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PR01190

Identifier
GLUCTRSPORT1  [View Relations]  [View Alignment]  
Accession
PR01190
No. of Motifs
3
Creation Date
15-APR-1999
Title
Glucose transporter type 1 (GLUT1) signature
Database References
PRINTS; PR00171 SUGRTRNSPORT; PR00172 GLUCTRNSPORT
PRODOM; PD012707
INTERPRO; IPR002439
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.
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).

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.
 
GLUT1 (also called HepG2) is the most ubiquitously distributed of the
glucose transporter isoforms. It is expressed in many foetal and adult
mammalian tissues, and cell lines, although frequently at low levels,
and in conjunction with other glucose transporter isoforms that show a
more limited expression pattern. The highest levels are found in foetal
tissues, and in adult tissues, brain microvessels containing the highest
levels. To date, it is the most extensively-studied glucose transporter,
and was initially biochemically characterised as the facilitated trans-
porter of human erythrocytes, prior to its cloning. It consists of 492
amino acid residues (human isoform), which are highly conserved between
species (98% amino acid identity, human vs. rat). It is thought to provide
glucose transport in various cells that form barriers between body tissues
and the blood supply. Thus it is found in epithelial and endothelial barrier
cells, such as those that constitute the blood-brain barrier, and also in 
the placenta.
 
GLUCTRSPORT1 is a 3-element fingerprint that provides a signature for the
mammalian glucose transporter type 1 isoform. The fingerprint was derived
from an initial alignment of 5 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise the glucose co-transporter type 1 isoform
but distinguish it from others - motif 1 encodes ~1/2 of the putative 
extracellular loop located between the first two presumed TM domains; and
motifs 2 and 3 encode the final 2/3 of the presumed cytoplasmic C-terminal
domain. Two iterations on SPTR37_9f were required to reach convergence, at
which point a true set comprising 6 sequences was identified.
Summary Information
6 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3666
2000
123
True Positives
GTR1_BOVIN    GTR1_CHICK    GTR1_HUMAN    GTR1_MOUSE    
GTR1_RABIT GTR1_RAT
Sequence Titles
GTR1_BOVIN  GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN - BOS TAURUS (BOVINE). 
GTR1_CHICK GLUCOSE TRANSPORTER TYPE 1 (GT1) - GALLUS GALLUS (CHICKEN).
GTR1_HUMAN GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN - HOMO SAPIENS (HUMAN).
GTR1_MOUSE GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN (GT1) - MUS MUSCULUS (MOUSE).
GTR1_RABIT GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN - ORYCTOLAGUS CUNICULUS (RABBIT).
GTR1_RAT GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_9f  2  300  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
EFYNQTWVHRYGE GTR1_HUMAN 42 42 -
EFYNQTWNHRYGE GTR1_RAT 42 42 -
EFYNQTWVQRYGE GTR1_BOVIN 42 42 -
EFYNQTWNHRIGE GTR1_MOUSE 42 42 -
DFYNHTWLYRYEE GTR1_CHICK 41 41 -

Motif 2 width=15
Element Seqn Id St Int Rpt
FRQGGASQSDKTPEE GTR1_HUMAN 467 412 -
FRQGGASQSDKTPEE GTR1_RAT 467 412 -
FRQGGASQSDKTPEE GTR1_BOVIN 467 412 -
FRQGGASQSDKTPEE GTR1_MOUSE 467 412 -
FRQGGASQSDKTPDE GTR1_CHICK 466 412 -

Motif 3 width=10
Element Seqn Id St Int Rpt
FHPLGADSQV GTR1_HUMAN 483 1 -
FHPLGADSQV GTR1_RAT 483 1 -
FHPLGADSQV GTR1_BOVIN 483 1 -
FHPLGADSQV GTR1_MOUSE 483 1 -
FHSLGADSQV GTR1_CHICK 481 0 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
EFYNQTWVHRYGE GTR1_HUMAN 42 42 -
EFYNQTWNHRYGE GTR1_RAT 42 42 -
EFYNQTWIHRYGE GTR1_RABIT 42 42 -
EFYNQTWVQRYGE GTR1_BOVIN 42 42 -
EFYNQTWNHRIGE GTR1_MOUSE 42 42 -
DFYNHTWLYRYEE GTR1_CHICK 41 41 -

Motif 2 width=15
Element Seqn Id St Int Rpt
FRQGGASQSDKTPEE GTR1_HUMAN 467 412 -
FRQGGASQSDKTPEE GTR1_RAT 467 412 -
FRQGGASQSDKTPEE GTR1_RABIT 467 412 -
FRQGGASQSDKTPEE GTR1_BOVIN 467 412 -
FRQGGASQSDKTPEE GTR1_MOUSE 467 412 -
FRQGGASQSDKTPDE GTR1_CHICK 466 412 -

Motif 3 width=10
Element Seqn Id St Int Rpt
FHPLGADSQV GTR1_HUMAN 483 1 -
FHPLGADSQV GTR1_RAT 483 1 -
FHPLGADSQV GTR1_RABIT 483 1 -
FHPLGADSQV GTR1_BOVIN 483 1 -
FHPLGADSQV GTR1_MOUSE 483 1 -
FHSLGADSQV GTR1_CHICK 481 0 -