P2RX7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004931 extracellularly ATP-gated monoatomic cation channel activity	IBA GO_REF:0000033	ACCEPT	Summary: The defining molecular function: a trimeric, non-selective cation channel opened by binding of extracellular ATP at the interfaces of the extracellular domains. Reason: Core molecular function, established for the human protein at its cloning and confirmed by single-channel recording and by full-length cryo-EM structures. This is the one assertion about P2X7 that no party to the current controversy disputes - the argument is about which cells express the receptor, not about what it does. Supporting Evidence: PMID:9038151 Brief applications (1-3 s) of ATP and 2', 3'-(4-benzoyl)-benzoyl-ATP elicited cation-selective currents. PMID:31587896 P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0070588 calcium ion transmembrane transport	IBA GO_REF:0000033	ACCEPT	Summary: Calcium entry through the open P2X7 channel; the receptor is notably calcium permeable and the resulting rise in cytosolic calcium is what drives its downstream effectors. Reason: Core biological process, directly downstream of the channel activity.
GO:0007166 cell surface receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: Generic parent of the purinergic signalling pathway term. Reason: Correct and a defensible assertion at a family node that spans all P2X receptors, though GO:0035590 purinergic nucleotide receptor signaling pathway - which this gene also carries - states it far more usefully for P2X7.
GO:0001614 purinergic nucleotide receptor activity	IEA GO_REF:0000002	ACCEPT	Summary: P2X7 is the ionotropic receptor for extracellular ATP; agonist binding and channel opening are the same event. Reason: Core molecular function, stating the receptor aspect of the same activity captured by GO:0004931. Supporting Evidence: PMID:9038151 Brief applications (1-3 s) of ATP and 2', 3'-(4-benzoyl)-benzoyl-ATP elicited cation-selective currents.
GO:0004931 extracellularly ATP-gated monoatomic cation channel activity	IEA GO_REF:0000120	ACCEPT	Summary: The defining molecular function: a trimeric, non-selective cation channel opened by binding of extracellular ATP at the interfaces of the extracellular domains. Reason: Core molecular function, established for the human protein at its cloning and confirmed by single-channel recording and by full-length cryo-EM structures. This is the one assertion about P2X7 that no party to the current controversy disputes - the argument is about which cells express the receptor, not about what it does. Supporting Evidence: PMID:9038151 Brief applications (1-3 s) of ATP and 2', 3'-(4-benzoyl)-benzoyl-ATP elicited cation-selective currents. PMID:31587896 P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP.
GO:0005216 monoatomic ion channel activity	IEA GO_REF:0000002	MODIFY	Summary: Correct but at the most general level in the channel branch. Reason: The gating stimulus and the ion class are both established for this protein, and the specific term is already carried by this gene with IDA and IBA support. Proposed replacements: extracellularly ATP-gated monoatomic cation channel activity
GO:0005524 ATP binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Literally true - the agonist is ATP - but the binding site is extracellular and the protein neither hydrolyses nor uses ATP. Reason: GO:0005524 is overwhelmingly used for intracellular ATP-consuming enzymes, and on a cell-surface receptor it invites exactly the wrong reading. The informative statement is GO:0004931, which says that ATP binding gates a cation channel. Retained because it is not false, and because the full-length structures did reveal a separate cytoplasmic guanosine nucleotide binding site, so nucleotide binding by this protein is not a single simple fact. Supporting Evidence: PMID:31587896 They show a second cytoplasmic element with a unique fold, the cytoplasmic ballast, which unexpectedly contains a zinc ion complex and a guanosine nucleotide binding site.
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0006811 monoatomic ion transport	IEA GO_REF:0000002	MODIFY	Summary: Correct but at the most general level. Reason: P2X7 conducts cations and not anions; the cation-specific term is already carried by this gene. Proposed replacements: monoatomic cation transmembrane transport
GO:0015748 organophosphate ester transport	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA rule-based assertion that P2X7 transports organophosphate esters. Reason: P2X7 binds ATP on the outside of the cell and opens a cation channel; it does not translocate ATP or other organophosphate esters across the membrane. The large-solute permeability that could motivate such a term was attributed to pannexin-1, and single-channel analysis argued against dilation of the P2X7 pore itself. This is a rule-based over-reach from the ligand to a transport activity. Supporting Evidence: PMID:17483156 Single-channel kinetics and permeation properties remained unchanged during receptor activation by up to 1 mM ATP(4-) for >1 min, arguing against a molecular correlate of pore dilation at the single P2X(7) channel level.
GO:0016020 membrane	IEA GO_REF:0000120	MODIFY	Summary: True but uninformative. Reason: The specific compartment is established and already annotated many times over in this set. Proposed replacements: plasma membrane
GO:0032060 bleb assembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Membrane blebbing following P2X7 activation, a classic phenotype attributable to the receptor's long cytoplasmic C-terminus. Reason: Well replicated and genuinely P2X7-specific among P2X receptors, but downstream: the blebbing is executed by calcium-dependent effectors including ANO6 and by the C-terminal EMP/PMP22 interactions, not by the channel itself. Supporting Evidence: PMID:12107182 We have shown that the C-terminal domain of the P2X(7) receptor is responsible for the cell blebbing phenotype.
