TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*2.A.57.1.1









Equilibrative nucleoside transporter (ENT1) (present in the membranes surrounding the cell as well as eukaryotic organelles) (Lee et al., 2006) Residues 334 and 338 in TMS8 determine inhibitor sensitivity, protein folding and catalytic turnover (Visser et al., 2007) Inhibited by nanomolar concentrations of various structurally distinct coronary vasodilator drugs, including dipyridamole, dilazep, draflazine, soluflazine and nitrobenzylmercaptopurine ribonucleoside (NBMPR) (Paproski et al., 2008).  Transports the A1 adenosine receptor agonist, tecadenoson (Lepist et al. 2013) and mediates gemcitabine (GEM) and folfirinox uptake, chemotheraputic agents for patients with metastatic pancreatic cancer (Orlandi et al. 2016).  The matricellular protein, cysteine-rich angiogenic inducer 61 (CYR61), negatively regulates synthesis of the nucleoside transporters hENT1 and hCNT3, both of which transport gemcitabine (Hesler et al. 2016).

Eukaryota
Metazoa
SLC29A1 or Ent1 of Homo sapiens
*2.A.57.1.2









Equilibrative nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter of 456 aas, ENT2 (Slc29a2).  In humans, the same gene product is the nucleolar protein, HNP36 (function unknown).

Eukaryota
Metazoa
ENT2 (HNP36) of Mus musculus (Q61672)
*2.A.57.1.3









Equilibrative high affinity nucleoside transporter (nitrobenzyl-thioinosine-sensitive) (transports thymidine, adenosine, cytosine, and guanosine; inosine and hypoxanthine are poorly transported).  Uridine uptake in the basolateral membrane of sertoli cells is selectively inhibited by 100 nM nitrobenzylmercaptopurine riboside (NBMPR, 6-S-[(4-nitrophenyl)methyl]-6-thioinosine) (Klein et al. 2013).

Eukaryota
Metazoa
rENT1 of Rattus norvegicus
*2.A.57.1.4









Equilibrative low affinity nucleoside transporter (nitrobenzyl-thioinosine-insensitive) (transports adenosine, inosine and hypoxanthine with high affinity; other nucleosides are transported with lower affinity)
Eukaryota
Metazoa
rENT2 of Rattus norvegicus
*2.A.57.1.5









The brain plasma membrane monoamine transporter, PMAT or ENT4, a polyspecific orgnaocation transporter. (transports serotonin [Km=110 μM), dopamine (Km=330 μM), metformin (Km=1.3 mM) and the neurotoxin, 1-methyl-4-phenylpyridinium (Km=33 μM)) (Nucleosides and nucleobases are not transported; transport is sensitive to the membrane potential, but is Na+ and Cl- independent.) (Engel et al., 2004).  Also expressed in kidney apical membranes where it transports MPP+ by a ΔΨ-dependent process (Xia et al., 2007). TMSs 1 - 6 bear the substrate recognition site, and Glu206 in TMS5 determines the catioin specificiity. An E206Q mutant lost cation selectivity and transported uridine (Zhou et al. 2007). Residues Ile89 and thr220 influence its organic cation transport activity and sensitivity to inhibition by dilazep (Ho et al., 2012).  May play a role in insulin secretion in β-cells (Kobayashi et al. 2016).

Eukaryota
Metazoa
SLC29A4 of Homo sapiens
*2.A.57.1.6









Equilibrative (Na+-independent) low affinity nucleoside transporter, hENT3 or SLC29A3 (transports nucleosides with broad selectivity and low affinity; also transports adenine). Relatively low sensitivity to classical nucleoside transport inhibitors, nitrobenzylthioinosine, dipyridamole, and dilazep. pH optimum=5.5; present in acidic intracellular compartments (Baldwin et al., 2005). (Present largely in the lysosomes). May cause histiocytosis, perturb lysosome function and upset macrophage homeostasis when defective (Hsu et al., 2012; Farooq et al., 2012).  A single nucleotide polymorphism (SNP) in ENT3 may be a risk factor for squamous cell carcioma (Li et al. 2010).  Mutations cause H syndrome, an autosomal recessive genodermatosis characterized by hyperpigmented and hypertrichotic skin (Liu et al. 2015).

Eukaryota
Metazoa
SLC29A3 of Homo sapiens
*2.A.57.1.7









The fluorouridine insensitive 1 (fur1) or Ent3 pyrimidine nucleoside transporter (Traub et al., 2007).
Eukaryota
Viridiplantae
Ent3 of Arabidopsis thaliana (Q9M0Y3)
*2.A.57.1.8









Equilibrative nucleoside transporter 2 (36 kDa nucleolar protein HNP36) (Delayed-early response protein 12) (Equilibrative nitrobenzylmercaptopurine riboside-insensitive nucleoside transporter) (Equilibrative NBMPR-insensitive nucleoside transporter) (Hydrophobic nucleolar protein, 36 kDa) (Nucleoside transporter, ei-type) (Solute carrier family 29 member 2)
Eukaryota
Metazoa
SLC29A2 of Homo sapiens
*2.A.57.1.9









Uncharacterized protein of 359 aas and 9 TMSs.

Eukaryota
Florideophyceae
UP of Chondrus crispus
*2.A.57.1.10









ENT7 of 417 aas and 11 TMSs, an equilibrative nucleoside transporter in contrast to most plant ENT proteins which are concentrative, functioning by H+ symport (Girke et al. 2015). Binding of purine and pyrimidine nucleosides to the purified recombinant protein, and binding of nucleobases has been demonstrated (Girke et al. 2015).

