| TCID | Name | Domain | Kingdom/Phylum | Protein(s) | |||
|---|---|---|---|---|---|---|---|
| 2.A.1.1: The Sugar Porter (SP) Family | |||||||
|
2.A.1.1.1 | 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 |
Pseudomonadota | GalP of E. coli (P0AEP1) | |||
|
2.A.1.1.2 | Arabinose (xylose; galactose):H+ symporter, AraE (low affinity high capacity) (Khlebnikov et al. 2001). | Bacteria |
Pseudomonadota | AraE of E. coli (P0AE24) | |||
|
2.A.1.1.3 | 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 ( | Bacteria |
Pseudomonadota | XylE of E. coli (P0AGF4) | |||
|
2.A.1.1.4 | Glucose uniporter | Bacteria |
Pseudomonadota | Glf of Zymomonas mobilis | |||
|
2.A.1.1.5 | Hexose uniporter | Eukaryota |
Fungi, Ascomycota | HxtO of Saccharomyces cerevisiae | |||
|
2.A.1.1.6 | 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). | Eukaryota |
Fungi, Ascomycota | Gal2 of Saccharomyces cerevisiae | |||
|
2.A.1.1.7 | Quinate:H+ symporter | Eukaryota |
Fungi, Ascomycota | Qay of Neurospora crassa | |||
|
2.A.1.1.8 | Myoinositol:H+ symporter
| Eukaryota |
Fungi, Ascomycota | ITR1 of Saccharomyces cerevisiae | |||
|
2.A.1.1.9 | Lactose, galactose:H+ symporter | Eukaryota |
Fungi, Ascomycota | LacP of Kluyveromyces lactis | |||
|
2.A.1.1.10 | 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). | Eukaryota |
Fungi, Ascomycota | MAL6 of Saccharomyces cerevisiae | |||
|
2.A.1.1.11 | 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). | Eukaryota |
Fungi, Ascomycota | AGT1 of Saccharomyces cerevisiae | |||
|
2.A.1.1.12 | 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). | Eukaryota |
Metazoa, Chordata | Gtr3 (Glut3) of Rattus norvegicus (rat) | |||
|
2.A.1.1.13 | 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).
| Eukaryota |
Metazoa, Chordata | SLC2A5 of Homo sapiens | |||
|
2.A.1.1.14 | 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). | Eukaryota |
Viridiplantae, Chlorophyta | Hup1 of Chlorella kessleri | |||
|
2.A.1.1.15 | Putative sugar transporter | Archaea |
Thermoproteota | Porter of Sulfolobus solfataricus | |||
|
2.A.1.1.16 | Low-affinity hexose (glucose, fructose, mannose, 2-deoxyglucose) uniporter. The evolution of hexose transporters in kinetoplastid protozoans has been studied (Pereira and Silber 2012). | Eukaryota |
Euglenozoa | Gtr2 (D2) of Leishmania donovani | |||
|
2.A.1.1.17 | Glucose transporter | Eukaryota |
Fungi, Ascomycota | Th2A of Trypanosoma brucei | |||
|
2.A.1.1.18 | 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). | Eukaryota |
Euglenozoa | Snf3p of Saccharomyces cerevisiae | |||
|
2.A.1.1.19 | 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). | Eukaryota |
Fungi, Ascomycota | Rgt2p of Saccharomyces cerevisiae | |||
|
2.A.1.1.20 | Myoinositol:H+ symporter, MIT | Eukaryota |
Euglenozoa | MIT of Leishmania donovani; most similar to ITRI of Saccharomyces cerevisiae | |||
|
2.A.1.1.21 | Hexose:H+ symporter, Ght2 (Glucose > Fructose) | Eukaryota |
Fungi, Ascomycota | Ght2 of Schizosaccharomyces pombe | |||
|
2.A.1.1.22 | Hexose:H+ symporter, Ght6 (Fructose > Glucose) | Eukaryota |
Fungi, Ascomycota | Ght6 of Schizosaccharomyces pombe | |||
|
2.A.1.1.23 | Gluconate:H+ symporter, Ght3 | Eukaryota |
Fungi, Ascomycota | Ght3 of Schizosaccharomyces pombe | |||
|
2.A.1.1.24 | 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). | Eukaryota |
Apicomplexa | PfHT1 of Plasmodium falciparum | |||
|
2.A.1.1.25 | 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). | Eukaryota |
Metazoa, Chordata | SLC2A13 of Homo sapiens | |||
|
2.A.1.1.26 | Major myoinositol:H+ symporter, IolT, of 473 aas and 12 TMSs in a 6 + 6 TMS pattern (Yoshida et al. 2002). | Bacteria |
Bacillota | IolT (YdjK) of Bacillus subtilis | |||
|
2.A.1.1.27 | Minor, low affinity myoinositol:H+ symporter, IolF, of 438 aas and 12 TMSs (Yoshida et al. 2002). | Bacteria |
Bacillota | IolF of Bacillus subtilis | |||
|
2.A.1.1.28 | 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). | Eukaryota |
Metazoa, Chordata | SLC2A1 of Homo sapiens | |||
|
2.A.1.1.29 | 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).
| Eukaryota |
Metazoa, Chordata | SLC2A2 of Homo sapiens | |||
|
2.A.1.1.30 | 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). | Eukaryota |
Fungi, Ascomycota | Hxt4 of Saccharomyces cerevisiae | |||
|
2.A.1.1.31 | 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 ( | Eukaryota |
Fungi, Ascomycota | Hxt6/Hxt7 of Saccharomyces cerevisiae Hxt6 (P39003) | |||
|
2.A.1.1.32 | Glucose/fructose:H+ symporter, GlcP (Zhang et al., 1989) | Bacteria |
Cyanobacteriota | GlcP of Synechocystis sp. (P15729) | |||
|
2.A.1.1.33 | Fructose:H+ symporter, Frt1 (Diezemann and Boles, 2003) | Eukaryota |
Fungi, Ascomycota | Frt1 of Kluyveromyces lactis (CAC79614) | |||
|
2.A.1.1.34 | The broad specificity sugar/sugar alcohol (myo-inositol, glycerol, ribose, sorbitol, mannitol, xylitol, erythritol, etc) H+ symporter, AtPLT5 (transports a wide range of hexoses, pentoses, tetroses, sugar alcohols and a sugar acid, but not disaccharides) (Reinders et al., 2005) (expressed in roots, leaves and floral organs) (Klepek et al., 2004) | Eukaryota |
Viridiplantae, Streptophyta | AtPLT5 of Arabidopsis thaliana (Q8VZ80) | |||
|
2.A.1.1.35 | The major glucose (or 2-deoxyglucose) uptake transporter, GlcP (van Wezel et al., 2005) | Bacteria |
Actinomycetota | GlcP of Streptomyces coelicolor (Q7BEC4) | |||
|
2.A.1.1.36 | The low affinity, glucose-inducible glucose transporter, MstE (Forment et al., 2006) | Eukaryota |
Fungi, Ascomycota | MstE of Aspergillus nidulans (Q400D8) | |||
|
2.A.1.1.37 | The glucose/fructose facilitator, Glut7 (SLC2A7) (a single mutation, I314V, results in loss of fructose transport but retention of glucose transport (Manolescu et al., 2005) | Eukaryota |
Metazoa, Chordata | SLC2A7 of Homo sapiens | |||
|
2.A.1.1.38 | The glycerol:H+ symporter, Stl1p (Ferreira et al., 2005) | Eukaryota |
Fungi, Ascomycota | Stl1p of Saccharomyces cerevisiae (NP_010825) | |||
|
2.A.1.1.39 | The high affinity glucose transporter, Hgt1 (Baruffini et al., 2006) | Eukaryota |
Fungi, Ascomycota | Hgt1 of Kluyveromyces lactis (P49374) | |||
|
2.A.1.1.40 | The xylose facilitator, Xylhp (Nobre et al., 1999) | Eukaryota |
Fungi, Ascomycota | Xylhp of Debaryomyces hansenii (AAR06925) | |||
|
2.A.1.1.41 | The D-xylose:H+ symporter, XylT (Km=220 μM; inhibited competitively by 6-deoxyglucose (Ki=220 μM), but not by other sugars tested) (Chaillou et al., 1998) | Bacteria |
Bacillota | XylT of Lactobacillus brevis (O52733) | |||
|
2.A.1.1.42 | The D-glucose:H+ symporter, GlcP (glucose uptake is inhibited by 2-deoxyglucose, mannose and galactose) (Parche et al., 2006) | Bacteria |
Actinomycetota | GlcP of Bifidobacterium longum (AAN25419) | |||
|
2.A.1.1.43 | The monosaccharide (MST) (glucose > mannose > galactose > fructose):H+ symporter, MST1 (Schussler et al., 2006). | Eukaryota |
Fungi, Mucoromycota | MST1 of Geosiphon pyriformis (A0ZXK6) | |||
|
2.A.1.1.44 | The hexose (glucose and fructose but not galactose) transporter (Glut11; SLC2A11) (Scheepers et al., 2005) | Eukaryota |
Metazoa, Chordata | SLC2A11 of Homo sapiens | |||
|
2.A.1.1.45 | Vacuolar (tonoplast) glucose transporter1, Vgt1 (important for seed germination and flowering) (Aluri and Büttner, 2007) | Eukaryota |
Viridiplantae, Streptophyta | Vgt1 of Arabidopsis thaliana (Q8L6Z8) | |||
|
2.A.1.1.46 | The blastocyst/testis glucose transporter, Glut8 (Doege et al., 2000) (insulin stimulated in blastocysts) (Carayannopoulos et al., 2000). | Eukaryota |
Metazoa, Chordata | Glut8 of Mus musculus (Q9JIF3) | |||
|
2.A.1.1.47 | 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). | Eukaryota |
Metazoa, Chordata | Glut9 of Mus musculus (Q5ERC7) | |||
|
2.A.1.1.48 | The pentose/hexose transporter (sugar transport protein 2), STP2. (Expressed during pollen maturation and early stages of gametophyte development) (Truernit et al., 1999) | Eukaryota |
Viridiplantae, Streptophyta | STP2 of Arabidopsis thaliana (Q9LNV3) | |||
|
2.A.1.1.49 | The sink-specific, stress-regulated monosaccharide uptake porter, STP4. (Induced upon wounding or infection with bacteria or fungi; expressed in roots and flowers) (Truernit et al., 1996) | Eukaryota |
Viridiplantae, Streptophyta | STP4 of Arabidopsis thaliana (Q39228) | |||
|
2.A.1.1.50 | 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). | Eukaryota |
Viridiplantae, Streptophyta | STP13 of Arabidopsis thaliana (Q94AZ2) | |||
|
2.A.1.1.51 | Glucose/xylose: H+ symporter, Gsx1 (Leandro et al., 2006) | Eukaryota |
Fungi, Ascomycota | Gsx1 of Candida intermedia (Q2MEV7) | |||
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2.A.1.1.52 | The glucose transport protein, GTP1 (Skelly et al., 1994) | Eukaryota |
Metazoa, Platyhelminthes | GTP1 of Schistosoma mansoni (Q26579) | |||
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2.A.1.1.53 | Myo-Inositol uptake porter, IolT1 (Km=0.2mM) (Krings et al., 2006). Can also transport D-glucose (Ikeda et al. 2011). | Bacteria |
Actinomycetota | IolT1 of Corynebacterium glutamicum (Q8NTX0) | |||
|
2.A.1.1.54 | Myo-Inositol (Km=0.45mM) uptake porter, IolT2 (Krings et al., 2006). Can not transport D-glucose (Ikeda et al. 2011). | Bacteria |
Actinomycetota | IolT2 of Corynebacterium glutamicum (Q8NL90) | |||
|
2.A.1.1.55 | 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 |
Bacillota | AraE of Bacillus subtilis (P96710) | |||
|
2.A.1.1.56 | High affinity monosaccharide (KM ≈ 20 µM):H+ symporter, Stp6 (takes up glucose, 3-O-methylglucose, mannose, fructose, galactose and to a lesser extent, xylose and ribulose. (Scholz-Starke et al., 2003) | Eukaryota |
Viridiplantae, Streptophyta | Stp6 of Arabidopsis thaliana (Q9SFG0) | |||
|
2.A.1.1.57 | High affinity (15 μM) glucose (monosaccharides including xylose):H+ symporter, MstA (Jørgensen et al., 2007). | Eukaryota |
Fungi, Ascomycota | MstA of Aspergillus niger (Q8J0V1) | |||
|
2.A.1.1.58 | Low affinity glucose:H+ symporter, MstC (Jørgensen et al., 2007). | Eukaryota |
Fungi, Ascomycota | MstC of Aspergillus niger (Q8J0U9) | |||
|
2.A.1.1.59 | The glucose transporter, GLUT10, was originally believed to be responsible for Type 2 diabetes. It is now believed to be responsible for arterial tortuosity, a rare autosomal recessive connective tissue disease (Callewaert et al., 2007). GLUT10 transports glucose and 2-deoxy glucose (Km=0.3 mM), and is inhibited by galactose and phloretin (Coucke et al., 2006). | Eukaryota |
Metazoa, Chordata | SLC2A10 of Homo sapiens | |||
|
2.A.1.1.60 | The major hexose transporter, Htr1 (mediates the active uptake of hexoses by sugar:H+ symport. Can transport glucose, 3-O-methylglucose, fructose, xylose, mannose, galactose, fucose, 2-deoxyglucose and arabinose. Confers sensitivity to galactose in seedlings. Km=20 uM for glucose) (Stadler et al., 2003; Boorer et al., 1994) | Eukaryota |
Viridiplantae, Streptophyta | Htr1 of Arabidopsis thaliana (P23586) | |||
|
2.A.1.1.61 | High affinity monosaccharide (Km = 25 µM) transporter (takes up glucose, galactose, mannose, xylose and 3-O-methylglucose, but not fructose and ribose), STP11 (expressed in pollen tubes) (Schneidereit et al., 2005). This protein is also called Sugar Transport Protein (STP). Expression profiles of homologues in cabbage have been studied (Zhang et al. 2019). | Eukaryota |
Viridiplantae, Streptophyta | STP11 of Arabidopsis thaliana (Q9FMX3) | |||
|
2.A.1.1.62 | High affinity (0.24mM) plasma membrane myoinositol-specific H+ symporter, INT4 (Schneider et al., 2006) | Eukaryota |
Viridiplantae, Streptophyta | INT4 of Arabidopsis thaliana (O23492) | |||
|
2.A.1.1.63 | Low affinity inositol (myoinsoitol (Km = 1 mM), scylloinositol, d-chiroinositol and mucoinositol):H+ symporter (expressed in the anther tapetum, the vasculature, and the leaf mesophyll (Schneider et al., 2007) | Eukaryota |
Viridiplantae, Streptophyta | INT2 of Arabidopsis thaliana (Q9C757) | |||
|
2.A.1.1.64 | The hexose sensor, Hxs1 (believed to be non-transporting) (Stasyk et al., 2008) | Eukaryota |
Fungi | Hxs1 of Hansenula polymorpha (B1PM37) | |||
|
2.A.1.1.65 | Glucose permease GlcP (Pimentel-Schmitt et al., 2008) (most similar to 2.A.1.1.32) | Bacteria |
Actinomycetota | GlcP of Mycobacterium smegmatis (A0QZX3) | |||
|
2.A.1.1.66 | The tonoplast H+:Inositol symporter 1, Int1 (mediates efflux from the tonoplast to the cytoplasm (Schneider et al., 2008) (most similar to 2.A.1.1.63 and 2.A.1.1.62). | Eukaryota |
Viridiplantae, Streptophyta | Int1 of Arabidopsis thaliana (Q8VZR6) | |||
|
2.A.1.1.67 | Glucose/xylose facilitator-1, GXF1 (functions by sugar uniport; low affinity (Leandro et al., 2008) | Eukaryota |
Fungi, Ascomycota | GXF1 of Candida intermedia (Q2MDH1) | |||
|
2.A.1.1.68 | The Glucose Transporter/Sensor Rgt2 | Eukaryota |
Fungi, Ascomycota | Rgt2 Pichia stipitis (A3M0N3) | |||
|
2.A.1.1.69 | Sugar & polyol transporter 1 (SPT1): broad specificity; takes up glucose (Schilling and Oesterhelt, 2007). Loss of the first 3 TMSs of the 12 TMSs does not prevent sugar uptake or sugar recognition but lowers substrate affinity & transport rate, and abolished H+ symport (Schilling and Oesterhelt, 2007). | Eukaryota |
Rhodophyta | SPT1 of Galdieria sulphuraria (A1Z264) | |||
|
2.A.1.1.70 | MFS Permease | Eukaryota |
Fungi, Ascomycota | MFS Permease of Phaeosphaeria nodurum | |||
|
2.A.1.1.71 | Hexose (glucose) transporter, GT4 (D2) (almost identical to 2.A.1.1.16). The L. infantum ortholog (A4I8N6) is 95% identical to this protein and is the dominant protein in the plasma membrane of this organims (Oliveira et al. 2020). | Eukaryota |
Euglenozoa | Hexose transporter, GT4 of Leishmania mexicana (B1PLM1) | |||
|
2.A.1.1.72 | The kidney basolateral urate efflux transporter (SLC2A9, URATv1 or GLUT9) (orthologue of 2.A.1.1.47) (Anzai et al., 2008). Human SLC2A9a and SLC2A9b isoforms mediate electrogenic transport of urate with different characteristics in the presence of hexoses (Witkowska et al., 2012). It transports hexoses, glucose and fructose, but not galactose, at a rate 50-fold slower than urate the latter by a uniport mechanism, thus catalyzing uptake as well as efflux. The ITM2B protein Q9Y287; 266 aas and 1 TMS) inhibits urate uptake and stimulates efflux (Mandal and Mount 2019). GLUT9's transcription is regulated by a hepatocyte nuclear factor, HNF4α (Prestin et al. 2014). Residues involved in urate transport have been identified (Long et al. 2017). Pathogenic variants of SLC22A12 (URAT1) and SLC2A9 (GLUT9) can give rise to renal hypouricemia (Perdomo-Ramirez et al. 2023). The structural basis for the transport and substrate selection have been described (He et al. 2024). Cryo-EM structures of human URAT1(R477S), its complex with urate, and its closely related homolog OAT4 have been determined. URAT1(R477S) and OAT4 exhibit major facilitator superfamily (MFS) folds with outward- and inward-open conformations, respectively. Structural comparison reveals a 30° rotation between the N-terminal and C-terminal domains, supporting an alternating access mechanism. A conserved arginine (OAT4-Arg473/URAT1-Arg477) is found to be essential for chloride-mediated inhibition (He et al. 2024). | Eukaryota |
Metazoa, Chordata | SLC2A9 of Homo sapiens | |||
|
2.A.1.1.73 | Glycerol uptake permease (Glycerol:H+ symporter) Stl1. (Involved in salt stress relief) (Kayingo et al. 2009) (similar to Stl1 of S. cerevisiae (2.A.1.1.38)) | Eukaryota |
Fungi, Ascomycota | Stl1 of Candida albicans (Q5A8J5) | |||
|
2.A.1.1.74 | The putative L-rhamnose porter, RhaY | Bacteria |
Bacillota | RhaY of Listeria monocytogenes (Q926Q9) | |||
|
2.A.1.1.75 | The fructose/xylose:H+ symporter, PMT1 (polyol monosaccharide transporter-1). Also transports other substrates at lower rates. PMT2 is largely of the same sequence and function. Both are present in pollen and young xylem cells (Klepek et al., 2005). A similar ortholog has been identifed in pollen grains of Petunia hybrida (Garrido et al. 2006). | Eukaryota |
Viridiplantae, Streptophyta | PMT1 of Arabidopsis thaliana (Q9XIH7) | |||
|
2.A.1.1.76 | Glucose transporter, GT1. GT1, 2, and 3 are homologues. GT2 and GT3 transport ribose as well as glucose at different rates. GT3 transports ribose with 6-fold lower efficiency due to two threonines in GT3 that are alanines in GT2. They are in two loops between TMSs 3, 4, and 7, 8 (Naula et al., 2010). GT1 is expressed in the flagellar membrane and may be both a glucose transporter and sensor, allowing the parasites to enter the stationary phase when they deplete glucose although in the absence of the sensor, they lose viability (Rodriguez-Contreras et al. 2015). | Eukaryota |
Euglenozoa | GT1 of Leishmania mexicana (Q9F315) | |||
|
2.A.1.1.77 | The D-glucose/D-ribose transporter, LmGT2 (Most similar to 1.A.1.1.18) (Naula et al., 2010). | Eukaryota |
Euglenozoa | LmGT2 of Leishmania mexicana (O61059) | |||
|
2.A.1.1.78 | The glucose transporter, LmGT3 (homologous to LmGT2 (1.A.1.1.75)). Two threonine residues located in the hydrophilic loops connecting TMSs 3 & 4 and 7 & 8 of GT3 prevent transport of D-ribose. Changing these two residues to alanine (as in GT2) allows transport of ribose. Thus, loops 3-4 and 7-8 partially determine substrate specificity (Naula et al., 2010). | Eukaryota |
Euglenozoa | LmGT3 of Leishmania mexicana (O61060) | |||
|
2.A.1.1.79 | Polyol (xylitol):H+ symporter, PLT4 (Kalliampakou et al., 2011)
| Eukaryota |
Viridiplantae, Streptophyta | PLT4 of Lotus japonicus (Q1XF07) | |||
|
2.A.1.1.80 | Insulin-responsive facilitative glucose transporter in skeletal and cardiac muscle, adipose, and other tissues, Glut4 (GTR4; SLC2A4; 509aas). Defects in Glut4 cause noninsulin-dependent diabetes mellitus (NIDDM). Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor (Gonzalez et al., 2011). The first luminal loop confers insulin responsiveness to GLUT4 (Kim and Kandror, 2012). Exercise increases Glut4 synthesis in a process involving several protein kinases, the Glut4 enhancer factor (GEF; SLC2A4 regulator; Q9NR83), and the myocyte enhancing factor 2 (MEF2; NP_001139257). (McGee and Hargreaves 2006; Wright 2007; Zorzano et al. 2005). monoclonal antibodies against the GLUT4 inward-open and outward-open states have been isoated (Tucker et al. 2018). It is phosphoryated by protein kinase C-β, PRKCB or PKCB (Lee et al. 2015). Insulin-induced GLUT4 transport is observed in the heart and brain in addition to the skeletal muscle and adipocytes, and hormones other than insulin can enhance GLUT4 transport (Wang et al. 2020). Prolonged preoperative fasting induces postoperative insulin resistance by ER-stress mediated Glut4 down-regulation in skeletal muscle (Lin et al. 2021). GLUT4 is the primary glucose transporter in adipose and skeletal muscle tissues, and its cellular trafficking is regulated by insulin signaling. Failed or reduced plasma membrane localization of GLUT4 is associated with diabetes. The cryo-EM structures of human GLUT4 bound to a small molecule inhibitor cytochalasin B (CCB) at resolutions of 3.3 Å which exhibits an inward-open conformation. The cryo-EM structure reveals an extracellular glycosylation site and an intracellular helix that is invisible in the crystal structure of GLUT1 (Yuan et al. 2022). Tectorigenin targets PKACα to promote GLUT4 expression in skeletal muscle and improve insulin resistance in vitro and in vivo (Yao et al. 2023). Key molecular players in insulin resistance (IR) are the insulin receptor and glucose transporter 4, and certain natural products, such as lipids, phenols, terpenes, antibiotics and alkaloids have beneficial effects on IR which are named "membrane-active immunomodulators" (MAIMs) (Izbicka and Streeper 2023). An example is the medium chain fatty acid ester diethyl azelate (DEA), which increases the fluidity of plasma membranes with subsequent downstream effects on cellular signaling and improves the symptoms of IR. The intracellular helical bundle of human glucose transporter GLUT4 is important for complex formation with ASP (Huang et al. 2023). Diabetes-induced electrophysiological alterations on neurosomes in ganglia of the peripheral nervous system have been reported (Leal-Cardoso et al. 2023). Regulated dynamic subcellular GLUT4 localization has been revealed by proximal proteome mapping in human muscle cells (Ray et al. 2023). In goats, this system is closely associate with lipid metabolism (Zhang et al. 2024). New compounds lowered the systolic blood pressure (from 149 to 120 mmHg), but only LQM312 and LQM319 improved the metabolic state of hypoxic cardiomyocytes mediated by GLUT1 and GLUT4 (Hernández-Serda et al. 2024). In silico studies suggested that Captopril and LQM312 mimic the interaction with the AMPK γ-subunit. Therefore, these compounds could activate AMPK, promoting the GLUT4 trafficking signaling pathway (Hernández-Serda et al. 2024). | Eukaryota |
Metazoa, Chordata | SLC2A4 of Homo sapiens | |||
|
2.A.1.1.81 | The glucose uptake porter, GluP (Araki et al., 2011). | Bacteria |
Actinomycetota | GluP of Rhodococcus jostii (Q0SE66) | |||
|
2.A.1.1.82 | The cellobiose/cellotriose/cellotetraose/latose/cellodextrin transporter, Cdt-1 of 579 aas and 12 TMSs. It is a proton symporter with a Km of about 4 μM (Galazka et al., 2010). | Eukaryota |
Fungi, Ascomycota | Cdt-1 of Neurospora crassa (Q7SCU1) | |||
|
2.A.1.1.83 | The cellobiose/cellotriose/cellodextrin/lactose transporter, Cdt-2, of 525 aas and 12 TMSs. It functions by facilitated diffusion but with low efficiency and high affinity (Km = 3 μM). Mutations can increase its activity substantially (Lian et al. 2014). It appears to be capable of catalyzing efflux of 2'-fucosyllactose (2'FL), the most abundant oligosaccharide in human breast milk, following genetic engineering (Hollands et al. 2019). It may also take up lactose (Tamayo et al. 2024). | Eukaryota |
Fungi, Ascomycota | Cdt2 of Neurospora crassa (Q7SD12) | |||
|
2.A.1.1.84 | The heteromeric TMT1/TMT2 glucose/sucrose:H+ antiporter. Catalyzes glucose/sucrose antiport into vacuoles (Schulz et al., 2011). | Eukaryota |
Viridiplantae, Streptophyta | The TMT1/2 sugar:H+ anti-porter of Arabidopsis thaliana. TMT1 (Q96290). TMT2 (Q8LPQ8). | |||
|
2.A.1.1.85 | Zebrafish Slc2A10 (Glut10) facilitative glucose transporter. | Eukaryota |
Metazoa, Chordata | Zebrafish Glut10 of Danio rerio (A8KB28) | |||
|
2.A.1.1.86 | The sea bream facilitative glucose transporter 1 (GLUT1) (Balmaceda-Aguilera et al., 2012). | Eukaryota |
Metazoa, Chordata | Glut1 of Sparus aurata (H9BPB6) | |||
|
2.A.1.1.87 | solute carrier family 2, member 12, Glut12 of 617 aas and 12 TMSs. In contrast to most mammalian members of this family, this protein has been reported to be a glucose:proton symporter (Wilson-O'Brien et al. 2010). | Eukaryota |
Metazoa, Chordata | SLC2A12 of Homo sapiens | |||
|
2.A.1.1.88 | solute carrier family 2 (facilitated glucose transporter), member 6 | Eukaryota |
Metazoa, Chordata | SLC2A6 of Homo sapiens | |||
|
2.A.1.1.89 | Solute carrier family 2, facilitated glucose transporter member 8 (Glucose transporter type 8) (GLUT-8) (Glucose transporter type X1) | Eukaryota |
Metazoa, Chordata | SLC2A8 of Homo sapiens | |||
|
2.A.1.1.90 | Solute carrier family 2, facilitated glucose transporter member 14 (Glucose transporter type 14) (GLUT-14) | Eukaryota |
Metazoa, Chordata | SLC2A14 of Homo sapiens | |||
|
2.A.1.1.91 | Solute carrier family 2, facilitated glucose transporter member 3 (Glucose transporter type 3, brain) (GLUT-3 or GLUT3). It mediates the facilitative uptake of glucose, 2-deoxyglucose, galactose, mannose, xylose and fucose, and probably dehydroascorbate, but not fructose (Seatter et al. 1998, Deng et al. 2015). GLUT3, a key neuronal transporter, exhibits multiple intermediate states (Sun and Zheng 2019). SLC2A3 may play a role in the progression of colorectal cancer (CRC) by regulating the epithelial-mesenchymal transition (EMT) classical pathway as well as PD-L1 mediated immune responses (Gao et al. 2021). GLUT3 is consistently upregulated in actively proliferating human oral squamous cell carcinoma cells (Paolini et al. 2022). GLUT-1 and GLUT-3 play roles in the development of some types of malignant tumors including glioblastoma, and expression of both is regulated by miRNAs (Beylerli et al. 2022). The overexpression of GLUT3 or GLUT1 may be monitored alone or in combination (GLUT1/GLUT3 ratio) as a biomarker for preeclampsia onset, phenotype, and progression (Agbani et al. 2023). | Eukaryota |
Metazoa, Chordata | SLC2A3 of Homo sapiens | |||
|
2.A.1.1.92 | Inner membrane metabolite transport protein YdjE | Bacteria |
Pseudomonadota | YdjE of E. coli | |||
|
2.A.1.1.93 | Vacuolar protein sorting-associated protein 73 | Eukaryota |
Fungi, Ascomycota | VPS73 of Saccharomyces cerevisiae | |||
|
2.A.1.1.94 | Putative metabolite transport protein YDL199C | Eukaryota |
Fungi, Ascomycota | YDL199C of Saccharomyces cerevisiae | |||
|
2.A.1.1.95 | Bacteria |
Pseudomonadota | |||||
|
2.A.1.1.96 | Probable metabolite transport protein YBR241C | Eukaryota |
Fungi, Ascomycota | YBR241C of Saccharomyces cerevisiae | |||
|
2.A.1.1.97 | Sugar transporter ERD6 (Early-responsive to dehydration protein 6) (Sugar transporter-like protein 1) | Eukaryota |
Viridiplantae, Streptophyta | ERD6 of Arabidopsis thaliana | |||
|
2.A.1.1.98 | Sugar transporter ERD6-like 6, ERD6L6, of 487 aas and 12 TMSs. It is 92% identical to ERD6L4 (488 aas and 12 TMSs) of A. thaliana, and ERD6-like 4 is candidate gene for foliar water-soluble carbohydrate accumulation in Trifolium repens (Pearson et al. 2022). Vacuolar sugar transporter EARLY RESPONSE TO DEHYDRATION 6-LIKE4 affects fructose signaling and plant growth (Khan et al. 2023). Regulation of intracellular sugar homeostasis is maintained by regulation of activities of sugar import and export proteins residing at the tonoplast. ERDL4 protein resides in the vacuolar membrane in Arabidopsis thaliana. Gene expression and subcellular fractionation studies indicated that ERDL4 participates in fructose allocation across the tonoplast, and modification of cytosolic fructose levels influences plant organ development and stress tolerance (Khan et al. 2023). . | Eukaryota |
Viridiplantae, Streptophyta | At1g75220 of Arabidopsis thaliana | |||
|
2.A.1.1.99 | Facilitated trehalose transporter Tret1-1 (DmTret1-1); transports trehalose with a Km of 11 mM (Kanamori et al. 2010). Tret1 orthologs of other insects examined have differing Km values (Apis mellifera, 9 mM; Anopheles gambiae, 46 mM, and Bombyx mori, 72 mM). | Eukaryota |
Metazoa, Arthropoda | Tret1-1 of Drosophila melanogaster | |||
|
2.A.1.1.100 | Probable metabolite transport protein YFL040W | Eukaryota |
Fungi, Ascomycota | YFL040W of Saccharomyces cerevisiae | |||
|
2.A.1.1.101 | Probable metabolite transport protein YDR387C | Eukaryota |
Fungi, Ascomycota | YDR387C of Saccharomyces cerevisiae | |||
|
2.A.1.1.102 | Plastidic glucose transporter 4 (AtpGlcT) | Eukaryota |
Viridiplantae, Streptophyta | At5g16150 of Arabidopsis thaliana | |||
|
2.A.1.1.103 | D-xylose-proton symporter-like 3, chloroplastic | Eukaryota |
Viridiplantae, Streptophyta | At5g59250 of Arabidopsis thaliana | |||
|
2.A.1.1.104 | Myo-inositol transporter 2 | Eukaryota |
Fungi, Ascomycota | ITR2 of Saccharomyces cerevisiae | |||
|
2.A.1.1.105 | Hexose transporter HXT11 (Low-affinity glucose transporter LGT3) | Eukaryota |
Fungi, Ascomycota | HXT11 of Saccharomyces cerevisiae | |||
|
2.A.1.1.106 | Probable metabolite transport protein CsbC | Bacteria |
Bacillota | CsbC of Bacillus subtilis | |||
|
2.A.1.1.107 | Hexose transporter HXT15 | Eukaryota |
Fungi, Ascomycota | HXT15 of Saccharomyces cerevisiae | |||
|
2.A.1.1.108 | 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). | Eukaryota |
Fungi, Ascomycota | HXT1 of Saccharomyces cerevisiae | |||
|
2.A.1.1.109 | Hexose transporter HXT14 | Eukaryota |
Fungi, Ascomycota | HXT14 of Saccharomyces cerevisiae | |||
|
2.A.1.1.110 | Hexose transporter HXT13 | Eukaryota |
Fungi, Ascomycota | HXT13 of Saccharomyces cerevisiae | |||
|
2.A.1.1.111 | High-affinity glucose transporter HXT2. Asp340 and Asn331 in part determine the high glucose affinity (Kasahara et al. 2007; Kasahara and Kasahara 2010). | Eukaryota |
Fungi, Ascomycota | HXT2 of Saccharomyces cerevisiae | |||
|
2.A.1.1.112 | High-affinity glucose transporter Ght1 (Hexose transporter 1) | Eukaryota |
Fungi, Ascomycota | Ght1 of Schizosaccharomyces pombe | |||
|
2.A.1.1.113 | Bacteria |
Bacillota | YyaJ of Bacillus subtilis | ||||
|
2.A.1.1.114 | Bacteria |
Pseudomonadota | YaaU of Escherichia coli | ||||
|
2.A.1.1.115 | Bacteria |
Pseudomonadota | YdjK of Escherichia coli | ||||
|
2.A.1.1.116 | Arabinose/xylose transporter, AraE (Wang et al. 2013). | Bacteria |
Actinomycetota | AraE of Coynebacterium glutamicum | |||
|
2.A.1.1.117 | 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). | Eukaryota |
Fungi, Ascomycota | MoST1 of Magnaporthe oryzae | |||
|
2.A.1.1.118 | MFS porter of 435 aas | Archaea |
Thermoproteota | MFS porter of Sulfolobus solfataricus | |||
|
2.A.1.1.119 | The galacturonic acid (galacturonate) uptake porter, GatA, of 518 aas and 12 TMSs (Sloothaak et al. 2014). | Eukaryota |
Fungi, Ascomycota | GatA of Aspergillus niger | |||
|
2.A.1.1.120 | Major myo-inositol transporter, IolT1, of 456 aas (Kröger et al. 2010). | Bacteria |
Pseudomonadota | IolT1 of Samonella enterica | |||
|
2.A.1.1.121 | Minor myo-inositol transporter, IolT2, of 478 aas (Kröger et al. 2010). | Bacteria |
Pseudomonadota | IolT2 of Salmonella enterica | |||
|
2.A.1.1.122 | 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). | Eukaryota |
Viridiplantae, Streptophyta | SOT2 of Pyrus pyrifolia (Chinese pear) (Pyrus serotina) | |||
|
2.A.1.1.123 | 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). | Eukaryota |
Viridiplantae, Streptophyta | SOT1 of Prunus salicina | |||
|
2.A.1.1.124 | 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). | Eukaryota |
Viridiplantae, Streptophyta | STP10 of Arabidopsis thaliana | |||
|
2.A.1.1.125 | 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). . | Eukaryota |
Fungi, Ascomycota | GT1 of Komagataella pastoris (Yeast) (Pichia pastoris) | |||
|
2.A.1.1.126 | 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). | Eukaryota |
Fungi, Ascomycota | Fst1 of Weissella confusa | |||
|
2.A.1.1.127 | 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). | Eukaryota |
Fungi, Basidiomycota | Hxt5 of Piriformospora indica | |||
|
2.A.1.1.128 | 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). | Eukaryota |
Metazoa, Arthropoda | HT1 of Nilaparvata lugens (Brown planthopper) | |||
|
2.A.1.1.129 | 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. | Eukaryota |
Metazoa, Arthropoda | TRET1 of Polypedilum vanderplanki (Sleeping chironomid) | |||
|
2.A.1.1.130 | 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). | Eukaryota |
Metazoa, Chordata | GLUT1 of Xenopus laevis (African clawed frog) | |||
|
2.A.1.1.131 | Myo-inositol-specific uptake transporter, ITR1 of 509 aas and 12 TMSs. The Km for myo-inositol is about 1 mM; glucose and other inositols are apparently not transported (Cushion et al. 2016). | Eukaryota |
Fungi, Ascomycota | ITR1 of Pneumocystis carinii | |||
|
2.A.1.1.132 | 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). | Eukaryota |
Viridiplantae, Streptophyta | Bloom1 of Glycine max (Soybean) (Glycine hispida) (Glycine soja) | |||
|
2.A.1.1.133 | 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). | Eukaryota |
Metazoa, Chordata | GLUT2 of Megalobrama amblycephala (Chinese blunt snout bream) (Brema carp) | |||
|
2.A.1.1.134 | Sugar (mannose, fructose, glucose, galactose xylose) transporter of 521 aas and 12 TMSs, STP2 (Liu et al. 2018). | Eukaryota |
Viridiplantae, Streptophyta | STP2 of Manihot esculenta (Cassava) (Jatropha manihot) | |||
|
2.A.1.1.135 | Galactose-specific uptake porter of 515 aas and 12 TMSs, STP16 (Liu et al. 2018). | Eukaryota |
Viridiplantae, Streptophyta | STP16 of Manihot esculenta (Cassava) (Jatropha manihot) | |||
|
2.A.1.1.136 | Monosaccharide uptake porter of 529 aas and 12 TMSs, STP7. Transports mannose, galactose, glucose and fructose, but not xylose (Liu et al. 2018). | Eukaryota |
Viridiplantae, Streptophyta | STP7 of Manihot esculenta (Cassava) (Jatropha manihot) | |||
|
2.A.1.1.137 | 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). | Eukaryota |
Fungi, Ascomycota | Glycerol porter of Wickerhamomyces anomalus | |||
|
2.A.1.1.138 | 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). | Eukaryota |
Fungi, Ascomycota | MAL2 of Pichia angusta (Yeast) (Hansenula polymorpha) | |||
|
2.A.1.1.139 | 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). | Eukaryota |
Metazoa, Chordata | Glut3 of Danio rerio | |||
|
2.A.1.1.140 | 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). | Eukaryota |
Fungi, Ascomycota | CtA of Aspergillus niger | |||
|
2.A.1.1.141 | Lactose permease of 533 aas and 12 TMSs; 45% identical to 2.A.1.1.140 (Havukainen et al. 2020). | Eukaryota |
Fungi, Ascomycota | Lactose permease of Aspergillus nidulans | |||
|
2.A.1.1.142 | MFS-type cellodextrin transporter, CdtG, of 538 aas and 12 TMSs (Havukainen et al. 2020). | Eukaryota |
Fungi, Ascomycota | CdtG of Penicillium sp. 2HH | |||
|
2.A.1.1.144 | 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). | Eukaryota |
Metazoa, Chordata | GLUT4 of Megalobrama amblycephala (Chinese blunt snout bream) (Brema carp) | |||
|
2.A.1.1.145 | 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. | Eukaryota |
Viridiplantae, Streptophyta | MFS porter of Triticum aestivum (bread wheat) | |||
|
2.A.1.1.146 | 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). | Eukaryota |
Fungi, Ascomycota | L-Arabinose transporter of Penicillium sp. | |||
|
2.A.1.1.147 | 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. | Eukaryota |
Fungi, Ascomycota | Mfs1 of Colletotrichum gloeosporioides | |||
|
2.A.1.1.148 | 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). | Eukaryota |
Metazoa, Platyhelminthes | GLUT1 of Echinococcus granulosus | |||
|
2.A.1.1.149 | 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). | Eukaryota |
Fungi, Ascomycota | HxtA of Emericella nidulans (Aspergillus nidulans) | |||
|
2.A.1.1.150 | 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). | Eukaryota |
Fungi, Ascomycota | GCR1 of Ogataea polymorpha (Hansenula polymorpha) | |||
|
2.A.1.1.151 | 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). | Eukaryota |
Metazoa, Arthropoda | Tret1-like transporter of Plutella xylostella | |||
|
2.A.1.1.152 | 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).
| Eukaryota |
Viridiplantae, Streptophyta | INT7 of Populus alba x Populus glandulosa | |||
|
2.A.1.1.153 | Sugar transporter of 529 aas and 12 TMSs. | Eukaryota |
Evosea | Sugar transporter of Planoprotostelium fungivorum | |||
|
2.A.1.1.154 | 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). | Eukaryota |
Metazoa, Cnidaria | Glucose transporter of Exaiptasia diaphana | |||
|
2.A.1.1.155 | 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). | Eukaryota |
Viridiplantae, Streptophyta | ERD6-like 4 of Triticum aestivum | |||
|
2.A.1.1.156 | 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). | Archaea |
Thermoproteota | MT of Pyrobaculum calidifontis | |||
|
2.A.1.1.157 | 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 | Bacteria |
Bacteroidota | MFS transporter of Alistipes sp. HGB5
| |||
|
2.A.1.1.158 | 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. | Eukaryota |
Viridiplantae, Streptophyta | pGlcT2 of Arabidopsis thaliana | |||
|
2.A.1.1.159 | 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). | Eukaryota |
Metazoa, Chordata | GLUT1 of Danio rerio | |||
| 2.A.1.2: The Drug:H+ Antiporter-1 (12 Spanner) (DHA1) Family | |||||||
|
2.A.1.2.1 | Pyridoxine, pyridoxal, pyridoxamine, amiloride:H+ cotransporter (Km (pyridoxine) = 22 μM) (Stolz et al., 2005). Also takes up thiamine (Vogl et al., 2008). | Eukaryota |
Fungi, Ascomycota | Bsu1 (Car1) of Schizosaccharomyces pombe (P33532) | |||
|
2.A.1.2.2 | Cycloheximide:H+ antiporter | Eukaryota |
Fungi, Ascomycota | CyhR of Candida maltosa | |||
|
2.A.1.2.3 | Chloramphenicol:H+ antiporter, CmlA; Cmr; MdfA. Multidrug exporter that also catalyzes efflux of arabinose (but not xylose) and isopropyl β-thiogalactoside (Koita and Rao 2012). | Bacteria |
Pseudomonadota | CmlA of Pseudomonas aeruginosa | |||
|
2.A.1.2.4 | Tetracycline:H+ antiporter | Bacteria |
Pseudomonadota | TetA of E. coli | |||
|
2.A.1.2.5 | Multidrug (14- and 15-membered macrolides, lincosamides, streptogramins, tetracyclines, daunomycin, ethidium bromide, etc.):H+ antiporter, LmrP. Two proton translocation pathways have been proposed (Bapna et al., 2007), but Schaedler and van Veen, 2010 have provided evidence that a flexible cation binding site in LmrP is associated with variable proton coupling. Basic residues R260 and K357 affect the conformational dynamics of LmrP (Wang and van Veen, 2012). Basic residues, R260 and K357 control the conformational dynamics of the protein (Wang and van Veen 2012). Also specifically catalyzes Ca2+:3H+ antiport with an affinity of 7 μM (Zhang et al. 2012). Two carboxylates (Asp-235 and Glu-327) are critical for Ca2+ binding. Protonation drives major conformational switches (Masureel et al. 2013). The system exhibits plasticity in proton interactions, which is a consequence of the flexibility in the location of key residues that are responsible for proton/multidrug antiport (Nair et al. 2016).
