TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*2.A.40.1.1









Uracil permease, UraA. The crystal structure of UraA with bound uracil at 2.8Å resolution is available (PDB: 3QE7) (Lu et al., 2011). UraA has a novel structural fold, with 14 transmembrane segments (TMSs) divided into two inverted repeats. A pair of antiparallel β-strands is located between TMS3 and TMS10 and has an important role in structural organization and substrate recognition. The structure is spatially arranged into a core domain and a gate domain. Uracil, located at the interface between the two domains, is coordinated mainly by residues from the core domain. Structural analysis suggests that alternating access of the substrate may be achieved through conformational changes of the gate domain.  Multiscale molecular dynamics simulations of the UraA symporter in phospholipid bilayers revealed a closed state with 3 high affinity binding sites for cardolipin (Kalli et al. 2015).The crystal structure of UraA bound to uracil in an occluded state at 2.5 A resolution (Yu et al. 2017). UraA shows substantial motions between the core domain and the gate domain as well as intra-domain rearrangements of the gate domain. The occluded UraA forms a dimer wherein the gate domains are sandwiched by two core domains. Dimer formation is necessary for transport activity (Yu et al. 2017).

Bacteria
Proteobacteria
UraA of E. coli (P0AGM7)
*2.A.40.1.2









High affinity uracil permease
Bacteria
Firmicutes
PyrP of Lactococcus lactis (gbCAB89870)
*2.A.40.1.3









Putative pyrimidine permease, RutG (Loh et al., 2006; Kim et al. 2010).

Bacteria
Proteobacteria
RutG of E. coli (P75892)
*2.A.40.1.4









Uracil permease
Bacteria
Firmicutes
PyrP of Bacillus subtilis
*2.A.40.2.1









Purine permease
Bacteria
Firmicutes
YcpX of Clostridium perfringens
*2.A.40.3.1









Xanthine permease
Bacteria
Firmicutes
PbuX (XanP) of Bacillus subtilis
*2.A.40.3.2









Uric acid permease
Bacteria
Firmicutes
PucJ of Bacillus subtilis
*2.A.40.3.3









Uric acid (urate) permease YgfU. YgfU exhibits low affinity (0.5 mM) but high capacity for urate and very poor activity for xanthine.  Essential residues were identified.  Coversion of Thr-100 to ala resulted in efficient xanthine transport (Papakostas and Frillingos 2012).  

Bacteria
Proteobacteria
YgfU of Escherichia coli
*2.A.40.4.1









High affinity uric acid-xanthine permease, UapA. Functionaly critical residues in transmembrane segments 1 and 3 have been identified (Amillis et al., 2011). The substrate recognition and transport pathway have been proposed (Kosti et al., 2012; Kosti et al. 2010).  UapA oligomerization is essential for membrane trafficking and turnover and is a common theme in fungi and mammalian cells (Martzoukou et al. 2015).  Specificity is determined by the interactions of a given substrate with the TMS8-9 loop and indirectly by interactions of this loop with TMS1 and TMS12 (Kosti et al. 2010).  UapA oligomerization is essential for membrane trafficking and turnover and is a common theme in fungi and mammalian cells (Martzoukou et al. 2015).  Specificity is determined by the interactions of a given substrate with the TMS8-9 loop and indirectly by interactions of this loop with TMS1 and TMS12 (Papageorgiou et al. 2008).

Eukaryota
Fungi
UapA of Emericella (Aspergillus) nidulans
*2.A.40.4.2









The putative xanthine permease, YicE (Karatza and Frillingos, 2005)
Bacteria
Proteobacteria
YicE of E. coli (POAGM9)
*2.A.40.4.3









The YgfO (XanQ) purine (xanthine) transporter. Residues involved in substrate binding have been identified (Georgopoulou et al., 2010). TMS3 functions in substrate recognition (Karena and Frillingos, 2011).  Many more essential residues have more recently been identified (Karena et al. 2015).

Bacteria
Proteobacteria
XanQ of E. coli (P67444)
*2.A.40.4.4









Purine (uric acid and xanthine) permease, UapC.  Present in many Ascomycetes (Krypotou and Diallinas 2014).

Eukaryota
Fungi
UapC of Emericella nidulans
*2.A.40.5.1









Putative purine permease, YbbY.  The ybbY gene is in an operon involved with allantoin metabolism, and is flanked by allB, encoding allantoinase, and the glxK gene, encoding glycerate kinase II. Downstream of glxK is YlbA, encoding S-uridoglycine aminohydrolase, the second enzyme involved in allantoin degradation (Moraes and Reithmeier 2012).

