Affinage

NT5C2

Cytosolic purine 5'-nucleotidase · UniProt P49902

Length
561 aa
Mass
65.0 kDa
Annotated
2026-04-29
100 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NT5C2 (cytosolic 5'-nucleotidase II, cN-II) is an allosterically regulated phosphohydrolase that dephosphorylates purine nucleoside monophosphates, thereby controlling intracellular purine nucleotide pools and influencing cell survival. The enzyme operates as an oligomer whose activity is governed by allosteric ATP activation, an autoinhibitory switch-off mechanism involving the arm segment, inter-monomeric cavity, and a C-terminal acidic tail, and whose mutant subunits can dominantly activate wild-type partners within hetero-oligomeric complexes (PMID:29990496, PMID:29535428). Gain-of-function NT5C2 mutations recurrently arise in relapsed acute lymphoblastic leukemia, where constitutive nucleotidase activity accelerates dephosphorylation and export of thiopurine metabolites to confer 6-mercaptopurine/6-thioguanine resistance, while simultaneously depleting intracellular purine pools and impairing leukemia cell proliferation and self-renewal (PMID:23377281, PMID:23377183, PMID:29342136, PMID:31358663). Loss of NT5C2 in zebrafish increases blood flow and arterial pulse with upregulation of hypertension markers, implicating NT5C2 in blood pressure regulation (PMID:32984406).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2008 Medium

    Establishing that cN-II activity is required for cell survival resolved whether the enzyme is dispensable or essential in proliferating cells, showing that its loss triggers apoptosis even without measurable changes in bulk nucleotide concentrations.

    Evidence shRNA knockdown in human astrocytoma cells with caspase-3, viability, and nucleotide measurements

    PMID:18445485

    Open questions at the time
    • Single cell line; mechanism linking enzyme loss to apoptosis remains unresolved
    • Bulk nucleotide measurements may miss compartmentalized pool changes
  2. 2012 Medium

    Identification of an allosteric inhibitor binding at effector site 1 (F354/I152) provided the first structural view of a druggable regulatory pocket on NT5C2.

    Evidence Virtual screening, enzymatic inhibition assay, and X-ray crystallography of truncated cN-II soaked with anthraquinone inhibitor

    PMID:23220537

    Open questions at the time
    • Inhibitor potency is millimolar (Ki 2.0 mM), limiting pharmacological utility
    • Only a truncated protein was crystallized
  3. 2013 High

    Two concurrent studies established that relapse-specific activating NT5C2 mutations are a direct genetic cause of thiopurine resistance in ALL, linking enzyme gain-of-function to clinical drug failure.

    Evidence Whole-exome/RNA sequencing of matched diagnosis–relapse ALL samples, in vitro enzymatic assays of mutant proteins, and expression of mutant NT5C2 in ALL lymphoblasts with drug-resistance readout

    PMID:23377183 PMID:23377281

    Open questions at the time
    • Structural basis of constitutive activation not yet resolved at this point
    • Fitness cost of mutations in vivo unknown
  4. 2017 Medium

    Genetic knockout of NT5C2 in mice showed the enzyme is dispensable for AMPK activation in contracting skeletal muscle, contradicting earlier knockdown/overexpression data and narrowing the physiological role of NT5C2 away from direct AMPK regulation.

    Evidence NT5C2 knockout mouse, electrically stimulated skeletal muscle contraction, adenine nucleotide and AMPK activity measurements

    PMID:28325731

    Open questions at the time
    • Does not rule out tissue-specific roles in other contexts
    • Compensatory mechanisms in constitutive knockout not addressed
  5. 2018 High

    Crystal structures of leukemia-associated mutants and biochemical reconstitution of hetero-oligomers revealed two distinct activation mechanisms — catalytic-center reconfiguration (K359Q, L375F) and disruption of the autoinhibitory switch-off (arm segment and inter-monomeric cavity mutations) — and showed that mutant subunits dominantly activate wild-type partners, explaining heterozygous gain-of-function.

