Q01959 (SC6A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	620 AA.
Sequence status	Complete.
Protein existence	Evidence 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, bradikinesia 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 process	Neurotransmitter transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dystonia Neurodegeneration Parkinsonism
Domain	Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenohypophysis development Inferred from electronic annotation. Source: Compara aging Inferred from electronic annotation. Source: Compara cell death Inferred from electronic annotation. Source: UniProtKB-KW dopamine biosynthetic process Inferred from electronic annotation. Source: Compara dopamine catabolic process Inferred from electronic annotation. Source: Compara dopamine transport Inferred from electronic annotation. Source: Compara lactation Inferred from electronic annotation. Source: Compara locomotory behavior Inferred from electronic annotation. Source: Compara neurotransmitter biosynthetic process Traceable author statement. Source: Reactome positive regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara prepulse inhibition Inferred from electronic annotation. Source: Compara regulation of dopamine metabolic process Inferred from electronic annotation. Source: Compara response to cAMP Inferred from electronic annotation. Source: Compara response to cocaine Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to iron ion Inferred from electronic annotation. Source: Compara response to nicotine Inferred from electronic annotation. Source: Compara sensory perception of smell Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from direct assay PubMed 12958153. Source: UniProtKB cytoplasm Traceable author statement PubMed 10823899. Source: ProtInc integral to membrane Traceable author statement PubMed 8628395. Source: ProtInc integral to 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_function	dopamine binding Inferred from electronic annotation. Source: Compara dopamine transmembrane transporter activity Traceable author statement PubMed 10823899. Source: ProtInc dopamine:sodium symporter activity Inferred from electronic annotation. Source: Compara drug binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

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	68	Cytoplasmic Potential
	Transmembrane	69 – 89	21	Helical; Name=1; Potential
	Transmembrane	96 – 116	21	Helical; Name=2; Potential
	Transmembrane	140 – 160	21	Helical; Name=3; Potential
	Topological domain	161 – 237	77	Extracellular Potential
	Transmembrane	238 – 256	19	Helical; Name=4; Potential
	Transmembrane	265 – 282	18	Helical; Name=5; Potential
	Transmembrane	318 – 335	18	Helical; Name=6; Potential
	Transmembrane	347 – 368	22	Helical; Name=7; Potential
	Transmembrane	401 – 420	20	Helical; Name=8; Potential
	Transmembrane	447 – 465	19	Helical; Name=9; Potential
	Transmembrane	481 – 501	21	Helical; Name=10; Potential
	Transmembrane	522 – 541	20	Helical; Name=11; Potential
	Transmembrane	560 – 578	19	Helical; Name=12; Potential
	Topological domain	579 – 620	42	Cytoplasmic Potential
	Region	561 – 590	30	Interaction with TGFB1I1
Amino acid modifications
	Glycosylation	181	1	N-linked (GlcNAc...) Potential
	Glycosylation	188	1	N-linked (GlcNAc...) Potential
	Glycosylation	205	1	N-linked (GlcNAc...) Potential
	Disulfide bond	306		Interchain Ref.14
Natural variations
	Natural variant	121	1	G → S in a breast cancer sample; somatic mutation. Ref.18		VAR_036158
	Natural variant	237	1	R → Q. Ref.16 Corresponds to variant rs6345 [ dbSNP | Ensembl ].		VAR_014180
	Natural variant	368	1	L → Q in PKDYS; loss of function. Ref.19		VAR_063771
	Natural variant	395	1	P → L in PKDYS; loss of function. Ref.19		VAR_063772
	Natural variant	471	1	V → I. Ref.20 Corresponds to variant rs75916702 [ dbSNP | Ensembl ].		VAR_064580
	Natural variant	544	1	R → S in a breast cancer sample; somatic mutation. Ref.18		VAR_036159
Experimental info
	Sequence conflict	35	1	K → M in AAB23443. Ref.2
	Sequence conflict	345	1	D → H Ref.11
	Sequence conflict	354	1	S → C in AAB23443. Ref.2
	Sequence conflict	367	1	F → S Ref.11

Sequences

	Sequence		Length	Mass (Da)
	Q01959 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: CD95009B6BA93108	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

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] [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. , 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. , 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 , 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.
IPI	IPI00219765.
PIR	A48980. I57937. I84455.
RefSeq	NP_001035.1. NM_001044.4.
UniGene	Hs.406.
3D structure databases
ProteinModelPortal	Q01959.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-576917.
STRING	9606.ENSP00000270349.
Protein family/group databases
TCDB	2.A.22.1.3. neurotransmitter:sodium symporter (NSS) family.
PTM databases
PhosphoSite	Q01959.
Polymorphism databases
DMDM	266667.
Proteomic databases
PaxDb	Q01959.
PRIDE	Q01959.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000270349; ENSP00000270349; ENSG00000142319. ENST00000453492; ENSP00000399806; ENSG00000142319.
GeneID	6531.
KEGG	hsa:6531.
UCSC	uc003jck.3. human.
Organism-specific databases
CTD	6531.
GeneCards	GC05M001392.
HGNC	HGNC:11049. SLC6A3.
HPA	CAB016249. HPA013602.
MIM	126455. gene. 613135. phenotype.
neXtProt	NX_Q01959.
Orphanet	238455. Infantile dystonia-parkinsonism.
PharmGKB	PA311.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0733.
HOGENOM	HOG000116406.
HOVERGEN	HBG071421.
InParanoid	Q01959.
KO	K05036.
OMA	SPNCSDA.
OrthoDB	EOG46HG9B.
PhylomeDB	Q01959.
Enzyme and pathway databases
Pathway_Interaction_DB	alphasynuclein_pathway. Alpha-synuclein signaling.
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules. REACT_20679. Amine compound SLC transporters.
SABIO-RK	Q01959.
Gene expression databases
ArrayExpress	Q01959.
Bgee	Q01959.
CleanEx	HS_SLC6A3.
Genevestigator	Q01959.
GermOnline	ENSG00000142319. Homo sapiens.
Family and domain databases
InterPro	IPR000175. Na/ntran_symport. IPR002436. Na/ntran_symport_dopamine. [Graphical view]
PANTHER	PTHR11616. PTHR11616. 1 hit.
Pfam	PF00209. SNF. 1 hit. [Graphical view]
PRINTS	PR01202. DOPTRANSPORT. PR00176. NANEUSMPORT.
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
BindingDB	Q01959.
ChEMBL	CHEMBL238.
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.
GenomeRNAi	6531.
NextBio	25411.
PMAP-CutDB	Q01959.
SOURCE	Search...

Entry information

Entry name

SC6A3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 139 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.