ID O67854_AQUAE Unreviewed; 513 AA. AC O67854; DT 01-AUG-1998, integrated into UniProtKB/TrEMBL. DT 01-AUG-1998, sequence version 1. DT 27-MAR-2024, entry version 150. DE SubName: Full=Na(+):neurotransmitter symporter (Snf family) {ECO:0000313|EMBL:AAC07817.1}; GN Name=snf {ECO:0000313|EMBL:AAC07817.1}; GN OrderedLocusNames=aq_2077 {ECO:0000313|EMBL:AAC07817.1}; OS Aquifex aeolicus (strain VF5). OC Bacteria; Aquificota; Aquificae; Aquificales; Aquificaceae; Aquifex. OX NCBI_TaxID=224324 {ECO:0000313|EMBL:AAC07817.1, ECO:0000313|Proteomes:UP000000798}; RN [1] {ECO:0000313|EMBL:AAC07817.1, ECO:0000313|Proteomes:UP000000798} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=VF5 {ECO:0000313|EMBL:AAC07817.1, RC ECO:0000313|Proteomes:UP000000798}; RX PubMed=9537320; DOI=10.1038/32831; RA Deckert G., Warren P.V., Gaasterland T., Young W.G., Lenox A.L., RA Graham D.E., Overbeek R., Snead M.A., Keller M., Aujay M., Huber R., RA Feldman R.A., Short J.M., Olson G.J., Swanson R.V.; RT "The complete genome of the hyperthermophilic bacterium Aquifex aeolicus."; RL Nature 392:353-358(1998). RN [2] {ECO:0007829|PDB:2A65} RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS). RX PubMed=16041361; DOI=10.1038/nature03978; RA Yamashita A., Singh S.K., Kawate T., Jin Y., Gouaux E.; RT "Crystal structure of a bacterial homologue of Na+/Cl--dependent RT neurotransmitter transporters."; RL Nature 437:215-223(2005). RN [3] {ECO:0007829|PDB:2Q6H, ECO:0007829|PDB:2Q72} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS). RX PubMed=17687333; DOI=10.1038/nature06038; RA Singh S.K., Yamashita A., Gouaux E.; RT "Antidepressant binding site in a bacterial homologue of neurotransmitter RT transporters."; RL Nature 448:952-956(2007). RN [4] {ECO:0007829|PDB:2QJU} RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 5-513. RX PubMed=17690258; DOI=10.1126/science.1147614; RA Zhou Z., Zhen J., Karpowich N.K., Goetz R.M., Law C.J., Reith M.E., RA Wang D.N.; RT "LeuT-desipramine structure reveals how antidepressants block RT neurotransmitter reuptake."; RL Science 317:1390-1393(2007). RN [5] {ECO:0007829|PDB:3F3A, ECO:0007829|PDB:3F3C} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS). RX PubMed=19074341; DOI=10.1126/science.1166777; RA Singh S.K., Piscitelli C.L., Yamashita A., Gouaux E.; RT "A competitive inhibitor traps LeuT in an open-to-out conformation."; RL Science 322:1655-1661(2008). RN [6] {ECO:0007829|PDB:3GWU, ECO:0007829|PDB:3GWV} RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS). RX PubMed=19430461; DOI=10.1038/nsmb.1602; RA Zhou Z., Zhen J., Karpowich N.K., Law C.J., Reith M.E., Wang D.N.; RT "Antidepressant specificity of serotonin transporter suggested by three RT LeuT-SSRI structures."; RL Nat. Struct. Mol. Biol. 16:652-657(2009). RN [7] {ECO:0007829|PDB:3GJC, ECO:0007829|PDB:3GJD} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS). RX PubMed=19307590; DOI=10.1073/pnas.0811322106; RA Quick M., Winther A.M., Shi L., Nissen P., Weinstein H., Javitch J.A.; RT "Binding of an octylglucoside