Affinage

NT5E

5'-nucleotidase · UniProt P21589

Length
574 aa
Mass
63.4 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NT5E (CD73) is a GPI-anchored ecto-5'-nucleotidase that catalyzes hydrolysis of extracellular AMP to adenosine, the rate-limiting step generating extracellular adenosine that signals through adenosine receptors to control inflammation, tissue homeostasis, and tumor biology (PMID:21288095, PMID:22011440). The catalytically generated adenosine acts in a receptor-subtype-specific manner: via A1R it inhibits spinal nociception and drives a CDC42→N-WASP→ARP2/3 cortical-actin program that maintains epithelial barrier integrity (PMID:22011440, PMID:26642367); via A2A it mediates apoptotic-cell- and microglia-associated immunosuppression and feed-forward neuroinflammation (PMID:30689733, PMID:28060378); and via A2B it promotes osteoblast differentiation and tumor-endothelial invasiveness (PMID:21882189, PMID:30926752). Loss-of-function NT5E mutations abolish enzyme activity and cause arterial and joint calcifications (CALJA), with adenosine treatment reversing the associated alkaline phosphatase elevation and calcification in patient fibroblasts (PMID:21288095). Disease-causing mutants are mistrafficked into the ER/secretory apparatus rather than reaching the plasma membrane (PMID:24887587), and surface CD73 abundance is further set by TRIM21-mediated ubiquitination at K133/K208/K262/K321, whose loss stabilizes CD73 and amplifies adenosine-driven CD8+ T cell suppression (PMID:36608132). Beyond adenosine production, CD73 supports tumor cell mitochondrial respiration, OXPHOS, and aspartate biosynthesis needed for proliferation (PMID:37261423), restrains cGAS-STING sensing of tumor DNA damage (PMID:36409930), and exerts enzyme-independent roles as a costimulatory molecule in T cell activation (requiring p56lck/CD45/TCR but neither catalytic activity nor the GPI anchor) and in matrix adhesion (PMID:9113412, PMID:16718268). CD73 additionally engages partner proteins directly, interacting with EGFR to activate AKT/mTOR signaling and with AURKA to inhibit its ubiquitination and downregulate p53 signaling (PMID:35813221, PMID:36778123).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1997 Medium

    Established that CD73 has signaling functions separable from its enzymatic role, showing it can costimulate T cell activation without catalysis or membrane anchoring.

    Evidence Jurkat T cell transfection with enzymatic-null and GPI-anchorless CD73 constructs plus functional activation assays

    PMID:9113412

    Open questions at the time
    • Molecular partner mediating non-enzymatic costimulation not identified
    • Dependence on p56lck/CD45/TCR defined functionally but not biochemically
  2. 2006 Medium

    Defined a CD73 adhesion function in extracellular matrix engagement independent of adenosine, linking it to integrins and lipid-raft organization.

    Evidence Density gradient fractionation, concanavalin A clustering, siRNA knockdown, and adhesion assays on tenascin C in melanoma cells

    PMID:16718268

    Open questions at the time
    • Direct CD73-integrin binding not demonstrated
    • Mechanism of tenascin C inhibition of activity unresolved
  3. 2011 High

    Identified NT5E as the causal gene for arterial and joint calcification, proving loss of AMP-to-adenosine activity drives ectopic mineralization and is reversible by adenosine.

    Evidence Targeted sequencing, enzyme assays, in vitro calcification, and wild-type rescue in patient fibroblasts across three families

    PMID:21288095

    Open questions at the time
    • Tissue-specific basis of vascular/joint vulnerability not explained
    • Link between adenosine loss and alkaline phosphatase elevation mechanistically incomplete
  4. 2011 High

    Demonstrated CD73 is a principal source of extracellular adenosine in nociceptive circuits, acting on A1R to inhibit pain.

    Evidence Fast-scan cyclic voltammetry, histochemistry, and behavioral assays in Pap/Nt5e double-knockout mice

    PMID:22011440

    Open questions at the time
    • Relative contribution of CD73 vs PAP across tissues not fully partitioned
  5. 2011 High

    Connected CD73-derived adenosine to bone biology, showing it drives osteoblast differentiation specifically through A2B receptor signaling.

    Evidence CD73-knockout mouse bone phenotyping plus MC3T3-E1 overexpression with A2B vs A2A antagonist dissection

    PMID:21882189

    Open questions at the time
    • Downstream transcriptional effectors of A2BAR in osteoblasts not defined
  6. 2013 Medium

    Showed CD73 promotes tumor angiogenesis through both adenosine-dependent and enzyme-independent mechanisms involving VEGF.

    Evidence CD73-deficient host mouse tumor models, endothelial knockdown tube/migration assays, VEGF ELISA, and anti-CD73 antibody treatment

    PMID:23982901

    Open questions at the time
    • Molecular basis of the non-enzymatic angiogenic function not defined
  7. 2014 High

    Explained why disease mutations abolish surface activity by showing mutant CD73 is retained intracellularly rather than trafficked to the plasma membrane.

