SLC18A2
entrez
6571
canonical
uniprot
Q05940
canonical
ensembl
ENSG00000165646
resolver
ensp
ENSP00000496339
resolver
genesymbol
SLC18A2
resolver
genesymbol_syn
SVMT
resolver
genesymbol_syn
VMAT2
resolver
hgnc
HGNC:10935
resolver
uniprot
B2RC96
resolver
uniprot
D3DRC4
resolver
uniprot
Q15876
resolver
uniprot
Q4G147
resolver
uniprot
Q5VW49
resolver
uniprot
Q9H3P6
resolver
uniprot_entry
VMAT2_HUMAN
resolver
uniprot_sec
B2RC96
resolver
uniprot_sec
D3DRC4
resolver
uniprot_sec
Q15876
resolver
uniprot_sec
Q4G147
resolver
uniprot_sec
Q5VW49
resolver
uniprot_sec
Q9H3P6
resolver
activity_regulation
ACTIVITY REGULATION: Strongly inhibited by reserpine and tetrabenazine (PubMed:37914936, PubMed:38081299, PubMed:38517752, PubMed:8643547, PubMed:8860238). Also inhibited to a lesser extent by ketanserin and fenfluramine (PubMed:38081299). Reserpine and ketanserin inhibit by blocking the substrate-binding pocket (PubMed:37914936, PubMed:38081299). Tetrabenazine traps SLC18A2/VMAT2 in an occluded conformation and its inhibition is specific to SLC18A2/VMAT2 but not SLC18A1/VMAT1 (PubMed:37914936, PubMed:38081299, PubMed:38517752). {ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0000269|PubMed:8643547, ECO:0000269|PubMed:8860238}.
uniprot
proteins
amino_acid_sequence
MALSELALVRWLQESRRSRKLILFIVFLALLLDNMLLTVVVPIIPSYLYSIKHEKNATEIQTARPVHTASISDSFQSIFSYYDNSTMVTGNATRDLTLHQTATQHMVTNASAVPSDCPSEDKDLLNENVQVGLLFASKATVQLITNPFIGLLTNRIGYPIPIFAGFCIMFVSTIMFAFSSSYAFLLIARSLQGIGSSCSSVAGMGMLASVYTDDEERGNVMGIALGGLAMGVLVGPPFGSVLYEFVGKTAPFLVLAALVLLDGAIQLFVLQPSRVQPESQKGTPLTTLLKDPYILIAAGSICFANMGIAMLEPALPIWMMETMCSRKWQLGVAFLPASISYLIGTNIFGILAHKMGRWLCALLGMIIVGVSILCIPFAKNIYGLIAPNFGVGFAIGMVDSSMMPIMGYLVDLRHVSVYGSVYAIADVAFCMGYAIGPSAGGAIAKAIGFPWLMTIIGIIDILFAPLCFFLRSPPAKEEKMAILMDHNCPIKTKMYTQNNIQSYPIGEDEESESD
uniprot
proteins
disease_involvement
DISEASE: Parkinsonism-dystonia 2, infantile-onset (PKDYS2) [MIM:618049]: 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. {ECO:0000269|PubMed:23363473}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
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: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). {ECO:0000250|UniProtKB:Q01827, ECO:0000250|UniProtKB:Q8BRU6, ECO:0000269|PubMed:23363473, ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0000269|PubMed:8643547, ECO:0000269|PubMed:8860238}.
uniprot
proteins
mass_dalton
55713
uniprot
proteins
mutagenesis
MUTAGEN 33; /note="D->A: Abolishes dopamine uptake."; MUTAGEN 33; /note="D->N: Abolishes dopamine uptake. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299"; MUTAGEN 34; /note="N->A: Abolishes binding to reserpine. Reduces binding to dihydrotetrabenazine. Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38517752"; MUTAGEN 34; /note="N->D: Abolishes binding to dihydrotetrabenazine. Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:38517752"; MUTAGEN 34; /note="N->Q: Reduces binding to dihydrotetrabenazine."; /evidence="ECO:0000269|PubMed:38517752"; MUTAGEN 34; /note="N->T: Abolishes binding to dihydrotetrabenazine. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:38517752"; MUTAGEN 37; /note="L->A: Abolishes binding to dihydrotetrabenazine."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 37; /note="L->F: Reduces sensitivity to tetrabenazine. Reduces fluorescent false neurotransmitter FFN206 uptake. Abolishes binding to dihydrotetrabenazine. Abolishes serotonin uptake. Largely reduces sensitivity to tetrabenazine and slightly reduces FFN206 uptake; when associated with V-308 and F-433."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38517752"; MUTAGEN 37; /note="L->Y: Abolishes binding to tetrabenazine. Reduces sensitivity to tetrabenazine."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 38; /note="T->A: Abolishes binding to dihydrotetrabenazine. Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 41; /note="V->A: Abolishes binding to dihydrotetrabenazine. Reduces dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 45; /note="P->A: Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 127; /note="E->A: Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:38517752"; MUTAGEN 135; /note="F->A: Abolishes binding to dihydrotetrabenazine. Reduces sensitivity to tetrabenazine. Abolishes FFN206 uptake. Abolishes binding to dihydrotetrabenazine. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38517752"; MUTAGEN 138; /note="K->A: Reduces dopamine uptake. Abolishes binding to dihydrotetrabenazine. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38517752"; MUTAGEN 189; /note="R->A: Abolishes binding to dihydrotetrabenazine. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38517752"; MUTAGEN 189; /note="R->K: Abolishes binding to dihydrotetrabenazine. Abolishes binding to tetrabenazine. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752"; MUTAGEN 189; /note="R->Q: Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 196; /note="S->A: Reduces dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 204; /note="M->A: Reduces dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 214; /note="D->A: Abolishes serotonin uptake; when associated with A-217."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 214; /note="D->N: Reduces dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 217; /note="R->A: Abolishes dopamine uptake. Abolishes serotonin uptake; when associated with A-214."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299"; MUTAGEN 221; /note="M->A: Reduces dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 225; /note="L->A: Reduces binding to reserpine."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 228; /note="L->A: Reduces sensitivity to reserpine."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 232; /note="V->A: Abolishes binding to dihydrotetrabenazine. Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 232; /note="V->F: Abolishes binding to reserpine."