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Protein

Sodium-dependent dopamine transporter

Gene

Slc6a3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi75 – 751Sodium 1; via carbonyl oxygenBy similarity
Metal bindingi77 – 771Sodium 2; via carbonyl oxygenBy similarity
Metal bindingi78 – 781Sodium 1; via carbonyl oxygenBy similarity
Metal bindingi82 – 821Sodium 2By similarity
Sitei105 – 1051Contributes to high-affinity binding to cocaineBy similarity
Metal bindingi320 – 3201Sodium 2By similarity
Metal bindingi352 – 3521Sodium 2By similarity
Metal bindingi417 – 4171Sodium 1; via carbonyl oxygenBy similarity
Metal bindingi420 – 4201Sodium 1By similarity
Metal bindingi421 – 4211Sodium 1By similarity

GO - Molecular functioni

  • dopamine:sodium symporter activity Source: RGD
  • dopamine binding Source: Ensembl
  • dopamine transmembrane transporter activity Source: RGD
  • drug binding Source: RGD
  • metal ion binding Source: UniProtKB-KW
  • protease binding Source: RGD
  • protein complex binding Source: RGD
  • protein phosphatase 2A binding Source: RGD
  • receptor binding Source: RGD

GO - Biological processi

  • adenohypophysis development Source: Ensembl
  • aging Source: RGD
  • dopamine biosynthetic process Source: Ensembl
  • dopamine catabolic process Source: Ensembl
  • dopamine transport Source: RGD
  • lactation Source: Ensembl
  • locomotory behavior Source: Ensembl
  • positive regulation of multicellular organism growth Source: Ensembl
  • prepulse inhibition Source: Ensembl
  • regulation of dopamine metabolic process Source: Ensembl
  • response to cAMP Source: RGD
  • response to cocaine Source: Ensembl
  • response to drug Source: RGD
  • response to ethanol Source: RGD
  • response to iron ion Source: RGD
  • response to nicotine Source: RGD
  • response to organic cyclic compound Source: RGD
  • sensory perception of smell Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Neurotransmitter transport, Symport, Transport

Keywords - Ligandi

Metal-binding, Sodium

Enzyme and pathway databases

ReactomeiR-RNO-379401. Dopamine clearance from the synaptic cleft.
R-RNO-442660. Na+/Cl- dependent neurotransmitter transporters.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium-dependent dopamine transporter
Short name:
DA transporter
Short name:
DAT
Alternative name(s):
Solute carrier family 6 member 3
Gene namesi
Name:Slc6a3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi3715. Slc6a3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6868CytoplasmicSequence analysisAdd
BLAST
Transmembranei69 – 8921Helical; Name=1Sequence analysisAdd
BLAST
Transmembranei96 – 11621Helical; Name=2Sequence analysisAdd
BLAST
Transmembranei140 – 16021Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini161 – 23676ExtracellularSequence analysisAdd
BLAST
Transmembranei237 – 25519Helical; Name=4Sequence analysisAdd
BLAST
Transmembranei264 – 28118Helical; Name=5Sequence analysisAdd
BLAST
Transmembranei317 – 33418Helical; Name=6Sequence analysisAdd
BLAST
Transmembranei346 – 36722Helical; Name=7Sequence analysisAdd
BLAST
Transmembranei400 – 41920Helical; Name=8Sequence analysisAdd
BLAST
Transmembranei446 – 46419Helical; Name=9Sequence analysisAdd
BLAST
Transmembranei480 – 50021Helical; Name=10Sequence analysisAdd
BLAST
Transmembranei521 – 54020Helical; Name=11Sequence analysisAdd
BLAST
Transmembranei559 – 57719Helical; Name=12Sequence analysisAdd
BLAST
Topological domaini578 – 61942CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • axon Source: Ensembl
  • cell surface Source: Ensembl
  • flotillin complex Source: Ensembl
  • integral component of plasma membrane Source: InterPro
  • neuronal cell body Source: Ensembl
  • neuron projection Source: RGD
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2094252.
GuidetoPHARMACOLOGYi927.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 619619Sodium-dependent dopamine transporterPRO_0000214754Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi180 ↔ 189By similarity
Glycosylationi181 – 1811N-linked (GlcNAc...)Sequence analysis
Glycosylationi188 – 1881N-linked (GlcNAc...)Sequence analysis
Glycosylationi196 – 1961N-linked (GlcNAc...)Sequence analysis
Glycosylationi204 – 2041N-linked (GlcNAc...)Sequence analysis
Disulfide bondi305 – 305InterchainBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP23977.

