Galactose:H⁺ symporter, GalP. Also transports glucose, xylose, fucose (6-deoxygalactose), 2-deoxygalactose and 2-deoxyglucose) (Henderson and Giddens 1977; Henderson et al. 1977; Hernández-Montalvo et al., 2001). Relative substrate affinities of wild-type and mutant forms of the E. coli sugar transporter GalP have been determined by solid-state NMR (Patching et al., 2008).  GalP may exist as a trimer with each subunit having a sugar transporting channel (Zheng et al. 2010).

Bacteria

GalP of E. coli (P0AEP1)

Maltotriose/maltose:H⁺ symporter, Mal6T or Mal61 (Dietvorst et al. 2005).  The orthologue (90% identical) in Saccharomyces pastorianus (Lager yeast) (Saccharomyces cerevisiae x Saccharomyces eubayanus), MTT1 or Mty1 of 615 aas, has higher affinity for maltotriose than maltose (Magalhães et al. 2016).

Yeast

MAL6 of Saccharomyces cerevisiae

Low-affinity glucose transporter HXT1 of 570 aas and 12 TMSs. Substitutions of equivalent salt bridge-forming residues in Hxt1, Rgt2, and Glut4 are predicted to lock them in an inward-facing conformation but lead to different functional consequences. The salt bridge networks in yeast and human glucose transporters and yeast glucose receptors may play different roles in maintaining their structural and functional integrity (Kim et al. 2023).

Fungi

HXT1 of Saccharomyces cerevisiae

General α-glucoside:H⁺ symporter, Gtr3, Mal11,Mal1T, Mtp1 or Agt1 . (Substrates include trehalose, maltotriose, maltose, turanose, isomaltose, α-methyl-glucoside, maltotriose, palatinose, and melezitose) (Smit et al., 2008).  Maltotriose is transported with higher affinity than maltose (Magalhães et al. 2016).

Yeast

AGT1 of Saccharomyces cerevisiae

High-affinity glucose transporter HXT2.  Asp340 and Asn331 in part determine the high glucose affinity (Kasahara et al. 2007; Kasahara and Kasahara 2010).

Fungi

HXT2 of Saccharomyces cerevisiae

Putative metabolite transport protein YyaJ

YyaJ of Bacillus subtilis

Putative metabolite transport protein YaaU

Bacteria

YaaU of Escherichia coli

Putative metabolite transport protein YdjK

Bacteria

YdjK of Escherichia coli

Arabinose/xylose transporter, AraE (Wang et al. 2013).

Actinobacteria

AraE of Coynebacterium glutamicum

Glucose transporter Rco-3 or MoST1. MoST1 plays a specific role in conidiation and mycelial melanization which is not shared by other hexose transporter family members in M. oryzae (Saitoh et al. 2013).

Fungi

MoST1 of Magnaporthe oryzae

MFS porter of 435 aas

Crenarchaea

MFS porter of Sulfolobus solfataricus

The galacturonic acid (galacturonate) uptake porter, GatA, of 518 aas and 12 TMSs (Sloothaak et al. 2014).

Fungi

GatA of Aspergillus niger

Glucose uniporter, Glut3 (also transports dehydro-ascorbate; Maulén et al., 2003). Down-regulated in the brains of Alzheimer's disease patients (Liu et al., 2008b).  The structure of the human orthologue with D-glucose bound was solved at 1.5 Å resolution in the outward occluded conformation (Deng et al. 2015).  Sugars are predominantly coordinated by polar residues in the C-terminal domain. The conformational transition from the outward-open to the outward-occluded states entails a prominent local rearrangement of the extracellular part of  TMS 7. Comparison of the outward-facing GLUT3 structures with inward-open GLUT1 provides insight into the alternating access cycle for GLUTs, whereby the C-terminal domain provides the primary substrate-binding site and the N-terminal domain undergoes rigid-body rotation with respect to the C-terminal domain (Deng et al. 2015). Glut3 is involved in several disease states in humans (Lechermeier et al. 2019). Resveratrol and soy isoflavones alone and in combination improve the learning and memory of aging rats. The mechanism may be related to up-regulating the expression of GLUT1 and GLUT3 genes and proteins in the hippocampus (Zhang et al. 2020).

Animals

Gtr3 (Glut3) of Rattus norvegicus (rat)

Major myo-inositol transporter, IolT1, of 456 aas (Kröger et al. 2010).

Proteobacteria

IolT1 of Samonella enterica

Minor myo-inositol transporter, IolT2, of 478 aas (Kröger et al. 2010).

Proteobacteria

IolT2 of Salmonella enterica

Sorbitol (glucitol):H⁺ co-transporter, SOT2 (Km for sorbitol of 0.81 mM) of 491 aas and 12 TMSs (Gao et al. 2003). SOT2 of Prunus cerasus is mainly expressed only early in fruit development and not in leaves (Gao et al. 2003).

