SC6A1_MUSCO
ID SC6A1_MUSCO Reviewed; 598 AA.
AC P48057;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 88.
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 Mus cookii (Cook's mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10098;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC TISSUE=Retina;
RX PubMed=7960586;
RA Ruiz M., Egal H., Sarthy V.P., Qian X.J., Sarkar H.K.;
RT "Cloning, expression, and localization of a mouse retinal gamma-
RT aminobutyric acid transporter.";
RL Invest. Ophthalmol. Vis. Sci. 35:4039-4048(1994).
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:7960586). The translocation of GABA, however,
CC may also occur in the reverse direction leading to the release of GABA
CC (By similarity). The direction and magnitude of GABA transport is a
CC consequence of the prevailing thermodynamic conditions, determined by
CC membrane potential and the intracellular and extracellular
CC concentrations of Na(+), Cl(-) and GABA (By similarity). Can also
CC mediate sodium- and chloride-dependent transport of hypotaurine but to
CC a much lower extent as compared to GABA (By similarity).
CC {ECO:0000250|UniProtKB:P23978, ECO:0000250|UniProtKB:P31648,
CC ECO:0000269|PubMed:7960586}.
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:7960586};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70688;
CC Evidence={ECO:0000305|PubMed:7960586};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70689;
CC Evidence={ECO:0000250|UniProtKB:P23978};
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 L-diaminobutyric acid, guvacine, cis-
CC 4-hydroxynipecotic acid, nipecotic acid, and 4,5,6,7-
CC tetrahydroisoxazolo [4,5c]-pyridin-3-ol. {ECO:0000269|PubMed:7960586}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.3 uM for GABA {ECO:0000269|PubMed:7960586};
CC -!- SUBUNIT: Interacts (via PDZ domain-binding motif) with PALS1;
CC interaction increases SLC6A1-mediated GABA uptake.
CC {ECO:0000250|UniProtKB:P31648}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P23978};
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: Retinal neurons. {ECO:0000269|PubMed:7960586}.
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; L32178; AAA37663.1; -; mRNA.
DR AlphaFoldDB; P48057; -.
DR SMR; P48057; -.
DR PRIDE; P48057; -.
DR MGI; MGI:95627; Slc6a1.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005332; F:gamma-aminobutyric acid:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
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; Glycoprotein; Membrane;
KW Neurotransmitter transport; Phosphoprotein; Symport; Synapse;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..598
FT /note="Sodium- and chloride-dependent GABA transporter 1"
FT /id="PRO_0000214745"
FT TOPO_DOM 1..52
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 53..73
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..80
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 81..100
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 101..123
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 124..144
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..211
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 212..229
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 238..255
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 256..290
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 291..308
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 320..341
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 342..373
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 374..393
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 394..420
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 421..439
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 440..455
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 456..476
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 477..496
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 497..516
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 517..534
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT TRANSMEM 535..553
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 554..598
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P23978"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 576..598
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 596..598
FT /note="PDZ-binding"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31648"
FT MOD_RES 590
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"
SQ SEQUENCE 598 AA; 66783 MW; 78FEC99402EC71C3 CRC64;
MATDNSKVAD GQISTEVSEA PVASDKPKTL VVKVQKKAGD LPDRDTWKGR FDFLMSCVGY
AIGLGNVWRF PYLCGKNGGG AFLIPYFLTL IFAGVPLFLL ECSLGQYTSI GGLGVWNVAP
MFKGVGLAAA VLSFWLNIYY IVIISWAIYY LYNSFTTTLP WKQCDNPWNT DRCFSNYSLV
NTTNMTSAVV EFWERNMHQM TDGLDKPGQI RCLAITLAIA WVLVYFCIWK GVGWTGKVVY
FSATYPYIML IILFFRGVTL PGAKEGILFY ITPNFRKLSD SEVWLDAATQ IFFSYGLGLG
SLIALGSYNS FHNNVYRDSI IVCCINSCTS MFAGFVIFSI VGFMAHVTKR SIADVAASGP
GLAFLAYPEA VTQLPISPLW AILFFSMLLM LGIDSQFCTV EGFITALVDE YSRLLRNRRE
LFIAAVCIVS YLIGLSNITQ GGIYVFKLFD YYSASGMSLL FLVFFECVSI SWFYGVNRFY
DNIQEMVGSR PCIWWKLCWS FFTPIIVAGV FLFSAVQMTP LTMGSYVFPK WGQGVGWLMA
LSSMVLIPGY MAYMFLTLKG SLKQRLQVMI QPSEDIVRPE NGPEQPQAGS SASKEAYI