    Evidence Confocal microscopy, subcellular fractionation, and Malachite green activity assay of DsRed-tagged constructs in COS-7 cells

    PMID:24887587

    Open questions at the time
    • Quality-control machinery recognizing mutant CD73 unidentified
  8. 2015 High

    Defined an A1R→CDC42→N-WASP→ARP2/3 cortical-actin axis through which CD73-derived adenosine maintains epithelial barrier integrity.

    Evidence CD73 knockout mice, pharmacological inhibition, A1R antagonism, and Rho GTPase/ARP2/3 pathway analysis in endometrial epithelium

    PMID:26642367

    Open questions at the time
    • Generality of this axis beyond endometrial epithelium not established
  9. 2017 High

    Distinguished CD73 from CD39 in resolving inflammation, showing CD73-generated adenosine specifically drives apoptotic-cell suppression of macrophage TNF via A2a.

    Evidence Enzymatic adenosine depletion, A2a inhibition, CD73-knockout macrophages, ectopic A2a/CD73 co-expression, and a peritonitis model

    PMID:28060378

    Open questions at the time
    • Spatial coupling of CD73 and CD39 in tandem nucleotide catabolism not resolved
  10. 2019 Medium

    Extended CD73's immunosuppressive role to neuroinflammation, defining a feed-forward A2AR loop in microglia in Parkinson's models.

    Evidence CD73 inactivation in MPTP mice, LPS-stimulated microglia, laser injury, and adenosine replenishment

    PMID:30689733

    Open questions at the time
    • Transcriptional basis of CD73/A2AR co-upregulation not defined
  11. 2019 Medium

    Localized CD73 function to tissue-specific compartments, showing perivascular CD73 prevents kidney fibrosis and endothelial CD73 drives glioblastoma invasion via A2B.

    Evidence Foxd1Cre conditional knockout with soluble CD73 rescue in kidney injury; CD73-FLK transgenic GBM models with A2B inhibition

    PMID:30926752 PMID:31364375

    Open questions at the time
    • A2B downstream effectors (e.g., MMP-2 induction) only partly mapped
    • Cross-tissue generalizability uncertain
  12. 2020 Medium

    Revealed regulated trafficking and transcriptional reprogramming of CD73 in NK cells that converts them to suppressive cells via STAT3-driven IL-10.

    Evidence Live-cell imaging of vesicular CD73 transport, 4-1BBL engagement, STAT3 inhibition, and T cell suppression assays

    PMID:31770109

    Open questions at the time
    • Trafficking machinery for CD73 exocytosis not identified
  13. 2022 Medium

    Identified upstream epigenetic control of NT5E expression through an AHR/TET2 axis controlling promoter methylation in Tregs.

    Evidence ChIP of AHR at the TET2 promoter, NT5E promoter methylation analysis, and kynurenine treatment of Tregs

    PMID:36314527

    Open questions at the time
    • Direct demethylation of NT5E by TET2 not shown biochemically
  14. 2022 Medium

    Connected CD73 to Treg tissue tropism and direct effector-T-cell binding during cardiac repair, and to epithelial stem cell self-renewal.

    Evidence CD73-knockout Treg adoptive transfer in myocardial infarction; FACS isolation and organoid assays of CD73+CD104+ esophageal progenitors

    PMID:35108658 PMID:35401839

    Open questions at the time
    • Binding partner mediating Treg-effector contact unidentified
    • Mechanism of CD73 in stem cell self-renewal undefined
  15. 2023 High

    Established post-translational control of CD73 stability via TRIM21-mediated ubiquitination, defining the lysine residues and the tumor-immunosuppressive consequence.

    Evidence Co-IP, ubiquitylation assays, site-directed mutagenesis of K133/K208/K262/K321, TRIM21 manipulation, and CD8+ T cell assays

    PMID:36608132

    Open questions at the time
    • Signals controlling TRIM21-CD73 engagement not identified
  16. 2023 High

    Uncovered enzyme-independent CD73 functions in cancer metabolism and DNA-damage sensing — supporting OXPHOS/aspartate biosynthesis and restraining cGAS-STING.

    Evidence Metabolomics, Seahorse respirometry, aspartate rescue in immune-deficient mice; CRISPR CD73/cGAS deletion in KPC tumor models with AB680

    PMID:36409930 PMID:37261423

    Open questions at the time
    • Molecular mechanism coupling CD73 to mitochondrial respiration unresolved
    • How CD73 loss elevates DNA damage not defined
  17. 2023 Medium

    Defined direct protein-protein interactions of CD73 with AURKA, stabilizing AURKA by blocking its ubiquitination and downregulating p53 in liver fibrosis.

