SLC18A2
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 (PubMed:23363473, PubMed:37914936, PubMed:38081299, PubMed:38517752, PubMed:8643547). 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 (PubMed:8860238).
Involvement in disease
Parkinsonism-dystonia 2, infantile-onset
PKDYS2
An autosomal recessive disorder characterized by infantile onset of abnormal movements, including parkinsonism, dystonia, and poor fine motor skills, as well as autonomic dysfunction, including abnormal sweating, cold extremities, and poor sleep. Some patients have variable degrees of developmental delay.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the major facilitator superfamily. Vesicular transporter family.
Tissue Specificity
Expressed in neuronal and neuroendocrine tissues. Detected in central and peripheral nervous system in particular in axonal and dendritic processes in dopaminergic cells of substantia nigra, histaminergic neuronal cell bodies of substantia nigra and tuberomammillary nucleus, in ganglion cells of sympathetic glia and in peripheral sympathetic nerve terminals in stomach and duodenum (at protein level). Highly expressed in chromaffin cells of the adrenal medulla and histamine-storing enterochromaffin-like cells of oxyntic mucosa (at protein level).
Cellular localization
- Cytoplasmic vesicle
- Secretory vesicle
- Synaptic vesicle membrane
- Multi-pass membrane protein
- Cytoplasmic vesicle
- Secretory vesicle membrane
- Multi-pass membrane protein
- Cell projection
- Axon
- Cell projection
- Dendrite
- Sorted to large dense core granules in neuroendocrine cells, presumably at the level of the trans-Golgi network. In neurons it is predominantly detected in somatodendritic tubulovesicular membranes, a distinct population of secretory vesicles that undergo calcium-dependent exocytosis in axons and dendrites upon depolarization. Localized at synaptic vesicles in axons.
Alternative names
SVMT, VMAT2, SLC18A2, Synaptic vesicular amine transporter, Solute carrier family 18 member 2, Vesicular amine transporter 2, Vesicular monoamine transporter 2, VAT2