Identification of a novel glucose transporter-like protein-GLUT-12.
Facilitative glucose transporters exhibit variable hexose affinity and tissue-specific expression. These characteristics contribute to specialized metabolic properties of cells. Here we describe the characterization of a novel glucose transporter-like molecule, GLUT-12. GLUT-12 was identified in MCF-7 breast cancer cells by homology to the insulin-regulatable glucose transporter GLUT-4. The GLUT-12 cDNA encodes 617 amino acids, which possess features essential for sugar transport. Di-leucine motifs are present in NH(2) and COOH termini at positions similar to the GLUT-4 FQQI and LL targeting motifs. GLUT-12 exhibits 29% amino acid identity with GLUT-4 and 40% to the recently described GLUT-10. Like GLUT-10, a large extracellular domain is predicted between transmembrane domains 9 and 10. Genomic organization of GLUT-12 is highly conserved with GLUT-10 but distinct from GLUTs 1-5. Immunofluorescence showed that, in the absence of insulin, GLUT-12 is localized to the perinuclear region in MCF-7 cells. Immunoblotting demonstrated GLUT-12 expression in skeletal muscle, adipose tissue, and small intestine. Thus GLUT-12 is potentially part of a second insulin-responsive glucose transport system.
Rogers
Suzanne
S
Department of Medicine, The University of Melbourne, St. Vincent's Hospital Melbourne, Fitzroy, Victoria 3065, Australia 4072.
Macheda
Maria L
ML
Docherty
Susan E
SE
Carty
Maynard D
MD
Henderson
Michael A
MA
Soeller
Walter C
WC
Gibbs
E Michael
EM
James
David E
DE
Best
James D
JD
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D001923:Brain Chemistry; D001943:Breast Neoplasms; D002462:Cell Membrane / Q000737:chemistry; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis / Q000737:chemistry; D004622:Embryo, Mammalian; D005091:Exons; D005260:Female; D005455:Fluorescent Antibody Technique; D015723:Gene Library; D051246:Glucose Transport Proteins, Facilitative; D051275:Glucose Transporter Type 4; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007328:Insulin / Q000494:pharmacology; D007438:Introns; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D009124:Muscle Proteins; D009928:Organ Specificity; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017385:Sequence Homology; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D051246:Glucose Transport Proteins, Facilitative; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C449579:SLC2A12 protein, human; C495692:SLC2A4 protein, human