P2X purinoceptor 7
Also known as: P2RX7
Function
ATP-gated nonselective transmembrane cation channel that requires high millimolar concentrations of ATP for activation. Upon ATP binding, it rapidly opens to allow the influx of small cations Na(+) and Ca(2+), and the K(+) efflux. Also has the ability to form a large pore in the cell membrane, allowing the passage of large cationic molecules. In microglia, may mediate NADPH transport across the plasma membrane. In immune cells, P2RX7 acts as a molecular sensor in pathological inflammatory states by detecting and responding to high local concentrations of extracellar ATP. In microglial cells, P2RX7 activation leads to the release of pro-inflammatory cytokines, such as IL-1beta and IL-18, through the activation of the NLRP3 inflammasome and caspase-1. Cooperates with KCNK6 to activate NLRP3 inflammasome (By similarity). Activates death pathways leading to apoptosis and autophagy. Activates death pathways leading to pyroptosis (By similarity).
Classification
- Family (Pfam)
- PF20478 P2RX7_C, PF00864 P2X_receptor
- InterPro
- P2RX7_C, P2X7_purinoceptor, P2X_extracellular_dom_sf, P2X_purnocptor, P2X_receptor, P2X_RECEPTOR_CS
- Functional cluster
- Membrane Channels & Lipid-Anchored Proteins
Experimental structures · PDB · 4
A predicted model is available from AlphaFold.
Gene Ontology · 47
- GO:0032059 bleb
- GO:0005911 cell-cell junction
- GO:0005737 cytoplasm
- GO:0009897 external side of plasma membrane
- GO:0016020 membrane
- GO:0031594 neuromuscular junction
- GO:0043025 neuronal cell body
- GO:0005886 plasma membrane
- GO:0098794 postsynapse
- GO:0005524 ATP binding
- GO:0004931 extracellularly ATP-gated monoatomic cation channel activity
- GO:0005525 GTP binding
- GO:0042802 identical protein binding
- GO:0001530 lipopolysaccharide binding
- GO:0046872 metal ion binding
- GO:0005267 potassium channel activity
- GO:0001614 purinergic nucleotide receptor activity
- GO:0005102 signaling receptor binding
- GO:0005272 sodium channel activity
- GO:0097190 apoptotic signaling pathway
- GO:0032060 bleb assembly
- GO:0070588 calcium ion transmembrane transport
- GO:0019722 calcium-mediated signaling
- GO:0007166 cell surface receptor signaling pathway
- GO:0071318 cellular response to ATP
- GO:0097191 extrinsic apoptotic signaling pathway
- GO:0051899 membrane depolarization
- GO:0045779 negative regulation of bone resorption
- GO:0045794 negative regulation of cell volume
- GO:0043409 negative regulation of MAPK cascade
- GO:0017121 plasma membrane phospholipid scrambling
- GO:0046931 pore complex assembly
- GO:1904172 positive regulation of bleb assembly
- GO:0030501 positive regulation of bone mineralization
- GO:0010524 positive regulation of calcium ion transport into cytosol
- GO:0051495 positive regulation of cytoskeleton organization
- GO:0010628 positive regulation of gene expression
- GO:0045821 positive regulation of glycolytic process
- GO:0032731 positive regulation of interleukin-1 beta production
- GO:0034767 positive regulation of monoatomic ion transmembrane transport
- GO:1900227 positive regulation of NLRP3 inflammasome complex assembly
- GO:0070207 protein homotrimerization
- GO:0035590 purinergic nucleotide receptor signaling pathway
- GO:0002028 regulation of sodium ion transport
- GO:0033198 response to ATP
- GO:0002931 response to ischemia
- GO:0019233 sensory perception of pain
Drugs targeting this protein · 4
- GSK1482160 negative allosteric modulator
- CE-224535 antagonist
- AZD9056 antagonist
- JNJ-54175446 antagonist
Related proteins · sequence + function similarity
- P2X purinoceptor 7 0.97
- P2X purinoceptor 7 0.97
- P2X purinoceptor 1 0.83
- P2X purinoceptor 1 0.82
- P2X purinoceptor 1 0.82
- P2X purinoceptor 4 0.81
- P2X purinoceptor 4 0.81
- P2X purinoceptor 4a 0.80
- P2X purinoceptor 4 0.80
- P2X purinoceptor 5 0.80
- P2X purinoceptor 4 0.79
- P2X purinoceptor 5 0.79
Co-cited proteins · studied together in the literature
- P2X purinoceptor 7 2 shared papers
- P2X purinoceptor 4 2 shared papers
- Epithelial membrane protein 2 1 shared papers
Literature · 26 cited papers
- Two serial filters control P2X7 cation selectivity, Ser342 in the central pore and lateral acidic residues at the cytoplasmic interface. PNAS Nexus · 2024
- The P2X7 receptor mediates NADPH transport across the plasma membrane. Biochem. Biophys. Res. Commun. · 2024
- Purinergic receptors P2RX4 and P2RX7 in familial multiple sclerosis. Hum. Mutat. · 2017
- Localization of the gate and selectivity filter of the full-length P2X7 receptor. Proc. Natl. Acad. Sci. U.S.A. · 2017
- Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1beta secretion in response to ATP. Nat. Commun. · 2016
- Plasma membrane cholesterol as a regulator of human and rodent P2X7 receptor activation and sensitization. J. Biol. Chem. · 2014
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- A rare functional haplotype of the P2RX4 and P2RX7 genes leads to loss of innate phagocytosis and confers increased risk of age-related macular degeneration. FASEB J. · 2013
- P2X(7) is a scavenger receptor for apoptotic cells in the absence of its ligand, extracellular ATP. J. Immunol. · 2011
- Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J. · 2010
- Mutation of putative N-linked glycosylation sites on the human nucleotide receptor P2X7 reveals a key residue important for receptor function. Biochemistry · 2010
- Palmitoylation of the P2X7 receptor, an ATP-gated channel, controls its expression and association with lipid rafts. FASEB J. · 2009
- … and 14 more in the literature graph