Sodium-dependent dopamine transporter

Details

Name
Sodium-dependent dopamine transporter
Synonyms
  • DA transporter
  • DAT1
  • Solute carrier family 6 member 3
Gene Name
SLC6A3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010450|Sodium-dependent dopamine transporter
MSKSKCSVGLMSSVVAPAKEPNAVGPKEVELILVKEQNGVQLTSSTLTNPRQSPVEAQDR
ETWGKKIDFLLSVIGFAVDLANVWRFPYLCYKNGGGAFLVPYLLFMVIAGMPLFYMELAL
GQFNREGAAGVWKICPILKGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC
NNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAEYFERGVLHLHQSHGIDDLGPPRWQL
TACLVLVIVLLYFSLWKGVKTSGKVVWITATMPYVVLTALLLRGVTLPGAIDGIRAYLSV
DFYRLCEASVWIDAATQVCFSLGVGFGVLIAFSSYNKFTNNCYRDAIVTTSINSLTSFSS
GFVVFSFLGYMAQKHSVPIGDVAKDGPGLIFIIYPEAIATLPLSSAWAVVFFIMLLTLGI
DSAMGGMESVITGLIDEFQLLHRHRELFTLFIVLATFLLSLFCVTNGGIYVFTLLDHFAA
GTSILFGVLIEAIGVAWFYGVGQFSDDIQQMTGQRPSLYWRLCWKLVSPCFLLFVVVVSI
VTFRPPHYGAYIFPDWANALGWVIATSSMAMVPIYAAYKFCSLPGSFREKLAYAIAPEKD
RELVDRGEVRQFTLRHWLKV
Number of residues
620
Molecular Weight
68494.255
Theoretical pI
6.92
GO Classification
Functions
dopamine / dopamine binding / dopamine transmembrane transporter activity / monoamine transmembrane transporter activity
Processes
adenohypophysis development / ammonium transmembrane transport / dopamine biosynthetic process / dopamine catabolic process / dopamine transport / dopamine uptake involved in synaptic transmission / lactation / locomotory behavior / monoamine transport / neurotransmitter biosynthetic process / positive regulation of multicellular organism growth / prepulse inhibition / regulation of dopamine metabolic process / response to cocaine / sensory perception of smell / synaptic transmission / transmembrane transport
Components
axon / cell surface / cytoplasm / flotillin complex / integral component of membrane / integral component of plasma membrane / neuronal cell body / plasma membrane
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Pfam Domain Function
Transmembrane Regions
69-89 96-116 140-160 238-256 265-282 318-335 347-368 401-420 447-465 481-501 522-541 560-578
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010451|Sodium-dependent dopamine transporter (SLC6A3)
ATGAGTAAGAGCAAATGCTCCGTGGGACTCATGTCTTCCGTGGTGGCCCCGGCTAAGGAG
CCCAATGCCGTGGGCCCGAAGGAGGTGGAGCTCATCCTTGTCAAGGAGCAGAACGGAGTG
CAGCTCACCAGCTCCACCCTCACCAACCCGCGGCAGAGCCCCGTGGAGGCCCAGGATCGG
GAGACCTGGGGCAAGAAGATCGACTTTCTCCTGTCCGTCATTGGCTTTGCTGTGGACCTG
GCCAACGTCTGGCGGTTCCCCTACCTGTGCTACAAAAATGGTGGCGGTGCCTTCCTGGTC
CCCTACCTGCTCTTCATGGTCATTGCTGGGATGCCACTTTTCTACATGGAGCTGGCCCTC
GGCCAGTTCAACAGGGAAGGGGCCGCTGGTGTCTGGAAGATCTGCCCCATACTGAAAGGT
GTGGGCTTCACGGTCATCCTCATCTCACTGTATGTCGGCTTCTTCTACAACGTCATCATC
GCCTGGGCGCTGCACTATCTCTTCTCCTCCTTCACCACGGAGCTCCCCTGGATCCACTGC
AACAACTCCTGGAACAGCCCCAACTGCTCGGATGCCCATCCTGGTGACTCCAGTGGAGAC
AGCTCGGGCCTCAACGACACTTTTGGGACCACACCTGCTGCCGAGTACTTTGAACGTGGC
GTGCTGCACCTCCACCAGAGCCATGGCATCGACGACCTGGGGCCTCCGCGGTGGCAGCTC
ACAGCCTGCCTGGTGCTGGTCATCGTGCTGCTCTACTTCAGCCTCTGGAAGGGCGTGAAG
ACCTCAGGGAAGGTGGTATGGATCACAGCCACCATGCCATACGTGGTCCTCACTGCCCTG
CTCCTGCGTGGGGTCACCCTCCCTGGAGCCATAGACGGCATCAGAGCATACCTGAGCGTT
GACTTCTACCGGCTCTGCGAGGCGTCTGTTTGGATTGACGCGGCCACCCAGGTGTGCTTC
TCCCTGGGCGTGGGGTTCGGGGTGCTGATCGCCTTCTCCAGCTACAACAAGTTCACCAAC
AACTGCTACAGGGACGCGATTGTCACCACCTCCATCAACTCCCTGACGAGCTTCTCCTCC
GGCTTCGTCGTCTTCTCCTTCCTGGGGTACATGGCACAGAAGCACAGTGTGCCCATCGGG
GACGTGGCCAAGGACGGGCCAGGGCTGATCTTCATCATCTACCCGGAAGCCATCGCCACG
CTCCCTCTGTCCTCAGCCTGGGCCGTGGTCTTCTTCATCATGCTGCTCACCCTGGGTATC
GACAGCGCCATGGGTGGTATGGAGTCAGTGATCACCGGGCTCATCGATGAGTTCCAGCTG
CTGCACAGACACCGTGAGCTCTTCACGCTCTTCATCGTCCTGGCGACCTTCCTCCTGTCC
