TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*2.A.21.1.1









Bacteria
Proteobacteria
PanF of E. coli
*2.A.21.2.1









Proline:Na+ symporter, PutP (Jung et al., 2012).  Extracellular loop 4 (eL4) controls periplasmic entry of substrate to the binding site (Raba et al. 2014).  Interactions between the tip of eL4 and the peptide backbone at the end of TMS 10 participate in coordinating conformational alterations underlying the alternating access mechanism of transport (Bracher et al. 2016).  TMS 6 plays a central role in substrate (both Na+ and proline) binding and release on the inner side of the membrane, and functionally relevant amino acids have been identified (Bracher et al. 2016).

Bacteria
Proteobacteria
PutP of E. coli
*2.A.21.2.2









Sodium/proline symporter (Proline permease)
Bacteria
Firmicutes
PutP of Staphylococcus aureus
*2.A.21.2.3









L-proline uptake porter, PutP.  Proline is used via this system as a carbon and nitrogen source.  Induced by proline (Johnson et al. 2008).

Bacteria
Proteobacteria
PutP of Pseudomonas aeruginoas
*2.A.21.2.4









The high affinity nutritional proline uptake porter, PutP.  PutP is inducible by external (but not internal) proline in a poorly defined process dependent on PutR (Moses et al. 2012). 

Bacteria
Firmicutes
PutP of Bacillus subtilis
*2.A.21.2.5









Proline uptake porter, OpuE (YerK) (von Blohn et al. 1997).  Regulated by osmotic stress (high osmolarity).  Induction involves σB and σA (Spiegelhalter and Bremer 1998).

Bacteria
Firmicutes
OpuE of Bacillus subtilis
*2.A.21.2.6









High affinity proline-specific Na+:proline symporter, PutP (Rivera-Ordaz et al. 2013).  Proline is a preferred source of energy for this microaerophilic bacterium.  PutP is efficiently inhibited by the proline analogs, 3,4-dehydro-D,L-proline and L-azetidine-2-carboxylic acid.

Bacteria
Proteobacteria
PutP of Helicobacter pylori
*2.A.21.3.1









Glucose or galactose:Na+ symporter, SGLT1 (galactose > glucose > fucose). Cotransports water against an osmotic gradient (Naftalin, 2008). TMS IV of the high-affinity sodium-glucose cotransporter participates in sugar binding (Liu et al., 2008).  Also participates in the uptake of resveratrol, an anti atherosclerosis polyphenol (Chen et al. 2013).  hSGLT1 is expressed as a disulfide bridged homodimer via C355; a portion of the intracellular 12-13 loop is re-entrant and readily accessible from the extracellular milieu (Sasseville et al. 2016).

Eukaryota
Metazoa
SLC5A1 of Homo sapiens
*2.A.21.3.2









Glucose or galactose:Na+ symporter, SglS or SglT. The 3.0Å structure is known (Faham et al., 2008). Sodium exit causes a reorientation of transmembrane helix 1 that opens an inner gate required for substrate exit (Watanabe et al., 2010). The involvement of aromatic residue pi interactions, especially with Na+ binding, has been examined (Jiang et al. 2012).

Bacteria
Proteobacteria
SglS of Vibrio parahaemolyticus
*2.A.21.3.3









Nucleoside or glucose(?):Na+ symporter
Eukaryota
Metazoa
SNST of Oryctolagus cuniculus
*2.A.21.3.4









Glucose:Na+ symporter 3 (low affinity)
Eukaryota
Metazoa
SAAT1 of Sus scrofa
*2.A.21.3.5









Myoinositol:Na+ symporter, SMIT1 (Aouameur et al., 2007).
Eukaryota
Metazoa
SMIT of Canis familiaris
*2.A.21.3.6









Myoinositol:Na+ symporter, SMIT2 (also transports D-chiro-inositol, D-glucose and D-xylose) (Coady et al., 2002; Aouameur et al., 2007).  A 5-state model includes cooperative binding of Na+, strong apparent asymmetry of the energy barriers, a rate limiting step which is likely associated with the translocation of the empty transporter, and a turnover rate of 21 s-1 (Sasseville et al. 2014).

Eukaryota
Metazoa
SLC5A11 of Homo sapiens
*2.A.21.3.7









Putative sialic acid uptake permease, NanP (D.A. Rodionov, pers. commun.)
Bacteria
Proteobacteria
NanP of Vibrio fischeri (Q5E733)
*2.A.21.3.8









The putative mannose porter, ManPll (Rodionov et al. 2010).

Bacteria
Proteobacteria
ManPll of Shewanella amazonensis (A1S2A8)
*2.A.21.3.9









The putative galactose porter, GalPll (Rodionov et al., 2010).

