同: dopamine transporter gene 1

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/28 03:29:14」(JST)

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The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release. Dopamine reuptake via DAT provides the primary mechanism through which dopamine is cleared from synapses, although there may be an exception in the prefrontal cortex, where evidence points to a possibly larger role of the norepinephrine transporter.^[1]

DAT is thought to be implicated in a number of dopamine-related disorders, including attention deficit hyperactivity disorder, bipolar disorder, clinical depression, and alcoholism. The gene that encodes the DAT protein is located on human chromosome 5, consists of 15 coding exons, and is roughly 64 kbp long. Evidence for the associations between DAT and dopamine related disorders has come from a type of genetic polymorphism, known as a VNTR, in the DAT gene (DAT1), which influences the amount of protein expressed.^[2]

Function[edit]

DAT is an integral membrane protein that removes dopamine from the synaptic cleft and deposits it into surrounding cells, thus terminating the signal of the neurotransmitter. Dopamine underlies several aspects of cognition, including reward, and DAT facilitates regulation of that signal.^[3]

Mechanism[edit]

DAT is a symporter that moves dopamine across the cell membrane by coupling the movement to the energetically-favorable movement of sodium ions moving from high to low concentration into the cell. DAT function requires the sequential binding and co-transport of two Na+ ions and one Cl- ion with the dopamine substrate. The driving force for DAT-mediated dopamine reuptake is the ion concentration gradient generated by the plasma membrane Na+/K+ ATPase.^[4]

In the most widely-accepted model for monoamine transporter function, sodium ions must bind to the extracellular domain of the transporter before dopamine can bind. Once dopamine binds, the protein undergoes a conformational change, which allows both sodium and dopamine to unbind on the intracellular side of the membrane.^[5]

Studies using electrophysiology and radioactive-labeled dopamine have confirmed that the dopamine transporter is similar to other monoamine transporters in that one molecule of neurotransmitter can be transported across the membrane with one or two sodium ions. Chloride ions are also needed to prevent a buildup of positive charge. These studies have also shown that transport rate and direction is totally dependent on the sodium gradient.^[6]

Because of the tight coupling of the membrane potential and the sodium gradient, activity-induced changes in membrane polarity can dramatically influence transport rates. In addition, the transporter may contribute to dopamine release when the neuron depolarizes.^[6]

Protein structure[edit]

The initial determination of the membrane topology of DAT was based upon hydrophobic sequence analysis and sequence similarities with the GABA transporter. These methods predicted twelve transmembrane domains (TMD) with a large extracellular loop between the third and fourth TMDs.^[7] Further characterization of this protein used proteases, which digest proteins into smaller fragments, and glycosylation, which occurs only on extracellular loops, and largely verified the initial predictions of membrane topology.^[8] The exact structure of the transporter was elucidated in 2013 by X-ray crystallography.^[9]

Location and distribution[edit]

Regional distribution of DAT has been found in areas of the brain with established dopaminergic circuitry including: nigrostriatal, mesolimbic, and mesocortical pathways.^[10] The nuclei that make up these pathways have distinct patterns of expression. Gene expression patterns in the adult mouse show high expression in the substantia nigra pars compacta.^[11]

Slc6a3 is expressed in the substantia nigra in the midbrain of the postnatal day 56 mouse. Allen Brain Atlases

DAT in the mesocortical pathway, labeled with radioactive antibodies, was found to be enriched in dendrites and cell bodies of neurons in the substantia nigra pars compacta and ventral tegmental area. This pattern makes sense for a protein that regulates dopamine levels in the synapse.

Staining in the striatum and nucleus accumbens of the mesolimbic pathway was dense and heterogeneous. In the striatum, DAT is localized in the plasma membrane of axon terminals. Double immunocytochemistry demonstrated DAT colocalization with two other markers of nigrostriatal terminals, tyrosine hydroxylase and D2 dopamine receptors. The latter was thus demonstrated to be an autoreceptor on cells that release dopamine.

Surprisingly, DAT was not identified within any synaptic active zones. These results suggest that striatal dopamine reuptake may occur outside of synaptic specializations once dopamine diffuses from the synaptic cleft.

