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Reviewed, UniProtKB/Swiss-Prot Q01959 (SC6A3_HUMAN)

Last modified June 16, 2009. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length620 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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. Ref.10 Ref.11 Ref.12

Subcellular location

Membrane; Multi-pass membrane protein.

Miscellaneous

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

Sequence similarities

Belongs to the sodium:neurotransmitter symporter (SNF) family.

Ontologies

Keywords
   Biological processNeurotransmitter transport
Symport
Transport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
   PTMDisulfide bond
Glycoprotein
Gene Ontology (GO)
   Biological processneurotransmitter transport

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentcytoplasm

Traceable author statement. Source: ProtInc

integral to plasma membrane

Inferred from electronic annotation. Source: InterPro

   Molecular functiondopamine:sodium symporter activity

Inferred from electronic annotation. Source: InterPro

protein binding Ref.10

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 620620Sodium-dependent dopamine transporter
PRO_0000214751

Regions

Topological domain1 – 6868Cytoplasmic Potential
Transmembrane69 – 89211 Potential
Transmembrane96 – 116212 Potential
Transmembrane140 – 160213 Potential
Topological domain161 – 23777Extracellular Potential
Transmembrane238 – 256194 Potential
Transmembrane265 – 282185 Potential
Transmembrane318 – 335186 Potential
Transmembrane347 – 368227 Potential
Transmembrane401 – 420208 Potential
Transmembrane447 – 465199 Potential
Transmembrane481 – 5012110 Potential
Transmembrane522 – 5412011 Potential
Transmembrane560 – 5781912 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.11

Natural variations

Natural variant1211G → S in a breast cancer sample; somatic mutation. Ref.15
VAR_036158
Natural variant2371R → Q: dbSNP rs6345. Ref.13
VAR_014180
Natural variant5441R → S in a breast cancer sample; somatic mutation. Ref.15
VAR_036159

Experimental info

Sequence conflict351K → M in AAB23443. Ref.2
Sequence conflict3451D → H Ref.8
Sequence conflict3541S → C in AAB23443. Ref.2
Sequence conflict3671F → S Ref.8

Sequences

Sequence LengthMass (Da)Tools
Q01959-1 [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: 1359373] [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: 1406597] [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: 8302271] [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: 9300814] [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: 10889531] [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: 11304827] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]NIEHS SNPs program
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]"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: 7637582] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-385.
[9]"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: 1353885] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 164-255.
[10]"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: 11343649] [Abstract]
Cited for: INTERACTION WITH PRKCABP.
[11]"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.
[12]"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: 12177201] [Abstract]
Cited for: INTERACTION WITH TGFB1I1.
[13]"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: 10391209] [Abstract]
Cited for: VARIANT GLN-237.
[14]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)
[15]"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: 16959974] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-121 AND SER-544.
+Additional computationally mapped references.

Web resources

NIEHS-SNPs
Wikipedia

Dopamine transporter entry

Cross-references

Sequence databases

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.
AY623110 Genomic DNA. Translation: AAT38106.1.
M96670 mRNA. Translation: AAA35770.1.
IPIIPI00219765.
PIRA48980.
I57937.
I84455.
RefSeqNP_001035.1.
UniGeneHs.406

3D structure databases

ModBaseSearch...

Protein family/group databases

TCDB2.A.22.1.3. neurotransmitter:sodium symporter (NSS) family.

PTM databases

PhosphoSiteQ01959.

Proteomic databases

PRIDEQ01959.

Genome annotation databases

EnsemblENSG00000142319. Homo sapiens. [Contig view]
GeneID6531.
KEGGhsa:6531.

Organism-specific databases

GeneCardsGC05M001423.
H-InvDBHIX0032119.
HGNCHGNC:11049. SLC6A3.
HPACAB016249.
HPA013602.
MIM126455. gene.
PharmGKBPA311.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ01959.
HOVERGENQ01959.
OMAQ01959. AWFYGVG.

Enzyme and pathway databases

Pathway_Interaction_DBalphasynuclein_pathway. Alpha-synuclein signaling.

Gene expression databases

BgeeQ01959.
CleanExHS_SLC6A3.
GermOnlineENSG00000142319. Homo sapiens.

Family and domain databases

InterProIPR000175. Na/ntran_symport.
IPR002436. Na/ntran_symport_dopamine.
[Graphical view]
PANTHERPTHR11616. Na/ntran_symport. 1 hit.
PfamPF00209. SNF. 1 hit.
[Graphical view]
PRINTSPR01202. DOPTRANSPORT.
PR00176. NANEUSMPORT.
ProDomPD000448. Na/ntran_symport. 1 hit.
[Graphical view] [Entries sharing at least one domain]
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 Resources

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.
NextBio25411.
PMAP-CutDBQ01959.
SOURCESearch...

Entry information

Entry nameSC6A3_HUMAN
AccessionPrimary (citable) accession number: Q01959
Secondary accession number(s): Q14996
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: June 16, 2009
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 5

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents