S22A6_HUMAN
ID S22A6_HUMAN Reviewed; 563 AA.
AC Q4U2R8; A8MY93; B2D0R6; O95187; O95742; Q7LDA0; Q8N192; Q9NQA6; Q9NQC2;
AC Q9UBG6; Q9UEQ8;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Solute carrier family 22 member 6;
DE AltName: Full=Organic anion transporter 1;
DE Short=hOAT1;
DE AltName: Full=PAH transporter;
DE Short=hPAHT;
DE AltName: Full=Renal organic anion transporter 1;
DE Short=hROAT1;
GN Name=SLC22A6; Synonyms=OAT1, PAHT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND FUNCTION.
RX PubMed=9762842; DOI=10.1159/000025863;
RA Reid G., Wolff N.A., Dautzenberg F.M., Burckhardt G.;
RT "Cloning of a human renal p-aminohippurate transporter, hROAT1.";
RL Kidney Blood Press. Res. 21:233-237(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP FUNCTION.
RC TISSUE=Kidney;
RX PubMed=9887087; DOI=10.1152/ajprenal.1999.276.1.f122;
RA Hosoyamada M., Sekine T., Kanai Y., Endou H.;
RT "Molecular cloning and functional expression of a multispecific organic
RT anion transporter from human kidney.";
RL Am. J. Physiol. 276:F122-F128(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=9950961; DOI=10.1152/ajprenal.1999.276.2.f295;
RA Lu R., Chan B.S., Schuster V.L.;
RT "Cloning of the human kidney PAH transporter: narrow substrate specificity
RT and regulation by protein kinase C.";
RL Am. J. Physiol. 276:F295-F303(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=10049739; DOI=10.1006/bbrc.1998.9978;
RA Race J.E., Grassl S.M., Williams W.J., Holtzman E.J.;
RT "Molecular cloning and characterization of two novel human renal organic
RT anion transporters (hOAT1 and hOAT3).";
RL Biochem. Biophys. Res. Commun. 255:508-514(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), GLYCOSYLATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=10462545; DOI=10.1124/mol.56.3.570;
RA Cihlar T., Lin D.C., Pritchard J.B., Fuller M.D., Mendel D.B., Sweet D.H.;
RT "The antiviral nucleotide analogs cidofovir and adefovir are novel
RT substrates for human and rat renal organic anion transporter 1.";
RL Mol. Pharmacol. 56:570-580(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 3 AND 4),
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=10964714; DOI=10.1006/bbrc.2000.3230;
RA Bahn A., Prawitt D., Buttler D., Reid G., Enklaar T., Wolff N.A.,
RA Ebbinghaus C., Hillemann A., Schulten H.-J., Gunawan B., Fuezesi L.,
RA Zabel B., Burckhardt G.;
RT "Genomic structure and in vivo expression of the human organic anion
RT transporter 1 (hOAT1) gene.";
RL Biochem. Biophys. Res. Commun. 275:623-630(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-104.
RG NIEHS SNPs program;
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12538807; DOI=10.1124/jpet.102.043455;
RA Groves C.E., Munoz L., Bahn A., Burckhardt G., Wright S.H.;
RT "Interaction of cysteine conjugates with human and rabbit organic anion
RT transporter 1.";
RL J. Pharmacol. Exp. Ther. 304:560-566(2003).
RN [12]
RP MUTAGENESIS OF ASN-39, AND GLYCOSYLATION AT ASN-39; ASN-56; ASN-92 AND
RP ASN-97.
RX PubMed=14749323; DOI=10.1074/jbc.m400197200;
RA Tanaka K., Xu W., Zhou F., You G.;
RT "Role of glycosylation in the organic anion transporter OAT1.";
RL J. Biol. Chem. 279:14961-14966(2004).
RN [13]
RP MUTAGENESIS OF LEU-30 AND THR-36.
RX PubMed=15145940; DOI=10.1074/jbc.m404686200;
RA Hong M., Zhou F., You G.;
RT "Critical amino acid residues in transmembrane domain 1 of the human
RT organic anion transporter hOAT1.";
RL J. Biol. Chem. 279:31478-31482(2004).
