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 24-JAN-2024, entry version 142. 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) CC (TC 2.A.22) family. {ECO:0000255|RuleBase:RU003732}. 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; 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 PDB; 7WGD; X-ray; 3.20 A; A=25-601. DR PDB; 7WGT; X-ray; 2.75 A; A=25-601. DR PDB; 7WLW; X-ray; 2.90 A; A=25-601. 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 PDBsum; 7WGD; -. DR PDBsum; 7WGT; -. DR PDBsum; 7WLW; -. DR AlphaFoldDB; Q7K4Y6; -. DR SMR; Q7K4Y6; -. DR IntAct; Q7K4Y6; 4. DR STRING; 7227.FBpp0303037; -. DR TCDB; 2.A.22.1.7; the neurotransmitter:sodium symporter (nss) family. DR GlyCosmos; Q7K4Y6; 8 sites, No reported glycans. DR GlyGen; Q7K4Y6; 8 sites. DR iPTMnet; Q7K4Y6; -. DR PaxDb; 7227-FBpp0086271; -. 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 AGR; FB:FBgn0034136; -. 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; WAIMGHF; -. 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 cell types or tissues. DR ExpressionAtlas; Q7K4Y6; baseline and differential. 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:0005886; C:plasma membrane; IDA:UniProtKB. 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 CDD; cd11556; SLC6sbd_SERT-like_u1; 1. DR InterPro; IPR000175; Na/ntran_symport. DR InterPro; IPR037272; SNS_sf. DR PANTHER; PTHR11616:SF311; SODIUM-DEPENDENT DOPAMINE TRANSPORTER; 1. DR PANTHER; PTHR11616; SODIUM/CHLORIDE DEPENDENT TRANSPORTER; 1. DR Pfam; PF00209; SNF; 1. DR PRINTS; PR00176; NANEUSMPORT. DR SUPFAM; SSF161070; SNF-like; 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:7WGT" FT HELIX 47..51 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 53..59 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 62..65 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 66..74 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 77..91 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 95..100 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 107..124 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 126..137 FT /evidence="ECO:0007829|PDB:7WGT" FT STRAND 140..142 FT /evidence="ECO:0007829|PDB:7WGT" 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:7WGT" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 211..218 FT /evidence="ECO:0007829|PDB:7WGT" FT TURN 219..221 FT /evidence="ECO:0007829|PDB:4XP4" FT HELIX 223..225 FT /evidence="ECO:0007829|PDB:7WGT" FT STRAND 227..230 FT /evidence="ECO:0007829|PDB:4XP4" FT HELIX 237..254 FT /evidence="ECO:0007829|PDB:7WGT" FT TURN 255..257 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 258..284 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 289..297 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 301..303 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 307..321 FT /evidence="ECO:0007829|PDB:7WGT" FT STRAND 324..326 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 327..333 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 341..373 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 378..381 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 386..390 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 392..397 FT /evidence="ECO:0007829|PDB:7WGT" FT STRAND 400..402 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 403..434 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 438..442 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 444..457 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 458..463 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 467..475 FT /evidence="ECO:0007829|PDB:7WGT" FT TURN 476..478 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 480..495 FT /evidence="ECO:0007829|PDB:7WGT" FT TURN 496..499 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 500..511 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 517..524 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 526..540 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 554..568 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 570..580 FT /evidence="ECO:0007829|PDB:7WGT" FT STRAND 584..586 FT /evidence="ECO:0007829|PDB:4XPH" FT HELIX 587..590 FT /evidence="ECO:0007829|PDB:7WGT" FT TURN 591..594 FT /evidence="ECO:0007829|PDB:7WGT" FT HELIX 598..600 FT /evidence="ECO:0007829|PDB:7WGT" 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 //