O88909 · S22A8_MOUSE

  • Protein
    Organic anion transporter 3
  • Gene
    Slc22a8
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (By similarity).
Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:17220594).
Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:12011098, PubMed:15075193, PubMed:17220594, PubMed:21325432).
E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange. Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule. Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate. Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (By similarity).
May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (By similarity).
May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H2-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (By similarity).
May contribute to the release of cortisol in the adrenals (By similarity).
Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (PubMed:12011098).
Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E2 and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (PubMed:15100168, PubMed:17220594).
Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB) (By similarity).
Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (By similarity).
In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity).

Catalytic activity

  • estrone 3-sulfate(out) + glutarate(in) = estrone 3-sulfate(in) + glutarate(out)
  • 2-oxoglutarate(out) + estrone 3-sulfate(in) = 2-oxoglutarate(in) + estrone 3-sulfate(out)
  • glutarate(in) + taurocholate(out) = glutarate(out) + taurocholate(in)
  • dehydroepiandrosterone 3-sulfate(out) + glutarate(in) = dehydroepiandrosterone 3-sulfate(in) + glutarate(out)
  • 2-oxoglutarate(out) + glutarate(in) = 2-oxoglutarate(in) + glutarate(out)
  • 2-oxoglutarate(out) + urate(in) = 2-oxoglutarate(in) + urate(out)
  • glutarate(in) + prostaglandin F2alpha(out) = glutarate(out) + prostaglandin F2alpha(in)
  • 2-oxoglutarate(in) + prostaglandin F2alpha(out) = 2-oxoglutarate(out) + prostaglandin F2alpha(in)
  • (R)-carnitine(out) + 2-oxoglutarate(in) = (R)-carnitine(in) + 2-oxoglutarate(out)
  • (R)-carnitine(out) + glutarate(in) = (R)-carnitine(in) + glutarate(out)
  • 2-oxoglutarate(in) + prostaglandin E2(out) = 2-oxoglutarate(out) + prostaglandin E2(in)
  • glutarate(in) + prostaglandin E2(out) = glutarate(out) + prostaglandin E2(in)
  • glutarate(out) + urate(in) = glutarate(in) + urate(out)
  • 2-oxoglutarate(in) + taurocholate(out) = 2-oxoglutarate(out) + taurocholate(in)
  • 2-oxoglutarate(in) + dehydroepiandrosterone 3-sulfate(out) = 2-oxoglutarate(out) + dehydroepiandrosterone 3-sulfate(in)
  • a dicarboxylate(in) + kynurenate(out) = a dicarboxylate(out) + kynurenate(in)
  • (indol-3-yl)acetate(out) + a dicarboxylate(in) = (indol-3-yl)acetate(in) + a dicarboxylate(out)
  • a dicarboxylate(in) + indoxyl sulfate(out) = a dicarboxylate(out) + indoxyl sulfate(in)
  • a dicarboxylate(in) + N-benzoylglycine(out) = a dicarboxylate(out) + N-benzoylglycine(in)
  • 3-carboxy-4-methyl-5-propyl-2-furanpropanoate(out) + a dicarboxylate(in) = 3-carboxy-4-methyl-5-propyl-2-furanpropanoate(in) + a dicarboxylate(out)
  • (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin(out) + a dicarboxylate(in) = (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin(in) + a dicarboxylate(out)
  • a dicarboxylate(in) + L-erythro-7,8-dihydrobiopterin(out) = a dicarboxylate(out) + L-erythro-7,8-dihydrobiopterin(in)
  • a dicarboxylate(in) + L-sepiapterin(out) = a dicarboxylate(out) + L-sepiapterin(in)

Activity regulation

Expression inhibited by androgens such as testosterone.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
61.9 nML-carnitine
4.01 μM6-mercaptopurine
53.9 nM5-fluorouracil
1.48 μMprostaglandin E2

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Molecular Functionantiporter activity
Molecular Functionorganic anion transmembrane transporter activity
Molecular Functionprostaglandin transmembrane transporter activity
Molecular Functionprotein kinase C binding
Molecular Functionquaternary ammonium group transmembrane transporter activity
Molecular Functionsolute:inorganic anion antiporter activity
Molecular Functionxenobiotic transmembrane transporter activity
Biological Processglutathione transport
Biological Processmonoatomic ion transport
Biological Processprostaglandin transport
Biological Processquaternary ammonium group transport
Biological Processresponse to toxic substance

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Organic anion transporter 3
  • Short names
    mOat3
  • Alternative names
    • Organic anion/dicarboxylate exchanger
    • Reduced in osteosclerosis transporter
      (Roct
      )
    • Solute carrier family 22 member 8

