ID NMDE2_MOUSE Reviewed; 1482 AA. AC Q01097; Q9DCB2; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 20-JUN-2001, sequence version 3. DT 27-MAR-2024, entry version 218. DE RecName: Full=Glutamate receptor ionotropic, NMDA 2B; DE Short=GluN2B; DE AltName: Full=Glutamate [NMDA] receptor subunit epsilon-2 {ECO:0000303|PubMed:1377365}; DE AltName: Full=N-methyl D-aspartate receptor subtype 2B; DE Short=NMDAR2B; DE Short=NR2B {ECO:0000303|PubMed:31424425}; DE Flags: Precursor; GN Name=Grin2b; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND RP TISSUE SPECIFICITY. RX PubMed=1377365; DOI=10.1038/358036a0; RA Kutsuwada T., Kashiwabuchi N., Mori H., Sakimura K., Kushiya E., Araki K., RA Meguro H., Masaki H., Kumanishi T., Arakawa M., Mishina M.; RT "Molecular diversity of the NMDA receptor channel."; RL Nature 358:36-41(1992). RN [2] RP SEQUENCE REVISION. RA Kutsuwada T., Kashiwabuchi N., Mori H., Sakimura K., Kushiya E., Araki K., RA Meguro H., Masaki H., Kumanishi T., Arakawa M., Mishina M.; RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-337. RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=8789948; DOI=10.1016/s0896-6273(00)80051-3; RA Kutsuwada T., Sakimura K., Manabe T., Takayama C., Katakura N., Kushiya E., RA Natsume R., Watanabe M., Inoue Y., Yagi T., Aizawa S., Arakawa M., RA Takahashi T., Nakamura Y., Mori H., Mishina M.; RT "Impairment of suckling response, trigeminal neuronal pattern formation, RT and hippocampal LTD in NMDA receptor epsilon 2 subunit mutant mice."; RL Neuron 16:333-344(1996). RN [5] RP SUBCELLULAR LOCATION. RX PubMed=10846156; DOI=10.1126/science.288.5472.1796; RA Setou M., Nakagawa T., Seog D.-H., Hirokawa N.; RT "Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor- RT containing vesicle transport."; RL Science 288:1796-1802(2000). RN [6] RP PHOSPHORYLATION AT TYR-1472. RX PubMed=12451687; RA Nakazawa T., Tezuka T., Yamamoto T.; RT "Regulation of NMDA receptor function by Fyn-mediated tyrosine RT phosphorylation."; RL Nihon Shinkei Seishin Yakurigaku Zasshi 22:165-167(2002). RN [7] RP IDENTIFICATION IN A COMPLEX WITH GRIN1 AND GRIN3B. RX PubMed=12008020; DOI=10.1016/s0169-328x(02)00173-0; RA Matsuda K., Kamiya Y., Matsuda S., Yuzaki M.; RT "Cloning and characterization of a novel NMDA receptor subunit NR3B: a RT dominant subunit that reduces calcium permeability."; RL Brain Res. Mol. Brain Res. 100:43-52(2002). RN [8] RP IDENTIFICATION IN A COMPLEX WITH GRIN1 AND GRIN3B. RX PubMed=14602821; DOI=10.1523/jneurosci.23-31-10064.2003; RA Matsuda K., Fletcher M., Kamiya Y., Yuzaki M.; RT "Specific assembly with the NMDA receptor 3B subunit controls surface RT expression and calcium permeability of NMDA receptors."; RL J. Neurosci. 23:10064-10073(2003). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200; RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.; RT "Comprehensive identification of phosphorylation sites in postsynaptic RT density preparations."; RL Mol. Cell. Proteomics 5:914-922(2006). RN [10] RP INTERACTION WITH HIP1. RX PubMed=17329427; DOI=10.1523/jneurosci.5175-06.2007; RA Metzler M., Gan L., Wong T.P., Liu L., Helm J., Liu L., Georgiou J., RA Wang Y., Bissada N., Cheng K., Roder J.C., Wang Y.T., Hayden M.R.; RT "NMDA receptor function and NMDA receptor-dependent phosphorylation of RT huntingtin is altered by the endocytic protein HIP1."; RL J. Neurosci. 27:2298-2308(2007). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain cortex; RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200; RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., RA Panse C., Schlapbach R., Mansuy I.M.; RT "Qualitative and quantitative analyses of protein phosphorylation in naive RT and stimulated mouse synaptosomal preparations."; RL Mol. Cell. Proteomics 6:283-293(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-962; TYR-1039; TYR-1109; RP TYR-1133 AND TYR-1155, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Brain; RX PubMed=18034455; DOI=10.1021/pr0701254; RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; RT "Large-scale identification and evolution