Plants

SOT2 of Pyrus pyrifolia (Chinese pear) (Pyrus serotina)

Sorbitol (D-Glucitol):H⁺ co-transporter, SOT1 (Km for sorbitol of 0.64 mM) of 509 aas and 12 TMSs (Gao et al. 2003). SOT1 of P. cerasus is expressed throughout fruit development, but especially when growth and sorbitol accumulation rates are highest. In leaves, PcSOT1 expression is highest in young, expanding tissues, but substantially less in mature leaves (Gao et al. 2003).

Plants

SOT1 of Prunus salicina

The high affinity sugar:H⁺ symporter (sugar uptake) porter of 514 aas and 12 TMSs, STP10. It transports glucose, galactose and mannose, and is therefore a hexose transporter (Rottmann et al. 2016). The 2.4 Å structure with glucose bound has been solved, explaining high affinity sugar recognition (Paulsen et al. 2019). The results suggest a proton donor/acceptor pair that links sugar transport to proton translocation. It contains a Lid domain, conserved in all sugar transport proteins, that locks the mobile transmembrane domains through a disulfide bridge, and creates a protected environment which allows efficient coupling of the proton gradient to drive sugar uptake (Paulsen et al. 2019).

STP10 of Arabidopsis thaliana

Glycerol:H⁺ symporter of 530 aas and 12 TMSs, GT1.  It is essnetial for the glycerol repression of the alcohol oxidase 1 (AOX1 gene (Zhan et al. 2016), and plays a role in glycerol and methanol metabolism in Pichia pastoris (Li et al. 2017).

.

GT1 of Komagataella pastoris (Yeast) (Pichia pastoris)

Myo inositol uptake porter of 574 aas and 12 TMSs, Fst1.  Also takes up the polyketide mycotoxin produced by Fusarium verticillioides during the colonization of maize kernels, Fumonisin B1 (FB1).  The activity was demonstrated with the orthologue in Weissella verticillioides (Niu et al. 2016). 

Fst1 of Weissella confusa

Hexose:proton symporter of 525 aas and 12 TMSs, Hxt5. Takes up D-glucose, D-fructose, D-xylose, D-mannose, D-galactose with decreasing affinity in this order (Rani et al. 2016).

Hxt5 of Piriformospora indica

Facilitative (Na⁺-independent) glucose-specific transporter (Km = 3 mM) of 486 aas and 12 TMSs, HT1; inhibited by cytochalasin B and localized to the midgut (Price et al. 2007).

HT1 of Nilaparvata lugens (Brown planthopper)

High-capacity facilitative transporter for trehalose, TRET1, required to induce anhydrobiosis. Anhydrobiotic larvae can survive almost complete dehydration. Does not transport maltose, sucrose or lactose. Transports trehalose synthesized in the fat body and incorporates trehalose into other tissues that require a carbon source, thereby regulating trehalose levels in the hemolymph (Kikawada et al. 2007; Kanamori et al. 2010).  70% identical to the Drosophila homologue, TC# 2.a.1.1.99.

TRET1 of Polypedilum vanderplanki (Sleeping chironomid)

Fructose uniporter, GLUT5.  The proteins from rat and cow have been crystalized and their structures have been determined in the open outward- and open inward-facing conformations, respectively. On the basis of comparisons of the inward-facing structures of GLUT5 and human GLUT1, a ubiquitous glucose transporter, a single point mutation proved to be enough to switch the substrate-binding preference from fructose to glucose. A comparison of the substrate-free structures of GLUT5 with occluded substrate-bound structures of E. coli XylE suggested that, in addition to a global rocker-switch-like re-orientation of the bundles, local asymmetric rearrangements of carboxy-terminal transmembrane bundle helices, TM7 and TM10, underlie a 'gated-pore' transport mechanism (Nomura et al. 2015).  GLUT5 is preferentially used for fructose uptake under (near) anoxic glycolysis to avoid feedback inhibition of phosphofructokinase (Park et al. 2017). Residues involved in fructose recognition have been identified (Ebert et al. 2017). Glucose (Glut-1 and 3) and fructose (Glut-2 and 5) transporter expression and regulation in the hummingbird occur independently of each other (Ali et al. 2020). Complex plastic mechanisms allow adaptation to environmental changes (Huang et al. 2023). C-3 modified 2,5-anhydromannitol (2,5-AM) compounds are inhibitory D-fructose analogues (Rana et al. 2023).  Discrimination of GLUTs by fructose isomers enables simultaneous screening of GLUT5 and GLUT2 activities in live cells (Gora et al. 2023). It may play a role in tumorigenesis (Hadzi-Petrushev et al. 2024).

