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Gene Review

DAT  -  Dopamine transporter

Drosophila melanogaster

Synonyms: CG8380, DmDAT, Dmel\CG8380, dDAT, fmn, ...
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High impact information on DAT

  • Major efforts have been focused on defining residues in DAT involved in cocaine binding [1].
  • Cocaine affinity decreased by mutations of aromatic residue phenylalanine 105 in the transmembrane domain 2 of dopamine transporter [1].
  • The combination of a DAT-like substrate selectivity and norepinephrine transporter-like inhibitor pharmacology within a single carrier, and results from phylogenetic analyses, suggest that dDAT represents an ancestral catecholamine transporter gene [2].
  • The substrate selectivity of dDAT parallels that of the mammalian DATs in that dopamine and tyramine are the preferred substrates, whereas octopamine is transported less efficiently, and serotonin not at all [2].
  • Voltage-clamp analysis of dDAT expressed in Xenopus laevis oocytes indicates that dDAT-mediated uptake is electrogenic; however, dDAT seems to lack the constitutive leak conductance that is characteristic of the mammalian catecholamine transporters [2].

Biological context of DAT

  • Cocaine has a moderately high affinity to the cloned dDAT (IC50 = 2.6 microM) [2].
  • The predicted moth DAT protein (TrnDAT) has greatest amino acid sequence identity with Drosophila melanogasterDAT (73%) and Caenorhabditis elegansDAT (51%) [3].
  • We show that fmn mutants have abnormally high levels of activity and reduced rest (sleep); genetic mapping, molecular analyses, and phenotypic rescue experiments demonstrate that these phenotypes result from mutation of the Drosophila dopamine transporter gene [4].

Anatomical context of DAT


Analytical, diagnostic and therapeutic context of DAT


  1. Cocaine affinity decreased by mutations of aromatic residue phenylalanine 105 in the transmembrane domain 2 of dopamine transporter. Wu, X., Gu, H.H. Mol. Pharmacol. (2003) [Pubmed]
  2. The antidepressant-sensitive dopamine transporter in Drosophila melanogaster: a primordial carrier for catecholamines. Pörzgen, P., Park, S.K., Hirsh, J., Sonders, M.S., Amara, S.G. Mol. Pharmacol. (2001) [Pubmed]
  3. Functionally distinct dopamine and octopamine transporters in the CNS of the cabbage looper moth. Gallant, P., Malutan, T., McLean, H., Verellen, L., Caveney, S., Donly, C. Eur. J. Biochem. (2003) [Pubmed]
  4. Dopamine is a regulator of arousal in the fruit fly. Kume, K., Kume, S., Park, S.K., Hirsh, J., Jackson, F.R. J. Neurosci. (2005) [Pubmed]
  5. Sp1 and Sp3 activate transcription of the human dopamine transporter gene. Wang, J., Bannon, M.J. J. Neurochem. (2005) [Pubmed]
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