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Gene Review

NT5C  -  5', 3'-nucleotidase, cytosolic

Homo sapiens

Synonyms: 5'(3')-deoxyribonucleotidase, cytosolic type, Cytosolic 5',3'-pyrimidine nucleotidase, DNT, DNT-1, DNT1, ...
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Disease relevance of NT5C

  • PN-I cDNA has been expressed in Escherichia coli, yielding a fully active recombinant enzyme, which was purified to homogeneity and extensively characterized [1].
  • These results inferred that quantification of DNT-Hb adducts provided an effective biomarker of toxicity and could be used to estimate the risk associated with a particular exposure to DNT [2].
  • In the present studies, we have investigated the relationship between human PN-I and a protease inhibitor derived from C6 glioma cells in culture that has neurite-promoting activity [3].
  • Biochemical and genetic evidence for meta-ring cleavage of 2,4, 5-trihydroxytoluene in Burkholderia sp. strain DNT [4].
  • Aerobic and anaerobic toluene degradation by a newly isolated denitrifying bacterium, Thauera sp. strain DNT-1 [5].

Psychiatry related information on NT5C


High impact information on NT5C

  • This ligand is functionally, biochemically and immunologically indistinguishable from protease-nexin I (PN-I), a serpin ligand of thrombin and uPA previously detected only in mesenchymal cells and astrocytes [7].
  • Testosterone treatment of castrated males rapidly restores PN-I mRNA levels, indicating that PN-I gene expression is under androgen control [7].
  • A survey of murine tissues indicates that PN-I mRNA is most abundant in seminal vesicles, where it represents 0.2-0.4% of the mRNAs [7].
  • The deduced amino acid sequence is 52% identical to that of a recently described cytosolic deoxyribonucleotidase (dNT-1) [8].
  • Interestingly, relatives without a Fas mutation and with no features of ALPS (n = 65) demonstrated a small but significant expansion of CD8(+) T cells, both DNT cell subsets, and CD5(+) B cells [9].

Chemical compound and disease context of NT5C


Biological context of NT5C


Anatomical context of NT5C


Associations of NT5C with chemical compounds

  • The two enzymes, indicated as PN-I and PN-II, preferentially hydrolyse pyrimidine 5'-monophosphates and 3'-monophosphates, respectively [19].
  • The protease nexins (PN-I, Mr approximately 38,000; PN-II, Mr approximately 95,000; and PN-III, Mr approximately 31,000) are recently described cell-secreted proteins that selectively link to regulatory serine proteases in the extracellular environment and mediate their cellular binding, internalization, and degradation [20].
  • In addition, whereas the ability of PN-I to link to thrombin is strongly modulated by heparin, PN-II and PN-III are essentially unaffected by heparin [20].
  • Overproduction of hkm-NT greatly increased excretion of inosine and guanosine but did not affect adenosine or deoxyribonucleosides. dNT-1 overproduction increased excretion of deoxycytidine, thymidine, and in particular deoxyuridine but also uridine and cytidine [17].
  • An additional advantage of this method is that it separates most of the TNT and DNT isomers, as demonstrated by applying the method to the analysis of headspace over military-grade TNT explosives [21].

Other interactions of NT5C

  • It was found that at least one reactive sulfhydryl group occurs in the UMPH1 isozyme but not in the UMPH2 isozyme [22].
  • We investigated the dephosphorylation of the 5'-phosphates of commonly used nucleoside analogs by two cytosolic (cN-II and dNT-1) and one mitochondrial (dNT-2) nucleotidase [23].
  • We analyzed cytosolic 5'-(3')-nucleotidase (dNT-1) mRNA expression by quantitative polymerase chain reaction at diagnosis in leukemic blasts from 114 patients with acute myeloid leukemia (AML) treated with ara-C [24].

Analytical, diagnostic and therapeutic context of NT5C

  • Furthermore, a functional analysis of the enzyme was carried out through site-directed mutagenesis designed on the basis of the sequence of the identified conserved regions as well as mutations observed in PN-I-deficient patients [1].
  • Multiple sequence alignment of PN-I and homologues proteins revealed the existence of conserved regions, whose importance in catalysis was examined by performing experiments designed to intercept covalent intermediates as strongly suggested by our previous kinetic studies [1].
  • PN-I cDNA sequence, coding for a 286-residue protein, has been retrieved from tag database, amplified by PCR, and expressed in Escherichia coli [25].
  • PN-I levels are much lower in immature animals, and strongly decreased upon castration [7].
  • We found a 47,000-dalton PNI, a thrombin- and urokinase-inhibiting serpin, in normal human CSF by Western blotting using a monospecific antibody [14].


