SC6A3_HUMAN
ID SC6A3_HUMAN Reviewed; 620 AA.
AC Q01959; A2RUN4; Q14996;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Sodium-dependent dopamine transporter;
DE Short=DA transporter;
DE Short=DAT;
DE AltName: Full=Solute carrier family 6 member 3;
GN Name=SLC6A3; Synonyms=DAT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1359373; DOI=10.1016/0169-328x(92)90165-8;
RA Vandenbergh D.J., Persico A.M., Uhl G.R.;
RT "A human dopamine transporter cDNA predicts reduced glycosylation, displays
RT a novel repetitive element and provides racially-dimorphic TaqI RFLPs.";
RL Brain Res. Mol. Brain Res. 15:161-166(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=1406597;
RA Giros B., el Mestikawy S., Godinot N., Zheng K., Han H., Yang-Feng T.,
RA Caron M.G.;
RT "Cloning, pharmacological characterization, and chromosome assignment of
RT the human dopamine transporter.";
RL Mol. Pharmacol. 42:383-390(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=8302271;
RA Pristupa Z.B., Wilson J.M., Hoffman B.J., Kish S.J., Niznik H.B.;
RT "Pharmacological heterogeneity of the cloned and native human dopamine
RT transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding.";
RL Mol. Pharmacol. 45:125-135(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9300814; DOI=10.1016/s0378-1119(97)00131-5;
RA Kawarai T., Kawakami H., Yamamura Y., Nakamura S.;
RT "Structure and organization of the gene encoding human dopamine
RT transporter.";
RL Gene 195:11-18(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10889531; DOI=10.1038/sj.mp.4000701;
RA Vandenbergh D.J., Thompson M.D., Cook E.H., Bendahhou E., Nguyen T.,
RA Krasowski M.D., Zarrabian D., Comings D., Sellers E.M., Tyndale R.F.,
RA George S.R., O'Dowd B.F., Uhl G.R.;
RT "Human dopamine transporter gene: coding region conservation among normal,
RT Tourette's disorder, alcohol dependence and attention-deficit hyperactivity
RT disorder populations.";
RL Mol. Psychiatry 5:283-292(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11304827;
RX DOI=10.1002/1096-8628(2001)9999:9999<::aid-ajmg1161>3.0.co;2-8;
RA Greenwood T.A., Alexander M., Keck P.E., McElroy S., Sadovnick A.D.,
RA Remick R.A., Kelsoe J.R.;
RT "Evidence for linkage disequilibrium between the dopamine transporter and
RT bipolar disorder.";
RL Am. J. Med. Genet. 105:145-151(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=17934207; DOI=10.1093/molbev/msm219;
RA Miller-Butterworth C.M., Kaplan J.R., Shaffer J., Devlin B., Manuck S.B.,
RA Ferrell R.E.;
RT "Sequence variation in the primate dopamine transporter gene and its
RT relationship to social dominance.";
RL Mol. Biol. Evol. 25:18-28(2008).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PRELIMINARY NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-385, AND TISSUE
RP SPECIFICITY.
RX PubMed=7637582; DOI=10.1016/0169-328x(95)00018-n;
RA Donovan D.M., Vandenbergh D.J., Perry M.P., Bird G.S., Ingersoll R.,
RA Nanthakumar E., Uhl G.R.;
RT "Human and mouse dopamine transporter genes: conservation of 5'-flanking
RT sequence elements and gene structures.";
RL Brain Res. Mol. Brain Res. 30:327-335(1995).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 164-255.
RX PubMed=1353885; DOI=10.1073/pnas.89.15.7095;
RA Bannon M.J., Poosch M.S., Xia Y., Goebel D.J., Cassin B., Kapatos G.;
RT "Dopamine transporter mRNA content in human substantia nigra decreases
RT precipitously with age.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7095-7099(1992).
RN [13]
RP INTERACTION WITH PRKCABP.
RX PubMed=11343649; DOI=10.1016/s0896-6273(01)00267-7;
RA Torres G.E., Yao W.-D., Mohn A.R., Quan H., Kim K.-M., Levey A.I.,
RA Staudinger J., Caron M.G.;
RT "Functional interaction between monoamine plasma membrane transporters and
RT the synaptic PDZ domain-containing protein PICK1.";
RL Neuron 30:121-134(2001).
