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Identification
HMDB Protein ID HMDBP07986
Secondary Accession Numbers
  • 13697
Name Solute carrier family 22 member 6
Synonyms
  1. Organic anion transporter 1
  2. PAH transporter
  3. Renal organic anion transporter 1
  4. hOAT1
  5. hPAHT
  6. hROAT1
Gene Name SLC22A6
Protein Type Transporter
Biological Properties
General Function Involved in ion transmembrane transporter activity
Specific 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). 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. 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
Pathways
  • Amiloride Pathway
  • Bendroflumethiazide Pathway
  • Blue diaper syndrome
  • Bumetanide Pathway
  • Chlorothiazide Pathway
  • Chlorthalidone Pathway
  • Cyclothiazide Pathway
  • Cystinuria
  • Eplerenone Pathway
  • Ethacrynic Acid pathway
  • Furosemide Pathway
  • Glucose Transporter Defect (SGLT2)
  • Glucose Transporter Defect (SGLT2)
  • Hartnup Disorder
  • Hydrochlorothiazide Pathway
  • Hydroflumethiazide Pathway
  • Ibuprofen Metabolism Pathway
  • Ibuprofen Pathway
  • Iminoglycinuria
  • Indapamide Pathway
  • Kidney Function
  • Lysinuric Protein Intolerance
  • Lysinuric protein intolerance (LPI)
  • Methyclothiazide Pathway
  • Metolazone Pathway
  • Polythiazide Pathway
  • Quinethazone Pathway
  • Spironolactone Pathway
  • Torsemide Pathway
  • Triamterene Pathway
  • Trichlormethiazide Pathway
Reactions Not Available
GO Classification
Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
transporter activity
Process
establishment of localization
transport
transmembrane transport
ion transport
Cellular Location
  1. Cell membrane
  2. Multi-pass membrane protein (Potential)
Gene Properties
Chromosome Location Chromosome:1
Locus 11q12.3
SNPs SLC22A6
Gene Sequence
>1692 bp
ATGGCCTTTAATGACCTCCTGCAGCAGGTGGGGGGTGTCGGCCGCTTCCAGCAGATCCAG
GTCACCCTGGTGGTCCTCCCCCTGCTCCTGATGGCTTCTCACAACACCCTGCAGAACTTC
ACTGCTGCCATCCCTACCCACCACTGCCGCCCGCCTGCCGATGCCAACCTCAGCAAGAAC
GGGGGGCTGGAGGTCTGGCTGCCCCGGGACAGGCAGGGGCAGCCTGAGTCCTGCCTCCGC
TTCACCTCCCCGCAGTGGGGACTGCCCTTTCTCAATGGCACAGAAGCCAATGGCACAGGG
GCCACAGAGCCCTGCACCGATGGCTGGATCTATGACAACAGCACCTTCCCATCTACCATC
GTGACTGAGTGGGACCTTGTGTGCTCTCACAGGGCCCTACGCCAGCTGGCCCAGTCCTTG
TACATGGTGGGGGTGCTGCTCGGAGCCATGGTGTTCGGCTACCTTGCAGACAGGCTAGGC
CGCCGGAAGGTACTCATCTTGAACTACCTGCAGACAGCTGTGTCAGGGACCTGCGCAGCC
TTCGCACCCAACTTCCCCATCTACTGCGCCTTCCGGCTCCTCTCGGGCATGGCTCTGGCT
GGCATCTCCCTCAACTGCATGACACTGAATGTGGAGTGGATGCCCATTCACACACGGGCC