Bacteria
Proteobacteria
YbbY of E. coli
*2.A.40.6.1









L-ascorbate:Na+ symporter, SVCT1. (L-ascorbate:Na+= 1:2; Mackenzie et al., 2008). Iron regulates SVCT1 in human intestinal Caco-2 cells (Scheers and Sandberg, 2011).

Eukaryota
Metazoa
SVCT1 of Rattus norvegicus
*2.A.40.6.2









Ca2+/Mg2+-dependent L-ascorbate:Na+ symporter, SVCT2; Na+:ascorbate = 2:1; binding order: Na+, ascorbate, Na+ (Na+ increases the affinity for ascorbate; Ca2+/Mg2+ are required for function) (Godoy et al., 2007; Bürzle et al. 2013).

Eukaryota
Metazoa
SLC23A2 of Homo sapiens
*2.A.40.6.3









High affinity (Km = 30 ┬ÁM) uric acid-xanthine transporter; leaf permease protein 1, LPE1 (necessary for proper chloroplast development in maize) (Argyrou et al., 2001)
Eukaryota
Viridiplantae
LPE1 of Zea mays (Q41760)
*2.A.40.6.4









solute carrier family 23 (nucleobase transporters), member 3, SVCT3 or SLC23A3.  Function not certain as of 1/2013 (Bürzle et al. 2013).

Eukaryota
Metazoa
SLC23A3 of Homo sapiens
*2.A.40.6.5









Solute carrier family 23 member 1 (Na+/L-ascorbic acid transporter 1; Sodium-dependent vitamin C transporter 1) (hSVCT1; Yolk sac permease-like molecule 3) (Bürzle et al. 2013).

Eukaryota
Metazoa
SLC23A1 of Homo sapiens
*2.A.40.6.6









Nucleobase-ascorbate transporter 12 (AtNAT12)
Eukaryota
Viridiplantae
NAT12 of Arabidopsis thaliana
*2.A.40.7.1









The purine (hypoxanthine/adenine/guanine) transporter, AzgA (Cecchetto et al., 2004).  Topological modeling has revealed a potential substrate binding cavity, and residues important for transport activity have been identified (Krypotou et al. 2014).

Eukaryota
Fungi
AzgA of Aspergillus (Emericella) nidulans (CAE00849)
*2.A.40.7.2









Hypoxanthine/guanosine uptake transporter, PbuG (Johansen et al., 2003)
Bacteria
Firmicutes
PbuG of Bacillus subtilis (CAB12456)
*2.A.40.7.3









The purine transporter Azg1 (takes up 8-azadenine and 8-azaguanine but not other toxic nucleobase analogues; similar to Azg2 of A. thaliana (Q84MA8); (Mansfield et al. 2009).
Eukaryota
Viridiplantae
Azg1 of Arabidopsis thaliana (Q9SRK7)
*2.A.40.7.4









  Adenine permease, YicO.  Also recognize with low micromolar affinity N(6)-benzoyladenine, 2,6-diaminopurine, and purine (Papakostas et al. 2013).

Bacteria
Proteobacteria
YicO of Escherichia coli
*2.A.40.7.5









Purine base permease, GhxP or YjcD.  Transports purines such as guanine, hypoxanthine, and xanthine.  Also transports mutagenic modified purines such as 6-N-hydroxylaminopurine (HAP), 2-amino-HAP (AHAP), 6-mercaptopurine, 6-thioguanine, 1-methylguanine, 8-azaguanine, 6-thioguanine and 2-aminopurine (Kozmin et al. 2013; Papakostas et al. 2013).  

Bacteria
Proteobacteria
YjcD (GhxP) of E. coli
*2.A.40.7.6









Adenine permease, PurP.  Also recognize with low micromolar affinity N(6)-benzoyladenine, 2,6-diaminopurine, and purine (Papakostas et al. 2013).

Bacteria
Proteobacteria
PurP of Escherichia coli
*2.A.40.7.7









Guanine/hypoxanthine uptake porter of 455 aas, YgfQ.  Also takes up mutagens such as 1-methylguanine, 8-azaguanine, 6-thioguanine, and 6-mercaptopurine (Papakostas et al. 2013).

Bacteria
Proteobacteria
YgfQ of E. coli