SC6A6_MOUSE
ID SC6A6_MOUSE Reviewed; 621 AA.
AC O35316; P31642; Q91WI2;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Sodium- and chloride-dependent taurine transporter;
DE AltName: Full=Solute carrier family 6 member 6;
GN Name=Slc6a6; Synonyms=Taut;
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, TISSUE SPECIFICITY, TRANSPORTER
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=1465453; DOI=10.1073/pnas.89.24.12145;
RA Liu Q.-R., Lopez-Corcuera B., Nelson H., Mandiyan S., Nelson N.;
RT "Cloning and expression of a cDNA encoding the transporter of taurine and
RT beta-alanine in mouse brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:12145-12149(1992).
RN [2]
RP SEQUENCE REVISION.
RA Liu Q.-R., Lopez-Corcuera B., Nelson H., Mandiyan S., Nelson N.;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=9375654; DOI=10.1046/j.1471-4159.1997.69062238.x;
RA Vinnakota S., Qian X., Egal H., Sarthy V., Sarkar H.K.;
RT "Molecular characterization and in situ localization of a mouse retinal
RT taurine transporter.";
RL J. Neurochem. 69:2238-2250(1997).
RN [4]
RP SEQUENCE REVISION.
RA Vinnakota S., Qian X., Egal H., Sarthy V., Sarkar H.K.;
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
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 [7]
RP TISSUE SPECIFICITY.
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 [8]
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 taurine
CC (PubMed:1465453, PubMed:9375654, PubMed:30270321). Can also mediate
CC transport of hypotaurine, beta-alanine and gamma-aminobutyric acid
CC (GABA) (PubMed:1465453, PubMed:9375654, PubMed:30270321).
CC {ECO:0000269|PubMed:1465453, ECO:0000269|PubMed:30270321,
CC ECO:0000269|PubMed:9375654}.
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:30270321,
CC ECO:0000269|PubMed:9375654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70688;
CC Evidence={ECO:0000305|PubMed:30270321};
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:1465453, ECO:0000269|PubMed:30270321,
CC ECO:0000269|PubMed:9375654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71224;
CC Evidence={ECO:0000269|PubMed:1465453};
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:1465453, ECO:0000269|PubMed:9375654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71248;
CC Evidence={ECO:0000305|PubMed:1465453};
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: Taurine tranport activity is inhibited by phorbol
CC 12-myristate 13-acetate, 3-guanidinopropionic acid, L-
CC 2,3- diaminopropionic acid, beta-alanine and hypotaurine.
CC {ECO:0000269|PubMed:1465453, ECO:0000269|PubMed:9375654}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.5 uM for taurine {ECO:0000269|PubMed:1465453};
CC KM=13.2 uM for taurine {ECO:0000269|PubMed:9375654};
CC KM=10.7 uM for hypotaurine {ECO:0000269|PubMed:30270321};
CC KM=56 uM for beta-alanine {ECO:0000269|PubMed:1465453};
CC pH dependence:
CC Optimum pH is 7.5-8.0 (for taurine transport).
CC {ECO:0000269|PubMed:9375654};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P31641};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:1465453, PubMed:22896705).
CC Highly expressed in the ciliary body of the eye (PubMed:9375654).
CC {ECO:0000269|PubMed:1465453, ECO:0000269|PubMed:22896705,
CC ECO:0000269|PubMed:9375654}.
CC -!- PTM: Taurine transport activity is down-regulated upon Ser-322
CC phosphorylation. {ECO:0000250|UniProtKB:Q00589}.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A6 subfamily. {ECO:0000305}.
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DR EMBL; L03292; AAB54039.2; -; mRNA.
DR EMBL; AF020194; AAB70922.2; -; mRNA.
DR EMBL; BC015245; AAH15245.1; -; mRNA.
DR CCDS; CCDS39570.1; -.
DR PIR; A47194; A47194.
DR RefSeq; NP_033346.2; NM_009320.4.
DR RefSeq; XP_006505933.1; XM_006505870.1.
DR RefSeq; XP_006505934.1; XM_006505871.3.
DR AlphaFoldDB; O35316; -.
DR SMR; O35316; -.
DR STRING; 10090.ENSMUSP00000032185; -.
DR GlyGen; O35316; 3 sites.
DR iPTMnet; O35316; -.
DR PhosphoSitePlus; O35316; -.
DR SwissPalm; O35316; -.
DR EPD; O35316; -.
