O35956 · S22A6_RAT
- ProteinSolute carrier family 22 member 6
- GeneSlc22a6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids551 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Secondary active transporter that functions as a Na+-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as alpha-ketoglutarate or glutarate (PubMed:14675047, PubMed:23832370, PubMed:9228014, PubMed:9374486).
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (By similarity).
Function 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).
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:9228014).
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:9228014).
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:23832370).
May transport glutamate (By similarity).
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:14675047, PubMed:9228014).
Uremic toxins include the indoxyl sulfate (IS), hippurate, indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate(CMPF) and urate (PubMed:14675047, PubMed:9228014).
Xenobiotics include the mycotoxin ochratoxin (OTA) (By similarity).
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (By similarity).
May also work as a bidirectional OA/dicarboxylate exchanger (PubMed:9228014).
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (By similarity).
Function 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).
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:9228014).
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:9228014).
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:23832370).
May transport glutamate (By similarity).
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:14675047, PubMed:9228014).
Uremic toxins include the indoxyl sulfate (IS), hippurate, indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate(CMPF) and urate (PubMed:14675047, PubMed:9228014).
Xenobiotics include the mycotoxin ochratoxin (OTA) (By similarity).
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (By similarity).
May also work as a bidirectional OA/dicarboxylate exchanger (PubMed:9228014).
Miscellaneous
Involved in the renal transport of a variety of drugs with well-known nephrotoxic potential, therefore may play a role in the etiology of the drug-associated nephrotoxicity (PubMed:10462545).
Uptakes the diagnostic agent PAH/para-aminohippurate and clinically used drugs (PubMed:10462545, PubMed:23832370, PubMed:9228014, PubMed:9374486).
Mediates the bidirectional transport of PAH/para-aminohippurate (By similarity).
Uptakes the diagnostic agent PAH/para-aminohippurate and clinically used drugs (PubMed:10462545, PubMed:23832370, PubMed:9228014, PubMed:9374486).
Mediates the bidirectional transport of PAH/para-aminohippurate (By similarity).
Catalytic activity
- (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)
- a dicarboxylate(in) + prostaglandin F2alpha(out) = a dicarboxylate(out) + prostaglandin F2alpha(in)
- a dicarboxylate(in) + prostaglandin E2(out) = a dicarboxylate(out) + prostaglandin E2(in)
- 3',5'-cyclic AMP(out) + a dicarboxylate(in) = 3',5'-cyclic AMP(in) + a dicarboxylate(out)
- 3',5'-cyclic GMP(out) + a dicarboxylate(in) = 3',5'-cyclic GMP(in) + a dicarboxylate(out)
- a dicarboxylate(in) + urate(out) = a dicarboxylate(out) + urate(in)
- glutarate(in) + kynurenate(out) = glutarate(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)
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
27.5 μM | hippurate/N-benzoylglycine | |||||
47.1 μM | indole acetate | |||||
17.7 μM | indoxyl sulfate | |||||
154 μM | 3-carboxy-4- methyl-5-propyl-2-furanpropionate |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
519 pmol/min/mg | for hippurate/N-benzoylglycine uptake | ||||
387 pmol/min/mg | for indole acetate uptake | ||||
350 pmol/min/mg | for indoxyl sulfate uptake | ||||
1669 pmol/min/mg | for 3-carboxy-4- methyl-5-propyl-2-furanpropionate uptake |
GO annotations
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSolute carrier family 22 member 6
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionO35956
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Basolateral cell membrane ; Multi-pass membrane protein
