S22A8_RAT
ID S22A8_RAT Reviewed; 536 AA.
AC Q9R1U7; Q66HN0;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 129.
DE RecName: Full=Solute carrier family 22 member 8;
DE AltName: Full=Organic anion transporter 3;
DE Short=rOat3;
GN Name=Slc22a8; Synonyms=Oat3;
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], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=10224140; DOI=10.1074/jbc.274.19.13675;
RA Kusuhara H., Sekine T., Utsunomiya-Tate N., Tsuda M., Kojima R., Cha S.H.,
RA Sugiyama Y., Kanai Y., Endou H.;
RT "Molecular cloning and characterization of a new multispecific organic
RT anion transporter from rat brain.";
RL J. Biol. Chem. 274:13675-13680(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [3]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11961115; DOI=10.1124/mol.61.5.982;
RA Nagata Y., Kusuhara H., Endou H., Sugiyama Y.;
RT "Expression and functional characterization of rat organic anion
RT transporter 3 (rOat3) in the choroid plexus.";
RL Mol. Pharmacol. 61:982-988(2002).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11861777; DOI=10.1124/jpet.300.3.746;
RA Hasegawa M., Kusuhara H., Sugiyama D., Ito K., Ueda S., Endou H.,
RA Sugiyama Y.;
RT "Functional involvement of rat organic anion transporter 3 (rOat3; Slc22a8)
RT in the renal uptake of organic anions.";
RL J. Pharmacol. Exp. Ther. 300:746-753(2002).
RN [5]
RP FUNCTION.
RX PubMed=12660303; DOI=10.1124/jpet.102.046847;
RA Hasegawa M., Kusuhara H., Endou H., Sugiyama Y.;
RT "Contribution of organic anion transporters to the renal uptake of anionic
RT compounds and nucleoside derivatives in rat.";
RL J. Pharmacol. Exp. Ther. 305:1087-1097(2003).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12684544; DOI=10.1124/jpet.103.049197;
RA Kikuchi R., Kusuhara H., Sugiyama D., Sugiyama Y.;
RT "Contribution of organic anion transporter 3 (Slc22a8) to the elimination
RT of p-aminohippuric acid and benzylpenicillin across the blood-brain
RT barrier.";
RL J. Pharmacol. Exp. Ther. 306:51-58(2003).
RN [7]
RP FUNCTION.
RX PubMed=12488248; DOI=10.1152/ajprenal.00405.2002;
RA Sweet D.H., Chan L.M., Walden R., Yang X.-P., Miller D.S., Pritchard J.B.;
RT "Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger
RT indirectly coupled to the Na+ gradient.";
RL Am. J. Physiol. 284:F763-F769(2003).
RN [8]
RP FUNCTION.
RX PubMed=15292460; DOI=10.1124/jpet.104.071621;
RA Kikuchi R., Kusuhara H., Abe T., Endou H., Sugiyama Y.;
RT "Involvement of multiple transporters in the efflux of 3-hydroxy-3-
RT methylglutaryl-CoA reductase inhibitors across the blood-brain barrier.";
RL J. Pharmacol. Exp. Ther. 311:1147-1153(2004).
RN [9]
RP FUNCTION.
RX PubMed=15319347;
RA Nagata Y., Kusuhara H., Hirono S., Endou H., Sugiyama Y.;
RT "Carrier-mediated uptake of H2-receptor antagonists by the rat choroid
RT plexus: involvement of rat organic anion transporter 3.";
RL Drug Metab. Dispos. 32:1040-1047(2004).
RN [10]
RP FUNCTION.
RX PubMed=15389674; DOI=10.1002/jps.20175;
RA Nagata Y., Kusuhara H., Imaoka T., Endou H., Sugiyama Y.;
RT "Involvement of rat organic anion transporter 3 in the uptake of an organic
RT herbicide, 2,4-dichlorophenoxyacetate, by the isolated rat choroid
RT plexus.";
RL J. Pharm. Sci. 93:2724-2732(2004).
RN [11]
RP FUNCTION.
RX PubMed=15846470; DOI=10.1007/s11095-005-2486-x;
RA Deguchi T., Kouno Y., Terasaki T., Takadate A., Otagiri M.;
RT "Differential contributions of rOat1 (Slc22a6) and rOat3 (Slc22a8) to the
RT in vivo renal uptake of uremic toxins in rats.";
RL Pharm. Res. 22:619-627(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Plays an important role in the excretion/detoxification of
CC endogenous and exogenous organic anions, especially from the brain and
CC kidney. Functions as one of the detoxification systems on the choroid
CC plexus (CP) by removing substrates from the cerebrospinal fluid (CSF).
