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P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7)

Written2008-01Pablo Pelegrin, Annmarie Surprenant
Faculty of Life Science, Michael Smith Building, University of Manchester, Manchester, M13 9PT, UK

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)MGC20089
P2X7
P2Z
HGNC (Hugo) P2RX7
HGNC Alias symbP2X7
MGC20089
HGNC Previous namepurinergic receptor P2X, ligand-gated ion channel, 7
LocusID (NCBI) 5027
Atlas_Id 41623
Location 12q24.31  [Link to chromosome band 12q24]
Location_base_pair Starts at 121132876 and ends at 121188032 bp from pter ( according to GRCh38/hg38-Dec_2013)  [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:
  • 25 amino acid intracellular N-terminus
  • 21 amino acid first transmembrane domain
  • 288 amino acid extracellular loop
  • 21 amino acid second transmembrane domain
  • 240 amino acid intracellular C-terminal region
  • 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:
  • Loss of protein function:
    946 G to A (Arg-307 to Gln)
    1068 G to A (Ala-348 to Thr)
    1513 A to C (Glu-496 to Ala)
    1729 T to A (Ile-568 to Asp)
  • Gain of protein function:
    489 C to T (His-155 to Tyr)
  • 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 ]


    External links

    Nomenclature
    HGNC (Hugo)P2RX7   8537
    Cards
    AtlasP2RX7ID41623ch12q24
    Entrez_Gene (NCBI)P2RX7    purinergic receptor P2X 7
    AliasesP2X7
    GeneCards (Weizmann)P2RX7
    Ensembl hg19 (Hinxton)ENSG00000089041 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000089041 [Gene_View]  ENSG00000089041 [Sequence]  chr12:121132876-121188032 [Contig_View]  P2RX7 [Vega]
    ICGC DataPortalENSG00000089041
    TCGA cBioPortalP2RX7
    AceView (NCBI)P2RX7
    Genatlas (Paris)P2RX7
    SOURCE (Princeton)P2RX7
    Genetics Home Reference (NIH)P2RX7
    Genomic and cartography
    GoldenPath hg38 (UCSC)P2RX7  -     chr12:121132876-121188032 +  12q24.31   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)P2RX7  -     12q24.31   [Description]    (hg19-Feb_2009)
    GoldenPathP2RX7 - 12q24.31 [CytoView hg19]  P2RX7 - 12q24.31 [CytoView hg38]
    ImmunoBaseENSG00000089041
    Genome Data Viewer NCBIP2RX7 [Mapview hg19]  
    OMIM602566   
    Gene and transcription
    Genbank (Entrez)AB209709 AF086044 AK090866 AK225163 AK290405
    RefSeq transcript (Entrez)NM_002562 NM_177427
    Consensus coding sequences : CCDS (NCBI)P2RX7
    Gene ExpressionP2RX7 [ NCBI-GEO ]   P2RX7 [ EBI - ARRAY_EXPRESS ]   P2RX7 [ SEEK ]   P2RX7 [ MEM ]
    Gene Expression Viewer (FireBrowse)P2RX7 [ Firebrowse - Broad ]
    GenevisibleExpression of P2RX7 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)5027
    GTEX Portal (Tissue expression)P2RX7
    Human Protein AtlasENSG00000089041-P2RX7 [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Conserved Domain (NCBI)P2RX7
    Human Protein Atlas [tissue]ENSG00000089041-P2RX7 [tissue]
    HPRD03977
    Protein Interaction databases
    BioGRIDP2RX7
    STRING (EMBL)P2RX7
    ZODIACP2RX7
    Ontologies - Pathways
    Litterature
    PubMed462 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    EVEXP2RX7
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Fri Oct 8 21:24:22 CEST 2021

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