    Evidence Co-immunoprecipitation, molecular docking, and CD73 modulation in hepatic stellate cells

    PMID:36778123

    Open questions at the time
    • Structural interface of CD73-AURKA not validated experimentally
    • Mechanism of ubiquitination inhibition unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD73's enzyme-independent scaffolding functions (EGFR, AURKA, integrin, costimulatory) are structurally and mechanistically integrated with its canonical catalytic role remains unresolved.
  • No unified structural model linking catalytic and scaffolding functions
  • EGFR interaction rests on single Co-IP
  • Determinants of CD73 partner selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140096 catalytic activity, acting on a protein 2 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 2 R-HSA-1643685 Disease 2 R-HSA-392499 Metabolism of proteins 2
Partners
AURKAEGFRTRIM21

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 NT5E/CD73 converts AMP to adenosine; loss-of-function mutations (nonsense p.S221X, missense p.C358Y, frameshift p.V537fsX7) abolish this enzyme activity and cause arterial and joint calcifications. Cultured fibroblasts from affected patients showed markedly reduced CD73 protein, absent enzyme activity, elevated alkaline phosphatase, and accumulated calcium phosphate crystals. Genetic rescue with wild-type NT5E normalized CD73 and alkaline phosphatase activity; adenosine treatment reduced alkaline phosphatase levels and calcification. Western blotting, enzyme activity assays, in vitro calcification assays, transduction rescue experiments, SNP analysis, targeted gene sequencing The New England journal of medicine High 21288095
2014 Disease-causing NT5E mutations (p.S221X, p.C358Y, p.V537fsX7) result in mistrafficking of NT5E protein away from the plasma membrane: mutant proteins accumulate in the cell synthetic apparatus (ER/vesicles) rather than reaching the cell surface, with reduced ER retention and absent NT5E enzymatic activity at the cell surface. Confocal microscopy, western blot of fractionated cell constituents, enzyme histochemistry (Malachite green assay), heterologous expression of DsRed-tagged wild-type and mutant NT5E in COS-7 cells PloS one High 24887587
1997 CD73 functions as a costimulatory molecule for T cell activation independently of its enzymatic activity and independently of its GPI anchor (demonstrated using a Jurkat T cell transfection model); however, expression of p56lck, CD45, and the T cell receptor are required for CD73-mediated T cell activation in vitro. Jurkat T cell transfection with CD73 cDNA constructs (enzymatic-activity-null and GPI-anchorless mutants), functional T cell activation assays Cellular signalling Medium 9113412
2012 CD73-generated adenosine promotes osteoblast differentiation via A2B adenosine receptor (A2BAR) signaling. CD73-deficient mice show osteopenia with reduced osteoblastic markers but normal osteoclastic markers. Overexpression of CD73 in MC3T3-E1 cells enhanced osteocalcin and bone sialoprotein expression, an effect blocked by an A2BAR antagonist but not an A2AAR antagonist. CD73-knockout mouse bone phenotyping, in vitro osteoblast differentiation assays, CD73 overexpression in MC3T3-E1 cells, pharmacological receptor antagonism Journal of cellular physiology High 21882189
2011 NT5E (CD73) and PAP are the principal ectonucleotidases generating adenosine in spinal nociceptive circuits. AMP hydrolysis was nearly abolished in dorsal root ganglia and spinal cord lamina II of Pap/Nt5e double-knockout mice. NT5E rapidly converts AMP to adenosine within seconds in lamina II (measured by fast-scan cyclic voltammetry), and the resulting adenosine inhibits nociception via the A1 adenosine receptor. Histochemical AMP hydrolysis, fast-scan cyclic voltammetry in spinal lamina II, behavioral nociception assays, Pap/Nt5e double-knockout mice, pharmacological A1 receptor analysis Molecular pain High 22011440
2015 CD73-generated adenosine induces cortical actin polymerization in endometrial epithelial cells via adenosine A1 receptor (A1R) activation of a Rho GTPase CDC42-dependent conformational change of the N-WASP subunit of the ARP2/3 complex. This cortical F-actin elevation increases membrane E-cadherin, β-catenin, and Na+K+ ATPase, maintaining epithelial integrity. Loss of CD73 reduces endometrial epithelial barrier function and increases migration/invasion. CD73 pharmacological inhibition, CD73 knockout mouse model, in vitro migration/invasion assays, co-localization of CD73 with cell-cell contacts and filopodia, A1R antagonism, Rho GTPase and ARP2/3 pathway analysis The Journal of clinical investigation High 26642367
2019 CD73-derived adenosine activates adenosine A2A receptor (A2AR) in a feed-forward manner in microglia, upregulating CD73 and A2AR to promote neuroinflammation in Parkinson's disease models. CD73 inactivation attenuated LPS-induced pro-inflammatory responses, enhanced microglial process extension and movement, and suppressed microglia-mediated neuroinflammation. A2AR-mediated pro-inflammation was restored by exogenous adenosine analogues. CD73 inactivation in MPTP mouse model, LPS-stimulated microglia assays, laser injury model, pharmacological adenosine replenishment, morphological analysis of microglia Brain : a journal of neurology Medium 30689733