Animals

SLC2A5 of Homo sapiens

Glucose transporter 1, GLUT1 or Slc2A1 of 491 aas and 12 TMSs.  Expression occurs in the mesodermal region of Xenopus embryos, especially in the dorsal blastopore lip at the gastrula stage.  It is an important player during gastrulation cell movement (Suzawa et al. 2007). This system is required for hepatocellular carcinoma proliferation and metastasis (Fang et al. 2021).

GLUT1 of Xenopus laevis (African clawed frog)

Myo-inositol-specific uptake transporter, ITR1 of 509 aas and 12 TMSs.  The K_m for myo-inositol is about 1 mM; glucose and other inositols are apparently not transported (Cushion et al. 2016).

ITR1 of Pneumocystis carinii

Bloom1 of 524 aas and 12 TMSs in a 6 + 6 arrangement. Mutations in the encoding gene give rise to shiny soybean seads with increased amounts of oil (Zhang et al. 2018). This protein is 50% identical to the sorbitol transporter of Prunus salicina (TC# 2.A.1.1.123).

Bloom1 of Glycine max (Soybean) (Glycine hispida) (Glycine soja)

Facilitative glucose transporter, GLUT2 of 503 aas and 12 TMSs.  Evidence suggests that the blunt snout bream is able to regulate its ability to metabolize glucose by improving GLUT2, GK, and PK expression levels (Liang et al. 2018).  The ortholog in grass carp (Ctenopharyngodon idellus) is exactly the same size and 98% identical throughout its length. It is found in the anterior and mid intestine as well as the liver (Liang et al. 2020).

GLUT2 of Megalobrama amblycephala (Chinese blunt snout bream) (Brema carp)

Sugar (mannose, fructose, glucose, galactose xylose) transporter of 521 aas and 12 TMSs, STP2 (Liu et al. 2018).

STP2 of Manihot esculenta (Cassava) (Jatropha manihot)

Galactose-specific uptake porter of 515 aas and 12 TMSs, STP16 (Liu et al. 2018).

STP16 of Manihot esculenta (Cassava) (Jatropha manihot)

Monosaccharide uptake porter of 529 aas and 12 TMSs, STP7. Transports mannose, galactose, glucose and fructose, but not xylose (Liu et al. 2018).

STP7 of Manihot esculenta (Cassava) (Jatropha manihot)

Glycerol:H⁺ symporter,WaStl1, of 561 aas and 12 TMSs. WaStl1 is a concentrative glycerol-H⁺ symporter with twice the affinity of S. cerevisiae. It is repressed by glucose and derepressed/induced by glycerol. This yeast, aerobically growing on glycerol, was found to produce ethanol, providing a redox escape to compensate the redox imbalance at the level of cyanide-resistant respiration (CRR) and glycerol 3P shuttle (da Cunha et al. 2019).

Glycerol porter of Wickerhamomyces anomalus

Maltose permease, HPMAL2, of 582 aas and 12 TMSs in a 1 + 5 + 6 TMS arrangement.  Expression of both of the adjacent HPMAL1 and HPMAL2 genes is coordinately regulated, repressed by glucose, and induced by maltose (Viigand et al. 2005).

MAL2 of Pichia angusta (Yeast) (Hansenula polymorpha)

Glut3 or Slc2a3a of 541 aas and 12 TMSs. Transcript analysis of zebrafish GLUT3 genes, slc2a3a and slc2a3b, have define overlapping as well as distinct expression domains in the central nervous system (Lechermeier et al. 2019).

Glut3 of Danio rerio

Hexose:H⁺ symporter of 534 aas and 12 TMSs.  Substrate accumulation can be up to 1500-fold;  one proton  is symporter per hexose taken up. Helices I, V, VII and XI interact with the sugar during translocation and line the transport path through the membrane (Tanner 2000).

Plants

Hup1 of Chlorella kessleri

Cellodextrin transporter, CtA or CDT-1, of 535 aas and 12 TMSs.  It transports cellobiose, cellotriose, cellotetraose and cellopeptaose, and its synthesis is induced by degradation products of cellulose (Lin et al., Feb. 2020, Identification and Characterization of a Cellodextrin Transporter in Aspergillus niger). It is 37% identical to the N crassa protein of the same specificity (TC# 2.A.1.1.82).

CtA of  Aspergillus niger

Lactose permease of 533 aas and 12 TMSs; 45% identical to 2.A.1.1.140 (Havukainen et al. 2020).

Lactose permease of Aspergillus nidulans

MFS-type cellodextrin transporter, CdtG, of 538 aas and 12 TMSs (Havukainen et al. 2020).

CdtG of Penicillium sp. 2HH

Facilitative glucose transporter 4, GLUT4, of 505 aas and 12 TMSs. MaGLUT4 is mainly distributed in muscle. Changes in the insulin, mRNA, and protein levels of MaGUT4 lagged far behind changes in blood glucose levels. This delay in insulin level changes and GLUT4 activation might be the reason for glucose intolerance of this fish species (Liang et al. 2020).

