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Q01959 (SC6A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium-dependent dopamine transporter

Short name=DA transporter
Short name=DAT
Alternative name(s):
Solute carrier family 6 member 3
Gene names
Name:SLC6A3
Synonyms:DAT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length620 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

Homooligomer; disulfide-linked. Interacts with PRKCABP and TGFB1I1. Interacts (via N-terminus) with SYNGR3 (via N-terminus) By similarity. Interacts with SLC18A2 By similarity. Ref.13 Ref.14 Ref.15

Subcellular location

Membrane; Multi-pass membrane protein.

Involvement in disease

Parkinsonism-dystonia infantile (PKDYS) [MIM:613135]: A neurodegenerative disorder characterized by infantile onset of parkinsonism and dystonia. Other neurologic features include global developmental delay, bradykinesia and pyramidal tract signs.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

Miscellaneous

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

Sequence similarities

Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A3 subfamily. [View classification]

Ontologies

Keywords
   Biological processNeurotransmitter transport
Symport
Transport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Dystonia
Neurodegeneration
Parkinsonism
   DomainTransmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenohypophysis development

Inferred from electronic annotation. Source: Ensembl

aging

Inferred from electronic annotation. Source: Ensembl

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

dopamine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

dopamine catabolic process

Inferred from electronic annotation. Source: Ensembl

dopamine transport

Inferred from electronic annotation. Source: Ensembl

lactation

Inferred from electronic annotation. Source: Ensembl

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

monoamine transport

Inferred from direct assay PubMed 16024787. Source: MGI

neurotransmitter biosynthetic process

Traceable author statement. Source: Reactome

positive regulation of multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

prepulse inhibition

Inferred from electronic annotation. Source: Ensembl

regulation of dopamine metabolic process

Inferred from electronic annotation. Source: Ensembl

response to cAMP

Inferred from electronic annotation. Source: Ensembl

response to cocaine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to iron ion

Inferred from electronic annotation. Source: Ensembl

response to nicotine

Inferred from electronic annotation. Source: Ensembl

sensory perception of smell

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement PubMed 8628395. Source: ProtInc

   Cellular_componentaxon

Inferred from direct assay PubMed 12958153. Source: UniProtKB

cytoplasm

Traceable author statement PubMed 10823899. Source: ProtInc

integral component of membrane

Traceable author statement PubMed 8628395. Source: ProtInc

integral component of plasma membrane

Inferred from electronic annotation. Source: InterPro

neuronal cell body

Inferred from direct assay PubMed 12958153. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.13PubMed 12958153. Source: UniProtKB

   Molecular_functiondopamine binding

Inferred from electronic annotation. Source: Ensembl

dopamine transmembrane transporter activity

Traceable author statement PubMed 10823899. Source: ProtInc

dopamine:sodium symporter activity

Inferred from electronic annotation. Source: Ensembl

drug binding

Inferred from electronic annotation. Source: Ensembl

monoamine transmembrane transporter activity

Inferred from direct assay PubMed 16024787. Source: MGI

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 620620Sodium-dependent dopamine transporter
PRO_0000214751

Regions

Topological domain1 – 6868Cytoplasmic Potential
Transmembrane69 – 8921Helical; Name=1; Potential
Transmembrane96 – 11621Helical; Name=2; Potential
Transmembrane140 – 16021Helical; Name=3; Potential
Topological domain161 – 23777Extracellular Potential
Transmembrane238 – 25619Helical; Name=4; Potential
Transmembrane265 – 28218Helical; Name=5; Potential
Transmembrane318 – 33518Helical; Name=6; Potential
Transmembrane347 – 36822Helical; Name=7; Potential
Transmembrane401 – 42020Helical; Name=8; Potential
Transmembrane447 – 46519Helical; Name=9; Potential
Transmembrane481 – 50121Helical; Name=10; Potential
Transmembrane522 – 54120Helical; Name=11; Potential
Transmembrane560 – 57819Helical; Name=12; Potential
Topological domain579 – 62042Cytoplasmic Potential
Region561 – 59030Interaction with TGFB1I1

Amino acid modifications

Glycosylation1811N-linked (GlcNAc...) Potential
Glycosylation1881N-linked (GlcNAc...) Potential
Glycosylation2051N-linked (GlcNAc...) Potential
Disulfide bond306Interchain Ref.14

Natural variations

Natural variant1211G → S in a breast cancer sample; somatic mutation. Ref.18
VAR_036158
Natural variant2371R → Q. Ref.16
Corresponds to variant rs6345 [ dbSNP | Ensembl ].
VAR_014180
Natural variant3681L → Q in PKDYS; loss of function. Ref.19
VAR_063771
Natural variant3951P → L in PKDYS; loss of function. Ref.19
VAR_063772
Natural variant4711V → I. Ref.20
Corresponds to variant rs75916702 [ dbSNP | Ensembl ].
VAR_064580
Natural variant5441R → S in a breast cancer sample; somatic mutation. Ref.18
VAR_036159

