{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q14957","secondaryAccessions":["B2RTT1"],"uniProtkbId":"NMDE3_HUMAN","entryAudit":{"firstPublicDate":"1997-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2010-11-30","entryVersion":213,"sequenceVersion":3},"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 ionotropic, NMDA 2C"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q00961"}],"value":"GluN2C"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q01098"}],"value":"Glutamate [NMDA] receptor subunit epsilon-3"}},{"fullName":{"value":"N-methyl D-aspartate receptor subtype 2C"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q00961"}],"value":"NMDAR2C"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9037519"}],"value":"NR2C"}]}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:4587"}],"value":"GRIN2C"},"synonyms":[{"value":"NMDAR2C"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P35438"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q01098"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26875626"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36309015"}],"value":"Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:26875626, PubMed:36309015). Participates in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current and long-term synaptic potentiation (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:36309015). NMDARs mediate simultaneously the potassium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626)"}],"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:0000269","source":"PubMed","id":"26875626"}]}},{"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":"P35438"}]}},{"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":"P35438"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q00961"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21300787"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26875626"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36309015"},{"evidenceCode":"ECO:0000305"}],"value":"Heterotetramer (PubMed:36309015). Forms heterotetrameric channels composed of two GluN1/zeta subunits (GRIN1), and two identical GluN2/epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) or GluN3 subunits (GRIN3A or GRIN3B) (in vitro) (PubMed:26875626, PubMed:36309015). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Interacts with PDZ domains of PATJ and DLG4 (By similarity). Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (PubMed:21300787)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q6UY14-3","geneName":"ADAMTSL4","intActId":"EBI-10173507"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q99767","geneName":"APBA2","intActId":"EBI-81711"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q66PJ3-4","geneName":"ARL6IP4","intActId":"EBI-5280499"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q96FT7-4","geneName":"ASIC4","intActId":"EBI-9089489"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q9H2G9","geneName":"BLZF1","intActId":"EBI-2548012"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q5PSV4","geneName":"BRMS1L","intActId":"EBI-5666615"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q9ULD4-2","geneName":"BRPF3","intActId":"EBI-23662416"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q9NSI6-4","geneName":"BRWD1","intActId":"EBI-10693038"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q3SXR2","geneName":"C3orf36","intActId":"EBI-18036948"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q96LL4","geneName":"C8orf48","intActId":"EBI-751596"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q5M9N0-2","geneName":"CCDC158","intActId":"EBI-21796846"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"P24941","geneName":"CDK2","intActId":"EBI-375096"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"O95674","geneName":"CDS2","intActId":"EBI-3913685"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q8WUX9","geneName":"CHMP7","intActId":"EBI-749253"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q9Y3D0","geneName":"CIAO2B","intActId":"EBI-744045"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"P02458-1","geneName":"COL2A1","intActId":"EBI-12375799"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q9UJU6","geneName":"DBNL","intActId":"EBI-751783"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q6ZN54-2","geneName":"DEF8","intActId":"EBI-12346463"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q8NDP9","geneName":"DKFZp547K2416","intActId":"EBI-25842538"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q12959","geneName":"DLG1","intActId":"EBI-357481"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q15700","geneName":"DLG2","intActId":"EBI-80426"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"Q92796","geneName":"DLG3","intActId":"EBI-80440"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14957","intActId":"EBI-8285963"},"interactantTwo":{"uniProtKBAccession":"P78352","geneNa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