Bacteria
Proteobacteria
GalPll of Shewanella pealeana (A8H019)
*2.A.21.3.10









Na+-dependent, smf-driven, sialic acid transporter, STM1128 (NanP) (Severi et al., 2010). Also transports the related sialic acids, N-glycolylneuraminic acid (Neu5Gc) and 3-keto-3-deoxy-d-glycero-d-galactonononic acid (KDN) (Hopkins et al. 2013). 

Bacteria
Proteobacteria
STM1128 (NanP) of Salmonella enterica (Q8ZQ35)
*2.A.21.3.11









The alginate oligosaccharide uptake porter, ToaA (Wargacki et al., 2012).

Bacteria
Proteobacteria
ToaA in Vibrio splendida (A3UWQ1) 
*2.A.21.3.12









The alginate oligosaccharide uptake porter, ToaB (Wargacki et al., 2012).

Bacteria
Proteobacteria
ToaB in Vibrio splendida (A3UWQ9)
*2.A.21.3.13









The alginate oligosaccharide uptake porter, ToaC (Wargacki et al., 2012).

Bacteria
Proteobacteria
ToaC in Vibrio splendida (A3UR54)
*2.A.21.3.14









Sodium/myo-inositol cotransporter (Na(+)/myo-inositol cotransporter) (Sodium/myo-inositol transporter 1) (SMIT1) (Solute carrier family 5 member 3)
Eukaryota
Metazoa
SLC5A3 of Homo sapiens
*2.A.21.3.15









Sodium/glucose cotransporter 5 (Na+/glucose cotransporter 5) (Solute carrier family 5 member 10)

Eukaryota
Metazoa
SLC5A10 of Homo sapiens
*2.A.21.3.16









Sodium/glucose cotransporter 2 (Na+/glucose cotransporter 2) (Low affinity sodium-glucose cotransporter) (Solute carrier family 5 member 2) of 672 aas and 14 TMSs.  Shows increased expression in human diabetic nephrophathy. Inhibition causes decreased renal lipid accumulation, inflamation and disease symptoms (Wang et al. 2017).

Eukaryota
Metazoa
SLC5A2 of Homo sapiens
*2.A.21.3.17









Sodium/glucose cotransporter 4 (Na+/glucose cotransporter 4) (hSGLT4) (Solute carrier family 5 member 9).  The involvement of aromatic residue pi interactions, especially with Na+ binding, has been examined (Jiang et al. 2012).

Eukaryota
Metazoa
SLC5A9 of Homo sapiens
*2.A.21.3.18









Low affinity sodium-glucose cotransporter (Sodium/glucose cotransporter 3) (Na+/glucose cotransporter 3) (Solute carrier family 5 member 4)

Eukaryota
Metazoa
SLC5A4 of Homo sapiens
*2.A.21.3.19









The putative arabinose porter, AraP (Rodionov D.A., personal communication). Regulated by arabinose regulon AraR.

Bacteria
Bacteroidetes/Chlorobi group
AraP (Q8AAV7) of Bacteroides thetaiotaomicron
*2.A.21.3.20









NanT sialic acid transporter of 500 aas (Anba-Mondoloni et al. 2013).

Bacteria
Firmicutes
NanT of Lactobacillus sakei
*2.A.21.3.21









Putative sugar:sodium symporter of 571 aas and 15 TMSs, YidK

Bacteria
Proteobacteria
YidK of E. coli
*2.A.21.3.22









Renal Na+:D-glucose symporter type 1 (Sglt1; Slc5a1) of 662 aas and 14 TMSs.  The distribution in renal tissues has been reported (Althoff et al. 2007). Loop 13, which is associated with phlorizin binding, is variable, as is the interaction with this inhibitor in various species. Immunoreaction was observed in the proximal tubular segments PIa and PIIa, the early distal tubule, and the collecting tubule. Thus, Leucoraja, in contrast to the mammalian kidney, employs only SGLT1 to reabsorb D-glucose in the early, as well as in the late segments of the proximal tubule and probably also in the late distal tubule. It differs from the kidney of the close relative, Squalus acanthias, which uses SGLT2 in more distal proximal tubular segments (Althoff et al. 2007).

Eukaryota
Metazoa
Sglt1 of Leucoraja erinacea (Little skate) (Raja erinacea)
*2.A.21.4.1









The monocarboxylate uptake (H+ symport?) permease, MctP (transports lactate (Km = 4.4 μM), pyruvate (Km = 3.8), propionate, butyrate (butanoic acid), α-hydroxybutyrate, L- and D-alanine (Km = 0.5 mM), and possibly cysteine and histidine) (Hosie et al., 2002).

