Q16572 · VACHT_HUMAN
- ProteinVesicular acetylcholine transporter
- GeneSLC18A3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids532 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Electrogenic antiporter that exchanges one cholinergic neurotransmitter, acetylcholine or choline, with two intravesicular protons across the membrane of synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to store neurotransmitters inside the vesicles prior to their release via exocytosis (By similarity) (PubMed:20225888, PubMed:8910293).
Determines cholinergic vesicular quantal size at presynaptic nerve terminals in developing neuro-muscular junctions with an impact on motor neuron differentiation and innervation pattern (By similarity).
Part of forebrain cholinergic system, regulates hippocampal synapse transmissions that underlie spatial memory formation (By similarity).
Can transport serotonin
Determines cholinergic vesicular quantal size at presynaptic nerve terminals in developing neuro-muscular junctions with an impact on motor neuron differentiation and innervation pattern (By similarity).
Part of forebrain cholinergic system, regulates hippocampal synapse transmissions that underlie spatial memory formation (By similarity).
Can transport serotonin
Catalytic activity
- acetylcholine(out) + 2 H+(in) = acetylcholine(in) + 2 H+(out)This reaction proceeds in the forward direction.acetylcholine (out)CHEBI:15355
+ 2 H+ (in)CHEBI:15378= acetylcholine (in)CHEBI:15355+ 2 H+ (out)CHEBI:15378 - choline(in) + 2 H+(out) = choline(out) + 2 H+(in)This reaction proceeds in the forward direction.
- 2 H+(out) + serotonin(in) = 2 H+(in) + serotonin(out)
Activity regulation
Potently inhibited by L-vesamicol, reserpine and tetrabenazine.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.97 mM | acetylcholine | |||||
0.75 mM | acetylcholine |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
0.58 nmol/min/mg | toward acetylcholine |
pH Dependence
Optimum pH is 7.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 193 | Important for transporter activity | ||||
Sequence: D | ||||||
Site | 398 | Important for transporter activity | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | AP-1 adaptor complex | |
Cellular Component | AP-2 adaptor complex | |
Cellular Component | clathrin-coated endocytic vesicle membrane | |
Cellular Component | clathrin-sculpted acetylcholine transport vesicle membrane | |
Cellular Component | plasma membrane | |
Cellular Component | synaptic vesicle membrane | |
Cellular Component | terminal bouton | |
Molecular Function | acetylcholine transmembrane transporter activity | |
Molecular Function | acetylcholine:proton antiporter activity | |
Molecular Function | monoamine:proton antiporter activity | |
Biological Process | acetylcholine uptake | |
Biological Process | chemical synaptic transmission | |
Biological Process | neurotransmitter transport | |
Biological Process | positive regulation of acetylcholine secretion, neurotransmission | |
Biological Process | positive regulation of long-term synaptic potentiation | |
Biological Process | positive regulation of neuromuscular junction development | |
Biological Process | serotonin uptake |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameVesicular acetylcholine transporter
- Short namesVAChT
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ16572
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-33 | Cytoplasmic | ||||
Sequence: MESAEPAGQARAAATKLSEAVGAALQEPRRQRR | ||||||
Transmembrane | 34-54 | Helical | ||||
Sequence: LVLVIVCVALLLDNMLYMVIV | ||||||
Topological domain | 55-125 | Lumenal, vesicle | ||||
Sequence: PIVPDYIAHMRGGGEGPTRTPEVWEPTLPLPTPANASAYTANTSASPTAAWPAGSALRPRYPTESEDVKIG | ||||||
Transmembrane | 126-146 | Helical | ||||
Sequence: VLFASKAILQLLVNPLSGPFI | ||||||
Topological domain | 147-152 | Cytoplasmic | ||||
Sequence: DRMSYD | ||||||
Transmembrane | 153-173 | Helical | ||||
Sequence: VPLLIGLGVMFASTVLFAFAE | ||||||
Topological domain | 174-182 | Lumenal, vesicle | ||||
Sequence: DYATLFAAR | ||||||
Transmembrane | 183-203 | Helical | ||||
Sequence: SLQGLGSAFADTSGIAMIADK | ||||||
Topological domain | 204-213 | Cytoplasmic | ||||
Sequence: YPEEPERSRA | ||||||
Transmembrane | 214-234 | Helical | ||||
Sequence: LGVALAFISFGSLVAPPFGGI | ||||||
Topological domain | 235-242 | Lumenal, vesicle | ||||
Sequence: LYEFAGKR | ||||||
Transmembrane | 243-263 | Helical | ||||
Sequence: VPFLVLAAVSLFDALLLLAVA | ||||||
Topological domain | 264-289 | Cytoplasmic | ||||
Sequence: KPFSAAARARANLPVGTPIHRLMLDP | ||||||
Transmembrane | 290-310 | Helical | ||||
Sequence: YIAVVAGALTTCNIPLAFLEP | ||||||
Topological domain | 311-325 | Lumenal, vesicle | ||||
Sequence: TIATWMKHTMAASEW | ||||||
Transmembrane | 326-346 | Helical | ||||
Sequence: EMGMAWLPAFVPHVLGVYLTV | ||||||
Topological domain | 347-356 | Cytoplasmic | ||||
Sequence: RLAARYPHLQ | ||||||
Transmembrane | 357-377 | Helical | ||||
Sequence: WLYGALGLAVIGASSCIVPAC | ||||||
Topological domain | 378-388 | Lumenal, vesicle | ||||
Sequence: RSFAPLVVSLC | ||||||
Transmembrane | 389-409 | Helical | ||||
Sequence: GLCFGIALVDTALLPTLAFLV | ||||||
Topological domain | 410-422 | Cytoplasmic | ||||
Sequence: DVRHVSVYGSVYA | ||||||
Transmembrane | 423-443 | Helical | ||||
Sequence: IADISYSVAYALGPIVAGHIV | ||||||
Topological domain | 444-447 | Lumenal, vesicle | ||||
Sequence: HSLG | ||||||
Transmembrane | 448-468 | Helical | ||||
Sequence: FEQLSLGMGLANLLYAPVLLL | ||||||
Topological domain | 469-532 | Cytoplasmic | ||||
Sequence: LRNVGLLTRSRSERDVLLDEPPQGLYDAVRLRERPVSGQDGEPRSPPGPFDACEDDYNYYYTRS |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Myasthenic syndrome, congenital, 21, presynaptic (CMS21)
- Note
- DescriptionA form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS21 is an autosomal recessive, pre-synaptic form characterized by ptosis, ophthalmoplegia, fatigable weakness, apneic crises, and deterioration of symptoms in cold water. Learning difficulties and left ventricular dysfunction may be present in some patients.
