NT5E (5-nucleotidase, ecto (CD73))

2012-04-01   Ping Zhou  , Jiayin Yang  

Department of Physiology, Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China

Identity

HGNC
LOCATION
6q14.3
IMAGE
Atlas Image
LEGEND
The NT5E gene is located on the long (q) arm of chromosome 6 between positions 14 and 21. More precisely, the NT5E gene is located from base pair 86159301 to base pair 86205508 on chromosome 6.
LOCUSID
ALIAS
CALJA,CD73,E5NT,NT,NT5,NTE,eN,eNT
FUSION GENES

DNA/RNA

Transcription

Two transcript variants encoding different isoforms have been found for this gene. Variant 1 represents the longer transcript and encodes the longer isoform 1, 9 exons, transcript length 3548 bps, translation length 574 residues; variant 2 lacks an alternate in-frame exon compared to variant 1, 8 exons, transcript length 3384 bps, translation length 524 residues.

Proteins

Description

There are two isoforms of NT5E. 5-nucleotidase isoform 1 preproprotein, 574 amino acids; 5-nucleotidase isoform 2 preproprotein, 524 amino acids. Isoform 2 has the same N- and C-termini but is shorter compared to isoform 1.
The NT5E preproprotein is further processed into a mature form, which consists of a dimer of 2 identical 70-kD subunits bound by a glycosyl phosphatidyl inositol linkage at its C-terminus to the external face of the plasma membrane.

Expression

CD73 is a cell surface enzyme found in most tissues and many cell types including subsets of lymphocytes, macrophages, dendritic cells, endothelial cells and epithelial cells. Hypoxia induces CD73 mRNA, protein expression and increases CD73 activity in mouse microvascular endothelial cells. Particularly, CD73 is highly expressed in many human solid tumors, and its elevated expression and activity are associated with tumor invasiveness and metastasis and with shorter patient survival. The RNA expression and enzyme activity of CD73 are variable in different breast cancer cell lines. For more details see gene expression pattern of NT5E.

Localisation

Plasma membrane.

Function

CD73 is an ectoenzyme (ecto-50-nucleotidase, EC 3.1.3.5). It catalyzes conversion of AMP to adenosine. Adenosine exerts its effects via adenosine receptor A1, adenosine receptor A2A, adenosine receptor A2B and adenosine receptor A3.
CD73 has many physiological roles, such as regulation of barrier function, adaptation to hypoxia, ischemic preconditioning, anti-inflammation, leukocyte extravasation.
Expression and activity of CD73 on cancer cells is associated with poor prognosis and may promote metastasis. CD73 facilitates the adhesion, migration, invasion of human breast cancer cells and proliferation of glioma cells and these process are dependent upon the enzymes production of adenosine.

Implicated in

Entity name
Melanoma
Note
Deregulation of NT5E expression in melanoma occurs via epigenetic changes in the NT5E CpG island. Confirmation of the results in larger clinical series would support the candidacy of NT5E as a clinical biomarker in melanoma, which could be applied in both primary and relapsed disease. Inhibition of NT5E may have therapeutic potential in melanoma, particularly in patients with more aggressive disease metastasis to viscera or the brain.
Entity name
Colorectal cancer
Note
CD73 expression in colorectal cancer is significantly higher than in normal colorectal tissues.
Prognosis
Patients with high expression of CD73 had a poorer overall survival rate compared with patients with low expression of CD73 in both cohorts. High expression of CD73 can be an independent and useful biomarker for predicting the poor survival of patients with colorectal cancer.
Entity name
Chronic lymphocytic leukemia
Note
CD73-generated extracellular adenosine in chronic lymphocytic leukemia increases cytoplasmic cAMP levels by activation of the ADO receptors, inhibiting chemotaxis and limiting spontaneous drug-induced apoptosis of chronic lymphocytic leukemia cells.
Entity name
Glioma
Note
Adenosine induced an increase in glioma cell adhesion. Ecto-5-NT/CD73, an important producer of extracellular adenosine, may modulate glioma cell adhesion and tumor cell-extracellular matrix interactions.
Entity name
Breast cancer
Note
CD73 plays an important role in breast cancer growth by affecting cell cycle progression and apoptosis. CD73 overexpression increased cell viability and promoted cell cycle progression, depending on its enzyme activity.
CD73 may facilitate the adhesion, migration and invasion of human breast cancer cells through its enzyme activity of generating adenosine.
Tumor-derived CD73 is a mechanism of tumor immune escape and tumor metastasis, and targeted therapy against CD73 can trigger adaptive anti-tumor immunity and inhibit metastasis of breast cancer.

