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    GRIN2B glutamate ionotropic receptor NMDA type subunit 2B [ Homo sapiens (human) ]

    Gene ID: 2904, updated on 17-Jun-2024

    Summary

    Official Symbol
    GRIN2Bprovided by HGNC
    Official Full Name
    glutamate ionotropic receptor NMDA type subunit 2Bprovided by HGNC
    Primary source
    HGNC:HGNC:4586
    See related
    Ensembl:ENSG00000273079 MIM:138252; AllianceGenome:HGNC:4586
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NR3; MRD6; NR2B; hNR3; DEE27; EIEE27; GluN2B; NMDAR2B
    Summary
    This gene encodes a member of the N-methyl-D-aspartate (NMDA) receptor family within the ionotropic glutamate receptor superfamily. The encoded protein is a subunit of the NMDA receptor ion channel which acts as an agonist binding site for glutamate. The NMDA receptors mediate a slow calcium-permeable component of excitatory synaptic transmission in the central nervous system. The NMDA receptors are heterotetramers of seven genetically encoded, differentially expressed subunits including NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, and schizophrenia. [provided by RefSeq, Aug 2017]
    Expression
    Biased expression in brain (RPKM 5.9) and testis (RPKM 0.2) See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See GRIN2B in Genome Data Viewer
    Location:
    12p13.1
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (13537337..13982134, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (13411758..13856548, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (13690271..14134536, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6035 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6036 Neighboring gene RNA, 5S ribosomal pseudogene 353 Neighboring gene RNA, U6 small nuclear 590, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:13651563-13652064 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:13652065-13652564 Neighboring gene MPRA-validated peak1577 silencer Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:13679281-13680273 Neighboring gene Sharpr-MPRA regulatory region 1907 Neighboring gene uncharacterized LOC105369668 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr12:13748291-13749049 Neighboring gene RN7SK pseudogene 162 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr12:13898035-13898963 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_26314 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr12:13902103-13902838 Neighboring gene uncharacterized LOC105369667 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:14138289-14139488 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6037 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr12:14279960-14280579 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr12:14304393-14304981 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6038 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:14372961-14374160 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 23 Neighboring gene MRPS18C pseudogene 4

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2019-09-25)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2019-09-25)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    A genome-wide association study of aging.
    EBI GWAS Catalog
    A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.
    EBI GWAS Catalog
    Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.
    EBI GWAS Catalog
    Genetic variants and environmental factors associated with hormonal markers of ovarian reserve in Caucasian and African American women.
    EBI GWAS Catalog
    Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
    EBI GWAS Catalog
    Genome-wide analysis reveals novel genes influencing temporal lobe structure with relevance to neurodegeneration in Alzheimer's disease.
    EBI GWAS Catalog
    Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease.
    EBI GWAS Catalog

