| Written | 2008-01 | Pablo Pelegrin, Annmarie Surprenant |
| Faculty of Life Science, Michael Smith Building, University of Manchester, Manchester, M13 9PT, UK |
| Identity |
| Alias_names | purinergic receptor P2X |
| Alias_symbol (synonym) | P2X7 |
| MGC20089 | |
| Other alias | P2Z |
| HGNC (Hugo) | P2RX7 |
| LocusID (NCBI) | 5027 |
| Atlas_Id | 41623 |
| Location | 12q24.31 [Link to chromosome band 12q24] |
| Location_base_pair | Starts at 121132828 and ends at 121186551 bp from pter ( according to hg19-Feb_2009) [Mapping P2RX7.png] |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| EVC (4p16.2) / P2RX7 (12q24.31) | P2RX4 (12q24.31) / P2RX7 (12q24.31) | P2RX7 (12q24.31) / COQ9 (16q21) | |
| SPCS3 (4q34.2) / P2RX7 (12q24.31) |
| DNA/RNA |
| Description | The P2RX7 gene is comprised of 13 coding exons. |
| Transcription | The full length transcript is 3135 bp long and 10 alternative splicing isoforms have been identified. |
| Pseudogene | Not known. |
| Protein |
| Description | The protein has 595 residues amino acids and compromises a 69 kDa calculated molecular weight. However, N-glycosylation in the extracellular loop increases the size of the P2X7 receptor to about 75-85 KDa; the protein is composed successively (from the N- to the C-terminus) by: |
| Expression | In a wide variety of tissues including heart, liver, pancreas, thymus, skeletal muscle and brain, although in brain the expression is mainly restricted to microglia. It also has relevant expression and function in immune cells (mainly in antigen presenting cells, such as monocytes, macrophages and dendritic cells). |
| Localisation | Mainly is found in the plasma membrane, however it also can be found in intracellular membrane compartments while trafficking to the plasma membrane. |
| Function | Acts as a ligand gated ion channel, sensing high concentration of extracellular ATP. Responsible for ATP-dependent activation and release of proinflammatory cytokines of the interleukin-1 family, mainly interleukin-1beta, interleukin-18 and interleukin-1alpha, playing a pivotal role in inflammatory responses. Prolonged stimulation of the P2X7 receptor can lead to plasma membrane bleb formation, opening of pannexin-1 dependent membrane pores and eventual cell death. |
| Homology | With other P2X receptors, with the higher homology with P2RX4. Excluding the unique C-terminal domain, homology is 39-49% with other P2X receptors. |
| Mutations |
| Germinal | The human P2X7 receptor gene is highly polymorphic and more then 260 SNP have been described, only four loss-of-function and one gain-of-function SNP have been described to date: |
| Somatic | Not known in human. |
| Implicated in |
| Note | |
| Entity | Extrapulmonary tuberculosis |
| Note | The P2RX7 1513C allele has been strongly associated with extrapulmonary tuberculosis. The allele was associated with a reduced killing of Mycobacterium tuberculosis by macrophages. |
| Entity | Chronic lymphoid leukemia (CLL) |
| Note | The 1513C allele of P2RX7 has been associated with the clinical course of patients affected by chronic lymphocytic leukemia (CLL). There is a possible role for the P2X7 receptor in the susceptibility to familial CLL or, alternately, the 1513C allele may be in linkage disequilibrium with a nearby susceptibility gene. |
| Entity | Various cancers, including breast cancer, prostate cancer, papillary thyroid cancer and neuroblastoma. |
| Note | P2X7 receptor is overexpressed in a variety of cancers (see above). A detailed understanding of the mechanistic contribution mediated by P2RX7 has yet to be established. However, there is substantial evidence that the P2X7 receptor may mediate cell survival and growth by increasing the efficiency of oxidative phosphorylation and total intracellular ATP stores. Finally it has been proposed that the P2X7 receptor may be a candidate marker of papillary thyroid cancer. |
| Bibliography |
| Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth. |
| Adinolfi E, Callegari MG, Ferrari D, Bolognesi C, Minelli M, Wieckowski MR, Pinton P, Rizzuto R, Di Virgilio F |
| Molecular biology of the cell. 2005 ; 16 (7) : 3260-3272. |
| PMID 15901833 |
| A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes. |
| Cabrini G, Falzoni S, Forchap SL, Pellegatti P, Balboni A, Agostini P, Cuneo A, Castoldi G, Baricordi OR, Di Virgilio F |
