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.
|Basic Information of SLC5A11|
|Protein Name||Sodium/myo-inositol cotransporter 2|
|Aliases||Na(+)/myo-inositol cotransporter 2, Sodium-dependent glucose cotransporter, Sodium/glucose cotransporter KST1, Sodium/myo-inositol transporter 2, SMIT2, Solute carrier family 5 member 11|
|Organism||Homo sapiens (Human)|
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
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.
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.
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.
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.
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
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