In the substantia nigra, DAT appears to be specifically transported into dendrites, where it can be found in smooth endoplasmic reticulum, plasma membrane, and pre- and postsynaptic active zones. These localizations suggest that DAT modulates the intracellular and extracellular dopamine levels of nigral dendrites.

Within the perikarya of pars compacta neurons, DAT was localized primarily to rough and smooth endoplasmic reticulum, Golgi complex, and multivesicular bodies, identifying probable sites of synthesis, modification, transport, and degradation.^[12]

Genetics and regulation[edit]

The gene for DAT, known as DAT1, is located on chromosome 5p15.^[2] The protein encoding region of the gene is over 64 kb long and comprises 15 coding segments or exons.^[13] This gene has a variable number tandem repeat (VNTR) at the 3’ end (rs28363170) and another in the intron 8 region.^[14] Differences in the VNTR have been shown to affect the basal level of expression of the transporter; consequentially, researchers have looked for associations with dopamine related disorders.^[15]

Nurr1, a nuclear receptor that regulates many dopamine related genes, can bind the promoter region of this gene and induce expression.^[16] This promoter may also be the target of the transcription factor Sp-1.

While transcription factors control which cells express DAT, functional regulation of this protein is largely accomplished by kinases. Both MAPK^[17] and PKC^[18] can modulate the rate at which the transporter moves dopamine or cause the internalization of DAT.

Biological role and disorders[edit]

The rate at which DAT removes dopamine from the synapse can have a profound effect on the amount of dopamine in the cell. This is best evidenced by the severe cognitive deficits, motor abnormalities, and hyperactivity of mice with no dopamine transporters.^[19] These characteristics have striking similarities to the symptoms of ADHD.

Differences in the functional VNTR have been identified as risk factors for bipolar disorder^[20] and ADHD.^[21] Data has emerged that suggests there is also an association with stronger withdrawal symptoms from alcoholism, although this is a point of controversy.^[22]^[23] Interestingly, an allele of the DAT gene with normal protein levels is associated with non-smoking behavior and ease of quitting.^[24] Additionally, male adolescents particularly those in high-risk families (ones marked by a disengaged mother and absence of maternal affection) who carry the 10-allele VNTR repeat show a statistically significant affinity for antisocial peers.^[25]^[26]

Increased activity of DAT is associated with several different disorders, including clinical depression.^[27] Decreasing levels of DAT expression are associated with aging, and likely underlie a compensatory mechanism for the decreases in dopamine release as a person ages.^[28]

Pharmacology[edit]

Mechanisms of Cocaine and Amphetamine DAT blocking

DAT is also the target of several "DAT-releasers" and “DAT-blockers” including amphetamines and cocaine. These chemicals inhibit the action of DAT and, to a lesser extent, the other monoamine transporters, but their effects are mediated by separate mechanisms.

Cocaine blocks DAT by binding directly to the transporter and reducing the rate of transport.^[7] In contrast, amphetamines trigger a signal cascade thought to involve PKC or MAPK that leads to the internalization of DAT molecules, which are normally expressed on the neuron’s surface.^[29]

Amphetamine on DAT also has a direct effect in the increased levels of secreted dopamine. Lipophilic AMPH diffuses into the cytoplasm and into the dopamine secretory vesicles disrupting the proton gradient established across the vesicle wall. This induces a leaky channel and DA diffuses out into the cytoplasm. Additionally, AMPH causes a reversal of normal DA flow at the DAT. Instead of DA reuptake, in the presence of AMPH, a reversal in the mechanism of DAT occurs causing an outflow of dopamine released into the cytoplasm into the synaptic space changing it from a symporter to an antiporter-like functionality.^[30]^[31]^[32]^[33] Both of these mechanisms result in less removal of dopamine from the synapse and increased signaling, which is thought to underlie the pleasurable feelings elicited by these substances.^[3]

Ligands[edit]

LBT-999

RTI-470

LBT-999^[34]^[35]^[36]^[37]^[38]
RTI-470^[39]

Interactions[edit]

Dopamine transporter has been shown to interact with:

Alpha-synuclein,^[40]^[41]
PICK1,^[42] and
TGFB1I1.^[43]

