S6A11_MOUSE
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 03-AUG-2022, entry version 152.
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,
GN Gat4 {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) (TC
CC 2.A.22) family. SLC6A11 subfamily. {ECO:0000305}.
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; 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; 2.
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 GlyGen; P31650; 3 sites.
DR iPTMnet; P31650; -.
DR PhosphoSitePlus; P31650; -.
DR SwissPalm; P31650; -.
DR jPOST; P31650; -.
DR MaxQB; P31650; -.
DR PaxDb; P31650; -.
DR PeptideAtlas; P31650; -.
DR PRIDE; P31650; -.
DR ProteomicsDB; 253388; -.
DR Antibodypedia; 26041; 133 antibodies from 26 providers.
DR DNASU; 243616; -.
DR Ensembl; ENSMUST00000032451; ENSMUSP00000032451; ENSMUSG00000030307.
DR GeneID; 243616; -.
DR KEGG; mmu:243616; -.
DR UCSC; uc009dhs.1; mouse.
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; NERGMWN; -.
DR OrthoDB; 250396at2759; -.
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 72 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 88 other tissues.
DR Genevisible; P31650; MM.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0005283; F:amino acid:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0005332; F:gamma-aminobutyric acid:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; ISO:MGI.
DR GO; GO:0042165; F:neurotransmitter binding; ISO:MGI.
DR GO; GO:0005369; F:taurine:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0015718; P:monocarboxylic acid transport; ISO:MGI.
DR GO; GO:0098810; P:neurotransmitter reuptake; ISO:MGI.
DR GO; GO:0006836; P:neurotransmitter transport; ISO:MGI.
DR GO; GO:0001504; P:neurotransmitter uptake; IMP: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; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01197; GAT3TRNSPORT.
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 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
