{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P42261","secondaryAccessions":["B7Z2S0","B7Z2W8","B7Z3F6","B7Z9G9","D3DQI4","E7ESV8","Q2NKM6"],"uniProtkbId":"GRIA1_HUMAN","entryAudit":{"firstPublicDate":"1995-11-01","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"2006-10-17","entryVersion":241,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Glutamate receptor 1"},"shortNames":[{"value":"GluR-1"}]},"alternativeNames":[{"fullName":{"value":"AMPA-selective glutamate receptor 1"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}],"value":"GluR-A"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}],"value":"GluR-K1"}},{"fullName":{"value":"Glutamate receptor ionotropic, AMPA 1"}}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:4571"}],"value":"GRIA1"},"synonyms":[{"value":"GLUA1"},{"value":"GLUH1"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1320959"}],"value":"GLUR1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1311100"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20805473"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21172611"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28628100"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35675825"}],"value":"Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:1311100, PubMed:20805473, PubMed:21172611, PubMed:28628100, PubMed:35675825). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG2 or CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611). Resensitization is blocked by CNIH2 through interaction with CACNG8 in the CACNG8-containing AMPA receptors complex (PubMed:21172611). Calcium (Ca(2+)) permeability depends on subunits composition and, heteromeric channels containing edited GRIA2 subunit are calcium-impermeable. Also permeable to other divalents cations such as strontium(2+) and magnesium(2+) and monovalent cations such as potassium(1+) and lithium(1+) (By similarity)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Ca(2+)(in) = Ca(2+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29671"},{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Na(+)(in) = Na(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:34963"},{"database":"ChEBI","id":"CHEBI:29101"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Mg(2+)(in) = Mg(2+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29827"},{"database":"ChEBI","id":"CHEBI:18420"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Li(+)(in) = Li(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:78551"},{"database":"ChEBI","id":"CHEBI:49713"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"K(+)(in) = K(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29463"},{"database":"ChEBI","id":"CHEBI:29103"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Sr(2+)(in) = Sr(2+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:78679"},{"database":"ChEBI","id":"CHEBI:35104"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20805473"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23739980"}],"value":"Homotetramer or heterotetramer of pore-forming glutamate receptor subunits; heteromeric assembly can be the result of both receptor subtype and flip or flop form and according the composition, one partner can be dominant with respect to the fast desensitizing current component, whereas the other can determine the steady-state component (By similarity). Tetramers may be formed by the dimerization of dimers (PubMed:23739980). Found in a complex with GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 (By similarity). Interacts with HIP1 and RASGRF2. Interacts with SYNDIG1 and GRIA2 (By similarity). Interacts with DLG1 (via C-terminus). Interacts with LRFN1. Interacts with PRKG2. Interacts with CNIH2 and CACNG2 (PubMed:20805473). Interacts with CACNG5; this interaction modulates the gating. Interacts (via C-terminus) with PDLIM4 (via LIM domain); this interaction as well as the interaction of PDLIM4 with alpha-actinin is required for their colocalization in early endosomes (By similarity). Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes. Interacts (via PDZ-binding motif) with SHANK3 (via PDZ domain) (By similarity). Interacts with CACNG3; associates GRIA1 with the adapter protein complex 4 (AP-4) to target GRIA1 to the somatodendritic compartment of neurons (By similarity). Interacts with CACNG2; this interaction mediates traffick to the plasma membrane and modulation of desensitization. Interacts with CNIH2 and CNIH3; this interaction promotes expression at the plasma membrane and extensively modulates their gating properties by slowing deactivation and desensitization kinetics (By similarity). Found in a complex with GRIA2, GRIA3, GRIA4, DLG4, CACNG8 and CNIH2 (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P42261","intActId":"EBI-6980805"},"interactantTwo":{"uniProtKBAccession":"Q6XD76","geneName":"ASCL4","intActId":"EBI-10254793"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P42261","intActId":"EBI-6980805"},"interactantTwo":{"uniProtKBAccession":"Q14457","geneName":"BECN1","intActId":"EBI-949378"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P42261","intActId":"EBI-6980805"},"interactantTwo":{"uniProtKBAccession":"Q9UIH9","geneName":"KLF15","intActId":"EBI-2796400"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P42261","intActId":"EBI-6980805"},"interactantTwo":{"uniProtKBAccession":"Q15907","geneName":"RAB11B","intActId":"EBI-722234"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P42261","intActId":"EBI-6980805"},"interactantTwo":{"uniProtKBAccession":"Q9UNY5","geneName":"ZNF232","intActId":"EBI-749023"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"}],"value":"Interaction with CACNG2, CNIH2 and CNIH3 promotes cell surface expression. Colocalizes with PDLIM4 in early endosomes. Displays a somatodendritic localization and is excluded from axons in neurons (By similarity). Localized to cone photoreceptor pedicles (By similarity)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23739980"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23739980"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}],"value":"Endoplasmic reticulum membrane","id":"SL-0097"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23739980"}],"value":"Postsynaptic cell membrane","id":"SL-0219"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23739980"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"}],"value":"Postsynaptic density membrane","id":"SL-0520"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"}],"value":"Cell projection, dendrite","id":"SL-0283"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"}],"value":"Cell projection, dendritic spine","id":"SL-0284"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}],"value":"Early endosome membrane","id":"SL-0093"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}],"value":"Recycling endosome membrane","id":"SL-0231"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"}],"value":"Presynapse","id":"SL-0516"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"}],"value":"Synapse","id":"SL-0258"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"Flop"},"isoformIds":["P42261-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"Flip"},"isoformIds":["P42261-2"],"sequenceIds":["VSP_053349"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P42261-3"],"sequenceIds":["VSP_045120"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["P42261-4"],"sequenceIds":["VSP_045119"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"isoformIds":["P42261-5"],"sequenceIds":["VSP_047024"],"isoformSequenceStatus":"Described"},{"name":{"value":"6"},"isoformIds":["P42261-6"],"sequenceIds":["VSP_047024","VSP_053349"],"isoformSequenceStatus":"Described"}]},{"texts":[{"value":"Widely expressed in brain"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23739980"}],"value":"The M4 transmembrane segment mediates tetramerization and is required for cell surface expression"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30135643"}],"value":"Palmitoylated. Depalmitoylated by CPT1C and upon L-glutamate stimulation (PubMed:30135643). ZDHHC3/GODZ specifically palmitoylates Cys-603, which leads to Golgi retention and decreased cell surface expression (PubMed:30135643). In contrast, Cys-829 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P19490"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P23818"}],"value":"Phosphorylated at Ser-645. Phosphorylated at Ser-710 by PKC. Phosphorylated at Ser-849 by PKC, PKA and CAMK2. Phosphorylated at Ser-863 by PKC, PKA and PRKG2 (By similarity). Phosphorylation of Ser-863 is reduced by induction of long-term depression and increased by induction of long-term potentiation (By similarity)"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Intellectual developmental disorder, autosomal dominant 67","diseaseAccession":"DI-06444","acronym":"MRD67","description":"An autosomal dominant disorder characterized by global development delay and impaired intellectual development apparent from infancy or early childhood. Additional features may include behavioral abnormalities, and language and sleeping difficulties.","diseaseCrossReference":{"database":"MIM","id":"619927"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23033978"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28628100"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35675825"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Intellectual developmental disorder, autosomal recessive 76","diseaseAccession":"DI-06445","acronym":"MRT76","description":"An autosomal recessive disorder characterized by global developmental delay, severely impaired intellectual development, absent speech, seizures, sleep disturbances, and feeding difficulties.","diseaseCrossReference":{"database":"MIM","id":"619931"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35675825"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1311100"}],"value":"The postsynaptic actions of L-glutamate are mediated by a variety of receptors that are named according to their selective agonists (PubMed:1311100). This receptor binds AMPA (quisqualate) > L-glutamate > kainate (PubMed:1311100)"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA1 subfamily"}],"commentType":"SIMILARITY"}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":18,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Chain","location":{"start":{"value":19,"modifier":"EXACT"},"end":{"value":906,"modifier":"EXACT"}},"description":"Glutamate receptor 1","featureId":"PRO_0000011529"},{"type":"Topological domain","location":{"start":{"value":19,"modifier":"EXACT"},"end":{"value":536,"modifier":"EXACT"}},"description":"Extracellular","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Transmembrane","location":{"start":{"value":537,"modifier":"EXACT"},"end":{"value":557,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Topological 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