ID NMDE2_HUMAN Reviewed; 1484 AA. AC Q13224; Q12919; Q13220; Q13225; Q14CU4; Q9UM56; DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 20-JUN-2001, sequence version 3. DT 27-MAR-2024, entry version 223. DE RecName: Full=Glutamate receptor ionotropic, NMDA 2B; DE Short=GluN2B; DE AltName: Full=Glutamate [NMDA] receptor subunit epsilon-2; DE AltName: Full=N-methyl D-aspartate receptor subtype 2B; DE Short=NMDAR2B {ECO:0000303|PubMed:7959773}; DE Short=NR2B; DE AltName: Full=N-methyl-D-aspartate receptor subunit 3; DE Short=NR3; DE Short=hNR3 {ECO:0000303|PubMed:7999784}; DE Flags: Precursor; GN Name=GRIN2B; Synonyms=NMDAR2B; 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], AND VARIANT ASN-407. RC TISSUE=Fetal brain; RX PubMed=7999784; DOI=10.1016/0167-4781(94)00189-a; RA Adams S.L., Foldes R.L., Kamboj R.K.; RT "Human N-methyl-D-aspartate receptor modulatory subunit hNR3: cloning and RT sequencing of the cDNA and primary structure of the protein."; RL Biochim. Biophys. Acta 1260:105-108(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT. RC TISSUE=Fetal brain; RX PubMed=8768735; RA Hess S.D., Daggett L.P., Crona J., Deal C., Lu C.-C., Urrutia A., RA Chavez-Noriega L., Ellis S.B., Johnson E.C., Velicelebi G.; RT "Cloning and functional characterization of human heteromeric N-methyl-D- RT aspartate receptors."; RL J. Pharmacol. Exp. Ther. 278:808-816(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Mandich P., Schito A.M., Pizzuti A., Ratti A.; RT "Cloning of GRIN2B human subunit."; RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-294 AND 661-1089. RX PubMed=7959773; DOI=10.1006/geno.1994.1366; RA Mandich P., Schito A.M., Bellone E., Antonacci R., Finelli P., Rocchi M., RA Ajmar F.; RT "Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome RT 12p12."; RL Genomics 22:216-218(1994). RN [6] RP TISSUE SPECIFICITY. RX PubMed=9547169; DOI=10.1016/s0304-3940(97)00853-7; RA Schito A.M., Pizzuti A., Di Maria E., Schenone A., Ratti A., Defferrari R., RA Bellone E., Mancardi G.L., Ajmar F., Mandich P.; RT "mRNA distribution in adult human brain of GRIN2B, a N-methyl-D-aspartate RT (NMDA) receptor subunit."; RL Neurosci. Lett. 239:49-53(1997). RN [7] RP INTERACTION WITH MAGI3. RX PubMed=10748157; DOI=10.1074/jbc.m909741199; RA Wu Y., Dowbenko D., Spencer S., Laura R., Lee J., Gu Q., Lasky L.A.; RT "Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, RT a novel membrane-associated guanylate kinase."; RL J. Biol. Chem. 275:21477-21485(2000). RN [8] RP IDENTIFICATION IN A COMPLEX WITH GRIN1 AND PRR7, AND INTERACTION WITH PRR7. RX PubMed=27458189; DOI=10.15252/embj.201593070; RA Kravchick D.O., Karpova A., Hrdinka M., Lopez-Rojas J., Iacobas S., RA Carbonell A.U., Iacobas D.A., Kreutz M.R., Jordan B.A.; RT "Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates RT NMDA-mediated excitotoxicity."; RL EMBO J. 35:1923-1934(2016). RN [9] RP CHROMOSOMAL TRANSLOCATIONS, VARIANT MRD6 CYS-682, AND CHARACTERIZATION OF RP VARIANT MRD6 CYS-682. RX PubMed=20890276; DOI=10.1038/ng.677; RA Endele S., Rosenberger G., Geider K., Popp B., Tamer C., Stefanova I., RA Milh M., Kortum F., Fritsch A., Pientka F.K., Hellenbroich Y., RA Kalscheuer V.M., Kohlhase J., Moog U., Rappold G., Rauch A., Ropers H.H., RA von Spiczak S., Tonnies H., Villeneuve N., Villard L., Zabel B., Zenker M., RA Laube B., Reis A., Wieczorek D., Van Maldergem L., Kutsche K.; RT "Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA RT receptors cause variable neurodevelopmental phenotypes."; RL Nat. Genet. 42:1021-1026(2010). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=26919761; DOI=10.1021/acs.jmedchem.5b02010; RA Volgraf M., Sellers B.D., Jiang Y., Wu G., Ly C.Q., Villemure E., RA Pastor R.M., Yuen P.W., Lu A., Luo X., Liu M., Zhang S., Sun L., Fu Y., RA Lupardus P.J., Wallweber H.J., Liederer B.M., Deshmukh G., Plise E., RA Tay S., Reynen P., Herrington J., Gustafson A., Liu Y., Dirksen A., RA Dietz M.G., Liu Y., Wang T.M., Hanson J.E., Hackos D., Scearce-Levie K., RA Schwarz J.B.; RT "Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators RT (PAMs): Tuning Deactivation Kinetics via Structure-Based Design."; RL J. Med. Chem. 59:2760-2779(2016). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=26875626; DOI=10.1016/j.neuron.2016.01.016; RA Hackos D.H., Lupardus P.J., Grand T., Chen Y., Wang T.M., Reynen P., RA Gustafson A., Wallweber H.J., Volgraf M., Sellers B.D., Schwarz J.B., RA Paoletti P., Sheng M., Zhou Q., Hanson J.E.; RT "Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct RT Modes of Action and Impacts on Circuit Function."; RL Neuron 89:983-999(2016). RN [12] RP INTERACTION WITH CAMK2A. RX PubMed=28130356; DOI=10.1523/jneurosci.2068-16.2017; RA Stephenson J.R., Wang X., Perfitt T.L., Parrish W.P., Shonesy B.C., RA Marks C.R., Mortlock D.P., Nakagawa T., Sutcliffe J.S., Colbran R.J.; RT "Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and RT Causes ASD-Related Behaviors."; RL J. Neurosci. 