Browse NT5E

Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane; Lipid-anchor, GPI-anchor.
Domain PF02872 5'-nucleotidase
PF00149 Calcineurin-like phosphoesterase
Function

Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.

> Gene Ontology
 
Biological Process GO:0006152 purine nucleoside catabolic process
GO:0006195 purine nucleotide catabolic process
GO:0006196 AMP catabolic process
GO:0006213 pyrimidine nucleoside metabolic process
GO:0007159 leukocyte cell-cell adhesion
GO:0009116 nucleoside metabolic process
GO:0009119 ribonucleoside metabolic process
GO:0009123 nucleoside monophosphate metabolic process
GO:0009125 nucleoside monophosphate catabolic process
GO:0009126 purine nucleoside monophosphate metabolic process
GO:0009128 purine nucleoside monophosphate catabolic process
GO:0009150 purine ribonucleotide metabolic process
GO:0009154 purine ribonucleotide catabolic process
GO:0009158 ribonucleoside monophosphate catabolic process
GO:0009161 ribonucleoside monophosphate metabolic process
GO:0009163 nucleoside biosynthetic process
GO:0009164 nucleoside catabolic process
GO:0009166 nucleotide catabolic process
GO:0009167 purine ribonucleoside monophosphate metabolic process
GO:0009169 purine ribonucleoside monophosphate catabolic process
GO:0009261 ribonucleotide catabolic process
GO:0016311 dephosphorylation
GO:0019439 aromatic compound catabolic process
GO:0031348 negative regulation of defense response
GO:0032102 negative regulation of response to external stimulus
GO:0034655 nucleobase-containing compound catabolic process
GO:0042278 purine nucleoside metabolic process
GO:0042451 purine nucleoside biosynthetic process
GO:0042454 ribonucleoside catabolic process
GO:0042455 ribonucleoside biosynthetic process
GO:0044270 cellular nitrogen compound catabolic process
GO:0046033 AMP metabolic process
GO:0046085 adenosine metabolic process
GO:0046086 adenosine biosynthetic process
GO:0046128 purine ribonucleoside metabolic process
GO:0046129 purine ribonucleoside biosynthetic process
GO:0046130 purine ribonucleoside catabolic process
GO:0046135 pyrimidine nucleoside catabolic process
GO:0046434 organophosphate catabolic process
GO:0046700 heterocycle catabolic process
GO:0050727 regulation of inflammatory response
GO:0050728 negative regulation of inflammatory response
GO:0072522 purine-containing compound biosynthetic process
GO:0072523 purine-containing compound catabolic process
GO:0072527 pyrimidine-containing compound metabolic process
GO:0072529 pyrimidine-containing compound catabolic process
GO:1901136 carbohydrate derivative catabolic process
GO:1901292 nucleoside phosphate catabolic process
GO:1901361 organic cyclic compound catabolic process
GO:1901565 organonitrogen compound catabolic process
GO:1901657 glycosyl compound metabolic process
GO:1901658 glycosyl compound catabolic process
GO:1901659 glycosyl compound biosynthetic process
Molecular Function GO:0008252 nucleotidase activity
GO:0008253 5'-nucleotidase activity
GO:0016791 phosphatase activity
GO:0042578 phosphoric ester hydrolase activity
Cellular Component GO:0031225 anchored component of membrane
> KEGG and Reactome Pathway
 
