ID   S6A11_RAT               Reviewed;         627 AA.
AC   P31647;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   27-MAR-2024, entry version 152.
DE   RecName: Full=Sodium- and chloride-dependent GABA transporter 3;
DE            Short=GAT-3;
DE   AltName: Full=Solute carrier family 6 member 11;
GN   Name=Slc6a11; Synonyms=Gabt3, Gat-3, Gat-b;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=1400419; DOI=10.1016/s0021-9258(19)36802-4;
RA   Borden L.A., Smith K.E., Hartig P.R., Branchek T.A., Weinshank R.L.;
RT   "Molecular heterogeneity of the gamma-aminobutyric acid (GABA) transport
RT   system. Cloning of two novel high affinity GABA transporters from rat
RT   brain.";
RL   J. Biol. Chem. 267:21098-21104(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX   PubMed=1497897; DOI=10.1016/0896-6273(92)90172-a;
RA   Clark J.A., Deutch A.Y., Gallipoli P.Z., Amara S.G.;
RT   "Functional expression and CNS distribution of a beta-alanine-sensitive
RT   neuronal GABA transporter.";
RL   Neuron 9:337-348(1992).
RN   [3]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=8731228;
RX   DOI=10.1002/(sici)1096-9861(19960415)367:4<595::aid-cne9>3.0.co;2-#;
RA   Ribak C.E., Tong W.M., Brecha N.C.;
RT   "GABA plasma membrane transporters, GAT-1 and GAT-3, display different
RT   distributions in the rat hippocampus.";
RL   J. Comp. Neurol. 367:595-606(1996).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Mediates sodium- and chloride-dependent transport of gamma-
CC       aminobutyric acid (GABA) (PubMed:1400419, PubMed:1497897). Can also
CC       mediate transport of beta-alanine and to a lower extent that of taurine
CC       and hypotaurine (By similarity). {ECO:0000250|UniProtKB:P31650,
CC       ECO:0000269|PubMed:1400419, ECO:0000269|PubMed:1497897}.
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:1400419,
CC         ECO:0000269|PubMed:1497897};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70688;
CC         Evidence={ECO:0000305|PubMed:1400419};
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:0000250|UniProtKB:P31650};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71224;
CC         Evidence={ECO:0000250|UniProtKB:P31650};
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:0000250|UniProtKB:P31650};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71248;
CC         Evidence={ECO:0000250|UniProtKB:P31650};
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:0000250|UniProtKB:P31650};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71244;
CC         Evidence={ECO:0000250|UniProtKB:P31650};
CC   -!- ACTIVITY REGULATION: GABA transport is inhibited by beta-alanine.
CC       {ECO:0000269|PubMed:1400419, ECO:0000269|PubMed:1497897}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=12 uM for GABA {ECO:0000269|PubMed:1400419};
CC         KM=2.3 uM for GABA {ECO:0000269|PubMed:1497897};
CC         Vmax=3 nmol/min/mg enzyme for GABA {ECO:0000269|PubMed:1400419};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8731228};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Brain and retina (PubMed:1400419, PubMed:1497897).
CC       Expressed predominantly within neurons (PubMed:1497897). Expressed in
CC       the hippocampus (at protein level) (PubMed:8731228).
CC       {ECO:0000269|PubMed:1400419, ECO:0000269|PubMed:1497897,
CC       ECO:0000269|PubMed:8731228}.
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; M95738; AAA41183.1; -; mRNA.
DR   EMBL; M95763; AAA40607.1; -; mRNA.
DR   EMBL; S42358; AAB22850.1; -; mRNA.
DR   PIR; JH0695; JH0695.
DR   RefSeq; NP_077348.1; NM_024372.2.
DR   AlphaFoldDB; P31647; -.
DR   SMR; P31647; -.
DR   BioGRID; 249422; 2.
DR   IntAct; P31647; 1.
DR   MINT; P31647; -.
DR   STRING; 10116.ENSRNOP00000008342; -.
DR   BindingDB; P31647; -.
DR   ChEMBL; CHEMBL2111478; -.
DR   GlyCosmos; P31647; 3 sites, No reported glycans.
DR   GlyGen; P31647; 3 sites.
DR   iPTMnet; P31647; -.
DR   PhosphoSitePlus; P31647; -.
DR   SwissPalm; P31647; -.
DR   PaxDb; 10116-ENSRNOP00000008342; -.
DR   Ensembl; ENSRNOT00000008342.6; ENSRNOP00000008342.3; ENSRNOG00000005697.6.
DR   Ensembl; ENSRNOT00055013751; ENSRNOP00055011042; ENSRNOG00055008132.
DR   Ensembl; ENSRNOT00060021963; ENSRNOP00060017380; ENSRNOG00060012908.
DR   Ensembl; ENSRNOT00065049209; ENSRNOP00065040353; ENSRNOG00065028538.
DR   GeneID; 79213; -.
DR   KEGG; rno:79213; -.
DR   UCSC; RGD:628737; rat.
DR   AGR; RGD:628737; -.
DR   CTD; 6538; -.
DR   RGD; 628737; Slc6a11.
DR   eggNOG; KOG3660; Eukaryota.
DR   GeneTree; ENSGT00940000157569; -.
DR   HOGENOM; CLU_006855_9_5_1; -.
DR   InParanoid; P31647; -.
DR   OMA; FLANPWH; -.
DR   OrthoDB; 3084493at2759; -.
DR   PhylomeDB; P31647; -.
DR   TreeFam; TF343812; -.
DR   Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
DR   Reactome; R-RNO-71288; Creatine metabolism.
DR   Reactome; R-RNO-888593; Reuptake of GABA.
DR   PRO; PR:P31647; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000005697; Expressed in frontal cortex and 6 other cell types or tissues.
DR   GO; GO:0042995; C:cell projection; IDA:RGD.
DR   GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR   GO; GO:0042734; C:presynaptic membrane; IDA:SynGO.
DR   GO; GO:0045202; C:synapse; ISO:RGD.
DR   GO; GO:0016597; F:amino acid binding; IDA:RGD.
DR   GO; GO:0005283; F:amino acid:sodium symporter activity; ISO:RGD.
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:RGD.
DR   GO; GO:0005369; F:taurine:sodium symporter activity; ISO:RGD.
DR   GO; GO:0015718; P:monocarboxylic acid transport; ISO:RGD.
DR   GO; GO:0006836; P:neurotransmitter transport; IDA:RGD.
DR   GO; GO:0001504; P:neurotransmitter uptake; ISO:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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; P31647; RN.
PE   1: Evidence at protein level;
KW   Cell membrane; Glycoprotein; Membrane; Neurotransmitter transport;
KW   Phosphoprotein; Reference proteome; Symport; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..627
FT                   /note="Sodium- and chloride-dependent GABA transporter 3"
FT                   /id="PRO_0000214786"
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:0007744|PubMed:22673903"
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;  69947 MW;  B0B3CC2F8B6D4327 CRC64;
     MTAEQALPLG NGKAAEEARG SEALGGGGGG 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 VSYFLGLVML TEGGMYIFQL FDSYAASGMC LLFVAIFECV
     CIGWVYGSNR FYDNIEDMIG YRPLSLIKWC WKVVTPGICA GIFIFFLVKY KPLKYNNVYT
     YPAWGYGIGW LMALSSMLCI PLWIFIKLWK TEGTLPEKLQ KLTVPSADLK MRGKLGASPR
     MVTVNDCEAK VKGDGTISAI TEKETHF
//