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O35956 (S22A6_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Solute carrier family 22 member 6
Alternative name(s):
Organic anion transporter 1
Short name=rOAT1
renal organic anion transporter 1
Short name=rROAT1
Gene names
Name:Slc22a6
Synonyms:Oat1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length551 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS), 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD) and edaravone sulfate. Mediates the sodium-independent uptake of p-aminohippurate (PAH), cidofovir, adefovir, 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF). PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), indomethacin, sulindac, diclofenac, carprofen, okadaic acid, benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, bumetamide, losartan, phenol red, urate and alpha-ketoglutarate By similarity. PAH uptake is inhibited by glutarate and probenecid. Ref.1 Ref.2

Subcellular location

Cell membrane; Multi-pass membrane protein Potential.

Tissue specificity

Highly expressed in kidney; in the particular segment of the proximal tubule and to a lower extent in brain. Found preferentially in the cortex and outer medulla and weakly in the inner medulla. Ref.1 Ref.2

Induction

Down-regulated by PGE2 and in ischemic kidney. Ref.6 Ref.7

Domain

Multiple cysteine residues are necessary for proper targeting to the plasma membrane By similarity.

Post-translational modification

Glycosylated. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane By similarity.

Sequence similarities

Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family. [View classification]

Biophysicochemical properties

Kinetic parameters:

KM=14.3 µM for PAH Ref.1 Ref.2 Ref.4 Ref.5

KM=238 µM for cidofovir

KM=270 µM for adefovir

KM=10.2 µM for 2,4-D

KM=27.5 µM for HA

KM=47.1 µM for IA

KM=17.7 µM for IS

KM=154 µM for CMPF

Vmax=1270 pmol/min/mg enzyme for 2,4-D uptake

Vmax=519 pmol/min/mg enzyme for HA uptake

Vmax=387 pmol/min/mg enzyme for IA uptake

Vmax=350 pmol/min/mg enzyme for IS uptake

Vmax=1669 pmol/min/mg enzyme for CMPF uptake

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   DomainTransmembrane
Transmembrane helix
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processalpha-ketoglutarate transport

Inferred from sequence or structural similarity. Source: UniProtKB

organic anion transport

Inferred from direct assay PubMed 15068970. Source: MGI

protein homooligomerization

Inferred from direct assay PubMed 18361503. Source: RGD

renal tubular secretion

Inferred from sequence or structural similarity. Source: UniProtKB

response to methotrexate

Inferred from expression pattern PubMed 16925582. Source: RGD

sodium-independent organic anion transport

Inferred from direct assay Ref.2. Source: RGD

   Cellular_componentbasolateral plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

caveola

Inferred from direct assay PubMed 16000875. Source: RGD

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 16000875. Source: RGD

protein complex

Inferred from direct assay PubMed 16000875. Source: RGD

   Molecular_functionanion:anion antiporter activity

Inferred from direct assay PubMed 18361503. Source: RGD

chloride ion binding

Inferred from direct assay PubMed 18361503. Source: RGD

inorganic anion exchanger activity

Inferred from sequence or structural similarity. Source: UniProtKB

organic anion transmembrane transporter activity

Inferred from direct assay PubMed 15068970. Source: MGI

protein binding

Inferred from physical interaction PubMed 16000875. Source: RGD

protein homodimerization activity

Inferred from direct assay PubMed 18361503. Source: RGD

sodium-independent organic anion transmembrane transporter activity

Inferred from direct assay Ref.2. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 551551Solute carrier family 22 member 6
PRO_0000324171

Regions

Topological domain1 – 99Cytoplasmic Potential
Transmembrane10 – 3021Helical; Potential
Topological domain31 – 135105Extracellular Potential
Transmembrane136 – 15621Helical; Potential
Topological domain157 – 1648Cytoplasmic Potential
Transmembrane165 – 18723Helical; Potential
Topological domain188 – 1958Extracellular Potential
Transmembrane196 – 21621Helical; Potential
Topological domain217 – 2248Cytoplasmic Potential
Transmembrane225 – 24521Helical; Potential
Topological domain246 – 2483Extracellular Potential
Transmembrane249 – 26921Helical; Potential
Topological domain270 – 33768Cytoplasmic Potential
Transmembrane338 – 35821Helical; Potential
Topological domain359 – 36810Extracellular Potential
Transmembrane369 – 38921Helical; Potential
Topological domain390 – 3956Cytoplasmic Potential
Transmembrane396 – 41621Helical; Potential
Topological domain417 – 4259Extracellular Potential
Transmembrane426 – 44621Helical; Potential
Topological domain447 – 48438Cytoplasmic Potential
Transmembrane485 – 50521Helical; Potential
Topological domain506 – 55146Extracellular Potential
Compositional bias527 – 53711Poly-Gln

Amino acid modifications

Glycosylation391N-linked (GlcNAc...) Potential
Glycosylation561N-linked (GlcNAc...) Potential
Glycosylation921N-linked (GlcNAc...) Potential
Glycosylation1131N-linked (GlcNAc...) Potential