References[edit]

^ Carboni E, Tanda GL, Frau R, Di Chiara G (September 1990). "Blockade of the noradrenaline carrier increases extracellular dopamine concentrations in the prefrontal cortex: evidence that dopamine is taken up in vivo by noradrenergic terminals". J. Neurochem. 55 (3): 1067–70. doi:10.1111/j.1471-4159.1990.tb04599.x. PMID 2117046.
^ ^a ^b Vandenbergh DJ, Persico AM, Hawkins AL, Griffin CA, Li X, Jabs EW, Uhl GR (December 1992). "Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR". Genomics 14 (4): 1104–6. doi:10.1016/S0888-7543(05)80138-7. PMID 1478653.
^ ^a ^b Schultz W (1998). "Predictive reward signal of dopamine neurons". J. Neurophysiol. 80 (1): 1–27. PMID 9658025.
^ Torres GE, Gainetdinov RR, Caron MG (2003). "Plasma membrane monoamine transporters: structure, regulation and function". Nat. Rev. Neurosci. 4 (1): 13–25. doi:10.1038/nrn1008. PMID 12511858.
^ Sonders MS, Zhu SJ, Zahniser NR, Kavanaugh MP, Amara SG (1997). "Multiple ionic conductances of the human dopamine transporter: the actions of dopamine and psychostimulants". J. Neurosci. 17 (3): 960–74. PMID 8994051.
^ ^a ^b Wheeler DD, Edwards AM, Chapman BM, Ondo JG (1993). "A model of the sodium dependence of dopamine uptake in rat striatal synaptosomes". Neurochem. Res. 18 (8): 927–936. doi:10.1007/BF00998279. PMID 8371835.
^ ^a ^b Kilty JE, Lorang D, Amara SG (1991). "Cloning and expression of a cocaine-sensitive rat dopamine transporter". Science 254 (5031): 578–579. doi:10.1126/science.1948035. PMID 1948035.
^ Vaughan RA, Kuhar MJ (1996). "Dopamine transporter ligand binding domains. Structural and functional properties revealed by limited proteolysis". J. Biol. Chem. 271 (35): 21672–21680. doi:10.1074/jbc.271.35.21672. PMID 8702957.
^ Penmatsa, Aravind; Wang, Kevin H.; Gouaux, Eric (15 September 2013). "X-ray structure of dopamine transporter elucidates antidepressant mechanism". Nature 503 (7474): 85–90. doi:10.1038/nature12533. Retrieved 12 November 2013.
^ Ciliax BJ, Drash GW, Staley JK, Haber S, Mobley CJ, Miller GW, Mufson EJ, Mash DC, Levey AI (June 1999). "Immunocytochemical localization of the dopamine transporter in human brain". J. Comp. Neurol. 409 (1): 38–56. doi:10.1002/(SICI)1096-9861(19990621)409:1<38::AID-CNE4>3.0.CO;2-1. PMID 10363710.
^ Liu Z, Yan SF, Walker JR, Zwingman TA, Jiang T, Li J, Zhou Y (2007). "Study of gene function based on spatial co-expression in a high-resolution mouse brain atlas". BMC Syst Biol 1: 19. doi:10.1186/1752-0509-1-19. PMC 1863433. PMID 17437647.
^ Hersch SM, Yi H, Heilman CJ, Edwards RH, Levey AI (1997). "Subcellular localization and molecular topology of the dopamine transporter in the striatum and substantia nigra". J. Comp. Neurol. 388 (2): 211–227. doi:10.1002/(SICI)1096-9861(19971117)388:2<211::AID-CNE3>3.0.CO;2-4. PMID 9368838.
^ Kawarai T, Kawakami H, Yamamura Y, Nakamura S (1997). "Structure and organization of the gene encoding human dopamine transporter". Gene 195 (1): 11–18. doi:10.1016/S0378-1119(97)00131-5. PMID 9300814.
^ Sano A, Kondoh K, Kakimoto Y, Kondo I (May 1993). "A 40-nucleotide repeat polymorphism in the human dopamine transporter gene". Hum. Genet. 91 (4): 405–6. doi:10.1007/BF00217369. PMID 8500798.
^ Miller GM, Madras BK (2002). "Polymorphisms in the 3'-untranslated region of human and monkey dopamine transporter genes affect reporter gene expression". Mol. Psychiatry 7 (1): 44–55. doi:10.1038/sj/mp/4000921. PMID 11803445.
