Human facilitative glucose transporters. Isolation, functional characterization, and gene localization of cDNAs encoding an isoform (GLUT5) expressed in small intestine, kidney, muscle, and adipose tissue and an unusual glucose transporter pseudogene-like sequence (GLUT6)

Abstract

Two novel facilitative glucose transporter-like cDNAs have been isolated from human small intestine and fetal skeletal muscle cDNA libraries by low stringency cross-hybridization with a fragment of the human erythrocyte/GLUT1 facilitative glucose transporter cDNA. One encodes a 501-amino acid facilitative glucose transporter, designated as the small intestine/GLUT5 isoform, having 41.7, 40.0, 38.7, and 41.6% identity with the previously described human erythrocyte/GLUT1, liver/GLUT2, brain/GLUT3, and muscle-fat/GLUT4 isoforms, respectively. GLUT5 mRNA is expressed at highest levels in small intestine and at much lower levels in kidney, skeletal muscle, and adipose tissue. Expression of in vitro synthesized human GLUT5 mRNA in Xenopus laevis oocytes indicates that the GLUT5 protein is a cytochalasin B-sensitive glucose carrier. The gene encoding the GLUT5 protein is located on the short arm of human chromosome 1. The second facilitative transporter-like cDNA sequence, designated GLUT6, is part of an 11-kilobase transcript that is expressed in all tissues examined. The sequence of a partial-length GLUT6 cDNA having an insert of 3.4 kilobase pairs revealed a region of 1.5 kilobase pairs that has 79.6% identity with the human brain/GLUT3 facilitative glucose transporter cDNA. However, because of the presence of multiple stop codons and frame shifts, this sequence cannot encode a functional glucose transporter protein. The region of facilitative glucose transporter nucleotide sequence homology in the GLUT6 transcript may have arisen by insertion of a reverse-transcribed GLUT3 transcript into the untranslated region of another gene. The GLUT6 gene is located on the long arm of human chromosome 5.