PROSITE documentation PDOC00190

Sugar transport proteins signatures

In mammalian cells the uptake of glucose is mediated by a family of closely related transport proteins which are called the glucose transporters [1,2,3]. At least seven of these transporters are currently known to exist (in Human they are encoded by the GLUT1 to GLUT7 genes).

These integral membrane proteins are predicted to comprise twelve membrane spanning domains. The glucose transporters show sequence similarities [4,5] with a number of other sugar or metabolite transport proteins listed below (references are only provided for recently determined sequences).

• Escherichia coli arabinose-proton symport (araE).
• Escherichia coli galactose-proton symport (galP).
• Escherichia coli and Klebsiella pneumoniae citrate-proton symport (also known as citrate utilization determinant) (gene cit).
• Escherichia coli α-ketoglutarate permease (gene kgtP).
• Escherichia coli proline/βine transporter (gene proP) [6].
• Escherichia coli xylose-proton symport (xylE).
• Zymomonas mobilis glucose facilitated diffusion protein (gene glf).
• Yeast high and low affinity glucose transport proteins (genes SNF3, HXT1 to HXT14).
• Yeast galactose transporter (gene GAL2).
• Yeast maltose permeases (genes MAL3T and MAL6T).
• Yeast myo-inositol transporters (genes ITR1 and ITR2).
• Yeast carboxylic acid transporter protein homolog JEN1.
• Yeast inorganic phosphate transporter (gene PHO84).
• Kluyveromyces lactis lactose permease (gene LAC12).
• Neurospora crassa quinate transporter (gene Qa-y), and Emericella nidulans quinate permease (gene qutD).
• Chlorella hexose carrier (gene HUP1).
• Arabidopsis thaliana glucose transporter (gene STP1).
• Spinach sucrose transporter.
• Leishmania donovani transporters D1 and D2.
• Leishmania enriettii probable transport protein (LTP).
• Yeast hypothetical proteins YBR241c, YCR98c and YFL040w.
• Caenorhabditis elegans hypothetical protein ZK637.1.
• Escherichia coli hypothetical proteins yabE, ydjE and yhjE.
• Haemophilus influenzae hypothetical proteins HI0281 and HI0418.
• Bacillus subtilis hypothetical proteins yxbC and yxdF.

It has been suggested [4] that these transport proteins have evolved from the duplication of an ancestral protein with six transmembrane regions, this hypothesis is based on the conservation of two G-R-[KR] motifs. The first one is located between the second and third transmembrane domains and the second one between transmembrane domains 8 and 9.

We have developed two patterns to detect this family of proteins. The first pattern is based on the G-R-[KR] motif; but because this motif is too short to be specific to this family of proteins, we have derived a pattern from a larger region centered on the second copy of this motif. The second pattern is based on a number of conserved residues which are located at the end of the fourth transmembrane segment and in the short loop region between the fourth and fifth segments.