KEGG hsa00230 Purine metabolism
hsa00240 Pyrimidine metabolism
hsa00760 Nicotinate and nicotinamide metabolism
hsa01100 Metabolic pathways
Reactome R-HSA-1430728: Metabolism
R-HSA-15869: Metabolism of nucleotides
R-HSA-196854: Metabolism of vitamins and cofactors
R-HSA-196849: Metabolism of water-soluble vitamins and cofactors
R-HSA-196807: Nicotinate metabolism
R-HSA-74259: Purine catabolism
R-HSA-73847: Purine metabolism
R-HSA-73621: Pyrimidine catabolism
R-HSA-73848: Pyrimidine metabolism
Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between NT5E and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between NT5E and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27245613Cervical CarcinomaInhibit immunityPKA also stimulated the binding of the coactivator p300 to HIF-1α to enhance its transcriptional activity and counteracted the inhibitory effect of asparaginyl hydroxylation on the association of p300 with HIF-1α. Furthermore, increased cAMP concentrations enhanced the expression of HIF target genes encoding CD39 and CD73, which are enzymes that convert extracellular adenosine 5'-triphosphate to adenosine, a molecule that enhances tumor immunosuppression and reduces heart rate and contractility.
26363007Ovarian CarcinomaInhibit immunity (T cell function)Furthermore, high levels of CD73 expression in ovarian tumor cells abolished the good prognosis associated with intraepithelial CD8(+) cells.
25403716MelanomaInhibit immunity (T cell function)The generation of adenosine via the CD39/CD73 pathway is recognized as a major mechanism of regulatory T cell (Treg) immunosuppressive function. Blockade of CD39 increases CTL- and NK cell–mediated killing.
29375567Ovarian CarcinomaInhibit immunityMetformin-induced reduction of CD39 and CD73 blocks myeloid-derived suppressor cell activity in patients with ovarian cancer. Metformin triggered activation of AMP-activated protein kinase α (AMPKα) and subsequently suppressed hypoxia-inducible factor-α (HIF-1α), which was critical for induction of CD39/CD73 expression in MDSC.
29374065Ovarian CarcinomaInhibit immunity (T cell function); immunotherapy targetMetformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.
27321181Ovarian carcinomaInhibit immunityAdenosine is a major determinant of the immunosuppressive tumor milieu. Sequential hydrolysis of extracellular ATP catalyzed by CD39 and CD73 is the main pathway for the generation of adenosine in the tumor interstitium. Preclinical data show that targeting the adenosine-generating pathway (that is, CD73) or adenosinergic receptors (that is, A2A) relieves immunosuppresion and potently inhibits tumor growth.\
21292811Colon Carcinoma; Lymphoma; Breast Carcinoma; MelanomaInhibit immunity (T cell function)We found that CD73 ablation significantly suppressed the growth of ovalbumin-expressing MC38 colon cancer, EG7 lymphoma, AT-3 mammary tumors, and B16F10 melanoma. The protective effect of CD73 deficiency on primary tumors was dependent on CD8(+) T cells and associated with an increased frequency of antigen-specific CD8(+) T cells in peripheral blood and tumors and increased antigen-specific IFN-γ production.
23776241Triple-Negative Breast CarcinomaInhibit immunity; immunotherapy targetUsing mouse models of breast cancer, we demonstrated that CD73 overexpression in tumor cells conferred chemoresistance to doxorubicin, a commonly used anthracycline, by suppressing adaptive antitumor immune responses via activation of A2A adenosine receptors. Targeted blockade of CD73 enhanced doxorubicin-mediated antitumor immune responses and significantly prolonged the survival of mice with established metastatic breast cancer. Taken together, our data suggest that CD73 constitutes a therapeutic target in TNBC.
23737488Malignant GliomaInhibit immunity (T cell function)We demonstrated that increased suppression of responder CD4(+) T-cell proliferation suppression was induced by CD4(+)CD39(+) T cells in the presence of CD73(+) glioma cells, which could be alleviated by the CD39 inhibitor ARL67156, the CD73 inhibitor APCP, or the adenosine receptor A2aR antagonist SCH58261. Our data indicate that glioma-derived CD73 contributes to local adenosine-mediated immunosuppression in synergy with CD39 from infiltrating CD4(+)CD39(+) T lymphocytes, which could become a potential therapeutic target for treatment of malignant glioma and other immunosuppressive diseases.
22396496Fibrosarcoma; Prostate Carcinoma; Metastatic Malignant Neoplasm in the LungInhibit immunity (T and NK cell function); immunotherapy targetCD73 deficiency suppressed the development of 3-methylcholanthrene (MCA)-induced fibrosarcomas through a mechanism relying upon IFN-γ, natural killer (NK) cells, and CD8(+) T cells. Importantly, treatment with an anti-CD73 monoclonal antibody effectively suppressed growth of established MCA-induced tumors or TRAMP-C1 prostate tumors and inhibited the development of TRAMP-C1 lung metastases.
29663369Squamous Cell CarcinomaInhibit immunity (T cell function); immunotherapy targetAltogether, these findings highlight the immunoregulatory role of CD73 in the development of HNSCC and we propose that CD73 may prove to be a promising immunotherapeutic target for the treatment of HNSCC.