2017 CD73 regulates anti-inflammatory signaling between apoptotic cells and endotoxin-conditioned macrophages. Adenosine generated by CD73 (AMP→adenosine) but not CD39 (ATP→AMP) is required for apoptotic cell-driven suppression of TNF in LPS-conditioned macrophages, acting through the adenosine A2a receptor (Adora2a). In mice, CD73 was required to limit neutrophil influx in a peritonitis model. Enzymatic depletion of adenosine, pharmacological A2a receptor inhibition, CD73-knockout macrophages, RAW264.7 ectopic co-expression of A2a and CD73, in vivo peritonitis model Cell death and differentiation High 28060378
2020 Tumor-infiltrating NK cells transport CD73 in intracellular vesicles to the cell surface and extracellular space via actin polymerization-dependent exocytosis, triggered by engagement of 4-1BBL on tumor cells. CD73-positive NK cells undergo transcriptional reprogramming with upregulated IL-10 production via STAT3 transcriptional activity, suppressing CD4+ T cell proliferation and IFN-γ production. Flow cytometry, live cell imaging of CD73-vesicle trafficking, cytokine assays, STAT3 inhibition, functional T cell suppression assays The Journal of clinical investigation Medium 31770109
2019 CD73 on glioblastoma endothelial cells promotes tumor invasiveness through A2B adenosine receptor (A2B AR) signaling, which induces matrix metalloproteinase-2 (MMP-2) expression. Inhibition of A2B AR signaling decreased multidrug resistance transporter expression (P-gp and MRP1) and potentiated temozolomide-induced cell death. The CD73-FLK mouse model demonstrated that endothelial CD73 drives tumor invasiveness and brain morphology distortion. CD73-knockout and CD73-FLK transgenic mouse GBM models, A2B AR inhibition, immunohistochemistry, tumor growth/vessel density measurement The Journal of neuroscience Medium 30926752
2023 TRIM21 is an E3 ubiquitin ligase that targets CD73 for ubiquitin-mediated proteolytic degradation. Lysine residues K133, K208, K262, and K321 on CD73 are required for TRIM21-mediated ubiquitylation and degradation. Loss of TRIM21 stabilizes CD73, enhancing CD73-catalyzed adenosine production and suppressing CD8+ T cell function, promoting tumor growth. Co-immunoprecipitation, ubiquitylation assays, site-directed mutagenesis of CD73 lysine residues, TRIM21 knockout/overexpression, CD8+ T cell functional assays Science advances High 36608132
2023 CD73 deficiency in pancreatic tumor cells leads to increased DNA damage and activation of the cGAS-STING pathway. cGAS expression in tumor cells was required for the antitumor activity of the CD73 inhibitor AB680 in vivo, linking CD73 to suppression of innate immune sensing of tumor DNA damage. CRISPR/genetic CD73 deletion in mouse KPC tumor cells, cGAS knockout, in vivo tumor models, pharmacogenomic analysis of human PDAC cell lines Cancer immunology research Medium 36409930
2023 CD73 significantly enhances tumor cell mitochondrial respiration, oxidative phosphorylation (OXPHOS), glycolytic reserve, and aspartate biosynthesis. Rescuing aspartate biosynthesis was sufficient to restore proliferation of CD73-deficient tumors in immune-deficient mice. Targeting CD73 decreased metabolic fitness, increased genomic instability, and suppressed PARP activity. Metabolomics, Seahorse analysis of large panel of mouse and human tumor cell lines, CD73-deficient tumor implantation in immune-deficient mice, aspartate rescue experiments eLife High 37261423
2023 NT5E/CD73 directly interacts with Aurora kinase A (AURKA) and inhibits AURKA ubiquitination. This interaction, confirmed by co-immunoprecipitation and molecular docking, downregulates p53 signaling and regulates hepatic stellate cell senescence and activation, thereby promoting alcohol-related liver fibrosis. Co-immunoprecipitation, molecular docking, KEGG pathway analysis, CD73 overexpression/knockdown in stellate cells, proteomic analysis International journal of biological sciences Medium 36778123
2019 CD73 perivascular cell expression (Foxd1+ lineage pericytes/fibroblasts) is required to suppress inflammation and prevent kidney fibrosis after ischemia-reperfusion injury. Conditional deletion of CD73 from perivascular cells increased collagen deposition, proinflammatory markers, and PDGFR-β immunoreactivity. Fibrosis and dysfunction were rescued by administration of soluble CD73 or by macrophage deletion. Conditional CD73 knockout (Foxd1Cre × CD73fl/fl), unilateral ischemia-reperfusion injury, folic acid nephropathy model, soluble CD73 rescue, macrophage depletion American journal of physiology. Renal physiology Medium 31364375
2013 CD73 promotes tumor angiogenesis through both enzymatic (adenosine-dependent) and non-enzymatic functions. Tumor-derived CD73 enhances VEGF production by tumor cells; host-derived CD73 is required for in vivo angiogenic responses; endothelial cells require CD73 expression for tube formation and migration. Anti-CD73 monoclonal antibody treatment significantly decreased tumor VEGF levels and suppressed angiogenesis in vivo. Mouse breast cancer model with CD73-deficient host cells, in vitro tube formation and migration assays with CD73-knockdown endothelial cells, VEGF ELISA, anti-CD73 antibody treatment International journal of cancer Medium 23982901