CTGTTCTGCGTCACCAACGGTGGCATCTACGTCTTCACGCTCCTGGACCATTTTGCAGCC
GGCACGTCCATCCTCTTTGGAGTGCTCATCGAAGCCATCGGAGTGGCCTGGTTCTATGGT
GTTGGGCAGTTCAGCGACGACATCCAGCAGATGACCGGGCAGCGGCCCAGCCTGTACTGG
CGGCTGTGCTGGAAGCTGGTCAGCCCCTGCTTTCTCCTGTTCGTGGTCGTGGTCAGCATT
GTGACCTTCAGACCCCCCCACTACGGAGCCTACATCTTCCCCGACTGGGCCAACGCGCTG
GGCTGGGTCATCGCCACATCCTCCATGGCCATGGTGCCCATCTATGCGGCCTACAAGTTC
TGCAGCCTGCCTGGGTCCTTTCGAGAGAAACTGGCCTACGCCATTGCACCCGAGAAGGAC
CGTGAGCTGGTGGACAGAGGGGAGGTGCGCCAGTTCACGCTCCGCCACTGGCTCAAGGTG
TAG
Chromosome Location
5
Locus
5p15.3
External Identifiers
ResourceLink
UniProtKB IDQ01959
UniProtKB Entry NameSC6A3_HUMAN
GenBank Protein ID553260
GenBank Gene IDM96670
GenAtlas IDSLC6A3
HGNC IDHGNC:11049
General References
  1. Vandenbergh DJ, Persico AM, Uhl GR: A human dopamine transporter cDNA predicts reduced glycosylation, displays a novel repetitive element and provides racially-dimorphic TaqI RFLPs. Brain Res Mol Brain Res. 1992 Sep;15(1-2):161-6. [PubMed:1359373]
  2. Giros B, el Mestikawy S, Godinot N, Zheng K, Han H, Yang-Feng T, Caron MG: Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. Mol Pharmacol. 1992 Sep;42(3):383-90. [PubMed:1406597]
  3. Pristupa ZB, Wilson JM, Hoffman BJ, Kish SJ, Niznik HB: Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding. Mol Pharmacol. 1994 Jan;45(1):125-35. [PubMed:8302271]
  4. Kawarai T, Kawakami H, Yamamura Y, Nakamura S: Structure and organization of the gene encoding human dopamine transporter. Gene. 1997 Aug 11;195(1):11-8. [PubMed:9300814]
  5. Vandenbergh DJ, Thompson MD, Cook EH, Bendahhou E, Nguyen T, Krasowski MD, Zarrabian D, Comings D, Sellers EM, Tyndale RF, George SR, O'Dowd BF, Uhl GR: Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations. Mol Psychiatry. 2000 May;5(3):283-92. [PubMed:10889531]
  6. Greenwood TA, Alexander M, Keck PE, McElroy S, Sadovnick AD, Remick RA, Kelsoe JR: Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder. Am J Med Genet. 2001 Mar 8;105(2):145-51. [PubMed:11304827]
  7. Miller-Butterworth CM, Kaplan JR, Shaffer J, Devlin B, Manuck SB, Ferrell RE: Sequence variation in the primate dopamine transporter gene and its relationship to social dominance. Mol Biol Evol. 2008 Jan;25(1):18-28. Epub 2007 Oct 13. [PubMed:17934207]
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  9. Donovan DM, Vandenbergh DJ, Perry MP, Bird GS, Ingersoll R, Nanthakumar E, Uhl GR: Human and mouse dopamine transporter genes: conservation of 5'-flanking sequence elements and gene structures. Brain Res Mol Brain Res. 1995 Jun;30(2):327-35. [PubMed:7637582]
  10. Bannon MJ, Poosch MS, Xia Y, Goebel DJ, Cassin B, Kapatos G: Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7095-9. [PubMed:1353885]
  11. Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, Staudinger J, Caron MG: Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron. 2001 Apr;30(1):121-34. [PubMed:11343649]
  12. Carneiro AM, Ingram SL, Beaulieu JM, Sweeney A, Amara SG, Thomas SM, Caron MG, Torres GE: The multiple LIM domain-containing adaptor protein Hic-5 synaptically colocalizes and interacts with the dopamine transporter. J Neurosci. 2002 Aug 15;22(16):7045-54. [PubMed:12177201]
  13. Torres GE, Sweeney AL, Beaulieu JM, Shashidharan P, Caron MG: Effect of torsinA on membrane proteins reveals a loss of function and a dominant-negative phenotype of the dystonia-associated DeltaE-torsinA mutant. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15650-5. Epub 2004 Oct 25. [PubMed:15505207]
  14. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed:10391209]
  15. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974]