| Bacteria |
Bacillota | LmrP of Lactococcus lactis | |||
|
2.A.1.2.6 | (Benomyl, cycloheximide, methotrexate, fluconazole, etc.):H+ antiporter, CaMDR1 (Basso et al., 2010; Cannon et al., 1998). MDR1 catalyzes efflux of commonly used azoles. The central cytoplasmic loop is critical for MDR function, but does not impart substrate specificity (Mandal et al., 2012). The structural basis for polyspecificity of MDR MFS transporters, based on studies with Mdr1, is the extended capacity brought by residues located at the periphery of a binding core to accomodate compounds differing in size and type (Redhu et al. 2018). Each domain in the protein is arranged in a pseudo-symmetric fold of two tandems of 3-TMSs that alternatly expose the drug-binding site towards the inside or the outside of the yeast to promote drug binding and release. Sharma et al. 2022 provided information on these motifs by having screened a library of 64 drug transport-deficient mutants and their corresponding suppressors spontaneously addressing the deficiency. They found that five strains recovered the drug-resistance capacity by expressing CaMdr1 with a secondary mutation. The pairs of debilitating/rescuing residues are distributed either in the same TMS or 3-TMS repeat, at the hinge of 3-TMS repeat tandems, and between the N- and C-domains. Most of these mutants belong to different signature motifs, highlighting a mechanistic role and interplay thought to be conserved among MFS proteins. Results point to the specific role of TMS 11 in the interplay between the N- and C-domains in the inward- to outward-open conformational transition (Sharma et al. 2022). | Eukaryota |
Fungi, Ascomycota | CaMDR1 of Candida albicans | |||
|
2.A.1.2.7 | Bicyclomycin, sulfathiazole, tetracycline, fosfomycin, acriflavin, etc.):H+ antiporter (Nishino and Yamaguchi 2001). Also exports L-cysteine (Yamada et al., 2006). | Bacteria |
Pseudomonadota | Bcr of E. coli | |||
|
2.A.1.2.8 | (Spermidine; fluoroquinolones, acriflavin, chloramphenicol, ethidium bromide, etc.):H+ antiporter (Woolridge et al. 1997). | Bacteria |
Bacillota | Blt of Bacillus subtilis | |||
|
2.A.1.2.9 | (Hydrophobic uncoupler e.g., CCCP, benzalkonium, SDS and other drugs):H+ antiporter, EmrD (Nishino and Yamaguchi 2001). The 3-d structure (3.5 Å resolution) has been determined (Yin et al., 2006). conformational dynamics studies have revealed details of the transport pathway and some motions of EmrD at an atomic level (Baker et al. 2012). Probably exports arabinose but not xylose (Koita and Rao 2012). | Bacteria |
Pseudomonadota | EmrD of E. coli | |||
|
2.A.1.2.10 | Quinolone (and other drug):H+ antiporter, NorA. Many synthetic inhibitors have been identified (Bhaskar et al. 2016). 1,8-Naphthyridines sulfonamides are NorA efflux pump inhibitors (Oliveira-Tintino et al. 2021). | Bacteria |
Bacillota | NorA of Staphylococcus aureus (P0A0J7) | |||
|
2.A.1.2.11 | Monoamine transporter; drug (doxorubicin, ethidium bromide-6-G):H+ antiporter | Eukaryota |
Metazoa, Chordata | VMAT1 of Rattus norvegicus | |||
|
2.A.1.2.12 | Chromaffin granule monoamine (and drug) transporter, VAT1. It is involved in the transport of biogenic monoamines such as serotonin from the cytoplasm into the secretory vesicles of neuroendocrine and endocrine cells (Essand et al. 2005). It is strongly inhibited by reserpine, and to a lesser extent by ketanserin and fenfluramine, but not by tetrabenazine (Erickson et al. 1996). Fine-tuning novel monoamine reuptake inhibitor selectivities has been acieved through manipulation of inhibitor stereochemistry (chirality) (Kalaba et al. 2023). | Eukaryota |
Metazoa, Chordata | SLC18A1 of Homo sapiens | |||
|
2.A.1.2.13 | Vesicular acetylcholine:H+ antiporter, UNC-17/VAChT. Mutants grow slowly and are uncoordinated, but the defects can be corrected by mutation of two interacting monotopic protein, synaptobrevin-1/SNB-1 (109 aas and 1 C-terminal TMS; Sandoval et al. 2006) and SUP-1 (103 aas and 1 C-terminal TMS (Mathews et al. 2012). | Eukaryota |
Metazoa, Nematoda | Unc17 of Caenorhabditis elegans | |||
|
2.A.1.2.14 | Putative arabinose efflux porter, AraJ. | Bacteria |
Pseudomonadota | AraJ of E. coli | |||
|
2.A.1.2.15 | Arabinose (but not xylose) and isopropyl β-D-thio-galactopyranoside:H+ antiporter, YdeA (Koita and Rao 2012). Overexpression of the gene for YdeA allows export of Lacto-N-triose (LNT II) and lacto-N-tetraose (LNT), human milk oligosaccharides (Sugita and Koketsu 2022). | Bacteria |
Pseudomonadota | YdeA of E. coli | |||
|
2.A.1.2.16 | Polyamines (spermine, spermidine, putrescine); paraquat; methylglyoxal bis(guanylhydrazone):H+ antiporter (in the plasma membrane) (activated by phosphorylation) (Uemura et al., 2005) | Eukaryota |
Fungi, Ascomycota | TPO1 (YLL028w) of Saccharomyces cerevisiae | |||
|
2.A.1.2.17 | Fluconazole:H+ antiporter | Eukaryota |
Fungi, Ascomycota | Flr1 of Saccharomyces cerevisiae | |||
|
2.A.1.2.18 | Lactose and melibiose (>>IPTG) efflux pump, SotB | Bacteria |
Pseudomonadota | SotB of Erwinia chrysanthemi | |||
|
2.A.1.2.19 | The multidrug (chloramphenicol, tetracycline, norfloxacin, doxorubicin, trimethoprim, acriflavin, ethidium bromide, tetraphenylphosphonium, TPP, benzalkonium, ciprofloxacin, thiamphenicol, IPTG) resistance exporter, MdfA (catalyzes both electrogenic and electroneutral transport) (Adler and Bibi, 2004). Can function as a Na+ (K+)/H+ antiporter (Lewinson and Bibi 2001; Higgins, 2007). Is known to provide resistance to a wide variety of dissimilar toxic compounds, including neutral, cationic and zwitterionic substances. Crystals that diffracted to 3.4 Å resolution and belonged to the hexagonal space group P6122 have been obtained (Nagarathinam et al. 2017). For review of MdfA see Lewinson et al., 2006. The conformational switch accompanying transport is induced by the promiscuous binding of substrates and/or inhibitors to the binding pocket (Fluman et al., 2009). MdfA normally extrudes monovalent cationic drugs in exchange for a single proton, but it transports divalent cationic drugs poorly. It can be mutated to antiport a divalent cationic drug for 2 protons (Tirosh et al., 2012). Transporters acting across the inner and outer membranes have synergistic effects with each other, but transporters acting across the same membrane are usually additive but can be synergistic under special circumstances, owing to a bifurcation controlled by the barrier constant (Saha et al. 2020). Promiscuity in the geometry of electrostatic interactions between MdfA and cationic substrates has been demonstrated (Adler and Bibi 2005). With respect to ethidium bromide, the inner membrane transporter MdfA is synergistic to the TolC-dependent efflux across the outer membrane (Saha et al. 2020). The conformational behavior of MdfA in response to substrate binding has been studied (Bahrenberg et al. 2021). Overexpression of the gene for MdfA allows export of Lacto-N-triose (LNT II) and lacto-N-tetraose (LNT), human milk oligosaccharides (Sugita and Koketsu 2022). It may also export ectoine and hydroxyectoine (Czech et al. 2022). | Bacteria |
Pseudomonadota | MdfA of E. coli (P0AEY8) | |||
|
2.A.1.2.20 | Broad specificity MDR efflux pump, MdtG (YceE) (under SoxSR control) (Fàbrega et al., 2010). Confer resistance to fosfomycin, fluoroquinolone and many other drugs (Nishino and Yamaguchi 2001). It may also export ectoine and hydroxyectoine (Czech et al. 2022). | Bacteria |
Pseudomonadota | MdtG of E. coli | |||
|
2.A.1.2.21 | The norfloxacin/enoxacin resistance protein, MdtH or YceL (Nishino and Yamaguchi 2001). | Bacteria |
Pseudomonadota | MdtH or YceL of E. coli (P69367) | |||
|
2.A.1.2.22 | The multidrug resistance protein, YidY (Nishino and Yamaguchi 2001). | Bacteria |
Pseudomonadota | YidY of E. coli | |||
|
2.A.1.2.23 | The fructose-specific facilitator (uniporter), Ffz1 (Pina et al., 2004) | Eukaryota |
Fungi, Ascomycota | Ffz1 of Zygosaccharomyces bailii (CAD56485) | |||
|
2.A.1.2.24 | The multidrug resistance efflux pump, CgMDR (exports fluoroquinolones and chloramphenicol) (Vardy et al., 2005) | Bacteria |
Actinomycetota | CgMDR of Corynebacterium glutamicum (NP_600365) | |||
|
2.A.1.2.25 | The purine base/nucleoside (nucleosides: inosine, adenosine and guanosine; bases: hypoxanthine, adenine, guanine, 2-fluoroadenine) efflux pump, YdhL (PbuE) (Johansen et al., 2003; Nygaard and Saxild, 2005; Zakataeva et al., 2007; Sheremet et al. 2011Sheremet et al. 2011). | Bacteria |
Bacillota | PbuE of Bacillus subtilis (O05504) | |||
|
2.A.1.2.26 | The purine ribonucleoside (inosine, adenosine, guanosine, 6-mercaptopurine ribonucleoside) efflux pump (H+ antiporter), NepI (YicM) (Gronskiy et al., 2005; Sheremet et al. 2011) | Bacteria |
Pseudomonadota | NepI of E. coli (P0ADL1) | |||
|
2.A.1.2.27 | The alcaligin siderophore exporter, AlcS (Brickman and Armstrong, 2005) | Bacteria |
Pseudomonadota | AlcS of Bordetella pertussis (CAE42734) | |||
|
2.A.1.2.28 | The vesicular acetylcholine transporter, VAChT (pumps acetylcholine into synaptic vesicles). The acetyl choline and vesamicol binding sites have been identified (Ojeda et al. 2004) and are near the luminal end of the transport pathway (Khare et al. 2010). The SLC18 family has been reviewed (Lawal and Krantz 2018). VAChT in the brain is an important presynaptic cholinergic biomarker (Hu et al. 2023). | Eukaryota |
Metazoa, Chordata | SLC18A3 of Homo sapiens | |||
|
2.A.1.2.29 | The vesicular monoamine transporter, VMAT2 (pumps dopamine, norepinephrine, serotonin and histamine into synaptic vesicles) (Cliburn et al. 2016). VMAT2 physically and functionally interacts with the enzymes responsible for dopamine synthesis (Cartier et al., 2010). Molecular hinge points mediating alternating access have been identified (Yaffe et al. 2013). The substituted amphetamine, 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy), is a widely used drug of abuse that induces non-exocytotic release of serotonin, dopamine, and norepinephrine through their cognate transporters as well as blocking the reuptake of neurotransmitter by the same transporters (Sealover et al. 2016). The slc18a2 gene is expressed at high levels in neuroepithelial cells (Pan et al. 2022). Synaptic vesicle proteins are selectively delivered to axons in mammalian neurons (Watson et al. 2023). VMAT2 may play a role in Parkinson's disease (Zhou et al. 2023). Dopaminergic cell protection and alleviation of neuropsychiatric disease symptoms are aleviated by VMAT2 expression (Lee et al. 2023). | Eukaryota |
Metazoa, Chordata | VMAT2 (SLC18A2) of Homo sapiens | |||
|
2.A.1.2.30 | The hippocampus abundant transcript-like 1 protein, HIATL1 or MFSD14B, of 506 aas and 12 TMSs (putative drug exporter) is a SLC18 family member. There is a correlation between a risk for colorectal cancer, alcohol consumption and variants in the 9q22.32/HIATL1 gene (Gong et al. 2016). MFSD14A (HIAT1) and MFSD14B (HIATL1) are in the mouse central nervous system throughout the adult brain (Lekholm et al. 2017). Expression of SLC22A18 regulates oxaliplatin resistance (Kim et al. 2022), and in cases of oxaliplatin resistance due to low SLC22A18 expression, resistance can be overcome by treatment with an ERK inhibitor (Kim et al. 2022). Two ammonia transporters, HIAT1alpha and HIAT1beta, in the American Horseshoe Crab, Limulus polyphemus, have been identified and characterized (Sachs et al. 2022). This gene is associated with milk production in buffalo and sheep breeds, as well as growth of chickens and goats, and drastically affect sperm formation (Luo et al. 2023). The functional InDel polymorphism (rs1089950828) reflects growth traits in domestic sheep populations (Luo et al. 2023). | Eukaryota |
Metazoa, Chordata | HIATL1 of Homo sapiens (NP_115947) | |||
|
2.A.1.2.31 | The multidrug transporter, QDR2, required for resistance to quinidine, barban, cisplatin, and bleomycin; may play a role in potassium uptake. | Eukaryota |
Fungi, Ascomycota | QDR2 of Saccharomyces cerevisiae (P40474) | |||
|
2.A.1.2.32 | The chloramphenicol resistance protein, ChlR | Bacteria |
Actinomycetota | ChlR of Streptomyces lividans (P31141) | |||
|
2.A.1.2.33 | The Hol1 MFS transporter (Mutation allows the uptake of histidinol and other cations (Wright et al., 1996). The N-terminal 200 residues show 22% identity with 2.A.1.2.1 and 2.A.1.2.16). | Eukaryota |
Fungi, Ascomycota | Hol1 of Saccharomyces cerevisiae (P53389) | |||
|
2.A.1.2.34 | The MDR efflux pump, PmrA (exports fluoroquinolone and other compounds) and other components including the antimicrobial peptide, colistin (Martinez-Garriga et al. 2007; Pamp et al., 2008). o-Cymen-5-ol nanoemulsion reverses colistin resistance in multidrug-resistant Klebsiella pneumoniae infections, and probably in other bacteria (Sheng et al. 2024). | Bacteria |
Bacillota | PmrA of Streptococcus pneumoniae (P0A4K4) | |||
|
2.A.1.2.35 | The caffeine resistance protein 5 (Caf5) (Benko et al., 2004) | Eukaryota |
Fungi, Ascomycota | Caf5 of Schizosaccharomyces pombe (O94528) | |||
|
2.A.1.2.36 | The multidrug resistance protein Aqr1 (YNL065w) (exports short chain monocarboxylates but not more hydrophobic acids such as octonate and quinidine. Also exports ketoconazole and crystal violet (Tenreiro et al., 2002)). | Eukaryota |
Fungi, Ascomycota | Aqr1 of Saccharomyces cerevisiae (P53943) | |||
|
2.A.1.2.37 | The legiobactin (siderophore) exporter (most similar to 2.A.1.2.9; 23% identity) (Allard et al., 2006) | Bacteria |
Pseudomonadota | IbtB of Legionella pneumophila LbtA (Q45RG2) LbtB (Q5WX21) | |||
|
2.A.1.2.38 | Tetracycline-specific exporter, TetA39 (most like 2.A.1.2.4) (Thompson et al., 2007). | Bacteria |
Pseudomonadota | TetA39 of Acinetobacter spp. (Q56RY7) | |||
|
2.A.1.2.39 | Tetracycline-specific exporter, TetA41 (most like 2.A.1.2.4) (Thompson et al., 2007). | Bacteria |
Pseudomonadota | TetA41 of Serratia marcescens (Q5JAK9) | |||
|
2.A.1.2.40 | The dityrosine exporter, Dtr1 (required for formation of the outer layer of the cell wall (Morishita and Engebrecht, 2008)). | Eukaryota |
Fungi, Ascomycota | Dtr1 of Saccharomyces cerevisiae (P38125) | |||
|
2.A.1.2.41 | The tetracycline resistance determinant, TetA42 from a deep terrestrial subsurface bacterium (Brown et al., 2008). | Bacteria |
Actinomycetota | TetA42 of Micrococcus sp. SMCC G8878 (B2YGG2) | |||
|
2.A.1.2.42 | The multidrug efflux pump, EmrD-3 (exports ethidium, linezolid, tetraphenylphosphonium chloride, rifampin, erythromycin, minocycline, trimethoprim, chloramphenicol, and rhodamine) (Smith et al., 2009). | Bacteria |
Pseudomonadota | EmrD-3 of Vibrio cholerae (Q9KMQ3) | |||
|
2.A.1.2.43 | The multidrug efflux pump, Qdr3 (exports polyamines, quinidine, barban, cisplatin and bleomycin). The two halves of the protein each have an N-terminal. 150 residue hydrophilic region found in many fungi followed by a 200 residue, 6 TMS, transmembrane region. This suggests that an intragenic duplication event gave rise to 12 TMS proteins independently of most other MFS carriers, but this has not been demonstrated, possibly because of extensive sequence divergence of the second half. | Eukaryota |
Fungi, Ascomycota | Qdr3 of Saccharomyces cerevisiae (P38227) | |||
|
2.A.1.2.44 | Diglucosyl-diacylglycerol exporter or flippase, LtaA (lipoteichoic acid protein A) (Gründling and Schneewind, 2007). | Bacteria |
Bacillota | LtaA of Staphylococcus aureus (Q2FZP8) | |||
|
2.A.1.2.45 | The fructose-specific uniporter, Ffz1 (69% identical to Ffz2 | Eukaryota |
Fungi, Ascomycota | Ffz1 of Zygosaccharomyces rouxii (C5E4Z7) | |||
|
2.A.1.2.46 | The fructose/glucose uniporter, Ffz2 (64% identical to 2.A.1.2.23). Both sugars are transported with similar affinities and efficiencies (Leandro et al., 2011). | Eukaryota |
Fungi, Ascomycota | Ffz2 of Zygosaccharomyces rouxii (C5DX43) | |||
|
2.A.1.2.47 | The multidrug resistance efflux pump, HsMDR (YfmO2). Exports drugs such as fluoroquinolones and chloramphenicol (Vardy et al., 2005). | Archaea |
Euryarchaeota | HsMDR of Halobacterium salinarum | |||
|
2.A.1.2.48 | tetracycline exporter | Eukaryota |
Fungi, Ascomycota | tetR exporter of Aspergillus niger (A2QTF4) | |||
|
2.A.1.2.49 | Putative tetracycline resistance protein | Archaea |
Thermoproteota | Putative tet resistance pump of Pyrobaculum aerophilum (Q8ZUX8) | |||
|
2.A.1.2.50 | MFS porter | Eukaryota |
Evosea | MFS porter of Dictyostelium purpureum (F0ZU09) | |||
|
2.A.1.2.51 | Chloramphenicol resistance pump, CraA (43% identical to MdfA of E. coli) (Roca et al., 2009). It is a broad specificity transporter exporting chloramphenicol, thiamphenicol, florfenicol, ethidium, dequalinium, chlorhexidine, benzalkonium, mitomycin C and TPP+. Glu-38 is essential for activity (Foong et al. 2019). | Bacteria |
Pseudomonadota | CraA of Acinetobacter baumannii (A3M9E9) | |||
|
2.A.1.2.52 | Puromycin resistance MDR protein, MdtM (Soo et al., 2011). Also catalyzes bile salt:H+ antiport, and binds cholate and deoxycholate to the protein with micromolar affinity. Functions as an MDR pump (Nishino and Yamaguchi 2001). Acts synergistically with AcrAB-TolC (Paul et al. 2014). The ortholog has been characterized in Salmonella enterica serovar Typhi, and specific residues have been shown to be important for transport and stability (Shaheen et al. 2021). | Bacteria |
Pseudomonadota | MdtM of E. coli (P39386) | |||
|
2.A.1.2.53 | MDR pump, SLC22A18 in lung cancer cells (Lei et al., 2012). It has 424 aas and 12 TMSs. Allelic loss in the absence of mutations in the polyspecific transporter gene BWR1A on 11p15.5 in hepatoblastoma has been shown (Albrecht et al. 2004). | Eukaryota |
Metazoa, Chordata | SLC22A18 of Homo sapiens | |||
|
2.A.1.2.54 | LigA-like protein | Bacteria |
Actinomycetota | LigA-like protein of Streptomyces coelicolor (Q9KYE9) | |||
|
2.A.1.2.55 | Peptide exporter (Ala-Gln and Ala-branched chain amino and dipeptides) (Hayashi et al., 2010). May also export arabinose (but not xylose) and function as an MDR pump (Koita and Rao 2012). | Bacteria |
Pseudomonadota | YdeE of E. coli (P31126) | |||
|
2.A.1.2.56 | NCL7 or MFSD8. Neuronal ceroid lipofuscinosis, NCL, a neuro-degenerative genetic disease, is caused by mutations in at least 8 different human genes, one of which, CLN7 (MFSD8), is associated with late infantile NCL. CLN7 is localized to lysosomes (Sharifi et al., 2010). Loss of this putative lysosomal transporter in the brain leads to lysosomal dysfunction, impaired constitutive autophagy and neurodegeneration late in the disease (Brandenstein et al. 2015). An in-frame deletion in the MFSD8 gene gave rise to neuronal ceroid lipofuscinosis type 7 (Hosseini Bereshneh and Garshasbi 2018). In D. discoideum, it interacts with cathepsin D (CtsD), as well as human orthologs of CLN3 (Cln3) and CLN5 (Cln5) (Huber et al. 2020). In humans the defect can also affect cardiac conducting cells and cardiomyocytes as well as basophilic degeneration of myocardium. (Iannaccone Farkašová et al. 2019). Moreover, loss of Mfsd8 alters the secretome during Dictyostelium aggregation (Huber et al. 2023). | Eukaryota |
Metazoa, Chordata | NCL7 of Homo sapiens (Q8NHS3) | |||
|
2.A.1.2.57 | MFS-type polyamine transporter SLC18B1 or VPAT (Solute carrier family 18 member B1) of 456 aas and 12 TMSs. Polyamines synthesized in neurons and astrocytes are stored in secretory vesicles and released upon depolarization. Vesicular storage is mediated in an ATP-dependent, reserpine-sensitive process. SLC18B1 is the fourth member of the SLC18 transporter family, which includes vesicular monoamine transporters and a vesicular acetylcholine transporter. Proteoliposomes containing purified human SLC18B1 protein actively transport spermine and spermidine in exchange of H+. The SLC18B1 protein is predominantly expressed in the hippocampus and is associated with vesicles in astrocytes. SLC18B1 gene knockdown decreased both the amount of the SLC18B1 protein and the spermine/spermidine contents of astrocytes (Hiasa et al. 2014). Slc18b1 knock out mice have reduced polyamine content in the brain These mice have impaired short and long term memory in novel object recognition, radial arm maze and self-administration paradigms (Fredriksson et al. 2019). Moreover, Slc18b1 KO mice have altered expression of genes involved in Long Term Potentiation, plasticity, calcium signalling and synaptic functions, and expression of components of GABA and glutamate signalling are alterred. These mutants show partial resistance to diazepam, manifested as lowered reduction in locomotion after diazepam treatment. Possibly, removal of Slc18b1 leads to reduction of polyamine contents in neurons, resulting in reduced GABA signalling due to a long-term reduction in glutamatergic signalling (Fredriksson et al. 2019). Polyamine release and vesicular polyamine transporter, SLC18B1; VPAT,. expression in megakaryoblastic cells and plateletshas been documented (Uehara et al. 2024). | Eukaryota |
Metazoa, Chordata | C6orf192 of Homo sapiens | |||
|
2.A.1.2.58 | Protein ZINC INDUCED FACILITATOR 1 | Eukaryota |
Viridiplantae, Streptophyta | ZIF1 of Arabidopsis thaliana | |||
|
2.A.1.2.59 | Uncharacterized MFS-type transporter C330.07c; YJ87 | Eukaryota |
Fungi, Ascomycota | YJ87 of Schizosaccharomyces pombe | |||
|
2.A.1.2.60 | YajR of 454 aas and 12 TMSs. The 3-D structure in the outward-facing conformation is available at 3.15Å resolution, and the cytoplasmic C-terminal YAM domain has been solved to 1.07Å resolution. This 65 aa YAM domain is thought to control the conformational states of the protein (Jiang et al. 2013; Jiang et al. 2014). | Bacteria |
Pseudomonadota | YajR of E. coli | |||
|
2.A.1.2.61 | SPX domain-containing membrane protein At1g63010, called Vacuolar Phosphate Transporter 1 (VPT1), It transports phosphate > sulphate > nitrate > chloride and malate. The vpt1 mutant plants were stunted and consistently retained less Pi than wild type plants, especially when grown in medium containing high levels of Pi. In seedlings, VPT1 was expressed primarily in younger tissues under normal conditions, but was strongly induced by high-Pi conditions in older tissues, suggesting that VPT1 functions in Pi storage in young tissues and in detoxification of high Pi in older tissues. As a result, disruption of VPT1 rendered plants hypersensitive to both low-Pi and high-Pi conditions, reducing the adaptability of plants to changing Pi availability (Liu et al. 2015). | Eukaryota |
Viridiplantae, Streptophyta | VPT1 or At1g63010 of Arabidopsis thaliana | |||
|
2.A.1.2.62 | Putative MDR pump, YdhC or PunC. It has been reporte to export arabinose but not xylose (Koita and Rao 2012). However, it also takes up adenosine, adenine, deoxyadenosine, and other purine nucleosides and nucleobases such as inosine and guanosine as sole nitrogen sources. It also takes up various sulfonamides such as sulfathiazole, sulfadiazine and sulfamethoxazole. Expression of the punC gene is reglulated by the positive transcription factor, PunR (YdhB) (Rodionova et al. 2021). | Bacteria |
Pseudomonadota | PunC (YdhC) of Escherichia coli | |||
|
2.A.1.2.63 | Probable drug/proton antiporter YHK8 | Eukaryota |
Fungi, Ascomycota | YHK8 of Saccharomyces cerevisiae | |||
|
2.A.1.2.64 | Polyamine exporter 4 (Igarashi and Kashiwagi 2010). | Eukaryota |
Fungi, Ascomycota | TPO4 of Saccharomyces cerevisiae | |||
|
2.A.1.2.65 | Bacteria |
Pseudomonadota | YdhP of Escherichia coli | ||||
|
2.A.1.2.66 | Polyamine exporter 3 (Igarashi and Kashiwagi 2010). | Eukaryota |
Fungi, Ascomycota | TPO3 of Saccharomyces cerevisiae | |||
|
2.A.1.2.67 | Polyamine exporter 2 (Igarashi and Kashiwagi 2010). | Eukaryota |
Fungi, Ascomycota | TPO2 of Saccharomyces cerevisiae | |||
|
2.A.1.2.68 | Tetracycline resistance protein, class B (TetA(B)) (Metal-tetracycline/H+ antiporter). Mutants defective in either transport or tetracycline binding have been isolated (Wright and Tate 2015). Several amino acid substitutions (i.e., D190C, E192C and S201C) alter the specificity of the porter so that it prefers deoxycycline (3x) and minochcline (6x) over tetracycline (Sapunaric and Levy 2005). | Bacteria |
Pseudomonadota | TetA of Escherichia coli | |||
|
2.A.1.2.69 | Bacteria |
Bacillota | YttB of Bacillus subtilis | ||||
|
2.A.1.2.70 | Multidrug resistance protein 1 (Multidrug-efflux transporter 1) | Bacteria |
Bacillota | Bmr of Bacillus subtilis | |||
|
2.A.1.2.71 | Uncharacterized MFS-type transporter Rv2456c/MT2531 | Bacteria |
Actinomycetota | Rv2456c of Mycobacterium tuberculosis | |||
|
2.A.1.2.72 | Major facilitator superfamily domain-containing protein 9 | Eukaryota |
Metazoa, Chordata | Mfsd9 of Mus musculus | |||
|
2.A.1.2.73 | Major facilitator superfamily domain-containing protein 10, MFSD10, a member of the SLC18 family. It is a tetracycline exporter-like protein. This protein is found in the inner nuclear membrane (Cheng et al. 2019) and is a disease protein in humans (Bagchi et al. 2020). Its gene shows increased expression with increased energy consumption (Bagchi et al. 2020). It may confers cellular resistance to apoptosis induced by the non-steroidal anti-inflammatory drugs, indomethacin and diclofenac. A microdeletion proximal to the mfsD10 gene is associated with mild Wolf-Hirschhorn syndrome (Hannes et al. 2012).
| Eukaryota |
Metazoa, Chordata | MfsD10 of Mus musculus | |||
|
2.A.1.2.74 | Multidrug resistance protein MdtL | Bacteria |
Pseudomonadota | MdtL of Shewanella sp. | |||
|
2.A.1.2.75 | Tetracycline resistance protein, class E (TetA(E)) | Bacteria |
Pseudomonadota | TetA of Escherichia coli | |||
|
2.A.1.2.76 | Major facilitator copper transporter 1, Mfc1. Takes up copper in meiotic sporulating cells; present in the forespore membrane. Induced under copper limitation. Required for normal forespore development and spore copper-dependent amine oxidase activity (Beaudoin et al. 2011). | Eukaryota |
Fungi, Ascomycota | Mfc1 of Schizosaccharomyces pombe | |||
|
2.A.1.2.77 | CefT confers phenylacetate resistance (Fernández-Aguado et al. 2012). It has been reported to be a hydrophilic beta-lactam transporter that is involved in the secretion of hydrophilic beta-lactams containing an α-aminoadipic acid side chain (isopenicillin N, penicillin N and deacetylcephalosporin C) (Cesareo et al. 2007; Ullán et al. 2002). | Eukaryota |
Fungi, Ascomycota | CefT of Acremonium chrysogenum | |||
|
2.A.1.2.78 | The PaaT (PenT) exporter. PaaT is involved in penicillin production, possibly through the translocation of side-chain precursors (phenylacetate and phenoxyacetate) from the cytosol to the peroxisomal lumen across the peroxisomal membrane of P. chrysogenum. It has a Pex19 (peroxisome biogenesis factor 19) binding sequence (residues 258 - 269) accounting for its peroxysomal location (Fernández-Aguado et al. 2012; Yang et al. 2012). | Eukaryota |
Fungi, Ascomycota | PaaT of Penicillum chysogenum (notatum) | |||
|
2.A.1.2.79 | The host-nonselective polyketide perylenequinone toxin, cercosporin, exporter, Ctb4 (Choquer et al. 2007). | Eukaryota |
Fungi, Ascomycota | Ctb4 of Cercospora nicotianae | |||
|
2.A.1.2.80 | Putative permease of 458 aas | Eukaryota |
Rhodophyta | Putative permease of Galdieria sulphuraria | |||
|
2.A.1.2.81 | Uncharacterized MFS permease; encoded by a gene adjacent to one encoding a peroxiredoxin (an electron donor and antioxidant; Hanschmann et al. 2013). | Bacteria |
Deinococcota | UP of Deinococcus peraridilitoris | |||
|
2.A.1.2.82 | Uncharacterized MFS permease of 402 aas and 12 TMSs | Bacteria |
Spirochaetota | UP of Leptospira interrogans | |||
|
2.A.1.2.83 | MmrA MFS protein. Homologous to drug exporter. RppA and MmrA are involved in amino acid uptake and efflux of antimicrobial agents including streptomycin, ethidium bromide and norfloxacin (Kimura et al. 2004). | Bacteria |
Myxococcota | MXAN_5906 of Myxococcus xanthus. | |||
|
2.A.1.2.84 | Probable siderophore-specific exporter of 407 aas and 12 TMSs, MxcK. | Bacteria |
Myxococcota | MxcK of Stigmatella aurantiaca | |||
|
2.A.1.2.85 | Peroxysomal phenylacetate/phenoxyacetate transporter, PaaT (CefT) of 564 aas (Fernández-Aguado et al. 2013). | Eukaryota |
Fungi, Ascomycota | PaaT of Penicillium chrysogenum (Penicillium notatum) | |||
|
2.A.1.2.86 | Peroxisomal isopenicillin N importer, PenM (Evers et al. 2004; Fernández-Aguado et al. 2014). | Eukaryota |
Fungi, Ascomycota | PenM of Penicillium chrysogenum (Penicillium notatum) | |||
|
2.A.1.2.87 | Purine efflux porter of 392 aas, CepA. Exports purine analogues, 6-mercaptopurine and 6-mercaptoguanine, but not to 2-aminopurine and purine nucleoside analogues. May show increased resistance to the antibiotics nalidixic acid and ampicillin (Sim et al. 2014). | Bacteria |
Actinomycetota | CepA of Corynebacterium glutamicum | |||
|
2.A.1.2.88 | MFS porter of 442 aas | Archaea |
Euryarchaeota | MFS porter of Pyrococcus furiosus | |||
|
2.A.1.2.89 | MFS porter of 454 aas | Bacteria |
Actinomycetota | MFS porter of Streptomyces coelicolor | |||
|
2.A.1.2.90 | UMF4F of 405 aas and 12 TMSs | Bacteria |
Bacillota | UMF4F of Aectobacterium woodii | |||
|
2.A.1.2.91 | MFS permease of 554 aas and 12 TMSs | Eukaryota |
Fungi, Ascomycota | Putative MFS carrier of Metarhizium robertsii (Metarhizium anisopliae) | |||
|
2.A.1.2.92 | The CefM protein of 482 aas and 12 TMSs. Probably involved in the translocation of penicillin N from the lumen of peroxisomes (or peroxisome-like microbodies) to the cytosol, where it is converted into cephalosporin C (Teijeira et al. 2009). A null mutant accumulates penicillin N, is unable to synthesize deacetoxy- and deacetyl-cephalosporin C as well as cephalosporin C, and shows impaired differentiation into arthrospores (Teijeira et al. 2009). | Eukaryota |
Fungi, Ascomycota | CefM of Acremonium chrysogenum (Cephalosporium acremonium) | |||
|
2.A.1.2.93 | Uncharacterized MFS permease of 433 aas and 12 TMSs | Bacteria |
Bacillota | UP of Lactobacillus buchneri | |||
|
2.A.1.2.94 | Uncharacterized MFS permease of 445 aas and 12 TMSs | Bacteria |
Actinomycetota | UP of Microbacterium maritypicum | |||
|
2.A.1.2.95 | Blt of 422 aas and 12 TMSs. Exports antibiotics such as fluoroquinolones and chloramphenicol (Vardy et al. 2005) | Bacteria |
Actinomycetota | Blt of Mycobacterium smegmatis | |||
|
2.A.1.2.96 | ZIF2 (Zinc-Induced Facilitator 2) of 484 aas and 12 TMSs localises primarily at the tonoplast of root cortical cells and is a functional transporter able to mediate Zn efflux from the cytoplasm (Remy et al. 2014). Activity is controlled by alternative RNA splicing. | Eukaryota |
Viridiplantae, Streptophyta | ZIF2 of Arabidopsis thaliana | |||
|
2.A.1.2.97 | Bcr/CflA family drug exporter, MSMEG_2991 of 428 aas and 12 TMSs. A pmf-dependent multidrug efflux pump that expels diverse groups of antibiotics including ciprofloxacin. May also be involved in biofilm enhancement (Bansal et al. 2016). | Bacteria |
Actinomycetota | Bcr-like exporter of Mycobacterium smegmatis | |||
|
2.A.1.2.98 | Uncharacterized MFS transporter of 427 aas and 12 TMSs. | Archaea |
Thermoproteota | UP of Aeropyrum camini | |||
|
2.A.1.2.99 | Putative siderophore exporter, SbnD of 418 aas and 12 TMSs (Marklevitz and Harris 2016). | Bacteria |
Bacillota | SbnD of Staphylococcus aureus | |||
|
2.A.1.2.100 | Bcr/CflA family drug resistance efflux transporter of 389 aas and 12 TMSs. Multidrug-resistance in S. aureus is inhibited by the endocannabinoid, anandamide (Sionov et al. 2022). Butyrolactone I enhances the efficacy of gentamycin in methicillin-resistant S. aureus (Jiang et al. 2024). | Bacteria |
Bacillota | MDR exporter of Staphylococcus aureus | |||
|
2.A.1.2.101 | Bmr-like protein SblA of 395 aas and 12 TMSs. | Bacteria |
Bacillota | SblA of Staphylococcus aureus | |||
|
2.A.1.2.102 | TetA class C (TetA(C)) of 396 aas and 12 TMSs. The TetA(C) of the transposon, Tn10, not only exports tetracycline by a proton antiport mechanism, it also increases susceptibility to cadmium, fusaric acid, bleomycin and several classes of cationic aminoglycoside antibiotics (Griffith et al. 1995). For this reason, it has been used to generate dual counter selection procedures (Li et al. 2013). It is not certain that this is due to import of these compounds as this increased susceptibility could be due to a secondary effect. | Bacteria |
Pseudomonadota | TetA(C) of E. coli | |||
|
2.A.1.2.103 | Tetracycline:H+ class D, (TetA(D)) antiporter of 286 aas and 12 TMSs. | Bacteria |
Pseudomonadota | TetA(D) of E. coli | |||
|
2.A.1.2.104 | MFS carrier of 490 aas and 12 TMSs, MfsD14a or Hiat1 (Hippocampus abundant transcript 1 protein) is a member of the SLC18 family. It is 76% identical to 2.A.1.2.30. Mutant mice (Mus musculus, strain 129S6Sv/Ev) were generated with the Mfsd14a gene disrupted with a LacZ reporter gene. Mutant mice are viable and healthy, but males are sterile due to a 100-fold reduction in the number of spermatozoa in the vas deferens. Male mice have adequate levels of testosterone and show normal copulatory behaviour. The few spermatozoa that are formed show rounded head defects similar to those found in humans with globozoospermia. Spermatogenesis proceeds normally up to the round spermatid stage, but the subsequent structural changes associated with spermiogenesis are severely disrupted with failure of acrosome formation, sperm head condensation and mitochondrial localization to the mid-piece of the sperm. Mfsd14a expression occurs in Sertoli cells, suggesting that MFSD14A may transport a solute from the bloodstream that is required for spermiogenesis (Doran et al. 2016). MFSD14A and MFSD14B are intracellular neuronal membrane-bound proteins, expressed in the Golgi and ER, and their levels of expression are affected by both starvation and a high fat diet to varying degrees in the mouse brain (Lekholm et al. 2017). It is associated with milk production in buffalo and sheep breeds, as well as growth of chickens and goats, and drastically affect s sperm morphogenesis (Luo et al. 2023). The functional InDel polymorphism (rs1089950828) reflects growth traits in domestic sheep populations (Luo et al. 2023). | Eukaryota |
Metazoa, Chordata | MfsD14a of Homo sapiens | |||
|
2.A.1.2.105 | MFSD9 of 474 aas and 12 TMSs. In the mouse, this protein and MFS4a localize to neurons in the brain; their mRNA expression levels are affected by diet (Perland et al. 2017). This protein is in the SLC18 family (Gyimesi and Hediger 2022). | Eukaryota |
Metazoa, Chordata | MFSD9 of Homo sapiens | |||
|
2.A.1.2.106 | Bacteria |
Bacillota | yvmA of Bacillus subtilis | ||||
|
2.A.1.2.107 | MFS porter of 399 aas and 12 TMSs, HepP, involved in the uptake of glycoside(s), with a specific physiological role in production of heterocyst exopolysaccharide, HEP (López-Igual et al. 2012). | Bacteria |
Cyanobacteriota | HepP of Anabaena or Nostoc sp. (strain PCC 7120) | |||
|
2.A.1.2.108 | Putative spermine uptake porter of 552 aas and 12 TMSs, SPBC409.08. Spermine and the spermine-precursor, spermidine, are implicated in ageing as they are involved in autophagy-dependent lifespan extension (Ellis et al. 2018). | Eukaryota |
Fungi, Ascomycota | SPBC409.08 of Schizosaccharomyces pombe | |||
|
2.A.1.2.109 | MFS porter of 414 aas and 12 TMSs. It has been suggested that it could be a citrate efflux porter (Braakman et al. 2017). | Bacteria |
Cyanobacteriota | MFS porter of Prochlorococcus marinus | |||
|
2.A.1.2.110 | Florfenicol-chloramphenicol resistance drug exporter, FloR of 404 aas and 12 TMSs (Braibant et al. 2005). This system in V. cholerae (98.8% identical) exports chlorampenicol (Saha et al. 2024). | Bacteria |
Pseudomonadota | FloR of Salmonella enterica subsp. enterica serovar Typhimurium str. DT104 | |||
|
2.A.1.2.111 | Zinc-induced facilitator-like protein 1, ZIFL1 or Tpo1p of 478 aas and 12 TMSs. It confers resistance to the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) and is transcriptionally activated in response to this herbicide. Tpo1p is required to reduce the intracellular concentration of 2,4-D (Cabrito et al. 2009). K+ may be its physiological substrate, and it may play a dual role in polar auxin transport and drought stress tolerance (Remy et al. 2013). It is also involved in auxin efflux and acts as a positive regulator of shootward transport at the root apex. Possibly, it may mediate proton efflux from the vacuolar compartment (Remy et al. 2013). | Eukaryota |
Viridiplantae, Streptophyta | Tpo1 of Arabidopsis thaliana | |||
|
2.A.1.2.112 | Uncharacterized protein of 904 aas with 16 TMSs in a 6 + 6 + 3 + 1 TMS arrangement, where the last 300 aas comprise the non-MFS integral membrane domain with at least 4, and maybe as many as 6 TMSs. May possibly play a role in lipid transport. | Eukaryota |
Fungi, Ascomycota | UP of Aspergillus ruber | |||
|
2.A.1.2.113 | Uncharacterized MFS transporter of 539 aas and 11 TMSs. It is probably similar in sequence to MfsT, described as a penicillin G (isopenicillin N) precursor in Monascus ruber (Ramzan et al. 2019). | Eukaryota |
Fungi, Ascomycota | MFS porter of Aspergillus clavatus | |||
|
2.A.1.2.114 | MFS1 of 728 aas and 12 TMSs. The MFS1 transporter contributes to Penicilliun digitatum fungicide resistance and fungal virulence during citrus fruit infection (de Ramón-Carbonell et al. 2019). | Eukaryota |
Fungi, Ascomycota | MFS1 of Penicillium digitatum | |||
|
2.A.1.2.115 | Multidrug resistance MDR exporter of 583 aas and 12 TMSs. It is involved in resistance to the antifungal drugs miconazole, tioconazole, clotrimazole and ketoconazole as well as to quinidine (Costa et al. 2013; Costa et al. 2016). It also plays a role in biofilm formation. Compared to the wild type, the C. glabrata ∆qdr2 mutant showed lower adhesion activity and higher fluconazole susceptibility when assessed as a biofilm. The mutant also showed decreased metabolic activity during biofilm formation and grew more slowly under neutral-basic pH conditions. The qdr2 deletion in C. glabrata resulted in an impaired ability to maintain pH homeostasis, which led in turn to a reduction of cell growth and of adherence to an artificial matrix (Widiasih Widiyanto et al. 2019). Mitochondrion-targeted antifungal drugs have been reviewed (Qin et al. 2023). | Eukaryota |
Fungi, Ascomycota | MDR pump of Candida glabrata (Yeast) (Torulopsis glabrata) | |||
|
2.A.1.2.116 | MDR efflux pump, Bcr/CflA, of 411 aas and 12 TMSs. Confer's chloramphenicol resistance (Yang et al. 2019). | Bacteria |
Myxococcota | Brc of Myxococcus xanthus | |||
|
2.A.1.2.117 | Uncharacterized protein of 510 aas and 12 TMSs. | Eukaryota |
Bacillariophyta | UP of Fistulifera solaris | |||
|
2.A.1.2.118 | Na+ (K+ or Li+)/H+ antiporter and multidrug:Na+ anitporter, MdrP of 424 aas and 12 TMSs. It exports ethidium and norfloxacin in exchange for Na+ taken up (Abdel-Motaal et al. 2018). D223 acts as a key determinant in the Na+ translocation coupled to norfloxacin efflux (R. Zhang, Abdel-Motaal et al, 2020). | Bacteria |
Bacillota | ||||
|
2.A.1.2.119 | AaMFS1 is an efflux pump for the transmembrane transport of tenuazonic acid (TeA) (Sun et al. 2022). See 4.C.1.1.19 for relevant information about the TeA synthetase that makes TeA before exporting it (Sun et al. 2022). The genes encoding these two proteins are adjacent to each other. | Eukaryota |
Fungi, Ascomycota | MFS1 of Alternaria alternata | |||
|
2.A.1.2.120 | Major Familitator, MFS6 of 550 aas and 12 TMSs in a 6 + 6 TMS arrangement with a central ~ 200 aa hydrophilic domain. The substrate is not known (Wichers et al. 2022). | Eukaryota |
Apicomplexa | MFS6 of Plasmodium malariae | |||
|
2.A.1.2.121 | MFS permease of 550 aas and 12 TMSs in a 6 + 6 TMS arrangement with a large central hydrophilic domain betweem residues 200 and 370. | Eukaryota |
Apicomplexa | MFS permease of Plasmodium ovale (malaria parasite P. ovale) | |||
|
2.A.1.2.122 | MfsC (Smlt0549), a probable diamide exporter of 379 aas and 12 TMSs in a 6 + 6 TMS arrangement. It is encoded within the mfsBC operon controlled by the DitR TetR-like transcript factor which binds diamide to displace the repressing factor from the DNA. MfsB (BeFL18) may be a sugar uptake porter (Boonyakanog et al. 2022). | Bacteria |
Pseudomonadota | MfsC of Stenotrophomonas maltophilia | |||
|
2.A.1.2.123 | Fluconazole resistance protein 1, Flu1 of 610 aas and 12 TMSs. It mediates resistance to structurally and functionally unrelated compounds including cycloheximide but also azoles such as fuconazole, ketoconazole and itraconazole (Calabrese et al. 2000). It mediates efflux of histatin 5, a salivary human antimicrobial peptide, and is responsible for reduction of its toxicity in C.albicans (Li et al. 2013, Hampe et al. 2017). Mutations in the Erg251 ergosterol biosynthetic enzyme can also give rise to azole resistance (Zhou et al. 2024). | Eukaryota |
Fungi, Ascomycota | Flu1 of Candida albicans | |||
|
2.A.1.2.124 | Putative MDR pump, MDT; MFS1, of 442 aas and 12 TMSs (Wunderlich 2022). | Eukaryota |
Apicomplexa | MDR pump of Plasmodium falciparum | |||
|
2.A.1.2.125 | MFS drug-resistance efflux pump of 401 aas and 12 TMSs. This system exports tetracycline and doxycycline and is induced by several drugs in addition to these compounds (Li et al. 2023). | Bacteria |
Bacillota | SAUSA300_09310 of Staphylococcus aureus | |||
|
2.A.1.2.126 | MFS permease of 405 aas and 12 TMSs, KpsrMFS (He et al. 2024). This efflux pump is a proton-driven transporter that can reduce the intracellular tetracycline concentration. In normal conditions, the expression of kpsrmfs was at a low level, while artificial overexpression of it led to increased endogenous reactive oxygen species (ROS) production. By comparing the functions of adjacent genes of kpsrmfs, another four genes that can confer similar phenotypes, indicating a special regulon that regulates cell growth.. | Bacteria |