Gene names

    • Name
      Slc22a8
    • Synonyms
      Oat3, Roct

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    O88909
  • Secondary accessions
    • Q3TZF9
    • Q8CCX3
    • Q8CFH5
    • Q91WJ9

Proteomes

Organism-specific databases

Subcellular Location

Basolateral cell membrane
; Multi-pass membrane protein
Note: Localized to the basolateral side of all renal epithelia except the glomerulus (PubMed:15944205).
Localizes on the brush border membrane of the choroid epithelial cells. Localizes to the basolateral membrane of the proximal tubular cells. Localizes on the abluminal and possibly, luminal membrane of the brain capillary endothelial cells (BCEC) (By similarity).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-11Cytoplasmic
Transmembrane12-32Helical
Topological domain33-123Extracellular
Transmembrane124-144Helical
Topological domain145-150Cytoplasmic
Transmembrane151-171Helical
Topological domain172-176Extracellular
Transmembrane177-197Helical
Topological domain198-212Cytoplasmic
Transmembrane213-233Helical
Topological domain234-236Extracellular
Transmembrane237-257Helical
Topological domain258-327Cytoplasmic
Transmembrane328-348Helical
Topological domain349-354Extracellular
Transmembrane355-375Helical
Topological domain376-383Cytoplasmic
Transmembrane384-404Helical
Topological domain405-411Extracellular
Transmembrane412-432Helical
Topological domain433-471Cytoplasmic
Transmembrane472-492Helical
Topological domain493-537Extracellular

Keywords

Phenotypes & Variants

Disruption phenotype

Mice appear healthy and are fertile. Exhibit a loss of taurocholate, estrone sulfate and para-aminohippurate transport in kidney and of fluorescein (FL) transport in choroid plexus.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 33 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, modified residue, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00002734411-537Organic anion transporter 3
Modified residue4Phosphoserine
Glycosylation81N-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed mainly in kidney (PubMed:10087192, PubMed:12011098, PubMed:15100168, PubMed:23389457).
In kidney, detected in almost all parts of the nephron, including macula densa cells (PubMed:15944205).
Expressed (at protein level) throughout the renal cortex (PubMed:17220594).
Widely distributed in the brain with no large regional differences (PubMed:21325432).
Expressed in the choroid plexus (CP, located in the ventricles of the brain) (PubMed:12011098).
Expressed in developing bone (PubMed:10087192).
Weakly expressed in brain and eye (PubMed:15100168).

Gene expression databases

Interaction

Protein-protein interaction databases

Chemistry

Miscellaneous

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region513-537Disordered

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    537
  • Mass (Da)
    59,246
  • Last updated
    2007-01-23 v2
  • Checksum
    F85FF82002AB26EB
MTFSEILDRVGSMGPFQYLHVTLLALPILGIANHNLLQIFTATTPDHHCRPPPNASLEPWVLPLGPNGKPEKCLRFVHLPNASLPNDTQGATEPCLDGWIYNSTRDTIVTEWDLVCGSNKLKEMAQSVFMAGILVGGPVFGELSDRFGRKPILTWSYLLLAASGSSAAFSPSLTVYMIFRFLCGCSISGISLSTIILNVEWVPTSTRAISSTTIGYCYTIGQFILPGLAYAVPQWRWLQLSVSAAFFIFSLLSWWVPESIRWLVLSGKFSKALKTLQRVATFNGKKEEGEKLTVEELKFNLQKDITSAKVKYGLSDLFRVSILRRVTFCLSLAWFATGFAYYSLAMGVEEFGVNIYILQIIFGGVDIPAKFITILSISYLGRRITQGFLLILAGVAILALIFVSSEMQLLRTALAVFGKGCLSGSFSCLFLYTSELYPTVLRQTGMGISNIWARVGSMIAPLVKITGELQPFIPNVIFGTMTLLGGSAAFFLLETLNRPLPETIEDIQDWYQQTKKTKQEPEAEKASQTIPLKTGGP

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict271in Ref. 1; AAC61265
Sequence conflict479in Ref. 2; BAC27624

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF078869
EMBL· GenBank· DDBJ
AAC61265.1
EMBL· GenBank· DDBJ
mRNA
AK031962
EMBL· GenBank· DDBJ
BAC27624.1
EMBL· GenBank· DDBJ
mRNA
AK044336
EMBL· GenBank· DDBJ
BAC31873.1
EMBL· GenBank· DDBJ
mRNA
AK157891
EMBL· GenBank· DDBJ
BAE34249.1
EMBL· GenBank· DDBJ
mRNA
BC014762
EMBL· GenBank· DDBJ
AAH14762.1
EMBL· GenBank· DDBJ
mRNA
AB079895
EMBL· GenBank· DDBJ
BAC53618.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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