SLC14A1 Membrane Protein Introduction

Introduction of SLC14A1

SLC14A1 is also known as urea transporter 1, type-B urea transporter, solute carrier family 14 member 1 and Urea transporter, erythrocyte. It belongs to urea transporters family which allows rapid urea movement across the cell membrane and is particularly important in the process of urinary concentration and for rapid urea equilibrium in non-renal tissues. SLC14A1 contains ten transmembrane spanning domains that are integrated into two internal hydrophobic repeats connected by a glycosylated extracellular loop.

Function of SLC14A1 Membrane Protein

The activity of SLC14A1 is mediated by urea and no saturation is observed up to a concentration of 200 mM. Urea transport is inhibited mostly by 0.5–0.7 mM phloretin and urea analogues. Transport mediated by type-B urea transporter is more sensitive to phloretin inhibition than type-A urea transporter with an IC50 of 75 and 230 μM, respectively. The most important role of urea transporters in mammals exist in the kidney where they serve as a major component of the urinary concentrating process, and the principal route for nitrogen disposal. The latter process, especially in ruminants, functions in concert with the urea nitrogen salvaging pathway that is mediated by urea transporters in the colon. Given the importance of urea transport in urinary concentration, urea transporters are a potential target for novel drug discovery in particular of diuretic agents. Regulation of SLC14A1 mediated urea transport is a potential future site for intervention to influence colonic microbial populations and hence human health.

Fig.1 Molecular structure of SLC14A1 membrane protein. (Esteva-Font, 2015)

Application of SLC14A1 Membrane Protein in Literature

1. Esteva-Font C., et al. Urea transporter proteins as targets for small-molecule diuretics. Nature reviews. Nephrology. 2015, 11(2):113-123. PubMed ID: 25488859
   
   

   This article reports that urea transport targeted inhibitors may be useful alone or in combination with conventional diuretics for therapy of various oedemas and hyponatraemias, potentially including those refractory to treatment with current diuretics.

2. Hou R., et al. SLC14A1: a novel target for human urothelial cancer. Clinical & Translational Oncology. 2017, 19(12):1438-1446. PubMed ID: 28589430
   
   

   This article discusses the SLC14A1 gene and UT-B protein properties and elucidates the expression behavior of SLC14A1 in human bladder cancer. The altered expression of SLC14A1 gene in human urothelial cancer may implicate its significance as a novel target for research.

3. Shayakul C., et al. The urea transporter family (SLC14): Physiological, pathological and structural aspects. Molecular Aspects of Medicine. 2013, 34(2):313-322. PubMed ID: 23506873
   
   

   This review provides an update of these advances and their implications for our current understanding of the SLC14 UTs and suggests that urea transports are a potential target for novel drug discovery in particular of diuretic agents.

4. Koutros S., et al. Differential urinary specific gravity as a molecular phenotype of the bladder cancer genetic association in the urea transporter gene, SLC14A1. International journal of cancer. Journal international du cancer. 2013, 133(12):3008-3013. PubMed ID: 23754249
   
   

   This article suggests that SLC14A1 could be a unique urea transporter in the bladder that has the ability to influence urine concentration and that this mechanism might explain the increased bladder cancer susceptibility associated with a representative genetic variant (rs10775480).

5. Garcia-Closas M., et al. A genome-wide association study of bladder cancer identifies a new susceptibility locus within SLC14A1, a urea transporter gene on chromosome 18q12.3. Hum. Mol. Genet. 2011, 20(21):4282-4289. PubMed ID: 21824976
   
   

   The results of this article show that SLC14A1 regulates urine volume and concentration whereas in erythrocytes it determines the Kidd blood groups and the genetic variation in SLC14A1 could provide new etiological insights into bladder carcinogenesis.

SLC14A1 Preparation Options

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Reference

1. Esteva-Font C., et al. (2015) Urea transporter proteins as targets for small-molecule diuretics. Nature reviews. Nephrology. 11(2):113-123.

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