GRIK2_HUMAN
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 03-AUG-2022, entry version 207.
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}.
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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. [Q13002-5]
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; 17.
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 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; Q13002; -.
DR PeptideAtlas; Q13002; -.
DR PRIDE; 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; 353 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 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; VFAFDSV; -.
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; 9 hits in 1070 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 150 other tissues.
DR ExpressionAtlas; Q13002; baseline and differential.
DR Genevisible; Q13002; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0032983; C:kainate selective glutamate receptor complex; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central.
DR GO; GO:0005234; F:extracellularly glutamate-gated ion channel activity; IMP:UniProtKB.
DR GO; GO:0008066; F:glutamate receptor activity; IBA:GO_Central.
DR GO; GO:0015277; F:kainate selective glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0099507; F:ligand-gated ion channel activity involved in regulation of presynaptic membrane potential; IEA:Ensembl.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; 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:0050804; P:modulation of chemical synaptic transmission; IDA:UniProtKB.
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: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: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 InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR019594; Glu/Gly-bd.
DR InterPro; IPR001508; Iono_rcpt_met.
DR InterPro; IPR001320; Iontro_rcpt.
DR InterPro; IPR028082; Peripla_BP_I.
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; SSF53822; 1.
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; ADH93570/
FT 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
