Reactome | UniProt:Q13002 GRIK2

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UniProt:Q13002 GRIK2 Show undefined attributes

chain	signal peptide:1-31 chain:32-908
checksum	5F34630524401E84
comment	FUNCTION 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).FUNCTION 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).CATALYTIC ACTIVITY Ca(2+)(in) = Ca(2+)(out)CATALYTIC ACTIVITY Na(+)(in) = Na(+)(out)ACTIVITY REGULATION 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.SUBUNIT 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 similarity).SUBCELLULAR LOCATION Expression is higher in cerebellum than in cerebral cortex.DOMAIN The gate of the ion channel is formed by four transmembrane M3 helices and it opens upon stimulation by positive allosteric modulators.PTM Sumoylation mediates kainate receptor-mediated endocytosis and regulates synaptic transmission. Sumoylation is enhanced by PIAS3 and desumoylated by SENP1 (By similarity).PTM Ubiquitinated. Ubiquitination regulates the GRIK2 levels at the synapse by leading kainate receptor degradation through proteasome (By similarity).PTM Phosphorylated by PKC at Ser-868 upon agonist activation, this directly enhance sumoylation.RNA EDITING Partially edited. The presence of Gln at position 621 (non-edited) determines channels with low calcium permeability, whereas Arg (edited) determines a higher calcium permeability especially if the preceding sites are fully edited. This receptor is nearly completely edited in all gray matter structures (90% of the receptors), whereas much less edited in the white matter (10% of the receptors) (By similarity). The unedited version (Q) assembles into a functional kainate-gated homomeric channel, whereas the edited version (R) is unable to produce channel activity when expressed alone (PubMed:8730589).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate > quisqualate > 6-cyano-7-nitroquinoxaline-2,3-dione > L-glutamate = 6,7-dinitroquinoxaline-2,3-dione > dihydrokainate.SIMILARITY Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK2 subfamily.
crossReference	[DatabaseIdentifier:12349741] RefSeq:NP_786944.1 [DatabaseIdentifier:12818550] ZINC - World Drugs:GRIK2_HUMAN [DatabaseIdentifier:12817425] ZINC target:Q13002 [DatabaseIdentifier:12813996] ZINC - Substances:GRIK2_HUMAN [DatabaseIdentifier:12810516] ZINC - Predictions - Purchasable:GRIK2_HUMAN [DatabaseIdentifier:12807630] ZINC - Metabolites:GRIK2_HUMAN [DatabaseIdentifier:12805912] ZINC - FDA approved:GRIK2_HUMAN [DatabaseIdentifier:12804833] ZINC - Biogenic:GRIK2_HUMAN [DatabaseIdentifier:11464476] ENSEMBL:ENSG00000164418 [DatabaseIdentifier:11559455] ENSEMBL:ENSP00000508130 [DatabaseIdentifier:11559453] ENSEMBL:ENSP00000508175 [DatabaseIdentifier:11559451] ENSEMBL:ENSP00000507424 [DatabaseIdentifier:11559452] ENSEMBL:ENSP00000358134 [DatabaseIdentifier:11559449] ENSEMBL:ENSP00000358130 [DatabaseIdentifier:11559454] ENSEMBL:ENSP00000405596 [DatabaseIdentifier:11559450] ENSEMBL:ENSP00000397026 [DatabaseIdentifier:11682154] ENSEMBL:ENST00000684068 [DatabaseIdentifier:11682150] ENSEMBL:ENST00000413795 [DatabaseIdentifier:11682149] ENSEMBL:ENST00000369138 [DatabaseIdentifier:11682153] ENSEMBL:ENST00000421544 [DatabaseIdentifier:11682151] ENSEMBL:ENST00000369134 [DatabaseIdentifier:11682148] ENSEMBL:ENST00000682090 [DatabaseIdentifier:11682152] ENSEMBL:ENST00000683215 [DatabaseIdentifier:11780939] Guide to Pharmacology - Targets:451 [DatabaseIdentifier:11796840] GeneCards:GRIK2 [DatabaseIdentifier:11812663] GlyGen:Q13002 [DatabaseIdentifier:11834129] HMDB Protein:HMDBP01813 [DatabaseIdentifier:11849805] HPA:ENSG00000164418-GRIK2 [DatabaseIdentifier:12134505] OpenTargets:ENSG00000164418 [DatabaseIdentifier:12137911] Orphanet:GRIK2 [DatabaseIdentifier:12234925] PDB:3QXM [DatabaseIdentifier:12234924] PDB:5CMM [DatabaseIdentifier:12257126] PRO:Q13002 [DatabaseIdentifier:12294666] Pharos - Targets:Q13002 [DatabaseIdentifier:12349742] RefSeq:XP_047274638.1 [DatabaseIdentifier:12349746] RefSeq:XP_054211218.1 [DatabaseIdentifier:12349744] RefSeq:NP_001159719.1 [DatabaseIdentifier:12349743] RefSeq:NP_068775.1 [DatabaseIdentifier:12349745] RefSeq:XP_054211219.1 [DatabaseIdentifier:12349740] RefSeq:XP_047274637.1
databaseName	UniProt
dbId	55686
description	recommendedName: Glutamate receptor ionotropic, kainate 2 shortName evidence="2"GluK2 alternativeName: Excitatory amino acid receptor 4 shortName: EAA4 alternativeName: Glutamate receptor 6 shortName: GluR-6 shortName: GluR6