CC Functions as an organic anion/dicarboxylate exchanger that couples
CC organic anion uptake indirectly to the sodium gradient. Mediates the
CC uptake from brain of organic anions, such as p-aminohippurate (PAH),
CC ochratoxin A, and estrone sulfate (ES) and a cationic compound,
CC cimetidine in a sodium independent manner. Mediates the uptake of
CC benzylpenicillin (PCG), 2,4-dichloro-phenoxyacetate (2,4-D) and PAH in
CC CP. Mediates the efflux of PAH, pravastatin, pitavastatin and PCG from
CC the cerebrum into the blood circulation across the blood-brain barrier
CC (BBB). Involved in regulating the CSF concentration of H(2)-receptor
CC antagonists at the CP. Mediates the renal uptake of indoxyl sulfate
CC (IS), 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) pravastatin,
CC PCG, dehydroepiandrosterone sulfate (DHEAS) and is partly involved in
CC the renal uptake of temocaprilat and ES. {ECO:0000269|PubMed:10224140,
CC ECO:0000269|PubMed:11861777, ECO:0000269|PubMed:11961115,
CC ECO:0000269|PubMed:12488248, ECO:0000269|PubMed:12660303,
CC ECO:0000269|PubMed:12684544, ECO:0000269|PubMed:15292460,
CC ECO:0000269|PubMed:15319347, ECO:0000269|PubMed:15389674,
CC ECO:0000269|PubMed:15846470}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane {ECO:0000305}; Multi-
CC pass membrane protein {ECO:0000305}. Note=Localizes on the brush border
CC membrane of the choroid epithelial cells. Localizes to the basolateral
CC membrane of the proximal tubular cells. Localizes on the abluminal and
CC possibly, luminal membrane of the brain capillary endothelial cells
CC (BCEC). {ECO:0000269|PubMed:11861777, ECO:0000269|PubMed:11961115,
CC ECO:0000269|PubMed:12684544}.
CC -!- TISSUE SPECIFICITY: Expressed in the liver, brain, kidney, choroid
CC plexus and eye. Moderately expressed in the brain capillary endothelial
CC cells (BCEC). {ECO:0000269|PubMed:10224140,
CC ECO:0000269|PubMed:11961115, ECO:0000269|PubMed:12684544}.
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; AB017446; BAA82552.1; -; mRNA.
DR EMBL; BC081777; AAH81777.1; -; mRNA.
DR RefSeq; NP_112622.1; NM_031332.1.
DR AlphaFoldDB; Q9R1U7; -.
DR SMR; Q9R1U7; -.
DR BioGRID; 249719; 1.
DR STRING; 10116.ENSRNOP00000024488; -.
DR BindingDB; Q9R1U7; -.
DR ChEMBL; CHEMBL2073666; -.
DR TCDB; 2.A.1.19.7; the major facilitator superfamily (mfs).
DR GlyGen; Q9R1U7; 2 sites.
DR iPTMnet; Q9R1U7; -.
DR PhosphoSitePlus; Q9R1U7; -.
DR PaxDb; Q9R1U7; -.
DR GeneID; 83500; -.
DR KEGG; rno:83500; -.
DR UCSC; RGD:632286; rat.
DR CTD; 9376; -.
DR RGD; 632286; Slc22a8.
DR eggNOG; KOG0255; Eukaryota.
DR InParanoid; Q9R1U7; -.
DR OrthoDB; 464838at2759; -.
DR PhylomeDB; Q9R1U7; -.
DR TreeFam; TF315847; -.
DR Reactome; R-RNO-561048; Organic anion transport.
DR PRO; PR:Q9R1U7; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005452; F:inorganic anion exchanger activity; ISO:RGD.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; IDA:RGD.
DR GO; GO:0005080; F:protein kinase C binding; IPI:RGD.
DR GO; GO:0015651; F:quaternary ammonium group transmembrane transporter activity; IDA:RGD.
DR GO; GO:0034635; P:glutathione transport; IDA:RGD.
DR GO; GO:0015697; P:quaternary ammonium group transport; IDA:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1250.20; -; 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 InterPro; IPR005829; Sugar_transporter_CS.
DR Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00898; 2A0119; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Detoxification; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..536
FT /note="Solute carrier family 22 member 8"
FT /id="PRO_0000273445"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..123
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..158
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 180
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..236
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..257
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 258..327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 328..348
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 349..354
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..375
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 376..383
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 384..404
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 405..411
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 412..432
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 433..471
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 472..492
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 493..536
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 515..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 515
FT /note="Q -> K (in Ref. 2; AAH81777)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 536 AA; 59186 MW; D821E57BFA31F8D9 CRC64;
MTFSEILDRV GSMGPFQYLH VTLLALPVLG IANHNLLQIF TATTPVHHCR PPPNASIGPW
VLPLDPNGKP EKCLRFVHLP NASLPNDTQR ATEPCLDGWI YNSTRDTIVI EWDLVCSSNK
LKEMAQSIFM AGILVGGPVI GELSDRFGRK PILTWSYLML AASGSGAAFS PSLPVYMIFR
FLCGCSISGI SLSTVILNVE WVPTSMRAIS STSIGYCYTI GQFILSGLAY AIPQWRWLQL
TSSAPFFIFS LLSWWVPESI RWLVLSGKYS KALKTLQRVA TFNGKKEEGK KLTIEELKFN
LQKDITSAKV KYGLSDLFRV SILRRVTFCL SLAWFSTGFA YYSLAMGVEE FGVNIYILQI
IFGGVDIPAK FITILSLSYL GRRITQSFLL LLAGGAILAL IFVPSEMQLL RTALAVFGKG
CLSGSFSCLF LYTSELYPTV LRQTGMGISN VWARVGSMIA PLVKITGELQ PFIPNVIFGT
TALLGGSAAF FLLETLNRPL PETIEDIQNW HKQVQKTKQE SEAEKASQII PLKTGG
