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Solute carrier family 22 member 6 (Organic anion transporter 1) (hOAT1) (PAH transporter) (hPAHT) (Renal organic anion transporter 1) (hROAT1)

 S22A6_HUMAN             Reviewed;         563 AA.
Q4U2R8; A8MY93; B2D0R6; O95187; O95742; Q7LDA0; Q8N192; Q9NQA6;
Q9NQC2; Q9UBG6; Q9UEQ8;
18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
19-JUL-2005, sequence version 1.
30-AUG-2017, entry version 127.
RecName: Full=Solute carrier family 22 member 6;
AltName: Full=Organic anion transporter 1;
Short=hOAT1;
AltName: Full=PAH transporter;
Short=hPAHT;
AltName: Full=Renal organic anion transporter 1;
Short=hROAT1;
Name=SLC22A6; Synonyms=OAT1, PAHT;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND FUNCTION.
PubMed=9762842; DOI=10.1159/000025863;
Reid G., Wolff N.A., Dautzenberg F.M., Burckhardt G.;
"Cloning of a human renal p-aminohippurate transporter, hROAT1.";
Kidney Blood Press. Res. 21:233-237(1998).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
FUNCTION.
TISSUE=Kidney;
PubMed=9887087;
Hosoyamada M., Sekine T., Kanai Y., Endou H.;
"Molecular cloning and functional expression of a multispecific
organic anion transporter from human kidney.";
Am. J. Physiol. 276:F122-F128(1999).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
TISSUE=Kidney;
PubMed=9950961;
Lu R., Chan B.S., Schuster V.L.;
"Cloning of the human kidney PAH transporter: narrow substrate
specificity and regulation by protein kinase C.";
Am. J. Physiol. 276:F295-F303(1999).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
TISSUE=Kidney;
PubMed=10049739; DOI=10.1006/bbrc.1998.9978;
Race J.E., Grassl S.M., Williams W.J., Holtzman E.J.;
"Molecular cloning and characterization of two novel human renal
organic anion transporters (hOAT1 and hOAT3).";
Biochem. Biophys. Res. Commun. 255:508-514(1999).
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), GLYCOSYLATION,
BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
TISSUE=Kidney;
PubMed=10462545;
Cihlar T., Lin D.C., Pritchard J.B., Fuller M.D., Mendel D.B.,
Sweet D.H.;
"The antiviral nucleotide analogs cidofovir and adefovir are novel
substrates for human and rat renal organic anion transporter 1.";
Mol. Pharmacol. 56:570-580(1999).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 3 AND 4),
BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
TISSUE=Kidney;
PubMed=10964714; DOI=10.1006/bbrc.2000.3230;
Bahn A., Prawitt D., Buttler D., Reid G., Enklaar T., Wolff N.A.,
Ebbinghaus C., Hillemann A., Schulten H.-J., Gunawan B., Fuezesi L.,
Zabel B., Burckhardt G.;
"Genomic structure and in vivo expression of the human organic anion
transporter 1 (hOAT1) gene.";
Biochem. Biophys. Res. Commun. 275:623-630(2000).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-104.
NIEHS SNPs program;
Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16554811; DOI=10.1038/nature04632;
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
Sakaki Y.;
"Human chromosome 11 DNA sequence and analysis including novel gene
identification.";
Nature 440:497-500(2006).
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[10]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Colon;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[11]
FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=12538807; DOI=10.1124/jpet.102.043455;
Groves C.E., Munoz L., Bahn A., Burckhardt G., Wright S.H.;
"Interaction of cysteine conjugates with human and rabbit organic
anion transporter 1.";
J. Pharmacol. Exp. Ther. 304:560-566(2003).
[12]
MUTAGENESIS OF ASN-39, AND GLYCOSYLATION AT ASN-39; ASN-56; ASN-92 AND
ASN-97.