RN [14]
RP INTERCHAIN DISULFIDE BOND, AND SUBUNIT.
RA Hastrup H., Karlin A., Javitch J.A.;
RT "Symmetrical homodimer of the human dopamine transporter revealed by cross-
RT linking Cys306 at the extracellular end of TM6.";
RL Abstr. - Soc. Neurosci. 27:1866-1866(2001).
RN [15]
RP INTERACTION WITH TGFB1I1.
RX PubMed=12177201; DOI=10.1523/jneurosci.22-16-07045.2002;
RA Carneiro A.M.D., Ingram S.L., Beaulieu J.-M., Sweeney A., Amara S.G.,
RA Thomas S.M., Caron M.G., Torres G.E.;
RT "The multiple LIM domain-containing adaptor protein Hic-5 synaptically
RT colocalizes and interacts with the dopamine transporter.";
RL J. Neurosci. 22:7045-7054(2002).
RN [16]
RP FUNCTION AS DOPAMINE TRANSPORTER, INTERACTION WITH TOR1A, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15505207; DOI=10.1073/pnas.0308088101;
RA Torres G.E., Sweeney A.L., Beaulieu J.M., Shashidharan P., Caron M.G.;
RT "Effect of torsinA on membrane proteins reveals a loss of function and a
RT dominant-negative phenotype of the dystonia-associated DeltaE-torsinA
RT mutant.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15650-15655(2004).
RN [17]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17296554; DOI=10.1016/j.neuron.2007.01.019;
RA Ihara M., Yamasaki N., Hagiwara A., Tanigaki A., Kitano A., Hikawa R.,
RA Tomimoto H., Noda M., Takanashi M., Mori H., Hattori N., Miyakawa T.,
RA Kinoshita M.;
RT "Sept4, a component of presynaptic scaffold and Lewy bodies, is required
RT for the suppression of alpha-synuclein neurotoxicity.";
RL Neuron 53:519-533(2007).
RN [18]
RP INTERACTION WITH ALPHA-SYNUCLEIN/SNCA.
RX PubMed=26442590; DOI=10.1074/jbc.m115.691592;
RA Butler B., Saha K., Rana T., Becker J.P., Sambo D., Davari P.,
RA Goodwin J.S., Khoshbouei H.;
RT "Dopamine Transporter Activity Is Modulated by alpha-Synuclein.";
RL J. Biol. Chem. 290:29542-29554(2015).
RN [19]
RP VARIANT GLN-237.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [20]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [21]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-121 AND SER-544.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [22]
RP VARIANTS PKDYS1 GLN-368 AND LEU-395, AND CHARACTERIZATION OF VARIANTS
RP PKDYS1 GLN-368 AND LEU-395.
RX PubMed=19478460; DOI=10.1172/jci39060;
RA Kurian M.A., Zhen J., Cheng S.Y., Li Y., Mordekar S.R., Jardine P.,
RA Morgan N.V., Meyer E., Tee L., Pasha S., Wassmer E., Heales S.J.,
RA Gissen P., Reith M.E., Maher E.R.;
RT "Homozygous loss-of-function mutations in the gene encoding the dopamine
RT transporter are associated with infantile parkinsonism-dystonia.";
RL J. Clin. Invest. 119:1595-1603(2009).
RN [23]
RP VARIANT ILE-471.
RX PubMed=21179162; DOI=10.1038/nature09629;
RA Bevilacqua L., Doly S., Kaprio J., Yuan Q., Tikkanen R., Paunio T.,
RA Zhou Z., Wedenoja J., Maroteaux L., Diaz S., Belmer A., Hodgkinson C.A.,
RA Dell'osso L., Suvisaari J., Coccaro E., Rose R.J., Peltonen L.,
RA Virkkunen M., Goldman D.;
RT "A population-specific HTR2B stop codon predisposes to severe
RT impulsivity.";
RL Nature 468:1061-1066(2010).
