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Gene Review

SLC5A1  -  solute carrier family 5 (sodium/glucose...

Homo sapiens

Synonyms: D22S675, High affinity sodium-glucose cotransporter, NAGT, Na(+)/glucose cotransporter 1, SGLT1, ...
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Disease relevance of SLC5A1


High impact information on SLC5A1

  • Cotransporters harness ion gradients to drive 'active' transport of substrates into cells, for example, the Na+/glucose cotransporter (SGLT1) couples sugar transport to Na+ gradients across the intestinal brush border [6].
  • Previously we showed that two sisters with GGM had a missense mutation in the SGLT1 gene [6].
  • Sequence analysis of the amplified products has revealed a single missense mutation in SGLT1 which cosegregates with the GGM phenotype and results in a complete loss of Na(+)-dependent glucose transport in Xenopus oocytes injected with this complementary RNA [7].
  • We have previously cloned and sequenced a Na+/glucose cotransporter from normal human ileum and shown that this gene, SGLT1, resides on the distal q arm of chromosome 22 [7].
  • We have now amplified SGLT1 complementary DNA and genomic DNA from members of a family affected with GGM by the polymerase chain reaction [7].

Chemical compound and disease context of SLC5A1


Biological context of SLC5A1


Anatomical context of SLC5A1


Associations of SLC5A1 with chemical compounds

  • By using immunogold labeling at the electron microscopy level, we demonstrated that phorbol myristyl acetate induced the redistribution of SGLT1 protein from intracellular sites to the plasma membrane [13].
  • When exposed to a maleimide-based fluorescent probe, wt SGLT1 was not significantly labeled but mutants C255A and C511A could be clearly labeled, indicating an accessible cysteine residue [9].
  • The Na+/glucose cotransporter (SGLT1) is an archetype for the SLC5 family, which is comprised of Na+-coupled transporters for sugars, myo-inositol, choline, and organic anions [9].
  • On the contrary phlorizin, the well-established inhibitor of SGLT1, decreased intrinsic fluorescence by a maximum of 50%, and induced a blue shift of maximum (5 nm) [16].
  • Kinetic analysis of hSGLT1 in proteoliposomes revealed sodium-dependent, secondary active, phlorizin-sensitive, and stereospecific alpha-methyl-d-glucopyranoside transport, demonstrating its full catalytic activity [16].

Physical interactions of SLC5A1


Regulatory relationships of SLC5A1

  • We showed that SGLT1 was positively regulated by Cl- and that optimal activity of CFTR was dependent on the presence of glucose [18].
  • SGLT1 alone is able to translocate glucose together with sodium; however, RS1 increases the Vmax of transport expressed by SGLT1 [19].

Other interactions of SLC5A1

  • Voltage-clamp experiments in oocytes expressing hSGLT1 demonstrated that hRS1 reduced the maximal substrate-induced currents but did not change substrate activation, membrane potential dependence, Na(+) dependence or substrate selectivity of hSGLT1 [20].
  • This review considers the structure and function of two premier members, SGLT1 and SGLT2, and their role in intestinal glucose absorption and renal glucose reabsorption [21].
  • At least three, and up to six, Na+-dependent glucose transporters (SGLT1-SGLT6; gene name SLC5A) have been identified [22].
  • RESULTS: Southern blot analysis of the amplicions revealed the expression of SGLT1 mRNA but not of GLUT1 mRNA in milk epithelial cells [12].
  • The abundance of mRNAs encoding the Na(+)-glucose cotransporter isoform SGLT1 and the facilitative glucose transporter isoforms GLUT2 and GLUT5 is developmentally modulated with highest levels in adult small intestine [23].

