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Gene Review

NT5C1A  -  5'-nucleotidase, cytosolic IA

Homo sapiens

Synonyms: CN-I, CN-IA, CN1, CN1A, CNI, ...
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Disease relevance of NT5C1A

  • Results: Our results show that cN-I can be transferred by recombinant retroviruses, and that enforced expression of cN-I protects murine fibroblast and hematopoietic progenitor cells from the cytotoxic effects of 2-CdA and/or 5-FU [1].
  • The role of AMP-selective 5'-nucleotidase (cN-I) in the heart, skeletal muscle and brain is highlighted. cN-I action is crucial during ischemia and important for the efficacy of some nucleoside-based drugs and in the regulation of the substrate pool for nucleic acids synthesis [2].

High impact information on NT5C1A

  • Messenger RNA for the cytosolic AMP-specific 5'-nucleotidase (CN-I) was not detected in human bronchial epithelial cells, suggesting that mucosal adenosine did not originate from intracellular pools [3].
  • Expression of cN-I also conferred a 22-fold increase in the IC(50) to 2',3'-difluorodeoxycytidine in HEK 293 cells and an 82-fold increase in the IC(50) to 2',3'-dideoxycytidine in Jurkat cells [4].
  • The recombinant cN-I showed high affinity toward dCMP and lower affinity toward AMP and IMP [4].
  • These data indicate that cN-I may play an important role in the regulation of physiological pyrimidine nucleotide pools and may also alter the therapeutic efficacy of certain nucleoside analogs [4].
  • Under the conditions tested in these cells, only cN-I plays a significant role in AMP breakdown to adenosine, whereas only cN-II breaks down IMP to inosine and GMP to guanosine [5].

Biological context of NT5C1A

  • No correlation for age, fibre type distribution and AMPD1 genotype was found for whole homogenate nucleotidase, total cN and cN-I using multiple linear regression analysis [6].

Anatomical context of NT5C1A

  • Using overexpression in COS-7 cells we showed that mcN-I, like the previously cloned pigeon cN-I, is activated by ADP and catalyses adenosine formation during ATP breakdown [7].
  • We report here a mouse cN-I (mcN-I) cloned from heart and testis [7].
  • The results indicate no changes in the relative expression or catalytic behaviour of cN-I in AMP deaminase-deficient human skeletal muscle, but suggest that increased turnover of AMP by cN-I in working skeletal muscle is due to higher substrate availability of AMP [6].

Associations of NT5C1A with chemical compounds

  • Expression of cN-I in Jurkat and HEK 293 cells conferred resistance to 2-chloro-2'-deoxyadenosine, with a 49-fold increase in the IC(50) in HEK 293 and a greater than 400-fold increase in the IC(50) in Jurkat cells [4].
  • Adenosine production catalysed by cytosolic 5'-nucleotidase (cN-I) regulates diverse physiological processes [7].
  • We also attempt to design a treatment strategy for the potential in vivo selection of cN-I-modified cells by administering 5-FU to mice prior to 2-CdA treatment [1].

Analytical, diagnostic and therapeutic context of NT5C1A

  • There were no significant differences between different groups in the activities of cN-I, whole homogenate 5'-nucleotidase and ectoN, or in cN-I expression on Western blots [6].


  1. Enforced expression of cytosolic 5'-nucleotidase I confers resistance to nucleoside analogues in vitro but systemic chemotherapy toxicity precludes in vivo selection. Gray, T., Morrey, E.L., Gangadharan, B., Sumter, T.F., Spychala, J., Archer, D.R., Spencer, H.T. Cancer Chemother. Pharmacol. (2006) [Pubmed]
  2. Adenosine as a metabolic regulator of tissue function: production of adenosine by cytoplasmic 5'-nucleotidases. Borowiec, A., Lechward, K., Tkacz-Stachowska, K., Składanowski, A.C. Acta Biochim. Pol. (2006) [Pubmed]
  3. Ecto 5'-nucleotidase and nonspecific alkaline phosphatase. Two AMP-hydrolyzing ectoenzymes with distinct roles in human airways. Picher, M., Burch, L.H., Hirsh, A.J., Spychala, J., Boucher, R.C. J. Biol. Chem. (2003) [Pubmed]
  4. Human cytosolic 5'-nucleotidase I: characterization and role in nucleoside analog resistance. Hunsucker, S.A., Spychala, J., Mitchell, B.S. J. Biol. Chem. (2001) [Pubmed]
  5. Distinct roles for recombinant cytosolic 5'-nucleotidase-I and -II in AMP and IMP catabolism in COS-7 and H9c2 rat myoblast cell lines. Sala-Newby, G.B., Freeman, N.V., Skladanowski, A.C., Newby, A.C. J. Biol. Chem. (2000) [Pubmed]
  6. Ecto- and cytosolic 5'-nucleotidases in normal and AMP deaminase-deficient human skeletal muscle. Hanisch, F., Hellsten, Y., Zierz, S. Biol. Chem. (2006) [Pubmed]
  7. Cloning of a mouse cytosolic 5'-nucleotidase-I identifies a new gene related to human autoimmune infertility-related protein. Sala-Newby, G.B., Newby, A.C. Biochim. Biophys. Acta (2001) [Pubmed]
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