WORKLIST ENTRIES (1):
GLUCTRNSPORT View alignment Mammalian facilitated glucose transporter family signature
Type of fingerprint: COMPOUND with 2 elements
Links:
PRINTS; PR00171 SUGRTRNSPORT; PR01190 GLUCTRSPORT1; PR01191 GLUCTRSPORT2
PRINTS; PR01192 GLUCTRSPORT3; PR01193 GLUCTRSPORT4; PR01194 GLUCTRSPORT5
INTERPRO; IPR000803
Creation date 13-MAY-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).
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.
GLUCTRNSPORT is a 2-element fingerprint that provides a signature for the
mammalian glucose transporters. The fingerprint was derived from an initial
alignment of 22 sequences: the motifs were drawn from the central portion
of the alignment: motifs 1 and 2 encode well-conserved regions of the large
putative cytoplasmic loop, which is located between presumed TM domains 6
and 7. Two iterations on SPTR37_9f were required to reach convergence, at
which point a true set comprising 24 sequences was identified.
SUMMARY INFORMATION
24 codes involving 2 elements
COMPOSITE FINGERPRINT INDEX
2| 24 24
--+-----------
| 1 2
True positives..
GTR1_BOVIN GTR1_RAT GTR1_MOUSE GTR1_HUMAN
GTR1_CHICK GTR1_RABIT GTR3_CANFA GTR3_SHEEP
GTR3_RAT GTR3_HUMAN GTR2_MOUSE GTR3_CHICK
GTR3_MOUSE GTR4_BOVIN GTR4_RAT GTR2_CHICK
GTR2_RAT GTR5_HUMAN Q14770 GTR5_RAT
GTR4_HUMAN GTR4_MOUSE GTR5_RABIT GTR2_HUMAN
PROTEIN TITLES
GTR1_BOVIN GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN - BOS TAURUS (
GTR1_RAT GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN - RATTUS NORVE
GTR1_MOUSE GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN (GT1) - MUS MU
GTR1_HUMAN GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN - HOMO SAPIENS
GTR1_CHICK GLUCOSE TRANSPORTER TYPE 1 (GT1) - GALLUS GALLUS (CHICKEN).
GTR1_RABIT GLUCOSE TRANSPORTER TYPE 1, ERYTHROCYTE/BRAIN - ORYCTOLAGUS
GTR3_CANFA GLUCOSE TRANSPORTER TYPE 3, BRAIN - CANIS FAMILIARIS (DOG).
GTR3_SHEEP GLUCOSE TRANSPORTER TYPE 3, BRAIN - OVIS ARIES (SHEEP).
GTR3_RAT GLUCOSE TRANSPORTER TYPE 3, BRAIN - RATTUS NORVEGICUS (RAT).
GTR3_HUMAN GLUCOSE TRANSPORTER TYPE 3, BRAIN - HOMO SAPIENS (HUMAN).
GTR2_MOUSE GLUCOSE TRANSPORTER TYPE 2, LIVER - MUS MUSCULUS (MOUSE).
GTR3_CHICK GLUCOSE TRANSPORTER TYPE 3 (CEF-GT3) - GALLUS GALLUS (CHICKE
GTR3_MOUSE GLUCOSE TRANSPORTER TYPE 3, BRAIN - MUS MUSCULUS (MOUSE).
GTR4_BOVIN GLUCOSE TRANSPORTER TYPE 4, INSULIN-RESPONSIVE - BOS TAURUS
GTR4_RAT GLUCOSE TRANSPORTER TYPE 4, INSULIN-RESPONSIVE - RATTUS NORV
GTR2_CHICK GLUCOSE TRANSPORTER TYPE 2, LIVER - GALLUS GALLUS (CHICKEN).
GTR2_RAT GLUCOSE TRANSPORTER TYPE 2, LIVER - RATTUS NORVEGICUS (RAT).
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
GTR4_HUMAN GLUCOSE TRANSPORTER TYPE 4, INSULIN-RESPONSIVE - HOMO SAPIEN
GTR4_MOUSE GLUCOSE TRANSPORTER TYPE 4, INSULIN-RESPONSIVE (GT2) - MUS M
GTR5_RABIT GLUCOSE TRANSPORTER TYPE 5, SMALL INTESTINE (FRUCTOSE TRANSP
GTR2_HUMAN GLUCOSE TRANSPORTER TYPE 2, LIVER - HOMO SAPIENS (HUMAN).
