The protein family of glucose transport facilitators: It's not only about glucose after all.
The protein family of facilitative glucose transporters comprises 14 isoforms that share common structural features such as 12 transmembrane domains, N- and C-termini facing the cytoplasm of the cell, and a N-glycosylation side either within the first or fifth extracellular loop. Based on their sequence homology, three classes can be distinguished: class I includes GLUT1-4 and GLUT14, class II the "odd transporters" GLUT5, 7, 9, 11, and class III the "even transporters" GLUT6, 8, 10, 12 and the proton driven myoinositol transporter HMIT (or GLUT13). With the cloning and characterization of the more recent class II and III isoforms, it became apparent that despite their structural similarities, the different isoforms not only show a distinct tissue-specific expression pattern but also show distinct characteristics such as alternative splicing, specific (sub)cellular localization, and affinities for a spectrum of substrates. This review summarizes the current understanding of the physiological role for the various transport facilitators based on human genetically inherited disorders or single-nucleotide polymorphisms and knockout mice models. The emphasis of the review will be on the potential functional role of the more recent isoforms.
Augustin
Robert
R
Department of Cardiometabolic Diseases Research, Boehringer-Ingelheim Pharma GmbH&Co KG, Biberach a.d. Riss, Germany. Robert.Augustin@boehringer-ingelheim.com
D000595:Amino Acid Sequence; D000818:Animals; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051272:Glucose Transporter Type 1 / Q000502:physiology; D051273:Glucose Transporter Type 2 / Q000172:deficiency / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000502:physiology; D051275:Glucose Transporter Type 4 / Q000378:metabolism / Q000502:physiology; D051296:Glucose Transporter Type 5 / Q000502:physiology; D006801:Humans; D051379:Mice; D010802:Phylogeny; D013379:Substrate Specificity
D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D051296:Glucose Transporter Type 5; C430746:SLC2A10 protein, human; C439386:SLC2A11 protein, human; C449579:SLC2A12 protein, human; C474630:SLC2A14 protein, human; C487892:SLC2A7 protein, human; C405325:SLC2A8 protein, human; C411811:SLC2A9 protein, human; D005947:Glucose