SC6A6_RAT
ID SC6A6_RAT Reviewed; 621 AA.
AC P31643;
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 taurine transporter;
DE AltName: Full=Solute carrier family 6 member 6;
GN Name=Slc6a6;
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], TISSUE SPECIFICITY, FUNCTION, TRANSPORTER
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=1435737;
RA Smith K.E., Borden L.A., Wang C.H.D., Hartig P.R., Branchek T.A.,
RA Weinshank R.L.;
RT "Cloning and expression of a high affinity taurine transporter from rat
RT brain.";
RL Mol. Pharmacol. 42:563-569(1992).
RN [2]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=18501699; DOI=10.1016/j.bbamem.2008.04.012;
RA Tomi M., Tajima A., Tachikawa M., Hosoya K.;
RT "Function of taurine transporter (Slc6a6/TauT) as a GABA transporting
RT protein and its relevance to GABA transport in rat retinal capillary
RT endothelial cells.";
RL Biochim. Biophys. Acta 1778:2138-2142(2008).
RN [3]
RP FUNCTION, AND TRANSPORTER ACTIVITY.
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 taurine
CC (PubMed:1435737, PubMed:18501699, PubMed:22896705). Mediates transport
CC of gamma-aminobutyric acid (GABA) (PubMed:18501699). Can also mediate
CC transport of beta-alanine and hypotaurine (By similarity).
CC {ECO:0000250|UniProtKB:O35316, ECO:0000269|PubMed:1435737,
CC ECO:0000269|PubMed:18501699, 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:18501699};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70688;
CC Evidence={ECO:0000305|PubMed:18501699};
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:1435737, ECO:0000269|PubMed:18501699,
CC ECO:0000269|PubMed:22896705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71224;
CC Evidence={ECO:0000305|PubMed:1435737};
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:O35316};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71248;
CC Evidence={ECO:0000250|UniProtKB:O35316};
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:O35316};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71244;
CC Evidence={ECO:0000250|UniProtKB:O35316};
CC -!- ACTIVITY REGULATION: Taurine transport activity is inhibited by beta-
CC alanine and gamma-aminobutyric acid (GABA) (PubMed:1435737). GABA
CC transport activity is inhibited by taurine and beta-alanine
CC (PubMed:18501699). {ECO:0000269|PubMed:1435737,
CC ECO:0000269|PubMed:18501699}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=43 uM for taurine {ECO:0000269|PubMed:1435737};
CC KM=2.0 mM for GABA {ECO:0000269|PubMed:18501699};
CC Vmax=0.96 nmol/min/mg enzyme for taurine
CC {ECO:0000269|PubMed:1435737};
CC Vmax=5.8 pmol/min/mg enzyme for GABA {ECO:0000269|PubMed:18501699};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18501699};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Brain and peripheral tissues.
CC {ECO:0000269|PubMed:1435737}.
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; M96601; AAA42304.1; -; mRNA.
DR PIR; I57939; I57939.
DR RefSeq; NP_058902.1; NM_017206.1.
DR RefSeq; XP_006236965.1; XM_006236903.3.
DR AlphaFoldDB; P31643; -.
DR SMR; P31643; -.
DR STRING; 10116.ENSRNOP00000012875; -.
DR GlyGen; P31643; 4 sites.
DR iPTMnet; P31643; -.
DR PhosphoSitePlus; P31643; -.
DR PaxDb; P31643; -.
DR PRIDE; P31643; -.
DR Ensembl; ENSRNOT00000012875; ENSRNOP00000012875; ENSRNOG00000009019.
DR GeneID; 29464; -.
DR KEGG; rno:29464; -.
DR CTD; 6533; -.
DR RGD; 61912; Slc6a6.
DR eggNOG; KOG3660; Eukaryota.
DR GeneTree; ENSGT00940000154583; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; P31643; -.
DR PhylomeDB; P31643; -.
DR TreeFam; TF343812; -.
DR Reactome; R-RNO-352230; Amino acid transport across the plasma membrane.
DR Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
DR PRO; PR:P31643; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000009019; Expressed in lung and 19 other tissues.
DR ExpressionAtlas; P31643; baseline and differential.
DR Genevisible; P31643; RN.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:ARUK-UCL.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:RGD.
DR GO; GO:0031528; C:microvillus membrane; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0098797; C:plasma membrane protein complex; IPI:ARUK-UCL.
DR GO; GO:0022858; F:alanine transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0001761; F:beta-alanine transmembrane transporter activity; ISO:RGD.
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:0030977; F:taurine binding; IDA:RGD.
DR GO; GO:0005368; F:taurine transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0005369; F:taurine:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0032328; P:alanine transport; ISO:RGD.
DR GO; GO:0089718; P:amino acid import across plasma membrane; ISO:RGD.
DR GO; GO:0001762; P:beta-alanine transport; ISO:RGD.
DR GO; GO:0051939; P:gamma-aminobutyric acid import; IDA:ARUK-UCL.
DR GO; GO:0098739; P:import across plasma membrane; IGI:ARUK-UCL.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:RGD.
DR GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR GO; GO:0071705; P:nitrogen compound transport; ISO:RGD.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
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; IDA:ARUK-UCL.
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_0000214769"
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 78..97
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..217
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..236
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..262
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..315
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 327..348
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..400
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..448
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TRANSMEM 465..485
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TRANSMEM 506..525
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TRANSMEM 545..563
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 564..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 CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 621 AA; 69869 MW; EA5613F20DC5C7CD CRC64;
MATKEKLQCL KDFHKDILKP SPGKSPGTRP EDEADGKPPQ REKWSSKIDF VLSVAGGFVG
LGNVWRFPYL CYKNGGGAFL IPYFIFLFGS GLPVFFLEVI IGQYTSEGGI TCWEKICPLF
SGIGYASIVI VSLLNVYYIV ILAWATYYLF QSFQKDLPWA HCNHSWNTPQ CMEDTLRRNE
SHWVSLSAAN FTSPVIEFWE RNVLSLSSGI DHPGSLKWDL ALCLLLVWLV CFFCIWKGVR
STGKVVYFTA TFPFAMLLVL LVRGLTLPGA GEGIKFYLYP NISRLEDPQV WIDAGTQIFF
SYAICLGAMT SLGSYNKYKY NSYRDCMLLG CLNSGTSFVS GFAIFSILGF MAQEQGVDIA
DVAESGPGLA FIAYPKAVTM MPLPTFWSIL FFIMLLLLGL DSQFVEVEGQ ITSLVDLYPS
FLRKGYRREI FIAIVCSISY LLGLTMVTEG GMYVFQLFDY YAASGVCLLW VAFFECFVIA
WIYGGDNLYD GIEDMIGYRP GPWMKYSWAV ITPALCVGCF IFSLVKYVPL TYNKVYRYPD
WAIGLGWGLA LSSMVCIPLV IVILLCRTEG PLRVRIKYLI TPREPNRWAV EREGATPFHS
RATLMNGALM KPSHVIVETM M
