ID   S22A6_BOVIN             Reviewed;         549 AA.
AC   Q864Z3; A7E342;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   18-MAR-2008, sequence version 2.
DT   08-NOV-2023, entry version 118.
DE   RecName: Full=Solute carrier family 22 member 6 {ECO:0000250|UniProtKB:Q4U2R8};
DE   AltName: Full=Organic anion transporter 1 {ECO:0000250|UniProtKB:Q4U2R8};
DE   AltName: Full=Renal organic anion transporter 1 {ECO:0000250|UniProtKB:Q4U2R8};
DE            Short=ROAT1;
GN   Name=SLC22A6 {ECO:0000250|UniProtKB:Q4U2R8}; Synonyms=OAT1;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Kidney;
RA   Geyer J., Petzinger E.;
RT   "Cloning of the organic anion transporter 1 from bovine kidney.";
RL   Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA   Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA   Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT   "Characterization of 954 bovine full-CDS cDNA sequences.";
RL   BMC Genomics 6:166-166(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=Hereford; TISSUE=Kidney;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Secondary active transporter that functions as a Na(+)-
CC       independent organic anion (OA)/dicarboxylate antiporter where the
CC       uptake of one molecule of OA into the cell is coupled with an efflux of
CC       one molecule of intracellular dicarboxylate such as 2-oxoglutarate or
CC       glutarate. Mediates the uptake of OA across the basolateral side of
CC       proximal tubule epithelial cells, thereby contributing to the renal
CC       elimination of endogenous OA from the systemic circulation into the
CC       urine. Functions as a biopterin transporters involved in the uptake and
CC       the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin
CC       (BH2) and sepiapterin to urine, thereby determining baseline levels of
CC       blood biopterins. Transports prostaglandin E2 (PGE2) and prostaglandin
CC       F2-alpha (PGF2-alpha) and may contribute to their renal excretion (By
CC       similarity). Also mediates the uptake of cyclic nucleotides such as
CC       cAMP and cGMP (By similarity). Involved in the transport of neuroactive
CC       tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may
CC       contribute to their secretion from the brain. May transport glutamate.
CC       Also involved in the disposition of uremic toxins and potentially toxic
CC       xenobiotics by the renal organic anion secretory pathway, helping
CC       reduce their undesired toxicological effects on the body. Uremic toxins
CC       include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA),
CC       indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate
CC       (CMPF) and urate. Xenobiotics include the mycotoxin ochratoxin (OTA).
CC       May also contribute to the transport of organic compounds in testes
CC       across the blood-testis-barrier (By similarity).
CC       {ECO:0000250|UniProtKB:O35956, ECO:0000250|UniProtKB:Q4U2R8}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin(out) + a
CC         dicarboxylate(in) = (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin(in) +
CC         a dicarboxylate(out); Xref=Rhea:RHEA:76071, ChEBI:CHEBI:28965,
CC         ChEBI:CHEBI:59560; Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a dicarboxylate(in) + L-erythro-7,8-dihydrobiopterin(out) = a
CC         dicarboxylate(out) + L-erythro-7,8-dihydrobiopterin(in);
CC         Xref=Rhea:RHEA:76075, ChEBI:CHEBI:28965, ChEBI:CHEBI:43029;
CC         Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a dicarboxylate(in) + L-sepiapterin(out) = a
CC         dicarboxylate(out) + L-sepiapterin(in); Xref=Rhea:RHEA:76079,
CC         ChEBI:CHEBI:28965, ChEBI:CHEBI:194527;
CC         Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a dicarboxylate(in) + prostaglandin F2alpha(out) = a
CC         dicarboxylate(out) + prostaglandin F2alpha(in); Xref=Rhea:RHEA:76119,
CC         ChEBI:CHEBI:28965, ChEBI:CHEBI:57404;
