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dopamine transporter (solute carrier family 6 member 3, DA transporter, DAT, DAT1, SLC6A3)
Function:
- amine transporter
- terminates the action of dopamine by its high affinity Na+-dependent reuptake into presynaptic terminals
- interacts with PRKCABP & TGFB1I1
Structure:
- homooligomer; disulfide-linked
- belongs to the Na+:neurotransmitter symporter (SNF) family
Compartment: membrane
Pathology:
- down-regulation of dopamine transporters in part compensates for loss of dopaminergic terminals
- down-regulation is mitigated by exogenous dopamine (from levodopa, Sinemet) shorteing duration of levodopa action
Pharmacology:
- SLC6A3 is the target of psychomotor stimulants such as amphetamines or cocaine
Interactions
molecular events
Related
dopamine (Inotropin, Dopastat)
dopamine transporter scan
General
adenosine triphosphatase (ATPase)
glycoprotein
plasma membrane protein
solute carrier family 6 (neurotransmitter transporter, SLC6, SLC6A)
Properties
SIZE: MW = 68 kD
entity length = 620 aa
COMPARTMENT: synaptic membrane
CELL-REGION: axon terminal
CELL: neuron
WITHIN: substantia nigra
WITHIN: striatum
MOTIF: cytoplasmic domain {1-68}
MOTIF: Ser phosphorylation site {N-TERMINAL}
Ser phosphorylation site {N-TERMINAL-2}
Thr phosphorylation site {N-TERMINAL-3}
transmembrane domain {69-89}
exoplasmic loop {90-95}
transmembrane domain {96-116}
MOTIF: leucine zipper
SITE: M2
FOR-BINDING-VIA: leucine zipper
cytoplasmic loop {117-139}
transmembrane domain {140-160}
exoplasmic loop {161-237}
MOTIF: N-glycosylation site {N181}
N-glycosylation site {N188}
N-glycosylation site {N205}
cysteine residue {exoplasmic loop [L2.1] }
MODIFICATION: cysteine residue {exoplasmic loop [L2.2] }
cysteine residue {exoplasmic loop [L2.2] }
MODIFICATION: cysteine residue {exoplasmic loop [L2.1] }
transmembrane domain {238-256}
cytoplasmic loop {257-264}
transmembrane domain {265-282}
exoplasmic loop {283-317}
transmembrane domain {318-335}
cytoplasmic loop {336-346}
MOTIF: Ser phosphorylation site {cytoplasmic loop {L2}}
transmembrane domain {347-368}
exoplasmic loop {369-400}
transmembrane domain {401-420}
cytoplasmic loop {421-446}
transmembrane domain {447-465}
MOTIF: leucine zipper
SITE: M9
FOR-BINDING-VIA: leucine zipper
exoplasmic loop {466-480}
transmembrane domain {481-501}
cytoplasmic loop {502-521}
transmembrane domain {522-541}
exoplasmic loop {542-559}
transmembrane domain {560-578}
cytoplasmic domain {579-620}
MOTIF: Thr phosphorylation site {C-TERMINAL}
Database Correlations
OMIM 126455
UniProt Q01959
Pfam PF00209
Entrez Gene 6531
Kegg hsa:6531
References
- UniProt :accession Q01959
- NIEHS-SNPs
http://egp.gs.washington.edu/data/slc6a3/
- Wikipedia; Note: dopamine transporter entry
http://en.wikipedia.org/wiki/dopamine_transporter
- Niznik HB et al
The dopamine transporter is absent in parkinsonian putamen
and reduced in the caudate nucleus.
J Neurochem 56:192 1991
PMID: 1987318
- Giros B, Caron MG.
Molecular characterization of the dopamine transporter.
Trends Pharmacol Sci. 1993 Feb;14(2):43-9. Review.
PMID: 8480373
- Troiano AR et al.
PET demonstrates reduced dopamine transporter expression in
PD with dyskinesias.
Neurology 2009 Apr 7; 72:1211.
PMID: 19020294
- Vingerhoets FJG.
Dyskinesia in Parkinson disease: Back for the future?
Neurology 2009 Apr 7; 72:1202.
PMID: 19349599