PTM databases

iPTMnetiP23977.
PhosphoSiteiP23977.

Expressioni

Gene expression databases

GenevisibleiP23977. RN.

Interactioni

Subunit structurei

Homooligomer; disulfide-linked (By similarity). Interacts with PRKCABP and TGFB1I1. Interacts (via N-terminus) with SYNGR3 (via N-terminus). Interacts with SLC18A2. Interacts with TOR1A (ATP-bound); TOR1A regulates SLC6A3 subcellular location (By similarity).By similarity

GO - Molecular functioni

  • protease binding Source: RGD
  • protein complex binding Source: RGD
  • protein phosphatase 2A binding Source: RGD
  • receptor binding Source: RGD

Protein-protein interaction databases

BioGridi247007. 5 interactions.
IntActiP23977. 1 interaction.
MINTiMINT-4589571.
STRINGi10116.ENSRNOP00000047272.

Chemistry

BindingDBiP23977.

Structurei

3D structure databases

ProteinModelPortaliP23977.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni560 – 58930Interaction with TGFB1I1By similarityAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3659. Eukaryota.
COG0733. LUCA.
GeneTreeiENSGT00760000118857.
HOGENOMiHOG000116406.
HOVERGENiHBG071421.
InParanoidiP23977.
KOiK05036.
OMAiYAAYKFC.
OrthoDBiEOG793B71.
PhylomeDBiP23977.
TreeFamiTF343812.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
IPR002436. Na/ntran_symport_dopamine.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 1 hit.
PfamiPF00209. SNF. 1 hit.
[Graphical view]
PRINTSiPR01202. DOPTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEiPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P23977-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSKSKCSVGP MSSVVAPAKE SNAVGPREVE LILVKEQNGV QLTNSTLINP
60 70 80 90 100
PQTPVEAQER ETWSKKIDFL LSVIGFAVDL ANVWRFPYLC YKNGGGAFLV
110 120 130 140 150
PYLLFMVIAG MPLFYMELAL GQFNREGAAG VWKICPVLKG VGFTVILISF
160 170 180 190 200
YVGFFYNVII AWALHYFFSS FTMDLPWIHC NNTWNSPNCS DAHASNSSDG
210 220 230 240 250
LGLNDTFGTT PAAEYFERGV LHLHQSRGID DLGPPRWQLT ACLVLVIVLL
260 270 280 290 300
YFSLWKGVKT SGKVVWITAT MPYVVLTALL LRGVTLPGAM DGIRAYLSVD
310 320 330 340 350
FYRLCEASVW IDAATQVCFS LGVGFGVLIA FSSYNKFTNN CYRDAIITTS
360 370 380 390 400
INSLTSFSSG FVVFSFLGYM AQKHNVPIRD VATDGPGLIF IIYPEAIATL
410 420 430 440 450
PLSSAWAAVF FLMLLTLGID SAMGGMESVI TGLVDEFQLL HRHRELFTLG
460 470 480 490 500
IVLATFLLSL FCVTNGGIYV FTLLDHFAAG TSILFGVLIE AIGVAWFYGV
510 520 530 540 550
QQFSDDIKQM TGQRPNLYWR LCWKLVSPCF LLYVVVVSIV TFRPPHYGAY
560 570 580 590 600
IFPDWANALG WIIATSSMAM VPIYATYKFC SLPGSFREKL AYAITPEKDH
610
QLVDRGEVRQ FTLRHWLLL
Length:619
Mass (Da):68,746
Last modified:March 1, 1992 - v1
Checksum:iDF3A30C981095D24
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti597 – 5971E → K in AAB21099 (PubMed:1765147).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M80233 mRNA. Translation: AAA41100.1.
M80570 mRNA. Translation: AAA73143.1.
S76145 mRNA. Translation: AAB21099.1.
PIRiI59558.
S20346.
RefSeqiNP_036826.1. NM_012694.2.
UniGeneiRn.10093.

