VAMP2

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)
End	8,163,546 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	68,983,210 bp
RNA expression pattern
	Top expressed in
	Top expressed in
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
	Sources:Amigo / QuickGO
Orthologs
	6844
	22318
	ENSG00000220205
	ENSMUSG00000020894
	P63027
	P63044
	NM_014232; NM_001330125
	NM_009497
	NP_001317054; NP_055047
	NP_033523
	Wikidata
View/Edit Human	View/Edit Mouse

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

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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000220205 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020894 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^a ^b "Entrez Gene: VAMP2 vesicle-associated membrane protein 2 (synaptobrevin 2)".
^ 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.
^ 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.
^ 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.
^ "OMIM entry: Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements".
^ 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.
^ 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.
^ ^a ^b 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.
^ ^a ^b 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000220205 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid1976629-5] 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.

[entrez-6] "Entrez Gene: VAMP2 vesicle-associated membrane protein 2 (synaptobrevin 2)".

[pmid11691998-7] 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.

[pmid30929742-8] 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.

[pmid32336483-9] 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.

[OMIM618760-10] "OMIM entry: Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements".

[pmid9341137-11] 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.

[pmid11524423-12] 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.

[pmid9030619-13] 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.

[pmid11832227-14] 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.

[pmid10820264-15] 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.

[pmid12828989-16] 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.

[pmid10713150-17] 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.

[pmid10449403-18] 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.

[pmid7553862-19] 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.

[pmid12093152-20] 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.

[pmid10100611-21] 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.

[pmid12517971-22] 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.

[pmid8760387-23] 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.

[pmid10194441-24] 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.

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