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PR01192

Identifier
GLUCTRSPORT3  [View Relations]  [View Alignment]  
Accession
PR01192
No. of Motifs
3
Creation Date
15-APR-1999
Title
Glucose transporter type 3 (GLUT3) signature
Database References
PRINTS; PR00171 SUGRTRNSPORT; PR00172 GLUCTRNSPORT
INTERPRO; IPR002945
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.
 
GLUT3 is the most prominent glucose transporter isoform expressed in adult
brain, where it tends to be preferentially located in neurones, rather
than in other cell types, such as glia or endothelial cells. It is also
widely distributed in other human tissues, having been detected in the
liver, kidney and placenta. In other species, it shows a more restricted
expression pattern. It consists of 496 amino acids (human isoform) and
shares 64% amino acid identity with GLUT1 and 52% with GLUT2.
 
GLUCTRSPORT3 is a 3-element fingerprint that provides a signature for the
mammalian glucose transporter type 3 isoform. The fingerprint was derived
from an initial alignment of 6 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 3
isoform but distinguish it from others - motif 1 lies at the N-terminus
of the first putative TM domain; motif 2 encodes ~1/2 the fourth presumed
TM domain; and motif 3 lies near the end of the cytoplasmic C-terminus. A
single iteration on SPTR37_9f was required to reach convergence, no further 
sequences being identified beyond the starting set.
Summary Information
6 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3666
2000
123
True Positives
GTR3_CANFA    GTR3_CHICK    GTR3_HUMAN    GTR3_MOUSE    
GTR3_RAT GTR3_SHEEP
Sequence Titles
GTR3_CANFA  GLUCOSE TRANSPORTER TYPE 3, BRAIN - CANIS FAMILIARIS (DOG). 
GTR3_CHICK GLUCOSE TRANSPORTER TYPE 3 (CEF-GT3) - GALLUS GALLUS (CHICKEN).
GTR3_HUMAN GLUCOSE TRANSPORTER TYPE 3, BRAIN - HOMO SAPIENS (HUMAN).
GTR3_MOUSE GLUCOSE TRANSPORTER TYPE 3, BRAIN - MUS MUSCULUS (MOUSE).
GTR3_RAT GLUCOSE TRANSPORTER TYPE 3, BRAIN - RATTUS NORVEGICUS (RAT).
GTR3_SHEEP GLUCOSE TRANSPORTER TYPE 3, BRAIN - OVIS ARIES (SHEEP).
Scan History
SPTR37_9f  1  200  NSINGLE    
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
SLVFAVTVATI GTR3_MOUSE 9 9 -
SLVFAVTVATI GTR3_RAT 9 9 -
SLIFALSIATI GTR3_CANFA 9 9 -
ALIFAITVATI GTR3_HUMAN 9 9 -
SLIYAVSVAAI GTR3_CHICK 10 10 -
PLIFAISIATI GTR3_SHEEP 9 9 -

Motif 2 width=8
Element Seqn Id St Int Rpt
FCGLCTGF GTR3_MOUSE 130 110 -
FCGLCTGF GTR3_RAT 130 110 -
FCGLCTGF GTR3_CANFA 130 110 -
FCGLCTGF GTR3_HUMAN 130 110 -
FCGLCTGF GTR3_CHICK 131 110 -
FCGLCTGF GTR3_SHEEP 130 110 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VELNSMQPVKE GTR3_MOUSE 478 340 -
VELNSMQPVKE GTR3_RAT 478 340 -
VEMNSMQPVKE GTR3_CANFA 481 343 -
MEMNSIEPAKE GTR3_HUMAN 481 343 -
VEMNSIEPDKE GTR3_CHICK 484 345 -
MEMNSIQPTKD GTR3_SHEEP 481 343 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
SLVFAVTVATI GTR3_MOUSE 9 9 -
SLVFAVTVATI GTR3_RAT 9 9 -
SLIFALSIATI GTR3_CANFA 9 9 -
ALIFAITVATI GTR3_HUMAN 9 9 -
SLIYAVSVAAI GTR3_CHICK 10 10 -
PLIFAISIATI GTR3_SHEEP 9 9 -

Motif 2 width=8
Element Seqn Id St Int Rpt
FCGLCTGF GTR3_MOUSE 130 110 -
FCGLCTGF GTR3_RAT 130 110 -
FCGLCTGF GTR3_CANFA 130 110 -
FCGLCTGF GTR3_HUMAN 130 110 -
FCGLCTGF GTR3_CHICK 131 110 -
FCGLCTGF GTR3_SHEEP 130 110 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VELNSMQPVKE GTR3_MOUSE 478 340 -
VELNSMQPVKE GTR3_RAT 478 340 -
VEMNSMQPVKE GTR3_CANFA 481 343 -
MEMNSIEPAKE GTR3_HUMAN 481 343 -
VEMNSIEPDKE GTR3_CHICK 484 345 -
MEMNSIQPTKD GTR3_SHEEP 481 343 -