DAT_DROME
ID DAT_DROME Reviewed; 631 AA.
AC Q7K4Y6; Q9NB97;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Sodium-dependent dopamine transporter {ECO:0000303|PubMed:11125028};
DE AltName: Full=Protein fumin {ECO:0000303|PubMed:16093388};
GN Name=DAT {ECO:0000312|FlyBase:FBgn0034136};
GN Synonyms=fmn {ECO:0000303|PubMed:16093388};
GN ORFNames=CG8380 {ECO:0000312|FlyBase:FBgn0034136};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|EMBL:AAK93003.1};
RN [1] {ECO:0000312|EMBL:AAF76882.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Head {ECO:0000312|EMBL:AAF76882.1};
RX PubMed=11125028; DOI=10.1124/mol.59.1.83;
RA Porzgen P., Park S.K., Hirsh J., Sonders M.S., Amara S.G.;
RT "The antidepressant-sensitive dopamine transporter in Drosophila
RT melanogaster: a primordial carrier for catecholamines.";
RL Mol. Pharmacol. 59:83-95(2001).
RN [2] {ECO:0000312|EMBL:AAL32055.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF MET-72.
RX PubMed=12606774; DOI=10.1124/mol.63.3.653;
RA Wu X., Gu H.H.;
RT "Cocaine affinity decreased by mutations of aromatic residue phenylalanine
RT 105 in the transmembrane domain 2 of dopamine transporter.";
RL Mol. Pharmacol. 63:653-658(2003).
RN [3] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5] {ECO:0000312|EMBL:AAK93003.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK93003.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAK93003.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16093388; DOI=10.1523/jneurosci.2048-05.2005;
RA Kume K., Kume S., Park S.K., Hirsh J., Jackson F.R.;
RT "Dopamine is a regulator of arousal in the fruit fly.";
RL J. Neurosci. 25:7377-7384(2005).
RN [7] {ECO:0000305}
RP DISULFIDE BOND.
RX PubMed=17131045; DOI=10.1007/s11010-006-9348-7;
RA Chen R., Wei H., Hill E.R., Chen L., Jiang L., Han D.D., Gu H.H.;
RT "Direct evidence that two cysteines in the dopamine transporter form a
RT disulfide bond.";
RL Mol. Cell. Biochem. 298:41-48(2007).
RN [8] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25232310; DOI=10.3389/fnbeh.2014.00303;
RA Ueno T., Kume K.;
RT "Functional characterization of dopamine transporter in vivo using
RT Drosophila melanogaster behavioral assays.";
RL Front. Behav. Neurosci. 8:303-303(2014).
RN [9] {ECO:0007744|PDB:4M48}
RP X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF 21-601 IN COMPLEX WITH SODIUM AND
RP INHIBITOR, FUNCTION, SUBCELLULAR LOCATION, AND DISULFIDE BOND.
RX PubMed=24037379; DOI=10.1038/nature12533;
RA Penmatsa A., Wang K.H., Gouaux E.;
RT "X-ray structure of dopamine transporter elucidates antidepressant
RT mechanism.";
RL Nature 503:85-90(2013).
RN [10] {ECO:0007744|PDB:4XP1, ECO:0007744|PDB:4XP4, ECO:0007744|PDB:4XP5}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 25-601 IN COMPLEX WITH SUBSTRATE;
RP SUBSTRATE ANALOG; SODIUM AND INHIBITORS, FUNCTION, SUBCELLULAR LOCATION,
RP DISULFIDE BOND, AND GLYCOSYLATION AT ASN-141.
RX PubMed=25970245; DOI=10.1038/nature14431;
RA Wang K.H., Penmatsa A., Gouaux E.;
RT "Neurotransmitter and psychostimulant recognition by the dopamine
RT transporter.";
RL Nature 521:322-327(2015).
RN [11] {ECO:0007744|PDB:4XNU, ECO:0007744|PDB:4XNX}
RP X-RAY CRYSTALLOGRAPHY (2.98 ANGSTROMS) OF 25-601 IN COMPLEX WITH
RP INHIBITORS, DISULFIDE BOND, AND MUTAGENESIS OF ASP-121 AND SER-426.
RX PubMed=25961798; DOI=10.1038/nsmb.3029;
RA Penmatsa A., Wang K.H., Gouaux E.;
RT "X-ray structures of Drosophila dopamine transporter in complex with
RT nisoxetine and reboxetine.";
RL Nat. Struct. Mol. Biol. 22:506-508(2015).
