Protein: Synaptic vesicular amine transporter (Solute carrier family 18 member 2) (Vesicular amine transporter 2) (VAT2) (Vesicular monoamine transporter 2) (Q05940)
Organism: Homo sapiens (Human)
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 (By similarity).
Subcellular location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000250|UniProtKB:Q01827}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250|UniProtKB:Q01827}; Multi-pass membrane protein {ECO:0000255}. Cell projection, axon {ECO:0000250|UniProtKB:Q01827}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q01827}. Note=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. {ECO:0000250|UniProtKB:Q01827}.
Sequence: MALSELALVRWLQESRRSRKLILFIVFLALLLDNMLLTVVVPIIPSYLYSIKHEKNATEIQTARPVHTASISDSFQSIFSYYDNSTMVTGNATRDLTLHQTATQHMVTNASAVPSDCPSEDKDLLNENVQVGLLFASKATVQLITNPFIGLLTNRIGYPIPIFAGFCIMFVSTIMFAFSSSYAFLLIARSLQGIGSSCSSVAGMGMLASVYTDDEERGNVMGIALGGLAMGVLVGPPFGSVLYEFVGKTAPFLVLAALVLLDGAIQLFVLQPSRVQPESQKGTPLTTLLKDPYILIAAGSICFANMGIAMLEPALPIWMMETMCSRKWQLGVAFLPASISYLIGTNIFGILAHKMGRWLCALLGMIIVGVSILCIPFAKNIYGLIAPNFGVGFAIGMVDSSMMPIMGYLVDLRHVSVYGSVYAIADVAFCMGYAIGPSAGGAIAKAIGFPWLMTIIGIIDILFAPLCFFLRSPPAKEEKMAILMDHNCPIKTKMYTQNNIQSYPIGEDEESESD
InterPro domains: - IPR011701: Major facilitator superfamily (family) [127-423]
- IPR036259: MFS transporter superfamily (homologous_superfamily) [17-482]
- IPR020846: Major facilitator superfamily domain (domain) [22-475]
- IPR050930: Major Facilitator Superfamily Vesicular Transporter (family) [11-479]
Interaction partners: - Alpha-synuclein
- Aromatic-L-amino-acid decarboxylase
- Sodium-dependent dopamine transporter
- Tyrosine 3-monooxygenase
- Vesicular inhibitory amino acid transporter
- Vesicular glutamate transporter 2
- Vesicular glutamate transporter 3
- Vesicular glutamate transporter 1
- Equilibrative nucleoside transporter 4
- Vesicular acetylcholine transporter
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005215 (transporter activity), GO:0022857 (transmembrane transporter activity), GO:0005515 (protein binding), GO:0015075 (monoatomic ion transmembrane transporter activity), GO:0015318 (inorganic molecular entity transmembrane transporter activity), GO:0022804 (active transmembrane transporter activity), GO:0022890 (inorganic cation transmembrane transporter activity), GO:0022853 (active monoatomic ion transmembrane transporter activity), GO:0008504 (monoamine transmembrane transporter activity), GO:0008324 (monoatomic cation transmembrane transporter activity), GO:0015291 (secondary active transmembrane transporter activity), GO:0015297 (antiporter activity), GO:0015078 (proton transmembrane transporter activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0002376 (immune system process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0051641 (cellular localization), GO:0065008 (regulation of biological quality), GO:0006955 (immune response), GO:0050794 (regulation of cellular process), GO:0051234 (establishment of localization), GO:0002252 (immune effector process), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0033036 (macromolecule localization), GO:0009892 (negative regulation of metabolic process), GO:0010876 (lipid localization), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0046907 (intracellular transport), GO:0006810 (transport), GO:0051649 (establishment of localization in cell), GO:0001505 (regulation of neurotransmitter levels), GO:0009895 (negative regulation of catabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0045087 (innate immune response), GO:0006869 (lipid transport), GO:0006836 (neurotransmitter transport), GO:0001504 (neurotransmitter uptake), GO:0098657 (import into cell), GO:0071705 (nitrogen compound transport), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0000723 (telomere maintenance), GO:0015850 (organic hydroxy compound transport), GO:0050863 (regulation of T cell activation), GO:0000228 (nuclear chromosome), GO:0071702 (organic substance transport), GO:0098810 (neurotransmitter reuptake), GO:0015850 (organic hydroxy compound transport), GO:0015695 (organic cation transport), GO:0015844 (monoamine transport), GO:0051937 (catecholamine transport), GO:0030301 (cholesterol transport), GO:0015872 (dopamine transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0031984 (organelle subcompartment), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0030141 (secretory granule), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0030133 (transport vesicle), GO:0098827 (endoplasmic reticulum subcompartment), GO:0042175 (nuclear outer membrane-endoplasmic reticulum membrane network), GO:0005783 (endoplasmic reticulum), GO:0043227 (membrane-bounded organelle), GO:0030658 (transport vesicle membrane), GO:0099503 (secretory vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0012506 (vesicle membrane), GO:0030667 (secretory granule membrane), GO:0030135 (coated vesicle), GO:0005789 (endoplasmic reticulum membrane), GO:0031982 (vesicle), GO:0030659 (cytoplasmic vesicle membrane), GO:0097708 (intracellular vesicle), GO:0030136 (clathrin-coated vesicle), GO:0030662 (coated vesicle membrane), GO:0030665 (clathrin-coated vesicle membrane)