GO:0032731 positive regulation of interleukin-1 beta production	IEA GO_REF:0000117	ACCEPT	Summary: P2X7 activation by extracellular ATP provides the second signal for NLRP3 inflammasome activation, caspase-1 processing and release of mature interleukin-1 beta. Reason: Core biological process and the best-established physiological output of this receptor, shown in macrophages and in primary human mononuclear cells and blocked by P2X7 antagonism. Note that the downstream dye-uptake pathway required for interleukin-1 beta release was assigned to pannexin-1 rather than to P2X7 itself. Supporting Evidence: PMID:17036048 Here, we identify pannexin-1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, as this dye-uptake pathway and show that signalling through pannexin-1 is required for processing of caspase-1 and release of mature IL-1beta induced by P2X(7) receptor activation. PMID:18089587 Release of interleukin-1 beta in both groups was blocked by preincubation with oxidized ATP, a P2X(7) receptor antagonist.
GO:0033198 response to ATP	IEA GO_REF:0000120	ACCEPT	Summary: P2X7 is the sensor for extracellular ATP, so responding to ATP is the process it initiates. Reason: Core biological process. Kept at this level rather than modified to the cellular child, since both are carried and both are accurate for a receptor whose ligand is extracellular ATP. Supporting Evidence: PMID:9038151 Brief applications (1-3 s) of ATP and 2', 3'-(4-benzoyl)-benzoyl-ATP elicited cation-selective currents.
GO:0035725 sodium ion transmembrane transport	IEA GO_REF:0000108	ACCEPT	Summary: Sodium influx is part of the inward cation current carried by P2X7. Reason: Core, and unusually well grounded for an inter-ontology inference: the GOA row is derived from GO:0005272, which rests on direct single-channel recordings in which sodium was the charge carrier.
GO:0046931 pore complex assembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: The macropore or dye-uptake pathway that follows sustained P2X7 activation. Reason: GOA carries both sides of a genuine dispute here. The permeabilisation is real and was recorded at the cloning of the human receptor. But single-channel analysis of the human receptor found no change in permeation properties during prolonged ATP exposure, arguing against dilation of the P2X7 pore itself, and the dye-uptake pathway was subsequently attributed to pannexin-1. So the phenotype is P2X7-dependent while the pore may not be P2X7. Retained, because the observation is solid and because the ARBA and IMP rows record a real requirement, but demoted from core pending resolution of what forms the pore. Supporting Evidence: PMID:9038151 Longer applications of agonists permeabilized the cells, as evidenced by uptake of the propidium dye YO-PRO1, but this was less marked than for cells expressing the rat P2X7 receptor. PMID:17483156 Single-channel kinetics and permeation properties remained unchanged during receptor activation by up to 1 mM ATP(4-) for >1 min, arguing against a molecular correlate of pore dilation at the single P2X(7) channel level. PMID:17036048 Here, we identify pannexin-1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, as this dye-uptake pathway and show that signalling through pannexin-1 is required for processing of caspase-1 and release of mature IL-1beta induced by P2X(7) receptor activation.
GO:0051049 regulation of transport	IEA GO_REF:0000117	MODIFY	Summary: Correct but at a near-root level of the regulation branch. Reason: ARBA rule-based transfer of a term so general it excludes almost nothing. The specific regulatory relationship this gene has evidence for is already annotated. Proposed replacements: positive regulation of monoatomic ion transmembrane transport
GO:0051130 positive regulation of cellular component organization	IEA GO_REF:0000117	MODIFY	Summary: Correct but at a near-root level of the regulation branch. Reason: ARBA rule-based transfer. The cellular component organisation that P2X7 actually promotes is membrane blebbing, which this gene already carries with IMP support. Proposed replacements: positive regulation of bleb assembly
GO:0060079 excitatory postsynaptic potential	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Excitatory postsynaptic potential, derived mechanically from the molecular function. Reason: The GOA row is GO_REF:0000108, an inter-ontology logical inference, with GO:0004931 in the WITH field. It therefore asserts nothing about P2X7 beyond the fact that it is an ATP-gated cation channel, and it would attach equally to every P2X receptor. For a protein whose neuronal expression is the central contested question, an automated inference from molecular function to a synaptic process is precisely the wrong basis for a neuronal annotation. The cell-type-specific knockout literature may well justify a neuronal process term for P2X7 - but it would have to be asserted from that evidence, not from this inference chain. Supporting Evidence: PMID:41672132 The most controversial, however, is the presence and role of P2X7R in neurons. PMID:41672132 We revisit the pharmacological regimen required to confirm the functional expression of the receptor and the mouse models that have aided in the investigation of neuronal P2X7R.
GO:0071805 potassium ion transmembrane transport	IEA GO_REF:0000108	ACCEPT	Summary: Potassium efflux through P2X7 is the event that lowers cytosolic potassium and licenses NLRP3 inflammasome assembly. Reason: Core biological process. Derived by inter-ontology inference from the potassium channel activity term, which is being modified here for its selectivity implication - but the flux itself is real, was measured directly, and is the mechanistic link to the interleukin-1 beta phenotype.
GO:0098655 monoatomic cation transmembrane transport	IEA GO_REF:0000002	ACCEPT	Summary: Non-selective cation flux through the open channel. Reason: Core biological process; the most accurate general statement of what the channel moves.
