SLC29A2 Membrane Protein Introduction

Introduction of SLC29A2

Solute carrier family 29 member 2 (SLC29A2), also known as Equilibrative nucleoside transporter 2 (ENT2), is a protein that in humans is encoded by the SLC29A2 gene. SLC29A2 belongs to the Equilibrative nucleoside transporter family, which plays a significant role in the uptake of nucleosides. The structure of SLC29A2 is characterized by 11 transmembrane (TM) domains connected to one another by hydrophilic loops. Most of the loops are small, except for 2 large loops connecting TM 1-2 and TM 6-7, among which, the loop connecting TM 1-2 has 2 potential N-glycosylation sites.

Function of SLC29A2 Membrane Protein

The most well-known function of SLC29A2 is to mediate equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine, which is essential for nucleotide synthesis by salvage pathways in cells that lack de novo biosynthetic pathways. SLC29A2 shows lower affinity than SLC29A1 for transport of thymidine, adenosine, cytidine, and guanosine following expression in porcine kidney cells, However, the affinity of SLC29A2 for inosine is 4-fold higher compared with SLC29A1. It is reported that SLC29A2 is the major transporter of adenosine and its metabolites (inosine and hypoxanthine) in tissues where ENT2 is predominantly expressed, such as skeletal muscle. Significantly, SLC29A1 and SLC29A2 in Xenopus oocytes present their potential ability to transport three 3-prime-deoxynucleoside analogs used in human immunodeficiency virus (HIV) therapy: 2-prime,3-prime-dideoxycytidine (ddC), 3-prime-azido-3-prime-deoxythymidine (AZT), and 2-prime,3-prime-dideoxyinosine (ddI).

Fig.1 Ent2 and the A2B receptor on the colonic intestinal epithelium provide a targetable signaling network to protect the inflamed colon. (Aherne, 2018)

Application SLC29A2 of Membrane Protein in Literature

1. Grañé-Boladeras N., et al. Novel nuclear hENT2 isoforms regulate cell cycle progression via controlling nucleoside transport and nuclear reservoir. Cellular and molecular life sciences. 2016, 73(23): 4559-4575. PubMed ID: 27271752
   
   

   This article indicates that hENT2 and its variants can mediate the nucleoside compartmentalization at the nuclear envelope and translocation into the nucleus, which is essential for effective DNA synthesis and cell proliferation.

2. Eckle T., et al. Crosstalk between the equilibrative nucleoside transporter ENT2 and alveolar Adora2b adenosine receptors dampens acute lung injury. The FASEB Journal. 2013, 27(8): 3078-3089. PubMed ID: 23603835
   
   

   This article reveals that A2B adenosine receptor (Adora2b) plays an important role in mediating ENT-dependent lung protection, and there is a crosstalk pathway between ENT2 and alveolar epithelial Adora2b in lung protection during acute lung injury (ALI) opens possibilities for combined therapies targeted to this protein set.

3. Elwi A.N., et al. Transepithelial fluxes of adenosine and 2′-deoxyadenosine across human renal proximal tubule cells: roles of nucleoside transporters hENT1, hENT2, and hCNT3. American Journal of Physiology-Renal Physiology. 2009, 296(6): F1439-F1451. PubMed ID: 19297449
   
   

   This study finds that apical hCNT3 and basolateral hENT2 are involved in proximal tubular reabsorption of adenosine and some nucleoside drugs. In addition, this article also reveals that apical hENT1 and basolateral hOATs are involved in proximal tubular secretion of 2'-deoxyadenosine.

4. Morote-Garcia J.C., et al. Hypoxia-inducible factor-dependent repression of equilibrative nucleoside transporter 2 attenuates mucosal inflammation during intestinal hypoxia. Gastroenterology. 2009, 136(2): 607-618. PubMed ID: 19105964
   
   

   The authors perform in vitro studies of epithelial adenosine uptake and nucleoside transport using cultured epithelial cells and suggest that HIF-1alpha-dependent repression of ENT2 increases mucosal adenosine signaling and attenuates hypoxia-associated inflammation of the intestine.

5. López-Guerra M., et al. Identification of TIGAR in the equilibrative nucleoside transporter 2-mediated response to fludarabine in chronic lymphocytic leukemia cells. Haematologica. 2008, 93(12): 1843-1851. PubMed ID: 18945750
   
   

   This article demonstrates that hENT2 plays a major role in the uptake of fludarabine into chronic lymphocytic leukemia cells, and presents a correlation between the recently described p53-inducible apoptosis gene TIGAR and both sensitivity to fludarabine and hENT2 expression in chronic lymphocytic leukemia cells.

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Reference

1. Aherne C M, et al. (2018). Coordination of ENT2-dependent adenosine transport and signaling dampens mucosal inflammation. JCI insight. 3(20).

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