Sodium/glucose cotransporter 2

Function

Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump. Unlike SLC5A1/SGLT1, requires the auxiliary protein PDZK1IP1/MAP17 for full transporter activity. Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (By similarity).

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 · 12

• 7VSI EM 2.95A
• 7YNJ EM 3.33A
• 7YNK EM 3.48A
• 8HB0 EM 2.90A
• 8HDH EM 3.10A
• 8HEZ EM 2.80A
• 8HG7 EM 3.10A
• 8HIN EM 3.30A
• 9KKQ EM 2.60A
• 9KKW EM 2.92A
• 9KL0 EM 3.16A
• 9KMN EM 2.47A

A predicted model is available from AlphaFold.

Gene Ontology · 15

• GO:0016324 apical plasma membrane
• GO:0070062 extracellular exosome
• GO:0016020 membrane
• 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:0005362 low-affinity D-glucose:sodium symporter activity
• GO:0046872 metal ion binding
• GO:0000017 alpha-glucoside transport
• GO:0005975 carbohydrate metabolic process
• GO:0098708 D-glucose import across plasma membrane
• GO:0008645 hexose transmembrane transport
• GO:0035623 renal D-glucose absorption
• GO:0098719 sodium ion import across plasma membrane

Disease associations

• familial renal glucosuria MONDO:0009297

Drugs targeting this protein · 16

• ERTUGLIFLOZIN inhibitor
• BEXAGLIFLOZIN inhibitor
• IPRAGLIFLOZIN inhibitor
• REMOGLIFLOZIN ETABONATE inhibitor
• DAPAGLIFLOZIN PROPANEDIOL inhibitor
• TOFOGLIFLOZIN inhibitor
• EMPAGLIFLOZIN inhibitor
• SOTAGLIFLOZIN inhibitor
• HENAGLIFLOZIN inhibitor
• YM-543 inhibitor
• LICOGLIFLOZIN inhibitor
• IPRAGLIFLOZIN L-PROLINE inhibitor
• DAPAGLIFLOZIN inhibitor
• SERGLIFLOZIN ETABONATE inhibitor
• CANAGLIFLOZIN inhibitor
• ERTUGLIFLOZIN PIDOLATE inhibitor

Related proteins · sequence + function similarity

• Sodium/glucose cotransporter 2 0.99
• Sodium/glucose cotransporter 2 0.98
• Sodium/glucose cotransporter 2 0.98
• Sodium/glucose cotransporter 4 0.95
• Sodium/myo-inositol cotransporter 2 0.94
• Sodium/myo-inositol cotransporter 2 0.93
• Sodium/myo-inositol cotransporter 2 0.93
• Sodium/myo-inositol cotransporter 2 0.92
• Sodium/myo-inositol cotransporter 2 0.92
• Sodium/glucose cotransporter 4 0.92
• Sodium/mannose cotransporter SLC5A10 0.92
• Sodium/mannose cotransporter SLC5A10 0.92

Co-cited proteins · studied together in the literature

• PDZK1-interacting protein 1 3 shared papers
• Sodium/glucose cotransporter 1 2 shared papers

Literature · 9 cited papers

• Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter. Nat. Struct. Mol. Biol. · 2024
• Structures of human SGLT in the occluded state reveal conformational changes during sugar transport. Nat. Commun. · 2023
• Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. Nature · 2022
• Characterization of the transport activity of SGLT2/MAP17, the renal low-affinity Na+-glucose cotransporter. Am. J. Physiol. · 2017
• Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am. J. Physiol. · 2011
• The sequence and analysis of duplication-rich human chromosome 16. Nature · 2004
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria. Hum. Genet. · 2004
• Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter. Am. J. Physiol. · 1992