- See alsoMIM:617239
Natural variants in CMS21
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_078030 | 186 | G>A | in CMS21; dbSNP:rs1057517665 | |
VAR_078031 | 398 | D>H | in CMS21; dbSNP:rs1057517666 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_029152 | 11 | in dbSNP:rs8187732 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_020034 | 13 | in dbSNP:rs8187733 | |||
Sequence: A → P | ||||||
Natural variant | VAR_020035 | 29 | in dbSNP:rs8187734 | |||
Sequence: R → W | ||||||
Natural variant | VAR_078030 | 186 | in CMS21; dbSNP:rs1057517665 | |||
Sequence: G → A | ||||||
Mutagenesis | 309 | Loss of activity. | ||||
Sequence: E → A or K | ||||||
Mutagenesis | 309 | Has normal transporter activity. Retains the transporter activity; when associated with E-398. | ||||
Sequence: E → D | ||||||
Mutagenesis | 309 | Has normal transporter activity. Loss of activity; when associated with N-398. | ||||
Sequence: E → Q | ||||||
Natural variant | VAR_078031 | 398 | in CMS21; dbSNP:rs1057517666 | |||
Sequence: D → H | ||||||
Mutagenesis | 398 | Loss of activity. | ||||
Sequence: D → N | ||||||
Natural variant | VAR_024638 | 520 | in dbSNP:rs8187730 | |||
Sequence: A → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 812 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000127517 | 1-532 | Vesicular acetylcholine transporter | |||
Sequence: MESAEPAGQARAAATKLSEAVGAALQEPRRQRRLVLVIVCVALLLDNMLYMVIVPIVPDYIAHMRGGGEGPTRTPEVWEPTLPLPTPANASAYTANTSASPTAAWPAGSALRPRYPTESEDVKIGVLFASKAILQLLVNPLSGPFIDRMSYDVPLLIGLGVMFASTVLFAFAEDYATLFAARSLQGLGSAFADTSGIAMIADKYPEEPERSRALGVALAFISFGSLVAPPFGGILYEFAGKRVPFLVLAAVSLFDALLLLAVAKPFSAAARARANLPVGTPIHRLMLDPYIAVVAGALTTCNIPLAFLEPTIATWMKHTMAASEWEMGMAWLPAFVPHVLGVYLTVRLAARYPHLQWLYGALGLAVIGASSCIVPACRSFAPLVVSLCGLCFGIALVDTALLPTLAFLVDVRHVSVYGSVYAIADISYSVAYALGPIVAGHIVHSLGFEQLSLGMGLANLLYAPVLLLLRNVGLLTRSRSERDVLLDEPPQGLYDAVRLRERPVSGQDGEPRSPPGPFDACEDDYNYYYTRS | ||||||
Glycosylation | 89 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 96 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with SEC14L1.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q16572 | CCDC167 Q9P0B6 | 3 | EBI-17598000, EBI-9083477 | |
BINARY | Q16572 | MFF Q9GZY8-5 | 3 | EBI-17598000, EBI-11956541 | |
BINARY | Q16572 | PEDS1-UBE2V1 I3L0A0 | 3 | EBI-17598000, EBI-12213001 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 471-532 | Mediates interaction with SEC14L1 | ||||
Sequence: NVGLLTRSRSERDVLLDEPPQGLYDAVRLRERPVSGQDGEPRSPPGPFDACEDDYNYYYTRS | ||||||
Region | 502-523 | Disordered | ||||
Sequence: RPVSGQDGEPRSPPGPFDACED |
Sequence similarities
Belongs to the major facilitator superfamily. Vesicular transporter family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length532
- Mass (Da)56,903
- Last updated2010-11-30 v2
- Checksum445CDF48F08ED31D
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U10554 EMBL· GenBank· DDBJ | AAB92675.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U09210 EMBL· GenBank· DDBJ | AAA20497.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313094 EMBL· GenBank· DDBJ | BAG35918.1 EMBL· GenBank· DDBJ | mRNA | ||
AC073366 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471187 EMBL· GenBank· DDBJ | EAW93093.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC007765 EMBL· GenBank· DDBJ | AAH07765.1 EMBL· GenBank· DDBJ | mRNA |