37:2216-2233(2017). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF MET-818. RX PubMed=28126851; DOI=10.1124/mol.116.106781; RA Chen W., Tankovic A., Burger P.B., Kusumoto H., Traynelis S.F., Yuan H.; RT "Functional evaluation of a de novo GRIN2A mutation identified in a patient RT with profound global developmental delay and refractory epilepsy."; RL Mol. Pharmacol. 91:317-330(2017). RN [14] {ECO:0007744|PDB:5EWJ, ECO:0007744|PDB:5EWL, ECO:0007744|PDB:5EWM} RP X-RAY CRYSTALLOGRAPHY (2.76 ANGSTROMS) OF 31-394 IN COMPLEX WITH GRIN1 AND RP SYNTHETIC INHIBITOR IFENPRODIL, SUBUNIT, GLYCOSYLATION AT ASN-74 AND RP ASN-341, AND DISULFIDE BONDS. RX PubMed=26912815; DOI=10.1124/mol.115.103036; RA Stroebel D., Buhl D.L., Knafels J.D., Chanda P.K., Green M., Sciabola S., RA Mony L., Paoletti P., Pandit J.; RT "A Novel Binding Mode Reveals Two Distinct Classes of NMDA Receptor GluN2B- RT selective Antagonists."; RL Mol. Pharmacol. 89:541-551(2016). RN [15] RP VARIANTS ILE-18; ASN-50; VAL-271; MET-362; VAL-825; ARG-1014; SER-1026; RP ARG-1342; LEU-1415; PHE-1424 AND PHE-1452. RX PubMed=22833210; DOI=10.1038/tp.2011.52; RG S2D team; RA Tarabeux J., Kebir O., Gauthier J., Hamdan F.F., Xiong L., Piton A., RA Spiegelman D., Henrion E., Millet B., Fathalli F., Joober R., RA Rapoport J.L., DeLisi L.E., Fombonne E., Mottron L., Forget-Dubois N., RA Boivin M., Michaud J.L., Drapeau P., Lafreniere R.G., Rouleau G.A., RA Krebs M.O.; RT "Rare mutations in N-methyl-D-aspartate glutamate receptors in autism RT spectrum disorders and schizophrenia."; RL Transl. Psychiatry 1:E55-E55(2011). RN [16] RP VARIANT MRD6 LEU-553. RX PubMed=23033978; DOI=10.1056/nejmoa1206524; RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., RA Veltman J.A., Vissers L.E.; RT "Diagnostic exome sequencing in persons with severe intellectual RT disability."; RL N. Engl. J. Med. 367:1921-1929(2012). RN [17] RP VARIANT MRD6 TYR-456. RX PubMed=23160955; DOI=10.1126/science.1227764; RA O'Roak B.J., Vives L., Fu W., Egertson J.D., Stanaway I.B., Phelps I.G., RA Carvill G., Kumar A., Lee C., Ankenman K., Munson J., Hiatt J.B., RA Turner E.H., Levy R., O'Day D.R., Krumm N., Coe B.P., Martin B.K., RA Borenstein E., Nickerson D.A., Mefford H.C., Doherty D., Akey J.M., RA Bernier R., Eichler E.E., Shendure J.; RT "Multiplex targeted sequencing identifies recurrently mutated genes in RT autism spectrum disorders."; RL Science 338:1619-1622(2012). RN [18] RP INVOLVEMENT IN DEE27, VARIANTS DEE27 HIS-540; ILE-615 AND GLY-618, AND RP CHARACTERIZATION OF VARIANTS DEE27 HIS-540; ILE-615 AND GLY-618. RX PubMed=24272827; DOI=10.1002/ana.24073; RA Lemke J.R., Hendrickx R., Geider K., Laube B., Schwake M., Harvey R.J., RA James V.M., Pepler A., Steiner I., Hortnagel K., Neidhardt J., Ruf S., RA Wolff M., Bartholdi D., Caraballo R., Platzer K., Suls A., De Jonghe P., RA Biskup S., Weckhuysen S.; RT "GRIN2B mutations in West syndrome and intellectual disability with focal RT epilepsy."; RL Ann. Neurol. 75:147-154(2014). RN [19] RP VARIANT MRD6 GLY-413, AND CHARACTERIZATION OF VARIANT MRD6 GLY-413. RX PubMed=24863970; DOI=10.1016/j.ymgme.2014.04.001; RA Adams D.R., Yuan H., Holyoak T., Arajs K.H., Hakimi P., Markello T.C., RA Wolfe L.A., Vilboux T., Burton B.K., Fajardo K.F., Grahame G., Holloman C., RA Sincan M., Smith A.C., Wells G.A., Huang Y., Vega H., Snyder J.P., RA Golas G.A., Tifft C.J., Boerkoel C.F., Hanson R.W., Traynelis S.F., RA Kerr D.S., Gahl W.A.; RT "Three rare diseases in one sib pair: RAI1, PCK1, GRIN2B mutations RT associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA RT receptor glutamate insensitivity."; RL Mol. Genet. Metab. 113:161-170(2014). RN [20] RP VARIANT MRD6 GLU-820. RX PubMed=25356899; DOI=10.1371/journal.pgen.1004772; RA Hamdan F.F., Srour M., Capo-Chichi J.M., Daoud H., Nassif C., Patry L., RA Massicotte C., Ambalavanan A., Spiegelman D., Diallo O., Henrion E., RA Dionne-Laporte A., Fougerat A., Pshezhetsky A.V., Venkateswaran S., RA Rouleau G.A., Michaud J.L.; RT "De novo mutations in moderate or severe intellectual disability."; RL PLoS Genet. 10:E1004772-E1004772(2014). RN [21] RP VARIANTS MRD6 ARG-436; PHE-461 AND HIS-696, CHARACTERIZATION OF VARIANTS RP MRD6 GLY-413; ARG-436; TYR-456; PHE-461; CYS-682 AND HIS-696, AND RP CHARACTERIZATION OF VARIANT DEE27 HIS-540. RX PubMed=27839871; DOI=10.1016/j.ajhg.2016.10.002; RA Swanger S.A., Chen W., Wells G., Burger P.B., Tankovic A., Bhattacharya S., RA Strong K.L., Hu C., Kusumoto H., Zhang J., Adams D.R., Millichap J.J., RA Petrovski S., Traynelis S.F., Yuan H.; RT "Mechanistic insight into NMDA receptor dysregulation by rare variants in RT the GluN2A and GluN2B agonist binding domains."; RL Am. J. Hum. Genet. 