DAT

Target id: 927

Nomenclature: DAT

Systematic Nomenclature: SLC6A3

Family: Monoamine transporter subfamily

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for DAT in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 620 5p15.3 SLC6A3 solute carrier family 6 member 3
Mouse - 619 13 40.10 cM Slc6a3 solute carrier family 6 (neurotransmitter transporter, dopamine), member 3
Rat - 619 1p11 Slc6a3 solute carrier family 6 member 3
Previous and Unofficial Names
DAT1 | dopamine transporter | DA transporter | sodium-dependent dopamine transporter | solute carrier family 6 (neurotransmitter transporter), member 3
Database Links
Specialist databases
Bioparadigms SLC Tables SLC6A3 (Hs)
Other databases
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
(-)-adrenaline Hs -
(-)-noradrenaline Hs -
dopamine Hs -
MPP+ Hs -
methamphetamine Hs -
amphetamine Hs -
Stoichiometry
1 dopamine: 1–2 Na+: 1 Cl- [8]

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]GBR12935 Hs Inhibition 8.5 pKd 11
pKd 8.5 (Kd 3x10-9 M) [11]
[3H]WIN35428 Hs Inhibition 8.0 pKd 11
pKd 8.0 (Kd 1x10-8 M) [11]
atomoxetine Hs Inhibition 6.0 pKd 3
pKd 6.0 (Kd 1.08x10-6 M) [3]
clomipramine Hs Inhibition 5.7 pKd 13
pKd 5.7 (Kd 2.19x10-6 M) [13]
mazindol Hs Inhibition 8.0 pKi
pKi 8.0 (Ki 1x10-8 M)
WIN35428 Hs Inhibition 7.9 pKi 12
pKi 7.9 (Ki 1.25x10-8 M) [12]
GBR12935 Hs Inhibition 7.6 pKi
pKi 7.6 (Ki 2.51x10-8 M)
dexmethylphenidate Hs Inhibition 7.6 pKi 9
pKi 7.6 (Ki 2.5x10-8 M) [9]
Description: Displacement of [3H]WIN-35428 from human DAT stably expressed in mouse N2A cells
dexamfetamine Hs Inhibition 7.0 pKi 1
pKi 7.0 (Ki 1.09x10-7 M) [1]
benzatropine Rn Inhibition 6.9 pKi 10
pKi 6.9 (Ki 1.18x10-7 M) [10]
Description: Displacement of [3H]WIN35,428 binding to homogenised rat caudate putamen.
sibutramine Hs Inhibition 6.3 pKi 2
pKi 6.3 (Ki 5.02x10-7 M) [2]
desvenlafaxine Hs Inhibition <6.1 pKi 6
pKi <6.1 (Ki >8.54x10-7 M) [6]
trimipramine Hs Inhibition 5.4 pKi 13
pKi 5.4 (Ki 3.78x10-6 M) [13]
modafinil Rn Inhibition 5.4 pKi 15
pKi 5.4 (Ki 3.8x10-6 M) [15]
Description: Inhibition of high affinity uptake by the dopamine transporter from rat synaptosomal nerve endings using [3H]dopamine as radioligand
phenelzine Hs Inhibition 5.1 pKi 13
pKi 5.1 (Ki 8.4x10-6 M) [13]
cocaine Rn Inhibition 7.1 pIC50 5
pIC50 7.1 (IC50 8.91x10-8 M) [5]
methylphenidate Hs Inhibition 7.1 pIC50 7
pIC50 7.1 (IC50 7.9x10-8 M) [7]
bupropion Hs Inhibition 6.3 pIC50 4
pIC50 6.3 (IC50 4.43x10-7 M) [4]
levomilnacipran Hs Inhibition 5.5 pIC50 14
pIC50 5.5 (IC50 3.2x10-6 M) [14]
compound 58 [PMID: 25037917] Hs Inhibition 5.2 pIC50 16
pIC50 5.2 (IC50 6.1x10-6 M) [16]
nomifensine Hs Inhibition - -
View species-specific inhibitor tables
Phenotypes, Alleles and Disease Models 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
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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11. 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]

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Contributors

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How to cite this page

Stefan Bröer.
Monoamine transporter subfamily: DAT. Last modified on 31/07/2015. Accessed on 20/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=927.