SC6A3_MACFA
ID SC6A3_MACFA Reviewed; 620 AA.
AC Q9GJT6;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 89.
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; Synonyms=DAT1;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Substantia nigra;
RX PubMed=11223167; DOI=10.1016/s0169-328x(00)00288-6;
RA Miller G.M., Yatin S.M., De La Garza R. II, Goulet M., Madras B.K.;
RT "Cloning of dopamine, norepinephrine and serotonin transporters from monkey
RT brain: relevance to cocaine sensitivity.";
RL Brain Res. Mol. Brain Res. 87:124-143(2001).
CC -!- FUNCTION: Amine transporter (By similarity). Terminates the action of
CC dopamine by its high affinity sodium-dependent reuptake into
CC presynaptic terminals (By similarity). Regulator of light-dependent
CC retinal hyaloid vessel regression, downstream of OPN5 signaling (By
CC similarity). {ECO:0000250|UniProtKB:P23977,
CC ECO:0000250|UniProtKB:Q01959, ECO:0000250|UniProtKB:Q61327}.
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:0000250|UniProtKB:Q01959};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q7K4Y6}. Cell
CC projection, neuron projection {ECO:0000250|UniProtKB:P23977}. Cell
CC projection, axon {ECO:0000250|UniProtKB:Q01959}. Note=Localizes to
CC neurite tips in neuronal cells (By similarity). Colocalizes with
CC SEPTIN4 at axon terminals, especially at the varicosities (By
CC similarity). {ECO:0000250|UniProtKB:P23977,
CC ECO:0000250|UniProtKB:Q61327}.
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}.
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DR EMBL; AF286447; AAG00538.1; -; mRNA.
DR RefSeq; NP_001270253.1; NM_001283324.1.
DR AlphaFoldDB; Q9GJT6; -.
DR SMR; Q9GJT6; -.
DR STRING; 9541.XP_005556612.1; -.
DR BindingDB; Q9GJT6; -.
DR ChEMBL; CHEMBL5032; -.
DR DrugCentral; Q9GJT6; -.
DR PRIDE; Q9GJT6; -.
DR Ensembl; ENSMFAT00000009368; ENSMFAP00000035133; ENSMFAG00000003977.
DR GeneID; 102142756; -.
DR CTD; 6531; -.
DR VEuPathDB; HostDB:ENSMFAG00000003977; -.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000161224; -.
DR OMA; IFPEWAN; -.
DR OrthoDB; 250396at2759; -.
DR PRO; PR:Q9GJT6; -.
DR Proteomes; UP000233100; Chromosome 6.
DR GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0016600; C:flotillin complex; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0035240; F:dopamine binding; IEA:Ensembl.
DR GO; GO:0005330; F:dopamine:sodium symporter activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0021984; P:adenohypophysis development; IEA:Ensembl.
DR GO; GO:0042416; P:dopamine biosynthetic process; IEA:Ensembl.
DR GO; GO:0042420; P:dopamine catabolic process; IEA:Ensembl.
DR GO; GO:0015872; P:dopamine transport; ISS:UniProtKB.
DR GO; GO:1990384; P:hyaloid vascular plexus regression; ISS:UniProtKB.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0001504; P:neurotransmitter uptake; IEA:Ensembl.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0060134; P:prepulse inhibition; IEA:Ensembl.
DR GO; GO:0042053; P:regulation of dopamine metabolic process; IEA:Ensembl.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0007608; P:sensory perception of smell; IEA:Ensembl.
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..620
FT /note="Sodium-dependent dopamine transporter"
FT /id="PRO_0000214752"
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..237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..256
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..282
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..335
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 347..368
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 401..420
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 447..465
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 481..501
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 522..541
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 560..578
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 579..620
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 561..590
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 321
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 353
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 418
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 BINDING 422
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 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 180..189
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT DISULFID 306
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q01959"
SQ SEQUENCE 620 AA; 68452 MW; 5A9B9379DFEDF0FC CRC64;
MSKSKCSVGL MSSVVAPAKE PNAMGPKEVE LILVKEQNGV QLTSSTLTNP RQSPVEAQDR
ETWGKKIDFL LSVIGFAVDL ANVWRFPYLC YKNGGGAFLV PYLLFMVIAG MPLFYMELAL
GQFNREGAAG VWKICPVLKG VGFTVILISL YVGFFYNVII AWALHYLFSS FTTELPWIHC
NNSWNSPNCS DAHSGDSGGN GPGLNDTFGT TPAAEYFERG VLHLHQSHGI DDLGPPRWQL
TACLVLVIVL LYFSLWKGVK TSGKVVWITA TMPYVVLTAL LLRGVTLPGA IDGIRAYLSV
DFYRLCEASV WIDAATQVCF SLGVGFGVLI AFSSYNKFTN NCYRDAIVTT SINSLTSFSS
GFVVFSFLGY MAQKHSVPIG DVAKDGPGLI FIIYPEAIAT LPLSSAWAVV FFIMLLTLGI
DSAMGGMESV ITGLIDEFQL LHRHRELFTL FIVLATFLLS LFCVTNGGIY VFTLLDHFAA
GTSILFGVLI EAIGVAWFYG VGQFSDDIQQ MTGQRPSLYW RLCWKLVSPC FLLFVVVVSI
VTFRPPHYGA YIFPDWANAL GWVIATSSMA MVPIYAAYKF CSLPGSFREK LAYAIAPEKD
RELVDRGEVR QFTLRHWLKV