RN [14]
RP FUNCTION.
RX PubMed=15644426; DOI=10.1124/jpet.104.080366;
RA Srimaroeng C., Chatsudthipong V., Aslamkhan A.G., Pritchard J.B.;
RT "Transport of the natural sweetener stevioside and its aglycone steviol by
RT human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8).";
RL J. Pharmacol. Exp. Ther. 313:621-628(2005).
RN [15]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15846473; DOI=10.1007/s11095-005-2503-0;
RA Tahara H., Shono M., Kusuhara H., Kinoshita H., Fuse E., Takadate A.,
RA Otagiri M., Sugiyama Y.;
RT "Molecular cloning and functional analyses of OAT1 and OAT3 from cynomolgus
RT monkey kidney.";
RL Pharm. Res. 22:647-660(2005).
RN [16]
RP MUTAGENESIS OF TYR-230; LYS-431 AND PHE-438, SUBSTRATE-BINDING SITES, AND
RP FUNCTION.
RX PubMed=17038320; DOI=10.1074/jbc.m608834200;
RA Perry J.L., Dembla-Rajpal N., Hall L.A., Pritchard J.B.;
RT "A three-dimensional model of human organic anion transporter 1: aromatic
RT amino acids required for substrate transport.";
RL J. Biol. Chem. 281:38071-38079(2006).
RN [17]
RP FUNCTION.
RX PubMed=17502342; DOI=10.1124/dmd.106.013912;
RA Mizuno N., Takahashi T., Iwase Y., Kusuhara H., Niwa T., Sugiyama Y.;
RT "Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8)
RT transport edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one) and its
RT sulfate conjugate.";
RL Drug Metab. Dispos. 35:1429-1434(2007).
RN [18]
RP VARIANT HIS-50, AND CHARACTERIZATION OF VARIANT HIS-50.
RX PubMed=15914676; DOI=10.1124/jpet.105.084301;
RA Bleasby K., Hall L.A., Perry J.L., Mohrenweiser H.W., Pritchard J.B.;
RT "Functional consequences of single nucleotide polymorphisms in the human
RT organic anion transporter hOAT1 (SLC22A6).";
RL J. Pharmacol. Exp. Ther. 314:923-931(2005).
RN [19]
RP VARIANTS PRO-7 AND HIS-50.
RX PubMed=16164626; DOI=10.1111/j.1523-1755.2005.00612.x;
RA Xu G., Bhatnagar V., Wen G., Hamilton B.A., Eraly S.A., Nigam S.K.;
RT "Analyses of coding region polymorphisms in apical and basolateral human
RT organic anion transporter (OAT) genes [OAT1 (NKT), OAT2, OAT3, OAT4, URAT
RT (RST)].";
RL Kidney Int. 68:1491-1499(2005).
CC -!- FUNCTION: Involved in the renal elimination of endogenous and exogenous
CC organic anions. Functions as organic anion exchanger when the uptake of
CC one molecule of organic anion is coupled with an efflux of one molecule
CC of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc).
