Alternative titles; symbols
HGNC Approved Gene Symbol: P2RX5
Cytogenetic location: 17p13.2 Genomic coordinates (GRCh38): 17:3,673,227-3,696,155 (from NCBI)
Mammalian P2X receptors, such as P2RX5, belong to a multigene family of nonselective cation channels activated by extracellular ATP.
Le et al. (1997) identified a human fetal brain cDNA related to the rat P2X5 gene. The predicted 422-amino acid human P2X5R protein shares 62% identity with rat P2X5, but has only 1 of the 2 transmembrane domains found in other P2X receptor subunits. In vitro translation of the human P2X5R cDNA produced a protein that migrated at 49 kD by SDS-PAGE. Using immunofluorescence, Le et al. (1997) showed that P2X5R localizes to the plasma membrane when expressed in human embryonic kidney cells. Quantitative dot blots revealed that P2X5R expression is highest in brain and immune system and is developmentally regulated. Le et al. (1997) identified a shorter cDNA in fetal and adult brain that resulted from alternative splicing.
By RT-PCR Adrian et al. (2000) found that 2 splice variants of P2X5 differing by 72 bp were highly expressed in normal blood leukocytes and more weakly expressed in a promyelocytic leukemia cell line.
Le et al. (1997) found that heterologous expression of P2X5 in Xenopus oocytes did not yield functional channels. However, expression of a chimera containing the human P2X5R N-terminal domain and rat P2X5 C-terminal domain led to formation of cationic ATP-gated ion channels.
Adrian et al. (2000) analyzed the expression of several purinergic receptors during differentiation in a promyelocytic leukemia cell line. Granulocytic differentiation was induced by dimethylsulfoxide, and a monocytic/macrophage phenotype was induced by phorbol esters. Upon granulocytic differentiation, P2X5 expression increased 2- to 5-fold. During monocytic differentiation, expression was upregulated 10- to 14-fold.
Ischemic pain, such as that caused by a heart attack or a 30-second sprint, occurs when muscle gets too little oxygen for its metabolic need. By whole-cell patch-clamp recordings of rat dorsal root sensory ganglia innervating thigh muscle, Birdsong et al. (2010) found that ATP at micromolar concentrations potentiated Asic3 currents evoked at pH values that occur during muscle ischemia. Coexpression and pharmacologic profiling indicated that P2x5 potentiated the Asic3 (ACCN3; 611741) current. Potentiation appeared to be due to physical proximity between Asic3 and P2x5 and was independent of intracellular calcium, direction of the P2x5 current, and ATP hydrolysis. Birdsong et al. (2010) hypothesized that ATP released from ischemic muscle binds to quiescent P2X5 receptors in a complex with ASIC3 and enhances ASIC3 sensitivity to a drop in extracellular pH.
By shotgun sequencing, Touchman et al. (2000) identified the P2RX5 gene within a BAC contig covering chromosome 17p13.
Using cytotoxic T-lymphocyte (CTL) assays and genetic linkage and real-time PCR analyses, de Rijke et al. (2005) identified a minor histocompatibility antigen, which they termed lymphoid-restricted histocompatibility antigen-1 (LHR1), that resulted from a homozygous frameshift polymorphism in exon 3 of the P2X5 gene in a male donor of HLA-identical bone marrow whose sister was being treated for chronic myelogenous leukemia. An epitope of LRH1 was presented by HLA-B7 to specific CD8 (see 186910)-positive CTLs. Real-time PCR and RT-PCR analysis of normal tissues revealed significant P2X5 expression in lymphoid lineage cells, with little or no expression in myeloid cells. Low to moderate expression was detected in adult neuronal and muscular tissues, and no expression was detected in organs targeted by graft-versus-host disease (GVHD; see 614395) (skin, liver, colon, and small intestine). De Rijke et al. (2005) concluded that LRH1-specific CD8-positive cytotoxic T cells have a role in selective graft-versus-leukemia reactivity in the absence of graft-versus-host disease.
Jeong et al. (2020) found that P2x5 -/- mice were more susceptible to infection by Listeria monocytogenes (Lm) than wildtype. P2x5 -/- mice displayed normal proinflammatory cytokine production and monocyte migration in response to Lm infection, but they had compromised Lm killing capacity by macrophages due to defective cytosolic Lm killing. In addition, P2x5 was required for Lm-induced inflammasome activation and production of the inflammasome-dependent cytokines Il1b (147720) and Il18 (600953), and consequently, loss of P2x5 resulted in reduced Lm killing. Analysis with mice with P2x7 (602566) deletion showed that P2x5-dependent anti-Lm immunity was not linked to P2x7 function. Furthermore, P2x5-dependent anti-Lm immunity was also independent of the P2x/P2x7 purinergic receptor agonist, extracellular ATP, suggesting that P2x5 does not use conventional ATP-triggered signaling for anti-Lm immunity.
Adrian, K., Bernhard, M. K., Breitinger, H.-G., Ogilvie, A. Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells. Biochim. Biophys. Acta 1492: 127-138, 2000. [PubMed: 11004484] [Full Text: https://doi.org/10.1016/s0167-4781(00)00094-4]
Birdsong, W. T., Fierro, L., Williams, F. G., Spelta, V., Naves, L. A., Knowles, M., Marsh-Haffner, J., Adelman, J. P., Almers, W., Elde, R. P., McCleskey, E. W. Sensing muscle ischemia: coincident detection of acid and ATP via interplay of two ion channels. Neuron 68: 739-749, 2010. [PubMed: 21092862] [Full Text: https://doi.org/10.1016/j.neuron.2010.09.029]
de Rijke, B., van Horssen-Zoetbrood, A., Beekman, J. M., Otterud, B., Maas, F., Woestenenk, R., Kester, M., Leppert, M., Schattenberg, A. V., de Witte, T., van de Wiel-van Kemenade, E., Dolstra, H. A frameshift polymorphism in P2X5 elicits an allogenic cytotoxic T lymphocyte response associated with remission of chronic myeloid leukemia. J. Clin. Invest. 115: 3506-3516, 2005. [PubMed: 16322791] [Full Text: https://doi.org/10.1172/JCI24832]
Jeong, Y. H., Walsh, M. C., Yu, J., Shen, H., Wherry, E. J., Choi, Y. Mice lacking the purinergic receptor P2X5 exhibit defective inflammasome activation and early susceptibility to Listeria monocytogenes. J. Immun. 205: 760-766, 2020. [PubMed: 32540996] [Full Text: https://doi.org/10.4049/jimmunol.1901423]
Le, K.-T., Paquet, M., Nouel, D., Babinski, K., Seguela, P. Primary structure and expression of a naturally truncated human P2X ATP receptor subunit from brain and immune system. FEBS Lett. 418: 195-199, 1997. [PubMed: 9414125] [Full Text: https://doi.org/10.1016/s0014-5793(97)01380-x]
Touchman, J. W., Anikster, Y., Dietrich, N. L., Maduro, V. V. B., McDowell, G., Shotelersuk, V., Bouffard, G. G., Beckstrom-Sternberg, S. M., Gahl, W. A., Green, E. D. The genomic region encompassing the nephropathic cystinosis gene (CTNS): complete sequencing of a 200-kb segment and discovery of a novel gene within the common cystinosis-causing deletion. Genome Res. 10: 165-173, 2000. [PubMed: 10673275] [Full Text: https://doi.org/10.1101/gr.10.2.165]