Solute carrier family 22 member 12

Details

Name
Solute carrier family 22 member 12
Kind
protein
Synonyms
  • OATL4
  • Organic anion transporter 4-like protein
  • Renal-specific transporter
  • RST
  • URAT1
  • Urate anion exchanger 1
  • Urate:anion antiporter SLC22A12
Gene Name
SLC22A12
UniProtKB Entry
Q96S37Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0008631|Solute carrier family 22 member 12
MAFSELLDLVGGLGRFQVLQTMALMVSIMWLCTQSMLENFSAAVPSHRCWAPLLDNSTAQ
ASILGSLSPEALLAISIPPGPNQRPHQCRRFRQPQWQLLDPNATATSWSEADTEPCVDGW
VYDRSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDRFGRRLVLTWSY
LQMAVMGTAAAFAPAFPVYCLFRFLLAFAVAGVMMNTGTLLMEWTAARARPLVMTLNSLG
FSFGHGLTAAVAYGVRDWTLLQLVVSVPFFLCFLYSWWLAESARWLLTTGRLDWGLQELW
RVAAINGKGAVQDTLTPEVLLSAMREELSMGQPPASLGTLLRMPGLRFRTCISTLCWFAF
GFTFFGLALDLQALGSNIFLLQMFIGVVDIPAKMGALLLLSHLGRRPTLAASLLLAGLCI
LANTLVPHEMGALRSALAVLGLGGVGAAFTCITIYSSELFPTVLRMTAVGLGQMAARGGA
ILGPLVRLLGVHGPWLPLLVYGTVPVLSGLAALLLPETQSLPLPDTIQDVQNQAVKKATH
GTLGNSVLKSTQF
Number of residues
553
Molecular Weight
59629.57
Theoretical pI
Not Available
GO Classification
Processes
cellular response to insulin stimulus / monoatomic ion transport / organic anion transport / renal urate salt excretion / response to xenobiotic stimulus
Components
membrane
General Function
Electroneutral antiporter that translocates urate across the apical membrane of proximal tubular cells in exchange for monovalent organic or inorganic anions (PubMed:12024214, PubMed:22194875, PubMed:35144162, PubMed:35462902). Involved in renal reabsorption of urate and helps maintaining blood levels of uric acid (PubMed:12024214, PubMed:22194875). Mediates urate uptake by an exchange with organic anions such as (S)-lactate and nicotinate, and inorganic anion Cl(-) (PubMed:12024214). Other inorganic anions such as Br(-), I(-) and NO3(-) may also act as counteranions that exchange for urate (PubMed:12024214). Also mediates orotate tubular uptake coupled with nicotinate efflux and to a lesser extent with lactate efflux, therefore displaying a potential role in orotate renal reabsorption (PubMed:21350910). Orotate transport is Cl(-)-dependent (PubMed:21350910)
Specific Function
PDZ domain binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
9-29 146-166 174-194 195-215 232-252 260-280 351-371 378-398 407-427 435-455 466-486 495-515
Cellular Location
Apical cell membrane
Gene sequence
>lcl|BSEQ0013316|Solute carrier family 22 member 12 (SLC22A12)
ATGGCATTTTCTGAACTCCTGGACCTCGTGGGTGGCCTGGGCAGGTTCCAGGTTCTCCAG
ACGATGGCTCTGATGGTCTCCATCATGTGGCTGTGTACCCAGAGCATGCTGGAGAACTTC
TCGGCCGCCGTGCCCAGCCACCGCTGCTGGGCACCCCTCCTGGACAACAGCACGGCTCAG
GCCAGCATCCTAGGGAGCTTGAGTCCTGAGGCCCTCCTGGCTATTTCCATCCCGCCGGGC
CCCAACCAGAGGCCCCACCAGTGCCGCCGCTTCCGCCAGCCACAGTGGCAGCTCTTGGAC
CCCAATGCCACGGCCACCAGCTGGAGCGAGGCCGACACGGAGCCGTGTGTGGATGGCTGG
GTCTATGACCGCAGCATCTTCACCTCCACAATCGTGGCCAAGTGGAACCTCGTGTGTGAC
TCTCATGCTCTGAAGCCCATGGCCCAGTCCATCTACCTGGCTGGGATTCTGGTGGGAGCT
GCTGCGTGCGGCCCTGCCTCAGACAGGTTTGGGCGCAGGCTGGTGCTAACCTGGAGCTAC
CTTCAGATGGCTGTGATGGTGATGGAGTGGACGGCGGCACGGGCCCGACCCTTGGTGATG
ACCTTGAACTCTCTGGGCTTCAGCTTCGGCCATGGCCTGACAGCTGCAGTGGCCTACGGT
GTGCGGGACTGGACACTGCTGCAGCTGGTGGTCTCGGTCCCCTTCTTCCTCTGCTTTTTG
TACTCCTGGTGGCTGGCAGAGTCGGCACGATGGCTCCTCACCACAGGCAGGCTGGATTGG
GGCCTGCAGGAGCTGTGGAGGGTGGCTGCCATCAACGGAAAGGGGGCAGTGCAGGACACC
CTGACCCCTGAGGTCTTGCTTTCAGCCATGCGGGAGGAGCTGAGCATGGGCCAGCCTCCT
GCCAGCCTGGGCACCCTGCTCCGCATGCCCGGACTGCGCTTCCGGACCTGTATCTCCACG
TTGTGCTGGTTCGCCTTTGGCTTCACCTTCTTCGGCCTGGCCCTGGACCTGCAGGCCCTG
GGCAGCAACATCTTCCTGCTCCAAATGTTCATTGGTGTCGTGGACATCCCAGCCAAGATG
GGCGCCCTGCTGCTGCTGAGCCACCTGGGCCGCCGCCCCACGCTGGCCGCATCCCTGTTG
