Protein detail
NMDE2
Glutamate receptor ionotropic, NMDA 2B (GluN2B) (Glutamate [NMDA] receptor subunit epsilon-2) (N-methyl D-aspartate receptor subtype 2B) (NMDAR2B) (NR2B) (N-methyl-D-aspartate receptor subunit 3) (NR3) (hNR3)
Protein symbol NMDE2 | UniProt ID | EVMP score 0.50 |
Frequency 3 | Transmembrane count 3 | Protein classification Disease related genesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsPredicted membrane proteinsRAS pathway related proteins |
Basic Information
Protein Names
Glutamate receptor ionotropic, NMDA 2B (GluN2B) (Glutamate [NMDA] receptor subunit epsilon-2) (N-methyl D-aspartate receptor subtype 2B) (NMDAR2B) (NR2B) (N-methyl-D-aspartate receptor subunit 3) (NR3) (hNR3)
Protein Class
Disease related genesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsPredicted membrane proteinsRAS pathway related proteins
Protein Function
- Human disease related genes:Other diseases:Mental and behavioural disorders
- Predicted intracellular proteins
- Human disease related genes:Nervous system diseases:Epilepsy
- RAS pathway related proteins
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Transmembrane
556..576; Helical; 628..647; Helical; 820..835; Helical
Transmembrane Count
3
Ensembl
Entrez Gene Symbol
Gene Synonym
GluN2BNMDAR2B
Gene Description
Glutamate ionotropic receptor NMDA type subunit 2B
Chromosome
12
Position
13437942-13982002
Frequency
3
EVMP Score
0.50
Fluorescence & Localization
Tissue SpecificlungCell SpecificcDCSingle-Nuclei Brain SpecificleukocyteBlood Cell SpecificeosinophilBlood Lineage Specificdendritic cells
Function & Pathway
Protein Function
- Human disease related genes:Other diseases:Mental and behavioural disorders
- Predicted intracellular proteins
- Human disease related genes:Nervous system diseases:Epilepsy
- RAS pathway related proteins
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component
- GO:0005737 cytoplasm
- GO:0005764 lysosome
- GO:0005770 late endosome
- GO:0005789 endoplasmic reticulum membrane
- GO:0005856 cytoskeleton
- GO:0005886 plasma membrane
- GO:0009986 cell surface
- GO:0014069 postsynaptic density
- GO:0017146 NMDA selective glutamate receptor complex
- GO:0043005 neuron projection
- GO:0045211 postsynaptic membrane
- GO:0097060 synaptic membrane
- GO:0098839 postsynaptic density membrane
Molecular Function
- GO:0001540 amyloid-beta binding
- GO:0004972 NMDA glutamate receptor activity
- GO:0005515 protein binding
- GO:0008270 zinc ion binding
- GO:0016594 glycine binding
- GO:0016595 glutamate binding
- GO:0022849 glutamate-gated calcium ion channel activity
- GO:0099507 ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
Biological Process
KEGG
- hsa04014 Ras signaling pathway
- KEGG:hsa04015 Rap1 signaling pathway
- KEGG:hsa04020 Calcium signaling pathway
- KEGG:hsa04024 cAMP signaling pathway
- KEGG:hsa04080 Neuroactive ligand-receptor interaction
- KEGG:hsa04082 Neuroactive ligand signaling
- KEGG:hsa04713 Circadian entrainment
- KEGG:hsa04720 Long-term potentiation
- KEGG:hsa04724 Glutamatergic synapse
- KEGG:hsa04728 Dopaminergic synapse
- KEGG:hsa05010 Alzheimer disease
- KEGG:hsa05014 Amyotrophic lateral sclerosis
- KEGG:hsa05016 Huntington disease
- KEGG:hsa05017 Spinocerebellar ataxia
- KEGG:hsa05020 Prion disease
- KEGG:hsa05022 Pathways of neurodegeneration - multiple diseases
- KEGG:hsa05030 Cocaine addiction
- KEGG:hsa05031 Amphetamine addiction
- KEGG:hsa05033 Nicotine addiction
- KEGG:hsa05034 Alcoholism
- KEGG:hsa05322 Systemic lupus erythematosus
Reactome
- R-hsa-9032500 activated ntrk2 signals through fyn
- R-hsa-442755 activation of nmda receptors and postsynaptic events