Pseudomonadota | KpsrMFS of Klebsiella pneumoniae | |||
| 2.A.1.3: The Drug:H+ Antiporter-2 (14 Spanner) (DHA2) Family | |||||||
|
2.A.1.3.1 | The main boron exporter in yeast, Atr1 (Kaya et al. 2009) (Aminotriazole, 4-nitroquinoline-N-oxide, etc.):H+ antiporter. Also exports L-cysteine (Yamada et al., 2006). | Eukaryota |
Fungi, Ascomycota | Atr1 of Saccharomyces cerevisiae | |||
|
2.A.1.3.2 | Exporter of CCCP, nalidixic acid, rhodamine 6G, methylviologen, deoxycholate, growth inhibitory steroid hormones (estradiol and progesterone) (Elkins and Mullis, 2006) SDS, organomercurials, etc. (Nishino and Yamaguchi 2001). | Bacteria |
Pseudomonadota | EmrB of E. coli (P0AEJ0) | |||
|
2.A.1.3.3 | (Acriflavin, ethidium bromide, fluoroquinolones, etc.):H+ antiporter (Li et al. 2004; Rodrigues et al. 2011). | Bacteria |
Actinomycetota | LfrA of Mycobacterium smegmatis | |||
|
2.A.1.3.4 | (Mono- and divalent organocation):H+ antiporter. Transmembrane helix 12 of QacA lines the bivalent cationic drug binding pocket (Hassan et al., 2007). Two sites, D34 and D411 are involved in substrate recognition, while E407 facilitates substrate efflux as a protonation site and plays a role as a substrate recognition site for the transport of dequalinium, a divalent quaternary ammonium compound (Majumder et al. 2019). TMS 12 and its external flanking loop are required for the structural and functional integrity of QacA, and they contain amino acids directly involved in their interactions with substrates (Dashtbani-Roozbehani et al. 2023). Cryo-EM structures of QacA from S. aureus revealed a novel extracellular loop with an allosteric role (Majumder et al. 2023). | Bacteria |
Bacillota | QacA of Staphylococcus aureus (P0A0J9) | |||
|
2.A.1.3.5 | (Pristinamycin I and II, rifamycin, etc.):H+ antiporter | Bacteria |
Actinomycetota | Ptr of Streptomyces pristinaespiralis | |||
|
2.A.1.3.6 | Me2+·tetracycline:2H+ or 2K+ antiporter (the optimal Me2+ = Co2+) (Also transports Na+ or K+out in exchange for 2H+.) | Bacteria |
Bacillota | TetK of Staphylococcus aureus (P02983) | |||
|
2.A.1.3.7 | Actinorhodin:H+ antiporter, ActVa or ActA (Tahlan et al., 2007) | Bacteria |
Actinomycetota | ActVa of Streptomyces coelicolor | |||
|
2.A.1.3.8 | Cephamycin:H+ antiporter | Bacteria |
Actinomycetota | CmcT of Nocardia lactamdurans | |||
|
2.A.1.3.9 | Lincomycin:H+ antiporter | Bacteria |
Actinomycetota | LmrA of Streptomyces lincolnensis | |||
|
2.A.1.3.10 | Methylenomycin:H+ antiporter | Bacteria |
Bacillota | MmrB of Bacillus subtilis | |||
|
2.A.1.3.11 | Puromycin:H+ antiporter | Bacteria |
Actinomycetota | Pur8 of Streptomyces lipmanii | |||
|
2.A.1.3.12 | Tetracenomycin:H+ antiporter | Bacteria |
Actinomycetota | TcmA of Streptomyces glaucescens | |||
|
2.A.1.3.13 | Unconjugated bile acid uptake transporter | Bacteria |
Bacillota | BaiG of Eubacterium sp. strain VPI 12708 | |||
|
2.A.1.3.14 | Methylviologen (paraquat):H+ antiporter, SmvA (also exports ethidium bromide, acriflavin, malachite green, pyronine B and benzyl viologen) (Villagra et al. 2008). | Bacteria |
Pseudomonadota | SmvA of Salmonella typhimurium | |||
|
2.A.1.3.15 | Rifamycin:H+ antiporter | Bacteria |
Actinomycetota | RifP of Amycolatopsis mediterranei | |||
|
2.A.1.3.16 | The Me2+·tetracycline:2H+ antiporter | Bacteria |
Bacillota | TetA(L) of Bacillus subtilis | |||
|
2.A.1.3.17 | The trimethoprim-sensitivity protein, YebQ (increases sensitivity to trimethoprim) | Bacteria |
Pseudomonadota | YebQ of E. coli | |||
|
2.A.1.3.18 | Efflux pump for plant-bacterial signaling molecules, phytoalexins, flavonoids and salicylate as well as drugs, RmrB | Bacteria |
Pseudomonadota | RmrB of Rhizobium etli | |||
|
2.A.1.3.19 | Paraquat efflux pump, PqrB (Cho et al., 2003) | Bacteria |
Actinomycetota | PqrB of Streptomyces coelicolor (AAG45950) | |||
|
2.A.1.3.20 | Long chain fatty acid efflux pump, FarB (Lee et al., 2003) (exports antimicrobial long chain fatty acids; functions with MFP auxillary protein, FarA (TC# 8.A.1.1.2)) (Lee et al., 2006) | Bacteria |
Pseudomonadota | FarB of Neisseria gonorrhoeae (AAD54074) | |||
|
2.A.1.3.21 | Siderophore, achromobactin efflux pump, YhcA (Franza et al., 2005) | Bacteria |
Pseudomonadota | YhcA of Erwinia (Pectobacterium) chrysanthemi (AAL14569) | |||
|
2.A.1.3.22 | The Tet38 tetracycline-resistance protein of 450 aas and 14 TMSs of S. aureus (Truong-Bolduc et al., 2005). Tet38 has distinct functions, including drug efflux and host cell attachment and internalization mediated by interaction with host cell CD36. Truong-Bolduc et al. 2021 identified key amino acids involved in different functions. Cysteine substitutions of arginine 106, situated at the junction of TMS 4 and external loop L2, and glycine 151 of motif C on TMS 5, resulted in 8- to 16-fold reductions in Tet38-mediated resistance to tetracycline, with minimal effect on A549 host cell internalization. In contrast, two three-amino-acid deletions, F411P412G413, in external loop L7, situated between TMSs 13 and 14, and D38D39L40, in external loop L1, situated between TMS 1 and 2, led to decreased tetracycline resistance, but only the former affected S. aureus internalization and impaired binding to CD36 (Truong-Bolduc et al. 2021). | Bacteria |
Bacillota | Tet38 of Staphylococcus aureus (AAV80464) | |||
|
2.A.1.3.23 | The NorB multidrug resistance pump (exports hydrophilic quinolones, ethidium bromide, cetrimide, sparfloxacin, moxifloxacin and tetracycline) (Truong-Bolduc et al., 2005) | Bacteria |
Bacillota | NorB of Staphylococcus aureus (BAB42529) | |||
|
2.A.1.3.24 | The VceAB multidrug (hydrophobic compounds including deoxycholate (DOC), antibiotics, such as chloramphenicol and nalidixic acid, and the proton motive force uncoupler, cyanide carbonyl m-chlorophenylhydrazone (CCCP)) resistance pump (functions with outer membrane VceC (TC#1.B.17.3.6) or OprM (2.A.6.2.21), an OMF family member; The C-terminal domain of the Pseudomonas aeruginosa OprM and the alpha-helical hairpin domain of Vibrio cholerae VceA play important roles in recognition/specificity/recruitment in the assembly of a functional, VceAB-OprM chimeric efflux pump (Bai et al., 2010). | Bacteria |
Pseudomonadota | VceAB of Vibrio cholerae VceB (MFS), NP_231054 VceA (MFP), NP_231053 | |||
|
2.A.1.3.25 | Actinorhodin (blue pigmented antibiiotic) transporter, ActII-2 | Bacteria |
Actinomycetota | ActII-2, Actinorhodin transporter of Streptomyces coelicolor (P46105). | |||
|
2.A.1.3.26 | Novobiocin/deoxycholate exporting MDR efflux pump, MdtD or YegB (Baranova and Nikaido, 2002). Also exports arabinose but not xylose (Koita and Rao 2012). Regulated by the transcription factor, BaeR (Nagakubo et al. 2002). | Bacteria |
Pseudomonadota | YegB of E. coli (P36554) | |||
|
2.A.1.3.27 | The vacuolar basic amino acid (Arg, Lys, His) transporter, Vba3 (Shimazu et al., 2005) | Eukaryota |
Fungi, Ascomycota | Vba3 of Saccharomyces cerevisiae (P25594) | |||
|
2.A.1.3.28 | MDR multidrug efflux pump, EbrE (involved in colony growth, dependent on Ca2+, Mg2+, Na+ and K+) (Lee et al., 2007) | Bacteria |
Actinomycetota | EbrE of Streptomyces lividans (Q939A4) | |||
|
2.A.1.3.29 | The metal:tetracycline/oxytetracycline resistance efflux pump, TctB (563 aas) | Bacteria |
Actinomycetota | TctB of Streptomyces rimosus (O69070) | |||
|
2.A.1.3.30 | Lincomycin resistance protein; Lincomycin:H+ antiporter, LmrB | Bacteria |
Bacillota | LmrB of Bacillus subtilis (O35018) | |||
|
2.A.1.3.31 | The hydrophilic fluoroquinolones efflux pump, QepA (Perichon et al., 2008). Exports hydrophilic quinolones, norfloxacin, and ciprofloxacin. | Bacteria |
Pseudomonadota | QepA of E. coli (A5H8A5) | |||
|
2.A.1.3.32 | Landomycin A efflux pump, LanJ (Otash et al., 2008) | Bacteria |
Actinomycetota | LanJ of Streptomyces cyanogenus (Q9ZGB6) | |||
|
2.A.1.3.33 | Multidrug (including novobiocin, streptomycin, and actinomycin D) resistance porter, MdtP (YusP) | Bacteria |
Bacillota | MdtP of Bacillus subtilis (O32182) | |||
|
2.A.1.3.34 | The P55 (MFS55) triglyceride (TAG)/drug efflux pump (Rv141Oc) (extrudes drugs including rifampicin and clifazimine, first- and second-line anti-tuberculosis drugs.) CCCP and valinomycin inhibited drug resistance (Ramón-García et al., 2009). P55 also exports malachite green, ethidium bromide, isoniazid and ethambutol (Bianco et al. 2011). It functions together with the outer membrane lipoprotein porin, LprG (P9WK45; TC# 9.B.138.1.1), also called P27 and Lpp-27 (Bianco et al. 2011; Farrow and Rubin 2008). MFS55 is required together with LprG for normal colony morphology and sliding motility, possibly due to alterred cell wall composition (Farrow and Rubin 2008). MFS transporter Rv1410 and the periplasmic lipoprotein, LprG, transport triacylglycerides (TAGs) that seal the mycomembrane. Remm et al. 2023 reported a 2.7 Å structure of a mycobacterial Rv1410 homologue, which adopts an outward-facing conformation and exhibits unusual transmembrane helix 11 and 12 extensions that protrude ~20 Å into the periplasm. A small, very hydrophobic cavity suitable for lipid transport is constricted by a functionally important ion-lock likely involved in proton coupling. Combining mutational analyses and MD simulations, the authors proposed that TAGs are extracted from the core of the inner membrane into the central cavity via lateral clefts present in the inward-facing conformation. The functional role of the periplasmic helix extensions is to channel the extracted TAG into the lipid binding pocket of LprG (Farrow and Rubin 2008). MFS55 is required together with LprG for normal colony morphology and sliding motility, possibly due to alterred cell wall composition (Farrow and Rubin 2008). MFS transporter Rv1410 and the periplasmic lipoprotein, LprG, transport triacylglycerides (TAGs) that seal the mycomembrane. Remm et al. 2023 reported a 2.7 Å structure of a mycobacterial Rv1410 homologue, which adopts an outward-facing conformation and exhibits unusual transmembrane helix 11 and 12 extensions that protrude ~20 Å into the periplasm. A small, very hydrophobic cavity suitable for lipid transport is constricted by a functionally important ion-lock likely involved in proton coupling. Combining mutational analyses and MD simulations, the authors proposed that TAGs are extracted from the core of the inner membrane into the central cavity via lateral clefts present in the inward-facing conformation. The functional role of the periplasmic helix extensions is to channel the extracted TAG into the lipid binding pocket of LprG (Remm et al. 2023). | Bacteria |
Actinomycetota | P55 drug efflux pump of Mycobacterium tuberculosis (P71678) | |||
|
2.A.1.3.36 | EmrKY-TolC MDR efflux pump (Nishino and Yamaguchi 2001). (also exports cysteine (Yamada et al., 2006)) (similar to 2.A.1.3.2) | Bacteria |
Pseudomonadota | EmrKY-TolC of E. coli EmrK (MFP) (C5W790) EmrY (MFS) (C5W789) | |||
|
2.A.1.3.37 | The uridine/deoxyuridine/5-fluorouridine uptake transporter, UriP (llmg_0856) (480aas; 14TMSs) (Martinussen et al., 2010) | Bacteria |
Bacillota | UriP of Lactococcus lactis (A2RJJ9) | |||
|
2.A.1.3.38 | MFS porter of unknown function | Bacteria |
Actinomycetota | MFS porter of Streptomyces viridochromogenes (D9X7X8) | |||
|
2.A.1.3.39 | The antimicrobial efflux pump, LmrS. Exports linezolid and tetraphenylphosphonium chloride (TPCL) > sodium dodecyl sulfate (SDS), trimethoprim, and chloramphenicol. (most similar to LmrB (2.A.1.3.30)) (Floyd et al., 2010). | Bacteria |
Bacillota | LmrS of Staphylococcus aureus (Q5HE38) | |||
|
2.A.1.3.40 | The phenazine resistance pump. It also exports D-alanyl-griseoluteic acid; possibly in conjunction with a chaperone protein, EhpR. The crystal structure of EhpR is known (Yu et al., 2011). Note: Phenazines are toxic redox active secondary metabolites that many bacteria secrete. It may be involved in the export of griseoluteic acid, an intermediate in the biosynthesis of the broad-spectrum phenazine antibiotic, D-alanylgriseoluteic acid (Dagher et al. 2021). | Bacteria |
Pseudomonadota | EhpJ of Panloea (Enterobacter) agglomerans (O32600) | |||
|
2.A.1.3.43 | MFS efflux pump, AmvA (AedF). Mediates drug, dye, detergent, antibiotic and disinfectant resistance (Rajamohan et al., 2010; Hassan et al. 2011). 98.6% identical to AdeF (2.A.1.3.46). | Bacteria |
Pseudomonadota | AmvA of Acinetobacter baumannii (C4PAW9) | |||
|
2.A.1.3.44 | MDR pump, AdeF (AmvA) exports ethidium, DAPI, and chlorhexidine (Hassan et al. 2011). 98.6% identical to AmvA (2.A.1.3.45). | Bacteria |
Pseudomonadota | AdeF of Acinetobacter baumannii (A3M6E0) | |||
|
2.A.1.3.46 | The phenicol (florfenicol/chloramphenicol) exporter, FexB (Liu et al., 2012) | Bacteria |
Bacillota | FexB of Enterococcus faecium (G9FS16) | |||
|
2.A.1.3.47 | The trichothecene efflux pump, TRI12 (Alexander et al., 1999; Wuchiyama et al., 2000). Trichothecenes are plant growth promoters and bio-control agents (See also Fang et al. (2012)). TRI12 secretes toxic trichothecene compounds like T-2 toxin, nivalenol and deoxynivalenol. | Eukaryota |
Fungi, Ascomycota | TRI12 of Fusarium sporotrichioides (Q9C1B3) | |||
|
2.A.1.3.48 | Multidrug-efflux transporter Rv1634/MT1670 of 471 aas and 14 TMSs. Both Rv1634 and Rv1258c are believed to play a major role in drug resistance by altering the protein pump that is required to remove the active drug compounds from the bacterial cell (Panja et al. 2019). Ciprofloxacin and norfloxacin are substrates, to which M. tuberculosis strains have become resistant. The expulsion of the drugs to the outside the bacterial cell occurs through the alternating-access mechanism of N and C-terminal domains (Singh and Akhter 2021). | Bacteria |
Actinomycetota | Rv1634 of Mycobacterium tuberculosis | |||
|
2.A.1.3.49 | Bacteria |
Actinomycetota | Stp of Myconbacterium tuberculosis | ||||
|
2.A.1.3.50 | Multidrug resistance protein 3 (Multidrug-efflux transporter 3) or Brm3, of 512 aas and 14 TMSs. Resistance to puromycin, tosofloxacin, norfloxacin, acriflavin, ethidium, and tetraphenyl phosphonium, but not ofloxacin, nalidixic acid or carbonyl cyanide m-chlorophenylhydrazone (Ohki and Murata 1997). A spontaneous B. subtilis mutant isolated in the presence of a high concentration of puromycin acquired a multidrug-resistant phenotype due to high level expression of the bmr3 gene (Ohki and Tateno 2004), and selection for improved synthesis of menaquinone-7 also caused increased expression (Cui et al. 2020). | Bacteria |
Bacillota | Bmr3 of Bacillus subtilis | |||
|
2.A.1.3.51 | Probable transport protein HsrA (High-copy suppressor of RspA) | Bacteria |
Pseudomonadota | HsrA of Escherichia coli | |||
|
2.A.1.3.52 | Drug resistance protein YOR378W. Does not export boron (Bozdag et al. 2011). | Eukaryota |
Fungi, Ascomycota | YOR378W of Saccharomyces cerevisiae | |||
|
2.A.1.3.53 | Azole resistance protein 1 | Eukaryota |
Fungi, Ascomycota | AZR1 of Saccharomyces cerevisiae | |||
|
2.A.1.3.54 | Protein SGE1 (10-N-nonyl acridine orange resistance protein) (Crystal violet resistance protein) | Eukaryota |
Fungi, Ascomycota | SGE1 of Saccharomyces cerevisiae | |||
|
2.A.1.3.55 | Bacteria |
Bacillota | YubD of Bacillus subtilis | ||||
|
2.A.1.3.56 | Putative MFS drug exporter of 461 aas and 14 TMSs. | Bacteria |
Bacillota | Porter of Paenibacillus polymyxa | |||
|
2.A.1.3.57 | Bacteria |
Bacillota | YwoD of Bacillus subtilis | ||||
|
2.A.1.3.58 | Bacteria |
Bacillota | YfiU of Bacillus subtilis | ||||
|
2.A.1.3.59 | MDR efflux pump, NorC (Truong-Bolduc et al. 2006). Proposed to be a quinolone resistance exporter, NorB (Marklevitz and Harris 2016). The 3-d x-ray structure at 3.6 Å resolution has been solved in an outward open configuration (Kumar et al. 2021). The structure shows that NorC specifically interacts with an organic cation, tetraphenylphosphonium. Multidrug-resistance in S. aureus is inhibited by the endocannabinoid, anandamide (Sionov et al. 2022). | Bacteria |
Bacillota | NorC (NorB) of Staphylococcus aureus | |||
|
2.A.1.3.60 | MDR efflux pump, SdrM. Exports norfloxacin, acriflavin and ethidium bromide (Yamada et al. 2006). Multidrug-resistance in S. aureus is inhibited by the endocannabinoid, anandamide (Sionov et al. 2022). | Bacteria |
Bacillota | SdrM of Staphylococcus aureus | |||
|
2.A.1.3.61 | MDR efflux pump, MdeA. Exports quaternary ammonium compounds and antibiotics (Huang et al. 2004). Also exports hoechst 33342, doxorubicin, daunorubicin, tetraphenyl phosphonium, ethidium bromide and rhodamine 6G (Yamada et al. 2006). Multidrug-resistance in S. aureus is inhibited by the endocannabinoid, anandamide (Sionov et al. 2022). | Bacteria |
Bacillota | MdeA of Staphylococcus aureus | |||
|
2.A.1.3.62 | MDR efflux pump, AedC (Hassan et al. 2011). Shown to export chloramphenicol and tetracycline. | Bacteria |
Pseudomonadota | AedC of Acinetobacter baumannii | |||
|
2.A.1.3.63 | Iron homeostasis protein, AedD; may function in siderophore export (Hassan et al. 2011). | Bacteria |
Pseudomonadota | AedD of Acinetobacter baumannii | |||
|
2.A.1.3.64 | Uptake permease for cholate (steroid) metabolites, CamM of 513 aas and 14 TMSs. Uptake of 3,7(R),12(S)-trihydroxy-9-oxo-9,10-seco-23,24-bisnorchola-1,3,5(10)-trien-22-oate was observed (Swain et al. 2012). | Bacteria |
Actinomycetota | CamM of Rhodococcus jostii | |||
|
2.A.1.3.65 | ThMFS1 of 563 aas and 14 TMSs. Catalyzes export of fungicides causing tolerance. It exports trichodermin, but it is not the only exporter of this secondary metabolite (Liu et al. 2012). Trichothecenes are the sesquiterpenes secreted by Trichoderma spp. residing in the rhizosphere. These compounds have been reported to act as plant growth promoters and bio-control agents (Chaudhary et al. 2016). | Eukaryota |
Fungi, Ascomycota | MFS1 of Trichoderma harzianum (Hypocrea lixii) | |||
|
2.A.1.3.66 | MFS permease of 413 aas and 12 TMSs. Encoded within the SoxR regulon; possibly a drug exporter (Naseer et al. 2014). | Bacteria |
Pseudomonadota | MFS permease of Pseudomonas aeruginosa | |||
|
2.A.1.3.67 | MFS porter of 462 aas and 14 TMSs | Bacteria |
Deinococcota | MFS porter of Deinococcus radiodurans | |||
|
2.A.1.3.68 | The PfMFS transporter (551 aas; 14 putative TMSs) is involved in the acid resistance and intracellular pH homeostasis of Penicillium funiculosum (Xu et al. 2014). This protein (AIJ02309) was not in UniProt when enterred into TCDB, and its closest orthologue, PmMFS of Penicillium marneffei, is therefore presented here. These two proteins are 82% identical. | Eukaryota |
Fungi, Ascomycota | PfMFS of Talaromyces (Penicillium) funiculosum | |||
|
2.A.1.3.69 | Drug resistance pump, YMR279c of 540 aas. When overexpressed, confers boron resistance, but is not induced by boron (Bozdag et al. 2011). | Eukaryota |
Fungi, Ascomycota | YMR279c of Saccharomyces cerevisiae (Baker's yeast) | |||
|
2.A.1.3.70 | Probable exporter of aromatic compounds of 559 aas and 16 putative TMSs in an apparent 4 + 4 + 4 + 4 arrangement. May function in aromatic compoound detoxification. Regulated by a MarR-like transcriptional regulator that is encoded in the same operon. A ten-fold induction occurs in response to aromatic aldehydes such as benzaldehyde (Fiorentino et al. 2007). The same MarR protein controls transcription of a gene encoding an NADH-dependent alcohol dehydrogenase (Sso2536). | Archaea |
Thermoproteota | Sso1351 of Sulfolobus solfataricus | |||
|
2.A.1.3.71 | Putative multidrug-resistance exporter of 553 aas and 14 putative TMSs, KNQ1. It is a drug efflux permease for several toxic compounds that in multiple copies confer increased dithiothreitol resistance. KNQ1 does not export dithiothreitol or function in recombinant protein secretion. KNQ1 gene amplification or deletion resulted in enhanced transcription of iron transport genes, suggesting, a role in iron homeostasis on which dithiothreitol tolerance may depend (Marchi et al. 2007). | Eukaryota |
Fungi, Ascomycota | KNQ1 of Kluyveromyces lactis (Yeast) (Candida sphaerica) | |||
|
2.A.1.3.72 | Riboflavin transporter of 456 aas and 14 TMSs, RibZ (Gutiérrez-Preciado et al. 2015). | Bacteria |
Bacillota | RibZ of Peptoclostridium difficile (Clostridium difficile) | |||
|
2.A.1.3.73 | Multidrug resistance Mfs1 protein of 583 aas and 14 TMSs. Exports natural mycotoxins and a variety of fungicides in Mycosphaerella graminicola (Roohparvar et al. 2007). Etridiazole (EDZ) is a thiadiazole-containing fungicide commonly used to control Pythium and Phytophthora spp. Studies have shown that EDZ is teratogenic. A zebrafish (Danio rerio; ZF) model has been used to explore the molecular pathways associated with EDZ toxicity, and itwas concluded that there are several (Vasamsetti et al. 2023). | Eukaryota |
Fungi, Ascomycota | MDR exporter, Mfs1 of Zymoseptoria tritici (Speckled leaf blotch fungus) (Septoria tritici) | |||
|
2.A.1.3.74 | Polyamine/cationinc amino acid exporter, CmgA. Exports L-lysine, L-arginine, L-citrulline, the diamine/polyamine, putrescine, cadaverine, and possibly spermdine and spermine (Nguyen et al. 2015 ;Lubitz et al. 2016). | Bacteria |
Actinomycetota | CmgA of Corynebacterium glutamicum | |||
|
2.A.1.3.75 | Erythromycin/macrolide export system of 499 aas and 14 TMSs, ErmB (Zhou et al. 2014). | Bacteria |
Bacillota | ErmB of Streptococcus pyogenes | |||
|
2.A.1.3.76 | MFS transporter of 530 aas and 14 TMSs, SgvT1. Exports griseoviridin and viridogrisein (etamycin) (Xie et al. 2017). | Bacteria |
Actinomycetota | SgvT1 of Streptomyces griseoviridis | |||
|
2.A.1.3.77 | Drug resistance efflux porter, SgvT3 of 464 aas and 14 TMSs. (Xie et al. 2017). | Bacteria |
Actinomycetota | SgvT3 of Streptomyces griseoviridis | |||
|
2.A.1.3.78 | Drug resistance pump, EfpA of 530 aas and 14 TMSs. May function with IniABC (see TC# 9.B.282), shown to influence resistance to several drugs (Colangeli et al. 2007). CryoEM structures of the essential drug efflux pump EfpA from Mycobacterium tuberculosis reveal the mechanisms of substrate transport and small-molecule inhibition (Wang et al. 2024). It exists in an outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A (TC# 2.A.2.3.8) in both overall structure and lipid binding sites and may function as a lipid flippase (Wang et al. 2024). | Bacteria |
Actinomycetota | EfpA of Mycobacterium tuberculosis | |||
|
2.A.1.3.79 | Multidrug resistance MFS exporter, MFS54 of 538 aas and 14 TMSs. A fungal mutant lacking AaMFS54 produced fewer conidia and showed increased sensitivity to many potent oxidants (potassium superoxide and singlet-oxygen generating compounds) as well as xenobiotics (2,3,5-triiodobenzoic acid and 2-chloro-5-hydroxypyridine), and fungicides (clotrimazole, fludioxonil, vinclozolin, and iprodione) (Lin et al. 2018). Virulence assays on citrus leaves inoculated by spraying with spores revealed that AaMFS54 mutant induced less severe lesions than wild-type. | Eukaryota |
Fungi, Ascomycota | MFS54 of Alternaria alternata | |||
|
2.A.1.3.80 | Uncharacterized EmrB/QacA-like durg resistance transporter of 540 aas and 14 TMSs. The gene encoding this protein is adjacent to a 3 component putative ABC drug exporter of TC# 3.A.1.122.32. | Bacteria |
Actinomycetota | U-MFS porter of Cellulomonas flavigena | |||
|
2.A.1.3.81 | multidrug (tetracycline, kanamycin, rhodamin 6G, ampicillin, acriflavine, ethidium bromide, and tetraphenylphosphonium chloride) resistance exporter, MdeA, of 453 aas and 14 TMSs (Kim et al. 2013). | Bacteria |
Bacillota | MdeA of Streptococcus mutans | |||
|
2.A.1.3.82 | Multidrug resistance transporter protein of 519 aas and 14 TMSs. It exports 2-thiocyanatopyridine derivatives (Nunvar et al. 2019). | Bacteria |
Pseudomonadota | MDR pump of Burkholderia cenocepacia (Burkholderia cepacia) | |||
|
2.A.1.3.83 | AflT efflux pump of 514 aas and 14 TMSs (Yu et al. 2004). Its gene is part of the gene cluster that mediates the biosynthesis of aflatoxins (Yu et al. 2004). | Eukaryota |
Fungi, Ascomycota | AflT of Aspergillus parasiticus | |||
|
2.A.1.3.84 | Trichothecene efflux pump, Tri12, of 590 aas and 14 TMSs (Lee et al. 2002). It may function as a phospholipid flippase, and five flippases (FgDnfA, B, C1, C2 and D have been identified (Yun et al. 2020). FgDnfA is critical for normal vegetative growth while the other flippases are dispensable. FgDnfA and FgDnfD are crucial for fungal pathogenesis, and a remarkable reduction in deoxynivalenol (DON) production was observed in DeltaFgDNFA and DeltaFgDNFD strains. Deletion of the FgDNFB gene increased DON production to about 30 fold. FgDnfA and FgDnfD play positive roles in the regulation of trichothecene (TRI) gene (TRI1, TRI4, TRI5, TRI6, TRI12, and TRI101) expression and toxisome reorganization, while FgDnfB acts as a negative regulator of DON synthesis. FgDnfB and FgDnfD have redundant functions in the regulation of phosphatidylcholine transport, and double deletion of FgDNFB and FgDnfD showed defects in fungal development, DON synthesis, and virulence. Thus, the distinct and specific functions of flippase family members in F. graminearum have been determined, and FgDnfA, FgDnfD, and FgDnfB have specific spatiotemporal roles during toxisome biogenesis (Yun et al. 2020). This protein is 76% identical to the protein with TC# 2.A.1.3.47, and they probably catalyze the same reaction(s). | Eukaryota |
Fungi, Ascomycota | Tri12 of Gibberella zeae (Wheat head blight fungus) (Fusarium graminearum) | |||
|
2.A.1.3.85 | Acinetobacter baumannii ATCC17978 MDR pump (A1S_0188) of the DHA2 family in the MFS (Hassan et al. 2011). It is of 463 aas with 14 TMSs. There are 6 DHA2 members in A. baumannii. One of these, called AadT, exports a variety of drugs (Naidu et al. 2023). | Bacteria |
Pseudomonadota | MDR pump AedA of Acinetobacter baumannii | |||
|
2.A.1.3.86 | Antimony, SbIII and SbV, resistance MFS efflux protein of xxx aas and 14 TMSs in a 6 + 2 + 6 TMS arrangement with both 6 TMS domains having a 2 + 2 + 2 TMS arrangement (Yang et al. 2024). AntB is encoded on the chromosome of the arsenite-oxidizing bacterium Ensifer adhaerens E-60 that confers resistance to Sb(III) and Sb(V). The antB gene is adjacent to a gene encoding a LysR family transcriptional regulator termed LysRars, which is an As(III)/Sb(III)-responsive transcriptional repressor that is predicted to control expression of antB. Similar antB and lysRars genes are found in related arsenic-resistant bacteria, especially strains of Ensifer adhaerens, and the lysRars gene adjacent to antB encodes a member of a divergent subgroup of putative LysR-type regulators. Closely related AntB and LysRars orthologs contain three conserved cysteine residues, which are Cys17, Cys99, and Cys350 in AntB and Cys81, Cys289 and Cys294 in LysRars, respectively. Expression of antB is induced by As(III), Sb(III), Sb(V) and Rox(III) (4-hydroxy-3-nitrophenyl arsenite). Heterologous expression of antB in E. coli AW3110 (Δars) conferred resistance to Sb(III) and Sb(V) and reduced the intracellular concentration of Sb(III) (Yang et al. 2024). | Bacteria |
Pseudomonadota | AntB of Ensifer
adhaerens | |||
| 2.A.1.4: The Organophosphate:Pi Antiporter (OPA) Family | |||||||
|
2.A.1.4.1 | Sugar-P:Pi antiporter (transports many sugar-phosphates - both 1- and 6-P esters) | Bacteria |
Pseudomonadota | UhpT of E. coli (P0AGC0) | |||
|
2.A.1.4.2 | P-glycerate:Pi antiporter, Pgt. Takes up phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate as sole sources of carbon and energy for rapid growth (Saier et al. 1975). Not present in E. coli K12, but is present in many intracellular pathogenic strains of E. coli (Tang and Saier, unpublished observations). | Bacteria |
Pseudomonadota | PgtP of Salmonella typhimurium | |||
|
2.A.1.4.3 | Glycerol-P:Pi antiporter (may function by a 'rocker switch' mechanism; Law et al., 2007). The 3-d structure is known (3.3Å resolution) (Huang et al., 2003; Lemieux et al., 2005; Lemieux, 2007). | Bacteria |
Pseudomonadota | GlpT of E. coli | |||
|
2.A.1.4.4 | Hexose-P:Pi antiporter regulatory protein; senses external glucose-6-P and transports it with high affinity and low efficiency | Bacteria |
Pseudomonadota | UhpC of E. coli | |||
|
2.A.1.4.5 | Microsomal (ER/Golgi) glucose-6-P:Pi antiporter (glycogen storage disease (GSD1b and 1c); Gierke''s disease protein) (SLC37A2 in mice, associated with white adipose tissue obesity and expressed at high levels in macrophage) (4 isoforms present in humans (Chen et al., 2008)). SLC37A1 and A2 can not substitute for A4. 91 mutations have been observed in human patients (Chou and Mansfield 2014). Inhibited by cholorogenic acid although SLC37A1 and A2 are not. SLC37A3 had not been characterized by 2014 (Chou and Mansfield 2014). | Eukaryota |
Metazoa, Chordata | SLC37A4 of Homo sapiens | |||
|
2.A.1.4.6 | Glucose-6-P:Pi antiporter, Hpt (may also transport other organophosphates including C3 organophosphates). | Bacteria |
Chlamydiota | Hpt of Chlamydia pneumoniae (spQ9Z7N9 & gi9979188) & pirA72050 | |||
|
2.A.1.4.7 | Putative glycerol-3-phosphate (G-3-P) transporter, G3PP (most similar to TC# 2.A.1.4.6, 22% identity). Has been shown to catalyze glucose 6-P:Pi antiport across the endoplasmic reticular membrane(Pan et al. 2011). | Eukaryota |
Metazoa, Chordata | SLC37A1 of Homo sapiens | |||
|
2.A.1.4.8 | solute carrier family 37 (putative glycerol-3-phosphate transporter), member 2. Has been shown to catalyze glucose 6-P:Pi antiport across the endoplasmic reticular membrane (Pan et al. 2011). N-glycosylation is critical for the function of bovine PepT2 (Wang et al. 2020). | Eukaryota |
Metazoa, Chordata | SLC37A2 of Homo sapiens | |||
|
2.A.1.4.9 | solute carrier family 37 (glycerol-3-phosphate transporter), member 3 | Eukaryota |
Metazoa, Chordata | SLC37A3 of Homo sapiens | |||
|
2.A.1.4.10 | 2-phosphonoacetate/2-phosponopropionate uptake porter of 428 aas, PhnB. The PhnA protein is a hydrolase, and PhnC is a positive transcriptional regulator. Induction occurs with either of the two substrates (Kulakova et al. 2001). | Bacteria |
Pseudomonadota | PhnB of Pseudomonas fluorescens | |||
|
2.A.1.4.11 | Glycerol-3-phosphate:inorganic phosphate antiporter, GlpT (Frohlich and Audia 2013). | Bacteria |
Pseudomonadota | GlpT of Rickettsia prowazekii | |||
| 2.A.1.5: The Oligosaccharide:H+ Symporter (OHS) Family | |||||||
|
2.A.1.5.1 | β- and α-galactopyranoside:H+ symporter, LacY. Transports lactose, melibiose, thio-β-methyl galactopyranoside (TMG), isopropyl-β-thiogalactoside (IPTG), 4-nitrophenyl-beta-D-galactopyranoside, 4-nitrophenyl-alpha-D-galactopyranoside and galactopyranosyl-1-glycerol. Single point mutations allow transport of sucrose and maltose (King and Wilson 1990). Crystal structures and modeling reveal the cytoplasmic open state and the periplasmic open state (PDB ID: 1PV7). A structure with a bound lactose homolog, beta-D-galactopyranosyl-1-thio-beta-D-galactopyranoside, revealed the sugar-binding site in a cavity, and residues that play major roles in substrate recognition and proton translocation were identified (Abramson et al., 2003; Pendse et al., 2010). The membrane lipid composition determines the topology of LacY (Dowhan and Bogdanov, 2011). Smirnova et al. (2011) have provided evidence that the opening of the periplasmic cavity in LacY is the limiting step for sugar binding. Evidence for an alternating sites mechanism of transport has been summarized (Smirnova et al., 2011). Eames and Kortemme (2012) have shown that when considering expression of the lac operon, LacY function (H+ co-transport) and not protein production is the primary origin of cost fitness. Homology threading of several MFS porters based on the LacY 3-d structure has been reported (Kasho et al., 2006). The alternating-access mechanism has been suggested to arise from inverted topological repeats (Radestock and Forrest, 2011; Madej et al. 2012), but this proposal has been contested (Västermark and Saier 2014; Västermark et al. 2014). Mechanistic features of LacY have been summarized (Kaback 2015). Insertion into the membrane depends on YidC (TC# 2.A.9.3.1) and may occur in a stepwise, stochastic manner employing multiple coexisting pathways to complete the folding process (Serdiuk et al. 2017). The glucose Enzyme IIA (Crr) protein binds LacY to allosterically inhibit its activity, promoting inducer exclusion (Hoischen et al. 1996; Hariharan et al. 2015). Protonated LacY binds D-galactopyranosides specifically, inducing an occluded state that can open to either side of the membrane (Kumar et al. 2014). LacY can form amyloid-like fibrils under destabilizing conditions (Stroobants et al. 2017). Multiple conformations of LacY have been solved (Kumar et al. 2018). Direct interactions between LacY and its lipid environment uniquely contribute to its membrane protein organization and function (Vitrac et al. 2020). The lactose permease purified from E. coli exhibiting varied phospholipid compositions has the same topology and function as in its membrane of origin (Vitrac et al. 2019). | Bacteria |
Pseudomonadota | LacY of E. coli | |||
|
2.A.1.5.2 | Raffinose:H+ symporter, RafB, can be mutated to transport maltose (Van Camp et al., 2007). | Bacteria |
Pseudomonadota | RafB of E. coli | |||
|
2.A.1.5.3 | Sucrose:H+ symporter, CscB, also transports maltose (Peng et al. 2009). CscB recognizes not just sucrose but also fructose and lactulose, but glucopyranosides are not transported and do not inhibit sucrose transport (Sugihara et al. 2011). Direct interactions between LacY and its lipid environment uniquely contribute to its membrane protein organization and function (Vitrac et al. 2020). | Bacteria |
Pseudomonadota | CscB of E. coli | |||
|
2.A.1.5.4 | Melibiose:H+ symporter, MelY (Shinnick et al., 2003). Transports melibiose and lactose, but not TMG, which does however bind to the transporter (Tavoulari and Frillingos, 2008) | Bacteria |
Pseudomonadota | MelY of Enterobacter cloacae | |||
|
2.A.1.5.6 | MFS transporter specific for fructooligosaccharides, FosT, of 412 aas and 12 TMSs (Schouler et al. 2009). | Bacteria |
Pseudomonadota | FosT of E. coli | |||
| 2.A.1.6: The Metabolite:H+ Symporter (MHS) Family | |||||||
|
2.A.1.6.1 | Citrate:H+ symporter | Bacteria |
Pseudomonadota | CitA of Klebsiella pneumoniae | |||
|
2.A.1.6.2 | α-Ketoglutarate (oxoglutarate):H+ symporter (Seol and Shatkin 1992; Seol and Shatkin 1992). May also export arabinose but not xylose ( | Bacteria |
Pseudomonadota | KgtP of E. coli (P0AEX3) | |||
|
2.A.1.6.3 | Dicarboxylate:H+ symporter. Transports and serves as a chemoreceptor for β-ketoadipate (Karimian and Ornston 1981). | Bacteria |
Pseudomonadota | PcaT of Pseudomonas putida | |||
|
2.A.1.6.4 | (Proline/glycine-betaine):(H+/Na+) symporter, ProP (also transports taurine, ectoine, pipecolate, proline-betaine, N,N-dimethylglycine, carnitine, and 1-carboxymethyl-pyridinium) (subject to osmotic activation). Transmembrane helix I and periplasmic loop 1 are involved in osmosensing and osmoprotectant transport (Keates et al., 2010). ProP detects the increase in cytoplasmic cation concentration associated with osmotically induced cell dehydration and mediates osmolyte uptake into bacteria (Ozturk et al. 2020). ProP is a 12-TMS protein with an α-helical, cytoplasmic C-terminal domain (CTD) linked to TMS XII. The CTD helix associates with the anionic membrane surface to lock ProP in an inactive conformation. The release of the CTD may activate ProP. Molecular dynamics simulations showed specific intrapeptide salt bridges forming when the CTD associated with the membrane. The salt bridge Lys447-Asp455 weakened CTD-lipid interactions at 0.25 M KCl, and gradual stiffening of the membrane with increasing salinity was obseerved. Thus, salt cations may affect CTD release and activate ProP by increasing the order of membrane phospholipids (Ozturk et al. 2020). ProP forestalls cellular dehydration by detecting environments with high osmotic pressure and mediating the accumulation of organic osmolytes by bacterial cells. Structural determinants and functional significance of dimerization have been described (Ozturk et al. 2023). | Bacteria |
Pseudomonadota | ProP of E. coli (P0C0L7) | |||
|
2.A.1.6.5 | 4-Methyl-o-phthalate:H+ symporter | Bacteria |
Pseudomonadota | MopB of Burkholderia cepacia | |||
|
2.A.1.6.6 | Shikimate:H+ symporter | Bacteria |
Pseudomonadota | ShiA of E. coli | |||
|
2.A.1.6.7 | The citrate/tricarballylate:H+ symporter (CitA or TcuC); probably orthologous to 2.A.1.6.1 (Lewis et al., 2004) | Bacteria |
Pseudomonadota | TcuC of Salmonella enterica serovar Typhimurium LT2 (P0A2G3) | |||
|
2.A.1.6.8 | The acetate/monochloroacetate (haloacid) permease, Deh4p (Km = 5.5 mμM for acetate; 9 mμM for monochloroacetate) (Yu et al., 2007; Su and Tsang 2012). | Bacteria |
Pseudomonadota | Deh4 of Burkholderia cepacia or sp. MBA4 (Q7X4L6) | |||
|
2.A.1.6.9 | YdfJ. Can function as an inward rectifying K+ channel when expressed in animal cells as measured by whole cell patch clamping. Blocked by barium and protopine (Tang et al., 2011). | Bacteria |
Pseudomonadota | YdfJ of E. coli (P77228) | |||
|
2.A.1.6.10 | Bacteria |
Pseudomonadota | YhjE of Escherichia coli | ||||
|
2.A.1.6.11 | Acetate/haloacid transporter, Dehp2, with a possible atypical topology (Tse et al. 2009). Transports acetate, chloroacetate, bromoacetate, 2-chloropropionate, and possibly, with low affinity, glycolate, lactate and pyruvate (based on weak inhibition results). Inducible by chloroacetate (Su and Tsang 2012). This protein is 79% identical to its paralogue, Deh4p (TC# 2.A.1.6.8) which differs in that it shows lower apparent affinity for 2-chloropropionate. | Bacteria |
Pseudomonadota | Dehp2 of Burkholderia caribensis (formerly sp. MBA4) | |||
|
2.A.1.6.12 | The putative thiazole transporter, ThiU. Regulatyed by TPP riboswitch (Rodionov et al. 2002) | Bacteria |
Pseudomonadota | ThiU of Haemophilus influenzae (P44699) | |||
|
2.A.1.6.13 | Acetate/monochloroacetate permease, Deh4p, of 468 aas and 12 TMSs. Transports various carboxylates. Dehalococcoides mccartyi degrades haloacids (Su et al. 2016). | Bacteria |
Chloroflexota | Deh4p of Dehalococcoides mccartyi | |||
|
2.A.1.6.14 | Proline/glycine betaine uptake transporter, ProP, of 466 aas and 12 TMSs. It is not the major proline transporter found in S. aureus (Lehman et al. 2023). | Bacteria |
Bacillota | ProP of Staphylococcus aureus | |||
| 2.A.1.7: The Fucose: H+ Symporter (FHS) Family | |||||||
|
2.A.1.7.1 | L-Fucose:H+ symporter. The x-ray structure (3.1Å resolution) with an outward open, amphipathic cavity has been solved. Asp46 and Glu135 can undergo cycles of protonation (Dang et al., 2010). | Bacteria |
Pseudomonadota | FucP of E. coli | |||
|
2.A.1.7.2 | Glucose/galactose porter | Bacteria |
Pseudomonadota | Ggp of Brucella abortus (P0C105) | |||
|
2.A.1.7.3 | Glucose/Mannose/Xylose: H+ symporter (Paulsen et al., 1998; G.Gosset, personal communication). | Bacteria |
Bacillota | GlcP of Bacillus subtilis | |||
|
2.A.1.7.4 | Rat kidney Na+-dependent glucose (methyl α-glucoside) transporter, NaGLT1 or SGLT1 (glucose:Na+:Na+=1:1) (Horiba et al., 2003). Position 170 of Rabbit Na+/glucose cotransporter (rSGLT1) lies in the Na+ pathway, and modulation of polarity/charge at this site regulates charge transfer and carrier turnover (Huntley et al. 2004). The fine-tuning of glucose uptake mechanisms is rendered by various glucose transporters with distinct transport characteristics. In the pancreatic islet, facilitative diffusion glucose transporters (GLUTs), and sodium-glucose cotransporters (SGLTs) contribute to glucose uptake and represent important components in the glucose-stimulated hormone release from endocrine cells, therefore playing a crucial role in blood glucose homeostasis (Berger and Zdzieblo 2020). SGLT1 and SGLT2 are therapeutic targets for various diseases (Sano et al. 2020), and function in glucose absorption in the small intestine (Vallon 2020). This glucose:Na+ symporter can transport the drug gastrodin, a seditive with a strcture of a phenolic glucoside (Huang et al. 2023). | Eukaryota |
Metazoa, Chordata | NaGLT1 of Rattus norvegicus (BAC57446) | |||
|
2.A.1.7.5 | 2-Deoxy-D-ribose porter, DeoP (Christensen et al., 2003). Plays a role in colonization of the mouse intestine (Martinez-Jéhanne et al. 2009). | Bacteria |
Pseudomonadota | DeoP of Salmonella typhimurium LT-2 (gi 16767076) | |||
|
2.A.1.7.6 | Sucrose permease, ScrT (Rodionov et al., 2010) | Bacteria |
Pseudomonadota | ScrT of Shewanella frigidimarina (ABI73814) | |||
|
2.A.1.7.7 | The Na+-dependent sugar transporter, HP1174 (transports glucose, galactose, mannose and 2-deoxyglucose (Psakis et al. 2009)). (most similar to 2.A.1.7.2; 49% identity) | Bacteria |
Campylobacterota | HP1174 of Helicobacter pylori (O25788) | |||
|
2.A.1.7.8 | N-acetylglucosamine porter, NagP (Rodionov et al. 2010). | Bacteria |
Pseudomonadota | NagP of Shewanella oneidensis (Q8EBL0) | |||
|
2.A.1.7.9 | The putative N-acetylgalactosamine porter, AgaP (Leyn et al. 2012). | Bacteria |
Pseudomonadota | AgaP of Shewanella amazonensis (A1S4V0) | |||
|
2.A.1.7.10 | The putative glucose porter, GlcP (Rodionov et al., 2010). | Bacteria |
Pseudomonadota | GlcP of Shewanella amazonensis (A1S5F4) | |||
|
2.A.1.7.11 | The putative mannose porter, ManPl (Rodionov et al., 2010). | Bacteria |
