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DAT

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Target not currently curated in GtoImmuPdb

Target id: 927

Nomenclature: DAT

Systematic Nomenclature: SLC6A3

Family: Monoamine transporter subfamily

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 12 620 5p15.33 SLC6A3 solute carrier family 6 member 3
Mouse 12 619 13 40.1 cM Slc6a3 solute carrier family 6 (neurotransmitter transporter, dopamine), member 3
Rat 12 619 1p11 Slc6a3 solute carrier family 6 member 3
Previous and Unofficial Names Click here for help
DAT1 | dopamine transporter | DA transporter | sodium-dependent dopamine transporter | solute carrier family 6 (neurotransmitter transporter), member 3 | solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 | solute carrier family 6 (neurotransmitter transporter
Database Links Click here for help
Specialist databases
Bioparadigms SLC Tables SLC6A3 (Hs)
RESOLUTE SLC6A3 (Hs)
Other databases
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
UniProtKB
Wikipedia
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
(-)-adrenaline Substrate is endogenous in the given species Hs -
(-)-noradrenaline Substrate is endogenous in the given species Hs -
dopamine Substrate is endogenous in the given species Hs -
MPP+ Hs -
methamphetamine Hs -
amphetamine Hs -
Stoichiometry Click here for help
1 dopamine: 1–2 Na+: 1 Cl- [10]

