TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
2.A.47.1.1









Anion transporter of unknown specificity
Archaea
Euryarchaeota
Anion transporter of Methanospirillum hungatei (Q2FMC1)
2.A.47.1.2









Renal sodium:sulfate cotransporter (Ssc, NaSi-1 or Nas1) (also transports tungstate, molybdate, thiosulfate and selenate) (Beck and Markovich 2000; Lee et al 2006; Li and Pajor, 2003; Bergeron et al. 2013).

Eukaryota
Metazoa, Chordata
Ssc of Rattus norvegicus
2.A.47.1.3









The brush boarder intestinal and renal electrogenic, Na -dependent, low affinity (0.1-4.0mM), dicarboxylate (succinate, fumarate, malate, α-ketoglutarate, oxaloacetate, L- and D-glutamate, and citrate):H cotransporter, NaDC-1 or SDCT1.  Functions in acid regulation.  An acidic pH  stimullates citrate uptake; acid stimulation is mediated by endothelin-1 (ET-1) and its receptor (Liu et al. 2010).

Eukaryota
Metazoa, Chordata
NaDC-1 or SDCT1 of Rattus norvegicus (O35055)
2.A.47.1.4









The basolateral intestinal and renal electrogenic, Na+-dependent high affinity (2-50µM) dicarboxylate:(Na+)3 cotransporter (NaDC-3) (substrate range similar to that of NDC-1 except that tricarboxylates are transported with very low affinity). Na+:succinate = 3:1. Also transports N-acetyl-L-aspartate, an abundant amino acid in the nervous system (Yodoya et al., 2006).
Eukaryota
Metazoa, Chordata
NaDC-3 of Rattus norvegicus
2.A.47.1.5









Basolateral Na+: di- and tricarboxylate (succinate cis-aconitate, citrate, etc.) cotransporter, fNaDC-3
Eukaryota
Metazoa, Chordata
fNaDC-3 of Pseudopleuronectes americanus (the winter flounder)
2.A.47.1.6









The tonoplast dicarboxylate (malate) transporter, AtDCT (Kovermann et al., 2007).  The ortholog (70% identity) in tomatos increases the malate while decreasing the citrate concentrations, influencing flavor (Liu et al. 2017).

Eukaryota
Viridiplantae, Streptophyta
AttDT of malate:Na+ symporter (and possibly malate:citrate antiporter) of Arabidopsis thaliana
2.A.47.1.7









Low affinity dicarboxylate:Na+ symporter, NaDC1 (INDY1) (relative affinities: succinate > fumarate > α-ketoglutarate > malate > lactate > maleate) (Fei et al., 2003).

Eukaryota
Metazoa, Nematoda
NaDC1 of Caenorhabditis elegans
2.A.47.1.8









High affinity dicarboxylate:Na+ symporter, NaDC2 (INDY2) (relative affinities: fumarate > malate > α-ketoglutarate > maleate > succinate > lactate) (Fei et al., 2003)
Eukaryota
Metazoa, Nematoda
NaDC2 of Caenorhabditis elegans
2.A.47.1.9









Na+-coupled citrate transporter (NaCT) (Km=20 μM) (also may transport dicarboxylates and other tricarboxylates with lower affinity) (Inoue et al., 2002b; Bergeron et al. 2013). Na+:citrate = 3-4:1 (Wada et al., 2006).Targeting longevity gene SLC13A5 provides a novel approach to preventing age-related bone fragility and osteoporosis (Zahn et al. 2023).  Novel homozygous variants of SLC13A5 expand the functional heterogeneity of a homogeneous syndrome of early infantile epileptic encephalopathy (Bergeron et al. 2013). Na+:citrate = 3-4:1 (Wada et al., 2006).Targeting longevity gene SLC13A5 provides a novel approach to preventing age-related bone fragility and osteoporosis (Zahn et al. 2023).  Novel homozygous variants of SLC13A5 expand the functional heterogeneity of a homogeneous syndrome of early infantile epileptic encephalopathy (Alsemari et al. 2024).

