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NT5E (5'-nucleotidase, ecto (CD73))

Written2012-04Ping Zhou, Jiayin Yang
Department of Physiology, Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China

(Note : for Links provided by Atlas : click)

Identity

Alias_namesNT5
5' nucleotidase (CD73)
5'-nucleotidase, ecto (CD73)
Alias_symbol (synonym)CD73
eN
eNT
CALJA
HGNC (Hugo) NT5E
LocusID (NCBI) 4907
Atlas_Id 44492
Location 6q14.3  [Link to chromosome band 6q14]
Location_base_pair Starts at 86159302 and ends at 86205509 bp from pter ( according to hg19-Feb_2009)  [Mapping NT5E.png]
 
  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.
Fusion genes
(updated 2016)
TTC7B (14q32.11) / NT5E (6q14.3)

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.

Protein

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 enzyme's production of adenosine.

Implicated in

Note
Entity 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 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 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 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 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.
  

Bibliography

Involvement of ecto-5'-nucleotidase/CD73 in U138MG glioma cell adhesion.
Cappellari AR, Vasques GJ, Bavaresco L, Braganhol E, Battastini AM.
Mol Cell Biochem. 2012 Jan;359(1-2):315-22. Epub 2011 Aug 21.
PMID 21858682
 
CD73 represses pro-inflammatory responses in human endothelial cells.
Grunewald JK, Ridley AJ.
J Inflamm (Lond). 2010 Feb 5;7(1):10.
PMID 20181103
 
Targeted disruption of cd73/ecto-5'-nucleotidase alters thromboregulation and augments vascular inflammatory response.
Koszalka P, Ozuyaman B, Huo Y, Zernecke A, Flogel U, Braun N, Buchheiser A, Decking UK, Smith ML, Sevigny J, Gear A, Weber AA, Molojavyi A, Ding Z, Weber C, Ley K, Zimmermann H, Godecke A, Schrader J.
Circ Res. 2004 Oct 15;95(8):814-21. Epub 2004 Sep 9.
PMID 15358667
 
CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death.
Serra S, Horenstein AL, Vaisitti T, Brusa D, Rossi D, Laurenti L, D'Arena G, Coscia M, Tripodo C, Inghirami G, Robson SC, Gaidano G, Malavasi F, Deaglio S.
Blood. 2011 Dec 1;118(23):6141-52. Epub 2011 Oct 13.
PMID 21998208
 
NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity.
Wang H, Lee S, Nigro CL, Lattanzio L, Merlano M, Monteverde M, Matin R, Purdie K, Mladkova N, Bergamaschi D, Harwood C, Syed N, Szlosarek P, Briasoulis E, McHugh A, Thompson A, Evans A, Leigh I, Fleming C, Inman GJ, Hatzimichael E, Proby C, Crook T.
Br J Cancer. 2012 Apr 10;106(8):1446-52. doi: 10.1038/bjc.2012.95. Epub 2012 Mar 27.
PMID 22454080
 
Ecto-5'-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells.
Wang L, Zhou X, Zhou T, Ma D, Chen S, Zhi X, Yin L, Shao Z, Ou Z, Zhou P.
J Cancer Res Clin Oncol. 2008 Mar;134(3):365-72. Epub 2007 Aug 2.
PMID 17671792
 
High expression of CD73 as a poor prognostic biomarker in human colorectal cancer.
Wu XR, He XS, Chen YF, Yuan RX, Zeng Y, Lian L, Zou YF, Lan N, Wu XJ, Lan P.
J Surg Oncol. 2012 Aug 1;106(2):130-7. doi: 10.1002/jso.23056. Epub 2012 Jan 27.
PMID 22287455
 
RNAi-mediated CD73 suppression induces apoptosis and cell-cycle arrest in human breast cancer cells.
Zhi X, Wang Y, Zhou X, Yu J, Jian R, Tang S, Yin L, Zhou P.
Cancer Sci. 2010 Dec;101(12):2561-9. doi: 10.1111/j.1349-7006.2010.01733.x. Epub 2010 Sep 28.
PMID 20874842
 
Overexpression of Ecto-5'-nucleotidase (CD73) promotes T-47D human breast cancer cells invasion and adhesion to extracellular matrix.
Zhou P, Zhi X, Zhou T, Chen S, Li X, Wang L, Yin L, Shao Z, Ou Z.
Cancer Biol Ther. 2007 Mar;6(3):426-31. Epub 2007 Mar 29.
PMID 17471030
 