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]GBR12935 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Inhibition 8.5 pKd 15
pKd 8.5 (Kd 3x10-9 M) [15]
[3H]WIN35428 Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Inhibition 8.0 pKd 15
pKd 8.0 (Kd 1x10-8 M) [15]
atomoxetine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.0 pKd 5
pKd 6.0 (Kd 1.08x10-6 M) [5]
clomipramine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.7 pKd 18
pKd 5.7 (Kd 2.19x10-6 M) [18]
vanoxerine Small molecule or natural product Hs Inhibition 9.0 pKi 1,11,13
pKi 9.0 (Ki 1x10-9 M) [1,11,13]
mazindol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.0 pKi
pKi 8.0 (Ki 1x10-8 M)
WIN35428 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.9 pKi 16
pKi 7.9 (Ki 1.25x10-8 M) [16]
GBR12935 Small molecule or natural product Hs Inhibition 7.6 pKi
pKi 7.6 (Ki 2.51x10-8 M)
dexmethylphenidate Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.6 pKi 12
pKi 7.6 (Ki 2.5x10-8 M) [12]
Description: Displacement of [3H]WIN-35428 from human DAT stably expressed in mouse N2A cells
dexamfetamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pKi 2
pKi 7.0 (Ki 1.09x10-7 M) [2]
benzatropine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Inhibition 6.9 pKi 14
pKi 6.9 (Ki 1.18x10-7 M) [14]
Description: Displacement of [3H]WIN35,428 binding to homogenised rat caudate putamen.
sibutramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.3 pKi 3
pKi 6.3 (Ki 5.02x10-7 M) [3]
desvenlafaxine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition <6.1 pKi 8
pKi <6.1 (Ki >8.54x10-7 M) [8]
trimipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 5.4 pKi 18
pKi 5.4 (Ki 3.78x10-6 M) [18]
modafinil Small molecule or natural product Approved drug Rn Inhibition 5.4 pKi 20
pKi 5.4 (Ki 3.8x10-6 M) [20]
Description: Inhibition of high affinity uptake by the dopamine transporter from rat synaptosomal nerve endings using [3H]dopamine as radioligand
phenelzine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.1 pKi 18
pKi 5.1 (Ki 8.4x10-6 M) [18]
solriamfetol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 4.8 pKi 4
pKi 4.8 (Ki 1.42x10-5 M) [4]
Description: In a radioligand binding assay using HEK293 cells expressing hDAT.
cocaine Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Rn Inhibition 7.1 pIC50 7
pIC50 7.1 (IC50 8.91x10-8 M) [7]
methylphenidate Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.1 pIC50 9
pIC50 7.1 (IC50 7.9x10-8 M) [9]
bupropion Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.3 pIC50 6
pIC50 6.3 (IC50 4.43x10-7 M) [6]
toludesvenlafaxine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.3 pIC50 17
pIC50 6.3 (IC50 4.91x10-7 M) [17]
solriamfetol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.5 pIC50 4
pIC50 5.5 (IC50 2.9x10-6 M) [4]
Description: In a DA reuptake assay in HEK293 cells expressing hDAT.
levomilnacipran Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.5 pIC50 19
pIC50 5.5 (IC50 3.2x10-6 M) [19]
compound 58 [PMID: 25037917] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.2 pIC50 21
pIC50 5.2 (IC50 6.1x10-6 M) [21]
nomifensine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition - -
View species-specific inhibitor tables
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Grin1tm1.1Rpa|Grin1tm1Rpa|Slc6a3+|Slc6a3tm1(cre)Xz Grin1tm1Rpa/Grin1tm1.1Rpa,Slc6a3tm1(cre)Xz/Slc6a3+
involves: 129S1/Sv
MGI:94862  MGI:95819  MP:0009748 abnormal behavioral response to addictive substance PMID: 18701073 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0003243 abnormal dopaminergic neuron morphology PMID: 20016108 
Grin1tm1.1Rpa|Grin1tm1Rpa|Slc6a3+|Slc6a3tm1(cre)Xz Grin1tm1Rpa/Grin1tm1.1Rpa,Slc6a3tm1(cre)Xz/Slc6a3+
involves: 129S1/Sv
MGI:94862  MGI:95819  MP:0002910 abnormal excitatory postsynaptic currents PMID: 18701073 
Grin1tm1.1Rpa|Grin1tm1Rpa|Slc6a3+|Slc6a3tm1(cre)Xz Grin1tm1Rpa/Grin1tm1.1Rpa,Slc6a3tm1(cre)Xz/Slc6a3+
involves: 129S1/Sv
MGI:94862  MGI:95819  MP:0004753 abnormal miniature excitatory postsynaptic currents PMID: 18701073 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 20016108 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0005322 abnormal serotonin concentration PMID: 20016108 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0001265 decreased body size PMID: 20016108 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0005643 decreased dopamine level PMID: 20016108 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0002757 decreased vertical activity PMID: 20016108 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0001399 hyperactivity PMID: 20016108 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0001402 hypoactivity PMID: 20016108 
Grin1tm1.1Rpa|Grin1tm1Rpa|Slc6a3+|Slc6a3tm1(cre)Xz Grin1tm1Rpa/Grin1tm1.1Rpa,Slc6a3tm1(cre)Xz/Slc6a3+
involves: 129S1/Sv
MGI:94862  MGI:95819  MP:0009712 impaired conditioned place preference behavior PMID: 18701073 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0001409 increased stereotypic behavior PMID: 20016108 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0003224 neuron degeneration PMID: 20016108 
Nr4a2tm2.1Tpe|Slc6a3tm1(cre)Lrsn Nr4a2tm2.1Tpe/Nr4a2tm2.1Tpe,Slc6a3tm1(cre)Lrsn/Slc6a3tm1(cre)Lrsn
involves: 129S1/Sv * 129X1/SvJ
MGI:1352456  MGI:94862  MP:0002082 postnatal lethality PMID: 20016108 
Grin1tm1.1Rpa|Grin1tm1Rpa|Slc6a3+|Slc6a3tm1(cre)Xz Grin1tm1Rpa/Grin1tm1.1Rpa,Slc6a3tm1(cre)Xz/Slc6a3+
involves: 129S1/Sv
MGI:94862  MGI:95819  MP:0001473 reduced long term potentiation PMID: 18701073 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Parkinsonism-dystonia, infantile; PKDYS
Synonyms: Infantile dystonia-parkinsonism [Orphanet: ORPHA238455]
OMIM: 613135
Orphanet: ORPHA238455
Disease:  Tobacco addiction, susceptibility to
OMIM: 188890
Role: 

References

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2. Arunotayanun W, Dalley JW, Huang XP, Setola V, Treble R, Iversen L, Roth BL, Gibbons S. (2013) An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'. Bioorg Med Chem Lett, 23 (11): 3411-5. [PMID:23602445]

3. Auerbach SS, DrugMatrix® and ToxFX® Coordinator National Toxicology Program. National Toxicology Program: Dept of Health and Human Services. Accessed on 02/05/2014. Modified on 02/05/2014. DrugMatrix, https://ntp.niehs.nih.gov/drugmatrix/index.html

4. Baladi MG, Forster MJ, Gatch MB, Mailman RB, Hyman DL, Carter LP, Janowsky A. (2018) Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor. J Pharmacol Exp Ther, 366 (2): 367-376. [PMID:29891587]

5. Carlier PR, Lo MM, Lo PC, Richelson E, Tatsumi M, Reynolds IJ, Sharma TA. (1998) Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group. Bioorg Med Chem Lett, 8 (5): 487-92. [PMID:9871604]

