GRIA4 encodes GluA4, an AMPA receptor subunit that converts glutamate binding into postsynaptic cation currents. Recombinant human flip GluA4 homomers show fast desensitization and recovery in HEK293 recordings. De novo variants cause neurodevelopmental disorder with variable seizures and gait abnormalities.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001540 amyloid-beta binding | NAS PMID:26719327 Amyloid-Ξ² Receptors: The Good, the Bad, and the Prion Protei... | MARK AS OVER ANNOTATED | Reason: Gria4 perturbation affected cellular binding, while biochemical assays favor GluR2-containing complexes. These results do not establish direct amyloid binding by human GRIA4. Supporting Evidence: PMID:20032460 ADDLs interact preferentially with GluR2-containing complexes |
| GO:0004970 glutamate-gated receptor activity | IEA GO_REF:0000117 | TOO GENERAL | Reason: The electronic receptor assignment is valid but broader than retained AMPA glutamate receptor activity (GO:0004971), with the same enables relation. |
| GO:0004970 glutamate-gated receptor activity | ISS GO_REF:0000024 | TOO GENERAL | Reason: The rat ortholog transfer is compatible with receptor function; retained AMPA glutamate receptor activity (GO:0004971) supplies the more specific enables annotation. |
| GO:0004971 AMPA glutamate receptor activity | IBA GO_REF:0000033 | ACCEPT | Reason: AN628 inherits AN396/PTN000438081. Human flip GluA4 plus Ξ³8 conducts glutamate-evoked current in HEK293T cells; target self-inclusion is legitimate descendant evidence. |
| GO:0004971 AMPA glutamate receptor activity | IDA PMID:21172611 Hippocampal AMPA receptor gating controlled by both TARP and... | ACCEPT | Reason: Human flip GluA4 coexpressed with Ξ³8 in HEK293T cells conducts glutamate-evoked current. These recombinant channel experiments support AMPA receptor activity without establishing a presynaptic preparation. Supporting Evidence: PMID:21172611 Channel resensitization is qualitatively similar when Ξ³-8 is co-expressed with each GluA1-4 subunit |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | TOO GENERAL | Reason: Retained AMPA glutamate receptor activity (GO:0004971) is a more specific channel function and preserves the enables relation. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | TOO GENERAL | Reason: PTN000437926 and PTN001826301 are distinct inherited assertions on the target lineage. Retained PSD-membrane activity entails this broader plasma-membrane activity. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | TOO GENERAL | Reason: Retained unextended located_in postsynaptic membrane (GO:0045211) is more specific than this plasma-membrane mapping, without changing its localization claim. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | TOO GENERAL | Reason: Retain the positive membrane placement through the more specific unextended located_in postsynaptic membrane annotations (GO:0045211). The distinct source date remains preserved. |
| GO:0005886 plasma membrane | TAS PMID:8589990 Cloning, expression and pharmacological characterization of ... | TOO GENERAL | Reason: The human expression study supports membrane receptor function; retained unextended located_in postsynaptic membrane (GO:0045211) provides more specific localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-399711 | TOO GENERAL | Reason: The channel complex contains plasma-membrane P48058. Retain this positive location through unextended located_in postsynaptic membrane (GO:0045211), which is more specific. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-399712 | TOO GENERAL | Reason: The calcium-permeable receptor set contains plasma-membrane P48058. Retained unextended located_in postsynaptic membrane (GO:0045211) provides more specific localization without generalizing calcium permeability across assemblies. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-416320 | TOO GENERAL | Reason: P48058 occurs in the plasma-membrane product of receptor insertion. Retained located_in postsynaptic membrane (GO:0045211) specifies this pool; GRIA4 is receptor cargo here. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-416639 | TOO GENERAL | Reason: The insertion product contains plasma-membrane P48058. Retained unextended located_in postsynaptic membrane (GO:0045211) is more specific; no trafficking-enzyme activity is assigned to GRIA4. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-416985 | TOO GENERAL | Reason: The receptor participant contains plasma-membrane P48058; NSF supplies the ATPase activity. Retained located_in postsynaptic membrane (GO:0045211) preserves the positive location more specifically. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-420975 | TOO GENERAL | Reason: The ligand-binding receptor set includes plasma-membrane P48058. Retained unextended located_in postsynaptic membrane (GO:0045211) gives the more specific location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-420977 | TOO GENERAL | Reason: The ligand-binding receptor set includes plasma-membrane P48058. Retained unextended located_in postsynaptic membrane (GO:0045211) gives the more specific location, preserving assembly-dependent permeability. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-420980 | TOO GENERAL | Reason: The sodium-conducting receptor complex includes plasma-membrane P48058. Retained unextended located_in postsynaptic membrane (GO:0045211) supplies more specific localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-421007 | TOO GENERAL | Reason: The internalization input contains plasma-membrane P48058. Retained located_in postsynaptic membrane (GO:0045211) specifies that pool; the phosphoserine label belongs to GluR2, not GRIA4. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-438037 | TOO GENERAL | Reason: The sodium-conducting catalyst complex resolves to plasma-membrane P48058. Retained unextended located_in postsynaptic membrane (GO:0045211) preserves that location at greater specificity. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8849881 | TOO GENERAL | Reason: The AMPA branch of the SALM2-associated receptor set explicitly contains plasma-membrane P48058. Retained located_in postsynaptic membrane (GO:0045211) is more specific; this is not an NMDA-subunit assignment. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | TOO GENERAL | Reason: Retained monoatomic ion transmembrane transport (GO:0034220) specifies the membrane-crossing process and retains the involved_in relation. |
| GO:0007215 glutamate receptor signaling pathway | TAS PMID:8589990 Cloning, expression and pharmacological characterization of ... | TOO GENERAL | Reason: Human receptor expression supports the assignment; retained ionotropic glutamate receptor signaling (GO:0035235) supplies the more specific involved_in process. |
| GO:0015276 ligand-gated monoatomic ion channel activity | IEA GO_REF:0000002 | TOO GENERAL | Reason: Retained AMPA glutamate receptor activity (GO:0004971) specifies the ligand-gated channel class with the same enables relation. |
| GO:0016020 membrane | IEA GO_REF:0000002 | TOO GENERAL | Reason: Retained located_in postsynaptic membrane (GO:0045211) and endocytic vesicle membrane (GO:0030666) identify specific membrane pools without a cell-type restriction. |
| GO:0030425 dendrite | IEA GO_REF:0000044 | ACCEPT | Reason: Dendritic localization is supported; spine comparators change relation or add hippocampal restriction. |
| GO:0030425 dendrite | ISS GO_REF:0000024 | ACCEPT | Reason: Retain dendritic localization; narrower spine localization is hippocampal-restricted, while unextended spine activity changes relation. Supporting Evidence: file:human/GRIA4/GRIA4-uniprot.txt dendrite |
| GO:0030666 endocytic vesicle membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: Explicit Reactome P48058 target chains independently support the endocytic-vesicle membrane pool. This is receptor trafficking, without implying channel activity inside that compartment. |
| GO:0030666 endocytic vesicle membrane | TAS Reactome:R-HSA-416320 | KEEP AS NON CORE | Reason: P48058 is an explicit endocytic-vesicle membrane member of the insertion input. Retain this trafficking pool without assigning the event's kinase activity to receptor cargo. |
| GO:0030666 endocytic vesicle membrane | TAS Reactome:R-HSA-416639 | KEEP AS NON CORE | Reason: The insertion input contains P48058 at endocytic-vesicle membrane. Retain this receptor trafficking pool; the event does not establish channel conduction within the vesicle. |
| GO:0030666 endocytic vesicle membrane | TAS Reactome:R-HSA-421007 | KEEP AS NON CORE | Reason: The internalization output explicitly contains P48058 at endocytic-vesicle membrane. This supports a trafficking location, without making GRIA4 the machinery that internalizes receptors. Supporting Evidence: Reactome:R-HSA-421007 internalization of GluR2 containing AMPA receptors into endosomes |
| GO:0032281 AMPA glutamate receptor complex | IBA GO_REF:0000033 | ACCEPT | Reason: AN396/PTN000438081 supports receptor-complex membership. GRIA4 is a pore-forming subunit; part_of does not imply that an isolated subunit is the assembled receptor. Supporting Evidence: file:human/GRIA4/GRIA4-uniprot.txt complex with GRIA1, GRIA2, GRIA3 |
| GO:0032281 AMPA glutamate receptor complex | ISS GO_REF:0000024 | ACCEPT | Reason: Retain membership in the AMPA receptor complex; the rat ortholog transfer agrees with independently reviewed target-family assembly evidence. |
| GO:0034220 monoatomic ion transmembrane transport | IEA GO_REF:0000120 | ACCEPT | Reason: The receptor supplies the ion-conducting pore, directly contributing to transmembrane transport rather than merely influencing transporter abundance. |
| GO:0034392 negative regulation of smooth muscle cell apoptotic process | IGI PMID:32151690 CircCBFB-mediated miR-28-5p facilitates abdominal aortic ane... | KEEP AS NON CORE | Reason: The abstract reports GRIA4 anti-apoptotic effects and rescue in vascular smooth muscle cells. Defer to the experimental curation, retaining this peripheral process; necessity alone does not establish the uninspected molecular mechanism. Supporting Evidence: PMID:32151690 GRIA4 and LYPD3 exerted anti-apoptosis effects in VSMCs |
