SC6A3_RAT
ID SC6A3_RAT Reviewed; 619 AA.
AC P23977;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Sodium-dependent dopamine transporter;
DE Short=DA transporter;
DE Short=DAT;
DE AltName: Full=Solute carrier family 6 member 3;
GN Name=Slc6a3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1948035; DOI=10.1126/science.1948035;
RA Kilty J.E., Lorang D., Amara S.G.;
RT "Cloning and expression of a cocaine-sensitive rat dopamine transporter.";
RL Science 254:578-579(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1948034; DOI=10.1126/science.1948034;
RA Shimada S., Kitayama S., Lin C.-L., Patel A., Nanthakumar E., Gregor P.,
RA Kuhar M., Uhl G.;
RT "Cloning and expression of a cocaine-sensitive dopamine transporter
RT complementary DNA.";
RL Science 254:576-578(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1765147; DOI=10.1016/0014-5793(91)81406-x;
RA Giros B., el Mestikawy S., Bertrand L., Caron M.G.;
RT "Cloning and functional characterization of a cocaine-sensitive dopamine
RT transporter.";
RL FEBS Lett. 295:149-154(1991).
RN [4]
RP MUTAGENESIS, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1502198; DOI=10.1073/pnas.89.16.7782;
RA Kitayama S., Shimada S., Xu H., Markham L., Donovan D.M., Uhl G.;
RT "Dopamine transporter site-directed mutations differentially alter
RT substrate transport and cocaine binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7782-7785(1992).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=32963038; DOI=10.1194/jlr.ra120001087;
RA Kuge H., Miyamoto I., Yagyu K.I., Honke K.;
RT "PLRP2 selectively localizes synaptic membrane proteins via acyl-chain
RT remodeling of phospholipids.";
RL J. Lipid Res. 61:1747-1763(2020).
CC -!- FUNCTION: Amine transporter (PubMed:1948035, PubMed:1948034,
CC PubMed:1765147, PubMed:1502198). Terminates the action of dopamine by
CC its high affinity sodium-dependent reuptake into presynaptic terminals
CC (Probable) (PubMed:1765147). Regulator of light-dependent retinal
CC hyaloid vessel regression, downstream of OPN5 signaling (By
CC similarity). {ECO:0000250|UniProtKB:Q61327, ECO:0000269|PubMed:1502198,
CC ECO:0000269|PubMed:1765147, ECO:0000269|PubMed:1948034,
CC ECO:0000269|PubMed:1948035, ECO:0000305}.
CC -!- SUBUNIT: Homooligomer; disulfide-linked (By similarity). Interacts with
CC PRKCABP and TGFB1I1 (By similarity). Interacts (via N-terminus) with
CC SYNGR3 (via N-terminus) (By similarity). Interacts with SLC18A2 (By
CC similarity). Interacts with TOR1A (ATP-bound); TOR1A regulates SLC6A3
CC subcellular location (By similarity). Interacts with alpha-
CC synuclein/SNCA (By similarity). Interacts with SEPTIN4 (By similarity).
CC {ECO:0000250|UniProtKB:Q01959, ECO:0000250|UniProtKB:Q61327}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1502198,
CC ECO:0000269|PubMed:1765147, ECO:0000269|PubMed:1948034,
CC ECO:0000269|PubMed:1948035}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7K4Y6}. Cell projection, neuron projection
CC {ECO:0000269|PubMed:32963038}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q01959}. Note=Localizes to neurite tips in
CC neuronal cells (PubMed:32963038). Colocalizes with SEPTIN4 at axon
CC terminals, especially at the varicosities (By similarity).
CC {ECO:0000250|UniProtKB:Q61327, ECO:0000269|PubMed:32963038}.
CC -!- MISCELLANEOUS: This protein is the target of psychomotor stimulants
CC such as amphetamines or cocaine.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A3 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M80233; AAA41100.1; -; mRNA.
DR EMBL; M80570; AAA73143.1; -; mRNA.
DR EMBL; S76145; AAB21099.1; -; mRNA.
DR PIR; I59558; I59558.
DR PIR; S20346; S20346.
DR RefSeq; NP_036826.1; NM_012694.2.
DR AlphaFoldDB; P23977; -.
DR SMR; P23977; -.
DR BioGRID; 247007; 5.
DR IntAct; P23977; 3.
DR MINT; P23977; -.
DR STRING; 10116.ENSRNOP00000047272; -.
