S6A13_MOUSE
ID S6A13_MOUSE Reviewed; 602 AA.
AC P31649;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Sodium- and chloride-dependent GABA transporter 2 {ECO:0000303|PubMed:22896705};
DE Short=GAT-2 {ECO:0000303|PubMed:22896705};
DE AltName: Full=Sodium- and chloride-dependent GABA transporter 3 {ECO:0000303|PubMed:8420981};
DE Short=GAT-3 {ECO:0000303|PubMed:8420981};
DE AltName: Full=Solute carrier family 6 member 13;
GN Name=Slc6a13;
GN Synonyms=Gabt2, Gabt3, Gat-3 {ECO:0000303|PubMed:8420981},
GN Gat2 {ECO:0000303|PubMed:22896705}, Gat3 {ECO:0000303|PubMed:8420981};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=8420981; DOI=10.1016/s0021-9258(18)53968-5;
RA Liu Q.-R., Lopez-Coecuera B., Mandiyan S., Nelson H., Nelson N.;
RT "Molecular characterization of four pharmacologically distinct gamma-
RT aminobutyric acid transporters in mouse brain.";
RL J. Biol. Chem. 268:2106-2112(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney, and Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-587, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-587 AND SER-591, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP TRANSPORTER ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
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).
RN [6]
RP FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=30270321; DOI=10.1248/bpb.b18-00168;
RA Nishimura T., Higuchi K., Yoshida Y., Sugita-Fujisawa Y., Kojima K.,
RA Sugimoto M., Santo M., Tomi M., Nakashima E.;
RT "Hypotaurine Is a Substrate of GABA Transporter Family Members GAT2/Slc6a13
RT and TAUT/Slc6a6.";
RL Biol. Pharm. Bull. 41:1523-1529(2018).
CC -!- FUNCTION: Mediates sodium- and chloride-dependent transport of gamma-
CC aminobutyric acid (GABA) (PubMed:8420981, PubMed:22896705,
CC PubMed:30270321). Can also mediate transport of beta-alanine, taurine
CC and hypotaurine and is the major taurine transporter in hepatocytes
CC (PubMed:8420981, PubMed:22896705, PubMed:30270321).
CC {ECO:0000269|PubMed:22896705, ECO:0000269|PubMed:30270321,
CC ECO:0000269|PubMed:8420981}.
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:22896705,
CC ECO:0000269|PubMed:30270321, ECO:0000269|PubMed:8420981};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70688;
CC Evidence={ECO:0000305|PubMed:8420981};
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, ECO:0000269|PubMed:30270321,
CC ECO:0000269|PubMed:8420981};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71224;
CC Evidence={ECO:0000305|PubMed:8420981};
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:0000269|PubMed:8420981};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71248;
CC Evidence={ECO:0000305|PubMed:8420981};
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:0000269|PubMed:30270321};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71244;
CC Evidence={ECO:0000305|PubMed:30270321};
CC -!- ACTIVITY REGULATION: Gamma-aminobutyric acid (GABA) transport is
CC inhibited by beta-alanine, taurine, hypotaurine, beta-
CC guanidinopropionic acid, 2,3-diaminopropionic acid, guvacine and
CC nipecotic acid (PubMed:8420981, PubMed:22896705). Beta-alanine
CC transport is inhibited by GABA (PubMed:8420981). Taurine transport is
CC inhibited by GABA, beta-alanine, SNAP-5114, nigericin, nipecotic acid
CC and ouabain (PubMed:22896705). {ECO:0000269|PubMed:22896705,
CC ECO:0000269|PubMed:8420981}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18 uM for GABA {ECO:0000269|PubMed:8420981};
CC KM=28 uM for beta-alanine {ECO:0000269|PubMed:8420981};
CC KM=540 uM for taurine {ECO:0000269|PubMed:8420981};
CC KM=210 uM for taurine {ECO:0000269|PubMed:22896705};
CC KM=10.6 uM for hypotaurine {ECO:0000269|PubMed:30270321};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22896705};
CC Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000269|PubMed:22896705}; Multi-pass membrane protein
CC {ECO:0000255}. Note=In the kidney, detected at the basolateral
CC membranes of parts of proximal tubules.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in liver, followed by
CC kidney and leptomeninges, and very low levels in the cerebellum (at
CC protein level). In the brain, detected in some blood vessels (at
CC protein level). In the kidney, expressed in the cortex, including parts
CC of the proximal tubules, but not in the medulla (at protein level). In
CC the liver, highest expression in periportal hepatocytes, with highest
CC density at the vascular side (at protein level). Also detected at low
CC levels in other organs, including skeletal muscle.
CC {ECO:0000269|PubMed:22896705, ECO:0000269|PubMed:8420981}.