detergent molecule in the second substrate RT (S2) site of LeuT establishes an inhibitor-bound conformation."; RL Proc. Natl. Acad. Sci. U.S.A. 106:5563-5568(2009). RN [8] {ECO:0007829|PDB:3MPN, ECO:0007829|PDB:3MPQ} RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 4-510. RX PubMed=20964375; DOI=10.1021/bi101148w; RA Kroncke B.M., Horanyi P.S., Columbus L.; RT "Structural origins of nitroxide side chain dynamics on membrane protein RT alpha-helical sites."; RL Biochemistry 49:10045-10060(2010). RN [9] {ECO:0007829|PDB:3QS4, ECO:0007829|PDB:3QS5} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS). RX PubMed=21952050; DOI=10.1038/emboj.2011.353; RA Piscitelli C.L., Gouaux E.; RT "Insights into transport mechanism from LeuT engineered to transport RT tryptophan."; RL EMBO J. 31:228-235(2012). RN [10] {ECO:0007829|PDB:4FXZ, ECO:0007829|PDB:4FY0} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS). RX PubMed=22836580; DOI=10.1038/embor.2012.110; RA Wang H., Gouaux E.; RT "Substrate binds in the S1 site of the F253A mutant of LeuT, a RT neurotransmitter sodium symporter homologue."; RL EMBO Rep. 13:861-866(2012). RN [11] {ECO:0007829|PDB:3USG, ECO:0007829|PDB:3USI} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH PHOSPHOCHOLINE. RX PubMed=22245965; DOI=10.1038/nsmb.2215; RA Wang H., Elferich J., Gouaux E.; RT "Structures of LeuT in bicelles define conformation and substrate binding RT in a membrane-like context."; RL Nat. Struct. Mol. Biol. 19:212-219(2012). RN [12] {ECO:0007829|PDB:3TT1, ECO:0007829|PDB:3TT3} RP X-RAY CRYSTALLOGRAPHY (2.99 ANGSTROMS). RX PubMed=22230955; DOI=10.1038/nature10737; RA Krishnamurthy H., Gouaux E.; RT "X-ray structures of LeuT in substrate-free outward-open and apo inward- RT open states."; RL Nature 481:469-474(2012). RN [13] {ECO:0007829|PDB:4MM4, ECO:0007829|PDB:4MM5} RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS). RX PubMed=24121440; DOI=10.1038/nature12648; RA Wang H., Goehring A., Wang K.H., Penmatsa A., Ressler R., Gouaux E.; RT "Structural basis for action by diverse antidepressants on biogenic amine RT transporters."; RL Nature 503:141-145(2013). RN [14] {ECO:0007829|PDB:4HMK, ECO:0007829|PDB:4HOD} RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS). RA Kantcheva A.K., Quick M., Shi L., Winther A.M.L., Stolzenberg S., RA Weinstein H., Javitch J.A., Nissen P.; RT "The chloride binding site of Neurotransmitter Sodium Symporters."; RL Proc. Natl. Acad. Sci. U.S.A. 0:0-0(2013). RN [15] {ECO:0007829|PDB:5JAE, ECO:0007829|PDB:5JAF} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS). RX PubMed=27221344; DOI=10.1038/ncomms11673; RA Malinauskaite L., Said S., Sahin C., Grouleff J., Shahsavar A., RA Bjerregaard H., Noer P., Severinsen K., Boesen T., Schiott B., Sinning S., RA Nissen P.; RT "A conserved leucine occupies the empty substrate site of LeuT in the RT Na(+)-free return state."; RL Nat. Commun. 