  1. Evidence for essential catalytic determinants for human erythrocyte pyrimidine 5'-nucleotidase. Amici, A., Ciccioli, K., Naponelli, V., Raffaelli, N., Magni, G. Cell. Mol. Life Sci. (2005) [Pubmed]
  2. Hemoglobin adducts in workers exposed to nitrotoluenes. Jones, C.R., Liu, Y.Y., Sepai, O., Yan, H., Sabbioni, G. Carcinogenesis (2005) [Pubmed]
  3. The glioma cell-derived neurite promoting activity protein is functionally and immunologically related to human protease nexin-I. Knauer, D.J., Orlando, R.A., Rosenblatt, D. J. Cell. Physiol. (1987) [Pubmed]
  4. Biochemical and genetic evidence for meta-ring cleavage of 2,4, 5-trihydroxytoluene in Burkholderia sp. strain DNT. Haigler, B.E., Johnson, G.R., Suen, W.C., Spain, J.C. J. Bacteriol. (1999) [Pubmed]
  5. Aerobic and anaerobic toluene degradation by a newly isolated denitrifying bacterium, Thauera sp. strain DNT-1. Shinoda, Y., Sakai, Y., Uenishi, H., Uchihashi, Y., Hiraishi, A., Yukawa, H., Yurimoto, H., Kato, N. Appl. Environ. Microbiol. (2004) [Pubmed]
  6. Triptans for migraine therapy: a comparison based on number needed to treat and doses needed to treat. Mullins, C.D., Weis, K.A., Perfetto, E.M., Subedi, P.R., Healey, P.J. Journal of managed care pharmacy : JMCP. (2005) [Pubmed]
  7. Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle. Vassalli, J.D., Huarte, J., Bosco, D., Sappino, A.P., Sappino, N., Velardi, A., Wohlwend, A., Ernø, H., Monard, D., Belin, D. EMBO J. (1993) [Pubmed]
  8. A deoxyribonucleotidase in mitochondria: involvement in regulation of dNTP pools and possible link to genetic disease. Rampazzo, C., Gallinaro, L., Milanesi, E., Frigimelica, E., Reichard, P., Bianchi, V. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  9. Immunophenotypic profiles in families with autoimmune lymphoproliferative syndrome. Bleesing, J.J., Brown, M.R., Straus, S.E., Dale, J.K., Siegel, R.M., Johnson, M., Lenardo, M.J., Puck, J.M., Fleisher, T.A. Blood (2001) [Pubmed]
  10. Purification and sequence analysis of 4-methyl-5-nitrocatechol oxygenase from Burkholderia sp. strain DNT. Haigler, B.E., Suen, W.C., Spain, J.C. J. Bacteriol. (1996) [Pubmed]
  11. Saturation mutagenesis of 2,4-DNT dioxygenase of Burkholderia sp. strain DNT for enhanced dinitrotoluene degradation. Leungsakul, T., Keenan, B.G., Yin, H., Smets, B.F., Wood, T.K. Biotechnol. Bioeng. (2005) [Pubmed]
  12. TNT and nitroaromatic compounds are chemoattractants for Burkholderia cepacia R34 and Burkholderia sp. strain DNT. Leungsakul, T., Keenan, B.G., Smets, B.F., Wood, T.K. Appl. Microbiol. Biotechnol. (2005) [Pubmed]
  13. Assignment of the human gene for uridine 5'-monophosphate phosphohydrolase (UMPH2) to the long arm of chromosome 17. Wilson, D.E., Swallow, D.M., Povey, S. Ann. Hum. Genet. (1986) [Pubmed]
  14. Protease nexin I, thrombin- and urokinase-inhibiting serpin, concentrated in normal human cerebrospinal fluid. Festoff, B.W., Rao, J.S., Chen, M. Neurology (1992) [Pubmed]
  15. Biomarkers of exposure, effect, and susceptibility in workers exposed to nitrotoluenes. Sabbioni, G., Jones, C.R., Sepai, O., Hirvonen, A., Norppa, H., Järventaus, H., Glatt, H., Pomplun, D., Yan, H., Brooks, L.R., Warren, S.H., Demarini, D.M., Liu, Y.Y. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  16. Mouse cytosolic and mitochondrial deoxyribonucleotidases: cDNA cloning of the mitochondrial enzyme, gene structures, chromosomal mapping and comparison with the human orthologs. Rampazzo, C., Kost-Alimova, M., Ruzzenente, B., Dumanski, J.P., Bianchi, V. Gene (2002) [Pubmed]
  17. Cytosolic high K(m) 5'-nucleotidase and 5'(3')-deoxyribonucleotidase in substrate cycles involved in nucleotide metabolism. Gazziola, C., Ferraro, P., Moras, M., Reichard, P., Bianchi, V. J. Biol. Chem. (2001) [Pubmed]
  18. Peripheral blood lymphocytes in SLE--hyperexpression of CD154 on T and B lymphocytes and increased number of double negative T cells. Devi, B.S., Van Noordin, S., Krausz, T., Davies, K.A. J. Autoimmun. (1998) [Pubmed]
  19. Pyrimidine nucleotidases/phosphotransferases from human erythrocyte. Amici, A., Emanuelli, M., Raffaelli, N., Ruggieri, S., Magni, G. Nucleosides Nucleotides (1999) [Pubmed]
  20. Protease nexins: cell-secreted proteins that mediate the binding, internalization, and degradation of regulatory serine proteases. Knauer, D.J., Thompson, J.A., Cunningham, D.D. J. Cell. Physiol. (1983) [Pubmed]
  21. Determination of nitroaromatic compounds in air samples at femtogram level using C18 membrane sampling and on-line extraction with LC-MS. Sánchez, C., Carlsson, H., Colmsjö, A., Crescenzi, C., Batlle, R. Anal. Chem. (2003) [Pubmed]
  22. Human erythrocyte pyrimidine 5'-nucleotidase isoenzymes: effect of sulfhydryl reagents and electrophoretic discrimination. Manco, L., Amorim, A. Electrophoresis (1993) [Pubmed]
  23. Cytosolic and mitochondrial deoxyribonucleotidases: activity with substrate analogs, inhibitors and implications for therapy. Mazzon, C., Rampazzo, C., Scaini, M.C., Gallinaro, L., Karlsson, A., Meier, C., Balzarini, J., Reichard, P., Bianchi, V. Biochem. Pharmacol. (2003) [Pubmed]
  24. 5'-(3')-nucleotidase mRNA levels in blast cells are a prognostic factor in acute myeloid leukemia patients treated with cytarabine. Galmarini, C.M., Cros, E., Graham, K., Thomas, X., Mackey, J.R., Dumontet, C. Haematologica (2004) [Pubmed]
  25. Human erythrocyte pyrimidine 5'-nucleotidase, PN-I. Amici, A., Magni, G. Arch. Biochem. Biophys. (2002) [Pubmed]
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