SLC17A3 Membrane Protein Introduction

Introduction of SLC17A3

Sodium-dependent phosphate transport protein 4, also known as solute carrier family 17 member 3 (SLC17A3), is a protein that in humans is encoded by the SLC17A3 gene. SLC17A3 is expressed in the kidney and localized to the apical side of renal tubules. SLC17A3 is a voltage-driven transporter that excretes intracellular urate and organic anions from the blood into renal tubule cells. Two transcript variants encoding different isoforms have been found for SLC17A3 gene. The longer isoform is a plasma membrane protein with transporter activity, while the shorter isoform is localized to the endoplasmic reticulum.

Basic Information of SLC17A3
Protein Name	Sodium-dependent phosphate transport protein 4
Gene Name	SLC17A3
Aliases	Na(+)/PI cotransporter 4, NPT4, Sodium/phosphate cotransporter 4, Solute carrier family 17 member 3
Organism	Homo sapiens (Human)
UniProt ID	O00476
Transmembrane Times	8
Length (aa)	420
Sequence	MATKTELSPTARESKNAQDMQVDETLIPRKVPSLCSARYGIALVLHFCNFTTIAQNVIMNITMVAMVNSTSPQSQLNDSSEVLPVDSFGGLSKAPKSLPAKSSILGGQFAIWEKWGPPQERSRLCSIALSGMLLGCFTAILIGGFISETLGWPFVFYIFGGVGCVCCLLWFVVIYDDPVSYPWISTSEKEYIISSLKQQVGSSKQPLPIKAMLRSLPIWSICLGCFSHQWLVSTMVVYIPTYISSVYHVNIRDNGLLSALPFIVAWVIGMVGGYLADFLLTKKFRLITVRKIATILGSLPSSALIVSLPYLNSGYITATALLTLSCGLSTLCQSGIYINVLDIAPRYSSFLMGASRGFSSIAPVIVPTVSGFLLSQDPEFGWRNVFFLLFAVNLLGLLFYLIFGEADVQEWAKERKLTRL

Function of SLC17A3 Membrane Protein

NPT4 (SLC17A3), classified as a type I sodium-phosphate cotransporter, serves as a voltage-driven organic anion efflux transporter at the apical side of renal proximal tubules. There are two splice variants of SLC17A3 mRNA. One variant, NPT4_L, contains an open reading frame encoding a putative 498-amino-acid protein, and the other, hNPT4_S, encodes a 420-amino-acid protein. SLC17A3 mediates the efflux of drugs such as para-aminohippurate (PAH) and diuretics and that containing endogenous substrates such as urate in a voltage-sensitive manner. It is documented that sialin uses proton co-transport to drive transmembrane movement of acidic sugars, while urate transport by SLC17A1 and SLC17A3, glutamate transport by the VGLUTs, and ATP transport by VNUT. The characterized transporters all exhibit dependence on Cl^- with the exception of sialin.

SLC17A3 Membrane Protein Introduction Fig.1 The uric acid transportasome. (Merriman, 2015)

Application of SLC17A3 Membrane Protein in Literature

Otani N., et al. Roles of organic anion transporters (OATs) in renal proximal tubules and their localization. Anat Sci Int. 2017, 92(2): 200-206. PubMed ID: 27614971

In this article, authors demonstrated that the diuretics entered proximal tubular cells via basolateral OAT1 and/or OAT3 and might then interfere with the NPT4-mediated apical urate efflux in the renal proximal tubule, which might lead to the induction of hyperuricemia.
Huang S., et al. The homocysteine associated variant rs548987 of SLC17A3 confers susceptibility to ischemic stroke in Chinese population. J Neurol Sci. 2016, 370: 78-81. PubMed ID: 27772792

The authors revealed that C allele of rs548987of SLC17A3 showed significant association with small vessel disease subtype of ischemic stroke.
Jutabha P., et al. Apical voltage-driven urate efflux transporter NPT4 in renal proximal tubule. Nucleosides Nucleotides Nucleic Acids. 2011, 30(12): 1302-1311. PubMed ID: 22132991

The authors proposed that NPT4 was an important transepithelial proximal tubular transporter that transported diuretic drugs and operated functionally with basolateral organic anion transporters 1/3 (OAT1/OAT3).
Jutabha P., et al. A novel human organic anion transporter NPT4 mediates the transport of ochratoxin A. J Pharmacol Sci. 2011, 116(4): 392-396. PubMed ID: 21778665

The authors found that the K(m) of OTxA for the efflux transporter hNPT4 was much higher than those for the uptake transporters hOAT1 and hOAT3, favoring the accumulation of OTxA in the tubular cell and leading to nephrotoxicity.
Melis D., et al. NPT4, a new microsomal phosphate transporter: mutation analysis in glycogen storage disease type Ic. J Inherit Metab Dis. 2004, 27(6): 725-733. PubMed ID: 15505377

This article revealed the genomic structure of NPT4 and analyzed the gene as a candidate for glycogen storage disease type Ic (GSD Ic).

SLC17A3 Preparation Options

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Reference

Merriman T R. (2015). An update on the genetic architecture of hyperuricemia and gout. Merriman Arthritis Research & Therapy. 17: 98.

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