    Evidence X-ray crystallography of wild-type and mutant NT5C2, mutagenesis, enzymatic assays, and reconstitution of hetero-oligomeric wild-type/mutant complexes

    PMID:29535428 PMID:29990496

    Open questions at the time
    • Full-length wild-type structure in inactive conformation not available
    • Dynamics of switch-off mechanism not captured by static crystal structures
  6. 2018 High

    A conditional mouse model demonstrated that constitutive NT5C2 R367Q activity depletes intracellular purine pools via excess purine export, explaining both chemoresistance and the fitness cost (impaired proliferation and self-renewal) of the mutation, and identifying IMPDH inhibition as a therapeutic vulnerability.

    Evidence Conditional-and-inducible NT5C2 R367Q knock-in leukemia mouse model with intracellular nucleotide pool measurements, leukemia-initiating cell assays, and IMPDH inhibitor treatment

    PMID:29342136

    Open questions at the time
    • Clinical validation of IMPDH inhibitor synergy in human patients not established
    • Whether all mutant alleles produce equivalent purine depletion unknown
  7. 2019 High

    Detailed metabolomic profiling showed that NT5C2 mutants exhibit neomorphic substrate preference toward thiopurine metabolites over endogenous purines, refining the mechanism of drug resistance beyond simple increased activity.

    Evidence Enzymatic assays comparing substrate specificity of wild-type and mutant NT5C2, intracellular metabolomics, and drug uptake/efflux measurements

    PMID:31358663

    Open questions at the time
    • Structural basis of altered substrate preference not resolved
    • In vivo metabolomic confirmation in animal models not provided
  8. 2020 Medium

    Loss-of-function studies in zebrafish linked NT5C2 to blood pressure regulation, expanding its physiological role beyond purine metabolism in hematopoietic cells.

    Evidence Morpholino knockdown and CRISPR knockout of nt5c2 in zebrafish larvae with hemodynamic and gene expression measurements

    PMID:32984406

    Open questions at the time
    • Mechanism connecting nucleotidase activity to vascular tone is unknown
    • Mammalian validation of cardiovascular phenotype not available
    • Relationship to GWAS blood pressure loci at NT5C2 locus not functionally demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of neomorphic substrate preference in mutant NT5C2, the mechanism linking nucleotidase loss to apoptosis, whether IMPDH-based combination therapy is effective against NT5C2-mutant ALL in patients, and how NT5C2 participates in cardiovascular regulation.
  • No structure of mutant NT5C2 bound to thiopurine substrate
  • Molecular pathway from NT5C2 loss to caspase activation uncharacterized
  • No clinical trial data for IMPDH inhibitor combination in NT5C2-mutant ALL

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 5
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4
Partners
CNNM2