TGCGTGGGCACCTTGATTGGCTATGTCTACAGCCTGGGCCAGTTCCTCCTGGCTGGTGTG
GCCTACGCTGTGCCCCACTGGCGCCACCTGCAGCTACTGGTCTCTGCGCCTTTTTTTGCC
TTCTTCATCTACTCCTGGTTCTTCATTGAGTCGGCCCGCTGGCACTCCTCCTCCGGGAGG
CTGGACCTCACCCTGAGGGCCCTGCAGAGAGTCGCCCGGATCAATGGGAAGCGGGAAGAA
GGAGCCAAATTGAGTATGGAGGTACTCCGGGCCAGTCTGCAGAAGGAGCTGACCATGGGC
AAAGGCCAGGCATCGGCCATGGAGCTGCTGCGCTGCCCCACCCTCCGCCACCTCTTCCTC
TGCCTCTCCATGCTGTGGTTTGCCACTAGCTTTGCATACTATGGGCTGGTCATGGACCTG
CAGGGCTTTGGAGTCAGCATCTACCTAATCCAGGTGATCTTTGGTGCTGTGGACCTGCCT
GCCAAGCTTGTGGGCTTCCTTGTCATCAACTCCCTGGGTCGCCGGCCTGCCCAGATGGCT
GCACTGCTGCTGGCAGGCATCTGCATCCTGCTCAATGGGGTGATACCCCAGGACCAGTCC
ATTGTCCGAACCTCTCTTGCTGTGCTGGGGAAGGGTTGTCTGGCTGCCTCCTTCAACTGC
ATCTTCCTGTATACTGGGGAACTGTATCCCACAATGATCCGGCAGACAGGCATGGGAATG
GGCAGCACCATGGCCCGAGTGGGCAGCATCGTGAGCCCACTGGTGAGCATGACTGCCGAG
CTCTACCCCTCCATGCCTCTCTTCATCTACGGTGCTGTTCCTGTGGCCGCCAGCGCTGTC
ACTGTCCTCCTGCCAGAGACCCTGGGCCAGCCACTGCCAGACACGGTGCAGGACCTGGAG
AGCAGGTGGGCCCCCACTCAGAAAGAAGCAGGGATATATCCCAGGAAAGGGAAACAGACG
CGACAGCAACAAGAGCACCAGAAGTATATGGTCCCACTGCAGGCCTCAGCACAAGAGAAG
AATGGACTCTGA
Protein Properties
Number of Residues 563
Molecular Weight 61815.8
Theoretical pI 8.88
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 10-30
  • 136-156
  • 165-187
  • 191-213
  • 225-245
  • 249-269
  • 338-358
  • 369-389
  • 396-416
  • 426-446
  • 456-475
  • 485-505
Protein Sequence
>Solute carrier family 22 member 6
MAFNDLLQQVGGVGRFQQIQVTLVVLPLLLMASHNTLQNFTAAIPTHHCRPPADANLSKN
GGLEVWLPRDRQGQPESCLRFTSPQWGLPFLNGTEANGTGATEPCTDGWIYDNSTFPSTI
VTEWDLVCSHRALRQLAQSLYMVGVLLGAMVFGYLADRLGRRKVLILNYLQTAVSGTCAA
FAPNFPIYCAFRLLSGMALAGISLNCMTLNVEWMPIHTRACVGTLIGYVYSLGQFLLAGV
AYAVPHWRHLQLLVSAPFFAFFIYSWFFIESARWHSSSGRLDLTLRALQRVARINGKREE
GAKLSMEVLRASLQKELTMGKGQASAMELLRCPTLRHLFLCLSMLWFATSFAYYGLVMDL
QGFGVSIYLIQVIFGAVDLPAKLVGFLVINSLGRRPAQMAALLLAGICILLNGVIPQDQS
IVRTSLAVLGKGCLAASFNCIFLYTGELYPTMIRQTGMGMGSTMARVGSIVSPLVSMTAE
LYPSMPLFIYGAVPVAASAVTVLLPETLGQPLPDTVQDLESRWAPTQKEAGIYPRKGKQT
RQQQEHQKYMVPLQASAQEKNGL
GenBank ID Protein 4579723
UniProtKB/Swiss-Prot ID Q4U2R8
UniProtKB/Swiss-Prot Entry Name S22A6_HUMAN
PDB IDs Not Available
GenBank Gene ID AB009697
GeneCard ID SLC22A6
GenAtlas ID SLC22A6
HGNC ID HGNC:10970
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed:16554811 ]
  3. Race JE, Grassl SM, Williams WJ, Holtzman EJ: Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Commun. 1999 Feb 16;255(2):508-14. [PubMed:10049739 ]
  4. Reid G, Wolff NA, Dautzenberg FM, Burckhardt G: Cloning of a human renal p-aminohippurate transporter, hROAT1. Kidney Blood Press Res. 1998;21(2-4):233-7. [PubMed:9762842 ]