  16. Kurian MA, Zhen J, Cheng SY, Li Y, Mordekar SR, Jardine P, Morgan NV, Meyer E, Tee L, Pasha S, Wassmer E, Heales SJ, Gissen P, Reith ME, Maher ER: Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia. J Clin Invest. 2009 Jun;119(6):1595-603. doi: 10.1172/JCI39060. Epub 2009 May 26. [PubMed:19478460]
  17. Bevilacqua L, Doly S, Kaprio J, Yuan Q, Tikkanen R, Paunio T, Zhou Z, Wedenoja J, Maroteaux L, Diaz S, Belmer A, Hodgkinson CA, Dell'osso L, Suvisaari J, Coccaro E, Rose RJ, Peltonen L, Virkkunen M, Goldman D: A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature. 2010 Dec 23;468(7327):1061-6. doi: 10.1038/nature09629. [PubMed:21179162]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00422Methylphenidateapproved, investigationalyesinhibitorDetails
DB00745Modafinilapproved, investigationalyesinhibitorDetails
DB01156BupropionapprovedyesinhibitorDetails
DB00191Phentermineapproved, illicityesinhibitorDetails
DB00476DuloxetineapprovedunknowninhibitorDetails
DB00579Mazindolapproved, investigationalyesinhibitorDetails
DB00721Procaineapproved, investigational, vet_approvedyesinhibitorDetails
DB00830Phenmetrazineapproved, illicityesinhibitorDetails
DB00907Cocaineapproved, illicityesinhibitorDetails
DB00937Diethylpropionapproved, illicityesinhibitorDetails
DB01161ChloroprocaineapprovedunknowninhibitorDetails
DB00182Amphetamineapproved, illicit, investigationalyesnegative modulatorDetails
DB00245BenzatropineapprovedyesinhibitorDetails
DB01463Fencamfaminexperimental, illicit, withdrawnyesinhibitorDetails
DB04947AltropaneinvestigationalunknownDetails
DB01576Dextroamphetamineapproved, illicityesnegative modulatorDetails
DB12305DasotralineinvestigationalunknownDetails
DB06156TesofensineinvestigationalunknownDetails
DB06333TrodusquemineinvestigationalunknownDetails
DB01149Nefazodoneapproved, withdrawnunknowninhibitorDetails
DB04821Nomifensineapproved, withdrawnunknownDetails
DB01104SertralineapprovedunknowninhibitorDetails
DB01146Diphenylpyralineapproved, investigationalunknowninhibitorDetails
DB01175EscitalopramapprovednoinhibitorDetails
DB00726TrimipramineapprovedunknowninhibitorDetails
DB01114ChlorpheniramineapprovedunknowninhibitorDetails
DB01105Sibutramineapproved, illicit, investigational, withdrawnyesinhibitorDetails
DB00285VenlafaxineapprovedunknowninhibitorDetails
DB00988DopamineapprovedyesinducerDetails
DB00865Benzphetamineapproved, illicitunknowninhibitorDetails
DB06701Dexmethylphenidateapproved, investigationalyesinhibitorDetails
DB01454Midomafetamineexperimental, illicit, investigationalunknownnegative modulatorDetails
DB00852PseudoephedrineapprovedyesinhibitorDetails
DB014724-Methoxyamphetamineexperimental, illicityesinhibitorDetails
DB01577Metamfetamineapproved, illicityesnegative modulatorDetails
DB01363Ephedra sinica rootnutraceuticalyesnegative modulatorDetails
DB01442MMDAexperimental, illicityesnegative modulatorDetails
DB01454Midomafetamineexperimental, illicit, investigationalunknownDetails
DB08824Ioflupane I-123approvednoDetails
DB00408LoxapineapprovedunknownbinderDetails
DB00458ImipramineapprovedunknowninhibitorDetails
DB00454MeperidineapprovedunknowninhibitorDetails
DB00543AmoxapineapprovedunknownbinderDetails
DB06148Mianserinapproved, investigationalunknownbinderDetails
DB06413Armodafinilapproved, investigationalyesantagonistinhibitorDetails
DB03701VanoxerineinvestigationalunknownDetails
DB09194EtoperidonewithdrawnunknowninhibitorDetails
DB14754SolriamfetolapprovedunknownDetails
DB01576Dextroamphetamineapproved, illicitunknownDetails
DB06700Desvenlafaxineapproved, investigationalunknowninhibitorDetails