| TCID | Name | Domain | Kingdom/Phylum | Protein(s) |
|---|---|---|---|---|
|
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). Asp55 and Asp59 are essential for Na+ binding. Asp124 may play a critical role by allowing Na+-induced conformational changes and sugar binding. Asp19 may facilitate melibiose binding (Granell et al., 2010). The alternate access mechanism fits better into a flexible gating mechanism rather than the archetypical helical rigid- body rocker-switch mechanism (Wang et al. 2016). Crystal structures of Salmonella typhimurium MelB in two conformations, representing an outward partially occluded and an outward inactive state (Ethayathulla et al. 2014). MelB adopts a typical MFS fold and contains a previously unidentified cation-binding motif. Three conserved acidic residues form a pyramidal-shaped cation-binding site for Na+, Li+ or H+, which is in close proximity to the sugar-binding site. Both cosubstrate-binding sites are mainly contributed by the residues from the amino-terminal domain (Ethayathulla et al. 2014). The Glucose Enzyme IIA protein of the PTS binds MelB either in the absence or presence of a galactoside, and binding decreases the affinity for melibiose, giving rise to inducer exclusion (Saier 1989; Hariharan and Guan 2014). A D55C mutant converted MelBSt to a solely H+-coupled symporter, and together with the free-energy perturbation calculation, Asp59 is the sole protonation site of MelBS of Salmonella typhimurium. Unexpectedly, the H+-coupled melibiose transport exhibited poor activities at greater bulky ΔpH and better activities at reversal ΔpH, supporting the novel theory of transmembrane-electrostatically localized protons and the associated membrane potential are the primary driving forces for H+-coupled symport mediated by MelBSt (Hariharan et al. 2024). MelBSt trapped by camelid single-domain nanobodies (Nbs) retained its physiological functions, and the trapped conformation is similar to that bound by the physiological regulator EIIAGlc (Katsube et al. 2023). | Bacteria |
Pseudomonadota | MelB of E. coli (A7ZUZ0) |
|
2.A.2.1.2 | Probable fucosyl-α-1,6-N-acetylglucosamine uptake porter, AlfD (next to and in an operon with a fucosidase (AlfA) specific for this disaccharide which is present in mammalian glycoproteins, glycolipids and milk (Rodríguez-Díaz et al. 2012). | Bacteria |
Bacillota | AlfD of Lactobacillus casei |
|
2.A.2.1.3 | Uncharacterized protein, probably a sugar:H+ symporter of 474 aas and 12 TMSs, YjmB, The gene was from a marine sediment metagenome. | Archaea |
Candidatus Lokiarchaeota | YjmB of Lokiarchaeum sp. GC14_75 |
|
2.A.2.2.1 | Lactose permease, LacS. Mediates uptake of β-galactooligosaccharides, lactitol, and a broad range of prebiotic β-galactosides that selectively stimulate beneficial gut microbiota (Andersen et al., 2011). | Bacteria |
Bacillota | LacS of Streptococcus thermophilus |
|
2.A.2.2.2 | Raffinose permease | Bacteria |
Bacillota | RafP of Pediococcus pentosaceus |
|
2.A.2.2.3 | Galactose permease of 462 aas and 12 TMSs. Transports galactose (Grossiord et al. 2003). | Bacteria |
Bacillota | GalP of Lactococcus lactis |
|
2.A.2.3.1 | Glucuronide permease, UidB, GusB, UidP (Liang et al., 2005; Moraes and Reithmeier 2012) | Bacteria |
Pseudomonadota | GusB of E. coli |
|
2.A.2.3.2 | Pentoside permease | Bacteria |
Bacillota | XynC (YnaJ) of Bacillus subtilis |
|
2.A.2.3.3 | Isoprimeverose (α-D xylopyranosyl-(1,6)-D-glucopyranose) permease [xylose is not a substrate] (Heuberger et al., 2001) | Bacteria |
Bacillota | XylP of Lactobacillus pentosus |
|
2.A.2.3.4 | Probable α-xyloside uptake permease, YicJ (Laikova et al., 2001) | Bacteria |
Pseudomonadota | YicJ of E. coli (P31435) |
|
2.A.2.3.5 | Probable β-xyloside uptake permease, YagG (Laikova et al., 2001) | Bacteria |
Pseudomonadota | YagG of E. coli (P75683) |
|