indexing of tyrosine RT phosphorylation sites from murine brain."; RL J. Proteome Res. 7:311-318(2008). RN [13] RP INTERACTION WITH NETO1. RX PubMed=19243221; DOI=10.1371/journal.pbio.1000041; RA Ng D., Pitcher G.M., Szilard R.K., Sertie A., Kanisek M., Clapcote S.J., RA Lipina T., Kalia L.V., Joo D., McKerlie C., Cortez M., Roder J.C., RA Salter M.W., McInnes R.R.; RT "Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for RT synaptic plasticity and learning."; RL PLoS Biol. 7:E41-E41(2009). RN [14] RP FUNCTION, PHOSPHORYLATION AT SER-1303, AND INTERACTION WITH DAPK1. RX PubMed=20141836; DOI=10.1016/j.cell.2009.12.055; RA Tu W., Xu X., Peng L., Zhong X., Zhang W., Soundarapandian M.M., Balel C., RA Wang M., Jia N., Zhang W., Lew F., Chan S.L., Chen Y., Lu Y.; RT "DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage RT in stroke."; RL Cell 140:222-234(2010). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-882; SER-917; SER-920; RP SER-1058; SER-1061; SER-1064; SER-1143; SER-1255; SER-1259 AND SER-1303, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT. 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 [17] RP SUBCELLULAR LOCATION, AND INTERACTION WITH TMEM25. RX PubMed=31424425; DOI=10.1172/jci122599; RA Zhang H., Tian X., Lu X., Xu D., Guo Y., Dong Z., Li Y., Ma Y., Chen C., RA Yang Y., Yang M., Yang Y., Liu F., Zhou R., He M., Xiao F., Wang X.; RT "TMEM25 modulates neuronal excitability and NMDA receptor subunit NR2B RT degradation."; RL J. Clin. Invest. 129:3864-3876(2019). 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:1377365, PubMed:26912815). Sensitivity to glutamate and channel CC kinetics depend on the subunit composition (PubMed:1377365). In concert CC with DAPK1 at extrasynaptic sites, acts as a central mediator for CC stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances CC synaptic NMDA receptor channel activity inducing injurious Ca2+ influx CC through them, resulting in an irreversible neuronal death CC (PubMed:20141836). Contributes to neural pattern formation in the CC developing brain (PubMed:8789948). Plays a role in long-term depression CC (LTD) of hippocampus membrane currents and in synaptic plasticity CC (PubMed:8789948). {ECO:0000269|PubMed:1377365, CC ECO:0000269|PubMed:20141836, ECO:0000269|PubMed:26912815, CC ECO:0000269|PubMed:8789948}. 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:1377365, PubMed:26912815). Can CC also form heterotetrameric channels that contain at least one zeta CC subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B CC (PubMed:12008020, PubMed:14602821). In vivo, the subunit composition CC may depend on the expression levels of the different subunits CC (Probable). Found in a complex with GRIN1, GRIN3A and PPP2CB (By CC similarity). Found in a complex with GRIN1 and GRIN3B (PubMed:12008020, CC PubMed:14602821). Interacts with MAGI3 (By similarity). Interacts with CC HIP1 and NETO1 (PubMed:17329427, PubMed:19243221). Interacts with PDZ CC domains of PATJ, DLG3 and DLG4. Interacts with DAPK1 (PubMed:20141836). CC Found in a complex with GRIN1 and PRR7. Interacts with PRR7 (By CC similarity). Interacts with CAMK2A (By similarity). Interacts with ARC; CC preventing ARC oligomerization (By similarity). Interacts with TMEM25 CC (PubMed:31424425). {ECO:0000250|UniProtKB:Q00960, CC ECO:0000250|UniProtKB:Q13224, ECO:0000269|PubMed:12008020, CC ECO:0000269|PubMed:1377365, ECO:0000269|PubMed:14602821, CC ECO:0000269|PubMed:17329427, ECO:0000269|PubMed:19243221, CC ECO:0000269|PubMed:20141836, ECO:0000269|PubMed:26912815, CC ECO:0000269|PubMed:31424425}. CC -!