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Sodium-dependent dopamine transporter (DA transporter) (DAT) (Solute carrier family 6 member 3)

 SC6A3_RAT               Reviewed;         619 AA.
P23977;
01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
01-MAR-1992, sequence version 1.
30-AUG-2017, entry version 134.
RecName: Full=Sodium-dependent dopamine transporter;
Short=DA transporter;
Short=DAT;
AltName: Full=Solute carrier family 6 member 3;
Name=Slc6a3;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=1948035; DOI=10.1126/science.1948035;
Kilty J.E., Lorang D., Amara S.G.;
"Cloning and expression of a cocaine-sensitive rat dopamine
transporter.";
Science 254:578-579(1991).
[2]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=1948034; DOI=10.1126/science.1948034;
Shimada S., Kitayama S., Lin C.-L., Patel A., Nanthakumar E.,
Gregor P., Kuhar M., Uhl G.;
"Cloning and expression of a cocaine-sensitive dopamine transporter
complementary DNA.";
Science 254:576-578(1991).
[3]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=1765147; DOI=10.1016/0014-5793(91)81406-X;
Giros B., el Mestikawy S., Bertrand L., Caron M.G.;
"Cloning and functional characterization of a cocaine-sensitive
dopamine transporter.";
FEBS Lett. 295:149-154(1991).
[4]
MUTAGENESIS, FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=1502198; DOI=10.1073/pnas.89.16.7782;
Kitayama S., Shimada S., Xu H., Markham L., Donovan D.M., Uhl G.;
"Dopamine transporter site-directed mutations differentially alter
substrate transport and cocaine binding.";
Proc. Natl. Acad. Sci. U.S.A. 89:7782-7785(1992).
-!- FUNCTION: Amine transporter. Terminates the action of dopamine by
its high affinity sodium-dependent reuptake into presynaptic
terminals. {ECO:0000269|PubMed:1502198,
ECO:0000269|PubMed:1765147, ECO:0000269|PubMed:1948034,
ECO:0000269|PubMed:1948035}.
-!- SUBUNIT: 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). {ECO:0000250|UniProtKB:Q01959,
ECO:0000250|UniProtKB:Q61327}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1502198,
ECO:0000269|PubMed:1765147, ECO:0000269|PubMed:1948034,
ECO:0000269|PubMed:1948035}; Multi-pass membrane protein
{ECO:0000250|UniProtKB:Q7K4Y6}.
-!- MISCELLANEOUS: This protein is the target of psychomotor
stimulants such as amphetamines or cocaine.
-!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF)
(TC 2.A.22) family. SLC6A3 subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
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EMBL; M80233; AAA41100.1; -; mRNA.
EMBL; M80570; AAA73143.1; -; mRNA.
EMBL; S76145; AAB21099.1; -; mRNA.
PIR; I59558; I59558.
PIR; S20346; S20346.
RefSeq; NP_036826.1; NM_012694.2.
UniGene; Rn.10093; -.
ProteinModelPortal; P23977; -.
SMR; P23977; -.
BioGrid; 247007; 5.
IntAct; P23977; 2.
MINT; MINT-4589571; -.
STRING; 10116.ENSRNOP00000047272; -.
BindingDB; P23977; -.
ChEMBL; CHEMBL338; -.
GuidetoPHARMACOLOGY; 927; -.
iPTMnet; P23977; -.
PhosphoSitePlus; P23977; -.
PaxDb; P23977; -.
Ensembl; ENSRNOT00000040291; ENSRNOP00000047272; ENSRNOG00000017302.
Ensembl; ENSRNOT00000079987; ENSRNOP00000070728; ENSRNOG00000017302.
GeneID; 24898; -.
KEGG; rno:24898; -.
UCSC; RGD:3715; rat.
CTD; 6531; -.
RGD; 3715; Slc6a3.
eggNOG; KOG3659; Eukaryota.
eggNOG; COG0733; LUCA.
GeneTree; ENSGT00760000118857; -.
HOGENOM; HOG000116406; -.
HOVERGEN; HBG071421; -.
InParanoid; P23977; -.
KO; K05036; -.
OMA; YAAYKFC; -.
OrthoDB; EOG091G08PX; -.
PhylomeDB; P23977; -.
TreeFam; TF343812; -.
Reactome; R-RNO-379401; Dopamine clearance from the synaptic cleft.
Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
PRO; PR:P23977; -.
Proteomes; UP000002494; Chromosome 1.
Bgee; ENSRNOG00000017302; -.
Genevisible; P23977; RN.
GO; GO:0030424; C:axon; IEA:Ensembl.
GO; GO:0009986; C:cell surface; IEA:Ensembl.
GO; GO:0016600; C:flotillin complex; IEA:Ensembl.
GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
GO; GO:0043005; C:neuron projection; IDA:RGD.
GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO; GO:0098793; C:presynapse; IEA:GOC.
GO; GO:0035240; F:dopamine binding; IEA:Ensembl.
GO; GO:0005329; F:dopamine transmembrane transporter activity; IDA:RGD.
GO; GO:0005330; F:dopamine:sodium symporter activity; IDA:RGD.
GO; GO:0008144; F:drug binding; IDA:RGD.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0002020; F:protease binding; IPI:RGD.
GO; GO:0032403; F:protein complex binding; IDA:RGD.
GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
GO; GO:0051721; F:protein phosphatase 2A binding; IPI:RGD.
GO; GO:0005102; F:receptor binding; IPI:RGD.
GO; GO:0021984; P:adenohypophysis development; IEA:Ensembl.
GO; GO:0007568; P:aging; IEP:RGD.