2.A.2.3.6 | The putative cellobiose porter, BglT (Rodionov et al. 2010) | Bacteria |
Pseudomonadota | BglT of Shewanella amazonensis (A1S5F2) |
|
2.A.2.3.7 | The putative arabinoside porter, AraT (Rodionov et al., 2010) | Bacteria |
Pseudomonadota | AraT of Shewanella sp. MR-4 (Q0HIQ0) |
|
2.A.2.3.8 | Major Facilitator Superfamily Domain containing 2A, MFSD2A or SLC59A1 (543aas, 12 TMSs). It is the omega-3-fatty acid transporter that plays a role in thermogenesis via β-adrenergic signaling. It takes up Tunicamycin (TM), a mixture of related species of nucleotide sugar analogs fatty-acylated with alkyl chains of varying lengths and degrees of unsaturation, produced by several Streptomyces species (Bassik and Kampmann, 2011; Reiling et al., 2011). It is a sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier endothelium. It is the primary route for import of docosahexaenoic acid and other long-chain fatty acids into foetal and adult brain, and is essential for mouse and human brain growth and function (Quek et al. 2016). In addition to a conserved sodium-binding site, three structural features were identified: A phosphate headgroup binding site, a hydrophobic cleft to accommodate a hydrophobic hydrocarbon tail, and three sets of ionic locks that stabilize the outward-open conformation. Ligand docking studies and biochemical assays identified Lys436 as a key residue for transport. It forms a salt bridge with the negative charge on the phosphate headgroup. Mfsd2a transports structurally related acylcarnitines but not a lysolipid without a negative charge, demonstrating the necessity of a negative charged headgroup interaction with Lys436 for transport. These findings support a novel transport mechanism by which LPCs are flipped within the transporter cavity by pivoting about Lys436 leading to net transport from the outer to the inner leaflet of the plasma membrane (Quek et al. 2016). Docosahexaenoic acid is an omega-3 fatty acid that is essential for neurological development and function, and it is supplied to the brain and eyes predominantly from dietary sources. This nutrient is transported across the blood-brain and blood-retina barriers as lysophosphatidylcholine. The structure of MFSD2A has been determined using single-particle cryo-EM (Cater et al. 2021). The transporter is in an inward-facing conformation and features a large amphipathic cavity that contains the Na+-binding site and a bound lysolipid substrate. This structure reveals details of how MFSD2A interacts with substrates and how Na+-dependent conformational changes allow for the release of these substrates into the membrane through a lateral gate. This atypical MFS transporter mediates the uptake of lysolipids into the brain. Homozygous variants in the MFSD2A gene cause severe primary microcephaly, brain malformations, developmental delay, and epilepsy (Khuller et al. 2021). Bi-allelic MFSD2A variants cause autosomal recessive primary microcephaly type 15 and broaden the phenotypic spectrum associated with these pathogenic variants, emphasizing the role of MFSD2A in early brain development. Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A have been documented (Bergman et al. 2023). Automated collective variables have been discovered for MFSD2A from molecular dynamics simulations (Oh et al. 2024). | Eukaryota |
Metazoa, Chordata | MFSD2A of Homo sapiens (Q8NA29) |
|
2.A.2.3.9 | Bacteria |
Pseudomonadota | ||
|
2.A.2.3.10 | Transmembrane protein 180 | Eukaryota |
Metazoa, Chordata | TMEM180 of Homo sapiens |
|
2.A.2.3.11 | Putative transporter | Eukaryota |
Euglenozoa | Putative transporter of Trypanosoma cruzi |
|
2.A.2.3.12 | Putative sugar transporter | Bacteria |
Deinococcota | TT_P0219 pf Thermus thermophilus |
|
2.A.2.3.13 | Probable sugar transporting MFS-2 symporter of 444 aas and 12 TMSs. | Archaea |
Candidatus Thorarchaeota | MFS carrier of Candidatus Thorarchaeota archaeon |
|
