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Protein

Sodium-dependent dopamine transporter

Gene

SLC6A3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.3 Publications

Miscellaneous

This protein is the target of psychomotor stimulants such as amphetamines or cocaine.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi75Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi77Sodium 2; via carbonyl oxygenBy similarity1
Metal bindingi78Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi82Sodium 2By similarity1
Sitei105Contributes to high-affinity binding to cocaineBy similarity1
Metal bindingi321Sodium 2By similarity1
Metal bindingi353Sodium 2By similarity1
Metal bindingi418Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi421Sodium 1By similarity1
Metal bindingi422Sodium 1By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processNeurotransmitter transport, Symport, Transport
LigandMetal-binding, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-379401 Dopamine clearance from the synaptic cleft
R-HSA-442660 Na+/Cl- dependent neurotransmitter transporters
R-HSA-5619081 Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)
R-HSA-5660724 Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)
SABIO-RKiQ01959

Protein family/group databases

TCDBi2.A.22.1.3 the neurotransmitter:sodium symporter (nss) family

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium-dependent dopamine transporter
Short name:
DA transporter
Short name:
DAT
Alternative name(s):
Solute carrier family 6 member 3
Gene namesi
Name:SLC6A3
Synonyms:DAT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000142319.17
HGNCiHGNC:11049 SLC6A3
MIMi126455 gene
neXtProtiNX_Q01959

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 68CytoplasmicSequence analysisAdd BLAST68
Transmembranei69 – 89Helical; Name=1Sequence analysisAdd BLAST21
Transmembranei96 – 116Helical; Name=2Sequence analysisAdd BLAST21
Transmembranei140 – 160Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini161 – 237ExtracellularSequence analysisAdd BLAST77
Transmembranei238 – 256Helical; Name=4Sequence analysisAdd BLAST19
Transmembranei265 – 282Helical; Name=5Sequence analysisAdd BLAST18
Transmembranei318 – 335Helical; Name=6Sequence analysisAdd BLAST18
Transmembranei347 – 368Helical; Name=7Sequence analysisAdd BLAST22
Transmembranei401 – 420Helical; Name=8Sequence analysisAdd BLAST20
Transmembranei447 – 465Helical; Name=9Sequence analysisAdd BLAST19
Transmembranei481 – 501Helical; Name=10Sequence analysisAdd BLAST21
Transmembranei522 – 541Helical; Name=11Sequence analysisAdd BLAST20
Transmembranei560 – 578Helical; Name=12Sequence analysisAdd BLAST19
Topological domaini579 – 620CytoplasmicSequence analysisAdd BLAST42

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Parkinsonism-dystonia infantile (PKDYS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by infantile onset of parkinsonism and dystonia. Other neurologic features include global developmental delay, bradykinesia and pyramidal tract signs.
See also OMIM:613135
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063771368L → Q in PKDYS; loss of function. 1 PublicationCorresponds to variant dbSNP:rs267607068EnsemblClinVar.1
Natural variantiVAR_063772395P → L in PKDYS; loss of function. 1 PublicationCorresponds to variant dbSNP:rs267607069EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Dystonia, Neurodegeneration, Parkinsonism

Organism-specific databases

DisGeNETi6531
MalaCardsiSLC6A3
MIMi613135 phenotype
OpenTargetsiENSG00000142319
Orphaneti238455 Infantile dystonia-parkinsonism
PharmGKBiPA311

Chemistry databases

ChEMBLiCHEMBL238
DrugBankiDB01472 4-Methoxyamphetamine
DB04947 Altropane
DB00543 Amoxapine
DB00182 Amphetamine
DB06413 Armodafinil
DB00289 Atomoxetine
DB00245 Benzatropine
DB00865 Benzphetamine
DB01156 Bupropion
DB01161 Chloroprocaine
DB01114 Chlorphenamine
DB00215 Citalopram
DB00907 Cocaine
DB06701 Dexmethylphenidate
DB01576 Dextroamphetamine
DB00937 Diethylpropion
DB01146 Diphenylpyraline
DB00988 Dopamine
DB00476 Duloxetine
DB01363 Ephedra
DB01175 Escitalopram
DB01463 Fencamfamine
DB00458 Imipramine
DB08824 Ioflupane I-123
DB01255 Lisdexamfetamine
DB00408 Loxapine
DB00579 Mazindol
DB01577 Methamphetamine
DB09543 Methyl salicylate
DB00422 Methylphenidate
DB06148 Mianserin
DB00370 Mirtazapine
DB01442 MMDA
DB00745 Modafinil
DB01149 Nefazodone
DB04821 Nomifensine
DB00454 Pethidine
DB00830 Phenmetrazine
DB00191 Phentermine
DB00721 Procaine
DB00852 Pseudoephedrine
DB01104 Sertraline
DB01105 Sibutramine
DB00726 Trimipramine
DB00285 Venlafaxine
GuidetoPHARMACOLOGYi927

