Molecular genetics of the human Na+/glucose cotransporter

Abstract

Recent success in expression cloning has revealed the primary structure of the Na+/glucose cotransporter from rabbit small intestine, and this has subsequently led to the cloning of the Na+/glucose cotransporters from human small intestine and human kidney. Close homology is evident between the rabbit and human intestinal Na+/glucose cotransporters at the DNA level, and the predicted amino acid and secondary structure levels. The Na+/glucose cotransporter amino acid sequence from human kidney is 57% identical with that from human small intestine. Significant homology also exists between these Na+/glucose cotransporters and the E. coli Na+/proline cotransporter (putP). The rabbit intestinal Na+/glucose cotransporter has 11 potential membrane spanning regions and 2 hydrophilic regions containing highly charged residues. The amino acid sequence shows two potential N-glycosylation sites (N-X-T/S). Using an in vitro translation approach we were able to determine that only one of these (Asn 248) is glycosylated. Expression experiments with Xenopus oocytes using the N-glycosylation inhibitor tunicamycin indicate that glycosylation of Asn 248 is required for functional expression of the transporter. The N-X-T/S sequence at Asn 248 is conserved in the human intestinal and the human renal Na+/glucose cotransporter. Chromosomal localization studies map the human intestinal Na+/glucose cotransporter gene (SGLT1) to the q11.2----qter region of chromosome 22 and the human renal Na+/glucose cotransporter gene (SGLT2) to the q-arm of chromosome 16.(ABSTRACT TRUNCATED AT 250 WORDS)