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 Activating mutations in NT5C2 (cytosolic 5'-nucleotidase II) confer increased nucleotidase activity in vitro and drive resistance to 6-mercaptopurine and 6-thioguanine chemotherapy when expressed in ALL lymphoblasts, identifying NT5C2 as the enzyme responsible for inactivation of nucleoside-analog chemotherapy drugs. Whole-exome sequencing of relapsed ALL samples, in vitro enzymatic activity assays of mutant proteins, expression of mutant NT5C2 in ALL lymphoblasts with chemotherapy resistance readout Nature medicine High 23377281
2013 Relapse-specific NT5C2 base substitution mutations confer increased enzymatic (5'-nucleotidase) activity and resistance to nucleoside analog therapies; all affected individuals harboring NT5C2 mutations relapsed early (within 36 months), consistent with outgrowth of drug-resistant clones. RNA sequencing of matched diagnosis/relapse bone marrow, full-exon sequencing of NT5C2, enzymatic analysis of mutant proteins showing increased activity Nature genetics High 23377183
2018 Crystal structures of NT5C2 mutants K359Q and L375F reveal they reconfigure the catalytic center for substrate access and catalysis in the absence of allosteric activator; most relapse-associated mutations in the arm segment and inter-monomeric cavity disrupt a built-in switch-off mechanism; the C-terminal acidic tail (lost in Q523X) functions to restrain NT5C2 activation. X-ray crystallography of wild-type and mutant NT5C2 proteins, functional enzymatic assays, mutagenesis Cancer cell High 29990496
2018 All leukemia-associated NT5C2 mutants are constitutively active independent of allosteric ATP effects; 90% of leukemia-specific alleles directly affect two regulatory hotspots (helix A region residues 355-365, and intersubunit interface helix B 232-242 and flexible loop L 400-418); activation is transmitted from mutant to wild-type subunits in hetero-oligomeric complexes, explaining dominant activity from heterozygous mutations. Structural mapping of mutations, biochemical characterization of hetero-oligomeric complexes combining wild-type and mutant subunits, enzymatic activity assays Leukemia High 29535428
2018 Expression of NT5C2 R367Q mutation induces resistance to 6-mercaptopurine at the cost of impaired leukemia cell growth and leukaemia-initiating cell activity due to excess export of purines to the extracellular space and depletion of the intracellular purine-nucleotide pool; inhibition of IMPDH increased cytotoxicity against NT5C2-mutant lymphoblasts. Conditional-and-inducible leukaemia mouse model expressing NT5C2 R367Q, intracellular purine nucleotide pool measurements, IMPDH inhibition experiments Nature High 29342136
2019 NT5C2 mutant proteins show elevated 5'-nucleotidase activity with preferential activity toward thiopurine metabolites over endogenous purine nucleotides (neomorphic substrate preference); mutant NT5C2 expression reduces thiopurine uptake and increases efflux of 6-MP metabolites, and causes global shifts in intracellular nucleotide homeostasis. Biochemical enzymatic assays with mutant vs. wild-type NT5C2, intracellular metabolomic profiling, drug uptake and efflux measurements in cells expressing mutant NT5C2 Molecular cancer therapeutics High 31358663
2019 NT5C2 mutations alter activating and autoregulatory switch-off mechanisms of the enzyme, resulting in constitutively increased nucleotidase activity; NT5C2 mutant leukemias are chemoresistant to 6-mercaptopurine but show impaired proliferation and self-renewal. Review synthesizing biochemical, structural, and mouse model data; referenced enzymatic and structural studies Blood Medium 30910786
2008 Knockdown of NT5C2 (cN-II) in human astrocytoma cells using shRNA reduces enzyme activity and causes apoptosis (increased caspase 3 activity, reduced cell viability) without altering intracellular nucleotide concentrations or energy charge, demonstrating that cN-II activity is essential for cell survival. shRNA knockdown of NT5C2 in ADF astrocytoma cells, enzymatic activity assay, MTT viability assay, caspase 3 activity measurement, nucleotide concentration measurement Biochimica et biophysica acta Medium 18445485
2017 Genetic deletion of NT5C2 in mice does not lead to enhanced AMP or ADP concentrations in response to skeletal muscle contraction, and does not potentiate AMPK activation, contradicting prior gene silencing/overexpression studies that suggested NT5C2 controls AMPK via IMP/inosine hydrolysis. NT5C2 knockout mouse model, electrically stimulated skeletal muscle, intracellular adenine nucleotide level measurement, AMPK activity assay American journal of physiology. Endocrinology and metabolism Medium 28325731
2012 Virtual screening identified an anthraquinone inhibitor (AdiS) of NT5C2 (cN-II) with a Ki of 2.0 mM; crystallographic soaking experiments at 2.9 Å resolution located AdiS interaction at F354/I152 in effector site 1 of cN-II, and the compound increased apoptosis in cancer cells combined with nucleoside analog drugs. In silico virtual screening, in vitro enzymatic inhibition assay, X-ray crystallography of truncated cN-II soaked with inhibitor, cell viability assays Biochemical pharmacology Medium 23220537
2020 Knockdown or knockout of nt5c2 in zebrafish larvae results in significantly higher blood flow, increased arterial pulse, and elevated linear velocity, along with increased expression of hypertension markers (crp and ace), and knockout of nt5c2a reduces expression of cnnm2a, indicating NT5C2 participates in blood pressure regulation. Morpholino knockdown and CRISPR knockout of nt5c2 in zebrafish larvae, blood flow and arterial pulse measurement, RT-qPCR of hypertension markers Frontiers in cardiovascular medicine Medium 32984406
2016 A schizophrenia protective allele disrupts miR-206 binding to the NT5C2 3'UTR, leading to increased NT5C2 expression, as confirmed by luciferase reporter assay, suggesting post-transcriptional regulation of NT5C2 by miR-206. Luciferase-based reporter assay testing allele-specific miR-206 binding to NT5C2 3'UTR European neuropsychopharmacology Low 27424800

