Q4U2R8 (S22A6_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
April 3, 2013.
Version 88.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Solute carrier family 22 member 6 Alternative name(s): Organic anion transporter 1 Short name=hOAT1 PAH transporter Short name=hPAHT Renal organic anion transporter 1 Short name=hROAT1 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 563 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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) 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. Ref.1 Ref.2 Ref.11 Ref.14 Ref.16 Ref.17 |
| Subcellular location | Cell membrane; Multi-pass membrane protein Potential. |
| 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. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 |
| Domain | Multiple cysteine residues are necessary for proper targeting to the plasma membrane By similarity. |
| Post-translational modification | Glycosylated. Glycosylation at Asn-113 may occur at a secondary level. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane. Ref.5 Ref.12 |
| 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=9.3 µM for PAH (isoform 1) Ref.5 Ref.6 Ref.11 Ref.15 KM=4 µM for PAH (isoform 2) KM=11 µM for edaravone KM=46 µM for cidofovir KM=30 µM for adefovir KM=5.77 µM for 2,4-D KM=23.5 µM for HA KM=14 µM for IA KM=20.5 µM for IS KM=141 µM for CMPF Vmax=534 pmol/min/mg enzyme for 2,4-D uptake Vmax=430 pmol/min/mg enzyme for HA uptake Vmax=110 pmol/min/mg enzyme for IA uptake Vmax=216 pmol/min/mg enzyme for IS uptake Vmax=801 pmol/min/mg enzyme for CMPF uptake |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| APPBP2 | Q92624 | 3 | EBI-749741,EBI-743771 |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q4U2R8-1) Also known as: OAT1-1; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q4U2R8-2) Also known as: OAT1-2; The sequence of this isoform differs from the canonical sequence as follows: 523-535: Missing. | ||||||
| Isoform 3 (identifier: Q4U2R8-3) Also known as: OAT1-3; The sequence of this isoform differs from the canonical sequence as follows: 455-498: Missing. 523-535: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: Q4U2R8-4) Also known as: OAT1-4; The sequence of this isoform differs from the canonical sequence as follows: 455-498: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 563 | 563 | Solute carrier family 22 member 6 | PRO_0000324166 | |||||
Regions | |||||||||
| Topological domain | 1 – 9 | 9 | Cytoplasmic Potential | ||||||
| Transmembrane | 10 – 30 | 21 | Helical; Potential | ||||||
| Topological domain | 31 – 135 | 105 | Extracellular Potential | ||||||
| Transmembrane | 136 – 156 | 21 | Helical; Potential | ||||||
| Topological domain | 157 – 164 | 8 | Cytoplasmic Potential | ||||||
| Transmembrane | 165 – 187 | 23 | Helical; Potential | ||||||
| Topological domain | 188 – 190 | 3 | Extracellular Potential | ||||||
| Transmembrane | 191 – 213 | 23 | Helical; Potential | ||||||
| Topological domain | 214 – 224 | 11 | Cytoplasmic Potential | ||||||
| Transmembrane | 225 – 245 | 21 | Helical; Potential | ||||||
| Topological domain | 246 – 248 | 3 | Extracellular Potential | ||||||
| Transmembrane | 249 – 269 | 21 | Helical; Potential | ||||||
| Topological domain | 270 – 337 | 68 | Cytoplasmic Potential | ||||||
| Transmembrane | 338 – 358 | 21 | Helical; Potential | ||||||
| Topological domain | 359 – 368 | 10 | Extracellular Potential | ||||||
| Transmembrane | 369 – 389 | 21 | Helical; Potential | ||||||
| Topological domain | 390 – 395 | 6 | Cytoplasmic Potential | ||||||
| Transmembrane | 396 – 416 | 21 | Helical; Potential | ||||||
| Topological domain | 417 – 425 | 9 | Extracellular Potential | ||||||
| Transmembrane | 426 – 446 | 21 | Helical; Potential | ||||||
| Topological domain | 447 – 455 | 9 | Cytoplasmic Potential | ||||||
| Transmembrane | 456 – 475 | 20 | Helical; Potential | ||||||
| Topological domain | 476 – 484 | 9 | Extracellular Potential | ||||||
| Transmembrane | 485 – 505 | 21 | Helical; Potential | ||||||
| Topological domain | 506 – 563 | 58 | Cytoplasmic Potential | ||||||
Sites | |||||||||
| Site | 230 | 1 | Important for interaction with cidofovir | ||||||
| Site | 438 | 1 | Important for interaction with cidofovir and PAH | ||||||
Amino acid modifications | |||||||||
| Glycosylation | 39 | 1 | N-linked (GlcNAc...) Ref.12 | ||||||
| Glycosylation | 56 | 1 | N-linked (GlcNAc...) Ref.12 | ||||||