CC Mediates the sodium-independent uptake of 2,3-dimercapto-1-
CC propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-
CC independent uptake of p-aminohippurate (PAH), ochratoxin (OTA),
CC acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD),
CC 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate
CC (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-
CC furanpropionate (CMPF), cidofovir, adefovir, 9-(2-
CC phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl)
CC diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited
CC by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate
CC (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By
CC similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC),
CC S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-
CC dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate
CC 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin,
CC furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red,
CC urate, and alpha-ketoglutarate. {ECO:0000250,
CC ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15644426,
CC ECO:0000269|PubMed:17038320, ECO:0000269|PubMed:17502342,
CC ECO:0000269|PubMed:9762842, ECO:0000269|PubMed:9887087}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.3 uM for PAH (isoform 1) {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC KM=4 uM for PAH (isoform 2) {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC KM=11 uM for edaravone {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC KM=46 uM for cidofovir {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC KM=30 uM for adefovir {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC KM=5.77 uM for 2,4-D {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC KM=23.5 uM for HA {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC KM=14 uM for IA {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC KM=20.5 uM for IS {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC KM=141 uM for CMPF {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
CC ECO:0000269|PubMed:15846473};
CC Vmax=534 pmol/min/mg enzyme for 2,4-D uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
CC ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
CC Vmax=430 pmol/min/mg enzyme for HA uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
CC ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
CC Vmax=110 pmol/min/mg enzyme for IA uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
CC ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
CC Vmax=216 pmol/min/mg enzyme for IS uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
CC ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
CC Vmax=801 pmol/min/mg enzyme for CMPF uptake
CC {ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
CC ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
CC -!- INTERACTION:
CC Q4U2R8; Q92624: APPBP2; NbExp=3; IntAct=EBI-749741, EBI-743771;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=OAT1-1;
CC IsoId=Q4U2R8-1; Sequence=Displayed;
CC Name=2; Synonyms=OAT1-2;
CC IsoId=Q4U2R8-2; Sequence=VSP_032169;
CC Name=3; Synonyms=OAT1-3;
CC IsoId=Q4U2R8-3; Sequence=VSP_032168, VSP_032169;
CC Name=4; Synonyms=OAT1-4;
CC IsoId=Q4U2R8-4; Sequence=VSP_032168;
CC -!- TISSUE SPECIFICITY: Strongly expressed in kidney and to a lower extent
CC in liver, skeletal muscle, brain and placenta. Found at the basolateral
CC membrane of the proximal tubule. {ECO:0000269|PubMed:10049739,
CC ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
CC ECO:0000269|PubMed:9887087, ECO:0000269|PubMed:9950961}.
CC -!- DOMAIN: Multiple cysteine residues are necessary for proper targeting
CC to the plasma membrane. {ECO:0000250}.
CC -!- PTM: Glycosylated. Glycosylation at Asn-113 may occur at a secondary
CC level. Glycosylation is necessary for proper targeting of the
CC transporter to the plasma membrane. {ECO:0000269|PubMed:10462545,
CC ECO:0000269|PubMed:14749323}.
CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily.
CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/slc22a6/";
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DR EMBL; AF057039; AAC70004.1; -; mRNA.
DR EMBL; AB009697; BAA75072.1; -; mRNA.
DR EMBL; AB009698; BAA75073.1; -; mRNA.
DR EMBL; AF104038; AAD10052.1; -; mRNA.
DR EMBL; AF097490; AAD19356.1; -; mRNA.
DR EMBL; AF124373; AAD55356.1; -; mRNA.
DR EMBL; AJ249369; CAB77184.1; -; Genomic_DNA.
DR EMBL; AJ251529; CAB94830.1; -; mRNA.
DR EMBL; AJ271205; CAB97249.1; -; mRNA.
DR EMBL; EU567146; ACB21049.1; -; Genomic_DNA.
DR EMBL; AP001858; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74129.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW74130.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW74131.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW74132.1; -; Genomic_DNA.
DR EMBL; BC033682; AAH33682.1; -; mRNA.
DR CCDS; CCDS31591.1; -. [Q4U2R8-1]
DR CCDS; CCDS44631.1; -. [Q4U2R8-4]
DR CCDS; CCDS44632.1; -. [Q4U2R8-3]
DR CCDS; CCDS8041.1; -. [Q4U2R8-2]
DR RefSeq; NP_004781.2; NM_004790.4. [Q4U2R8-1]
DR RefSeq; NP_695008.1; NM_153276.2. [Q4U2R8-2]
DR RefSeq; NP_695009.1; NM_153277.2. [Q4U2R8-3]
DR RefSeq; NP_695010.1; NM_153278.2. [Q4U2R8-4]
DR AlphaFoldDB; Q4U2R8; -.
DR SMR; Q4U2R8; -.
DR BioGRID; 114759; 37.
DR IntAct; Q4U2R8; 19.
DR STRING; 9606.ENSP00000367102; -.
DR BindingDB; Q4U2R8; -.
