S6A11_RAT
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 03-AUG-2022, entry version 143.
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) (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; 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 GlyGen; P31647; 3 sites.
DR iPTMnet; P31647; -.
DR PhosphoSitePlus; P31647; -.
DR SwissPalm; P31647; -.
DR PaxDb; P31647; -.
DR PRIDE; P31647; -.
DR Ensembl; ENSRNOT00000008342; ENSRNOP00000008342; ENSRNOG00000005697.
DR GeneID; 79213; -.
DR KEGG; rno:79213; -.
DR UCSC; RGD:628737; rat.
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; NERGMWN; -.
DR OrthoDB; 250396at2759; -.
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 tissues.
DR Genevisible; P31647; RN.
DR GO; GO:0042995; C:cell projection; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0005332; F:gamma-aminobutyric acid:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0042165; F:neurotransmitter binding; IDA:RGD.
DR GO; GO:0005369; F:taurine:sodium symporter activity; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0015718; P:monocarboxylic acid transport; ISO:RGD.
DR GO; GO:0098810; P:neurotransmitter reuptake; IMP:SynGO.
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; 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; 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