Pseudomonadota | ManPl of Shewanella amazonensis (A1S297) | |||
|
2.A.1.7.12 | The putative trehalose porter, TreT (Rodionov et al., 2010) | Bacteria |
Pseudomonadota | TreT of Shewanella frigidimarina (Q07XD1) | |||
|
2.A.1.7.13 | Bypass of stop codon protein 6 | Eukaryota |
Fungi, Ascomycota | BSC6 of Saccharomyces cerevisiae S288c | |||
|
2.A.1.7.14 | Protein TsgA, also called GutS, YhfC, YhfH. tsgA i(gutS) gene expression is up-regulated by tellurite and selenite (Guzzo and Dubow 2000). | Bacteria |
Pseudomonadota | TgsA of E. coli | |||
|
2.A.1.7.15 | Major facilitator superfamily domain-containing protein 4-A, MFSD4A, of 526 aas and 12 TMSs. | Eukaryota |
Metazoa, Chordata | MfsD4a of Danio rerio | |||
|
2.A.1.7.16 | The putative mannose porter, ManP (Rodionov D.A., personal communication). Regulated by mannose regulon ManR. | Bacteria |
Bacteroidota | ManP (Q8A5Y0) of Bacteroides thetaiotaomicron | |||
|
2.A.1.7.17 | The putative fructose porter, FruP (Rodionov D.A., personal communication). Regulated by fructose oligosaccharide utilization regulon. | Bacteria |
Bacteroidota | FruP (Q8A6W8) of Bacteroides thetaiotaomicron | |||
|
2.A.1.7.18 | The putative N-acetylglucosamine porter, NagP (Rodionov D.A., personal communication). Regulated by heparin utilization regulon. | Bacteria |
Bacteroidota | NagP (Q89YS8) of Bacteroides thetaiotaomicron | |||
|
2.A.1.7.19 | Probable glucose transporter encoded by a gene sandwiched in between two genes encoding a glucose 1-dehydrogenase and a gluconolactonase. | Bacteria |
Chlamydiota | Glucose permease of Parachlamydia acanthamoebae | |||
|
2.A.1.7.20 | Uncharacterized MFS protein of 392 aas and 12 TMSs. | Bacteria |
Bdellovibrionota | UMFS of Bdellovibrio exovorus | |||
|
2.A.1.7.21 | Uncharacterized protein of the MFS of 505 aas and 12 TMSs | Eukaryota |
Viridiplantae, Chlorophyta | UP of Chlamydomonas reinhardtii (Chlamydomonas smithii) | |||
|
2.A.1.7.22 | Uncharacterized protein of 494 aas and 12 TMSs. | Eukaryota |
Viridiplantae, Chlorophyta | UP of Chlamydomonas reinhardtii (Chlamydomonas smithii) | |||
|
2.A.1.7.23 | Na+-dependent glucose transporter 1, Mfsd4b, of 491 aas and 12 TMSs. May also serve as a channels for urea in the inner medulla of the kidney. | Eukaryota |
Metazoa, Chordata | Mfsd4b of Xenopus laevis (African clawed frog) | |||
|
2.A.1.7.24 | MFS porter, MFSD4a or SLC60A1, of 514 aas and 12 TMSs. In the mouse, this protein and MFSD9 localize to neurons in the brain, and their mRNA expression levels are affected by diet (Perland et al. 2017). They are associated with cancer and have anti-tumor activities (Yang et al. 2022). It may play a role in the excretion of nitrogen metabolites (Honerlagen et al. 2021). | Eukaryota |
Metazoa, Chordata | MFSD4a of Homo sapiens | |||
|
2.A.1.7.25 | Uncharacterized protein of 894 aas and 19 TMSs in a 7 + 12 TMS arrangement. The first 7 TMSs comprise a CFEM domain, while the last 12 TMSs are homologous to MFS porters. There are many such proteins in the NCBI database, most from fungi. | Eukaryota |
Fungi, Ascomycota | UP of Leptosphaeria maculans | |||
|
2.A.1.7.26 | Na+:glucose co-transporter of 672 aas and about 14 TMSs, SGLT2. It has a Na+ to glucose coupling ratio of 1:1 (Brown et al. 2019). Efficient substrate transport in the mammalian kidney is provided by the concerted action of a low affinity high capacity and a high affinity low capacity Na+/glucose cotransporter arranged in series along kidney proximal tubules. Inhibitors are antidiabetic agents (Li 2019; Singh and Singh 2020). They are also useful as theraputic agents of non-alcoholic fatty liver disease and chronic kidney disease (Kanbay et al. 2020). Marein, an active component of the Coreopsis tinctoria Nutt plant, ameliorates diabetic nephropathy by inhibiting renal sodium glucose transporter 2 and activating the AMPK signaling pathway (Guo et al. 2020). NHE-3 (TC# 2.A.53.2.18) was markedly downregulated, while the Na+-HCO3--cotransporter (NBC-1; TC# 2.A.31.2.12) and SGLT2 were upregulated after kidney transplantation (Velic et al. 2004). Pharmacological inhibition of hSGLT2 by oral small-molecule inhibitors, such as empagliflozin, leads to enhanced excretion of glucose and is widely used in the clinic to manage blood glucose levels for the treatment of type 2 diabetes. Niu et al. 2021 determined the cryogenic electron microscopic structure of the hSGLT2-MAP17 complex in the empagliflozin-bound state to a resolution of 2.95 Å. MAP17 interacts with transmembrane helix 13 of hSGLT2. Empagliflozin occupies both the sugar-substrate-binding site and the external vestibule to lock hSGLT2 in an outward-open conformation, thus inhibiting the transport cycle (Niu et al. 2021). There is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker, linagliptin, are used (Xiong et al. 2022). Canagliflozin, dapagliflozin and ipragliflozin significantly inhibit the growth of different cancer cell lines in the micromolar range; SGLT2 inhibitors have antiproliferation, anti-tumorigenesis, and anti-migration effects and may induce apoptosis in cancer cells. Treatment with SGLT2 inhibitors also results in the downregulation of selected genes (Bardaweel and Issa 2022). SGLT2 inhibitor treatment results in symptomatic and functional well-being, especially in relieving pain (Calderon-Rivera et al. 2022). Effects of SGLT2 inhibitors affect the heart and kidney to promote autophagic flux, nutrient deprivation signaling and transmembrane sodium transport (Zannad et al. 2022). Empagliflozin (EMPA), mainly acting on SGLT2, prevented DNA methylation changes induced by high glucose and provided evidence of a new mechanism by which SGLT2i can exert cardio-beneficial effects (Scisciola et al. 2023). A diversifiable synthetic platform for the discovery of new carbasugar SGLT2 inhibitors using azide-alkyne click chemistry has been described (Kitamura et al. 2023). SGLT2 is inhibited by empagliflozin (Raven et al. 2023). SGLT2 inhibitors not only suppress hyperglycemia but also reduce renal, heart, and cardiovascular diseases (Unno et al. 2023). In fact, SGLT2 may also be related to other functions, such as bone metabolism, longevity, and cognitive functions based on mouse models (Unno et al. 2023). Complex effects of different SGLT2 inhibitors on alphaKlotho gene expression (see TC family 8.A.49) and protein secretion in renal MDCK and HK-2 cells have been observed (Wolf et al. 2023). Ferulic acid-grafted chitosan (FA-g-CS) stimulates the transmembrane transport of anthocyanins by SGLT1 and GLUT2 (Ma et al. 2022). SGLT2 Inhibitors are potential anticancer agents (Basak et al. 2023). Analyses of the effects of SGLT2 inhibitors on renal tubular sodium, water and chloride homeostasis as well as their roles in influencing heart failure outcomes has appeared (Packer et al. 2023). The SGLT2 inhibitor, empagliflozin, alleviates cardiac remodeling and contractile anomalies in a FUNDC1-dependent manner in experimental Parkinson's disease (Yu et al. 2023). Type 2 diabetes guidance proposes offering SGLT2-inhibitor therapy to people with established atherosclerotic cardiovascular disease (ASCVD) or heart failure, but this suggestion has been questioned (Young et al. 2023). SGLT2 inhibition in a non-diabetic rat model of salt-sensitive hypertension blunts the development of salt-induced hypertension independent of sex (Kravtsova et al. 2023). | Eukaryota |
Metazoa, Chordata | GLUT2 of Homo sapiens | |||
|
2.A.1.7.27 | Na+/Glucose co-transporter, SGLT1, SLC60A2 or MfsD4B, of 518 aas and 12 TMSs (Perland et al. 2017). | Eukaryota |
Metazoa, Chordata | MfsD4B of Homo sapiens | |||
| 2.A.1.8: The Nitrate/Nitrite Porter (NNP) family | |||||||
|
2.A.1.8.1 | Nitrate/H+ symporter (K1);Nitrate/nitrite antiporter (K2). The 3-d structure is available revealing a positively charged pathway for nitrate/nitrite lined with arginine residues with no apparent proton pathway suggesting exchange transport is the primary or sole mechanism. The pathway is between the two halves of the protein and a rocker switch mechanism was proposed (Zheng et al. 2013). In an in vitro reconstituted system, NarK appeared to be a nitrate/nitrite antiporter. High-resolution crystal structures in the nitrate-bound occluded, nitrate-bound inward-open and apo inward-open states have been solved (Fukuda et al. 2015). | Bacteria |
Pseudomonadota | NarK (NarK1-K2) of E. coli | |||
|
2.A.1.8.2 | Nitrate uptake porter | Bacteria |
Bacillota | NasA of Bacillus subtilis | |||
|
2.A.1.8.3 | Nitrate/nitrite uptake porter | Bacteria |
Cyanobacteriota | NrtP of Synechococcus PCC7002 | |||
|
2.A.1.8.4 | Nitrate transporter | Eukaryota |
Bacillariophyta | Nitrate porter of Cylindrotheca fusiformis | |||
|
2.A.1.8.5 | Nitrate/nitrite transporter/antiporter, CrnA/NrtA (Unkles et al., 1991; Beckham et al. 2010). The nitrate signature sequences (NS1 and NS2) in TMSs 5 and 11 and arg residues in TMSs 2 and 8 may influence substrate binding (Unkles et al., 2012). | Eukaryota |
Fungi, Ascomycota | CrnA of Emericella nidulans | |||
|
2.A.1.8.6 | Nitrate transporter | Eukaryota |
Viridiplantae, Chlorophyta | Nitrate porter of Chlamydomonas reinhardtii | |||
|
2.A.1.8.7 | Eukaryota |
Viridiplantae, Chlorophyta | |||||
|
2.A.1.8.8 | NO2- extrusion, NO3-/NO2- exchange permease, NarK1 | Bacteria |
Deinococcota | NarK1 of Thermus thermophilus HB8 | |||
|
2.A.1.8.9 | NO2- extrusion, NO3-/NO2- exchange permease, NarK2 | Bacteria |
Deinococcota | NarK2 of Thermus thermophilus HB8 | |||
|
2.A.1.8.10 | NO3-/NO2- transporter (NO3- uptake permease; NO2- exporter) (probable NO3-/NO2- antiporter) (stress-induced; Clegg et al., 2006; Jia et al. 2009) | Bacteria |
Pseudomonadota | NarU of E. coli | |||
|
2.A.1.8.11 | The 24 TMS, 2 domain, NarK1-NarK2 porter (NarK1 = a NO3-/H+ symporter; NarK2 = a NO3-/NO2- antiporter). NarK1 is a nitrate/proton symporter with high affinity for nitrate while NarK2 is a nitrate/nitrite antiporter with lower affinity for nitrate (Goddard et al., 2008). Each transporter requires two conserved arginine residues for activity. A transporter consisting of inactivated NarK1 fused to active NarK2 has a dramatically increased affinity for nitrate compared with NarK2 alone, implying a functional interaction between the two domains (Goddard et al., 2008). | Bacteria |
Pseudomonadota | NarK1/NarK2 of Roseobacter denitrificans (Q166T6) | |||
|
2.A.1.8.12 | The root cortical and epidermal cell, high affinity, plasma membrane, NO3- uptake transporter, NRT2.1 (Wirth et al., 2007). Also functions in nitrate sensing and signaling (Miller et al., 2007; Girin et al., 2010). Activity only occurs when NRT2.1 is complexed with NAR2.1 (WR3; 8.A.20.1.1) in a 2:2 tetrameric complex (Yong et al., 2010). NAR2.1 has an N-terminal and a C-terminal TMS and has been annotated as a calcineurin-like phosphoesterase family member (Yong et al., 2010). Ntr transporters may also play a role in gaseous NO2 uptake by leaves (Hu et al. 2014). The Medicago truncatula orthologue has been characterized (Pellizzaro et al. 2014). An NRT2 homologue in wheat has been identifed and partially characterized (Kumar et al. 2022). Nitrate is the main form of inorganic nitrogen that crops absorb, and nitrate transporters 2 (NRT2) are high affinity nitrate uptake porters. When the available nitrate is limiting, the high affinity transport systems are activated. Most NRT2s cannot transport nitrates alone and require the assistance of helper proteins belonging to nitrate assimilation related family (NAR2; TC# 8.A.20.1.1) to complete the transport of nitrate (Zhao et al. 2023). Crop nitrogen utilization efficiency is affected by environmental conditions, and there are differences between different plant varieties. Sorghum bicolor has high stress tolerance and is efficient in soil nitrogen utilization. The S. bicolor genome database was scanned for gene structures, chromosomal localizations, physicochemical properties, secondary structures and transmembrane domains, signal peptides and subcellular localizations, promoter region cis-acting elements, phylogenetic evolution, SNP recognition and annotation, and selection pressure of gene family members (Zhao et al. 2023). Through bioinformatics analysis, 5 NRT2 gene members (designated as SbNRT2-1a, SbNRT2-1b, SbNRT2-2, SbNRT2-3, and SbNRT2-4) and 2 NAR2 gene members (designated SbNRT3-1 and SbNRT3-2) were identified, the number of which was less than that of foxtail millet. SbNRT2/3 could be divided into four subfamilies. All were present in the plasma membrane; SbNRT2 proteins lacked signal peptides, but SbNRT3 proteins contained them. Expression was responsive to plant hormones and stress response elements (Zhao et al. 2023). | Eukaryota |
Viridiplantae, Streptophyta | NRT2.1 of Arabidopsis thaliana (O82811) | |||
|
2.A.1.8.13 | High affinity nitrate/nitrite antiporter and uptake porter, NrtB (Unkles et al., 1991; 2011; Wang et al. 2008). | Eukaryota |
Fungi, Ascomycota | NrtB of Emericella (Aspergillus) nidulans (Q8X193) | |||
|
2.A.1.8.14 | Nitrate/nitrite uptake porter, NapA (Wang et al., 2000) | Bacteria |
Cyanobacteriota | NapA of Trichodesmium sp. WH 9601 (Q9RA38) | |||
|
2.A.1.8.15 | Probable nitrate transporter NarT of 388 aas and 12 TMSs in a 6 + 6 TMS arrangement. In Corynebacterium pseudotuberculosis, an insertional mutation in the MFS transporter, NarT, may influence pathogenesis (Hiller et al. 2024).
| Bacteria |
Bacillota | NarT of Staphylococcus carnosus | |||
|
2.A.1.8.16 | MFS porter of 430 aas | Bacteria |
Pseudomonadota | MFS porter of Rhizobium loti | |||
|
2.A.1.8.17 | Nitrate/nitrite transporter, NarK2, of 468 aas and 12 TMSs. The narK1 and narK2 genes are located in an operon, narK1K2GHJI, with the structural genes for the nitrate reductase complex. Utilizing an isogenic narK1 mutant, a narK2 mutant, and a narK1K2 double mutant, Sharma et al. 2006 explored the effect on growth under denitrifying conditions. While the ΔnarK1::Gm mutant was only slightly affected, but both the ΔnarK2::Gm and double mutants exhibited poor nitrate-dependent, anaerobic growth although all three strains had wild-type levels of nitrate reductase activity. Nitrate uptake measurements showed that NarK2 has most of the activity. E. coli narK rescued both mutants. | Bacteria |
Pseudomonadota | NarK2 of Pseudomonas aeruginosa | |||
|
2.A.1.8.18 | NRT2.1 high affinity Na+-dependent nitrate uptake porter of 517 aas and 12 TMSs. It functions with the aoxillary protein, NAR2 (TC# 8.A.20.1.2) (Rubio et al. 2019). Functional characterization of the GhNRT2.1e gene revealed its role in improving nitrogen use efficiency in Gossypium hirsutum (Zhang et al. 2023). | Eukaryota |
Viridiplantae, Streptophyta | NTR2.1 of Zostera marina | |||
| 2.A.1.9: The Phosphate: H+ Symporter (PHS) Family | |||||||
|
2.A.1.9.1 |
High affinity Pi uptake porter, SUL1, Sul-1, SFP2 of 859 aas and 10 TMSs. (also functions in Mn2+ homeostasis); may transport a phosphate·Mn2+ complex (Jensen et al., 2003). Also takes up selenite (Lazard et al., 2010). May be a "transceptor", combining transport and receptor functions (Diallinas 2017).
| Eukaryota |
Fungi, Ascomycota | Pho84 of Saccharomyces cerevisiae (P25297) | |||
|
2.A.1.9.2 | Phosphate-repressible, high affinity Pi uptake porter, Pho84 or Pho-5 of 570 aas and 12 TMSs (Versaw 1995). | Eukaryota |
Fungi, Ascomycota | Pho-84 of Neurospora crassa (Q7RVX9) | |||
|
2.A.1.9.3 | Pi uptake porter. Four close paralogues in Medicago truncatula (PT1-4), all localized to roots, show differing affinities for phosphate (Liu et al. 2008). | Eukaryota |
Viridiplantae, Streptophyta | PT1 of Solanum tuberosum | |||
|
2.A.1.9.4 | Pht1;2(1;4) (PT2), a low affinity Pi uptake transporter, functioning throughout the plant (Ai et al., 2009) (76% identical to 2.A.1.9.3). | Eukaryota |
Viridiplantae, Streptophyta | Pht1;2(1;4) of Oryza sativa (Q01MW8) | |||
|
2.A.1.9.5 | Pht1;6 (PT6), a high affinity Pi uptake transporter, functioning thoughout the plant (Ai et al., 2009) (75% identical to 2.A.1.9.3) | Eukaryota |
Viridiplantae, Streptophyta | Pht1;6 (PT6) of Oryza sativa (Q8H6H0) | |||
|
2.A.1.9.6 | Phosphate transporter-5, PT5. Catalyzes phosphate:H+ symport (Liu et al., 2008). | Eukaryota |
Viridiplantae, Streptophyta | PT5 of Medicago truncatula (A5H2U6) | |||
|
2.A.1.9.7 | Organic phosphate (glycerophosphoinositol and glycerophosphocholine, the products of phospholipase-B mediated deacylation of phosphatidylinositol and phosphatidylcholine, respectively) transport protein GIT1 (Almaguer et al. 2006). | Eukaryota |
Fungi, Ascomycota | GIT1 of Saccharomyces cerevisiae | |||
|
2.A.1.9.8 | Putative inorganic phosphate transporter C23D3.12 | Eukaryota |
Fungi, Ascomycota | SPAC23D3.12 of Schizosaccharomyces pombe | |||
|
2.A.1.9.9 | Inorganic phosphate transporter 1-1 (AtPht1;1; APT2, PHT1) (H+/Pi cotransporter). A Brassica napus homologue, Pht1;4, catalyzes phosphate uptake and affects root architecture (Ren et al. 2014). The phylogeny and expression levels in plant tissues of the proteins of this family in potato have been examined (Liu et al. 2017). The chrysanthemum Pht1;2 is induced in the roots by phosphate starvation (Liu et al. 2018). It is induced by low inorganic phosphate in Spirodela polyrrhiza, a floating plant widely used in biomass utilization and eutrophication phytoremediation (Deng et al. 2021). There are five PHT families in A. thaliana, Pht1 - 5, not all of which are homologous; 57 PHTs are present in soybean (Glycine max), belonging to the PHT1 - 5 families with TC#s (1) 2.A.1.9, (2) 2.A.20, (3) 2.A.29, (4) 2.A.1.14 and (5) 2.A.1.2.61 (Wei et al. 2022). | Eukaryota |
Viridiplantae, Streptophyta | PHT1-1 of Arabidopsis thaliana | |||
|
2.A.1.9.10 | High affinity (25 mμM) phosphate uptake porter, PiPT (Yadav et al. 2010). The high resolution structure has been determined by x-ray crystallography (Pedersen et al. 2013). | Eukaryota |
Fungi, Basidiomycota | PiPT of Piriformospora indica | |||
|
2.A.1.9.11 | Phosphate transporter, PT, of 543 aas and 12 TMSs. It has a micormolar Km for phosphate uptake, is found in the plasma membrane and is induced by low medium phosphate concentrations (Wang et al. 2014). | Eukaryota |
Fungi, Basidiomycota | PT in the ectomycorrhizal fungus, Boletus edulis | |||
|
2.A.1.9.12 | Phosphate transporter and receptor (transceptor) of 543 aas and 12 TMSs. Important for signalling and uptake of phosphate. The majority of terrestrial vascular plants can form mutualistic associations with obligate biotrophic arbuscular mycorrhizal (AM) fungi from the phylum Glomeromycota. This mutualistic symbiosis provides carbohydrates to the fungus, and reciprocally improves plant phosphate uptake. AM fungal transporters can acquire phosphate from the soil through the hyphal networks. Xie et al. 2016 reported a high-affinity phosphate transporter GigmPT that is required for AM symbiosis. GigmPT functions as a phosphate transceptor for the activation of the phosphate signaling pathway as well as the protein kinase A signaling cascade. | Eukaryota |
Fungi, Mucoromycota | PT of Gigaspora margarita | |||
|
2.A.1.9.13 | High-affinity phosphate transporter of 511 aas and 12 TMSs, PHT1. It is root inducible by phosphate starvation but is not expressed in leaves (Ahmadi et al. 2018). | Eukaryota |
Viridiplantae, Streptophyta | PHT1 of Elaeis guineensis var. tenera (Oil palm) | |||
| 2.A.1.10: The Nucleoside: H+ Symporter (NHS) Family | |||||||
|
2.A.1.10.1 | Nucleoside porter, NupG. Guanosine, inosine, cytidine and thymidine but not uridine, adenosine and xanthosine are transported (Patching et al. 2005). ADP-glucose is also a substrate of this system (Almagro et al. 2018Almagro et al. 2018). | Bacteria |
Pseudomonadota | NupG of E. coli (P0AFF4) | |||
|
2.A.1.10.2 | Xanthosine porter, XapB. Xanthosine, inosine, adenosine, cytidine and thymidine but not guanosine and uridine are transported (Seeger et al. 1995). The Km for Xanthosine is 136 μM (Nørholm and Dandanell 2001). The transporter is encoded within an operon with xanthosine phosphorylase which is inactive in S. enterica but can be mutated to the active form (Hansen et al. 2006). | Bacteria |
Pseudomonadota | XapB of E. coli | |||
|
2.A.1.10.3 | Bacteria |
Pseudomonadota | YegT of Escherichia coli | ||||
| 2.A.1.11: The Oxalate:Formate Antiporter (OFA) Family | |||||||
|
2.A.1.11.1 | The oxalate:formate antiporter. Residues and TMSs involved in the translocation pathway and substrate binding have been identified (Fu and Maloney 1998; Fu et al. 2001; Ye and Maloney 2002; Wang et al. 2006). Beuming and Weinstein 2005 developed a method to predict the structures of membrane proteins consisting of (1) identifying TMSs from sequence; (2) assigning buried and lipid-exposed faces of the TMSs; and (3) assembling the TMSs into a bundle, based on geometric restraints obtained from EM data. The OxlT structure was modeled (Beuming and Weinstein 2005). | Bacteria |
Pseudomonadota | OxlT of Oxalobacter formigenes | |||
|
2.A.1.11.2 | Putative MFS transporter of 399 aas; 12 TMSs. | Bacteria |
Pseudomonadota | MFS porter of Pseudomonas aeruginosa (Q9I458) | |||
|
2.A.1.11.3 | Inner membrane protein BtsT or YhjX (probably a pyruvate:proton symporter that can also function as an exporter) (Vilhena et al. 2017). Regulated by Crp as well as the LytS-like histidine sensor kinase, BtsS or YehU, and the corresponding LytTR-like response regulator, BtsR or YehT (Kristoficova et al. 2017). Possibly induced by peptides as cells enter the stationary growth phase because they release extracellular pyruvate, the true inducer (Kristoficova et al. 2017). Forms a complex with the BtsT (CsiA; YjiY) transporter (TC# 2.A.114.1.9) and two sensor kinase/response regulator pairs, BtsS/BtsR (YehU/YehT) and YdpA/YdpB, both of which respond to extracellular pyruvate, but with differing affinities (Behr et al. 2014). The carbon storage regulator A (CsrA) is involved in posttranscriptional regulation of both BtsT (YjiY) and YjiX, a 67 aa soluble protein of unknown function (Behr et al. 2014). The two proteins, YhjX (TC# 2.A.1.11.3) and YjiY (TC# 2.A.114.1.9) may function together as an oligomer, and confusingly, have both been given the designation: BtsT (see UniProt entries). | Bacteria |
Pseudomonadota | BtsT or YhjX of Escherichia coli | |||
|
2.A.1.11.4 | Uncharacterized membrane protein YJL163C | Eukaryota |
Fungi, Ascomycota | YJL163C of Saccharomyces cerevisiae | |||
|
2.A.1.11.5 | MFS-type transporter YcxA (ORF5) of 408 aas and 12 TMSs. Capable of exporting the peptide antibiotic, surfactin, synthsized by a non-ribosome mechanism in B. subtilis (Li et al. 2015). | Bacteria |
Bacillota | YcxA of Bacillus subtilis | |||
|
2.A.1.11.6 | Bacteria |
Bacillota | YbfB of Bacillus subtilis | ||||
|
2.A.1.11.7 | Uncharacterized protein of 512 aas and 12 TMSs. | Eukaryota |
Rhodophyta | UP of Chondrus crispus | |||
|
2.A.1.11.8 | Uncharacterized protein of 404 aas | Bacteria |
Pseudomonadota | UP of Pseudomonas aeruginosa | |||
|
2.A.1.11.9 | Uncharacterized MFS porter of 508 aas and 12 TMSs. | Eukaryota |
Evosea | UP of Entamoeba histolytica | |||
|
2.A.1.11.10 | MFS carrier of 577 aas and 12 TMSs | Eukaryota |
Evosea | MFS protein of Entamoeba histolytica | |||
|
2.A.1.11.11 | PfMFSDT (PF3D7_0210300) is a drug exporter (Maurya et al. 2024). It confers resistance to antifungal agents, ketoconazole and itraconazole. The nanomolar inhibitory effects of the drugs on the intra-erythrocytic growth of Plasmodium falciparum highlight their antimalarial properties. | Eukaryota |
Apicomplexa | PfMFSDT of Plasmodium falciparum | |||
| 2.A.1.12: The Sialate:H+ Symporter (SHS) Family | |||||||
|
2.A.1.12.1 | The sialic acid porter, NanT, of 496 aas and 14 TMSs. N-acetylneuraminic acid (Neu5Ac) serves as a sole source of carbon and nitrogen for E. coli. It is a mucus-derived carbon source in the mammalian gut. NanT can also take up and allow efficient growth on the related sialic acids, N-glycolylneuraminic acid (Neu5Gc) and 3-keto-3-deoxy-d-glycero-d-galactonononic acid (KDN) (Hopkins et al. 2013). In animals, N-glycolylneuraminic acid is transported by exo- and endo-cytosis (He et al. 2023). | Bacteria |
Pseudomonadota | NanT of E. coli | |||
|
2.A.1.12.2 | The lactate/pyruvate:H+ symporter of 616 aas and 12 TMSs. Residues in the substrate translocation pathway have been reported (Soares-Silva et al., 2011). This systems and its orthologs in fungi have been reviewed (Guo et al. 2018). | Eukaryota |
Fungi, Ascomycota | Jen1 (YKL217w) of Saccharomyces cerevisiae | |||
|
2.A.1.12.3 | Jen2 of 513 aas and 12 TMSs. It is a dicarboxylic acid (succinate, malate, fumarate) uptake porter, and is subject to catabolite repression by glucose. It is induced during infection, being upregulated following the phagocytosis of C. albicans cells by neutrophils and macrophages. It may be important during early stages of virulence (Vieira et al. 2010). In the acid-tolerant yeast, Pichia kudriavzevii, it transports the above mentioned dicarboxylates as well as α-ketoglutarate (sometimes) and citrate, and possibly lactate (Xi et al. 2021). | Eukaryota |
Fungi, Ascomycota | Jen2 of Candida albicans | |||
|
2.A.1.12.4 | Jen1 of 541 aas and 12 TMSs. Zt is a monocarboxylate (lactate) uptake porter that is upregulated following the phagocytosis of Candida albicans cells by neutrophils and macrophages. It may be important for virulence (Soares-Silva et al. 2013; Vieira et al. 2010). It may be the only lactate uptake porter and is subject to glucose catabolite repression. However, growth on lactate affects biofilm formation, morphology and susceptibility to fluconazole, and both Jen1 and Jen2 may play a role in these processes. Thus, the adaptation of Candida cells to the carbon source present in the host niches affects their pathogenicity (Alves et al. 2017; Alves et al. 2020). | Eukaryota |
Fungi, Ascomycota | Jen1 of C. albicans | |||
| 2.A.1.13: The Monocarboxylate Transporter (MCT) Family (Halestrap, 2011) | |||||||
MCTs play roles in the absorption, tissue distribution, and clearance of both endogenous and exogenous compounds. MCTs are required for the transport of essential cell nutrients and for cellular metabolic and pH regulation (Jones and Morris 2016). | |||||||
|
2.A.1.13.1 | The low affinity proton-linked monocarboxylate (lactate, pyruvate, mevalonate, branched chain oxo acids, β-hydroxybutyrate, γ-hydroxybutyrate, butyrate, acetoacetate, acetate and formate, succinate) uptake/efflux porter (Moschen et al. 2012; Reddy et al. 2020). pH-gated succinate secretion regulates muscle remodeling in response to exercise (Reddy et al. 2020). The structural basis of MCT1 inhibition by anti-cancer drugs has been considered (Wang et al. 2020). MCT1 also transports anti-tumor alkylating agents, 3-bromopyruvate and dichloroacetate (Cooper et al. 1989; Su et al. 2016; Bailey et al. 2019) as well as artemisinin (Girardi et al. 2020). Activity is stimulated by direct interaction with carbonic anhydrase isoform II (Becker et al., 2005). This transporter interacts physically with the chaperone protein Basigin (CD147; TC #8.A.23.1.1) which is required both for targetting to the plasma membrane and for activity. Mct-2 uses a different chaperone protein, GP70. Mct-1 also transports the methionine hydroxy analogue 2-hydroxy (4-methylthio) butanate (Martin-Venegas et al., 2007; Becker and Deitmer, 2008). MCT1, 3 and 4 require the ancillary protein, basigin (P35613; 8.A.23.1.1) for plasma membrane localization (Ovens et al., 2010). It partially localizes to the peroxysomal membrane (Visser et al. 2007). MCT1 is regulated by CD147 proteins, and this association is important for lactate export and cell proliferation in certain cancer cells (Walters et al. 2013). It is upregulated in some cancers and maintains the metabolic phenotype of these cancer cells by mediating lactate efflux together with a proton, promoting pH homeostasis (Baltazar et al. 2014). MCT-1 functions as a positive regulator of osteoblast differentiation via suppression of p53 (Sasa et al. 2018). It plays a role in aggressive breast cancer subtypes (Li et al. 2018) as well as other cancers (Park et al. 2018). The SLC16A1 gene is a potential marker to predict race performance in Arabian horses (Ropka-Molik et al. 2019). MCT1 is a negative regulator and MCT2 and a positive regulator of osteoclast differentiation, while MCT2 is required for bone resorption by osteoclasts (Imai et al. 2019). MCTs 1 and 4 are present in increased amounts in solid tumors, and inhibitors as potential therapeutics have been reviewed (Puri and Juvale 2020). Interleukin-1beta induces monocarboxylate transporter-1 in an oxygen tension-dependent manner (Tanaka et al. 2022). Substrate protonation is a pivotal step in the mechanisms of several MCT-unrelated weak acid translocating proteins, but utilization of the proton binding and transfer capabilities of the transporter-bound substrate is probably a universal theme for weak acid anion/H+ cotransport (Geistlinger et al. 2023). This transporter is over expressed in breast cancer (Arponen et al. 2023). Fasting upregulates MCT1 at the rat blood-brain barrier through PPAR δ activation (Chasseigneaux et al. 2024). The anticancer effect of androgen deprivation therapy can be enhanced by an MCT1 inhibitor in prostate cancer cells (Kim et al. 2024). Sulforaphane (SFN) inhibits non-small cell lung cancer (NSCLC) growth and metastasis by reducing lactate production by regulating the expressions of monocarboxylate transporter 1 (MCT1) and MCT4 that transport lactate across cell membrane (Shi et al. 2024). | Eukaryota |
Metazoa, Chordata | MCT1 (SLC16A1) of Homo sapiens | |||
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2.A.1.13.2 | The low affinity aromatic amino acid (Tyr, Trp, Phe) transporter, TAT1 (T-type amino acid transporter), MCT10, Slc16a10. Also transports N-methyl amino acids and thyroid hormones. Essential for aromatic amino acid homeostasis in various tissues of mice (Mariotta et al. 2012). MCT10 is 58% identical to MCT8. Both transporters mediate T3 transport, but while MCT8 also transports rT3 and T4, these compounds are not efficiently transported by MCT10. A few amino acyl residue substitutions in the human orthologue broadens the substrate specificity of this porter (Johannes et al. 2016). The Six1 trahscription factor promotes a skeletal muscle thyroid hormone response through regulation of the MCT10 transporter (Girgis et al. 2021). | Eukaryota |
Metazoa, Chordata | Tat1 of Rattus norvegicus | |||
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2.A.1.13.3 | The thyroid hormone transporter, MCT8 (transports L- and D-isomers of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3) and 3,3'-diiodothyronine [Km values = 2-5 μM; Leu, Phe, Trp and Tyr were not transported]) (Friesema et al., 2003). Loss of function mutations in MCT8 leads to Allan-Herndon-Dudley syndrome, severe X-linked psychomotor retardation and elevated serum T3 levels (Jansen et al., 2008). Essential molecular determinants for thyroid hormone transport and their structural implications are presented by Kinne et al. (2010). Induced by retinoic acid (Kogai et al., 2010). Mediates energy-independent bidirectional transport. MCT8 is specific for L-iodothyronines and requires at least one iodine atom per aromatic ring. Thyronamines, decarboxylated metabolites of iodothyronines, triiodothyroacetic acid and tetraiodothyroacetic acid, TH derivatives lacking both chiral center and amino group, are not substrates (Kinne et al., 2010). A deficiency causes altered thyroid morphology and a persistent high triiodothyronine/thyroxine ratio after thyroidectomy (Wirth et al., 2011). Primary and secondary thyroid hormone transporters have been reviewed (Kinne et al., 2011). A differential effect of a shortage of thyroid hormone was observed compared with a knockout of thyroid hormone transporters Mct8 and Mct10 on murine macrophage polarization (Hoen et al. 2024). | Eukaryota |
Metazoa, Chordata | MCT8 of Mus musculus (O70324) | |||
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2.A.1.13.4 | The high affinity (17 μM) facilitated diffusion, riboflavin-regulated riboflavin uptake system, Mch5 (Reihl and Stolz, 2005) | Eukaryota |
Fungi, Ascomycota | Mch5 of Saccharomyces cerevisiae (NP_014951) | |||
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2.A.1.13.5 | Low affinity monocarboxylate transporter-2 (MCT2). Transports γ-hydroxybutyrate (Wang and Morris, 2007). MCT2 requires the ancillary protein, embigin (Q6PCB8; 8.A.23.1.2) for plasma membrane localization (Ovens et al., 2010). It is present in neurons but not astrocytes where the low affinity MCT1 and MCT4 predominate (Hertz and Dienel 2013). Partially localizes to the peroxysomal membrane (Visser et al. 2007). MCT1 is a negative regulator and MCT2 a positive regulator of osteoclast differentiation, while MCT2 is required for bone resorption by osteoclasts (Imai et al. 2019). Atorvastatin exerts more selective inhibitory effects on hMCT2 than on hMCT1 and hMCT4 (Yamaguchi et al. 2023). | Eukaryota |
Metazoa, Chordata | MCT2 (SLC16A7) of Homo sapiens | |||
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2.A.1.13.6 | Plasma membrane proton-linked monocarboxylate transporter, MCT4 or MCT-4 (SLC16A3). It catalyzes the rapid low affinity plasma membrane transport of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. It is the main transporter that catalyzes lactate efflux from glycolyzing cells (Halestrap 2013; Papakonstantinou et al. 2021). Residues binding high affinity inhibitors have been identified (Nancolas et al. 2015). It forms a complex with binding partner, CD147/BSG, which regulates the transport activity (Fisel et al. 2015). It plays a role in aggressive breast cancer subtypes (Li et al. 2018) as well as other cancers (Park et al. 2018). MCT4 may be a therapeutic target for colorectal cancer (Kim et al. 2018). MCTs 1 and 4 are present in increased amounts in solid tumors, and inhibitors are potential therapeutics (Puri and Juvale 2020). Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT-4/lactate-mediated intracellular acidosis (Li et al. 2022). Dietary folate deficiency promotes lactate metabolic disorders that sensitize lung cancer metastasis through mTOR-signaling-mediated targets (Chen et al. 2023). Shikonin reduced MCT4 expression and activation, resulting in inhibition of aerobic glycolysis in cancer-associated fibroblasts (CAFs) and overcoming CAF-induced gemcitabine resistance in pancreatic cancer (PC). Shikonin is a promising chemosensitizing phytochemical agent when used in combination with gemcitabine for PC treatment. The results suggest that disrupting the metabolic coupling between cancer cells and stromal cells might provide an attractive strategy for improving gemcitabine efficacy (Hu et al. 2024). Sulforaphane (SFN) inhibits non-small cell lung cancer (NSCLC) growth and metastasis by reducing lactate production by regulating the expressions of monocarboxylate transporter 1 (MCT1) and MCT4 that transport lactate across cell membrane (Shi et al. 2024). | Eukaryota |
Metazoa, Chordata | MCT4 (SLC16A3) of Homo sapiens | |||
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2.A.1.13.7 | Monocarboxylate transporter-5 (MCT5 or SLC16A4; sometimes referred to as MCT4). Lactate transport via the MCT5 is non enzymatically stimulated by carbonic anhydrase II (Becker et al., 2010). MCTs require an ancillary 1TMS glycoprotein, either Embigin (Q6PCB8; TC# 8.A.23.1.2) or basigin (P35613; TC# 8.A.23.1.1) for plasma membrane localization (Ovens et al., 2010). Upregulated in some cancers and maintains the metabolic phenotype of these cancer cells by mediating lactate efflux together with a proton, promoting pH homeostasis (Baltazar et al. 2014). Also transports the chemotheraputic agent, 3-bromopyruvate (Baltazar et al. 2014). | Eukaryota |
Metazoa, Chordata | SLC16A4 of Homo sapiens | |||
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2.A.1.13.8 | Monocarboxylate transporter, MCT10. Transports thyroid horomones as well as aromatic amino acids (Visser et al., 2010). Primary and secondary thyroid hormone transporters have been reviewed (Kinne et al., 2011). Deafness and loss of cochlear hair cells occurs in the absence of thyroid hormone transporters, Slc16a2 (Mct8) and Slc16a10 (Mct10) (Sharlin et al. 2018). Tissue-specific functions of thyroid hormone transporters in mice, including MCT8, MCT10 and Oatp1c1 have been reviewed (Salveridou et al. 2020). | Eukaryota |
Metazoa, Chordata | SLC16A10 of Homo sapiens | |||
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2.A.1.13.9 | Short chain monocarboxylate (lactate) transporter 3, MCT3. MCT1, 3 and 4 require the ancillary protein, basigin (P35613; 8.A.23.1.1) for plasma membrane localization (Ovens et al., 2010). | Eukaryota |
Metazoa, Chordata | SLC16A8 of Homo sapiens | |||
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2.A.1.13.10 | MCT8 (SLC16a2) homodimeric monocarboxylate thyroid hormone transporter 8 of 613 or 539 aas and 12 TMSs (Visser et al. 2009; Arjona et al., 2011). It is the X-linked mental retardation Allan-Herndon-Dudley syndrome (AHDS) (a severe psychomotor retardation syndrome) protein (Schweizer and Köhrle 2012; Boccone et al. 2010; Johannes et al. 2016). Lack of MCT8 function produces serious neurological disturbances, most likely due to impaired transport of thyroid hormones across brain barriers during development, resulting in severe brain hypothyroidism (Grijota-Martínez et al. 2020). Arg residues important for function have been identified (Groeneweg et al. 2013). Thyroid hormone (TH) transporters in the brain and across the blood brain barrier have been reviewed (Wirth et al. 2014; Bernal et al. 2015). The product facilitates both TH uptake and efflux across the cell membrane. The disease goes together with low serum T4 and high T3 levels. The mechanisms underlying MCT8-deficient brain development in various animal models including humans has been reviewed (Vancamp and Darras 2017). Together with OATP1C1 (TC# 2.A.60.1.15), MCT8 controls skeletal muscle regeneration (Mayerl et al. 2018). Deafness and loss of cochlear hair cells occurs in the absence of thyroid hormone transporters, Slc16a2 (Mct8) and Slc16a10 (Mct10) (Sharlin et al. 2018). Stable levels of MCT8 protein in endothelial cells of the blood-brain barrier, choroid plexus epithelial cells and tanycytes during postnatal development has been demonstrated (Wilpert et al. 2020). Oligomerization involves noncovalent interactions between the N-terminal halves of MCT8 proteins (Groeneweg et al. 2020). Genetic variants in MCT8, cause intellectual and motor disability and abnormal serum thyroid function tests, known as MCT8 deficiency (van Geest et al. 2020). Shaji 2021 identified natural inhibitors against MCT8. Emodin exhibited the best binding energy of -8.6 kcal/mol followed by helenaquinol, cercosporamide and resveratrol. Emodin and helenaquinol exhibit high binding energy. Cercosporamide and resveratrol exhibited higher binding energy than triac and desipramine and showed the binding energy similar to silychristin. Thus, these compounds could be promising candidates for further evaluation for AHDS prevention. MCT8 deficiency induces severe X-linked psychomotor retardation (Iwayama et al. 2021). It is common and severe in homozygous males (one X chromosome) but mild in heterozygous females (XX) (Dumitrescu et al. 2004). Thyroid normone transporters MCT8 and OATP1C1 are expressed in pyramidal neurons and interneurons in the adult motor cortex of human and macaque brains (Wang et al. 2023). Thyroid hormone transporters MCT8 and OATP1C1 are expressed in projection neurons and interneurons of basal ganglia and motor thalamus in adult human brains (Wang et al. 2023). MCT8 plays a vital role in maintaining brain thyroid hormone homeostasis. This transporter is expressed at the brain barriers, as the blood-brain barrier (BBB), and in neural cells, being the sole known thyroid hormone-specific transporter to date. Inactivating mutations in the MCT8 gene cause the Allan-Herndon-Dudley Syndrome (AHDS) or MCT8 deficiency, a rare X-linked disease characterized by delayed neurodevelopment and severe psychomotor disorders as well as BBB leakage (Guillén-Yunta et al. 2023). A novel SLC16A2 gene mutation produced a rare case of delayed myelination with dysthyroidism, v Allan-Herndon-Dudley syndrome (Mahesan et al. 2023). MCT8 inhibitors include methylmercury, bisphenol-AF and bisphenol-Z as well as previously known MCT8 inhibitors (Wagenaars et al. 2024). | Eukaryota |
Metazoa, Chordata | SLC16A2 of Homo sapiens | |||
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2.A.1.13.11 | Solute carrier family 16, member 5 (monocarboxylic acid transporter 6) of 505 aas and 12 TMSs. Found on the luminal side of small intestinal epithelial cells (Kohyama et al. 2013). MCT6 mediates uptake of nateglinide, an oral hypoglycemic agent. The K(t) for nateglinide is 46 μM. Thus, MCT6 may play a role in the intestinal absorption of nateglinide, although other transporters are also likely to be involved (Kohyama et al. 2013). | Eukaryota |
Metazoa, Chordata | SLC16A5 of Homo sapiens | |||
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2.A.1.13.12 | Solute carrier family 16, member 14 (monocarboxylic acid transporter 14), ATBo or MCT14. Transports carnitine with low affinity (~ 1 mM) (Ingoglia et al. 2015). Its tissue localization in the mouse has been determined (Roshanbin et al. 2016).