2006 Ecto-5'-nucleotidase (CD73) in melanoma cells is catalytically active and is located in lipid rafts. Concanavalin A-induced clustering of CD73 causes its redistribution to heavier cytoskeletal fractions along with co-expressed integrins (αv, α5, β1, β3), caveolin-1, and CD44. Tenascin C inhibits CD73 activity and adenosine generation. Knockdown of CD73 in WM9 cells significantly reduces cell adhesion to tenascin C, indicating a CD73 role in adhesion to extracellular matrix independent of adenosine generation. Density gradient centrifugation, enzyme activity assays, concanavalin A clustering, siRNA knockdown of CD73, cell adhesion assay on ECM proteins Melanoma research Medium 16718268
2022 CD73 deficiency on Foxp3+ regulatory T cells impairs their tissue tropism and immunosuppressive function during cardiac healing post-myocardial infarction. CD73-deficient Tregs showed impaired ability to inhibit inflammatory cytokine production in effector T cells. CD73 on Tregs was found to bind to FoxP3- effector T cells directly. CD73-knockout Treg adoptive transfer, flow cytometry, permanent coronary ligation mouse model, cytokine assays, IL-2/anti-IL-2 complex Treg expansion Theranostics Medium 35401839
2023 Hypoxic conditioning increases the frequency of CD73+ CD4+ T cells and promotes HIV latency. CD73 or adenosine receptor blockade facilitates latent HIV reactivation in vitro, mechanistically linking CD73-mediated adenosine signaling to viral quiescence. CD73+ CD4+ T cells harbor a functional HIV reservoir and can reinitiate productive infection ex vivo. Systems transcriptomics, hypoxic culture, CD73/adenosine receptor blockade, ex vivo HIV reactivation assay, tissue imaging of lymph nodes from HIV-infected individuals Cell reports Medium 37910505
2022 CD73 expression defines CD73+CD104+ epithelial progenitor cells in the esophagus with enhanced organoid-forming capacity. Knockdown of CD73 decreases organoid formation rate, demonstrating a functional role of CD73 in esophageal epithelial stem cell self-renewal. IL-4 and IL-13 (via STAT6 signaling) deplete the CD73+CD104+ population, which is associated with basal cell hyperplasia in eosinophilic esophagitis. Fluorescence-activated cell sorting of CD73+CD104+ vs CD73-CD104+ populations, organoid formation assays, RNA interference knockdown of CD73, single-cell RNA sequencing, STAT6 inhibition Cellular and molecular gastroenterology and hepatology Medium 35108658
2022 CD73 knockdown in pancreatic cancer cells inhibited ERK/STAT3 pathway activation and activated the E-cadherin pathway, leading to inhibition of cell growth, migration, and G1 cell cycle arrest. A CRISPR/Cas9 protein kinase library screen identified Pbk, Fastk, Cdk19, Adck5, Trim28, and Pfkp as potential regulators of CD73. CRISPR/Cas9 CD73 knockout in human and murine pancreatic cancer cell lines, flow cytometry cell cycle analysis, migration assay, western blotting of ERK/STAT3 and E-cadherin pathways, kinase library CRISPR screen Cancers Medium 37835536
2022 CD73 in lung adenocarcinoma cells physically interacts with EGFR (demonstrated by immunoprecipitation) and promotes activation of the AKT/mTOR signaling pathway, driving proliferation, migration, and invasion. Immunoprecipitation of CD73-EGFR interaction, siRNA knockdown and overexpression of CD73 in A549 cells, western blotting of AKT/mTOR pathway, proliferation, colony formation, wound healing, and Transwell invasion assays BioMed research international Low 35813221
2019 CD73 knockdown in pancreatic ductal adenocarcinoma inhibited cell growth and induced G1 phase arrest via the AKT/ERK/cyclin D signaling pathway. TNFR2 was identified as involved in CD73-induced AKT and ERK signaling pathway activation in PDAC cells. CD73 knockdown, cell cycle analysis, western blotting of AKT/ERK/cyclin D, TNFR2 inhibition experiments Journal of molecular medicine Low 30927045
2021 Structure-based design of methylenephosphonic acid CD73 inhibitors exploited key binding interactions of the known inhibitor AMPCP with human CD73, demonstrating that the catalytic site of CD73 can accommodate this class of competitive inhibitors with high potency and selectivity against related ectonucleotidases. Structure-based drug design using hCD73 crystal structure with AMPCP, in vitro enzymatic inhibition assays, selectivity profiling against related ectonucleotidases, pharmacokinetic analysis Journal of medicinal chemistry Medium 33399453
2014 CD73 catalytic activity (AMP to adenosine conversion) can be harnessed to instruct supramolecular hydrogelation: CD73 dephosphorylation of AMP precursors triggers self-assembly of nanofibers forming hydrogels, demonstrating that CD73 enzymatic activity can be coupled to materials formation. Enzymatic supramolecular hydrogelation assay, nanofiber characterization Journal of colloid and interface science Low 25524006
2022 AHR promotes TET2 expression by binding to the TET2 promoter (kynurenine-dependent), and TET2 in turn regulates NT5E promoter methylation status to control CD73 expression on regulatory T cells. Downregulation of the AHR/TET2/NT5E axis in SLE Tregs is associated with reduced CD73 expression and impaired immunosuppressive function. ChIP assay (AHR binding to TET2 promoter), methylation-specific analysis of NT5E promoter, kynurenine treatment of Tregs and Jurkat T cells, flow cytometry, adenosine receptor pathway analysis Immunology Medium 36314527