CC -!- FUNCTION: Amine transporter (PubMed:1406597, PubMed:8302271,
CC PubMed:15505207). Terminates the action of dopamine by its high
CC affinity sodium-dependent reuptake into presynaptic terminals (By
CC similarity). Regulator of light-dependent retinal hyaloid vessel
CC regression, downstream of OPN5 signaling (By similarity).
CC {ECO:0000250|UniProtKB:P23977, ECO:0000250|UniProtKB:Q61327,
CC ECO:0000269|PubMed:1406597, ECO:0000269|PubMed:15505207,
CC ECO:0000269|PubMed:8302271}.
CC -!- SUBUNIT: Homooligomer; disulfide-linked (Ref.14). Interacts with
CC PRKCABP and TGFB1I1 (PubMed:11343649, PubMed:12177201). Interacts (via
CC N-terminus) with SYNGR3 (via N-terminus) (By similarity). Interacts
CC with SLC18A2 (By similarity). Interacts with TOR1A (ATP-bound); TOR1A
CC regulates SLC6A3 subcellular location (PubMed:15505207). Interacts with
CC alpha-synuclein/SNCA (PubMed:26442590). Interacts with SEPTIN4 (By
CC similarity). {ECO:0000250|UniProtKB:Q61327,
CC ECO:0000269|PubMed:15505207, ECO:0000269|PubMed:26442590}.
CC -!- INTERACTION:
CC Q01959; P14416: DRD2; NbExp=4; IntAct=EBI-6661445, EBI-2928178;
CC Q01959; O15354: GPR37; NbExp=2; IntAct=EBI-6661445, EBI-15639515;
CC Q01959; Q99578: RIT2; NbExp=5; IntAct=EBI-6661445, EBI-365914;
CC Q01959; P37840: SNCA; NbExp=3; IntAct=EBI-6661445, EBI-985879;
CC Q01959; Q5T9L3: WLS; NbExp=2; IntAct=EBI-6661445, EBI-2868748;
CC Q01959; Q9EP80: Pick1; Xeno; NbExp=2; IntAct=EBI-6661445, EBI-77728;
CC Q01959; Q5BJQ5: Rit2; Xeno; NbExp=2; IntAct=EBI-6661445, EBI-11686902;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1406597,
CC ECO:0000269|PubMed:15505207, ECO:0000269|PubMed:8302271}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:15505207}. Cell projection, neuron
CC projection {ECO:0000250|UniProtKB:P23977}. Cell projection, axon
CC {ECO:0000269|PubMed:17296554}. Note=Localizes to neurite tips in
CC neuronal cells (By similarity). Colocalizes with SEPTIN4 at axon
CC terminals, especially at the varicosities (By similarity).
CC {ECO:0000250|UniProtKB:P23977, ECO:0000250|UniProtKB:Q61327}.
CC -!- TISSUE SPECIFICITY: Highly expressed in substantia nigra
CC (PubMed:7637582). Expressed in axonal varicosities in dopaminergic
CC nerve terminals (at protein level) (PubMed:17296554). Expressed in the
CC striatum (at protein level) (PubMed:17296554).
CC {ECO:0000269|PubMed:17296554, ECO:0000269|PubMed:7637582}.
CC -!- DISEASE: Parkinsonism-dystonia 1, infantile-onset (PKDYS1)
CC [MIM:613135]: An autosomal recessive neurodegenerative disorder
CC characterized by infantile onset of parkinsonism and dystonia. Other
CC neurologic features include global developmental delay, bradykinesia
CC and pyramidal tract signs. {ECO:0000269|PubMed:19478460}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: This protein is the target of psychomotor stimulants
CC such as amphetamines or cocaine.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A3 subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/slc6a3/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Dopamine transporter entry;
CC URL="https://en.wikipedia.org/wiki/Dopamine_transporter";
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DR EMBL; M95167; AAC41720.1; -; mRNA.
DR EMBL; S46955; AAA11754.1; -; mRNA.
DR EMBL; S44626; AAB23443.1; -; mRNA.
DR EMBL; L24178; AAA19560.1; -; mRNA.
DR EMBL; D88570; BAA22511.1; -; Genomic_DNA.
DR EMBL; AF119117; AAC50179.2; -; Genomic_DNA.
DR EMBL; AF321321; AAG33844.1; -; Genomic_DNA.