2.A.2.3.14 | Probable sugar:cation symporter, MFSD13A or TMEM180, with 517 aas and 12 TMSs with the N- and C-termini reported to be exposed extracellularly (Anzai and Matsumura 2019). It has anti-tumor activity (Yasunaga et al. 2019) and is highly expressed in colorectal cancer (CRC) (Anzai et al. 2021; Shiraishi et al. 2021). It is also a schizophrenia risk factor (Wang et al. 2021). | Eukaryota |
Metazoa, Chordata | TMEM180 of Homo sapiens |
|
2.A.2.3.15 | Probable sulfoquinovose importer of 467 aas and 12 TMSs (Denger et al. 2014). Sulphoquinovose (SQ, 6-deoxy-6-sulphoglucose) is the polar headgroup of the plant sulpholipid in the photosynthetic membranes of all higher plants, mosses, ferns, algae, most photosynthetic bacteria, and some non-photosynthetic bacteria. It is part of the surface layer of some Archaea. The estimated annual production of SQ is 10,000,000,000 tonnes (10 petagrams) (Denger et al. 2014). | Bacteria |
Pseudomonadota | Sulfoquinovose importer of E. coli |
|
2.A.2.3.16 | MfsD2B or SLC59A2 protein of 504 aas and 12 TMSs (). It is a cation-dependent lipid transporter that specifically mediates export of sphingosine-1-phosphate from red blood cells and platelets (Vu et al. 2017). Sphingosine-1-phosphate is a signaling sphingolipid, and its export from red blood cells into in the plasma is required for red blood cell morphology. It does not transport lysophosphatidylcholine (LPC). | Eukaryota |
Metazoa, Chordata | MfsD2B of Homo sapiens |
|
2.A.2.3.17 | Putative sugar: cation symporter, GPH, of 548 aas and 12 TMSs in a 6 + 6 TMS arrangement (Wunderlich 2022). | Eukaryota |
Apicomplexa | GPH of Plasmodium falciparum |
|
2.A.2.4.1 | Liu et al. 2023Sucrose:H+ symporter, Suc1 or Sut1. It provides osmotic driving force for anther dehiscence, pollen germination and pollen tube growth and also transports other glucosides such as maltose and phenylglucosides. Km (sucrose)= 0.5 mM. (Stadler et al., 1999)). In wheat (Triticum aesticum), there are at least three isoforms designated Sut2A, Sut2B and Sut2D (Deol et al. 2013). The ortholog in the common bean, Phaseolus vulgaris (SUT1.1), has been characterized as a high affinity sucrose:H+ symporter (Santiago et al. 2020). SUTs in rice play a role in the apoplastic loading as a major phloem loading strategy (Wang et al. 2021). Some Suts can transport sucrose, glucose, fructose and mannose (Liu et al. 2023).
| Eukaryota |
Viridiplantae, Streptophyta | 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). Sut1 is a sucrose protein symporter. Protons can move in the absence of sucrose (Carpaneto et al., 2010), but upon addition of sucrose, it becomes a symporter. Arg-188 in the rice orthologue and homologues are essential (Sun and Ward 2012). | Eukaryota |
Viridiplantae, Streptophyta | Sut1 of Zea mays (BAA83501) |
|
2.A.2.4.3 | Sucrose:H+ symporter, Suc3 or Sut3 of 464 aas. 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). | Eukaryota |
Viridiplantae, Streptophyta | Suc3 of Arabidopsis thaliana (O80605) |
|
2.A.2.4.4 | The brain proton:associated sugar (glucose) transporter, PAST-A (Shimokawa et al., 2002) | Eukaryota |
Metazoa, Chordata | PAST-A of Rattus norvegicus (Q8K4S3) |
|
2.A.2.4.5 | The proton:sucrose uptake symporter, Sut1 (Zhang & Turgeon et al., 2009). | Eukaryota |
Viridiplantae, Streptophyta | Sut1 of Verbascum phoeniceum (D1GC38) |
|
2.A.2.4.6 | Vacuolar sucrose;H+ symporter, Suc4, catalyzes sucrose export from vacuoles (Schulz et al., 2011). The interactome of the sucrose transporter, StSUT4, in potato is connected to ethylene and calcium signaling (Garg et al. 2022). | Eukaryota |
Viridiplantae, Streptophyta | Suc4 of Arabidopsis thaliana (Q9FE59) |
|
2.A.2.4.7 | Solute carrier family 45, member 4, SLC45A4. Transports sucrose by a proton symport mechanism. Found ubiquitously throughout the tissues of the body (Bartölke et al. 2014). SLC45A4 encodes a mitochondrial putrescine transporter that promotes γ-aminobutyric acid (GABA) de novo synthesis (Colson et al. 2024). The expression of SLC45A4 also has a strong positive correlation with the cellular level of GABA. | Eukaryota |
