WORKLIST ENTRIES (1): GLUCTRSPORT5 View alignment Fructose transporter (GLUT5) signature Type of fingerprint: COMPOUND with 3 elements Links: PRINTS; PR00172 GLUCTRNSPORT; PR01190 GLUCTRSPORT1; PR01191 GLUCTRSPORT2 PRINTS; PR01192 GLUCTRSPORT3; PR01193 GLUCTRSPORT4 INTERPRO; IPR002442 Creation date 15-APR-1999 1. GOULD, G.W. AND BELL, G.I. Facilitative glucose transporters: an expanding family. TRENDS BIOCHEM.SCI. 15 18-23 (1990). 2. BELL, G.I., BURANT, C.F., TAKEDA, J. AND GOULD, G.W. Structure and function of mammalian facilitative sugar transporters. J.BIOL.CHEM. 268 19161-19164 (1993). 3. MUECKLER, M. Facilitative glucose transporters. EUR.J.BIOCHEM. 219 713-725 (1994). 4. KAYANO, T., BURANT, C.F., FUKUMOTO, H., GOULD, G.W., FAN, Y.S., EDDY, R.L., BYERS, M.G., SHOWS, T.B., SEINO, S. AND 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 13278-13282 (1990). 5. BURCHELL, A. A re-evaluation of GLUT 7. BIOCHEM.J. 331 973 (1998). 6. MAIDEN, M.C.J., DAVIS, E.O., BALDWIN, S.A., MOORE, D.C.M. AND HENDERSON, P.J.F. Mammalian and bacterial sugar transport proteins are homologous. NATURE 325 641-643 (1987). 7. MARGER, M.D. AND SAIER, M.H., JR. A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport. TRENDS BIOCHEM.SCI. 18 13-20 (1993). 8. HEDIGER, M.A., COADY, M.J., IKEDA, T.S. AND WRIGHT, E.M. Expression cloning and cDNA sequencing of the Na+/glucose co-transporter. NATURE 330 379-381 (1987). 9. BURANT, C.F., TAKEDA, J., BROT-LAROCHE, E., BELL, G.I. AND DAVIDSON, N.O. Fructose transporter in human spermatozoa and small intestine is GLUT5. J.BIOL.CHEM. 267 14523-14526 (1992). The ability to transport glucose across the plasma membrane is a feature common to nearly all cells, from simple bacteria through to highly specialised mammalian neurones. Facilitative glucose (and fructose) transport is mediated by members of the GLUT transporter family. These are glycosylated transmembrane (TM) proteins that transport glucose in a passive (i.e., energy-independent) manner. In consequence, they can only transport glucose down its concentration gradient. Currently, five such mammalian transporters have been cloned and functionally characterised [1-3]. Four of these transport glucose (GLUT1-4), whereas GLUT5 prefer- entially transports fructose. A sixth cDNA, encoding an apparent glucose transporter, was cloned but was found to be a pseudo-gene (GLUT6) . Similarly, another cDNA thought to encode a glucose transporter that was targeted to the endoplasmic reticulum was eventually realised to be an experimental cloning artefact (GLUT7) . The five confirmed isoforms are expressed in a tissue and cell-specific manner, and have been found to exhibit distinct kinetic and regulatory properties, presumably reflecting their specific functional roles in these locations. Hydropathy analysis reveals they have 12 presumed TM domains, and that they belong to a much larger 'major facilitator superfamily' of 12 TM transporters that are involved in the transport of a variety of hexoses and other carbon compounds, including: bacterial sugar-proton symporters (H+/xylose and H+/arabinose); bacterial transporters of carboxylic acids and antibiotics; and sugar transporters in various yeast, protozoa and higher plants. Nevertheless, amino acid identity within the superfamily may be as low as ~25% [6,7]. Besides the 12 presumed TM domains, the most characteristic structural feature of the superfamily is the presence of a five residue motif (RXGRR, where X is any amino acid). In the GLUT transporters, this motif is present in the presumed cytoplasmic loops connecting TM domains 2 with 3, and also 8 with 9. The 12 TM transporter superfamily appears to be structurally unrelated to the Na+-coupled, Na+/glucose co-transporters (SGLT1-3) found in the intestine and kidney, which are able to transport glucose against its concentration gradient . Comparison of the hydropathy profiles for GLUT1-5 reveals that they are virtually superimposable, despite the fact that their primary structures may differ by up to 60%. Of the presumed TM domains, the fourth, fifth and sixth are the most highly conserved, and conserved residues are also found in the short exofacial loops joining the putative TM regions. The presumed cytoplasmic N- and C-termini, and the extracellular loop between the first and second TM domains, show the greatest divergence, both in terms of primary structure and size. GLUT5 exhibits the weakest inter-isoform similarity of any of the members of the GLUT family. This is consistent with its identity as a fructose rather than a glucose transporter . It is expressed abundantly in the upper small intestine, where it is located in the epithelial brush border. Here it likely forms the principal route for dietary fructose uptake. It is also found in high levels in the plasma membrane of spermatozoa, consistent with their ability to utilise the fructose in seminal fluid as an energy source. GLUT5 has also been found in the brain endothelium, muscle and fat cells, although its function in these locations is unknown. It consists of 501 amino acids (human isoform) and shares ~40% amino acid identity with the other isoforms. GLUCTRSPORT5 is a 3-element fingerprint that provides a signature for the mammalian fructose transporter (GLUT5). The fingerprint was derived from an initial alignment of 3 sequences: the motifs were drawn from conserved regions spanning virtually the full alignment length, focusing on those sections that characterise the GLUT5 (fructose) co-transporter isoform but distinguish it from others - motif 1 lies on the first putative extra- cellular loop, located between the first two presumed TM domains; motif 2 encodes ~1/3 of the second TM domain; and motif 3 lies near the end of the presumed cytoplasmic C-terminus. Two iterations on SPTR37_9f were required to reach convergence, at which point a true set comprising 4 sequences was identified. SUMMARY INFORMATION 4 codes involving 3 elements 0 codes involving 2 elements COMPOSITE FINGERPRINT INDEX 3| 4 4 4 2| 0 0 0 --+---------------- | 1 2 3 True positives.. GTR5_HUMAN Q14770 GTR5_RAT GTR5_RABIT PROTEIN TITLES GTR5_HUMAN GLUCOSE TRANSPORTER TYPE 5, SMALL INTESTINE (FRUCTOSE TRANSP Q14770 FRUCTOSE TRANSPORTER - HOMO SAPIENS (HUMAN). GTR5_RAT GLUCOSE TRANSPORTER TYPE 5, SMALL INTESTINE (FRUCTOSE TRANSP GTR5_RABIT GLUCOSE TRANSPORTER TYPE 5, SMALL INTESTINE (FRUCTOSE TRANSP
SCAN HISTORY SPTR37_9f 2 300 NSINGLE INITIAL MOTIF SETS GLUCTRSPORT51 Length of motif = 14 Motif number = 1 Fructose transporter (GLUT5) motif I - 1 PCODE ST INT QQFYNETYYGRTGE GTR5_HUMAN 47 47 TEFYNDTYYDRTGE GTR5_RABIT 48 48 QQFYNDTYYDRNKE GTR5_RAT 46 46 GLUCTRSPORT52 Length of motif = 7 Motif number = 2 Fructose transporter (GLUT5) motif II - 1 PCODE ST INT MFPFGGF GTR5_HUMAN 77 16 MFPSGGF GTR5_RABIT 78 16 MFPFGGF GTR5_RAT 76 16 GLUCTRSPORT53 Length of motif = 8 Motif number = 3 Fructose transporter (GLUT5) motif III - 1 PCODE ST INT EVYPEKEE GTR5_HUMAN 483 399 EVSPDREE GTR5_RABIT 469 384 DVYPEKEE GTR5_RAT 482 399 FINAL MOTIF SETS GLUCTRSPORT51 Length of motif = 14 Motif number = 1 Fructose transporter (GLUT5) motif I - 2 PCODE ST INT QQFYNETYYGRTGE GTR5_HUMAN 47 47 QQFYNETYYGRTGE Q14770 27 27 QQFYNDTYYDRNKE GTR5_RAT 46 46 TEFYNDTYYDRTGE GTR5_RABIT 48 48 GLUCTRSPORT52 Length of motif = 7 Motif number = 2 Fructose transporter (GLUT5) motif II - 2 PCODE ST INT MFPFGGF GTR5_HUMAN 77 16 MFPFGGF Q14770 57 16 MFPFGGF GTR5_RAT 76 16 MFPSGGF GTR5_RABIT 78 16 GLUCTRSPORT53 Length of motif = 8 Motif number = 3 Fructose transporter (GLUT5) motif III - 2 PCODE ST INT EVYPEKEE GTR5_HUMAN 483 399 EVYPEKEE Q14770 463 399 DVYPEKEE GTR5_RAT 482 399 EVSPDREE GTR5_RABIT 469 384
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