CC -!- FUNCTION: Sodium-dependent dopamine transporter which terminates the
CC action of dopamine by its high affinity sodium-dependent reuptake into
CC presynaptic terminals (PubMed:11125028, PubMed:12606774,
CC PubMed:24037379, PubMed:25970245). Also transports tyramine and
CC norepinephrine, shows less efficient transport of octopamine and does
CC not transport serotonin (PubMed:11125028, PubMed:12606774). Plays a
CC role in the regulation of the rest/activity cycle (PubMed:16093388,
CC PubMed:25232310). {ECO:0000269|PubMed:11125028,
CC ECO:0000269|PubMed:12606774, ECO:0000269|PubMed:16093388,
CC ECO:0000269|PubMed:24037379, ECO:0000269|PubMed:25232310,
CC ECO:0000269|PubMed:25970245}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24037379,
CC ECO:0000269|PubMed:25970245}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:24037379, ECO:0000269|PubMed:25970245}.
CC -!- TISSUE SPECIFICITY: Expression is restricted to dopaminergic neurons in
CC the central nervous system. {ECO:0000269|PubMed:11125028}.
CC -!- DEVELOPMENTAL STAGE: Low levels in 0-4 hour embryos with strong
CC expression in late embryos at 12-24 hours and during larval
CC development. Expression decreases during pupal development and
CC increases again in adult flies with heads showing higher levels than
CC bodies. {ECO:0000269|PubMed:11125028}.
CC -!- DISRUPTION PHENOTYPE: No effect on fertility or longevity but mutants
CC display longer periods of daily activity than controls, reduced rest,
CC enhanced sensitivity to mechanical stimuli when inactive and decreased
CC rest rebound in response to rest deprivation (PubMed:16093388).
CC Impaired aversive olfactory memory due to excessive dopaminergic
CC signaling (PubMed:25232310). RNAi-mediated knockdown in neurons causes
CC significant reduction in the sleep-like rest state with total daily
CC resting periods decreased to about half of that of control flies
CC (PubMed:25232310). {ECO:0000269|PubMed:16093388,
CC ECO:0000269|PubMed:25232310}.
CC -!- MISCELLANEOUS: 10-fold less sensitive to cocaine than mammalian
CC dopamine transporter SLC6A3. {ECO:0000269|PubMed:12606774}.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. {ECO:0000255|RuleBase:RU003732}.
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DR EMBL; AF260833; AAF76882.1; -; mRNA.
DR EMBL; AF439752; AAL32055.1; -; mRNA.
DR EMBL; AE013599; AAF57986.2; -; Genomic_DNA.
DR EMBL; AY051579; AAK93003.1; -; mRNA.
DR RefSeq; NP_523763.2; NM_079039.4.
DR PDB; 4M48; X-ray; 2.96 A; A=21-601.
DR PDB; 4XNU; X-ray; 2.98 A; A=25-599.
DR PDB; 4XNX; X-ray; 3.00 A; A=25-601.
DR PDB; 4XP1; X-ray; 2.89 A; A=25-600.
DR PDB; 4XP4; X-ray; 2.80 A; A=21-601.
DR PDB; 4XP5; X-ray; 3.30 A; A=25-599.
DR PDB; 4XP6; X-ray; 3.10 A; A=25-599.
DR PDB; 4XP9; X-ray; 2.80 A; C=25-601.
DR PDB; 4XPA; X-ray; 2.95 A; A=21-601.
DR PDB; 4XPB; X-ray; 3.05 A; A=21-601.
DR PDB; 4XPF; X-ray; 3.27 A; A=21-601.
DR PDB; 4XPG; X-ray; 3.21 A; A=21-601.
DR PDB; 4XPH; X-ray; 2.90 A; A=25-599.
DR PDB; 4XPT; X-ray; 3.36 A; A=25-599.
DR PDB; 6M0F; X-ray; 3.30 A; A=25-599.
DR PDB; 6M0Z; X-ray; 2.88 A; A=25-601.
DR PDB; 6M2R; X-ray; 2.80 A; A=25-601.
DR PDB; 6M38; X-ray; 3.00 A; A=25-599.
DR PDB; 6M3Z; X-ray; 3.11 A; A=25-601.
DR PDB; 6M47; X-ray; 3.25 A; A=25-599.
DR PDBsum; 4M48; -.
DR PDBsum; 4XNU; -.
DR PDBsum; 4XNX; -.
DR PDBsum; 4XP1; -.
DR PDBsum; 4XP4; -.
DR PDBsum; 4XP5; -.
DR PDBsum; 4XP6; -.
DR PDBsum; 4XP9; -.