^ Sacchetti P, Mitchell TR, Granneman JG, Bannon MJ (2001). "Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism". J. Neurochem. 76 (5): 1565–1572. doi:10.1046/j.1471-4159.2001.00181.x. PMID 11238740.
^ Morón JA, Zakharova I, Ferrer JV, Merrill GA, Hope B, Lafer EM, Lin ZC, Wang JB, Javitch JA, Galli A, Shippenberg TS (September 2003). "Mitogen-activated protein kinase regulates dopamine transporter surface expression and dopamine transport capacity". J. Neurosci. 23 (24): 8480–8. PMID 13679416.
^ Pristupa ZB, McConkey F, Liu F, Man HY, Lee FJ, Wang YT, Niznik HB (September 1998). "Protein kinase-mediated bidirectional trafficking and functional regulation of the human dopamine transporter". Synapse 30 (1): 79–87. doi:10.1002/(SICI)1098-2396(199809)30:1<79::AID-SYN10>3.0.CO;2-K. PMID 9704884.
^ Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG (1999). "Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity". Science 283 (5400): 397–401. doi:10.1126/science.283.5400.397. PMID 9888856.
^ Greenwood TA, Alexander M, Keck PE, McElroy S, Sadovnick AD, Remick RA, Kelsoe JR (March 2001). "Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder". Am. J. Med. Genet. 105 (2): 145–51. doi:10.1002/1096-8628(2001)9999:9999<::AID-AJMG1161>3.0.CO;2-8. PMID 11304827.
^ Yang B, Chan RC, Jing J, Li T, Sham P, Chen RY (2007). "A meta-analysis of association studies between the 10-repeat allele of a VNTR polymorphism in the 3'-UTR of dopamine transporter gene and attention deficit hyperactivity disorder". Am. J. Med. Genet. B Neuropsychiatr. Genet. 144 (4): 541–550. doi:10.1002/ajmg.b.30453. PMID 17440978.
^ Sander T, Harms H, Podschus J, Finckh U, Nickel B, Rolfs A, Rommelspacher H, Schmidt LG (February 1997). "Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium". Biol. Psychiatry 41 (3): 299–304. doi:10.1016/S0006-3223(96)00044-3. PMID 9024952.
^ Ueno S, Nakamura M, Mikami M, Kondoh K, Ishiguro H, Arinami T, Komiyama T, Mitsushio H, Sano A, Tanabe H (November 1999). "Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism". Mol. Psychiatry 4 (6): 552–7. doi:10.1038/sj.mp.4000562. PMID 10578237.
^ Ueno S (February 2003). "Genetic polymorphisms of serotonin and dopamine transporters in mental disorders". J. Med. Invest. 50 (1–2): 25–31. PMID 12630565.
^ Beaver KM, Wright JP, DeLisi M (September 2008). "Delinquent peer group formation: evidence of a gene x environment correlation". J Genet Psychol 169 (3): 227–44. doi:10.3200/GNTP.169.3.227-244. PMID 18788325.
^ Florida State University (2008-10-02). "Specific Gene Found In Adolescent Men With Delinquent Peers". ScienceDaily. Retrieved 2008-10-08.
^ Laasonen-Balk T, Kuikka J, Viinamäki H, Husso-Saastamoinen M, Lehtonen J, Tiihonen J (1999). "Striatal dopamine transporter density in major depression". Psychopharmacology (Berl.) 144 (3): 282–285. doi:10.1007/s002130051005. PMID 10435396.
^ Bannon MJ, Poosch MS, Xia Y, Goebel DJ, Cassin B, Kapatos G (1992). "Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age". Proc. Natl. Acad. Sci. U.S.A. 89 (15): 7095–7099. doi:10.1073/pnas.89.15.7095. PMC 49652. PMID 1353885.
^ Kahlig KM, Javitch JA, Galli A (March 2004). "Amphetamine regulation of dopamine transport. Combined measurements of transporter currents and transporter imaging support the endocytosis of an active carrier". J. Biol. Chem. 279 (10): 8966–75. doi:10.1074/jbc.M303976200. PMID 14699142.