  5. 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. 1999 Jan;276(1 Pt 2):F122-8. [PubMed:9887087 ]
  6. Lu R, Chan BS, Schuster VL: Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C. Am J Physiol. 1999 Feb;276(2 Pt 2):F295-303. [PubMed:9950961 ]
  7. Cihlar T, Lin DC, Pritchard JB, Fuller MD, Mendel DB, Sweet DH: The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1. Mol Pharmacol. 1999 Sep;56(3):570-80. [PubMed:10462545 ]
  8. Bahn A, Prawitt D, Buttler D, Reid G, Enklaar T, Wolff NA, Ebbinghaus C, Hillemann A, Schulten HJ, Gunawan B, Fuzesi L, Zabel B, Burckhardt G: Genomic structure and in vivo expression of the human organic anion transporter 1 (hOAT1) gene. Biochem Biophys Res Commun. 2000 Aug 28;275(2):623-30. [PubMed:10964714 ]
  9. Groves CE, Munoz L, Bahn A, Burckhardt G, Wright SH: Interaction of cysteine conjugates with human and rabbit organic anion transporter 1. J Pharmacol Exp Ther. 2003 Feb;304(2):560-6. [PubMed:12538807 ]
  10. Tanaka K, Xu W, Zhou F, You G: Role of glycosylation in the organic anion transporter OAT1. J Biol Chem. 2004 Apr 9;279(15):14961-6. Epub 2004 Jan 28. [PubMed:14749323 ]
  11. Hong M, Zhou F, You G: Critical amino acid residues in transmembrane domain 1 of the human organic anion transporter hOAT1. J Biol Chem. 2004 Jul 23;279(30):31478-82. Epub 2004 May 15. [PubMed:15145940 ]
  12. Srimaroeng C, Chatsudthipong V, Aslamkhan AG, Pritchard JB: Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). J Pharmacol Exp Ther. 2005 May;313(2):621-8. Epub 2005 Jan 11. [PubMed:15644426 ]
  13. 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. 2005 Apr;22(4):647-60. Epub 2005 Apr 7. [PubMed:15846473 ]
  14. Perry JL, Dembla-Rajpal N, Hall LA, Pritchard JB: A three-dimensional model of human organic anion transporter 1: aromatic amino acids required for substrate transport. J Biol Chem. 2006 Dec 8;281(49):38071-9. Epub 2006 Oct 11. [PubMed:17038320 ]
  15. 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. 2007 Aug;35(8):1429-34. Epub 2007 May 14. [PubMed:17502342 ]
  16. Bleasby K, Hall LA, Perry JL, Mohrenweiser HW, Pritchard JB: Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6). J Pharmacol Exp Ther. 2005 Aug;314(2):923-31. Epub 2005 May 24. [PubMed:15914676 ]
  17. Xu G, Bhatnagar V, Wen G, Hamilton BA, Eraly SA, Nigam SK: Analyses of coding region polymorphisms in apical and basolateral human organic anion transporter (OAT) genes [OAT1 (NKT), OAT2, OAT3, OAT4, URAT (RST)]. Kidney Int. 2005 Oct;68(4):1491-9. [PubMed:16164626 ]