7:11673-11673(2016). RN [16] {ECO:0007829|PDB:6NLE} RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 4-508. RX PubMed=30755521; DOI=10.1073/pnas.1816247116; RA Campbell N.G., Shekar A., Aguilar J.I., Peng D., Navratna V., Yang D., RA Morley A.N., Duran A.M., Galli G., O'Grady B., Ramachandran R., RA Sutcliffe J.S., Sitte H.H., Erreger K., Meiler J., Stockner T., RA Bellan L.M., Matthies H.J.G., Gouaux E., Mchaourab H.S., Galli A.; RT "Structural, functional, and behavioral insights of dopamine dysfunction RT revealed by a deletion in SLC6A3."; RL Proc. Natl. Acad. Sci. U.S.A. 116:3853-3862(2019). RN [17] {ECO:0007829|PDB:6XWM} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS). RX PubMed=32081981; DOI=10.1038/s41467-020-14735-w; RA Gotfryd K., Boesen T., Mortensen J.S., Khelashvili G., Quick M., RA Terry D.S., Missel J.W., LeVine M.V., Gourdon P., Blanchard S.C., RA Javitch J.A., Weinstein H., Loland C.J., Nissen P., Gether U.; RT "X-ray structure of LeuT in an inward-facing occluded conformation reveals RT mechanism of substrate release."; RL Nat. Commun. 11:1005-1005(2020). RN [18] {ECO:0007829|PDB:7LQJ, ECO:0007829|PDB:7LQK} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS). RX PubMed=34002696; DOI=10.7554/elife.68039; RA Aguilar J.I., Cheng M.H., Font J., Schwartz A.C., Ledwitch K., Duran A., RA Mabry S.J., Belovich A.N., Zhu Y., Carter A.M., Shi L., Kurian M.A., RA Fenollar-Ferrer C., Meiler J., Ryan R.M., Mchaourab H.S., Bahar I., RA Matthies H.J., Galli A.; RT "Psychomotor impairments and therapeutic implications revealed by a RT mutation associated with infantile Parkinsonism-Dystonia. ."; RL Elife 10:e68039-e68039(2021). RN [19] {ECO:0007829|PDB:7DII, ECO:0007829|PDB:7DIX} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS). RX PubMed=33811858; DOI=10.1016/j.jbc.2021.100609; RA Fan J., Xiao Y., Quick M., Yang Y., Sun Z., Javitch J.A., Zhou X.; RT "Crystal structures of LeuT reveal conformational dynamics in the outward- RT facing states."; RL J. Biol. Chem. 296:100609-100609(2021). RN [20] {ECO:0007829|PDB:8FT4, ECO:0007829|PDB:8FT5} RP X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS). RA Karasawa A., Liu H., Quick M., Hendrickson W.A., Liu Q.; RT "Crystallographic characterization of sodium ions in a bacterial RT leucine/sodium symporter."; RL Submitted (JAN-2023) to the PDB data bank. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004141}; Multi- CC pass membrane protein {ECO:0000256|ARBA:ARBA00004141}. 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; AE000657; AAC07817.1; -; Genomic_DNA. DR PIR; B70478; B70478. DR RefSeq; NP_214423.1; NC_000918.1. DR RefSeq; WP_010881359.1; NC_000918.1. DR PDB; 2A65; X-ray; 1.65 A; A=1-513. DR PDB; 2Q6H; X-ray; 1.85 A; A=1-513. DR PDB; 2Q72; X-ray; 1.70 A; A=1-513. DR PDB; 2QB4; X-ray; 1.90 A; A=1-513. DR PDB; 2QEI; X-ray; 1.85 A; A=1-513. DR PDB; 2QJU; X-ray; 2.90 A; A=5-513. DR PDB; 3F3A; X-ray; 2.00 A; A=1-513. DR PDB; 3F3C; X-ray; 2.10 A; A=1-513. DR PDB; 3F3D; X-ray; 2.30 A; A=1-513. DR PDB; 3F3E; X-ray; 1.80 A; A=1-513. DR PDB; 3F48; X-ray; 1.90 A; A=1-513. DR PDB; 3F4I; X-ray; 1.95 A; A=1-513. DR PDB; 3F4J; X-ray; 2.15 A; A=1-513. DR