O88909 · S22A8_MOUSE
- ProteinOrganic anion transporter 3
- GeneSlc22a8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids537 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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)estrone 3-sulfate (out)CHEBI:60050
+ glutarate (in)CHEBI:30921= estrone 3-sulfate (in)CHEBI:60050+ glutarate (out)CHEBI:30921 - 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 nM | L-carnitine | |||||
4.01 μM | 6-mercaptopurine | |||||
53.9 nM | 5-fluorouracil | |||||
1.48 μM | prostaglandin E2 |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | basolateral plasma membrane | |
Molecular Function | antiporter activity | |
Molecular Function | organic anion transmembrane transporter activity | |
Molecular Function | prostaglandin transmembrane transporter activity | |
Molecular Function | protein kinase C binding | |
Molecular Function | quaternary ammonium group transmembrane transporter activity | |
Molecular Function | solute:inorganic anion antiporter activity | |
Molecular Function | xenobiotic transmembrane transporter activity | |
Biological Process | glutathione transport | |
Biological Process | monoatomic ion transport | |
Biological Process | prostaglandin transport | |
Biological Process | quaternary ammonium group transport | |
Biological Process | response to toxic substance |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameOrganic anion transporter 3
- Short namesmOat3
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO88909
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-11 | Cytoplasmic | ||||
Sequence: MTFSEILDRVG | ||||||
Transmembrane | 12-32 | Helical | ||||
Sequence: SMGPFQYLHVTLLALPILGIA | ||||||
Topological domain | 33-123 | Extracellular | ||||
Sequence: NHNLLQIFTATTPDHHCRPPPNASLEPWVLPLGPNGKPEKCLRFVHLPNASLPNDTQGATEPCLDGWIYNSTRDTIVTEWDLVCGSNKLKE | ||||||
Transmembrane | 124-144 | Helical | ||||
Sequence: MAQSVFMAGILVGGPVFGELS | ||||||
Topological domain | 145-150 | Cytoplasmic | ||||
Sequence: DRFGRK | ||||||
Transmembrane | 151-171 | Helical | ||||
Sequence: PILTWSYLLLAASGSSAAFSP | ||||||
Topological domain | 172-176 | Extracellular | ||||
Sequence: SLTVY | ||||||
Transmembrane | 177-197 | Helical | ||||
Sequence: MIFRFLCGCSISGISLSTIIL | ||||||
Topological domain | 198-212 | Cytoplasmic | ||||
Sequence: NVEWVPTSTRAISST | ||||||
Transmembrane | 213-233 | Helical | ||||
Sequence: TIGYCYTIGQFILPGLAYAVP | ||||||
Topological domain | 234-236 | Extracellular | ||||
Sequence: QWR | ||||||
Transmembrane | 237-257 | Helical | ||||
Sequence: WLQLSVSAAFFIFSLLSWWVP | ||||||
Topological domain | 258-327 | Cytoplasmic | ||||
Sequence: ESIRWLVLSGKFSKALKTLQRVATFNGKKEEGEKLTVEELKFNLQKDITSAKVKYGLSDLFRVSILRRVT | ||||||
Transmembrane | 328-348 | Helical | ||||
Sequence: FCLSLAWFATGFAYYSLAMGV | ||||||
Topological domain | 349-354 | Extracellular | ||||
Sequence: EEFGVN | ||||||
Transmembrane | 355-375 | Helical | ||||
Sequence: IYILQIIFGGVDIPAKFITIL | ||||||
Topological domain | 376-383 | Cytoplasmic | ||||
Sequence: SISYLGRR | ||||||
Transmembrane | 384-404 | Helical | ||||
Sequence: ITQGFLLILAGVAILALIFVS | ||||||
Topological domain | 405-411 | Extracellular | ||||
Sequence: SEMQLLR | ||||||
Transmembrane | 412-432 | Helical | ||||
Sequence: TALAVFGKGCLSGSFSCLFLY | ||||||
Topological domain | 433-471 | Cytoplasmic | ||||
Sequence: TSELYPTVLRQTGMGISNIWARVGSMIAPLVKITGELQP | ||||||
Transmembrane | 472-492 | Helical | ||||
Sequence: FIPNVIFGTMTLLGGSAAFFL | ||||||
Topological domain | 493-537 | Extracellular | ||||
Sequence: LETLNRPLPETIEDIQDWYQQTKKTKQEPEAEKASQTIPLKTGGP |
Keywords
- Cellular component
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.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000273441 | 1-537 | Organic anion transporter 3 | |||
Sequence: MTFSEILDRVGSMGPFQYLHVTLLALPILGIANHNLLQIFTATTPDHHCRPPPNASLEPWVLPLGPNGKPEKCLRFVHLPNASLPNDTQGATEPCLDGWIYNSTRDTIVTEWDLVCGSNKLKEMAQSVFMAGILVGGPVFGELSDRFGRKPILTWSYLLLAASGSSAAFSPSLTVYMIFRFLCGCSISGISLSTIILNVEWVPTSTRAISSTTIGYCYTIGQFILPGLAYAVPQWRWLQLSVSAAFFIFSLLSWWVPESIRWLVLSGKFSKALKTLQRVATFNGKKEEGEKLTVEELKFNLQKDITSAKVKYGLSDLFRVSILRRVTFCLSLAWFATGFAYYSLAMGVEEFGVNIYILQIIFGGVDIPAKFITILSISYLGRRITQGFLLILAGVAILALIFVSSEMQLLRTALAVFGKGCLSGSFSCLFLYTSELYPTVLRQTGMGISNIWARVGSMIAPLVKITGELQPFIPNVIFGTMTLLGGSAAFFLLETLNRPLPETIEDIQDWYQQTKKTKQEPEAEKASQTIPLKTGGP | ||||||
Modified residue | 4 | Phosphoserine | ||||
Sequence: S | ||||||
Glycosylation | 81 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
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).
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
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 513-537 | Disordered | ||||
Sequence: QTKKTKQEPEAEKASQTIPLKTGGP |
Sequence similarities
Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length537
- Mass (Da)59,246
- Last updated2007-01-23 v2
- ChecksumF85FF82002AB26EB
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 271 | in Ref. 1; AAC61265 | ||||
Sequence: K → R | ||||||
Sequence conflict | 479 | in Ref. 2; BAC27624 | ||||
Sequence: G → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |