title: Structure of the human Na+/glucose cotransporter gene SGLT1.
abstract: 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.
authors.affiliation: Department of Physiology, UCLA School of Medicine 90024-1751.
authors.forename: E
authors.initials: E
authors.lastname: Turk
authors.forename: M G
authors.initials: MG
authors.lastname: Martín
authors.forename: E M
authors.initials: EM
authors.lastname: Wright
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D003001:Cloning, Molecular; D004247:DNA; D005091:Exons; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007438:Introns; D008286:Malabsorption Syndromes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins; D009154:Mutation; D017433:Protein Structure, Secondary; D015183:Restriction Mapping; D012964:Sodium / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D004247:DNA; D012964:Sodium; D005947:Glucose; D005690:Galactose