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 232; /note="V->L: Abolishes serotonin uptake. Abolishes binding to tetrabenazine. Reduces sensitivity to reserpine and tetrabenazine. Reduces binding to dihydrotetrabenazine."; /evidence="ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752"; MUTAGEN 244; /note="E->A: Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 305; /note="N->A: Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 308; /note="I->A: Abolishes binding to dihydrotetrabenazine. Abolishes dopamine uptake. Reduces FFN206 uptake. Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299"; MUTAGEN 308; /note="I->V: Reduces sensitivity to tetrabenazine. Largely reduces sensitivity to tetrabenazine and slightly reduces FFN206 uptake; when associated with F-37 and F-433."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 312; /note="E->A: Abolishes binding to dihydrotetrabenazine. Abolishes dopamine uptake. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299"; MUTAGEN 312; /note="E->N: Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 312; /note="E->Q: Abolishes dopamine uptake. Abolishes serotonin uptake. Reduces binding to dihydrotetrabenazine. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752"; MUTAGEN 313; /note="P->A: Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 316; /note="P->A: Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 318; /note="W->A: Abolishes binding to dihydrotetrabenazine. Abolishes dopamine uptake. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38517752"; MUTAGEN 318; /note="W->F: Reduces binding to dihydrotetrabenazine. Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:38517752"; MUTAGEN 318; /note="W->H: Reduces binding to dihydrotetrabenazine. Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:38517752"; MUTAGEN 318; /note="W->R: Abolishes binding to dihydrotetrabenazine."; /evidence="ECO:0000269|PubMed:38517752"; MUTAGEN 334; /note="F->A: Abolishes binding to dihydrotetrabenazine. Reduces binding to reserpine. Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 338; /note="S->A: Reduces dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 338; /note="S->F: Abolishes serotonin uptake. Abolishes binding to reserpine."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 339; /note="I->A,N: Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 341; /note="Y->A: Reduces binding to dihydrotetrabenazine. Reduces binding to reserpine. Abolishes dopamine uptake. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299"; MUTAGEN 357; /note="R->A: Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 357; /note="R->Q: Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:38081299"; MUTAGEN 395; /note="I->A: Reduces binding to reserpine."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 399; /note="D->A,N: Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 403; /note="M->A: Reduces binding to reserpine. Reduces dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 411; /note="D->A: Reduces dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 411; /note="D->N: Reduces dopamine uptake. Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299"; MUTAGEN 418; /note="Y->S: Binds reserpine in the absence of a proton gradient. Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 422; /note="Y->A: Reduces dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 426; /note="D->A: Abolishes dopamine uptake."; /evidence="ECO:0000269|PubMed:37914936"; MUTAGEN 426; /note="D->N: Abolishes dopamine uptake. Abolishes serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299"; MUTAGEN 429; /note="F->A: Abolishes binding to reserpine. Reduces serotonin uptake."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38517752"; MUTAGEN 433; /note="Y->A: Abolishes binding to dihydrotetrabenazine. Slightly reduces binding to reserpine and FFN206 uptake. Reduces dopamine uptake. Reduces sensitivity to tetrabenazine."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38517752"; MUTAGEN 433; /note="Y->F: Slightly reduces sensitivity to tetrabenazine and FFN206 uptake. Reduces serotonin uptake. Reduces sensitivity to reserpine. Largely reduces sensitivity to tetrabenazine and slightly reduces FFN206 uptake; when associated with F-37 and V-308."; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299
uniprot
proteins
protein_family
Major facilitator superfamily
uniprot
proteins
protein_family
Vesicular transporter family
uniprot
proteins
pubmed
11443533
uniprot
proteins
pubmed
12009896
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
23363473
uniprot
proteins
pubmed
37914936
uniprot
proteins
pubmed
38081299
uniprot
proteins
pubmed
38517752
uniprot
proteins
pubmed
7905859
uniprot
proteins
pubmed
8095030
uniprot
proteins
pubmed
8245983
uniprot
proteins
pubmed
8373557
uniprot
proteins
pubmed
8643547
uniprot
proteins
pubmed
8860238
uniprot
proteins
sequence_length
514
uniprot
proteins
subcellular_location
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}.
uniprot
proteins
transmembrane_region
TRANSMEM 21..41; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 130..150; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 160..180; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 190..210; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 220..242; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 249..271; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 292..311; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 329..352; /note="Helical; Name=8"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 358..378; /note="Helical; Name=9"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 390..410; /note="Helical; Name=10"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 415..435; /note="Helical; Name=11"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR"; TRANSMEM 441..462; /note="Helical; Name=12"; /evidence="ECO:0000269|PubMed:37914936, ECO:0000269|PubMed:38081299, ECO:0000269|PubMed:38517752, ECO:0007744|PDB:8JSW, ECO:0007744|PDB:8JT9, ECO:0007744|PDB:8JTA, ECO:0007744|PDB:8JTC, ECO:0007744|PDB:8T69, ECO:0007744|PDB:8T6A, ECO:0007744|PDB:8T6B, ECO:0007744|PDB:8THR
uniprot
proteins