SLC5A2

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Solute carrier family 5 (sodium/glucose cotransporter), member 2
Identifiers
Symbols SLC5A2 ; SGLT2
External IDs OMIM182381 MGI2181411 HomoloGene2289 ChEMBL: 3884 GeneCards: SLC5A2 Gene
Orthologs
Species Human Mouse
Entrez 6524 246787
Ensembl ENSG00000140675 ENSMUSG00000030781
UniProt P31639 Q923I7
RefSeq (mRNA) NM_003041 NM_133254
RefSeq (protein) NP_003032 NP_573517
Location (UCSC) Chr 16:
31.49 – 31.5 Mb
Chr 7:
128.27 – 128.27 Mb
PubMed search [1] [2]

The sodium/glucose cotransporter 2 (SGLT2) is a protein that in humans is encoded by the SLC5A2 (solute carrier family 5 (sodium/glucose cotransporter)) gene.[1]

Function[edit]

SGLT2 is a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. SGLT2 is the major cotransporter involved in glucose reabsorption in the kidney.[2]

SGLT2 inhibitors for diabetes[edit]

Inhibition of SGLT2 leads to a reduction in blood glucose levels. Therefore, SGLT2 inhibitors have potential use in the treatment of type II diabetes. Several drug candidates have been developed or are currently undergoing clinical trials, including:[3]

Clinical significance[edit]

Mutations in this gene are also associated with renal glucosuria.[6]

Model organisms[edit]

Model organisms have been used in the study of SLC5A2 function. A conditional knockout mouse line, called Slc5a2tm1a(KOMP)Wtsi[12][13] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[14][15][16]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[10][17] Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: males displayed increased drinking behaviour.[10]

See also[edit]

References[edit]

  1. ^ Wells RG, Mohandas TK, Hediger MA (September 1993). "Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere". Genomics 17 (3): 787–9. doi:10.1006/geno.1993.1411. PMID 8244402. 
  2. ^ "Entrez Gene: solute carrier family 5 (sodium/glucose cotransporter)". 
  3. ^ InsightPharma (2010). "Diabetes Pipeline: Intense Activity to Meet Unmet Need". p. vii. 
  4. ^ Invokana, First in New Class of Diabetes Drugs, Approved, MPR, March 29, 2013
  5. ^ a b c SGLT2 inhibitor approval race
  6. ^ Calado J, Loeffler J, Sakallioglu O, Gok F, Lhotta K, Barata J, Rueff J (March 2006). "Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting". Kidney Int. 69 (5): 852–5. doi:10.1038/sj.ki.5000194. PMID 16518345. 
  7. ^ "Indirect calorimetry data for Slc5a2". Wellcome Trust Sanger Institute. 
  8. ^ "Salmonella infection data for Slc5a2". Wellcome Trust Sanger Institute. 
  9. ^ "Citrobacter infection data for Slc5a2". Wellcome Trust Sanger Institute. 
  10. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. 
  11. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  12. ^ "International Knockout Mouse Consortium". 
  13. ^ "Mouse Genome Informatics". 
  14. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  15. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  16. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  17. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 

Further reading[edit]