Sodium/glucose cotransporter 1
Also known as: NAGT, SGLT1, SLC5A1
Function
Electrogenic Na(+)-coupled sugar symporter 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. 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 (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. 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.
Classification
- Family (Pfam)
- PF00474 SSF
- InterPro
- Na/Glc_symporter_sf, Na/solute_symporter, Na/solute_symporter_CS
- Functional cluster
- Membrane Transporters & GPCRs
Experimental structures · PDB · 4
A predicted model is available from AlphaFold.
Gene Ontology · 29
- GO:0016324 apical plasma membrane
- GO:0031526 brush border membrane
- GO:0005769 early endosome
- GO:0070062 extracellular exosome
- GO:0097708 intracellular vesicle
- GO:0048471 perinuclear region of cytoplasm
- GO:0005886 plasma membrane
- GO:0015151 alpha-glucoside transmembrane transporter activity
- GO:0055056 D-glucose transmembrane transporter activity
- GO:0005412 D-glucose:sodium symporter activity
- GO:0015150 fucose transmembrane transporter activity
- GO:0005354 galactose transmembrane transporter activity
- GO:0015371 galactose:sodium symporter activity
- GO:0005367 myo-inositol:sodium symporter activity
- GO:0015146 pentose transmembrane transporter activity
- GO:0005372 water transmembrane transporter activity
- GO:0000017 alpha-glucoside transport
- GO:0098708 D-glucose import across plasma membrane
- GO:1904659 D-glucose transmembrane transport
- GO:0015756 fucose transmembrane transport
- GO:0015757 galactose transmembrane transport
- GO:0001951 intestinal D-glucose absorption
- GO:0106001 intestinal hexose absorption
- GO:0015798 myo-inositol transport
- GO:0015750 pentose transmembrane transport
- GO:0035623 renal D-glucose absorption
- GO:0098719 sodium ion import across plasma membrane
- GO:0035377 transepithelial water transport
- GO:0150104 transport across blood-brain barrier
Disease associations
- glucose-galactose malabsorption MONDO:0011731
Drugs targeting this protein · 2
- SOTAGLIFLOZIN inhibitor
- LICOGLIFLOZIN inhibitor
Related proteins · sequence + function similarity
- Sodium/glucose cotransporter 1 0.99
- Sodium/glucose cotransporter 1 0.99
- Sodium/glucose cotransporter 1 0.99
- Sodium/glucose cotransporter 1 0.99
- Sodium/glucose cotransporter 1 0.99
- Solute carrier family 5 member 4 0.98
- Probable glucose sensor protein SLC5A4 0.96
- Solute carrier family 5 member 4A 0.95
- Solute carrier family 5 member 4 0.95
- Solute carrier family 5 member 4B 0.94
- Sodium/glucose cotransporter 4 0.93
- Sodium/myo-inositol cotransporter 0.91
Co-cited proteins · studied together in the literature
- Sodium/glucose cotransporter 4 1 shared papers
- Sodium/glucose cotransporter 1 1 shared papers
- Sodium/glucose cotransporter 2 2 shared papers
- PDZK1-interacting protein 1 1 shared papers
Literature · 17 cited papers
- Structures of human SGLT in the occluded state reveal conformational changes during sugar transport. Nat. Commun. · 2023
- Structural basis of the selective sugar transport in sodium-glucose cotransporters. J. Mol. Biol. · 2022
- Structure and mechanism of the SGLT family of glucose transporters. Nature · 2022
- Loss of Endometrial Sodium Glucose Cotransporter SGLT1 is Detrimental to Embryo Survival and Fetal Growth in Pregnancy. Sci. Rep. · 2017
- The Sodium Glucose Cotransporter SGLT1 Is an Extremely Efficient Facilitator of Passive Water Transport. J. Biol. Chem. · 2016
- Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am. J. Physiol. · 2011
- A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Glucose accumulation can account for the initial water flux triggered by Na+/glucose cotransport. Biophys. J. · 2004
- A missense mutation in the Na(+)/glucose cotransporter gene SGLT1 in a patient with congenital glucose-galactose malabsorption: normal trafficking but inactivation of the mutant protein. Biochim. Biophys. Acta · 2001
- The DNA sequence of human chromosome 22. Nature · 1999
- Missense mutations in SGLT1 cause glucose-galactose malabsorption by trafficking defects. Biochim. Biophys. Acta · 1999
- … and 5 more in the literature graph