ID   S6A11_MOUSE             Reviewed;         627 AA.
AC   P31650; Q8BWA7;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 161.
DE   RecName: Full=Sodium- and chloride-dependent GABA transporter 3;
DE            Short=GAT-3;
DE   AltName: Full=Sodium- and chloride-dependent GABA transporter 4 {ECO:0000303|PubMed:8420981};
DE            Short=GAT-4 {ECO:0000303|PubMed:8420981};
DE   AltName: Full=Solute carrier family 6 member 11;
GN   Name=Slc6a11;
GN   Synonyms=Gabt3, Gabt4, Gat-4 {ECO:0000303|PubMed:8420981}, Gat3, Gat4
GN   {ECO:0000303|PubMed:8420981};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=8420981; DOI=10.1016/s0021-9258(18)53968-5;
RA   Liu Q.-R., Lopez-Coecuera B., Mandiyan S., Nelson H., Nelson N.;
RT   "Molecular characterization of four pharmacologically distinct gamma-
RT   aminobutyric acid transporters in mouse brain.";
RL   J. Biol. Chem. 268:2106-2112(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Head, and Medulla oblongata;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   PROTEIN SEQUENCE OF 20-35 AND 206-220, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=30270321; DOI=10.1248/bpb.b18-00168;
RA   Nishimura T., Higuchi K., Yoshida Y., Sugita-Fujisawa Y., Kojima K.,
RA   Sugimoto M., Santo M., Tomi M., Nakashima E.;
RT   "Hypotaurine Is a Substrate of GABA Transporter Family Members GAT2/Slc6a13
RT   and TAUT/Slc6a6.";
RL   Biol. Pharm. Bull. 41:1523-1529(2018).
CC   -!- FUNCTION: Mediates sodium- and chloride-dependent transport of gamma-
CC       aminobutyric acid (GABA) (PubMed:8420981, PubMed:30270321). Can also
CC       mediate transport of beta-alanine and to a lower extent that of taurine
CC       and hypotaurine (PubMed:8420981, PubMed:30270321).
CC       {ECO:0000269|PubMed:30270321, ECO:0000269|PubMed:8420981}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-aminobutanoate(out) + chloride(out) + 2 Na(+)(out) = 4-
CC         aminobutanoate(in) + chloride(in) + 2 Na(+)(in);
CC         Xref=Rhea:RHEA:70687, ChEBI:CHEBI:17996, ChEBI:CHEBI:29101,
CC         ChEBI:CHEBI:59888; Evidence={ECO:0000269|PubMed:30270321,
CC         ECO:0000269|PubMed:8420981};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70688;
CC         Evidence={ECO:0000305|PubMed:8420981};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + 2 Na(+)(out) + taurine(out) = chloride(in) + 2
CC         Na(+)(in) + taurine(in); Xref=Rhea:RHEA:71223, ChEBI:CHEBI:17996,
CC         ChEBI:CHEBI:29101, ChEBI:CHEBI:507393;
CC         Evidence={ECO:0000269|PubMed:8420981};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71224;
CC         Evidence={ECO:0000305|PubMed:8420981};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-alanine(out) + chloride(out) + 2 Na(+)(out) = beta-
CC         alanine(in) + chloride(in) + 2 Na(+)(in); Xref=Rhea:RHEA:71247,
CC         ChEBI:CHEBI:17996, ChEBI:CHEBI:29101, ChEBI:CHEBI:57966;
CC         Evidence={ECO:0000269|PubMed:8420981};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71248;
CC         Evidence={ECO:0000305|PubMed:8420981};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + hypotaurine(out) + 2 Na(+)(out) = chloride(in)
CC         + hypotaurine(in) + 2 Na(+)(in); Xref=Rhea:RHEA:71243,
CC         ChEBI:CHEBI:17996, ChEBI:CHEBI:29101, ChEBI:CHEBI:57853;
CC         Evidence={ECO:0000269|PubMed:30270321};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71244;
CC         Evidence={ECO:0000305|PubMed:30270321};
CC   -!- ACTIVITY REGULATION: GABA transport is inhibited by beta-alanine,
CC       taurine, hypotaurine, beta-guanidinopropionic acid and 2,3-
CC       diaminopropionic acid (PubMed:8420981). Beta-alanine transport is
CC       inhibited by GABA (PubMed:8420981). {ECO:0000269|PubMed:8420981}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.8 uM for GABA {ECO:0000269|PubMed:8420981};
CC         KM=2.24 uM for GABA {ECO:0000269|PubMed:30270321};
CC         KM=99 uM for beta-alanine {ECO:0000269|PubMed:8420981};
CC         KM=1.4 mM for taurine {ECO:0000269|PubMed:8420981};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P31647};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Brain. {ECO:0000269|PubMed:8420981}.
