S6A13_RAT
ID S6A13_RAT Reviewed; 602 AA.
AC P31646;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Sodium- and chloride-dependent GABA transporter 2;
DE Short=GAT-2;
DE AltName: Full=Solute carrier family 6 member 13;
GN Name=Slc6a13; Synonyms=Gabt2, Gat-2;
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, TISSUE
RP SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
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 FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, TRANSPORTER ACTIVITY,
RP AND ACTIVITY REGULATION.
RX PubMed=22896705; DOI=10.1074/jbc.m112.368175;
RA Zhou Y., Holmseth S., Guo C., Hassel B., Hofner G., Huitfeldt H.S.,
RA Wanner K.T., Danbolt N.C.;
RT "Deletion of the gamma-aminobutyric acid transporter 2 (GAT2 and SLC6A13)
RT gene in mice leads to changes in liver and brain taurine contents.";
RL J. Biol. Chem. 287:35733-35746(2012).
CC -!- FUNCTION: Mediates sodium- and chloride-dependent transport of gamma-
CC aminobutyric acid (GABA) (PubMed:1400419, PubMed:22896705). Mediates
CC transport of taurine and is the major taurine transporter in
CC hepatocytes (PubMed:22896705). Can also mediate transport of beta-
CC alanine and hypotaurine (By similarity). {ECO:0000250|UniProtKB:P31649,
CC ECO:0000269|PubMed:1400419, ECO:0000269|PubMed:22896705}.
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:22896705};
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:0000269|PubMed:22896705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71224;
CC Evidence={ECO:0000305|PubMed:22896705};
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:P31649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71248;
CC Evidence={ECO:0000250|UniProtKB:P31649};
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:P31649};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71244;
CC Evidence={ECO:0000250|UniProtKB:P31649};
CC -!- ACTIVITY REGULATION: GABA transport is inhibited by beta-alanine, L-
CC 2,4-Diaminobutyric acid, hypotaurine and nipecotic acid
CC (PubMed:1400419, PubMed:22896705). Taurine transport is inhibited by
CC hypotaurine, beta-alanine and nipecotic acid (PubMed:22896705).
CC {ECO:0000269|PubMed:1400419, ECO:0000269|PubMed:22896705}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8 uM for GABA {ECO:0000269|PubMed:1400419};
CC Vmax=2.5 nmol/min/mg enzyme for GABA {ECO:0000269|PubMed:1400419};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22896705};
CC Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:P31649}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Brain, retina, and peripheral tissues. Expressed in
CC hepatocytes (at protein level). {ECO:0000269|PubMed:1400419,
CC ECO:0000269|PubMed:22896705}.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A13 subfamily. {ECO:0000305}.
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DR EMBL; M95762; AAA40602.1; -; mRNA.
DR PIR; A45078; A45078.
DR RefSeq; NP_598307.1; NM_133623.1.
DR RefSeq; XP_006237282.1; XM_006237220.3.
DR RefSeq; XP_006237283.1; XM_006237221.2.
DR AlphaFoldDB; P31646; -.
DR SMR; P31646; -.
DR STRING; 10116.ENSRNOP00000018083; -.
DR BindingDB; P31646; -.
DR ChEMBL; CHEMBL4889; -.
DR DrugCentral; P31646; -.
DR GuidetoPHARMACOLOGY; 930; -.
DR GlyGen; P31646; 4 sites.
DR PaxDb; P31646; -.
DR PRIDE; P31646; -.
DR Ensembl; ENSRNOT00000018083; ENSRNOP00000018083; ENSRNOG00000012876.
DR GeneID; 171163; -.
DR KEGG; rno:171163; -.
DR UCSC; RGD:620788; rat.
DR CTD; 6540; -.
DR RGD; 620788; Slc6a13.
DR eggNOG; KOG3660; Eukaryota.
DR InParanoid; P31646; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P31646; -.
DR TreeFam; TF343812; -.
DR Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-RNO-888593; Reuptake of GABA.
DR PRO; PR:P31646; -.
DR Proteomes; UP000002494; Chromosome 4.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
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:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0005308; F:creatine transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015185; F:gamma-aminobutyric acid transmembrane transporter activity; IDA:ARUK-UCL.
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:0005368; F:taurine transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0005369; F:taurine:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0089718; P:amino acid import across plasma membrane; ISO:RGD.
DR GO; GO:0015881; P:creatine transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:0051939; P:gamma-aminobutyric acid import; IDA:ARUK-UCL.
DR GO; GO:0015718; P:monocarboxylic acid transport; ISO:RGD.
DR GO; GO:0006836; P:neurotransmitter transport; IDA:RGD.
DR GO; GO:0071705; P:nitrogen compound transport; IDA:ARUK-UCL.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0015734; P:taurine transport; IMP:ARUK-UCL.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002981; Na/ntran_symport_GABA_GAT2.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01196; GAT2TRNSPORT.
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; Disulfide bond; Glycoprotein; Membrane;
KW Neurotransmitter transport; Phosphoprotein; Reference proteome; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..602
FT /note="Sodium- and chloride-dependent GABA transporter 2"
FT /id="PRO_0000214794"
FT TOPO_DOM 1..40
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..61
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 121..141
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 142..206
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..227
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..302
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..339
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 366..386
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 418..438
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 453..473
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 490..510
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 528..548
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 549..602
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 587
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P31649"
FT MOD_RES 591
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31649"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 269
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 153..162
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
SQ SEQUENCE 602 AA; 68263 MW; CB7510EFA6ABFE8C CRC64;
MDNRVSGTTS NGETKPVCPV MEKVEEDGTL EREQWTNKME FVLSVAGEII GLGNVWRFPY
LCYKNGGGAF FIPYLIFLFT CGIPVFFLET ALGQYTNQGG ITAWRKICPI FEGIGYASQM
IVSLLNVYYI VVLAWALFYL FSSFTTDLPW GSCSHEWNTE NCVEFQKTNN SLNVTSENAT
SPVIEFWERR VLKISDGIQH LGSLRWELVL CLLLAWIICY FCIWKGVKST GKVVYFTATF
PYLMLVVLLI RGVTLPGAAQ GIQFYLYPNI TRLWDPQVWM DAGTQIFFSF AICLGCLTAL
GSYNKYHNNC YRDCVALCIL NSSTSFVAGF AIFSILGFMS QEQGVPISEV AESGPGLAFI
AYPRAVVMLP FSPLWACCFF FMVVLLGLDS QFVCVESLVT ALVDMYPRVF RKKNRREILI
LIVSVVSFFI GLIMLTEGGM YVFQLFDYYA ASGMCLLFVA IFESLCVAWV YGASRFYDNI
EDMIGYKPWP LIKYCWLFFT PAVCLATFLF SLIKYTPLTY NKKYTYPWWG DALGWLLALS
SMVCIPAWSI YKLRTLKGPL RERLRQLVCP AEDLPQKSQP ELTSPATPMT SLLRLTELES
NC