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 CD39 and CD73 in immunity and inflammation. Trends in molecular medicine 1013 23601906
2011 NT5E mutations and arterial calcifications. The New England journal of medicine 382 21288095
2023 CD39/CD73/A2AR pathway and cancer immunotherapy. Molecular cancer 298 36859386
1998 Ecto-enzyme and signaling functions of lymphocyte CD73. Immunological reviews 274 9553767
2012 CD73-deficient mice are resistant to carcinogenesis. Cancer research 179 22396496
2020 CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment. The Journal of clinical investigation 173 31770109
2014 The roles of CD73 in cancer. BioMed research international 168 25126561
2013 Anti-CD73 therapy impairs tumor angiogenesis. International journal of cancer 148 23982901
2015 CD73 and CD39 ectonucleotidases in T cell differentiation: Beyond immunosuppression. FEBS letters 146 26226423
2013 CD73 and adenosine generation in the creation of regulatory microenvironments. Clinical and experimental immunology 144 23199317
2020 Targeting CD73 to augment cancer immunotherapy. Current opinion in pharmacology 137 32777746
2017 CD73/NT5E is a target of miR-30a-5p and plays an important role in the pathogenesis of non-small cell lung cancer. Molecular cancer 128 28158983
2018 Targeting the CD73-adenosine axis in immuno-oncology. Immunology letters 123 29758241
2018 CD73 as a potential opportunity for cancer immunotherapy. Expert opinion on therapeutic targets 122 30556751
2020 CD73 Blockade Promotes Dendritic Cell Infiltration of Irradiated Tumors and Tumor Rejection. Cancer immunology research 116 32047024
2019 CD73: an emerging checkpoint for cancer immunotherapy. Immunotherapy 111 31223045
2016 CD73-adenosine: a next-generation target in immuno-oncology. Immunotherapy 110 26808918
2017 CD73 Promotes Resistance to HER2/ErbB2 Antibody Therapy. Cancer research 103 28855210
2012 CD73-generated adenosine promotes osteoblast differentiation. Journal of cellular physiology 103 21882189
2007 VAP-1 and CD73, endothelial cell surface enzymes in leukocyte extravasation. Arteriosclerosis, thrombosis, and vascular biology 93 17962625
2019 Cell type- and tissue-specific functions of ecto-5'-nucleotidase (CD73). American journal of physiology. Cell physiology 92 31461341
2006 Expression of ecto-5'-nucleotidase (eN, CD73) in cell lines from various stages of human melanoma. Melanoma research 89 16718268
2018 Controlling the Immune Suppressor: Transcription Factors and MicroRNAs Regulating CD73/NT5E. Frontiers in immunology 88 29720980
2012 NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity. British journal of cancer 83 22454080
2016 The SLC28 (CNT) and SLC29 (ENT) nucleoside transporter families: a 30-year collaborative odyssey. Biochemical Society transactions 81 27284054
2019 CD73-derived adenosine controls inflammation and neurodegeneration by modulating dopamine signalling. Brain : a journal of neurology 80 30689733
2015 Loss of CD73-mediated actin polymerization promotes endometrial tumor progression. The Journal of clinical investigation 76 26642367
2020 CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers. Frontiers in immunology 70 32351498
2019 CD73 Promotes Glioblastoma Pathogenesis and Enhances Its Chemoresistance via A2B Adenosine Receptor Signaling. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 30926752
2019 Targeting the Immunomodulatory CD73/Adenosine System to Improve the Therapeutic Gain of Radiotherapy. Frontiers in immunology 67 31024543
2016 Oridonin, a Promising ent-Kaurane Diterpenoid Lead Compound. International journal of molecular sciences 65 27563888
2023 CD73 Inhibits cGAS-STING and Cooperates with CD39 to Promote Pancreatic Cancer. Cancer immunology research 59 36409930
2017 CD73 regulates anti-inflammatory signaling between apoptotic cells and endotoxin-conditioned tissue macrophages. Cell death and differentiation 59 28060378
2021 The elegant complexity of mammalian ecto-5'-nucleotidase (CD73). Trends in cell biology 55 34116887
2019 The distinct role of CD73 in the progression of pancreatic cancer. Journal of molecular medicine (Berlin, Germany) 53 30927045