DR EMBL; AF306558; AAG33844.1; JOINED; Genomic_DNA.
DR EMBL; AF321320; AAG33844.1; JOINED; Genomic_DNA.
DR EMBL; AF306559; AAG33844.1; JOINED; Genomic_DNA.
DR EMBL; AF306560; AAG33844.1; JOINED; Genomic_DNA.
DR EMBL; AF306561; AAG33844.1; JOINED; Genomic_DNA.
DR EMBL; AF306562; AAG33844.1; JOINED; Genomic_DNA.
DR EMBL; AF306563; AAG33844.1; JOINED; Genomic_DNA.
DR EMBL; AF306564; AAG33844.1; JOINED; Genomic_DNA.
DR EMBL; EF174603; ABO77644.1; -; mRNA.
DR EMBL; AY623110; AAT38106.1; -; Genomic_DNA.
DR EMBL; CH471102; EAX08159.1; -; Genomic_DNA.
DR EMBL; BC132977; AAI32978.1; -; mRNA.
DR EMBL; BC133003; AAI33004.1; -; mRNA.
DR EMBL; M96670; AAA35770.1; -; mRNA.
DR CCDS; CCDS3863.1; -.
DR PIR; A48980; A48980.
DR PIR; I57937; I57937.
DR PIR; I84455; I84455.
DR RefSeq; NP_001035.1; NM_001044.4.
DR AlphaFoldDB; Q01959; -.
DR SMR; Q01959; -.
DR BioGRID; 112422; 18.
DR DIP; DIP-41827N; -.
DR IntAct; Q01959; 9.
DR MINT; Q01959; -.
DR STRING; 9606.ENSP00000270349; -.
DR BindingDB; Q01959; -.
DR ChEMBL; CHEMBL238; -.
DR DrugBank; DB01472; 4-Methoxyamphetamine.
DR DrugBank; DB04947; Altropane.
DR DrugBank; DB00543; Amoxapine.
DR DrugBank; DB00182; Amphetamine.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB06413; Armodafinil.
DR DrugBank; DB00245; Benzatropine.
DR DrugBank; DB00865; Benzphetamine.
DR DrugBank; DB01156; Bupropion.
DR DrugBank; DB01161; Chloroprocaine.
DR DrugBank; DB01114; Chlorpheniramine.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB12305; Dasotraline.
DR DrugBank; DB06700; Desvenlafaxine.
DR DrugBank; DB06701; Dexmethylphenidate.
DR DrugBank; DB01576; Dextroamphetamine.
DR DrugBank; DB00937; Diethylpropion.
DR DrugBank; DB01146; Diphenylpyraline.
DR DrugBank; DB00988; Dopamine.
DR DrugBank; DB00476; Duloxetine.
DR DrugBank; DB01363; Ephedra sinica root.
DR DrugBank; DB01175; Escitalopram.
DR DrugBank; DB09194; Etoperidone.
DR DrugBank; DB01463; Fencamfamin.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB08824; Ioflupane I-123.
DR DrugBank; DB00408; Loxapine.
DR DrugBank; DB00579; Mazindol.
DR DrugBank; DB00454; Meperidine.
DR DrugBank; DB01577; Metamfetamine.
DR DrugBank; DB00422; Methylphenidate.
DR DrugBank; DB06148; Mianserin.
DR DrugBank; DB01454; Midomafetamine.
DR DrugBank; DB01442; MMDA.
DR DrugBank; DB00745; Modafinil.
DR DrugBank; DB01149; Nefazodone.
DR DrugBank; DB04821; Nomifensine.
DR DrugBank; DB00830; Phenmetrazine.
DR DrugBank; DB00191; Phentermine.
DR DrugBank; DB00721; Procaine.
DR DrugBank; DB00852; Pseudoephedrine.
DR DrugBank; DB16629; Serdexmethylphenidate.
DR DrugBank; DB01104; Sertraline.
DR DrugBank; DB01105; Sibutramine.
DR DrugBank; DB14754; Solriamfetol.
DR DrugBank; DB06156; Tesofensine.
DR DrugBank; DB00726; Trimipramine.
DR DrugBank; DB06333; Trodusquemine.