Eukaryota
Metazoa, Chordata
SLC13A5 of Homo sapiens
2.A.47.1.10









Cation-independent, electroneutral tri- and di-carboxylate transporter with a preference for tricarboxylates, Indy (I'm not dead yet) [When Indy is mutated flies live about twice as long as wild type] (Inoue et al., 2002)
Eukaryota
Metazoa, Arthropoda
Indy of Drosophila melanogaster (Q9VVT2)
2.A.47.1.11









The Na+ (or Li+):dicarboxylate (2:1) symporter, SdcS (catalyzes succinate:succinate antiport as well as electroneutral symport in reconstituted proteoliposomes (Hall and Pajor, 2007; Joshi and Pajor, 2009).  Transports succinate, malate and fumarate with similar affiinities (7 μM, 8 μM and 15 μM, respectively), but aspartate and α-ketoglutarate with very low affinities (Hall and Pajor 2005; Hall and Pajor 2007). 

Bacteria
Bacillota
SdcS of Staphylococcus aureus (Q2FFH9)
2.A.47.1.12









The aerobic dicarboxylate (succinate (Km, 30 μM), fumarate (Km, 79 μM), malate (Km, 360 μM)) transporter, DcsT or DccT.  Also transports oxaloacetate with low affinity (Ebbighausen et al. 1991; Teramoto et al., 2008; Youn et al. 2008Youn et al. 2008).

Bacteria
Actinomycetota
DcsT (DccT) of Corynebacterium glutamicum (A4QAL6)
2.A.47.1.13









The Na+-coupled dicarboxylate (succinate; malate; fumarate) transporter, SdcL (transports aspartate, α-ketoglutarate and oxaloacetate with low affinity). Km for succinate, ~6 μM; Km for Na+, 0.9 mM; Na :substrate = 2:1 (Strickler et al., 2009).

Bacteria
Bacillota
SdcL of Bacillus licheniformis (Q65NC0)
2.A.47.1.14









solute carrier family 13 (sodium/sulfate symporters), member 4, NaS2.  Transports anions such as sulfate, thiosulfate and selenate (Bergeron et al. 2013).

Eukaryota
Metazoa, Chordata
SLC13A4 of Homo sapiens
2.A.47.1.15









Solute carrier family 13 member 3, SLC13A3 (Na+/dicarboxylate cotransporter 3; NaDC-3; hNaDC3; SDCT2) (Sodium-dependent high-affinity dicarboxylate transporter 2) of 602 aas with about 16 TMSs in a possible 4 - 7 + 9 or 10 TMS arrangement.  (Bergeron et al. 2013; Schlosser et al. 2023). The SLC13A3 gene encodes a plasma membrane-localized Na+/dicarboxylate cotransporter 3 (NaDC3) primarily expressed in the kidney, astrocytes and choroid plexus. In addition to three Na+ ions, it brings four to six carbon dicarboxylates into the cytosol (Hussain et al. 2023).  Patients with acute reversible leukoencephalopathy and α-ketoglutarate accumulation (ARLIAK) carry pathogenic mutations in the SLC13A3 gene (Hussain et al. 2023).

Eukaryota
Metazoa, Chordata
SLC13A3 of Homo sapiens
2.A.47.1.16









Solute carrier family 13 member 1 (Renal and intestinal sodium/sulfate cotransporter) (Na+/sulfate cotransporter) (hNaSi-1).  Also transports thiosulfate and selenium.  It is inhibited by many di- and tri-valent organic and inorganic anions (Markovich 2013).