GO:0098794 postsynapse	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Postsynaptic localisation, asserted with no postsynaptic evidence at all. Reason: This is a two-step mechanical inference, not an observation. The GOA row is GO_REF:0000108 (inter-ontology logical inference) with GO:0060079 in the WITH field, and that excitatory postsynaptic potential row is itself GO_REF:0000108 derived from the molecular function GO:0004931. So the chain is: P2X7 is an ATP-gated cation channel, therefore it could generate an excitatory postsynaptic potential, therefore it is postsynaptic. Every P2X receptor would inherit this. Given that neuronal expression of P2X7 specifically is the single most contested claim about this protein, deriving a postsynaptic compartment from its molecular function is exactly the inference that should not be made here. Supporting Evidence: PMID:41672132 The most controversial, however, is the presence and role of P2X7R in neurons.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: Bare protein binding, from high-throughput interactome screens and from targeted co-immunoprecipitation. Reason: Per project guidance, bare GO:0005515 carries no functional information. Where the interaction matters it is already stated better elsewhere in this annotation set - self- association as GO:0042802 and GO:0070207, the EMP/PMP22 C-terminal interaction through the bleb-assembly terms, and the ANO6 relationship through the scrambling and ion-transport terms. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Bare protein binding, from high-throughput interactome screens and from targeted co-immunoprecipitation. Reason: Per project guidance, bare GO:0005515 carries no functional information. Where the interaction matters it is already stated better elsewhere in this annotation set - self- association as GO:0042802 and GO:0070207, the EMP/PMP22 C-terminal interaction through the bleb-assembly terms, and the ANO6 relationship through the scrambling and ion-transport terms. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0001530 lipopolysaccharide binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Assertion that P2X7 binds lipopolysaccharide, transferred by orthology and by curator sequence-similarity judgement. Reason: This traces to a putative LPS-binding motif identified in the rodent P2X7 C-terminal tail, not to a structurally resolved binding site; the full-length P2X7 structures assign that region to the C-cys anchor and the cytoplasmic ballast, with no LPS site. Biologically, P2X7 sits downstream of LPS in the inflammasome pathway as the ATP sensor providing signal 2, while TLR4 is the LPS receptor providing signal 1. Annotating P2X7 as an LPS binder conflates the two signals of a two-signal pathway.
GO:0005911 cell-cell junction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology transfer of an experimental mouse localisation to cell-cell junctions. Reason: No mechanism connects P2X7 function to a junctional pool, and nothing else in this annotation set supports it. Retained rather than removed because the mouse annotation is experimental (IDA) and its full text was not read here, but it is peripheral.
GO:0009897 external side of plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: The large ATP-binding ectodomain of P2X7 faces the extracellular space; transferred by orthology from an experimental mouse localisation. Reason: Defensible for a receptor with a large extracellular domain, but it adds nothing to the plasma-membrane annotation and is potentially misleading for a polytopic protein. Retained because the mouse source is an experimental curator call whose full text was not read here.
GO:0015267 channel activity	IEA GO_REF:0000107	MODIFY	Summary: Correct but at the most general level in the channel branch. Reason: Orthology transfer of a generic channel term. The specific ATP-gated cation channel term is already carried by this gene with direct experimental support. Proposed replacements: extracellularly ATP-gated monoatomic cation channel activity
GO:0019233 sensory perception of pain	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: P2X7 contributes to inflammatory and neuropathic pain, transferred from mouse knockout studies. Reason: A well-supported organismal phenotype and the basis of a drug programme, but a whole-animal sensory outcome rather than something the P2X7 protein does. It is also mechanistically attributed largely to microglial P2X7, which places it inside the cell-type question rather than outside it. Supporting Evidence: PMID:41672132 The most controversial, however, is the presence and role of P2X7R in neurons. PMID:38777288 Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. PMID:38777288 In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice.
GO:0031594 neuromuscular junction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuromuscular junction localisation, transferred by orthology from an experimental mouse study. Reason: Same cell-type caveat as the other neuronal localisations, with the additional point that the mouse source concerns presynaptic motor terminals. Retained as peripheral; the receptor's established cellular home is the myeloid lineage. Supporting Evidence: PMID:41672132 The most controversial, however, is the presence and role of P2X7R in neurons. PMID:38777288 Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. PMID:38777288 In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice.
GO:0038023 signaling receptor activity	IEA GO_REF:0000120	MODIFY	Summary: Correct but at the most general level in the receptor branch. Reason: The ligand and the transduction mechanism are both known; the purinergic nucleotide receptor term is already carried by this gene with IDA support. Proposed replacements: purinergic nucleotide receptor activity
GO:0042802 identical protein binding	IEA GO_REF:0000107	ACCEPT	Summary: P2X7 assembles as a homotrimer, so self-association is a real and mechanistically meaningful molecular function rather than a bare binding assertion. Reason: Unlike bare protein binding, identical protein binding is informative for this protein: the trimer is the functional unit and the structures resolve it directly. Supporting Evidence: PMID:31587896 P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP.
GO:0043025 neuronal cell body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuronal cell body localisation, transferred by orthology from two experimental mouse studies. Reason: Recorded as non-core because the cellular setting is disputed. P2X7 expression is uncontested in myeloid cells, and a 2026 Neuropharmacology review states that neuronal expression is the most controversial claim in the field, turning on antibody specificity and on the pharmacological regimen used to demonstrate functional expression. Against that, cell-type-specific P2rx7 deletion in neurons changes the seizure phenotype in the opposite direction to microglial deletion, human single-cell data show P2RX7 in hippocampal neurons in temporal lobe epilepsy, and two 2026 papers treat neuronal P2rx7 as established. Note that what is disputed is which cells express the receptor, not what the protein does: its molecular function as an ATP-gated cation channel is not in question. Supporting Evidence: PMID:41672132 The most controversial, however, is the presence and role of P2X7R in neurons. PMID:38777288 Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. PMID:38777288 In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice.
GO:0045202 synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Synaptic localisation, transferred by orthology from an experimental mouse study. Reason: Recorded as non-core because the cellular setting is disputed. P2X7 expression is uncontested in myeloid cells, and a 2026 Neuropharmacology review states that neuronal expression is the most controversial claim in the field, turning on antibody specificity and on the pharmacological regimen used to demonstrate functional expression. Against that, cell-type-specific P2rx7 deletion in neurons changes the seizure phenotype in the opposite direction to microglial deletion, human single-cell data show P2RX7 in hippocampal neurons in temporal lobe epilepsy, and two 2026 papers treat neuronal P2rx7 as established. Note that what is disputed is which cells express the receptor, not what the protein does: its molecular function as an ATP-gated cation channel is not in question. Supporting Evidence: PMID:41672132 The most controversial, however, is the presence and role of P2X7R in neurons. PMID:38777288 Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. PMID:38777288 In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice.
GO:0045794 negative regulation of cell volume	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ATP-induced cell shrinkage downstream of P2X7 activation, mediated by ANO6. Reason: Downstream of the calcium influx rather than a direct property of the receptor. Supporting Evidence: PMID:25651887 Inhibition or knockdown of ANO6 attenuates ATP-induced cell shrinkage, cell migration and phospholipid scrambling.
GO:1900227 positive regulation of NLRP3 inflammasome complex assembly	IEA GO_REF:0000107	ACCEPT	Summary: Potassium efflux through P2X7 is a canonical trigger for NLRP3 inflammasome assembly. Reason: Core biological process, mechanistically continuous with the potassium transmembrane transport and interleukin-1 beta production annotations.
GO:0005886 plasma membrane	EXP PMID:23303206 A rare functional haplotype of the P2RX4 and P2RX7 genes lea...	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0005886 plasma membrane	EXP PMID:28326637 Purinergic receptors P2RX4 and P2RX7 in familial multiple sc...	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0004931 extracellularly ATP-gated monoatomic cation channel activity	IDA PMID:17483156 Influence of extracellular monovalent cations on pore and ga...	ACCEPT	Summary: The defining molecular function: a trimeric, non-selective cation channel opened by binding of extracellular ATP at the interfaces of the extracellular domains. Reason: Core molecular function, established for the human protein at its cloning and confirmed by single-channel recording and by full-length cryo-EM structures. This is the one assertion about P2X7 that no party to the current controversy disputes - the argument is about which cells express the receptor, not about what it does. Supporting Evidence: PMID:9038151 Brief applications (1-3 s) of ATP and 2', 3'-(4-benzoyl)-benzoyl-ATP elicited cation-selective currents. PMID:31587896 P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP.
GO:0005267 potassium channel activity	IDA PMID:17483156 Influence of extracellular monovalent cations on pore and ga...	MODIFY	Summary: Single-channel recordings of human P2X7 with potassium as the charge carrier. The term nevertheless names a potassium-selective channel, which P2X7 is not. Reason: The underlying measurement is real - the same study substituted extracellular sodium with alkali and organic cations and recorded the resulting currents - but P2X7 is a non-selective cation channel, so a potassium channel term misdescribes the selectivity. The ATP-gated cation channel term covers the permeation without the false selectivity claim, and the potassium flux itself is separately recorded as GO:0071805. Not removed: this is an experimental annotation and the conductance is genuine. Proposed replacements: extracellularly ATP-gated monoatomic cation channel activity Supporting Evidence: PMID:17483156 Substitution of extracellular Na(+) by any other alkali or organic cation drastically increased the open probability of the channels by prolonging the mean open time.
GO:0005272 sodium channel activity	IDA PMID:17483156 Influence of extracellular monovalent cations on pore and ga...	MODIFY	Summary: Single-channel recordings with sodium as the charge carrier. As with the potassium term, the label names a sodium-selective channel, which P2X7 is not. Reason: Same reasoning as the potassium channel row. The sodium flux is real and is separately recorded as GO:0035725; the selectivity implied by the molecular-function term is not. Proposed replacements: extracellularly ATP-gated monoatomic cation channel activity
GO:0070207 protein homotrimerization	IDA PMID:31587896 Full-Length P2X(7) Structures Reveal How Palmitoylation Prev...	ACCEPT	Summary: Full-length cryo-EM structures of P2X7 in apo and ATP-bound states, resolving the trimer. Reason: Assembly into the trimer is a prerequisite for the channel activity, and is directly observed. Supporting Evidence: PMID:31587896 P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP.
GO:1900227 positive regulation of NLRP3 inflammasome complex assembly	ISS GO_REF:0000024	ACCEPT	Summary: Potassium efflux through P2X7 is a canonical trigger for NLRP3 inflammasome assembly. Reason: Core biological process, mechanistically continuous with the potassium transmembrane transport and interleukin-1 beta production annotations.
GO:0019722 calcium-mediated signaling	TAS PMID:12151016 P2Y and P2X purinoceptor mediated Ca2+ signalling in glial c...	KEEP AS NON CORE	Summary: The calcium signal generated by P2X7 opening propagates into calcium-dependent signalling. Reason: One step downstream of the calcium influx that GO:0070588 and GO:0010524 already record. Real, but it describes what the cell does with the calcium rather than what the receptor does.
GO:0035590 purinergic nucleotide receptor signaling pathway	TAS PMID:12151016 P2Y and P2X purinoceptor mediated Ca2+ signalling in glial c...	ACCEPT	Summary: The signalling pathway initiated by ATP binding to P2X7. Reason: Core biological process, and the appropriately specific child of cell surface receptor signaling pathway for a purinergic receptor.
GO:0071318 cellular response to ATP	TAS PMID:12151016 P2Y and P2X purinoceptor mediated Ca2+ signalling in glial c...	ACCEPT	Summary: The cellular programme triggered when extracellular ATP reaches P2X7. Reason: Core biological process.
GO:0097191 extrinsic apoptotic signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sustained P2X7 activation engages extrinsic apoptotic signalling. Reason: Same reasoning as the parent apoptotic signalling pathway term; downstream cell-fate consequence.
GO:0042802 identical protein binding	ISS GO_REF:0000024	ACCEPT	Summary: P2X7 assembles as a homotrimer, so self-association is a real and mechanistically meaningful molecular function rather than a bare binding assertion. Reason: Unlike bare protein binding, identical protein binding is informative for this protein: the trimer is the functional unit and the structures resolve it directly. Supporting Evidence: PMID:31587896 P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP.
GO:0002931 response to ischemia	NAS PMID:12849743 Up-regulation of P2X2, P2X4 receptor and ischemic cell death...	MARK AS OVER ANNOTATED	Summary: Response to ischemia, asserted from a non-traceable author statement. Reason: The weakest evidence code in this annotation set, and the cited paper's abstract concerns the up-regulation of P2X2 and P2X4, not P2X7, in ischemic neuronal death. The full text was not available here, so this is flagged rather than removed, but a NAS annotation whose abstract names two different receptors should not be treated as support for P2X7. Supporting Evidence: PMID:12849743 In particular, P2X2 and P2X4 proteins became significantly up-regulated, although to different extent and in different cellular phenotypes.
GO:0005886 plasma membrane	TAS PMID:17299767 Involvement of P2X4 and P2Y12 receptors in ATP-induced micro...	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0005515 protein binding	IPI PMID:25651887 Anoctamin 6 mediates effects essential for innate immunity d...	REMOVE	Summary: Bare protein binding, from high-throughput interactome screens and from targeted co-immunoprecipitation. Reason: Per project guidance, bare GO:0005515 carries no functional information. Where the interaction matters it is already stated better elsewhere in this annotation set - self- association as GO:0042802 and GO:0070207, the EMP/PMP22 C-terminal interaction through the bleb-assembly terms, and the ANO6 relationship through the scrambling and ion-transport terms. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0017121 plasma membrane phospholipid scrambling	IDA PMID:25651887 Anoctamin 6 mediates effects essential for innate immunity d...	KEEP AS NON CORE	Summary: Stimulation of P2X7 in macrophages triggers phosphatidylserine exposure - but the scramblase is ANO6 (TMEM16F), activated by the calcium that enters through P2X7. Reason: The paper this annotation comes from is explicit that the scrambling activity belongs to ANO6 and that P2X7 is upstream of it; knockdown of ANO6 attenuates the scrambling while P2X7 is intact. An involved_in annotation on P2X7 is therefore defensible as upstream participation but invites the reading that P2X7 scrambles lipids, which it does not. A positive regulation term would state the relationship correctly and is proposed in proposed_new_terms. Compare TMC1 in this batch, where the same distinction between being necessary for scrambling and performing it had to be drawn. Supporting Evidence: PMID:25651887 Here we demonstrate that the stimulation of P2X7 receptors activates anoctamin 6 (ANO6, TMEM16F), a protein that functions as Ca(2+) dependent phospholipid scramblase and Ca(2+)-activated Cl(-) channel. PMID:25651887 Inhibition or knockdown of ANO6 attenuates ATP-induced cell shrinkage, cell migration and phospholipid scrambling.
GO:0034767 positive regulation of monoatomic ion transmembrane transport	IMP PMID:25651887 Anoctamin 6 mediates effects essential for innate immunity d...	KEEP AS NON CORE	Summary: P2X7 stimulation activates large ANO6-mediated currents in macrophages. Reason: A real regulatory relationship, but it is P2X7 acting through calcium on a different channel rather than a property of P2X7 itself. Supporting Evidence: PMID:25651887 Here we demonstrate that the stimulation of P2X7 receptors activates anoctamin 6 (ANO6, TMEM16F), a protein that functions as Ca(2+) dependent phospholipid scramblase and Ca(2+)-activated Cl(-) channel.
GO:0035590 purinergic nucleotide receptor signaling pathway	IMP PMID:25651887 Anoctamin 6 mediates effects essential for innate immunity d...	ACCEPT	Summary: The signalling pathway initiated by ATP binding to P2X7. Reason: Core biological process, and the appropriately specific child of cell surface receptor signaling pathway for a purinergic receptor.
GO:0045794 negative regulation of cell volume	IMP PMID:25651887 Anoctamin 6 mediates effects essential for innate immunity d...	KEEP AS NON CORE	Summary: ATP-induced cell shrinkage downstream of P2X7 activation, mediated by ANO6. Reason: Downstream of the calcium influx rather than a direct property of the receptor. Supporting Evidence: PMID:25651887 Inhibition or knockdown of ANO6 attenuates ATP-induced cell shrinkage, cell migration and phospholipid scrambling.
GO:0046931 pore complex assembly	IMP PMID:25651887 Anoctamin 6 mediates effects essential for innate immunity d...	KEEP AS NON CORE	Summary: The macropore or dye-uptake pathway that follows sustained P2X7 activation. Reason: GOA carries both sides of a genuine dispute here. The permeabilisation is real and was recorded at the cloning of the human receptor. But single-channel analysis of the human receptor found no change in permeation properties during prolonged ATP exposure, arguing against dilation of the P2X7 pore itself, and the dye-uptake pathway was subsequently attributed to pannexin-1. So the phenotype is P2X7-dependent while the pore may not be P2X7. Retained, because the observation is solid and because the ARBA and IMP rows record a real requirement, but demoted from core pending resolution of what forms the pore. Supporting Evidence: PMID:9038151 Longer applications of agonists permeabilized the cells, as evidenced by uptake of the propidium dye YO-PRO1, but this was less marked than for cells expressing the rat P2X7 receptor. PMID:17483156 Single-channel kinetics and permeation properties remained unchanged during receptor activation by up to 1 mM ATP(4-) for >1 min, arguing against a molecular correlate of pore dilation at the single P2X(7) channel level. PMID:17036048 Here, we identify pannexin-1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, as this dye-uptake pathway and show that signalling through pannexin-1 is required for processing of caspase-1 and release of mature IL-1beta induced by P2X(7) receptor activation.
GO:1904172 positive regulation of bleb assembly	IMP PMID:25651887 Anoctamin 6 mediates effects essential for innate immunity d...	KEEP AS NON CORE	Summary: P2X7-dependent bleb formation requires ANO6. Reason: Same reasoning as bleb assembly - a real but downstream consequence of calcium entry.
GO:0005515 protein binding	IPI PMID:12107182 Epithelial membrane proteins induce membrane blebbing and in...	REMOVE	Summary: Bare protein binding, from high-throughput interactome screens and from targeted co-immunoprecipitation. Reason: Per project guidance, bare GO:0005515 carries no functional information. Where the interaction matters it is already stated better elsewhere in this annotation set - self- association as GO:0042802 and GO:0070207, the EMP/PMP22 C-terminal interaction through the bleb-assembly terms, and the ANO6 relationship through the scrambling and ion-transport terms. No more informative molecular function is supportable from this evidence, so the row is removed rather than rewritten. Removal does not imply the reported interaction is false.
GO:0005886 plasma membrane	IDA PMID:12107182 Epithelial membrane proteins induce membrane blebbing and in...	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0032060 bleb assembly	IDA PMID:12107182 Epithelial membrane proteins induce membrane blebbing and in...	KEEP AS NON CORE	Summary: Membrane blebbing following P2X7 activation, a classic phenotype attributable to the receptor's long cytoplasmic C-terminus. Reason: Well replicated and genuinely P2X7-specific among P2X receptors, but downstream: the blebbing is executed by calcium-dependent effectors including ANO6 and by the C-terminal EMP/PMP22 interactions, not by the channel itself. Supporting Evidence: PMID:12107182 We have shown that the C-terminal domain of the P2X(7) receptor is responsible for the cell blebbing phenotype.
GO:0097190 apoptotic signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sustained P2X7 activation is cytotoxic and engages apoptotic signalling. Reason: Real and long-established, but a downstream cellular fate rather than a molecular role of the receptor, and it only follows prolonged high-concentration agonist exposure.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-139855	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-419490	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-877187	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-877198	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9660822	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9665515	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0045821 positive regulation of glycolysis	IMP PMID:22898868 The P2X7 receptor is a key modulator of aerobic glycolysis.	KEEP AS NON CORE	Summary: P2X7 expression reprograms cells towards aerobic glycolysis, raising lactate output and glycolytic enzyme levels. Reason: A real and reproducible consequence of chronic P2X7 expression, but a metabolic reprogramming several steps downstream of the channel activity and observed largely in transfected and tumour cell lines. Supporting Evidence: PMID:22898868 In HEK293-P2X7 cells, glucose deprivation increases lactate production, expression of glycolytic enzymes and ph-Akt/PKB level.
GO:0010628 positive regulation of gene expression	IMP PMID:22898868 The P2X7 receptor is a key modulator of aerobic glycolysis.	MARK AS OVER ANNOTATED	Summary: Positive regulation of gene expression, from the same aerobic-glycolysis study. Reason: Near-root term carrying no functional information. Almost any signalling receptor changes the expression of something; the specific metabolic reprogramming is already recorded by the glycolysis term on the same reference.
GO:0001614 purinergic nucleotide receptor activity	IDA PMID:9038151 The permeabilizing ATP receptor, P2X7. Cloning and expressio...	ACCEPT	Summary: P2X7 is the ionotropic receptor for extracellular ATP; agonist binding and channel opening are the same event. Reason: Core molecular function, stating the receptor aspect of the same activity captured by GO:0004931. Supporting Evidence: PMID:9038151 Brief applications (1-3 s) of ATP and 2', 3'-(4-benzoyl)-benzoyl-ATP elicited cation-selective currents.
GO:0001530 lipopolysaccharide binding	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Assertion that P2X7 binds lipopolysaccharide, transferred by orthology and by curator sequence-similarity judgement. Reason: This traces to a putative LPS-binding motif identified in the rodent P2X7 C-terminal tail, not to a structurally resolved binding site; the full-length P2X7 structures assign that region to the C-cys anchor and the cytoplasmic ballast, with no LPS site. Biologically, P2X7 sits downstream of LPS in the inflammasome pathway as the ATP sensor providing signal 2, while TLR4 is the LPS receptor providing signal 1. Annotating P2X7 as an LPS binder conflates the two signals of a two-signal pathway.
GO:0005737 cytoplasm	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Curator sequence-similarity transfer placing P2X7 in the cytoplasm. Reason: P2X7 is a two-transmembrane cell-surface receptor. Its C-terminal ballast is cytoplasmic, and the protein is of course synthesised and trafficked through intracellular compartments, but located_in cytoplasm is not a useful or defensible statement of where this receptor is or acts, and it conflicts with the plasma-membrane annotations that the rest of the set agrees on.
GO:0007166 cell surface receptor signaling pathway	ISS GO_REF:0000024	ACCEPT	Summary: Generic parent of the purinergic signalling pathway term. Reason: Correct and a defensible assertion at a family node that spans all P2X receptors, though GO:0035590 purinergic nucleotide receptor signaling pathway - which this gene also carries - states it far more usefully for P2X7.
GO:0019233 sensory perception of pain	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: P2X7 contributes to inflammatory and neuropathic pain, transferred from mouse knockout studies. Reason: A well-supported organismal phenotype and the basis of a drug programme, but a whole-animal sensory outcome rather than something the P2X7 protein does. It is also mechanistically attributed largely to microglial P2X7, which places it inside the cell-type question rather than outside it. Supporting Evidence: PMID:41672132 The most controversial, however, is the presence and role of P2X7R in neurons. PMID:38777288 Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. PMID:38777288 In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice.
GO:0030501 positive regulation of bone mineralization	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Bone mineralisation phenotype transferred from P2rx7 knockout mice. Reason: An organismal skeletal phenotype, several steps removed from the receptor's molecular function.
GO:0032059 bleb	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: P2X7 activation drives membrane blebbing, and the receptor is present in the resulting blebs. Reason: A consequence of the receptor being a plasma-membrane protein in a cell that is blebbing, rather than a distinct functional location.
GO:0032060 bleb assembly	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Membrane blebbing following P2X7 activation, a classic phenotype attributable to the receptor's long cytoplasmic C-terminus. Reason: Well replicated and genuinely P2X7-specific among P2X receptors, but downstream: the blebbing is executed by calcium-dependent effectors including ANO6 and by the C-terminal EMP/PMP22 interactions, not by the channel itself. Supporting Evidence: PMID:12107182 We have shown that the C-terminal domain of the P2X(7) receptor is responsible for the cell blebbing phenotype.
GO:0032731 positive regulation of interleukin-1 beta production	IDA PMID:17036048 Pannexin-1 mediates large pore formation and interleukin-1be...	ACCEPT	Summary: P2X7 activation by extracellular ATP provides the second signal for NLRP3 inflammasome activation, caspase-1 processing and release of mature interleukin-1 beta. Reason: Core biological process and the best-established physiological output of this receptor, shown in macrophages and in primary human mononuclear cells and blocked by P2X7 antagonism. Note that the downstream dye-uptake pathway required for interleukin-1 beta release was assigned to pannexin-1 rather than to P2X7 itself. Supporting Evidence: PMID:17036048 Here, we identify pannexin-1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, as this dye-uptake pathway and show that signalling through pannexin-1 is required for processing of caspase-1 and release of mature IL-1beta induced by P2X(7) receptor activation. PMID:18089587 Release of interleukin-1 beta in both groups was blocked by preincubation with oxidized ATP, a P2X(7) receptor antagonist.
GO:0033198 response to ATP	IDA PMID:9038151 The permeabilizing ATP receptor, P2X7. Cloning and expressio...	ACCEPT	Summary: P2X7 is the sensor for extracellular ATP, so responding to ATP is the process it initiates. Reason: Core biological process. Kept at this level rather than modified to the cellular child, since both are carried and both are accurate for a receptor whose ligand is extracellular ATP. Supporting Evidence: PMID:9038151 Brief applications (1-3 s) of ATP and 2', 3'-(4-benzoyl)-benzoyl-ATP elicited cation-selective currents.
GO:0043409 negative regulation of MAPK cascade	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Negative regulation of the MAPK cascade, transferred by curator sequence similarity from an experimental mouse annotation. Reason: Flagged for the direction of the sign: P2X7 activation is more commonly reported to stimulate MAPK signalling, and the mouse source uses acts_upstream_of_or_within, which does not commit to a direction in the way the human involved_in transfer does. Retained rather than removed because the source is experimental and its full text was not read here.
GO:0045779 negative regulation of bone resorption	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Reduced bone resorption phenotype transferred from P2rx7 knockout mice. Reason: Organismal skeletal phenotype; osteoclasts are of myeloid origin, so this is at least in the right cell lineage, but it remains distal.
GO:0046931 pore complex assembly	IDA PMID:9038151 The permeabilizing ATP receptor, P2X7. Cloning and expressio...	KEEP AS NON CORE	Summary: The macropore or dye-uptake pathway that follows sustained P2X7 activation. Reason: GOA carries both sides of a genuine dispute here. The permeabilisation is real and was recorded at the cloning of the human receptor. But single-channel analysis of the human receptor found no change in permeation properties during prolonged ATP exposure, arguing against dilation of the P2X7 pore itself, and the dye-uptake pathway was subsequently attributed to pannexin-1. So the phenotype is P2X7-dependent while the pore may not be P2X7. Retained, because the observation is solid and because the ARBA and IMP rows record a real requirement, but demoted from core pending resolution of what forms the pore. Supporting Evidence: PMID:9038151 Longer applications of agonists permeabilized the cells, as evidenced by uptake of the propidium dye YO-PRO1, but this was less marked than for cells expressing the rat P2X7 receptor. PMID:17483156 Single-channel kinetics and permeation properties remained unchanged during receptor activation by up to 1 mM ATP(4-) for >1 min, arguing against a molecular correlate of pore dilation at the single P2X(7) channel level. PMID:17036048 Here, we identify pannexin-1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, as this dye-uptake pathway and show that signalling through pannexin-1 is required for processing of caspase-1 and release of mature IL-1beta induced by P2X(7) receptor activation.
GO:0051495 positive regulation of cytoskeleton organization	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Positive regulation of cytoskeleton organisation, transferred by curator sequence similarity. Reason: Consistent with the blebbing and cell-shrinkage phenotypes, but generic and downstream.
GO:0002028 regulation of sodium ion transport	ISS PMID:17785580 Evidence for functional P2X4/P2X7 heteromeric receptors.	KEEP AS NON CORE	Summary: Regulation of sodium ion transport, transferred by sequence similarity from the P2X4/P2X7 heteromer study. Reason: Rests on the contested claim that P2X4 and P2X7 form functional heteromers. Sodium flux through P2X7 itself is already recorded directly as GO:0035725; this row adds a regulatory claim about a different subunit's currents. Supporting Evidence: PMID:17785580 Here, we provide biochemical and electrophysiological evidence for an association between P2X4 and P2X7 that increases the diversity of receptor currents mediated via these two subtypes.
GO:0004931 extracellularly ATP-gated monoatomic cation channel activity	IDA PMID:9038151 The permeabilizing ATP receptor, P2X7. Cloning and expressio...	ACCEPT	Summary: The defining molecular function: a trimeric, non-selective cation channel opened by binding of extracellular ATP at the interfaces of the extracellular domains. Reason: Core molecular function, established for the human protein at its cloning and confirmed by single-channel recording and by full-length cryo-EM structures. This is the one assertion about P2X7 that no party to the current controversy disputes - the argument is about which cells express the receptor, not about what it does. Supporting Evidence: PMID:9038151 Brief applications (1-3 s) of ATP and 2', 3'-(4-benzoyl)-benzoyl-ATP elicited cation-selective currents. PMID:31587896 P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP.
GO:0005102 signaling receptor binding	ISS PMID:17785580 Evidence for functional P2X4/P2X7 heteromeric receptors.	KEEP AS NON CORE	Summary: Generic receptor-binding term, supported by sequence-similarity curation from the P2X4/P2X7 heteromer study. Reason: Two problems, neither fatal. The term is uninformative - it says only that P2X7 binds a receptor. And the underlying claim, that P2X4 and P2X7 form functional heteromers, is itself contested; the paper behind it was published with an accompanying commentary, and the field has not settled on heteromeric assembly. Retained at low weight rather than removed. Supporting Evidence: PMID:17785580 Here, we provide biochemical and electrophysiological evidence for an association between P2X4 and P2X7 that increases the diversity of receptor currents mediated via these two subtypes.
GO:0005524 ATP binding	IC PMID:9038151 The permeabilizing ATP receptor, P2X7. Cloning and expressio...	KEEP AS NON CORE	Summary: Literally true - the agonist is ATP - but the binding site is extracellular and the protein neither hydrolyses nor uses ATP. Reason: GO:0005524 is overwhelmingly used for intracellular ATP-consuming enzymes, and on a cell-surface receptor it invites exactly the wrong reading. The informative statement is GO:0004931, which says that ATP binding gates a cation channel. Retained because it is not false, and because the full-length structures did reveal a separate cytoplasmic guanosine nucleotide binding site, so nucleotide binding by this protein is not a single simple fact. Supporting Evidence: PMID:31587896 They show a second cytoplasmic element with a unique fold, the cytoplasmic ballast, which unexpectedly contains a zinc ion complex and a guanosine nucleotide binding site.
GO:0005886 plasma membrane	ISS PMID:17785580 Evidence for functional P2X4/P2X7 heteromeric receptors.	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0005886 plasma membrane	IC PMID:9038151 The permeabilizing ATP receptor, P2X7. Cloning and expressio...	ACCEPT	Summary: P2X7 is a cell-surface receptor whose ATP-binding site faces the extracellular space. Reason: Core location, asserted consistently across phylogenetic, electronic, experimental and pathway-database evidence, and not in dispute.
GO:0010524 positive regulation of calcium ion transport into cytosol	IDA PMID:9038151 The permeabilizing ATP receptor, P2X7. Cloning and expressio...	ACCEPT	Summary: ATP application to P2X7-expressing cells raises cytosolic calcium. Reason: Core biological process, measured directly in the human cloning study.
GO:0016020 membrane	IDA PMID:17785580 Evidence for functional P2X4/P2X7 heteromeric receptors.	MODIFY	Summary: True but uninformative. Reason: The specific compartment is established and already annotated many times over in this set. Proposed replacements: plasma membrane
GO:0032731 positive regulation of interleukin-1 beta production	IDA PMID:18089587 Interleukin-1 beta secretion from cord blood mononuclear cel...	ACCEPT	Summary: P2X7 activation by extracellular ATP provides the second signal for NLRP3 inflammasome activation, caspase-1 processing and release of mature interleukin-1 beta. Reason: Core biological process and the best-established physiological output of this receptor, shown in macrophages and in primary human mononuclear cells and blocked by P2X7 antagonism. Note that the downstream dye-uptake pathway required for interleukin-1 beta release was assigned to pannexin-1 rather than to P2X7 itself. Supporting Evidence: PMID:17036048 Here, we identify pannexin-1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, as this dye-uptake pathway and show that signalling through pannexin-1 is required for processing of caspase-1 and release of mature IL-1beta induced by P2X(7) receptor activation. PMID:18089587 Release of interleukin-1 beta in both groups was blocked by preincubation with oxidized ATP, a P2X(7) receptor antagonist.
GO:0051899 membrane depolarization	IDA PMID:9038151 The permeabilizing ATP receptor, P2X7. Cloning and expressio...	ACCEPT	Summary: Cation influx through P2X7 depolarises the plasma membrane. Reason: Core biological process, an immediate electrical consequence of the channel activity.

Gene Description

Proposed New Ontology Terms

positive regulation of plasma membrane phospholipid scrambling

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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