DR ChEMBL; CHEMBL1641347; -.
DR DrugBank; DB00659; Acamprosate.
DR DrugBank; DB00819; Acetazolamide.
DR DrugBank; DB06151; Acetylcysteine.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB00787; Acyclovir.
DR DrugBank; DB00718; Adefovir dipivoxil.
DR DrugBank; DB00770; Alprostadil.
DR DrugBank; DB00345; Aminohippuric acid.
DR DrugBank; DB01424; Aminophenazone.
DR DrugBank; DB01060; Amoxicillin.
DR DrugBank; DB01435; Antipyrine.
DR DrugBank; DB00168; Aspartame.
DR DrugBank; DB05016; Ataluren.
DR DrugBank; DB16098; Atogepant.
DR DrugBank; DB11817; Baricitinib.
DR DrugBank; DB01053; Benzylpenicillin.
DR DrugBank; DB12151; Brincidofovir.
DR DrugBank; DB01237; Bromodiphenhydramine.
DR DrugBank; DB00887; Bumetanide.
DR DrugBank; DB11751; Cabotegravir.
DR DrugBank; DB04519; Caprylic acid.
DR DrugBank; DB01197; Captopril.
DR DrugBank; DB00578; Carbenicillin.
DR DrugBank; DB00821; Carprofen.
DR DrugBank; DB00520; Caspofungin.
DR DrugBank; DB01414; Cefacetrile.
DR DrugBank; DB01140; Cefadroxil.
DR DrugBank; DB09008; Cefaloridine.
DR DrugBank; DB00456; Cefalotin.
DR DrugBank; DB01326; Cefamandole.
DR DrugBank; DB01327; Cefazolin.
DR DrugBank; DB00535; Cefdinir.
DR DrugBank; DB01329; Cefoperazone.
DR DrugBank; DB00493; Cefotaxime.
DR DrugBank; DB00229; Cefotiam.
DR DrugBank; DB01333; Cefradine.
DR DrugBank; DB00438; Ceftazidime.
DR DrugBank; DB01415; Ceftibuten.
DR DrugBank; DB01332; Ceftizoxime.
DR DrugBank; DB01212; Ceftriaxone.
DR DrugBank; DB00567; Cephalexin.
DR DrugBank; DB00446; Chloramphenicol.
DR DrugBank; DB00880; Chlorothiazide.
DR DrugBank; DB00672; Chlorpropamide.
DR DrugBank; DB00369; Cidofovir.
DR DrugBank; DB01597; Cilastatin.
DR DrugBank; DB00501; Cimetidine.
DR DrugBank; DB00827; Cinoxacin.
DR DrugBank; DB00155; Citrulline.
DR DrugBank; DB00286; Conjugated estrogens.
DR DrugBank; DB02527; Cyclic adenosine monophosphate.
DR DrugBank; DB02315; Cyclic GMP.
DR DrugBank; DB00091; Cyclosporine.
DR DrugBank; DB00606; Cyclothiazide.
DR DrugBank; DB08912; Dabrafenib.
DR DrugBank; DB04133; Degraded Cephaloridine.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB00586; Diclofenac.
DR DrugBank; DB00900; Didanosine.
DR DrugBank; DB00861; Diflunisal.
DR DrugBank; DB01160; Dinoprost tromethamine.
DR DrugBank; DB00917; Dinoprostone.
DR DrugBank; DB08930; Dolutegravir.
DR DrugBank; DB00254; Doxycycline.
DR DrugBank; DB12243; Edaravone.
DR DrugBank; DB08846; Ellagic acid.
DR DrugBank; DB00584; Enalapril.
DR DrugBank; DB13874; Enasidenib.
DR DrugBank; DB00903; Etacrynic acid.
DR DrugBank; DB00311; Ethoxzolamide.
DR DrugBank; DB00749; Etodolac.
DR DrugBank; DB00927; Famotidine.
DR DrugBank; DB12466; Favipiravir.
DR DrugBank; DB12265; Fexinidazole.
DR DrugBank; DB02266; Flufenamic acid.