GLUT4 of Megalobrama amblycephala (Chinese blunt snout bream) (Brema carp)

Plant MFS porter of 521 aas and 12 TMSs. This system affects nutrient minerals concentrations in wheat grains and showed a pleiotropic effect on Ca²⁺, K⁺, Mg²⁺, Mn²⁺, and Sulfur (Alomari et al. 2021). In view of its association with sugar uptake porters, we suggest that it is a sugar transporter, and sugar uptake increases the energy of the grains so as to stimulate elemental ion uptake.

MFS porter of Triticum aestivum (bread wheat)

MFS-type sugar/inositol transporter of 510 aas and 12 TMSs. An orthologous system has been shown to be a highly specific L-arabinose transporter from Trichoderma reesei (Havukainen et al. 2021). Considering the high affinity for L-arabinose and low inhibition by D-glucose or D-xylose, Trire2_104072 could serve as a good candidate for improving the existing pentose-utilizing yeast strains (Havukainen et al. 2021).

L-Arabinose transporter of Penicillium sp.

MFS glucose transporter, Mfs1, of 550 aas and 12 TMSs. It is required for sugar transport, oxidative stress resistance, and pathogenicity of Colletotrichum gloeosporioides in Hevea brasiliensis (Liu et al. 2021). C. gloeosporioides is the causal agent of anthracnose in various plant species.

Mfs1 of Colletotrichum gloeosporioides

Glucose transporter 1, GLUT1, of 500 aas and 12 TMSs. EgGLUT1 Is crucial for the viability of Echinococcus granulosus sensu stricto metacestode and may be a new therapeutic target (Amahong et al. 2021).

GLUT1 of Echinococcus granulosus

High affinity hexose transporter, HxtA of 531 aas and 12 TMSs. HxtA is induced in vegetative hyphae upon starvation and in ascogenous hyphae during cleistothecium formation (Wei et al. 2004).

HxtA of Emericella nidulans (Aspergillus nidulans)

Hexose transporter-like protein, GCR1, of 541 aas and 12 TMSs. Substrates include glucose, mannose and fructose. It functions in catabolite repression (as does Snf3p in S. cerevisiae (TC# 2.A.1.1.18)) of peroxisome biogenesis and of peroxisomal enzymes (Stasyk et al. 2004).

GCR1 of Ogataea polymorpha (Hansenula polymorpha)

Facilitated trehalose transporter, Tret1-like, of 485 aas and 12 TMSs in a 6 + 6 TMS arrangement. Trehalose is the main blood sugar in insects and plays an important role in energy metabolism and stress resistance. Plutella xylostella (L.) is an agricultural pest worldwide. Tret1-like was cloned, knoched out and studied (Zhou et al. 2022). It was found that expression of the gene encoding PxTret1-like was affected by ambient temperature. A knockout mutation of PxTret1-like was generated, and the trehalose content and trehalase activity of the mutant increased at different developmental stages. The trehalose content increased in the fat body of the fourth-instar and decreased in the hemolymph. There was no significant change in glucose in the fat body and hemolymph. Mutant deletion strains of P. xylostella showed a significantly reduced survival rate, fecundity and ability to withstand extreme temperatures. Thus, PxTret1-like could affect the development, reproduction and temperature adaptability of P. xylostella by regulating the trehalose content in the fat body and hemolymph (Zhou et al. 2022).

Tret1-like transporter of Plutella xylostella

INT7 of 504 aas and 12 TMSs in a 6 + 6 TMS pattern. There are nine INT homologues in Populus trichocarpa, all presumed to transport inositor, and they are involved in stress responses (Zhang et al. 2023).

INT7 of Populus alba x Populus glandulosa

Sugar transporter of 529 aas and 12 TMSs.

Sugar transporter of Planoprotostelium fungivorum

Solute carrier family 2, facilitated glucose transporter member 8 of 509 aas and 12 TMSs. Symbiotic cnidarians such as corals and anemones form highly productive and biodiverse coral reef ecosystems in nutrient-poor ocean environments, a phenomenon known as Darwin's paradox (Cui et al. 2023). Using the sea anemone Aiptasia, we show that during symbiosis, the increased availability of glucose and the presence of the algae jointly induce the coordinated up-regulation and relocalization of glucose and ammonium transporters. These molecular responses are critical to support symbiont functioning and organism-wide nitrogen assimilation through glutamine synthetase/glutamate synthase-mediated amino acid biosynthesis (Cui et al. 2023). 

Glucose transporter of Exaiptasia diaphana

Sugar transporter ERD6-like 4 of 496 aas and 12 TMSs. Vacuolar sugar transporter EARLY RESPONSE TO DEHYDRATION 6-LIKE4 affects fructose signaling and plant growth (Khan et al. 2023).