| Eukaryota |
Metazoa, Chordata | SLC16A14 of Homo sapiens | |||
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2.A.1.13.13 | solute carrier family 16, member 11 (monocarboxylic acid transporter 11) | Eukaryota |
Metazoa, Chordata | SLC16A11 of Homo sapiens | |||
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2.A.1.13.14 | Solute carrier family 16, member 12, SLC16A12, or monocarboxylic acid transporter 12; MCT12. Facilitative monocarboxylate transporter that mediates creatine transport across the plasma membrane (Abplanalp et al. 2013; Takahashi et al. 2020). It is the cataract and glucosuria associated monocarboxylate transporter. | Eukaryota |
Metazoa, Chordata | SLC16A12 of Homo sapiens | |||
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2.A.1.13.15 | Monocarboxylate transporter 7 (MCT 7; mTORC1) (Monocarboxylate transporter 6) (MCT 6) (Solute carrier family 16 member 6) of 523 aas and 12 TMSs in a 6 + 6 TMS arrangement. SLC16a6, mTORC1, and autophagy regulate ketone body excretion in intestinal cells (Uebanso et al. 2023). | Eukaryota |
Metazoa, Chordata | SLC16A6 of Homo sapiens | |||
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2.A.1.13.16 | Monocarboxylate transporter 9 (MCT 9) (Solute carrier family 16 member 9) | Eukaryota |
Metazoa, Chordata | SLC16A9 of Homo sapiens | |||
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2.A.1.13.17 | Monocarboxylate transporter 13 (MCT 13) (Solute carrier family 16 member 13) | Eukaryota |
Metazoa, Chordata | SLC16A13 of Homo sapiens | |||
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2.A.1.13.18 | Probable transporter MCH2 | Eukaryota |
Fungi, Ascomycota | MCH2 of Saccharomyces cerevisiae S288c | |||
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2.A.1.13.19 | Probable transporter MCH4 | Eukaryota |
Fungi, Ascomycota | MCH4 of Saccharomyces cerevisiae | |||
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2.A.1.13.20 | Putative permease of 468 aas | Eukaryota |
Rhodophyta | Putative permease of Galdieria sulphuraria | |||
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2.A.1.13.21 | MFS porter of 392 aas | Bacteria |
Pseudomonadota | MSF porter of Pseudomonas stutzeri | |||
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2.A.1.13.22 | SLC16 Family protein of 771 aas and 12 TMSs, GEM-1. GEM-1 acts in parallel to the GON-2 channel (TC# 1.A.4.5.10) to promote cation uptake within the developing gonad (Kemp et al. 2009). | Eukaryota |
Metazoa, Nematoda | Gem1 of Caenorhabditis elegans | |||
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2.A.1.13.23 | Chicken MCT8 of 509 aas and 12 TMSs. Transports pro-thyroid hormone, T4, with high affiinity, and T3 as well (Nele Bourgeois et al. 2016). | Eukaryota |
Metazoa, Chordata | MCT8 of Gallus gallus (Chicken) | |||
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2.A.1.13.24 | MCT10 (SLC16A10) of 400 aas and 11 TMSs. Transports thyroid hormones, especially T3 (Nele Bourgeois et al. 2016). | Eukaryota |
Metazoa, Chordata | MTC10 of Gallus gallus (chicken) | |||
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2.A.1.13.25 | Thyroid hormones (TH) transporter, MCT8 of 526 aas and 12 TMSs (Zada et al. 2017). The mechanisms underlying MCT8-deficient brain development in various animal models including zebra fish and humans has been reviewed (Vancamp and Darras 2017). | Eukaryota |
Metazoa, Chordata | TH transporter of Danio rerio (Zebrafish) (Brachydanio rerio) | |||
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2.A.1.13.26 | Thyroid hormones (TH) transporter, MCT10 of 505 aas and 12 TMSs. | Eukaryota |
Metazoa, Chordata | MCT10 of Danio rerio (Zebrafish) (Brachydanio rerio) | |||
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2.A.1.13.27 | MfsG of 447 aas and 12 TMSs. Exports fungicides such as glucosinolates and isothiocyanates. Exposure to glucosinolate-breakdown products induces expression of mfsG. MfsG functions in fungitoxic compound efflux (Vela-Corcía et al. 2019). | Eukaryota |
Fungi, Ascomycota | MfsG of Botryotinia fuckeliana (Noble rot fungus) (Botrytis cinerea) | |||
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2.A.1.13.28 | Uncharacterized protein of 652 aas and 12 TMSs | Eukaryota |
Metazoa, Arthropoda | UP of Trachymyrmex zeteki | |||
| 2.A.1.14: The Anion:Cation Symporter (ACS) Family | |||||||
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2.A.1.14.1 | Glucarate porter | Bacteria |
Bacillota | GudT of Bacillus subtilis | |||
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2.A.1.14.2 | Hexuronate (glucuronate; galacturonate) porter, ExuT (Nemoz et al. 1976). It also transports D-glucose (Kim et al. 2020). | Bacteria |
Pseudomonadota | ExuT of E. coli (P0AA78) | |||
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2.A.1.14.3 | Putative tartrate porter, TtuB or TUB3, of 449 aas and 12 TMSs. | Bacteria |
Pseudomonadota | TtuB of Agrobacterium vitis | |||
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2.A.1.14.4 | Dipeptide (e.g., Gly-Leu), allantoate, ureidosuccinate, allantoin porter (Cai et al., 2007). | Eukaryota |
Fungi, Ascomycota | Dal5 of Saccharomyces cerevisiae | |||
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2.A.1.14.5 | Phthalate porter, Pht1 of 451 aas and 11 or 12 TMSs. | Bacteria |
Pseudomonadota | Pht1 of Pseudomonas putida | |||
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2.A.1.14.6 | Na:Pi symporter, NPT1 or SLC17A1. (Renal chloride-dependent polyspecific anion exporter; transports organic acids such as p-aminohippurate, ureate, and acetylsalicylate (asprin)). Catalyzes ureate excretion. A mutant form shows increased risk of gout in humans. | Eukaryota |
Metazoa, Chordata | Npt1 of Mus musculus | |||
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2.A.1.14.7 | Galactonate transporter | Bacteria |
Pseudomonadota | DgoT (YidT) of E. coli (P0AA76) | |||
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2.A.1.14.8 | Phthalate porter | Bacteria |
Pseudomonadota | OphD of Burkholderia cepacia | |||
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2.A.1.14.9 | Putative p-hydroxyphenylacetate porter | Bacteria |
Pseudomonadota | HpaX of Salmonella dublin | |||
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2.A.1.14.10 | Lysosomal sialate transporter (Salla disease and infantile sialate storage disease protein, Sialin, of 419 aas and 12 TMSs (Morin et al., 2004)). Also transports glucuronic acid and aspartate. Structure-function studies have identify crucial residues and substrate-induced conformational changes (Courville et al., 2010). Also called SLC17A5. The substrate binding pocket has been identified based on modeling studies (Pietrancosta et al., 2012). NAAG (N-acetylaspartylglutamate) an abundant neuropeptide in the vertebrate nervous system that is released from synaptic terminals in a calcium-dependent manner and acts as an agonist at the type II metabotropic glutamate receptor mGluR3, is transported into synaptic vesicles before it is secreted. Lodder-Gadaczek et al. 2013 demonstrate that vesicular uptake of NAAG and the related peptide NAAG2 (N-acetylaspartylglutamylglutamate) is mediated by sialin (SLC17A5). Sialin is probably the only vesicular transporter for NAAG and NAAG2, because transport of both peptides was not detectable in vesicles isolated from sialin-deficient mice. Sialin also transports nitrate in the plasma membrane of salivary glands (Qin et al. 2012). Sialin interacts with nitrate and participates in the regulation of NO production and cell biological functions for body homeostasis (Wang and Qin 2022). Sialin mediates the flux of sialic acid from lysosomes to the cytoplasm (Li et al. 2022). Altered sialin mRNA expression in the main tissues of male type 2 diabetes rats has been documented (Yousefzadeh et al. 2023). Base editing corrects the common Salla disease SLC17A5 c.115C>T variant (Harb et al. 2023). | Eukaryota |
Metazoa, Chordata | SLC17A5 of Homo sapiens | |||
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2.A.1.14.11 | Plasma membrane, high affinity nicotinate permease, Tna1 | Eukaryota |
Fungi, Ascomycota | Tna1 of Saccharomyces cerevisiae | |||
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2.A.1.14.12 | Plasma membrane, high affinity biotin:H+ symporter, Vht1 | Eukaryota |
Fungi, Ascomycota | Vht1 of Saccharomyces cerevisiae | |||
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2.A.1.14.13 | Broad specificity brain synaptic vesicle anion:Na+ symporter (transports glutamate, phosphate, chloride, etc.)(BNPI, EAT-4, VGLUT1) Chloride and ketone bodies regulate VGLUT activities (Omote et al., 2011). | Eukaryota |
Metazoa, Chordata | BNPI of Rattus norvegicus | |||
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2.A.1.14.14 | Probable D-galactarate (glucarate?):H+ symporter, GarP or YhaU. May also function as a glucarate:glycerate antiporter (Moraes and Reithmeier 2012) and a glucose transporter. This sequence is incomplete. | Bacteria |
Pseudomonadota | GarP (YhaU) of E. coli | |||
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2.A.1.14.15 | Apical membrane renal proximal tubular voltage-driven but Na+-independent organic anion transporter, OATv1 (transports p-aminohippurate; probably transports organic anions but not cations and not inorganic phosphate. It may catalyze excretion of various drugs, xenobiotics, and their metabolites) (Jutabha et al., 2003) | Eukaryota |
Metazoa, Chordata | OATv1 of Sus scrofa (Q7YQJ7) | |||
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2.A.1.14.16 | The broad specificity brain synaptic vesicle anion transporter, VGLUT-2 (transports glutamate in a Δψ-dependent fashion requiring Cl-, but phosphate by a Na+-dependent mechanism via a different pathway/mechanism (Juge et al., 2006). VGLUT1-3 concentrate glutamate into synaptic vesicles before its exocytotic release. Two distinct roles for Cl- in both allosteric activation and permeation have been proposed (Chang et al. 2018). The 3-D structure has been solved at 3.8 Å resolution revealing mechanisms of substrate recognition and allosteric activation by low pH and Cl-. It shows how the activities of VGLUTs are coordinated by changes in proton and chloride concentration during the synaptic vesicle cycle (Li et al. 2020). | Eukaryota |
Metazoa, Chordata | VGLUT2 of Rattus norvegicus (Q9JI12) | |||
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2.A.1.14.17 | Pantothenate:H+ symporter, Liz1 (mutants cause abnormal mitosis due to a defect in ribonucleotide reductase) (Stolz et al., 2004) | Eukaryota |
Fungi, Ascomycota | Liz1 of Schizosaccharomyces pombe (O43000) | |||
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2.A.1.14.18 | Pantothenate:H+ symporter, Fen2 | Eukaryota |
Fungi, Ascomycota | Fen2 of Saccharomyces cerevisiae (P25621) | |||
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2.A.1.14.19 | Plasma membrane, high affinity vitamin H transporter 1 (H+:biotin symporter), Vht1 (Stolz, 2003) | Eukaryota |
Fungi, Ascomycota | Vht1 of Schizosaccharomyces pombe (O13880) | |||
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2.A.1.14.20 | Endoplasmic reticular cysteine transporter, Yct1 (Kaur and Bachhawat, 2007) | Eukaryota |
Fungi, Ascomycota | Yct1 of Saccharomyces cerevisiae (Q12235) | |||
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2.A.1.14.21 | The vesicular purine nucleotide (ADP, ATP, GTP) transporter, VNUT or SLC17A9. It is found in synaptic vesicles and chromafin granules (Sawada et al., 2008)) and is associated with disseminated superficial actinic porokeratosis (DSAP), a rare autosomal dominant genodermatosis (Cui et al. 2014). It plays a key role in purinergic signaling through its ability to transport nucleotides using the pmf. It catalyzes Cl--dependent transport activity involving essential arginines in the transmembrane region. Ketoacids inhibit these transporters through modulation of Cl- activation, but Cl- and the arginine residues are not important for ATP binding (Iwai et al. 2019). High expression of SLC17A9 correlates with a poor prognosis for colorectal cancer (Yang et al. 2019). | Eukaryota |
Metazoa, Chordata | SLC17A9 of Homo sapiens | |||
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2.A.1.14.22 | The chloroplast thylakoid Na+:phosphate symporter, ANTR1 (512aas) (Pavón et al., 2008). Residues essential for function have been identified (Ruiz-Pavón et al., 2010). | Eukaryota |
Viridiplantae, Streptophyta | ANTR1 of Arabidopsis thaliana (O82390) | |||
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2.A.1.14.23 | Vesicular glutamate transporter #3 (VGLUT3) [Its absence in mice causes sensorineural deafness and seizures]. 70% identical to VGLUT2 (TC# 2.A.1.14.16) (Gras et al., 2002). VGLUT1-3 concentrate glutamate into synaptic vesicles before its exocytotic release and contribute to the regulation of serotonergic transmission and anxiety (Amilhon et al., 2010). It may catalyze uptake of the neurotransmitter coupled with H+ export and K+ uptake (Farsi et al. 2016). | Eukaryota |
Metazoa, Chordata | VGLUT3 of Mus musculus (Q8BFU8) | |||
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2.A.1.14.24 | Intestinal mucosal sodium/phosphate symporter, SLC17A4. Maintains phosphate homeostasis; mediates intestinal absorption, bone deposition and resorption and renal excretion. | Eukaryota |
Metazoa, Chordata | SLC17A4 of Homo sapiens | |||
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2.A.1.14.25 | The putative D-mannuronate porter, AlgT (Rodionov et al., 2010). | Bacteria |
Pseudomonadota | AlgT of Shewanella frigidimarina (Q07YH1) | |||
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2.A.1.14.26 | The plasma membrane Lethal (2)01810 glutamate uptake porter (Km=0.07μM) (Inhibited by aspartate) (Shim et al., 2011) | Eukaryota |
Metazoa, Arthropoda | L(2)01810 of Drosophila melanogaster (F2YPN7) | |||
|
2.A.1.14.27 | Voltage-driven Na+:phosphate cotransporter; solute carrier family 17, member 1. Orthologous to 2.A.1.14.6. Transports other anions including urate; functions in urate cell elimination at the renal apical membrane (Prestin et al. 2014). | Eukaryota |
Metazoa, Chordata | SLC17A1 of Homo sapiens | |||
|
2.A.1.14.28 | Solute carrier family 17 (sodium phosphate), member 3. Catalyzes voltage-driven Na+:phosphate cotransport, but also functions in cell elimination of urate at renal tubular cell apical membranes (Prestin et al. 2014). | Eukaryota |
Metazoa, Chordata | SLC17A3 of Homo sapiens | |||
|
2.A.1.14.29 | Sodium-dependent phosphate transport protein 3 (Na(+)/PI cotransporter 3) (Sodium/phosphate cotransporter 3) (Solute carrier family 17 member 2) | Eukaryota |
Metazoa, Chordata | SLC17A2 of Homo sapiens | |||
|
2.A.1.14.30 | Vesicular glutamate transporter 1, VGluT1 or PNP1 of 560 aas and 12 TMSs. Brain-specific Na+-dependent inorganic phosphate cotransporter; Solute carrier family 17 member 7). Several proteins must be retrieved to the synaptic vesicle before it can export neurotransmitters, and cargo retrieval is a collective cargo-driven process, dependent on VGluT1 (Pan et al. 2015). The amino-terminal and carboxyl-terminal regions of VGLUT2 in membranes face the cytoplasm (Jung et al. 2006). It is involved in nervous system diseases (Du et al. 2020). VGLUT1 and VGLUT2, selectively label and define functionally distinct neuronal subpopulations at each relay level of the neural hierarchies comprising spinal and trigeminal sensory systems (Zhang et al. 2018). An overview of the physiologic sites for VGLUT regulation that can modulate glutamate release in an over-active synapse or in a disease state has been presented (Pietrancosta et al. 2020). | Eukaryota |
Metazoa, Chordata | SLC17A7 of Homo sapiens | |||
|
2.A.1.14.31 | Vesicular glutamate transporter 2 (VGluT2) (Differentiation-associated BNPI) (Differentiation-associated Na+-dependent inorganic phosphate cotransporter) (Solute carrier family 17 member 6, SLC17A6). It has 582 aas with 12 probable TMSs. It is expressed in different nerve fibre populations that selectively contact pulmonary neuroepithelial bodies (Brouns et al. 2004). | Eukaryota |
Metazoa, Chordata | SLC17A6 of Homo sapiens | |||
|
2.A.1.14.32 | Vesicular glutamate transporter 3 (VGluT3) (Solute carrier family 17 member 8). Loss in mice produces circadian-dependent hyperdopaminergia and amiliorates motor disfunction and dopa-mediated dyskinesias in a model
of Parkinson's Disease (Divito et al. 2015). VGLUT3 is expressed selectively in the inner hair cells (IHCs) and transports the neurotransmitter
glutamate into synaptic vesicles. Mutation of the SLC17A8 gene is
associated with DFNA25 (deafness, autosomal dominant 25), a non-syndromic
hearing loss (ADNSHL) in humans (Ryu et al. 2016). Glut3 contributes to stress response and related psychopathologies (Horváth et al. 2018). An adeno-associated virus carrying the Slc17a8 gene restored vesicular Glut3 in the inner hair cells of the cochlea, thereby rescuing loss in mice that lacked Glut3 (Mathiesen et al. 2023). | Eukaryota |
Metazoa, Chordata | SLC17A8 (VGluT3) of Homo sapiens | |||
|
2.A.1.14.33 | Bacteria |
Pseudomonadota | YjjL of Escherichia coli | ||||
|
2.A.1.14.34 | Putative inorganic phosphate cotransporter | Eukaryota |
Metazoa, Arthropoda | Picot of Drosophila melanogaster | |||
|
2.A.1.14.35 | Inner membrane transport protein RhmT | Bacteria |
Pseudomonadota | RhmT of Escherichia coli | |||
|
2.A.1.14.36 | Thiamine pathway transporter THI73 | Eukaryota |
Fungi, Ascomycota | THI73 of Saccharomyces cerevisiae | |||
|
2.A.1.14.37 | Probable transporter SEO1 | Eukaryota |
Fungi, Ascomycota | SEO1 of Saccharomyces cerevisiae | |||
|
2.A.1.14.38 | Transporter YIL166c (Hellborg et al. 2008) of 542 aas and 12 TMSs. May transport inorganic sulfur-containing compounds such as sulfate, sulfite, thiosulfate and sulfonates. | Eukaryota |
Fungi, Ascomycota | YIL166c of Saccharomyces cerevisiae | |||
|
2.A.1.14.39 | Uncharacterized transporter YybO | Bacteria |
Bacillota | YybO of Bacillus subtilis | |||
|
2.A.1.14.40 | Glucarate transporter, GudP. Encoded in an operon with GudD, a glucarate dehydratase (Moraes and Reithmeier 2012). | Bacteria |
Pseudomonadota | GudP of E. coli | |||
|
2.A.1.14.41 | The Aldohexuronate (glucuronate, galacturonate) uptake porter (Valmeekam et al. 2001). | Bacteria |
Pseudomonadota | ExuT of Erwinia chrysanthemi This sequence is incomplete. | |||
|
2.A.1.14.42 | Vesicular glutamate transporter, EAT-4/VGLUT of 576 aas (Serrano-Saiz et al. 2013). EAT-4 is responsible for loading glutamate into synaptic vesicles, and thus in defining the glutamatergic phenotype of a neuron (Serrano-Saiz et al. 2013). | Eukaryota |
Metazoa, Nematoda | EAT-4 of Caenorhabditis elegans | |||
|
2.A.1.14.43 | Uncharacterized but putative sulfonate (and other inorganic sulfur-containing compounds) uptake transporter of 537 aas and 12 TMSs. | Eukaryota |
Fungi, Ascomycota | UP of Ashbya gossypii (Yeast) (Eremothecium gossypii) | |||
|
2.A.1.14.44 | Vesicular Glutamate transporter, VGlut of 632 aas and 10 TMSs with the N- and C-termini in the cytoplasm (Fei et al. 2007). | Eukaryota |
Metazoa, Arthropoda | VGlut of Drosophila melanogaster
| |||
|
2.A.1.14.45 | AtPHT4;4, or ANTR2 of 541 aas and 12 TMSs, an ascorbate transporter in the chloroplast envelope membrane. It may be required for tolerance to strong light stress (Miyaji et al. 2015). | Eukaryota |
Viridiplantae, Streptophyta | ANTR2 of Arabidopsis thaliana | |||
|
2.A.1.14.46 | Vesicular glutamate transporter, VGLU-2, of 573 aas and 12 TMSs. In addition to being present in nerve cells, it may play a role in collagen trafficking in the skin. The C. elegans SLC17A6/7/8 family members probaly have diverse functions within and outside the nervous system (Serrano-Saiz et al. 2019). | Eukaryota |
Metazoa, Nematoda | VGLU-2 of Homo sapiens | |||
|
2.A.1.14.47 | MFS2 of 1379 aas and 12 TMSs in a 6 + 6 TMS arrangement at the C-terminal end of the protein (residues 800 - 1379). The N-terminal 800 residues are strongly hydrophilic (Wunderlich 2022). | Eukaryota |
Apicomplexa | MFS2 of Plasmodium falciparum | |||
|
2.A.1.14.48 | MFS general substrate transporter of 451 aas and 12 TMSs, MFS-3-6. It facilitates the export of lactate from the cell under acidic conditions (Tian et al. 2022). | Bacteria |
Bacillota | MFS-3-6 of Weizmannia coagulans (strain 2-6) (Bacillus coagulans) | |||
|
2.A.1.14.49 | Uncharacterized MFS carrier of 453 aas and probably 12 TMSs in a 6 + 6 TMS arrangement. The encoding gene is responsive to the presence of Ivermectin (Dube et al. 2023). | Eukaryota |
Metazoa, Nematoda | UP of Caenorhabditis elegans | |||
|
2.A.1.14.50 | MFS carrier, a putative drug exporter of 450 aas and 12 TMSs in a 6 + 6 TMS arrangement. It exports polymyxin B, CCCP and verapamil (Gao et al. 2023). | Bacteria |
Pseudomonadota | Polymyxin exporter of Pandoraea pnomenusa | |||
| 2.A.1.15: The Aromatic Acid:H+ Symporter (AAHS) Family | |||||||
|
2.A.1.15.1 | 4-Hydroxybenzoate/protocatechuate porter (Nichols and Harwood 1997). | Bacteria |
Pseudomonadota | PcaK of Pseudomonas putida | |||
|
2.A.1.15.2 | MhpT. A specific 3-(3-hydroxyphenyl)propionate (3HPP) transporter; vital for E. coli K-12 W3110 to grow on this substrate. Transports 3HPP but not benzoate, 3-hydroxybenzoate or gentisate (Xu et al. 2013). May also export arabinose but not xylose (Koita and Rao 2012). | Bacteria |
Pseudomonadota | MhpT of E. coli | |||
|
2.A.1.15.3 | 2,4-Dichlorophenoxyacetate porter (Hawkins and Harwood 2002). | Bacteria |
Pseudomonadota | TfdK of Ralstonia eutropha | |||
|
2.A.1.15.4 | cis,cis-muconate porter, MucK (Williams and Shaw 1997). | Bacteria |
Pseudomonadota | MucK of Acinetobacter sp. ADP1 | |||
|
2.A.1.15.5 | Benzoate porter, BenK | Bacteria |
Pseudomonadota | BenK of Acinetobacter sp. ADPP1 | |||
|
2.A.1.15.6 | Vanillate porter, VanK | Bacteria |
Pseudomonadota | VanK of Acinetobacter sp. ADP1 | |||
|
2.A.1.15.7 | Aromatic compound (benzoate) uptake transporter of 450 aas (Clark et al. 2002). | Bacteria |
Pseudomonadota | BenK of Acinetobacter baylyi | |||
|
2.A.1.15.8 | Probable 1-hydroxy-2-naphthoate transporter, orf1 (Iwabuchi and Harayama, 1997). | Bacteria |
Actinomycetota | Orf1 of Nocardioides sp. (O24723) | |||
|
2.A.1.15.9 | Probable 4-methylmuconolactone transporter, MmlH (Erb et al., 1998) | Bacteria |
Pseudomonadota | MmlH of Ralstonia eutropha (O51798) | |||
|
2.A.1.15.10 | The gentisate (2,5-dihydroxybenzoate) uptake porter, GenK (does not take up either benzoate or 3-hydoxybenzoate). | Bacteria |
Actinomycetota | GenK of Corynebacterium glutamicum (Q8NLB7) | |||
|
2.A.1.15.11 | The Vanillate porter, VanK | Bacteria |
Actinomycetota | VanK of Corynebacterium glutamicum (Q6M372) | |||
|
2.A.1.15.12 | Inner membrane transport protein YdiM. Catalyzes export of medium chain alcohols such as isoprenol (Wang et al. 2015). | Bacteria |
Pseudomonadota | YdiM of Escherichia coli | |||
|
2.A.1.15.13 | Inner membrane transport protein, YdiN (similar to 2.A.1.15.12). Induced under carbon limitation but not phosphate limitation (Johansson and Lidén 2006). | Bacteria |
Pseudomonadota | YdiN of Escherichia coli | |||
|
2.A.1.15.14 | Probable uptake transporter for 2,4-dichlorophenoxyacetic acid (2,4-D), CadK (Kitagawa et al. 2002). | Bacteria |
Pseudomonadota | CadK of Bradyrhizobium sp. HW13 | |||
|
2.A.1.15.15 | Unncharacterized permease of 436 aas and 12 TMSs. | Bacteria |
Spirochaetota | UP of Treponema brennaborense | |||
|
2.A.1.15.16 | Aromatic/benzoate uptake transporter of 442 aas and 12 TMSs, BenK (Choudhary et al. 2017). | Bacteria |
Pseudomonadota | BenK of Pseudomonas putida | |||
| 2.A.1.16: The Siderophore-Iron Transporter (SIT) Family | |||||||
|
2.A.1.16.1 | Siderophore-iron (ferrioxamine):H+ symporter, Sit1 (Arn3) (in vesicles) | Eukaryota |
Fungi, Ascomycota | Sit1 (YEL065w) of Saccharomyces cerevisiae | |||
|
2.A.1.16.2 | The ferric enterobactin:H+ symporter, Enb1 | Eukaryota |
Fungi, Ascomycota | Enb1 (YOL158c) of Saccharomyces cerevisiae | |||
|
2.A.1.16.3 | The ferric triacetylfusarinine C:H+ symporter, Taf1 | Eukaryota |
Fungi, Ascomycota | Taf1 (YHL047c) of Saccharomyces cerevisiae | |||
|
2.A.1.16.4 | The ferrichrome:H+ symporter, Arn1p (Moore et al., 2003) | Eukaryota |
Fungi, Ascomycota | Arn1 of Saccharomyces cerevisiae (NP_011823) | |||
|
2.A.1.16.5 | Siderophore iron transporter 2 | Eukaryota |
Fungi, Ascomycota | str2 of Schizosaccharomyces pombe | |||
|
2.A.1.16.6 | Eukaryota |
Fungi, Ascomycota | Str1 of Schizosaccharomyces pombe | ||||
|
2.A.1.16.7 | Ferri-siderophore transporter, MirB. Transports hydroxamate siderophores such as triacetylfusarinine C (TAFC) (Raymond-Bouchard et al. 2012). | Eukaryota |
Fungi, Ascomycota | MirB of Emericella nidulans | |||
|
2.A.1.16.8 | Fusarum iron-related protein, Fir1 of 585 aas and 14 TMSs. Probably an iron-siderophre transporter (López-Errasquín et al. 2006). | Eukaryota |
Fungi, Ascomycota | Fir1 if Gibberella moniliformis (Maize ear and stalk rot fungus) (Fusarium verticillioides) | |||
|
2.A.1.16.9 | Siderophore iron transporter 3, Str3 of 630 aas and 14 TMSs in a 6 + 7 + 1 TMS arrangement. It transports siderophore iron and so plays a role in iron homeostasis (Pelletier et al. 2003). It also transports heme, and the peroxiredoxin, Tpx1 (Q74887; 192 aas and 0 - 2 possible TMSs), is a binding partner of Str3 (Normant et al. 2020). Under microaerobic conditions, cells deficient in heme biosynthesis and lacking the heme receptor Shu1 exhibit poor hemin-dependent growth in the absence of Tpx1, a cytoplasmic heme binding protein. Tpx1 exhibits an equilibrium constant value of 0.26 muM for hemin. The association of Tpx1 with hemin protects hemin from degradation by H2O2, and the peroxidase activity of hemin is lowered when it is bound to Tpx1 (Normant et al. 2020).