Basal cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-9 | Cytoplasmic | ||||
Sequence: MAFNDLLKQ | ||||||
Transmembrane | 10-30 | Helical | ||||
Sequence: VGGVGRFQLIQVTMVVAPLLL | ||||||
Topological domain | 31-135 | Extracellular | ||||
Sequence: MASHNTLQNFTAAIPPHHCRPPANANLSKDGGLEAWLPLDKQGQPESCLRFTSPQWGPPFYNGTEANGTRVTEPCIDGWVYDNSTFPSTIVTEWNLVCSHRAFRQ | ||||||
Transmembrane | 136-156 | Helical | ||||
Sequence: LAQSLYMVGVLLGAMVFGYLA | ||||||
Topological domain | 157-164 | Cytoplasmic | ||||
Sequence: DRLGRRKV | ||||||
Transmembrane | 165-187 | Helical | ||||
Sequence: LILNYLQTAVSGTCAAYAPNYTV | ||||||
Topological domain | 188-195 | Extracellular | ||||
Sequence: YCVFRLLS | ||||||
Transmembrane | 196-216 | Helical | ||||
Sequence: GMSLASIAINCMTLNVEWMPI | ||||||
Topological domain | 217-224 | Cytoplasmic | ||||
Sequence: HTRAYVGT | ||||||
Transmembrane | 225-245 | Helical | ||||
Sequence: LIGYVYSLGQFLLAGIAYAVP | ||||||
Topological domain | 246-248 | Extracellular | ||||
Sequence: HWR | ||||||
Transmembrane | 249-269 | Helical | ||||
Sequence: HLQLVVSVPFFIAFIYSWFFI | ||||||
Topological domain | 270-337 | Cytoplasmic | ||||
Sequence: ESARWYSSSGRLDLTLRALQRVARINGKQEEGAKLSIEVLRTSLQKELTLSKGQASAMELLRCPTLRH | ||||||
Transmembrane | 338-358 | Helical | ||||
Sequence: LFLCLSMLWFATSFAYYGLVM | ||||||
Topological domain | 359-368 | Extracellular | ||||
Sequence: DLQGFGVSMY | ||||||
Transmembrane | 369-389 | Helical | ||||
Sequence: LIQVIFGAVDLPAKFVCFLVI | ||||||
Topological domain | 390-395 | Cytoplasmic | ||||
Sequence: NSMGRR | ||||||
Transmembrane | 396-416 | Helical | ||||
Sequence: PAQMASLLLAGICILVNGIIP | ||||||
Topological domain | 417-425 | Extracellular | ||||
Sequence: KSHTIIRTS | ||||||
Transmembrane | 426-446 | Helical | ||||
Sequence: LAVLGKGCLASSFNCIFLYTG | ||||||
Topological domain | 447-484 | Cytoplasmic | ||||
Sequence: ELYPTVIRQTGLGMGSTMARVGSIVSPLVSMTAEFYPS | ||||||
Transmembrane | 485-505 | Helical | ||||
Sequence: MPLFIFGAVPVVASAVTALLP | ||||||
Topological domain | 506-551 | Extracellular | ||||
Sequence: ETLGQPLPDTVQDLKSRSRGKQNQQQQEQQKQMMPLQASTQEKNGL |
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000324171 | 1-551 | Solute carrier family 22 member 6 | |||
Sequence: MAFNDLLKQVGGVGRFQLIQVTMVVAPLLLMASHNTLQNFTAAIPPHHCRPPANANLSKDGGLEAWLPLDKQGQPESCLRFTSPQWGPPFYNGTEANGTRVTEPCIDGWVYDNSTFPSTIVTEWNLVCSHRAFRQLAQSLYMVGVLLGAMVFGYLADRLGRRKVLILNYLQTAVSGTCAAYAPNYTVYCVFRLLSGMSLASIAINCMTLNVEWMPIHTRAYVGTLIGYVYSLGQFLLAGIAYAVPHWRHLQLVVSVPFFIAFIYSWFFIESARWYSSSGRLDLTLRALQRVARINGKQEEGAKLSIEVLRTSLQKELTLSKGQASAMELLRCPTLRHLFLCLSMLWFATSFAYYGLVMDLQGFGVSMYLIQVIFGAVDLPAKFVCFLVINSMGRRPAQMASLLLAGICILVNGIIPKSHTIIRTSLAVLGKGCLASSFNCIFLYTGELYPTVIRQTGLGMGSTMARVGSIVSPLVSMTAEFYPSMPLFIFGAVPVVASAVTALLPETLGQPLPDTVQDLKSRSRGKQNQQQQEQQKQMMPLQASTQEKNGL | ||||||
Glycosylation | 39 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 56 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 92 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 113 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Glycosylated. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in kidney; in the particular segment of the proximal tubule (PubMed:9228014, PubMed:9374486).
In kidney, found preferentially in the cortex and outer medulla and weakly in the inner medulla (PubMed:9228014).
Expressed to a lower extent in brain (PubMed:9228014).
In kidney, found preferentially in the cortex and outer medulla and weakly in the inner medulla (PubMed:9228014).
Expressed to a lower extent in brain (PubMed:9228014).
Induction
Down-regulated by PGE2 and in ischemic kidney.
Gene expression databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 514-551 | Disordered | ||||
Sequence: DTVQDLKSRSRGKQNQQQQEQQKQMMPLQASTQEKNGL |
Domain
Multiple cysteine residues are necessary for proper targeting to the plasma membrane.
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
- Length551
- Mass (Da)60,766
- Last updated1998-01-01 v1
- Checksum8BA47BE628324BF2
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF008221 EMBL· GenBank· DDBJ | AAC18772.1 EMBL· GenBank· DDBJ | mRNA | ||
AB004559 EMBL· GenBank· DDBJ | BAA22086.1 EMBL· GenBank· DDBJ | mRNA | ||
BC104692 EMBL· GenBank· DDBJ | AAI04693.1 EMBL· GenBank· DDBJ | mRNA |