| Glycosylation | 92 | 1 | N-linked (GlcNAc...) Ref.12 | ||||||
| Glycosylation | 97 | 1 | N-linked (GlcNAc...) Ref.12 | ||||||
| Glycosylation | 113 | 1 | N-linked (GlcNAc...) | ||||||
Natural variations | |||||||||
| Alternative sequence | 455 – 498 | 44 | Missing in isoform 3 and isoform 4. | VSP_032168 | |||||
| Alternative sequence | 523 – 535 | 13 | Missing in isoform 2 and isoform 3. | VSP_032169 | |||||
| Natural variant | 7 | 1 | L → P. Ref.19 | VAR_039682 | |||||
| Natural variant | 50 | 1 | R → H Lower Vmax; increase in substrate affinity and increase in the affinity for the nucleoside phosphonate analogs cidofovir, adefovir and tenofovir. Ref.18 Ref.19 Corresponds to variant rs11568626 [ dbSNP | Ensembl ]. | VAR_039683 | |||||
| Natural variant | 104 | 1 | P → L. Ref.7 Corresponds to variant rs11568627 [ dbSNP | Ensembl ]. | VAR_047878 | |||||
| Natural variant | 293 | 1 | R → W Increase in substrate affinity. Corresponds to variant rs45607933 [ dbSNP | Ensembl ]. | VAR_039684 | |||||
Experimental info | |||||||||
| Mutagenesis | 30 | 1 | L → A: Complete loss of PAH transport activity. Ref.13 | ||||||
| Mutagenesis | 36 | 1 | T → A: Complete loss of PAH transport activity. Ref.13 | ||||||
| Mutagenesis | 39 | 1 | N → Q: Complete loss of PAH transport activity. Ref.12 | ||||||
| Mutagenesis | 230 | 1 | Y → A: Loss of membrane protein expression and little uptake of cidofovir. Ref.16 | ||||||
| Mutagenesis | 431 | 1 | K → A: Decrease in the level of membrane protein expression and 70 % loss of PAH uptake. Ref.16 | ||||||
| Mutagenesis | 438 | 1 | 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. Ref.16 | ||||||
| Sequence conflict | 14 | 1 | G → S in AAD10052. Ref.3 | ||||||
| Sequence conflict | 563 | 1 | L → F in AAC70004. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning of a human renal p-aminohippurate transporter, hROAT1." Reid G., Wolff N.A., Dautzenberg F.M., Burckhardt G. Kidney Blood Press. Res. 21:233-237(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION. |
| [2] | "Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney." Hosoyamada M., Sekine T., Kanai Y., Endou H. Am. J. Physiol. 276:F122-F128(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, FUNCTION. Tissue: Kidney. |
| [3] | "Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C." Lu R., Chan B.S., Schuster V.L. Am. J. Physiol. 276:F295-F303(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Kidney. |
| [4] | "Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3)." Race J.E., Grassl S.M., Williams W.J., Holtzman E.J. Biochem. Biophys. Res. Commun. 255:508-514(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Kidney. |
| [5] | "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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), GLYCOSYLATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Tissue: Kidney. |
| [6] | "Genomic structure and in vivo expression of the human organic anion transporter 1 (hOAT1) gene." 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. Biochem. Biophys. Res. Commun. 275:623-630(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 3 AND 4), BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Tissue: Kidney. |
| [7] | NIEHS SNPs program Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-104. |
| [8] | "Human chromosome 11 DNA sequence and analysis including novel gene identification." 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. Sakaki Y.Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [9] | 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. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [10] | "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] (ISOFORM 2). Tissue: Colon. |
| [11] | "Interaction of cysteine conjugates with human and rabbit organic anion transporter 1." Groves C.E., Munoz L., Bahn A., Burckhardt G., Wright S.H. J. Pharmacol. Exp. Ther. 304:560-566(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES. |
| [12] | "Role of glycosylation in the organic anion transporter OAT1." Tanaka K., Xu W., Zhou F., You G. J. Biol. Chem. 279:14961-14966(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASN-39, GLYCOSYLATION AT ASN-39; ASN-56; ASN-92 AND ASN-97. |
| [13] | "Critical amino acid residues in transmembrane domain 1 of the human organic anion transporter hOAT1." Hong M., Zhou F., You G. J. Biol. Chem. 279:31478-31482(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LEU-30 AND THR-36. |