ERD6-like 4 of Triticum aestivum

Mannosyltransferase  with 3 C-terminal TMSs in a 2 + 1 TMS arrangement. It is involved in N-Glycan biosynthesis and displays an unexpected minimal cellulose-synthase-like fold (Gandini et al. 2020).

MT of Pyrobaculum calidifontis

Putative sugar uptake transporter of 456 aas and 18 TMSs in a 6 + 6 + 6 TMS arrangement.  This protein has an N-terminal 6 TMSs that are not related to the MFS transporters, but the last 12 TMSs are homologous to members of MFS family 2.A.1.1. The N-terminal 6 TMSs are not related to sequences of the MFS but are homologous to members of the

MFS transporter of Alistipes sp. HGB5

Plastid glucose transporter 2, pGlcT2, of 493 aas and 12 TMSs. pGlcT2-GFP localized to the chloroplast envelope and is mainly produced in seedlings and in the rosette centers of mature Arabidopsis plants. Therefore, pGlcT2 acts as a glucose importer that can limit cytosolic glucose availability in developing pGlcT2-overexpressing seedlings (Valifard et al. 2023). Possibly pGlcT2 contributes to a release of glucose derived from starch mobilization late in the light phase.

pGlcT2 of Arabidopsis thaliana

Solute carrier family 2, facilitated glucose transporter member 1a, Glut1 of 488 aas and 12 TMSs. Bisphenol S inhibits Glucose Transporter 1, leading to ATP excitotoxicity in the Zebrafish brain (Wang et al. 2024).

GLUT1 of Danio rerio

Low-affinity hexose (glucose, fructose, mannose, 2-deoxyglucose) uniporter.  The evolution of hexose transporters in kinetoplastid protozoans has been studied (Pereira and Silber 2012).

Protozoa

Gtr2 (D2) of Leishmania donovani

Glucose/mannose/fructose transporter and high affinity sensor, Snf3p, (regulates glucose transport via other systems).  Residues involved in ligand preference are similar to those involved in transport (Dietvorst et al. 2010).  Snf3p in Candida glabrata is essential for growth in low glucose media but not high glucose media, and plays a role in the induction of severall hexose transporters (Ng et al. 2015).

Yeast

Snf3p of Saccharomyces cerevisiae

Glucose transporter and low affinity sensor, Rgt2p (regulates glucose transport in conjunction with Snf3p). Rgt2 generates an intracellular signal in response to glucose that leads to inhibition of the Rgt1 transcriptional repressor and consequently to derepression of HXT genes encoding glucose transporters. They have unusually long C-terminal tails that bind to Mth1 and Std1, paralogous proteins that regulate the function of the Rgt1 transcription factor. Scharff-Poulsen et al. 2018 showed that the C-terminal tail of Rgt2 is not responsible for its inability to transport glucose. RGT2 mutations that cause constitutive signal generation alter evolutionarily-conserved amino acids in the transmembrane spanning regions involved in maintaining an outward-facing conformation or the substrate binding site. These mutations may cause Rgt2 to adopt inward-facing or occluded conformations that generate the glucose signal. The cytoplasmic C-terminal domains of the yeast cell surface receptors Rgt2 and Snf3 play multiple roles in glucose sensing and signaling (Kim et al. 2024).

Yeast

Rgt2p of Saccharomyces cerevisiae

Arabinose (xylose; galactose):H⁺ symporter, AraE (low affinity high capacity) (Khlebnikov et al. 2001).

Bacteria

AraE of E. coli (P0AE24)

Hexose (Glucose and Fructose) transporter, PfHT1 of 504 aas and 12 TMSs. This is the only hexose transporter, and it is found in the plasma membrane. It is an antimalarial drug target (Meier et al. 2018; Wunderlich 2022).

Protozoa

PfHT1 of Plasmodium falciparum

Myoinositol:H⁺ symporter, HMIT (also transport other inositols including scyllo-, muco- and chiro-, but not allo-inositol) (Aouameur et al., 2007). Expressed in the Golgi of the hippocampus and cortex. May also transport inositoltriphosphate (Di Daniel et al., 2009). Interacts directly with γ-secretase (9.B.47.1.1) to regulate its activity and the production of Abeta production, important in Alzheimer's disease (Teranishi et al. 2015).

Animals

SLC2A13 of Homo sapiens

Major myoinositol:H⁺ symporter, IolT, of 473 aas and 12 TMSs in a 6 + 6 TMS pattern (Yoshida et al. 2002).

Bacteria

IolT (YdjK) of Bacillus subtilis

Minor, low affinity myoinositol:H⁺ symporter, IolF, of 438 aas and 12 TMSs (Yoshida et al. 2002).