Genome annotation databases

EnsembliENSRNOT00000040291; ENSRNOP00000047272; ENSRNOG00000017302.
ENSRNOT00000079987; ENSRNOP00000070728; ENSRNOG00000017302.
GeneIDi24898.
KEGGirno:24898.
UCSCiRGD:3715. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M80233 mRNA. Translation: AAA41100.1.
M80570 mRNA. Translation: AAA73143.1.
S76145 mRNA. Translation: AAB21099.1.
PIRiI59558.
S20346.
RefSeqiNP_036826.1. NM_012694.2.
UniGeneiRn.10093.

3D structure databases

ProteinModelPortaliP23977.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247007. 5 interactions.
IntActiP23977. 1 interaction.
MINTiMINT-4589571.
STRINGi10116.ENSRNOP00000047272.

Chemistry

BindingDBiP23977.
ChEMBLiCHEMBL2094252.
GuidetoPHARMACOLOGYi927.

PTM databases

iPTMnetiP23977.
PhosphoSiteiP23977.

Proteomic databases

PaxDbiP23977.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000040291; ENSRNOP00000047272; ENSRNOG00000017302.
ENSRNOT00000079987; ENSRNOP00000070728; ENSRNOG00000017302.
GeneIDi24898.
KEGGirno:24898.
UCSCiRGD:3715. rat.

Organism-specific databases

CTDi6531.
RGDi3715. Slc6a3.

Phylogenomic databases

eggNOGiKOG3659. Eukaryota.
COG0733. LUCA.
GeneTreeiENSGT00760000118857.
HOGENOMiHOG000116406.
HOVERGENiHBG071421.
InParanoidiP23977.
KOiK05036.
OMAiYAAYKFC.
OrthoDBiEOG793B71.
PhylomeDBiP23977.
TreeFamiTF343812.

Enzyme and pathway databases

ReactomeiR-RNO-379401. Dopamine clearance from the synaptic cleft.
R-RNO-442660. Na+/Cl- dependent neurotransmitter transporters.

Miscellaneous databases

NextBioi604786.
PROiP23977.

Gene expression databases

GenevisibleiP23977. RN.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
IPR002436. Na/ntran_symport_dopamine.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 1 hit.
PfamiPF00209. SNF. 1 hit.
[Graphical view]
PRINTSiPR01202. DOPTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEiPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Cloning and expression of a cocaine-sensitive rat dopamine transporter."
    Kilty J.E., Lorang D., Amara S.G.
    Science 254:578-579(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
  2. "Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA."
    Shimada S., Kitayama S., Lin C.-L., Patel A., Nanthakumar E., Gregor P., Kuhar M., Uhl G.
    Science 254:576-578(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
  3. "Cloning and functional characterization of a cocaine-sensitive dopamine transporter."
    Giros B., el Mestikawy S., Bertrand L., Caron M.G.
    FEBS Lett. 295:149-154(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
  4. "Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding."
    Kitayama S., Shimada S., Xu H., Markham L., Donovan D.M., Uhl G.
    Proc. Natl. Acad. Sci. U.S.A. 89:7782-7785(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS, FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiSC6A3_RAT
AccessioniPrimary (citable) accession number: P23977
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: May 11, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

This protein is the target of psychomotor stimulants such as amphetamines or cocaine.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.