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. 2007 Apr;8(2):113-28.
doi: 10.2174/138920207780368187.

Functional Properties and Genomics of Glucose Transporters

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Free PMC article

Functional Properties and Genomics of Glucose Transporters

Feng-Qi Zhao et al. Curr Genomics. .
Free PMC article

Abstract

Glucose is the major energy source for mammalian cells as well as an important substrate for protein and lipid synthesis. Mammalian cells take up glucose from extracellular fluid into the cell through two families of structurallyrelated glucose transporters. The facilitative glucose transporter family (solute carriers SLC2A, protein symbol GLUT) mediates a bidirectional and energy-independent process of glucose transport in most tissues and cells, while the NaM(+)/glucose cotransporter family (solute carriers SLC5A, protein symbol SGLT) mediates an active, Na(+)-linked transport process against an electrochemical gradient. The GLUT family consists of thirteen members (GLUT1-12 and HMIT). Phylogenetically, the members of the GLUT family are split into three classes based on protein similarities. Up to now, at least six members of the SGLT family have been cloned (SGLT1-6). In this review, we report both the genomic structure and function of each transporter as well as intra-species comparative genomic analysis of some of these transporters. The affinity for glucose and transport kinetics of each transporter differs and ranges from 0.2 to 17mM. The ability of each protein to transport alternative substrates also differs and includes substrates such as fructose and galactose. In addition, the tissue distribution pattern varies between species. There are different regulation mechanisms of these transporters. Characterization of transcriptional control of some of the gene promoters has been investigated and alternative promoter usage to generate different protein isoforms has been demonstrated. We also introduce some pathophysiological roles of these transporters in human.

Keywords: Bioinformatics; comparative genomics; gene promoter; genomic organization; glucose transporters.

Figures

Fig. (1)
Fig. (1)
A. Multiple sequence alignment of the deduced amino acid sequence of human facilitative transporters. The GenBank protein identification numbers of these transporters are NP_006507.1 (GLUT1), NP_000331.1 (GLUT2), NP_008862.1 (GLUT3), NP_001033.1 (GLUT4), NP_003030.1 (GLUT5), NP_060055.1 (GLUT6), NP_997303.1 (GLUT7), NP_055395.2 (GLUT8), NP_064425.2 (GLUT9), NP_110404.1 (GLUT10), NP_110434.2 (GLUT11), NP_660159.1 (GLUT12) and NP_443117.2 (HMIT). The alignment was performed with the CLUSTAL W program with open gap cost = 10 and gap extension cost = 0.2. Residues that are highlighted by black shading background represent absolutely conserved amino acids and the gray shading indicates six or more conserved residues at that position. Positions of presumed membrane-spanning helices (TM) of the GLUT proteins (Joost and Thorens, 2001) are given by the numbered dashed lines at the top of the sequence alignment. In addition, the highly conserved amino acids are shown on the bottom of the sequence alignment. B. Phylogenetic tree of the facilitative glucose transporters drawn from the multiple sequence alignment by CLUSTAL W. The numbers represent tree weights. The three classes of GLUT proteins are indicated.
Fig. (1)
Fig. (1)
A. Multiple sequence alignment of the deduced amino acid sequence of human facilitative transporters. The GenBank protein identification numbers of these transporters are NP_006507.1 (GLUT1), NP_000331.1 (GLUT2), NP_008862.1 (GLUT3), NP_001033.1 (GLUT4), NP_003030.1 (GLUT5), NP_060055.1 (GLUT6), NP_997303.1 (GLUT7), NP_055395.2 (GLUT8), NP_064425.2 (GLUT9), NP_110404.1 (GLUT10), NP_110434.2 (GLUT11), NP_660159.1 (GLUT12) and NP_443117.2 (HMIT). The alignment was performed with the CLUSTAL W program with open gap cost = 10 and gap extension cost = 0.2. Residues that are highlighted by black shading background represent absolutely conserved amino acids and the gray shading indicates six or more conserved residues at that position. Positions of presumed membrane-spanning helices (TM) of the GLUT proteins (Joost and Thorens, 2001) are given by the numbered dashed lines at the top of the sequence alignment. In addition, the highly conserved amino acids are shown on the bottom of the sequence alignment. B. Phylogenetic tree of the facilitative glucose transporters drawn from the multiple sequence alignment by CLUSTAL W. The numbers represent tree weights. The three classes of GLUT proteins are indicated.
Fig. (2)
Fig. (2)
Multiple sequence alignments of the deduced amino acid sequences of human, mouse, rat, rabbit, bovine, chicken and fish GLUT1 (A) and GLUT4 (B). The GenBank protein identification numbers of these transporters are NP_006507.1 (human GLUT1), NP_035530.1 (mouse GLUT1), NP_620182.1 (rat GLUT1), NP_777027.1 (bovine GLUT1), NP_990540.1 (chicken GLUT1), ABA39726.1 (fish GLUT1), NP_001033.1 (human GLUT4), NP_033230.1 (mouse GLUT4), AAR04439.1 (rabbit GLUT4), NP_036883.1 (rat GLUT4), NP_777029.1 (bovine GLUT4), and AAM22227.1 (fish GLUT4). The alignment was performed with the CLUSTAL W program with open gap cost = 10 and gap extension cost = 0.2. Residues that are highlighted by black shading background represent absolutely conserved amino acids and the gray shading indicates four or more conserved residues at that position. Positions of presumed membrane-spanning helices (TM) (Joost and Thorens, 2001) are given by the numbered dashed lines at the bottom of the sequence alignments. In addition, in (B) the N-terminal FQQI and C-terminal dileucine motifs of GLUT4 are indicated.
Fig. (2)
Fig. (2)
Multiple sequence alignments of the deduced amino acid sequences of human, mouse, rat, rabbit, bovine, chicken and fish GLUT1 (A) and GLUT4 (B). The GenBank protein identification numbers of these transporters are NP_006507.1 (human GLUT1), NP_035530.1 (mouse GLUT1), NP_620182.1 (rat GLUT1), NP_777027.1 (bovine GLUT1), NP_990540.1 (chicken GLUT1), ABA39726.1 (fish GLUT1), NP_001033.1 (human GLUT4), NP_033230.1 (mouse GLUT4), AAR04439.1 (rabbit GLUT4), NP_036883.1 (rat GLUT4), NP_777029.1 (bovine GLUT4), and AAM22227.1 (fish GLUT4). The alignment was performed with the CLUSTAL W program with open gap cost = 10 and gap extension cost = 0.2. Residues that are highlighted by black shading background represent absolutely conserved amino acids and the gray shading indicates four or more conserved residues at that position. Positions of presumed membrane-spanning helices (TM) (Joost and Thorens, 2001) are given by the numbered dashed lines at the bottom of the sequence alignments. In addition, in (B) the N-terminal FQQI and C-terminal dileucine motifs of GLUT4 are indicated.

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