Sodium/glucose cotransporter 1

Details

Kind

protein

Synonyms

High affinity sodium-glucose cotransporter
Na(+)/glucose cotransporter 1
NAGT
SGLT1
Solute carrier family 5 member 1

Gene Name

SLC5A1

UniProtKB Entry

P13866Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0008603|Sodium/glucose cotransporter 1
MDSSTWSPKTTAVTRPVETHELIRNAADISIIVIYFVVVMAVGLWAMFSTNRGTVGGFFL
AGRSMVWWPIGASLFASNIGSGHFVGLAGTGAASGIAIGGFEWNALVLVVVLGWLFVPIY
IKAGVVTMPEYLRKRFGGQRIQVYLSLLSLLLYIFTKISADIFSGAIFINLALGLNLYLA
IFLLLAITALYTITGGLAAVIYTDTLQTVIMLVGSLILTGFAFHEVGGYDAFMEKYMKAI
PTIVSDGNTTFQEKCYTPRADSFHIFRDPLTGDLPWPGFIFGMSILTLWYWCTDQVIVQR
CLSAKNMSHVKGGCILCGYLKLMPMFIMVMPGMISRILYTEKIACVVPSECEKYCGTKVG
CTNIAYPTLVVELMPNGLRGLMLSVMLASLMSSLTSIFNSASTLFTMDIYAKVRKRASEK
ELMIAGRLFILVLIGISIAWVPIVQSAQSGQLFDYIQSITSYLGPPIAAVFLLAIFWKRV
NEPGAFWGLILGLLIGISRMITEFAYGTGSCMEPSNCPTIICGVHYLYFAIILFAISFIT
IVVISLLTKPIPDVHLYRLCWSLRNSKEERIDLDAEEENIQEGPKETIEIETQVPEKKKG
IFRRAYDLFCGLEQHGAPKMTEEEEKAMKMKMTDTSEKPLWRTVLNVNGIILVTVAVFCH
AYFA

Number of residues

664

Molecular Weight

73497.275

Theoretical pI

Not Available

GO Classification

Functions

glucose

Processes

glucose transmembrane transport

Components

apical plasma membrane / brush border membrane / extracellular exosome / plasma membrane

General 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 (PubMed:20980548, PubMed:34880492, PubMed:35077764, PubMed:8563765). 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) (PubMed:8563765). 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 (PubMed:28974690). 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

Specific Function

Alpha-glucoside transmembrane transporter activity

Pfam Domain Function

SSF (PF00474)

Signal Regions

Not Available

Transmembrane Regions

29-49 65-85 106-126 143-163 179-201 209-229 278-298 314-334 381-401 424-444 456-476 485-505 644-664

