SLC5A11 Membrane Protein Introduction

Introduction of SLC5A11

SLC5A11 (solute carrier family 5 member 11), also known as putative sodium-coupled cotransporter RKST1, homolog of rabbit KST1, KST1, RKST1, SGLT6, or SLGTX, is an approximately 74 kDa transmembrane protein that comprises 675 amino acids. In humans, it is encoded by the SLC5A11 gene which located on the chromosome 16p12.1. SLC5A11 belongs to the sodium-glucose cotransporter (SGLT) family (the SLC5A gene family) that consists of 12 members implicated in the Na-coupled transport of sugars, iodide, vitamins, and monocarboxylates. Also, it is a putative member of the LeuT structural family, which is believed to present an inverted repeat of five-transmembrane (TM) segments. It is detected that SLC5A11 has highest expression in heart, kidney, liver, placenta, etc., and weaker expression in brain, lung, and spleen.

Function of SLC5A11 Membrane Protein

Cotransporters are molecular machines inserted in biological membranes that make use of the electrochemical energy gradient of one molecule to transport a given substrate. SLC5A11 as a cotransporter represents a principle class of proteins using ion gradients to drive active transport for the cellular accumulation of neurotransmitters, nutrients, osmolytes, and ions. Currently, the product of SLC5A11 genes has been identified as a Na-coupled Myo-inositol transporter and specially expressed in the intestinal epithelium and proximal tubules, where it mediates apical sodium-dependent cotransport of Myo-inositol with a stoichiometry of Na(+): MI =2:1 and is involved in the intestinal absorption. Furthermore, it might play a part in the regulation of MI concentration in serum, involving the reabsorption at least in the proximal tubule of the kidney. SLC5A11 also can transport D-chiro-inositol (DCI) and shows an a stereospecific cotransport of D-glucose and D-xylose. Recent studies conclude that SLC5A11 is implicated with several immune effects and interacts with immune-related genes, consistent with its function as an autoimmune modifier gene. It may induce apoptosis by the tumor necrosis factor-alpha (TNF-alpha), programmed cell death 1 (PDCD1) pathway.

Fig.1 Function of gene products in tubular cells, Slc5a11 encodes the sodium Myo-inositol transporter Smit2. (Gil, 2018)

Application of SLC5A11 Membrane Protein in Literature

1. Gil R.B., et al. Increased urinary osmolyte excretion indicates chronic kidney disease severity and progression rate. Nephrol Dial Transplant. 2018, 8(1): 299-314. PubMed ID: 29554320
   
   

   Renal organic osmolytes, Myo-inositol, and betaine play an important role in protecting renal cells from hyperosmotic stress. Kidney tissue transcriptomics of murine preclinical experimentation confirms that the reduced expression of Slc6a12 and Slc5a11 mRNA in renal tissue is consistent with defective tubular transport of the osmolytes.

2. Park J.Y., et al. Drosophila SLC5A11 mediates hunger by regulating K+ channel activity. Curr Biol. 2016, 26(15): 1965-1974. PubMed ID: 27397890
   
   

   The study finds that a knockdown of dKCNQ in SLC5A11-expressing neurons produces hunger-driven behaviors even in fed flies, imitating the overexpression of SLC5A11. The starvation is proposed to increase SLC5A11 expressions, which heightens the excitability of SLC5A11-expressing neurons by restraining dKCNQ channels, accordingly conferring the hunger state.

3. Raffler J., et al. Genome-wide association study with targeted and non-targeted NMR metabolomics identifies 15 novel loci of urinary human metabolic individuality. PLoS Genet. 2015, 111(9): e1005487. PubMed ID: 26352407
   
   

   This report is regarding the largest genome-wide association study with metabolic traits (mGWAS) to date. There are 22 loci identified and replicated with significant connections with urinary traits, 15 of which are novel, including HIBCH, CPS1, SLC5A11, etc. Further, two-thirds of urinary loci have a metabolite correlation in the blood.

4. Sasseville L.J., et al. The transport mechanism of the human sodium/myo-inositol transporter 2 (SMIT2/SGLT6), a member of the LeuT structural family. Am J Physiol Cell Physiol. 2014, 307(5): C431-441. PubMed ID: 24944204
   
   

   The two-electrode voltage-clamp technique is used to measure the steady-state and pre-steady-state currents regulated by human SMIT2 after expression in Xenopus laevis oocytes. The proposed model is a proof of concept for kinetic modeling of electrogenic transporters and permits insight into the transport mechanism of the LeuT family members at the millisecond timescale.

5. Fu H., et al. Contributions in astrocytes of SMIT1/2 and HMIT to myo-inositol uptake at different concentrations and pH. Neurochem Int. 2012, 61(2): 187-194. PubMed ID: 22564531
   
   

   It is important for Myo-inositol to mediate cell signaling both in the cytoplasm and intracellular organelles. At a low concentration, where SMIT1/2 activity gains importance, Myo-inositol uptake is declined by ammonia-induced intracellular acidification, accordant with the transporter's pH sensitivity reported in previous literature.

SLC5A11 Preparation Options

In order to obtain an intact membrane protein, we have established a series of reconstitution formats and active forms for these proteins. Our available Magic™ membrane protein production platform ensures many flexible options for worldwide customers, from which they usually can select the optical one to suit their needs on research. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC5A11 antibody development services.

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Today, Creative Biolabs acts as a leading custom service provider in biological market that has successfully accomplished quantities of membrane protein preparations. We are good at providing mature membrane protein preparation services for clients’ specific projects. If you are interested, please feel free to contact us.

Reference

1. Gil R B, et al. (2018). Increased urinary osmolyte excretion indicates chronic kidney disease severity and progression rate. Nephrol Dial Transplant. 33(12), 2156-2164.

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