1 Institut fuer Pharmakologie und Toxikologie, Medizinische Fakultaet der RWTH Aachen, 52057 Aachen, Germany; 2 University of Chicago, Howard Hughes Medical Institute, Chicago, Illinois 60637; 3 St. Vincent's Hospital, Department of Medicine, Melbourne 3065; and 8 University of Queensland, Institute for Molecular Bioscience, St. Lucia, Queensland 4072, Australia; 4 University of Pennsylvania School of Medicine, Howard Hughes Medical Institute, Philadelphia, Pennsylvania 19104; 5 Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461; 6 Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina 27710; 7 Division of Chemical Biology, Molecular Pharmacology, Stanford University Medical Center, Stanford, California 94305; 9 Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142; Departments of 10 Obstetrics and Gynecology, 11 Surgery, and 12 Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110; 15 Department of Cellular and Molecular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; and 16 Institute of Pharmacology and Toxicology, CH1005 Lausanne, Switzerland
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ABSTRACT |
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The recent identification of several additional members of the family of sugar transport facilitators (gene symbol SLC2A, protein symbol GLUT) has created a heterogeneous and, in part, confusing nomenclature. Therefore, this letter provides a summary of the family members and suggests a systematic nomenclature for SLC2A and GLUT symbols.
membrane transport; glucose transporters; glucose transporter genes
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ARTICLE |
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THE ENTRY OF SUGARS INTO MAMMALIAN CELLS is catalyzed by a family of transport facilitators (gene symbol SLC2A, protein symbol GLUT) that are characterized by the presence of 12 membrane-spanning helices and several conserved sequence motifs (6, 7, 11, 12, 14). Recently, additional family members have been identified on the basis of sequence similarity (1-5, 8-10, 13, 15-17). Because some of these novel transporters have been described independently by different groups, a heterogeneous and sometimes confusing nomenclature has developed. Therefore, herein we provide a summary of the known members of the family, along with their aliases and accession numbers, and we present a suggestion for a systematic nomenclature.
As is summarized in Table 1, it is suggested that a GLUT numbering
scheme be used that is identical with the numbering of the genes in the
SLC2A nomenclature of the sugar transporter genes as approved by the
Human Genome Organization Gene Nomenclature Committee. According to
this system, one of the proteins initially designated GLUT9
(2) was renamed GLUT6 (9). The symbol GLUT6 was previously used for a pseudogene (SLC2A3P) derived from the GLUT3
gene (11). However, it seems more appropriate to use this symbol for an expressed gene rather than a pseudogene. Note also that
two transport facilitators that will now receive the symbols GLUT11
(SLC2A11, Ref. 4) and GLUT12 (SLC2A12) have been
described in preliminary publications as GLUT10 (3)
and GLUT8 (16), respectively. In addition, we suggest
using the symbols GLUT8 (1, 5) and GLUT9
(15) rather than their aliases GLUTX1 (8) and
GLUTX (16), respectively. Finally, the symbol GLUT7, which had previously been assigned to a now withdrawn sequence, will be
used for one of the novel genes (SLC2A7).
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According to a dendrogram depicting the sequence similarities
(Fig. 1), the family can be divided into
three subclasses. Class I is comprised of
the extensively characterized glucose transporters GLUT1 to GLUT4,
which can be distinguished on the basis of their distinct tissue
distributions (GLUT1, erythrocytes, brain microvessels; GLUT2, liver,
pancreatic islets; GLUT3, neuronal cells; GLUT4, muscle, adipose
tissue) and their hormonal regulation (e.g., insulin sensitivity of
GLUT4). Class II is comprised of the fructose-specific transporter
GLUT5 and three related proteins, GLUT7, GLUT9, and GLUT11. For GLUT11,
fructose-inhibitable glucose transport activity has been demonstrated
in a system of reconstituted vesicles (4). Class III is
characterized by the lack of a glycosylation site in the first
extracellular linker domain and by the presence of such a site in loop
9. As is also shown in the tree, the recently cloned proton-myoinositol
symporter (HMIT1, Ref. 18) can be included in the class
III GLUTs (10). Glucose transport activity has been
demonstrated for GLUT6 and GLUT8. It should be emphasized, however,
that the designation of the family does not necessarily reflect the
substrate specificity of its members, which may transport sugars or
polyols other than glucose (e.g., GLUT5, fructose; HMIT1, myoinositol).
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FOOTNOTES |
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Address for reprint requests and other correspondence: H.-G. Joost, Institut fuer Pharmakologie und Toxikologie, Medizinische Fakultaet der RWTH Aachen, Wendlingweg 2, 52057 Aachen, Germany (E-mail: joost{at}rwth-aachen.de).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/ajpendo.00407.2001
Received 14 September 2001; accepted in final form 6 November 2001.
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