Article Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 4907
MIM: 129190
HGNC: 8021
Ensembl: ENSG00000135318

Variants:

dbSNP: 4907
ClinVar: 4907
TCGA: ENSG00000135318
COSMIC: NT5E

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000135318ENST00000257770P21589
ENSG00000135318ENST00000369646Q96B60
ENSG00000135318ENST00000369651P21589
ENSG00000135318ENST00000416334H0Y7R7
ENSG00000135318ENST00000437581H0Y3X5

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Purine metabolismKEGGko00230
Pyrimidine metabolismKEGGko00240
Nicotinate and nicotinamide metabolismKEGGko00760
Purine metabolismKEGGhsa00230
Pyrimidine metabolismKEGGhsa00240
Nicotinate and nicotinamide metabolismKEGGhsa00760
Metabolic pathwaysKEGGhsa01100
MetabolismREACTOMER-HSA-1430728
Metabolism of nucleotidesREACTOMER-HSA-15869
Purine metabolismREACTOMER-HSA-73847
Purine catabolismREACTOMER-HSA-74259
Pyrimidine metabolismREACTOMER-HSA-73848
Pyrimidine catabolismREACTOMER-HSA-73621
Metabolism of vitamins and cofactorsREACTOMER-HSA-196854
Metabolism of water-soluble vitamins and cofactorsREACTOMER-HSA-196849
Nicotinate metabolismREACTOMER-HSA-196807

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
370556752024Human plasmacytoid dendritic cells express the functional purinergic halo (CD39/CD73).1
374021022024ENTPD1 (CD39) and NT5E (CD73) expression in human glioblastoma: an in silico analysis.0
382276542024CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway.1
382669692024CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing hemodialysis.0
389783042024The immunomodulatory ballet of tumour-derived extracellular vesicles and neutrophils orchestrating the dynamic CD73/PD-L1 pathway in cancer.1
370556752024Human plasmacytoid dendritic cells express the functional purinergic halo (CD39/CD73).1
374021022024ENTPD1 (CD39) and NT5E (CD73) expression in human glioblastoma: an in silico analysis.0
382276542024CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway.1
382669692024CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing hemodialysis.0
389783042024The immunomodulatory ballet of tumour-derived extracellular vesicles and neutrophils orchestrating the dynamic CD73/PD-L1 pathway in cancer.1
363145272023AHR/TET2/NT5E axis downregulation is associated with the risk of systemic lupus erythematosus and its progression.2
366081322023Proteolytic regulation of CD73 by TRIM21 orchestrates tumor immunogenicity.8
367200422023CD73-Dependent Adenosine Signaling through Adora2b Drives Immunosuppression in Ductal Pancreatic Cancer.10
367768662023The ectonucleotidases CD39 and CD73 on T cells: The new pillar of hematological malignancy.5
367781232023CD73/NT5E-mediated ubiquitination of AURKA regulates alcohol-related liver fibrosis via modulating hepatic stellate cell senescence.1

Citation

Ping Zhou ; Jiayin Yang

NT5E (5-nucleotidase, ecto (CD73))

Atlas Genet Cytogenet Oncol Haematol. 2012-04-01

Online version: http://atlasgeneticsoncology.org/gene/44492/js/lib/haematological-explorer/gene-fusions-explorer/