ID GRIK2_HUMAN Reviewed; 908 AA. AC Q13002; A6NMY9; B5MCV0; D7RWZ3; D7RWZ4; D7RWZ5; D7RWZ6; D7RWZ7; Q8WWS1; AC Q96KS6; Q96KS7; Q96KS8; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 216. DE RecName: Full=Glutamate receptor ionotropic, kainate 2; DE Short=GluK2; DE AltName: Full=Excitatory amino acid receptor 4; DE Short=EAA4; DE AltName: Full=Glutamate receptor 6; DE Short=GluR-6; DE Short=GluR6; DE Flags: Precursor; GN Name=GRIK2; Synonyms=GLUR6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=7536611; RA Hoo K.H., Nutt S.L., Fletcher E.J., Elliott C.E., Korczak B., RA Deverill R.M., Rampersad V., Fantaske R.P., Kamboj R.K.; RT "Functional expression and pharmacological characterization of the human RT EAA4 (GluR6) glutamate receptor: a kainate selective channel subunit."; RL Recept. Channels 2:327-337(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8034316; DOI=10.1006/geno.1994.1198; RA Paschen W., Blackstone C.D., Huganir R.L., Ross C.A.; RT "Human GluR6 kainate receptor (GRIK2): molecular cloning, expression, RT polymorphism, and chromosomal assignment."; RL Genomics 20:435-440(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RA Langer A., Xu D., Kuehcke K., Fehse B., Abdallah S., Lother H.; RT "Myeloid progenitor cell growth and apoptosis involves know and cell- RT specific ionotropic glutamate receptor."; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), AND GENE ORGANIZATION. RX PubMed=11675011; DOI=10.1016/s0378-1119(01)00611-4; RA Barbon A., Vallini I., Barlati S.; RT "Genomic organization of the human GRIK2 gene and characterization of RT multiple splicing variants."; RL Gene 274:187-197(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 5; 6 AND 7), AND ALTERNATIVE RP SPLICING. RC TISSUE=Brain; RX PubMed=20230879; DOI=10.1016/j.gene.2010.03.002; RA Zhawar V.K., Kaur G., deRiel J.K., Kaur G.P., Kandpal R.P., Athwal R.S.; RT "Novel spliced variants of ionotropic glutamate receptor GluR6 in normal RT human fibroblast and brain cells are transcribed by tissue specific RT promoters."; RL Gene 459:1-10(2010). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP RNA EDITING OF POSITION 621. RX PubMed=7523595; DOI=10.1046/j.1471-4159.1994.63051596.x; RA Paschen W., Hedreen J.C., Ross C.A.; RT "RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human RT brain tissue."; RL J. Neurochem. 63:1596-1602(1994). RN [9] RP RNA EDITING OF POSITIONS 567; 571 AND 621. RC TISSUE=Brain; RX PubMed=7696618; DOI=10.1097/00001756-199412000-00055; RA Nutt S.L., Kamboj R.K.; RT "RNA editing of human kainate receptor subunits."; RL NeuroReport 5:2625-2629(1994). RN [10] RP INTERACTION WITH DLG4. RX PubMed=11744724; DOI=10.1074/jbc.m109453200; RA Piserchio A., Pellegrini M., Mehta S., Blackman S.M., Garcia E.P., RA Marshall J., Mierke D.F.; RT "The PDZ1 domain of SAP90. Characterization of structure and binding."; RL J. Biol. Chem. 277:6967-6973(2002). RN [11] RP PHOSPHORYLATION AT SER-846 AND SER-868, AND SUMOYLATION AT LYS-886. RX PubMed=22808340; DOI=10.4161/cib.19195; RA Wilkinson K.A., Konopacki F., Henley J.M.; RT "Modification and movement: Phosphorylation and SUMOylation regulate RT endocytosis of GluK2-containing kainate receptors."; RL Commun. Integr. Biol. 5:223-226(2012). RN [12] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=31474366; DOI=10.1016/j.cell.2019.07.034; RA Gong J., Liu J., Ronan E.A., He F., Cai W., Fatima M., Zhang W., Lee H., RA Li Z., Kim G.H., Pipe K.P., Duan B., Liu J., Xu X.Z.S.; RT "A Cold-Sensing Receptor Encoded by a Glutamate Receptor Gene."; RL Cell 178:1375-1386.e11(2019). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 429-806 IN COMPLEX WITH AGONIST. RX PubMed=21893069; DOI=10.1016/j.jmb.2011.08.043; RA Unno M., Shinohara M., Takayama K., Tanaka H., Teruya K., Doh-ura K., RA Sakai R., Sasaki M., Ikeda-Saito M.; RT "Binding and selectivity of the marine toxin neodysiherbaine A and its RT synthetic analogues to GluK1 and GluK2 kainate receptors."; RL J. Mol. Biol. 413:667-683(2011). RN [14] RP VARIANT [LARGE SCALE ANALYSIS] GLN-187. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [15] RP INVOLVEMENT IN MRT6. RX PubMed=17847003; DOI=10.1086/521275; RA Motazacker M.M., Rost B.R., Hucho T., Garshasbi M., Kahrizi K., Ullmann R., RA Abedini S.S., Nieh S.E., Amini S.H., Goswami C., Tzschach A., Jensen L.R., RA Schmitz D., Ropers H.H., Najmabadi H., Kuss A.W.; RT "A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated RT with autosomal recessive mental retardation."; RL Am. J. Hum. Genet. 81:792-798(2007). RN [16] RP INVOLVEMENT IN NEDLAS, VARIANT NEDLAS THR-657, VARIANT ILE-867, RP CHARACTERIZATION OF VARIANT NEDLAS THR-657, AND FUNCTION. RX PubMed=28180184; DOI=10.1212/nxg.0000000000000129; RA Guzman Y.F., Ramsey K., Stolz J.R., Craig D.W., Huentelman M.J., RA Narayanan V., Swanson G.T.; RT "A gain-of-function mutation in the GRIK2 gene causes neurodevelopmental RT deficits."; RL Neurol. Genet. 3:E129-E129(2017). RN [17] RP INVOLVEMENT IN NEDLAS, VARIANTS NEDLAS THR-657; ARG-660; LYS-660 AND RP THR-668, CHARACTERIZATION OF VARIANTS NEDLAS THR-657; ARG-660; LYS-660 AND RP THR-668, AND SUBCELLULAR LOCATION. RX PubMed=34375587; DOI=10.1016/j.ajhg.2021.07.007; RA Stolz J.R., Foote K.M., Veenstra-Knol H.E., Pfundt R., Ten Broeke S.W., RA de Leeuw N., Roht L., Pajusalu S., Part R., Rebane I., Ounap K., Stark Z., RA Kirk E.P., Lawson J.A., Lunke S., Christodoulou J., Louie R.J., RA Rogers R.C., Davis J.M., Innes A.M., Wei X.C., Keren B., Mignot C., RA Lebel R.R., Sperber S.M., Sakonju A., Dosa N., Barge-Schaapveld D.Q.C.M., RA Peeters-Scholte C.M.P.C.D., Ruivenkamp C.A.L., van Bon B.W., Kennedy J., RA Low K.J., Ellard S., Pang L., Junewick J.J., Mark P.R., Carvill G.L., RA Swanson G.T.; RT "Clustered mutations in the GRIK2 kainate receptor subunit gene underlie RT diverse neurodevelopmental disorders."; RL Am. J. Hum. Genet. 108:1692-1709(2021). CC -!- FUNCTION: Ionotropic glutamate receptor. L-glutamate acts as an CC excitatory neurotransmitter at many synapses in the central nervous CC system. Binding of the excitatory neurotransmitter L-glutamate induces CC a conformation change, leading to the opening of the cation channel, CC and thereby converts the chemical signal to an electrical impulse. The CC receptor then desensitizes rapidly and enters a transient inactive CC state, characterized by the presence of bound agonist CC (PubMed:28180184). Modulates cell surface expression of NETO2 (By CC similarity). {ECO:0000250|UniProtKB:P39087, CC ECO:0000269|PubMed:28180184}. CC -!- FUNCTION: Independent of its ionotropic glutamate receptor activity, CC acts as a thermoreceptor conferring sensitivity to cold temperatures CC (PubMed:31474366). Functions in dorsal root ganglion neurons (By CC similarity). {ECO:0000250|UniProtKB:P39087, CC ECO:0000269|PubMed:31474366}. CC -!