SPECIAL COMMUNICATION
Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators

Hans-Georg Joost1, Graeme I. Bell2, James D. Best3, Morris J. Birnbaum4, Maureen J. Charron5, Y. T. Chen6, Holger Doege7, David E. James8, Harvey F. Lodish9, Kelle H. Moley10, Jeffrey F. Moley11, Mike Mueckler12, Suzanne Rogers3, Annette Schürmann1, Susumu Seino15, and Bernard Thorens16

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


    ABSTRACT
TOP
ABSTRACT
ARTICLE
REFERENCES

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


    ARTICLE
TOP
ABSTRACT
ARTICLE
REFERENCES

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).

                              
View this table:
[in this window]
[in a new window]
 
Table 1.   Summary of the extended GLUT family

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).


View larger version (19K):
[in this window]
[in a new window]
 
Fig. 1.   Dendrogram of a multiple alignment of all members of the extended GLUT family. The alignment was performed with the clustree program (Heidelberg UNIX sequence analysis resources package from the Deutsches Krebsforschungszentrum, Heidelberg, Germany). The results were corrected for multiple substitutions, and positions with gaps were excluded. Branch lengths reflect the degree of difference between the sequences. Reproduced from Ref. 10, with permission of Taylor & Francis Ltd.


    FOOTNOTES

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.


    REFERENCES
TOP
ABSTRACT
ARTICLE
REFERENCES

1.   Carayannopoulos, MO, Chi MMY, Cui Y, Pingsterhaus JM, McKnight RA, Mueckler M, Devaskar SU, and Moley KH. GLUT8 is a glucose transporter responsible for insulin-stimulated glucose uptake in the blastocyst. Proc Natl Acad Sci USA 13: 7313-7318, 2000.

2.   Doege, H, Bocianski A, Joost HG, and Schürmann A. Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel member of the family of sugar transport facilitators predominantly expressed in brain and leukocytes. Biochem J 350: 771-776, 2000[ISI][Medline].

3.   Doege, H, Bocianski A, Scheepers A, Axer H, Eckel J, Joost HG, and Schürmann A. Characterization of glucose transporter 10 (GLUT10), a novel heart and skeletal muscle-specific sugar transport facilitator. Diabetes 50, Suppl 2: A277-A278, 2001[ISI].

4.   Doege, H, Bocianski A, Scheepers A, Axer H, Eckel J, Joost HG, and Schürmann A. Characterization of the human glucose transporter GLUT11, a novel sugar transport facilitator specifically expressed in heart and skeletal muscle. Biochem J 359: 443-449, 2001[ISI][Medline].

5.   Doege, H, Schürmann A, Bahrenberg G, Brauers A, and Joost HG. Glucose transporter 8 (GLUT): a novel sugar transport facilitator with glucose transport activity. J Biol Chem 275: 16275-16280, 2000[Abstract/Free Full Text].

6.   Fukumoto, H, Kayano T, Buse JB, Edwards Y, Pilch PF, Bell GI, and Seino S. Cloning and characterization of the major insulin-responsive glucose transporter expressed in human skeletal muscle and other insulin-responsive tissues. J Biol Chem 264: 7776-7779, 1989[Abstract/Free Full Text].

7.   Fukumoto, H, Seino S, Imura H, Seino Y, Eddy RL, Fukushima Y, Byers MG, Shows TB, and Bell GI. Sequence, tissue distribution, and chromosomal localization of mRNA encoding a human glucose transporter-like protein. Proc Natl Acad Sci USA 85: 5434-5438, 1988[Abstract].

8.   Ibberson, M, Uldry M, and Thorens B. GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues. J Biol Chem 275: 4607-4612, 2000[Abstract/Free Full Text].

9.   Joost, HG, Doege H, Bocianski A, and Schürmann A. Erratum: nomenclature of the GLUT family of sugar transport facilitators. GLUT6, GLUT9, GLUT10, and GLUT11. Biochem J 358: 791-792, 2001[ISI].

10.   Joost, HG, and Thorens B. The extended GLUT-family of sugar/polyol transport facilitators---nomenclature, sequence characteristics, and potential function of its novel members. Molec Membr Biol 18: 247-256, 2001[ISI][Medline].

11.   Kayano, T, Burant CF, Fukumoto H, Gould GW, Fan Y, Eddy RL, Byers MG, Seino S, and Bell GI. 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: 13267-13282, 1990.

12.   Kayano, T, Fukumoto H, Eddy RL, Fan YS, Byers MG, Shows TB, and Bell GI. 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[Abstract/Free Full Text].

13.   McVie-Wylie, AJ, Lamson DR, and Chen YT. Molecular cloning of a novel member of the GLUT family of transporters, SLC2A10 (GLUT10), localized on chromosome 20q13.1: a candidate gene for NIDDM susceptibility. Genomics 72: 113-117, 2001[ISI][Medline].

14.   Mueckler, M, Caruso C, Baldwin SA, Panico M, Blench I, Morris HR, Allard WJ, Lienhard GE, and Lodish HF. Sequence and structure of human glucose transporter. Science 229: 941-945, 1985[ISI][Medline].

15.   Phay, JE, Hussain HB, and Moley JF. Cloning and expression analysis of a novel member of the facilitative glucose transporter family, SLC2A9 (GLUT9). Genomics 66: 217-220, 2000[ISI][Medline].

16.   Rogers, S, James DE, and Best JD. Identification of novel facilitative transporter like protein-GLUT8 (Abstract). Diabetes 47, Suppl 1: A45, 1998[ISI].

17.  Tartaglia LA and Weng X. Nucleic acid molecules encoding GLUTX and uses thereof. US Patent No. 5: 942, 398, 1999.

18.   Uldry, M, Ibberson M, Riederer B, Chatton JY, Horisberger JD, and Thorens B. Identification of a novel H+-myo-inositol symporter expressed predominantly in the brain. EMBO J 20: 4467-4477, 2001[Abstract/Free Full Text].


Am J Physiol Endocrinol Metab 282(4):E974-E976
0193-1849/02 $5.00 Copyright © 2002 the American Physiological Society