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Gene Review

SLC29A1  -  solute carrier family 29 (equilibrative...

Homo sapiens

Synonyms: ENT1, Equilibrative NBMPR-sensitive nucleoside transporter, Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter, Equilibrative nucleoside transporter 1, Nucleoside transporter, es-type, ...
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Disease relevance of SLC29A1

  • CONCLUSION: In summary, human pancreatic adenocarcinoma cells overexpress hENT1, although they retain the ability to express a functional hCNT1 transporter, an isoform that confers sensitivity to gemcitabine [1].
  • Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma [2].
  • Chronic lymphocytic leukemia (CLL) cells express both SLC28- and SLC29-related mRNA, although transport function seems to be mostly related to ENT-type transporters [2].
  • Mitochondrial expression of the human equilibrative nucleoside transporter 1 (hENT1) results in enhanced mitochondrial toxicity of antiviral drugs [3].
  • Human equilibrative nucleoside transporter-1 (hENT1) is required for the transcriptomic response of the nucleoside-derived drug 5'-DFUR in breast cancer MCF7 cells [4].

Psychiatry related information on SLC29A1


High impact information on SLC29A1


Chemical compound and disease context of SLC29A1


Biological context of SLC29A1

  • This 456-residue protein is 46% identical in amino acid sequence with hENT1 and corresponds to a full-length form of the delayed-early proliferative response gene product HNP36, a protein of unknown function previously cloned in a form bearing a sequence deletion [12].
  • In this study we identified down-regulation of ENT1 as the factor responsible for Ara-C resistance, and this knowledge may be used to devise a clinical regimen that will overcome the resistance [13].
  • Accordingly, Ara-C-resistant cells showed low growth rates, which were restored by transfection with ENT1 [13].
  • The best-characterised members of the family, hENT1 and hENT2, possess similar broad substrate specificities for purine and pyrimidine nucleosides, but hENT2 in addition efficiently transports nucleobases [14].
  • The observed modification in es activity was probably due to a CK2alpha'-mediated change in the phosphorylation state of the ENT1 protein, or an interacting protein, effecting an increase in the plasma membrane lifetime of the transport proteins [15].

Anatomical context of SLC29A1

  • The first mammalian examples of the equilibrative nucleoside transporter family to be characterized, hENT1 and hENT2, were passive transporters located predominantly in the plasma membranes of human cells [16].
  • RESULTS: All of the cell lines take up gemcitabine mostly via the hENT1 transporter, which is expressed at high levels [1].
  • In HeLa cells with recombinant human concentrative nucleoside transporter (hCNT) 1 or hCNT3 and pharmacologically blocked hENT1 and hENT2, transport of 10 microM[3H]TaraC and [3H]araC was not detected [17].
  • Uptake studies demonstrated that the majority of adenosine transport was mediated by hENT1, which was localized to both apical and basolateral membranes, with a smaller hENT2-mediated component in basolateral membranes [18].
  • In contrast, recombinant hENT1 and rENT1 mediated negligible oocyte fluxes of hypoxanthine relative to hENT2 and rENT2 [19].

Associations of SLC29A1 with chemical compounds


Regulatory relationships of SLC29A1

  • We also observed that p53 status influenced correlations between ENT1 transporter gene RNA levels and sensitivity to the drugs tiazafurin, AZQ and 3-deazauridine [22].
  • However, ADP responses were significantly enhanced in the presence of the ENT1 nucleoside transporter inhibitors dipyridamole and NBTI and were significantly inhibited by adenosine deaminase, indicating a role for extracellular adenosine [23].

