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PR01194

Identifier
GLUCTRSPORT5  [View Relations]  [View Alignment]  
Accession
PR01194
No. of Motifs
3
Creation Date
15-APR-1999
Title
Fructose transporter (GLUT5) signature
Database References
PRINTS; PR00171 SUGRTRNSPORT; PR00172 GLUCTRNSPORT
PRODOM; PD015322
INTERPRO; IPR002442
Literature References
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.BIOCHEMISTRY 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
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.
BIOCHEMISTRY 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). 

Documentation
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) [4].
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) [5].
 
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 [8].
 
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 [9]. 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 Feature Index
3444
2000
123
True Positives
GTR5_HUMAN    GTR5_RABIT    GTR5_RAT      Q14770        
Sequence Titles
GTR5_HUMAN  GLUCOSE TRANSPORTER TYPE 5, SMALL INTESTINE (FRUCTOSE TRANSPORTER) - HOMO SAPIENS (HUMAN). 
GTR5_RABIT GLUCOSE TRANSPORTER TYPE 5, SMALL INTESTINE (FRUCTOSE TRANSPORTER) - ORYCTOLAGUS CUNICULUS (RABBIT).
GTR5_RAT GLUCOSE TRANSPORTER TYPE 5, SMALL INTESTINE (FRUCTOSE TRANSPORTER) - RATTUS NORVEGICUS (RAT).
Q14770 FRUCTOSE TRANSPORTER - HOMO SAPIENS (HUMAN).
Scan History
SPTR37_9f  2  300  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
QQFYNETYYGRTGE GTR5_HUMAN 47 47 -
QQFYNDTYYDRNKE GTR5_RAT 46 46 -
TEFYNDTYYDRTGE GTR5_RABIT 48 48 -

Motif 2 width=7
Element Seqn Id St Int Rpt
MFPFGGF GTR5_HUMAN 77 16 -
MFPFGGF GTR5_RAT 76 16 -
MFPSGGF GTR5_RABIT 78 16 -

Motif 3 width=8
Element Seqn Id St Int Rpt
EVYPEKEE GTR5_HUMAN 483 399 -
DVYPEKEE GTR5_RAT 482 399 -
EVSPDREE GTR5_RABIT 469 384 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
QQFYNETYYGRTGE GTR5_HUMAN 47 47 -
QQFYNETYYGRTGE Q14770 27 27 -
QQFYNDTYYDRNKE GTR5_RAT 46 46 -
TEFYNDTYYDRTGE GTR5_RABIT 48 48 -

Motif 2 width=7
Element Seqn Id St Int Rpt
MFPFGGF GTR5_HUMAN 77 16 -
MFPFGGF Q14770 57 16 -
MFPFGGF GTR5_RAT 76 16 -
MFPSGGF GTR5_RABIT 78 16 -

Motif 3 width=8
Element Seqn Id St Int Rpt
EVYPEKEE GTR5_HUMAN 483 399 -
EVYPEKEE Q14770 463 399 -
DVYPEKEE GTR5_RAT 482 399 -
EVSPDREE GTR5_RABIT 469 384 -