TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*2.A.23.1.1









Glutamate/aspartate:H+ symporter, GltP; has 8 TMSs with 2 re-entrant loops as for GltPh (TC# 2.A.23.1.5).  GltP residues involved in substrate binding and transport have been identified, especially in transmembrane helices VII and VIII (Rahman et al. 2016).

Bacteria
Proteobacteria
GltP of E. coli
*2.A.23.1.2









Glutamate/aspartate:Na+ + H+ symporter
Bacteria
Firmicutes
GltT of Bacillus stearothermophilus
*2.A.23.1.3









C4-dicarboxylate transporter (substrates: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate, mesaconate)
Bacteria
Proteobacteria
DctA of Rhizobium leguminosarum
*2.A.23.1.4









The L-cystine/L-selenocystine:H+ symporter, TcyP (YhcL) (Burguière et al., 2004)

Bacteria
Firmicutes
TcyP (YhcL) of Bacillus subtilis (P54596)
*2.A.23.1.5









Archaeal aspartate transporter, Gltph (GltPh) (3-D structure known; 3V8F and 3V8G) (Boudker et al., 2007; Yernool et al., 2004). Cotransports aspartate with 2 Na+ (Ryan et al., 2009) or 3 Na+ (Groeneveld and Slotboom, 2010) or 1Na+ plus 1 H+ plus 1 K+ (Machtens et al. 2015). Reyes et al. (2009) have solved the structure of the inward facing state by cysteine crosslinking. The loop between TMSs 3 and 4 plays an essential role in transport (Compton et al., 2010). Gltph shows opposite movement of the external gate upon binding cotransported sodium compared with substrate (Focke et al., 2011).  The transport pathway and the conformational changes involved have been suggested based on modeling studies (Stolzenberg et al. 2012).  Individual transport domains may alternate between periods of quiescence and periods of rapid transitions.  The switch to the dynamic mode may be due to separation of the transport domain from the trimeric scaffold which precedes domain movements across the bilayer (Akyuz et al. 2013). This spontaneous dislodging of the substrate-loaded transport domain is approximately 100-fold slower than subsequent transmembrane movements and may be rate determining in the transport cycle.  Interactions between the transporter and specific lipids in artificial membranes have revealed effects on activity, and mechanisms have been proposed (McIlwain et al. 2015).  The system can also function as an anion channel (Machtens et al. 2015).

Archaea
Euryarchaeota
Gltph of Pyrococcus horikoshii (LXFHA)
*2.A.23.1.6









The dicarboxylate (succinate, fumarate, malate and oxaloacetate):H+ symporter, DctA (probably 3H+ are transported per succinate taken up (Groeneveld et al., 2010).      

Bacteria
Firmicutes
DctA of Bacillus subtilis (P96603)
*2.A.23.1.7









Aerobic dicarboxylate transporter, DctA. Interacts with the DcuS sensor kinase (Witan et al., 2012).  The interaction of DctA with DcuS has been studied extensively and reviewed (Unden et al. 2016).

Bacteria
Proteobacteria
DctA of E. coli (P0A830)
*2.A.23.1.8









Cystine transporter, YdjN, of 463 aas.  Also transports L-selenaproline (L-selenazolidine-4-carboxylic acid) and L-selenocystine, both toxic analogues that inhibit growth of urinary tract pathogenic  E. coli  (Deutch et al. 2014). 

Bacteria
Proteobacteria
YdjN of E. coli
*2.A.23.1.9









Fumarate:H+ symporter of 442 aas and 14 established TMSs, DctA. Responsible for the transport of dicarboxylates such as succinate, fumarate, and malate.  The 3-d structure has been solved (Geertsma et al. 2015). It reveals an inward facing transmembrane domain of two 7 TMS intertwined inverted repeats similar to that of UraA as well as a STAS domain (Geertsma et al. 2015).

Bacteria
Deinococcus-Thermus
Fumarate transporter of Deinococcus geothermalis
*2.A.23.1.10









Organic acid uptake porter, DctA of 444 aas and 8 - 10 putative TMSs.  Based on mutant analyses, it may transport succinate, benzoate, acetate, fumarate and malate (Nam et al. 2003).  A dctA mutant colonized tobacco roots to a lesser extent than the wild-type during early seedling development. Colonization by the dctA mutant, as compared to the wild type, also reduced the level of systemically induced resistance against the soft rot pathogen Erwinia carotovora SCC1 (Nam et al. 2006).

