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O35956

- S22A6_RAT

UniProt

O35956 - S22A6_RAT

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Protein

Solute carrier family 22 member 6

Gene

Slc22a6

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

Functioni

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.By similarity2 Publications

Kineticsi

  1. KM=14.3 µM for PAH4 Publications
  2. KM=238 µM for cidofovir4 Publications
  3. KM=270 µM for adefovir4 Publications
  4. KM=10.2 µM for 2,4-D4 Publications
  5. KM=27.5 µM for HA4 Publications
  6. KM=47.1 µM for IA4 Publications
  7. KM=17.7 µM for IS4 Publications
  8. KM=154 µM for CMPF4 Publications

Vmax=1270 pmol/min/mg enzyme for 2,4-D uptake4 Publications

Vmax=519 pmol/min/mg enzyme for HA uptake4 Publications

Vmax=387 pmol/min/mg enzyme for IA uptake4 Publications

Vmax=350 pmol/min/mg enzyme for IS uptake4 Publications

Vmax=1669 pmol/min/mg enzyme for CMPF uptake4 Publications

GO - Molecular functioni

  1. anion:anion antiporter activity Source: RGD
  2. chloride ion binding Source: RGD
  3. inorganic anion exchanger activity Source: UniProtKB
  4. organic anion transmembrane transporter activity Source: MGI
  5. protein homodimerization activity Source: RGD
  6. sodium-independent organic anion transmembrane transporter activity Source: RGD

GO - Biological processi

  1. alpha-ketoglutarate transport Source: UniProtKB
  2. organic anion transport Source: MGI
  3. protein homooligomerization Source: RGD
  4. renal tubular secretion Source: UniProtKB
  5. response to methotrexate Source: RGD
  6. sodium-independent organic anion transport Source: RGD
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_196407. Organic anion transport.

Protein family/group databases

TCDBi2.A.1.19.4. the major facilitator superfamily (mfs).

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Slc22a6
Synonyms:Oat1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 1

Organism-specific databases

RGDi69338. Slc22a6.

Subcellular locationi

GO - Cellular componenti

  1. basolateral plasma membrane Source: UniProtKB
  2. caveola Source: RGD
  3. extracellular vesicular exosome Source: Ensembl
  4. integral component of plasma membrane Source: UniProtKB
  5. plasma membrane Source: RGD
  6. protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 551551Solute carrier family 22 member 6PRO_0000324171Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi39 – 391N-linked (GlcNAc...)Sequence Analysis
Glycosylationi56 – 561N-linked (GlcNAc...)Sequence Analysis
Glycosylationi92 – 921N-linked (GlcNAc...)Sequence Analysis
Glycosylationi113 – 1131N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein

Proteomic databases

PRIDEiO35956.

Expressioni

Tissue specificityi

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.2 Publications

Inductioni

Down-regulated by PGE2 and in ischemic kidney.2 Publications

Gene expression databases

ExpressionAtlasiO35956. baseline.
GenevestigatoriO35956.

Interactioni

Protein-protein interaction databases

IntActiO35956. 1 interaction.
MINTiMINT-8292692.
STRINGi10116.ENSRNOP00000024756.

Structurei

3D structure databases

ProteinModelPortaliO35956.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 99CytoplasmicSequence Analysis
Topological domaini31 – 135105ExtracellularSequence AnalysisAdd
BLAST
Topological domaini157 – 1648CytoplasmicSequence Analysis
Topological domaini188 – 1958ExtracellularSequence Analysis
Topological domaini217 – 2248CytoplasmicSequence Analysis
Topological domaini246 – 2483ExtracellularSequence Analysis
Topological domaini270 – 33768CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini359 – 36810ExtracellularSequence Analysis
Topological domaini390 – 3956CytoplasmicSequence Analysis
Topological domaini417 – 4259ExtracellularSequence Analysis
Topological domaini447 – 48438CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini506 – 55146ExtracellularSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei10 – 3021HelicalSequence AnalysisAdd
BLAST
Transmembranei136 – 15621HelicalSequence AnalysisAdd
BLAST
Transmembranei165 – 18723HelicalSequence AnalysisAdd
BLAST
Transmembranei196 – 21621HelicalSequence AnalysisAdd
BLAST
Transmembranei225 – 24521HelicalSequence AnalysisAdd
BLAST
Transmembranei249 – 26921HelicalSequence AnalysisAdd
BLAST
Transmembranei338 – 35821HelicalSequence AnalysisAdd
BLAST
Transmembranei369 – 38921HelicalSequence AnalysisAdd
BLAST
Transmembranei396 – 41621HelicalSequence AnalysisAdd
BLAST
Transmembranei426 – 44621HelicalSequence AnalysisAdd
BLAST
Transmembranei485 – 50521HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi527 – 53711Poly-GlnAdd
BLAST

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0477.
GeneTreeiENSGT00760000118852.
HOGENOMiHOG000234569.
HOVERGENiHBG108433.
InParanoidiO35956.
KOiK08203.
OMAiMIRQTGM.
OrthoDBiEOG7C8GH9.
PhylomeDBiO35956.
TreeFamiTF315847.