Metazoa, Chordata | SLC45A4 of Homo sapiens |
|
2.A.2.4.8 | solute carrier family 45, member 3, Slc45A3. Sucrose:proton symporter associated with prostate cancer and myelination (Bartölke et al. 2014). Four members of the SLC45 family, SLC45A1-SLC45A4, were differentially expressed in melanoma, but only SLC45A2 and SLC45A3 had prognostic guiding values (Xie et al. 2021). | Eukaryota |
Metazoa, Chordata | SLC45A3 of Homo sapiens |
|
2.A.2.4.9 | Solute carrier family 45, member 2, Slc45A2, also called melanocyte-restricted antigen or melanoma antigen, PatP or Aim1. Transports sucrose, glucose and fructose with protons, possibly into vesicular structures that contain melanin (Vitavska et al. 2018). Found in skin and hair; involved in pigmentation (Bartölke et al. 2014). Defects give rise to oculocutaneous albinism (Meyer et al. 2011). One such mutation in dogs, G493D in TMS 11, gives rise to albinisms (Wijesena and Schmutz 2015). OCA type IV (OCA4, OMIM) develops due to homozygous or compound heterozygous mutations in the solute carrier family 45, member 2 (SLC45A2) gene, and many mutations in this human gene have been identified (Inagaki et al. 2006; Tóth et al. 2017). It interacts with 14-3-3 proteins (see TC# 8.A.98). Multiple pathogenic variants in SLC45A2 give rise to oculocutaneous albinism (Lewis and Girisha 2019). Reviewed by Wiriyasermkul et al. 2020. Four members of the SLC45 family, SLC45A1-SLC45A4, were differentially expressed in melanoma, but only SLC45A2 and SLC45A3 had prognostic guiding values (Xie et al. 2021). | Eukaryota |
Metazoa, Chordata | SLC45A2 of Homo sapiens |
|
2.A.2.4.10 | Proton:glucose symporter A; proton-associated sugar transporter A (PAST-A) (present in brain and deleted in neuroblastoma 5 (DNb-5). Solute carrier family 45 member 1, SLC45A1 (Bartölke et al. 2014). | Eukaryota |
Metazoa, Chordata | SLC45A1 of Homo sapiens |
|
2.A.2.4.11 | Sucrose transport protein SUT5 (Sucrose permease 5) (Sucrose transporter 5) (OsSUT5) (Sucrose-proton symporter 5). Sucrose transporter proteins (SUTs) play roles in the phloem loading and unloading of sucrose. The SUT gene family was identified in four Solanaceae species (Capsicum annuum, Solanum lycopersicum, S. melongena, and S. tuberosum) and 14 other plant species ranging from lower and higher plants. The analysis was performed by integration of chromosomal distribution, gene structure, conserved motifs, evolutionary relationship and expression profiles during pepper growth under stresses (Chen et al. 2022). | Eukaryota |
Viridiplantae, Streptophyta | SUT5 of Oryza sativa subsp. japonica |
|
2.A.2.4.12 | Sucrose:H+ symporter, SUC5. Also transports biotin and possibly maltose (Pommerrenig et al. 2012). | Eukaryota |
Viridiplantae, Streptophyta | SUC5 of Arabidopsis thaliana |
|
2.A.2.4.13 | Scratch, orthologue 1, SCRT; SLC45A2; transports sucrose into pigment-containing vesicles or granules. Mutations give rise to oculocutaneous albinism (Meyer et al. 2011). | Eukaryota |
Metazoa, Arthropoda | SCRT of Drosophila melanogaster |
|
2.A.2.4.14 | Melanocyte-specific antigen or melanoma antigen, MatP, Slc45a2, Aim-1, AIM1, at the mouse underwhite locus. Regulated by a melanocyte-specific transcription factor essential for pigmentation, MITF (Du and Fisher 2002). Mutations in MatP in humans cause oculocutaneous albinism type IV (OCA4), an autosomal recessive inherited disorder which is characterized by reduced biosynthesis of melanin pigmentation in skin, hair and eyes. The MATP protein consists of 530 amino acids which contains 12 TMSs (Kamaraj and Purohit 2016). The D93N mutation causes oculocutaneous albinism 4 (OCA4), and the L374F mutatioin correlates with light