{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q13002","secondaryAccessions":["A6NMY9","B5MCV0","D7RWZ3","D7RWZ4","D7RWZ5","D7RWZ6","D7RWZ7","Q8WWS1","Q96KS6","Q96KS7","Q96KS8"],"uniProtkbId":"GRIK2_HUMAN","entryAudit":{"firstPublicDate":"1997-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1996-11-01","entryVersion":226,"sequenceVersion":1},"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":{"value":"Glutamate receptor ionotropic, kainate 2"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P42260"}],"value":"GluK2"}]},"alternativeNames":[{"fullName":{"value":"Excitatory amino acid receptor 4"},"shortNames":[{"value":"EAA4"}]},{"fullName":{"value":"Glutamate receptor 6"},"shortNames":[{"value":"GluR-6"},{"value":"GluR6"}]}],"flag":"Precursor"},"genes":[{"geneName":{"value":"GRIK2"},"synonyms":[{"value":"GLUR6"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P39087"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14511640"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28180184"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34375587"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7536611"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8730589"}],"value":"Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid (PubMed:7536611, PubMed:8730589, PubMed:14511640). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system (By similarity). Binding of the excitatory neurotransmitter L-glutamate induces a conformational change leading to the opening of the cation channel, converting the chemical signal to an electrical impulse (By similarity). The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist (PubMed:14511640, PubMed:28180184, PubMed:34375587, PubMed:7536611, PubMed:8730589). Modulates cell surface expression of NETO2 (By similarity). In association with GRIK3, involved in presynaptic facilitation of glutamate release at hippocampal mossy fiber synapses (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P39087"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31474366"}],"value":"Independent of its ionotropic glutamate receptor activity, acts as a thermoreceptor conferring sensitivity to cold temperatures (PubMed:31474366). Functions in dorsal root ganglion neurons (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:0000269","source":"PubMed","id":"7536611"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Na(+)(in) = Na(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:34963"},{"database":"ChEBI","id":"CHEBI:29101"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7536611"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P42260"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31474366"}],"value":"Ionotropic glutamate receptor activity is promoted by positive allosteric modulators that inhibit receptor desensitization (By similarity). Ionotropic glutamate receptor activity is inhibited by ion channel blockers (By similarity).Cold receptor activity is activated by temperatures between 10-19 degrees Celsius"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P39087"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P42260"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11744724"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8730589"}],"value":"Homotetramer; formed by the dimerization of dimers via its N-terminal domain (By similarity). Assembles into a kainate-gated homomeric channel that does not bind AMPA (By similarity). Can form functional heteromeric receptors with GRIK5 (PubMed:8730589). Can form functional heteromeric receptors with GRIK3 and GRIK4 (By similarity). Interacts with DLG4 (PubMed:11744724). Interacts with NETO2 (By similarity). Interacts (via C-terminus) with KLHL17 (via kelch repeats); the interaction targets GRIK2 for degradation via ubiquitin-proteasome pathway (By 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Sumoylation is enhanced by PIAS3 and desumoylated by SENP1 (By similarity)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P42260"}],"value":"Ubiquitinated. 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MRT6 patients display mild to severe intellectual disability and psychomotor development delay in early childhood. Patients do not have neurologic problems, congenital malformations, or facial dysmorphism. Body height, weight, and head circumference are normal.","diseaseCrossReference":{"database":"MIM","id":"611092"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17847003"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Neurodevelopmental disorder with impaired language and ataxia and with or without seizures","diseaseAccession":"DI-06241","acronym":"NEDLAS","description":"An autosomal dominant disorder characterized by axial hypotonia and global developmental delay. Affected individuals show impaired intellectual development, delayed walking, poor speech, and behavioral abnormalities. 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