Sodium-dependent dopamine transporter

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Reviewed, UniProtKB/Swiss-Prot Q01959 (SC6A3_HUMAN)

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

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

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Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	620 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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.

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Ontologies

Keywords
Biological process	Neurotransmitter transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	neurotransmitter transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Traceable author statement. Source: ProtInc integral to plasma membrane Inferred from electronic annotation. Source: InterPro
Molecular function	dopamine:sodium symporter activity Inferred from electronic annotation. Source: InterPro protein binding Ref.10 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 620

620

Sodium-dependent dopamine transporter

PRO_0000214751

Regions

Topological domain

1 – 68

Cytoplasmic Potential

Transmembrane

69 – 89

1 Potential

Transmembrane

96 – 116

2 Potential

Transmembrane

140 – 160

3 Potential

Topological domain

161 – 237

Extracellular Potential

Transmembrane

238 – 256

4 Potential

Transmembrane

265 – 282

5 Potential

Transmembrane

318 – 335

6 Potential

Transmembrane

347 – 368

7 Potential

Transmembrane

401 – 420

8 Potential

Transmembrane

447 – 465

9 Potential

Transmembrane

481 – 501

10 Potential

Transmembrane

522 – 541

11 Potential

Transmembrane

560 – 578

12 Potential

Topological domain

579 – 620

Cytoplasmic Potential

Region

561 – 590

Interaction with TGFB1I1

Amino acid modifications

Glycosylation

181

N-linked (GlcNAc...) Potential

Glycosylation

188

N-linked (GlcNAc...) Potential

Glycosylation

205

N-linked (GlcNAc...) Potential

Disulfide bond

306

Interchain Ref.11

Natural variations

Natural variant

121

G → S in a breast cancer sample; somatic mutation. Ref.15

VAR_036158

Natural variant

237

R → Q: dbSNP rs6345. Ref.13

VAR_014180

Natural variant

544

R → S in a breast cancer sample; somatic mutation. Ref.15

VAR_036159

Experimental info

Sequence conflict

K → M in AAB23443. Ref.2

Sequence conflict

345

D → H Ref.8

Sequence conflict

354

S → C in AAB23443. Ref.2

Sequence conflict

367

F → S Ref.8

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Sequences

Sequence

Length

Mass (Da)

Tools

Q01959-1 [UniParc].

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

620

68,495

        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

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References

	« Hide 'large scale' referencesShow '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. 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.

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Web resources

NIEHS-SNPs

Wikipedia

Dopamine transporter entry

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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 AF306564 Genomic DNA. Translation: AAG33844.1. AY623110 Genomic DNA. Translation: AAT38106.1. M96670 mRNA. Translation: AAA35770.1.
IPI	IPI00219765.
PIR	A48980. I57937. I84455.
RefSeq	NP_001035.1.
UniGene	Hs.406
3D structure databases
ModBase	Search...
Protein family/group databases
TCDB	2.A.22.1.3. neurotransmitter:sodium symporter (NSS) family.
PTM databases
PhosphoSite	Q01959.
Proteomic databases
PRIDE	Q01959.
Genome annotation databases
Ensembl	ENSG00000142319. Homo sapiens. [Contig view]
GeneID	6531.
KEGG	hsa:6531.
Organism-specific databases
GeneCards	GC05M001423.
H-InvDB	HIX0032119.
HGNC	HGNC:11049. SLC6A3.
HPA	CAB016249. HPA013602.
MIM	126455. gene.
PharmGKB	PA311.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q01959.
HOVERGEN	Q01959.
OMA	Q01959. AWFYGVG.
Enzyme and pathway databases
Pathway_Interaction_DB	alphasynuclein_pathway. Alpha-synuclein signaling.
Gene expression databases
Bgee	Q01959.
CleanEx	HS_SLC6A3.
GermOnline	ENSG00000142319. Homo sapiens.
Family and domain databases
InterPro	IPR000175. Na/ntran_symport. IPR002436. Na/ntran_symport_dopamine. [Graphical view]
PANTHER	PTHR11616. Na/ntran_symport. 1 hit.
Pfam	PF00209. SNF. 1 hit. [Graphical view]
PRINTS	PR01202. DOPTRANSPORT. PR00176. NANEUSMPORT.
ProDom	PD000448. Na/ntran_symport. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00610. NA_NEUROTRAN_SYMP_1. 1 hit. PS00754. NA_NEUROTRAN_SYMP_2. 1 hit. PS50267. NA_NEUROTRAN_SYMP_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00182. 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.
NextBio	25411.
PMAP-CutDB	Q01959.
SOURCE	Search...

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Entry information

Entry name

SC6A3_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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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)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents