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Protein

Solute carrier family 22 member 8

Gene

Slc22a8

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Functions as one of the detoxification systems on the choroid plexus (CP) by removing substrates from the cerebrospinal fluid (CSF). Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient. Mediates the uptake from brain of organic anions, such as p-aminohippurate (PAH), ochratoxin A, and estrone sulfate (ES) and a cationic compound, cimetidine in a sodium independent manner. Mediates the uptake of benzylpenicillin (PCG), 2,4-dichloro-phenoxyacetate (2,4-D) and PAH in CP. Mediates the efflux of PAH, pravastatin, pitavastatin and PCG from the cerebrum into the blood circulation across the blood-brain barrier (BBB). Involved in regulating the CSF concentration of H(2)-receptor antagonists at the CP. Mediates the renal uptake of indoxyl sulfate (IS), 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) pravastatin, PCG, dehydroepiandrosterone sulfate (DHEAS) and is partly involved in the renal uptake of temocaprilat and ES.10 Publications

GO - Molecular functioni

  • organic anion transmembrane transporter activity Source: RGD
  • protein kinase C binding Source: RGD
  • quaternary ammonium group transmembrane transporter activity Source: RGD

GO - Biological processi

  • glutathione transport Source: RGD
  • quaternary ammonium group transport Source: RGD
  • response to methotrexate Source: RGD
  • response to toxic substance Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Detoxification, Ion transport, Transport

Protein family/group databases

TCDBi2.A.1.19.7. the major facilitator superfamily (mfs).

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 22 member 8
Alternative name(s):
Organic anion transporter 3
Short name:
rOat3
Gene namesi
Name:Slc22a8
Synonyms:Oat3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi632286. Slc22a8.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1111CytoplasmicSequence analysisAdd
BLAST
Transmembranei12 – 3221HelicalSequence analysisAdd
BLAST
Topological domaini33 – 12391ExtracellularSequence analysisAdd
BLAST
Transmembranei124 – 14421HelicalSequence analysisAdd
BLAST
Topological domaini145 – 15814CytoplasmicSequence analysisAdd
BLAST
Transmembranei159 – 17921HelicalSequence analysisAdd
BLAST
Topological domaini180 – 1801ExtracellularSequence analysis
Transmembranei181 – 20121HelicalSequence analysisAdd
BLAST
Topological domaini202 – 21211CytoplasmicSequence analysisAdd
BLAST
Transmembranei213 – 23321HelicalSequence analysisAdd
BLAST
Topological domaini234 – 2363ExtracellularSequence analysis
Transmembranei237 – 25721HelicalSequence analysisAdd
BLAST
Topological domaini258 – 32770CytoplasmicSequence analysisAdd
BLAST
Transmembranei328 – 34821HelicalSequence analysisAdd
BLAST
Topological domaini349 – 3546ExtracellularSequence analysis
Transmembranei355 – 37521HelicalSequence analysisAdd
BLAST
Topological domaini376 – 3838CytoplasmicSequence analysis
Transmembranei384 – 40421HelicalSequence analysisAdd
BLAST
Topological domaini405 – 4117ExtracellularSequence analysis
Transmembranei412 – 43221HelicalSequence analysisAdd
BLAST
Topological domaini433 – 47139CytoplasmicSequence analysisAdd
BLAST
Transmembranei472 – 49221HelicalSequence analysisAdd
BLAST
Topological domaini493 – 53644ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

  • basolateral plasma membrane Source: RGD
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2073666.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 536536Solute carrier family 22 member 8PRO_0000273445Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei4 – 41PhosphoserineCombined sources
Glycosylationi81 – 811N-linked (GlcNAc...)Sequence analysis
Glycosylationi86 – 861N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9R1U7.
PRIDEiQ9R1U7.

PTM databases

iPTMnetiQ9R1U7.

Expressioni

Tissue specificityi

Expressed in the liver, brain, kidney, choroid plexus and eye. Moderately expressed in the brain capillary endothelial cells (BCEC).3 Publications

Interactioni

GO - Molecular functioni

  • protein kinase C binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000024488.

Chemistry

BindingDBiQ9R1U7.

Structurei

3D structure databases

ProteinModelPortaliQ9R1U7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0255. Eukaryota.
COG0477. LUCA.
HOGENOMiHOG000234569.
HOVERGENiHBG108433.
InParanoidiQ9R1U7.
KOiK08205.
OrthoDBiEOG7C8GH9.
PhylomeDBiQ9R1U7.
TreeFamiTF315847.

Family and domain databases

InterProiIPR020846. MFS_dom.
IPR005828. MFS_sugar_transport_like.
IPR004749. Orgcat_transp/SVOP.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00898. 2A0119. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9R1U7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTFSEILDRV GSMGPFQYLH VTLLALPVLG IANHNLLQIF TATTPVHHCR
60 70 80 90 100
PPPNASIGPW VLPLDPNGKP EKCLRFVHLP NASLPNDTQR ATEPCLDGWI
110 120 130 140 150
YNSTRDTIVI EWDLVCSSNK LKEMAQSIFM AGILVGGPVI GELSDRFGRK
160 170 180 190 200
PILTWSYLML AASGSGAAFS PSLPVYMIFR FLCGCSISGI SLSTVILNVE
210 220 230 240 250
WVPTSMRAIS STSIGYCYTI GQFILSGLAY AIPQWRWLQL TSSAPFFIFS
260 270 280 290 300
LLSWWVPESI RWLVLSGKYS KALKTLQRVA TFNGKKEEGK KLTIEELKFN
310 320 330 340 350
LQKDITSAKV KYGLSDLFRV SILRRVTFCL SLAWFSTGFA YYSLAMGVEE
360 370 380 390 400
FGVNIYILQI IFGGVDIPAK FITILSLSYL GRRITQSFLL LLAGGAILAL
410 420 430 440 450
IFVPSEMQLL RTALAVFGKG CLSGSFSCLF LYTSELYPTV LRQTGMGISN
460 470 480 490 500
VWARVGSMIA PLVKITGELQ PFIPNVIFGT TALLGGSAAF FLLETLNRPL
510 520 530
PETIEDIQNW HKQVQKTKQE SEAEKASQII PLKTGG
Length:536
Mass (Da):59,186
Last modified:May 1, 2000 - v1
Checksum:iD821E57BFA31F8D9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti515 – 5151Q → K in AAH81777 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017446 mRNA. Translation: BAA82552.1.
BC081777 mRNA. Translation: AAH81777.1.
RefSeqiNP_112622.1. NM_031332.1.
UniGeneiRn.23348.

Genome annotation databases

GeneIDi83500.
KEGGirno:83500.
UCSCiRGD:632286. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017446 mRNA. Translation: BAA82552.1.
BC081777 mRNA. Translation: AAH81777.1.
RefSeqiNP_112622.1. NM_031332.1.
UniGeneiRn.23348.

3D structure databases

ProteinModelPortaliQ9R1U7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000024488.

Chemistry

BindingDBiQ9R1U7.
ChEMBLiCHEMBL2073666.

Protein family/group databases

TCDBi2.A.1.19.7. the major facilitator superfamily (mfs).

PTM databases

iPTMnetiQ9R1U7.

Proteomic databases

PaxDbiQ9R1U7.
PRIDEiQ9R1U7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi83500.
KEGGirno:83500.
UCSCiRGD:632286. rat.

Organism-specific databases

CTDi9376.
RGDi632286. Slc22a8.

Phylogenomic databases

eggNOGiKOG0255. Eukaryota.
COG0477. LUCA.
HOGENOMiHOG000234569.
HOVERGENiHBG108433.
InParanoidiQ9R1U7.
KOiK08205.
OrthoDBiEOG7C8GH9.
PhylomeDBiQ9R1U7.
TreeFamiTF315847.

Miscellaneous databases

PROiQ9R1U7.

Family and domain databases

InterProiIPR020846. MFS_dom.
IPR005828. MFS_sugar_transport_like.
IPR004749. Orgcat_transp/SVOP.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00898. 2A0119. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain."
    Kusuhara H., Sekine T., Utsunomiya-Tate N., Tsuda M., Kojima R., Cha S.H., Sugiyama Y., Kanai Y., Endou H.
    J. Biol. Chem. 274:13675-13680(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Kidney.
  3. "Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus."
    Nagata Y., Kusuhara H., Endou H., Sugiyama Y.
    Mol. Pharmacol. 61:982-988(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  4. "Functional involvement of rat organic anion transporter 3 (rOat3; Slc22a8) in the renal uptake of organic anions."
    Hasegawa M., Kusuhara H., Sugiyama D., Ito K., Ueda S., Endou H., Sugiyama Y.
    J. Pharmacol. Exp. Ther. 300:746-753(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  5. "Contribution of organic anion transporters to the renal uptake of anionic compounds and nucleoside derivatives in rat."
    Hasegawa M., Kusuhara H., Endou H., Sugiyama Y.
    J. Pharmacol. Exp. Ther. 305:1087-1097(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Contribution of organic anion transporter 3 (Slc22a8) to the elimination of p-aminohippuric acid and benzylpenicillin across the blood-brain barrier."
    Kikuchi R., Kusuhara H., Sugiyama D., Sugiyama Y.
    J. Pharmacol. Exp. Ther. 306:51-58(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  7. "Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na+ gradient."
    Sweet D.H., Chan L.M., Walden R., Yang X.-P., Miller D.S., Pritchard J.B.
    Am. J. Physiol. 284:F763-F769(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Involvement of multiple transporters in the efflux of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors across the blood-brain barrier."
    Kikuchi R., Kusuhara H., Abe T., Endou H., Sugiyama Y.
    J. Pharmacol. Exp. Ther. 311:1147-1153(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Carrier-mediated uptake of H2-receptor antagonists by the rat choroid plexus: involvement of rat organic anion transporter 3."
    Nagata Y., Kusuhara H., Hirono S., Endou H., Sugiyama Y.
    Drug Metab. Dispos. 32:1040-1047(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Involvement of rat organic anion transporter 3 in the uptake of an organic herbicide, 2,4-dichlorophenoxyacetate, by the isolated rat choroid plexus."
    Nagata Y., Kusuhara H., Imaoka T., Endou H., Sugiyama Y.
    J. Pharm. Sci. 93:2724-2732(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Differential contributions of rOat1 (Slc22a6) and rOat3 (Slc22a8) to the in vivo renal uptake of uremic toxins in rats."
    Deguchi T., Kouno Y., Terasaki T., Takadate A., Otagiri M.
    Pharm. Res. 22:619-627(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiS22A8_RAT
AccessioniPrimary (citable) accession number: Q9R1U7
Secondary accession number(s): Q66HN0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.