SLC5A1

Solute carrier family 5 (sodium/glucose cotransporter), member 1

Identifiers

SLC5A1 ; D22S675; NAGT; SGLT1

External IDs

OMIM: 182380 MGI: 107678 HomoloGene: 55456 ChEMBL: 4979 GeneCards: SLC5A1 Gene

Gene ontology
Molecular function	• glucose:sodium symporter activity • protein binding
Cellular component	• plasma membrane • integral component of plasma membrane • cell-cell junction • apical plasma membrane • brush border membrane • extracellular exosome
Biological process	• metanephros development • carbohydrate metabolic process • sodium ion transport • hexose transport • glucose transport • small molecule metabolic process • intestinal absorption • transmembrane transport
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 22:
32.04 – 32.11 Mb

Chr 5:
33.1 – 33.16 Mb

PubMed search

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.^[1]^[2]

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.^[3] 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.^[4] The SLC5A1 gene encodes a protein that is involved in the active transport of glucose and galactose into eukaryotic and some prokaryotic cells.^[2]

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.^[5] 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.^[5]

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.^[6] 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.^[7]

Interactions

SLC5A1 has been shown to interact with PAWR.^[8]

References

↑ 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.
1 2 "Entrez Gene: SLC5A1 solute carrier family 5 (sodium/glucose cotransporter), member 1".
↑ 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.
↑ 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.
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.
↑ 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.
↑ 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 = Revista Brasileira De Pesquisas MéDicas E BiolóGicas / Sociedade Brasileira De BiofíSica ... [Et Al.] 43 (11): 1019–26. doi:10.1590/S0100-879X2010007500115. PMID 21049241.
↑ 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.

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 297707. 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.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)

By group

SLC1–10

(1):	high affinity glutamate and neutral amino-acid transporter SLC1A1 2 3 4 5 6 7

(2):	facilitative GLUT transporter SLC2A1 2 3 4 5 6 7 8 9 10 11 12 13 14

(3):	heavy subunits of heterodimeric amino-acid transporters SLC3A1 2

(4):	bicarbonate transporter SLC4A1 2 3 4 5 6 7 8 9 10 11

(5):	sodium glucose cotransporter SLC5A1 2 3 4 5 6 7 8 9 10 11 12

(6):	sodium- and chloride- dependent sodium:neurotransmitter symporters SLC6A1 SLC6A2 SLC6A3 SLC6A4 SLC6A5 SLC6A6 SLC6A7 SLC6A8 SLC6A9 SLC6A10 SLC6A11 SLC6A12 SLC6A13 SLC6A14 SLC6A15 SLC6A16 SLC6A17 SLC6A18 SLC6A19 SLC6A20

(7):	cationic amino-acid transporter/glycoprotein-associated SLC7A1 SLC7A2 SLC7A3 SLC7A4 glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters SLC7A5 SLC7A6 SLC7A7 SLC7A8 SLC7A9 SLC7A10 SLC7A11 SLC7A13 SLC7A14

(8):	Na⁺/Ca²⁺ exchanger SLC8A1 SLC8A2 SLC8A3

(9):	Na⁺/H⁺ exchanger SLC9A1 SLC9A2 SLC9A3 SLC9A4 SLC9A5 SLC9A6 SLC9A7 SLC9A8 SLC9A9 SLC9A10 SLC9A11

(10):	sodium bile salt cotransport SLC10A1 SLC10A2 SLC10A3 SLC10A4 SLC10A5 SLC10A6 SLC10A7 10A1 10A2 10A3 10A7

SLC11–20

(11):	proton coupled metal ion transporter SLC11A1 SLC11A2 11A3

(12):	electroneutral cation-Cl cotransporter SLC12A1 SLC12A2 SLC12A3 SLC12A4 SLC12A5 SLC12A6 SLC12A7 SLC12A8 SLC12A9

(13):	human Na⁺-sulfate/carboxylate cotransporter SLC13A1 SLC13A2 SLC13A3 SLC13A4 SLC13A5

(14):	urea transporter SLC14A1 SLC14A2

(15):	proton oligopeptide cotransporter SLC15A1 SLC15A2 SLC15A3 SLC15A4

(16):	monocarboxylate transporter SLC16A1 SLC16A2 SLC16A3 SLC16A4 SLC16A5 SLC16A6 SLC16A7 SLC16A8 SLC16A9 SLC16A10 SLC16A11 SLC16A12 SLC16A13 SLC16A14

(17):	Vesicular glutamate transporter 1 SLC17A1 SLC17A2 SLC17A3 SLC17A4 SLC17A5 SLC17A6 SLC17A7 SLC17A8 SLC17A9

(18):	vesicular monoamine transporter SLC18A1 SLC18A2 SLC18A3

(19):	folate/thiamine transporter SLC19A1 SLC19A2 SLC19A3

(20):	type III Na⁺-phosphate cotransporter SLC20A1 SLC20A2

SLC21–30

(21):	Organic anion-transporting polypeptide SLCO1A2 SLCO1B1 SLCO1B3 SLCO1B4 SLCO1C1 SLCO2A1 SLCO2B1 SLCO3A1 SLCO4A1 SLCO4C1 SLCO5A1(SLCO6A1)

(22):	organic cation/anion/zwitterion transporter SLC22A1 SLC22A2 SLC22A3 SLC22A4 SLC22A5 SLC22A6 SLC22A7 SLC22A8 SLC22A9 SLC22A10 SLC22A11 SLC22A12 SLC22A13 SLC22A14 SLC22A15 SLC22A16 SLC22A17 SLC22A18 SLC22A19 SLC22A20

(23):	Na+-dependent ascorbic acid transporter SLC23A1 SLC23A2 SLC23A3 SLC23A4

(24):	Na⁺/(Ca²⁺-K⁺) exchanger SLC24A1 SLC24A2 SLC24A3 SLC24A4 SLC24A5 SLC24A6

(25):	mitochondrial carrier SLC25A1 SLC25A2 SLC25A3 SLC25A4 SLC25A5 SLC25A6 SLC25A7 SLC25A8 SLC25A9 SLC25A10 SLC25A11 SLC25A12 SLC25A13 SLC25A14 SLC25A15 SLC25A16 SLC25A17 SLC25A18 SLC25A19 SLC25A20 SLC25A21 SLC25A22 SLC25A23 SLC25A24 SLC25A25 SLC25A26 SLC25A27 SLC25A28 SLC25A29 SLC25A30 SLC25A31 SLC25A32 SLC25A33 SLC25A34 SLC25A35 SLC25A36 SLC25A37 SLC25A38 SLC25A39 SLC25A40 SLC25A41 SLC25A42 SLC25A43 SLC25A44 SLC25A45 SLC25A46

(26):	multifunctional anion exchanger SLC26A1 SLC26A2 SLC26A3 SLC26A4 SLC26A5 SLC26A6 SLC26A7 SLC26A8 SLC26A9 SLC26A10 SLC26A11

(27):	fatty acid transport proteins SLC27A1 SLC27A2 SLC27A3 SLC27A4 SLC27A5 SLC27A6

(28):	Na⁺-coupled nucleoside transport (SLC28A1 SLC28A2 SLC28A3

(29):	facilitative nucleoside transporter SLC29A1 SLC29A2 SLC29A3 SLC29A4

(30):	zinc efflux SLC30A1 SLC30A2 SLC30A3 SLC30A4 SLC30A5 SLC30A6 SLC30A7 SLC30A8 SLC30A9 SLC30A10

SLC31–40

(31):	copper transporter SLC31A1

(32):	Vesicular glutamate transporter 1 SLC32A1

(33):	Acetyl-CoA transporter SLC33A1

(34):	type II Na⁺-phosphate cotransporter SLC34A1 SLC34A2 SLC34A3

(35):	nucleoside-sugar transporter SLC35A1 SLC35A2 SLC35A3 SLC35A4 SLC35A5 SLC35B1 SLC35B2 SLC35B3 SLC35B4 SLC35C1 SLC35C2 SLC35D1 SLC35D2 SLC35D3 SLC35E1 SLC35E2 SLC35E3 SLC35E4

(36):	proton-coupled amino-acid transporter SLC36A1 SLC36A2 SLC36A3 SLC36A436A2

(37):	sugar-phosphate/phosphate exchanger SLC37A1 SLC37A2 SLC37A3 SLC37A4

(38):	System A & N, sodium-coupled neutral amino-acid transporter SLC38A1 SLC38A2 SLC38A3 SLC38A4 SLC38A5 SLC38A6 SLC38A10

(39):	metal ion transporter SLC39A1 SLC39A2 SLC39A3 SLC39A4 SLC39A5 SLC39A6 SLC39A7 SLC39A8 SLC39A9 SLC39A10 SLC39A11 SLC39A12 SLC39A13 SLC39A14

(40):	basolateral iron transporter SLC40A1

SLC41–48

(41):	Magnesium transporter E SLC41A1 SLC41A2 SLC41A3

(42):	Ammonia transporter RhAG RhBG RhCG

(43):	Na⁺-independent, system-L like amino-acid transporter SLC43A1 SLC43A2 SLC43A3

(44):	Choline-like transporter SLC44A1 SLC44A2 SLC44A3 SLC44A4 SLC44A5

(45):	Putative sugar transporter SLC45A1 SLC45A2 SLC54A3 SLC45A4

(46):	Folate transporter SLC46A1 SLC46A2

(47):	multidrug and toxin extrusion SLC47A1 SLC47A2

(48):	Heme transporter

SLCO1–4

O1A2 O1B1 O1B3 O2B1 O431 O4A1

Ion pumps

Symporter, Cotransporter	Na⁺/K⁺,Cl⁻ Na⁺/P_i3 Na⁺/Cl⁻ Na⁺/glucose Na⁺/I⁻ Cl⁻/K⁺ 4 5

Antiporter (exchanger)	Na⁺/H⁺ Na⁺/Ca²⁺ Na⁺/(Ca²⁺-K⁺) - Cl⁻/HCO− 3 (Band 3) Cl⁻-formate Cl⁻-oxalate

see also solute carrier disorders

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