Synaptic vesicular amine transporter
Also known as: SLC18A2, SVMT, VMAT2
Function
Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to accumulate high concentrations of monoamines inside the vesicles prior to their release via exocytosis. Transports a variety of catecholamines such as dopamine, adrenaline and noradrenaline, histamine, and indolamines such as serotonin. Regulates the transvesicular monoaminergic gradient that determines the quantal size. Mediates somatodendritic dopamine release in hippocampal neurons, likely as part of a regulated secretory pathway that integrates retrograde synaptic signals (By similarity). Acts as a primary transporter for striatal dopamine loading ensuring impulse-dependent release of dopamine at the synaptic cleft (By similarity). Responsible for histamine and serotonin storage and subsequent corelease from mast cell granules.
Classification
- Family (Pfam)
- PF07690 MFS_1
- InterPro
- MFS, MFS_dom, MFS_trans_sf, MFS_Vesicular_Transporter
- Functional cluster
- Mixed Regulatory & Membrane Proteins
Experimental structures · PDB · 32
- 8JSW EM 2.84A
- 8JSX EM 3.16A
- 8JT5 EM 3.06A
- 8JT9 EM 2.97A
- 8JTA EM 3.36A
- 8JTB EM 2.93A
- 8JTC EM 3.52A
- 8T69 EM 2.89A
- 8T6A EM 3.17A
- 8T6B EM 3.72A
- 8THR EM 3.12A
- 8UCJ EM 3.20A
- … and 20 more
A predicted model is available from AlphaFold.
Gene Ontology · 25
- GO:0030424 axon
- GO:0070083 clathrin-sculpted monoamine transport vesicle membrane
- GO:0030425 dendrite
- GO:0098691 dopaminergic synapse
- GO:0016020 membrane
- GO:0005886 plasma membrane
- GO:0030667 secretory granule membrane
- GO:0008021 synaptic vesicle
- GO:0030672 synaptic vesicle membrane
- GO:0043195 terminal bouton
- GO:0008504 monoamine transmembrane transporter activity
- GO:0015311 monoamine:proton antiporter activity
- GO:0005335 serotonin:sodium:chloride symporter activity
- GO:0015842 aminergic neurotransmitter loading into synaptic vesicle
- GO:0007268 chemical synaptic transmission
- GO:0015872 dopamine transport
- GO:0002553 histamine secretion by mast cell
- GO:0051615 histamine uptake
- GO:0015844 monoamine transport
- GO:1903427 negative regulation of reactive oxygen species biosynthetic process
- GO:0098700 neurotransmitter loading into synaptic vesicle
- GO:0006836 neurotransmitter transport
- GO:0002552 serotonin secretion by mast cell
- GO:0051610 serotonin uptake
- GO:0099123 somato-dendritic dopamine secretion
Disease associations
- brain dopamine-serotonin vesicular transport disease MONDO:0018130
Drugs targeting this protein · 13
- TETRABENAZINE inhibitor
- DESERPIDINE inhibitor
- DEXTROAMPHETAMINE ADIPATE inhibitor
- LISDEXAMFETAMINE DIMESYLATE inhibitor
- RESCINNAMINE inhibitor
- VALBENAZINE inhibitor
- DEUTETRABENAZINE inhibitor
- BENZPHETAMINE HYDROCHLORIDE inhibitor
- DEXTROAMPHETAMINE SULFATE inhibitor
- VALBENAZINE TOSYLATE inhibitor
- DEXTROAMPHETAMINE SACCHARATE inhibitor
- DEXTROAMPHETAMINE inhibitor
- RESERPINE inhibitor
Related proteins · sequence + function similarity
- Synaptic vesicular amine transporter 0.99
- Synaptic vesicular amine transporter 0.99
- Synaptic vesicular amine transporter 0.99
- Chromaffin granule amine transporter 0.92
- Chromaffin granule amine transporter 0.88
- Chromaffin granule amine transporter 0.88
- Major facilitator superfamily domain-containing protein 8 0.75
- Major facilitator superfamily domain-containing protein 8 0.73
- Major facilitator superfamily domain-containing protein 8 0.73
- Major facilitator superfamily domain-containing protein 8 0.71
- Solute carrier family 60 member 2 0.70
- Glucose-6-phosphate exchanger SLC37A2 0.68
Co-cited proteins · studied together in the literature
- Chromaffin granule amine transporter 1 shared papers
- Synaptic vesicular amine transporter 1 shared papers
Literature · 16 cited papers
- Structural mechanisms for VMAT2 inhibition by tetrabenazine. Elife · 2024
- Transport and inhibition mechanisms of human VMAT2. Nature · 2024
- Mechanisms of neurotransmitter transport and drug inhibition in human VMAT2. Nature · 2023
- Brain dopamine-serotonin vesicular transport disease and its treatment. N. Engl. J. Med. · 2013
- Phosphoproteome of resting human platelets. J. Proteome Res. · 2008
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- The DNA sequence and comparative analysis of human chromosome 10. Nature · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Identification of human vesicle monoamine transporter (VMAT2) lumenal cysteines that form an intramolecular disulfide bond. Biochemistry · 2002
- Exon/intron boundaries, novel polymorphisms, and association analysis with schizophrenia of the human synaptic vesicle monoamine transporter (SVMT) gene. Mol. Psychiatry · 2001
- Reserpine- and tetrabenazine-sensitive transport of (3)H-histamine by the neuronal isoform of the vesicular monoamine transporter. J. Mol. Neurosci. · 1995
- Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc. Natl. Acad. Sci. U.S.A. · 1996
- … and 4 more in the literature graph