99:1261-1280(2016). RN [22] RP VARIANT DEE27 MET-15, AND VARIANT ALA-1439. RX PubMed=27864847; DOI=10.1002/humu.23149; RG Clinical Study Group; RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D., RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S., RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.; RT "Diagnostic targeted resequencing in 349 patients with drug-resistant RT pediatric epilepsies identifies causative mutations in 30 different RT genes."; RL Hum. Mutat. 38:216-225(2017). RN [23] RP CHARACTERIZATION OF VARIANT MRD6 LEU-553, AND MUTAGENESIS OF PRO-553. RX PubMed=28095420; DOI=10.1371/journal.pgen.1006536; RA Ogden K.K., Chen W., Swanger S.A., McDaniel M.J., Fan L.Z., Hu C., RA Tankovic A., Kusumoto H., Kosobucki G.J., Schulien A.J., Su Z., Pecha J., RA Bhattacharya S., Petrovski S., Cohen A.E., Aizenman E., Traynelis S.F., RA Yuan H.; RT "Molecular mechanism of disease-associated mutations in the pre-M1 helix of RT NMDA receptors and potential rescue pharmacology."; RL PLoS Genet. 13:E1006536-E1006536(2017). CC -!- FUNCTION: Component of NMDA receptor complexes that function as CC heterotetrameric, ligand-gated ion channels with high calcium CC permeability and voltage-dependent sensitivity to magnesium. Channel CC activation requires binding of the neurotransmitter glutamate to the CC epsilon subunit, glycine binding to the zeta subunit, plus membrane CC depolarization to eliminate channel inhibition by Mg(2+) CC (PubMed:8768735, PubMed:26919761, PubMed:26875626, PubMed:28126851). CC Sensitivity to glutamate and channel kinetics depend on the subunit CC composition (PubMed:8768735, PubMed:26875626). In concert with DAPK1 at CC extrasynaptic sites, acts as a central mediator for stroke damage. Its CC phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor CC channel activity inducing injurious Ca2+ influx through them, resulting CC in an irreversible neuronal death. Contributes to neural pattern CC formation in the developing brain. Plays a role in long-term depression CC (LTD) of hippocampus membrane currents and in synaptic plasticity (By CC similarity). {ECO:0000250|UniProtKB:Q01097, CC ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, CC ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:8768735}. CC -!- SUBUNIT: Heterotetramer. Forms heterotetrameric channels composed of CC two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, CC GRIN2C or GRIN2D) (in vitro) (PubMed:8768735, PubMed:26919761, CC PubMed:26875626, PubMed:28126851, PubMed:26912815). Can also form CC heterotetrameric channels that contain at least one zeta subunit CC (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (By CC similarity). In vivo, the subunit composition may depend on the CC expression levels of the different subunits (Probable). Found in a CC complex with GRIN1 and GRIN3B. Found in a complex with GRIN1, GRIN3A CC and PPP2CB. Interacts with PDZ domains of PATJ, DLG3 and DLG4. CC Interacts with HIP1 and NETO1 (By similarity). Interacts with MAGI3 CC (PubMed:10748157). Interacts with DAPK1 (By similarity). Found in a CC complex with GRIN1 and PRR7 (PubMed:27458189). Interacts with PRR7 CC (PubMed:27458189). Interacts with CAMK2A (PubMed:28130356). Interacts CC with ARC; preventing ARC oligomerization (By similarity). Interacts CC with TMEM25 (By similarity). {ECO:0000250|UniProtKB:Q00960, CC ECO:0000250|UniProtKB:Q01097, ECO:0000269|PubMed:10748157, CC ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26912815, CC ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:27458189, CC ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:28130356, CC ECO:0000269|PubMed:8768735}. CC -!- INTERACTION: CC Q13224; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-2256942, EBI-1383687; CC Q13224; Q12959: DLG1; NbExp=4; IntAct=EBI-2256942, EBI-357481; CC Q13224; P78352: DLG4; NbExp=4; IntAct=EBI-2256942, EBI-80389; CC Q13224; Q05586-1: GRIN1; NbExp=2; IntAct=EBI-2256942, EBI-27070564; CC Q13224; Q62936: Dlg3; Xeno; NbExp=4; IntAct=EBI-2256942, EBI-349596; CC Q13224; P31016: Dlg4; Xeno; NbExp=2; IntAct=EBI-2256942, EBI-375655; CC Q13224; P62139: PPP1CA; Xeno; NbExp=2; IntAct=EBI-2256942, EBI-2008988; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26875626, CC ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28126851, CC ECO:0000269|PubMed:8768735}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:Q00960}. Postsynaptic cell membrane CC {ECO:0000250|UniProtKB:Q00960}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:Q00960}. Late endosome CC {ECO:0000250|UniProtKB:Q01097}. Lysosome CC {ECO:0000250|UniProtKB:Q01097}. Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:Q01097}. Note=Co-localizes with the motor CC protein KIF17 along microtubules. {ECO:0000250|UniProtKB:Q01097}. CC -!- TISSUE SPECIFICITY: Primarily found in the fronto-parieto-temporal CC cortex and hippocampus pyramidal cells, lower expression in the basal CC ganglia. {ECO:0000269|PubMed:9547169}. CC -!- DOMAIN: A hydrophobic region that gives rise to the prediction of a CC transmembrane span does not cross the membrane, but is part of a CC discontinuously helical region that dips into the membrane and is CC probably part of the pore and of the selectivity filter. CC {ECO:0000250|UniProtKB:Q00960}. CC -!