Q01827 · VMAT2_RAT
- ProteinSynaptic vesicular amine transporter
- GeneSlc18a2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids515 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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:1438304, PubMed:25355561, PubMed:8125935, PubMed:8606801, PubMed:8860238).
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 (PubMed:16301178).
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) (PubMed:8860238).
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 (PubMed:16301178).
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) (PubMed:8860238).
Catalytic activity
- 2 H+(out) + serotonin(in) = 2 H+(in) + serotonin(out)This reaction proceeds in the forward direction.
2 H+ (out)CHEBI:15378+ serotonin (in)CHEBI:350546= 2 H+ (in)CHEBI:15378+ serotonin (out)CHEBI:350546 - dopamine(in) + 2 H+(out) = dopamine(out) + 2 H+(in)This reaction proceeds in the forward direction.
- 2 H+(out) + histamine(in) = 2 H+(in) + histamine(out)This reaction proceeds in the forward direction.
Activity regulation
Inhibited by reserpine, ketanserin and tetrabenazine. Not significantly inhibited by vesamicol.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.19 μM | serotonin |
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSynaptic vesicular amine transporter
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ01827
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane ; Multi-pass membrane protein
Cytoplasmic vesicle, secretory vesicle membrane ; Multi-pass membrane protein
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.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-20 | Cytoplasmic | ||||
Sequence: MALSDLVLLRWLRDSRHSRK | ||||||
Transmembrane | 21-41 | Helical | ||||
Sequence: LILFIVFLALLLDNMLLTVVV | ||||||
Topological domain | 42-130 | Lumenal, vesicle | ||||
Sequence: PIIPSYLYSIKHEKNSTEIQTTRPELVVSTSESIFSYYNNSTVLITGNATGTLPGGQSHKATSTQHTVANTTVPSDCPSEDRDLLNENV | ||||||
Transmembrane | 131-151 | Helical | ||||
Sequence: QVGLLFASKATVQLLTNPFIG | ||||||
Topological domain | 152-160 | Cytoplasmic | ||||
Sequence: LLTNRIGYP | ||||||
Transmembrane | 161-181 | Helical | ||||
Sequence: IPMFAGFCIMFISTVMFAFSS | ||||||
Topological domain | 182-190 | Lumenal, vesicle | ||||
Sequence: SYAFLLIAR | ||||||
Transmembrane | 191-211 | Helical | ||||
Sequence: SLQGIGSSCSSVAGMGMLASV | ||||||
Topological domain | 212-220 | Cytoplasmic | ||||
Sequence: YTDDEERGK | ||||||
Transmembrane | 221-243 | Helical | ||||
Sequence: PMGIALGGLAMGVLVGPPFGSVL | ||||||
Topological domain | 244-249 | Lumenal, vesicle | ||||
Sequence: YEFVGK | ||||||
Transmembrane | 250-272 | Helical | ||||
Sequence: TAPFLVLAALVLLDGAIQLFVLQ | ||||||
Topological domain | 273-292 | Cytoplasmic | ||||
Sequence: PSRVQPESQKGTPLTTLLKD | ||||||
Transmembrane | 293-312 | Helical | ||||
Sequence: PYILIAAGSICFANMGIAML | ||||||
Topological domain | 313-329 | Lumenal, vesicle | ||||
Sequence: EPALPIWMMETMCSRKW | ||||||
Transmembrane | 330-353 | Helical | ||||
Sequence: QLGVAFLPASISYLIGTNIFGILA | ||||||
Topological domain | 354-358 | Cytoplasmic | ||||
Sequence: HKMGR | ||||||
Transmembrane | 359-379 | Helical | ||||
Sequence: WLCALLGMVIVGISILCIPFA | ||||||
Topological domain | 380-390 | Lumenal, vesicle | ||||
Sequence: KNIYGLIAPNF | ||||||
Transmembrane | 391-411 | Helical | ||||
Sequence: GVGFAIGMVDSSMMPIMGYLV | ||||||