Experimental info

Sequence conflict351K → M in AAB23443. Ref.2
Sequence conflict3451D → H Ref.11
Sequence conflict3541S → C in AAB23443. Ref.2
Sequence conflict3671F → S Ref.11

Sequences

Sequence LengthMass (Da)Tools
Q01959 [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: CD95009B6BA93108

FASTA62068,495
        10         20         30         40         50         60 
MSKSKCSVGL MSSVVAPAKE PNAVGPKEVE LILVKEQNGV QLTSSTLTNP RQSPVEAQDR 

        70         80         90        100        110        120 
ETWGKKIDFL LSVIGFAVDL ANVWRFPYLC YKNGGGAFLV PYLLFMVIAG MPLFYMELAL 

       130        140        150        160        170        180 
GQFNREGAAG VWKICPILKG VGFTVILISL YVGFFYNVII AWALHYLFSS FTTELPWIHC 

       190        200        210        220        230        240 
NNSWNSPNCS DAHPGDSSGD SSGLNDTFGT TPAAEYFERG VLHLHQSHGI DDLGPPRWQL 

       250        260        270        280        290        300 
TACLVLVIVL LYFSLWKGVK TSGKVVWITA TMPYVVLTAL LLRGVTLPGA IDGIRAYLSV 

       310        320        330        340        350        360 
DFYRLCEASV WIDAATQVCF SLGVGFGVLI AFSSYNKFTN NCYRDAIVTT SINSLTSFSS 

       370        380        390        400        410        420 
GFVVFSFLGY MAQKHSVPIG DVAKDGPGLI FIIYPEAIAT LPLSSAWAVV FFIMLLTLGI 

       430        440        450        460        470        480 
DSAMGGMESV ITGLIDEFQL LHRHRELFTL FIVLATFLLS LFCVTNGGIY VFTLLDHFAA 

       490        500        510        520        530        540 
GTSILFGVLI EAIGVAWFYG VGQFSDDIQQ MTGQRPSLYW RLCWKLVSPC FLLFVVVVSI 

       550        560        570        580        590        600 
VTFRPPHYGA YIFPDWANAL GWVIATSSMA MVPIYAAYKF CSLPGSFREK LAYAIAPEKD 

       610        620 
RELVDRGEVR QFTLRHWLKV 

« Hide

References

« Hide 'large scale' references
[1]"A human dopamine transporter cDNA predicts reduced glycosylation, displays a novel repetitive element and provides racially-dimorphic TaqI RFLPs."
Vandenbergh D.J., Persico A.M., Uhl G.R.
Brain Res. Mol. Brain Res. 15:161-166(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter."
Giros B., el Mestikawy S., Godinot N., Zheng K., Han H., Yang-Feng T., Caron M.G.
Mol. Pharmacol. 42:383-390(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding."
Pristupa Z.B., Wilson J.M., Hoffman B.J., Kish S.J., Niznik H.B.
Mol. Pharmacol. 45:125-135(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[4]"Structure and organization of the gene encoding human dopamine transporter."
Kawarai T., Kawakami H., Yamamura Y., Nakamura S.
Gene 195:11-18(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations."
Vandenbergh D.J., Thompson M.D., Cook E.H., Bendahhou E., Nguyen T., Krasowski M.D., Zarrabian D., Comings D., Sellers E.M., Tyndale R.F., George S.R., O'Dowd B.F., Uhl G.R.
Mol. Psychiatry 5:283-292(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder."
Greenwood T.A., Alexander M., Keck P.E., McElroy S., Sadovnick A.D., Remick R.A., Kelsoe J.R.
Am. J. Med. Genet. 105:145-151(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"Sequence variation in the primate dopamine transporter gene and its relationship to social dominance."
Miller-Butterworth C.M., Kaplan J.R., Shaffer J., Devlin B., Manuck S.B., Ferrell R.E.
Mol. Biol. Evol. 25:18-28(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[8]NIEHS SNPs program
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[11]"Human and mouse dopamine transporter genes: conservation of 5'-flanking sequence elements and gene structures."
Donovan D.M., Vandenbergh D.J., Perry M.P., Bird G.S., Ingersoll R., Nanthakumar E., Uhl G.R.
Brain Res. Mol. Brain Res. 30:327-335(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-385.
[12]"Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age."
Bannon M.J., Poosch M.S., Xia Y., Goebel D.J., Cassin B., Kapatos G.
Proc. Natl. Acad. Sci. U.S.A. 89:7095-7099(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 164-255.
[13]"Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1."
Torres G.E., Yao W.-D., Mohn A.R., Quan H., Kim K.-M., Levey A.I., Staudinger J., Caron M.G.
Neuron 30:121-134(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKCABP.
[14]"Symmetrical homodimer of the human dopamine transporter revealed by cross-linking Cys306 at the extracellular end of TM6."
Hastrup H., Karlin A., Javitch J.A.
Abstr. - Soc. Neurosci. 27:1866-1866(2001)
Cited for: INTERCHAIN DISULFIDE BOND.
[15]"The multiple LIM domain-containing adaptor protein Hic-5 synaptically colocalizes and interacts with the dopamine transporter."
Carneiro A.M.D., Ingram S.L., Beaulieu J.-M., Sweeney A., Amara S.G., Thomas S.M., Caron M.G., Torres G.E.
J. Neurosci. 22:7045-7054(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFB1I1.
[16]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-237.
[17]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
[18]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-121 AND SER-544.
[19]"Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia."
Kurian M.A., Zhen J., Cheng S.Y., Li Y., Mordekar S.R., Jardine P., Morgan N.V., Meyer E., Tee L., Pasha S., Wassmer E., Heales S.J., Gissen P., Reith M.E., Maher E.R.
J. Clin. Invest. 119:1595-1603(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKDYS GLN-368 AND LEU-395, CHARACTERIZATION OF VARIANTS PKDYS GLN-368 AND LEU-395.
[20]"A population-specific HTR2B stop codon predisposes to severe impulsivity."
Bevilacqua L., Doly S., Kaprio J., Yuan Q., Tikkanen R., Paunio T., Zhou Z., Wedenoja J., Maroteaux L., Diaz S., Belmer A., Hodgkinson C.A., Dell'osso L., Suvisaari J., Coccaro E., Rose R.J., Peltonen L., Virkkunen M., Goldman D.
Nature 468:1061-1066(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ILE-471.
+Additional computationally mapped references.