PubMed=14749323; DOI=10.1074/jbc.M400197200;
Tanaka K., Xu W., Zhou F., You G.;
"Role of glycosylation in the organic anion transporter OAT1.";
J. Biol. Chem. 279:14961-14966(2004).
[13]
MUTAGENESIS OF LEU-30 AND THR-36.
PubMed=15145940; DOI=10.1074/jbc.M404686200;
Hong M., Zhou F., You G.;
"Critical amino acid residues in transmembrane domain 1 of the human
organic anion transporter hOAT1.";
J. Biol. Chem. 279:31478-31482(2004).
[14]
FUNCTION.
PubMed=15644426; DOI=10.1124/jpet.104.080366;
Srimaroeng C., Chatsudthipong V., Aslamkhan A.G., Pritchard J.B.;
"Transport of the natural sweetener stevioside and its aglycone
steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3
(SLC22A8).";
J. Pharmacol. Exp. Ther. 313:621-628(2005).
[15]
BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=15846473; DOI=10.1007/s11095-005-2503-0;
Tahara H., Shono M., Kusuhara H., Kinoshita H., Fuse E., Takadate A.,
Otagiri M., Sugiyama Y.;
"Molecular cloning and functional analyses of OAT1 and OAT3 from
cynomolgus monkey kidney.";
Pharm. Res. 22:647-660(2005).
[16]
MUTAGENESIS OF TYR-230; LYS-431 AND PHE-438, SUBSTRATE-BINDING SITES,
AND FUNCTION.
PubMed=17038320; DOI=10.1074/jbc.M608834200;
Perry J.L., Dembla-Rajpal N., Hall L.A., Pritchard J.B.;
"A three-dimensional model of human organic anion transporter 1:
aromatic amino acids required for substrate transport.";
J. Biol. Chem. 281:38071-38079(2006).
[17]
FUNCTION.
PubMed=17502342; DOI=10.1124/dmd.106.013912;
Mizuno N., Takahashi T., Iwase Y., Kusuhara H., Niwa T., Sugiyama Y.;
"Human organic anion transporters 1 (hOAT1/SLC22A6) and 3
(hOAT3/SLC22A8) transport edaravone (MCI-186; 3-methyl-1-phenyl-2-
pyrazolin-5-one) and its sulfate conjugate.";
Drug Metab. Dispos. 35:1429-1434(2007).
[18]
VARIANT HIS-50, AND CHARACTERIZATION OF VARIANT HIS-50.
PubMed=15914676; DOI=10.1124/jpet.105.084301;
Bleasby K., Hall L.A., Perry J.L., Mohrenweiser H.W., Pritchard J.B.;
"Functional consequences of single nucleotide polymorphisms in the
human organic anion transporter hOAT1 (SLC22A6).";
J. Pharmacol. Exp. Ther. 314:923-931(2005).
[19]
VARIANTS PRO-7 AND HIS-50.
PubMed=16164626; DOI=10.1111/j.1523-1755.2005.00612.x;
Xu G., Bhatnagar V., Wen G., Hamilton B.A., Eraly S.A., Nigam S.K.;
"Analyses of coding region polymorphisms in apical and basolateral
human organic anion transporter (OAT) genes [OAT1 (NKT), OAT2, OAT3,
OAT4, URAT (RST)].";
Kidney Int. 68:1491-1499(2005).
-!- 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) (By
similarity). Mediates the sodium-independent uptake of p-
aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-
3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-
phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA),
indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-
furanpropionate (CMPF), cidofovir, adefovir, 9-(2-
phosphonylmethoxyethyl) guanine (PMEG), 9-(2-
phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone
sulfate. PAH uptake is inhibited by p-
chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate
(DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic
acid (By similarity). PAH uptake is inhibited by
benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine
(CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC),
furosemide, steviol, phorbol 12-myristate 13-acetate (PMA),
calcium ionophore A23187, benzylpenicillin, furosemide,
indomethacin, bumetamide, losartan, probenecid, phenol red, urate,
and alpha-ketoglutarate. {ECO:0000250,
ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15644426,
ECO:0000269|PubMed:17038320, ECO:0000269|PubMed:17502342,
ECO:0000269|PubMed:9762842, ECO:0000269|PubMed:9887087}.
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=9.3 uM for PAH (isoform 1) {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
KM=4 uM for PAH (isoform 2) {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
KM=11 uM for edaravone {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
KM=46 uM for cidofovir {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
KM=30 uM for adefovir {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
KM=5.77 uM for 2,4-D {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
KM=23.5 uM for HA {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
KM=14 uM for IA {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
KM=20.5 uM for IS {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
KM=141 uM for CMPF {ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:12538807,
ECO:0000269|PubMed:15846473};
Vmax=534 pmol/min/mg enzyme for 2,4-D uptake
{ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
Vmax=430 pmol/min/mg enzyme for HA uptake
{ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
Vmax=110 pmol/min/mg enzyme for IA uptake
{ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
Vmax=216 pmol/min/mg enzyme for IS uptake
{ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
Vmax=801 pmol/min/mg enzyme for CMPF uptake
{ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:10964714,
ECO:0000269|PubMed:12538807, ECO:0000269|PubMed:15846473};
-!- INTERACTION:
Q92624:APPBP2; NbExp=3; IntAct=EBI-749741, EBI-743771;
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass
membrane protein {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=4;
Name=1; Synonyms=OAT1-1;
IsoId=Q4U2R8-1; Sequence=Displayed;
Name=2; Synonyms=OAT1-2;
IsoId=Q4U2R8-2; Sequence=VSP_032169;
Name=3; Synonyms=OAT1-3;
IsoId=Q4U2R8-3; Sequence=VSP_032168, VSP_032169;
Note=No experimental confirmation available.;
Name=4; Synonyms=OAT1-4;
IsoId=Q4U2R8-4; Sequence=VSP_032168;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Strongly expressed in kidney and to a lower
extent in liver, skeletal muscle, brain and placenta. Found at the
basolateral membrane of the proximal tubule.
{ECO:0000269|PubMed:10049739, ECO:0000269|PubMed:10462545,
ECO:0000269|PubMed:10964714, ECO:0000269|PubMed:9887087,
ECO:0000269|PubMed:9950961}.
-!- DOMAIN: Multiple cysteine residues are necessary for proper
targeting to the plasma membrane. {ECO:0000250}.
-!- PTM: Glycosylated. Glycosylation at Asn-113 may occur at a
secondary level. Glycosylation is necessary for proper targeting
of the transporter to the plasma membrane.
{ECO:0000269|PubMed:10462545, ECO:0000269|PubMed:14749323}.
-!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1)
superfamily. Organic cation transporter (TC 2.A.1.19) family.
{ECO:0000305}.
-!- WEB RESOURCE: Name=NIEHS-SNPs;
URL="http://egp.gs.washington.edu/data/slc22a6/";
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EMBL; AF057039; AAC70004.1; -; mRNA.
EMBL; AB009697; BAA75072.1; -; mRNA.
EMBL; AB009698; BAA75073.1; -; mRNA.
EMBL; AF104038; AAD10052.1; -; mRNA.
EMBL; AF097490; AAD19356.1; -; mRNA.
EMBL; AF124373; AAD55356.1; -; mRNA.
EMBL; AJ249369; CAB77184.1; -; Genomic_DNA.
EMBL; AJ251529; CAB94830.1; -; mRNA.
EMBL; AJ271205; CAB97249.1; -; mRNA.
EMBL; EU567146; ACB21049.1; -; Genomic_DNA.
EMBL; AP001858; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471076; EAW74129.1; -; Genomic_DNA.
EMBL; CH471076; EAW74130.1; -; Genomic_DNA.
EMBL; CH471076; EAW74131.1; -; Genomic_DNA.
EMBL; CH471076; EAW74132.1; -; Genomic_DNA.
EMBL; BC033682; AAH33682.1; -; mRNA.
CCDS; CCDS31591.1; -. [Q4U2R8-1]
CCDS; CCDS44631.1; -. [Q4U2R8-4]
CCDS; CCDS44632.1; -. [Q4U2R8-3]
CCDS; CCDS8041.1; -. [Q4U2R8-2]
RefSeq; NP_004781.2; NM_004790.4. [Q4U2R8-1]
RefSeq; NP_695008.1; NM_153276.2. [Q4U2R8-2]
RefSeq; NP_695009.1; NM_153277.2. [Q4U2R8-3]
RefSeq; NP_695010.1; NM_153278.2. [Q4U2R8-4]
UniGene; Hs.369252; -.
ProteinModelPortal; Q4U2R8; -.
BioGrid; 114759; 22.
IntAct; Q4U2R8; 2.
MINT; MINT-1474237; -.
STRING; 9606.ENSP00000367102; -.
BindingDB; Q4U2R8; -.
ChEMBL; CHEMBL1641347; -.
DrugBank; DB00316; Acetaminophen.
DrugBank; DB00819; Acetazolamide.
DrugBank; DB06151; Acetylcysteine.
DrugBank; DB00945; Acetylsalicylic acid.
DrugBank; DB00787; Aciclovir.
DrugBank; DB00718; Adefovir Dipivoxil.
DrugBank; DB00345; Aminohippuric acid.
DrugBank; DB01424; Aminophenazone.
DrugBank; DB01060; Amoxicillin.
DrugBank; DB01435; Antipyrine.
DrugBank; DB00168; Aspartame.
DrugBank; DB01053; Benzylpenicillin.
DrugBank; DB01237; Bromodiphenhydramine.
DrugBank; DB00887; Bumetanide.
DrugBank; DB04519; Caprylic acid.
DrugBank; DB01197; Captopril.
DrugBank; DB00578; Carbenicillin.
DrugBank; DB00821; Carprofen.
DrugBank; DB00520; Caspofungin.
DrugBank; DB01414; Cefacetrile.
DrugBank; DB01140; Cefadroxil.
DrugBank; DB00456; Cefalotin.
DrugBank; DB01326; Cefamandole.
DrugBank; DB01327; Cefazolin.
DrugBank; DB01329; Cefoperazone.
DrugBank; DB00493; Cefotaxime.
DrugBank; DB00229; Cefotiam.
DrugBank; DB01333; Cefradine.
DrugBank; DB00438; Ceftazidime.
DrugBank; DB01212; Ceftriaxone.
DrugBank; DB00567; Cephalexin.
DrugBank; DB00446; Chloramphenicol.
DrugBank; DB00880; Chlorothiazide.
DrugBank; DB00672; Chlorpropamide.
DrugBank; DB00369; Cidofovir.
DrugBank; DB01597; Cilastatin.
DrugBank; DB00501; Cimetidine.
DrugBank; DB00827; Cinoxacin.
DrugBank; DB01147; Cloxacillin.
DrugBank; DB00286; Conjugated Equine Estrogens.
DrugBank; DB02527; Cyclic Adenosine Monophosphate.
DrugBank; DB02315; Cyclic Guanosine Monophosphate.
DrugBank; DB00091; Cyclosporine.
DrugBank; DB00606; Cyclothiazide.
DrugBank; DB08912; Dabrafenib.
DrugBank; DB04133; Degraded Cephaloridine.
DrugBank; DB00586; Diclofenac.
DrugBank; DB00900; Didanosine.
DrugBank; DB00861; Diflunisal.
DrugBank; DB01160; Dinoprost Tromethamine.
DrugBank; DB00917; Dinoprostone.
DrugBank; DB00254; Doxycycline.
DrugBank; DB08846; Ellagic Acid.
DrugBank; DB00584; Enalapril.