Other interactions of SLC29A1


Analytical, diagnostic and therapeutic context of SLC29A1


  1. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2',2'-difluorodeoxycytidine- induced cytotoxicity. García-Manteiga, J., Molina-Arcas, M., Casado, F.J., Mazo, A., Pastor-Anglada, M. Clin. Cancer Res. (2003) [Pubmed]
  2. Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Marcé, S., Molina-Arcas, M., Villamor, N., Casado, F.J., Campo, E., Pastor-Anglada, M., Colomer, D. Haematologica (2006) [Pubmed]
  3. Mitochondrial expression of the human equilibrative nucleoside transporter 1 (hENT1) results in enhanced mitochondrial toxicity of antiviral drugs. Lai, Y., Tse, C.M., Unadkat, J.D. J. Biol. Chem. (2004) [Pubmed]
  4. Human equilibrative nucleoside transporter-1 (hENT1) is required for the transcriptomic response of the nucleoside-derived drug 5'-DFUR in breast cancer MCF7 cells. Molina-Arcas, M., Moreno-Bueno, G., Cano-Soldado, P., Hern??ndez-Vargas, H., Casado, F.J., Palacios, J., Pastor-Anglada, M. Biochem. Pharmacol. (2006) [Pubmed]
  5. Distribution of CNT2 and ENT1 transcripts in rat brain: selective decrease of CNT2 mRNA in the cerebral cortex of sleep-deprived rats. Guillén-Gómez, E., Calbet, M., Casado, J., de Lecea, L., Soriano, E., Pastor-Anglada, M., Burgaya, F. J. Neurochem. (2004) [Pubmed]
  6. HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. Eltzschig, H.K., Abdulla, P., Hoffman, E., Hamilton, K.E., Daniels, D., Schönfeld, C., Löffler, M., Reyes, G., Duszenko, M., Karhausen, J., Robinson, A., Westerman, K.A., Coe, I.R., Colgan, S.P. J. Exp. Med. (2005) [Pubmed]
  7. Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. Mackey, J.R., Yao, S.Y., Smith, K.M., Karpinski, E., Baldwin, S.A., Cass, C.E., Young, J.D. J. Natl. Cancer Inst. (1999) [Pubmed]
  8. Gene expression and thioguanine nucleotide disposition in acute lymphoblastic leukemia after in vivo mercaptopurine treatment. Zaza, G., Cheok, M., Yang, W., Panetta, J.C., Pui, C.H., Relling, M.V., Evans, W.E. Blood (2005) [Pubmed]
  9. Nitric oxide reduces adenosine transporter ENT1 gene (SLC29A1) promoter activity in human fetal endothelium from gestational diabetes. Farías, M., San Martín, R., Puebla, C., Pearson, J.D., Casado, J.F., Pastor-Anglada, M., Casanello, P., Sobrevia, L. J. Cell. Physiol. (2006) [Pubmed]
  10. Transport of antiviral 3'-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Yao, S.Y., Ng, A.M., Sundaram, M., Cass, C.E., Baldwin, S.A., Young, J.D. Mol. Membr. Biol. (2001) [Pubmed]
  11. Identification of the mitochondrial targeting signal of the human equilibrative nucleoside transporter 1 (hENT1): implications for interspecies differences in mitochondrial toxicity of fialuridine. Lee, E.W., Lai, Y., Zhang, H., Unadkat, J.D. J. Biol. Chem. (2006) [Pubmed]
  12. Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. Griffiths, M., Yao, S.Y., Abidi, F., Phillips, S.E., Cass, C.E., Young, J.D., Baldwin, S.A. Biochem. J. (1997) [Pubmed]
  13. Gene-expression profiling reveals down-regulation of equilibrative nucleoside transporter 1 (ENT1) in Ara-C-resistant CCRF-CEM-derived cells. Takagaki, K., Katsuma, S., Kaminishi, Y., Horio, T., Nakagawa, S., Tanaka, T., Ohgi, T., Yano, J. J. Biochem. (2004) [Pubmed]
  14. The equilibrative nucleoside transporter family, SLC29. Baldwin, S.A., Beal, P.R., Yao, S.Y., King, A.E., Cass, C.E., Young, J.D. Pflugers Arch. (2004) [Pubmed]
  15. Subtype-specific regulation of equilibrative nucleoside transporters by protein kinase CK2. Stolk, M., Cooper, E., Vilk, G., Litchfield, D.W., Hammond, J.R. Biochem. J. (2005) [Pubmed]
