SLC6A19 Membrane Protein Introduction

Introduction of SLC6A19

SLC6A19 is encoded by SLC6A19 gene. It belongs to the solute carrier family 6 which has been extensively studied during the past few decades because it offers numerous possibilities for therapeutic applications. SLC6A19 is a sodium-dependent neutral amino acid transporter, removes neutral amino acids across apical membrane in the kidney and intestine. SLC6A19 is a secondary active co-transporter that drives the transport of several di- and tripeptides as well as peptide-mimetic molecules into a variety of cells by using an inwardly directed proton electrochemical gradient. Meanwhile, recent studies show that the causative gene SLC6A19 is present in the autosomal recessive defect of renal and gastrointestinal neutral amino acid transport can cause the hartnup disorder.

Function of SLC6A19 Membrane Protein

SLC6A19, also named as solute carrier family 6 (neurotransmitter transporter), member 18, plays a decisive role in neutral amino acid transport which is presented in kidney, intestine, and liver. The neutral amino acid transporter SLC6A19 has recently been identified as a possible target for treatment of type 2 diabetes and related disorders. It mediates the Na⁺-dependent uptake of all neutral amino acids. For surface expression and catalytic activity, SLC6A19 requires coexpression of collectrin (TMEM27). In addition, research conducted on SLC6A19 indicates that its variants are associated with iminoglycinuria.

Fig.1 Phylogenetic tree analysis among known Slc6a15-20 family. (Soma, 2014)

Application of SLC6A19 Membrane Protein in Literature

1. Tian W., et al. SLC6A19 is a novel putative gene, induced by dioxins via AhR in human hepatoma HepG2 cells. Environ Pollut. 2018, 237:508-514. PubMed ID: 29522993
   
   

   This article analyzes the expression level of SLC6A19 in HepG2 cells. These results indicate that SLC6A19 is a novel putative target gene of AhR activation in HepG2 cells.

2. Soma S., et al. Spatial mRNA expression and response to fasting and refeeding of neutral amino acid transporters slc6a18 and slc6a19a in the intestinal epithelium of mozambique tilapia. Front Physiol. 2018, 9:212. PubMed ID: 29593569
   
   

   This article analyzes the expression levels of slc6a18 and slc6a19a in the five segments (HL, PMC, GL, DMC, and TS) of the intestine of Mozambique tilapia. These results indicate that slc6a18 is mainly expressed in the middle (GL) and posterior (DMC and TS) intestines, while slc6a19a is specifically expressed in the anterior intestine (HL and PMC).

3. Cheng Q., et al. Identification of novel inhibitors of the amino acid transporter B0 AT1 (SLC6A19), a potential target to induce protein restriction and to treat type 2 diabetes. Br J Pharmacol. 2017, 174(6):468-482. PubMed ID: 28176326
   
   

   Authors in this group establish a high-throughput screening assay to identify the potential inhibitors of the B0AT1 transporter. The data suggest benztropine is a competitive inhibitor of the SLC6A19.

4. Margheritis E., et al. Amino acid transporter B(0)AT1 (slc6a19) and ancillary protein: impact on function. Pflugers Arch. 2016, 468(8):1363-74. PubMed ID: 27255547
   
   

   Authors in this group determine the function of slc6a19 on substrate specificity, apparent affinities and the ionic dependence in the presence of specific collectrin. These results indicate that slc6a19 helps to understand the regulatory mechanism of essential nutrient absorption.

5. Rimoldi S., et al. Intestinal B(0)AT1 (SLC6A19) and PEPT1 (SLC15A1) mRNA levels in European sea bass (Dicentrarchus labrax) reared in fresh water and fed fish and plant protein sources. J Nutr Sci. 2015, 4:e21. PubMed ID: 26097704
   
   

   Authors first isolate the neutral amino acid transporter SLC6A19 in sea bass by molecular cloning and sequence a full-length cDNA. Meanwhile, they also analyze diet-induced changes in the mRNA copies of SLC6A19 and PEPT1 genes in different portions of sea bass intestine.

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Reference

1. Soma S, et al. (2018). Spatial mRNA expression and response to fasting and refeeding of neutral amino acid transporters slc6a18 and slc6a19a in the intestinal epithelium of mozambique tilapia. Front Physiol. 9, 212.

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