DrugBank; DB00903; Etacrynic acid.
DrugBank; DB00311; Ethoxzolamide.
DrugBank; DB00749; Etodolac.
DrugBank; DB02266; Flufenamic Acid.
DrugBank; DB00693; Fluorescein.
DrugBank; DB00712; Flurbiprofen.
DrugBank; DB00158; Folic Acid.
DrugBank; DB00529; Foscarnet.
DrugBank; DB00695; Furosemide.
DrugBank; DB01004; Ganciclovir.
DrugBank; DB00798; Gentamicin.
DrugBank; DB03553; Glutaric Acid.
DrugBank; DB01016; Glyburide.
DrugBank; DB00365; Grepafloxacin.
DrugBank; DB00999; Hydrochlorothiazide.
DrugBank; DB01050; Ibuprofen.
DrugBank; DB00328; Indomethacin.
DrugBank; DB01009; Ketoprofen.
DrugBank; DB00709; Lamivudine.
DrugBank; DB01137; Levofloxacin.
DrugBank; DB00678; Losartan.
DrugBank; DB00939; Meclofenamic acid.
DrugBank; DB00703; Methazolamide.
DrugBank; DB00563; Methotrexate.
DrugBank; DB01017; Minocycline.
DrugBank; DB00607; Nafcillin.
DrugBank; DB00779; Nalidixic Acid.
DrugBank; DB00788; Naproxen.
DrugBank; DB00731; Nateglinide.
DrugBank; DB01059; Norfloxacin.
DrugBank; DB01051; Novobiocin.
DrugBank; DB01165; Ofloxacin.
DrugBank; DB03585; Oxyphenbutazone.
DrugBank; DB00595; Oxytetracycline.
DrugBank; DB03783; Phenacetin.
DrugBank; DB00812; Phenylbutazone.
DrugBank; DB00319; Piperacillin.
DrugBank; DB00554; Piroxicam.
DrugBank; DB00175; Pravastatin.
DrugBank; DB01032; Probenecid.
DrugBank; DB00140; Riboflavin.
DrugBank; DB00936; Salicylic acid.
DrugBank; DB00649; Stavudine.
DrugBank; DB01082; Streptomycin.
DrugBank; DB00605; Sulindac.
DrugBank; DB04348; Taurocholic Acid.
DrugBank; DB00300; Tenofovir.
DrugBank; DB00759; Tetracycline.
DrugBank; DB01124; Tolbutamide.
DrugBank; DB00500; Tolmetin.
DrugBank; DB00432; Trifluridine.
DrugBank; DB08844; Uric Acid.
DrugBank; DB00577; Valaciclovir.
DrugBank; DB00313; Valproic Acid.
DrugBank; DB00512; Vancomycin.
DrugBank; DB00943; Zalcitabine.
DrugBank; DB00495; Zidovudine.
GuidetoPHARMACOLOGY; 1025; -.
TCDB; 2.A.1.19.31; the major facilitator superfamily (mfs).
iPTMnet; Q4U2R8; -.
PhosphoSitePlus; Q4U2R8; -.
BioMuta; SLC22A6; -.
DMDM; 74762955; -.
EPD; Q4U2R8; -.
PaxDb; Q4U2R8; -.
PeptideAtlas; Q4U2R8; -.
PRIDE; Q4U2R8; -.
DNASU; 9356; -.
Ensembl; ENST00000360421; ENSP00000353597; ENSG00000197901. [Q4U2R8-2]
Ensembl; ENST00000377871; ENSP00000367102; ENSG00000197901. [Q4U2R8-1]
Ensembl; ENST00000421062; ENSP00000404441; ENSG00000197901. [Q4U2R8-4]
Ensembl; ENST00000458333; ENSP00000396401; ENSG00000197901. [Q4U2R8-3]
GeneID; 9356; -.
KEGG; hsa:9356; -.
UCSC; uc001nwj.4; human. [Q4U2R8-1]
CTD; 9356; -.