  16. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. Baldwin, S.A., Yao, S.Y., Hyde, R.J., Ng, A.M., Foppolo, S., Barnes, K., Ritzel, M.W., Cass, C.E., Young, J.D. J. Biol. Chem. (2005) [Pubmed]
  17. The role of human nucleoside transporters in cellular uptake of 4'-thio-beta-D-arabinofuranosylcytosine and beta-D-arabinosylcytosine. Clarke, M.L., Damaraju, V.L., Zhang, J., Mowles, D., Tackaberry, T., Lang, T., Smith, K.M., Young, J.D., Tomkinson, B., Cass, C.E. Mol. Pharmacol. (2006) [Pubmed]
  18. Coupling of CFTR-mediated anion secretion to nucleoside transporters and adenosine homeostasis in Calu-3 cells. Szkotak, A.J., Ng, A.M., Man, S.F., Baldwin, S.A., Cass, C.E., Young, J.D., Duszyk, M. J. Membr. Biol. (2003) [Pubmed]
  19. Functional and molecular characterization of nucleobase transport by recombinant human and rat equilibrative nucleoside transporters 1 and 2. Chimeric constructs reveal a role for the ENT2 helix 5-6 region in nucleobase translocation. Yao, S.Y., Ng, A.M., Vickers, M.F., Sundaram, M., Cass, C.E., Baldwin, S.A., Young, J.D. J. Biol. Chem. (2002) [Pubmed]
  20. Kinetic and pharmacological properties of cloned human equilibrative nucleoside transporters, ENT1 and ENT2, stably expressed in nucleoside transporter-deficient PK15 cells. Ent2 exhibits a low affinity for guanosine and cytidine but a high affinity for inosine. Ward, J.L., Sherali, A., Mo, Z.P., Tse, C.M. J. Biol. Chem. (2000) [Pubmed]
  21. Molecular Determinants of Substrate Selectivity of a Novel Organic Cation Transporter (PMAT) in the SLC29 Family. Zhou, M., Xia, L., Engel, K., Wang, J. J. Biol. Chem. (2007) [Pubmed]
  22. Correlation of nucleoside and nucleobase transporter gene expression with antimetabolite drug cytotoxicity. Lu, X., Gong, S., Monks, A., Zaharevitz, D., Moscow, J.A. J. Exp. Ther. Oncol. (2002) [Pubmed]
  23. A novel mechanism of vasoregulation: ADP-induced relaxation of the porcine isolated coronary artery is mediated via adenosine release. Rayment, S.J., Ralevic, V., Barrett, D.A., Cordell, R., Alexander, S.P. FASEB J. (2007) [Pubmed]
  24. The ENT family of eukaryote nucleoside and nucleobase transporters: recent advances in the investigation of structure/function relationships and the identification of novel isoforms. Hyde, R.J., Cass, C.E., Young, J.D., Baldwin, S.A. Mol. Membr. Biol. (2001) [Pubmed]
  25. Molecular requirements of the human nucleoside transporters hCNT1, hCNT2, and hENT1. Chang, C., Swaan, P.W., Ngo, L.Y., Lum, P.Y., Patil, S.D., Unadkat, J.D. Mol. Pharmacol. (2004) [Pubmed]
  26. 2-Chloroadenosine but not adenosine induces apoptosis in rheumatoid fibroblasts independently of cell surface adenosine receptor signalling. Koshiba, M., Kosaka, H., Nakazawa, T., Hayashi, N., Saura, R., Kitamura, N., Kumagai, S. Br. J. Pharmacol. (2002) [Pubmed]
  27. Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells. Molina-Arcas, M., Marcé, S., Villamor, N., Huber-Ruano, I., Casado, F.J., Bellosillo, B., Montserrat, E., Gil, J., Colomer, D., Pastor-Anglada, M. Leukemia (2005) [Pubmed]
  28. Ribavirin uptake by cultured human choriocarcinoma (BeWo) cells and Xenopus laevis oocytes expressing recombinant plasma membrane human nucleoside transporters. Yamamoto, T., Kuniki, K., Takekuma, Y., Hirano, T., Iseki, K., Sugawara, M. Eur. J. Pharmacol. (2007) [Pubmed]
  29. The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Spratlin, J., Sangha, R., Glubrecht, D., Dabbagh, L., Young, J.D., Dumontet, C., Cass, C., Lai, R., Mackey, J.R. Clin. Cancer Res. (2004) [Pubmed]
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