6. Carroll FI, Blough BE, Abraham P, Mills AC, Holleman JA, Wolckenhauer SA, Decker AM, Landavazo A, McElroy KT, Navarro HA et al.. (2009) Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction. J Med Chem, 52 (21): 6768-81. [PMID:19821577]

7. Carroll FI, Runyon SP, Abraham P, Navarro H, Kuhar MJ, Pollard GT, Howard JL. (2004) Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers. J Med Chem, 47 (25): 6401-9. [PMID:15566309]

8. Dreyfus N, Myers JK, Badescu VO, de Frutos O, de la Puente ML, Ding C, Filla SA, Fynboe K, Gernert DL, Heinz BA et al.. (2013) Discovery of a potent, dual serotonin and norepinephrine reuptake inhibitor. ACS Med Chem Lett, 4 (6): 560-4. [PMID:24900709]

9. Froimowitz M, Gu Y, Dakin LA, Nagafuji PM, Kelley CJ, Parrish D, Deschamps JR, Janowsky A. (2007) Slow-onset, long-duration, alkyl analogues of methylphenidate with enhanced selectivity for the dopamine transporter. J Med Chem, 50 (2): 219-32. [PMID:17228864]

10. Gu H, Wall SC, Rudnick G. (1994) Stable expression of biogenic amine transporters reveals differences in inhibitor sensitivity, kinetics, and ion dependence. J Biol Chem, 269 (10): 7124-30. [PMID:8125921]

11. Heikkila RE, Manzino L. (1984) Behavioral properties of GBR 12909, GBR 13069 and GBR 13098: specific inhibitors of dopamine uptake. Eur J Pharmacol, 103 (3-4): 241-8. [PMID:6237922]

12. Lapinsky DJ, Velagaleti R, Yarravarapu N, Liu Y, Huang Y, Surratt CK, Lever JR, Foster JD, Acharya R, Vaughan RA et al.. (2011) Azido-iodo-N-benzyl derivatives of threo-methylphenidate (Ritalin, Concerta): Rational design, synthesis, pharmacological evaluation, and dopamine transporter photoaffinity labeling. Bioorg Med Chem, 19 (1): 504-12. [PMID:21129986]

13. Melia KF, Spealman RD. (1991) Pharmacological characterization of the discriminative-stimulus effects of GBR 12909. J Pharmacol Exp Ther, 258 (2): 626-32. [PMID:1678014]

14. Newman AH, Kline RH, Allen AC, Izenwasser S, George C, Katz JL. (1995) Novel 4'-substituted and 4',4"-disubstituted 3 alpha-(diphenylmethoxy)tropane analogs as potent and selective dopamine uptake inhibitors. J Med Chem, 38 (20): 3933-40. [PMID:7562926]

15. Pristupa ZB, Wilson JM, Hoffman BJ, Kish SJ, Niznik HB. (1994) Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding. Mol Pharmacol, 45 (1): 125-35. [PMID:8302271]

16. Reith ME, Xu C, Zhang L, Coffey LL. (1996) Translocation of dopamine and binding of WIN 35,428 measured under identical conditions in cells expressing the cloned human dopamine transporter. Naunyn Schmiedebergs Arch Pharmacol, 354 (3): 295-304. [PMID:8878059]

17. Subbaiah MAM. (2019) Correction to "Triple Reuptake Inhibitors as Potential Therapeutics for Depression and Other Disorders: Design Paradigm and Developmental Challenges". J Med Chem, 62 (21): 10003. [PMID:31617718]

18. Tatsumi M, Groshan K, Blakely RD, Richelson E. (1997) Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol, 340 (2-3): 249-58. [PMID:9537821]

19. Vickers T, Dyck B, Tamiya J, Zhang M, Jovic F, Grey J, Fleck BA, Aparicio A, Johns M, Jin L et al.. (2008) Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors. Bioorg Med Chem Lett, 18 (11): 3230-5. [PMID:18468895]

20. Zhou J, He R, Johnson KM, Ye Y, Kozikowski AP. (2004) Piperidine-based nocaine/modafinil hybrid ligands as highly potent monoamine transporter inhibitors: efficient drug discovery by rational lead hybridization. J Med Chem, 47 (24): 5821-4. [PMID:15537337]

21. Zipp GG, Barbosa J, Green MA, Terranova KM, Fink C, Yu XC, Nouraldeen A, Wilson A, Savelieva K, Lanthorn TH et al.. (2014) Novel inhibitors of the high-affinity L-proline transporter as potential therapeutic agents for the treatment of cognitive disorders. Bioorg Med Chem Lett, 24 (16): 3886-90. [PMID:25037917]

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