GO; GO:0042416; P:dopamine biosynthetic process; IEA:Ensembl.
GO; GO:0042420; P:dopamine catabolic process; IEA:Ensembl.
GO; GO:0015872; P:dopamine transport; IDA:RGD.
GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IBA:GO_Central.
GO; GO:0007595; P:lactation; IEA:Ensembl.
GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
GO; GO:0060134; P:prepulse inhibition; IEA:Ensembl.
GO; GO:0042053; P:regulation of dopamine metabolic process; IEA:Ensembl.
GO; GO:0051591; P:response to cAMP; IDA:RGD.
GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
GO; GO:0042493; P:response to drug; IEP:RGD.
GO; GO:0045471; P:response to ethanol; IDA:RGD.
GO; GO:0010039; P:response to iron ion; IEP:RGD.
GO; GO:0035094; P:response to nicotine; IEP:RGD.
GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
GO; GO:0007608; P:sensory perception of smell; IEA:Ensembl.
InterPro; IPR000175; Na/ntran_symport.
InterPro; IPR002436; Na/ntran_symport_dopamine.
PANTHER; PTHR11616; PTHR11616; 1.
Pfam; PF00209; SNF; 1.
PRINTS; PR01202; DOPTRANSPORT.
PRINTS; PR00176; NANEUSMPORT.
PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
2: Evidence at transcript level;
Cell membrane; Complete proteome; Disulfide bond; Glycoprotein;
Membrane; Metal-binding; Neurotransmitter transport;
Reference proteome; Sodium; Symport; Transmembrane;
Transmembrane helix; Transport.
CHAIN 1 619 Sodium-dependent dopamine transporter.
/FTId=PRO_0000214754.
TOPO_DOM 1 68 Cytoplasmic. {ECO:0000255}.
TRANSMEM 69 89 Helical; Name=1. {ECO:0000255}.
TRANSMEM 96 116 Helical; Name=2. {ECO:0000255}.
TRANSMEM 140 160 Helical; Name=3. {ECO:0000255}.
TOPO_DOM 161 236 Extracellular. {ECO:0000255}.
TRANSMEM 237 255 Helical; Name=4. {ECO:0000255}.
TRANSMEM 264 281 Helical; Name=5. {ECO:0000255}.
TRANSMEM 317 334 Helical; Name=6. {ECO:0000255}.
TRANSMEM 346 367 Helical; Name=7. {ECO:0000255}.
TRANSMEM 400 419 Helical; Name=8. {ECO:0000255}.
TRANSMEM 446 464 Helical; Name=9. {ECO:0000255}.
TRANSMEM 480 500 Helical; Name=10. {ECO:0000255}.
TRANSMEM 521 540 Helical; Name=11. {ECO:0000255}.
TRANSMEM 559 577 Helical; Name=12. {ECO:0000255}.
TOPO_DOM 578 619 Cytoplasmic. {ECO:0000255}.
REGION 560 589 Interaction with TGFB1I1. {ECO:0000250}.
METAL 75 75 Sodium 1; via carbonyl oxygen.
{ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 77 77 Sodium 2; via carbonyl oxygen.
{ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 78 78 Sodium 1; via carbonyl oxygen.
{ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 82 82 Sodium 2. {ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 320 320 Sodium 2. {ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 352 352 Sodium 2. {ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 417 417 Sodium 1; via carbonyl oxygen.
{ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 420 420 Sodium 1. {ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 421 421 Sodium 1. {ECO:0000250|UniProtKB:Q7K4Y6}.
SITE 105 105 Contributes to high-affinity binding to
cocaine. {ECO:0000250|UniProtKB:Q61327}.
CARBOHYD 181 181 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 188 188 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 196 196 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 204 204 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 180 189 {ECO:0000250|UniProtKB:Q7K4Y6}.
DISULFID 305 305 Interchain.
{ECO:0000250|UniProtKB:Q01959}.
CONFLICT 597 597 E -> K (in Ref. 3; AAB21099).
{ECO:0000305}.
SEQUENCE 619 AA; 68746 MW; DF3A30C981095D24 CRC64;
MSKSKCSVGP MSSVVAPAKE SNAVGPREVE LILVKEQNGV QLTNSTLINP PQTPVEAQER
ETWSKKIDFL LSVIGFAVDL ANVWRFPYLC YKNGGGAFLV PYLLFMVIAG MPLFYMELAL
GQFNREGAAG VWKICPVLKG VGFTVILISF YVGFFYNVII AWALHYFFSS FTMDLPWIHC
NNTWNSPNCS DAHASNSSDG LGLNDTFGTT PAAEYFERGV LHLHQSRGID DLGPPRWQLT
ACLVLVIVLL YFSLWKGVKT SGKVVWITAT MPYVVLTALL LRGVTLPGAM DGIRAYLSVD
FYRLCEASVW IDAATQVCFS LGVGFGVLIA FSSYNKFTNN CYRDAIITTS INSLTSFSSG
FVVFSFLGYM AQKHNVPIRD VATDGPGLIF IIYPEAIATL PLSSAWAAVF FLMLLTLGID
SAMGGMESVI TGLVDEFQLL HRHRELFTLG IVLATFLLSL FCVTNGGIYV FTLLDHFAAG
TSILFGVLIE AIGVAWFYGV QQFSDDIKQM TGQRPNLYWR LCWKLVSPCF LLYVVVVSIV
TFRPPHYGAY IFPDWANALG WIIATSSMAM VPIYATYKFC SLPGSFREKL AYAITPEKDH
QLVDRGEVRQ FTLRHWLLL


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