CC   -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF)
CC       (TC 2.A.22) family. SLC6A11 subfamily. {ECO:0000305}.
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DR   EMBL; L04662; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AK053078; BAC35259.1; -; mRNA.
DR   EMBL; AK140423; BAE24379.1; -; mRNA.
DR   EMBL; CH466523; EDK99507.1; -; Genomic_DNA.
DR   CCDS; CCDS39597.1; -.
DR   PIR; B44409; B44409.
DR   RefSeq; NP_766478.1; NM_172890.3.
DR   AlphaFoldDB; P31650; -.
DR   SMR; P31650; -.
DR   BioGRID; 232540; 4.
DR   STRING; 10090.ENSMUSP00000032451; -.
DR   BindingDB; P31650; -.
DR   ChEMBL; CHEMBL3699; -.
DR   DrugCentral; P31650; -.
DR   TCDB; 2.A.22.3.7; the neurotransmitter:sodium symporter (nss) family.
DR   GlyCosmos; P31650; 3 sites, No reported glycans.
DR   GlyGen; P31650; 4 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P31650; -.
DR   PhosphoSitePlus; P31650; -.
DR   SwissPalm; P31650; -.
DR   jPOST; P31650; -.
DR   MaxQB; P31650; -.
DR   PaxDb; 10090-ENSMUSP00000032451; -.
DR   PeptideAtlas; P31650; -.
DR   ProteomicsDB; 253388; -.
DR   Pumba; P31650; -.
DR   Antibodypedia; 26041; 169 antibodies from 26 providers.
DR   DNASU; 243616; -.
DR   Ensembl; ENSMUST00000032451.9; ENSMUSP00000032451.7; ENSMUSG00000030307.9.
DR   GeneID; 243616; -.
DR   KEGG; mmu:243616; -.
DR   UCSC; uc009dhs.1; mouse.
DR   AGR; MGI:95630; -.
DR   CTD; 6538; -.
DR   MGI; MGI:95630; Slc6a11.
DR   VEuPathDB; HostDB:ENSMUSG00000030307; -.
DR   eggNOG; KOG3660; Eukaryota.
DR   GeneTree; ENSGT00940000157569; -.
DR   HOGENOM; CLU_006855_9_5_1; -.
DR   InParanoid; P31650; -.
DR   OMA; FLANPWH; -.
DR   OrthoDB; 3084493at2759; -.
DR   PhylomeDB; P31650; -.
DR   TreeFam; TF343812; -.
DR   Reactome; R-MMU-442660; Na+/Cl- dependent neurotransmitter transporters.
DR   Reactome; R-MMU-71288; Creatine metabolism.
DR   Reactome; R-MMU-888593; Reuptake of GABA.
DR   BioGRID-ORCS; 243616; 4 hits in 77 CRISPR screens.
DR   PRO; PR:P31650; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; P31650; Protein.
DR   Bgee; ENSMUSG00000030307; Expressed in lumbar subsegment of spinal cord and 89 other cell types or tissues.