Bacteria
Proteobacteria
DctA of Pseudomonas chlororaphis (Pseudomonas aureofaciens)
*2.A.23.1.11









Dicarboxylate transporter, DctA of 458 aas and 10 TMSs. Transports L-aspartate, succinate and fumarate.  Functions under high oxygen conditions although constitutively synthesized (Wösten et al. 2017).

Bacteria
Proteobacteria
DctA of Campylobacter jejuni
*2.A.23.2.1









Glutamate/aspartate:Na+ symporter, GLAST or EAAT1, Structural rearrangements have been probed by Leighton et al., 2006). EAAT1 interacts directly with the Na+, K+-ATPase (TC #3.A.3.1) (Rose et al., 2009). CEAT1 couples glutamate uptake to the symport of 3 Na+ and 1 H+ followed by the antiport of 1 K+. It can function as an uncoupled anion, water and/or urea channel (Vandenberg et al., 2011). Large collective motions regulate the functional properties of EAAT1 trimers (Jiang et al., 2011).  The reentrant helical hairpin loop, HP1, functions during the transport cycle as the proposed internal gate.  HP1 is packed against transmembrane domain, TMS 2 and TMS5 in its closed state, and two residues located in TM2 and HP2 of EAAT1 are in close proximity (Zhang et al. 2014).  In EAAT1, R388 is a critical element for the structural coupling between the substrate translocation and the gating mechanisms of the EAAT-associated anion channel, and conversion to E or D creates a constitutively open anion channel (Torres-Salazar et al. 2015).

Eukaryota
Metazoa
Glutamate/aspartate permease (excitatory amino acid transporter-1, EAAT1) of Rattus norvegicus
*2.A.23.2.2









Glutamate/aspartate:Na+ symporter, GLT1; GLUT-R; EAAT2. Interacts directly with the Na+, K+-ATPase (TC #3.A.3.1) (Rose et al., 2009). Cotransports glutamic acid with three Na+ followed by countertransport of K+ (Teichman et al., 2009). The C-terminal 74aa domain regulates transport activity (Leinenweber et al., 2011). Hippocampal glutamate transporter 1 (GLT-1) levels parallel memory training (Heo et al., 2011). GLT-1 is regulated by MAGI-1 (Zou et al., 2011).  Venom from the spider Parawixia bistriata and a purified compound (Parawixin1) stimulate EAAT2 activity and protect retinal tissue from ischemic damage (Mortensen et al. 2015).  Determinants of this stimulation are at the interface of the trimerization and substrate transport domains ((Mortensen et al. 2015). TMS4 of GLT-1 undergoes a complex conformational shift during substrate translocation (Rong et al. 2016).

 

Eukaryota
Metazoa
Glutamate permease (excitatory amino acid transporter-2, EAAT2) of Rattus norvegicus
*2.A.23.2.3









Glutamate/aspartate/cysteine:Na+ symporter, EAAC1; EAAT3 (Li+ can replace Na+; EAAC1 also mediates glutamate-independent anion conductance.) Cotransports glutamic acid with three Na+ followed by countertransport of K+(Teichman et al., 2009). The 50 residue 4B-4C loop (following TMS4) binds Na+ (Koch et al., 2007). (The dicarboxylic aminoaciduria protein in humans; NP_004161; Bröer, 2008a; 2008b). Neutralizing aspartate 83 modifies substrate translocation (Hotzy et al., 2012).  An SLC1A1 deletion segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family (Myles-Worsley et al. 2013).  Thr101 in TMS3 is essential for Na+ binding (Tao et al. 2010).  Klotho, a 1012 aa protein with N- and C-terminal TMSs, is a regulator of the excitatory amino acid transporters EAAT3 and EAAT4 (Almilaji et al. 2013).

Eukaryota
Metazoa
SLC1A1 of Homo sapiens
*2.A.23.2.4









Aspartate/taurine (not glutamate):Na+ symporter, dEAAT2 (mediates both uptake and heteroexchange of its two substrates, both dependent on external Na+ (with taurine outside and Asp inside)); L-glutamate is transported with low affinity and efficiency (Besson et al., 2005).

Eukaryota
Metazoa
dEAAT2 of Drosophila melanogaster (E1JHQ6)
*2.A.23.2.5









solute carrier family 1 (glutamate transporter), member 7
Eukaryota
Metazoa
SLC1A7 of Homo sapiens
*2.A.23.2.6









Excitatory amino acid transporter 1 (EAAT1) (Sodium-dependent glutamate/aspartate transporter 1) (GLAST-1) (Solute carrier family 1 member 3).  Mutations cause episodic ataxia type 6 (EA6) (Choi et al. 2016).  EAAT1 regulates the extent and duration of glutamate-mediated signals by the clearance of glutamate after synaptic release. It also has an anion channel activity that prevents additional glutamate release.

