SLC5A1

SLC5A1
Identifiers
Aliases SLC5A1, D22S675, NAGT, SGLT1, solute carrier family 5 member 1
External IDs OMIM: 182380 MGI: 107678 HomoloGene: 55456 GeneCards: SLC5A1
Targeted by Drug
canagliflozin anhydrous, dapagliflozin, empagliflozin, sergliflozin etabonate[1]
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

6523

20537

Ensembl

ENSG00000100170

ENSMUSG00000011034

UniProt

P13866

Q8C3K6

RefSeq (mRNA)

NM_000343
NM_001256314

NM_019810

RefSeq (protein)

NP_000334.1
NP_001243243.1

NP_062784.3

Location (UCSC) Chr 22: 32.04 – 32.11 Mb Chr 5: 33.1 – 33.16 Mb
PubMed search [2] [3]
Wikidata
View/Edit HumanView/Edit Mouse

Sodium/glucose cotransporter 1 also known as solute carrier family 5 member 1 is a protein that in humans is encoded by the SLC5A1 gene.[4][5]

Function

Glucose transporters are integral membrane proteins that mediate the transport of glucose and structurally related substances across cellular membranes. The role of the sodium-glucose cotransporters is to not only absorb glucose, but to also absorb sodium and to then reabsorb the sodium and glucose from the tubule of the nephron.[6] Two families of glucose transporter have been identified: the facilitated diffusion glucose transporter family (GLUT family), also known as 'uniporters,' and the sodium-dependent glucose transporter family (SGLT family), also known as 'cotransporters' or 'symporters.[7] The SLC5A1 gene encodes a protein that is involved in the active transport of glucose and galactose into eukaryotic and some prokaryotic cells.[5]

Cloning

Co-transport proteins of mammalian cell membranes had eluded efforts of purification with classical biochemical methods until the late 1980s. These proteins had proven difficult to isolate because they contain hydrophilic and hydrophobic sequences and exist in membranes only in very low abundance (<0.2% of membrane proteins). The rabbit form of SGLT1 was the first mammalian co-transport protein ever to be cloned and sequenced, and this was reported in 1987.[8] To circumvent the difficulties with traditional isolation methods, a novel expression cloning technique was used. Size-fractionation of large amounts of rabbit intestinal mRNA with preparative gel electrophoresis were then sequentially injected into Xenopus oocytes to ultimately find the RNA species that induced the expression of sodium-glucose cotransport.[8]

Mutations

SLC5A1 is important because of its role in the absorption of glucose and sodium, however, mutations in the gene can cause serious effects. A mutation in the SLC5A1 gene can cause problems creating the SGLT1 protein, leading to a rare glucose-galactose malabsorption disease. Glucose-galactose malabsorption occurs when the lining of the intestinal cells can't take in glucose and galactose which prevents the use of those molecules in catabolism and anabolism. The disease has symptoms that consist of watery and/or acidic diarrhea which is the result of water retention in the intestinal lumen and osmotic loss created by non-absorbed glucose, galactose and sodium.[9] Glucose-Galactose malabsorption can cause death, due to loss of water from diarrhea, if the disease isn't treated soon. To counteract the disaes, oral rehydration therapy is performed using sodium, glucose, and water for intestinal reabsorption.

Tissue distribution

The SLC5A1 cotransporter is mainly expressed in the lumen of the small intestine, kidney, parotid glands, submandibular glands and in the heart.[10]

See also

Interactions

SLC5A1 has been shown to interact with PAWR.[11]

References

  1. ↑ "Drugs that physically interact with Sodium/glucose cotransporter 1 view/edit references on wikidata".
  2. ↑ "Human PubMed Reference:".
  3. ↑ "Mouse PubMed Reference:".
  4. ↑ Turk E, Martín MG, Wright EM (June 1994). "Structure of the human Na+/glucose cotransporter gene SGLT1". J Biol Chem. 269 (21): 15204–9. PMID 8195156.
  5. 1 2 "Entrez Gene: SLC5A1 solute carrier family 5 (sodium/glucose cotransporter), member 1".
  6. ↑ Hamilton KL, Butt AG (2013). "Glucose transport into everted sacs of the small intestine of mice". Advances in Physiology Education. 37 (4): 415–26. doi:10.1152/advan.00017.2013. PMID 24292921.
  7. ↑ Wright EM, Loo DD, Panayotova-Heiermann M, Lostao MP, Hirayama BH, Mackenzie B, Boorer K, Zampighi G (1994). "'Active' sugar transport in eukaryotes" (PDF). The Journal of Experimental Biology. 196: 197–212. PMID 7823022.
  8. 1 2 Hediger MA, Coady MJ, Ikeda TS, Wright EM (1987). "Expression cloning and cDNA sequencing of the Na+/glucose co-transporter". Nature. 330 (6146): 379–81. doi:10.1038/330379a0. PMID 2446136.
  9. ↑ Wright EM, Turk E, Martin MG (2002). "Molecular basis for glucose-galactose malabsorption". Cell Biochemistry and Biophysics. 36 (2-3): 115–21. doi:10.1385/CBB:36:2-3:115. PMID 12139397.
  10. ↑ Sabino-Silva R, Mori RC, David-Silva A, Okamoto MM, Freitas HS, Machado UF (2010). "The Na(+)/glucose cotransporters: from genes to therapy". Brazilian Journal of Medical and Biological Research. 43 (11): 1019–26. doi:10.1590/S0100-879X2010007500115. PMID 21049241.
  11. ↑ Xie J, Guo Q (July 2004). "Par-4 inhibits choline uptake by interacting with CHT1 and reducing its incorporation on the plasma membrane". J. Biol. Chem. 279 (27): 28266–75. doi:10.1074/jbc.M401495200. PMID 15090548.

Further reading

  • Anderson NL, Anderson NG (2003). "The human plasma proteome: history, character, and diagnostic prospects". Mol. Cell Proteomics. 1 (11): 845–67. doi:10.1074/mcp.R200007-MCP200. PMID 12488461. 
  • Turk E, Zabel B, Mundlos S, Dyer J, Wright EM (1991). "Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter". Nature. 350 (6316): 354–6. doi:10.1038/350354a0. PMID 2008213. 
  • Hediger MA, Turk E, Wright EM (1989). "Homology of the human intestinal Na+/glucose and Escherichia coli Na+/proline cotransporters". Proc. Natl. Acad. Sci. U.S.A. 86 (15): 5748–52. doi:10.1073/pnas.86.15.5748. PMC 297707Freely accessible. PMID 2490366. 
  • Delézay O, Baghdiguian S, Fantini J (1995). "The development of Na(+)-dependent glucose transport during differentiation of an intestinal epithelial cell clone is regulated by protein kinase C". J. Biol. Chem. 270 (21): 12536–41. doi:10.1074/jbc.270.21.12536. PMID 7759499. 
  • Turk E, Klisak I, Bacallao R, Sparkes RS, Wright EM (1993). "Assignment of the human Na+/glucose cotransporter gene SGLT1 to chromosome 22q13.1". Genomics. 17 (3): 752–4. doi:10.1006/geno.1993.1399. PMID 8244393. 
  • Martín MG, Turk E, Lostao MP, Kerner C, Wright EM (1996). "Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption". Nat. Genet. 12 (2): 216–20. doi:10.1038/ng0296-216. PMID 8563765. 
  • Turk E, Kerner CJ, Lostao MP, Wright EM (1996). "Membrane topology of the human Na+/glucose cotransporter SGLT1". J. Biol. Chem. 271 (4): 1925–34. doi:10.1074/jbc.271.4.1925. PMID 8567640. 
  • Lam JT, Martín MG, Turk E, Hirayama BA, Bosshard NU, Steinmann B, Wright EM (1999). "Missense mutations in SGLT1 cause glucose-galactose malabsorption by trafficking defects". Biochim. Biophys. Acta. 1453 (2): 297–303. doi:10.1016/s0925-4439(98)00109-4. PMID 10036327. 
  • Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208. 
  • Obermeier S, Hüselweh B, Tinel H, Kinne RH, Kunz C (2001). "Expression of glucose transporters in lactating human mammary gland epithelial cells". European Journal of Nutrition. 39 (5): 194–200. doi:10.1007/s003940070011. PMID 11131365. 
  • Kasahara M, Maeda M, Hayashi S, Mori Y, Abe T (2001). "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. 1536 (2–3): 141–7. doi:10.1016/s0925-4439(01)00043-6. PMID 11406349. 
  • Roll P, Massacrier A, Pereira S, Robaglia-Schlupp A, Cau P, Szepetowski P (2002). "New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families". Gene. 285 (1–2): 141–8. doi:10.1016/S0378-1119(02)00416-X. PMID 12039040. 
  • Ikari A, Nakano M, Kawano K, Suketa Y (2002). "Up-regulation of sodium-dependent glucose transporter by interaction with heat shock protein 70". J. Biol. Chem. 277 (36): 33338–43. doi:10.1074/jbc.M200310200. PMID 12082088. 

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