- R-hsa-9609736 assembly and cell surface presentation of nmda receptors
- R-hsa-442742 creb1 phosphorylation through nmda receptor mediated activation of ras signaling
- R-hsa-3928662 ephb mediated forward signaling
- R-hsa-2682334 eph ephrin signaling
- R-hsa-9620244 long term potentiation
- R-hsa-5684996 mapk1 mapk3 signaling
- R-hsa-5683057 mapk family signaling cascades
- R-hsa-9022699 mecp2 regulates neuronal receptors and channels
- R-hsa-9617324 negative regulation of nmda receptor mediated neuronal transmission
- R-hsa-9675108 nervous system development
- R-hsa-6794361 neurexins and neuroligins
- R-hsa-112316 neuronal system
- R-hsa-112314 neurotransmitter receptors and postsynaptic signal transmission
- R-hsa-6794362 protein protein interactions at synapses
- R-hsa-442982 ras activation upon ca2 influx through nmda receptor
- R-hsa-73857 rna polymerase ii transcription
- R-hsa-9006115 signaling by ntrk2 trkb
- R-hsa-166520 signaling by ntrks
- R-hsa-9006934 signaling by receptor tyrosine kinases
- R-hsa-8849932 synaptic adhesion like molecules
- R-hsa-8986944 transcriptional regulation by mecp2
- R-hsa-112315 transmission across chemical synapses
- R-hsa-438066 unblocking of nmda receptors glutamate binding and activation
Mediation Categories
Clinical-translation mediationFusion and delivery mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
41 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| GRIN2B | SRC | P12931 | Y | 1,474 | phosphorylation | Sparser_ProtMapperPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDRLIMS-P_ProtMapperKEASIGNOR_ProtMapper | HPRD:11024032ProtMapper:11483655ProtMapper:18184784KEA:11024032SIGNOR:11483655KEA:11483655HPRD:11483655 |
| GRIN2B | PRKACA | P17612 | S | 1,166 | phosphorylation | PhosphoSite | |
| GRIN2B | DAPK1 | P53355 | S | 1,303 | phosphorylation | Sparser_ProtMapperProtMapperRLIMS-P_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:28731405ProtMapper:27447806ProtMapper:23880846ProtMapper:23144645ProtMapper:20141836 |
| GRIN2B | BDNF | P23560 | Y | 1,474 | phosphorylation | RLIMS-P_ProtMapperSparser_ProtMapperProtMapper | ProtMapper:15788764ProtMapper:17045972ProtMapper:26252487 |
| GRIN2B | DRD5 | P21918 | Y | 1,474 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:25100942 |
| GRIN2B | PSD | A5PKW4 | Y | 1,474 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:12950452 |
| GRIN2B | CSK | P41240 | Y | 1,474 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:25100942 |
| GRIN2B | CSK | P41240 | Y | 1,336 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:30740518 |
| GRIN2B | EPHB2 | P29323 | Y | 1,474 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:29423241 |
| GRIN2B | IL1B | P01584 | Y | 1,474 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:28851400 |
Ligand-Receptor Signaling
40 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| ion_channel | ion_channel | OmniPath | No | Yes | No | No | No |
| transmembrane | transmembrane | UniProt_location | No | No | No | No | No |
| transmembrane | transmembrane | UniProt_topology | No | No | No | No | No |
| transmembrane | transmembrane | UniProt_keyword | No | No | No | No | No |
| transmembrane | transmembrane | GO_Intercell | No | No | No | No | No |
| transmembrane | transmembrane | CellPhoneDB | No | No | No | No | No |
| transmembrane | transmembrane | TopDB | No | No | No | No | No |
| transmembrane | transmembrane | LOCATE | No | No | No | No | No |
| transmembrane | transmembrane | Ramilowski_location | No | No | No | No | No |
| transmembrane | transmembrane | OmniPath | No | No | No | No | No |
Regulatory Interaction Network
18 records.
