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Protein

Sodium-dependent dopamine transporter

Gene

SLC6A3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

Complete GO annotation...

Keywords - Biological processi

Neurotransmitter transport, Symport, Transport

Keywords - Ligandi

Metal-binding, Sodium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000142319-MONOMER.
ReactomeiR-HSA-379401. Dopamine clearance from the synaptic cleft.
R-HSA-442660. Na+/Cl- dependent neurotransmitter transporters.
SABIO-RKQ01959.

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

HGNCiHGNC:11049. SLC6A3.

Subcellular locationi

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

GO - Cellular componenti

  • axon Source: UniProtKB
  • cell surface Source: UniProtKB
  • cytoplasm Source: ProtInc
  • flotillin complex Source: UniProtKB
  • integral component of membrane Source: ProtInc
  • integral component of plasma membrane Source: GO_Central
  • membrane raft Source: ParkinsonsUK-UCL
  • neuronal cell body Source: UniProtKB
  • neuron projection Source: ParkinsonsUK-UCL
  • plasma membrane Source: UniProtKB
  • presynapse Source: GOC
Complete GO annotation...

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 rs267607068dbSNPEnsembl.1
Natural variantiVAR_063772395P → L in PKDYS; loss of function. 1 PublicationCorresponds to variant rs267607069dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Dystonia, Neurodegeneration, Parkinsonism

Organism-specific databases

DisGeNETi6531.
MalaCardsiSLC6A3.
MIMi613135. phenotype.
OpenTargetsiENSG00000142319.
ENSG00000276996.
Orphaneti238455. Infantile dystonia-parkinsonism.
PharmGKBiPA311.

Chemistry databases

ChEMBLiCHEMBL238.
DrugBankiDB00543. 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.
DB00422. Methylphenidate.
DB06148. Mianserin.
DB00370. Mirtazapine.
DB00745. Modafinil.
DB01149. Nefazodone.
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...)Sequence analysis1
Glycosylationi188N-linked (GlcNAc...)Sequence analysis1
Glycosylationi205N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi306Interchain1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ01959.
PeptideAtlasiQ01959.
PRIDEiQ01959.

PTM databases

iPTMnetiQ01959.
PhosphoSitePlusiQ01959.

Miscellaneous databases

PMAP-CutDBQ01959.

Expressioni

Tissue specificityi

Highly expressed in substantia nigra.1 Publication

Gene expression databases

BgeeiENSG00000142319.
CleanExiHS_SLC6A3.
GenevisibleiQ01959. HS.

Organism-specific databases

HPAiCAB016249.
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

WithEntry#Exp.IntActNotes
DRD2P144164EBI-6661445,EBI-2928178
SNCAP378403EBI-6661445,EBI-985879

Protein-protein interaction databases

BioGridi112422. 13 interactors.
DIPiDIP-41827N.
IntActiQ01959. 4 interactors.
MINTiMINT-576917.
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.
OMAiYAAYKFC.
OrthoDBiEOG091G08PX.
PhylomeDBiQ01959.
TreeFamiTF343812.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
IPR002436. Na/ntran_symport_dopamine.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 1 hit.
PfamiPF00209. SNF. 1 hit.
[Graphical view]
PRINTSiPR01202. DOPTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEiPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]

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 rs760871529dbSNPEnsembl.1
Natural variantiVAR_014180237R → Q.1 PublicationCorresponds to variant rs6345dbSNPEnsembl.1
Natural variantiVAR_063771368L → Q in PKDYS; loss of function. 1 PublicationCorresponds to variant rs267607068dbSNPEnsembl.1
Natural variantiVAR_063772395P → L in PKDYS; loss of function. 1 PublicationCorresponds to variant rs267607069dbSNPEnsembl.1
Natural variantiVAR_064580471V → I.1 PublicationCorresponds to variant rs75916702dbSNPEnsembl.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

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. 13 interactors.
DIPiDIP-41827N.
IntActiQ01959. 4 interactors.
MINTiMINT-576917.
STRINGi9606.ENSP00000270349.

Chemistry databases

BindingDBiQ01959.
ChEMBLiCHEMBL238.
DrugBankiDB00543. 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.
DB00422. Methylphenidate.
DB06148. Mianserin.
DB00370. Mirtazapine.
DB00745. Modafinil.
DB01149. Nefazodone.
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.

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.
GeneCardsiSLC6A3.
HGNCiHGNC:11049. SLC6A3.
HPAiCAB016249.
HPA013602.
MalaCardsiSLC6A3.
MIMi126455. gene.
613135. phenotype.
neXtProtiNX_Q01959.
OpenTargetsiENSG00000142319.
ENSG00000276996.
Orphaneti238455. Infantile dystonia-parkinsonism.
PharmGKBiPA311.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000142319-MONOMER.
ReactomeiR-HSA-379401. Dopamine clearance from the synaptic cleft.
R-HSA-442660. Na+/Cl- dependent neurotransmitter transporters.
SABIO-RKQ01959.

Miscellaneous databases

GeneWikiiDopamine_transporter.
GenomeRNAii6531.
PMAP-CutDBQ01959.
PROiQ01959.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142319.
CleanExiHS_SLC6A3.
GenevisibleiQ01959. HS.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
IPR002436. Na/ntran_symport_dopamine.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 1 hit.
PfamiPF00209. SNF. 1 hit.
[Graphical view]
PRINTSiPR01202. DOPTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEiPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSC6A3_HUMAN
AccessioniPrimary (citable) accession number: Q01959
Secondary accession number(s): A2RUN4, Q14996
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: November 30, 2016
This is version 177 of the entry and version 1 of the sequence. [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

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.