- PTM: Phosphorylated on tyrosine residues (By similarity). CC Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor CC channel activity (By similarity). {ECO:0000250|UniProtKB:Q00960, CC ECO:0000250|UniProtKB:Q01097}. CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 6, CC with or without seizures (MRD6) [MIM:613970]: A disorder characterized CC by significantly below average general intellectual functioning CC associated with impairments in adaptive behavior and manifested during CC the developmental period. MRD6 additional features may include CC seizures, hypotonia, abnormal movements, such as dystonia, and autistic CC features. {ECO:0000269|PubMed:20890276, ECO:0000269|PubMed:23033978, CC ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:24863970, CC ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:27839871, CC ECO:0000269|PubMed:28095420}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Developmental and epileptic encephalopathy 27 (DEE27) CC [MIM:616139]: A form of epileptic encephalopathy, a heterogeneous group CC of severe early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. {ECO:0000269|PubMed:24272827, CC ECO:0000269|PubMed:27839871, ECO:0000269|PubMed:27864847}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Note=A chromosomal aberrations involving GRIN2B has been found CC in patients with intellectual disability. Translocations CC t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint CC in 12p13.1. CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) CC family. NR2B/GRIN2B 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; U90278; AAB49993.1; -; mRNA. DR EMBL; U88963; AAD00659.1; -; mRNA. DR EMBL; U11287; AAB60368.1; -; mRNA. DR EMBL; BC113618; AAI13619.1; -; mRNA. DR EMBL; BC113620; AAI13621.1; -; mRNA. DR EMBL; U28758; AAA74930.1; -; mRNA. DR EMBL; U28861; AAA69919.1; -; mRNA. DR EMBL; U28862; AAA69920.1; -; mRNA. DR CCDS; CCDS8662.1; -. DR PIR; I39066; I39066. DR PIR; S52086; S52086. DR RefSeq; NP_000825.2; NM_000834.3. DR RefSeq; XP_011518930.1; XM_011520628.2. DR RefSeq; XP_011518931.1; XM_011520629.2. DR RefSeq; XP_016874708.1; XM_017019219.1. DR PDB; 5EWJ; X-ray; 2.77 A; B/D=31-394. DR PDB; 5EWL; X-ray; 2.98 A; B/D=31-394. DR PDB; 5EWM; X-ray; 2.76 A; B/D=31-394. DR PDB; 7EU8; EM; 4.07 A; B/D=1-842. DR PDB; 7KL0; X-ray; 2.40 A; C/D=1289-1310. DR PDB; 7KL1; X-ray; 2.40 A; C/D=1289-1310. DR PDB; 7KL2; X-ray; 2.56 A; B=1289-1310. DR PDB; 7UIS; X-ray; 2.58 A; B=1289-1310. DR PDB; 7UJP; X-ray; 2.56 A; C/D=1289-1310. DR PDB; 7UJQ; X-ray; 2.25 A; C/D=1289-1310. DR PDB; 7UJR; X-ray; 1.95 A; B=1289-1310. DR PDB; 7UJS; X-ray; 2.75 A; B=1289-1310. DR PDB; 7UJT; X-ray; 2.10 A; B=1289-1310. DR PDBsum; 5EWJ; -. DR PDBsum; 5EWL; -. DR PDBsum; 5EWM; -. DR PDBsum; 7EU8; -. DR PDBsum; 7KL0; -. DR PDBsum; 7KL1; -. DR PDBsum; 7KL2; -. DR PDBsum; 7UIS; -. DR PDBsum; 7UJP; -. DR PDBsum; 7UJQ; -. DR PDBsum; 7UJR; -. DR PDBsum; 7UJS; -. DR PDBsum; 7UJT; -. DR AlphaFoldDB; Q13224; -. DR EMDB; EMD-31309; -. DR SMR; Q13224; -. DR BioGRID; 109161; 45. DR ComplexPortal; CPX-285; NMDA receptor complex, GluN1-GluN2B. DR ComplexPortal; CPX-294; NMDA receptor complex, GluN1-GluN2A-GluN2B. DR DIP; DIP-41002N; -. DR IntAct; Q13224; 18. DR MINT; Q13224; -. DR STRING; 9606.ENSP00000477455; -. DR BindingDB; Q13224; -. DR ChEMBL; CHEMBL1904; -. DR DrugBank; DB00659; Acamprosate. DR DrugBank; DB06151; Acetylcysteine. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB00289; Atomoxetine. DR DrugBank; DB00647; Dextropropoxyphene. DR DrugBank; DB00843; Donepezil. DR DrugBank; DB00228; Enflurane. DR DrugBank; DB11823; Esketamine. DR DrugBank; DB05956; EVT-101. DR DrugBank; DB00949; Felbamate. DR DrugBank; DB13146; Fluciclovine (18F). DR DrugBank; DB06741; Gavestinel. DR DrugBank; DB00142; Glutamic acid. DR DrugBank; DB00874; Guaifenesin. DR DrugBank; DB00502; Haloperidol. DR DrugBank; DB08954; Ifenprodil. DR DrugBank; DB06738; Ketobemidone. DR DrugBank; DB06077; Lumateperone. DR DrugBank; DB09409; Magnesium acetate tetrahydrate. DR DrugBank; DB09481; Magnesium carbonate. DR DrugBank; DB01043; Memantine. DR DrugBank; DB00454; Meperidine. DR DrugBank; DB00333; Methadone. DR DrugBank; DB04896; Milnacipran. DR DrugBank; DB00312; Pentobarbital. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB01708; Prasterone. DR DrugBank; DB00418; Secobarbital. DR DrugBank; DB01956; Taurine. DR DrugBank; DB01520; Tenocyclidine. DR DrugBank; DB00193; Tramadol. DR DrugCentral; Q13224; -. DR GuidetoPHARMACOLOGY; 457; -. DR GlyCosmos; Q13224; 7 sites, No reported glycans. DR GlyGen; Q13224; 7 sites. DR iPTMnet; Q13224; -. DR PhosphoSitePlus; Q13224; -. DR BioMuta; GRIN2B; -. DR DMDM; 14548162; -. DR jPOST; Q13224; -. DR MassIVE; Q13224; -. DR PaxDb; 9606-ENSP00000477455; -. DR PeptideAtlas; Q13224; -. DR ProteomicsDB; 59232; -. DR ABCD; Q13224; 1 sequenced antibody. DR Antibodypedia; 71655; 1515 antibodies from 48 providers. DR DNASU; 2904; -. DR Ensembl; ENST00000609686.4; ENSP00000477455.1; ENSG00000273079.7. DR GeneID; 2904; -. DR KEGG; hsa:2904; -. DR MANE-Select; ENST00000609686.4; ENSP00000477455.1; NM_000834.5; NP_000825.2. DR UCSC; uc001rbt.3; human. DR AGR; HGNC:4586; -. DR CTD; 2904; -. DR DisGeNET; 2904; -. DR GeneCards; GRIN2B; -. DR GeneReviews; GRIN2B; -. DR HGNC; HGNC:4586; GRIN2B. DR HPA; ENSG00000273079; Tissue enriched (brain). DR MalaCards; GRIN2B; -. DR MIM; 138252; gene. DR MIM; 613970; phenotype. DR MIM; 616139; phenotype. DR neXtProt; NX_Q13224; -. DR OpenTargets; ENSG00000273079; -. DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability. DR Orphanet; 589547; GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder. DR Orphanet; 3451; Infantile spasms syndrome. DR PharmGKB; PA28980; -. DR VEuPathDB; HostDB:ENSG00000273079; -. DR eggNOG; KOG1053; Eukaryota. DR GeneTree; ENSGT00940000155964; -. DR HOGENOM; CLU_002598_1_0_1; -. DR InParanoid; Q13224; -. DR OMA; KNDRYSG; -. DR OrthoDB; 1034721at2759; -. DR PhylomeDB; Q13224; -. DR TreeFam; TF314731; -. DR PathwayCommons; Q13224; -. DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling. DR Reactome; R-HSA-438066; Unblocking of NMDA receptors, glutamate binding and activation. DR Reactome; R-HSA-442982; Ras activation upon Ca2+ influx through NMDA receptor. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6794361; Neurexins and neuroligins. DR Reactome; R-HSA-8849932; Synaptic adhesion-like molecules. DR Reactome; R-HSA-9022699; MECP2 regulates neuronal receptors and channels. DR Reactome; R-HSA-9032500; Activated NTRK2 signals through FYN. DR Reactome; R-HSA-9609736; Assembly and cell surface presentation of NMDA receptors. DR Reactome; R-HSA-9617324; Negative regulation of NMDA receptor-mediated neuronal transmission. DR Reactome; R-HSA-9620244; Long-term potentiation. DR SignaLink; Q13224; -. DR SIGNOR; Q13224; -. DR BioGRID-ORCS; 2904; 15 hits in 1150 CRISPR screens. DR ChiTaRS; GRIN2B; human. DR GeneWiki; GRIN2B; -. DR GenomeRNAi; 2904; -. DR Pharos; Q13224; Tclin. DR PRO; PR:Q13224; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q13224; Protein. DR Bgee; ENSG00000273079; Expressed in buccal mucosa cell and 114 other cell types or tissues. DR ExpressionAtlas; Q13224; baseline and differential. DR GO; GO:0009986; C:cell surface; ISS:ARUK-UCL. DR GO; GO:0005737; C:cytoplasm; ISS:ARUK-UCL. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005770; C:late endosome; ISS:UniProtKB. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0043005; C:neuron projection; ISS:BHF-UCL. DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB. DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central. DR GO; GO:0045211; C:postsynaptic membrane; TAS:ARUK-UCL. DR GO; GO:0097060; C:synaptic membrane; ISS:ARUK-UCL. DR GO; GO:0001540; F:amyloid-beta binding; NAS:ARUK-UCL. DR GO; GO:0016595; F:glutamate binding; ISS:UniProtKB. DR GO; GO:0022849; F:glutamate-gated calcium ion channel activity; IDA:UniProtKB. DR GO; GO:0016594; F:glycine binding; IDA:UniProtKB. DR GO; GO:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IDA:SynGO. DR GO; GO:0004972; F:NMDA glutamate receptor activity; IDA:UniProtKB. DR GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0007420; P:brain development; NAS:ARUK-UCL. DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; IDA:UniProtKB. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0098976; P:excitatory chemical synaptic transmission; NAS:ARUK-UCL. DR GO; GO:0060079; P:excitatory postsynaptic potential; IBA:GO_Central. DR GO; GO:0007215; P:glutamate receptor signaling pathway; TAS:ProtInc. DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISO:ComplexPortal. DR GO; GO:0007611; P:learning or memory; ISS:ARUK-UCL. DR GO; GO:0060291; P:long-term synaptic potentiation; IBA:GO_Central. DR GO; GO:0098655; P:monoatomic cation transmembrane transport; ISS:ComplexPortal. DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; ISS:ARUK-UCL. DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; ISS:ARUK-UCL. DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISO:ComplexPortal. DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISO:ComplexPortal. DR GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB. DR GO; GO:1904062; P:regulation of monoatomic cation transmembrane transport; ISS:ComplexPortal. DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; NAS:ComplexPortal. DR GO; GO:0048167; P:regulation of synaptic plasticity; NAS:ARUK-UCL. DR GO; GO:0045471; P:response to ethanol; IDA:UniProtKB. DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IBA:GO_Central. DR CDD; cd06378; PBP1_iGluR_NMDA_NR2; 1. DR CDD; cd13718; PBP2_iGluR_NMDA_Nr2; 1. DR Gene3D; 3.40.50.2300; -; 2. DR Gene3D; 3.40.190.10; Periplasmic binding protein-like II; 3. 