displayName	UniProt:Q13002 GRIK2
geneName	GRIK2 GLUR6
identifier	Q13002
isSequenceChanged	false
keyword	3D-structure Alternative splicing Cell membrane Disease variant Disulfide bond Epilepsy Glycoprotein Intellectual disability Ion channel Ion transport Isopeptide bond Ligand-gated ion channel Membrane Phosphoprotein Postsynaptic cell membrane Proteomics identification Receptor Reference proteome RNA editing Signal Synapse Transmembrane Transmembrane helix Transport Ubl conjugation
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	GRIK2
otherIdentifier	11741955_a_at 11746867_a_at 11758524_s_at 11762583_at 11762584_x_at 1555375_PM_at 1555375_at 1560142_PM_at 1560142_at 1560265_3p_at 1560265_PM_at 1560265_at 1563754_PM_at 1563754_at 17011217 213845_PM_at 213845_at 215655_PM_at 215655_at 2898 2918947 2918981 2918983 2918984 2918986 2918987 2919001 2919002 2919003 2919016 2919017 2919018 2919029 2919032 2919033 2919036 2919037 2919042 2919044 2919045 2919046 2919047 2919048 2919049 2919056 2919057 2919058 2919059 2919060 2919061 2919062 2919063 2919068 2919072 2919080 2919081 2919082 2919083 2919084 2919085 2919087 2919088 2919089 2919090 3928259 39572_at 39573_at 8121225 A_14_P105881 A_14_P108416 A_14_P139842 A_23_P250136 A_24_P935839 A_32_P115796 A_33_P3307133 A_33_P3307144 A_33_P3307147 GE493132 GE82629 GO:0000149 GO:0001662 GO:0004970 GO:0005216 GO:0005234 GO:0005886 GO:0006811 GO:0006874 GO:0007215 GO:0007268 GO:0008066 GO:0008328 GO:0014069 GO:0015276 GO:0015277 GO:0016020 GO:0019228 GO:0019722 GO:0022849 GO:0030165 GO:0030424 GO:0030425 GO:0031624 GO:0031625 GO:0032839 GO:0032983 GO:0034220 GO:0035235 GO:0035249 GO:0038023 GO:0042391 GO:0042734 GO:0042802 GO:0043025 GO:0043113 GO:0043195 GO:0043204 GO:0043226 GO:0043524 GO:0043525 GO:0045202 GO:0045211 GO:0046328 GO:0048169 GO:0048172 GO:0050804 GO:0050806 GO:0051402 GO:0051967 GO:0055085 GO:0060079 GO:0060080 GO:0097110 GO:0097471 GO:0098686 GO:0098815 GO:0098839 GO:0098978 GO:0099171 GO:0099505 GO:0099507 GO:0120169 GO:1904315 HMNXSV003019918 HMNXSV003056832 Hs.301676.0.S2_3p_at Hs.306651.0.S1_3p_at Hs2.301676.2.S1_3p_at Hs2.301676.4.S1_3p_at Hs2.301676.4.S1_3p_s_at Hs2.301676.5.S1_3p_at Hs2.301676.5.S1_3p_x_at Hs2.420694.1.A1_3p_at Hs2.420694.1.A1_3p_s_at Hs2.420694.1.A1_3p_x_at ILMN_1661376 ILMN_1666934 ILMN_2396697 ILMN_2396702 PH_hs_0023669 TC06000836.hg TC06002957.hg U16126_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-450192] GRIK2 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-451318] Edited GRIK2 (GluR6) [plasma membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000164418] ENSEMBL:ENSG00000164418 GRIK2 [ReferenceDNASequence:12733767] UCSC:Q13002 GRIK2 [ReferenceDNASequence:11328757] BioGPS Gene:2898 GRIK2 [ReferenceDNASequence:11393211] COSMIC - genes:GRIK2 GRIK5 [ReferenceDNASequence:11415744] CTD Gene:2898 Q8IY40 [ReferenceDNASequence:11428744] dbSNP Gene:2898 Q8IY40 [ReferenceDNASequence:11828552] HGNC:4580 GRIK2 [ReferenceDNASequence:11870897] KEGG:hsa:2898 GRIK2 [ReferenceDNASequence:11958546] Monarch:2898 GRIK2 [ReferenceDNASequence:12042639] NCBI Gene:2898 GRIK2 [ReferenceDNASequence:12118677] OMIM:138244 GRIK2
referenceTranscript	[ReferenceRNASequence:12531596] RefSeq:XM_047418682.1 GRIK2 [ReferenceRNASequence:12531598] RefSeq:XM_047418681.1 GRIK2 [ReferenceRNASequence:12531601] RefSeq:NM_001166247.1 GRIK2 [ReferenceRNASequence:12531600] RefSeq:XM_054355244.1 GRIK2 [ReferenceRNASequence:12531597] RefSeq:NM_175768.3 GRIK2 [ReferenceRNASequence:12531599] RefSeq:NM_021956.5 GRIK2 [ReferenceRNASequence:12531602] RefSeq:XM_054355243.1 GRIK2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	GRIK2_HUMAN A6NMY9 B5MCV0 D7RWZ3 D7RWZ4 D7RWZ5 D7RWZ6 D7RWZ7 Q8WWS1 Q96KS6 Q96KS7 Q96KS8
sequenceLength	908
species	[Species:48887] Homo sapiens
stId	uniprot:Q13002
url	http://purl.uniprot.org/uniprot/Q13002

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-450192] GRIK2 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-451318] Edited GRIK2 (GluR6) [plasma membrane]
(referenceSequence)	[ModifiedResidue:451284] 3-(S-L-cysteinyl)-L-tyrosine at 571 [ReplacedResidue:451289] L-glutamine 621 replaced with L-arginine [ReplacedResidue:451273] L-isoleucine 567 replaced with L-valine

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