2023 The Clinical Significance of CD73 in Cancer. International journal of molecular sciences 52 37511518
2021 CD73, Tumor Plasticity and Immune Evasion in Solid Cancers. Cancers 52 33430239
2019 Generation and Function of Non-cell-bound CD73 in Inflammation. Frontiers in immunology 52 31404305
1997 T cell signalling through CD73. Cellular signalling 52 9113412
2015 The expression and clinical significance of CD73 molecule in human rectal adenocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 50 25677906
2022 CD4+FoxP3+CD73+ regulatory T cell promotes cardiac healing post-myocardial infarction. Theranostics 49 35401839
2011 PAP and NT5E inhibit nociceptive neurotransmission by rapidly hydrolyzing nucleotides to adenosine. Molecular pain 48 22011440
2019 CD73 (Cluster of Differentiation 73) and the Differences Between Mice and Humans. Arteriosclerosis, thrombosis, and vascular biology 44 30676071
2021 Regulation of immune responses through CD39 and CD73 in cancer: Novel checkpoints. Life sciences 42 34265363
2018 CD73 expression and clinical significance in human metastatic melanoma. Oncotarget 42 29928476
2023 CD73-Dependent Adenosine Signaling through Adora2b Drives Immunosuppression in Ductal Pancreatic Cancer. Cancer research 40 36720042
2016 Anti-CD73 immunotherapy: A viable way to reprogram the tumor microenvironment. Oncoimmunology 40 27757316
2004 The pea gene LH encodes ent-kaurene oxidase. Plant physiology 39 14988475
2016 MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma. Oncotarget 38 27281619
2024 Neutrophil extracellular traps promote immune escape in hepatocellular carcinoma by up-regulating CD73 through Notch2. Cancer letters 37 38969159
2022 The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells. Frontiers in immunology 37 35711418
2017 Targeting of NT5E by miR-30b and miR-340 attenuates proliferation, invasion and migration of gallbladder carcinoma. Biochimie 35 29155108
2019 NT5E/CD73 as Correlative Factor of Patient Survival and Natural Killer Cell Infiltration in Glioblastoma. Journal of clinical medicine 34 31547570
2022 The regulation of CD73 in non-small cell lung cancer. European journal of cancer (Oxford, England : 1990) 32 35598361
2019 CD73 expression in normal and pathological human hepatobiliopancreatic tissues. Cancer immunology, immunotherapy : CII 32 30607549
2014 Roles of the adenosine receptor and CD73 in the regulatory effect of γδ T cells. PloS one 31 25268760
2020 PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E. Molecular cancer research : MCR 30 33037085
2022 CD73+ Epithelial Progenitor Cells That Contribute to Homeostasis and Renewal Are Depleted in Eosinophilic Esophagitis. Cellular and molecular gastroenterology and hepatology 29 35108658
2019 Downregulation of CD73 associates with T cell exhaustion in AML patients. Journal of hematology & oncology 29 31014364
2023 Proteolytic regulation of CD73 by TRIM21 orchestrates tumor immunogenicity. Science advances 28 36608132
2021 Discovery of Potent and Selective Methylenephosphonic Acid CD73 Inhibitors. Journal of medicinal chemistry 28 33399453
2020 CD73 Overexpression Promotes Progression and Recurrence of Papillary Thyroid Carcinoma. Cancers 28 33086655
2015 A Systems Oncology Approach Identifies NT5E as a Key Metabolic Regulator in Tumor Cells and Modulator of Platinum Sensitivity. Journal of proteome research 27 26629888
2024 Regulatory role of CD39 and CD73 in tumor immunity. Future oncology (London, England) 26 38652041
2022 Reshaping hypoxia and silencing CD73 via biomimetic gelatin nanotherapeutics to boost immunotherapy. Journal of controlled release : official journal of the Controlled Release Society 26 36165836
2015 Calcification of joints and arteries: second report with novel NT5E mutations and expansion of the phenotype. Journal of human genetics 26 26178434
2019 Perivascular CD73+ cells attenuate inflammation and interstitial fibrosis in the kidney microenvironment. American journal of physiology. Renal physiology 25 31364375
2020 ent-Labdane and ent-kaurane diterpenoids from Chelonopsis odontochila with α-glucosidase inhibitory activity. Bioorganic chemistry 23 31927318