Bacteria

IolF of Bacillus subtilis

The erythrocyte/brain hexose facilitator, glucose transporter-1, Gtr1. SLC2a1 or Glut1. Transports D-glucose, dehydroascorbate, arsenite and the flavonone, quercetin, via one pathway and water via a distinct channel. Sugar transport has been suggested to function via a sliding mechanism involving several sugar binding sites (Cunningham et al., 2006). Glut1 is the receptor for human T-cell leukemia virus (HTLV)) (Manel et al., 2003). The orientation of the 12 TMSs and the conformation of the exofacial glucose binding site of GLUT1 have been proposed (Mueckler and Makepeace 2004). It is regulated by stomatin (TC# 8.A.21) to take up dehydroascorbate (Montel-Hagen et al., 2008). Mutations cause Glut1 deficiency syndrome, a human encephalopathy that results from decreased glucose flux through the blood brain barrier (Pascual et al., 2008).  Mueckler and Makepeace (2009) have presented a model of the exofacial substrate-binding site and helical folding of Glut1. Glut1, 2, 4 and 9 are functional both in the plasma membrane and the endoplasmic reticulum (Takanaga and Frommer, 2010). Glut1 is down-regulated in the brains of Alzheimer's disease patients (Liu et al., 2008b). Metabolic stress rapidly stimulates blood-brain barrier endothelial cell sugar transport by acute up-regulation of plasma membrane GLUT1 levels, possibly involving an AMP-activated kinase activity (Cura and Carruthers, 2010). Serves as a receptor for neuropilin-1 (923aas; 2 TMSs; O14786) and heparan sulfate proteoglycans (HSPGs) (Hoshino, 2012). Glut1 has a nucleotide binding site, and nucleotide binding affects transport activity (Yao and Bajjalieh 2009).  The protein serves as a receptor for dermatin and β-adducin which help link the spectrin-actin junctional complex to the erythrocyte plasma membrane (Khan et al. 2008).  May play a role in paroxysmal dyskinesias (Erro et al. 2017). GLUT1 mediates infection of CD4+ lymphocytes by human T cell leukemia virus type 1 (Jin et al. 2006). Mutations in disordered regions can cause disease by introducing dileucine motifs, For example, mutations that are causative of GLUT1 deficiency syndrome are of this type, and the mutated protein mislocalizes to intracellular compartments (Meyer et al. 2018). Glucose transits along a transmembrane pathway through significant rotational motions while maintaining hydrogen bonds with the protein (Galochkina et al. 2019). It is phosphoryated by protein kinase C-B (TC# 8.A.104.1.4) (Lee et al. 2015). GLUT1-mediated exchange of fluorosugars has been studied (Shishmarev et al. 2018). Resveratrol and soy isoflavones alone and in combination improve the learning and memory of aging rats. The mechanism may be related to up-regulating the expression of GLUT1 and GLUT3 genes in the hippocampus (Zhang et al. 2020). The pore diameters of the transmembrane glucose transporters of all Class I GLUT proteins are constricted upon depletion of unsaturated fatty acids in the membranes (Weijers 2020). Diclofenac inhibits tumor cell glycolysis and growth by decreasing GLUT1 expression (Yang et al. 2021). Almost the entire populations of Glut1 and three other transmembrane proteins are immobilized by either the incorporation within large multiprotein complexes or entrapment within the protein network of the cortical spectrin cytoskeleton (Kodippili et al. 2020). This system is required for hepatocellular carcinoma proliferation and metastasis (Fang et al. 2021). The main triggers FoR activation of transport are located within the solvent accessible linker regions in the extramembranous zones (Gonzalez-Resines et al. 2021). DHHC9-mediated GLUT1 S-palmitoylation is requuired for plasma membrane localization and promotes glioblastoma glycolysis and tumorigenesis (Zhang et al. 2021). An ancient family of arrestin-fold proteins, termed alpha-arrestins, have conserved roles in regulating nutrient transporter trafficking and cellular metabolism as adaptor proteins. One alpha-arrestin, TXNIP (thioredoxin-interacting protein), is known to regulate myocardial glucose uptake, but the in vivo role of the related alpha-arrestin, ARRDC4 (arrestin domain-containing protein 4), was unknown. Interactions of ARRDC4 with GLUT1 prove to mediate metabolic stress in the ischemic heart (Nakayama et al. 2022). Mercury (Hg²⁺) decreased membrane deformability, impairing RBC capacity to deal with the shear forces in the circulation, increasing membrane fragmentation, and affecting transport (Notariale et al. 2022). GLUT-1 and GLUT-3 play important roles in the development of some types of malignant tumors, including glioblastoma, and expression of both is regulated by miRNAs (Beylerli et al. 2022). Glucose uptake inhibitors via Glut1 are potential anticancer agents (Hung et al. 2022). GLUT1 deficiency syndrome (GLUT1DS1) is a rare genetic metabolic disease, characterized by infantile-onset epileptic encephalopathy, global developmental delay, progressive microcephaly, and movement disorders (e.g., spasticity and dystonia) (Mauri et al. 2022). It is caused by heterozygous mutations in the SLC2A1 gene, which encodes the GLUT1 protein, a glucose transporter across the blood-brain barrier (BBB). Most commonly, these variants (~2 dozen) arise de novo, resulting in sporadic cases, although several familial cases with AD inheritance pattern have been described (Mauri et al. 2022). Fluoride exposure affects the expression of glucose transporters (GLUT1 and 3) and ATP synthesis (Chen et al. 2023). GLUT1 is necessary for the flexor digitorum brevis (FDB) to survive hypoxia, but overexpression of GLUT1 was insufficient to rescue other skeletal muscles from hypoxic damage (Amorese et al. 2023). The role of GLUT inhibitors, micro-RNAs, and long non-coding RNAs that aid in inhibiting glucose uptake by cancer cells have been discussed as potential theraputics (Chamarthy and Mekala 2023). GLUT1 overexpression in tumor cells is a potential target for drug therapy (Zhao et al. 2023). HSP90B1-mediated plasma membrane localization of GLUT1 promotes radioresistance of glioblastomas (Li et al. 2023).  The core genes (Fgf2, Pdgfra, Ptpn11, Slc2a1) are highly expressed in sevoflurane anesthesia brain tissue samples. The 4 core genes (Fgf2, Pdgfra, Ptpn11, and Slc2a1) are associated with neurodegenerative diseases, brain injuries, memory disorders, cognitive disorders, neurotoxicity, drug-induced abnormalities, neurological disorders, developmental disorders, and intellectual disabilities. Fgf2 and Ptpn11 are highly expressed in brain tissue after sevoflurane anesthesia, the higher the expression level of Fgf2 and Ptpn11, the worse the prognosis (Zhang and Xu 2023). Target separation and potential anticancer activity of withanolide-based glucose transporter protein 1 inhibitors from Physalis angulata var. villosa have been evaluated (Zhang et al. 2023).  PIGT is a subunit of the glycosylphosphatidylinositol transamidase which is involved in tumorigenesis and invasiveness.  PIGT promotes cell growth, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking (Tan et al. 2024).  PDGF-stimulated glucose uptake via Glut1 has been reported to be dependent on receptor/transporter endocytosis (Tsutsumi et al. 2024).  Glucose transporter-1 deficiency syndrome gives rise to extreme phenotypic variability in a five-generation family carrying a novel SLC2A1 variant (Giugno et al. 2024).  A 4-furanylvinylquinoline derivative is a new scaffold for the design of oxidative stress initiator and a glucose transporter inhibitor via GLUT1 (Kuczak et al. 2024).