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 STING is a direct innate immune sensor of cyclic di-GMP. Nature 1291 21947006
2000 Guanylyl cyclases and signaling by cyclic GMP. Pharmacological reviews 910 10977868
2017 Cyclic di-GMP: second messenger extraordinaire. Nature reviews. Microbiology 751 28163311
2015 Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases. Proceedings of the National Academy of Sciences of the United States of America 588 26371324
2008 Riboswitches in eubacteria sense the second messenger cyclic di-GMP. Science (New York, N.Y.) 534 18635805
1993 Intracellular cyclic GMP receptor proteins. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 512 7680013
2005 C-di-GMP: the dawning of a novel bacterial signalling system. Molecular microbiology 501 16045609
2006 Mechanisms of cyclic-di-GMP signaling in bacteria. Annual review of genetics 492 16895465
2019 Cyclic GMP-AMP signalling protects bacteria against viral infection. Nature 440 31533127
2004 Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation. Molecular microbiology 414 15255898
2009 Structural and mechanistic determinants of c-di-GMP signalling. Nature reviews. Microbiology 398 19756011
1994 Cyclic GMP and calcium mediate phytochrome phototransduction. Cell 330 8156599
2009 Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacology & therapeutics 326 19306895
2013 Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nature medicine 275 23377281
2006 Allosteric control of cyclic di-GMP signaling. The Journal of biological chemistry 238 16923812
2013 Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nature genetics 228 23377183
2017 Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. Annual review of biochemistry 223 28399655
1996 Nitric oxide and cyclic GMP signaling. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 203 8594612
2008 Control of lipolysis by natriuretic peptides and cyclic GMP. Trends in endocrinology and metabolism: TEM 186 18337116
2007 Bacterial c-di-GMP is an immunostimulatory molecule. Journal of immunology (Baltimore, Md. : 1950) 183 17277122
2004 Cyclic di-GMP as a bacterial second messenger. Microbiology (Reading, England) 178 15289546
1990 Properties of GMP-140, an inducible granule membrane protein of platelets and endothelium. Blood cells 159 1693535
2001 NO, nitrotyrosine, and cyclic GMP in signal transduction. Medical science monitor : international medical journal of experimental and clinical research 158 11433215
1986 Cyclic GMP as mediator and biological marker of atrial natriuretic factor. Journal of hypertension. Supplement : official journal of the International Society of Hypertension 156 2873213
2003 Wnt signaling, Ca2+, and cyclic GMP: visualizing Frizzled functions. Science (New York, N.Y.) 115 12791979
2011 Cyclic di-GMP activation of polynucleotide phosphorylase signal-dependent RNA processing. Journal of molecular biology 111 21320509
1999 Guanylin regulatory peptides: structures, biological activities mediated by cyclic GMP and pathobiology. Regulatory peptides 105 10395405
2018 Clonal evolution mechanisms in NT5C2 mutant-relapsed acute lymphoblastic leukaemia. Nature 99 29342136
2005 Role of cyclic GMP in gene regulation. Frontiers in bioscience : a journal and virtual library 98 15769622
1988 Cyclic GMP and cell death in rat cerebellar slices. Neuroscience 95 2901694
2012 Evidence for cyclic Di-GMP-mediated signaling in Bacillus subtilis. Journal of bacteriology 92 22821967
2005 Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. The EMBO journal 89 15635450
2004 Cyclic GMP transporters. Neurochemistry international 85 15312981
1987 Phosphorylation of tyrosine hydroxylase by cyclic GMP-dependent protein kinase. Journal of neurochemistry 83 2879892
2017 Cyclic-di-GMP regulation of virulence in bacterial pathogens. Wiley interdisciplinary reviews. RNA 82 28990312
2004 Nitric oxide-cyclic GMP pathway with some emphasis on cavernosal contractility. International journal of impotence research 76 15229623