DR DrugBank; DB03701; Vanoxerine.
DR DrugBank; DB00285; Venlafaxine.
DR DrugCentral; Q01959; -.
DR GuidetoPHARMACOLOGY; 927; -.
DR TCDB; 2.A.22.1.3; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; Q01959; 3 sites.
DR iPTMnet; Q01959; -.
DR PhosphoSitePlus; Q01959; -.
DR SwissPalm; Q01959; -.
DR BioMuta; SLC6A3; -.
DR DMDM; 266667; -.
DR MassIVE; Q01959; -.
DR PaxDb; Q01959; -.
DR PeptideAtlas; Q01959; -.
DR PRIDE; Q01959; -.
DR Antibodypedia; 2799; 458 antibodies from 46 providers.
DR DNASU; 6531; -.
DR Ensembl; ENST00000270349.12; ENSP00000270349.9; ENSG00000142319.18.
DR Ensembl; ENST00000621716.2; ENSP00000479597.1; ENSG00000276996.2.
DR GeneID; 6531; -.
DR KEGG; hsa:6531; -.
DR MANE-Select; ENST00000270349.12; ENSP00000270349.9; NM_001044.5; NP_001035.1.
DR UCSC; uc003jck.4; human.
DR CTD; 6531; -.
DR DisGeNET; 6531; -.
DR GeneCards; SLC6A3; -.
DR GeneReviews; SLC6A3; -.
DR HGNC; HGNC:11049; SLC6A3.
DR HPA; ENSG00000142319; Tissue enriched (brain).
DR MalaCards; SLC6A3; -.
DR MIM; 126455; gene.
DR MIM; 613135; phenotype.
DR neXtProt; NX_Q01959; -.
DR OpenTargets; ENSG00000142319; -.
DR Orphanet; 238455; Infantile dystonia-parkinsonism.
DR PharmGKB; PA311; -.
DR VEuPathDB; HostDB:ENSG00000142319; -.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000161224; -.
DR HOGENOM; CLU_006855_9_0_1; -.
DR InParanoid; Q01959; -.
DR OMA; IFPEWAN; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; Q01959; -.
DR TreeFam; TF343812; -.
DR PathwayCommons; Q01959; -.
DR Reactome; R-HSA-379401; Dopamine clearance from the synaptic cleft.
DR Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-HSA-5619081; Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS).
DR Reactome; R-HSA-5660724; Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS).
DR SABIO-RK; Q01959; -.
DR SignaLink; Q01959; -.
DR SIGNOR; Q01959; -.
DR BioGRID-ORCS; 6531; 10 hits in 1069 CRISPR screens.
DR GeneWiki; Dopamine_transporter; -.
DR GenomeRNAi; 6531; -.
DR Pharos; Q01959; Tclin.
DR PRO; PR:Q01959; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q01959; protein.
DR Bgee; ENSG00000142319; Expressed in substantia nigra and 62 other tissues.
DR Genevisible; Q01959; HS.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0098691; C:dopaminergic synapse; IEA:Ensembl.
DR GO; GO:0016600; C:flotillin complex; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043005; C:neuron projection; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0032809; C:neuronal cell body membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central.
DR GO; GO:0043176; F:amine binding; IEA:Ensembl.
DR GO; GO:0035240; F:dopamine binding; IEA:Ensembl.
DR GO; GO:0005330; F:dopamine:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:1901363; F:heterocyclic compound binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008504; F:monoamine transmembrane transporter activity; IDA:MGI.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0005334; F:norepinephrine:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl.
DR GO; GO:0021984; P:adenohypophysis development; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0042416; P:dopamine biosynthetic process; IEA:Ensembl.
DR GO; GO:0042420; P:dopamine catabolic process; IEA:Ensembl.
DR GO; GO:0015872; P:dopamine transport; IDA:UniProtKB.
DR GO; GO:0090494; P:dopamine uptake; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IBA:GO_Central.
DR GO; GO:1990384; P:hyaloid vascular plexus regression; ISS:UniProtKB.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0015844; P:monoamine transport; IDA:MGI.
DR GO; GO:0006836; P:neurotransmitter transport; ISS:ARUK-UCL.