Animals

SLC2A1 of Homo sapiens

Glucosamine/glucose/fructose uniporter, Glut-2, Glut2 or ATG9A; it may also transport dehydroascorbate (Mardones et al., 2011; Maulén et al., 2003), and cotransports water against an osmotic gradient (Naftalin, 2008).  Mutations may give rise to the rare autosomal recessive Fanconi-Bickel syndrome (Batool et al. 2019). It mediates intestinal transport of quercetrin (Li et al. 2020) and can transport the drug gastrodin, a seditive with a strcture of a phenolic glucoside (Huang et al. 2023). It also functions in autophagy. The cryoEM structure of the human ATG9A isoform at 2.9-Å resolution has been solved (Guardia et al. 2020). The structure reveals a fold with a homotrimeric domain-swapped architecture, multiple membrane spans, and a network of branched cavities, consistent with ATG9A being a membrane transporter. Mutational analyses support a role for the cavities in the functions of ATG9A. Structure-guided molecular simulations predict that ATG9A causes membrane bending, explaining the localization of this protein to small vesicles and highly curved edges of growing autophagosomes (Guardia et al. 2020). Both GLUT2 and GLUT3 have been expressed in yeast and exhibit most of the characteristics of the proteins expressed in humans (Schmidl et al. 2020). Autophagy is a highly conserved pathway that the cell uses to maintain homeostasis, degrade damaged organelles, combat invading pathogens, and survive pathological conditions. A set of proteins, called ATG proteins, comprise the core autophagy machinery and work together in a defined hierarchy. ATG9A vesicles are at the heart of autophagy, as they control the rapid de novo synthesis of an organelle called the phagophore. ATG9A is present in different membrane compartments (van Vliet et al. 2023).  Metformin increases the uptake of glucose into the gut from the circulation in high-fat diet-fed male mice, which is enhanced by a reduction in whole-body Slc2a2 expression (Morrice et al. 2023).  Increased expression of Glucose Transporter 2 (GLUT2) is observed on the peripheral blood insulin-producing cells (PB-IPC) in type 1 diabetic patients after receiving stem cell educator therapy (Zhao et al. 2024).