Analytical, diagnostic and therapeutic context of SLC5A1


  1. Regulation of glucose transporter SGLT1 by ubiquitin ligase Nedd4-2 and kinases SGK1, SGK3, and PKB. Dieter, M., Palmada, M., Rajamanickam, J., Aydin, A., Busjahn, A., Boehmer, C., Luft, F.C., Lang, F. Obes. Res. (2004) [Pubmed]
  2. Structure of the human Na+/glucose cotransporter gene SGLT1. Turk, E., Martín, M.G., Wright, E.M. J. Biol. Chem. (1994) [Pubmed]
  3. Employing Escherichia coli to functionally express, purify, and characterize a human transporter. Quick, M., Wright, E.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  4. Carboxy-terminal vesicular stomatitis virus G protein-tagged intestinal Na+-dependent glucose cotransporter (SGLT1): maintenance of surface expression and global transport function with selective perturbation of transport kinetics and polarized expression. Turner, J.R., Lencer, W.I., Carlson, S., Madara, J.L. J. Biol. Chem. (1996) [Pubmed]
  5. Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. Miyauchi, S., Gopal, E., Fei, Y.J., Ganapathy, V. J. Biol. Chem. (2004) [Pubmed]
  6. Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption. Martín, M.G., Turk, E., Lostao, M.P., Kerner, C., Wright, E.M. Nat. Genet. (1996) [Pubmed]
  7. Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Turk, E., Zabel, B., Mundlos, S., Dyer, J., Wright, E.M. Nature (1991) [Pubmed]
  8. Purification and functional reconstitution of a truncated human Na(+)/glucose cotransporter (SGLT1) expressed in E. coli. Panayotova-Heiermann, M., Leung, D.W., Hirayama, B.A., Wright, E.M. FEBS Lett. (1999) [Pubmed]
  9. Identification of a disulfide bridge linking the fourth and the seventh extracellular loops of the Na+/glucose cotransporter. Gagnon, D.G., Bissonnette, P., Lapointe, J.Y. J. Gen. Physiol. (2006) [Pubmed]
  10. Luminal glucose sensing in the rat intestine has characteristics of a sodium-glucose cotransporter. Freeman, S.L., Bohan, D., Darcel, N., Raybould, H.E. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  11. 'Active' sugar transport in eukaryotes. Wright, E.M., Loo, D.D., Panayotova-Heiermann, M., Lostao, M.P., Hirayama, B.H., Mackenzie, B., Boorer, K., Zampighi, G. J. Exp. Biol. (1994) [Pubmed]
  12. Expression of glucose transporters in lactating human mammary gland epithelial cells. Obermeier, S., Hüselweh, B., Tinel, H., Kinne, R.H., Kunz, C. European journal of nutrition. (2000) [Pubmed]
  13. The development of Na(+)-dependent glucose transport during differentiation of an intestinal epithelial cell clone is regulated by protein kinase C. Delézay, O., Baghdiguian, S., Fantini, J. J. Biol. Chem. (1995) [Pubmed]
  14. More than apical: Distribution of SGLT1 in Caco-2 cells. Kipp, H., Khoursandi, S., Scharlau, D., Kinne, R.K. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  15. Sergliflozin, a Novel Selective Inhibitor of Low-Affinity Sodium Glucose Cotransporter (SGLT2), Validates the Critical Role of SGLT2 in Renal Glucose Reabsorption and Modulates Plasma Glucose Level. Katsuno, K., Fujimori, Y., Takemura, Y., Hiratochi, M., Itoh, F., Komatsu, Y., Fujikura, H., Isaji, M. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  16. High-yield functional expression of human sodium/d-glucose cotransporter1 in Pichia pastoris and characterization of ligand-induced conformational changes as studied by tryptophan fluorescence. Tyagi, N.K., Goyal, P., Kumar, A., Pandey, D., Siess, W., Kinne, R.K. Biochemistry (2005) [Pubmed]
  17. Decreased polyphenol transport across cultured intestinal cells by a salivary proline-rich protein. Cai, K., Hagerman, A.E., Minto, R.E., Bennick, A. Biochem. Pharmacol. (2006) [Pubmed]
  18. Interrelationship between the Na+/glucose cotransporter and CFTR in Caco-2 cells: relevance to cystic fibrosis. Mailleau, C., Capeau, J., Brahimi-Horn, M.C. J. Cell. Physiol. (1998) [Pubmed]
  19. Function and presumed molecular structure of Na(+)-D-glucose cotransport systems. Koepsell, H., Spangenberg, J. J. Membr. Biol. (1994) [Pubmed]
  20. Downregulation of the Na(+)- D-glucose cotransporter SGLT1 by protein RS1 (RSC1A1) is dependent on dynamin and protein kinase C. Veyhl, M., Wagner, C.A., Gorboulev, V., Schmitt, B.M., Lang, F., Koepsell, H. J. Membr. Biol. (2003) [Pubmed]
  21. Active sugar transport in health and disease. Wright, E.M., Hirayama, B.A., Loo, D.F. J. Intern. Med. (2007) [Pubmed]
  22. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Wood, I.S., Trayhurn, P. Br. J. Nutr. (2003) [Pubmed]
  23. Human intestinal glucose transporter expression and localization of GLUT5. Davidson, N.O., Hausman, A.M., Ifkovits, C.A., Buse, J.B., Gould, G.W., Burant, C.F., Bell, G.I. Am. J. Physiol. (1992) [Pubmed]
  24. Assignment of the human Na+/glucose cotransporter gene SGLT1 to chromosome 22q13.1. Turk, E., Klisak, I., Bacallao, R., Sparkes, R.S., Wright, E.M. Genomics (1993) [Pubmed]
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