Eukaryota
Metazoa
SLC1A3 of Homo sapiens
*2.A.23.2.7









Excitatory amino acid transporter 2 (Glutamate/aspartate transporter II) (Sodium-dependent glutamate/aspartate transporter 2) (Solute carrier family 1 member 2)
Eukaryota
Metazoa
SLC1A2 of Homo sapiens
*2.A.23.2.8









Excitatory amino acid transporter 4, EAAT4 (Sodium-dependent glutamate/aspartate transporter) (Solute carrier family 1 member 6).  Klotho, a 1012 aa protein with N- and C-terminal TMSs, is a regulator of the excitatory amino acid transporters EAAT3 and EAAT4 (Almilaji et al. 2013).

Eukaryota
Metazoa
SLC1A6 of Homo sapiens
*2.A.23.2.9









Putative sodium-dependent excitatory amino acid transporter Glt-3
Eukaryota
Metazoa
Glt-3 of Caenorhabditis elegans
*2.A.23.2.10









Excitatory amino acid transporter (Sodium-dependent glutamate/ aspartate transporter)
Eukaryota
Metazoa
Glt-1 of Caenorhabditis elegans
*2.A.23.2.11









EAAT homologue, a glutamate/aspartate preferring transporter of 483 aas.  TMS8 includes residues important for substrate and cation binding (Wang et al. 2013).

Eukaryota
Metazoa
EAAT homoloue of Culex quinquefasciatus (Southern house mosquito) (Culex pungens)
*2.A.23.2.12









Dicarboxylic acid over dicarboxylic amino acid  preferring EAAT3 homologue of 483 aas (Wang et al. 2013).

Eukaryota
Metazoa
EAAT3 homologue of Culex quinquefasciatus (Southern house mosquito) (Culex pungens)
*2.A.23.3.1









Neutral amino acid (alanine, serine, cysteine, threonine):Na+ symporter. Also transports homocysteine (Jiang et al., 2007). AscT1 is the Syncytin-1 (Q9UQF0) receptor. Syncytin-1, of 538 aas with 4-7 TMSs, is a viral fusion protein and is involved in the development of multiple sclerosis (Antony et al. 2007). Mutation causes nuerological problems including global developmental delay, severe progressive microcephaly, seizures, spasticity and thin corpus callosum (CC) (Heimer et al. 2015).

Eukaryota
Metazoa
SLC1A4 of Homo sapiens
*2.A.23.3.2









Insulin-activated amino acid (serine, alanine, glutamate and others):Na+ symporter. Also transports homocysteine (Jiang et al., 2007).
Eukaryota
Metazoa
Insulin-dependent amino acid transporter B of Mus musculus, AscT2
*2.A.23.3.3









Broad-specificity amino acid:Na+ symporter, LAT1 or SLC7A5 (transports most zwitterionic and dibasic amino acids) (Required for intracellular multiplication of Legionella pneumophila (Wieland et al., 2005). SLC7A5 with accessory protein SLC3A2 (the heavy chain; TC# 8.A.9.2.2) mediates bidirectional transport of amino acids and regulates mTOR and autophagy (Nicklin et al., 2009; Estrach et al. 2014).  LAT1 is the sole transport competent subunit of the heterodimer (Napolitano et al. 2015). l-Leucine inhibits uptake of LAT1 substrates as well as cell growth, and it potentiates the efficacy of bestatin and cisplatin, even at low concentrations (25 muM) (Huttunen et al. 2016).  Transports certain thyroid hormones and their derivatives (<Estrach et al. 2014).  LAT1 is the sole transport competent subunit of the heterodimer (Napolitano et al. 2015). l-Leucine inhibits uptake of LAT1 substrates as well as cell growth, and it potentiates the efficacy of bestatin and cisplatin, even at low concentrations (25 muM) (Huttunen et al. 2016).  Transports certain thyroid hormones and their derivatives (Krause and Hinz 2017).

Eukaryota
Metazoa
SLC1A5 of Homo sapiens
*2.A.23.3.4









Uncharaterized protein of 409 aas and 10 TMSs.

Bacteria
Spirochaetes
UP of Treponema denticola
*2.A.23.4.1









Serine/threonine:Na+ symporter, SstT
Bacteria
Proteobacteria
SstT (YgjU) of E. coli (P0AGE4)