SLC17A1 Membrane Protein Introduction

Introduction of SLC17A1

Sodium-dependent phosphate transport protein 1 (SLC17A1) is a protein that in humans is encoded by the SLC17A1 gene. The SLC17 family of transporters is a group of nine structurally related proteins that mediate the transmembrane transport of organic anions. The first characterized members of this family are the type I phosphate transporters. SLC17A1 is expressed in the brush border membrane of the proximal tubule in the kidney and to a lesser extent in the sinusoidal membrane of hepatocytes in the liver. Hepatocyte nuclear factor 1 alpha (HNF1α) has been shown to upregulate SLC17A1 expression and alter their splicing patterns.

Function of SLC17A1 Membrane Protein

Human sodium-dependent phosphate cotransporter type 1 (NPT1/SLC17A1) is one of the urate transporters. This protein is expressed in the sinusoidal membrane of hepatocytes, in the proximal tubules of the kidneys and in the proximal tubules, where it acts as a renal transporter of uric acid and mediates the co-transport of sodium and inorganic phosphate. Additionally, SLC17A1 SNPs (single nucleotide polymorphisms) are associated with kidney function indicators, such as suppressed serum uric levels and gout. Sodium-dependent transporter 1 may contain an I269T allele to protect against gout, resulting in increased activity of sodium-dependent transporter 1. The SLC17A1 locus has the third strongest effect on serum urate and has been associated with gout in candidate gene studies in Japanese, European, and Polynesian ascertained by clinical assessment.

Fig.1 Proposed physiologic model of renal urate secretion via sodium-dependent phosphate cotransporter type 1 (NPT1) in humans. (Chiba, 2015)

Application of SLC17A1 Membrane Protein in Literature

1. Sakiyama M., et al. Expression of a human NPT1/SLC17A1 missense variant which increases urate export. Nucleosides Nucleotides Nucleic Acids. 2016, 35(10-12): 536-542. PubMed ID: 27906618
   
   

   The study reveals that a common NPT1 missense variant, I269T (rs1165196), can decrease the risk of renal underexcretion gout. Moreover, they demonstrate that human NPT1 is localized to the apical membrane of the renal proximal tubule and that I269T is the gain-of-function variant which increases the NPT1-mediated urate export.

2. Koyama T., et al. Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men. Sci Rep. 2015, 5: 15888. PubMed ID: 26524967
   
   

   This article reveals that genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinemia in Japanese men.

3. Zhou Z.W., et al. Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males: a case-control study. BMC Med Genet. 2015, 16: 66. PubMed ID: 26290326
   
   

   This article demonstrates that three SUA correlated SNPs in the Caucasian population, rs780094 in GCKR, rs1183201 in SLC17A1 and rs505802 in SLC22A12 are confirmed to be associated with gout arthritis and uric acid concentrations in Han Chinese males.

4. Chiba T., et al. NPT1/SLC17A1 is a renal urate exporter in humans and its common gain-of-function variant decreases the risk of renal underexcretion gout. Arthritis Rheumatol. 2015, 67(1): 281-287. PubMed ID: 25252215
   
   

   This article demonstrates that NPT1 is a urate exporter located in the renal proximal tubule in humans and that its common gain-of-function variant, rs1165196, causes RUE gout, a major subtype of gout.

5. Moffatt J.E.H., et al. The renal urate transporter SLC17A1 locus: confirmation of association with gout. Arthritis Res Ther. 2012, 14(2): R92. PubMed ID: 22541845
   
   

   This article confirms that the renal urate transporter SLC17A1 is associated with gout at a genome-wide level of significance.

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Reference

1. Chiba Toshinori. (2015). NPT1/SLC17A1 Is a Renal Urate Exporter in Humans and Its Common Gain-of-Function Variant Decreases the Risk of Renal Underexcretion Gout. Arthritis Rheumatol. 67(1): 281-287.

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