2018 Nitric oxide and cyclic GMP functions in bone. Nitric oxide : biology and chemistry 70 29550520
1983 Transducin and the cyclic GMP phosphodiesterase: amplifier proteins in vision. Cold Spring Harbor symposia on quantitative biology 69 6327179
1975 Cyclic GMP and lectin-induced lymphocyte activation. Journal of immunology (Baltimore, Md. : 1950) 64 171310
2000 Guanylin peptides: renal actions mediated by cyclic GMP. American journal of physiology. Renal physiology 60 10662722
1994 Cyclic GMP and regulation of cyclic nucleotide hydrolysis. Advances in pharmacology (San Diego, Calif.) 57 8038108
2022 Cyclic GMP and PKG Signaling in Heart Failure. Frontiers in pharmacology 56 35479330
2009 Prevailing concepts of c-di-GMP signaling. Contributions to microbiology 56 19494585
1999 Role of cyclic GMP in glutamate neurotoxicity in primary cultures of cerebellar neurons. Neuropharmacology 55 10608283
2020 Reciprocal c-di-GMP signaling: Incomplete flagellum biogenesis triggers c-di-GMP signaling pathways that promote biofilm formation. PLoS genetics 54 32176702
2008 A new role for a classical gene: white transports cyclic GMP. The Journal of experimental biology 53 18310115
2018 GMP CAR-T cell production. Best practice & research. Clinical haematology 50 29909913
2017 Circular RNA circ-NT5C2 acts as an oncogene in osteosarcoma proliferation and metastasis through targeting miR-448. Oncotarget 49 29383123
1990 Cyclic GMP and photoreceptor function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 49 1697545
1987 Regulation and role of guanylate cyclase-cyclic GMP in vascular relaxation. Progress in clinical and biological research 47 2890172
2009 Regulation of c-di-GMP metabolism in biofilms. Future microbiology 46 19327118
2021 OpaR Controls the Metabolism of c-di-GMP in Vibrio parahaemolyticus. Frontiers in microbiology 45 34163453
2012 Phosphodiesterases and cyclic GMP regulation in heart muscle. Physiology (Bethesda, Md.) 43 22875455
1988 Cyclic GMP-phosphodiesterase of rd retina: biosynthesis and content. Experimental eye research 43 2832200
2020 Dysfunctional telomeres trigger cellular senescence mediated by cyclic GMP-AMP synthase. The Journal of biological chemistry 42 32540968
2018 Structure and Mechanisms of NT5C2 Mutations Driving Thiopurine Resistance in Relapsed Lymphoblastic Leukemia. Cancer cell 42 29990496
2013 A cyclic GMP-dependent signalling pathway regulates bacterial phytopathogenesis. The EMBO journal 42 23881098
2008 Knockdown of cytosolic 5'-nucleotidase II (cN-II) reveals that its activity is essential for survival in astrocytoma cells. Biochimica et biophysica acta 42 18445485
2000 Mechanisms of guanylin action via cyclic GMP in the kidney. Annual review of physiology 42 10845107
2018 BrlR from Pseudomonas aeruginosa is a receptor for both cyclic di-GMP and pyocyanin. Nature communications 41 29967320
2019 Genetics and mechanisms of NT5C2-driven chemotherapy resistance in relapsed ALL. Blood 40 30910786
2016 Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 40 27004590
1995 Biochemical characterization of human GMP synthetase. The Journal of biological chemistry 40 7706277
2010 Cyclic-di-GMP reaches out into the bacterial RNA world. Science signaling 35 21098727
2014 Serum and supplement optimization for EU GMP-compliance in cardiospheres cell culture. Journal of cellular and molecular medicine 34 24444305
2016 Role of Phosphodiesterase 5 and Cyclic GMP in Hypertension. Current hypertension reports 32 27079836
1983 Cyclic GMP-dependent protein phosphorylation in mammalian brain. Federation proceedings 32 6313433
2010 Cyclic GMP pathways in hepatic encephalopathy. Neurological and therapeutic implications. Metabolic brain disease 31 20195723
1997 Models of persistent pulmonary hypertension of the newborn (PPHN) and the role of cyclic guanosine monophosphate (GMP) in pulmonary vasorelaxation. Seminars in perinatology 31 9352612
1999 Cyclic GMP and outer hair cell electromotility. Hearing research 30 10545631
