2.A.2 The Glycoside-Pentoside-Hexuronide (GPH):Cation Symporter Family GPH:cation symporters catalyze uptake of sugars (mostly, but not exclusively, glycosides) in symport with a monovalent cation (H⁺ or Na⁺). Mutants of two groups of these symporters (the melibiose permeases of enteric bacteria and the lactose permease of Streptococcus thermophilus) have been isolated and in which altered cation specificity is observed or in which sugar transport is uncoupled from cation symport (i.e., uniport is catalyzed). The various members of the family can use Na⁺, H⁺ or Li, Na⁺ or Li⁺, H⁺ or Li⁺, or only H⁺ as the symported cation. Most functionally characterized and sequenced members of the family are from bacteria except the distantly related sucrose:H⁺ symporters of plants and a yeast maltose/sucrose:H⁺ symporter of S. pombe. This yeast protein is about 24% identical to the plant sucrose:H⁺ symporters and is more distantly related to the bacterial members of the GPH family (Reinders and Ward, 2001). Homologues are found in archaea and all eukaryotic kingdoms. Proteins of the GHP family are generally about 500 amino acids in length, although the Gram-positive bacterial lactose permeases are larger, due to a C-terminal hydrophilic domain that is involved in regulation by the phosphotransferase system (TC #4.A.1). All of these proteins possess twelve putative transmembrane α-helical spanners. Limited sequence similarity of some of these proteins with members of the major facilitator superfamily (MFS, TC #2.A.1) has been observed. PSI-BLAST results substantiate the conclusion that the GPH family is a member of the MFS. One member of the GPH family, LacS of Streptococcus thermophilus, appears to be a cooperative dimer with one sugar translocation pathway per monomer (Veenhoff et al., 2001). The generalized transport reaction catalyzed by the GPH:cation symporter family is: Sugar (out) + [H⁺ or Na⁺] (out) → Sugar (in) + [H⁺ or Na⁺] (in).
This family belongs to the MFS Superfamily.
References:
Carpaneto, A., D. Geiger, E. Bamberg, N. Sauer, J. Fromm, and R. Hedrich. (2005). Phloem-localized, proton-coupled sucrose carrier ZmSUT1 mediates sucrose efflux under the control of the sucrose gradient and the proton motive force. J. Biol. Chem. 280: 21437-21443.
Chaillou, S., P.W. Postma, and P.H. Pouwels. (1998). Functional expression in Lactobacillus plantarum of xylP encoding the isoprimeverose transporter of Lactobacillus pentosus. J. Bacteriol. 180: 4011-4014.
Grossiord, B.P., E.J. Luesink, E.E. Vaughan, A. Arnaud, and W.M. de Vos. (2003). Characterization, expression, and mutation of the Lactococcus lactis galPMKTE genes, involved in galactose utilization via the Leloir pathway. J. Bacteriol. 185: 870-878.
Heuberger, E.H., E. Smits, and B. Poolman. (2001). Xyloside transport by XylP, a member of the galactoside-pentoside-hexuronide family. J. Biol. Chem. 276: 34465-34472.
Hugouvieux-Cotte-Pattat, N. and S. Reverchon. (2001). Two transporters, TogT and TogMNAB, are responsible for oligogalacturonide uptake in Erwinia chrysanthemi 3937. Molec. Microbiol. 41: 1125-1132.
Laikova, O.N., A.A. Mironov, and M.S. Gelfand. (2001). Computational analysis of the transcriptional regulation of pentose utilization systems in the gamma subdivision of Proteobacteria. FEMS Microbiol. Lett. 205: 315-322.
Liang, W.-J., K.J. Wilson, H. Xie, J. Knol, S. Suzuki, N.G. Rutherford, P.J.F. Henderson, and R.A. Jefferson. (2005). The gusBC genes of Escherichia coli encode a glucuronide transport system. J. Bacteriol. 187: 2377-2385.
Lohmiller, S., K. Hantke, S.I. Patzer, and V. Braun. (2008). TonB-dependent maltose transport by Caulobacter crescentus. Microbiology 154: 1748-1754.
Meyer S., M. Melzer, E. Truernit, C. Hümmer, R. Besenbeck, R. Stadler, N. Sauer. (2000). AtSUC3, a gene encoding a new Arabidopsis sucrose transporter, is expressed in cells adjacent to the vascular tissue and in a carpel cell layer. Plant J. 24: 869-882
Naderi, S. and M.H. Saier, Jr. (1996). Plant sucrose:H⁺ symporters are homologous to the melibiose permease of Escherichia coli. Molec. Microbiol. 22: 389-391.
Poolman, B., J. Knol, C. van der Does, P.J.F. Henderson, W.-J. Liang, G. Leblanc, T. Pourcher, and I. Mus-Veteau. (1996). Cation and sugar selectivity determinants in a novel family of transport proteins. Molec. Microbiol. 19: 911-922.
Reinders, A. and J.M. Ward. (2001). Functional characteristic of the α-glucoside transporter Sut1p from Schizosaccharomyces pombe, the first fungal homologue of plant sucrose transporters. Molec. Microbiol. 39: 445-454.
Reizer, J., A. Reizer, and M.H. Saier, Jr. (1994). A functional superfamily of sodium/solute symporters. Biochim. Biophys. Acta 1197: 133-166.
Shimokawa, N., J. Okada, K. Haglund, I. Dikic, N. Koibuchi, and M. Miura. (2002). Past-A, a novel proton-associated sugar transporter, regulates glucose homeostasis in the brain. J. Neurosci. 22: 9160-9165.
Stadler R., E. Truernit, M. Gahrtz, N. Sauer. (1999). The AtSUC1 sucrose carrier may represent the osmotic driving force for anther dehiscence and pollen tube growth in Arabidopsis. Plant J. 19: 269-278.
Veenhoff, L.M., Heuberger, E.H.M.L., and B. Poolman. (2001). The lactose transport protein is a cooperative dimer with two sugar translocation pathways. EMBO J. 20: 3056-3062.
Yousef, M.S. and L. Guan. (2009). A 3D structure model of the melibiose permease of Escherichia coli represents a distinctive fold for Na⁺ symporters. Proc. Natl. Acad. Sci. USA 106: 15291-15296.
Examples:
TC#	Name	Organismal Type	Example
2.A.2.1.1	Melibiose permease. Catalyzes the coupled stoichiometric symport of a galactoside with a cation (either Na⁺, Li⁺, or H⁺). Based on LacY, a 3-d model has been derived (Yousef and Guan, 2009).	Gram-negative bacteria	*MelB of E. coli* (A7ZUZ0)**

Examples:
TC#	Name	Organismal Type	Example
2.A.2.2.1	Lactose permease	Gram-positive bacteria	LacS of Streptococcus thermophilus

2.A.2.2.2	Raffinose permease	Gram-positive bacteria	RafP of Pediococcus pentosaceus

2.A.2.2.3	Galactose permease	Gram-positive bacteria	GalP of Lactococcus lactis

Examples:
TC#	Name	Organismal Type	Example
2.A.2.3.1	*Glucuronide permease (Liang et al., 2005)*	Gram-negative bacteria	GusB of E. coli

2.A.2.3.2	Pentoside permease	Gram-positive bacteria	XynC (YnaJ) of Bacillus subtilis

2.A.2.3.3	Isoprimeverose (α-D xylopyrano- syl-(1,6)-D-glucopyranose) permease [xylose is not a substrate] (Heuberger et al., 2001)	Gram-positive bacteria	XylP of Lactobacillus pentosus

2.A.2.3.4	*Probable α-xyloside uptake permease, YicJ (Laikova et al., 2001)*	Bacteria	*YicJ of E. coli* (P31435)**

2.A.2.3.5	*Probable β-xyloside uptake permease, YagG (Laikova et al., 2001)*	Bacteria	*YagG of E. coli* (P75683)**

2.A.2.3.6	The putative cellobiose porter, BglT	Proteobacteria	*BglT of Shewanella amazonensis* (A1S5F2)**

2.A.2.3.7	The putative arabinoside porter, AraT	Proteobacteria	*AraT of Shewanella sp. MR-4* (Q0HIQ0)**

2.A.2.3.8	Probable sugar GPH permease, MFSD2A (543aas, 12 TMSs) (Plays a role in thermogenesis via β-adrenergic signaling)	Animals	*MFSD2A of Homo sapiens* (Q8NA29)**

Examples:
TC#	Name	Organismal Type	Example
2.A.2.4.1	Sucrose:H⁺ symporter, Suc1 (provides osmotic driving force for anther dehiscence, pollen germination and pollen tube growth; also transports other glucosides such as maltose and ?- and ?-phenylglucosides. Km (sucrose)= 0.5 mM. (Stadler et al., 1999)).	Plants	Suc1 of Arabidopsis thaliana

2.A.2.4.2	*Phloem-localized sucrose:H⁺ symporter, Sut1 (mediates sucrose uptake or efflux dependent on the sucrose gradient and the pmf; Carpaneto et al., 2005)*	Plants	*Sut1 of Zea mays* (BAA83501)**

2.A.2.4.3	*Sucrose:H⁺ symporter, Suc3 (expressed in cells adjacent to the vascular tissue and in a carpel cell layer) Km (sucrose)= 1.9 mM; maltose is a competitor (Meyer et al., 2000).*	Plants	Suc3 of Arabidopsis thaliana (O80605)

2.A.2.4.4	*The brain proton:associated sugar (glucose) transporter, PAST-A (Shimokawa et al., 2002)*	Animals	*PAST-A of Rattus norvegicus* (Q8K4S3)**

Examples:
TC#	Name	Organismal Type	Example
2.A.2.5.1	Saturated and unsaturated oligogalacturonide transporter, TogT (transports di- to tetrasaccharide pectin degradation products which consist of D-galacuronate, sometimes with 4-deoxy-L-threo-5- hexosulose uronate at the reducing position)	Bacteria	*TogT of Erwinia chrysanthemi* 3937**

2.A.2.5.2	The putative rhamnogalacturonide porter, RhiT	Enterobacteria	*RhiT of Erwinia carotovora subsp. atroseptica* (Q6D188)**

Examples:
TC#	Name	Organismal Type	Example
2.A.2.6.1	Maltose/sucrose H⁺: symporter, Sut1 (maltose, Km = 6 μM; sucrose, Km = 36 μM)	Yeast	Sut1 of Schizosaccharomyces pombe

2.A.2.6.2	*The maltose/moltooligosaccharide transporter, MalI (541 aas) (Lohmiller et al., 2008).*	Bacteria	*MalI of Caulobacter crescentus* (Q9A612)**

2.A.2.6.3	The putative maltose porter, MalT	Proteobacteria	*MalT of Shewanella oneidensis* (Q8EEC4)**