Solute carrier family 22 member 6

NameSolute carrier family 22 member 6
Synonyms
  • hOAT1
  • hPAHT
  • hROAT1
  • OAT1
  • Organic anion transporter 1
  • PAH transporter
  • PAHT
  • Renal organic anion transporter 1
Gene NameSLC22A6
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037120|Solute carrier family 22 member 6
MAFNDLLQQVGGVGRFQQIQVTLVVLPLLLMASHNTLQNFTAAIPTHHCRPPADANLSKN
GGLEVWLPRDRQGQPESCLRFTSPQWGLPFLNGTEANGTGATEPCTDGWIYDNSTFPSTI
VTEWDLVCSHRALRQLAQSLYMVGVLLGAMVFGYLADRLGRRKVLILNYLQTAVSGTCAA
FAPNFPIYCAFRLLSGMALAGISLNCMTLNVEWMPIHTRACVGTLIGYVYSLGQFLLAGV
AYAVPHWRHLQLLVSAPFFAFFIYSWFFIESARWHSSSGRLDLTLRALQRVARINGKREE
GAKLSMEVLRASLQKELTMGKGQASAMELLRCPTLRHLFLCLSMLWFATSFAYYGLVMDL
QGFGVSIYLIQVIFGAVDLPAKLVGFLVINSLGRRPAQMAALLLAGICILLNGVIPQDQS
IVRTSLAVLGKGCLAASFNCIFLYTGELYPTMIRQTGMGMGSTMARVGSIVSPLVSMTAE
LYPSMPLFIYGAVPVAASAVTVLLPETLGQPLPDTVQDLESRWAPTQKEAGIYPRKGKQT
RQQQEHQKYMVPLQASAQEKNGL
Number of residues563
Molecular Weight61815.78
Theoretical pI8.78
GO Classification
Functions
  • inorganic anion exchanger activity
  • organic anion transmembrane transporter activity
  • sodium-independent organic anion transmembrane transporter activity
  • chloride ion binding
Processes
  • response to methotrexate
  • protein homooligomerization
  • sodium-independent organic anion transport
  • alpha-ketoglutarate transport
  • organic anion transport
  • renal tubular secretion
  • anion transmembrane transport
  • transmembrane transport
Components
  • caveola
  • protein complex
  • plasma membrane
  • extracellular exosome
  • integral component of plasma membrane
  • basolateral plasma membrane
General FunctionSodium-independent organic anion transmembrane transporter activity
Specific FunctionInvolved 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.
Pfam Domain Function
Transmembrane Regions10-30 136-156 165-187 191-213 225-245 249-269 338-358 369-389 396-416 426-446 456-475 485-505
GenBank Protein ID3831566
UniProtKB IDQ4U2R8
UniProtKB Entry NameS22A6_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0010747|Solute carrier family 22 member 6 (SLC22A6)
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
GenBank Gene IDAF057039
GeneCard IDNot Available
GenAtlas IDhROAT1
HGNC IDHGNC:10970
Chromosome Location11
LocusNot Available
References
  1. 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. 9762842
  2. 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. 9887087
  3. 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. 9950961
  4. 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. 10049739
  5. 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. 10462545
  6. 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. 10964714
  7. 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. 16554811
  8. 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. 15489334
  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. 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. 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. 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. 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. 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. 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. 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. 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. 16164626