DR GO; GO:0015874; P:norepinephrine transport; IBA:GO_Central.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0060134; P:prepulse inhibition; IEA:Ensembl.
DR GO; GO:0042053; P:regulation of dopamine metabolic process; IEA:Ensembl.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007608; P:sensory perception of smell; IEA:Ensembl.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002436; Na/ntran_symport_dopamine.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01202; DOPTRANSPORT.
DR PRINTS; PR00176; NANEUSMPORT.
DR SUPFAM; SSF161070; SSF161070; 1.
DR PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
DR PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
DR PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Disease variant; Disulfide bond; Dystonia;
KW Glycoprotein; Membrane; Metal-binding; Neurodegeneration;
KW Neurotransmitter transport; Parkinsonism; Reference proteome; Sodium;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..620
FT /note="Sodium-dependent dopamine transporter"
FT /id="PRO_0000214751"
FT TOPO_DOM 1..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..116
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..256
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..282
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..335
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..368
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 401..420
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 447..465
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 481..501
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 522..541
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 560..578
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 579..620
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 561..590
FT /note="Interaction with TGFB1I1"
FT /evidence="ECO:0000269|PubMed:12177201"
FT BINDING 75
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 77
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 78
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 82
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 321
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 353
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 418
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 421
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 422
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT SITE 105
FT /note="Contributes to high-affinity binding to cocaine"
FT /evidence="ECO:0000250|UniProtKB:Q61327"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 180..189
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT DISULFID 306
FT /note="Interchain"
FT /evidence="ECO:0000269|Ref.14"
FT VARIANT 121
FT /note="G -> S (in a breast cancer sample; somatic mutation;
FT dbSNP:rs760871529)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036158"
FT VARIANT 237
FT /note="R -> Q (in dbSNP:rs6345)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014180"
FT VARIANT 368
FT /note="L -> Q (in PKDYS1; loss of function;
FT dbSNP:rs267607068)"
FT /evidence="ECO:0000269|PubMed:19478460"
FT /id="VAR_063771"
FT VARIANT 395
FT /note="P -> L (in PKDYS1; loss of function;
FT dbSNP:rs267607069)"
FT /evidence="ECO:0000269|PubMed:19478460"
FT /id="VAR_063772"
FT VARIANT 471
FT /note="V -> I (in dbSNP:rs75916702)"
FT /evidence="ECO:0000269|PubMed:21179162"
FT /id="VAR_064580"
FT VARIANT 544
FT /note="R -> S (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036159"
FT CONFLICT 35
FT /note="K -> M (in Ref. 2; AAB23443)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="S -> C (in Ref. 2; AAB23443)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 620 AA; 68495 MW; CD95009B6BA93108 CRC64;
MSKSKCSVGL MSSVVAPAKE PNAVGPKEVE LILVKEQNGV QLTSSTLTNP RQSPVEAQDR
ETWGKKIDFL LSVIGFAVDL ANVWRFPYLC YKNGGGAFLV PYLLFMVIAG MPLFYMELAL
GQFNREGAAG VWKICPILKG VGFTVILISL YVGFFYNVII AWALHYLFSS FTTELPWIHC
NNSWNSPNCS DAHPGDSSGD SSGLNDTFGT TPAAEYFERG VLHLHQSHGI DDLGPPRWQL
TACLVLVIVL LYFSLWKGVK TSGKVVWITA TMPYVVLTAL LLRGVTLPGA IDGIRAYLSV
DFYRLCEASV WIDAATQVCF SLGVGFGVLI AFSSYNKFTN NCYRDAIVTT SINSLTSFSS
GFVVFSFLGY MAQKHSVPIG DVAKDGPGLI FIIYPEAIAT LPLSSAWAVV FFIMLLTLGI
DSAMGGMESV ITGLIDEFQL LHRHRELFTL FIVLATFLLS LFCVTNGGIY VFTLLDHFAA
GTSILFGVLI EAIGVAWFYG VGQFSDDIQQ MTGQRPSLYW RLCWKLVSPC FLLFVVVVSI
VTFRPPHYGA YIFPDWANAL GWVIATSSMA MVPIYAAYKF CSLPGSFREK LAYAIAPEKD
RELVDRGEVR QFTLRHWLKV