DisGeNET; 9356; -.
GeneCards; SLC22A6; -.
HGNC; HGNC:10970; SLC22A6.
MIM; 607582; gene.
neXtProt; NX_Q4U2R8; -.
OpenTargets; ENSG00000197901; -.
PharmGKB; PA388; -.
eggNOG; KOG0255; Eukaryota.
eggNOG; COG0477; LUCA.
GeneTree; ENSGT00760000118852; -.
HOVERGEN; HBG108433; -.
InParanoid; Q4U2R8; -.
KO; K08203; -.
OMA; GVVPQDQ; -.
OrthoDB; EOG091G07CO; -.
PhylomeDB; Q4U2R8; -.
TreeFam; TF315847; -.
Reactome; R-HSA-561048; Organic anion transport.
GeneWiki; Organic_anion_transporter_1; -.
GenomeRNAi; 9356; -.
PRO; PR:Q4U2R8; -.
Proteomes; UP000005640; Chromosome 11.
Bgee; ENSG00000197901; -.
ExpressionAtlas; Q4U2R8; baseline and differential.
Genevisible; Q4U2R8; HS.
GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
GO; GO:0005901; C:caveola; IEA:Ensembl.
GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0043234; C:protein complex; IEA:Ensembl.
GO; GO:0015301; F:anion:anion antiporter activity; TAS:Reactome.
GO; GO:0031404; F:chloride ion binding; IEA:Ensembl.
GO; GO:0005452; F:inorganic anion exchanger activity; IDA:UniProtKB.
GO; GO:0008514; F:organic anion transmembrane transporter activity; IDA:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
GO; GO:0015347; F:sodium-independent organic anion transmembrane transporter activity; IDA:UniProtKB.
GO; GO:0015143; F:urate transmembrane transporter activity; IBA:GO_Central.
GO; GO:0015742; P:alpha-ketoglutarate transport; IDA:UniProtKB.
GO; GO:0015711; P:organic anion transport; IDA:UniProtKB.
GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl.
GO; GO:0097254; P:renal tubular secretion; IMP:UniProtKB.
GO; GO:0031427; P:response to methotrexate; IEA:Ensembl.
GO; GO:0043252; P:sodium-independent organic anion transport; IDA:UniProtKB.
GO; GO:0015747; P:urate transport; IBA:GO_Central.
CDD; cd06174; MFS; 1.
InterPro; IPR020846; MFS_dom.
InterPro; IPR005828; MFS_sugar_transport-like.
InterPro; IPR004749; Orgcat_transp/SVOP.
Pfam; PF00083; Sugar_tr; 1.
SUPFAM; SSF103473; SSF103473; 1.
TIGRFAMs; TIGR00898; 2A0119; 1.
PROSITE; PS50850; MFS; 1.
1: Evidence at protein level;
Alternative splicing; Cell membrane; Complete proteome; Glycoprotein;
Membrane; Polymorphism; Reference proteome; Transmembrane;
Transmembrane helix.
CHAIN 1 563 Solute carrier family 22 member 6.
/FTId=PRO_0000324166.
TOPO_DOM 1 9 Cytoplasmic. {ECO:0000255}.
TRANSMEM 10 30 Helical. {ECO:0000255}.
TOPO_DOM 31 135 Extracellular. {ECO:0000255}.
TRANSMEM 136 156 Helical. {ECO:0000255}.
TOPO_DOM 157 164 Cytoplasmic. {ECO:0000255}.
TRANSMEM 165 187 Helical. {ECO:0000255}.
TOPO_DOM 188 190 Extracellular. {ECO:0000255}.
TRANSMEM 191 213 Helical. {ECO:0000255}.
TOPO_DOM 214 224 Cytoplasmic. {ECO:0000255}.
TRANSMEM 225 245 Helical. {ECO:0000255}.
TOPO_DOM 246 248 Extracellular. {ECO:0000255}.
