Equilibrative nucleoside transporter 1 (ENT1) is a protein that in humans is encoded by the SLC29A1gene. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene.
This gene is a member of the equilibrative nucleoside transporter family. The gene encodes a transmembrane glycoprotein that localizes to the plasma and mitochondrial membranes and mediates the cellular uptake of nucleosides from the surrounding medium. The protein is categorized as an equilibrative (as opposed to concentrative) transporter that is sensitive to inhibition by nitrobenzylmercaptopurine ribonucleoside (NBMPR). Nucleoside transporters are required for nucleotide synthesis in cells that lack de novo nucleoside synthesis pathways, and are also necessary for the uptake of cytotoxic nucleosides used for cancer and viral chemotherapies.
The gene encoding this protein is located on the short arm of chromosome 6 at 6p21.2-p21.1 on the Watson (plus) strand. It is 14,647 bases in length. The encoded protein has 456 amino acid residues with 11 predicted transmembrane domains. The predicted molecular weight is 50.219 kiloDaltons. The protein is post translationally glycosylated and expressed in all tissue with the apparent exception of skeletal muscle. The highest levels are found in the liver, heart, testis, spleen, lung, kidney and brain.
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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Sundaram M, Yao SY, Ingram JC, et al. (2002). "Topology of a human equilibrative, nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporter (hENT1) implicated in the cellular uptake of adenosine and anti-cancer drugs". J. Biol. Chem. 276 (48): 45270–5. doi:10.1074/jbc.M107169200. PMID11584005.
SenGupta DJ, Lum PY, Lai Y, et al. (2002). "A single glycine mutation in the equilibrative nucleoside transporter gene, hENT1, alters nucleoside transport activity and sensitivity to nitrobenzylthioinosine". Biochemistry. 41 (5): 1512–9. doi:10.1021/bi015833w. PMID11814344.
Yao SY, Ng AM, Vickers MF, et al. (2002). "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". J. Biol. Chem. 277 (28): 24938–48. doi:10.1074/jbc.M200966200. PMID12006583.
Lai Y, Bakken AH, Unadkat JD (2002). "Simultaneous expression of hCNT1-CFP and hENT1-YFP in Madin-Darby canine kidney cells. Localization and vectorial transport studies". J. Biol. Chem. 277 (40): 37711–7. doi:10.1074/jbc.M204986200. PMID12097333.
Reiman T, Clarke ML, Dabbagh L, et al. (2003). "Differential expression of human equilibrative nucleoside transporter 1 (hENT1) protein in the Reed-Sternberg cells of Hodgkin's disease". Leuk. Lymphoma. 43 (7): 1435–40. doi:10.1080/1042819022386725. PMID12389626.
Mangravite LM, Xiao G, Giacomini KM (2003). "Localization of human equilibrative nucleoside transporters, hENT1 and hENT2, in renal epithelial cells". Am. J. Physiol. Renal Physiol. 284 (5): F902–10. doi:10.1152/ajprenal.00215.2002. PMID12527552.
Szkotak AJ, Ng AM, Man SF, et al. (2003). "Coupling of CFTR-mediated anion secretion to nucleoside transporters and adenosine homeostasis in Calu-3 cells". J. Membr. Biol. 192 (3): 169–79. doi:10.1007/s00232-002-1073-x. PMID12820662.
Lai Y, Tse CM, Unadkat JD (2004). "Mitochondrial expression of the human equilibrative nucleoside transporter 1 (hENT1) results in enhanced mitochondrial toxicity of antiviral drugs". J. Biol. Chem. 279 (6): 4490–7. doi:10.1074/jbc.M307938200. PMID14607828.
Lehner B, Semple JI, Brown SE, et al. (2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics. 83 (1): 153–67. doi:10.1016/S0888-7543(03)00235-0. PMID14667819.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.