Eukaryota
Viridiplantae
ENT7 of Arabidopsis thaliana (Mouse-ear cress)
*2.A.57.1.11









Putative transporter
Bacteria
Fusobacteria
Putative transporter of Fusobacterium nucleatum (gi 19704274)
*2.A.57.2.1









Concentrative nucleoside (adenosine, uridine, cytosine, tubercidin):H+ symporter, NT1.1 (The Leishmania major orthologue, NT1.1 (Q4QF58), also transports tubercidin) (Stein et al., 2003).  The intracellular and extracellular gates have been defined by modeling FucP (Valdés et al. 2012; Valdés et al. 2014).

Eukaryota
Kinetoplastida
NT1.1 of Leishmania donovani
*2.A.57.2.2









Nucleoside (nucleobase drug) transporter
Eukaryota
Kinetoplastida
TbAT1 of Trypanosoma brucei
*2.A.57.2.3









High affinity, concentrative nucleoside (inosine, formycin, guanosine):H+ symporter, NT2 (Stein et al., 2003)
Eukaryota
Kinetoplastida
NT2 of Leishmania donovani
*2.A.57.2.4









High-affinity (<5 μM) adenosine/inosine transporter, NT2
Eukaryota
Kinetoplastida
NT2 of Trypanosoma brucei
*2.A.57.2.5









High-affinity nucleobase transporter (transports adenine, hypoxanthine, xanthine, guanine, guanosine, allopurinol, and inosine) (Burchmore et al., 2003)
Eukaryota
Kinetoplastida
NBT1 of Trypanosoma brucei brucei (AAO60071)
*2.A.57.2.6









High affinity purine nucleobase (hypoxanthine, guanine, xanthine, adenine, allopurinol) transporter, NT3 (Ortiz et al., 2007)
Eukaryota
Kinetoplastida
NT3 of Leishmania major (Q4QG33)
*2.A.57.2.7









Low affinity adenine transporter, NT4 (Ortiz et al., 2007)
Eukaryota
Kinetoplastida
NT4 of Leishmania major (Q4QH25)
*2.A.57.2.8









Nucleotide transporter 2, NT2, specific for inosine and guanosine, but mutations in TMS 4 which may line the channel allow uptake of adenosine (Arendt & Ullman et al., 2010). (Most similar to 2.A.57.2.3).

Eukaryota
Kinetoplastida
NT2 of Crithidia fasciculata (Q9GTP4)
*2.A.57.2.9









High affinity adenosine-specific nucleoside transporter (Arendt 2013).  Similar to 2.A.547.2.1.  A lysine residue in TMS4 plays an important role in substrate affinity.

Eukaryota
Kinetoplastida
Adenosine transporter of Crithidia fasciculata
*2.A.57.3.1









Nucleoside (uridine, adenosine, cytidine) transporter, Fun26p (intraorganellar)
Eukaryota
Fungi
Fun26p of Saccharomyces cerevisiae
*2.A.57.4.1









The parasite plasma membrane nucleoside transporter, PfNT1. Both L- and D-nucleosides of both purines and pyrimidines are transported; L-nucleosides are transported with low affinity (transports adenosine, inosine and thymidine (KM values=1-2mM) (Downie et al., 2006)). Transmembrane segment 11 appears to line the purine permeation pathway of PfENT1 (Riegelhaupt et al., 2010).

Eukaryota
Apicomplexa
PfNT1 of Plasmodium falciparum
*2.A.57.4.2









The intracellular (endoplasmic reticulum) nucleoside transporter. Transports purine nucleosides and 5-fluorouridine (PfNT-2; Downie et al., 2010)

Eukaryota
Apicomplexa
PfNT2 of Plasmodium falciparum (Q8IB78)
*2.A.57.5.1









Battenin (BTN) or ceroid lipofuscinosis neuronal-3 (CLN3), with 6 TMSs and the N- and C-termini in the cytoplasm (Nugent et al. 2008).  May function in trafficking from the Golgi to the plasma membrane (Tecedor et al. 2013).  Mutations give rise to the disease, juvenile neuronal ceroid lipofuscinosis (JNCL) or Batten disease in humans, a fatal childhood-onset neurodegenerative disorder caused by mutations in CLN3.  May indirectly regulate activity of the Na+,K+-ATPase (Uusi-Rauva et al. 2008).

Eukaryota
Metazoa
Cln3 of Mus musculus
*2.A.57.5.2









Protein BTN1
Eukaryota
Fungi
YHC3 of Saccharomyces cerevisiae
*2.A.57.5.3









Protein BTN1
Eukaryota
Fungi
BTN1 of Candida albicans
*2.A.57.5.4









10 TMS homologue

Eukaryota
Trichomonadida
10 TMS homologue of Trichomonas vaginalis
*2.A.57.5.5









Cln3 family protein of 513 aas and 11 putative TMSs.

Eukaryota
Intramacronucleata
Cln3 family protein of Oxytricha trifallax
*2.A.57.5.6









Uncharacterized protein of 5432 aas

Eukaryota
Kinetoplastida
UP of Trypanosoma cruzi
*2.A.57.6.1









Uncharacterized protein of 418 aas and 10 - 11 TMSs

Eukaryota
Fungi
UP of Mycosphaerella pini (Red band needle blight fungus) (Dothistroma septosporum)