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; IPR018884; NMDAR2_C. DR InterPro; IPR028082; Peripla_BP_I. DR InterPro; IPR001638; Solute-binding_3/MltF_N. DR PANTHER; PTHR18966:SF382; GLUTAMATE RECEPTOR IONOTROPIC, NMDA 2B; 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 Pfam; PF10565; NMDAR2_C; 1. DR Pfam; PF00497; SBP_bac_3; 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; Q13224; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Cell membrane; Chromosomal rearrangement; Cytoplasm; KW Cytoskeleton; Disease variant; Disulfide bond; Endosome; Epilepsy; KW Glycoprotein; Intellectual disability; Ion channel; Ion transport; KW Ligand-gated ion channel; Lysosome; Magnesium; Membrane; Metal-binding; KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome; KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport; Zinc. FT SIGNAL 1..26 FT /evidence="ECO:0000255" FT CHAIN 27..1484 FT /note="Glutamate receptor ionotropic, NMDA 2B" FT /id="PRO_0000011577" FT TOPO_DOM 27..557 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT TRANSMEM 558..576 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT TOPO_DOM 577..603 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT INTRAMEM 604..623 FT /note="Discontinuously helical" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT TOPO_DOM 624..630 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT TRANSMEM 631..646 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT TOPO_DOM 647..817 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT TRANSMEM 818..837 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT TOPO_DOM 838..1484 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT REGION 604..623 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:A7XY94" FT REGION 1074..1097 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1161..1194 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1271..1301 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1292..1304 FT /note="Interaction with DAPK1" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOTIF 1482..1484 FT /note="PDZ-binding" FT /evidence="ECO:0000250" FT COMPBIAS 1079..1097 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1271..1291 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 127 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT BINDING 284 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT BINDING 514 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT BINDING 519 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT BINDING 690..691 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT BINDING 732 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT SITE 615 FT /note="Functional determinant of NMDA receptors" FT /evidence="ECO:0000250" FT MOD_RES 882 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 886 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT MOD_RES 917 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 920 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 962 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1039 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1058 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1061 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1064 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1109 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1133 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1143 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1155 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1255 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1259 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1303 FT /note="Phosphoserine; by DAPK1" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT MOD_RES 1474 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q01097" FT CARBOHYD 74 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 341 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 348 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 444 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 491 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 542 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 688 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 86..321 FT /evidence="ECO:0000250|UniProtKB:Q00960" FT DISULFID 429..456 FT /evidence="ECO:0000250|UniProtKB:Q00960" FT DISULFID 436..457 FT /evidence="ECO:0000250|UniProtKB:Q00960" FT DISULFID 746..801 FT /evidence="ECO:0000250|UniProtKB:Q00960" FT VARIANT 15 FT /note="V -> M (in DEE27; uncertain significance; FT dbSNP:rs1057519553)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078235" FT VARIANT 18 FT /note="V -> I (in dbSNP:rs201094029)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079943" FT VARIANT 50 FT /note="I -> N (found in a patient with schizophrenia; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079944" FT VARIANT 271 FT /note="A -> V (in dbSNP:rs138098032)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079945" FT VARIANT 362 FT /note="L -> M (found