Structure of, and functional insight into the GLUT family of membrane transporters

Figures & data

Table 1 Summary of the GLUT family proteins and their characteristics

GLUT classes	GLUT isoforms	Gene name	Tissue distribution	Substrate specificity	Trans-acceleration	Crystal structure/computer model
I	GLUT1	SLC2A1	Red blood cells, Ubiquitous	Glucose/Galactose/Dehydroacetic Acid	Yes	Crystal structure
I	GLUT3 (GLUT14)	SLC2A3 (SLC2A14)	Neurons (Testis)	Glucose/Galatose/ Dehydroacetic Acid	Yes	Computer model
I	GLUT4	SLC2A4	Muscle cells, Fat cells (Adipocytes)	Glucose/Dehydroacetic Acid	No	Computer model
I	GLUT2	SLC2A2	Intestine, Liver, Kidney, Beta cells	Glucose/Fructose/ Galatose/Glucosamine/Dehydroacetic Acid	No	N/A
II	GLUT5	SLC2A5	Intestine, Kidney Muscle, Sperm, Brain	Fructose	N/A	Computer model
II	GLUT7	SLC2A7	Intestine, Colon	Fructose/Glucose	N/A	Computer model
II	GLUT9	SLC2A9	Kidney, Liver, Placenta, Colon	Urate/Fructose/Glucose	Yes	Computer model
II	GLUT11	SLC2A11	Muscle, Heart, Placenta, Kidney, Pancreas, Fat	Glucose	N/A	N/A
III	GLUT6	SLC2A6	Brain, Spleen	Glucose	N/A	N/A
III	GLUT8	SLC2A8	Testes, Brain, Fat, Liver, Spleen	Glucose/Fructose	N/A	N/A
III	GLUT10	SLC2A10	Heart, Lung	Glucose	N/A	N/A
III	GLUT12	SLC2A12	Insulin-sensitive tissues	Glucose/Fructose	N/A	N/A
III	GLUT13 (HMIT)	SLC2A13	Brain	Myo-inositol	N/A	N/A

Note: GLUT14 is grouped together with GLUT3 because GLUT14 has 94.5% identity with GLUT3.

Abbreviation: N/A, no data available.

Figure 1 Amino acid sequences alignments of the GLUT family of proteins.

Notes: Transmembrane domains are highlighted in yellow based on the new GLUT1 crystal structure. Highly conserved residues are colored in red. Residues highlighted in blue in TM10 are believed to be the cytochalasin B recognition/binding sites. Residues highlighted in blue in TM7 are believed to be the critical hydrophobic residues responsible for substrate selectivities.

Figure 2 Molecular models of the human hGLUT9 and hGLUT5 transporters comparing possible hydrophobic interactions.

Notes: (A) Computer model of hGLUT9a based on the human hGLUT1 crystal structure. (B and C) Views from the intracellular face and extracellular face. (D) Potential interactions of I335 indicate a hydrophobic network with residues within TM10. (E) Structural model of the mutant SLC2A9 I335V was generated, demonstrating that the intricate linkage to helix 10 is disrupted when I335 is converted to Val. (F) In SLC2A5, Ile296, the equivalent of Ile335 in SLC2A9, forms a more extensive hydrophobic cluster with neighboring residues in TM10 and TM12. (G) Structural model of the mutant SLC2A5 I296V, highlighting loss of the hydrophobic network, which subsequently leads to alteration in substrate specificity. Copyright © 2015 American Society for Biochemistry and Molecular Biology. Adapted from Long W, Panwar P, Witkowska K, et al. Critical roles of two hydrophobic residues within human glucose transporter 9 (hSLC2A9) in substrate selectivity and urate transport. J Biol Chem. 2015;290: 15292–15303.⁶¹

Long W, Panwar P, Witkowska K, et al. Critical roles of two hydrophobic residues within human glucose transporter 9 (hSLC2A9) in substrate selectivity and urate transport. J Biol Chem. 2015;290:15292–15303.

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