DR DrugBank; DB00693; Fluorescein.
DR DrugBank; DB00712; Flurbiprofen.
DR DrugBank; DB00158; Folic acid.
DR DrugBank; DB00529; Foscarnet.
DR DrugBank; DB16628; Fosdenopterin.
DR DrugBank; DB00695; Furosemide.
DR DrugBank; DB01004; Ganciclovir.
DR DrugBank; DB03553; Glutaric Acid.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB00365; Grepafloxacin.
DR DrugBank; DB08843; GS 0573.
DR DrugBank; DB00999; Hydrochlorothiazide.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB01050; Ibuprofen.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB11757; Istradefylline.
DR DrugBank; DB01009; Ketoprofen.
DR DrugBank; DB00709; Lamivudine.
DR DrugBank; DB00654; Latanoprost.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB00601; Linezolid.
DR DrugBank; DB00678; Losartan.
DR DrugBank; DB00939; Meclofenamic acid.
DR DrugBank; DB00703; Methazolamide.
DR DrugBank; DB00563; Methotrexate.
DR DrugBank; DB01017; Minocycline.
DR DrugBank; DB00607; Nafcillin.
DR DrugBank; DB00779; Nalidixic acid.
DR DrugBank; DB00788; Naproxen.
DR DrugBank; DB00731; Nateglinide.
DR DrugBank; DB01059; Norfloxacin.
DR DrugBank; DB01051; Novobiocin.
DR DrugBank; DB01165; Ofloxacin.
DR DrugBank; DB11837; Osilodrostat.
DR DrugBank; DB03585; Oxyphenbutazone.
DR DrugBank; DB00595; Oxytetracycline.
DR DrugBank; DB15413; Pafolacianine.
DR DrugBank; DB03783; Phenacetin.
DR DrugBank; DB00812; Phenylbutazone.
DR DrugBank; DB00319; Piperacillin.
DR DrugBank; DB00554; Piroxicam.
DR DrugBank; DB01324; Polythiazide.
DR DrugBank; DB15822; Pralsetinib.
DR DrugBank; DB00175; Pravastatin.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB00140; Riboflavin.
DR DrugBank; DB01045; Rifampicin.
DR DrugBank; DB06176; Romidepsin.
DR DrugBank; DB12332; Rucaparib.
DR DrugBank; DB00936; Salicylic acid.
DR DrugBank; DB09298; Silibinin.
DR DrugBank; DB00649; Stavudine.
DR DrugBank; DB00605; Sulindac.
DR DrugBank; DB11644; Tafamidis.
DR DrugBank; DB04348; Taurocholic acid.
DR DrugBank; DB01606; Tazobactam.
DR DrugBank; DB14126; Tenofovir.
DR DrugBank; DB09299; Tenofovir alafenamide.
DR DrugBank; DB00300; Tenofovir disoproxil.
DR DrugBank; DB00759; Tetracycline.
DR DrugBank; DB01124; Tolbutamide.
DR DrugBank; DB00500; Tolmetin.
DR DrugBank; DB01685; Topiroxostat.
DR DrugBank; DB00432; Trifluridine.
DR DrugBank; DB15328; Ubrogepant.
DR DrugBank; DB08844; Uric acid.
DR DrugBank; DB00577; Valaciclovir.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB00943; Zalcitabine.
DR DrugBank; DB00495; Zidovudine.
DR DrugCentral; Q4U2R8; -.
DR GuidetoPHARMACOLOGY; 1025; -.
DR TCDB; 2.A.1.19.31; the major facilitator superfamily (mfs).
DR GlyGen; Q4U2R8; 5 sites.
DR iPTMnet; Q4U2R8; -.
DR PhosphoSitePlus; Q4U2R8; -.
DR BioMuta; SLC22A6; -.
DR DMDM; 74762955; -.
DR EPD; Q4U2R8; -.
DR MassIVE; Q4U2R8; -.
DR PaxDb; Q4U2R8; -.
DR PeptideAtlas; Q4U2R8; -.
DR PRIDE; Q4U2R8; -.
