VAMP2

VAMP2

VAMP2

Protein-coding gene in the species Homo sapiens

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

Quick Facts Available structures, PDB ...
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:

References

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