Biology:SLC22A12
 Generic protein structure example |
Solute carrier family 22 (organic anion/cation transporter), member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the SLC22A12 gene.[1][2]
Function
The protein encoded by this gene is a urate transporter and urate-anion exchanger which regulates the level of urate in the blood. This protein is an integral membrane protein primarily found in kidney. Two transcript variants encoding different isoforms have been found for this gene.[1]
Clinical significance
Numerous single nucleotide polymorphisms of this gene are significantly associated with altered (increased or decreased) reabsorption of uric acid by the kidneys.[3][4] Respectively, these altered rates of reabsorption contribute to hyperuricemia and hypouricemia.
Interactions
SLC22A12 has been shown to have a protein-protein interaction with PDZK1.[5]
Inhibition
Lesinurad,Ruzinurad and dotinurad are urate transporter inhibitors that have been approved to treat gout.[6][7] Lesinurad enhances urate excretion by inhibition the tubular re-absorption. Probenecid also facilitates uric acid secretion.[8][9]
See also
References
- ↑ 1.0 1.1 "Entrez Gene: SLC22A12 solute carrier family 22 (organic anion/cation transporter), member 12". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=116085.
- ↑ "Molecular identification of a renal urate anion exchanger that regulates blood urate levels". Nature 417 (6887): 447–52. May 2002. doi:10.1038/nature742. PMID 12024214. Bibcode: 2002Natur.417..447E.
- ↑ "Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population". Arthritis Rheum. 54 (1): 292–300. January 2006. doi:10.1002/art.21499. PMID 16385546.
- ↑ "Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia". J. Clin. Endocrinol. Metab. 90 (4): 2169–74. April 2005. doi:10.1210/jc.2004-1111. PMID 15634722.
- ↑ "PDZK1: I. a major scaffolder in brush borders of proximal tubular cells". Kidney Int. 64 (5): 1733–45. November 2003. doi:10.1046/j.1523-1755.2003.00266.x. PMID 14531806.
- ↑ "FDA approves Zurampic to treat high blood uric acid levels associated with gout". United States Food and Drug Administration. 22 December 2015. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm478791.htm.
- ↑ "List of Approved Products". Pharmaceuticals and Medical Devices Agency. https://www.pmda.go.jp/files/000235289.pdf.
- ↑ "Interactions of organic anions with the organic cation transporter in renal BBMV". The American Journal of Physiology 254 (1 Pt 2): F56–61. Jan 1988. doi:10.1152/ajprenal.1988.254.1.F56. PMID 2962517.
- ↑ "Probenecid, a gout remedy, inhibits pannexin 1 channels". American Journal of Physiology. Cell Physiology 295 (3): C761–7. September 2008. doi:10.1152/ajpcell.00227.2008. PMID 18596212.
Further reading
- "Molecular physiology of urate transport.". Physiology 20 (2): 125–33. 2005. doi:10.1152/physiol.00039.2004. PMID 15772301.
- "Molecular identification of a renal urate anion exchanger that regulates blood urate levels.". Nature 417 (6887): 447–52. 2002. doi:10.1038/nature742. PMID 12024214. Bibcode: 2002Natur.417..447E.
- "PDZK1: I. a major scaffolder in brush borders of proximal tubular cells.". Kidney Int. 64 (5): 1733–45. 2004. doi:10.1046/j.1523-1755.2003.00266.x. PMID 14531806.
- "Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion.". J. Am. Soc. Nephrol. 15 (1): 164–73. 2004. doi:10.1097/01.ASN.0000105320.04395.D0. PMID 14694169.
- "The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus.". J. Biol. Chem. 279 (44): 45942–50. 2004. doi:10.1074/jbc.M406724200. PMID 15304510.
- "A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese.". Kidney Int. 66 (3): 935–44. 2004. doi:10.1111/j.1523-1755.2004.00839.x. PMID 15327384.
- "Recurrent URAT1 gene mutations and prevalence of renal hypouricemia in Japanese.". Pediatr. Nephrol. 20 (5): 576–8. 2005. doi:10.1007/s00467-005-1830-z. PMID 15772829.
- "A common mutation in an organic anion transporter gene, SLC22A12, is a suppressing factor for the development of gout.". Arthritis Rheum. 52 (8): 2576–7. 2005. doi:10.1002/art.21242. PMID 16059895.
- "Association between intronic SNP in urate-anion exchanger gene, SLC22A12, and serum uric acid levels in Japanese.". Life Sci. 79 (23): 2234–7. 2006. doi:10.1016/j.lfs.2006.07.030. PMID 16920156.
- "Human uric acid transporter 1 gene analysis in familial renal hypo-uricemia associated with exercise-induced acute renal failure.". Pediatrics International 49 (2): 235–7. 2007. doi:10.1111/j.1442-200X.2007.02337.x. PMID 17445045.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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