CC         Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a dicarboxylate(in) + prostaglandin E2(out) = a
CC         dicarboxylate(out) + prostaglandin E2(in); Xref=Rhea:RHEA:76123,
CC         ChEBI:CHEBI:28965, ChEBI:CHEBI:606564;
CC         Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3',5'-cyclic AMP(out) + a dicarboxylate(in) = 3',5'-cyclic
CC         AMP(in) + a dicarboxylate(out); Xref=Rhea:RHEA:76127,
CC         ChEBI:CHEBI:28965, ChEBI:CHEBI:58165;
CC         Evidence={ECO:0000250|UniProtKB:O35956};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3',5'-cyclic GMP(out) + a dicarboxylate(in) = 3',5'-cyclic
CC         GMP(in) + a dicarboxylate(out); Xref=Rhea:RHEA:76131,
CC         ChEBI:CHEBI:28965, ChEBI:CHEBI:57746;
CC         Evidence={ECO:0000250|UniProtKB:O35956};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a dicarboxylate(in) + urate(out) = a dicarboxylate(out) +
CC         urate(in); Xref=Rhea:RHEA:76135, ChEBI:CHEBI:17775,
CC         ChEBI:CHEBI:28965; Evidence={ECO:0000250|UniProtKB:O35956};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glutarate(in) + kynurenate(out) = glutarate(out) +
CC         kynurenate(in); Xref=Rhea:RHEA:75999, ChEBI:CHEBI:30921,
CC         ChEBI:CHEBI:58454; Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(indol-3-yl)acetate(out) + a dicarboxylate(in) = (indol-3-
CC         yl)acetate(in) + a dicarboxylate(out); Xref=Rhea:RHEA:75983,
CC         ChEBI:CHEBI:28965, ChEBI:CHEBI:30854;
CC         Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a dicarboxylate(in) + indoxyl sulfate(out) = a
CC         dicarboxylate(out) + indoxyl sulfate(in); Xref=Rhea:RHEA:75987,
CC         ChEBI:CHEBI:28965, ChEBI:CHEBI:144643;
CC         Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a dicarboxylate(in) + N-benzoylglycine(out) = a
CC         dicarboxylate(out) + N-benzoylglycine(in); Xref=Rhea:RHEA:75991,
CC         ChEBI:CHEBI:28965, ChEBI:CHEBI:606565;
CC         Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3-carboxy-4-methyl-5-propyl-2-furanpropanoate(out) + a
CC         dicarboxylate(in) = 3-carboxy-4-methyl-5-propyl-2-furanpropanoate(in)
CC         + a dicarboxylate(out); Xref=Rhea:RHEA:75995, ChEBI:CHEBI:28965,
CC         ChEBI:CHEBI:194524; Evidence={ECO:0000250|UniProtKB:Q4U2R8};
CC   -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC       {ECO:0000250|UniProtKB:Q4U2R8}; Multi-pass membrane protein
CC       {ECO:0000305}. Basal cell membrane {ECO:0000250|UniProtKB:Q4U2R8};
CC       Multi-pass membrane protein {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q864Z3-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q864Z3-2; Sequence=VSP_032167;
CC   -!- DOMAIN: Multiple cysteine residues are necessary for proper targeting
CC       to the plasma membrane. {ECO:0000250|UniProtKB:Q8VC69}.
CC   -!- PTM: Glycosylated. Glycosylation is necessary for proper targeting of
CC       the transporter to the plasma membrane. {ECO:0000250|UniProtKB:Q4U2R8}.
CC   -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily.
CC       Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}.
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DR   EMBL; AJ549816; CAD71145.1; -; mRNA.
DR   EMBL; BT021760; AAX46607.1; -; mRNA.
DR   EMBL; BC151704; AAI51705.1; -; mRNA.
DR   RefSeq; NP_001001143.1; NM_001001143.2.
DR   AlphaFoldDB; Q864Z3; -.
DR   SMR; Q864Z3; -.
DR   STRING; 9913.ENSBTAP00000018132; -.
DR   GlyCosmos; Q864Z3; 3 sites, No reported glycans.
DR   PaxDb; 9913-ENSBTAP00000018132; -.
DR   GeneID; 407180; -.
DR   KEGG; bta:407180; -.
DR   CTD; 9356; -.
DR   eggNOG; KOG0255; Eukaryota.
DR   InParanoid; Q864Z3; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0009925; C:basal plasma membrane; ISS:UniProtKB.
DR   GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0015139; F:alpha-ketoglutarate transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0015297; F:antiporter activity; ISS:UniProtKB.