2017 Optogenetic Module for Dichromatic Control of c-di-GMP Signaling. Journal of bacteriology 29 28320886
2023 c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella. Nature communications 28 37980414
2014 Cyclic GMP is involved in auxin signalling during Arabidopsis root growth and development. Journal of experimental botany 28 24591051
2005 Cyclic GMP signaling and regulation of SERCA activity during cardiac myocyte contraction. Cell calcium 28 15670873
1990 Cyclic GMP-activated protein kinase from Dictyostelium discoideum. Biochimica et biophysica acta 27 2166585
2018 Relapsed acute lymphoblastic leukemia-specific mutations in NT5C2 cluster into hotspots driving intersubunit stimulation. Leukemia 26 29535428
2018 Cyclic di-GMP integrates functionally divergent transcription factors into a regulation pathway for antioxidant defense. Nucleic acids research 26 29982829
2017 Effects of genetic deletion of soluble 5'-nucleotidases NT5C1A and NT5C2 on AMPK activation and nucleotide levels in contracting mouse skeletal muscles. American journal of physiology. Endocrinology and metabolism 26 28325731
2013 Therapeutic perspectives for cN-II in cancer. Current medicinal chemistry 26 23992314
2012 Identification and characterization of inhibitors of cytoplasmic 5'-nucleotidase cN-II issued from virtual screening. Biochemical pharmacology 26 23220537
2013 Identification of c-di-GMP derivatives resistant to an EAL domain phosphodiesterase. Biochemistry 24 23256840
2016 Schizophrenia risk variants affecting microRNA function and site-specific regulation of NT5C2 by miR-206. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 23 27424800
2012 Identification of Drosophila and human 7-methyl GMP-specific nucleotidases. The Journal of biological chemistry 23 23223233
2005 A role for cyclic-GMP dependent protein kinase in anoikis. Cellular signalling 23 16139477
2006 Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate kinase. Proteins 22 16288457
2022 Design and manufacture of a lyophilised faecal microbiota capsule formulation to GMP standards. Journal of controlled release : official journal of the Controlled Release Society 21 35963468
2020 c-di-GMP inhibits LonA-dependent proteolysis of TfoY in Vibrio cholerae. PLoS genetics 21 32589664
2010 Cyclic GMP kinase I modulates glucagon release from pancreatic α-cells. Diabetes 21 20978093
2003 Towards the ideal GMP: homologous recombination and marker gene excision. Journal of plant physiology 21 12940543
2002 Cyclic guanosine 5' monophosphate (GMP) prevents expression of neuronal nitric oxide synthase and apoptosis in motor neurons deprived of trophic factors in rats. Neuroscience letters 21 12095656
2019 Mechanisms of NT5C2-Mediated Thiopurine Resistance in Acute Lymphoblastic Leukemia. Molecular cancer therapeutics 20 31358663
2021 c-di-GMP Inhibits Early Sporulation in Clostridioides difficile. mSphere 19 34878288
2020 Studies in Zebrafish Demonstrate That CNNM2 and NT5C2 Are Most Likely the Causal Genes at the Blood Pressure-Associated Locus on Human Chromosome 10q24.32. Frontiers in cardiovascular medicine 19 32984406
2019 NosP Modulates Cyclic-di-GMP Signaling in Legionella pneumophila. Biochemistry 19 31576744
1987 Mechanism of vasodilation by nitrates: role of cyclic GMP. Cardiology 19 2886220
2018 Cyclic di-GMP Positively Regulates DNA Repair in Vibrio cholerae. Journal of bacteriology 18 29610212
1994 Cloning and sequencing of the GMP synthetase-encoding gene of Saccharomyces cerevisiae. Gene 18 8112582
2020 Legionella quorum sensing meets cyclic-di-GMP signaling. Current opinion in microbiology 17 32045871
2018 Expanding the clinical relevance of the 5'-nucleotidase cN-II/NT5C2. Purinergic signalling 17 30362044
2008 Differential allelic expression in leukoblast from patients with acute myeloid leukemia suggests genetic regulation of CDA, DCK, NT5C2, NT5C3, and TP53. Drug metabolism and disposition: the biological fate of chemicals 17 18775979