5'-Nucleotidase: molecular structure and functional aspects.
Zimmermann H.
Biochem J. 1992 Jul 15;285 (Pt 2):345-65. (REVIEW)
PMID 1637327
 

Citation

This paper should be referenced as such :
Zhou, P ; Yang, J
NT5E (5'-nucleotidase, ecto (CD73))
Atlas Genet Cytogenet Oncol Haematol. 2012;16(9):655-657.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/NT5EID44492ch6q14.html


External links

Nomenclature
HGNC (Hugo)NT5E   8021
Cards
AtlasNT5EID44492ch6q14
Entrez_Gene (NCBI)NT5E  4907  5'-nucleotidase ecto
AliasesCALJA; CD73; E5NT; NT; 
NT5; NTE; eN; eNT
GeneCards (Weizmann)NT5E
Ensembl hg19 (Hinxton)ENSG00000135318 [Gene_View]  chr6:86159302-86205509 [Contig_View]  NT5E [Vega]
Ensembl hg38 (Hinxton)ENSG00000135318 [Gene_View]  chr6:86159302-86205509 [Contig_View]  NT5E [Vega]
ICGC DataPortalENSG00000135318
TCGA cBioPortalNT5E
AceView (NCBI)NT5E
Genatlas (Paris)NT5E
WikiGenes4907
SOURCE (Princeton)NT5E
Genetics Home Reference (NIH)NT5E
Genomic and cartography
GoldenPath hg19 (UCSC)NT5E  -     chr6:86159302-86205509 +  6q14-q21   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)NT5E  -     6q14-q21   [Description]    (hg38-Dec_2013)
EnsemblNT5E - 6q14-q21 [CytoView hg19]  NT5E - 6q14-q21 [CytoView hg38]
Mapping of homologs : NCBINT5E [Mapview hg19]  NT5E [Mapview hg38]
OMIM129190   211800   
Gene and transcription
Genbank (Entrez)AK075008 AK075083 AK314661 BC015940 BC065937
RefSeq transcript (Entrez)NM_001204813 NM_002526
RefSeq genomic (Entrez)NC_000006 NC_018917 NG_028214 NT_025741 NW_004929327
Consensus coding sequences : CCDS (NCBI)NT5E
Cluster EST : UnigeneHs.153952 [ NCBI ]
CGAP (NCI)Hs.153952
Alternative Splicing GalleryENSG00000135318
Gene ExpressionNT5E [ NCBI-GEO ]   NT5E [ EBI - ARRAY_EXPRESS ]   NT5E [ SEEK ]   NT5E [ MEM ]
Gene Expression Viewer (FireBrowse)NT5E [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4907
GTEX Portal (Tissue expression)NT5E
Protein : pattern, domain, 3D structure
UniProt/SwissProtP21589   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP21589  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP21589
Splice isoforms : SwissVarP21589
Catalytic activity : Enzyme3.1.3.5 [ Enzyme-Expasy ]   3.1.3.53.1.3.5 [ IntEnz-EBI ]   3.1.3.5 [ BRENDA ]   3.1.3.5 [ KEGG ]   
PhosPhoSitePlusP21589
Domaine pattern : Prosite (Expaxy)5_NUCLEOTIDASE_1 (PS00785)    5_NUCLEOTIDASE_2 (PS00786)   
Domains : Interpro (EBI)5'-Nucleotdase_C    5'-Nucleotdase_CS    5_nucleotidase/apyrase    Calcineurin-like_PHP_apaH    Metallo-depent_PP-like   
Domain families : Pfam (Sanger)5_nucleotid_C (PF02872)    Metallophos (PF00149)   
Domain families : Pfam (NCBI)pfam02872    pfam00149   
Conserved Domain (NCBI)NT5E
DMDM Disease mutations4907
Blocks (Seattle)NT5E
PDB (SRS)4H1S    4H1Y    4H2B    4H2F    4H2G    4H2I   
PDB (PDBSum)4H1S    4H1Y    4H2B    4H2F    4H2G    4H2I   
PDB (IMB)4H1S    4H1Y    4H2B    4H2F    4H2G    4H2I   
PDB (RSDB)4H1S    4H1Y    4H2B    4H2F    4H2G    4H2I   
Structural Biology KnowledgeBase4H1S    4H1Y    4H2B    4H2F    4H2G    4H2I   
SCOP (Structural Classification of Proteins)4H1S    4H1Y    4H2B    4H2F    4H2G    4H2I   
CATH (Classification of proteins structures)4H1S    4H1Y    4H2B    4H2F    4H2G    4H2I   
SuperfamilyP21589
Human Protein AtlasENSG00000135318
Peptide AtlasP21589
HPRD00552
IPIIPI00009456   IPI00552444   IPI00552302   IPI00647259   
Protein Interaction databases
DIP (DOE-UCLA)P21589
IntAct (EBI)P21589