- INTERACTION: CC Q01097; Q9JI91: Actn2; NbExp=2; IntAct=EBI-400125, EBI-299169; CC Q01097; P17426: Ap2a1; NbExp=2; IntAct=EBI-400125, EBI-775189; CC Q01097; P11798: Camk2a; NbExp=5; IntAct=EBI-400125, EBI-400384; CC Q01097; Q80YE7: Dapk1; NbExp=8; IntAct=EBI-400125, EBI-2584874; CC Q01097; Q62108: Dlg4; NbExp=19; IntAct=EBI-400125, EBI-300895; CC Q01097; P35438: Grin1; NbExp=11; IntAct=EBI-400125, EBI-400084; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1377365, CC ECO:0000269|PubMed:26912815}; 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:0000269|PubMed:31424425}. Lysosome {ECO:0000269|PubMed:31424425}. CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10846156}. Note=Co- CC localizes with the motor protein KIF17 along microtubules. CC {ECO:0000269|PubMed:10846156}. CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level) CC (PubMed:8789948). Detected throughout the brain, and in brain stem CC trigeminal nucleus (PubMed:8789948). Detected in forebrain CC (PubMed:1377365). {ECO:0000269|PubMed:1377365, CC ECO:0000269|PubMed:8789948}. 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 (PubMed:12451687). CC Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor CC channel activity (PubMed:20141836). {ECO:0000269|PubMed:12451687, CC ECO:0000269|PubMed:20141836}. CC -!- DISRUPTION PHENOTYPE: Mutant pups are born at the expected Mendelian CC rate and appear grossly normal, but lack suckling behavior. As a CC consequence, all die shortly after birth, except when they are fed CC manually via a soft tube that delivers milk directly into the stomach. CC While mutant neonate brain structures are grossly normal, the mutant CC brain stem trigeminal complex lacks the neural repeating units called CC barrelettes that correspond to whisker-associated nerve fibers. Primary CC afferent nerve fibers from whiskers fail to show normal clustering in CC the region where barrelette structures form in wild-type. In contrast, CC nasolabial motor neurons appear normal. Contrary to wild-type neonates, CC brain slices from the mutant neonate hippocampus CA1 region lack NMDA CC receptor-type ion channel activity. Contrary to wild-type pups, CC prolonged low frequency stimulation of afferent fibers does not induce CC long-term depression (LTD) in the hippocampus. CC {ECO:0000269|PubMed:8789948}. 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; D10651; BAA01498.2; -; mRNA. DR EMBL; AK002963; BAB22483.1; -; mRNA. DR CCDS; CCDS20648.1; -. DR PIR; I49704; I49704. DR RefSeq; NP_032197.3; NM_008171.3. DR AlphaFoldDB; Q01097; -. DR SMR; Q01097; -. DR BioGRID; 200069; 127. DR ComplexPortal; CPX-291; NMDA receptor complex, GluN1-GluN2B. DR ComplexPortal; CPX-296; NMDA receptor complex, GluN1-GluN2A-GluN2B. DR CORUM; Q01097; -. DR DIP; DIP-31568N; -. DR IntAct; Q01097; 43. DR MINT; Q01097; -. DR STRING; 10090.ENSMUSP00000062284; -. DR BindingDB; Q01097; -. DR ChEMBL; CHEMBL3442; -. DR GlyConnect; 2351; 11 N-Linked glycans (6 sites). DR GlyCosmos; Q01097; 7 sites, 11 glycans. DR GlyGen; Q01097; 9 sites, 11 N-linked glycans (6 sites), 1 O-linked glycan (2 sites). DR iPTMnet; Q01097; -. DR PhosphoSitePlus; Q01097; -. DR SwissPalm; Q01097; -. DR CPTAC; non-CPTAC-4053; -. DR MaxQB; Q01097; -. DR PaxDb; 10090-ENSMUSP00000062284; -. DR ProteomicsDB; 293864; -. DR ABCD; Q01097; 3 sequenced antibodies. DR DNASU; 14812; -. DR GeneID; 14812; -. DR KEGG; mmu:14812; -. DR AGR; MGI:95821; -. DR CTD; 2904; -. DR MGI; MGI:95821; Grin2b. DR eggNOG; KOG1053; Eukaryota. DR InParanoid; Q01097; -. DR OrthoDB; 1034721at2759; -. DR PhylomeDB; Q01097; -. DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling. DR Reactome; R-MMU-438066; Unblocking of NMDA receptors, glutamate binding and activation. DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade. DR Reactome; R-MMU-8849932; Synaptic adhesion-like molecules. DR Reactome; R-MMU-9609736; Assembly and cell surface presentation of NMDA receptors. DR BioGRID-ORCS; 14812; 0 hits in 77 CRISPR screens. DR ChiTaRS; Grin2b; mouse. DR PRO; PR:Q01097; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; Q01097; Protein. DR GO; GO:0097440; C:apical dendrite; ISO:MGI. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0044307; C:dendritic branch; ISO:MGI. DR GO; GO:0043197; C:dendritic spine; ISO:MGI. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; ISO:MGI. DR GO; GO:0005770; C:late endosome; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0043005; C:neuron projection; IDA:BHF-UCL. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; IPI:MGI. DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0098794; C:postsynapse; IDA:ParkinsonsUK-UCL. DR GO; GO:0014069; C:postsynaptic density; IDA:BHF-UCL. DR GO; GO:0098839; C:postsynaptic density membrane; IDA:SynGO. DR GO; GO:0045211; C:postsynaptic membrane; IDA:MGI. DR GO; GO:0048787; C:presynaptic active zone membrane; ISO:MGI. DR GO; GO:0042734; C:presynaptic membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IDA:MGI. DR GO; GO:0043083; C:synaptic cleft; ISO:MGI. DR GO; GO:0097060; C:synaptic membrane; IDA:ARUK-UCL. DR GO; GO:0008021; C:synaptic vesicle; IDA:MGI. DR GO; GO:0043195; C:terminal bouton; ISO:MGI. DR GO; GO:0030658; C:transport vesicle membrane; TAS:Reactome. DR GO; GO:0030018; C:Z disc; ISO:MGI. DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI. DR GO; GO:0005262; F:calcium channel activity; IMP:MGI. DR GO; GO:0050839; F:cell adhesion molecule binding; ISO:MGI. DR GO; GO:0031749; F:D2 dopamine receptor binding; ISO:MGI. DR GO; GO:0005234; F:extracellularly glutamate-gated ion channel activity; ISO:MGI. DR GO; GO:0016595; F:glutamate binding; ISS:UniProtKB. DR GO; GO:0022849; F:glutamate-gated calcium ion channel activity; ISS:UniProtKB. DR GO; GO:0004970; F:glutamate-gated receptor activity; ISO:MGI. DR GO; GO:0016594; F:glycine binding; ISO:MGI. DR GO; GO:1901363; F:heterocyclic compound binding; ISO:MGI. DR GO; GO:0005149; F:interleukin-1 receptor binding; ISO:MGI. DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISO:MGI. DR GO; GO:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; ISO:MGI. DR GO; GO:0005261; F:monoatomic cation channel activity; IGI:MGI. DR GO; GO:0099583; F:neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:0099529; F:neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential; IMP:SynGO. DR GO; GO:0004972; F:NMDA glutamate receptor activity; IMP:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI. DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI. DR GO; GO:0036094; F:small molecule binding; ISO:MGI. DR GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; ISO:MGI. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0001508; P:action potential; ISO:MGI. DR GO; GO:0008306; P:associative learning; ISO:MGI. DR GO; GO:0001662; P:behavioral fear response; IMP:MGI. DR GO; GO:0048266; P:behavioral response to pain; IMP:MGI. DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISS:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; IMP:MGI. DR GO; GO:0007268; P:chemical synaptic transmission; IMP:MGI. DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IMP:MGI. DR GO; GO:0060079; P:excitatory postsynaptic potential; IMP:MGI. DR GO; GO:0042596; P:fear response; IMP:MGI. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; ISO:MGI. DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISO:MGI. DR GO; GO:0007612; P:learning; IDA:MGI. DR GO; GO:0007611; P:learning or memory; ISO:MGI. DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:MGI. DR GO; GO:0007613; P:memory; IDA:MGI. DR GO; GO:0098655; P:monoatomic cation transmembrane transport; ISS:ComplexPortal. DR GO; GO:0006812; P:monoatomic cation transport; IGI:MGI. DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; IGI:ARUK-UCL. DR GO; GO:0098989; P:NMDA selective glutamate receptor signaling pathway; ISO:MGI. DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISO:MGI. DR GO; GO:0014049; P:positive regulation of glutamate secretion; ISO:MGI. DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISO:MGI. DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISO:MGI. DR GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB. DR GO; GO:0043113; P:receptor clustering; ISO:MGI. DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; ISO:MGI. DR GO; GO:0043408; P:regulation of MAPK cascade; ISO:MGI. DR GO; GO:1904062; P:regulation of monoatomic cation transmembrane transport; ISS:ComplexPortal. DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; TAS:UniProtKB. DR GO; GO:0099566; P:regulation of postsynaptic cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:0060078; P:regulation of postsynaptic membrane potential; IMP:MGI. DR GO; GO:0010738; P:regulation of protein kinase A signaling; IMP:MGI. DR GO; GO:0048167; P:regulation of synaptic plasticity; IMP:MGI. DR GO; GO:0045471; P:response to ethanol; IMP:MGI. DR GO; GO:0001666; P:response to hypoxia; ISO:MGI. DR GO; GO:0010243; P:response to organonitrogen compound; ISO:MGI. DR GO; GO:0048511; P:rhythmic process; ISO:MGI. DR GO; GO:0046960; P:sensitization; ISO:MGI. DR GO; GO:0007423; P:sensory organ development; IMP:MGI. DR GO; GO:0001964; P:startle response; IMP:MGI. DR GO; GO:0001967; P:suckling behavior; IMP:MGI. 