DR PDBsum; 4XPA; -.
DR PDBsum; 4XPB; -.
DR PDBsum; 4XPF; -.
DR PDBsum; 4XPG; -.
DR PDBsum; 4XPH; -.
DR PDBsum; 4XPT; -.
DR PDBsum; 6M0F; -.
DR PDBsum; 6M0Z; -.
DR PDBsum; 6M2R; -.
DR PDBsum; 6M38; -.
DR PDBsum; 6M3Z; -.
DR PDBsum; 6M47; -.
DR AlphaFoldDB; Q7K4Y6; -.
DR SMR; Q7K4Y6; -.
DR IntAct; Q7K4Y6; 4.
DR STRING; 7227.FBpp0086271; -.
DR TCDB; 2.A.22.1.7; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; Q7K4Y6; 8 sites.
DR iPTMnet; Q7K4Y6; -.
DR PaxDb; Q7K4Y6; -.
DR PRIDE; Q7K4Y6; -.
DR ABCD; Q7K4Y6; 1 sequenced antibody.
DR DNASU; 36849; -.
DR EnsemblMetazoa; FBtr0087125; FBpp0086271; FBgn0034136.
DR GeneID; 36849; -.
DR KEGG; dme:Dmel_CG8380; -.
DR UCSC; CG8380-RA; d. melanogaster.
DR CTD; 36849; -.
DR FlyBase; FBgn0034136; DAT.
DR VEuPathDB; VectorBase:FBgn0034136; -.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000173306; -.
DR HOGENOM; CLU_006855_9_0_1; -.
DR InParanoid; Q7K4Y6; -.
DR OMA; IMGHFAF; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; Q7K4Y6; -.
DR Reactome; R-DME-379401; Dopamine clearance from the synaptic cleft.
DR Reactome; R-DME-442660; Na+/Cl- dependent neurotransmitter transporters.
DR BioGRID-ORCS; 36849; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 36849; -.
DR PRO; PR:Q7K4Y6; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0034136; Expressed in ectoderm anlage and 23 other tissues.
DR ExpressionAtlas; Q7K4Y6; baseline and differential.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
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:0019811; F:cocaine binding; IDA:FlyBase.
DR GO; GO:0005330; F:dopamine:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:FlyBase.
DR GO; GO:0042745; P:circadian sleep/wake cycle; IDA:FlyBase.
DR GO; GO:0015872; P:dopamine transport; IDA:UniProtKB.
DR GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IBA:GO_Central.
DR GO; GO:0015874; P:norepinephrine transport; IBA:GO_Central.
DR GO; GO:0099509; P:regulation of presynaptic cytosolic calcium ion concentration; IMP:FlyBase.
DR GO; GO:1990834; P:response to odorant; IMP:FlyBase.
DR GO; GO:0030431; P:sleep; IMP:FlyBase.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 2.
DR Pfam; PF00209; SNF; 1.
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 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; Membrane;
KW Metal-binding; Neurotransmitter transport; Reference proteome; Sodium;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..631
FT /note="Sodium-dependent dopamine transporter"
FT /id="PRO_0000435626"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 34..59
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TOPO_DOM 60..63
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 64..87
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TOPO_DOM 88..107
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 108..138
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TOPO_DOM 139..235
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 236..256
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TOPO_DOM 257..259
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 260..284
FT /note="Helical; Name=5"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TOPO_DOM 285..308
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 309..334
FT /note="Helical; Name=6"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245"
FT TOPO_DOM 335..340
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 341..364
FT /note="Helical; Name=7"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245"
FT TOPO_DOM 365..404
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 405..430
FT /note="Helical; Name=8"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245"
FT TOPO_DOM 431..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 446..466
FT /note="Helical; Name=9"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245"
FT TOPO_DOM 467
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 468..494
FT /note="Helical; Name=10"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245"
FT TOPO_DOM 495..524
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 525..547
FT /note="Helical; Name=11"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245"
FT TOPO_DOM 548..550
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT TRANSMEM 551..571
FT /note="Helical; Name=12"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245"
FT TOPO_DOM 572..631
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25961798, ECO:0000269|PubMed:25970245"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 42
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4XP1"
FT BINDING 44
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4XP1"
FT BINDING 45
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4XP1"
FT BINDING 46
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4XP1"
FT BINDING 49
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4XP1"
FT BINDING 117
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4XP1"
FT BINDING 121
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4XP1"
FT BINDING 320
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4XP1"
FT BINDING 352
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4XP1"
FT BINDING 417
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4XP1"
FT BINDING 420
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4XP1"
FT BINDING 421
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24037379,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4XP1"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine; atypical"
FT /evidence="ECO:0000269|PubMed:25970245,
FT ECO:0007744|PDB:4XP1"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 148..157
FT /evidence="ECO:0000269|PubMed:17131045,
FT ECO:0000269|PubMed:24037379, ECO:0000269|PubMed:25961798,
FT ECO:0000269|PubMed:25970245, ECO:0007744|PDB:4M48,
FT ECO:0007744|PDB:4XNU, ECO:0007744|PDB:4XNX,
FT ECO:0007744|PDB:4XP1"
FT MUTAGEN 72
FT /note="M->F: 3-fold increase in sensitivity to cocaine
FT inhibition of transport."