in a patient with schizophrenia; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079946" FT VARIANT 407 FT /note="S -> N" FT /evidence="ECO:0000269|PubMed:7999784" FT /id="VAR_011317" FT VARIANT 413 FT /note="E -> G (in MRD6; decreased protein abundance; FT decreased localization to the cell membrane; changed FT glutamate-gated calcium ion channel activity characterized FT by decreased glutamate potency; dbSNP:rs527236034)" FT /evidence="ECO:0000269|PubMed:24863970, FT ECO:0000269|PubMed:27839871" FT /id="VAR_079947" FT VARIANT 436 FT /note="C -> R (in MRD6; decreased protein abundance; FT decreased localization to the cell membrane; FT dbSNP:rs1565478152)" FT /evidence="ECO:0000269|PubMed:27839871" FT /id="VAR_079948" FT VARIANT 456 FT /note="C -> Y (in MRD6; decreased protein abundance; FT decreased localization to the cell membrane; changed FT glutamate-gated calcium ion channel activity characterized FT by increased glutamate and glycine potency and increased FT open probability; dbSNP:rs397514555)" FT /evidence="ECO:0000269|PubMed:23160955, FT ECO:0000269|PubMed:27839871" FT /id="VAR_076764" FT VARIANT 461 FT /note="C -> F (in MRD6; decreased protein abundance; FT decreased localization to the cell membrane; decreased FT glutamate-gated calcium ion channel activity characterized FT by decreased glutamate potency and increased glycine FT potency; dbSNP:rs1949427787)" FT /evidence="ECO:0000269|PubMed:27839871" FT /id="VAR_079949" FT VARIANT 540 FT /note="R -> H (in DEE27; decreased protein abundance; FT decreased localization to the cell membrane; increased FT glutamate-gated calcium ion channel activity via an FT allosteric effect which is characterized by increased FT glutamate and glycine potency and increased open FT probability; the mutant channel is less sensitive to FT magnesium inhibition and has increased calcium permeability FT compared to wild-type; dbSNP:rs672601378)" FT /evidence="ECO:0000269|PubMed:24272827, FT ECO:0000269|PubMed:27839871" FT /id="VAR_072663" FT VARIANT 553 FT /note="P -> L (in MRD6; no effect on localization to the FT cell membrane; loss of glutamate-gated calcium ion channel FT activity; dbSNP:rs397514556)" FT /evidence="ECO:0000269|PubMed:23033978, FT ECO:0000269|PubMed:28095420" FT /id="VAR_069384" FT VARIANT 615 FT /note="N -> I (in DEE27; severe phenotype with early onset FT seizures; gain of function mutation; results in neuronal FT hyperexcitability; the mutant channel is not inhibited by FT magnesium and has increased calcium permeability compared FT to wild-type; dbSNP:rs672601377)" FT /evidence="ECO:0000269|PubMed:24272827" FT /id="VAR_072664" FT VARIANT 618 FT /note="V -> G (in DEE27; severe phenotype with early onset FT seizures; gain of function mutation; results in neuronal FT hyperexcitability; the mutant channel is not inhibited by FT magnesium and has increased calcium permeability compared FT to wild-type; dbSNP:rs672601376)" FT /evidence="ECO:0000269|PubMed:24272827" FT /id="VAR_072665" FT VARIANT 682 FT /note="R -> C (in MRD6; decreased protein abundance; no FT effect on localization to the cell membrane; no significant FT effect on calcium ion transmembrane import into cytosol; FT analysis of agonist dose-response curves for glutamate and FT glycine are not consistent; dbSNP:rs387906636)" FT /evidence="ECO:0000269|PubMed:20890276, FT ECO:0000269|PubMed:27839871" FT /id="VAR_065900" FT VARIANT 696 FT /note="R -> H (in MRD6; decreased protein abundance; FT decreased localization to the cell membrane; changed FT glutamate-gated calcium ion channel activity characterized FT by increased glutamate and glycine potency; FT dbSNP:rs1555103971)" FT /evidence="ECO:0000269|PubMed:27839871" FT /id="VAR_079950" FT VARIANT 820 FT /note="G -> E (in MRD6; dbSNP:rs797044849)" FT /evidence="ECO:0000269|PubMed:25356899" FT /id="VAR_078647" FT VARIANT 825 FT /note="L -> V (found in a patient with autism spectrum FT disorder; uncertain significance; dbSNP:rs1948651813)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079951" FT VARIANT 1014 FT /note="Q -> R (found in a patient with schizophrenia; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079952" FT VARIANT 1026 FT /note="G -> S (in dbSNP:rs201963596)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079953" FT VARIANT 1342 FT /note="M -> R" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079954" FT VARIANT 1415 FT /note="S -> L (found in a patient with autism spectrum FT disorder; uncertain significance; dbSNP:rs201463390)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079955" FT VARIANT 1424 FT /note="L -> F (in dbSNP:rs748128078)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079956" FT VARIANT 1439 FT /note="P -> A (found in a patient with Landau-Kleffner FT syndrome; uncertain significance; dbSNP:rs758042475)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078236" FT VARIANT 1452 FT /note="S -> F (found in a patient with schizophrenia; FT