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SLC5A2 Membrane Protein Introduction

Introduction of SLC5A2

SLC5A2, also known as solute carrier family 5 (sodium/glucose cotransporter) member 2, solute carrier family 5 (sodium/glucose transporter) member 2, Na(+)/glucose cotransporter 2, or SGLT2, is an approximately 73 kDa membrane protein that consists of 672 amino acids. In humans, it is encoded by the SLC5A2 gene located on the chromosome 16p11.2. The product of SLC5A2 is a low-affinity, high-capacity cotransporter which belongs to the sodium solute symporter (SSF) family. It shows a sodium-to-glucose coupling ratio of 1:1 under physiological conditions, responsible for a bulk of filtered glucose (about 90%) reabsorption in the kidney and promoting glucose excretion. SLC5A2 is found in the early proximal convoluted tubule, especially in the S1 segment.

Basic Information of SLC5A2
Protein Name Sodium/glucose cotransporter 2
Gene Name SLC5A2
Aliases Na(+)/glucose cotransporter 2, Low-affinity sodium-glucose cotransporter, Solute carrier family 5 member 2
Organism Homo sapiens (Human)
UniProt ID P31639
Transmembrane Times 14
Length (aa) 672
Sequence MEEHTEAGSAPEMGAQKALIDNPADILVIAAYFLLVIGVGLWSMCRTNRGTVGGYFLAGRSMVWWPVGASLFASNIGSGHFVGLAGTGAASGLAVAGFEWNALFVVLLLGWLFAPVYLTAGVITMPQYLRKRFGGRRIRLYLSVLSLFLYIFTKISVDMFSGAVFIQQALGWNIYASVIALLGITMIYTVTGGLAALMYTDTVQTFVILGGACILMGYAFHEVGGYSGLFDKYLGAATSLTVSEDPAVGNISSFCYRPRPDSYHLLRHPVTGDLPWPALLLGLTIVSGWYWCSDQVIVQRCLAGKSLTHIKAGCILCGYLKLTPMFLMVMPGMISRILYPDEVACVVPEVCRRVCGTEVGCSNIAYPRLVVKLMPNGLRGLMLAVMLAALMSSLASIFNSSSTLFTMDIYTRLRPRAGDRELLLVGRLWVVFIVVVSVAWLPVVQAAQGGQLFDYIQAVSSYLAPPVSAVFVLALFVPRVNEQGAFWGLIGGLLMGLARLIPEFSFGSGSCVQPSACPAFLCGVHYLYFAIVLFFCSGLLTLTVSLCTAPIPRKHLHRLVFSLRHSKEEREDLDADEQQGSSLPVQNGCPESAMEMNEPQAPAPSLFRQCLLWFCGMSRGGVGSPPPLTQEEAAAAARRLEDISEDPSWARVVNLNALLMMAVAVFLWGFYA

Function of SLC5A2 Membrane Protein

SLC5A2 is a key transport protein in renal glucose reabsorption. Besides, there are another transporter SLC5A1 (SGLT1) also a major member in this process. SLC5A2 shares 59% amino acid similarity with SLC5A1, and more than 90% of glucose is reabsorbed by the former and nearly 3% by the later. Some studies have shown that the majority of glucose is reabsorbed by the high-capacity SLC5A2 transporter at the S1 segment, while the remaining glucose entering the S3 segment is reabsorbed by the high-affinity SLC5A1 transporter. In the early proximal tubule, SLC5A2 driven by the electrochemical Na+ gradient formed by the Na+/K+-ATPase reabsorbs the bull of the filtered glucose. Additionally, SLC5A2 is reported to represent a novel concept in the therapy of type-2 diabetes mellitus (T2DM). Its inhibition increases circulating glucagon concentrations and enhances hepatic glucose production. Several types of SLC5A2 inhibitors have been synthesized to be studied, including C-glycosides, N-glycosides, and O-glycosides, such as canagliflozin, phlorizin, dapagliflozin, and empagliflozin.

A model for Na/glucose transport in the kidney.Fig.1 A model for Na/glucose transport in the kidney. (Andrianesis, 2013)

Application of SLC5A2 Membrane Protein in Literature

  1. Dong L., et al. Insight into the interaction mechanism of human SGLT2 with its inhibitors: 3D-QSAR studies, homology modeling, and molecular docking and molecular dynamics simulations. J Mol Model. 2018, 24(4): 86. PubMed ID: 29511885

    Considering binding affinity, the findings showed that hydrogen-bond interactions of Asn51 and Glu75, mapped at the active site of human SGLT2, with compound 40 are critical. This study elucidated the interaction model between inhibitors and human SGLT2 and was likely to contribute to the development of C-aryl glucoside SGLT2 inhibitors.

  2. Wang X., et al. Genetic analysis and literature review of Chinese patients with familial renal glucosuria: Identification of a novel SLC5A2 mutation. Clin Chim Acta. 2017, 469: 105-110. PubMed ID: 28365451

    The novel pathogenic SLC5A2 mutation p.S293C was responsible for the pathological process of familial renal glucosuria (FRG). The study further identified the co-dominant inheritance trait with variable penetrances and expanded the clinical, genetic spectrum of FRG.

  3. Ordelheide A.M., et al. Common variation in the sodium/glucose cotransporter 2 gene SLC5A2 does neither affect fasting nor glucose-suppressed plasma glucagon concentrations. PLoS One. 2017, 12(5): e0177148. PubMed ID: 28472182

    This article could not get statistically significant evidence for a role of common SLC5A2 variants in the regulation of glucagon release in the fasting state or upon glucose challenge. Besides, the reported nominal influences of individual SLC5A2 variants on fasting and post-challenge glucose levels were not likely to be mediated by altered glucagon release.

  4. Gong S., et al. Clinical and genetic features of patients with type 2 diabetes and renal glycosuria. J Clin Endocrinol Metab. 2017, 102(5): 1548-1556. PubMed ID: 28324025

    The findings in this study supposed that there were subtypes of type 2 diabetes mellitus (T2DM) characterized by different urinary glucose excretion and cardiovascular risk factors. And mutations in SLC5A2 and HNF1A partially explained the mechanism of renal glycosuria in patients with T2DM.

  5. Koepsell H. The Na+-D-glucose cotransporters SGLT1 and SGLT2 are targets for the treatment of diabetes and cancer. Pharmacol Ther. 2017, 170, 148-165. PubMed ID: 27773781

    This article summarized the knowledge of SGLT2 functions and the pathophysiology of type 2 diabetes (T2D) as well as diabetic follow-up diseases. Additionally, the proposed mechanisms of therapeutic effects and of side-effects of SGLT2 inhibitors are described. Lastly, there was a discussion regarding the possibility to employ SGLT1 and SGLT2 as targets for anticancer therapy.

SLC5A2 Preparation Options

To gain a soluble and intact target protein, we have already established active forms and reconstitution formats for these membrane proteins. Our available Magic™ membrane protein production platform enables flexible options for all users, from which they always select the optimal one to achieve their objectives. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC5A2 antibody development services.


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Reference

  1. Andrianesis V and Doupis J. (2013). The role of kidney in glucose homeostasis-SGLT2 inhibitors, a new approach in diabetes treatment. Expert Rev Clin Pharmacol. 6(5), 519-539.

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