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Protein Complex Composition
6 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| N-methyl-D-aspartate selective glutamate receptor complex | GRIN1GRIN2AGRIN2BGRIN2CGRIN2DGRIN3AGRIN3B | O15399O60391Q05586Q12879Q13224Q14957Q8TCU5 | 1:1:1:1:1:1:1 | Compleat | Compleat:HC1274 | 104809381173522417997397 |
| NMDA receptor complexGluN1-GluN2A-GluN2B | GRIN1GRIN2AGRIN2B | Q05586Q12879Q13224 | 1:1:1 | ComplexPortal | 19793963243865751475529225556790262829252224643418184566 | |
| NMDA receptor_2B | GRIN1GRIN2B | Q05586Q13224 | 2:2 | CellChatDBKEGG-MEDICUSCellPhoneDBSIGNORComplexPortalPDB | SIGNOR:SIGNOR-C348PDB:8vuuCellPhoneDB:Glutamate_NMDA_1_2B_complexintact:EBI-11303087PDB:9iypPDB:8vuvPDB:7eu8PDB:9iyq | 248764891979396324386575147552922555679034321660262829252224643418184566 |
| ARHGAP32CDC42GRIN2BNCF1NEBPAK6PIK3R1RAP1AVAV1 | A7KAX9P14598P15498P20929P27986P60953P62834Q13224Q9NQU5 | 1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC7964 | ||
| ARHGAP32CDC42GRIN2BILKAPLIMK1PAK2PLEKHG2RAP1BSH3PXD2ASNX33 | A7KAX9P53667P60953P61224Q13177Q13224Q5TCZ1Q8WV41Q9H0C8Q9H7P9 | 1:1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC5250 | ||
| GRIN1GRIN2BGRIN2D | O15399Q05586Q13224 | 1:2:1 | PDB | PDB:9d39PDB:9d3cPDB:9d3bPDB:9d38PDB:9d3aPDB:9d37 |
Sequence, Structure & Domains
Sequences
Length
1,484
Mass
166,367
Sequence
MKPRAECCSPKFWLVLAVLAVSGSRARSQKSPPSIGIAVILVGTSDEVAIKDAHEKDDFHHLSVVPRVELVAMNETDPKSIITRICDLMSDRKIQGVVFADDTDQEAIAQILDFISAQTLTPILGIHGGSSMIMADKDESSMFFQFGPSIEQQASVMLNIMEEYDWYIFSIVTTYFPGYQDFVNKIRSTIENSFVGWELEEVLLLDMSLDDGDSKIQNQLKKLQSPIILLYCTKEEATYIFEVANSVGLTGYGYTWIVPSLVAGDTDTVPAEFPTGLISVSYDEWDYGLPARVRDGIAIITTAASDMLSEHSFIPEPKSSCYNTHEKRIYQSNMLNRYLINVTFEGRNLSFSEDGYQMHPKLVIILLNKERKWERVGKWKDKSLQMKYYVWPRMCPETEEQEDDHLSIVTLEEAPFVIVESVDPLSGTCMRNTVPCQKRIVTENKTDEEPGYIKKCCKGFCIDILKKISKSVKFTYDLYLVTNGKHGKKINGTWNGMIGEVVMKRAYMAVGSLTINEERSEVVDFSVPFIETGISVMVSRSNGTVSPSAFLEPFSADVWVMMFVMLLIVSAVAVFVFEYFSPVGYNRCLADGREPGGPSFTIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVWAFFAVIFLASYTANLAAFMIQEEYVDQVSGLSDKKFQRPNDFSPPFRFGTVPNGSTERNIRNNYAEMHAYMGKFNQRGVDDALLSLKTGKLDAFIYDAAVLNYMAGRDEGCKLVTIGSGKVFASTGYGIAIQKDSGWKRQVDLAILQLFGDGEMEELEALWLTGICHNEKNEVMSSQLDIDNMAGVFYMLGAAMALSLITFICEHLFYWQFRHCFMGVCSGKPGMVFSISRGIYSCIHGVAIEERQSVMNSPTATMNNTHSNILRLLRTAKNMANLSGVNGSPQSALDFIRRESSVYDISEHRRSFTHSDCKSYNNPPCEENLFSDYISEVERTFGNLQLKDSNVYQDHYHHHHRPHSIGSASSIDGLYDCDNPPFTTQSRSISKKPLDIGLPSSKHSQLSDLYGKFSFKSDRYSGHDDLIRSDVSDISTHTVTYGNIEGNAAKRRKQQYKDSLKKRPASAKSRREFDEIELAYRRRPPRSPDHKRYFRDKEGLRDFYLDQFRTKENSPHWEHVDLTDIYKERSDDFKRDSVSGGGPCTNRSHIKHGTGDKHGVVSGVPAPWEKNLTNVEWEDRSGGNFCRSCPSKLHNYSTTVTGQNSGRQACIRCEACKKAGNLYDISEDNSLQELDQPAAPVAVTSNASTTKYPQSPTNSKAQKKNRNKLRRQHSYDTFVDLQKEEAALAPRSVSLKDKGRFMDGSPYAHMFEMSAGESTFANNKSSVPTAGHHHHNNPGGGYMLSKSLYPDRVTQNPFIPTFGDDQCLLHGSKSYFFRQPTVAGASKARPDFRALVTNKPVVSALHGAVPARFQKDICIGNQSNPCVPNNKNPRAFNGSSNGHVYEKLSSIESDV