Animals

SLC2A2 of Homo sapiens

Xylose (xylopyranose):H⁺ symporter of 491 aas and 12 TMSs (Wambo et al. 2017).  Also transports and binds D-glucose and 6-bromo-6-deoxy-D-glucose.  The 3-d structure is known in three conformers, outward occluded, inward occluded and inward open (Sun et al. 2012: Quistgaard et al. 2013).  Most of the sugar-binding residues are conserved with the human Glut-1, 2, 3 and 4 homologues.  The coalescence of intramolecular tunnels and cavities has been postulated to account for facilitated diffusion of sugars (Cunningham and Naftalin 2014). Protonation of a conserved aspartate triggers a conformational transition from the outward-facing to the inward-facing state. This transition only occurs in the presence of substrate xylose, while the inhibitor glucose locks the transporter in the outward-facing state (Jia et al. 2020).

Bacteria

XylE of E. coli (P0AGF4)

Low affinity, constitutive, glucose (hexose; xylose) uniporter, Hxt4 (LGT1; Rag1) (also transports arsenic trioxide [As(OH)₃] as do Hxtl, 3, 5, 7 and 9) (Liu et al., 2004).  The Kluyveromyces lactis ortholog is 73% identical and is similarly regulated (Rolland et al. 2006). Key residues for efficient glucose transport by the hexose transporter CgHxt4 in the high sugar fermentation yeast Candida glycerinogenes.have been identified (Qiao et al. 2021).

Yeast

Hxt4 of Saccharomyces cerevisiae

High affinity, glucose-repressible, glucose (hexose) uniporter (Hxt6/Hxt7). Asn331 and hydrophobic residue side chains in TMS5 determine substrate affinity (Kasahara et al., 2011; Kasahara and Kasahara 2010).  Also transports xylose (Wang et al. 2013).

Yeast

Hxt6/Hxt7 of Saccharomyces cerevisiae
Hxt6 (P39003)

The low affinity, glucose-inducible glucose transporter, MstE (Forment et al., 2006)

Fungi

MstE of Aspergillus nidulans (Q400D8)

The monosaccharide (MST) (glucose > mannose > galactose > fructose):H⁺ symporter, MST1 (Schussler et al., 2006).

Fungi

MST1 of Geosiphon pyriformis (A0ZXK6)

Vacuolar (tonoplast) glucose transporter1, Vgt1 (important for seed germination and flowering) (Aluri and Büttner, 2007)

Plants

Vgt1 of Arabidopsis thaliana (Q8L6Z8)

The blastocyst/testis glucose transporter, Glut8 (Doege et al., 2000) (insulin stimulated in blastocysts) (Carayannopoulos et al., 2000).

Animals

Glut8 of Mus musculus (Q9JIF3)

The embryonic liver, kidney, and other tissue uric acid (urate) transporter, Glut9 (SLC2A9) (Wright et al. 2010). Mutations in this transporter cause severe renal hyperuricemia.  It transports hexoses as well as urate, the latter by an electrogenic uniport mechanism.  It's transcription is regulated by a hepatocyte nuclear factor, HNF4α (Prestin et al. 2014).

Animals

Glut9 of Mus musculus (Q5ERC7)

The glucose/fructose:H⁺ symporter, STP13 (sugar transport protein 13). Expressed in vascular tissues and induced during programmed cell death (Norholm et al., 2006).  Used to combat bacterial infection by competing with them for sugars by phosphorylation of STP13 by the BAK1 receptor kinase (Yamada et al. 2016).

Plants

STP13 of Arabidopsis thaliana (Q94AZ2)

Myo-Inositol uptake porter, IolT1 (Km=0.2mM) (Krings et al., 2006).  Can also transport D-glucose (Ikeda et al. 2011).

Bacteria

IolT1 of Corynebacterium glutamicum (Q8NTX0)

Myo-Inositol (Km=0.45mM) uptake porter, IolT2 (Krings et al., 2006).  Can not transport D-glucose (Ikeda et al. 2011).

Actinobacteria

IolT2 of Corynebacterium glutamicum (Q8NL90)

L-arabinose:proton symporter, AraE (Sa-Nogueira and Ramos, 1997). Also transports xylose, galactose and α-1,5 arabinobiose (Ferreira and Sá-Nogueira, 2010).

Bacteria

AraE of Bacillus subtilis (P96710)

High affinity (15 μM) glucose (monosaccharides including xylose):H⁺ symporter, MstA (Jørgensen et al., 2007).

Fungi

MstA of Aspergillus niger
(Q8J0V1)

Low affinity glucose:H⁺ symporter, MstC (Jørgensen et al., 2007).

Fungi

MstC of Aspergillus niger
(Q8J0U9)

Galactose, glucose uniporter, Gal2. Also transports xylose (Wang et al. 2013).  This transporter has been engineered by mutation (N376F) to transport xylose without being inhibited by glucose or transporting other hexoses (Farwick et al. 2014).  The 3-d structure is known (Wang et al. 2015).

Yeast

Gal2 of Saccharomyces cerevisiae