^ Moore KE (June 1977). "The actions of amphetamine on neurotransmitters: a brief review". Biol. Psychiatry 12 (3): 451–62. PMID 17437.
^ Johnson LA, Guptaroy B, Lund D, Shamban S, Gnegy ME (March 2005). "Regulation of amphetamine-stimulated dopamine efflux by protein kinase C beta". J. Biol. Chem. 280 (12): 10914–10919. doi:10.1074/jbc.M413887200. PMID 15647254.
^ Kahlig KM, Binda F, Khoshbouei H (March 2005). "Amphetamine induces dopamine efflux through a dopamine transporter channel". Proc. Natl. Acad. Sci. U.S.A. 102 (9): 3495–3500. doi:10.1073/pnas.0407737102. PMC 549289. PMID 15728379.
^ Khoshbouei H, Sen N, Guptaroy B, Johnson L', Lund D, Gnegy ME, Galli A, Javitch JA (March 2004). "N-terminal phosphorylation of the dopamine transporter is required for amphetamine-induced efflux". PLoS Biol. 2 (3): E78. doi:10.1371/journal.pbio.0020078. PMC 368172. PMID 15024426. Lay summary – PLoS Biology.
^ Dollé F, Emond P, Mavel S, et al. (February 2006). "Synthesis, radiosynthesis and in vivo preliminary evaluation of [11C]LBT-999, a selective radioligand for the visualisation of the dopamine transporter with PET". Bioorg. Med. Chem. 14 (4): 1115–25. doi:10.1016/j.bmc.2005.09.035. PMID 16219467.
^ Chalon S, Hall H, Saba W, et al. (April 2006). "Pharmacological characterization of (E)-N-(4-fluorobut-2-enyl)-2beta-carbomethoxy-3beta-(4'-tolyl)nortropane (LBT-999) as a highly promising fluorinated ligand for the dopamine transporter". J. Pharmacol. Exp. Ther. 317 (1): 147–52. doi:10.1124/jpet.105.096792. PMID 16339913.
^ Saba W, Valette H, Schöllhorn-Peyronneau MA, et al. (January 2007). "[11C]LBT-999: a suitable radioligand for investigation of extra-striatal dopamine transporter with PET". Synapse 61 (1): 17–23. doi:10.1002/syn.20337. PMID 17068778.
^ Riss PJ, Roesch F (November 2009). "Efficient microwave-assisted direct radiosynthesis of [(18)F]PR04.MZ and [(18)F]LBT999: selective dopamine transporter ligands for quantitative molecular imaging by means of PET". Bioorg. Med. Chem. 17 (22): 7630–4. doi:10.1016/j.bmc.2009.09.054. PMID 19846314.
^ Leung K (2004). "8-((E)-4-Fluoro-but-2-enyl)-3β-p-tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid [11C]methyl ester". Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. PMID 20641911.
^ Carroll FI, Howard JL, Howell LL, Fox BS, Kuhar MJ (2006). "Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse". AAPS J 8 (1): E196–203. doi:10.1208/aapsj080124. PMC 2751440. PMID 16584128.
^ Wersinger C, Sidhu A (2003). "Attenuation of dopamine transporter activity by alpha-synuclein". Neurosci. Lett. 340 (3): 189–92. doi:10.1016/S0304-3940(03)00097-1. PMID 12672538.
^ Lee FJ, Liu F, Pristupa ZB, Niznik HB (2001). "Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis". FASEB J. 15 (6): 916–26. doi:10.1096/fj.00-0334com. PMID 11292651.
^ Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, Staudinger J, Caron MG (2001). "Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1". Neuron 30 (1): 121–34. doi:10.1016/S0896-6273(01)00267-7. PMID 11343649.
^ Carneiro AM, Ingram SL, Beaulieu JM, Sweeney A, Amara SG, Thomas SM, Caron MG, Torres GE (2002). "The multiple LIM domain-containing adaptor protein Hic-5 synaptically colocalizes and interacts with the dopamine transporter". J. Neurosci. 22 (16): 7045–54. PMID 12177201.

