SLC23A2 Membrane Protein Introduction

Introduction of SLC23A2

Solute carrier family 23 member 2 is a protein that in humans is encoded by the SLC23A2 gene. The SLC23A2 gene maps to chromosome 20p12.2-12.3 and is ten times larger than SLC23A1, being 158398 bp long and containing 17 exons. The SLC23A2 variant is a truncated protein resulting from a 345 bp deletion, which excludes the 5 and 6 TM domains and part of the 4 TM domain. SLC23A2 mRNA levels are increased by fetal bovine serum and epidermal growth factor in the human trophoblast cell line and by glucocorticoids, zinc and Ca²⁺ phosphate ions in osteoblastic cells.

Function of SLC23A2 Membrane Protein

SLC23A2 is modulated by Ca²⁺ and Mg²⁺ ions, that switch the transporter from an inactive form into an active form. In addition, SLC23A2 may be localized intracellularly or on the plasma membrane. A human trophoblast cell line and human first-trimester chorionic villi can express SLC23A2, which is crucial for vitamin C transplacental transfer from the maternal to the fetal circulation. In the brain, SLC23A2 is present in neuroepithelial cells of the choroid plexus, allowing the ascorbate transport in cerebrospinal fluid, as well as in neurons. Indeed, SLC23A2-deficient neuronal cells showed reduced neurite outgrowth and neuronal activity, as well as increased susceptibility to oxidative damage. SLC23A2 is located at the basolateral surface, where it should be involved in vitamin C transport from blood into enterocytes. SLC23A2 overexpression leads to osteoblast differentiation, mineralization and calcium deposition. SLC23A2 also mediates ascorbate uptake in chondrocytes, allowing cartilage to store vitamin C needed for the synthesis of type II collagen in the extracellular matrix.

Fig.1 Schematic model of the uptake and compartmentalization of vitamin C in the CNS. (Nualart, 2014)

Application of SLC23A2 Membrane Protein in Literature

1. Zheleznyakova G.Y., et al. Methylation levels of SLC23A2 and NCOR2 genes correlate with spinal muscular atrophy severity. PLoS One. 2015, 10(3): e0121964. PubMed ID: 25821969
   
   

   The article shows that significant methylation changes in the SLC23A2 and NCOR2 regulatory regions correlate with spinal muscular atrophy severity.

2. Santiago M.B., et al. SLC23A2-05 (rs4987219) and KRAS-LCS6 (rs61764370) polymorphisms in patients with squamous cell carcinoma of the head and neck. Oncol Lett. 2014, 7(6): 1803-1811. PubMed ID: 24932237
   
   

   The article reveals that squamous cell carcinoma of the head and neck is highly affected by environmental factors when compared with the effect of SLC23A2-05 and KRAS-LCS6 polymorphisms.

3. Minegaki T., et al. Genetic polymorphisms in SLC23A2 as predictive biomarkers of severe acute toxicities after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma. Int J Med Sci. 2014, 11(4): 321-326. PubMed ID: 24578608
   
   

   Authors give a conclusion that further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2.

4. Eck P., et al. The human sodium-dependent ascorbic acid transporters SLC23A1 and SLC23A2 do not mediate ascorbic acid release in the proximal renal epithelial cell. Physiol Rep. 2013, 1(6): e00136. PubMed ID: 24400138
   
   

   This article demonstrates a high gene expression of SLC23A1 but no expression of SLC23A2 in the proximal convoluted and straight tubules of humans.

5. Chen A.A., et al. Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer. Carcinogenesis. 2009, 30(6): 977-981. PubMed ID: 19346260
   
   

   This article shows that SLC23A2 genetic variation alters the risk of HPV16-associated head and neck cancer, while also highlights the important role of citrus exposure in this disease.

SLC23A2 Preparation Options

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Reference

1. Nualart F, et al. (2014). Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts. J Stem Cell Res Ther. 4(5): 209.

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