Family and domain databases

InterProiIPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR004749. Orgcat_transp.
IPR005828. Sub_transporter.
[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.

O35956-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPPHHCR
60 70 80 90 100
PPANANLSKD GGLEAWLPLD KQGQPESCLR FTSPQWGPPF YNGTEANGTR
110 120 130 140 150
VTEPCIDGWV YDNSTFPSTI VTEWNLVCSH RAFRQLAQSL YMVGVLLGAM
160 170 180 190 200
VFGYLADRLG RRKVLILNYL QTAVSGTCAA YAPNYTVYCV FRLLSGMSLA
210 220 230 240 250
SIAINCMTLN VEWMPIHTRA YVGTLIGYVY SLGQFLLAGI AYAVPHWRHL
260 270 280 290 300
QLVVSVPFFI AFIYSWFFIE SARWYSSSGR LDLTLRALQR VARINGKQEE
310 320 330 340 350
GAKLSIEVLR TSLQKELTLS KGQASAMELL RCPTLRHLFL CLSMLWFATS
360 370 380 390 400
FAYYGLVMDL QGFGVSMYLI QVIFGAVDLP AKFVCFLVIN SMGRRPAQMA
410 420 430 440 450
SLLLAGICIL VNGIIPKSHT IIRTSLAVLG KGCLASSFNC IFLYTGELYP
460 470 480 490 500
TVIRQTGLGM GSTMARVGSI VSPLVSMTAE FYPSMPLFIF GAVPVVASAV
510 520 530 540 550
TALLPETLGQ PLPDTVQDLK SRSRGKQNQQ QQEQQKQMMP LQASTQEKNG

L
Length:551
Mass (Da):60,766
Last modified:January 1, 1998 - v1
Checksum:i8BA47BE628324BF2
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF008221 mRNA. Translation: AAC18772.1.
AB004559 mRNA. Translation: BAA22086.1.
BC104692 mRNA. Translation: AAI04693.1.
RefSeqiNP_058920.1. NM_017224.2.
UniGeneiRn.87849.

Genome annotation databases

EnsembliENSRNOT00000024757; ENSRNOP00000024756; ENSRNOG00000018215.
GeneIDi29509.
KEGGirno:29509.
UCSCiRGD:69338. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF008221 mRNA. Translation: AAC18772.1 .
AB004559 mRNA. Translation: BAA22086.1 .
BC104692 mRNA. Translation: AAI04693.1 .
RefSeqi NP_058920.1. NM_017224.2.
UniGenei Rn.87849.

3D structure databases

ProteinModelPortali O35956.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi O35956. 1 interaction.
MINTi MINT-8292692.
STRINGi 10116.ENSRNOP00000024756.

Chemistry

BindingDBi O35956.
ChEMBLi CHEMBL1777665.

Protein family/group databases

TCDBi 2.A.1.19.4. the major facilitator superfamily (mfs).

Proteomic databases

PRIDEi O35956.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000024757 ; ENSRNOP00000024756 ; ENSRNOG00000018215 .
GeneIDi 29509.
KEGGi rno:29509.
UCSCi RGD:69338. rat.

Organism-specific databases

CTDi 9356.
RGDi 69338. Slc22a6.

Phylogenomic databases

eggNOGi COG0477.
GeneTreei ENSGT00760000118852.
HOGENOMi HOG000234569.
HOVERGENi HBG108433.
InParanoidi O35956.
KOi K08203.
OMAi MIRQTGM.
OrthoDBi EOG7C8GH9.
PhylomeDBi O35956.
TreeFami TF315847.

Enzyme and pathway databases

Reactomei REACT_196407. Organic anion transport.

Miscellaneous databases

NextBioi 609428.
PROi O35956.

Gene expression databases

ExpressionAtlasi O35956. baseline.
Genevestigatori O35956.

Family and domain databases

InterProi IPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR004749. Orgcat_transp.
IPR005828. Sub_transporter.
[Graphical view ]
Pfami PF00083. Sugar_tr. 1 hit.
[Graphical view ]
SUPFAMi SSF103473. SSF103473. 1 hit.
TIGRFAMsi TIGR00898. 2A0119. 1 hit.
PROSITEi PS50850. MFS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiS22A6_RAT
AccessioniPrimary (citable) accession number: O35956
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: January 1, 1998
Last modified: October 29, 2014
This is version 107 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

External Data

Dasty 3