DR   GO; GO:0008514; F:organic anion transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0015132; F:prostaglandin transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0015347; F:sodium-independent organic anion transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0005452; F:solute:inorganic anion antiporter activity; ISS:UniProtKB.
DR   GO; GO:0022857; F:transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0042910; F:xenobiotic transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0015742; P:alpha-ketoglutarate transport; ISS:UniProtKB.
DR   GO; GO:0015711; P:organic anion transport; ISS:UniProtKB.
DR   GO; GO:0015732; P:prostaglandin transport; ISS:UniProtKB.
DR   GO; GO:0097254; P:renal tubular secretion; ISS:UniProtKB.
DR   CDD; cd17446; MFS_SLC22A6_OAT1_like; 1.
DR   Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1.
DR   InterPro; IPR020846; MFS_dom.
DR   InterPro; IPR005828; MFS_sugar_transport-like.
DR   InterPro; IPR036259; MFS_trans_sf.
DR   InterPro; IPR004749; Orgcat_transp/SVOP.
DR   NCBIfam; TIGR00898; 2A0119; 1.
DR   PANTHER; PTHR24064; SOLUTE CARRIER FAMILY 22 MEMBER; 1.
DR   PANTHER; PTHR24064:SF294; SOLUTE CARRIER FAMILY 22 MEMBER 6; 1.
DR   Pfam; PF00083; Sugar_tr; 1.
DR   SUPFAM; SSF103473; MFS general substrate transporter; 1.
DR   PROSITE; PS50850; MFS; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cell membrane; Glycoprotein; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..549
FT                   /note="Solute carrier family 22 member 6"
FT                   /id="PRO_0000324165"
FT   TOPO_DOM        1..23
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        24..44
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        45..135
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        136..156
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        157..164
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        165..185
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        186..195
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        196..216
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        217..224
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        225..245
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        246..248
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        249..269
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        270..337
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        338..358
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        359..368
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        369..389
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        390..395
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        396..416
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        417..425
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        426..446
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        447..456
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        457..477
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        478..484
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        485..505
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        506..549
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          521..549
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        534..549
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        56
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        92
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        113
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..130
FT                   /note="MAFNDLLLQLGGVGRFQKIQVTLVILPLILLASHNTLQNFTAAIPTHHCRPP
FT                   ADTNLSEDGDLEAWLPRDGQGRPESCLLFTSPQRGPPFPNGTETNGTGATEPCPHGWIY
FT                   DNSTFPSTIVTEWDLVCSH -> MGRGGPSPASSSPPPSGDRPFPMAQRPTAQGPQSPV
FT                   PTAGSTTTAPSLPPSSL (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_032167"
FT   CONFLICT        162
FT                   /note="R -> Q (in Ref. 1; CAD71145 and 2; AAX46607)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   549 AA;  60184 MW;  8D4793CC3C408B69 CRC64;
     MAFNDLLLQL GGVGRFQKIQ VTLVILPLIL LASHNTLQNF TAAIPTHHCR PPADTNLSED
     GDLEAWLPRD GQGRPESCLL FTSPQRGPPF PNGTETNGTG ATEPCPHGWI YDNSTFPSTI
     VTEWDLVCSH RALRQLAQSL YMMGVLLGAM TFGCLADRLG RRKVLIFNYL QTAVSGTCAA
     FAPNFPAYCA FRFLSGMSTA GVVLNCMTLN VEWMPIHTRA YVGTLTGYVY SLGQFLLAGM
     AYAVPHWRYL QLLVSAPFFA FFIYSWFFIE SARWYASSGR LDLTLRNLQR VAWINGKQEE
     GANLSMEALQ ASLKKELTTG KSQASALELI RCPALRRLFL CLSMLWFATS FAYYGLVMDL
     QGFGVSIYLI QVIFGAVDLP AKLVSFLVIN NVGRRPAQMA SLLLAGICIL INGVVPKDKS
     IVRTSLAVLG KGCLASSFNC IFLYTGEVYP TMIRQTGLGM GSTLARVGSI VSPLVSMTAE
     LYPSVPLFIY GAVPVAASAA IALLPETLGQ PLPDTVQDVE NRRRGKTRKQ QEELQKQMVP
     LQASAQVKN
//