FT /evidence="ECO:0000269|PubMed:12606774"
FT MUTAGEN 121
FT /note="D->G: Increased binding affinity for cocaine."
FT /evidence="ECO:0000269|PubMed:25961798"
FT MUTAGEN 426
FT /note="S->M: Increased binding affinity for cocaine."
FT /evidence="ECO:0000269|PubMed:25961798"
FT CONFLICT 16
FT /note="H -> R (in Ref. 1; AAF76882)"
FT /evidence="ECO:0000305"
FT HELIX 33..44
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 53..59
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 66..75
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 77..91
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 95..102
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 104..107
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 108..120
FT /evidence="ECO:0007829|PDB:4XP4"
FT TURN 121..124
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 125..137
FT /evidence="ECO:0007829|PDB:4XP4"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:4XP4"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:4XP4"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:4XP9"
FT STRAND 204..207
FT /evidence="ECO:0007829|PDB:4XPT"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:4M48"
FT HELIX 211..218
FT /evidence="ECO:0007829|PDB:4XP4"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:4XP4"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 237..254
FT /evidence="ECO:0007829|PDB:4XP4"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:6M2R"
FT HELIX 258..284
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 289..297
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 301..305
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 307..320
FT /evidence="ECO:0007829|PDB:4XP4"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:4XPB"
FT HELIX 327..332
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 341..373
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 378..381
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 386..390
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 392..399
FT /evidence="ECO:0007829|PDB:4XP4"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:4XPA"
FT HELIX 403..436
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 438..442
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 444..458
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 459..463
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 467..477
FT /evidence="ECO:0007829|PDB:4XP4"
FT STRAND 478..481
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 482..495
FT /evidence="ECO:0007829|PDB:4XP4"
FT TURN 496..499
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 500..511
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 517..524
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 526..540
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 554..568
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 570..579
FT /evidence="ECO:0007829|PDB:4XP4"
FT STRAND 580..582
FT /evidence="ECO:0007829|PDB:4XP1"
FT HELIX 586..593
FT /evidence="ECO:0007829|PDB:4XP4"
FT HELIX 597..600
FT /evidence="ECO:0007829|PDB:4XP9"
SQ SEQUENCE 631 AA; 70330 MW; E7582D17F81E31E6 CRC64;
MSPTGHISKS KTPTPHDNDN NSISDERETW SGKVDFLLSV IGFAVDLANV WRFPYLCYKN
GGGAFLVPYG IMLVVGGIPL FYMELALGQH NRKGAITCWG RLVPLFKGIG YAVVLIAFYV
DFYYNVIIAW SLRFFFASFT NSLPWTSCNN IWNTPNCRPF ESQNASRVPV IGNYSDLYAM
GNQSLLYNET YMNGSSLDTS AVGHVEGFQS AASEYFNRYI LELNRSEGIH DLGAIKWDMA
LCLLIVYLIC YFSLWKGIST SGKVVWFTAL FPYAVLLILL IRGLTLPGSF LGIQYYLTPN
FSAIYKAEVW VDAATQVFFS LGPGFGVLLA YASYNKYHNN VYKDALLTSF INSATSFIAG
FVIFSVLGYM AHTLGVRIED VATEGPGLVF VVYPAAIATM PASTFWALIF FMMLLTLGLD
SSFGGSEAII TALSDEFPKI KRNRELFVAG LFSLYFVVGL ASCTQGGFYF FHLLDRYAAG
YSILVAVFFE AIAVSWIYGT NRFSEDIRDM IGFPPGRYWQ VCWRFVAPIF LLFITVYGLI
GYEPLTYADY VYPSWANALG WCIAGSSVVM IPAVAIFKLL STPGSLRQRF TILTTPWRDQ
QSMAMVLNGV TTEVTVVRLT DTETAKEPVD V