Topological domain | 412-415 | Cytoplasmic | ||||
Sequence: DLRH | ||||||
Transmembrane | 416-436 | Helical | ||||
Sequence: VSVYGSVYAIADVAFCMGYAI | ||||||
Topological domain | 437-441 | Lumenal, vesicle | ||||
Sequence: GPSAG | ||||||
Transmembrane | 442-463 | Helical | ||||
Sequence: GAIAKAIGFPWLMTIIGIIDIA | ||||||
Topological domain | 464-515 | Cytoplasmic | ||||
Sequence: FAPLCFFLRSPPAKEEKMAILMDHNCPIKRKMYTQNNVQSYPIGDDEESESD |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 180-182 | Loss of activity. Abolishes histamine uptake. | ||||
Sequence: SSS → AAA | ||||||
Mutagenesis | 477 | Does not alter sorting to large dense granules. | ||||
Sequence: K → A | ||||||
Mutagenesis | 478-479 | Impairs sorting to large dense granules. Delivered to the plasma membrane instead. Abolishes exocytosis in dendrites. Reduces exocytosis in axons. | ||||
Sequence: EE → AA | ||||||
Mutagenesis | 480 | Does not alter sorting to large dense granules. | ||||
Sequence: K → A | ||||||
Mutagenesis | 481 | Does not alter sorting to large dense granules. | ||||
Sequence: M → A | ||||||
Mutagenesis | 483-484 | Impairs sorting to large dense granules. Delivered to the plasma membrane instead. | ||||
Sequence: IL → AA |
Chemistry
PTM/Processing
Features
Showing features for chain, glycosylation, disulfide bond, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000127516 | 1-515 | Synaptic vesicular amine transporter | |||
Sequence: MALSDLVLLRWLRDSRHSRKLILFIVFLALLLDNMLLTVVVPIIPSYLYSIKHEKNSTEIQTTRPELVVSTSESIFSYYNNSTVLITGNATGTLPGGQSHKATSTQHTVANTTVPSDCPSEDRDLLNENVQVGLLFASKATVQLLTNPFIGLLTNRIGYPIPMFAGFCIMFISTVMFAFSSSYAFLLIARSLQGIGSSCSSVAGMGMLASVYTDDEERGKPMGIALGGLAMGVLVGPPFGSVLYEFVGKTAPFLVLAALVLLDGAIQLFVLQPSRVQPESQKGTPLTTLLKDPYILIAAGSICFANMGIAMLEPALPIWMMETMCSRKWQLGVAFLPASISYLIGTNIFGILAHKMGRWLCALLGMVIVGISILCIPFAKNIYGLIAPNFGVGFAIGMVDSSMMPIMGYLVDLRHVSVYGSVYAIADVAFCMGYAIGPSAGGAIAKAIGFPWLMTIIGIIDIAFAPLCFFLRSPPAKEEKMAILMDHNCPIKRKMYTQNNVQSYPIGDDEESESD | ||||||
Glycosylation | 56 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 80 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 81 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 89 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 111 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 118↔325 | |||||
Sequence: CPSEDRDLLNENVQVGLLFASKATVQLLTNPFIGLLTNRIGYPIPMFAGFCIMFISTVMFAFSSSYAFLLIARSLQGIGSSCSSVAGMGMLASVYTDDEERGKPMGIALGGLAMGVLVGPPFGSVLYEFVGKTAPFLVLAALVLLDGAIQLFVLQPSRVQPESQKGTPLTTLLKDPYILIAAGSICFANMGIAMLEPALPIWMMETMC | ||||||
Modified residue | 512 | Phosphoserine; by CK2 | ||||
Sequence: S | ||||||
Modified residue | 514 | Phosphoserine; by CK2 | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Sequence
- Sequence statusComplete
- Length515
- Mass (Da)55,690
- Last updated2003-09-19 v2
- Checksum627A904C1D35D552
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2JSJ6 | A0A0G2JSJ6_RAT | Slc18a2 | 515 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 220-221 | in Ref. 2; AAA41627 | ||||
Sequence: KP → NA | ||||||
Sequence conflict | 397 | in Ref. 1; AAA42190 | ||||
Sequence: G → F | ||||||
Sequence conflict | 493 | in Ref. 2; AAA41627 | ||||
Sequence: R → T |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M97381 EMBL· GenBank· DDBJ | AAA42190.1 EMBL· GenBank· DDBJ | mRNA | ||
L00603 EMBL· GenBank· DDBJ | AAA41627.1 EMBL· GenBank· DDBJ | mRNA |