PDB; 3GJC; X-ray; 2.80 A; A/B=1-513. DR PDB; 3GJD; X-ray; 2.00 A; A=1-513. DR PDB; 3GWU; X-ray; 2.14 A; A=1-513. DR PDB; 3GWV; X-ray; 2.35 A; A=1-513. DR PDB; 3GWW; X-ray; 2.46 A; A=1-513. DR PDB; 3MPN; X-ray; 2.25 A; A=5-511. DR PDB; 3MPQ; X-ray; 2.25 A; A=4-510. DR PDB; 3QS4; X-ray; 2.63 A; A=1-513. DR PDB; 3QS5; X-ray; 2.60 A; A=1-513. DR PDB; 3QS6; X-ray; 2.80 A; A=1-513. DR PDB; 3TT1; X-ray; 3.10 A; A/B=1-513. DR PDB; 3TT3; X-ray; 3.22 A; A=1-513. DR PDB; 3TU0; X-ray; 2.99 A; A=1-513. DR PDB; 3USG; X-ray; 2.50 A; A=1-513. DR PDB; 3USI; X-ray; 3.11 A; A/B=1-513. DR PDB; 3USJ; X-ray; 3.50 A; A/B=1-513. DR PDB; 3USK; X-ray; 4.50 A; A/B/C/D=1-513. DR PDB; 3USL; X-ray; 2.71 A; A=1-513. DR PDB; 3USM; X-ray; 3.01 A; A=1-513. DR PDB; 3USO; X-ray; 4.50 A; A/B=1-513. DR PDB; 3USP; X-ray; 2.10 A; A=1-513. DR PDB; 4FXZ; X-ray; 2.60 A; A=1-513. DR PDB; 4FY0; X-ray; 3.00 A; A=1-513. DR PDB; 4HMK; X-ray; 3.00 A; A/B=1-513. DR PDB; 4HOD; X-ray; 3.30 A; A=1-513. DR PDB; 4MM4; X-ray; 2.89 A; A/B=1-513. DR PDB; 4MM5; X-ray; 3.20 A; A=1-513. DR PDB; 4MM6; X-ray; 3.10 A; A=1-513. DR PDB; 4MM7; X-ray; 2.85 A; A=1-513. DR PDB; 4MM8; X-ray; 3.31 A; A=1-513. DR PDB; 4MM9; X-ray; 2.90 A; A=1-513. DR PDB; 4MMA; X-ray; 3.30 A; A=1-513. DR PDB; 4MMB; X-ray; 2.25 A; A=1-513. DR PDB; 4MMC; X-ray; 2.30 A; A=1-513. DR PDB; 4MMD; X-ray; 2.30 A; A/B=1-513. DR PDB; 4MME; X-ray; 2.50 A; A/B=1-513. DR PDB; 4MMF; X-ray; 2.70 A; A/B=1-513. DR PDB; 5JAE; X-ray; 2.50 A; A/B=1-513. DR PDB; 5JAF; X-ray; 3.02 A; A=1-513. DR PDB; 5JAG; X-ray; 2.58 A; A=1-513. DR PDB; 6NLE; X-ray; 2.62 A; A=4-508. DR PDB; 6XWM; X-ray; 2.60 A; A/B=1-513. DR PDB; 7DII; X-ray; 2.40 A; A/B=1-513. DR PDB; 7DIX; X-ray; 3.49 A; A/B=1-513. DR PDB; 7DJ1; X-ray; 3.53 A; A/B=1-513. DR PDB; 7DJ2; X-ray; 2.40 A; A/B=1-513. DR PDB; 7DJC; X-ray; 2.70 A; A=1-513. DR PDB; 7LQJ; X-ray; 2.14 A; A=1-513. DR PDB; 7LQK; X-ray; 2.10 A; A=1-513. DR PDB; 7LQL; X-ray; 2.60 A; A=1-513. DR PDB; 8FT4; X-ray; 4.00 A; A=1-513. DR PDB; 8FT5; X-ray; 3.80 A; A=1-513. DR PDBsum; 2A65; -. DR PDBsum; 2Q6H; -. DR PDBsum; 2Q72; -. DR PDBsum; 2QB4; -. DR PDBsum; 2QEI; -. DR PDBsum; 2QJU; -. DR PDBsum; 3F3A; -. DR PDBsum; 3F3C; -. DR PDBsum; 3F3D; -. DR PDBsum; 3F3E; -. DR PDBsum; 3F48; -. DR PDBsum; 3F4I; -. DR PDBsum; 3F4J; -. DR PDBsum; 3GJC; -. DR PDBsum; 3GJD; -. DR PDBsum; 3GWU; -. DR PDBsum; 3GWV; -. DR PDBsum; 3GWW; -. DR PDBsum; 3MPN; -. DR PDBsum; 3MPQ; -. DR PDBsum; 3QS4; -. DR PDBsum; 3QS5; -. DR PDBsum; 3QS6; -. DR PDBsum; 3TT1; -. DR PDBsum; 3TT3; -. DR PDBsum; 3TU0; -. DR PDBsum; 3USG; -. DR PDBsum; 3USI; -. DR PDBsum; 3USJ; -. DR PDBsum; 3USK; -. DR PDBsum; 3USL; -. DR PDBsum; 3USM; -. DR PDBsum; 3USO; -. DR PDBsum; 3USP; -. DR PDBsum; 4FXZ; -. DR PDBsum; 4FY0; -. DR PDBsum; 4HMK; -. DR PDBsum; 4HOD; -. DR PDBsum; 4MM4; -. DR PDBsum; 4MM5; -. DR PDBsum; 4MM6; -. DR PDBsum; 4MM7; -. DR PDBsum; 4MM8; -. DR PDBsum; 4MM9; -. DR PDBsum; 4MMA; -. DR PDBsum; 4MMB; -. DR PDBsum; 4MMC; -. DR PDBsum; 4MMD; -. DR PDBsum; 4MME; -. DR PDBsum; 4MMF; -. DR PDBsum; 5JAE; -. DR PDBsum; 