Bacteria
Proteobacteria
MctP of Rhizobium leguminosarum
*2.A.21.4.2









Uncharacterized symporter YodF.  It is regulated by the global transcriptional regulator responding to nitrogen availablity, TnrA, suggesting the YodF transports a nitrogenous compound (Yoshida et al. 2003).

Bacteria
Firmicutes
YodF of Bacillus subtilis
*2.A.21.5.1









Sodium iodide symporter (NIS; also transports other monovalent anions including: ClO3-, SCN-, SeCN-, NO3-, Br-, BF4-, IO4- and BrO3-). It mediates electroneutral active transport of the environmental pollutant perchlorate (Dohan et al., 2007). Five beta-OH group-containing residues (Thr-351, Ser-353, Thr-354, Ser-356, and Thr-357) and Asn-360, all of which putatively face the same side of the helix in TMS IX, plus Asp-369, located in the membrane/cytosol interface, play key roles in NIS function and seem to be involved in Na+ binding/translocation (De la Vieja et al. 2007). Thr-354 is essential for iodide uptake (Tatsumi et al., 2010). The stoichiometry is Na+:I-= 2:1. The G39R mutant (congenital) is inactive. G93 is a pivot for the inwardly to outwardly conformational change (Paroder-Belenitsky et al., 2011).  The protein is present as a dimer (Huc-Brandt et al. 2011).  Functionally equivalent systems have been reviewed (Darrouzet et al. 2014). mutations cause congenital I- transport defects (ITD; Li et al. 2013).  The physiological, medical and mechanistic features of NIS have been reviewed (Portulano et al. 2014).

Eukaryota
Metazoa
SLC5A5 of Homo sapiens
*2.A.21.5.2









Na+-dependent multivitamin (pantothenate, biotin, lipoate) transporter (de Carvalho and Quick 2011). Broad specificity. May be useful for drug delivery using biotin-conjugated drugs such as Biotin-Acyclovir (B-ACV) (Vadlapudi et al. 2012).  Present in the inclusion membrane that encases Chlamydia trachomatis where it transports vitamins such as biotin (Fisher et al. 2012).  May also take up iodide (de Carvalho and Quick 2011).

Eukaryota
Metazoa
SMVT of Rattus norvegicus
*2.A.21.5.3









Na+-dependent short chain fatty acid transporter SLC5A8 (tumor suppressor gene product, down-regulated in colon cancer) (substrates: lactate, pyruvate, acetate, propionate, butyrate (Km ≈1 mM)) [propionate:Na+ = 1:3] (Miyauchi et al., 2004). Pyroglutamate (5-oxoproline) is also transported in a Na+- coupled mechanism (Miyauchi et al., 2010). SMCT1 and SMCT2 may transport monocarboxylate drugs (e.g. nicotinate and its derivatives) across the intestinal brush boarder membrane (Gopal et al., 2007; Frank et al. 2008). Wilson et al., 2009 have proposed mechanistic details. SMCT1 can transport urate in a testosterone regulated process (Hosoyamada et al., 2010).  It's phsiological functions have been reviewed (Halestrap 2013). Transports anti-tumor agents, 3-bromopyruvate anddichloroacetate (Su et al. 2016).

Eukaryota
Metazoa
SLC5A8 of Homo sapiens
*2.A.21.5.4









The low affinity (Km (lactate) = 2mM) electroneutral Na+:monocarboxylate (lactate, pyruvate, butyrate, nicotinate) transporter, SMCTn (Plata et al., 2007)
Eukaryota
Metazoa
SMCTn of Danio rerio
(Q7T384)
*2.A.21.5.5









The high affinity (Km (lactate) = 0.2mM) electrogenic Na+ monocarboxylate (lactate, pyruvate, butyrate, nicotinate) transporter, SMCTe (Plata et al., 2007).
Eukaryota
Metazoa
SMCTe of Danio rerio
(Q3ZMH1)
*2.A.21.5.6









Sodium-coupled monocarboxylate transporter 2 (Electroneutral sodium monocarboxylate cotransporter) (Low-affinity sodium-lactate cotransporter) (Solute carrier family 5 member 12)
Eukaryota
Metazoa
SLC5A12 of Homo sapiens
*2.A.21.5.7









Sodium-dependent multivitamin transporter (Na+-dependent multivitamin transporter) (Solute carrier family 5 member 6)

Eukaryota
Metazoa
SLC5A6 of Homo sapiens
*2.A.21.5.8









Sodium-coupled transporter, SLC5A11 or cupcake of 600 aas.  A mutant lacking this protein is insensitive to the nutritional value of sugars. It is most similar to mammalian sodium/monocarboxylate co-transporters.  It was prominently expressed in 10-13 pairs of R4 neurons of the ellipsoid body in the brain and functioned in these neurons for selecting appropriate foods (Dus et al. 2013).