Web resources

NIEHS-SNPs
Wikipedia

Dopamine transporter entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , 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.
PIRA48980.
I57937.
I84455.
RefSeqNP_001035.1. NM_001044.4.
UniGeneHs.406.

3D structure databases

ProteinModelPortalQ01959.
SMRQ01959. Positions 59-600.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112422. 14 interactions.
IntActQ01959. 3 interactions.
MINTMINT-576917.
STRING9606.ENSP00000270349.

Chemistry

BindingDBQ01959.
ChEMBLCHEMBL2363064.
DrugBankDB00182. Amphetamine.
DB00245. Benztropine.
DB01156. Bupropion.
DB01161. Chloroprocaine.
DB00907. Cocaine.
DB01576. Dextroamphetamine.
DB00937. Diethylpropion.
DB00476. Duloxetine.
DB01463. Fencamfamine.
DB00579. Mazindol.
DB00422. Methylphenidate.
DB00745. Modafinil.
DB00830. Phenmetrazine.
DB00191. Phentermine.
DB00721. Procaine.
GuidetoPHARMACOLOGY927.

Protein family/group databases

TCDB2.A.22.1.3. the neurotransmitter:sodium symporter (nss) family.

PTM databases

PhosphoSiteQ01959.

Polymorphism databases

DMDM266667.

Proteomic databases

PaxDbQ01959.
PRIDEQ01959.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000270349; ENSP00000270349; ENSG00000142319.
ENST00000453492; ENSP00000399806; ENSG00000142319.
GeneID6531.
KEGGhsa:6531.
UCSCuc003jck.3. human.

Organism-specific databases

CTD6531.
GeneCardsGC05M001392.
HGNCHGNC:11049. SLC6A3.
HPACAB016249.
HPA013602.
MIM126455. gene.
613135. phenotype.
neXtProtNX_Q01959.
Orphanet238455. Infantile dystonia-parkinsonism.
PharmGKBPA311.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0733.
HOGENOMHOG000116406.
HOVERGENHBG071421.
InParanoidQ01959.
KOK05036.
OMASPNCSDA.
OrthoDBEOG793B71.
PhylomeDBQ01959.
TreeFamTF343812.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.
REACT_20679. Amine compound SLC transporters.
SABIO-RKQ01959.

Gene expression databases

ArrayExpressQ01959.
BgeeQ01959.
CleanExHS_SLC6A3.
GenevestigatorQ01959.

Family and domain databases

InterProIPR000175. Na/ntran_symport.
IPR002436. Na/ntran_symport_dopamine.
[Graphical view]
PANTHERPTHR11616. PTHR11616. 1 hit.
PfamPF00209. SNF. 1 hit.
[Graphical view]
PRINTSPR01202. DOPTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDopamine_transporter.
GenomeRNAi6531.
NextBio25411.
PMAP-CutDBQ01959.
PROQ01959.
SOURCESearch...

Entry information

Entry nameSC6A3_HUMAN
AccessionPrimary (citable) accession number: Q01959
Secondary accession number(s): A2RUN4, Q14996
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: April 16, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM