P2rx7
entrez
29665
canonical
uniprot
Q64663
canonical
ensembl
ENSRNOG00000001296
resolver
ensp
ENSRNOP00000001746
resolver
ensp
ENSRNOP00000094617
resolver
enst
ENSRNOT00000001746
resolver
genesymbol
P2rx7
resolver
uniprot
A0A8L2Q078
resolver
uniprot
C8YIX5
resolver
uniprot_entry
A0A8L2Q078_RAT
resolver
uniprot_entry
P2RX7_RAT
resolver
uniprot_sec
C8YIX5
resolver
activity_regulation
ACTIVITY REGULATION: Activated by high extracellular ATP levels (0.1-2.5 mM) (PubMed:39107314, PubMed:8614837). The synthetic analog 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP) acts as a potent agonist. Does not undergo desensitization, instead, undergoes a facilitation process where currents progressively increase with repetitive or prolonged agonist application (PubMed:31587896). Palmitoylation prevents channel desensitization (PubMed:31587896). The permeability of the P2RX7 channel is modulated by the amount of cholesterol in the plasma membrane (By similarity). {ECO:0000250|UniProtKB:Q99572, ECO:0000269|PubMed:31587896, ECO:0000269|PubMed:39107314, ECO:0000269|PubMed:8614837}.
uniprot
proteins
amino_acid_sequence
MPACCSWNDVFQYETNKVTRIQSVNYGTIKWILHMTVFSYVSFALMSDKLYQRKEPLISSVHTKVKGVAEVTENVTEGGVTKLVHGIFDTADYTLPLQGNSFFVMTNYLKSEGQEQKLCPEYPSRGKQCHSDQGCIKGWMDPQSKGIQTGRCIPYDQKRKTCEIFAWCPAEEGKEAPRPALLRSAENFTVLIKNNIDFPGHNYTTRNILPGMNISCTFHKTWNPQCPIFRLGDIFQEIGENFTEVAVQGGIMGIEIYWDCNLDSWSHRCQPKYSFRRLDDKYTNESLFPGYNFRYAKYYKENGMEKRTLIKAFGVRFDILVFGTGGKFDIIQLVVYIGSTLSYFGLATVCIDLIINTYASTCCRSRVYPSCKCCEPCAVNEYYYRKKCEPIVEPKPTLKYVSFVDEPHIWMVDQQLLGKSLQDVKGQEVPRPQTDFLELSRLSLSLHHSPPIPGQPEEMQLLQIEAVPRSRDSPDWCQCGNCLPSQLPENRRALEELCCRRKPGQCITTSELFSKIVLSREALQLLLLYQEPLLALEGEAINSKLRHCAYRSYATWRFVSQDMADFAILPSCCRWKIRKEFPKTQGQYSGFKYPY
uniprot
proteins
function
FUNCTION: ATP-gated nonselective transmembrane cation channel that requires high millimolar concentrations of ATP for activation (PubMed:10204537, PubMed:39107314, PubMed:8614837). Upon ATP binding, it rapidly opens to allow the influx of small cations Na(+) and Ca(2+), and the K(+) efflux (PubMed:8614837). Also has the ability to form a large pore in the cell membrane, allowing the passage of large cationic molecules (PubMed:17036048, PubMed:18852304). In microglia, may mediate the transmembrane transport of exogenous NADPH (By similarity). 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 (By similarity). Activates death pathways leading to pyroptosis (By similarity). Involved in the homeostatic wound healing response to tissue injury, a multistep cascade that guides neutrophil migration to necrotic sites while avoiding collateral damage of healthy tissues. Senses ATP released from necrotic cells triggering activation of NLRP3 inflammasome and neutrophil adhesion to the vascular endothelium close to the injury site. {ECO:0000250|UniProtKB:Q99572, ECO:0000250|UniProtKB:Q9Z1M0, ECO:0000269|PubMed:10204537, ECO:0000269|PubMed:17036048, ECO:0000269|PubMed:18852304, ECO:0000269|PubMed:39107314, ECO:0000269|PubMed:8614837}.; FUNCTION: [Isoform 2]: Has a higher affinity for ATP, slower deactivation and an increased propensity to form large cation-permeable pores. {ECO:0000269|PubMed:19546214}.
uniprot
proteins
mass_dalton
68392
uniprot
proteins
mutagenesis
MUTAGEN 88; /note="F->A: Decreases inhibitory potencies of antagonists."; /evidence="ECO:0000269|PubMed:39365862"; MUTAGEN 103; /note="F->A: Decreases inhibitory potencies of antagonists."; /evidence="ECO:0000269|PubMed:39365862"; MUTAGEN 125; /note="R->A: Moderately decreases the affinity for BzATP. Does not affect the binding affinity of ATP."; /evidence="ECO:0000269|PubMed:39107314"; MUTAGEN 143; /note="Q->A: Reduces the affinity for both ATP and BzATP."; /evidence="ECO:0000269|PubMed:39107314"; MUTAGEN 214; /note="I->A: Does not significantly affect the affinity for either ATP or BzATP."; /evidence="ECO:0000269|PubMed:39107314"; MUTAGEN 297; /note="K->V: Does not affect the inhibitory potency of the tested antagonists."; /evidence="ECO:0000269|PubMed:39365862
uniprot
proteins
post_translational_modification
PTM: Phosphorylation results in its inactivation. {ECO:0000250|UniProtKB:Q99572}.; PTM: ADP-ribosylation at Arg-125 is necessary and sufficient to activate P2RX7 and gate the channel. {ECO:0000250|UniProtKB:Q9Z1M0}.; PTM: Palmitoylation of several cysteines in the C-terminal cytoplasmic tail is required for efficient localization to cell surface (By similarity). Palmitoylation prevents channel desensitization by physically anchoring the palmitoylated groups to the membrane (PubMed:31587896). {ECO:0000250|UniProtKB:Q99572, ECO:0000269|PubMed:31587896}.
uniprot
proteins
protein_family
P2X receptor family
uniprot
proteins
pubmed
10204537
uniprot
proteins
pubmed
17036048
uniprot
proteins
pubmed
18852304
uniprot
proteins
pubmed
19546214
uniprot
proteins
pubmed
24090084
uniprot
proteins
pubmed
31587896
uniprot
proteins
pubmed
39107314
uniprot
proteins
pubmed
39365862
uniprot
proteins
pubmed
8614837
uniprot
proteins
sequence_length
595
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q99572}; Multi-pass membrane protein {ECO:0000269|PubMed:31587896, ECO:0000269|PubMed:39107314}.
uniprot
proteins
transmembrane_region
TRANSMEM 23..46; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:31587896, ECO:0007744|PDB:6U9V"; TRANSMEM 329..353; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:31587896, ECO:0007744|PDB:6U9V
uniprot
proteins