Polymorphism and mutation databases

BioMutaiSLC6A3
DMDMi266667

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002147511 – 620Sodium-dependent dopamine transporterAdd BLAST620

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi180 ↔ 189By similarity
Glycosylationi181N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi188N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi205N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi306Interchain1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ01959
PeptideAtlasiQ01959
PRIDEiQ01959
ProteomicsDBi58021

PTM databases

iPTMnetiQ01959
PhosphoSitePlusiQ01959

Miscellaneous databases

PMAP-CutDBiQ01959

Expressioni

Tissue specificityi

Highly expressed in substantia nigra.1 Publication

Gene expression databases

BgeeiENSG00000142319 Expressed in 60 organ(s), highest expression level in substantia nigra
CleanExiHS_SLC6A3
GenevisibleiQ01959 HS

Organism-specific databases

HPAiCAB016249
CAB078172
HPA012763
HPA013602

Interactioni

Subunit structurei

Homooligomer; disulfide-linked (Ref. 14). Interacts with PRKCABP and TGFB1I1 (PubMed:11343649, PubMed:12177201). Interacts (via N-terminus) with SYNGR3 (via N-terminus). Interacts with SLC18A2. Interacts with TOR1A (ATP-bound); TOR1A regulates SLC6A3 subcellular location (By similarity).By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112422, 14 interactors
DIPiDIP-41827N
IntActiQ01959, 8 interactors
MINTiQ01959
STRINGi9606.ENSP00000270349

Chemistry databases

BindingDBiQ01959

Structurei

3D structure databases

ProteinModelPortaliQ01959
SMRiQ01959
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni561 – 590Interaction with TGFB1I11 PublicationAdd BLAST30

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3659 Eukaryota
COG0733 LUCA
GeneTreeiENSGT00760000118857
HOGENOMiHOG000116406
HOVERGENiHBG071421
InParanoidiQ01959
KOiK05036
OMAiGMATFIF
OrthoDBiEOG091G08PX
PhylomeDBiQ01959
TreeFamiTF343812

Family and domain databases

InterProiView protein in InterPro
IPR000175 Na/ntran_symport
IPR002436 Na/ntran_symport_dopamine
IPR037272 SNS_sf
PANTHERiPTHR11616 PTHR11616, 1 hit
PfamiView protein in Pfam
PF00209 SNF, 1 hit
PRINTSiPR01202 DOPTRANSPORT
PR00176 NANEUSMPORT
SUPFAMiSSF161070 SSF161070, 1 hit
PROSITEiView protein in PROSITE
PS00610 NA_NEUROTRAN_SYMP_1, 1 hit
PS00754 NA_NEUROTRAN_SYMP_2, 1 hit
PS50267 NA_NEUROTRAN_SYMP_3, 1 hit

Sequencei

Sequence statusi: Complete.