SCAN HISTORY
SPTR37_9f 2 300 NSINGLE
INITIAL MOTIF SETS
GLUCTRNSPORT1 Length of motif = 8 Motif number = 1
Mammalian facilitated glucose transporter family motif I - 1
PCODE ST INT
PRFLLINR GTR1_MOUSE 211 211
PRFLLINR GTR1_HUMAN 211 211
PRFLLINR GTR1_BOVIN 211 211
PRFLLINR GTR1_RAT 211 211
PRFLLINR GTR1_CHICK 210 210
PRYLYLNL GTR2_RAT 241 241
PRYLYIKL GTR2_MOUSE 242 242
PRYLYIKL GTR2_HUMAN 243 243
PRYLYIKL GTR2_CHICK 255 255
PRFLLINR GTR3_HUMAN 209 209
PRFLLINK GTR3_MOUSE 209 209
PRFLLINR GTR3_RAT 209 209
PRFLLINR GTR3_CANFA 209 209
PRFLLINR GTR3_SHEEP 209 209
PRFLLINK GTR3_CHICK 210 210
PRYLYIIQ GTR4_HUMAN 227 227
PRYLYIIR GTR4_RAT 227 227
PRYLYIIR GTR4_BOVIN 227 227
PRYLYIIR GTR4_MOUSE 229 229
PRYLLIQK GTR5_HUMAN 217 217
PRYLLIGQ GTR5_RABIT 215 215
PRYLLIQK GTR5_RAT 216 216
GLUCTRNSPORT2 Length of motif = 9 Motif number = 2
Mammalian facilitated glucose transporter family motif II - 1
PCODE ST INT
SVLKKLRGT GTR1_MOUSE 226 7
SVLKKLRGT GTR1_HUMAN 226 7
SVLKKLRGT GTR1_BOVIN 226 7
SVLKKLRGT GTR1_RAT 226 7
SVLKKLRGT GTR1_CHICK 225 7
KSLKRLRGT GTR2_RAT 256 7
KSLKRLRGT GTR2_MOUSE 257 7
QSLKRLRGY GTR2_HUMAN 258 7
KSLKRLRGN GTR2_CHICK 270 7
QILQRLWGT GTR3_HUMAN 224 7
EILQRLWGT GTR3_MOUSE 224 7
EILQRLWGT GTR3_RAT 224 7
EILQRLWGT GTR3_CANFA 224 7
EILQRLWGT GTR3_SHEEP 224 7
TVLQKLRGT GTR3_CHICK 225 7
KSLKRLTGW GTR4_HUMAN 242 7
KSLKRLTGW GTR4_RAT 242 7
KSLKRLTGW GTR4_BOVIN 242 7
KSLKPLTGW GTR4_MOUSE 244 7
KALQTLRGW GTR5_HUMAN 232 7
KALQSLRGW GTR5_RABIT 229 6
KALQTLRGW GTR5_RAT 231 7
FINAL MOTIF SETS
GLUCTRNSPORT1 Length of motif = 8 Motif number = 1
Mammalian facilitated glucose transporter family motif I - 2
PCODE ST INT
PRFLLINR GTR1_BOVIN 211 211
PRFLLINR GTR1_RAT 211 211
PRFLLINR GTR1_MOUSE 211 211
PRFLLINR GTR1_HUMAN 211 211
PRFLLINR GTR1_CHICK 210 210
PRFLLINR GTR1_RABIT 211 211
PRFLLINR GTR3_CANFA 209 209
PRFLLINR GTR3_SHEEP 209 209
PRFLLINR GTR3_RAT 209 209
PRFLLINR GTR3_HUMAN 209 209
PRYLYIKL GTR2_MOUSE 242 242
PRFLLINK GTR3_CHICK 210 210
PRFLLINK GTR3_MOUSE 209 209
PRYLYIIR GTR4_BOVIN 227 227
PRYLYIIR GTR4_RAT 227 227
PRYLYIKL GTR2_CHICK 255 255
PRYLYLNL GTR2_RAT 241 241
PRYLLIQK GTR5_HUMAN 217 217
PRYLLIQK Q14770 197 197
PRYLLIQK GTR5_RAT 216 216
PRYLYIIQ GTR4_HUMAN 227 227
PRYLYIIR GTR4_MOUSE 229 229
PRYLLIGQ GTR5_RABIT 215 215
PRYLYIKL GTR2_HUMAN 243 243
GLUCTRNSPORT2 Length of motif = 9 Motif number = 2
Mammalian facilitated glucose transporter family motif II - 2
PCODE ST INT
SVLKKLRGT GTR1_BOVIN 226 7
SVLKKLRGT GTR1_RAT 226 7
SVLKKLRGT GTR1_MOUSE 226 7
SVLKKLRGT GTR1_HUMAN 226 7
SVLKKLRGT GTR1_CHICK 225 7
SVLKKLRGN GTR1_RABIT 226 7
EILQRLWGT GTR3_CANFA 224 7
EILQRLWGT GTR3_SHEEP 224 7
EILQRLWGT GTR3_RAT 224 7
QILQRLWGT GTR3_HUMAN 224 7
KSLKRLRGT GTR2_MOUSE 257 7
TVLQKLRGT GTR3_CHICK 225 7
EILQRLWGT GTR3_MOUSE 224 7
KSLKRLTGW GTR4_BOVIN 242 7
KSLKRLTGW GTR4_RAT 242 7
KSLKRLRGN GTR2_CHICK 270 7
KSLKRLRGT GTR2_RAT 256 7
KALQTLRGW GTR5_HUMAN 232 7
KALQTLRGW Q14770 212 7
KALQTLRGW GTR5_RAT 231 7
KSLKRLTGW GTR4_HUMAN 242 7
KSLKPLTGW GTR4_MOUSE 244 7
KALQSLRGW GTR5_RABIT 229 6
QSLKRLRGY GTR2_HUMAN 258 7
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