Eukaryota
Metazoa
Cupcake of Drosophila melanogaster
*2.A.21.6.1









Urea active transporter (also transports polyamines; Uemura et al., 2007; Kashiwagi and Igarashi, 2011).

Eukaryota
Fungi
DUR3 of Saccharomyces cerevisiae
*2.A.21.6.2









The major transporter for high-affinity urea transport across the plasma membrane of nitrogen-deficient Arabidopsis roots, Dur3 (Kojima et al., 2006; Mérigout et al., 2008). An orthologue of the same function has been characterized in corn (ZmDUR3) (Liu et al. 2014),

Eukaryota
Viridiplantae
Dur3 of Arabidopsis thaliana (Q9FHJ8)
*2.A.21.6.3









Rice Dur3 (like 2.A.21.6.2; Wang et al., 2012)

Eukaryota
Viridiplantae
DUR3 of Oryza sativa (Q7XBS0)
*2.A.21.6.4









Probable histatin 5 antimicrobial peptide uptake system. May also take up spermidine and be required for morphogenesis (Mayer et al., 2012).

Eukaryota
Fungi
Dur31 of Candida albicans (Q59VF2)
*2.A.21.6.5









Fungal SSS homologue

Eukaryota
Fungi
TRP homologue of Neurospora crassa
*2.A.21.6.6









Urea transporter, UreA of 693 aas.  A three-dimensional model of UreA which, combined with mutagenesis studies, led to the identification of residues important for binding, recognition and translocation of urea, and in the sorting of UreA to the membrane. Residues W82, Y106, A110, T133, N275, D286, Y388, Y437 and S446, located in transmembrane helixes 2, 3, 7 and 11, were found to be involved in the binding, recognition and/or translocation of urea and the sorting of UreA to the membrane. Y106, A110, T133 and Y437 seem to play a role in substrate selectivity, while S446 is necessary for proper sorting of UreA to the membrane (Sanguinetti et al. 2014).

Eukaryota
Fungi
UreA of Emericella nidulans (Aspergillus nidulans)
*2.A.21.7.1









Phenylacetate permease, Ppa
Bacteria
Proteobacteria
Phenylacetate permease Ppa of Pseudomonas putida
*2.A.21.7.2









Acetate/glyoxylate permease, ActP (Gimenez et al., 2003).  Also transports tellurite (TeO32-) (Elías et al. 2015).

Bacteria
Proteobacteria
ActP (YjcG) of E. coli (NP_418491)
*2.A.21.7.3









Pyruvate/acetate/propionate: H+ symporter, MctC (DhlC; cg0953).
Bacteria
Actinobacteria
MctC of Corynebacterium glutamicum (Q8NS49)
*2.A.21.7.4









Acetate uptake permease, ActP1; also takes up tellurite (Borghese and Zannoni 2010; Borghese et al. 2011Borghese et al. 2011).

Bacteria
Proteobacteria
ActP1 of Rhodobacter capsulatus
*2.A.21.7.5









Acetate permease ActP-2/ActP2/ActP3 (Borghese and Zannoni 2010; Borghese et al. 2011).  Also takes up tellurite (TeO32-) (Borghese et al. 2016).

Bacteria
Proteobacteria
ActP2 of Rhodobacter capsulatus
*2.A.21.8.1









High affinity neuronal choline:Na+ symporter, CHT1 (chloride-dependent).  Present in presynaptic terminals of cholinergic neurons.  Has 13 TMSs (Haga 2014).

Eukaryota
Metazoa
CHT1 of Rattus norvegicus
*2.A.21.8.2









High affinity choline transporter 1 (Hemicholinium-3-sensitive choline transporter) (CHT1) (Solute carrier family 5 member 7).  It is required for synthesis of acetyl choline in cholinergic nerve terminals.  It's 13 TMS topology has been verified with an extracellular N-terminus and an intracellular C-terminus.  It is likely to be a homooligomer (Okuda et al. 2012).  It is defective in hereditary motor neuropathy (Barwick et al. 2012).

Eukaryota
Metazoa
SLC5A7 of Homo sapiens
*2.A.21.8.3









Putative porter of 436 aas and 13 TMSs

Bacteria
Spirochaetes
Porter of Leptospira biflexa
*2.A.21.9.1









The nitrogen sensor-receptor domain of the CbrA sensor kinase
Bacteria
Proteobacteria
CbrA sensor domain of Pseudomonas aeruginosa
*2.A.21.9.2









The proline sensor-receptor domain of the PrlS sensor kinase
Bacteria
Proteobacteria
PrlS of Aeromonas hydrophila