Structure of the human Na+/glucose cotransporter gene SGLT1.
Intestinal uptake of dietary glucose and galactose is mediated by the SGLT1 Na+/glucose cotransporter of the brush border. An SGLT1 missense mutation underlies hereditary glucose/galactose malabsorption, characterized by potentially fatal diarrhea; conversely, oral rehydration therapy exploits normal transport to alleviate life-threatening diarrhea of infectious origin. We have mapped the entire human SGLT1 Na+/glucose cotransporter gene from cosmid and lambda phage clones representing a genomic region of 112 kilobases. Transcription initiation occurred from a site 27 base pairs 3' of a TATAA sequence. All exon-flanking regions were sequenced, and the entire 112-kilobase region mapped with four restriction enzymes. SGLT1 is comprised of 15 exons (spanning 72 kilobases); a possible evolutionary origin from a six-membrane-span ancestral precursor via a gene duplication event is suggested from comparison of exons against protein secondary structure and from sequence considerations. A new missense mutation in exon 1 causing glucose/galactose malabsorption is also described. This is the first Na(+)-dependent cotransporter gene structure reported. These data facilitate the search for new glucose/galactose malabsorption-related mutations in this important gene and provide a basis for future evolutionary comparisons with other Na(+)-dependent cotransporters.[1]References
- Structure of the human Na+/glucose cotransporter gene SGLT1. Turk, E., Martín, M.G., Wright, E.M. J. Biol. Chem. (1994) [Pubmed]
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