DR ProteomicsDB; 62263; -. [Q4U2R8-1]
DR ProteomicsDB; 62264; -. [Q4U2R8-2]
DR ProteomicsDB; 62265; -. [Q4U2R8-3]
DR ProteomicsDB; 62266; -. [Q4U2R8-4]
DR Antibodypedia; 28866; 298 antibodies from 32 providers.
DR DNASU; 9356; -.
DR Ensembl; ENST00000360421.9; ENSP00000353597.4; ENSG00000197901.12. [Q4U2R8-2]
DR Ensembl; ENST00000377871.7; ENSP00000367102.3; ENSG00000197901.12. [Q4U2R8-1]
DR Ensembl; ENST00000421062.2; ENSP00000404441.2; ENSG00000197901.12. [Q4U2R8-4]
DR Ensembl; ENST00000458333.6; ENSP00000396401.2; ENSG00000197901.12. [Q4U2R8-3]
DR GeneID; 9356; -.
DR KEGG; hsa:9356; -.
DR MANE-Select; ENST00000360421.9; ENSP00000353597.4; NM_153276.3; NP_695008.1. [Q4U2R8-2]
DR UCSC; uc001nwj.4; human. [Q4U2R8-1]
DR CTD; 9356; -.
DR DisGeNET; 9356; -.
DR GeneCards; SLC22A6; -.
DR HGNC; HGNC:10970; SLC22A6.
DR HPA; ENSG00000197901; Tissue enriched (kidney).
DR MIM; 607582; gene.
DR neXtProt; NX_Q4U2R8; -.
DR OpenTargets; ENSG00000197901; -.
DR PharmGKB; PA388; -.
DR VEuPathDB; HostDB:ENSG00000197901; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000157004; -.
DR HOGENOM; CLU_001265_33_3_1; -.
DR InParanoid; Q4U2R8; -.
DR OMA; PWHCTGV; -.
DR OrthoDB; 464838at2759; -.
DR PhylomeDB; Q4U2R8; -.
DR TreeFam; TF315847; -.
DR PathwayCommons; Q4U2R8; -.
DR Reactome; R-HSA-561048; Organic anion transport.
DR SABIO-RK; Q4U2R8; -.
DR SignaLink; Q4U2R8; -.
DR BioGRID-ORCS; 9356; 9 hits in 1071 CRISPR screens.
DR ChiTaRS; SLC22A6; human.
DR GeneWiki; Organic_anion_transporter_1; -.
DR GenomeRNAi; 9356; -.
DR Pharos; Q4U2R8; Tclin.
DR PRO; PR:Q4U2R8; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q4U2R8; protein.
DR Bgee; ENSG00000197901; Expressed in adult mammalian kidney and 46 other tissues.
DR ExpressionAtlas; Q4U2R8; baseline and differential.
DR Genevisible; Q4U2R8; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0015301; F:anion:anion antiporter activity; TAS:Reactome.
DR GO; GO:0031404; F:chloride ion binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0005452; F:inorganic anion exchanger activity; IDA:UniProtKB.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015347; F:sodium-independent organic anion transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015742; P:alpha-ketoglutarate transport; IDA:UniProtKB.
DR GO; GO:0015711; P:organic anion transport; IDA:UniProtKB.
DR GO; GO:0097254; P:renal tubular secretion; IMP:UniProtKB.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0043252; P:sodium-independent organic anion transport; IDA:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR005828; MFS_sugar_transport-like.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR004749; Orgcat_transp/SVOP.