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 DisProt; DP01492; -. 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. PE 1: Evidence at protein level; KW Calcium; Cell membrane; Cytoplasm; Cytoskeleton; Disulfide bond; Endosome; KW Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; KW Lysosome; Magnesium; Membrane; Metal-binding; Phosphoprotein; KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse; KW Transmembrane; Transmembrane helix; Transport; Zinc. FT SIGNAL 1..26 FT /evidence="ECO:0000255" FT CHAIN 27..1482 FT /note="Glutamate receptor ionotropic, NMDA 2B" FT /id="PRO_0000011578" 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..1482 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 1162..1194 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1266..1301 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1292..1304 FT /note="Interaction with DAPK1" FT /evidence="ECO:0000269|PubMed:20141836" FT MOTIF 1480..1482 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 1266..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:0007744|PubMed:21183079" FT MOD_RES 886 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q00960" FT MOD_RES 917 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 920 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 962 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18034455" FT MOD_RES 1039 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18034455" FT MOD_RES 1058 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1061 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1064 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1109 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18034455" FT MOD_RES 1133 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18034455" FT MOD_RES 1143 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1155 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18034455" FT MOD_RES 1255 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1259 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 1303 FT /note="Phosphoserine; by DAPK1" FT /evidence="ECO:0000269|PubMed:20141836, FT ECO:0007744|PubMed:21183079" FT MOD_RES 1472 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:12451687" 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 CONFLICT 99 FT /note="L -> F (in Ref. 3; BAB22483)" FT /evidence="ECO:0000305" SQ SEQUENCE 1482 AA; 165959 MW; B8C3FA10E9A4B36D CRC64; MKPSAECCSP KFWLVLAVLA VSGSKARSQK SAPSIGIAVI LVGTSDEVAI KDAHEKDDFH HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVLA DDTDQEAIAQ ILDFISAQTL TPILGIHGGS SMIMADKDES SMFFQFGPSI EQQASVMLNI MEEYDWYIFS IVTTYFPGYQ DFVNKIRSTI ENSFVGWELE EVLLLDMSLD DGDSKIQNQL KKLQSPIILL YCTKEEATYI FEVANSVGLT GYGYTWIVPS LVAGDTDTVP SEFPTGLISV SYDEWDYGLP ARVRDGIAII TTAASDMLSE HSFIPEPKSS CYNTHEKRIY QSNMLNRYLI NVTFEGRNLS FSEDGYQMHP KLVIILLNKE RKWERVGKWK DKSLQMKYYV WPRMCPETEE QEDDHLSIVT LEEAPFVIVE SVDPLSGTCM RNTVPCQKRI ISENKTDEEP 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 PHSIGSTSSI DGLYDCDNPP FTTQPRSISK KPLDIGLPSS KHSQLSDLYG KFSFKSDRYS GHDDLIRSDV SDISTHTVTY GNIEGNAAKR RKQQYKDSLK KRPASAKSRR EFDEIELAYR RRPPRSPDHK RYFRDKEGLR DFYLDQFRTK ENSPHWEHVD LTDIYKERSD DFKRDSVSGG GPCTNRSHLK HGTGDKHGVV GGVPAPWEKN LTNVDWEDRS GGNFCRSCPS KLHNYSSTVA GQNSGRQACI RCEACKKAGN LYDISEDNSL QELDQPAAPV AVSSNASTTK YPQSPTNSKA QKKNRNKLRR QHSYDTFVDL QKEEAALAPR SVSLKDKGRF MDGSPYAHMF EMPAGESSFA NKSSVTTAGH HHNNPGSGYM LSKSLYPDRV TQNPFIPTFG DDQCLLHGSK SYFFRQPTVA GASKTRPDFR ALVTNKPVVS ALHGAVPGRF QKDICIGNQS NPCVPNNKNP RAFNGSSNGH VYEKLSSIES DV //