Eukaryota
Metazoa, Chordata
SLC13A1 of Homo sapiens
2.A.47.1.17









Solute carrier family 13 member 2 (Na /di- and tricarboxylate cotransporter 1) (NaDC-1) (Renal sodium/dicarboxylate cotransporter).  Transports citrate and other Krebs cycle intermediates across the apical membrane of kidney proximal tubules and small intestinal cells (Pajor and Sun 2010; Bergeron et al. 2013). Transmembrane helices 7 and 11 in NaDC1 contains residues critical for function (Pajor and Sun 2010; Pajor et al. 2011). The mouse ortholog can transport succinate and adipate, but the rabbit transporter transports only succinate. Multiple amino acids in TMSs 8, 9 and 10 contribute to the transport of adipate, and A504 plays an important role while TMSs 3 and 4 function in substrate recognitioin (Oshiro and Pajor 2006; Oshiro et al. 2006). Pajor and Randolph 2005 have provided evidence for large-scale changes in the structure of NaDC-1 during the transport cycle.

 

Eukaryota
Metazoa, Chordata
SLC13A2 or NaDC1 of Homo sapiens
2.A.47.1.18









Organic acid transporter, SdcF.  Transports succinate, malate, fumarate, tartrate and oxaloacetate (A. Pajor, personal communication)

Bacteria
Bacillota
SdcF of Bacillus licheniformis
2.A.47.1.19









Solute carrier family 13, Slc13a1; Sodium/sulfate symporter, member 1, NaS1 of 583 aas and 14 TMSs.  Na+-sulfate cotransport is inhibited by thiosulfate, selenate, molybdate and tungstate (Markovich et al. 2008).

Eukaryota
Metazoa, Chordata
NaS1 of Danio ririo
2.A.47.2.1









Inorganic phosphate transporter, Pho87 of 923 aas and 12 TMSs. Also transports selenite (Lazard et al., 2010).

Eukaryota
Fungi, Ascomycota
Pho87 of Saccharomyces cerevisiae
2.A.47.2.2









Vacuolar low affinity phosphate transporter, Pho91 (Estrella et al., 2008) with 12 C-terminal TMSs and an N-terminal 360 hydrophilic region. Also transports selenite (Lazard et al., 2010). Pyrophosphate stimulates the phosphate-sodium symporter of Trypanosoma brucei (TC# 2.A.47.2.4) acidocalcisomes and Saccharomyces cerevisiae vacuoles (this protein) (Potapenko et al. 2019).

Eukaryota
Fungi, Ascomycota
Pho91 of Saccharomyces cerevisiae (P27514)
2.A.47.2.3









Low affinity phosphate transporters (881aas). Also transports selenite (Lazard et al., 2010).

 

Eukaryota
Fungi, Ascomycota
Pho90 of Saccharomyces cerevisiae (P39535)
2.A.47.2.4









Contractile vacuole phosphate:Na+ symporter of 727 aas and 12 TMSs, Pho91 (Pho90; Pho87).  Has an N-terminal SPX domain and a C-terminal anion permease domain. Plays an indirect role in pyrophosphate and oligophosphate synthesis (Jimenez and Docampo 2015).  Pyrophosphate stimulates the phosphate-sodium symporter of Trypanosoma brucei acidocalcisomes and Saccharomyces cerevisiae vacuoles (Potapenko et al. 2019).

Eukaryota
Euglenozoa
Pho91 of Trypanosoma cruzi
2.A.47.3.1









2-oxoglutarate:malate antiporter (SodiTl)
Eukaryota
Viridiplantae, Streptophyta
SodiTl of Spinacia oleracea
2.A.47.3.2









Citrate:succinate antiporter (Pos et al. 1998).  Binds and presumably regulates the heterodimeric citrate lyase, CitE/CitF which converts citrate to succinate and acetate (Quentmeier et al. 1987).  These proteins form a metabolon which together catalyze citrate fermentation under anaerobic conditions.

Bacteria
Pseudomonadota
CitT of E. coli (P0AE74)
2.A.47.3.3









L-tartrate:succinate antiporter, TtdT (YgjE). (also takes up meso and L-tartrate and succinate; does not transport D-tartrate) (Kim and Unden, 2007).  It is induced in the presence of L- or meso tartrate under anaerobic conditions in the presence of TtdR (Kim et al. 2009).

