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PR01191

Identifier
GLUCTRSPORT2  [View Relations]  [View Alignment]  
Accession
PR01191
No. of Motifs
3
Creation Date
15-APR-1999
Title
Glucose transporter type 2 (GLUT2) signature
Database References
PRINTS; PR00171 SUGRTRNSPORT; PR00172 GLUCTRNSPORT
PRODOM; PD020009
INTERPRO; IPR002440
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.
 
GLUT2 is the major glucose transporter isoform expressed in hepatocytes,
insulin-secreting pancreatic beta cells, and absorptive epithelial cells
of the intestinal mucosa and kidney. It functions as a low affinity,
high-turnover transport system; together with the enzyme glucokinase, it
is thought to act as a glucose-sensing apparatus that plays a role in blood
glucose homeostasis, by responding to changes in blood glucose concentration
(such as might occur following a meal) and altering the rate of glucose 
uptake into liver cells, where it can be stored as glycogen. It consists of
524 amino acids (human isoform) and is ~55% identical to GLUT1 at the amino 
acid level. GLUT2 has received attention as a molecule that could be 
involved in the pathogenesis of diabetes mellitus. Reductions in pancreatic
beta cell GLUT2 levels have been observed in several animal models of 
diabetes, as well as human patients; whether this is causative, or an 
epiphenomenon remains to be resolved.
 
GLUCTRSPORT2 is a 3-element fingerprint that provides a signature for the
mammalian glucose transporter type 2 isoform. The fingerprint was derived
from an initial alignment of 4 sequences: the motifs were drawn from
conserved regions spanning ~60% of the alignment length, focusing on those
sections that characterise the glucose co-transporter type 2 isoform but
distinguish it from others - motif 1 encodes ~1/4 of the putative extra-
cellular loop located between the first two presumed TM domains; motif 2
encodes the C-terminus of the second presumed TM domain, leading into the
first intracellular loop; and motif 3 lies on the large presumed intra-
cellular loop in the centre of the sequence. A single iteration on
SPTR37_9f was required to reach convergence, no further sequences being
identified beyond the starting set.
Summary Information
4 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3444
2000
123
True Positives
GTR2_CHICK    GTR2_HUMAN    GTR2_MOUSE    GTR2_RAT      
Sequence Titles
GTR2_CHICK  GLUCOSE TRANSPORTER TYPE 2, LIVER - GALLUS GALLUS (CHICKEN). 
GTR2_HUMAN GLUCOSE TRANSPORTER TYPE 2, LIVER - HOMO SAPIENS (HUMAN).
GTR2_MOUSE GLUCOSE TRANSPORTER TYPE 2, LIVER - MUS MUSCULUS (MOUSE).
GTR2_RAT GLUCOSE TRANSPORTER TYPE 2, LIVER - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_9f  1  300  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
HYRHVLGVPLDDRKA GTR2_MOUSE 41 41 -
HYRHVLGVPLDDRRA GTR2_RAT 41 41 -
HYRHVLGVPLDDRKA GTR2_HUMAN 41 41 -
HYGRMLGAIPMVRHA GTR2_CHICK 48 48 -

Motif 2 width=7
Element Seqn Id St Int Rpt
GWLGDKL GTR2_MOUSE 115 59 -
GWLGDKL GTR2_RAT 114 58 -
GWLGDTL GTR2_HUMAN 116 60 -
GWIGDRL GTR2_CHICK 128 65 -

Motif 3 width=9
Element Seqn Id St Int Rpt
QLFTDANYR GTR2_MOUSE 292 170 -
QLFTDPNYR GTR2_RAT 291 170 -
QLFTNSSYR GTR2_HUMAN 293 170 -
QLFSSSKYR GTR2_CHICK 305 170 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
HYRHVLGVPLDDRKA GTR2_MOUSE 41 41 -
HYRHVLGVPLDDRRA GTR2_RAT 41 41 -
HYRHVLGVPLDDRKA GTR2_HUMAN 41 41 -
HYGRMLGAIPMVRHA GTR2_CHICK 48 48 -

Motif 2 width=7
Element Seqn Id St Int Rpt
GWLGDKL GTR2_MOUSE 115 59 -
GWLGDKL GTR2_RAT 114 58 -
GWLGDTL GTR2_HUMAN 116 60 -
GWIGDRL GTR2_CHICK 128 65 -

Motif 3 width=9
Element Seqn Id St Int Rpt
QLFTDANYR GTR2_MOUSE 292 170 -
QLFTDPNYR GTR2_RAT 291 170 -
QLFTNSSYR GTR2_HUMAN 293 170 -
QLFSSSKYR GTR2_CHICK 305 170 -