| Eukaryota |
Fungi, Ascomycota | Str3 of Schizosaccharomyces pombe (Fission yeast) | |||
| 2.A.1.17: The Cyanate Porter (CP) Family | |||||||
|
2.A.1.17.1 | Cyanate transport system, CynT. Encoded with cyanate aminohydrolase, CynS, and carbonic anhydrase, CynX (Anderson et al. 1990; Moraes and Reithmeier 2012). | Bacteria |
Pseudomonadota | CynX of E. coli | |||
|
2.A.1.17.2 | Glucose transporter, OEOE_0819. Does not transport fructose (Kim et al., 2011) | Bacteria |
Bacillota | OEOE_0819 of Oenococcus onei (Q04FN1) | |||
|
2.A.1.17.3 | Inner membrane transport protein, NimT or YeaN of 393 aas and 12 TMSs. It exports 2-nitroimidazole from the cytoplasm, confering resistance to this anitbiotic, and transcription of this gene as well as NimO, within the same operon, is regulated by the repressor, NimR (YeaM) (Ogasawara et al. 2015). | Bacteria |
Pseudomonadota | NimT or YeaN of Escherichia coli | |||
|
2.A.1.17.4 | MFS porter of 390 aas and 12 TMSs | Bacteria |
Campylobacterota | MFS porter of Campylobacter peloridis | |||
| 2.A.1.18: The Polyol Porter (PP) Family | |||||||
|
2.A.1.18.1 | D-Arabinitol:H+ symporter of 425 aas and 12 TMSs, DalT (Heuel et al. 1997; Heuel et al. 1998). | Bacteria |
Pseudomonadota | DalT of Klebsiella pneumoniae | |||
|
2.A.1.18.2 | Ribitol:H+ symporter of 427 aas and 12 TMSs, RbtT (Heuel et al. 1997; Heuel et al. 1998). | Bacteria |
Pseudomonadota | RbtT of Klebsiella pneumoniae | |||
|
2.A.1.18.3 | Alpha-ketoglutarate permease of 435 aas and 12 TMSs (Gomez and Cutting 1997). | Bacteria |
Bacillota | CsbX of Bacillus subtilis | |||
| 2.A.1.19: The Organic Cation Transporter (OCT) Family (The SLC22A family including OCT1-3, OCTN1-3 and OAT1-5 of H. sapiens) | |||||||
This family has been described by Koepsell 2013. It contains 13 functionally characterized human plasma membrane proteins.The family includes organic cation transporters (OCTs), organic zwitterion/cation transporters (OCTNs), and organic anion transporters (OATs). The transporters operate as (1) uniporters which mediate facilitated diffusion (OCTs and some OCTNs), (2) anion exchangers (OATs), and (3) some Na+/zwitterion cotransporters (OCTNs). They participate in small intestinal absorption and hepatic and renal excretion of drugs, xenobiotics and endogenous compounds and perform homeostatic functions in the brain and heart. Important endogeneous substrates include monoamine neurotransmitters, l-carnitine, alpha-ketoglutarate, cAMP, cGMP, prostaglandins and urate. Mutations in the SLC22 genes cause specific diseases like primary systemic carnitine deficiency and idiopathic renal hypouricemia and are correlated with diseases such as Crohn's disease and gout. Drug-drug interactions at individual transporters may change pharmacokinetics and toxicities of drugs (Koepsell 2013). Models of Octs resemble GLUT3 (PDB ID# 5C65) and have an intracellular three/four-helix loop between TMH6 and TMH7 containing putative phosphorylation sites for precise regulation of hOCTs. The models allow prediction of substrate binding sites (Dakal et al. 2017). Interactions with therapeutic herbal products, dietary supplements, and clinically important drugs are discussed, and the significance of these transporters in modulating the severity of drug-related side effects and toxicity mechanisms have been reviewed (Mor et al. 2018). OCTs are highly expressed on the plasma membranes of polarized epithelia, thus, playing a key role in intestinal absorption and renal reabsorption of nutrients (e.g., choline and carnitine), in the elimination of waste products (e.g., trimethylamine and trimethylamine N-oxide), and in the kinetic profile and therapeutic index of several drugs (e.g., metformin and platinum derivatives) (Samodelov et al. 2020). SLC22 is a family of drug/metabolite exporters (i.e., OAT1) speicific for (1) drugs and natural products, (2) antibiotics (i.e., cefazolin) and antiviral agents (i.ie., adefovir), (3) chemo-theraputic agents (i.e., methotrexate), (4) antioxidants (i.e., uric acid) that decrease oxidative stress and aging, (5) protaglandins (i.e., PG F2a), (6) gut microbial metabolites (i.e., hippuric acid and trimethylamine oxide, TMAO), (7) other compounds including bile acids (Granados et al. 2021; Zhang et al. 2021). Their functions are similar in flies and mammals. | |||||||
|
2.A.1.19.1 | The basolateral multivalent, potential-sensitive, organic cation (tetramethyl-ammonium; N'-methylnicotinamide; cationic drugs, xenobiotics, vitamins, neuro-transmitters, etc.) transporter (uni-porter)-1, Oct1. Cysteyl residues essential for transport and substrate binding have been identified (Sturm et al. 2007). Subtype-specific affinity of rat organic cation transporters rOCT1 and rOCT2 for corticosterone depends on three amino acids within the substrate binding region (Gorboulev et al. 2005). Differences in metformin and thiamine uptake between human and mouse Oct1 transporters have been demonstrated (Meyer et al. 2020). | Eukaryota |
Metazoa, Chordata | Oct1 of Rattus norvegicus (Q63089) | |||
|
2.A.1.19.2 | The ergothionine/carnitine/hydroxyurea/organic zwitterion transporter, OCTN1 or SVOP (SLC22A4). It is upregulated in polycythemia vera hematopoietic stem and progenitor cells (Tan and Meier-Abt 2021). It is associated with rheumatoid arthritis (Barton et al., 2005). Acetylcholine is a physiological substrate, and its transport could be involved in nonneuronal cholinergic functions (Pochini et al. 2013). OCTN1 and OCTN2 are associated with several pathologies, such as inflammatory bowel disease, primary carnitine deficiency, diabetes, neurological disorders, and cancer. It transports TEA, and transoirts acetylcholine better than acetylcarnitine (Pochini et al. 2015). Molecular perturbations across several metabolite classes precede autism. The cyclic dipeptide cyclo-leucine-proline and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy and with variants near SLC22A4 and SLC22A5 coding for transmembrane carnitine transporter proteins involved in controlling intracellular carnitine levels (Ottosson et al. 2024). | Eukaryota |
Metazoa, Chordata | SLC22A4 (OCTN1) of Homo sapiens (O14546) | |||
|
2.A.1.19.3 | The polyspecific organic cation (L- and D-carnitine, butyryl-L-carnitine, acetyl carnitine, γ-butyro-betaine, glycinebetaine, β-lactam antibiotics with a quaternary nitrogen such as cephaloridine, and others):Na+ symporter, OCTN2 (SLC22A5). Carnitine is transporter with high affinity (2 - 20 μM0 (Ingoglia et al. 2015). Associated with Crohn''s disease (Barton et al., 2005) as well as primary carnitine deficiency. The protein is glycosylated on extracytoplasmic asparagines, and these residues are in a region important for function and turnover (Filippo et al. 2011). OCTN2 maintains the carnitine homeostasis, resulting from intestinal absorption, distribution to tissues, and renal excretion/reabsorption (Pochini et al. 2013). OCTN1 and OCTN2 are associated with several pathologies, such as inflammatory bowel disease, primary carnitine deficiency, diabetes, neurological disorders, and cancer. OCTN2 is activated in a process dependent on Caveolin1 (Q03135) which interacts directly with OCTN2 and by protein kinase C which does not phosphorylate OCTN2 directly (Czeredys et al. 2013). Cholesterol stimulates the cellular uptake of L-carnitine by the carnitine/organic cation transporter novel 2 (OCTN2) (Zhang et al. 2020). A dataset of OCTN2 variant functions and localization has been created, revealing important disease-causing mechanisms (Koleske et al. 2022). Primary carnitine deficiency (PCD) is caused by pathogenic variants of the SLC22A5 gene, which encodes a high affinity carnitine transporter. Carnitine is essential for the transport of acyl-CoA, produced from fatty acids, into the mitochondria where they are oxidised to produce energy (Khries et al. 2023). OctN2 transports doxorubicin (Yi et al. 2023). A novel pathogenic variant in the carnitine transporter gene, SLC22A5, is associated with metabolic carnitine deficiency and cardiomyopathy features (Jolfayi et al. 2024). Molecular perturbations across several metabolite classes precede autism. The cyclic dipeptide cyclo-leucine-proline and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy and with variants near SLC22A4 and SLC22A5 coding for transmembrane carnitine transporter proteins involved in controlling intracellular carnitine levels (Ottosson et al. 2024). | Eukaryota |
Metazoa, Chordata | SLC22A5 (OCTN2) of Homo sapiens | |||
|
2.A.1.19.4 | The polyspecific organic anion, cation and neutral molecule transporter, Oat1 (Slc22a6) (transports neutral compounds such as cardiac glycosides [i.e., ouabain] and steroids [i.e., aldosterone; cortisol; dexamethasone]; cationic compounds such as N-propylajmalinium, and anionic compounds such as p-aminohippurate, dicarboxylates, cyclic nucleotides, prostaglandins, urate, β-lactam antibiotics, nonsteroidal anti-inflammatory drugs, diuretics, bile salts and steroid conjugates [i.e., estrone-3-sulfate and estradiol-17-glucuronide]) transporter (H+ symporter or uniporter) Probably catalyzes organic anion (uptake):dicarboxylate (efflux) antiport in the basolateral membrane of kidney proximal tubules) (Eraly et al., 2003a,b). A 3-dimensional model of OAT1 has led to the identification of residues involved in differential transport of substrates such as p-aminohippurate and cidofovir (Perry et al., 2006). Oat1 transports many antiviral agents (Truong et al., 2008). The human orthologue (Q4U2R8; 563aas) has been shown to be a multispecific organic anion transporter on the basolateral membrane of the proximal tubule in human kidney (Hosoyamada et al. 1999). A substrate binding hinge domain is required for transport-related structural changes (Egenberger et al., 2012). Transports environmental toxins and clinically important drugs including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories (Duan et al., 2011). hOAT1 has two GXXXG motifs in TMSs 2 and 5 which play critical roles in stability (Duan et al., 2011). Both OAT1 and OAT3 of humans are inhibited by caffeic acid (Ki ~ 17 μM) (Uwai et al. 2011). | Eukaryota |
Metazoa, Chordata | Oat1 of Rattus norvegicus (O35956) | |||
|
2.A.1.19.5 | The putative apical polyspecific organic cation transporter (cation:H+ or cation:cation antiporter), Oct2 (substrates include monoamine neurotransmitters such as dopamine, noradrenaline, adrenaline and 5-hydroxytryptamine) (Oct2 exhibits some properties of an ion channel with an inner diameter of ~4 Å. Selectivity: Cs+ > Rb+ > K+ > Na+ %u2248 Li+ (Schmitt and Koepsell, 2005)) Chloride dependent, but a single mutation (R466K) abolishes this dependency (Rizwan et al., 2007). Also transports ochratoxin (Rizwan et al., 2007) and cisplatin and oxaliplatin (Yonezama et al., 2006). | Eukaryota |
Metazoa, Chordata | Oct2 of Sus scrofa (O02713) | |||
|
2.A.1.19.6 | The polyspecific potential-sensitive organic cation uptake transporter, Oct3 (transport substrates include the neurotoxin 1-methyl-4-phenylpyridinium and monoamine neurotransmitters such as dopamine). Mediates paraquat (herbicide) neurotoxicity (Rappold et al., 2011). SLC22 transporters involved in drug elimination and organ distribution are polyspecific. The cryo-EM structure of SLC22A3 (OCT3) is available (Meyer-Tönnies and Tzvetkov 2023). OCT3 and MATE2 genetic polymorphisms can give rise to poor responses to metformin in type 2 diabetes mellitus (Naem et al. 2024). | Eukaryota |
Metazoa, Chordata | Oct3 of Rattus norvegicus (O88446) | |||
|
2.A.1.19.7 | The polyspecific organic anion (and cation) (anions: p-aminohippurate, ochratoxin A, estrone sulfate, anionic drugs, anionic neurotransmitter metabolites; cation: cimetidine) transporter, Oat3 (slc22a8) (catalyzes organic anion (uptake): dicarboxylate (efflux) antiport in the basolateral membrane of the renal proximal tubule) (Eraly et al., 2003a,b); transports many antiviral agents (Truong et al., 2008). | Eukaryota |
Metazoa, Chordata | Oat3 of Rattus norvegicus (Q9R1U7) | |||
|
2.A.1.19.8 | The human organic cation transporter, SLC22A17. The rat orthologue may be inactive (Bennett et al. 2011). It is also the cell surface receptor for Lipocalin-2 (LCN2) that plays a key role in iron homeostasis and transport. It is able to bind iron-LCN2, followed by internalization and release of iron, thereby increasing intracellular iron concentration and leading to inhibition of apoptosis (Cabedo Martinez et al. 2016). It also binds iron-free LCN2, followed by internalization and its association with an intracellular siderophore, leading to iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentrations and resulting in apoptosis. The SLC22A17/lipocalin-2 receptor plays a role in renal endocytosis of proteins involved in metalloproteins, particularly on iron- and cadmium-binding proteins (Thévenod et al. 2023). Other renal functions of SLC22A17 include its contribution to osmotic stress adaptation, protection against urinary tract infection, and renal carcinogenesis. | Eukaryota |
Metazoa, Chordata | SLC22A17 of Homo sapiens | |||
|
2.A.1.19.9 | The osteosclerosis protein, Roct (organic anion transporter 3, Oat3) (Slc22a8) (catalyzes organic anion (uptake):di-carboxylate (efflux) antiport in the basolateral membrane of the renal proximal tubule) (Eraly et al., 2003a,b); transports glutathione and many antiviral agents (Truong et al., 2008). It is a multispecific drug transporter, critical for the renal handling of common drugs (e.g, antibiotics, antivirals, diuretics) and toxins. Probably handles hydroxylated and glucouronidated metabolites, consistent with the "remote sensing and signaling hypothesis" (Wu et al. 2013). It may also handle dietary flavonoids and antioxidants. | Eukaryota |
Metazoa, Chordata | Roct (Oat3) of Mus musculus (O88909) | |||
|
2.A.1.19.10 | The apical proximal tubular kidney/placenta organic anion transporter 4, Oat4 (Slc22a11) (transports estrone sulfate (Km = 1 µM), dehydroepiandrosterone sulfate (Km = 60µM), many anionic drugs, diuretics, bile salts, urate and ochratoxin A). Catalyzes Na+-independent efflux, possibly using glutamate as a counter anion in an exchange reaction, especially in the placenta (Lofthouse et al. 2015). Functions in renal urate reabsorption (Prestin et al. 2014). Chlorine decreases the expression of the gene encoding this transporter (Suman et al. 2023). hOAT4 is mainly expressed in the kidney and placenta, and is essential for the disposition of numerous drugs, toxins, and endogenous substances. It is regulated by insulin-like growth factor and portein kinase B (Yu et al. 2023). FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of methotraxate (MTX), whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells (Bai et al. 2024). | Eukaryota |
Metazoa, Chordata | SLC22A11 (Oat4) of Homo sapiens | |||
|
2.A.1.19.11 | The apical proximal tubular renal urate:anion exchanger, URAT1 (Slc22a12). Catalyzes Na+-independent anion efflux (secretion) and reabsorption (Eraly et al., 2003a,b; Anzai and Endou, 2011; Prestin et al. 2014) Regulated by the PDZK1 protein; Anzai et al., 2004). Also transports orotate, a precursor of pyrimidine biosynthesis (Miura et al., 2011). Mutations in URAT1 cause hereditary renal hypouricemia/gaut. Residues involved in urea and inhibitor binding have been identified (Tan et al. 2016). Mutations can cause renal hypouricemia (RHUC), a heterogeneous genetic disorder that is characterized by decreased serum uric acid concentrations and increased fractional excretion of uric acid (Zhou et al. 2018; Kaynar et al. 2022). Mutation in transmembrane domain 8 of the human urate transporter 1 (residue K393) disrupts uric acid recognition and transport (Lan et al. 2022). Pathogenic variants of SLC22A12 (URAT1) and SLC2A9 (GLUT9) can give rise to renal hypouricemia (Perdomo-Ramirez et al. 2023). Biphenyl carboxylic acid derivatives are potent URAT1 inhibitors (Hou et al. 2023). | Eukaryota |
Metazoa, Chordata | URAT1/SLC22A12 of Homo sapiens | |||
|
2.A.1.19.12 | The high affinity L-carnitine transporter, CT2, present in the luminal membranes of epididymal epithelia and Sertoli cells of the testis (Enomoto et al., 2002b). It also catalyzes uptake of the anticancer polyamine analogue, bleomycin-A5 (Aouida et al. 2010). Carnitine transport and metabolism have been reviewed (Nałęcz and Nałęcz 2017). SLC22A16 (CG6126) transports ergothioneine (Zhang et al. 2021). | Eukaryota |
Metazoa, Chordata | SLC22A16 of Homo sapiens | |||
|
2.A.1.19.13 | The organic cation transporter, Oct1 (transports L-carnitine; expressed in vascular tissues of various organs and at sites of lateral root formation) (Lelandais-Briere et al, 2007). It also transports spermine and other polyamines and is induced by them (Sagor et al. 2016). It protects against the polyamine, cadaverine, which affects root length (Strohm et al. 2015). | Eukaryota |
Viridiplantae, Streptophyta | Oct1 of Arabidopsis thaliana (Q9CAT6) | |||
|
2.A.1.19.14 | Brush border glycosylated urate (Km= 1.2 mM) tranporter, RST. Orthologous to the human URAT1. Inhibited by 50 μM benzbromarone, 1 mM probenecid and 10 mM lactate which may also be transported and trans-stimulate urate uptake. May be orthologous to 2.A.1.19.11 as well (Hosoyamada et al., 2004). Involved in urate absorption across the apical membrane, but probably not the primary route (Eraly et al. 2008; Prestin et al. 2014). | Eukaryota |
Metazoa, Chordata | RST/Slc22a12 of Mus musculus (Q8CFZ5) | |||
|
2.A.1.19.15 | The liver multispecific organic anion transporter, NLT or OAT2. Transports salicylate, KM=90µM, acetylsalicylate, prostaglandin E2, dicarboxylate, p-aminohippurate, etc. (Sekine et al., 1998) | Eukaryota |
Metazoa, Chordata | NLT of Rattus norvegicus (Q63314) | |||
|
2.A.1.19.16 | The organic anion transporter, Oat6 or SLC22a20 of 556 aas and 12 TMSs. Binding and transport rates for 40 anionic substrates have been studied and compared with those for Oat1 (TC# 1.A.1.19.4) (Kaler et al., 2007). Oat6 transports many antiviral agents (Truong et al., 2008). It can bind odorants and is present in the mouse olfactory mucosa; it has been proposed to be an odorant receptor and/or odorant transporter (Wu et al. 2015). Mouse OAT6 is expressed predominantly in olfactory mucosa but not in kidney or brain (Monte et al. 2004). | Eukaryota |
Metazoa, Chordata | Oat6 of Mus musculus (Q80UJ1) | |||
|
2.A.1.19.17 | Kidney organic cation transporter-like 3 ORCTL-3 (OAT10; SLC22A13; Like-3) (Bahn et al., 2008) (transports nicotinate, p-aminohippurate and urate; KM=20-40 mμM) via exchange for lactate). Activated by tumorigeneic mutations in this antitumor gene to promote apoptosis (AbuAli and Grimm 2014). Functions in urate reabsorption (Prestin et al. 2014). Substrate binding and lipid-mediated allostery in the human organic anion transporter 1 have been examined at the atomic-scale (Janaszkiewicz et al. 2023). | Eukaryota |
Metazoa, Chordata | SLC22A13 of Homo sapiens | |||
|
2.A.1.19.18 | Oranic anion transporter, Oat7 (exchanges sulfate conjugates (steroids) and other anions for butyrate) (Shin et al., 2007) | Eukaryota |
Metazoa, Chordata | SLC22A9 of Homo sapiens | |||
|
2.A.1.19.19 | The rat kidney basolateral potential-driven symport carrier, Oct2 (transports tetraethylammonium and many other organic cations) (Sweet and Pritchard 1999). A cysteyl residue critical for substrate binding and transport has been identified (Sturm et al. 2007). Subtype-specific affinity of rat organic cation transporters rOCT1 and rOCT2 for corticosterone depends on three amino acids within the substrate binding region (Gorboulev et al. 2005). | Eukaryota |
Metazoa, Chordata | Oct2 of Rattus norvegicus (Q9R0W2) | |||
|
2.A.1.19.20 | Prostaglandin (PGE2, PGE2α, and PGD(2)) -specific organic anion transporter. Exhibits Na+ -independent and saturable transport. Shows narrow substrate selectivity and high affinity (Shiraya et al., 2010). | Eukaryota |
Metazoa, Chordata | Slc22a22 (OAT-PG) of Mus musculus (Q8R0S9) | |||
|
2.A.1.19.21 | solute carrier family 22, member 24 | Eukaryota |
Metazoa, Chordata | SLC22A24 of Homo sapiens | |||
|
2.A.1.19.22 | solute carrier family 22, member 14, Slc22a14, is crucial for sperm motility and male fertility in mice. It is expressed specifically in male germ cells, and mice lacking the Slc22a14 gene show severe male infertility as well as sperm morphological changes (Maruyama et al. 2016). | Eukaryota |
Metazoa, Chordata | SLC22A14 of Homo sapiens | |||
|
2.A.1.19.23 | solute carrier family 22, member 31 | Eukaryota |
Metazoa, Chordata | SLC22A31 of Homo sapiens | |||
|
2.A.1.19.24 | Solute carrier family 22 member 3 (Extraneuronal monoamine transporter) (EMT) (Organic cation transporter 3) of 556 aas and 12 TMSs. Induction of astrocytic Slc22a3 (EMT) regulates sensory processing through histone serotonylation (Sardar et al. 2023). | Eukaryota |
Metazoa, Chordata | SLC22A3 of Homo sapiens | |||
|
2.A.1.19.25 | Solute carrier family 22 member 7 (liver transporter) (Organic anion transporter 2) (hOAT2), transports cyclic nucleotodes and the anti-viral drug, acyclovir (Dahlin et al. 2013). Expressed mostly in liver, but also in kidney, brain and red blood cells (Sager et al. 2018). slc22 transporter homologs in flies, worms, and humans clarify the phylogeny of organic anion (OATs) and cation (OCTs) transporters (Eraly et al. 2004). | Eukaryota |
Metazoa, Chordata | SLC22A7 of Homo sapiens | |||
|
2.A.1.19.26 | SLC22 OAT ortholog, Multispecific anion transporter, oat-1 (George et al. 1999) | Eukaryota |
Metazoa, Nematoda | oat-1 of Caenorhabditis elegans | |||
|
2.A.1.19.27 | Solute carrier family 22 member 10 (Organic anion transporter 5) | Eukaryota |
Metazoa, Chordata | SLC22A10 of Homo sapiens | |||
|
2.A.1.19.28 | Solute carrier family 22 member 23. The rat orthologue may be inactive (Bennett et al. 2011). Human SLC22A23 is expressed in many tissues including brain (brain organic cation transporter (BOCT2) (Bennett et al. 2011). | Eukaryota |
Metazoa, Chordata | SLC22A23 of Homo sapiens | |||
|
2.A.1.19.29 | Solute carrier family 22 member 1 (Organic cation transporter 1) (hOCT1). May be a primary polyamine uptake porter (Abdulhussein and Wallace 2013). Amino acids in TMS1 confer major functional differences between human and mouse orthologs of the polyspecific membrane transporter, OCT1. Reduced function alleles of OCT1 associate significantly with high LDL cholesterol levels (Yee et al. 2023). | Eukaryota |
Metazoa, Chordata | SLC22A1 of Homo sapiens | |||
|
2.A.1.19.30 | Solute carrier family 22 member 2 (Organic cation transporter 2) (hOCT2). Oct2 is a low affinity high efficiency choline transporter, enriched in synaptic vesicles of cholinergic neurons (Nakata et al. 2013). May also transport peptides and peptide derivatives (Volková et al. 2015). It also transports L-carnitine (Adeva-Andany et al. 2017). OCT2 is a multispecific transporter with cholesterol-dependent allosteric features. The role of cholesterol recognition/interaction amino acid consensus sequences (CRAC and CARC) in the allosteric binding to 1-methyl-4-phenylpyridinium (MPP+) has been reported (Sutter et al. 2021). Comparisons of the inhibitory potential of elacridar and imazalil on metformin uptake with that on MPP uptake revealed substrate-dependent differences in hOCT2 and mOct2 for both inhibitors (Kuehne et al. 2022). | Eukaryota |
Metazoa, Chordata | SLC22A2 or Oct2 of Homo sapiens | |||
|
2.A.1.19.31 | Solute carrier family 22 member 6 (Organic anion transporter 1) (hOAT1) (PAH transporter) (hPAHT) (Renal organic anion transporter 1) (hROAT1), Probably orthologous to 2.A.1.19.4. Functions in anti-oxidant transport, and in urate uptake from the circulation across the basolateral membrane of tubular cells (Prestin et al. 2014). It transports methotrexate (anticancer), acyclovir (antiviral), and adefovir (antiviral) (Nigam 2015). | Eukaryota |
Metazoa, Chordata | SLC22A6 of Homo sapiens | |||
|
2.A.1.19.32 | Solute carrier family 22 member 15 (Fly-like putative transporter 1) (Flipt 1). This system is required for hepatocellular carcinoma proliferation and metastasis (Fang et al. 2021). SLC22A15 (FLIPT1) prefers zwitterionic compounds over cations and anions. Eight zwitterions transported include ergothioneine, carnitine, carnosine, gabapentin, as well as four cations including MPP+ , thiamine and cimetidine. Carnosine was a specific substrate of SLC22A15 among the transporters in the SLC22A family. SLC22A15 transport was sodium-dependent and exhibited higher Km values for ergothioneine, carnitine, and carnosine compared to previously identified transporters for these ligands (Yee et al. 2020). Many carnitine derivatives (i.e., (R)-3-hydrixybutryl carnitine, hexanoyl carnitine and glutaryl carnitine amoung others) are also transported. In mice, SLC22a15 transports carnitine derivatives, a range of anti-oxidants, signalling molecules, hormones, neurotransmitters, nutrientYee et al. 2020). Many carnitine derivatives (i.e., (R)-3-hydrixybutryl carnitine, hexanoyl carnitine and glutaryl carnitine amoung others) are also transported. In mice, SLC22a15 transports carnitine derivatives, a range of anti-oxidants, signalling molecules, hormones, neurotransmitters, nutrients and lipid metabolites (P Zhang & S Nigam, personal communication). | Eukaryota |
Metazoa, Chordata | SLC22A15 of Homo sapiens | |||
|
2.A.1.19.33 | Solute carrier family 22 member 25 (Organic anion transporter UST6). Expressed exclusively in liver in both embryo and adult (Eraly et al. 2004). It may take up a nucleobase-containing compound (Meixner et al. 2020). | Eukaryota |
Metazoa, Chordata | SLC22A25 of Homo sapiens | |||
|
2.A.1.19.34 | Multispecific drug transporter, solute carrier family 22 member 8 (Organic anion transporter 3) (hOAT3). Both OAT1 and OAT3 of humans are inhibited by caffeic acid (Ki ~ 17 μM) (Uwai et al. 2011; Wu et al. 2013). It is the principal uptake system for steviol glucuronide (SVG), the major metabolite derived from steviol, the aglycone of stevioside and rebaudioside A (Wang et al. 2015). Also functions in urate uptake from the circulation across the basolateral membrane of renal tubular cells (Prestin et al. 2014). Inhibition of the proteasome, but not the lysosome, upregulates organic anion transporter 3 (Fan et al. 2022). See also 2.A.1.19.9. | Eukaryota |
Metazoa, Chordata | SLC22A8 of Homo sapiens | |||
|
2.A.1.19.35 | Solute carrier family 22 member 20 (Organic anion transporter 6; OAT6) of 555 aas and 12 probable TMSs. This protein is an apparent anionic odorant transporter in the olfactory epithelium of mice (Monte et al. 2004; Kaler et al. 2006). | Eukaryota |
Metazoa, Chordata | SLC22A20 of Homo sapiens | |||
|
2.A.1.19.36 | Organic cation transporter-like protein, OrcT, of 548 aas and 12 TMSs (Taylor et al. 1997). | Eukaryota |
Metazoa, Arthropoda | OrcT of Drosophila melanogaster | |||
|
2.A.1.19.37 | Organic cation transporter 1 (CeOCT1) of 568 aas and 12 TMSs. It transports tetraethylammonium ions and has broad substrate specificity (Wu et al. 1999). | Eukaryota |
Metazoa, Nematoda | Oct-1 of Caenorhabditis elegans | |||
|
2.A.1.19.38 | Uncharacterized MFS-type transporter PB1E7.08c | Eukaryota |
Fungi, Ascomycota | SPAPB1E7.08c of Schizosaccharomyces pombe | |||
|
2.A.1.19.39 | Organic cation/carnitine transporter 6 (AtOCT6) | Eukaryota |
Viridiplantae, Streptophyta | OCT6 of Arabidopsis thaliana | |||
|
2.A.1.19.40 | Organic anion transporter, Oat9. A splice variant with 443 aas and 8 TMSs (Oa9S) was reported to transport L-carnitine (3 μM), cimetidine (16 μM) and salicylic acid (175 μM), but the full length protein of 551 aas and 12 TMSs (Oat9L) was reported to be inactive (Tsuchida et al. 2010). | Eukaryota |
Metazoa, Chordata | Oat9 of Mus musculus | |||
|
2.A.1.19.41 | Organocation transporter, OCTN3. Identified only in mouse; mediates carnitine transport (Pochini et al. 2013). 81% identical to 2.A.1.19.3. Also called SLC22a21 and SLC22a9. | Eukaryota |
Metazoa, Chordata | OctN3 of Mus musculus | |||
|
2.A.1.19.42 | Slc22 homologue of 580 aas. | Eukaryota |
Viridiplantae, Chlorophyta | Slc19 homologue of Ostreococcus tauri | |||
|
2.A.1.19.43 | Organocation transporter, Oct4 of 526 aas and 12 TMSs. It is induced under drought conditioins. | Eukaryota |
Viridiplantae, Streptophyta | Oct4 of Arabidopsis thaliana (Mouse-ear cress) | |||
|
2.A.1.19.44 | Uncharacterized protein of 556 aas | Eukaryota |
Viridiplantae, Chlorophyta | UP of Chlorella variabilis (Green alga) | |||
|
2.A.1.19.45 | MFS transporter of 569 aas | Eukaryota |
Ciliophora | MFS transporter of Tetrahymena thermophila | |||
|
2.A.1.19.46 | MFS transporter of 593 aas | Eukaryota |
Ciliophora | MFS porter of Oxytricha trifallax | |||
|
2.A.1.19.47 | MFS porter of 691 aas | Eukaryota |
Viridiplantae, Chlorophyta | MFS porter of Volvox carteri (Green alga) | |||
|
2.A.1.19.48 | Fungal MFS homologue of 520 aas | Eukaryota |
Fungi, Ascomycota | UP of Aspergillus terreus | |||
|
2.A.1.19.49 | Putative glucose transporter 1 (Gluct1) of 569 aas and 12 TMSs. Constitutively synthesized in many tissues. Serves as the receptor of white spot syndrom virus (WSSV) (Huang et al. 2012). | Eukaryota |
Metazoa, Arthropoda | Gluct1 of Litopenaeus vannamei (Whiteleg shrimp) (Penaeus vannamei) | |||
|
2.A.1.19.50 | Uncharacterized solute carrier family 22 member 15-like of 543 aas and 12 TMSs (Posavi et al. 2020). | Eukaryota |
Metazoa, Arthropoda | UP of Eurytemora affinis | |||
| 2.A.1.20: The Sugar Efflux Transporter (SET) Family | |||||||
|
2.A.1.20.1 | Sugar efflux transporter A, SetA. Exports lactose, glucose, aromatic glucosides and galactosides, cellobiose, maltose, α-methylglucoside and isopropyl β-thiogalactosides (IPTG); amino-glycosides, streptomycin and kanamycin are weakly expelled (Liu et al. 1999). Regulated by SgrR (a transcriptional regulator of sgrS) and SgrS (a small RNA that represses trascription of setA). These two regulatory genes are upstream of the setA gene. Uses a pmf-dependent mechanism of energization. Induced in response to glucose-phosphate stress which occurs when a sugar phosphates accumulate in the cytoplam (Sun and Vanderpool 2011). Overexpression of the gene for SetA allows export of Lacto-N-triose (LNT II) and lacto-N-tetraose (LNT), human milk oligosaccharides (Sugita and Koketsu 2022). | Bacteria |
Pseudomonadota | SetA (YabM) of E. coli | |||
|
2.A.1.20.2 | Sugar efflux system, SetB, for lactose and glucose, but not IPTG or galactose (Liu et al. 1999). Overexpression of the gene for SetB allows export of Lacto-N-triose (LNT II) and lacto-N-tetraose (LNT), human milk oligosaccharides (Sugita and Koketsu 2022). | Bacteria |
Pseudomonadota | SetB (YeiO) of E. coli | |||
|
2.A.1.20.3 | Arabinose (but not xylose) exporter, SetC (Koita and Rao 2012). | Bacteria |
Pseudomonadota | SetC (YicK) of E. coli | |||
|
2.A.1.20.4 | Efflux system for arabinose and IPTG (>>lactose), SotA | Bacteria |
Pseudomonadota | SotA of Erwinia chrysanthemi | |||
| 2.A.1.21: The Drug:H+ Antiporter-3 (12 Spanner) (DHA3) Family | |||||||
|
2.A.1.21.1 | The macrolide (erythromycin; oleandomycin; azithromycin; telithromycin) efflux pump, MefA, of 405 aas and 12 TMSs (Cantón et al. 2005; Bley et al. 2011). Iannelli et al. 2018 suggested that MefA can function with an ATPase, MsrD (TC# 3.A.1.121.6), and therefore function as an ABC drug exporter. However, the data presented seem inconsistent with this suggestion. The two genes encoding these two proteins are adjacent to each other, suggesting that they may function together (Iannelli et al. 2018). Predicted transmembrane proteins with homology to MefA do not complement a mefA deletion in the MefA-MsrD macrolide efflux system in Streptococcus pneumoniae (Fox et al. 2021). Note: MsrD is an ATPase of the ABC superfamily, so it can not be certain that MefA and MsrD function together. Coupling of an MFS carrier with an ABC-type energizer is very rare, maybe non-existent. | Bacteria |
Bacillota | MefA of Streptococcus pyogenes | |||
|
2.A.1.21.2 | The multidrug (erythromycin, tetracycline, puromycin, bleomycin) resistance protein, Cmr | Bacteria |
Actinomycetota | Cmr of Corynebacterium glutamicum | |||
|
2.A.1.21.3 | The tetracycline resistance determinant, TetV | Bacteria |
Actinomycetota | TetV of Mycobacterium smegmatis | |||
|
2.A.1.21.4 | Multidrug resistance efflux pump, Tap | Bacteria |
Actinomycetota | Tap of Mycobacterium fortuitum | |||
|
2.A.1.21.5 | The putative bacilysin exporter, BacE | Bacteria |
Bacillota | BacE of Bacillus subtilis (P39642) | |||
|
2.A.1.21.6 | The tetracycline resistance efflux pump, TetA(P) (Bannam et al., 2004) (21% identity (e-07) with 2.A.1.21.5 and 22% identity (2xe-7) with 2.A.1.2.10). It may be the link between DHA1 and DHA3. | Bacteria |
Bacillota | TetA (P) of Clostridium perfringens (Q46305) | |||
|
2.A.1.21.7 | The Staphyloferrin A (siderophore) exporter, NWMN-2081 (Beasley et al. 2009). Independently suggested to be a macrolide exporter (Marklevitz and Harris 2016). | Bacteria |
Bacillota | NWMN-2081 of Staphylococcus aureus (A6QJ21) | |||
|
2.A.1.21.8 | The putative macrolide exporter, TIGR00900 (most similar to 2.A.1.21.1). | Bacteria |
Bacillota | TIGR00900 of Bacillus clausii (Q5WAS7) | |||
|
2.A.1.21.9 | MFS carrier of unknown function | Archaea |
Candidatus Thermoplasmatota | MFS carrier of Thermoplasma acidophilum (Q9HLP1) | |||
|
2.A.1.21.10 | MFS porter | Archaea |
Thermoproteota | MFS porter of Sulfolobus islandicus (D2PCQ8) | |||
|
2.A.1.21.11 | MFS porter | Bacteria |
Actinomycetota | MFS porter of Stackebrandtia nassauensis (D3Q871) | |||
|
2.A.1.21.12 | Multidrug-efflux transporter, Rv1258c/MT1297, of 419 aas and 12 TMSs. Both Rv1634 and Rv1258c are believed to play major roles in drug resistance by altering the protein pump that is required to remove the active drugs from the bacterial cell (Panja et al. 2019). | Bacteria |
Actinomycetota | Rv1258c of Mycobacterium tuberculosis | |||
|
2.A.1.21.13 | Uncharacterized MFS-type transporter yjbB | Bacteria |
Bacillota | YjbB of Bacillus subtilis | |||
|
2.A.1.21.14 | Uncharacterized MFS-type transporter Mb0038c | Bacteria |
Actinomycetota | Mb0038c of Mycobacterium bovis | |||
|
2.A.1.21.15 | MFS Homologue | Bacteria |
Actinomycetota | MFS homologue of Streptomyces coelicolor (Q9X9Y0) | |||
|
2.A.1.21.16 | MFS Homologue | Bacteria |
Actinomycetota | MFS homologue of Streptomyces coelicolor (Q9X8T4) | |||
|
2.A.1.21.17 | Bacteria |
Bacillota | YxaM of Bacillus subtilis | ||||
|
2.A.1.21.18 | Uncharacterized protein | Bacteria |
Actinomycetota | Uncharacterized protein of Streptomyces coelicolor | |||
|
2.A.1.21.19 | Bacteria |
Actinomycetota | UMF of Streptomyces coelicolor | ||||
|
2.A.1.21.20 | Bacteria |
Pseudomonadota | UMF of Pseudomonas syringae | ||||
|
2.A.1.21.21 | Bacteria |
Actinomycetota | UMF of Saccharomonospora marina | ||||
|
2.A.1.21.22 | Macrolide efflux pump, MefE (Mef; MefA) of 405 aas. Induced by erythromycin and the antimicrobial peptide, LL-37 (Zähner et al. 2010). May act in conjunction with Mel (Q93QE4), an ABC-type ATPase that is encoded in the same operon with the mefA gene (Ambrose et al. 2005). | Bacteria |
Bacillota | MefE of Streptococcus pneumoniae | |||
|
2.A.1.21.23 | Uncharacterized MFS permease of 433 aas and 12 TMSs | Bacteria |
Deinococcota | UP of Deinococcus geothermalis | |||
|
2.A.1.21.24 | MFS_1 protein of 476 aas and 12 TMSs. | Bacteria |
Actinomycetota | MFS_1 of Bifidobacterium longum | |||
| 2.A.1.22: The Vesicular Neurotransmitter Transporter (VNT) Family (Related to the SP Family (TC #2.1.1)) | |||||||
|
2.A.1.22.1 | Synaptic vesicle glycoprotein neurotransmitter (e.g., dopamine) transporter, SV2A or SLC22B1. This protein localizes to neurotransmitter-containing vesicles and has a nucleotide binding site (Yao and Bajjalieh 2009). The SV2 family is comprised of three paralogues: SV2A, SV2B, and SV2C. They are present in secretory vesicles, including synaptic vesicles, and are critical to neurotransmission. Structural and functional studies suggest that SV2 proteins may play several roles to promote proper vesicular function. Among these roles are their potential to stabilize the transmitter content of vesicles, to maintain and orient the releasable pool of vesicles, and to regulate vesicular calcium sensitivity to ensure efficient, coordinated release of the transmitter (Stout et al. 2019). SV2A plays a role in neuronal excitability and as such is the specific target for the antiepileptic drug levetiracetam as well as seletracetam and brivaracetam. SV2 proteins also act as the target by which potent neurotoxins, particularly botulinum, gain access to neurons and exert their toxicity. Both SV2B and SV2C are increasingly implicated in diseases such as Alzheimer's disease and Parkinson's disease. Despite decades of intensive research, their exact functions were elusive in 2019 (Stout et al. 2019), but the systems may transport galactose.The human (Q70J3) and rat orthologs are 99% identical. The structure, function, and disease relevance of GP2 (SV2) transporters have been reviewed (Stout et al. 2019). More than one percent of people have epilepsy worldwide. Levetiracetam (LEV) is a successful new-generation antiepileptic drug (AED), and its derivative, brivaracetam (BRV), shows improved efficacy. Synaptic vesicle glycoprotein 2a (SV2A), a membrane transporter in the synaptic vesicles (SVs), has been identified as a target of LEV and BRV. SV2A also serves as a receptor for botulinum neurotoxin (BoNT) (Yamagata et al. 2024). The structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A have been ellucidated (Yamagata et al. 2024). | Eukaryota |
Metazoa, Chordata | SV2 of Rattus norvegicus | |||
|
2.A.1.22.2 | Synaptic vesicle glycoprotein 2B of 556 aas | Eukaryota |
Metazoa, Arthropoda | Glycoprotein 2B of Tribolium castaneum | |||
|
2.A.1.22.3 | AgaP of 537 aas | Eukaryota |
Metazoa, Arthropoda | AgaP of Anopheles gambiae | |||
|
2.A.1.22.4 | Uncharacterized protein of 537 aas | Eukaryota |
Metazoa, Arthropoda | UP of Acyrthosiphon pisum | |||
|
2.A.1.22.5 | Uncharacterized protein of 561 aas | Eukaryota |
Metazoa, Placozoa | UP of Trichoplax adhaerens (Trichoplax reptans) | |||
|
2.A.1.22.6 | Synaptic vesicle 2C, SV2C or SLC22B3, of 727 aas and 11 TMSs. Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by selectively cleaving core components of the vesicular fusion machinery. The synaptic vesicle proteins Synaptotagmin-I and -II act as receptors for BoNT/B and BoNT/G. Mahrhold et al. 2006 showed that BoNT/A also interacts with a synaptic vesicle protein, the synaptic vesicle glycoprotein 2C (SV2C), but not with the homologous proteins SV2A and SV2B. Binding of BoNT/A occurs at the membrane juxtaposed region preceding transmembrane domain 8. A peptide comprising the intravesicular domain between transmembrane domains 7 and 8 specifically reduces the neurotoxicity of BoNT/A at phrenic nerve preparations, demonstrating the physiological relevance of this interaction (Mahrhold et al. 2006). The interactions of SV2C with BoNT have been reviewed (Li et al. 2020). SV2C is implicated in diseases such as Alzheimer's disease and Parkinson's disease (Stout et al. 2019). It seems to play roles in vesicle trafficking, exocytosis and neurotransmission (Hu et al. 2017). | Eukaryota |
Metazoa, Chordata | SV2C of Homo sapiens | |||
|
2.A.1.22.7 | Synaptic vesicle glycoprotein 2B, SV2B or SLC22B2, of 683 aas and 12 TMSs in a 6 + 1 + 5 TMS arrangement. SV2B, ephrin B1 and the receptors of angiotensin II are expressed in the podocyte, and their expressions were altered in anti-nephrin antibody-induced nephropathy. These proteins may be involved in the development of proteinuria (Kawachi et al. 2009). SV2B and SV2C may be involved in the pathogenesis of epilepsy as well as other neurodegenerative diseases (Löscher et al. 2016) such as Alzheimer's disease and Parkinson's disease (Stout et al. 2019). Defective lysosomal acidification may provide a prognostic marker and therapeutic target for neurodegenerative diseases (Lo and Zeng 2023). | Eukaryota |
Metazoa, Chordata | SV2B of Homo sapiens | |||
| 2.A.1.23: The Conjugated Bile Salt Transporter (BST) Family | |||||||
|
2.A.1.23.1 | Conjugated bile salt:H+ symporter, CbsT1 of 452 aas and 12 TMSs. Its gene is in an operon with those for CbsT2 and CbsH, a conjugated bile salt hydrolase, and such operons are common amoung the lactobacilli including Lactobacillus acidophilus (Elkins et al. 2001). | Bacteria |
Bacillota | CbsT1 of Lactobacillus johnsonii 100-100 | |||
|
2.A.1.23.2 | Taurocholate:cholate antiporter, CbsT2 of 451 aas and 12 TMSs (Elkins and Savage 2003). | Bacteria |
Bacillota | CbsT2 of Lactobacillus johnsonii 100-100 (AAC34380) | |||
| 2.A.1.24: The Vacuolar Basic Amino Acid Transporter (VBAAT) Family | |||||||
|
2.A.1.24.1 | 58.8 KDa protein, YCL038c | Eukaryota |
Fungi, Ascomycota | YCL038c of Saccharomyces cerevisiae | |||
|
2.A.1.24.2 | Vacuolar amino acid (Arg, Lys, His) transporter, Atg22 (Autophagy-related protein-22) (Sugimoto et al. 2011). | Eukaryota |
Fungi, Ascomycota | Atg22 of Schizosaccharomyces pombe (Q09812) | |||
|
2.A.1.24.3 | MFS permease | Bacteria |
Chloroflexota | MFS permease of Chloroflexus aurantiacus (A9WGR7) | |||
|
2.A.1.24.4 | MFS permease | Bacteria |
Myxococcota | MFS permease of Myxococcus xanthus (Q1CWQ3) | |||
|
2.A.1.24.5 | MFS permease | Bacteria |
Actinomycetota | MFS permease of Micrococcus luteus (Micrococcus lysodeikticus) | |||
|
2.A.1.24.6 | MFS porter of 474 aas | Bacteria |
Pseudomonadota | MFS porter of Hyphomonas neptunium | |||
|
2.A.1.24.7 | Uncharacterized MFS carrier protein of 524 aas. | Eukaryota |
Evosea | UP of Entamoeba histolytica | |||
| 2.A.1.25: The Peptide/Acetyl-Coenzyme A/Drug Transporter (PAT) Family | |||||||
|
2.A.1.25.1 | The endoplasmic reticular/Golgi acetyl-CoA:CoA antiporter 1, ACATN/ACATN1 (SLC33A1). Allows acetylation of sialic acid residues in gangliosides and lysine residues in membrane proteins. It is associated with neurodegenerative disorders such as sporadic amyotrophic laterial sclerosis (ALS) and Spastic Paraplegia 42, and it is essential for motor neuron viability (Hirabayashi et al. 2013). Abnormal concentrations of acetylated amino acids in cerebrospinal fluid are observed in acetyl-CoA transporter deficiency (Šikić et al. 2022). | Eukaryota |
Metazoa, Chordata | SLC33A1 of Homo sapiens | |||
|
2.A.1.25.2 | Cell wall degradation product (peptides and glycopeptides including N-acetylglucosaminyl β-1,4-anhydro-N-acetyl-muramyl-tri or tetra-peptide) as well as penicillin derivative uptake porter, AmpG (Cheng and Park 2002). The AmpG permease is also required for AmpC beta-lactamase induction (Chahboune et al. 2005; Park and Uehara 2008). AmpG mediates a dynamic relationship between serine beta-lactamase induction and biofilm-formation (Mallik et al. 2018). | Bacteria |
Pseudomonadota | AmpG of E. coli (P0AE16) | |||
|
2.A.1.25.3 | The AmpG peptidoglycan degradation product uptake porter is part of the peptidoglycan recycling pathway (Garcia and Dillard, 2008). It also plays a role in peptidoglycan remodeling, recycling, and toxic fragment release as well as pathogenesis (Schaub and Dillard 2019). | Bacteria |
Pseudomonadota | AmpG of Neisseria gonorrhoeae (Q5F6G0) | |||
|
2.A.1.25.4 | Putative peptide/acetyl-CoA transporter of 560 aas and 12 TMSs. | Eukaryota |
Fungi, Ascomycota | Uncharacterized protein of Saccharomyces cerevisiae (Baker's yeast) | |||
|
2.A.1.25.5 | Transporter of meuropeptides, N-acetylglucosamine anhydrous N-acetylmuramyl peptides, AmpG (Kong et al. 2010). Necessary for induction of ampC, β-lactamase, and ampicillin resistance (Zhang et al. 2010). Amino acyl residues essential for proper mRNA production and for catalytic activity have been identified (Li et al. 2016). | Bacteria |