Q01959-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSKSKCSVGL MSSVVAPAKE PNAVGPKEVE LILVKEQNGV QLTSSTLTNP
60 70 80 90 100
RQSPVEAQDR ETWGKKIDFL LSVIGFAVDL ANVWRFPYLC YKNGGGAFLV
110 120 130 140 150
PYLLFMVIAG MPLFYMELAL GQFNREGAAG VWKICPILKG VGFTVILISL
160 170 180 190 200
YVGFFYNVII AWALHYLFSS FTTELPWIHC NNSWNSPNCS DAHPGDSSGD
210 220 230 240 250
SSGLNDTFGT TPAAEYFERG VLHLHQSHGI DDLGPPRWQL TACLVLVIVL
260 270 280 290 300
LYFSLWKGVK TSGKVVWITA TMPYVVLTAL LLRGVTLPGA IDGIRAYLSV
310 320 330 340 350
DFYRLCEASV WIDAATQVCF SLGVGFGVLI AFSSYNKFTN NCYRDAIVTT
360 370 380 390 400
SINSLTSFSS GFVVFSFLGY MAQKHSVPIG DVAKDGPGLI FIIYPEAIAT
410 420 430 440 450
LPLSSAWAVV FFIMLLTLGI DSAMGGMESV ITGLIDEFQL LHRHRELFTL
460 470 480 490 500
FIVLATFLLS LFCVTNGGIY VFTLLDHFAA GTSILFGVLI EAIGVAWFYG
510 520 530 540 550
VGQFSDDIQQ MTGQRPSLYW RLCWKLVSPC FLLFVVVVSI VTFRPPHYGA
560 570 580 590 600
YIFPDWANAL GWVIATSSMA MVPIYAAYKF CSLPGSFREK LAYAIAPEKD
610 620
RELVDRGEVR QFTLRHWLKV
Length:620
Mass (Da):68,495
Last modified:April 1, 1993 - v1
Checksum:iCD95009B6BA93108
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti35K → M in AAB23443 (PubMed:1406597).Curated1
Sequence conflicti354S → C in AAB23443 (PubMed:1406597).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036158121G → S in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs760871529Ensembl.1
Natural variantiVAR_014180237R → Q1 PublicationCorresponds to variant dbSNP:rs6345Ensembl.1
Natural variantiVAR_063771368L → Q in PKDYS; loss of function. 1 PublicationCorresponds to variant dbSNP:rs267607068EnsemblClinVar.1
Natural variantiVAR_063772395P → L in PKDYS; loss of function. 1 PublicationCorresponds to variant dbSNP:rs267607069EnsemblClinVar.1
Natural variantiVAR_064580471V → I1 PublicationCorresponds to variant dbSNP:rs75916702Ensembl.1
Natural variantiVAR_036159544R → S in a breast cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M95167 mRNA Translation: AAC41720.1
S46955 mRNA Translation: AAA11754.1
S44626 mRNA Translation: AAB23443.1
L24178 mRNA Translation: AAA19560.1
D88570 Genomic DNA Translation: BAA22511.1
AF119117 Genomic DNA Translation: AAC50179.2
AF321321
, AF306558, AF321320, AF306559, AF306560, AF306561, AF306562, AF306563, AF306564 Genomic DNA Translation: AAG33844.1
EF174603 mRNA Translation: ABO77644.1
AY623110 Genomic DNA Translation: AAT38106.1
CH471102 Genomic DNA Translation: EAX08159.1
BC132977 mRNA Translation: AAI32978.1
BC133003 mRNA Translation: AAI33004.1
M96670 mRNA Translation: AAA35770.1
CCDSiCCDS3863.1
PIRiA48980
I57937
I84455
RefSeqiNP_001035.1, NM_001044.4
UniGeneiHs.406

Genome annotation databases

EnsembliENST00000270349; ENSP00000270349; ENSG00000142319
ENST00000621716; ENSP00000479597; ENSG00000276996
GeneIDi6531
KEGGihsa:6531
UCSCiuc003jck.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Dopamine transporter entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M95167 mRNA Translation: AAC41720.1
S46955 mRNA Translation: AAA11754.1
S44626 mRNA Translation: AAB23443.1
L24178 mRNA Translation: AAA19560.1
D88570 Genomic DNA Translation: BAA22511.1
AF119117 Genomic DNA Translation: AAC50179.2
AF321321
, AF306558, AF321320, AF306559, AF306560, AF306561, AF306562, AF306563, AF306564 Genomic DNA Translation: AAG33844.1
EF174603 mRNA Translation: ABO77644.1
AY623110 Genomic DNA Translation: AAT38106.1
CH471102 Genomic DNA Translation: EAX08159.1
BC132977 mRNA Translation: AAI32978.1
BC133003 mRNA Translation: AAI33004.1
M96670 mRNA Translation: AAA35770.1
CCDSiCCDS3863.1
PIRiA48980
I57937
I84455
RefSeqiNP_001035.1, NM_001044.4
UniGeneiHs.406

3D structure databases

ProteinModelPortaliQ01959
SMRiQ01959
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112422, 14 interactors
DIPiDIP-41827N
IntActiQ01959, 8 interactors
MINTiQ01959
STRINGi9606.ENSP00000270349