| [14] | "Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8)." Srimaroeng C., Chatsudthipong V., Aslamkhan A.G., Pritchard J.B. J. Pharmacol. Exp. Ther. 313:621-628(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [15] | "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. |
| [16] | "A three-dimensional model of human organic anion transporter 1: aromatic amino acids required for substrate transport." Perry J.L., Dembla-Rajpal N., Hall L.A., Pritchard J.B. J. Biol. Chem. 281:38071-38079(2006) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-230; LYS-431 AND PHE-438, SUBSTRATE-BINDING SITES, FUNCTION. |
| [17] | "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." Mizuno N., Takahashi T., Iwase Y., Kusuhara H., Niwa T., Sugiyama Y. Drug Metab. Dispos. 35:1429-1434(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [18] | "Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6)." Bleasby K., Hall L.A., Perry J.L., Mohrenweiser H.W., Pritchard J.B. J. Pharmacol. Exp. Ther. 314:923-931(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HIS-50, CHARACTERIZATION OF VARIANT HIS-50. |
| [19] | "Analyses of coding region polymorphisms in apical and basolateral human organic anion transporter (OAT) genes [OAT1 (NKT), OAT2, OAT3, OAT4, URAT (RST)]." Xu G., Bhatnagar V., Wen G., Hamilton B.A., Eraly S.A., Nigam S.K. Kidney Int. 68:1491-1499(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PRO-7 AND HIS-50. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF057039 mRNA. Translation: AAC70004.1. AB009697 mRNA. Translation: BAA75072.1. AB009698 mRNA. Translation: BAA75073.1. AF104038 mRNA. Translation: AAD10052.1. AF097490 mRNA. Translation: AAD19356.1. AF124373 mRNA. Translation: AAD55356.1. AJ249369 Genomic DNA. Translation: CAB77184.1. AJ251529 mRNA. Translation: CAB94830.1. AJ271205 mRNA. Translation: CAB97249.1. EU567146 Genomic DNA. Translation: ACB21049.1. AP001858 Genomic DNA. No translation available. CH471076 Genomic DNA. Translation: EAW74129.1. CH471076 Genomic DNA. Translation: EAW74130.1. CH471076 Genomic DNA. Translation: EAW74131.1. CH471076 Genomic DNA. Translation: EAW74132.1. BC033682 mRNA. Translation: AAH33682.1. |
| IPI | IPI00006296. IPI00011035. IPI00645624. IPI00654872. |
| RefSeq | NP_004781.2. NM_004790.4. NP_695008.1. NM_153276.2. NP_695009.1. NM_153277.2. NP_695010.1. NM_153278.2. |
| UniGene | Hs.369252. |
3D structure databases | |
| ProteinModelPortal | Q4U2R8. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q4U2R8. 1 interaction. |
| MINT | MINT-1474237. |
Polymorphism databases | |
| DMDM | 74762955. |
Proteomic databases | |
| PaxDb | Q4U2R8. |
| PRIDE | Q4U2R8. |
Protocols and materials databases | |
| DNASU | 9356. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000360421; ENSP00000353597; ENSG00000197901. ENST00000377871; ENSP00000367102; ENSG00000197901. ENST00000421062; ENSP00000404441; ENSG00000197901. ENST00000458333; ENSP00000396401; ENSG00000197901. |
| GeneID | 9356. |
| KEGG | hsa:9356. |
| UCSC | uc001nwj.3. human. uc001nwk.3. human. uc001nwl.3. human. uc001nwm.3. human. |
Organism-specific databases | |
| CTD | 9356. |
| GeneCards | GC11M062744. |
| HGNC | HGNC:10970. SLC22A6. |
| MIM | 607582. gene. |
| neXtProt | NX_Q4U2R8. |
| PharmGKB | PA388. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | COG0477. |
| HOVERGEN | HBG108433. |
| InParanoid | Q4U2R8. |
| KO | K08203. |
| OMA | APFFAFF. |
| OrthoDB | EOG418BPG. |
Enzyme and pathway databases | |
| Reactome | REACT_15518. Transmembrane transport of small molecules. |
Gene expression databases | |
| ArrayExpress | Q4U2R8. |
| Bgee | Q4U2R8. |
| Genevestigator | Q4U2R8. |
Family and domain databases | |
| InterPro | IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR004749. Orgcat_transp. IPR005828. Sub_transporter. [Graphical view] |
| Pfam | PF00083. Sugar_tr. 1 hit. [Graphical view] |
| SUPFAM | SSF103473. MFS_gen_substrate_transporter. 1 hit. |
| TIGRFAMs | TIGR00898. 2A0119. 1 hit. |
| PROSITE | PS50850. MFS. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| BindingDB | Q4U2R8. |
| ChEMBL | CHEMBL1641347. |
| GenomeRNAi | 9356. |
| NextBio | 35037. |
| SOURCE | Search... |
Entry information
| Entry name | S22A6_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q4U2R8 Secondary accession number(s): A8MY93 Q9UEQ8 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
