SC6A1_RAT
ID SC6A1_RAT Reviewed; 599 AA.
AC P23978;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Sodium- and chloride-dependent GABA transporter 1;
DE Short=GAT-1;
DE AltName: Full=Solute carrier family 6 member 1;
GN Name=Slc6a1; Synonyms=Gabt1, Gat-1, Gat1;
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], PARTIAL PROTEIN SEQUENCE, FUNCTION, TRANSPORTER
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=1975955; DOI=10.1126/science.1975955;
RA Guastella J., Nelson N., Nelson H., Czyzyk L., Keynan S., Miedel M.C.,
RA Davidson N., Lester H.A., Kanner B.I.;
RT "Cloning and expression of a rat brain GABA transporter.";
RL Science 249:1303-1306(1990).
RN [2]
RP TOPOLOGY.
RX PubMed=9169433; DOI=10.1074/jbc.272.23.14695;
RA Clark J.A.;
RT "Analysis of the transmembrane topology and membrane assembly of the GAT-1
RT gamma-aminobutyric acid transporter.";
RL J. Biol. Chem. 272:14695-14704(1997).
RN [3]
RP INTERACTION WITH PALS1, AND SUBCELLULAR LOCATION.
RX PubMed=15234345; DOI=10.1016/j.mcn.2004.03.006;
RA McHugh E.M., Zhu W., Milgram S., Mager S.;
RT "The GABA transporter GAT1 and the MAGUK protein Pals1: interaction, uptake
RT modulation, and coexpression in the brain.";
RL Mol. Cell. Neurosci. 26:406-417(2004).
RN [4]
RP FUNCTION, AND TRANSPORTER ACTIVITY.
RX PubMed=18054861; DOI=10.1016/j.neuron.2007.10.021;
RA Wu Y., Wang W., Diez-Sampedro A., Richerson G.B.;
RT "Nonvesicular inhibitory neurotransmission via reversal of the GABA
RT transporter GAT-1.";
RL Neuron 56:851-865(2007).
RN [5]
RP FUNCTION, AND TRANSPORTER ACTIVITY.
RX PubMed=21775701; DOI=10.1152/ajpcell.00120.2011;
RA Bertram S., Cherubino F., Bossi E., Castagna M., Peres A.;
RT "GABA reverse transport by the neuronal cotransporter GAT1: influence of
RT internal chloride depletion.";
RL Am. J. Physiol. 301:C1064-C1073(2011).
RN [6]
RP IDENTIFICATION BY 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 transport of gamma-aminobutyric acid (GABA) together
CC with sodium and chloride and is responsible for the reuptake of GABA
CC from the synapse (PubMed:1975955, PubMed:18054861). The translocation
CC of GABA, however, may also occur in the reverse direction leading to
CC the release of GABA (PubMed:18054861, PubMed:21775701). The direction
CC and magnitude of GABA transport is a consequence of the prevailing
CC thermodynamic conditions, determined by membrane potential and the
CC intracellular and extracellular concentrations of Na(+), Cl(-) and GABA
CC (PubMed:18054861, PubMed:21775701). Also mediates sodium- and chloride-
CC dependent transport of hypotaurine (By similarity).
CC {ECO:0000250|UniProtKB:P31648, ECO:0000269|PubMed:18054861,
CC ECO:0000269|PubMed:1975955, ECO:0000269|PubMed:21775701}.
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:18054861,
CC ECO:0000269|PubMed:1975955, ECO:0000269|PubMed:21775701};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70688;
CC Evidence={ECO:0000305|PubMed:1975955};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70689;
CC Evidence={ECO:0000305|PubMed:18054861, ECO:0000305|PubMed:21775701};
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:P31648};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71244;
CC Evidence={ECO:0000250|UniProtKB:P31648};
CC -!- ACTIVITY REGULATION: Inhibited by nipecotic acid, cis-3-
CC aminocyclohexane carboxylic acid and 2,4-diaminobutyric acid.
CC {ECO:0000269|PubMed:1975955}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.4 uM for GABA {ECO:0000269|PubMed:1975955};
CC -!- SUBUNIT: Interacts (via PDZ domain-binding motif) with PALS1;
CC interaction increases SLC6A1-mediated GABA uptake.
CC {ECO:0000269|PubMed:15234345}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15234345};
CC Multi-pass membrane protein {ECO:0000255}. Presynapse
CC {ECO:0000250|UniProtKB:P31648}. Note=Localized at the presynaptic
CC terminals of interneurons. {ECO:0000250|UniProtKB:P31648}.
CC -!- TISSUE SPECIFICITY: Brain. {ECO:0000269|PubMed:1975955}.
CC -!- MISCELLANEOUS: This protein is the target of psychomotor stimulants
CC such as amphetamines or cocaine.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A1 subfamily. {ECO:0000305}.
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DR EMBL; M59742; AAA63487.1; -; mRNA.
DR PIR; A35918; ACRTGT.
DR RefSeq; NP_077347.1; NM_024371.2.
DR RefSeq; XP_006237121.1; XM_006237059.2.