29574275Malignant Ovarian NeoplasmInhibit immunity (T cell function); immunotherapy targetIn order to further enhance the therapeutic efficacy, anti-CD73 and anti-OX40 immunostimulants were combined with mCTH-ANXA5, resulting in an increase of survival by 100% from 12 to 24 days post-therapy and decrease tumor burden in mice with orthotopic metastatic ovarian cancer.
23964122B16 Malignant MelanomaInhibit immunityCD73 inhibits antitumor immunity through the activation of adenosine receptors expressed on multiple immune subsets. CD73 also enhances tumor metastasis, although the nature of the immune subsets and adenosine receptor subtypes involved in this process are largely unknown.
20080644Breast CarcinomaInhibit immunityAnti-CD73 antibody therapy inhibits breast tumor growth and metastasis.In addition to its immunosuppressive effect, CD73 enhanced tumor-cell chemotaxis, suggesting a role for CD73-derived adenosine in tumor metastasis. In conclusion, our study identified tumor-derived CD73 as a mechanism of tumor immune escape and tumor metastasis.
29145561Triple-Negative Breast CarcinomaInhibit immunityCD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Our results demonstrated that high levels of CD73 expression on epithelial tumor cells were significantly associated with reduced disease-free survival, overall survival and negatively correlated with tumor immune infiltration (Spearman's R= -0.50, p < 0.0001).
28652246MelanomaInhibit immunity; Resistant to immunotherapyHere we found that induction of CD73, the enzyme that generates immunosuppressive adenosine, is linked to melanoma phenotype switching. We also detected CD73 upregulation in melanoma patients progressing under adoptive T-cell transfer or immune checkpoint blockade, arguing for an adaptive resistance mechanism.
27993599Breast CarcinomaInhibit immunity; Resistant to immunotherapyOur results showed that intravenous administration of CD73-specific siRNA-loaded NPs led to reduced expression of CD73 in tumor cells which was associated with decreased tumor growth and metastasis, and improved mice survival. In conclusion, our findings indicate that the use of CD73-specific siRNA-loaded NPs provides an immune potentiating function, thereby improves the efficacy of DC based cancer immunotherapy.
22826317MelanomaInhibit immunity (T cell function)Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanoma. CD73 is a cell surface enzyme that suppresses T cell-mediated immune responses by producing extracellular adenosine. In this study, we demonstrate that administration of a specific CD73 inhibitor, adenosine 5'-(α,β-methylene)diphosphate (APCP), to melanoma-bearing mice induced a significant tumor regression by promoting the release of Th1- and Th17-associated cytokines in the tumor microenvironment.
20179192Ovarian CarcinomaInhibit immunityCD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression. Because the ecto-5'-nucleotidase activity of CD73 catalyzes AMP breakdown to immunosuppressive adenosine, we hypothesized that CD73-generated adenosine prevents tumor destruction by inhibiting antitumor immunity. We confirmed this hypothesis by showing that combining tumor CD73 knockdown and tumor-specific T-cell transfer cured all tumor-bearing mice.
25205101melanomaInhibit immunityHowever, current protocols for ex vivo programming of Th17 cells, which include TGFbeta exposure, increase the expression of CD39 and CD73, two cell surface ATP ectonucleotidases that reduce T-cell effector functions and promote immunosuppression
Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of NT5E in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of NT5E in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.9910.226
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.9640.623
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-1.0070.503
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.3630.388
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.4410.788
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.2640.897
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1330.84
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0370.98
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2060.907
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.1940.901
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.5240.459
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.6360.00139
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of NT5E in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.16.24.91
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 592011.18.91
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.305.30.507
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NT5E. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NT5E. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NT5E.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NT5E. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of NT5E expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between NT5E and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolNT5E
Name5'-nucleotidase, ecto (CD73)
Aliases CD73; eN; eNT; CALJA; 5' nucleotidase (CD73); E5NT; Purine 5-Prime-Nucleotidase; CD antigen CD73
Chromosomal Location6q14-q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting NT5E collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting NT5E.
ID Name Drug Type Targets #Targets
DB00806PentoxifyllineSmall MoleculeADORA1, ADORA2A, NT5E, PDE4A, PDE4B, PDE5A6