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Other entities represented in this entry:
HGNC Approved Gene Symbol: SLC2A3
Cytogenetic location: 12p13.31 Genomic coordinates (GRCh38): 12:7,919,230-7,936,187 (from NCBI)
The mRNA levels encoding glucose transporter (see SLC2A1; 138140 and SLC2A2; 138160) are very low in skeletal muscle, an important site of peripheral glucose uptake and utilization, suggesting that another protein may be responsible for glucose uptake by this tissue. Reasoning that there might be a family of structurally related glucose transport proteins in mammalian cells, just as there is a family of related proteins involved in sugar and nutrient uptake in Escherichia coli, Kayano et al. (1988) screened a human fetal skeletal muscle cDNA library using low-stringency conditions to identify clones that cross-hybridize with a hepatoma-derived glucose transporter cDNA. The mRNA encoding this protein was present in most if not all tissues, although the amounts varied widely. The 496-amino acid fetal muscle glucose transporter-like protein shares 64.4% and 51.6% identity with the previously described GLUT1 (138140) and GLUT2 (138160) sequences, respectively.
PSEUDOGENE
By the homology screening approach, Kayano et al. (1990) identified a glucose transporter-like transcript, called GLUT6 by them, with an apparently ubiquitous tissue distribution. Sequence analysis of a cDNA clone for this transcript revealed a high level of base identity (79.6%) with GLUT3. However, the cDNA was found to contain multiple stop codons and frameshifts, indicating that it probably does not encode a functional glucose transporter. The extensive identity of the GLUT6 cDNA with the GLUT3 cDNA sequence suggested that the GLUT-like region of the GLUT6 transcript may have arisen by the insertion of a reverse-transcribed copy of GLUT3 into the noncoding region of a ubiquitously expressed gene--a 'hitchhiking' phenomenon. (This pseudogene is also symbolized SLC2A3P and GLUT3P1.)
Gould and Holman (1993), who provided a review of the glucose transporter family, referred to GLUT3 as the brain-type glucose transporter. It appears that high GLUT3 protein expression is confined generally to tissues that exhibit a high glucose demand, such as brain and nerve. Hauguel-de Mouzon et al. (1997) examined the cellular localization of GLUT3 mRNA and protein. In situ hybridization showed that GLUT3 mRNA was present in the trophoblast cell layer and in vascular endothelium with a heterogeneous distribution pattern. GLUT3 protein, migrating at an apparent molecular mass of 49 kD, was detected by immunoblotting in membranes from whole placenta and endothelial cells derived from intraplacental microvessels, but not in isolated trophoblast cells. This cell-specific pattern of expression was confirmed by immunocytochemical studies showing localization of GLUT3 protein in vascular endothelium. Based on the cell-specific distribution of GLUT3 protein at the fetal interface, the authors suggested that this protein may be important in the transport of glucose from the placenta to the fetal circulation.
Crystal Structure
Deng et al. (2015) determined the structure of human GLUT3 in complex with D-glucose at 1.5-angstrom resolution in an outward-occluded conformation. The high-resolution structure allowed discrimination of both alpha- and beta-anomers of D-glucose. Two additional structures of GLUT3 bound to the exofacial inhibitor maltose were obtained at 2.6 angstroms in the outward-open and 2.4 angstroms in the outward-occluded states. In all 3 structures, the ligands were predominantly coordinated by polar residues from the carboxy terminal domain.
By in situ hybridization to metaphase chromosomes, Kayano et al. (1988) assigned the gene encoding this protein to 12p13.3.
PSEUDOGENE
By hybridization of a cDNA probe to a panel of somatic cell hybrids and by in situ hybridization, Fan et al. (1989) showed that the GLUT3 pseudogene GLUT6 is located on chromosome 5.
Deng, D., Sun, P., Yan, C., Ke, M., Jiang, X., Xiong, L., Ren, W., Hirata, K., Yamamoto, M., Fan, S., Yan, N. Molecular basis of ligand recognition and transport by glucose transporters. Nature 526: 391-396, 2015. [PubMed: 26176916] [Full Text: https://doi.org/10.1038/nature14655]
Fan, Y.-S., Eddy, R. L., Byers, M. G., Haley, L. L., Henry, W. M., Kayano, T., Shows, T. B., Bell, G. I. Assignment of genes encoding three human glucose transporter/transporter-like proteins (GLUT4, GLUT5 and GLUT6) to chromosomes 17, 1 and 5, respectively. (Abstract) Cytogenet. Cell Genet. 51: 997 only, 1989.
Gould, G. W., Holman, G. D. The glucose transporter family: structure, function and tissue-specific expression. Biochem. J. 295: 329-341, 1993. [PubMed: 8240230] [Full Text: https://doi.org/10.1042/bj2950329]
Hauguel-de Mouzon, S., Challier, J. C., Kacemi, A., Cauzac, M., Malek, A., Girard, J. The GLUT3 glucose transporter isoform is differentially expressed within human placental cell types. J. Clin. Endocr. Metab. 82: 2689-2694, 1997. [PubMed: 9253355] [Full Text: https://doi.org/10.1210/jcem.82.8.4147]
Kayano, T., Burant, C. F., Fukumoto, H., Gould, G. W., Fan, Y. S., Eddy, R. L., Byers, M. G., Shows, T. B., Seino, S., Bell, G. I. 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). J. Biol. Chem. 265: 13276-13282, 1990. [PubMed: 1695905]
Kayano, T., Fukumoto, H., Eddy, R. L., Fan, Y.-S., Byers, M. G., Shows, T. B., Bell, G. I. Evidence for a family of human glucose transporter-like proteins: sequence and gene localization of a protein expressed in fetal skeletal muscle and other tissues. J. Biol. Chem. 263: 15245-15248, 1988. [PubMed: 3170580]