DR RefSeq; XP_006237122.1; XM_006237060.3.
DR AlphaFoldDB; P23978; -.
DR SMR; P23978; -.
DR BioGRID; 249421; 2.
DR STRING; 10116.ENSRNOP00000009705; -.
DR BindingDB; P23978; -.
DR ChEMBL; CHEMBL4054; -.
DR DrugCentral; P23978; -.
DR GlyGen; P23978; 3 sites.
DR iPTMnet; P23978; -.
DR PhosphoSitePlus; P23978; -.
DR SwissPalm; P23978; -.
DR PaxDb; P23978; -.
DR PRIDE; P23978; -.
DR Ensembl; ENSRNOT00000009705; ENSRNOP00000009705; ENSRNOG00000006527.
DR GeneID; 79212; -.
DR KEGG; rno:79212; -.
DR UCSC; RGD:620533; rat.
DR CTD; 6529; -.
DR RGD; 620533; Slc6a1.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000156027; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; P23978; -.
DR OMA; GMATFIF; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P23978; -.
DR TreeFam; TF343812; -.
DR Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-RNO-888593; Reuptake of GABA.
DR PRO; PR:P23978; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000006527; Expressed in Ammon's horn and 4 other tissues.
DR Genevisible; P23978; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0009986; C:cell surface; 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:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0015185; F:gamma-aminobutyric acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0005332; F:gamma-aminobutyric acid:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0015378; F:sodium:chloride symporter activity; ISO:RGD.
DR GO; GO:0008306; P:associative learning; ISO:RGD.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:RGD.
DR GO; GO:0051939; P:gamma-aminobutyric acid import; IDA:RGD.
DR GO; GO:0098658; P:inorganic anion import across plasma membrane; ISO:RGD.
DR GO; GO:0007612; P:learning; IMP:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:0032229; P:negative regulation of synaptic transmission, GABAergic; IMP:RGD.
DR GO; GO:0098810; P:neurotransmitter reuptake; IMP:SynGO.
DR GO; GO:0014054; P:positive regulation of gamma-aminobutyric acid secretion; IMP:RGD.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0042220; P:response to cocaine; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0010035; P:response to inorganic substance; ISO:RGD.
DR GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IMP:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
DR GO; GO:0014074; P:response to purine-containing compound; IMP:RGD.
DR GO; GO:0009744; P:response to sucrose; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IMP:RGD.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0050808; P:synapse organization; ISO:RGD.
DR CDD; cd11506; SLC6sbd_GAT1; 1.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002980; Na/ntran_symport_GABA_GAT1.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01195; GAT1TRNSPORT.
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; Cell projection; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Membrane; Metal-binding; Neurotransmitter transport;
KW Phosphoprotein; Reference proteome; Sodium; Symport; Synapse;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..599
FT /note="Sodium- and chloride-dependent GABA transporter 1"
FT /id="PRO_0000214746"
FT TOPO_DOM 1..52
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 53..73
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..80
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 81..100
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 101..123
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 124..144
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..211
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 212..230
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 239..256
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..291
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 292..309
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 310..320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 321..342
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 343..374
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 375..394
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 395..421
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 422..440
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 441..456
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 457..477
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 478..497
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 498..517
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 518..535
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:9169433"
FT TRANSMEM 536..554
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 555..599
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:9169433"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 577..599
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 597..599
FT /note="PDZ-binding"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 59
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 61
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 62
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 66
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 295
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 327
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 392
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 395
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 396
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31648"
FT MOD_RES 591
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31648"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 164..173
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
SQ SEQUENCE 599 AA; 67001 MW; 4FEF85092DC1D045 CRC64;
MATDNSKVAD GQISTEVSEA PVASDKPKTL VVKVQKKAGD LPDRDTWKGR FDFLMSCVGY
AIGLGNVWRF PYLCGKNGGG AFLIPYFLTL IFAGVPLFLL ECSLGQYTSI GGLGVWKLAP
MFKGVGLAAA VLSFWLNIYY IVIISWAIYY LYNSFTTTLP WKQCDNPWNT DRCFSNYSLV
NTTNMTSAVV EFWERNMHQM TDGLDKPGQI RWPLAITLAI AWVLVYFCIW KGVGWTGKVV
YFSATYPYIM LIILFFRGVT LPGAKEGILF YITPNFRKLS DSEVWLDAAT QIFFSYGLGL
GSLIALGSYN SFHNNVYRDS IIVCCINSCT SMFAGFVIFS IVGFMAHVTK RSIADVAASG
PGLAFLAYPE AVTQLPISPL WAILFFSMLL MLGIDSQFCT VEGFITALVD EYPRLLRNRR
ELFIAAVCIV SYLIGLSNIT QGGIYVFKLF DYYSASGMSL LFLVFFECVS ISWFYGVNRF
YDNIQEMVGS RPCIWWKLCW SFFTPIIVAG VFLFSAVQMT PLTMGSYVFP KWGQGVGWLM
ALSSMVLIPG YMAYMFLTLK GSLKQRLQVM IQPSEDIVRP ENGPEQPQAG SSASKEAYI