| Journal of immunology (Baltimore, Md. : 1950). 2005 ; 175 (1) : 82-89. |
| PMID 15972634 |
| Identification and characterization of splice variants of the human P2X7 ATP channel. |
| Cheewatrakoolpong B, Gilchrest H, Anthes JC, Greenfeder S |
| Biochemical and biophysical research communications. 2005 ; 332 (1) : 17-27. |
| PMID 15896293 |
| Association of the 1513C polymorphism in the P2X7 gene with familial forms of chronic lymphocytic leukaemia. |
| Dao-Ung LP, Fuller SJ, Sluyter R, SkarRatt KK, Thunberg U, Tobin G, Byth K, Ban M, Rosenquist R, Stewart GJ, Wiley JS |
| British journal of haematology. 2004 ; 125 (6) : 815-817. |
| PMID 15180873 |
| A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical cancer cells antagonizes the full-length P2X7 receptor through hetero-oligomerization. |
| Feng YH, Li X, Wang L, Zhou L, Gorodeski GI |
| The Journal of biological chemistry. 2006 ; 281 (25) : 17228-17237. |
| PMID 16624800 |
| A polymorphism in the P2X7 gene increases susceptibility to extrapulmonary tuberculosis. |
| Fernando SL, Saunders BM, Sluyter R, Skarratt KK, Goldberg H, Marks GB, Wiley JS, Britton WJ |
| American journal of respiratory and critical care medicine. 2007 ; 175 (4) : 360-366. |
| PMID 17095747 |
| The P2X7 receptor: a key player in IL-1 processing and release. |
| Ferrari D, Pizzirani C, Adinolfi E, Lemoli RM, Curti A, Idzko M, Panther E, Di Virgilio F |
| Journal of immunology (Baltimore, Md. : 1950). 2006 ; 176 (7) : 3877-3883. |
| PMID 16547218 |
| An Arg307 to Gln polymorphism within the ATP-binding site causes loss of function of the human P2X7 receptor. |
| Gu BJ, Sluyter R, Skarratt KK, Shemon AN, Dao-Ung LP, Fuller SJ, Barden JA, Clarke AL, Petrou S, Wiley JS |
| The Journal of biological chemistry. 2004 ; 279 (30) : 31287-31295. |
| PMID 15123679 |
| A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor. |
| Gu BJ, Zhang W, Worthington RA, Sluyter R, Dao-Ung P, Petrou S, Barden JA, Wiley JS |
| The Journal of biological chemistry. 2001 ; 276 (14) : 11135-11142. |
| PMID 11150303 |
| Molecular physiology of P2X receptors. |
| North RA |
| Physiological reviews. 2002 ; 82 (4) : 1013-1067. |
| PMID 12270951 |
| Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. |
| Pelegrin P, Surprenant A |
| The EMBO journal. 2006 ; 25 (21) : 5071-5082. |
| PMID 17036048 |
| The P2X7 receptor sustains the growth of human neuroblastoma cells through a substance P-dependent mechanism. |
| Raffaghello L, Chiozzi P, Falzoni S, Di Virgilio F, Pistoia V |
| Cancer research. 2006 ; 66 (2) : 907-914. |
| PMID 16424024 |
| The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA. |
| Rassendren F, Buell GN, Virginio C, Collo G, North RA, Surprenant A |
| The Journal of biological chemistry. 1997 ; 272 (9) : 5482-5486. |
| PMID 9038151 |
| Differentiation between cancerous and normal hyperplastic lobules in breast lesions. |
| Slater M, Danieletto S, Pooley M, Cheng Teh L, Gidley-Baird A, Barden JA |
| Breast cancer research and treatment. 2004 ; 83 (1) : 1-10. |
| PMID 14997049 |
| Increased P2X7 receptor expression and function in thyroid papillary cancer: a new potential marker of the disease? |
| Solini A, Cuccato S, Ferrari D, Santini E, Gulinelli S, Callegari MG, Dardano A, Faviana P, Madec S, Di Virgilio F, Monzani F |
| Endocrinology. 2008 ; 149 (1) : 389-396. |
| PMID 17947359 |
| The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). |
| Surprenant A, Rassendren F, Kawashima E, North RA, Buell G |
| Science (New York, N.Y.). 1996 ; 272 (5262) : 735-738. |
| PMID 8614837 |
| An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor. |
| Wiley JS, Dao-Ung LP, Li C, Shemon AN, Gu BJ, Smart ML, Fuller SJ, Barden JA, Petrou S, Sluyter R |
| The Journal of biological chemistry. 2003 ; 278 (19) : 17108-17113. |
| PMID 12586825 |
| Citation |
| This paper should be referenced as such : |
| Pelegrin, P ; Surprenant, A |
| P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7) |
| Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):377-378. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/P2RX7ID41623ch12q24.html |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Tue Nov 6 12:51:19 CET 2018 |
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