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O35956

- S22A6_RAT

UniProt

O35956 - S22A6_RAT

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
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    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 binding Source: RGD
    6. protein homodimerization activity Source: RGD
    7. 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

    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. integral component of plasma membrane Source: UniProtKB
    4. plasma membrane Source: RGD
    5. protein complex Source: RGD

    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

    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.
    GeneTreeiENSGT00750000117345.
    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

    MAFNDLLKQV GGVGRFQLIQ VTMVVAPLLL MASHNTLQNF TAAIPPHHCR    50
    PPANANLSKD GGLEAWLPLD KQGQPESCLR FTSPQWGPPF YNGTEANGTR 100
    VTEPCIDGWV YDNSTFPSTI VTEWNLVCSH RAFRQLAQSL YMVGVLLGAM 150
    VFGYLADRLG RRKVLILNYL QTAVSGTCAA YAPNYTVYCV FRLLSGMSLA 200
    SIAINCMTLN VEWMPIHTRA YVGTLIGYVY SLGQFLLAGI AYAVPHWRHL 250
    QLVVSVPFFI AFIYSWFFIE SARWYSSSGR LDLTLRALQR VARINGKQEE 300
    GAKLSIEVLR TSLQKELTLS KGQASAMELL RCPTLRHLFL CLSMLWFATS 350
    FAYYGLVMDL QGFGVSMYLI QVIFGAVDLP AKFVCFLVIN SMGRRPAQMA 400
    SLLLAGICIL VNGIIPKSHT IIRTSLAVLG KGCLASSFNC IFLYTGELYP 450
    TVIRQTGLGM GSTMARVGSI VSPLVSMTAE FYPSMPLFIF GAVPVVASAV 500
    TALLPETLGQ PLPDTVQDLK SRSRGKQNQQ QQEQQKQMMP LQASTQEKNG 550
    L 551
    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 ENSGT00750000117345.
    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

    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

    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 1, 2014
    This is version 106 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