P54219 · VMAT1_HUMAN
- ProteinChromaffin granule amine transporter
- GeneSLC18A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids525 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Isoform 1
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 catecholamines and indolamines with higher affinity for serotonin (PubMed:16326835, PubMed:23337945, PubMed:8643547).
Regulates the transvesicular monoaminergic gradient that determines the quantal size. Mediates presynaptic monoaminergic vesicle transport in the amygdala and prefrontal brain regions related with emotion processing in response to environmental stimuli (PubMed:23337945).
Regulates the transvesicular monoaminergic gradient that determines the quantal size. Mediates presynaptic monoaminergic vesicle transport in the amygdala and prefrontal brain regions related with emotion processing in response to environmental stimuli (PubMed:23337945).
Isoform 2
Unable to uptake serotonin.
Catalytic activity
Isoform 1
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:350546Isoform 1
(R)-noradrenaline(in) + 2 H+(out) = (R)-noradrenaline(out) + 2 H+(in)This reaction proceeds in the forward direction.Isoform 1
dopamine(in) + 2 H+(out) = dopamine(out) + 2 H+(in)This reaction proceeds in the forward direction.
Activity regulation
Isoform 1
Strongly inhibited by reserpine. Also inhibited to a lesser extent by ketanserin and fenfluramine. Not significantly inhibited by tetrabenazine.
Kinetics
Isoform 1
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
1.3 μM | serotonin |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | clathrin-sculpted monoamine transport vesicle membrane | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | presynapse | |
Cellular Component | secretory granule membrane | |
Cellular Component | synaptic vesicle membrane | |
Cellular Component | terminal bouton | |
Molecular Function | monoamine transmembrane transporter activity | |
Molecular Function | monoamine:proton antiporter activity | |
Molecular Function | serotonin:sodium:chloride symporter activity | |
Molecular Function | xenobiotic transmembrane transporter activity | |
Biological Process | aminergic neurotransmitter loading into synaptic vesicle | |
Biological Process | dopamine uptake | |
Biological Process | monoamine transport | |
Biological Process | norepinephrine uptake | |
Biological Process | serotonin uptake |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameChromaffin granule amine transporter
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP54219
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cytoplasmic vesicle, secretory vesicle membrane ; Multi-pass membrane protein
Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane ; Multi-pass membrane protein
Isoform 1
Cytoplasmic vesicle, secretory vesicle membrane ; Multi-pass membrane protein
Isoform 2
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-21 | Cytoplasmic | ||||
Sequence: MLRTILDAPQRLLKEGRASRQ | ||||||
Transmembrane | 22-42 | Helical | ||||
Sequence: LVLVVVFVALLLDNMLFTVVV | ||||||
Topological domain | 43-138 | Lumenal, vesicle | ||||
Sequence: PIVPTFLYDMEFKEVNSSLHLGHAGSSPHALASPAFSTIFSFFNNNTVAVEESVPSGIAWMNDTASTIPPPATEAISAHKNNCLQGTGFLEEEITR | ||||||
Transmembrane | 139-158 | Helical | ||||
Sequence: VGVLFASKAVMQLLVNPFVG | ||||||
Topological domain | 159-167 | Cytoplasmic | ||||
Sequence: PLTNRIGYH | ||||||
Transmembrane | 168-188 | Helical | ||||
Sequence: IPMFAGFVIMFLSTVMFAFSG | ||||||
Topological domain | 189-197 | Lumenal, vesicle | ||||
Sequence: TYTLLFVAR | ||||||
Transmembrane | 198-218 | Helical | ||||
Sequence: TLQGIGSSFSSVAGLGMLASV | ||||||
Topological domain | 219-227 | Cytoplasmic | ||||
Sequence: YTDDHERGR | ||||||
Transmembrane | 228-250 | Helical | ||||
Sequence: AMGTALGGLALGLLVGAPFGSVM | ||||||
Topological domain | 251-256 | Lumenal, vesicle | ||||
Sequence: YEFVGK | ||||||
Transmembrane | 257-279 | Helical | ||||
Sequence: SAPFLILAFLALLDGALQLCILQ | ||||||
Topological domain | 280-299 | Cytoplasmic | ||||
Sequence: PSKVSPESAKGTPLFMLLKD | ||||||
Transmembrane | 300-319 | Helical | ||||
Sequence: PYILVAAGSICFANMGVAIL | ||||||
Topological domain | 320-335 | Lumenal, vesicle | ||||
Sequence: EPTLPIWMMQTMCSPK | ||||||
Transmembrane | 336-360 | Helical | ||||
Sequence: WQLGLAFLPASVSYLIGTNLFGVLA | ||||||
Topological domain | 361-365 | Cytoplasmic | ||||
Sequence: NKMGR | ||||||
Transmembrane | 366-386 | Helical | ||||
Sequence: WLCSLIGMLVVGTSLLCVPLA | ||||||
Topological domain | 387-397 | Lumenal, vesicle | ||||
Sequence: HNIFGLIGPNA | ||||||
Transmembrane | 398-418 | Helical | ||||
Sequence: GLGLAIGMVDSSMMPIMGHLV | ||||||
Topological domain | 419-422 | Cytoplasmic | ||||
Sequence: DLRH | ||||||
Transmembrane | 423-443 | Helical | ||||