Pseudomonadota | AmpG of Pseudomonas aeruginosa | |||
|
2.A.1.25.6 | Uptake transporter, AmpG, of 433 aas and 12 TMSs, specific for muropeptides, fragments of the peptidoglycan cell walls of bacteria (Ruscitto et al. 2017). | Bacteria |
Bacteroidota | AmpG of Tannerella forsythia | |||
|
2.A.1.25.7 | Putative acetyl-CoA:CoA antiporter, ACT or AT1, of 590 aas and 12 or 13 TMSs in a 6 or 7 + 6 TMS arrangement (Wunderlich 2022). | Eukaryota |
Apicomplexa | ACT lf Plasmodium falciparum | |||
| 2.A.1.26: The Drug:H+ Antiporter-4 (DHA4) Family Family | |||||||
|
2.A.1.26.1 | 41.4 KDa Protein, YcaD. It may export ectoine and hydroxyectoine (Czech et al. 2022). | Bacteria |
Pseudomonadota | YcaD of E. coli | |||
|
2.A.1.26.2 | MFS porter, YfkF; possible drug exporter | Bacteria |
Bacillota | YfkF of Bacillus subtilis (O34929) | |||
|
2.A.1.26.3 | Multidrug resistance efflux porter, BC3310 of 396 aas and 12 TMSs. Exports ethidium bromide, sodium dodecyl sulfate and silver nitrate. D105 in TMS4 is essential for activity (Kroeger et al. 2015). | Bacteria |
Bacillota | BC3310 of Bacillus cereus | |||
| 2.A.1.27: The Phenyl Propionate Permease (PPP) Family | |||||||
|
2.A.1.27.1 | The phenylpropionate porter, HcaT (YfhS) (Díaz et al. 1998). | Bacteria |
Pseudomonadota | HcaT (YfhS) of E. coli | |||
|
2.A.1.27.2 | MFS permease of 406 aas and 12 TMSs. | Bacteria |
Pseudomonadota | MFS porter of Methylobacterium nodulans | |||
|
2.A.1.27.3 | Putative metabolite transporter of 393 aas and 12 TMSs. | Bacteria |
Campylobacterota | Porter of Sulfurimonas denitrificans (Thiomicrospira denitrificans | |||
| 2.A.1.28: The Feline Leukemia Virus Subgroup C Receptor (FLVCR)/Heme Importer Family | |||||||
|
2.A.1.28.1 | Cell surface receptor (C-receptor) for anemia-inducing feline leukemia virus subgroup C (FLCVR, Slc49A1 or Mfsd7d) of 555 aas and 12 TMSs. It may function in choline transport (Kenny et al. 2023) or haem export in haemopoietic cells (Latunde-Dada et al., 2006; Khan and Quigley, 2011) and may cause Diamond-Blackfan anemia when defective (Keel et al., 2008). Mutations of FLVCR1 in posterior column ataxia and retinitis pigmentosa result in the loss of heme export activity (Yanatori et al., 2012). Heme accumulation causes toxicity (Khan and Quigley 2018). FLVCR1 is co-induced upon iron insufficiency in the placenta with the LDL receptor-related protein 1 (LRP1) heme receptor, and these two proteins may be important for neonatal iron status (Cao et al. 2014). FLVCR1 is required for erythroid and αβ-, CD4 and CD8 T- cell development (Philip et al. 2015). A splice-site variant of FLVCR1 produces retinitis pigmentosa without posterior column ataxia (Yusuf et al. 2018). Protocols suitable for purification of FLVCR1a, antibody generation and structural characterization of the transporter have been reported (Chiabrando et al. 2020). FLVCR1-related disease is a rare cause of retinitis pigmentosa and hereditary sensory autonomic neuropathy (Grudzinska Pechhacker et al. 2020). More recently, integrative genetic analyses identified FLVCR1 as a plasma-membrane choline transporter in mammals (Kenny et al. 2023). Heme allocation in eukaryotic cells relies on mitochondrial heme export through FLVCR1b to cytosolic GAPDH (Jayaram et al. 2024). | Eukaryota |
Metazoa, Chordata | C-receptor of Homo sapiens | |||
|
2.A.1.28.2 | The MFS-Domain7 protein of 516 aas and 12 TMSs. The MFS-D7 mRNA is expressed in many human tissues, especially in lungs and testis, but its transport substrate is not known (Khan and Quigley 2018). | Eukaryota |
Metazoa, Chordata | MFSD7 of Mus musculus | |||
|
2.A.1.28.3 | Unknown major facilitator of 407 aas and 12 TMSs. | Bacteria |
Actinomycetota | UMF of Coriobacterium glomerans (F2NBU7) | |||
|
2.A.1.28.4 | The Fowler syndrome-associated protein, feline leukemia virus subgroup C receptor-related protein 2, FLVCR2, or SLC49A2, is probably a heme importer (Duffy et al., 2010). Mutations of SLC49A2 are observed in Fowler syndrome, a rare proliferative vascular disorder of the brain (Khan and Quigley 2018). | Eukaryota |
Metazoa, Chordata | FLVCR2 of Homo sapiens (Q9UPI3) | |||
|
2.A.1.28.5 | MFS porter of 401 aas and 12 TMSs. | Bacteria |
Spirochaetota | MFS porter of Leptospira biflexa (B0SL69) | |||
|
2.A.1.28.6 | Electrogenic DIRC2 (Disrupted in renal carcinoma 2) or SLC49A4. It is glycosylated and proteolytically processed (Savalas et al., 2011)) and is targeted to lysosomes via an N-terminal dileueine motif. It is implicated in hereditary renal carcinomas (Khan and Quigley 2018). DIRC2 is an electrogenic lysosomal metabolite transporter which is subjected to and presumably modulated by limited proteolytic processing (Savalas et al. 2011). | Eukaryota |
Metazoa, Chordata | DIRC2 of Homo sapiens (Q96SL1) | |||
|
2.A.1.28.7 | Feline leukemia virus subgroup C receptor-related protein 1 | Eukaryota |
Metazoa, Chordata | FLVCR1 of Felis catus | |||
|
2.A.1.28.8 | MFSD7, FLVCR2 or SLC49A3 of 560 aas and 12 TMSs. It is the feline leukemia virus subgroup C receptor-2 (FLVCR2), a member of the SLC49 family of four paralogous genes in humans (Khan and Quigley 2018). It is a cell surface heme transporter, essential for erythropoiesis and systemic iron homeostasis. Mutations of SLC49A2, encoding FLVCR1, are noted in patients with Fowler syndrome (Khan and Quigley 2018). FLVCR2 is 30% identical to FLVCR1 (TC# 2.A.1.28.1). | Eukaryota |
Metazoa, Chordata | FLCR2 of Homo sapiens | |||
| 2.A.1.29: The Potential Heme Import (HemeI) Family | |||||||
|
2.A.1.29.1 | Archaeal open reading frame | Archaea |
Euryarchaeota | Orf of Archaeoglobus fulgidus | |||
|
2.A.1.29.2 | Archaeal open reading frame | Archaea |
Thermoproteota | Orf of Aeropyrum pernix | |||
|
2.A.1.29.3 | Bacterial unknown major facilitator | Bacteria |
Actinomycetota | UMF3 member of Frankia sp. Eul1c (E3J3E7) | |||
| 2.A.1.30: The Putative Abietane Diterpenoid Transporter (ADT) Family | |||||||
|
2.A.1.30.1 | Putative abietane uptake permease (in a gene cluster for degradation of abietane diterpenoids), DitE, of 547 aas and 12 TMSs (Martin and Mohn 2000). Abietane diterpenoids are defense compounds synthesized by trees that are abundant in natural environments and occur as significant pollutants from pulp and paper production (Smith et al. 2007). | Bacteria |
Pseudomonadota | DitE of Pseudomonas abietaniphila BKME-9 | |||
|
2.A.1.30.2 | Uncharacterized MFS transporter of 410 aas and 12 TMSs. | Bacteria |
Actinomycetota | MFS porter of Actinomadura macra | |||
|
2.A.1.30.3 | Enterobactin exporter, EntS (gene, tetv1) of 549 aas and 12 TMSs. | Bacteria |
Pseudomonadota | EntS of Stenotrophomonas maltophilia | |||
| 2.A.1.31: The Nickel Resistance (Nre) Family | |||||||
|
2.A.1.31.1 | The Ni2+ efflux pump, NreB (Ni2+ inductible) | Bacteria |
Pseudomonadota | NreB of Achromobacter xylosoxidans plasmid pTOM | |||
|
2.A.1.31.2 | The Ni2+ resistance protein, NrsD | Bacteria |
Cyanobacteriota | NrsD of Synechocystis PCC6803 | |||
|
2.A.1.31.3 | The unknown porter, YfiS | Bacteria |
Bacillota | YfiS of Bacillus subtilis (O31561) | |||
|
2.A.1.31.4 | Kurstakin/surfactin exporter of 417 aas (in B. subtilis) (Li et al. 2015). This protein is an orthologue of the B. subtilis protein (Li et al. 2015). | Bacteria |
Bacillota | KrsE of Bacillus cereus | |||
|
2.A.1.31.5 | Uncharacterized MFS porter of 455 aas | Eukaryota |
Viridiplantae, Chlorophyta | UP of Chlamydomonas reinhardtii (Chlamydomonas smithii) | |||
|
2.A.1.31.6 | Uncharacterized MFS porter (residiues 1 - 450) with hydrophilic C-terminal protein kinase domain. The protein is of 858 aas. | Eukaryota |
Viridiplantae, Chlorophyta | UP of Chlamydomonas reinhardtii (Chlamydomonas smithii) | |||
|
2.A.1.31.7 | Putative bacilysin exporter, BacE, of 484 aas and10 - 11 TM | Archaea |
Candidatus Heimdallarchaeota | BacE of Candidatus Heimdallarchaeota archaeon AB_125 | |||
|
2.A.1.31.8 | Nickel resistance membrane nickel efflux protein NirA of 432 aas and 12 TMSs. This protein is 99.7% identical to a trunkated homolog from Klebsiella oxytoca (Park et al. 2008). | Bacteria |
Pseudomonadota | NirA of Enterobacter cloacae | |||
| 2.A.1.32: The Putative Aromatic Compound/Drug Exporter (ACDE) Family | |||||||
|
2.A.1.32.1 | Putative aromatic compound/drug exporter. Enhances expression of the sigma X gene that functions to modify the cell envelope (Turner and Helmann, 2000). yitG is reported to be a mutator gene that inhibits transition base substitutions (Sasaki and Kurusu, 2004). | Bacteria |
Bacillota | YitG of Bacillus subtilis | |||
|
2.A.1.32.2 | Bacillibactin exporter, YmfE (199aas; 6TMSs) (Miethke et al., 2008) (resembles the 2nd half of YitG of B. subtilis (2.A.1.32.1). The sequence provided under acc# O31763 is only a fragment of the full length gene. | Bacteria |
Bacillota | YmfE of Bacillus subtilis (O31763) | |||
|
2.A.1.32.3 | Putative copper/multidrug efflux protein, YfmO. The yfmPO operon is autoregulated by the MerR homologue, YfmP (a repressor). The copZA operon encodes CopA, a copper ATPase (TC# 3.A.3.5.18) which is induced by a copper dependent mechanism. Since a yfmP null mutant had poor copZA induction but elevated levels of the YfmO efflux pump, YfmO could catalyze copper efflux and be responsible for reduced copZA induction. Consistent with this model, a yfmP yfmO double mutant showed normal induction by copper (Gaballa et al. 2003). | Bacteria |
Bacillota | YfmO of Bacillus subtilis | |||
| 2.A.1.33: The Putative YqgE Transporter (YqgE) Family | |||||||
These proteins are most closely related to TC#s 2.A.1.21 and 2.A.1.46, and therefore may be MDR exporters. | |||||||
|
2.A.1.33.1 | MFS homologue, YqgE. It is cotranscribed with ftsI, encoding the peptidoglycan transpeptidase that crosslinks peptidoglycan strands, releasing free D-alanine. Possibly YqgE is a D-alanine uptake porter. Its expression causes a decrease in the amount of sigma W synthesis, the sigma factor for genes involved in detoxification and antimicrobial synthesis (Turner and Helmann 2000). | Bacteria |
Bacillota | YqgE of Bacillus subtilis (P54487) | |||
|
2.A.1.33.2 | YqgE homologue | Bacteria |
Bacteroidota | YqgE homologue of Bacteroides ovatus (A7LYG9) | |||
|
2.A.1.33.3 | YqgE homologue (encoded near an α-glucuronidase; GH31 family; divergently transcribed). Therefore could be an uptake system for glucouronides. | Archaea |
Thermoproteota | YqgE homologue of Sulfolobus tokodaii (Q96XI6) | |||
|
2.A.1.33.4 | Uncharacterized protein of 385 aas and 12 TMSs. | Bacteria |
Candidatus Beckwithbacteria | UP of Candidatus Beckwithbacteria bacterium | |||
| 2.A.1.34: The Sensor Kinase-MFS Fusion (SK-MFS) Family | |||||||
|
2.A.1.34.1 | Sensor kinase (N-terminal 400 residues)/MFS fusion protein. The N-terminal domain resembles the sensor kinase of 414 aas of Anaeromyxobacter sp. KJ (ACG71775). The C-terminal MFS domain most resembles those of TC family 2.A.1.2 (DHA1). | Bacteria |
Pseudomonadota | Fusion protein of Bordetella pertussis (Q7VWI9) | |||
|
2.A.1.34.2 | MFS carrier with N-terminal hydrophilic domain with 3 putative TMSs of about 2880 aas. The protein is of 676 aas with 15 TMSs. | Bacteria |
Pseudomonadota | MFS permease fusion protein of Fodinicurvata fenggangensis | |||
|
2.A.1.34.3 | MFS carrier of 526 aas and an N-terminal hydrophilic domain with 1 TMS. | Bacteria |
Pseudomonadota | MFS carrier fusion protein of Herbaspirillum huttiense | |||
| 2.A.1.35: The Fosmidomycin Resistance (Fsr) Family | |||||||
|
2.A.1.35.1 | The fosmidomycin resistance (Fsr) protein (confers fosmidomycin, trimethoprim and carbonylcyanide m-chlorophenylhydrazone (CCCP) resistance) (Fujisaki et al. 1996). | Bacteria |
Pseudomonadota | Fsr of E. coli | |||
|
2.A.1.35.2 | The cationic microbial peptide resistance (RosA) protein | Bacteria |
Pseudomonadota | RosA of Yersinia enterocolitica | |||
|
2.A.1.35.3 | MFS transporter of 388 aas and 12 TMSs | Bacteria |
Bacillota | MFS porter of Sulfobacillus acidophilus | |||
| 2.A.1.36: The Acriflavin-sensitivity (YnfM) Family | |||||||
|
2.A.1.36.1 | The acriflavin-sensitivity protein, YnfM (increases sensitivity to acriflavin specifically). Also exports arabinose but not xylose (Koita and Rao 2012). | Bacteria |
Pseudomonadota | YnfM of E. coli | |||
|
2.A.1.36.2 | Hypothetical MFS carrier of 411 aas and 12 TMSs. | Bacteria |
Pseudomonadota | MFS carrier of Serratia proteamaculans (A8GHT9) | |||
|
2.A.1.36.3 | Bacteria |
Pseudomonadota | YgaY of Escherichia coli | ||||
|
2.A.1.36.4 | MdrA. Putative MDR transporter that may export cationic and hydrophobic compounds, Sco4007. Regulated by a TetR-like repressor that binds drugs (Hayashi et al. 2013). | Bacteria |
Actinomycetota | MdrA (Sco4007) of Streptomyces coelicolor | |||
|
2.A.1.36.5 | MFS carrier of 389 aas | Bacteria |
Pseudomonadota | MFS carrier of Rhizobium loti | |||
|
2.A.1.36.6 | Succinate/dicarboxylate transporter, YnfM, of 416 aas and 12 TMSs. It exports succinate under both aerobic and anaerobic conditions (Fukui et al. 2019). | Bacteria |
Actinomycetota | YnfM of Corynebacterium glutamicum | |||
| 2.A.1.37: The Uncharacterized Major Facilitator-4 (UMF4) Family | |||||||
This family possibly includes drug exporters | |||||||
|
2.A.1.37.1 | Unknown Major Facilitator-4 family member, UMF4A, of 396 aas and 12 TMSs. | Bacteria |
Spirochaetota | UMF4A of Brachyspira pilosicoli | |||
|
2.A.1.37.2 | UMF4 family member of 399 aas and 12 TMSs, UMF4B. | Bacteria |
Spirochaetota | UMF4B of Brachyspira murdochii | |||
|
2.A.1.37.3 | UMF4C of 407 aas and 12 TMSs. | Archaea |
Candidatus Thermoplasmatota | UMF4C of Ferroplasma sp. | |||
|
2.A.1.37.4 | UMF4D of 399 aas and 12 TMSs | Bacteria |
Spirochaetota | UMF4D of Sphaerochaeta pleomorpha | |||
|
2.A.1.37.5 | UMF4E of 373 aas and 12 TMSs | Archaea |
Thermoproteota | UMF4E of Caldisphaera lagunensis | |||
| 2.A.1.38: The Enterobactin (Siderophore) Exporter (EntS) Family | |||||||
|
2.A.1.38.1 | The enterobactin (siderophore) exporter, EntS or YbdA (Bleuel et al., 2005). May also export arabinose but not xylose (Koita and Rao 2012). | Bacteria |
Pseudomonadota | EntS (YbdA) of E. coli | |||
|
2.A.1.38.2 | The putative siderophore exporter (DUF 894; Pfam 05977), VabS | Bacteria |
Pseudomonadota | VabS of Listonella anguillarum (Q0E7C5) | |||
|
2.A.1.38.3 | Enterobactin exporter, EntS (Crouch et al., 2008) (probably orthologous to 2.A.1.38.1). | Bacteria |
Pseudomonadota | EntS of Salmonella typhimurium (Q8ZR35) | |||
|
2.A.1.38.4 | Uncharacterized MFS protein of 429 aas and 12 TMSs. | Bacteria |
Bacillota | UP of Lactobacillus rhamnosus | |||
| 2.A.1.39: The Vibrioferrin (Siderophore) Exporter (PrsC) Family | |||||||
|
2.A.1.39.1 | The vibrioferrin (siderophore) exporter, PrsC (Tanabe et al., 2003; Tanabe et al., 2006) | Bacteria |
Pseudomonadota | PrsC of Vibrio parahaemolyticus (BAC16546) | |||
|
2.A.1.39.2 | MFS permease of 398 aas and 12 TMSs. | Bacteria |
Pseudomonadota | MFS permease of Xanthomonas campestris | |||
|
2.A.1.39.3 | Putative efflux pump of 383 aas and 12 TMSs. | Bacteria |
Actinomycetota | Efflux pump of Kitasatospora setae (Streptomyces setae) | |||
| 2.A.1.40: The Major Facilitator Superfamily Domain-containing Protein (MFS-DP) Family | |||||||
|
2.A.1.40.1 | Major facilitator superfamily domain-containing protein 5, MfsD5 or SLC61A1) of 481 aas and 13 TMSs in a 7 + 6 TMS arrangement. | Eukaryota |
Metazoa, Chordata | MfsD5 of Danio rerio | |||
|
2.A.1.40.2 | Major facilitator superfamily domain-containing protein 5, MFSD5 or SLC61A1, of 450 aas and 13 TMSs in a 5 + 2 + 6 TMS arrangement. It mediates high-affinity (550 nM Km) intracellular uptake of the rare oligo-element molybdenum. It is probably a molybdate (the oxianion molybdate)/anion uptake porter (Tejada-Jiménez et al. 2011). In mammals, it is expressed in the brain and may play a role in energy homeostasis (Perland et al. 2016).
| Eukaryota |
Metazoa, Chordata | Molybdate uptake porter of Homo sapiens | |||
|
2.A.1.40.3 | Major facilitator superfamily domain-containing protein 5 | Eukaryota |
Metazoa, Chordata | mfsd5 of Xenopus tropicalis | |||
| 2.A.1.41: The Putative Bacteriochlorophyll Delivery (BCD) Family | |||||||
|
2.A.1.41.1 | Putative pigment transporter (Young and Beatty, 1998) | Bacteria |
Pseudomonadota | LhaA of Rhodobacter capsulatus | |||
|
2.A.1.41.2 | Putative pigment transporter (Young and Beatty, 1998) | Bacteria |
Pseudomonadota | PucC of Rhodobacter capsulatus | |||
|
2.A.1.41.3 | Putative bacteriochlorophyll synthase | Bacteria |
Pseudomonadota | Bch2 of Rhodobacter capsulatus | |||
| 2.A.1.42: The Lysophospholipid Transporter (LplT) Family | |||||||
|
2.A.1.42.1 | The lysophospholipid (LPL) transporter, LplT (Harvat et al., 2005). Substrates include lyso-PE, lyso-cardiolipin, diacylcardiolipin, fully-deacylated cardiolipin and lyso-phosphatidylglycerol, but not lysophosphatidylcholine, lysophosphatidic acid or phosphatidic acid (Lin et al. 2016). Reacylation by acyltransferase/acyl-acyl carrier protein synthetase then occurs on the inner leaflet of the membrane.Thus, a fatty acid chain is not required for LplT transport. A "sideways sliding" mechanism was proposed to explain how a conserved membrane-embedded α-helical interface excludes diacylphospholipids from the LplT binding site to facilitate efficient flipping of lysophospho-lipids across the cell membrane (Lin et al. 2016). Thus, a fatty acid chain is not required for LplT transport. Fruther, LplT cannot transport lysophosphatidic acid, and its substrate binding was not inhibited by either orthophosphate or glycerol 3-phosphate, indicating that either a glycerol or ethanolamine headgroup is the chemical determinant for substrate recognition. Diacyl forms of PE, phosphatidylglycerol, or the tetra-acylated form of cardiolipin could not serve as competitive inhibitors .A "sideways sliding" mechanism was proposed to explain how a conserved membrane-embedded α-helical interface can exclude diacylphospholipids from the LplT binding site. A dual substrate-accessing mechanism, in which LplT recruits LPLs to its substrate-binding site via two routes, either from its extracellular entry site, or through a membrane-embedded groove between transmembrane helices, and it then moves them towards the inner membrane leaflet (Lin et al. 2018). | Bacteria |
Pseudomonadota | LplT of E. coli (NP_417312) | |||
|
2.A.1.42.2 | The lysophospholipid transporter-2-acyl glycerophosphoethanolamine acyl transferase/acyl ACP synthetase (LplT-Pls-ACS) fusion protein (Harvat et al., 2005). | Bacteria |
Pseudomonadota | The fused LplT-PlsC-ACS of Bradyrhizobium japonicum (BAC47589) | |||
| 2.A.1.43: The Putative Magnetosome Permease (PMP) Family | |||||||
|
2.A.1.43.1 | The putative magnetosomal permease, MamH (Schubbe et al., 2003) | Bacteria |
Pseudomonadota | MamH of Magnetospirillum gryphiswaldense (Q6NE63) | |||
|
2.A.1.43.2 | The magnetosome permease fused to a C-terminal YedZ-like domain, MamZ (von Rozycki et al., 2004). This protein has 649 aas and 18 TMSs with a C-terminal YedZ domain and is therefore in the YedZ superfamily as well as the MFS. The two MFS proteins in the magnetosome membrane, MamZ and MamH (44% identical to MamZ), appear to overlap in function as deletion of their two genes have additive effects (Raschdorf et al. 2013). Magnetosome biogenesis has been reviewed (). | Bacteria |
Pseudomonadota | PMP of Magnetospirillum magneticum (Q2W8K5) | |||
| 2.A.1.44: The L-Amino Acid Transporter-3 (LAT3) Family | |||||||
This family is also called the SLC43 family. | |||||||
|
2.A.1.44.1 | The L-amino acid transporter-3, LAT3 (transports neutral amino acids such as L-leucine, L-isoleucine, L-valine, and L-phenylalanine by a Na+-independent, electroneutral, facilitated diffusion process; it also transports amino acid alcohols and thyroid hormones such as 3,3'-T2) (Prostate cancer up-regulated gene product) (Krause and Hinz 2019). | Eukaryota |
Metazoa, Chordata | SLC43A1 of Homo sapiens | |||
|
2.A.1.44.2 | L-amino acid transporter-4 (LAT4) has the same specificity and is 57% identity to LAT3. Na+, Cl- and pH independent; not trans-stimulated; it has been reported to have two kinetic components, a low affinity component sensitive to NEM, and a high affinity component insensitive to NEM. It is found in the basolateral membrane of epithelial cells in the distal tubule and collecting duct of the kidney and the crypt cells in the intestine (Bodoy et al., 2005). It can transport throid hormones such as 3,3'-T2 (Krause and Hinz 2019). | Eukaryota |
Metazoa, Chordata | SLC43A2 of Homo sapiens | |||
|
2.A.1.44.3 | solute carrier family 43, member 3 | Eukaryota |
Metazoa, Chordata | SLC43A3 of Homo sapiens | |||
|
2.A.1.44.4 | Similar to MFS transporter Fmp4; of 614 aas and 12 TMSs in a 6 + 6 TMS arrangement where the two 6 TMS units are separated by a large hydrophilic domain. | Eukaryota |
Fungi, Ascomycota | MFS porter of Leptosphaeria maculans | |||
| 2.A.1.45: The 2,4-diacetylphloroglucinol (PHL) Exporter (PHL-E) Family | |||||||
This family is most closely related to TC# 2.A.1.15. | |||||||
|
2.A.1.45.1 | The 2,4-diacetylphloroglucinol resistance/general stress porter, PhlE (Abbas et al., 2004) | Bacteria |
Pseudomonadota | PhlE of Pseudomonas fluorescens (CAD65845) | |||
|
2.A.1.45.2 | Probable metabolite transporter of 440 aas and 12 TMSs. | Bacteria |
Pseudomonadota | Porter of Pseudomonas syringae | |||
|
2.A.1.45.3 | Putative aromatic acid uptake porter of 450 aas and 12 TMSs. | Bacteria |
Pseudomonadota | Porter of Erwinia billingiae | |||
| 2.A.1.46: The Uncharacterized Major Facilitator-5 (UMF5) Family | |||||||
This family includes probable MDR pumps. | |||||||
|
2.A.1.46.1 | Probable MDR efflux transporter of 396 aas and 12 TMSs. The closest homolologues are MDR pumps in subfamilies 2.A.1.2 and 2.A.1.3. | Bacteria |
Pseudomonadota | Probable MDR transporter of Bordetella pertussis (Q7W0Q7) | |||
|
2.A.1.46.2 | Putative MDR efflux transporter of 390 aas and 12 TMSs. The closest homolologues are MDR pumps in subfamilies 2.A.1.2 and 2.A.1.3. | Bacteria |
Actinomycetota | Putative transporter of Tropheryma whipplei (Q83N16) | |||
|
2.A.1.46.3 | Putative drug resistance UMF5 family member | Eukaryota |
Euglenozoa | Putative MDR pump of Leishmania infantum | |||
|
2.A.1.46.4 | UMF15 family member | Archaea |
Euryarchaeota | UMF5 homologue of Methanosphaerula palustris (B8GFY3) | |||
|
2.A.1.46.5 | Putative quinolone resistance protein | Bacteria |
Bacillota | MFS porter of Bacillus cereus (C2UR80) | |||
|
2.A.1.46.6 | UPF0226 protein YfcJ. Catalyzes export of arabinose but not xylose (Koita and Rao 2012). | Bacteria |
Pseudomonadota | YfcJ of E. coli | |||
|
2.A.1.46.7 | UPF0226 protein, YhhS. Exports arabinose but not xylose (Koita and Rao 2012). Also may export the herbicide, glyphosate (Staub et al. 2012). | Bacteria |
Pseudomonadota | YhhS of E. coli | |||
|
2.A.1.46.8 | MFS carrier of 366 aa | Archaea |
Thermoproteota | MFS carrier of Sulfolobus solfataricus | |||
|
2.A.1.46.9 | Uncharacterized MFS porter of 430 aas | Archaea |
Euryarchaeota | MFS porter of Halosimplex carlsbadense | |||
|
2.A.1.46.10 | Probable staphylopine exporter, CntE. Staphylopine is a broad spectrum metalophore similar to plant nicotianamine that binds several divalent ions (nickel, cobalt, zinc, copper and iron) (Ghssein et al. 2016). The uptake system for metal bound staphylpine is TC# 3.A.1.5.43). CntE is downstream of the genes coding for the uptake system, CntABCDF (Ghssein et al. 2016). | Bacillota | CntE of Staphylococcus aureus | ||||
|
2.A.1.46.11 | Uncharacterized MFS porter of 403 aas and 12 TMSs. | Bacteria |
Candidatus Wolfebacteria | UP of Candidatus Wolfebacteria bacterium | |||
|
2.A.1.46.12 | Uncharacterized MFS permease of 406 aas and 12 TMSs. | Bacteria |
Candidatus Saccharibacteria | UP of Candidatus Saccharibacteria bacterium | |||
|
2.A.1.46.13 | Membrane protein of unknown function of 406 aas and 12 TMSs | Bacteria |
Candidatus Saccharibacteria | Membrane protein of unknown function of Canditatus Saccharibacteria bacterium | |||
| 2.A.1.47: The Uncharacterized Major Facilitator-6 (UMF6) Family | |||||||
These porters may be drug exporters. | |||||||
|
2.A.1.47.1 | Putative transporter | Bacteria |
Bacillota | Putative transporter of Lactobacillus plantarum (NP_784357) | |||
|
2.A.1.47.2 | UMF6 family member | Bacteria |
Bacillota | MFS carrier of Streptococcus suis (A4VY05) | |||
|
2.A.1.47.3 | Possible antibiotic peptide exporter (encoded in an operon together with lantibiotic biosynthesis enzymes) | Bacteria |
Bacillota | UMF6 family member of Streptococcus pneumoniae (B2IRN2) | |||
|
2.A.1.47.4 | MFS permease of 408 aas | Bacteria |
Bacillota | MFS permease of Streptococcus pneumoniae | |||
| 2.A.1.48: The Vacuolar Basic Amino Acid Transporter (V-BAAT) Family | |||||||
|
2.A.1.48.1 | The vacuolar basic amino acid (histidine, lysine and arginine) transporter, Vba1 (catalyzes uptake into the vacuoles (equivalent to efflux from the cytoplasm)) (most similar to family 2.A.1.3; DHA2; 13-14 putative TMSs) (Shimazu et al., 2005) | Eukaryota |
Fungi, Ascomycota | Vba1 of Saccharomyces cerevisiae (NP_013806) | |||
|
2.A.1.48.2 | The vacuolar basic amino acid (Arg, Lys, His) transporter, Vba2 (Shimazu et al., 2005) | Eukaryota |
Fungi, Ascomycota | Vba2 of Saccharomyces cerevisiae (P38358) | |||
|
2.A.1.48.3 | Vacuolar G0 arrest protein, Fnx1; involved in amino acid (e.g., his, lys, ile, asn, etc) uptake into the vacuole (Chardwiriyapreecha et al., 2008). | Eukaryota |
Fungi, Ascomycota | Fnx1 of Schizosaccharomyces pombe (Q09752) | |||
|
2.A.1.48.4 | Vacuolar amino acid uptake system, Fnx2 (Chardiwiriyapreecha et al., 2008) | Eukaryota |
Fungi, Ascomycota | Fnx2 of Schizosaccharomyces pombe (O59726) | |||
|
2.A.1.48.5 | Originally considered to be vacuolar basic amino acid transporter 4, but it my not act on amino acids, but exports drugs such as azoles. May also play a role in vacuolar morphology (Kawano-Kawada et al. 2015). | Eukaryota |
Fungi, Ascomycota | VBA4 of Saccharomyces cerevisiae S288c | |||
| 2.A.1.49: The Endosomal Spinster (Spinster) Family | |||||||
|
2.A.1.49.1 | The spinster protein, spin1 or spns1 gene product (involved in synaptic growth regulation; interacts with Bcl-2/Bcl-xL, affecting programmed cell death) (Nakano et al., 2001; Sanyal and Ramaswami, 2002; Yanagisawa et al., 2003). Probably transports sphingosine-1-phosphate (Fukuhara et al. 2012), but polymorphisms in spns1 are associated with alterred triglyceride levels (Västermark et al. 2012). | Eukaryota |
Metazoa, Arthropoda | Spinster of Drosophila melanogaster (AAG43825) | |||
|
2.A.1.49.2 | The spinster homologue, Spin1 or Spns1 (SLC63A1) of 528 aas and 12 TMSs. It interacts with Bc1-2/Bc1-XL to induce a caspase-independent autophagic cell death (Yanagisawa et al., 2003). It is a spingosine-1-phosphate (S1P) (or sphingolipid) exporter (Nijnik et al. 2012). S1P is important for lymphocyte trafficking, immune responses, vascular and embryonic development, cancer, bone homeostasis (Zhu et al. 2018). S1P is produced intracellularly and then secreted into the circulation to engage in the above physiological or pathological processes by regulating the proliferation, differentiation and survival of target cells. SPNS2 acts as a mediator of intracellular S1P release. The SPNS1-dependent lysosomal lipid transport pathway enables cell survival under choline limitation (Scharenberg et al. 2023). The orphan lysosomal transmembrane protein SPNS1 is critical for cell survival under choline limitation. SPNS1 loss leads to intralysosomal accumulation of lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). SPNS1 is a proton gradient-dependent transporter of LPC species from the lysosome for their re-esterification into phosphatidylcholine in the cytosol (Scharenberg et al. 2023). | Eukaryota |
Metazoa, Chordata | Spin1 of Homo sapiens (Q9H2V7) | |||
|
2.A.1.49.3 | Eukaryota |
Viridiplantae, Streptophyta | Spinster homologue 3 of Arabidopsis thaliana (F4IKF6) | ||||
|
2.A.1.49.4 | Protein Spinster homologue 2 (Spns2 or protein two of hearts). Exports sphingosine-1-P (S1P) and the immunomodulating agent, FTY720 (Hisano et al. 2011; Nijnik et al. 2012). S1P is a secreted lipid mediator that functions in vascular development. In the yolk syncytial layer, Spns2 functions in S1P secretion, thereby regulating myocardial precursor migration (Kawahara et al. 2009). | Eukaryota |
Metazoa, Chordata | Spns2 of Danio rerio | |||
|
2.A.1.49.5 | Eukaryota |
Viridiplantae, Streptophyta | At5g65687 of Arabidopsis thaliana | ||||
|
2.A.1.49.6 | Sphingosine-1-phosphate/dehydrosphingosine-1-P transport protein, Spinster 2, SPNS2 of 549 aas and 12 TMSs. It is involved in immune development and lymphocyte trafficing (Nijnik et al. 2012; Fukuhara et al. 2012). The functions and the mechanisms of SPNS2 in the pathogenesis of cancer have been reviewed (Fang et al. 2020). | Eukaryota |
Metazoa, Chordata | SPNS2 of Homo sapiens | |||
|
2.A.1.49.7 | Bacteria |
Myxococcota | Spinster homologue of Myxococcus xanthus | ||||
|
2.A.1.49.8 | Bacteria |
Acidobacteriota | Spinster homologue of Terriglobus saanensis | ||||
|
2.A.1.49.9 | The cis, cis muconate transporter of 508 aas. | Eukaryota |
Metazoa, Arthropoda | MucK of Bombyx mori (Silk moth) | |||
|
2.A.1.49.10 | MFS multidrug exporter of 429 aas and 12 TMSs. Exports capreomycin and ethidium bromide, and deletion mutants grow faster than wild type cells (Zhang et al. 2015). | Bacteria |
Actinomycetota | MDR pump of Mycobacterium smegmatis | |||
|
2.A.1.49.11 | Uncharacterized protein of 656 aas and 12 TMSs | Eukaryota |
Viridiplantae, Chlorophyta | UP of Chlamydomonas reinhardtii (Chlamydomonas smithii) | |||
|
2.A.1.49.12 | Spinster 3, SPNS3 (SLC63A3), of 512 aas and 12 TMSs. The evolutionary conservation, predicted structure and neuronal expression have been characterized (Perland et al. 2017). It probably exports sphigosine-1- phosphate. | Eukaryota |
Metazoa, Chordata | SPNS3 of Homo sapiens | |||
|
2.A.1.49.13 | MFS porter, MFR1, of 853 aas and 12 TMSs in an apparent 6 + 2 + 4 TMS arrangement. | Eukaryota |
Apicomplexa | MFR1 of Plasmodium falciparum | |||
| 2.A.1.50: The Proton Coupled Folate Transporter/Heme Carrier Protein (PCFT/HCP) Family | |||||||
|
2.A.1.50.1 | The apical intestinal and choroid plexus proton-coupled, high affinity folate transporter, the hereditary folate malabsorption (HFM) protein, PCFT/HCP1 (Shin et al. 2010). Also reported to mediate heme-iron uptake from the gut lumen with duodenal epithelial cells (Shayeghi et al., 2005; Latunde-Dada et al., 2006; Subramanian et al., 2008, Shin et al., 2012b), but it shows a higher affinity for folate than heme) (Qiu et al., 2006). Responsible for folate uptake by choroid plexus epithelial cells (Wollack et al., 2007) and placenta (Yasuda et al., 2008). The rat orthologue (Q5EBA8) catalyzes H+-dependent folate uptake in the intestine (Inoue et al., 2008; Zhao and Goldman, 2007; Qiu et al., 2006; Shin et al., 2012). Evidence for a 12 TMS topology with a renetrant loop between TMSs 2 and 3 has been presented (Zhao et al., 2010; Qiu et al., 2006; Zhao et al., 2011; Wilson et al. 2014). Downregulated in Chronic Kidney Disease (CKD) in heart, liver, and brain, causing malabsorption (Bukhari et al., 2011). An IGXXG motif in TMS5 is important for folate binding and a GXXXG motif is involved in dimerization (Zhao et al., 2012). It is inhibited by bicarbonate, bisulfite, nitrite and other anions (Zhao et al. 2013). Its role in antifolate cancer chemotherapy has been reviewed (Matherly et al. 2014). TMSs 3 and 6 may provide critical interfaces for formation of hPCFT oligomers, facilitated by the GXXXG motifs in TMS2 and TMS4 (Wilson et al. 2015). The extracellular gate has been identified (Zhao et al. 2016), and mechanistic aspects have been considered (Date et al. 2016). Residues in the seventh and eighth TMSs play roles in the translocation pathway and folate binding (Aluri et al. 2017). The mutation, N411K-PCFT, is responsible for HFM (Aluri et al. 2018). PCFT is ubiquitously expressed in solid tumors to which it delivers antifolates, particularly pemetrexed, into cancer cells in a concentrative fashion (Zhao et al. 2018). Substitutions have been identified that lock and unlock PCFT into an inward-open conformation (Aluri et al. 2019). The nanodisc lipid composition influences the cell-free expression of PCFT (Do et al. 2021). Iron deficiency promotes hepatocellular carcinoma metastasis, and the loss of SLC46A1 expression leads to iron deficiency in liver tumor tissues (Wang et al. 2022). Cell-free expression of PCFT in the presence of nanodiscs has been reported (Do and Jansen 2022). Biological and therapeutic applications of the proton-coupled folate transporter have been reviewed (Matherly et al. 2022). FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of methotraxate (MTX), whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells (Bai et al. 2024). | Eukaryota |
Metazoa, Chordata | SLC46A1 or PCFT of Homo sapiens | |||
|
2.A.1.50.2 | Thymic stromal cotransporter, TSCOT (Kim et al. 2000) | Eukaryota |
Metazoa, Chordata | SLC46A2 of Homo sapiens | |||
|
2.A.1.50.3 | solute carrier family 46, member 3 | Eukaryota |
Metazoa, Chordata | SLC46A3 of Homo sapiens | |||
|
2.A.1.50.4 | Multidrug efflux transporter, MET, of 507 aas and 12 TMSs (Chahine et al. 2012). Exposure to dietary methotrexate was associated with increased fluid secretion rate and increased flux of methotrexate, but not salicylate. Exposure to methotrexate in the diet resulted in increases in the expression of a multidrug efflux transporter gene (MET; CG30344) in the Malpighian tubules. There were also increases in expression of genes for either a Drosophila multidrug resistance-associated protein (dMRP; CG6214; TC# 3.A.1.208.39) or an organic anion transporting polypeptide (OATP; CG3380; TC# 2.A.60.1.27), depending on the concentration of methotrexate in the diet. MET probably does not export methotrexate (Chahine et al. 2012). | Eukaryota |
Metazoa, Arthropoda | MET of Drosophila melanogaster (Fruit fly) | |||
| 2.A.1.51: The Uncharacterized Major Facilitator-7 (UMF7) Family | |||||||
This family may include aromatic acid porters. | |||||||
|
2.A.1.51.1 | Putative permease | Bacteria |
Pseudomonadota | Putative transporter of Azoarcus sp. EbN1 (CAI06874) | |||
|
2.A.1.51.2 | YjiJ MFS porter, a member of the DUF2118 family in Pfam. | Bacteria |
Pseudomonadota | YjiJ of E. coli (D6IHN4) | |||
|
2.A.1.51.3 | MFS permease | Bacteria |
Deinococcota | MFS permease of Thermus thermophilus (F6DF77) | |||
|
2.A.1.51.4 | Uncharacterized MFS permease | Bacteria |
Pseudomonadota | UP of Pseudomonas aeruginosa | |||
| 2.A.1.52: The Glycerophosphodiester Uptake (GlpU) Family | |||||||
|
2.A.1.52.1 | MFS permease, YihN, of 423 aas and 11 TMSs. It may transport aromatic fluorophores (fluorescent dyes) (Salcedo-Sora et al. 2021). | Bacteria |
Pseudomonadota | YihN of E. coli (P32135) | |||
|
2.A.1.52.2 | YqcE putative transporter | Bacteria |
Pseudomonadota | YqcE pf E. coli (F4TJX1) | |||
|
2.A.1.52.3 | MFS permease | Bacteria |
Actinomycetota | MFS permease of Propionibacterium acnes | |||
|
2.A.1.52.4 | The glycerophosphodiester, glycerophosphocholine uptake porter, GlpU. The cytoplasmic compound is hydrolyzed to α-glycerolphosphate and choline (Großhennig et al. 2013). | Bacteria |
Mycoplasmatota | GlpU of Mycoplasma pneumoniae | |||
| 2.A.1.53: The Proteobacterial Intraphagosomal Amino Acid Transporter (Pht) Family | |||||||
|
2.A.1.53.1 | The threonine uptake permease, PhtA (Sauer et al., 2005) (required for maximal growth in macrophages and Acanthamoeba castellanii) | Bacteria |
Pseudomonadota | PhtA of Legionella pneumophila (YP_094583) | |||
|
2.A.1.53.2 | The valine uptake permease, PhtJ (required for maximal growth in macrophages and Acanthamoeba castellanii) (Chen et al., 2008) | Bacteria |
Pseudomonadota | PhtJ of Legionella pneumophila (YP_095910) | |||
|
2.A.1.53.3 | The MFSD1 (SMAP4) transporter (465 aas; 12 TMSs). Expression is increased in mice by amino acid starvation and decreased by a high fat diet (Perland et al. 2016). This lysosomal transporter is essential for liver homeostasis and critically depends on its accessory subunit GLMP (Massa López et al. 2019). MFSD1 is not N-glycosylated but contains a dileucine-based sorting motif needed for its transport to lysosomes. Mfsd1 knockout mice develop splenomegaly and severe liver disease. GLMP (406 aas and at least 2 TMSs, N- and C-terminal) physically interacts with MFSD1 and is a critical accessory subunit. GLMP is essential for the maintenance of normal levels of MFSD1 in lysosomes and vice versa. Glmp knockout mice mimic the phenotype of Mfsd1 knockout mice (Massa López et al. 2019). The two lysosomal integral membrane proteins MFSD1 and GLMP form a tight complex that confers protection of both interaction partners against lysosomal proteolysis. López et al. 2020 refined the molecular interaction of the two proteins and found that the luminal domain of GLMP alone, but not its transmembrane domain or its short cytosolic tail, conveys protection and mediates the interaction with MFSD1. The interaction is essential for the stabilization of the complex. N-glycosylation of GLMP is essential for protection. The interaction of both proteins starts in the endoplasmic reticulum, and quantitatively depends on each other. Both proteins can affect their intracellular trafficking to lysosomes. MFSD1 can form homodimers both in vitro and in vivo (López et al. 2020). | Eukaryota |
Metazoa, Chordata | MFSDI/GLMP of Homo sapiens (A6NID9) | |||
|
2.A.1.53.4 | Uncharacterized protein of 575 aas and 14 TMSs. | Eukaryota |
Rhodophyta | UP of Cyanidioschyzon merolae | |||
|
2.A.1.53.5 | Putative amino acid transporter of 478 aas and 12 TMSs, CG8602, isoform A. May play a role in macrophage migration in the Drosophila embryo (Dr. Daria Siekhaus, personal communication). | Eukaryota |
Metazoa, Arthropoda | SG8602A of Drosophila melanogaster (Fruit fly) | |||
|
2.A.1.53.6 | MFS uptake permease specific for pyrimidines, PhtC of 422 aas and 12 TMSs. Together with PhtD (TC# 2.A.1.53.6), it contributes to protection of L. pneumophila from dTMP starvation, protects the cell from 5-fluorodeoxyuridine (FUdR) toxicity and is required for growth of L. pneumophila in macrophage (Fonseca et al. 2014). | Bacteria |
Pseudomonadota | PhtC of Legionella pneumophila | |||
|
2.A.1.53.7 | MFS uptake permease, probably specific for pyrimidines, PhtD of 427 aas and 12 TMSs. Together with PhtC (TC# 2.A.1.53.6), it contributes to protection of L. pneumophila from dTMP starvatioin, protects the cell from 5-fluorodeoxyuridine (FUdR) toxicity and is required for growth of L. pneumophila in macrophage (Fonseca et al. 2014). | Bacteria |
Pseudomonadota | PhtD of Legionella pneumophila | |||
|
2.A.1.53.8 | PhtB of 431 aas | Bacteria |
Pseudomonadota | PhtB of Legionella pneumophila | |||
|
2.A.1.53.9 | PhtE of 430 aas | Bacteria |
Pseudomonadota | PhtE of Legionella pneumophila | |||
|
2.A.1.53.10 | PhtF of 425 aas | Bacteria |
Pseudomonadota | PhtF of Legionella pneumophila | |||
|
2.A.1.53.11 | PhtG of 432 aas | Bacteria |
Pseudomonadota | PhtG of Legionella pneumophila | |||
|
2.A.1.53.12 | PhtH of 430 aas | Bacteria |
Pseudomonadota | PhtH of Legionella pneumophila | |||
|
2.A.1.53.13 | PhtI of 390 aas | Bacteria |
Pseudomonadota | PhtI of Legionella pneumophila | |||
|
2.A.1.53.14 | PhtK of 410 aas | Bacteria |
Pseudomonadota | PhtK of Legionella pneumophila | |||
| 2.A.1.54: The Uncharacterized Major Facilitator-9 (UMF9) Family | |||||||
The proteins of this family are related to 2.A.1.54; amino acid/nucleobase porters. Members are mainly found in bacteria and archaea. | |||||||
|
2.A.1.54.1 | The archaeal uptake permease, MMP0835 (function unknown) (31% I, 49% S with PhtA) | Archaea |
Euryarchaeota | MMP0835 of Methanococcus maripaludis (CAF30391) | |||
|
2.A.1.54.2 | UMF-9 homologue of 414 aa | Bacteria |
Thermodesulfobacteriota | UMF9 homologue of Geobacter sulfurreducens (Q747F2) | |||
|
2.A.1.54.3 | Functionally uncharacterized MFS porter of 414 aas | Bacteria |
Bacillota | UP of Syntrophothermus lipocalidus | |||
| 2.A.1.55: The Uncharacterized Major Facilitator-8 (UMF8) Family | |||||||
These systems may be MDR pumps. | |||||||
|
2.A.1.55.1 | Uncharacterized MFS porter of 397 aas and 12 TMSs | Archaea |
Euryarchaeota | UP of Halorubrum distributum | |||
|
2.A.1.55.2 | Uncharacterized protein of 390 aas | Archaea |
Euryarchaeota | UP of Natrinema versiforme | |||
|
2.A.1.55.3 | Uncharacterized protein of 406 aas | Archaea |
Euryarchaeota | UP of Haloterrigena salina | |||
|
2.A.1.55.4 | Putative phthalate porter of 377 aas | Archaea |
Euryarchaeota | UP of Haloferax gibbonsii | |||
|
2.A.1.55.5 | MFS protein of 373 aas and 11 TMSs. The protein is probably N-terminally truncated due to an error, and probably has 12 TMSs in a 6 + 6 TMS arrangement. | Bacteria |
Pseudomonadota | MFS porter of Labrenzia sp. THAF82 | |||
| 2.A.1.56: The 1,3-Dihydroxybenzene/Drug Transporter (DHB-T) Family | |||||||
|
2.A.1.56.1 | The 1,3-dihydroxybenzene (resorcinol) uptake permease, MFS_1 (Darley et al., 2007) of 402 aas and 12 TMSs. | Bacteria |
Pseudomonadota | MFS_1 of Azoarcus anaerobius (YP_285101) | |||
|
2.A.1.56.2 | Uncharacterized protein of 405 aas and 12 TMSs. | Bacteria |
Pseudomonadota | UP of Bradyrhizobium japonicum | |||
| 2.A.1.57: The Ferripyochelin Transporter (FptX) Family | |||||||
|
2.A.1.57.1 | The Ferripyochelin uptake permease, FptX (Michel et al., 2007). Also transports N-acetylglucosamine anhydrous N-acetylmuramyl peptides and is called AmpP or AmpGh1 (Kong et al. 2010). However, it does not play a role in the induction of β-lactam resistance (Zhang et al. 2010). | Bacteria |
Pseudomonadota | FptX or AmpP of Pseudomonas aeruginosa (Q9HWG8) | |||
|
2.A.1.57.2 | The ferric rhizbactin 1021 uptake porter, RhtX (Cuív et al. 2004). | Bacteria |
Pseudomonadota | RhtX of Sinorhizobium meliloti | |||
|
2.A.1.57.3 | Iron-yersiniabactin (Ybt) transporter of 467 aas and 12 TMSs, YbtX (Bobrov et al. 2014). Yersiniabactin can also bind zinc ions with high affinity and feed the Zn2+ into this MFS transporter, YbtX (Bobrov et al. 2014). In fact, the siderophore, Ybt, is required for growth under Zn2+-deficient conditions in a strain lacking ZnuABC (see 3.A.1.15.5 for the E. coli ortholog). This MFS porter is similar to the Irp8 piscibactin secretion porter of Vibrio anguillarum (Lages et al. 2022). | Bacteria |
Pseudomonadota | YbtX of Yersinia pestis | |||
|
2.A.1.57.4 | Siderophore transporter, RhtX/FptX family | Bacteria |
Myxococcota | Siderophore transporter of Myxococcus xanthus | |||
|
2.A.1.57.5 | The iron (Fe3+)·pyridine-2,6-bis(thiocarboxylic acid (PDTC)) uptake transporter, PdtE. Functions with the OMR, PdtK, 1.B.14.8.2 (most similar to 2.A.1.57.4) (Leach and Lewis 2006). | Bacteria |
Pseudomonadota | PdtE of Pseudomonas putida (ABC8353) | |||
|
2.A.1.57.6 | Major facilitator superfamily domain-containing protein 3, MFSD3. Function unknown. The human ortholog has Uniprotein acc # of Q96ES6 with 412 aas and 12 TMSs. | Eukaryota |
Metazoa, Chordata | Mfsd3 of Rattus norvegicus | |||
| 2.A.1.58: The N-Acetylglucosamine Transporter (NAG-T) Family | |||||||
|
2.A.1.58.1 | The N-acetylglucosamine:H+ symporter, Ngt1 (Alvarez and Konopka, 2007) | Eukaryota |
Fungi, Ascomycota | Ngt1 of Candida albicans (Q5A7S4) | |||
|
2.A.1.58.2 | May contribute to coordination of muscle contraction as regulatory subunit of a nonessential potassium channel complex. Subunit structure: May form a complex with sup-9 and sup-10 where unc-93 and sup-10 act as regulatory subunits of the two pore potassium channel sup-9.
