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*193001
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SOLUTE CARRIER FAMILY 18 (VESICULAR MONOAMINE), MEMBER 2; SLC18A2
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| Alternative titles; symbols |
VESICULAR AMINE TRANSPORTER 2; VAT2
VESICULAR MONOAMINE TRANSPORTER 2; VMAT2
SYNAPTIC VESICLE MONOAMINE TRANSPORTER, BRAIN; SVMT
SYNAPTIC VESICLE AMINE TRANSPORTER, BRAIN; SVAT |
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| HGNC Approved Gene Symbol: SLC18A2 |
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Cytogenetic location: 10q25.3
Genomic coordinates (GRCh37): 10:119,000,583-119,038,940 (from NCBI)
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| TEXT |
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Description
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The vesicular monoamine transporter acts to accumulate cytosolic monoamines into synaptic vesicles, using the proton gradient maintained across the synaptic vesicular membrane. Its proper function is essential to the correct activity of the monoaminergic systems that have been implicated in several human neuropsychiatric disorders. The transporter is a site of action of important drugs, including reserpine and tetrabenazine (summary by Peter et al., 1993). 
See also SLC18A1 (193002). |
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Cloning and Expression
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| Liu et al. (1992) and Erickson et al. (1992) investigated cDNAs encoding the synaptic vesicular monoamine transporter in rat brain. Using sequences from rat brain SVMT, Surratt et al. (1993) identified the human homolog. Human SVMT shares 92% amino acid identity with the rat sequence but displays one less consensus site for asparagine N-linked glycosylation and one more consensus site for phosphorylation by protein kinase C. |
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Gene Function
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Tritsch et al. (2012) demonstrated that activation of dopamine neurons in striatal slices rapidly inhibits action potential firing in both direct- and indirect-pathway striatal projection neurons through vesicular release of the inhibitory transmitter GABA. GABA is released directly from dopaminergic axons but in a manner that is independent of the vesicular GABA transporter VGAT (SLC32A1; 616440). Instead, GABA release requires activity of the vesicular monoamine transporter VMAT2, which is the vesicular transporter for dopamine. Furthermore, VMAT2 expression in GABAergic neurons lacking VGAT is sufficient to sustain GABA release. Tritsch et al. (2012) concluded that their findings expand the repertoire of synaptic mechanisms used by dopamine neurons to influence basal ganglia circuits, show a new substrate whose transport is dependent on VMAT2, and demonstrate that GABA can function as a bona fide cotransmitter in monoaminergic neurons.
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Mapping
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By Southern blot analysis of human/rodent hybrid cell lines and fluorescence in situ hybridization, Surratt et al. (1993) mapped the human SLC18A2 gene to chromosome 10q25. They also demonstrated a TaqI polymorphism that may prove useful in assessing the gene's involvement in neuropsychiatric disorders involving monoaminergic brain systems. Peter et al. (1993) likewise assigned the SLC18A2 gene to chromosome 10q25 using a panel of mouse/human hybrids and in situ hybridization.
Roghani et al. (1996) showed that the mouse Slc18a2 gene maps to mouse chromosome 19 by linkage analysis. |
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Molecular Genetics
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| Lin et al. (2005) sequenced the 17.4-kb SLC18A2 promoter region in 23 Caucasian individuals and identified 47 polymorphisms that conferred 13 haplotypes. In vitro analysis showed a 20% difference in promoter activity between 2 frequent haplotypes and identified some of the SNPs that influenced promoter activity. In 144 alcoholic patients and 189 controls, they found that haplotypes with -14234G (rs363371) and -2504C of the SLC18A2 promoter region represented a protective factor against alcoholism (p = 0.0038). |
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Animal Model
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| For a discussion of a Drosophila vesicular monoamine transporter model, see SLC18A1 (193002). |
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| REFERENCES |
| 1. |
Erickson, J. D., Eiden, L. E., Hoffman, B. J.
Expression cloning of a reserpine-sensitive vesicular monoamine transporter.
Proc. Nat. Acad. Sci. 89: 10993-10997, 1992.
[PubMed: 1438304, related citations]
[Full Text]
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| 2. |
Lin, Z., Walther, D., Yu, X.-Y., Li, S., Drgon, T., Uhl, G. R.
SLC18A2 promoter haplotypes and identification of a novel protective factor against alcoholism.
Hum. Molec. Genet. 14: 1393-1404, 2005.
[PubMed: 15829504, related citations]
[Full Text]
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| 3. |
Liu, Y., Peter, D., Roghani, A., Schuldiner, S., Prive, G. G., Eisenberg, D., Brecha, N., Edwards, R. H.
A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter.
Cell 70: 539-551, 1992.
[PubMed: 1505023, related citations]
[Full Text]
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| 4. |
Peter, D., Finn, J. P., Klisak, I., Liu, Y., Kojis, T., Heinzmann, C., Roghani, A., Sparkes, R. S., Edwards, R. H.
Chromosomal localization of the human vesicular amine transporter genes.
Genomics 18: 720-723, 1993.
[PubMed: 7905859, related citations]
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| 5. |
Roghani, A., Welch, C., Xia, Y.-R., Liu, Y., Peter, D., Finn, J. P., Edwards, R. H., Lusis, A. J.
Assignment of the mouse vesicular monoamine transporter genes, Slc18a1 and Slc18a2, to chromosomes 8 and 19 by linkage analysis.
Mammalian Genome 7: 393-394, 1996.
[PubMed: 8661734, related citations]
[Full Text]
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| 6. |
Surratt, C. K., Persico, A. M., Yang, X.-D., Edgar, S. R., Bird, G. S., Hawkins, A. L., Griffin, C. A., Li, X., Jabs, E. W., Uhl, G. R.
A human synaptic vesicle monoamine transporter cDNA predicts posttranslational modifications, reveals chromosome 10 gene localization and identifies TaqI RFLPs.
FEBS Lett. 318: 325-330, 1993.
[PubMed: 8095030, related citations]
[Full Text]
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| 7. |
Tritsch, N. X., Ding, J. B., Sabatini, B. L.
Dopaminergic neurons inhibit striatal output through non-canonical release of GABA.
Nature 490: 262-266, 2012.
[PubMed: 23034651, related citations]
[Full Text]
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| ▸ Contributors: |
Ada Hamosh - updated : 10/25/2012 |
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George E. Tiller - updated : 5/30/2008
John Logan Black, III - updated : 6/2/2006 |
| Creation Date: |
Victor A. McKusick : 9/24/1993 |
| ▸ Edit History: |
mgross : 06/25/2015 |
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alopez : 11/1/2012
terry : 10/25/2012
carol : 1/20/2011
wwang : 6/5/2008
terry : 5/30/2008
wwang : 6/7/2006
terry : 6/2/2006
cwells : 11/12/2003
jenny : 3/31/1997
terry : 6/14/1996
terry : 6/11/1996
carol : 2/1/1994
carol : 9/24/1993 |
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