uncertain significance; dbSNP:rs756790727)" FT /evidence="ECO:0000269|PubMed:22833210" FT /id="VAR_079957" FT MUTAGEN 553 FT /note="P->R: Changed glutamate-gated calcium ion channel FT activity characterized by increased glutamate and glycine FT potency and slowed response rise time and deactivation time FT course." FT /evidence="ECO:0000269|PubMed:28095420" FT MUTAGEN 818 FT /note="M->V: Increased glutamate and glycine agonist FT potency." FT /evidence="ECO:0000269|PubMed:28126851" FT CONFLICT 434 FT /note="V -> A (in Ref. 3; AAD00659)" FT /evidence="ECO:0000305" FT CONFLICT 745 FT /note="G -> A (in Ref. 5; AAA69920)" FT /evidence="ECO:0000305" FT CONFLICT 773 FT /note="K -> N (in Ref. 5; AAA69920/AAA74930)" FT /evidence="ECO:0000305" FT CONFLICT 796 FT /note="W -> C (in Ref. 5; AAA69920/AAA74930)" FT /evidence="ECO:0000305" FT CONFLICT 888 FT /note="T -> P (in Ref. 5; AAA69920/AAA74930)" FT /evidence="ECO:0000305" FT CONFLICT 902 FT /note="L -> V (in Ref. 5; AAA69920/AAA74930)" FT /evidence="ECO:0000305" FT CONFLICT 920..921 FT /note="SA -> RP (in Ref. 1; AAB60368)" FT /evidence="ECO:0000305" FT CONFLICT 958 FT /note="L -> S (in Ref. 5; AAA69920/AAA74930)" FT /evidence="ECO:0000305" FT CONFLICT 980..982 FT /note="VYQ -> DHY (in Ref. 5; AAA69920)" FT /evidence="ECO:0000305" FT CONFLICT 1056 FT /note="I -> M (in Ref. 5; AAA69920)" FT /evidence="ECO:0000305" FT CONFLICT 1167 FT /note="V -> I (in Ref. 2; AAB49993)" FT /evidence="ECO:0000305" FT STRAND 34..44 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 47..50 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 62..73 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 78..91 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 94..100 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 107..119 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 123..127 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 128..131 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 143..147 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 150..164 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 168..173 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 179..191 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 193..195 FT /evidence="ECO:0007829|PDB:5EWL" FT STRAND 198..204 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 215..221 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 226..232 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 234..246 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 260..263 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 278..282 FT /evidence="ECO:0007829|PDB:5EWM" FT TURN 284..286 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 289..311 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 321..323 FT /evidence="ECO:0007829|PDB:5EWJ" FT HELIX 324..327 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:5EWM" FT HELIX 336..339 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 355..359 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 362..367 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 373..379 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 384..387 FT /evidence="ECO:0007829|PDB:5EWM" FT STRAND 1304..1306 FT /evidence="ECO:0007829|PDB:7UJR" SQ SEQUENCE 1484 AA; 166367 MW; 40AEB12BE6E50CEF CRC64; MKPRAECCSP KFWLVLAVLA VSGSRARSQK SPPSIGIAVI LVGTSDEVAI KDAHEKDDFH HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVFA DDTDQEAIAQ ILDFISAQTL TPILGIHGGS SMIMADKDES SMFFQFGPSI EQQASVMLNI MEEYDWYIFS IVTTYFPGYQ DFVNKIRSTI ENSFVGWELE EVLLLDMSLD DGDSKIQNQL KKLQSPIILL YCTKEEATYI FEVANSVGLT GYGYTWIVPS LVAGDTDTVP AEFPTGLISV SYDEWDYGLP ARVRDGIAII TTAASDMLSE HSFIPEPKSS CYNTHEKRIY QSNMLNRYLI NVTFEGRNLS FSEDGYQMHP KLVIILLNKE RKWERVGKWK DKSLQMKYYV WPRMCPETEE QEDDHLSIVT LEEAPFVIVE SVDPLSGTCM RNTVPCQKRI VTENKTDEEP GYIKKCCKGF CIDILKKISK SVKFTYDLYL VTNGKHGKKI NGTWNGMIGE VVMKRAYMAV GSLTINEERS EVVDFSVPFI ETGISVMVSR SNGTVSPSAF LEPFSADVWV MMFVMLLIVS AVAVFVFEYF SPVGYNRCLA DGREPGGPSF TIGKAIWLLW GLVFNNSVPV QNPKGTTSKI MVSVWAFFAV IFLASYTANL AAFMIQEEYV DQVSGLSDKK FQRPNDFSPP FRFGTVPNGS TERNIRNNYA EMHAYMGKFN QRGVDDALLS LKTGKLDAFI YDAAVLNYMA GRDEGCKLVT IGSGKVFAST GYGIAIQKDS GWKRQVDLAI LQLFGDGEME ELEALWLTGI CHNEKNEVMS SQLDIDNMAG VFYMLGAAMA LSLITFICEH LFYWQFRHCF MGVCSGKPGM VFSISRGIYS CIHGVAIEER QSVMNSPTAT MNNTHSNILR LLRTAKNMAN LSGVNGSPQS ALDFIRRESS VYDISEHRRS FTHSDCKSYN NPPCEENLFS DYISEVERTF GNLQLKDSNV YQDHYHHHHR PHSIGSASSI DGLYDCDNPP FTTQSRSISK KPLDIGLPSS KHSQLSDLYG KFSFKSDRYS GHDDLIRSDV SDISTHTVTY GNIEGNAAKR RKQQYKDSLK KRPASAKSRR EFDEIELAYR RRPPRSPDHK RYFRDKEGLR DFYLDQFRTK ENSPHWEHVD LTDIYKERSD DFKRDSVSGG GPCTNRSHIK HGTGDKHGVV SGVPAPWEKN LTNVEWEDRS GGNFCRSCPS KLHNYSTTVT GQNSGRQACI RCEACKKAGN LYDISEDNSL QELDQPAAPV AVTSNASTTK YPQSPTNSKA QKKNRNKLRR QHSYDTFVDL QKEEAALAPR SVSLKDKGRF MDGSPYAHMF EMSAGESTFA NNKSSVPTAG HHHHNNPGGG YMLSKSLYPD RVTQNPFIPT FGDDQCLLHG SKSYFFRQPT VAGASKARPD FRALVTNKPV VSALHGAVPA RFQKDICIGN QSNPCVPNNK NPRAFNGSSN GHVYEKLSSI ESDV //