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 23-FEB-2022, entry version 212. 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 PKDYS GLN-368 AND LEU-395, AND CHARACTERIZATION OF VARIANTS PKDYS RP 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 infantile (PKDYS) [MIM:613135]: A CC neurodegenerative disorder characterized by infantile onset of CC parkinsonism and dystonia. Other neurologic features include global CC developmental delay, bradykinesia and pyramidal tract signs. CC {ECO:0000269|PubMed:19478460}. Note=The disease is caused by variants CC affecting the gene represented in this 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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; 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; ENSP00000270349; ENSG00000142319. DR Ensembl; ENST00000621716; ENSP00000479597; ENSG00000276996. 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; SDWADNS; -. 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; 6 hits in 1036 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 73 other tissues. DR Genevisible; Q01959; HS. DR GO; GO:0030424; C:axon; IDA:UniProtKB. 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: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 METAL 75 FT /note="Sodium 1; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6" FT METAL 77 FT /note="Sodium 2; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6" FT METAL 78 FT /note="Sodium 1; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6" FT METAL 82 FT /note="Sodium 2" FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6" FT METAL 321 FT /note="Sodium 2" FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6" FT METAL 353 FT /note="Sodium 2" FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6" FT METAL 418 FT /note="Sodium 1; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6" FT METAL 421 FT /note="Sodium 1" FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6" FT METAL 422 FT /note="Sodium 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 PKDYS; loss of function; FT dbSNP:rs267607068)" FT /evidence="ECO:0000269|PubMed:19478460" FT /id="VAR_063771" FT VARIANT 395 FT /note="P -> L (in PKDYS; 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 //