| Eukaryota |
Metazoa, Nematoda | Unc-93 of Caenorhabditis elegans (Q93380) | |||
|
2.A.1.58.3 | UNC93-like protein MFSD11 (Major facilitator superfamily domain-containing protein 11; Protein ET) of 449 aas and 12 TMSs It seems to be involved in intracellular transport in mammals and has been suggested to be a sugar:H+ symporter (Zhang et al. 2018). It is expressed in testis, small intestine, spleen, prostate, and ovary, and mutations can give rise to ovarian cancer (Liu et al. 2002). Mfsd11 is abundantly expressed in the mouse brain and plays a potential role in energy homeostasis (Perland et al. 2016). Its transcript is highly enriched in Aedes aegypti during arbovirus infection (Campbell et al. 2011). UNC93A and SV2 (TC# 2.A.1.22.1) may play a role in virus assembly or budding (Campbell et al. 2011). TMEM132C, UNC93A and TTLL2 (the latter two genes being adjacent) are associated with pulmonary function (Son et al. 2015). It may be involved in psoriasis, a common chronic autoimmune inflammatory skin disease (Li et al. 2020). | Eukaryota |
Metazoa, Chordata | MFSD11 of Mus musculus | |||
|
2.A.1.58.4 | MFS permease of 467 aas | Eukaryota |
Viridiplantae, Streptophyta | MFS permease of Oryza sativa | |||
|
2.A.1.58.5 | Duf895 protein of 450 aas | Eukaryota |
Fungi, Ascomycota | Duf895 protein of Verticillium albo-atrum | |||
|
2.A.1.58.6 | MFS permease of 425 aas | Eukaryota |
Evosea | MFS permease of Dictyostellium discoideum | |||
|
2.A.1.58.7 | Unc-93 family homologue B1, Unc-93b1 or Unc93b1, of 597 aas and 12 TMSs, plays a role in innate and adaptive immunity by regulating nucleotide-sensing Toll-like receptor (TLR) signaling (Pelka et al. 2014). It is required for the transport of a subset of TLRs (including TLR3, TLR7 and TLR9) from the endoplasmic reticulum to endolysosomes where they can engage pathogen nucleotides (e.g., of viral nucleic acids) and activate signaling cascades. Unc93B1 may play a role in autoreactive B-cells removal (Isnardi et al. 2008). It induces apoptotic cell death and is cleaved by host and viral proteases (Harris and Coyne 2015). UNC93B1 may play a role in human oral squamous cell carcinomas growth by controlling the secretion of granulocyte macrophage colony-stimulating factor (GM-CSF) (Wagai et al. 2019). UNC93B1 regulates Toll-like receptor stability independently of endosomal TLR transport (Pelka et al. 2018). A missense variant affecting the C-terminal tail of UNC93B1 in dogs is responsible for a Exfoliative Cutaneous Lupus Erythematosus (ECLE) condition (Leeb et al. 2020). Compartmentalization of TLRs in the endosome limits their activation by self-derived nucleic acids and reduces the possibility of autoimmune reactions. UNC93B1 is indispensable for the trafficking of TLRs from the endoplasmic reticulum to the endosome. Ishida et al. 2021 reported two cryo-EM structures of human and mouse TLR3-UNC93B1 complexes and a human TLR7-UNC93B1 complex. UNC93B1 exhibits structural similarity to other MFS porters. Both TLRs interact with the UNC93B1 amino-terminal six-helix bundle through their transmembrane and luminal juxtamembrane regions, but the complexes of TLR3 and TLR7 with UNC93B1 differ in their oligomerization state (Ishida et al. 2021). The mammalian trafficking chaperone protein UNC93B1 maintains the ER calcium sensor STIM1 in a dimeric state primed for translocation to the ER cortex (Wang and Demaurex 2022).
| Eukaryota |
Metazoa, Chordata | Unc93b1 of Homo sapiens | |||
|
2.A.1.58.8 | MFS permease of 418 aas and 12 TMSs. | Eukaryota |
Evosea | MFS permease of Entamoeba histolytica | |||
|
2.A.1.58.9 | Unc93A of 457 aas and 12 TMSs. | Eukaryota |
Metazoa, Chordata | Unc93A of Homo sapiens | |||
| 2.A.1.59: The Uncharacterized Major Facilitator-10 (UMF10) Family | |||||||
These porters are mostly from Archaea but some are from bacteria; they are closely related to 2.A.1.46, possible drug exporters. | |||||||
|
2.A.1.59.1 | UMF10a of unknown function, (COG2270). | Archaea |
Euryarchaeota | UMF10a of Methanococcus aeolicus (A6UVW2) | |||
|
2.A.1.59.2 | Bacteria |
Cyanobacteriota | |||||
|
2.A.1.59.3 | MFS permease, AF1541 | Archaea |
Euryarchaeota | AF1541 of Archaeoglobus fulgidus (O28731) | |||
|
2.A.1.59.4 | MFS permease, LepA | Bacteria |
Aquificota | LepA of Hydrogenivirga sp.128-5-R1-1 (A8UT57) | |||
|
2.A.1.59.5 | Putative pantothenate:H+ importer of 417 aas and 12 TMSs (Wunderlich 2022). | Eukaryota |
Apicomplexa | Putative pantothenate uptake porter of Plasmodium falciparum | |||
| 2.A.1.60: The Rhizopine-related MocC (MocC) Family | |||||||
|
2.A.1.60.1 | The rhizopine related transporter, MocC (could either transport a precursor for rhizopine biosynthesis into bacteroids or the finished product from the bacteroids) (Murphy et al., 1993) | Bacteria |
Pseudomonadota | MocC of Sinorhizobium meliloti (Q07609) | |||
|
2.A.1.60.2 | Inner membrane protein YbjJ | Bacteria |
Pseudomonadota | YbjJ of Escherichia coli | |||
|
2.A.1.60.3 | The multidrug (quinolone; tetarcycline) resistance pump, TcrA (Chang et al. 2011). | Bacteria |
Pseudomonadota | TcrA of Stenotrophomonas maltophilia (F2WVP9) | |||
| 2.A.1.61: The Microcin C51 Immunity Protein (MccC) Family | |||||||
May also export various drugs. | |||||||
|
2.A.1.61.1 | The MccC microcin C51 immunity protein (exports the peptide-nucleotide 'Trojan horse' antibiotic) (Fomenko et al., 2003; Kazakov et al., 2007) | Bacteria |
Pseudomonadota | MccC of E. coli (Q83Y57) | |||
|
2.A.1.61.2 | MFS porter of 411 aas and 12 TMSs. | Bacteria |
Pseudomonadota | Porter of Bartonella washoensis | |||
|
2.A.1.61.3 | MFS porter of 413 aas and 12 TMSs. | Bacteria |
Chlamydiota | Porter of Parachlamydia acanthamoebae | |||
| 2.A.1.62: The Uncharacterized Major Facilitator-11 (UMF11) Family | |||||||
Possibly involved in transport of amino acids and their derivatives. | |||||||
|
2.A.1.62.1 | The UMF11 homologue | Bacteria |
Bacillota | UMF11 of Staphylococcus aureus (A8YZ14) | |||
|
2.A.1.62.2 | Bacteria |
Fusobacteriota | P-MEP of Fusobacterium sp. 7_1 (C3WVU9) | ||||
|
2.A.1.62.3 | UMF11 (links UMF11 with UMF13) | Bacteria |
Bacillota | UMF11 of Bacillus clausii (Q5WGH2) | |||
|
2.A.1.62.4 | Uncharacterized protein of 406 aas and 12 TMSs. Gives an alignment with a ferroportin homolog, 2.A.100.2.1 including almost all of both proteins with a TC BLAST score of e-12. | Bacteria |
Bacillota | UP of Clostridium diolis | |||
|
2.A.1.62.5 | Putative MFS efflux pump of 389 aas and 12 TMSs. Expression of the gene encoding this transporter is governed by a quorum sensing (QS) system, and it impacts the expression of multiple virulence factors, accounting for QS-dependent antibiotic susceptibility (Chang et al. 2022). | Bacteria |
Bacillota | MFS porter of Streptococcus pyogenes | |||
| 2.A.1.63: The Uncharacterized Major Facilitator-12 (UMF12) Family | |||||||
May export drugs. | |||||||
|
2.A.1.63.1 | The UMF12 protein | Archaea |
Euryarchaeota | UMF12 of Methanosarcina barkeri (Q467Y6) | |||
|
2.A.1.63.2 | UMF12 Possible amino acid exporter | Archaea |
Euryarchaeota | UMF12 of Methanosarcina mazei (Q8PRW9) | |||
|
2.A.1.63.3 | Possible nucleotide or oligonucleotide uptake porter, UMF12 | Bacteria |
Deinococcota | UMF12 of Deinococcus radiodurans (Q9RXM0)
| |||
|
2.A.1.63.4 | MFS carrier | Eukaryota |
Fungi, Ascomycota | MFS carrier of Saccharomyces cerevisiae K7 (P47159) | |||
| 2.A.1.64: The Unidentified Major Facilitator-13 (UMF13) Family | |||||||
Similar to 2.A.1.62; may transport amino acids and their derivatives. | |||||||
|
2.A.1.64.1 | The UMF13 protein | Bacteria |
Bacillota | UMF13 of Streptococcus thermophilus (Q5M4L1) | |||
|
2.A.1.64.2 | Uncharacterized protein RP255 | Bacteria |
Pseudomonadota | RP255 of Rickettsia prowazekii | |||
|
2.A.1.64.3 | Uncharacterized protein of 611 aas | Bacteria |
Mycoplasmatota | UP of Spiroplasma diminutum | |||
| 2.A.1.65: The Uncharacterized Major Facilitator-14 (UMF14) Family | |||||||
Possibly this family includes members that transport metabolites such as aromatic acids. | |||||||
|
2.A.1.65.1 | The putative MFS carrier, Sugar Baby (Sug, isoform D); has a hydrophilic domain between TMSs 3 and 4. Overexpression causes an increased lifespan by 17%. It has 12 TMSs in a 3 + 3 + 6 TMS arrangement. | Eukaryota |
Metazoa, Arthropoda | Sugar Baby of Drosophila melanogaster (Q7KUF9) | |||
|
2.A.1.65.2 | Unknown MFS homologue; e-6 with 2.A.1.5 family members; has a hydrophilic domain between TMSs 3 and 4. | Eukaryota |
Metazoa, Arthropoda | UMF14 of Culex quinquefasciatus (B0W435) | |||
|
2.A.1.65.3 | Unknown MFS homologue UMF14 ( 833 aas, 12 TMSs in a 3+9 arrangement ) | Eukaryota |
Metazoa, Arthropoda | UMF14 of Anopheles gambiae (Q7Q0Z9) | |||
|
2.A.1.65.4 | Uncharacterized protein of 474 aas | Eukaryota |
Metazoa, Cnidaria | UP of Nematostella vectensis (Starlet sea anemone) | |||
|
2.A.1.65.5 | MFS porter | Eukaryota |
Metazoa, Arthropoda | MFS porter of Daphnia pulex (E9I268) | |||
|
2.A.1.65.6 | Macrophage MHC Class I receptor 2, Mmr2 or MFSD6. The ortholog of this protein in humans is a also called MFSD6 and is 90% identical to the mouse protein (Bagchi et al. 2020). This disease protein shows increased expression levels with increased energy consumption (Bagchi et al. 2020). | Eukaryota |
Metazoa, Chordata | Mmr2 of Mus musculus (Q8CBH5) | |||
|
2.A.1.65.7 | MFS porter | Eukaryota |
Viridiplantae, Chlorophyta | MFS porter of Chlorella variablis (E1ZG13) | |||
|
2.A.1.65.8 | MFS permease | Bacteria |
Bacillota | MFS permease of Thermoanaerobacter tengcongensis (Q8R7B7) | |||
|
2.A.1.65.9 | Maltose permease | Bacteria |
Bacillota | MalA of Geobacillus stearothermophilus | |||
|
2.A.1.65.10 | Major facilitator superfamily domain-containing protein 6-like, MfsD6Ls, of 586 aas and 12 TMSs. Mutations can cause pediatric cataracts (Aldahmesh et al. 2012). | Eukaryota |
Metazoa, Chordata | MFSD6L of Homo sapiens | |||
|
2.A.1.65.11 | Duplicated MFS permease (901 amino acyl residues; ~24 TMSs) | Eukaryota |
Viridiplantae, Chlorophyta | Duplicated MFS permease of Chlamydomonas reinhardtii | |||
|
2.A.1.65.12 | MFS_1_like domain-containing protein, MFSD6, of 630 aas and 12 TMSs in a 3 + 3 + 6 TMS arrangement. It seems to regulate neural circuit activity (McCulloch et al. 2017). | Eukaryota |
Metazoa, Nematoda | MfsD6 of Caenorhabditis elegans | |||
|
2.A.1.65.13 | MFSD6 of 791 aas and 12 TMSs in a 3 + 3 + 6 TMS arrangement. Mutations in the mfsd-6 gene influence the regulation of neural circuit activity (McCulloch et al. 2017). MfsD6 may transport sugars. | Eukaryota |
Metazoa, Chordata | MfsD6 of Homo sapiens | |||
| 2.A.1.66: The Uncharacterized Major Facilitator-15 (UMF15) Family | |||||||
Most similar to family 2.A.1.49 which functions to transport sphingosine-1-P or sphingosyl lipids. | |||||||
|
2.A.1.66.1 | MFS permease of unknown function (First half resembles 2.A.1.3.7 (e-11) and 2.A.1.15.3 (e-8)). Very likely to be a galactoside/galactose transporter; encoded within a gene cluster with β-galactosidase and galactose metabolic genes. | Archaea |
Thermoproteota | MFS permease of Thermofilum pendens (A1RW34) | |||
|
2.A.1.66.2 | Bacteria |
Spirochaetota | MFS1 of Leptospira interrogans (Q8F7L4) | ||||
|
2.A.1.66.3 | UMF15 Homologue | Eukaryota |
Bacillariophyta | UMF15 homologue of Thalassiosira pseudonana (B8BU21) | |||
|
2.A.1.66.4 | MFS transporter of 531 aas. Present in the membrane of the organelle called the rhoptries which is involved in host invasion and hijacking host cell functions (Peter Bradley, personal communication). | Eukaryota |
Apicomplexa | MFS porter of Toxoplasma gondii | |||
|
2.A.1.66.5 | MFS transporter of 428 aas. Present in the membrane of the organelle called the rhoptries which is involved in host invasion and hijacking host cell functions (Peter Bradley, personal communication). | Eukaryota |
Apicomplexa | Porter of Toxoplasma gondii | |||
|
2.A.1.66.6 | Uncharacterized protein of 646 aas and 12 TMSs | Eukaryota |
Viridiplantae, Chlorophyta | UP of Chlorella variabilis (Green alga) | |||
|
2.A.1.66.7 | Putative MFS carrier of 809 aas and 12 TMSs in a 2 + 4 + 6 TMS arrangement. | Eukaryota |
Apicomplexa | MFS carrier of Plasmodium falciparum | |||
|
2.A.1.66.8 | Pantothenate:H+ symporter, PAT or TMP1 of 565 aas and 12 TMSs in a 6 + 6 TMS arrangement (Wunderlich 2022). | Eukaryota |
Apicomplexa | PAT of Plasmodium falciparum | |||
| 2.A.1.67: The Uncharacterized Major Facilitator-16 (UMF16) Family | |||||||
Most similar to 2.A.21,39 and 51; may export drugs, aromatic acids and/or siderophores | |||||||
|
2.A.1.67.1 | MFS permease of unknown function (second half distantly resembles the first half of 2.A.1.41.3/e value of 0.001) | Bacteria |
Actinomycetota | UMF16 of Kribbella flavida (D2PP09) | |||
|
2.A.1.67.2 | MFS porter | Bacteria |
Actinomycetota | MFS porter of Arthrobacter aurescens (A1R564) | |||
|
2.A.1.67.3 | MFS porter | Bacteria |
Pseudomonadota | MFS porter of Erwinia pyrifoliae (D0FNI7) | |||
|
2.A.1.67.4 | MFS porter of 402 aas and 12 TMSs. | Bacteria |
Actinomycetota | MFS porter of Propionibacterium acnes (D1YEI1) | |||
|
2.A.1.67.6 | MfsB (Smlt0548) (B2FL18) of 404 aas and 12 TMSs in a 6 + 6 TMS arrangement. Its function is not known (Boonyakanog et al. 2022). | Bacteria |
Pseudomonadota | MfsB of Stenotrophomonas maltophilia | |||
| 2.A.1.68: The Glucose Transporter (GT) Family | |||||||
|
2.A.1.68.1 | The glucose transporter, OEOE_1574; does not transport fructose (Kim et al., 2011). | Bacteria |
Bacillota | OEOE_1574 of Oenococcus onei (Q04DP6) | |||
|
2.A.1.68.2 | MFS porter of 409 aas | Archaea |
Euryarchaeota | MFS porter of Methanofollis ethanolicus | |||
|
2.A.1.68.3 | MFS porter | Bacteria |
Bacillota | MFS porter of Blautia producta | |||
| 2.A.1.69: The Uncharacterized Major Facilitator-17 (UMF17) Family | |||||||
|
2.A.1.69.1 | The UMF17A porter | Bacteria |
Actinomycetota | UMF17A porter of Streptomyces coelicolor (Q9KZY0) | |||
|
2.A.1.69.2 | MFS permease of 438 aas | Bacteria |
Actinomycetota | MFS porter of Geodermatophilus obscurus | |||
| 2.A.1.70: The Arsenite/Antimonite Exporter (ArsK) Family | |||||||
One member of this family (2.A.1.70.9) has been characterized as an arsenite/antimonite exporter (Shi et al. 2018). | |||||||
|
2.A.1.70.1 | UMF18A, May be a monocarboxylate uptake transporter based on its sequence similarity with families 2.A.1.11 and 2.A.1.13. | Bacteria |
Actinomycetota | UMF18A of Streptomyces coelicolor (Q9L223) | |||
|
2.A.1.70.2 | UMF18B | Bacteria |
Actinomycetota | UMF18B of Saccharomonospora azurea (G4JJZ0) | |||
|
2.A.1.70.3 | UMF18C | Bacteria |
Actinomycetota | UMF18C of Salinispora tropica (A4X2L1) | |||
|
2.A.1.70.4 | Uncharacterized MFS protein of 412 aas and 12 TMSs. | Bacteria |
Deinococcota | UP of Meiothermus timidus | |||
|
2.A.1.70.5 | Uncharacterized MFS porter of 401 aas and 12 TMSs. | Bacteria |
Pseudomonadota | UP of Belnapia rosea | |||
|
2.A.1.70.6 | Uncharacteerized MFS porter of 434 aas and 12 TMSs | Bacteria |
Bacillota | UP of Halalkalibacillus halophilus | |||
|
2.A.1.70.7 | Uncharacterized MFS porter of 401 aas and 12 TMSs. | Bacteria |
Chloroflexota | UP of Dehalococcoidia bacterium | |||
|
2.A.1.70.8 | Uncharacterized MFS porter of 397 aas and 12 TMSs, annotated in Uniprot as ArsP. The encoding gene is next to genes encoding ArsH (Q1LRL2), an NADPH-dependent FMN reductase, ArsC1, an arsenate reductase (Q1LRL1) and an arsenite efflux pump, ArsB or Acr3 of 10 TMSs (ArsB; Q1LRL0; ACR family, TC# 2.A.59). This MFS family shows greatest similarity with families 2.A.1.11 and 2.A.1.13, both which transport anionic speices, for example, oxalate, formate and pyruvate (TC# 2.A.1.11) and monocarboxylates (TC# 2.A.1.13). It is 32% identical and 52% similar to ArsK (TC# 2.A.1.70.9) which is an arsenite/antimonite exporter (Shi et al. 2018). | Bacteria |
Pseudomonadota | ArsP of Cupriavidus metallidurans (Ralstonia metallidurans) | |||
|
2.A.1.70.9 | ArsK, exporter of arsenite, antimonite, trivalent roxarsone and methylarsenite (Shi et al. 2018). Expression of arsK is induced by arsenite [As(III)], antimonite [Sb(III)], trivalent roxarsone [Rox(III)], methylarsenite [MAs(III)] and arsenate [As(V)], and heterologous expression of ArsK in an arsenic-hypersensitive E. coli strain showed that ArsK is essential for resistance to As(III), Sb(III), Rox(III) and MAs(III) but not to As(V), dimethylarsenite [Dimethyl-As(III)] or Cd(II). ArsK reduces the cellular accumulation of As(III), Sb(III), Rox(III) and MAs(III) but not to As(V) or Dimethyl-As(III). An arsenic regulator gene arsR2 is cotranscribed with arsK, and ArsR2 interacts with the arsR2-arsK promoter region without metalloids but is derepressed by As(III), Sb(III), Rox(III) and MAs(III). Thus, ArsK is an arsenic efflux protein and is regulated by ArsR2 (Shi et al. 2018).
| Bacteria |
Pseudomonadota | ArsK of Rhizobium radiobacter (Agrobacterium tumefaciens; Agrobacterium radiobacter)
| |||
| 2.A.1.71: The Valanimycin-resistance (Val-R) Family | |||||||
|
2.A.1.71.1 | The Valanimycin-resistance determinant, VlmF (probably a valanimycin:H antiporter (Ma et al., 2000)) | Bacteria |
Actinomycetota | VlmF of Streptomyces viridifaciens (Q9LA76) | |||
|
2.A.1.71.2 | The UMF19a porter | Bacteria |
Actinomycetota | UMF19a porter of Streptomyces coelicolor (Q93J85) | |||
|
2.A.1.71.3 | MFS transporter of 375 aas and 11 TMSs | Bacteria |
Actinomycetota | UP of Patulibacter americanus | |||
| 2.A.1.72: The Uncharacterized Major Facilitator-20 (UMF20) Family | |||||||
These proteins are probable MDR exporters. | |||||||
|
2.A.1.72.1 | The UMF20A porter | Bacteria |
Actinomycetota | UMF20A of Streptomyces coelicolor (Q9RL01) | |||
|
2.A.1.72.2 | MFS_1 of 429 aas | Bacteria |
Actinomycetota | MFS_1 of Propionimicrobium lymphophilum | |||
|
2.A.1.72.3 | MFS_1 of 390 aas | Bacteria |
Pseudomonadota | MFS_1 of Mesorhizobium loti | |||
| 2.A.1.73: The Unidentified Major Facilitator-21 (UMF21) Family | |||||||
Most similar to TC# 2.A.1.80. | |||||||
|
2.A.1.73.1 | The UMF21A porter | Bacteria |
Actinomycetota | UMF21A porter of Streptomyces coelicolor (Q9L102) | |||
|
2.A.1.73.2 | MFS permease of 397 aas | Bacteria |
Actinomycetota | MFS permease of Actinoplanes friuliensis | |||
|
2.A.1.73.3 | MFS_1, MilK of 442 aas. | Bacteria |
Actinomycetota | MilK of Streptomyces rimofaciens | |||
| 2.A.1.74: The Uncharacterized Major Facilitator-22 (UMF22) Family | |||||||
Family members may be MDR pumps. | |||||||
|
2.A.1.74.1 | UMF22a porter | Bacteria |
Actinomycetota | UMF22 porter of Streptomyces coelicolor (Q9S243) | |||
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2.A.1.74.2 | MFS_1 of 408 aas | Bacteria |
Bacillota | MFS_1 of Bacillus marmarensis | |||
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2.A.1.74.3 | MFS_1 of 389 aas | Bacteria |
Pseudomonadota | MFS_1 of Variovorax paradoxus | |||
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2.A.1.74.4 | MFS_1 of 401 aas | Bacteria |
Pseudomonadota | MFS_1 of Marinobacter santoriniensis | |||
| 2.A.1.75: The Uncharacterized Major Facilitator-23 (UMF23) Family | |||||||
Most closely related to TC# 2.A.1.11, mono- and di-carboxylate transporters | |||||||
|
2.A.1.75.1 | Probable transporter MCH1. Although the name, "monocarboxylate transporter homologue 1" implies that this system transports monocarboxylates such as lactate, pyruvate and acetate, no evidence for this possibility was obtained (Makuc et al. 2001). Instead, the mch1-5 mutant strain, lacking all 5 such paralogues in yeast showed strongly reduced biomass yields in aerobic glucose-limited chemostat cultures, pointing to the involvement of Mch transporters in mitochondrial metabolism. Indeed, intracellular localization studies indicated that at least some of the Mch proteins reside in intracellular membranes.Thus, the yeast monocarboxylate transporter-homologs perform other functions other than do their mammalian counterparts (Makuc et al. 2001). Possibly they function in intracellular, organellar transport of these acids. | Eukaryota |
Fungi, Ascomycota | MCH1 of Saccharomyces cerevisiae | |||
|
2.A.1.75.2 | MFS putative monocarboxylic acid transporter, UMF23B | Eukaryota |
Fungi, Ascomycota | Mct of Coccidioides posadasii (E9CYW5) | |||
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2.A.1.75.3 | Uncharacterized major facilitator, UMF23C | Eukaryota |
Fungi, Ascomycota | UMF23C of Candida albicans | |||
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2.A.1.75.4 | Uncharacterized major facilitator UMF23D | Eukaryota |
Heterolobosea | UMF23D of Naegleria gruberi | |||
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2.A.1.75.5 | UMF23 permease of 572 aa | Eukaryota |
Viridiplantae, Streptophyta | UMF23 of Arabidopsis thaliana | |||
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2.A.1.75.6 | Uncharacterized protein of 591 aas and 12 TMSs | Eukaryota |
Viridiplantae, Chlorophyta | UP of Chlamydomonas reinhardtii (Chlamydomonas smithii) | |||
|
2.A.1.75.7 | Uncharacterized MFS permease of 530 aas and 12 TMSs. | Eukaryota |
Evosea | UP of Entamoeba histolytica | |||
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2.A.1.75.8 | PICLORAM RESISTANT30 (PIC30) protein of 601 aas and 12 or 14 TMSs. It is a plasma membrane anion uptake porter, transporting picloram and other picolinate herbicides as well as nitrate, chlorate and chloride anions (Kathare et al. 2019). | Eukaryota |
Viridiplantae, Streptophyta | PIC30 of Arabidopsis thaliana | |||
| 2.A.1.76: The Uncharacterized Major Facilitator-24 (UMF24) Family | |||||||
Most similar to 2.A.1.15, aromatic acid porters. | |||||||
|
2.A.1.76.1 | Bacteria |
Mycoplasmatota | Mhp246 of Mycoplasma hyopneumoniae | ||||
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2.A.1.76.2 | Uncharacterized Mycoplama MFS carrier, UMF24B | Bacteria |
Mycoplasmatota | UMF24B of Mycoplasma capricolum | |||
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2.A.1.76.3 | Uncharacterized MFS carrier, UMF24C | Bacteria |
Bacillota | UMF24C of Lactobacillus salivarius | |||
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2.A.1.76.4 | MFS carrier of 525 aas and 12 TMSs. | Bacteria |
Mycoplasmatota | MFS porter of Mycoplasma galisepticum | |||
| 2.A.1.77: The Uncharacterized Major Facilitator-25 (UMF25) Family | |||||||
Most closely related to TC# 2.A.1.15, transporters for organic carboxylates. | |||||||
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2.A.1.77.1 | Unknown Major Facilitator UMF25a | Bacteria |
Planctomycetota | UMF25a of Rhodopirellula baltica | |||
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2.A.1.77.2 | Unknown Major Facilitator, UMF25b | Bacteria |
Planctomycetota | UMF25b of Planctomyces limnophilus | |||
| 2.A.1.78: The Uncharacterized Major Facilitator-26 (UMF26) Family | |||||||
These transporters may be drug porters. | |||||||
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2.A.1.78.1 | UMF26a of 416 aas and 12 TMSs. Encoded by a gene that is adjacent to two ATP hydrolyzing subunits homologous to ABC proteins of the peptide transporters of TC family 3.A.1.5. | Bacteria |
Chlamydiota | UMF26a of Parachlamydia acanthaemoebae (F8KXQ8) | |||
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2.A.1.78.2 | UMF26b of 419 aas and 12 TMSs | Bacteria |
Chlamydiota | UMF26b of Simkania negevensis (F8L9E4) | |||
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2.A.1.78.3 | Bacteria |
Planctomycetota | UMF26c of Phycisphaera mikurensis (I0II84) | ||||
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2.A.1.78.4 | Bacteria |
Verrucomicrobiota | UMF26d of Verrucomicrobiae bacterium (B5JEI3) | ||||
| 2.A.1.79: The Uncharacterized Major Facilitator-27 (UMF27) Family | |||||||
Most similar to TC#2.A.1.11 (carboxylate transporters) and 2.A.1.55 (MDR pumps). | |||||||
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2.A.1.79.1 | MFS permease of 485 aas | Eukaryota |
Rhodophyta | MFS permease of Cyanidioschyzon merolae | |||
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2.A.1.79.2 | Uncharacterized MFS proter of 724 aas and 12 TMSs with a C-terminal hydrophilic extension. | Eukaryota |
Rhodophyta | UP of Chondrus crispus (Carrageen Irish moss) (Polymorpha crispa) | |||
| 2.A.1.80: The Uncharacterized Major Facilitator-28 (UMF28) Family | |||||||
Most similar to TC# 2.A.1.73. | |||||||
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2.A.1.80.1 | Uncharacterized MFS permease of 515 aas | Eukaryota |
Rhodophyta | Putative peremease of Galdieria sulphuraria | |||
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2.A.1.80.2 | MFS_1 of 395 aas | Bacteria |
Myxococcota | MFS1 of Plesiocystis pacifica | |||
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2.A.1.80.3 | MFS_1 of 398 aas. | Bacteria |
Thermodesulfobacteriota | MFS_1 of Desulfobulbus propionicus | |||
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2.A.1.80.4 | MFS transporter of 410 aas. | Bacteria |
Pseudomonadota | MFS1 of Octadecabacter antarcticus | |||
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2.A.1.80.5 | MFS_1 of 401 aas | Bacteria |
Cyanobacteriota | MFS_1 of Crocosphaera watsonii | |||
| 2.A.1.81: The Copper Uptake Porter (Cu-UP) | |||||||
Most similar to TC# 2.A.1.2, MDR pumps. | |||||||
|
2.A.1.81.1 | The copper (Cu2+) uptake porter, CcoA of 405 aas and 12 TMSs. CcoA-mediated Cu2+ import relies on conserved Met and His residues that could act as metal ligands at the membrane-embedded Cu2+-binding domain (Khalfaoui-Hassani et al. 2016). It provides cytoplasmic Cu needed for cbb3-type cytochrome c oxidase (cbb3-Cox) biogenesis (Khalfaoui-Hassani et al. 2021). Residues important for and/or esstential for function have been identified. CcoA undergoes a thiol:disulfide oxidoreduction cycle, which is important for its Cu import activity (Khalfaoui-Hassani et al. 2021). | Bacteria |
Pseudomonadota | CcoA of Rhodobacter capsulatus | |||
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2.A.1.81.2 | Putative copper uptake porter, MFS_1 of 420 aas | Bacteria |
Chloroflexota | MFS_1 of Chloroflexus aggregans | |||
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2.A.1.81.3 | MFS permease of 403 aas. | Bacteria |
Actinomycetota | MFSA permease of Corynebacterium glutamicum | |||
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2.A.1.81.4 | MFS porter of 350 aas | Archaea |
Nitrososphaerota | MFS porter of Candidatus Caldiarchaeum subterraneum | |||
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2.A.1.81.5 | Riboflavin uptake transporter of 398 aas and 12 TMSs, RfnT (Gutiérrez-Preciado et al. 2015). | Bacteria |
Pseudomonadota | RfnT of Ochrobactrum anthropi | |||
| 2.A.1.82: The Plant Copper Uptake Porter (Pl-Cu-UP) | |||||||
Shows very substantial similarity with TC#s 2.A.1.15 (specific for aromatic acids), 2.A.1.19 (specific for organic cations) and 2.A.1.22 (specific for neurotransmitters). | |||||||
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2.A.1.82.1 | The barley copper uptake porter, CT-1 of 749 aas; nearly identical to the wheat orthologue (Li et al. 2013). | Eukaryota |
Viridiplantae, Streptophyta | CT-1 of Hordeum vulgare (F2CRE4) | |||
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2.A.1.82.2 | The putative copper uptake porter, CT1, of 825 aas. The C-terminal domain of 300 aas is a DUF572 (COG5134) domain. | Eukaryota |
Viridiplantae, Chlorophyta | CT1 of Ostreococcus tauri (Q010B9) | |||
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2.A.1.82.3 | Synaptic vesicle 2-related protein (SV2-related protein), SVOP or SLC22B4. This protein localizes to neurotransmitter-containing vesicles and has a nucleotide binding site (Yao and Bajjalieh 2009). ATP, GTP, TTP, CTP and NAD biind, with the highest affinity for NAD, in contrast to SV2 (TC# 2.A.1.22.1), which binds both NAD and ATP with equal affinity. May transport nicotinate. | Eukaryota |
Metazoa, Chordata | Sv2p of Mus musculus | |||
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2.A.1.82.4 | Niacin uptake porter NiaP (Jeanguenin et al. 2012) | Bacteria |
Bacillota | YceI of Bacillus subtilis (O34691) | |||
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2.A.1.82.5 | Uncharacterized MFS protein of 460 aas | Eukaryota |
Viridiplantae, Chlorophyta | UP of Volvox carteri (Green alga) | |||
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2.A.1.82.6 | Synaptic vesicle 2-related protein, SVOPL, of 492 aas and 12 TMSs in a 6 + 1 + 5 TMS arrangement. Gene disruption gives rise to neurocognitive disabilities (Nilsson et al. 2017), and mutations can give rise to retinal dystrophies, hereditary blinding disorders (Patel et al. 2018). SVOPL is also a potential cell survival gene that undergoes allelic switching (Boot et al. 2019). | Eukaryota |
Metazoa, Chordata | SVOPL of Homo sapiens | |||
| 2.A.1.83: The 1-arseno-3-phosphoglycerate exporter (APGE) Family | |||||||
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2.A.1.83.1 | MFS porter; 1-arseno-3-phosphoglycerate (1As3PGA) exporter, ArsJ. Encoded in an operon concerned with arsenic resistance, encoding the enzymes and transporters of a new pathway of arsenic biotransformation. The adjacent gene encodes a 3-phosphoglycerate dehydrogenase homologue that probably forms the substrate of this MFS porter which could be expelled from the cell (Chen et al. 2016). | Bacteria |
Pseudomonadota | ArsJ of Aliivibrio (Vibrio) salmonicida | |||
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2.A.1.83.2 | Putative 1-arseno-3-phosphoglycerate exporter, MFS-83. | Bacteria |
Pseudomonadota | MFS-83 of Ferrimonas balearica | |||
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2.A.1.83.3 | Putative 1-arseno-3-phosphoglycerate exporter of 460 aas (see 2.A.1.83.1). | Eukaryota |
MFS-83 of Ectocarpus siliculosus (Brown alga | ||||
| 2.A.1.84: The 1-arseno-3-phosphoglycerate exporter (APGE) Family | |||||||
This family shows greatest sequence similarity with TC# 2.A.1.2 and 2.A.1.24, MDR export porters. | |||||||
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2.A.1.84.1 | Putative MFS permease of 467 aas and 12 TMSs | Bacteria |
Spirochaetota | MFS permease of Treponema denticola | |||
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2.A.1.84.2 | Uncharacterized protein of 435 aas and 12 TMSs. | Bacteria |
Actinomycetota | UP of Slackia heliotrinireducens (Peptococcus heliotrinreducens) | |||
|
2.A.1.84.3 | Uncharacterized protein | Bacteria |
Actinomycetota | UP of Streptosporangium roseum | |||
| 2.A.1.85: The Uncharacterized Major Facilitator-29 (UMF29) Family | |||||||
The members of this family are not closely related to any other MFS family. | |||||||
| 2.A.1.86: The Uncharacterized Major Facilitator-30 (UMF30) Family | |||||||
|
2.A.1.86.1 | MFS uptake permease. The gene is adjacent to a putative SAM-dependent methyl transferase, one homologue of which is a puromycin methyl transferase. Perhaps the transport substrate is a drug that is modified by methylation for detoxification purposes. This family is most closely, but distantly related to the AAHS family (2.A.1.15). | Bacteria |
Myxococcota | MFS uptake permease of Myxococcus xanthus | |||
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2.A.1.86.2 | Bacteria |
Pseudomonadota | Fused protein of Thiocapsa marina | ||||
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2.A.1.86.3 | Uncharacterized protein of 512 aas and 7 TMSs. | Bacteria |
Pseudomonadota | UP of Candidatus Thiodiazotropha endoloripes | |||
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2.A.1.86.4 | Uncharacterized putative S-adenosyl-L-methionine-dependent methyltransferase with a 7 TMS N-terminus (Pegg and Michael 2010). | Bacteria |
Pseudomonadota | UP of Magnetospirillum gryphiswaldense | |||
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2.A.1.86.5 | Polyamine aminopropyltransferase or spermidine synthase of 516 aas and 7 N-terminal TMSs. | Bacteria |
Pseudomonadota | SpeE of Comamonas testosteroni | |||
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2.A.1.86.6 | Putative MFS transporter, SVOPL or SLC22B5 (in humans), of 706 aas and 13 TMSs with two repeats of 6 TMSs with the 13th TMS being the extra one. | Bacteria |
Candidatus Tectomicrobia | MFS porter of Candidatus Entotheonella palauensis | |||
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2.A.1.86.7 | Uncharacterized protein of 212 aas and 6 TMSs. | Bacteria |
Pseudomonadota | UP of Legionella maceachernii (Tatlockia maceachernii) | |||
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2.A.1.86.8 | Uncharacterized protein of 688 aas and 14 TMSs in a 7 TMS + large hydrophilic domain + 7 more TMSs. | Bacteria |
Thermodesulfobacteriota | UP of Desulfosarcina alkanivorans | |||
| 2.A.1.87: The Uncharacterized Major Facilitator-31 (UMF31) Family | |||||||
|
2.A.1.87.1 | Uncharacterized protein of 435 aas and 12 TMSs in a 6 + 6 arrangement. It most resembles 2.A.1.3.53, an azole resistance protein. Therefore, this protein might be a drug exporter. | Bacteria |
Actinomycetota | UP of Gardnerella vaginalis | |||
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2.A.1.87.2 | Uncharacterized MFS protein of 431 aas and 12 TMSs. | Bacteria |
Actinomycetota | UP of Arcanobacterium haemolyticum | |||
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2.A.1.87.3 | Uncharacterized MFS protein of 423 aas and 12 TMSs. | Bacteria |
Pseudomonadota | UP of Kushneria konosiri | |||
| 2.A.1.88: The Uncharacterized Major Facilitator-32 (UMF32) Family | |||||||
|
2.A.1.88.1 | Uncharacterized protein of 434 aas and 12 TMSs. | Archaea |
Candidatus Lokiarchaeota | UP of Lokiarchaeum sp. | |||
|
2.A.1.88.2 | Uncharacterized protein of 430 aas and 12 TMSs. | Archaea |
Candidatus Lokiarchaeota | UP of Lokiarchaeum sp. | |||
| 2.A.1.89: The Uncharacterized Major Facilitator-33 (UMF33) Family | |||||||
|
2.A.1.89.1 | UP of 535 aas and 11 TMSs | Archaea |
Candidatus Lokiarchaeota | UP of Candidatus Lokiarchaeota archaeon CR_4 | |||
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2.A.1.89.2 | Uncharacteerized protein of 563 aas and 12 TMSs in a 6 + 6 TMS arrangement. | Archaea |
Candidatus Lokiarchaeota | UP of Candidatus Lokiarchaeota archaeon CR_4 | |||
| 2.A.1.90: The Uncharacterized Major Facilitator-34 (UMF34) Family | |||||||
|
2.A.1.90.1 | MFS porter, MFR3, putative amino acid transporter of 579 aas and 12 TMSs in a 1 + 3 + 2 + 6 TMS arrangement (Wunderlich 2022). | Eukaryota |
Apicomplexa | MFR3 of Plasmodium falciparum | |||
|
2.A.1.90.2 | Putative amino acid transporter, MFR2, of 711 aas and 12 TMSs in a 1 + 5 + 6 TMS arrangement (Wunderlich 2022). | Eukaryota |
Apicomplexa | MFR2 of Plasmodium falciparum | |||
|
2.A.1.90.3 | MFS porter, MFR4 or ApiAT2, of 516 aas and 12 TMSs in a 1 + 5 + 6 TMS arrangement (Wunderlich 2022). | Eukaryota |
Apicomplexa | MFR4 of Plasmodium falciparum | |||
|
2.A.1.90.4 | Putative amino acid transporter, MFR5 or ApiAT4 of 609 aas and 12 TMSs in a 1 + 5 + 6 TMS arrangement (Wunderlich 2022). | Eukaryota |
Apicomplexa | MFR5 of Plasmodium falciparum | |||
|
2.A.1.90.5 | Uncharacterized MFS porter, NPT1 or ApiAT8, of 577 aas and 12 TMSs in a 1 + 5 + 6 TMS arrangement (Wunderlich 2022). | Eukaryota |
Apicomplexa | NPT1 of Plasmodium falciparum | |||
| 2.A.1.91: The Uncharacterized Major Facilitator-35 (UMF35) Family | |||||||
|
2.A.1.91.1 | MFS porter of unknown function, P115, of 1283 aas and 12 TMSs in a 1 + 2 + 3 + 6 TMS arrangement (Wunderlich 2022). | Eukaryota |
Apicomplexa | P115 of Plasmodium falciparum | |||
|
2.A.1.91.2 | Uncharacterized MFS domain-containing protein, P115, of 984 aas and 12 TMSs in a 1 + 2 + 3 + 6 TMS arrangement. | Eukaryota |
Apicomplexa | P115 of Plasmodium chabaudi chabaudi | |||
|
2.A.1.91.3 | Uncharacterized protein of 1156 aas with 12 TMSs in a 1 (N-terminal) + 2 (residues 140 - 200) + 3 (residues 370 - 470) + 6 (residues 940 - 1140) TMS arrangement. | Eukaryota |
Apicomplexa | UP of Plasmodium malariae | |||
|
2.A.1.91.4 | Plasmodium protein of 1061 aas and 10 = 12 TMSs in a 1 + 2 + 3 + 4 - 6 TMS arrangement. | Eukaryota |
Apicomplexa | Conserved protein of Plasmodium ovale curtisi | |||