DR Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00898; 2A0119; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..563
FT /note="Solute carrier family 22 member 6"
FT /id="PRO_0000324166"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..135
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157..164
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..190
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..224
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 246..248
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..269
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..368
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 390..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 396..416
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 417..425
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 426..446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 447..455
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 456..475
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 476..484
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 485..505
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 506..563
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 525..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 230
FT /note="Important for interaction with cidofovir"
FT SITE 438
FT /note="Important for interaction with cidofovir and PAH"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14749323"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14749323"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14749323"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14749323"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10462545"
FT VAR_SEQ 455..498
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10964714"
FT /id="VSP_032168"
FT VAR_SEQ 523..535
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10049739,
FT ECO:0000303|PubMed:10462545, ECO:0000303|PubMed:10964714,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9762842,
FT ECO:0000303|PubMed:9887087, ECO:0000303|PubMed:9950961"
FT /id="VSP_032169"
FT VARIANT 7
FT /note="L -> P (in dbSNP:rs1415632329)"
FT /evidence="ECO:0000269|PubMed:16164626"
FT /id="VAR_039682"
FT VARIANT 50
FT /note="R -> H (lower Vmax; increase in substrate affinity
FT and increase in the affinity for the nucleoside phosphonate
FT analogs cidofovir, adefovir and tenofovir;
FT dbSNP:rs11568626)"
FT /evidence="ECO:0000269|PubMed:15914676,
FT ECO:0000269|PubMed:16164626"
FT /id="VAR_039683"
FT VARIANT 104
FT /note="P -> L (in dbSNP:rs11568627)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_047878"
FT VARIANT 293
FT /note="R -> W (increase in substrate affinity;
FT dbSNP:rs45607933)"
FT /id="VAR_039684"
FT MUTAGEN 30
FT /note="L->A: Complete loss of PAH transport activity."
FT /evidence="ECO:0000269|PubMed:15145940"
FT MUTAGEN 36
FT /note="T->A: Complete loss of PAH transport activity."
FT /evidence="ECO:0000269|PubMed:15145940"
FT MUTAGEN 39
FT /note="N->Q: Complete loss of PAH transport activity."
FT /evidence="ECO:0000269|PubMed:14749323"
FT MUTAGEN 230
FT /note="Y->A: Loss of membrane protein expression and little
FT uptake of cidofovir."
FT /evidence="ECO:0000269|PubMed:17038320"
FT MUTAGEN 431
FT /note="K->A: Decrease in the level of membrane protein
FT expression and 70 % loss of PAH uptake."
FT /evidence="ECO:0000269|PubMed:17038320"
FT MUTAGEN 438
FT /note="F->A: Decrease in the level of membrane protein
FT expression, 70 % loss of PAH uptake, increased affinity for
FT cidofovir, lower Vmax for PAH, and lower Km and Vmax for
FT cidofovir."
FT /evidence="ECO:0000269|PubMed:17038320"
FT CONFLICT 14
FT /note="G -> S (in Ref. 3; AAD10052)"
FT /evidence="ECO:0000305"
FT CONFLICT 563
FT /note="L -> F (in Ref. 1; AAC70004)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 563 AA; 61816 MW; 74AD3EA2678032E4 CRC64;
MAFNDLLQQV GGVGRFQQIQ VTLVVLPLLL MASHNTLQNF TAAIPTHHCR PPADANLSKN
GGLEVWLPRD RQGQPESCLR FTSPQWGLPF LNGTEANGTG ATEPCTDGWI YDNSTFPSTI
VTEWDLVCSH RALRQLAQSL YMVGVLLGAM VFGYLADRLG RRKVLILNYL QTAVSGTCAA
FAPNFPIYCA FRLLSGMALA GISLNCMTLN VEWMPIHTRA CVGTLIGYVY SLGQFLLAGV
AYAVPHWRHL QLLVSAPFFA FFIYSWFFIE SARWHSSSGR LDLTLRALQR VARINGKREE
GAKLSMEVLR ASLQKELTMG KGQASAMELL RCPTLRHLFL CLSMLWFATS FAYYGLVMDL
QGFGVSIYLI QVIFGAVDLP AKLVGFLVIN SLGRRPAQMA ALLLAGICIL LNGVIPQDQS
IVRTSLAVLG KGCLAASFNC IFLYTGELYP TMIRQTGMGM GSTMARVGSI VSPLVSMTAE
LYPSMPLFIY GAVPVAASAV TVLLPETLGQ PLPDTVQDLE SRWAPTQKEA GIYPRKGKQT
RQQQEHQKYM VPLQASAQEK NGL