Chemistry databases

BindingDBiQ01959
ChEMBLiCHEMBL238
DrugBankiDB01472 4-Methoxyamphetamine
DB04947 Altropane
DB00543 Amoxapine
DB00182 Amphetamine
DB06413 Armodafinil
DB00289 Atomoxetine
DB00245 Benzatropine
DB00865 Benzphetamine
DB01156 Bupropion
DB01161 Chloroprocaine
DB01114 Chlorphenamine
DB00215 Citalopram
DB00907 Cocaine
DB06701 Dexmethylphenidate
DB01576 Dextroamphetamine
DB00937 Diethylpropion
DB01146 Diphenylpyraline
DB00988 Dopamine
DB00476 Duloxetine
DB01363 Ephedra
DB01175 Escitalopram
DB01463 Fencamfamine
DB00458 Imipramine
DB08824 Ioflupane I-123
DB01255 Lisdexamfetamine
DB00408 Loxapine
DB00579 Mazindol
DB01577 Methamphetamine
DB09543 Methyl salicylate
DB00422 Methylphenidate
DB06148 Mianserin
DB00370 Mirtazapine
DB01442 MMDA
DB00745 Modafinil
DB01149 Nefazodone
DB04821 Nomifensine
DB00454 Pethidine
DB00830 Phenmetrazine
DB00191 Phentermine
DB00721 Procaine
DB00852 Pseudoephedrine
DB01104 Sertraline
DB01105 Sibutramine
DB00726 Trimipramine
DB00285 Venlafaxine
GuidetoPHARMACOLOGYi927

Protein family/group databases

TCDBi2.A.22.1.3 the neurotransmitter:sodium symporter (nss) family

PTM databases

iPTMnetiQ01959
PhosphoSitePlusiQ01959

Polymorphism and mutation databases

BioMutaiSLC6A3
DMDMi266667

Proteomic databases

PaxDbiQ01959
PeptideAtlasiQ01959
PRIDEiQ01959
ProteomicsDBi58021

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000270349; ENSP00000270349; ENSG00000142319
ENST00000621716; ENSP00000479597; ENSG00000276996
GeneIDi6531
KEGGihsa:6531
UCSCiuc003jck.4 human

Organism-specific databases

CTDi6531
DisGeNETi6531
EuPathDBiHostDB:ENSG00000142319.17
GeneCardsiSLC6A3
HGNCiHGNC:11049 SLC6A3
HPAiCAB016249
CAB078172
HPA012763
HPA013602
MalaCardsiSLC6A3
MIMi126455 gene
613135 phenotype
neXtProtiNX_Q01959
OpenTargetsiENSG00000142319
Orphaneti238455 Infantile dystonia-parkinsonism
PharmGKBiPA311
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3659 Eukaryota
COG0733 LUCA
GeneTreeiENSGT00760000118857
HOGENOMiHOG000116406
HOVERGENiHBG071421
InParanoidiQ01959
KOiK05036
OMAiGMATFIF
OrthoDBiEOG091G08PX
PhylomeDBiQ01959
TreeFamiTF343812

Enzyme and pathway databases

ReactomeiR-HSA-379401 Dopamine clearance from the synaptic cleft
R-HSA-442660 Na+/Cl- dependent neurotransmitter transporters
R-HSA-5619081 Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)
R-HSA-5660724 Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)
SABIO-RKiQ01959

Miscellaneous databases

ChiTaRSiSLC6A3 human
GeneWikiiDopamine_transporter
GenomeRNAii6531
PMAP-CutDBiQ01959
PROiPR:Q01959
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142319 Expressed in 60 organ(s), highest expression level in substantia nigra
CleanExiHS_SLC6A3
GenevisibleiQ01959 HS

Family and domain databases

InterProiView protein in InterPro
IPR000175 Na/ntran_symport
IPR002436 Na/ntran_symport_dopamine
IPR037272 SNS_sf
PANTHERiPTHR11616 PTHR11616, 1 hit
PfamiView protein in Pfam
PF00209 SNF, 1 hit
PRINTSiPR01202 DOPTRANSPORT
PR00176 NANEUSMPORT
SUPFAMiSSF161070 SSF161070, 1 hit
PROSITEiView protein in PROSITE
PS00610 NA_NEUROTRAN_SYMP_1, 1 hit
PS00754 NA_NEUROTRAN_SYMP_2, 1 hit
PS50267 NA_NEUROTRAN_SYMP_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSC6A3_HUMAN
AccessioniPrimary (citable) accession number: Q01959
Secondary accession number(s): A2RUN4, Q14996
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: September 12, 2018
This is version 192 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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