FunCoupENSG00000135318
BioGRIDNT5E
STRING (EMBL)NT5E
ZODIACNT5E
Ontologies - Pathways
QuickGOP21589
Ontology : AmiGOnucleotide binding  cytoplasm  plasma membrane  plasma membrane  purine nucleotide biosynthetic process  purine nucleotide catabolic process  AMP catabolic process  DNA metabolic process  leukocyte cell-cell adhesion  brain development  ferrous iron binding  5'-nucleotidase activity  5'-nucleotidase activity  cell surface  response to aluminum ion  membrane  dephosphorylation  anchored component of membrane  adenosine biosynthetic process  pyrimidine nucleoside catabolic process  positive regulation of lipid biosynthetic process  negative regulation of inflammatory response  extracellular exosome  synaptic membrane  
Ontology : EGO-EBInucleotide binding  cytoplasm  plasma membrane  plasma membrane  purine nucleotide biosynthetic process  purine nucleotide catabolic process  AMP catabolic process  DNA metabolic process  leukocyte cell-cell adhesion  brain development  ferrous iron binding  5'-nucleotidase activity  5'-nucleotidase activity  cell surface  response to aluminum ion  membrane  dephosphorylation  anchored component of membrane  adenosine biosynthetic process  pyrimidine nucleoside catabolic process  positive regulation of lipid biosynthetic process  negative regulation of inflammatory response  extracellular exosome  synaptic membrane  
Pathways : KEGGPurine metabolism    Pyrimidine metabolism    Nicotinate and nicotinamide metabolism   
REACTOMEP21589 [protein]
REACTOME PathwaysR-HSA-74259 Purine catabolism [pathway]
REACTOME PathwaysR-HSA-73621 Pyrimidine catabolism [pathway]
NDEx NetworkNT5E
Atlas of Cancer Signalling NetworkNT5E
Wikipedia pathwaysNT5E
Orthology - Evolution
OrthoDB4907
GeneTree (enSembl)ENSG00000135318
Phylogenetic Trees/Animal Genes : TreeFamNT5E
HOVERGENP21589
HOGENOMP21589
Homologs : HomoloGeneNT5E
Homology/Alignments : Family Browser (UCSC)NT5E
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerNT5E [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)NT5E
dbVarNT5E
ClinVarNT5E
1000_GenomesNT5E 
Exome Variant ServerNT5E
ExAC (Exome Aggregation Consortium)NT5E (select the gene name)
Genetic variants : HAPMAP4907
Genomic Variants (DGV)NT5E [DGVbeta]
DECIPHER (Syndromes)6:86159302-86205509  ENSG00000135318
CONAN: Copy Number AnalysisNT5E 
Mutations
ICGC Data PortalNT5E 
TCGA Data PortalNT5E 
Broad Tumor PortalNT5E
OASIS PortalNT5E [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICNT5E  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDNT5E
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch NT5E
DgiDB (Drug Gene Interaction Database)NT5E
DoCM (Curated mutations)NT5E (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)NT5E (select a term)
intoGenNT5E
NCG5 (London)NT5E
Cancer3DNT5E(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM129190    211800   
Orphanet20749   
MedgenNT5E
Genetic Testing Registry NT5E
NextProtP21589 [Medical]
TSGene4907
GENETestsNT5E
Huge Navigator NT5E [HugePedia]
snp3D : Map Gene to Disease4907
BioCentury BCIQNT5E
ClinGenNT5E
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4907
Chemical/Pharm GKB GenePA31804
Clinical trialNT5E
Miscellaneous
canSAR (ICR)NT5E (select the gene name)
Probes
Litterature
PubMed110 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineNT5E
EVEXNT5E
GoPubMedNT5E
iHOPNT5E
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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