External links[edit]

Dopamine transporter-related Associations, Experiments, Publications and Clinical Trials
Dopamine Transporter at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 注意欠陥多動性障害：疫学、病因、臨床的特徴、経過、評価、および診断 attention deficit hyperactivity disorder in adults epidemiology pathogenesis clinical features course assessment and diagnosis

English Journal

Pharmacogenetic role of dopamine transporter (SLC6A3) variation on response to disulfiram treatment for cocaine addiction.

Kampangkaew JP, Spellicy CJ, Nielsen EM, Harding MJ, Ye A, Hamon SC, Kosten TR, Nielsen DA.
The American journal on addictions. 2019 May;().
Disulfiram has been beneficial in treating cocaine addiction in several studies. Patients with two SLC6A3 (DAT1) rs28363170 10-repeat alleles who have with genetically high dopamine transporter (DAT) levels may benefit from increased dopamine levels resulting from disulfiram treatment. After stabili
PMID 31087723

Interactive effects of dopamine transporter genotype and aging on resting-state functional networks.

Baeuchl C, Chen HY, Su YS, Hämmerer D, Klados MA, Li SC.
PloS one. 2019 ;14(5)e0215849.
Aging and dopamine modulation have both been independently shown to influence the functional connectivity of brain networks during rest. Dopamine modulation is known to decline during the course of aging. Previous evidence also shows that the dopamine transporter gene (DAT1) influences the re-uptake
PMID 31067250

Emotional insecurity as a mediator of the moderating role of dopamine genes in the association between interparental conflict and youth externalizing problems.

Davies PT, Pearson JK, Cicchetti D, Martin MJ, Cummings EM.
Development and psychopathology. 2019 May;()1-16.
This study tested whether the association between interparental conflict and adolescent externalizing symptoms was moderated by a polygenic composite indexing low dopamine activity (i.e., 7-repeat allele of DRD4; Val alleles of COMT; 10-repeat variants of DAT1) in a sample of seventh-grade adolescen
PMID 31057130

Japanese Journal

Lack of Association between the Dopamine Transporter Gene 3'VNTR Polymorphism and Attention Deficit Hyperactivity Disorder in Chinese Han Children : Case-control and Family-based Studies

The Kobe journal of the medical sciences 53(6), 327-333, 2007-12
NAID 120000943086

Lack of Association between the Dopamine Transporter Gene 3'VNTR Polymorphism and Attention Deficit Hyperactivity Disorder in Chinese Han Children : Case-control and Family-based Studies

The Kobe journal of the medical sciences 53(6), 327-333, 2007-12
NAID 110006648064

Identification and Characterization of the Hesr1/Hey1 as a Candidate trans-Acting Factor on Gene Expression through the 3' Non-Coding Polymorphic Region of the Human Dopamine Transporter (DAT1) Gene

The journal of biochemistry 137(2), 205-216, 2005-02-01
NAID 10017343257

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★リンクテーブル★

「DAT」

Solute carrier family 6 (neurotransmitter transporter, dopamine), member 3
Identifiers
Symbols	SLC6A3; DAT; DAT1; PKDYS
External IDs	OMIM: 126455 MGI: 94862 HomoloGene: 55547 GeneCards: SLC6A3 Gene
Gene Ontology
Molecular function	• receptor binding; • dopamine transmembrane transporter activity; • dopamine:sodium symporter activity; • protein binding; • drug binding; • monoamine transmembrane transporter activity; • protein complex binding; • dopamine binding; • protein N-terminus binding;
Cellular component	• cytoplasm; • plasma membrane; • integral to plasma membrane; • integral to membrane; • axon; • neuronal cell body;
Biological process	• transport; • synaptic transmission; • aging; • lactation; • sensory perception of smell; • locomotory behavior; • cell death; • response to iron ion; • monoamine transport; • dopamine transport; • adenohypophysis development; • response to nicotine; • positive regulation of multicellular organism growth; • regulation of dopamine metabolic process; • neurotransmitter biosynthetic process; • response to cocaine; • dopamine biosynthetic process; • dopamine catabolic process; • response to drug; • response to ethanol; • response to cAMP; • transmembrane transport; • prepulse inhibition;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

「DA」

　　[★]

[pmid2117046-1] Carboni E, Tanda GL, Frau R, Di Chiara G (September 1990). "Blockade of the noradrenaline carrier increases extracellular dopamine concentrations in the prefrontal cortex: evidence that dopamine is taken up in vivo by noradrenergic terminals". J. Neurochem. 55 (3): 1067–70. doi:10.1111/j.1471-4159.1990.tb04599.x. PMID 2117046.

