7yni

Structural highlights

Disease

SC5A1_HUMAN Glucose-galactose malabsorption. The disease is caused by variants affecting the gene represented in this entry.

Function

SC5A1_HUMAN Electrogenic Na(+)-coupled sugar simporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:35077764, PubMed:8563765, PubMed:34880492). Has a primary role in the transport of dietary monosaccharides from enterocytes to blood. Responsible for the absorption of D-glucose or D-galactose across the apical brush-border membrane of enterocytes, whereas basolateral exit is provided by GLUT2. Additionally, functions as a D-glucose sensor in enteroendocrine cells, triggering the secretion of the incretins GCG and GIP that control food intake and energy homeostasis (PubMed:8563765) (By similarity). Together with SGLT2, functions in reabsorption of D-glucose from glomerular filtrate, playing a nonredundant role in the S3 segment of the proximal tubules (By similarity). Transports D-glucose into endometrial epithelial cells, controlling glycogen synthesis and nutritional support for the embryo as well as the decidual transformation of endometrium prior to conception (PubMed:28974690). Acts as a water channel enabling passive water transport across the plasma membrane in response to the osmotic gradient created upon sugar and Na(+) uptake. Has high water conductivity, comparable to aquaporins, and therefore is expected to play an important role in transepithelial water permeability, especially in the small intestine.[UniProtKB:Q8C3K6]^{[1] [2] [3] [4] [5] [6] [7]}

References

1. ↑ Gagnon MP, Bissonnette P, Deslandes LM, Wallendorff B, Lapointe JY. Glucose accumulation can account for the initial water flux triggered by Na+/glucose cotransport. Biophys J. 2004 Jan;86(1 Pt 1):125-33. doi: 10.1016/S0006-3495(04)74090-4. PMID:14695256 doi:http://dx.doi.org/10.1016/S0006-3495(04)74090-4
2. ↑ Hummel CS, Lu C, Loo DD, Hirayama BA, Voss AA, Wright EM. Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am J Physiol Cell Physiol. 2011 Jan;300(1):C14-21. doi:, 10.1152/ajpcell.00388.2010. Epub 2010 Oct 27. PMID:20980548 doi:http://dx.doi.org/10.1152/ajpcell.00388.2010
3. ↑ Erokhova L, Horner A, Ollinger N, Siligan C, Pohl P. The Sodium Glucose Cotransporter SGLT1 Is an Extremely Efficient Facilitator of Passive Water Transport. J Biol Chem. 2016 Apr 29;291(18):9712-20. doi: 10.1074/jbc.M115.706986. Epub 2016, Mar 4. PMID:26945065 doi:http://dx.doi.org/10.1074/jbc.M115.706986
4. ↑ Salker MS, Singh Y, Zeng N, Chen H, Zhang S, Umbach AT, Fakhri H, Kohlhofer U, Quintanilla-Martinez L, Durairaj RRP, Barros FSV, Vrljicak P, Ott S, Brucker SY, Wallwiener D, Vrhovac Madunic I, Breljak D, Sabolic I, Koepsell H, Brosens JJ, Lang F. Loss of Endometrial Sodium Glucose Cotransporter SGLT1 is Detrimental to Embryo Survival and Fetal Growth in Pregnancy. Sci Rep. 2017 Oct 3;7(1):12612. doi: 10.1038/s41598-017-11674-3. PMID:28974690 doi:http://dx.doi.org/10.1038/s41598-017-11674-3
5. ↑ Han L, Qu Q, Aydin D, Panova O, Robertson MJ, Xu Y, Dror RO, Skiniotis G, Feng L. Structure and mechanism of the SGLT family of glucose transporters. Nature. 2022 Jan;601(7892):274-279. doi: 10.1038/s41586-021-04211-w. Epub 2021, Dec 8. PMID:34880492 doi:http://dx.doi.org/10.1038/s41586-021-04211-w
6. ↑ Kamitori K, Shirota M, Fujiwara Y. Structural Basis of the Selective Sugar Transport in Sodium-Glucose Cotransporters. J Mol Biol. 2022 Mar 15;434(5):167464. doi: 10.1016/j.jmb.2022.167464. Epub 2022 , Jan 22. PMID:35077764 doi:http://dx.doi.org/10.1016/j.jmb.2022.167464
7. ↑ Martin MG, Turk E, Lostao MP, Kerner C, Wright EM. Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption. Nat Genet. 1996 Feb;12(2):216-20. doi: 10.1038/ng0296-216. PMID:8563765 doi:http://dx.doi.org/10.1038/ng0296-216