SC6A6_CANLF
ID SC6A6_CANLF Reviewed; 620 AA.
AC Q00589;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Sodium- and chloride-dependent taurine transporter;
DE AltName: Full=Solute carrier family 6 member 6;
GN Name=SLC6A6;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, ACTIVITY REGULATION, AND
RP INDUCTION.
RC STRAIN=Cocker spaniel; TISSUE=Kidney;
RX PubMed=1518851; DOI=10.1073/pnas.89.17.8230;
RA Uchida S., Kwon H.M., Yamauchi A., Preston A.S., Marumo F., Handler J.S.;
RT "Molecular cloning of the cDNA for an MDCK cell Na(+)- and Cl(-)-dependent
RT taurine transporter that is regulated by hypertonicity.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8230-8234(1992).
RN [2]
RP PHOSPHORYLATION AT SER-322, MUTAGENESIS OF SER-45; THR-175; SER-215;
RP THR-242; SER-322 AND THR-581, FUNCTION, TRANSPORTER ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10477138; DOI=10.1681/asn.v1091874;
RA Han X., Budreau A.M., Chesney R.W.;
RT "Ser-322 is a critical site for PKC regulation of the MDCK cell taurine
RT transporter (pNCT).";
RL J. Am. Soc. Nephrol. 10:1874-1879(1999).
CC -!- FUNCTION: Mediates sodium- and chloride-dependent transport of taurine
CC (PubMed:1518851, PubMed:10477138). Can also mediate transport of beta-
CC alanine, hypotaurine and gamma-aminobutyric acid (GABA) (By
CC similarity). {ECO:0000250|UniProtKB:O35316,
CC ECO:0000269|PubMed:10477138, ECO:0000269|PubMed:1518851}.
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:0000250|UniProtKB:O35316};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70688;
CC Evidence={ECO:0000250|UniProtKB:O35316};
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:10477138, ECO:0000269|PubMed:1518851};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71224;
CC Evidence={ECO:0000269|PubMed:1518851};
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
CC hypotaurine and beta-alanine. {ECO:0000269|PubMed:1518851}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12 uM for taurine {ECO:0000269|PubMed:1518851};
CC KM=7.3 uM for taurine {ECO:0000269|PubMed:10477138};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P31641};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Renal cortex and medulla, ileal mucosa, brain,
CC liver and heart. {ECO:0000269|PubMed:1518851}.
CC -!- INDUCTION: Up-regulated in response to hypertonic stress.
CC {ECO:0000269|PubMed:1518851}.
CC -!- PTM: Taurine transport activity is down-regulated upon Ser-322
CC phosphorylation by PKC. {ECO:0000269|PubMed:10477138}.
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; M95495; AAA30876.1; -; mRNA.
DR PIR; A46270; A46270.
DR PIR; A48299; A48299.
DR RefSeq; NP_001003311.1; NM_001003311.1.
DR AlphaFoldDB; Q00589; -.
DR SMR; Q00589; -.
DR STRING; 9615.ENSCAFP00000043856; -.
DR iPTMnet; Q00589; -.
DR PaxDb; Q00589; -.
DR GeneID; 404000; -.
DR CTD; 6533; -.
DR eggNOG; KOG3660; Eukaryota.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; Q00589; -.
DR OMA; WAHCNHT; -.
DR OrthoDB; 250396at2759; -.
DR TreeFam; TF343812; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005332; F:gamma-aminobutyric acid:sodium symporter activity; ISS:UniProtKB.
DR GO; GO:0005369; F:taurine: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 GO; GO:0015734; P:taurine transport; IBA:GO_Central.
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..620
FT /note="Sodium- and chloride-dependent taurine transporter"
FT /id="PRO_0000214766"
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..620
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:0000269|PubMed:10477138"
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 MUTAGEN 45
FT /note="S->A: No effect on taurine uptake; no effect on
FT phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:10477138"
FT MUTAGEN 175
FT /note="T->A: No effect on taurine uptake; no effect on
FT phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:10477138"
FT MUTAGEN 215
FT /note="S->A: No effect on taurine uptake; no effect on
FT phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:10477138"
FT MUTAGEN 242
FT /note="T->A: No effect on taurine uptake; no effect on
FT phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:10477138"
FT MUTAGEN 322
FT /note="S->A: 3-fold activation of taurine uptake; abolishes
FT phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:10477138"
FT MUTAGEN 581
FT /note="T->A: No effect on taurine uptake; no effect on
FT phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:10477138"
SQ SEQUENCE 620 AA; 69729 MW; 4FF74DC06E11D181 CRC64;
MATKEKLQCL KDFHKDILKP SPGKSPGTRP EDEAEGKPPQ REKWSSKIDF VLSVAGGFVG
LGNVWRFPYL CYKNGGGAFL IPYFIFLFGG GLPVFFLEVI IGQYTSEGGI TCWEKICPLF
SGIGYASIVI VSLLNIYYVI ILAWATYYLF QSFQSELPWA HCNHSWNTPQ CMEDTMRKNK
SLWITLSTKN FTSPVTEFWE RNVLSLSSGI DDPGSLKWDL ALCLLLVWLV CFFCIWKGVK
STGKVVYFTA TFPFAMLLVL LVRGLTLPGA GAGIKFYLYP DISRLEDPQV WIDAGTQIFF
SYAICLGAMT SLGSYNKYKY NSYRDCMLLG CLNSGTSFVS GFAIFSILGF MAQEQGVDIA
DVAESGPGLA FIAYPKAVTM MPLPTFWSIL FFIMLLLLGL DSQFVEVEGQ VTSLVDLYPS
FLRKGFRREI FIAFMCSISY LLGLSMVTEG GMYVFQLFDY YAASGVCLLW VAFFECFVIA
WIYGSDNLYD GIEDMIGYRP GPWMKYSWAV VTPVLCVGCF IFSLVKYVPL TYNKVYVYPT
WAIGLGWSLA LSSMMCVPLV MVIRLCQTEG PFLVRLKYLL TPREPNRWAV EREGATPYSS
RLAVNGALMK PTHIIVETMM