Cellular Location

Apical cell membrane

Gene sequence

>lcl|BSEQ0017525|Sodium/glucose cotransporter 1 (SLC5A1)
ATGGACAGTAGCACCTGGAGCCCCAAGACCACCGCGGTCACCCGGCCTGTTGAGACCCAC
GAGCTCATTCGCAATGCAGCCGATATCTCCATCATCGTTATCTACTTCGTGGTAGTGATG
GCCGTCGGACTGTGGGCTATGTTTTCCACCAATCGTGGGACTGTTGGAGGCTTCTTCCTG
GCAGGCCGAAGTATGGTGTGGTGGCCGATTGGAGCCTCCCTCTTTGCTAGTAACATTGGA
AGTGGCCACTTTGTGGGGCTGGCCGGGACTGGGGCAGCTTCAGGCATCGCCATTGGAGGC
TTTGAATGGAATGCCCTGGTTTTGGTGGTTGTGCTGGGCTGGCTGTTTGTCCCCATCTAT
ATTAAGGCTGGGGTGGTGACAATGCCAGAGTACCTGAGGAAGCGGTTTGGAGGCCAGCGG
ATCCAGGTCTACCTTTCCCTTCTGTCCCTGCTGCTCTACATTTTCACCAAGATCTCGGCA
GACATCTTCTCGGGGGCCATATTCATCAATCTGGCCTTAGGCCTGAATCTGTATTTAGCC
ATCTTTCTCTTATTGGCAATCACTGCCCTTTACACAATTACAGGGGGCCTGGCGGCGGTG
ATTTACACGGACACCTTGCAGACGGTGATCATGCTGGTGGGGTCTTTAATCCTGACTGGG
TTTGCTTTTCACGAAGTGGGAGGCTATGACGCCTTCATGGAAAAGTACATGAAAGCCATT
CCAACCATAGTGTCTGATGGCAACACCACCTTTCAGGAAAAATGCTACACTCCAAGGGCC
GACTCCTTCCACATCTTCCGAGATCCCCTCACGGGAGACCTCCCATGGCCTGGGTTCATC
TTTGGGATGTCCATCCTTACCTTGTGGTACTGGTGCACAGATCAGGTCATTGTGCAGCGC
TGCCTCTCAGCCAAGAATATGTCTCACGTGAAGGGTGGCTGCATCCTGTGTGGGTATCTA
AAGCTGATGCCCATGTTCATCATGGTGATGCCAGGAATGATCAGCCGCATTCTGTACACA
GAAAAAATTGCCTGTGTCGTCCCTTCAGAATGTGAGAAATATTGCGGTACCAAGGTTGGC
TGTACCAACATCGCCTATCCAACCTTAGTGGTGGAGCTCATGCCCAATGGACTGCGAGGC
CTGATGCTATCAGTCATGCTGGCCTCCCTCATGAGCTCCCTGACCTCCATCTTCAACAGC
GCCAGCACCCTCTTCACCATGGACATCTACGCCAAGGTCCGCAAGAGAGCATCTGAGAAA
GAGCTCATGATTGCCGGAAGGTTGTTTATCCTGGTGCTGATTGGCATCAGCATCGCCTGG
GTGCCCATTGTGCAGTCAGCACAAAGTGGGCAACTCTTCGATTACATCCAGTCCATCACC
AGTTACTTGGGACCACCCATTGCGGCTGTCTTCCTGCTTGCTATTTTCTGGAAGAGAGTC
AATGAGCCAGGAGCCTTTTGGGGACTGATCCTAGGACTTCTGATTGGGATTTCACGTATG
ATTACTGAGTTTGCTTATGGAACCGGGAGCTGCATGGAGCCCAGCAACTGTCCCACGATT
ATCTGTGGGGTGCACTACTTGTACTTTGCCATTATCCTCTTCGCCATTTCTTTCATCACC
ATCGTGGTCATCTCCCTCCTCACCAAACCCATTCCGGATGTGCATCTCTACCGTCTGTGT
TGGAGCCTGCGCAACAGCAAAGAGGAGCGTATTGACCTGGATGCGGAAGAGGAGAACATC
CAAGAAGGCCCTAAGGAGACCATTGAAATAGAAACACAAGTTCCTGAGAAGAAAAAAGGA
ATCTTCAGGAGAGCCTATGACCTATTTTGTGGGCTAGAGCAGCACGGTGCACCCAAGATG
ACTGAGGAAGAGGAGAAAGCCATGAAGATGAAGATGACGGACACCTCTGAGAAGCCTTTG
TGGAGGACAGTGTTGAACGTCAATGGCATCATCCTGGTGACCGTGGCTGTCTTTTGCCAT
GCATATTTTGCCTGA

Chromosome Location

Locus

22q12.3

External Identifiers

Resource	Link
UniProtKB ID	P13866
UniProtKB Entry Name	SC5A1_HUMAN
GeneCard ID	SLC5A1
HGNC ID	HGNC:11036
PDB ID(s)	7SL8, 7SLA, 7WMV, 7YNI
KEGG ID	hsa:6523
IUPHAR/Guide To Pharmacology ID	915
NCBI Gene ID	6523

General References

Hediger MA, Turk E, Wright EM: Homology of the human intestinal Na+/glucose and Escherichia coli Na+/proline cotransporters. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5748-52. [Article]
Turk E, Martin MG, Wright EM: Structure of the human Na+/glucose cotransporter gene SGLT1. J Biol Chem. 1994 May 27;269(21):15204-9. [Article]
Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. Epub 2004 Sep 30. [Article]
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [Article]
Turk E, Kerner CJ, Lostao MP, Wright EM: Membrane topology of the human Na+/glucose cotransporter SGLT1. J Biol Chem. 1996 Jan 26;271(4):1925-34. [Article]
Turk E, Zabel B, Mundlos S, Dyer J, Wright EM: Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Nature. 1991 Mar 28;350(6316):354-6. [Article]
Lam JT, Martin MG, Turk E, Hirayama BA, Bosshard NU, Steinmann B, Wright EM: Missense mutations in SGLT1 cause glucose-galactose malabsorption by trafficking defects. Biochim Biophys Acta. 1999 Feb 24;1453(2):297-303. [Article]
Kasahara M, Maeda M, Hayashi S, Mori Y, Abe T: 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 May 31;1536(2-3):141-7. [Article]

Associated Data

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
Dextrose, unspecified form	approved, vet_approved	unknown	transporter	substrate	Details
D-glucose	approved, investigational, vet_approved	no	transporter	substrate	Details
Clavulanic acid	approved, vet_approved	unknown	transporter	inducer	Details
Sotagliflozin	approved, investigational	yes	target	inhibitor	Details
Migalastat	approved, investigational	no	transporter	substrateinhibitor	Details
Phlorizin	experimental	yes	target	inhibitor	Details
Licogliflozin	investigational	yes	target	inhibitor	Details