| GO:0035235 ionotropic glutamate receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Reason: Glutamate-evoked channel opening is a direct step of ionotropic receptor signaling. This supports participation without requiring a separate intracellular catalytic activity. |
| GO:0035249 synaptic transmission, glutamatergic | IBA GO_REF:0000033 | ACCEPT | Reason: Inherited AN72/PTN001826301 supports glutamatergic transmission. GRIA4 receptor conductance performs the postsynaptic signaling step; no presynaptic release function is implied. |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000002 | TOO GENERAL | Reason: The signaling-receptor assignment is entailed by retained AMPA glutamate receptor activity (GO:0004971); the narrower enables annotation identifies the mechanism. |
| GO:0043025 neuronal cell body | ISS GO_REF:0000024 | KEEP AS NON CORE | Reason: Retain the curator-supported rat hippocampal soma localization as a peripheral receptor pool; human transfer and cell restriction remain explicit. |
| GO:0043197 dendritic spine | IBA GO_REF:0000033 | ACCEPT | Reason: Target descent from AN396/PTN000438081 supports dendritic-spine activity. Postsynaptic density membrane is not a descendant of dendritic spine; both contexts remain informative. |
| GO:0043197 dendritic spine | ISS GO_REF:0000024 | ACCEPT | Reason: Rat hippocampal GluR4 localization supports this restricted spine assignment. Preserve human transfer; neither direct amyloid binding nor universal localization follows. |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000044 | ACCEPT | Reason: Curated postsynaptic placement supports this principal receptor location. Supporting Evidence: file:human/GRIA4/GRIA4-uniprot.txt Postsynaptic cell membrane |
| GO:0045211 postsynaptic membrane | ISS GO_REF:0000024 | ACCEPT | Reason: Rat-donor postsynaptic placement agrees with independently supported target localization. |
| GO:0045211 postsynaptic membrane | ISS GO_REF:0000024 | ACCEPT | Reason: Human GRIA2 is the literal donor; target postsynaptic localization is independently supported. |
| GO:0050804 modulation of chemical synaptic transmission | IBA GO_REF:0000033 | ACCEPT | Reason: AN72/PTN001826301 supports inherited synaptic modulation. No supported narrower modulation process occurs in the current annotation set. |
| GO:0060078 regulation of postsynaptic membrane potential | IEA GO_REF:0000108 | ACCEPT | Reason: The inherited postsynaptic channel activity (GO:1904315) directly supports this process projection; the annotation preserves the receptor's contribution to postsynaptic potential. |
| GO:0098839 postsynaptic density membrane | IBA GO_REF:0000033 | ACCEPT | Reason: AN72/PTN001826301 supports the target's postsynaptic density membrane activity context. Preserve the ancestral assertion without assigning it to the short isoform. |
| GO:0099505 regulation of presynaptic membrane potential | IEA GO_REF:0000108 | REMOVE | Reason: This electronic process derives solely from GO:0099507. Dropping the unsupported presynaptic context from that activity removes the basis for this propagation. |
| GO:0099507 ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential | IDA PMID:12670305 Kinetic properties of human AMPA-type glutamate receptors ex... | MODIFY | Reason: Patch-clamp recordings establish channel activity in transfected cells, without testing presynaptic membrane regulation. Proposed replacements: AMPA glutamate receptor activity Context of precomposed term: context dropped |
| GO:0099507 ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential | IMP PMID:12670305 Kinetic properties of human AMPA-type glutamate receptors ex... | MODIFY | Reason: The heterologous recordings support AMPA receptor activity; the asserted presynaptic context was not tested. Proposed replacements: AMPA glutamate receptor activity Context of precomposed term: context dropped |
| GO:0099507 ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential | NAS PMID:12670305 Kinetic properties of human AMPA-type glutamate receptors ex... | MODIFY | Reason: Human GluR4 was recorded in HEK293 cells without a presynaptic preparation. Retain AMPA receptor activity and drop the unsupported context. Proposed replacements: AMPA glutamate receptor activity Context of precomposed term: context dropped |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | UNDECIDED | Reason: The abstract establishes human cerebrospinal-fluid vesicle proteomics, but the GRIA4 protein-group and peptide assignment has not been inspected. Preserve the HDA assertion and fluid extension pending target-level evidence. |
| GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | IBA GO_REF:0000033 | ACCEPT | Reason: AN72/PTN001826301 supports this postsynaptic channel function. AMPA selectivity and postsynaptic channel activity are complementary; neither term is an ancestor of the other. |
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Q: Which GRIA4 protein or peptide assignment supports the cerebrospinal-fluid extracellular-vesicle annotation?
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