5JAF; -. DR PDBsum; 5JAG; -. DR PDBsum; 6NLE; -. DR PDBsum; 6XWM; -. DR AlphaFoldDB; O67854; -. DR PCDDB; O67854; -. DR SMR; O67854; -. DR STRING; 224324.aq_2077; -. DR DrugBank; DB08472; (R)-Fluoxetine. DR DrugBank; DB08544; (S)-Fluoxetine. DR TCDB; 2.A.22.4.2; the neurotransmitter:sodium symporter (nss) family. DR ABCD; O67854; 2 sequenced antibodies. DR EnsemblBacteria; AAC07817; AAC07817; aq_2077. DR KEGG; aae:aq_2077; -. DR eggNOG; COG0733; Bacteria. DR HOGENOM; CLU_006855_3_3_0; -. DR InParanoid; O67854; -. DR OrthoDB; 9762833at2; -. DR EvolutionaryTrace; O67854; -. DR Proteomes; UP000000798; Chromosome. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central. DR CDD; cd10333; LeuT-like_sbd; 1. DR InterPro; IPR000175; Na/ntran_symport. DR InterPro; IPR037272; SNS_sf. DR NCBIfam; NF037979; Na_transp; 1. DR PANTHER; PTHR42948; TRANSPORTER; 1. DR PANTHER; PTHR42948:SF1; TRANSPORTER; 1. DR Pfam; PF00209; SNF; 2. DR PRINTS; PR00176; NANEUSMPORT. DR SUPFAM; SSF161070; SNF-like; 1. DR PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1. PE 1: Evidence at protein level; KW 3D-structure {ECO:0007829|PDB:2A65, ECO:0007829|PDB:2Q6H}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius}; KW Reference proteome {ECO:0000313|Proteomes:UP000000798}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, KW ECO:0000256|SAM:Phobius}; Transport {ECO:0000256|ARBA:ARBA00022448}. FT TRANSMEM 12..29 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 41..61 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 92..111 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 166..185 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 197..215 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 243..268 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 289..314 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 342..367 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 379..399 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 405..427 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 447..469 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 481..504 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT BINDING 88 FT /ligand="phosphocholine" FT /ligand_id="ChEBI:CHEBI:295975" FT /ligand_label="2" FT /evidence="ECO:0007829|PDB:3USM" FT BINDING 88 FT /ligand="phosphocholine" FT /ligand_id="ChEBI:CHEBI:295975" FT /ligand_label="1" FT /evidence="ECO:0007829|PDB:3USL" SQ SEQUENCE 513 AA; 57408 MW; 409A7B590C58D8BA CRC64; MEVKREHWAT RLGLILAMAG NAVGLGNFLR FPVQAAENGG GAFMIPYIIA FLLVGIPLMW IEWAMGRYGG AQGHGTTPAI FYLLWRNRFA KILGVFGLWI PLVVAIYYVY IESWTLGFAI KFLVGLVPEP PPNATDPDSI LRPFKEFLYS YIGVPKGDEP ILKPSLFAYI VFLITMFINV SILIRGISKG IERFAKIAMP TLFILAVFLV IRVFLLETPN GTAADGLNFL WTPDFEKLKD PGVWIAAVGQ IFFTLSLGFG AIITYASYVR KDQDIVLSGL TAATLNEKAE VILGGSISIP AAVAFFGVAN AVAIAKAGAF NLGFITLPAI FSQTAGGTFL GFLWFFLLFF AGLTSSIAIM QPMIAFLEDE LKLSRKHAVL WTAAIVFFSA HLVMFLNKSL DEMDFWAGTI GVVFFGLTEL IIFFWIFGAD KAWEEINRGG IIKVPRIYYY VMRYITPAFL AVLLVVWARE YIPKIMEETH WTVWITRFYI IGLFLFLTFL VFLAERRRNH ESA //