Sequence: TSVYGSVYAIADVAFCMGFAI | ||||||
Topological domain | 444-448 | Lumenal, vesicle | ||||
Sequence: GPSTG | ||||||
Transmembrane | 449-470 | Helical | ||||
Sequence: GAIVKAIGFPWLMVITGVINIV | ||||||
Topological domain | 471-525 | Cytoplasmic | ||||
Sequence: YAPLCYYLRSPPAKEEKLAILSQDCPMETRMYATQKPTKEFPLGEDSDEEPDHEE |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_021856 | 4 | in dbSNP:rs2270641 | |||
Sequence: T → P | ||||||
Natural variant | VAR_087305 | 10 | found in a patient with bipolar disorder; has no significant effect on monoamine vesicular uptake; dbSNP:rs150204882 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_052002 | 11 | in dbSNP:rs17092144 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_024632 | 74 | in dbSNP:rs17215815 | |||
Sequence: A → V | ||||||
Natural variant | VAR_029149 | 82 | in dbSNP:rs17215822 | |||
Sequence: F → C | ||||||
Natural variant | VAR_024633 | 84 | found in patients with bipolar disorder; increases the vesicular uptake of noradrenaline and dopamine; dbSNP:rs17215801 | |||
Sequence: F → S | ||||||
Natural variant | VAR_020033 | 98 | in dbSNP:rs2270637 | |||
Sequence: S → T | ||||||
Natural variant | VAR_024634 | 101 | found in a patient with bipolar disorder; decreases the vesicular uptake of noradrenaline, dopamine and serotonin; dbSNP:rs17222218 | |||
Sequence: A → P | ||||||
Natural variant | VAR_012065 | 136 | decreases the vesicular uptake of noradrenaline, dopamine and serotonin; may predispose carriers to a increased cortical response to negative stimuli and reduced threat-related amygdala reactivity; dbSNP:rs1390938 | |||
Sequence: I → T | ||||||
Natural variant | VAR_087306 | 138 | found in patients with bipolar disorder; decreases the vesicular uptake of noradrenaline, dopamine and serotonin; dbSNP:rs148468662 | |||
Sequence: R → L | ||||||
Natural variant | VAR_029150 | 140 | in dbSNP:rs17215808 | |||
Sequence: G → R | ||||||
Natural variant | VAR_024635 | 164 | in dbSNP:rs17222092 | |||
Sequence: I → M | ||||||
Natural variant | VAR_029151 | 202 | in dbSNP:rs17222120 | |||
Sequence: I → T | ||||||
Natural variant | VAR_024636 | 249 | in dbSNP:rs17215759 | |||
Sequence: V → I | ||||||
Natural variant | VAR_024637 | 392 | decreases the vesicular uptake of noradrenaline and dopamine; dbSNP:rs17092104 | |||
Sequence: L → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 948 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000127510 | 1-525 | UniProt | Chromaffin granule amine transporter | |||
Sequence: MLRTILDAPQRLLKEGRASRQLVLVVVFVALLLDNMLFTVVVPIVPTFLYDMEFKEVNSSLHLGHAGSSPHALASPAFSTIFSFFNNNTVAVEESVPSGIAWMNDTASTIPPPATEAISAHKNNCLQGTGFLEEEITRVGVLFASKAVMQLLVNPFVGPLTNRIGYHIPMFAGFVIMFLSTVMFAFSGTYTLLFVARTLQGIGSSFSSVAGLGMLASVYTDDHERGRAMGTALGGLALGLLVGAPFGSVMYEFVGKSAPFLILAFLALLDGALQLCILQPSKVSPESAKGTPLFMLLKDPYILVAAGSICFANMGVAILEPTLPIWMMQTMCSPKWQLGLAFLPASVSYLIGTNLFGVLANKMGRWLCSLIGMLVVGTSLLCVPLAHNIFGLIGPNAGLGLAIGMVDSSMMPIMGHLVDLRHTSVYGSVYAIADVAFCMGFAIGPSTGGAIVKAIGFPWLMVITGVINIVYAPLCYYLRSPPAKEEKLAILSQDCPMETRMYATQKPTKEFPLGEDSDEEPDHEE | |||||||
Glycosylation | 58 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 87 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 104 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue (large scale data) | 517 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed primarily in neuroendocrine tissues. Highly expressed in chromaffin cells of the adrenal medulla (at protein level). Detected in peripheral sympathetic ganglia (at protein level). Found in some paracrine cells in stomach and duodenum (at protein level) (PubMed:8643547).
Expressed in substantia nigra (PubMed:23337945).
Expressed in substantia nigra (PubMed:23337945).
Isoform 1
Expressed in gastrointestinal tract.
Isoform 2
Expressed in gastrointestinal tract.
Gene expression databases
Organism-specific databases
Interaction
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 503-525 | Disordered | ||||
Sequence: ATQKPTKEFPLGEDSDEEPDHEE |
Sequence similarities
Belongs to the major facilitator superfamily. Vesicular transporter family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
P54219-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length525
- Mass (Da)56,257
- Last updated1996-10-01 v1
- Checksum041F2959F4F2BFBC
P54219-2
- Name2
- SynonymsVMAT1delta15
- Differences from canonical
- 445-525: PSTGGAIVKAIGFPWLMVITGVINIVYAPLCYYLRSPPAKEEKLAILSQDCPMETRMYATQKPTKEFPLGEDSDEEPDHEE → YSESGLPHGDPDVCNPEAHEGISSGGGQ
P54219-3
- Name3
- Differences from canonical
- 307-338: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U39905 EMBL· GenBank· DDBJ | AAC50472.1 EMBL· GenBank· DDBJ | mRNA | ||
AC025853 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC006317 EMBL· GenBank· DDBJ | AAH06317.1 EMBL· GenBank· DDBJ | mRNA |