DR   GO; GO:0042995; C:cell projection; ISO:MGI.
DR   GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR   GO; GO:0042734; C:presynaptic membrane; ISO:MGI.
DR   GO; GO:0045202; C:synapse; IDA:SynGO.
DR   GO; GO:0016597; F:amino acid binding; ISO:MGI.
DR   GO; GO:0005283; F:amino acid:sodium symporter activity; IDA:UniProtKB.
DR   GO; GO:0005332; F:gamma-aminobutyric acid:sodium:chloride symporter activity; IDA:UniProtKB.
DR   GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0005369; F:taurine:sodium symporter activity; IDA:UniProtKB.
DR   GO; GO:0015718; P:monocarboxylic acid transport; ISO:MGI.
DR   GO; GO:0006836; P:neurotransmitter transport; ISO:MGI.
DR   GO; GO:0001504; P:neurotransmitter uptake; IDA:SynGO.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR   CDD; cd11508; SLC6sbd_GAT3; 1.
DR   InterPro; IPR000175; Na/ntran_symport.
DR   InterPro; IPR002982; Na/ntran_symport_GABA_GAT3.
DR   InterPro; IPR037272; SNS_sf.
DR   PANTHER; PTHR11616:SF124; SODIUM- AND CHLORIDE-DEPENDENT GABA TRANSPORTER 3; 1.
DR   PANTHER; PTHR11616; SODIUM/CHLORIDE DEPENDENT TRANSPORTER; 1.
DR   Pfam; PF00209; SNF; 1.
DR   PRINTS; PR01197; GAT3TRNSPORT.
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.
DR   Genevisible; P31650; MM.
PE   1: Evidence at protein level;
KW   Cell membrane; Direct protein sequencing; Glycoprotein; Membrane;
KW   Neurotransmitter transport; Phosphoprotein; Reference proteome; Symport;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..627
FT                   /note="Sodium- and chloride-dependent GABA transporter 3"
FT                   /id="PRO_0000214785"
FT   TOPO_DOM        1..53
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        54..74
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        82..101
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        126..146
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        147..220
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        221..239
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        248..265
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        301..318
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        330..351
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        384..403
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        433..451
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        468..488
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        509..528
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        548..566
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        567..627
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..36
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         21
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P31647"
FT   CARBOHYD        182
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        185
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   627 AA;  69961 MW;  7BCCFA2000DB024F CRC64;
     MTAEQALPLG NGKAAEEARG SETLGGGGGG AAGTREARDK AVHERGHWNN KVEFVLSVAG
     EIIGLGNVWR FPYLCYKNGG GAFLIPYVVF FICCGIPVFF LETALGQFTS EGGITCWRRV
     CPLFEGIGYA TQVIEAHLNV YYIIILAWAI FYLSNCFTTE LPWATCGHEW NTEKCVEFQK
     LNFSNYSHVS LQNATSPVME FWERRVLAIS DGIEHIGNLR WELALCLLAA WTICYFCIWK
     GTKSTGKVVY VTATFPYIML LILLIRGVTL PGASEGIKFY LYPDLSRLSD PQVWVDAGTQ
     IFFSYAICLG CLTALGSYNN YNNNCYRDCI MLCCLNSGTS FVAGFAIFSV LGFMAYEQGV
     PIAEVAESGP GLAFIAYPKA VTMMPLSPLW ATLFFMMLIF LGLDSQFVCV ESLVTAVVDM
     YPKVFRRGYR RELLILALSI ISYFLGLVML TEGGMYIFQL FDSYAASGMC LLFVAIFECV
     CIGWVYGSNR FYDNIEDMIG YRPLSLIKWC WKVVTPGICA GIFIFFLVKY KPLKYNNVYT
     YPAWGYGIGW LMALSSMLCI PLWIFIKLWK TEGTLPEKLQ KLTVPSADLK MRGKLGASPR
     TVTVNDCEAK VKGDGTISAI TEKETHF
//