2023 Tumor intrinsic and extrinsic functions of CD73 and the adenosine pathway in lung cancer. Frontiers in immunology 22 37033953
2023 Combining High-Z Sensitized Radiotherapy with CD73 Blockade to Boost Tumor Immunotherapy. ACS nano 21 37327456
2021 CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma. Cancer immunology, immunotherapy : CII 21 33416944
2019 Monitoring and characterizing soluble and membrane-bound ectonucleotidases CD73 and CD39. PloS one 21 31652269
2019 Ent-abietane and ent-pimarane diterpenoids from Croton mubango (Euphorbiaceae). Phytochemistry 21 31812109
2018 Ecto-5'-nucleotidase (CD73) is a potential target of hepatocellular carcinoma. Journal of cellular physiology 21 30417547
2018 Activity of ecto-5'-nucleotidase (NT5E/CD73) is increased in papillary thyroid carcinoma and its expression is associated with metastatic lymph nodes. Molecular and cellular endocrinology 20 30184475
2022 CD73 (NT5E) Promotes the Proliferation and Metastasis of Lung Adenocarcinoma through the EGFR/AKT/mTOR Pathway. BioMed research international 19 35813221
2018 Extracellular ATP Regulates CD73 and ABCC6 Expression in HepG2 Cells. Frontiers in molecular biosciences 18 30155470
2016 ent-Pimarane and ent-Kaurane Diterpenes from Aldama discolor (Asteraceae) and Their Antiprotozoal Activity. Molecules (Basel, Switzerland) 18 27649126
2024 Regulation of CD73 on NAD metabolism: Unravelling the interplay between tumour immunity and tumour metabolism. Cell communication and signaling : CCS 17 39090604
2023 The hypoxia-regulated ectonucleotidase CD73 is a host determinant of HIV latency. Cell reports 17 37910505
2022 AHR/TET2/NT5E axis downregulation is associated with the risk of systemic lupus erythematosus and its progression. Immunology 17 36314527
2024 Blockade of CD73 potentiates radiotherapy antitumor immunity and abscopal effects via STING pathway. Cell death discovery 16 39285178
2023 CD73/NT5E-mediated ubiquitination of AURKA regulates alcohol-related liver fibrosis via modulating hepatic stellate cell senescence. International journal of biological sciences 16 36778123
2023 The CD73 immune checkpoint promotes tumor cell metabolic fitness. eLife 16 37261423
2022 Functional expression of CD73 on human natural killer cells. Cancer immunology, immunotherapy : CII 16 35622118
2021 Transcriptome Profiling Reveals CD73 and Age-Driven Changes in Neutrophil Responses against Streptococcus pneumoniae. Infection and immunity 16 34310891
2025 CD39 and CD73: biological functions, diseases and therapy. Molecular biomedicine 15 41188606
2022 CD73 and PD-L1 as Potential Therapeutic Targets in Gallbladder Cancer. International journal of molecular sciences 15 35163489
2021 Influence of NSAIDs and methotrexate on CD73 expression and glioma cell growth. Purinergic signalling 15 33745072
2018 En route into chloroplasts: preproteins' way home. Photosynthesis research 15 29943212
2006 Synthesis of ent-25-hydroxycholesterol. Steroids 15 16519912
2023 5'-Ectonucleotidase CD73/NT5E supports EGFR-mediated invasion of HPV-negative head and neck carcinoma cells. Journal of biomedical science 14 37620936
1998 CD73 and adhesion of B-cells to follicular dendritic cells. Leukemia & lymphoma 14 9638974
2023 Impact of CRISPR/Cas9-Mediated CD73 Knockout in Pancreatic Cancer. Cancers 13 37835536
2022 The Effects of CD73 on Gastrointestinal Cancer Progression and Treatment. Journal of oncology 13 35620732
2020 MicroRNA-30a suppresses self-renewal and tumorigenicity of glioma stem cells by blocking the NT5E-dependent Akt signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 32067282
2017 Ent-Abietanoids Isolated from Isodon serra. Molecules (Basel, Switzerland) 12 28218684
2014 NT5E mutations that cause human disease are associated with intracellular mistrafficking of NT5E protein. PloS one 12 24887587
2023 Small molecular CD73 inhibitors: Recent progress and future perspectives. European journal of medicinal chemistry 11 38086190
2014 The first CD73-instructed supramolecular hydrogel. Journal of colloid and interface science 11 25524006

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