Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2010 Nov 05;28545:35123-32. doi: 10.1074/jbc.M110.121301.
Show Gene links
Show Anatomy links
Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate.
Jutabha P, Anzai N, Kitamura K, Taniguchi A, Kaneko S, Yan K, Yamada H, Shimada H, Kimura T, Katada T, Fukutomi T, Tomita K, Urano W, Yamanaka H, Seki G, Fujita T, Moriyama Y, Yamada A, Uchida S, Wempe MF, Endou H, Sakurai H.
???displayArticle.abstract???
The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elevated serum urate has predisposed man to hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various cardiovascular diseases. Human serum urate levels are largely determined by urate reabsorption and secretion in the kidney. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and basolateral URATv1/GLUT9 (SLC2A9). In contrast, the molecular mechanism(s) for renal urate secretion remain unknown. In this report, we demonstrate that an orphan transporter hNPT4 (human sodium phosphate transporter 4; SLC17A3) was a multispecific organic anion efflux transporter expressed in the kidneys and liver. hNPT4 was localized at the apical side of renal tubules and functioned as a voltage-driven urate transporter. Furthermore, loop diuretics, such as furosemide and bumetanide, substantially interacted with hNPT4. Thus, this protein is likely to act as a common secretion route for both drugs and may play an important role in diuretics-induced hyperuricemia. The in vivo role of hNPT4 was suggested by two hyperuricemia patients with missense mutations in SLC17A3. These mutated versions of hNPT4 exhibited reduced urate efflux when they were expressed in Xenopus oocytes. Our findings will complete a model of urate secretion in the renal tubular cell, where intracellular urate taken up via OAT1 and/or OAT3 from the blood exits from the cell into the lumen via hNPT4.
Anzai,
Organic anion transporter family: current knowledge.
2006, Pubmed
Anzai,
Organic anion transporter family: current knowledge.
2006,
Pubmed Anzai,
New insights into renal transport of urate.
2007,
Pubmed Anzai,
Drug discovery for hyperuricemia.
2007,
Pubmed Anzai,
Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans.
2008,
Pubmed
,
Xenbase Anzai,
The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus.
2004,
Pubmed Augustin,
Identification and characterization of human glucose transporter-like protein-9 (GLUT9): alternative splicing alters trafficking.
2004,
Pubmed
,
Xenbase Avner,
Polypeptide growth factors in metanephric growth and segmental nephron differentiation.
1990,
Pubmed Caulfield,
SLC2A9 is a high-capacity urate transporter in humans.
2008,
Pubmed
,
Xenbase Dantzler,
Renal organic anion transport: a comparative and cellular perspective.
2002,
Pubmed Dehghan,
Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study.
2008,
Pubmed Emmerson,
The management of gout.
1996,
Pubmed Enomoto,
Molecular identification of a renal urate anion exchanger that regulates blood urate levels.
2002,
Pubmed
,
Xenbase Eraly,
Multiple organic anion transporters contribute to net renal excretion of uric acid.
2008,
Pubmed Hediger,
Molecular physiology of urate transport.
2005,
Pubmed Horita,
Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities.
2005,
Pubmed
,
Xenbase Jutabha,
Identification of a novel voltage-driven organic anion transporter present at apical membrane of renal proximal tubule.
2003,
Pubmed
,
Xenbase Krishnamurthy,
Role of ABCG2/BCRP in biology and medicine.
2006,
Pubmed Kusano,
Cholinergic and catecholaminergic receptors in the Xenopus oocyte membrane.
1982,
Pubmed
,
Xenbase Li,
The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts.
2007,
Pubmed Melis,
NPT4, a new microsomal phosphate transporter: mutation analysis in glycogen storage disease type Ic.
2004,
Pubmed Møller,
Renal organic anion transport system: pharmacological, physiological, and biochemical aspects.
1982,
Pubmed Mount,
Renal urate transport.
2006,
Pubmed Murer,
The sodium phosphate cotransporter family SLC34.
2004,
Pubmed Pascual,
Gout, diuretics and the kidney.
2006,
Pubmed Pritchard,
Mechanisms mediating renal secretion of organic anions and cations.
1993,
Pubmed Rafey,
Uric acid transport.
2003,
Pubmed Reimer,
Organic anion transport is the primary function of the SLC17/type I phosphate transporter family.
2004,
Pubmed Roch-Ramel,
Renal Transport of Urate in Humans.
1999,
Pubmed Ruddy,
A 1.1-Mb transcript map of the hereditary hemochromatosis locus.
1997,
Pubmed Russel,
Molecular aspects of renal anionic drug transport.
2002,
Pubmed Tsuchida,
Identification of a novel organic anion transporter mediating carnitine transport in mouse liver and kidney.
2010,
Pubmed
,
Xenbase Uchino,
p-aminohippuric acid transport at renal apical membrane mediated by human inorganic phosphate transporter NPT1.
2000,
Pubmed Van Aubel,
Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites.
2005,
Pubmed Vitart,
SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout.
2008,
Pubmed
,
Xenbase Watanabe,
Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity.
2002,
Pubmed Woodward,
Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout.
2009,
Pubmed
,
Xenbase Wu,
Two independent mutational events in the loss of urate oxidase during hominoid evolution.
1992,
Pubmed Wu,
Hyperuricemia and urate nephropathy in urate oxidase-deficient mice.
1994,
Pubmed Yamauchi,
Acceleration of serotonin transporter transport-associated current by 3,4-methylenedioxymethamphetamine (MDMA) under acidic conditions.
2007,
Pubmed
,
Xenbase