Sequences

Sequence LengthMass (Da)Tools
O35956 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 8BA47BE628324BF2

FASTA55160,766
        10         20         30         40         50         60 
MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPPHHCR PPANANLSKD 

        70         80         90        100        110        120 
GGLEAWLPLD KQGQPESCLR FTSPQWGPPF YNGTEANGTR VTEPCIDGWV YDNSTFPSTI 

       130        140        150        160        170        180 
VTEWNLVCSH RAFRQLAQSL YMVGVLLGAM VFGYLADRLG RRKVLILNYL QTAVSGTCAA 

       190        200        210        220        230        240 
YAPNYTVYCV FRLLSGMSLA SIAINCMTLN VEWMPIHTRA YVGTLIGYVY SLGQFLLAGI 

       250        260        270        280        290        300 
AYAVPHWRHL QLVVSVPFFI AFIYSWFFIE SARWYSSSGR LDLTLRALQR VARINGKQEE 

       310        320        330        340        350        360 
GAKLSIEVLR TSLQKELTLS KGQASAMELL RCPTLRHLFL CLSMLWFATS FAYYGLVMDL 

       370        380        390        400        410        420 
QGFGVSMYLI QVIFGAVDLP AKFVCFLVIN SMGRRPAQMA SLLLAGICIL VNGIIPKSHT 

       430        440        450        460        470        480 
IIRTSLAVLG KGCLASSFNC IFLYTGELYP TVIRQTGLGM GSTMARVGSI VSPLVSMTAE 

       490        500        510        520        530        540 
FYPSMPLFIF GAVPVVASAV TALLPETLGQ PLPDTVQDLK SRSRGKQNQQ QQEQQKQMMP 

       550 
LQASTQEKNG L 

« Hide

References

« Hide 'large scale' references
[1]"Expression cloning and characterization of ROAT1. The basolateral organic anion transporter in rat kidney."
Sweet D.H., Wolff N.A., Pritchard J.B.
J. Biol. Chem. 272:30088-30095(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, TISSUE SPECIFICITY.
Tissue: Kidney.
[2]"Expression cloning and characterization of a novel multispecific organic anion transporter."
Sekine T., Watanabe N., Hosoyamada M., Kanai Y., Endou H.
J. Biol. Chem. 272:18526-18529(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, FUNCTION.
Strain: Sprague-Dawley.
Tissue: Kidney.
[3]"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.
[4]"The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1."
Cihlar T., Lin D.C., Pritchard J.B., Fuller M.D., Mendel D.B., Sweet D.H.
Mol. Pharmacol. 56:570-580(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[5]"Molecular cloning and functional analyses of OAT1 and OAT3 from cynomolgus monkey kidney."
Tahara H., Shono M., Kusuhara H., Kinoshita H., Fuse E., Takadate A., Otagiri M., Sugiyama Y.
Pharm. Res. 22:647-660(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[6]"Prostaglandin E2 inhibits its own renal transport by downregulation of organic anion transporters rOAT1 and rOAT3."
Sauvant C., Holzinger H., Gekle M.
J. Am. Soc. Nephrol. 17:46-53(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY PGE2.
[7]"Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced acute renal failure."
Matsuzaki T., Watanabe H., Yoshitome K., Morisaki T., Hamada A., Nonoguchi H., Kohda Y., Tomita K., Inui K., Saito H.
Kidney Int. 71:539-547(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF008221 mRNA. Translation: AAC18772.1.
AB004559 mRNA. Translation: BAA22086.1.
BC104692 mRNA. Translation: AAI04693.1.
RefSeqNP_058920.1. NM_017224.2.
UniGeneRn.87849.

3D structure databases

ProteinModelPortalO35956.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO35956. 1 interaction.
MINTMINT-8292692.
STRING10116.ENSRNOP00000024756.

Chemistry

BindingDBO35956.
ChEMBLCHEMBL1777665.

Protein family/group databases

TCDB2.A.1.19.4. the major facilitator superfamily (mfs).

Proteomic databases

PRIDEO35956.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000024757; ENSRNOP00000024756; ENSRNOG00000018215.
GeneID29509.
KEGGrno:29509.
UCSCRGD:69338. rat.

Organism-specific databases

CTD9356.
RGD69338. Slc22a6.

Phylogenomic databases

eggNOGCOG0477.
GeneTreeENSGT00750000117345.
HOGENOMHOG000234569.
HOVERGENHBG108433.
InParanoidO35956.
KOK08203.
OMAMIRQTGM.
OrthoDBEOG7C8GH9.
PhylomeDBO35956.
TreeFamTF315847.

Gene expression databases

GenevestigatorO35956.

Family and domain databases

InterProIPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR004749. Orgcat_transp.
IPR005828. Sub_transporter.
[Graphical view]
PfamPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMSSF103473. SSF103473. 1 hit.
TIGRFAMsTIGR00898. 2A0119. 1 hit.
PROSITEPS50850. MFS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio609428.
PROO35956.

Entry information

Entry nameS22A6_RAT
AccessionPrimary (citable) accession number: O35956
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: January 1, 1998
Last modified: June 11, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families