NT5E
NT5E | |||
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Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process | |||
Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 6: 85.45 – 85.5 Mb | Chr 9: 88.21 – 88.25 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73 (cluster of differentiation 73), is an enzyme that in humans is encoded by the NT5E gene.[5] CD73 commonly serves to convert AMP to adenosine.[6]
Transcription factor binding sites
NT5E contains binding sites for
Function
Ecto-5-prime-nucleotidase (5-prime-ribonucleotide phosphohydrolase; EC 3.1.3.5) catalyzes the conversion at neutral pH of purine 5-prime mononucleotides to nucleosides, the preferred substrate being
Immunosuppression
NT5E (CD73) is a surface
As a drug target
Some tumours have upregulation and overexpression of CD73 so it has been proposed as a drug target for cancer therapy.[14][15][16]
An anti-CD73 antibody CPI-006 has started early stage clinical trials as a treatment for advanced cancers.[17]
Systemic lupus erythematosus
Specialized immune cells such as myeloid-derived suppressor cells and regulatory T cells also mediate their effects via adenosine generated by local ectonucleotidase. In some cases of lupus patients, adequate T cell expression of CD73 is missing, which shows an impaired regulatory function of T cells.[18]
Cancer
NT5E can act as an immune inhibitory control molecule. Free adenosine generated by NT5E inhibits cellular immune responses and thereby promotes immune escape of tumor cells.
miRNA
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000135318 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032420 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 2129526.
- S2CID 208035622, retrieved 2020-11-28
- PMID 29720980.
- ^ "Entrez Gene: NT5E 5′-nucleotidase, ecto (CD73)".
- PMID 21288095.
- PMID 13149051.
- ^ Online Mendelian Inheritance in Man (OMIM): 211800
- PMID 27665459.
- ^ PMID 29720980.
- ^ Targeting adenosine for cancer immunotherapy 2018
- ^ Anti-CD73 in Cancer Immunotherapy: Awakening New Opportunities 2016
- S2CID 58767911.
- ^ Anti-CD73 antibody agent appears safe, shows promise in advanced cancers
- PMID 29942314.
- ^ PMID 28158983.
- PMID 31980601.
- S2CID 190909472.
- PMID 30568661.
- PMID 26820227.
Further reading
- Resta R, Thompson LF (February 1997). "T cell signalling through CD73". Cellular Signalling. 9 (2): 131–9. PMID 9113412.
- Kirchhoff C, Hale G (March 1996). "Cell-to-cell transfer of glycosylphosphatidylinositol-anchored membrane proteins during sperm maturation". Molecular Human Reproduction. 2 (3): 177–84. PMID 9238677.
- Resta R, Yamashita Y, Thompson LF (February 1998). "Ecto-enzyme and signaling functions of lymphocyte CD73". Immunological Reviews. 161: 95–109. S2CID 29930691.
- Rosi F, Carlucci F, Marinello E, Tabucchi A (March 2002). "Ecto-5'-nucleotidase in B-cell chronic lymphocytic leukemia". Biomedicine & Pharmacotherapy. 56 (2): 100–4. PMID 12000134.
- Babiychuk EB, Draeger A (June 2006). "Regulation of ecto-5'-nucleotidase activity via Ca2+-dependent, annexin 2-mediated membrane rearrangement?". Biochemical Society Transactions. 34 (Pt 3): 374–6. S2CID 8728207.
- Stefanovic V, Mandel P, Rosenberg A (July 1976). "Ecto-5'-nucleotidase of intact cultured C6 rat glioma cells". The Journal of Biological Chemistry. 251 (13): 3900–5. PMID 819433.
- Thomson LF, Ruedi JM, Glass A, Moldenhauer G, Moller P, Low MG, et al. (January 1990). "Production and characterization of monoclonal antibodies to the glycosyl phosphatidylinositol-anchored lymphocyte differentiation antigen ecto-5'-nucleotidase (CD73)". Tissue Antigens. 35 (1): 9–19. PMID 2137649.
- Klemens MR, Sherman WR, Holmberg NJ, Ruedi JM, Low MG, Thompson LF (November 1990). "Characterization of soluble vs membrane-bound human placental 5'-nucleotidase". Biochemical and Biophysical Research Communications. 172 (3): 1371–7. PMID 2173922.
- Boyle JM, Hey Y, Guerts van Kessel A, Fox M (December 1988). "Assignment of ecto-5'-nucleotidase to human chromosome 6". Human Genetics. 81 (1): 88–92. S2CID 22488106.
- Vlahović P, Stefanović V (1995). "Effect of dopamine on ecto-5'-nucleotidase expression in human glomerular mesangial cells". Archives Internationales de Physiologie, de Biochimie et de Biophysique. 102 (3): 171–3. PMID 8000038.
- Hansen KR, Resta R, Webb CF, Thompson LF (December 1995). "Isolation and characterization of the promoter of the human 5'-nucleotidase (CD73)-encoding gene". Gene. 167 (1–2): 307–12. PMID 8566797.
- Airas L, Jalkanen S (September 1996). "CD73 mediates adhesion of B cells to follicular dendritic cells". Blood. 88 (5): 1755–64. PMID 8781432.
- Airas L, Niemelä J, Salmi M, Puurunen T, Smith DJ, Jalkanen S (January 1997). "Differential regulation and function of CD73, a glycosyl-phosphatidylinositol-linked 70-kD adhesion molecule, on lymphocytes and endothelial cells". The Journal of Cell Biology. 136 (2): 421–31. PMID 9015312.
- Strohmeier GR, Lencer WI, Patapoff TW, Thompson LF, Carlson SL, Moe SJ, et al. (June 1997). "Surface expression, polarization, and functional significance of CD73 in human intestinal epithelia". The Journal of Clinical Investigation. 99 (11): 2588–601. PMID 9169488.
- Aumüller G, Renneberg H, Schiemann PJ, Wilhelm B, Seitz J, Konrad L, Wennemuth G (1997). "The Role of Apocrine Released Proteins in the Post-Testicular Regulation of Human Sperm Function". The Fate of the Male Germ Cell. Advances in Experimental Medicine and Biology. Vol. 424. pp. 193–219. PMID 9361795.
- Rosi F, Agostinho AB, Carlucci F, Zanoni L, Porcelli B, Marinello E, et al. (1998). "Behaviour of human lymphocytic isoenzymes of 5'-nucleotidase". Life Sciences. 62 (25): 2257–66. PMID 9651114.
External links
- NT5E+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P21589 (5′-nucleotidase) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.