[Vandenbergh_DJ_1992_1104.E2.80.931106-2] Vandenbergh DJ, Persico AM, Hawkins AL, Griffin CA, Li X, Jabs EW, Uhl GR (December 1992). "Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR". Genomics 14 (4): 1104–6. doi:10.1016/S0888-7543(05)80138-7. PMID 1478653.

[Schultz-3] Schultz W (1998). "Predictive reward signal of dopamine neurons". J. Neurophysiol. 80 (1): 1–27. PMID 9658025.

[4] Torres GE, Gainetdinov RR, Caron MG (2003). "Plasma membrane monoamine transporters: structure, regulation and function". Nat. Rev. Neurosci. 4 (1): 13–25. doi:10.1038/nrn1008. PMID 12511858.

[5] Sonders MS, Zhu SJ, Zahniser NR, Kavanaugh MP, Amara SG (1997). "Multiple ionic conductances of the human dopamine transporter: the actions of dopamine and psychostimulants". J. Neurosci. 17 (3): 960–74. PMID 8994051.

[wheeler-6] Wheeler DD, Edwards AM, Chapman BM, Ondo JG (1993). "A model of the sodium dependence of dopamine uptake in rat striatal synaptosomes". Neurochem. Res. 18 (8): 927–936. doi:10.1007/BF00998279. PMID 8371835.

[kilty-7] Kilty JE, Lorang D, Amara SG (1991). "Cloning and expression of a cocaine-sensitive rat dopamine transporter". Science 254 (5031): 578–579. doi:10.1126/science.1948035. PMID 1948035.

[8] Vaughan RA, Kuhar MJ (1996). "Dopamine transporter ligand binding domains. Structural and functional properties revealed by limited proteolysis". J. Biol. Chem. 271 (35): 21672–21680. doi:10.1074/jbc.271.35.21672. PMID 8702957.

[9] Penmatsa, Aravind; Wang, Kevin H.; Gouaux, Eric (15 September 2013). "X-ray structure of dopamine transporter elucidates antidepressant mechanism". Nature 503 (7474): 85–90. doi:10.1038/nature12533. Retrieved 12 November 2013.

[pmid10363710-10] Ciliax BJ, Drash GW, Staley JK, Haber S, Mobley CJ, Miller GW, Mufson EJ, Mash DC, Levey AI (June 1999). "Immunocytochemical localization of the dopamine transporter in human brain". J. Comp. Neurol. 409 (1): 38–56. doi:10.1002/(SICI)1096-9861(19990621)409:1<38::AID-CNE4>3.0.CO;2-1. PMID 10363710.

[pmid17437647-11] Liu Z, Yan SF, Walker JR, Zwingman TA, Jiang T, Li J, Zhou Y (2007). "Study of gene function based on spatial co-expression in a high-resolution mouse brain atlas". BMC Syst Biol 1: 19. doi:10.1186/1752-0509-1-19. PMC 1863433. PMID 17437647.

[12] Hersch SM, Yi H, Heilman CJ, Edwards RH, Levey AI (1997). "Subcellular localization and molecular topology of the dopamine transporter in the striatum and substantia nigra". J. Comp. Neurol. 388 (2): 211–227. doi:10.1002/(SICI)1096-9861(19971117)388:2<211::AID-CNE3>3.0.CO;2-4. PMID 9368838.

[13] Kawarai T, Kawakami H, Yamamura Y, Nakamura S (1997). "Structure and organization of the gene encoding human dopamine transporter". Gene 195 (1): 11–18. doi:10.1016/S0378-1119(97)00131-5. PMID 9300814.

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