SLC14A2 Membrane Protein Introduction

Introduction of SLC14A2

SLC14A2 is also known as urea transporter B (UT-B), urea transporter 2, solute carrier family 14 member 2 and urea transporter, kidney. It belongs to the urea transporters (UTs) which are a family of integral membrane proteins mediating the rapid and passive diffusion of urea down its concentration gradient. Two genes encode for UTs in mammals: SLC14A1 and SLC14A2. The SLC14A1 gene contains a single UT domain encoding the protein UT-B. In contrast, the SLC14A2 gene, which encodes UT-A, contains two UT domains in tandem.

Function of SLC14A2 Membrane Protein

In mammals, there are two types of urea transporters, UT-A and UT-B, encoded by the solute carrier family SLC14A2 and SLC14A1 genes, respectively. These genes share a high degree of homology and are aligned in tandem at chromosome 18q12.3 in humans. UT-A urea transporters are mainly expressed in kidney epithelial cells while SLC14A2 transporters demonstrate a broader tissue distribution including bladder. SLC14A2 also serves as a determinant antigen of the Kidd blood group on erythrocytes. Urea transporters (mainly SLC14A2) in non-renal tissues function as scavengers that prevent intracellular urea aggregation and intoxication. Studies in SLC14A2 knockout mice demonstrate that absence of SLC14A2 results in notable urea accumulation, abnormal morphology in the hippocampus and depression-like behavior and he urothelium urea concentration is 9 times higher in SLC14A2 knockout mice, which is accompanied by increased cell DNA damage, apoptosis and malfunction of arginine metabolism. In addition, SLC14A2 suppresses tumor growth, overexpression of SLC14A2 inhibits colony formation of lung cancer cell lines.

Fig.1 Structure of SLC14A2 membrane protein. (Levin, 2012)

Application of SLC14A2 Membrane Protein in Literature

1. Hou R., et al. Identification of a Novel UT-B Urea Transporter in Human Urothelial Cancer. Frontiers in Physiology. 2017, 8:245. PubMed ID: 28503151
   
   

   This article reports that UT-B (SLC14A2) protein expression is significantly changed in bladder cancers and the aberrant UT-B expression may promote bladder cancer development or facilitate carcinogenesis induced by other carcinogens.

2. Dong Z., et al. Urea Transporter UT-B Deletion Induces DNA Damage and Apoptosis in Mouse Bladder Urothelium. PLoS ONE. 2013, 8(10):e76952. PubMed ID: 24204711
   
   

   This article reveals that UT-B (SLC14A2) may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B (SLC14A2) function induces DNA damage and apoptosis in the bladder, which can result in bladder disorders.

3. Collins D., et al. Differential protein abundance and function of UT-B urea transporters in human colon. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2010, 298(3):G345-G351. PubMed ID: 19926813
   
   

   This article illustrates UT-B protein (SLC14A2) expresses in different sections of the human colon and the results of this article suggest that UT-B urea transporters play an important role in maintaining the symbiotic relationship between humans and their gut bacteria.

4. Levin E.J., et al. Structure and permeation mechanism of a mammalian urea transporter. Proceedings of the National Academy of Sciences of the United States of America. 2012, 109(28):11194-11199. PubMed ID: 22733730
   
   

   The function studies show that the rate of urea conduction in UT-B (SLC14A2) is increased by hypoosmotic stress, and that the site of osmoregulation coincides with the location of the energy barrier.

5. Li C., et al. Clinical significance of the reduction of UT-B expression in urothelial carcinoma of the bladder. Pathology - Research and Practice. 2014, 210(12):799-803. PubMed ID: 25445116
   
   

   The results of this article suggest that the reduction or loss of UT-B (SLC14A2) expression may be related to the incidence, progression and invasiveness of bladder urothelial carcinoma and UT-B may be a novel diagnostic or prognostic biomarker, as well as a potential therapeutic target in urothelial carcinoma of the bladder.

SLC14A2 Preparation Options

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Reference

1. Levin E J., et al. (2012) Structure and permeation mechanism of a mammalian urea transporter. Proceedings of the National Academy of Sciences of the United States of America. 109(28):11194-11199.

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