TRANSMEM 249 269 Helical. {ECO:0000255}.
TOPO_DOM 270 337 Cytoplasmic. {ECO:0000255}.
TRANSMEM 338 358 Helical. {ECO:0000255}.
TOPO_DOM 359 368 Extracellular. {ECO:0000255}.
TRANSMEM 369 389 Helical. {ECO:0000255}.
TOPO_DOM 390 395 Cytoplasmic. {ECO:0000255}.
TRANSMEM 396 416 Helical. {ECO:0000255}.
TOPO_DOM 417 425 Extracellular. {ECO:0000255}.
TRANSMEM 426 446 Helical. {ECO:0000255}.
TOPO_DOM 447 455 Cytoplasmic. {ECO:0000255}.
TRANSMEM 456 475 Helical. {ECO:0000255}.
TOPO_DOM 476 484 Extracellular. {ECO:0000255}.
TRANSMEM 485 505 Helical. {ECO:0000255}.
TOPO_DOM 506 563 Cytoplasmic. {ECO:0000255}.
SITE 230 230 Important for interaction with cidofovir.
SITE 438 438 Important for interaction with cidofovir
and PAH.
CARBOHYD 39 39 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:14749323}.
CARBOHYD 56 56 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:14749323}.
CARBOHYD 92 92 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:14749323}.
CARBOHYD 97 97 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:14749323}.
CARBOHYD 113 113 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:10462545}.
VAR_SEQ 455 498 Missing (in isoform 3 and isoform 4).
{ECO:0000303|PubMed:10964714}.
/FTId=VSP_032168.
VAR_SEQ 523 535 Missing (in isoform 2 and isoform 3).
{ECO:0000303|PubMed:10049739,
ECO:0000303|PubMed:10462545,
ECO:0000303|PubMed:10964714,
ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:9762842,
ECO:0000303|PubMed:9887087,
ECO:0000303|PubMed:9950961}.
/FTId=VSP_032169.
VARIANT 7 7 L -> P. {ECO:0000269|PubMed:16164626}.
/FTId=VAR_039682.
VARIANT 50 50 R -> H (lower Vmax; increase in substrate
affinity and increase in the affinity for
the nucleoside phosphonate analogs
cidofovir, adefovir and tenofovir;
dbSNP:rs11568626).
{ECO:0000269|PubMed:15914676,
ECO:0000269|PubMed:16164626}.
/FTId=VAR_039683.
VARIANT 104 104 P -> L (in dbSNP:rs11568627).
{ECO:0000269|Ref.7}.
/FTId=VAR_047878.
VARIANT 293 293 R -> W (increase in substrate affinity;
dbSNP:rs45607933).
/FTId=VAR_039684.
MUTAGEN 30 30 L->A: Complete loss of PAH transport
activity. {ECO:0000269|PubMed:15145940}.
MUTAGEN 36 36 T->A: Complete loss of PAH transport
activity. {ECO:0000269|PubMed:15145940}.
MUTAGEN 39 39 N->Q: Complete loss of PAH transport
activity. {ECO:0000269|PubMed:14749323}.
MUTAGEN 230 230 Y->A: Loss of membrane protein expression
and little uptake of cidofovir.
{ECO:0000269|PubMed:17038320}.
MUTAGEN 431 431 K->A: Decrease in the level of membrane
protein expression and 70 % loss of PAH
uptake. {ECO:0000269|PubMed:17038320}.
MUTAGEN 438 438 F->A: Decrease in the level of membrane
protein expression, 70 % loss of PAH
uptake, increased affinity for cidofovir,
lower Vmax for PAH, and lower Km and Vmax
for cidofovir.
{ECO:0000269|PubMed:17038320}.
CONFLICT 14 14 G -> S (in Ref. 3; AAD10052).
{ECO:0000305}.
CONFLICT 563 563 L -> F (in Ref. 1; AAC70004).
{ECO:0000305}.
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


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