DR BindingDB; P23977; -.
DR ChEMBL; CHEMBL338; -.
DR DrugCentral; P23977; -.
DR GuidetoPHARMACOLOGY; 927; -.
DR GlyGen; P23977; 4 sites.
DR iPTMnet; P23977; -.
DR PhosphoSitePlus; P23977; -.
DR SwissPalm; P23977; -.
DR PaxDb; P23977; -.
DR PRIDE; P23977; -.
DR Ensembl; ENSRNOT00000040291; ENSRNOP00000047272; ENSRNOG00000017302.
DR GeneID; 24898; -.
DR KEGG; rno:24898; -.
DR UCSC; RGD:3715; rat.
DR CTD; 6531; -.
DR RGD; 3715; Slc6a3.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000161224; -.
DR InParanoid; P23977; -.
DR OMA; IFPEWAN; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P23977; -.
DR TreeFam; TF343812; -.
DR Reactome; R-RNO-379401; Dopamine clearance from the synaptic cleft.
DR Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
DR PRO; PR:P23977; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000017302; Expressed in thymus and 1 other tissue.
DR Genevisible; P23977; RN.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0043679; C:axon terminus; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0098691; C:dopaminergic synapse; IDA:SynGO.
DR GO; GO:0016600; C:flotillin complex; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0032809; C:neuronal cell body membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central.
DR GO; GO:0043176; F:amine binding; IDA:RGD.
DR GO; GO:0035240; F:dopamine binding; ISO:RGD.
DR GO; GO:0005330; F:dopamine:sodium symporter activity; IDA:RGD.
DR GO; GO:1901363; F:heterocyclic compound binding; IPI:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008504; F:monoamine transmembrane transporter activity; ISO:RGD.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; ISO:RGD.
DR GO; GO:0005334; F:norepinephrine:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IPI:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IPI:RGD.
DR GO; GO:0021984; P:adenohypophysis development; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0042416; P:dopamine biosynthetic process; ISO:RGD.
DR GO; GO:0042420; P:dopamine catabolic process; ISO:RGD.
DR GO; GO:0015872; P:dopamine transport; IDA:RGD.
DR GO; GO:0090494; P:dopamine uptake; ISO:RGD.
DR GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IBA:GO_Central.
DR GO; GO:1990384; P:hyaloid vascular plexus regression; ISS:UniProtKB.
DR GO; GO:0007595; P:lactation; ISO:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0015844; P:monoamine transport; ISO:RGD.
DR GO; GO:0006836; P:neurotransmitter transport; ISO:RGD.
DR GO; GO:0001504; P:neurotransmitter uptake; ISO:RGD.
DR GO; GO:0015874; P:norepinephrine transport; IBA:GO_Central.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0060134; P:prepulse inhibition; ISO:RGD.
DR GO; GO:0042053; P:regulation of dopamine metabolic process; ISO:RGD.
DR GO; GO:0051591; P:response to cAMP; IDA:RGD.
DR GO; GO:0042220; P:response to cocaine; ISO:RGD.
DR GO; GO:0045471; P:response to ethanol; IDA:RGD.
DR GO; GO:0010039; P:response to iron ion; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007608; P:sensory perception of smell; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002436; Na/ntran_symport_dopamine.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01202; DOPTRANSPORT.
DR PRINTS; PR00176; NANEUSMPORT.
DR SUPFAM; SSF161070; SSF161070; 1.
DR PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
DR PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
DR PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Disulfide bond; Glycoprotein; Membrane;
KW Metal-binding; Neurotransmitter transport; Reference proteome; Sodium;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..619
FT /note="Sodium-dependent dopamine transporter"
FT /id="PRO_0000214754"
FT TOPO_DOM 1..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..116
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..236
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..255
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..281
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 317..334
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 346..367
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 400..419
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..464
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..500
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 521..540
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 559..577
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 578..619
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 560..589
FT /note="Interaction with TGFB1I1"
FT /evidence="ECO:0000250"
FT BINDING 75
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 77
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 78
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 82
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 320
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 352
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 417
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 420
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 421
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT SITE 105
FT /note="Contributes to high-affinity binding to cocaine"
FT /evidence="ECO:0000250|UniProtKB:Q61327"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 180..189
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT DISULFID 305
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q01959"
FT CONFLICT 597
FT /note="E -> K (in Ref. 3; AAB21099)"
FT /evidence="ECO:0000305"
SQ 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