CC -!- DEVELOPMENTAL STAGE: Abundant in neonatal brain, but not in adult
CC brain. {ECO:0000269|PubMed:8420981}.
CC -!- DISRUPTION PHENOTYPE: Mutant animals are born at the expected Mendelian
CC ratio. They appear normal, fertile, with a normal life span. Tissue
CC taurine levels are altered, with 50% decrease in the liver and 20%
CC increase in the brain. {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; L04663; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC023117; AAH23117.1; -; mRNA.
DR EMBL; BC029637; AAH29637.1; -; mRNA.
DR CCDS; CCDS20490.1; -.
DR PIR; A44409; A44409.
DR RefSeq; NP_653095.1; NM_144512.2.
DR AlphaFoldDB; P31649; -.
DR SMR; P31649; -.
DR STRING; 10090.ENSMUSP00000066779; -.
DR BindingDB; P31649; -.
DR ChEMBL; CHEMBL5205; -.
DR DrugCentral; P31649; -.
DR TCDB; 2.A.22.3.8; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; P31649; 4 sites.
DR iPTMnet; P31649; -.
DR PhosphoSitePlus; P31649; -.
DR SwissPalm; P31649; -.
DR jPOST; P31649; -.
DR MaxQB; P31649; -.
DR PaxDb; P31649; -.
DR PeptideAtlas; P31649; -.
DR PRIDE; P31649; -.
DR ProteomicsDB; 256908; -.
DR Antibodypedia; 62641; 87 antibodies from 18 providers.
DR DNASU; 14412; -.
DR Ensembl; ENSMUST00000064580; ENSMUSP00000066779; ENSMUSG00000030108.
DR GeneID; 14412; -.
DR KEGG; mmu:14412; -.
DR UCSC; uc009doi.1; mouse.
DR CTD; 6540; -.
DR MGI; MGI:95629; Slc6a13.
DR VEuPathDB; HostDB:ENSMUSG00000030108; -.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000157478; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; P31649; -.
DR OMA; TIWFVSR; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P31649; -.
DR TreeFam; TF343812; -.
DR Reactome; R-MMU-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-MMU-888593; Reuptake of GABA.
DR BioGRID-ORCS; 14412; 0 hits in 71 CRISPR screens.
DR PRO; PR:P31649; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P31649; protein.
DR Bgee; ENSMUSG00000030108; Expressed in meninx of telencephalon and 123 other tissues.
DR ExpressionAtlas; P31649; baseline and differential.
DR Genevisible; P31649; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
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:MGI.
DR GO; GO:0005283; F:amino acid:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0005308; F:creatine transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015185; F:gamma-aminobutyric acid transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005332; F:gamma-aminobutyric acid:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; ISO:MGI.
DR GO; GO:0042165; F:neurotransmitter binding; ISO:MGI.
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:MGI.
DR GO; GO:0015881; P:creatine transmembrane transport; ISO:MGI.
DR GO; GO:0051939; P:gamma-aminobutyric acid import; ISO:MGI.
DR GO; GO:0015718; P:monocarboxylic acid transport; ISO:MGI.
DR GO; GO:0006836; P:neurotransmitter transport; ISO:MGI.
DR GO; GO:0071705; P:nitrogen compound transport; ISO:MGI.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; ISO:MGI.
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_0000214793"
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:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 591
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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; 68285 MW; 372FE77F3126ABEA CRC64;
MENRASGTTS NGETKPVCPA MEKVEEDGTL EREHWNNKME FVLSVAGEII GLGNVWRFPY
LCYKNGGGAF FIPYLIFLFT CGIPVFFLET ALGQYTNQGG ITAWRRICPI FEGIGYASQM
IVSLLNVYYI VVLAWALFYL FSSFTTDLPW GSCSHEWNTE NCVEFQKAND SMNVTSENAT
SPVIEFWERR VLKLSDGIQH LGSLRWELVL CLLLAWIICY FCIWKGVKST GKVVYFTATF
PYLMLVVLLI RGVTLPGAAQ GIQFYLYPNI TRLWDPQVWM DAGTQIFFSF AICLGCLTAL
GSYNKYHNNC YRDCIALCIL NSSTSFMAGF AIFSILGFMS QEQGVPISEV AESGPGLAFI
AYPRAVVMLP FSPLWACCFF FMVVLLGLDS QFVCVESLVT ALVDMYPRVF RKKNRREVLI
LIVSVISFFI GLIMLTEGGM YVFQLFDYYA ASGMCLLFVA IFESLCVAWV YGAGRFYDNI
EDMIGYKPWP LIKYCWLFFT PAVCLATFLF SLIKYTPLTY NKKYTYPWWG DALGWLLALS
SMICIPAWSI YKLRTLKGPL RERLRQLVCP AEDLPQKNQP EPTAPATPMT SLLRLTELES
NC
