-SNAP-25-syntaxin-1a complex SNARE complex synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex voltage-gated potassium channel complex trans-Golgi network synaptic vesicle vesicle perinuclear region of cytoplasm neuron projection terminus clathrin-coated vesicle membrane Biological process natural killer cell degranulation mucus secretion regulation of histamine secretion by mast cell neutrophil degranulation glutamate secretion vesicle fusion eosinophil degranulation vesicle-mediated transport exocytosis response to glucose membrane fusion regulation of delayed rectifier potassium channel activity calcium-ion regulated exocytosis regulation of exocytosis positive regulation of intracellular protein transport protein transport Golgi to plasma membrane protein transport synaptic vesicle exocytosis cellular response to insulin stimulus long-term potentiation regulation of vesicle-mediated transport membrane organization protein-containing complex assembly post-Golgi vesicle-mediated transport neurotransmitter secretion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6844 22318 Ensembl ENSG00000220205 ENSMUSG00000020894 UniProt P63027 P63044 RefSeq (mRNA) NM_014232 NM_001330125 NM_009497 RefSeq (protein) NP_001317054 NP_055047 NP_033523 Location (UCSC) Chr 17: 8.16 – 8.16 Mb Chr 11: 68.98 – 68.98 Mb PubMed search [3] [4]
Wikidata
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Hypothetic models of VAMP2 conformations and engagement in SNARE complex assembly for neurotransmitter release

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.^[7] The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and complexin. It also forms a distinct complex with synaptophysin.^[6]

Clinical significance

Heterozygous mutations in VAMP2 cause a neurodevelopmental disorder with hypotonia and autistic features (with or without hyperkinetic movements).^[8][9][10]

Interactions

VAMP2 has been shown to interact with:

• RABAC1,^[11]
• SNAP-25,^[12][13][14]
• SNAP23,^[15][16][17]
• STX1A,^{[13][14][18][19][20][21]} and
• STX4.^{[15][22][23][24]}

References

1. GRCh38: Ensembl release 89: ENSG00000220205 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020894 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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. doi:10.1016/S0021-9258(17)44898-8. PMID 1976629.
6. "Entrez Gene: VAMP2 vesicle-associated membrane protein 2 (synaptobrevin 2)".
7. 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. Bibcode:2001Sci...294.1117S. doi:10.1126/science.1064335. PMID 11691998. S2CID 40321111.
8. Salpietro V, Malintan NT, Llano-Rivas I, et al. (Apr 2019). "Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment". The American Journal of Human Genetics. 104 (4): 721–730. doi:10.1016/j.ajhg.2019.02.016. PMC 6451933. PMID 30929742.
9. Sunaga Y, Muramatsu K, Kosaki K, et al. (Apr 2020). "Variant in the neuronal vesicular SNARE VAMP2 (synaptobrevin-2): First report in Japan". Brain and Development. 42 (7): 529–533. doi:10.1016/j.braindev.2020.04.001. PMID 32336483. S2CID 216095891.
10. "OMIM entry: Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements".
11. 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.
12. 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.
13. 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. doi:10.1523/JNEUROSCI.17-05-01596.1997. PMC 6573372. PMID 9030619.
14. 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. S2CID 17878965.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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. S2CID 675343.
20. 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. S2CID 23927545.
21. 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. S2CID 9115709.
22. 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.
23. 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.
24. 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. doi:10.1182/blood.V93.8.2617. 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. doi:10.4049/jimmunol.155.12.5750. PMID 7499863. S2CID 32809167.
• 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. doi:10.1002/j.1460-2075.1995.tb06994.x. 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. doi:10.1016/S0021-9258(18)47003-2. 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. S2CID 799315.
• 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. doi:10.1523/JNEUROSCI.17-05-01596.1997. PMC 6573372. 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. doi:10.1242/jcs.112.6.845. 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. S2CID 9115709.
• 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.