Bacteria
Pseudomonadota
TtdT (YgjE) of E. coli (P39414)
2.A.47.3.4









The pmf-dependent citrate uptake system, Cit1 (Urbany and Neuhaus, 2008)
Bacteria
Pseudomonadota
Cit1 of Erwinia carotovora subsp. atroseptica (Q6D017)
2.A.47.3.5









Putative anion (tri- or di-carboxylic acid) transporter of 477 aas, YbhI.

Bacteria
Pseudomonadota
YbhI of E. coli
2.A.47.4.1









Sulfur-deprivation response protein
Bacteria
Cyanobacteriota
SdrP of Synechocystis
2.A.47.4.2









Antimonite resistance protein (inducible by both arsenite and antimonite).

Archaea
Euryarchaeota
ArsB of Halobacterium spNRC-1 (AAG20642)
2.A.47.4.3









The Na+/sulfate symporter, Slt1 (Pootakham et al., 2010).

Eukaryota
Viridiplantae, Chlorophyta
Slt1 of Chlamydomonas reinhardtii (A8IJF8)
2.A.47.4.4









The Na+/sulfate symporter, Slt2 (Pootakham et al., 2010).

Eukaryota
Viridiplantae, Chlorophyta
Slt2 of Chlamydomonas reinhardtii (A8IHV5)
2.A.47.4.5









Na+:SO4= symporter

Bacteria
Bacillota
Na+:So4 symporter of Bacillus halodurans (Q9K7H7)
2.A.47.4.6









The oxyanion (molybdate, sulfate, tungstate and vanidate) permease PerO (Gisin et al., 2010).

Bacteria
Pseudomonadota
PerO of Rhodobacter capsulatus (D5AQ60)
2.A.47.4.7









Uncharacterized protein of 426 aas.

Bacteria
Pseudomonadota
UP of E. coli
2.A.47.4.8









Putative uncharacterized permease of 610 aas, YfbS

Bacteria
Pseudomonadota
YfbS of E. coli
2.A.47.5.1









Hypothetical Na+ cotransporter, Orfl
Archaea
Euryarchaeota
Orfl of Methanococcus jannaschii
2.A.47.5.2









Dicarboxylate (succinate, fumarate, malate) transporter, vcINDY.  The 3-d structure is known to 3.2 Å resolution with citrate and Na+ bound (Mancusso et al. 2012).  INDY may also transport citrate, glutamate and sulfate with low affinity.  It can use Na+ or Li+ as the cotransported cation.  MtrF (TC# 2.A.68.1.2) and YdaH (TC# 2.A.68.1.4) have been shown to have similar 3-d folds as vcINDY (Vergara-Jaque et al. 2015), confirming the assignment of these two families to the same superfamily (Prakash et al. 2003). Solvent accessibility studies suggested differential substrate effects in a multistep mechanism where Na+ binding drives a conformational change, involving rearrangement of the substrate binding site-associated re-entrant hairpin loops (Sampson et al. 2020).

Bacteria
Pseudomonadota
INDY of Vibrio cholerae
2.A.47.5.3









The Na+-dependent C4-dicarboxylate (fumarate, succinate) uptake transporter, SdcA of 425 aas and 15 TMSs (Rhie et al. 2014).

Bacteria
Pseudomonadota
SdcA of Actinobacillus succinogene
2.A.47.6.1









Putative cation transporter of 370 aas and 11 TMSs.

Archaea
Euryarchaeota
The putative cation transporter of Methanosarcina mazei (gi 21227352)
2.A.47.6.2









DUF1646 protein of 351 aas and 10 TMSs

Archaea
Thermoproteota
DUF1646 protein of Pyrobaculum neutrophilum (Thermoproteus neutrophilus)
2.A.47.6.3









DUF1646 protein of 359 aas and 10 TMSs

Bacteria
Bacillota
DUF1646 protein of Caldicellulosiruptor obsidiansis