CTGGCAGGGCTCTGCATTCTGGCCAACACGCTGGTGCCCCACGAAATGGGGGCTCTGCGC
TCAGCCTTGGCCGTGCTGGGGCTGGGCGGGGTGGGGGCTGCCTTCACCTGCATCACCATC
TACAGCAGCGAGCTCTTCCCCACTGTGCTCAGGATGACGGCAGTGGGCTTGGGCCAGATG
GCAGCCCGTGGAGGAGCCATCCTGGGGCCTCTGGTCCGGCTGCTGGGTGTCCATGGCCCC
TGGCTGCCCTTGCTGGTGTATGGGACGGTGCCAGTGCTGAGTGGCCTGGCCGCACTGCTT
CTGCCCGAGACCCAGAGCTTGCCGCTGCCCGACACCATCCAAGATGTGCAGAACCAGGCA
GTAAAGAAGGCAACACATGGCACGCTGGGGAACTCTGTCCTAAAATCCACACAGTTTTAG
Chromosome Location
11
Locus
11q13.1
External Identifiers
ResourceLink
UniProtKB IDQ96S37
UniProtKB Entry NameS22AC_HUMAN
GeneCard IDSLC22A12
HGNC IDHGNC:17989
KEGG IDhsa:116085
IUPHAR/Guide To Pharmacology ID1031
NCBI Gene ID116085
General References
  1. Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H: Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature. 2002 May 23;417(6887):447-52. Epub 2002 Apr 14. [Article]
  2. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. 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. [Article]
  5. 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. [Article]
  6. Vazquez-Mellado J, Jimenez-Vaca AL, Cuevas-Covarrubias S, Alvarado-Romano V, Pozo-Molina G, Burgos-Vargas R: Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout. Rheumatology (Oxford). 2007 Feb;46(2):215-9. Epub 2006 Jul 11. [Article]
  7. Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H: PDZK1: I. a major scaffolder in brush borders of proximal tubular cells. Kidney Int. 2003 Nov;64(5):1733-45. [Article]
  8. Anzai N, Miyazaki H, Noshiro R, Khamdang S, Chairoungdua A, Shin HJ, Enomoto A, Sakamoto S, Hirata T, Tomita K, Kanai Y, Endou H: The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus. J Biol Chem. 2004 Oct 29;279(44):45942-50. Epub 2004 Aug 10. [Article]
  9. Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, Hosoya T: Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion. J Am Soc Nephrol. 2004 Jan;15(1):164-73. [Article]
  10. Iwai N, Mino Y, Hosoyamada M, Tago N, Kokubo Y, Endou H: A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese. Kidney Int. 2004 Sep;66(3):935-44. [Article]
  11. Wakida N, Tuyen DG, Adachi M, Miyoshi T, Nonoguchi H, Oka T, Ueda O, Tazawa M, Kurihara S, Yoneta Y, Shimada H, Oda T, Kikuchi Y, Matsuo H, Hosoyamada M, Endou H, Otagiri M, Tomita K, Kitamura K: Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia. J Clin Endocrinol Metab. 2005 Apr;90(4):2169-74. Epub 2005 Jan 5. [Article]
  12. Cheong HI, Kang JH, Lee JH, Ha IS, Kim S, Komoda F, Sekine T, Igarashi T, Choi Y: Mutational analysis of idiopathic renal hypouricemia in Korea. Pediatr Nephrol. 2005 Jul;20(7):886-90. Epub 2005 May 24. [Article]
  13. Graessler J, Graessler A, Unger S, Kopprasch S, Tausche AK, Kuhlisch E, Schroeder HE: Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population. Arthritis Rheum. 2006 Jan;54(1):292-300. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Probenecidapproved, investigationalunknowntransporterinhibitorDetails
LosartanapprovedunknowntransporterinhibitorDetails
Lesinuradapproved, investigationalyestargetinhibitorDetails
SulfinpyrazoneapprovedyestargetinhibitorDetails
Favipiravirapproved, investigationalunknowntransporterinhibitorDetails
Suprofenapproved, withdrawnunknowntransporterinhibitorDetails
MorinexperimentalyestargetinhibitorDetails
VerinuradinvestigationalyestargetmodulatorDetails
RuzinuradinvestigationalyestargetinhibitorDetails
PF-05089771investigationalyestargetinhibitorDetails
Benzbromaroneinvestigational, withdrawnyestargetinhibitorDetails
DotinuradinvestigationalyestargetinhibitorDetails