ID:S22A6_HUMAN DESCRIPTION: 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; 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. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=9.3 uM for PAH (isoform 1); KM=4 uM for PAH (isoform 2); KM=11 uM for edaravone; KM=46 uM for cidofovir; KM=30 uM for adefovir; KM=5.77 uM for 2,4-D; KM=23.5 uM for HA; KM=14 uM for IA; KM=20.5 uM for IS; KM=141 uM 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; INTERACTION: Q92624:APPBP2; NbExp=3; IntAct=EBI-749741, EBI-743771; 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. DOMAIN: Multiple cysteine residues are necessary for proper targeting to the plasma membrane (By similarity). 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. SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/slc22a6/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 103473 - MFS general substrate transporter
ModBase Predicted Comparative 3D Structure on Q4U2R8
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK298374 - Homo sapiens cDNA FLJ55736 complete cds, highly similar to Homo sapiens solute carrier family 22, member 6, transcript variant 2, mRNA. BC033682 - Homo sapiens solute carrier family 22 (organic anion transporter), member 6, mRNA (cDNA clone MGC:45260 IMAGE:5190748), complete cds. AB009698 - Homo sapiens mRNA for hOAT1-2, complete cds. AK091879 - Homo sapiens cDNA FLJ34560 fis, clone KIDNE2001857, highly similar to Homo sapiens solute carrier family 22, member 6, transcript variant 2, mRNA. AK055764 - Homo sapiens cDNA FLJ31202 fis, clone KIDNE2003188, highly similar to Homo sapiens solute carrier family 22 (organic anion transporter), member 6 (SLC22A6), transcript variant 5, mRNA. AF057039 - Homo sapiens putative renal organic anion transporter 1 (hROAT1) mRNA, complete cds. AF104038 - Homo sapiens para-aminohippurate transporter mRNA, complete cds. AF124373 - Homo sapiens organic anion transporter 1 (SLC22A6) mRNA, complete cds. AB009697 - Homo sapiens mRNA for hOAT1-1, complete cds. JD038409 - Sequence 19433 from Patent EP1572962. JD043749 - Sequence 24773 from Patent EP1572962. JD097098 - Sequence 78122 from Patent EP1572962. JD121255 - Sequence 102279 from Patent EP1572962. AF097490 - Homo sapiens organic anion transporter 1 (OAT1) mRNA, complete cds. AJ251529 - Homo sapiens mRNA for putative organic anion transporter (OAT1 gene, splice variant OAT1-3). AJ271205 - Homo sapiens mRNA for putative organic anion transporter (OAT1-4 gene). DQ895273 - Synthetic construct Homo sapiens clone IMAGE:100009733; FLH182966.01L; RZPDo839E03139D solute carrier family 22 (organic anion transporter), member 6 (SLC22A6) gene, encodes complete protein. KJ892754 - Synthetic construct Homo sapiens clone ccsbBroadEn_02148 SLC22A6 gene, encodes complete protein. KR710848 - Synthetic construct Homo sapiens clone CCSBHm_00017644 SLC22A6 (SLC22A6) mRNA, encodes complete protein. DQ892080 - Synthetic construct clone IMAGE:100004710; FLH182970.01X; RZPDo839E03140D solute carrier family 22 (organic anion transporter), member 6 (SLC22A6) gene, encodes complete protein. CU689694 - Synthetic construct Homo sapiens gateway clone IMAGE:100019841 5' read SLC22A6 mRNA. JD060333 - Sequence 41357 from Patent EP1572962. JD204744 - Sequence 185768 from Patent EP1572962. JD438046 - Sequence 419070 from Patent EP1572962. JD178056 - Sequence 159080 from Patent EP1572962. JD304088 - Sequence 285112 from Patent EP1572962. JD444479 - Sequence 425503 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q4U2R8 (Reactome details) participates in the following event(s):
R-HSA-561041 OAT1-3 transport organic anions with antiport of dicarboxylic acids R-HSA-561048 Organic anion transport R-HSA-549132 Organic cation/anion/zwitterion transport R-HSA-425366 Transport of bile salts and organic acids, metal ions and amine compounds R-HSA-425407 SLC-mediated transmembrane transport R-HSA-382551 Transport of small molecules