3D Structural Models
Turn
53..55; 284..286; 414..416; 424..426; 502..504; 556..559; 576..580; 751..754; 815..818
Helix
47..50; 78..91; 107..119; 128..131; 150..164; 179..191; 215..221; 234..246; 260..263; 289..311; 324..327; 328..330; 336..339; 460..471; 497..501; 517..520; 560..575; 602..613; 626..653; 669..672; 690..698; 700..705; 714..723; 733..741; 744..746; 773..786; 788..796; 820..839
Beta Strand
34..44; 62..73; 94..100; 123..127; 143..147; 168..173; 193..195; 198..204; 209..211; 226..232; 255..258; 278..282; 321..323; 344..346; 355..359; 362..367; 373..379; 384..387; 405..410; 417..420; 434..437; 455..459; 475..480; 483..486; 488..490; 493..496; 523..525; 535..538; 550..554; 665..668; 677..679; 687..689; 727..731; 1304..1306
3D Structure
Electron microscopy (11); X-ray crystallography (12)
Domain & Motif Annotations
Compositional Bias
1272..1289; Polar residues; 1290..1301; Basic residues
Motif
1482..1484; PDZ-binding
Domain (CC)
The extracellular N-terminal domain (NTD) endows NMDARs with a unique capacity for allosteric modulation, harboring several binding sites for small molecule ligands that act as subunit-specific allosteric modulators of ion channel activity.; DOMAIN: A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.
Region
604..623; Pore-forming; 1074..1097; Disordered; 1161..1194; Disordered; 1271..1301; Disordered; 1292..1304; Interaction with DAPK1
Protein Families
- Glutamate-gated ion channel (TC 1.A.10.1) family
- NR2B/GRIN2B subfamily
Sequence Similarities
Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2B/GRIN2B subfamily.
Clinical Relevance
Disease Involvement
Disease variantEpilepsyFDA approved drug targetsIntellectual disability
Drug Targets
FDA approved drug targets
Drugs
AMANTADINE HYDROCHLORIDEFELBAMATEMETHYLPHENIDATE HYDROCHLORIDENULLLY233053HOMOQUINOLINIC ACID[3H]MDL105519CLOZAPINETRAXOPRODILRADIPRODILRISPERIDONE[3H]CGS19755GW468816ASPARTIC ACIDEVT-101DIZOCILPINEINDANTADOL[3H]DIZOCILPINENVP-AAM077ACAMPROSATE CALCIUMESKETAMINESERINE, D-RALFINAMIDEMG2+NEBOGLAMINERAPASTINELAPIMOSTINELAV-101ORPHENADRINE CITRATEESKETAMINE HYDROCHLORIDEGV196771A[3H]CGP396535,7-DICHLOROKYNURENIC ACIDUBP141CNS-5161MEMANTINE HYDROCHLORIDEAZD8108(+)-HA966DIMIRACETAMLATREPIRDINE(RS)-(TETRAZOL-5-YL)GLYCINEKETAMINE HYDROCHLORIDESELFOTELGRP94 INHIBITOR 54DEXANABINOLLANICEMINENERAMEXANEL701324DELUCEMINEVALPROIC ACIDSAGE-718SEMAPIMODPERZINFOTELRISLENEMDAZ[3H]CPPSEVOFLURANE[3H]L689560CGP37849NERAMEXANE MESYLATEL689560NBQXPHENCYCLIDINES-DESCHLOROKETAMINED-CCPENECOMPOUND 18C [PMID: 25901531]CONANTOKIN-GQUETIAPINE FUMARATE[3H]CGP61594HALOPERIDOL DECANOATEONFASPRODILGLYCINE[3H]D-ASPARTIC ACIDORPHENADRINE HYDROCHLORIDEELIPRODILNMDAN1-DANSYL-SPERMINED-AP5
Interaction Protein
ENSG00000070808ENSG00000075711ENSG00000132535
Interaction Count
3
Interaction Dataset
intact_biogrid