NMDE2_HUMAN
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 03-AUG-2022, entry version 214.
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=3; IntAct=EBI-2256942, EBI-357481;
CC Q13224; P78352: DLG4; NbExp=3; 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}.
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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 SMR; Q13224; -.
DR BioGRID; 109161; 44.
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; 20.
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; 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 GlyGen; Q13224; 7 sites.
DR iPTMnet; Q13224; -.
DR PhosphoSitePlus; Q13224; -.
DR BioMuta; GRIN2B; -.
DR DMDM; 14548162; -.
DR jPOST; Q13224; -.
DR MassIVE; Q13224; -.
DR PaxDb; Q13224; -.
DR PeptideAtlas; Q13224; -.
DR PRIDE; Q13224; -.
DR ProteomicsDB; 59232; -.
DR ABCD; Q13224; 1 sequenced antibody.
DR Antibodypedia; 71655; 1394 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 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; 188544at2759; -.
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 1066 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 tissues.
DR ExpressionAtlas; Q13224; baseline and differential.
DR Genevisible; Q13224; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
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:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0004972; F:NMDA glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; 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:0098655; P:cation transmembrane transport; IC:ComplexPortal.
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; IC: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: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; IC:ComplexPortal.
DR GO; GO:1901216; P:positive regulation of neuron death; ISS:ARUK-UCL.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IC:ComplexPortal.
DR GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; IC:ComplexPortal.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IC:ComplexPortal.
DR GO; GO:0048167; P:regulation of synaptic plasticity; NAS:ARUK-UCL.
DR GO; GO:0045471; P:response to ethanol; IDA:UniProtKB.
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; IPR018884; NMDAR2_C.
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 Pfam; PF10565; NMDAR2_C; 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; 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; unknown pathological 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 unknown pathological 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 unknown pathological 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)"
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 (probable disease-associated variant found in
FT a patient with autism spectrum disorder)"
FT /evidence="ECO:0000269|PubMed:22833210"
FT /id="VAR_079951"
FT VARIANT 1014
FT /note="Q -> R (found in a patient with schizophrenia;
FT unknown pathological 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; unknown pathological significance;
FT 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; unknown pathological significance;
FT 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 unknown pathological 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:7KL1"
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