DR jPOST; O35316; -.
DR PaxDb; O35316; -.
DR PeptideAtlas; O35316; -.
DR PRIDE; O35316; -.
DR ProteomicsDB; 255474; -.
DR Antibodypedia; 10999; 169 antibodies from 26 providers.
DR DNASU; 21366; -.
DR Ensembl; ENSMUST00000032185; ENSMUSP00000032185; ENSMUSG00000030096.
DR GeneID; 21366; -.
DR KEGG; mmu:21366; -.
DR UCSC; uc009cyh.2; mouse.
DR CTD; 6533; -.
DR MGI; MGI:98488; Slc6a6.
DR VEuPathDB; HostDB:ENSMUSG00000030096; -.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000154583; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; O35316; -.
DR OMA; WAHCNHT; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; O35316; -.
DR TreeFam; TF343812; -.
DR Reactome; R-MMU-352230; Amino acid transport across the plasma membrane.
DR Reactome; R-MMU-442660; Na+/Cl- dependent neurotransmitter transporters.
DR BioGRID-ORCS; 21366; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Slc6a6; mouse.
DR PRO; PR:O35316; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; O35316; protein.
DR Bgee; ENSMUSG00000030096; Expressed in ciliary body and 270 other tissues.
DR ExpressionAtlas; O35316; baseline and differential.
DR Genevisible; O35316; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
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:0031528; C:microvillus membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0098797; C:plasma membrane protein complex; ISO:MGI.
DR GO; GO:0022858; F:alanine transmembrane transporter activity; ISO:MGI.
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: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:0030977; F:taurine binding; ISO:MGI.
DR GO; GO:0005368; F:taurine transmembrane transporter activity; IDA:MGI.
DR GO; GO:0005369; F:taurine:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0032328; P:alanine transport; ISO:MGI.
DR GO; GO:0089718; P:amino acid import across plasma membrane; ISO:MGI.
DR GO; GO:0051939; P:gamma-aminobutyric acid import; ISO:MGI.
DR GO; GO:0098739; P:import across plasma membrane; ISO:MGI.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:SynGO.
DR GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR GO; GO:0071705; P:nitrogen compound transport; ISO:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; 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; IDA:MGI.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002434; Na/ntran_symport_taurine.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR00176; NANEUSMPORT.
DR PRINTS; PR01200; TAUTRANSPORT.
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..621
FT /note="Sodium- and chloride-dependent taurine transporter"
FT /id="PRO_0000214768"
FT TOPO_DOM 1..49
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 50..70
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 144..215
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..236
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 290..310
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 332..352
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 380..400
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..450
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 465..485
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 508..528
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 545..565
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..621
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..42
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 322
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00589"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 340
FT /note="S -> L (in Ref. 3; AAB70922)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 621 AA; 69856 MW; 4D3E4ACFDB7D7EA2 CRC64;
MATKEKLQCL KDFHKDILKP SPGKSPGTRP EDEADGKPPQ REKWSSKIDF VLSVAGGFVG
LGNVWRFPYL CYKNGGGAFL IPYFIFLFGS GLPVFFLEVI IGQYTSEGGI TCWEKICPLF
SGIGYASIVI VSLLNVYYIV ILAWATYYLF HSFQKDLPWA HCNHSWNTPQ CMEDTLRRNE
SHWVSLSTAN FTSPVIEFWE RNVLSLSSGI DNPGSLKWDL ALCLLLVWLV CFFCIWKGVR
STGKVVYFTA TFPFAMLLVL LVRGLTLPGA GEGIKFYLYP DISRLGDPQV WIDAGTQIFF
SYAICLGAMT SLGSYNKYKY NSYRDCMLLG CLNSGTSFVS GFAIFSILGF MAQEQGVDIA
DVAESGPGLA FIAYPKAVTM MPLPTFWSIL FFIMLLLLGL DSQFVEVEGQ ITSLVDLYPS
FLRKGYRREI FIAILCSISY LLGLTMVTEG GMYVFQLFDY YAASGVCLLW VAFFECFVIA
WIYGGDNLYD GIEDMIGYRP GPWMKYSWAV ITPALCVGCF VFSLVKYVPL TYNKVYRYPD
WAIGLGWGLA LSSMLCIPLV IVILLCRTEG PLRVRIKYLI TPREPNRWAV EREGATPFHS
RVTLMNGALM KPSHVIVETM M
