SC6A3_BOVIN
ID SC6A3_BOVIN Reviewed; 693 AA.
AC P27922;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 117.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=1722321; DOI=10.1073/pnas.88.24.11168;
RA Usdin T.B., Mezey E., Chen C., Brownstein M.J., Hoffman B.J.;
RT "Cloning of the cocaine-sensitive bovine dopamine transporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:11168-11171(1991).
CC -!- FUNCTION: Amine transporter (PubMed:1722321). 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:Q61327, ECO:0000269|PubMed:1722321}.
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:1722321};
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 -!- TISSUE SPECIFICITY: Expressed in the neurons of the substantia nigra of
CC the brain. {ECO:0000269|PubMed:1722321}.
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; M80234; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A41617; A41617.
DR AlphaFoldDB; P27922; -.
DR SMR; P27922; -.
DR STRING; 9913.ENSBTAP00000021061; -.
DR BindingDB; P27922; -.
DR ChEMBL; CHEMBL2986; -.
DR DrugCentral; P27922; -.
DR PRIDE; P27922; -.
DR InParanoid; P27922; -.
DR OrthoDB; 250396at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0032809; C:neuronal cell body membrane; IBA:GO_Central.
DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central.
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:0005334; F:norepinephrine:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0015872; P:dopamine transport; ISS:UniProtKB.
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:0015874; P:norepinephrine transport; IBA:GO_Central.
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..693
FT /note="Sodium-dependent dopamine transporter"
FT /id="PRO_0000214750"
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 97..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..234
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 235..253
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..279
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 315..332
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 344..365
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 398..417
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 444..462
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..498
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 519..538
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 557..575
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 576..693
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 558..587
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 318
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 350
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 415
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
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 419
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 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 180..189
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT DISULFID 303
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q01959"
SQ SEQUENCE 693 AA; 75691 MW; 0023A6F6D0698660 CRC64;
MSEGRCSVAH MSSVVAPAKE ANAMGPKAVE LVLVKEQNGV QLTNSTLLNP PQSPTEAQDR
ETWSKKADFL LSVIGFAVDL ANVWRFPYLC YKNGGGAFLV PYLFFMVVAG VPLFYMELAL
GQFNREGAAG VWKICPILRG VGYTAILISL YIGFFYNVII AWALHYLLSS FTTELPWTHC
NHSWNSPRCS DARAPNASSG PNGTSRTTPA AEYFERGVLH LHESQGIDDL GPPRWQLTSC
LVLVIVLLYF SLWKGVKTSG KVVWITATMP YVVLFALLLR GITLPGAVDA IRAYLSVDFH
RLCEASVWID AAIQICFSLG VGLGVLIAFS SYNKFTNNCY RDAIITTSVN SLTSFSSGFV
VFSFLGYMAQ KHSVPIGDVA KDGPGLIFII YPEALATLPL SSVWAVVFFV MLLTLGIDSA
MGGMESVITG LADEFQLLHR HRELFTLLVV LATFLLSLFC VTNGGIYVFT LLDHFAAGTS
ILFGVLMEVI GVAWFYGVWQ FSDDIKQMTG RRPSLYWRLC WKFVSPCFLL FVVVVSIATF
RPPHYGAYVF PEWATALGWA IAASSMSVVP IYAAYKLCSL PGSSREKLAY AITPETEHGR
VDSGGGAPVH APPLARGVGR WRKRKSCWVP SRGPGRGGPP TPSPRLAGHT RAFPWTGAPP
VPRELTPPST CRCVPPLVCA HPAVESTGLC SVY