pigmentation in European populations. Corresponding mutations were produced in the related and well-characterized sucrose transporter from rice, OsSUT1, and transport activity was measured by heterologous expression in Xenopus laevis oocytes and 14C-sucrose uptake in yeast. The D93N mutant had completly lost transport activity while the L374F mutant showed a 90% decrease in transport activity, although the substrate affinity was unaffected (Kamaraj and Purohit 2016). Mutations in MATP protein showed loss of stability and became more flexible, which alter its structural conformation and function (Kamaraj and Purohit 2016). | Eukaryota |
Metazoa, Chordata | Aim1 of Mus musculus |
|
2.A.2.4.15 | Putative glycoside transporter of 401 aas and 12 TMSs. | Eukaryota |
Evosea | UP of Entamoeba histolytica |
|
2.A.2.4.16 | Maltose/sucrose H+:symporter, Sut1 (maltose, Km = 6 μM; sucrose, Km = 36 μM) of 553 aas and 12 TMSs in a 4 + 2 + 2 + 4 TMS arrangement (Reinders and Ward 2001). Thus, unlike S. cerevisiae, S. pombe utilizes maltose transporters derived from a protein from an ancestor of the plant SUTs. | Eukaryota |
Fungi, Ascomycota | Sut1 of Schizosaccharomyces pombe |
|
2.A.2.4.17 | High affinity sucrose transporter of 617 aas and 12 TMSs, Sut1B. It is regulated by the protein CBF1 (NCBI acc # WJK44481.1) in the pineapple (Ananas comosus). This sucrose transporter AcSUT1B, regulated by AcCBF1, exhibits enhanced cold tolerance in transgenic Arabidopsis (Long et al. 2024).
| Viruses |
Orthornavirae, Negarnaviricota | Sucrose transporter, AcSUT1B, of Ananas comosus |
|
2.A.2.5.1 | Bacteria |
Pseudomonadota | TogT of Erwinia chrysanthemi 3937 | |
|
2.A.2.5.2 | The putative rhamnogalacturonide porter, RhiT (Rodionov et al. 2004). | Bacteria |
Pseudomonadota | RhiT of Erwinia carotovora subsp. atroseptica (Q6D188) |
|
2.A.2.6.2 | The maltose/maltooligosaccharide transporter, MalI (541 aas) (Lohmiller et al., 2008). | Bacteria |
Pseudomonadota | MalI of Caulobacter crescentus (Q9A612) |
|
2.A.2.6.3 | The putative maltose porter, MalT (Rodionov et al., 2010) | Bacteria |
Pseudomonadota | MalT of Shewanella oneidensis (Q8EEC4) |
|
2.A.2.7.1 | The insect Bm-re (Bombyx mori red eye) protein; mutants lose ommochromes as well as pigmentation of eggs, eyes, and bodies. May function in pigment transport (Osanai-Futahashi et al., 2012). | Eukaryota |
Metazoa, Arthropoda | Bm-re of Bombyx mori (I0IYT1) |
|
2.A.2.7.2 | Bm-re homologue of Tribolium castaneum (Osanai-Futahashi et al., 2012). | Eukaryota |
Metazoa, Arthropoda | Bm-re homologue of Tribolium castaneum (D6W6W0) |
|
2.A.2.7.3 | MFSD12, melanosome and lysosome cysteine transporter, of 480 aas and 12 TMSs. It is associated with skin pigmentation in humans, mice, dogs and horses (Crawford et al. 2017; Adhikari et al. 2019; Hédan et al. 2019; Tanaka et al. 2019). Its upregulated expression is observed in melanomas, and elevated MFSD12 levels promote cell proliferation by promoting cell cycle progression (Wei et al. 2019). MFSD12 interference inhibited tumor growth and lung metastasis in melanoma. It mediates the import of cysteine into melanosomes and lysosomes (Adelmann et al. 2020). MFSD12 is required to maintain normal levels of cystine - the oxidized dimer of cysteine - in melanosomes, and to produce cysteinyldopas, the precursors of pheomelanin synthesis made in melanosomes via cysteine oxidation. MFSD12 is necessary for the import of cysteine into melanosomes and, in non-pigmented cells, lysosomes. Loss of MFSD12 reduced the accumulation of cystine in lysosomes of fibroblasts from patients with cystinosis, a lysosomal-storage disease caused by inactivation of the lysosomal cystine exporter, cystinosin (TC# 2.A.43.1.1). Thus, MFSD12 is an essential component of the cysteine importer for melanosomes and lysosomes (Adelmann et al. 2020). | Eukaryota |
Metazoa, Chordata | MFSD12 of Homo sapiens |