- ACTIVITY REGULATION: Cold receptor activity activated by temperatures CC between 10-19 degrees Celsius. {ECO:0000269|PubMed:31474366}. CC -!- SUBUNIT: Homotetramer or heterotetramer of pore-forming glutamate CC receptor subunits. Tetramers may be formed by the dimerization of CC dimers (Probable). Assembles into a kainate-gated homomeric channel CC that does not bind AMPA. GRIK2 associated to GRIK5 forms functional CC channels that can be gated by AMPA (By similarity). Interacts with CC DLG4. Interacts with NETO2 (By similarity). Interacts (via C-terminus) CC with KLHL17 (via kelch repeats); the interaction targets GRIK2 for CC degradation via ubiquitin-proteasome pathway (By similarity). CC {ECO:0000250, ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:34375587}; CC Multi-pass membrane protein. Postsynaptic cell membrane; Multi-pass CC membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; Synonyms=A; CC IsoId=Q13002-1; Sequence=Displayed; CC Name=2; Synonyms=B; CC IsoId=Q13002-2; Sequence=VSP_022335; CC Name=3; CC IsoId=Q13002-3; Sequence=VSP_022337; CC Name=4; CC IsoId=Q13002-4; Sequence=VSP_022334; CC Name=5; Synonyms=C; CC IsoId=Q13002-5; Sequence=VSP_022336; CC Name=6; Synonyms=D; CC IsoId=Q13002-6; Sequence=VSP_044388, VSP_022335; CC Name=7; Synonyms=E; CC IsoId=Q13002-7; Sequence=VSP_044389, VSP_022336; CC -!- TISSUE SPECIFICITY: Expression is higher in cerebellum than in cerebral CC cortex. CC -!- PTM: Sumoylation mediates kainate receptor-mediated endocytosis and CC regulates synaptic transmission. Sumoylation is enhanced by PIAS3 and CC desumoylated by SENP1 (By similarity). {ECO:0000250}. CC -!- PTM: Ubiquitinated. Ubiquitination regulates the GRIK2 levels at the CC synapse by leading kainate receptor degradation through proteasome (By CC similarity). {ECO:0000250}. CC -!- PTM: Phosphorylated by PKC at Ser-868 upon agonist activation, this CC directly enhance sumoylation. {ECO:0000269|PubMed:22808340}. CC -!- RNA EDITING: Modified_positions=567 {ECO:0000269|PubMed:7696618}, 571 CC {ECO:0000269|PubMed:7696618}, 621 {ECO:0000269|PubMed:7523595, CC ECO:0000269|PubMed:7696618}; Note=Partially edited. The presence of Gln CC at position 621 (non-edited) determines channels with low calcium CC permeability, whereas Arg (edited) determines a higher calcium CC permeability especially if the preceding sites are fully edited. This CC receptor is nearly completely edited in all gray matter structures (90% CC of the receptors), whereas much less edited in the white matter (10% of CC the receptors).; CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 6 CC (MRT6) [MIM:611092]: A disorder characterized by significantly below CC average general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. MRT6 CC patients display mild to severe intellectual disability and psychomotor CC development delay in early childhood. Patients do not have neurologic CC problems, congenital malformations, or facial dysmorphism. Body height, CC weight, and head circumference are normal. CC {ECO:0000269|PubMed:17847003}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Neurodevelopmental disorder with impaired language and ataxia CC and with or without seizures (NEDLAS) [MIM:619580]: An autosomal CC dominant disorder characterized by axial hypotonia and global CC developmental delay. Affected individuals show impaired intellectual CC development, delayed walking, poor speech, and behavioral CC abnormalities. Some patients have a more severe phenotype with early- CC onset seizures resembling epileptic encephalopathy, inability to walk CC or speak, and hypomyelination on brain imaging. CC {ECO:0000269|PubMed:28180184, ECO:0000269|PubMed:34375587}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: The postsynaptic actions of Glu are mediated by a CC variety of receptors that are named according to their selective CC agonists. This receptor binds domoate > kainate > quisqualate > 6- CC cyano-7-nitroquinoxaline-2,3-dione > L-glutamate = 6,7- CC dinitroquinoxaline-2,3-dione > dihydrokainate. CC -!- MISCELLANEOUS: [Isoform 6]: Seems to be specific for non-neuronal CC cells. May not function as active channel. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 7]: Seems to be specific for non-neuronal CC cells. May not function as active channel. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) CC family. GRIK2 subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U16126; AAC50420.1; -; mRNA. DR EMBL; AJ252246; CAC81020.1; -; mRNA. DR EMBL; AJ301608; CAC67485.1; -; mRNA. DR EMBL; AJ301609; CAC67486.1; -; mRNA. DR EMBL; AJ301610; CAC67487.1; -; mRNA. DR EMBL; HM149335; ADH93569.1; -; mRNA. DR EMBL; HM149336; ADH93570.1; -; mRNA. DR EMBL; HM149337; ADH93571.1; -; mRNA. DR EMBL; HM149338; ADH93572.1; -; mRNA. DR EMBL; HM149339; ADH93573.1; -; mRNA. DR EMBL; AL109919; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP002528; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP002529; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP002530; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48448.1; -; Genomic_DNA. DR CCDS; CCDS5048.1; -. [Q13002-1] DR CCDS; CCDS5049.1; -. [Q13002-2] DR CCDS; CCDS55045.1; -. [Q13002-5] DR PIR; A54260; A54260. DR RefSeq; NP_001159719.1; NM_001166247.1. [Q13002-5] DR RefSeq; NP_068775.1; NM_021956.4. [Q13002-1] DR RefSeq; NP_786944.1; NM_175768.3. [Q13002-2] DR RefSeq; XP_005267002.1; XM_005266945.2. DR RefSeq; XP_011534079.1; XM_011535777.2. DR RefSeq; XP_011534080.1; XM_011535778.2. DR PDB; 3QXM; X-ray; 1.65 A; A/B=429-544, A/B=667-806. DR PDB; 5CMM; X-ray; 1.27 A; A=667-806. DR PDBsum; 3QXM; -. DR PDBsum; 5CMM; -. DR AlphaFoldDB; Q13002; -. DR SMR; Q13002; -. DR BioGRID; 109155; 22. DR IntAct; Q13002; 3. DR STRING; 9606.ENSP00000397026; -. DR BindingDB; Q13002; -. DR ChEMBL; CHEMBL3683; -. DR DrugBank; DB03425; 2s,4r-4-Methylglutamate. DR DrugBank; DB01351; Amobarbital. DR DrugBank; DB01352; Aprobarbital. DR DrugBank; DB01483; Barbital. DR DrugBank; DB00237; Butabarbital. DR DrugBank; DB00241; Butalbital. DR DrugBank; DB01353; Butobarbital. DR DrugBank; DB01496; Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedione. DR DrugBank; DB02852; Domoic Acid. DR DrugBank; DB00142; Glutamic acid. DR DrugBank; DB01354; Heptabarbital. DR DrugBank; DB01355; Hexobarbital. DR DrugBank; DB00463; Metharbital. DR DrugBank; DB00849; Methylphenobarbital. DR DrugBank; DB00312; Pentobarbital. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB00794; Primidone. DR DrugBank; DB02999; Quisqualic acid. DR DrugBank; DB00418; Secobarbital. DR DrugBank; DB00306; Talbutal. DR DrugBank; DB00599; Thiopental. DR DrugBank; DB00273; Topiramate. DR DrugCentral; Q13002; -. DR GuidetoPHARMACOLOGY; 451; -. DR GlyCosmos; Q13002; 9 sites, No reported glycans. DR GlyGen; Q13002; 10 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q13002; -. DR PhosphoSitePlus; Q13002; -. DR SwissPalm; Q13002; -. DR BioMuta; GRIK2; -. DR DMDM; 2492627; -. DR jPOST; Q13002; -. DR MassIVE; Q13002; -. DR MaxQB; Q13002; -. DR PaxDb; 9606-ENSP00000397026; -. DR PeptideAtlas; Q13002; -. DR ProteomicsDB; 59089; -. [Q13002-1] DR ProteomicsDB; 59090; -. [Q13002-2] DR ProteomicsDB; 59091; -. [Q13002-3] DR ProteomicsDB; 59092; -. [Q13002-4] DR ProteomicsDB; 59093; -. [Q13002-5] DR Antibodypedia; 3038; 407 antibodies from 36 providers. DR DNASU; 2898; -. DR Ensembl; ENST00000369134.9; ENSP00000358130.6; ENSG00000164418.22. [Q13002-1] DR Ensembl; ENST00000369138.5; ENSP00000358134.1; ENSG00000164418.22. [Q13002-5] DR Ensembl; ENST00000413795.5; ENSP00000405596.1; ENSG00000164418.22. [Q13002-2] DR Ensembl; ENST00000421544.6; ENSP00000397026.1; ENSG00000164418.22. [Q13002-1] DR Ensembl; ENST00000682090.1; ENSP00000508130.1; ENSG00000164418.22. [Q13002-1] DR Ensembl; ENST00000683215.1; ENSP00000507424.1; ENSG00000164418.22. [Q13002-1] DR Ensembl; ENST00000684068.1; ENSP00000508175.1; ENSG00000164418.22. [Q13002-5] DR GeneID; 2898; -. DR KEGG; hsa:2898; -. DR MANE-Select; ENST00000369134.9; ENSP00000358130.6; NM_021956.5; NP_068775.1. DR UCSC; uc003pqo.5; human. [Q13002-1] DR AGR; HGNC:4580; -. DR CTD; 2898; -. DR DisGeNET; 2898; -. DR GeneCards; GRIK2; -. DR HGNC; HGNC:4580; GRIK2. DR HPA; ENSG00000164418; Tissue enriched (brain). DR MalaCards; GRIK2; -. DR MIM; 138244; gene. DR MIM; 611092; phenotype. DR MIM; 619580; phenotype. DR neXtProt; NX_Q13002; -. DR OpenTargets; ENSG00000164418; -. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR PharmGKB; PA164741600; -. DR VEuPathDB; HostDB:ENSG00000164418; -. DR eggNOG; KOG1052; Eukaryota. DR GeneTree; ENSGT00940000155610; -. DR InParanoid; Q13002; -. DR OMA; YHRWREV; -. DR OrthoDB; 511851at2759; -. DR PhylomeDB; Q13002; -. DR TreeFam; TF334668; -. DR PathwayCommons; Q13002; -. DR Reactome; R-HSA-451307; Activation of Na-permeable kainate receptors. DR Reactome; R-HSA-451308; Activation of Ca-permeable Kainate Receptor. DR SignaLink; Q13002; -. DR SIGNOR; Q13002; -. DR BioGRID-ORCS; 2898; 10 hits in 1150 CRISPR screens. DR ChiTaRS; GRIK2; human. DR GeneWiki; GRIK2; -. DR GenomeRNAi; 2898; -. DR Pharos; Q13002; Tclin. DR PRO; PR:Q13002; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q13002; Protein. DR Bgee; ENSG00000164418; Expressed in cerebellar vermis and 152 other cell types or tissues. DR ExpressionAtlas; Q13002; baseline and differential. DR GO; GO:0032839; C:dendrite cytoplasm; IEA:Ensembl. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl. DR GO; GO:0032983; C:kainate selective glutamate receptor complex; IBA:GO_Central. DR GO; GO:0097471; C:mossy fiber rosette; IEA:Ensembl. DR GO; GO:0043204; C:perikaryon; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central. DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central. DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl. DR GO; GO:0005234; F:extracellularly glutamate-gated ion channel activity; IMP:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0015277; F:kainate selective glutamate receptor activity; IDA:UniProtKB. DR GO; GO:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IEA:Ensembl. DR GO; GO:0030165; F:PDZ domain binding; IEA:Ensembl. DR GO; GO:0097110; F:scaffold protein binding; IEA:Ensembl. DR GO; GO:0000149; F:SNARE binding; IEA:Ensembl. DR GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central. DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IEA:Ensembl. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl. DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0120169; P:detection of cold stimulus involved in thermoception; ISS:UniProtKB. DR GO; GO:0007215; P:glutamate receptor signaling pathway; TAS:ProtInc. DR GO; GO:0060080; P:inhibitory postsynaptic potential; IEA:Ensembl. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IDA:UniProtKB. DR GO; GO:0098815; P:modulation of excitatory postsynaptic potential; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0019228; P:neuronal action potential; IEA:Ensembl. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0050806; P:positive regulation of synaptic transmission; IMP:UniProtKB. DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0043113; P:receptor clustering; IEA:Ensembl. DR GO; GO:0046328; P:regulation of JNK cascade; IEA:Ensembl. DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl. DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; IMP:UniProtKB. DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IBA:GO_Central. DR CDD; cd06382; PBP1_iGluR_Kainate; 1. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 3.40.50.2300; -; 2. DR Gene3D; 3.40.190.10; Periplasmic binding protein-like II; 1. DR InterPro; IPR001828; ANF_lig-bd_rcpt. DR InterPro; IPR019594; Glu/Gly-bd. DR InterPro; IPR001508; Iono_Glu_rcpt_met. DR InterPro; IPR015683; Ionotropic_Glu_rcpt. DR InterPro; IPR001320; Iontro_rcpt_C. DR InterPro; IPR028082; Peripla_BP_I. DR PANTHER; PTHR18966:SF38; GLUTAMATE RECEPTOR IONOTROPIC, KAINATE 2; 1. DR PANTHER; PTHR18966; IONOTROPIC GLUTAMATE RECEPTOR; 1. DR Pfam; PF01094; ANF_receptor; 1. DR Pfam; PF00060; Lig_chan; 1. DR Pfam; PF10613; Lig_chan-Glu_bd; 1. DR PRINTS; PR00177; NMDARECEPTOR. DR SMART; SM00918; Lig_chan-Glu_bd; 1. DR SMART; SM00079; PBPe; 1. DR SUPFAM; SSF53822; Periplasmic binding protein-like I; 1. DR SUPFAM; SSF53850; Periplasmic binding protein-like II; 1. DR Genevisible; Q13002; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; Epilepsy; Glycoprotein; Intellectual disability; KW Ion channel; Ion transport; Isopeptide bond; Ligand-gated ion channel; KW Membrane; Phosphoprotein; Postsynaptic cell membrane; Receptor; KW Reference proteome; RNA editing; Signal; Synapse; Transmembrane; KW Transmembrane helix; Transport; Ubl conjugation. FT SIGNAL 1..31 FT /evidence="ECO:0000255" FT CHAIN 32..908 FT /note="Glutamate receptor ionotropic, kainate 2" FT /id="PRO_0000011544" FT TOPO_DOM 32..561 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 562..582 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 583..635 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 636..656 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 657..819 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 820..840 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 841..908 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT BINDING 516..518 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250|UniProtKB:P42260" FT BINDING 523 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250|UniProtKB:P42260" FT BINDING 689..690 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250|UniProtKB:P42260" FT BINDING 738 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250|UniProtKB:P42260" FT MOD_RES 846 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000269|PubMed:22808340" FT MOD_RES 868 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000269|PubMed:22808340" FT CARBOHYD 67 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 73 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 275 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 378 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 412 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 423 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 430 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 546 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 751 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 96..347 FT /evidence="ECO:0000250|UniProtKB:P42260" FT CROSSLNK 886 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1)" FT /evidence="ECO:0000269|PubMed:22808340" FT VAR_SEQ 509..695 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:20230879" FT /id="VSP_044388" FT VAR_SEQ 510..714 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:20230879" FT /id="VSP_044389" FT VAR_SEQ 547..622 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11675011" FT /id="VSP_022334" FT VAR_SEQ 585..908 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11675011" FT /id="VSP_022337" FT VAR_SEQ 855..908 FT /note="RSFCSAMVEELRMSLKCQRRLKHKPQAPVIVKTEEVINMHTFNDRRLPGKET FT MA -> ESSIWLVPPYHPDTV (in isoform 2 and isoform 6)" FT /evidence="ECO:0000303|PubMed:11675011, FT ECO:0000303|PubMed:20230879" FT /id="VSP_022335" FT VAR_SEQ 856..908 FT /note="SFCSAMVEELRMSLKCQRRLKHKPQAPVIVKTEEVINMHTFNDRRLPGKETM FT A -> AKTKLPQDYVFLPILESVSISTVLSSSPSSSSLSSCS (in isoform 5 FT and isoform 7)" FT /evidence="ECO:0000303|PubMed:20230879, ECO:0000303|Ref.3" FT /id="VSP_022336" FT VARIANT 187 FT /note="E -> Q (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035694" FT VARIANT 567 FT /note="I -> V (in RNA edited version)" FT /id="VAR_000305" FT VARIANT 571 FT /note="Y -> C (in RNA edited version)" FT /id="VAR_000306" FT VARIANT 621 FT /note="Q -> R (in RNA edited version)" FT /id="VAR_000307" FT VARIANT 657 FT /note="A -> T (in NEDLAS; gain of function; when FT incorporated into kainate receptor, produces constitutively FT active channels with significantly altered gating kinetics; FT may decrease cell surface expression; dbSNP:rs1790057505)" FT /evidence="ECO:0000269|PubMed:28180184, FT ECO:0000269|PubMed:34375587" FT /id="VAR_078426" FT VARIANT 660 FT /note="T -> K (in NEDLAS; causes profound slowing of FT channel deactivation and constitutive tonic current FT activation compared to wild-type, indicating altered FT channel gating kinetics; may decrease cell surface FT expression)" FT /evidence="ECO:0000269|PubMed:34375587" FT /id="VAR_086335" FT VARIANT 660 FT /note="T -> R (in NEDLAS; causes profound slowing of FT channel deactivation and constitutive tonic current FT activation compared to wild-type, indicating altered FT channel gating kinetics; may decrease cell surface FT expression)" FT /evidence="ECO:0000269|PubMed:34375587" FT /id="VAR_086336" FT VARIANT 668 FT /note="I -> T (in NEDLAS; causes markedly reduced peak FT current amplitudes and very fast gating kinetics; no effect FT on homomeric receptor localization to the plasma membrane FT when expressed in heterologous cells)" FT /evidence="ECO:0000269|PubMed:34375587" FT /id="VAR_086337" FT VARIANT 766 FT /note="V -> I (in dbSNP:rs3213608)" FT /id="VAR_049186" FT VARIANT 867 FT /note="M -> I (in dbSNP:rs2235076)" FT /evidence="ECO:0000269|PubMed:28180184" FT /id="VAR_037633" FT CONFLICT 20 FT /note="L -> P (in Ref. 3; CAC81020 and 5; FT ADH93570/ADH93571/ADH93572/ADH93573)" FT /evidence="ECO:0000305" FT CONFLICT 789 FT /note="G -> S (in Ref. 2)" FT /evidence="ECO:0000305" FT STRAND 433..437 FT /evidence="ECO:0007829|PDB:5CMM" FT TURN 441..443 FT /evidence="ECO:0007829|PDB:5CMM" FT STRAND 444..446 FT /evidence="ECO:0007829|PDB:5CMM" FT HELIX 455..458 FT /evidence="ECO:0007829|PDB:5CMM" FT STRAND 459..461 FT /evidence="ECO:0007829|PDB:5CMM" FT HELIX 462..474 FT /evidence="ECO:0007829|PDB:5CMM" FT STRAND 478..482 FT /evidence="ECO:0007829|PDB:5CMM" FT TURN 493..495 FT /evidence="ECO:0007829|PDB:3QXM" FT HELIX 500..506 FT /evidence="ECO:0007829|PDB:3QXM" FT STRAND 511..513 FT /evidence="ECO:0007829|PDB:3QXM" FT HELIX 521..524 FT /evidence="ECO:0007829|PDB:3QXM" FT STRAND 527..529 FT /evidence="ECO:0007829|PDB:3QXM" FT STRAND 533..536 FT /evidence="ECO:0007829|PDB:3QXM" FT STRAND 538..544 FT /evidence="ECO:0007829|PDB:3QXM" FT HELIX 671..675 FT /evidence="ECO:0007829|PDB:5CMM" FT STRAND 678..683 FT /evidence="ECO:0007829|PDB:5CMM" FT HELIX 689..696 FT /evidence="ECO:0007829|PDB:5CMM" FT HELIX 700..711 FT /evidence="ECO:0007829|PDB:5CMM" FT HELIX 713..716 FT /evidence="ECO:0007829|PDB:5CMM" FT STRAND 717..720 FT /evidence="ECO:0007829|PDB:5CMM" FT HELIX 721..730 FT /evidence="ECO:0007829|PDB:5CMM" FT STRAND 731..738 FT /evidence="ECO:0007829|PDB:5CMM" FT HELIX 739..748 FT /evidence="ECO:0007829|PDB:5CMM" FT STRAND 752..756 FT /evidence="ECO:0007829|PDB:5CMM" FT STRAND 762..764 FT /evidence="ECO:0007829|PDB:5CMM" FT STRAND 767..769 FT /evidence="ECO:0007829|PDB:5CMM" FT HELIX 774..787 FT /evidence="ECO:0007829|PDB:5CMM" FT HELIX 790..799 FT /evidence="ECO:0007829|PDB:5CMM" SQ SEQUENCE 908 AA; 102583 MW; 5F34630524401E84 CRC64; MKIIFPILSN PVFRRTVKLL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSFE ASKKACDQLS LGVAAIFGPS HSSSANAVQS ICNALGVPHI QTRWKHQVSD NKDSFYVSLY PDFSSLSRAI LDLVQFFKWK TVTVVYDDST GLIRLQELIK APSRYNLRLK IRQLPADTKD AKPLLKEMKR GKEFHVIFDC SHEMAAGILK QALAMGMMTE YYHYIFTTLD LFALDVEPYR YSGVNMTGFR ILNTENTQVS SIIEKWSMER LQAPPKPDSG LLDGFMTTDA ALMYDAVHVV SVAVQQFPQM TVSSLQCNRH KPWRFGTRFM SLIKEAHWEG LTGRITFNKT NGLRTDFDLD VISLKEEGLE KIGTWDPASG LNMTESQKGK PANITDSLSN RSLIVTTILE EPYVLFKKSD KPLYGNDRFE GYCIDLLREL STILGFTYEI RLVEDGKYGA QDDANGQWNG MVRELIDHKA DLAVAPLAIT YVREKVIDFS KPFMTLGISI LYRKPNGTNP GVFSFLNPLS PDIWMYILLA YLGVSCVLFV IARFSPYEWY NPHPCNPDSD VVENNFTLLN SFWFGVGALM QQGSELMPKA LSTRIVGGIW WFFTLIIISS YTANLAAFLT VERMESPIDS ADDLAKQTKI EYGAVEDGAT MTFFKKSKIS TYDKMWAFMS SRRQSVLVKS NEEGIQRVLT SDYAFLMEST TIEFVTQRNC NLTQIGGLID SKGYGVGTPM GSPYRDKITI AILQLQEEGK LHMMKEKWWR GNGCPEEESK EASALGVQNI GGIFIVLAAG LVLSVFVAVG EFLYKSKKNA QLEKRSFCSA MVEELRMSLK CQRRLKHKPQ APVIVKTEEV INMHTFNDRR LPGKETMA //