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of glutamate receptor, ionotropic, N-methyl D-aspartate 2B (GRIN2B) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 induced-neurotoxicity involves upregulation of NR2B and downregulation of PSD-95 expressions in neuron cells PubMed
    env HIV-1 gp120-induced dephosphorylation of KV2.1 is dependent on NMDA receptor-mediated activation of protein phosphatase 2B or calcineurin PubMed
    env HIV-1 gp120 activates forward trafficking and surface clustering of NMDA receptors in membrane microdomains by a PKA-dependent phosphorylation of the NR1 C-terminal Ser897, followed by a PKC-dependent phosphorylation of Ser896 PubMed
    env HIV-1 gp120-induced synapse loss requires sequential activation of CXCR4, IL-1beta receptor, and NMDA receptor PubMed
    env HIV-1 gp120 activates NMDA receptor directly and phosphorylates JNK through a gp120-mediated apoptotic pathway in human neuroblastoma cells PubMed
    env HIV-1 clade B gp120 significantly downregulates NMDA receptor gene and protein expression and levels of glutamine compared to clade C gp120 PubMed
    env HIV-1 gp120-mediated human cell death involves the NMDA receptor complex; antagonists of the NMDA receptor reverse the gp120-mediated effects PubMed
    env HIV-1 gp120 causes an activation of phospholipase A2, resulting in the increased release of arachidonic acid, which may sensitize the NMDA receptor PubMed
    env HIV-1 gp120 binds to cells expressing epsilon1/zeta1 or epsilon2/zeta1 combined NMDA receptor subunits, but not to cells expressing a single epsilon1, epsilon2, or zeta1 NMDA receptor subunit PubMed
    Tat tat The gene expression of GRIN2B is significantly upregulated in both clade B and clade C Tat treated SK-N-MC neuroblastoma cells PubMed
    tat Ca(2+) influx through the NMDA receptor is necessary for HIV-1 Tat-induced synapse loss PubMed
    tat HIV-1 Tat upregulates the expression of NMDARs for the apoptosis of retinal pigmen epithelium (RPE) cells. Silencing of NMDARs by siRNA abolishes Tat-induced RPE apoptosis PubMed
    tat HIV-1 Tat-induced activation of spermine oxidase (SMO) activity involves NMDAR stimulation in human neuroblastoma PubMed
    tat HIV-1 Tat-induced loss of presynaptic terminals is recovered by ifenprodil, an NR2B subunit-selective NMDA receptor antagonist PubMed
    tat HIV-1 Tat and methamphetamine inhibit the normal conjunction of signaling between D1 and NMDA receptors, resulting in neural dysfunction and death PubMed
    tat HIV-1 Tat interacts with NMDA receptors in primary neuronal-glial cultures and in hippocampal slice cultures PubMed
    tat Tat treatment causes activation of neuronal nitric oxide synthase (nNOS) through association with NMDA receptors PubMed
    tat HIV-1 Tat treatment induces the formation of complexes involving the low-density lipoprotein receptor-related protein (LRP), postsynaptic density protein-95 (PSD-95), and N-methyl-d-aspartic acid (NMDA) receptors at the neuron surface PubMed
    tat HIV-1 Tat-induced NMDA receptor activation is clade dependent. The Cys 30-Cys 31 motif in Tat is critical for the NMDA receptor activation PubMed
    tat HIV-1 Tat induces apoptosis of neurons and neurotoxicity through the activation of both NMDA and non-NMDA receptors PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC142178, MGC142180

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables NMDA glutamate receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables NMDA glutamate receptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables NMDA glutamate receptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables NMDA glutamate receptor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables amyloid-beta binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables glutamate binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables glutamate-gated calcium ion channel activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables glutamate-gated calcium ion channel activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables glycine binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables zinc ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Process Evidence Code Pubs
    involved_in brain development NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in calcium ion transmembrane import into cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in calcium ion transmembrane import into cytosol IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in calcium-mediated signaling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in chemical synaptic transmission TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in excitatory chemical synaptic transmission NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in excitatory postsynaptic potential IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in glutamate receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in ionotropic glutamate receptor signaling pathway ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in ionotropic glutamate receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in learning or memory ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in long-term synaptic potentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in monoatomic cation transmembrane transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of dendritic spine maintenance ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of cysteine-type endopeptidase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in positive regulation of excitatory postsynaptic potential ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in positive regulation of excitatory postsynaptic potential ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of synaptic transmission, glutamatergic ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in positive regulation of synaptic transmission, glutamatergic ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in protein heterotetramerization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of monoatomic cation transmembrane transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of neuronal synaptic plasticity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in regulation of presynaptic membrane potential IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of synaptic plasticity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in response to ethanol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in synaptic transmission, glutamatergic IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Component Evidence Code Pubs
    part_of NMDA selective glutamate receptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of NMDA selective glutamate receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of NMDA selective glutamate receptor complex ISO
    Inferred from Sequence Orthology
    more info
     
    part_of NMDA selective glutamate receptor complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    part_of NMDA selective glutamate receptor complex TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in cell surface ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    located_in cytoskeleton IEA
    Inferred from Electronic Annotation
    more info
     
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    located_in late endosome ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in lysosome ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in neuron projection ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane ISO
    Inferred from Sequence Orthology
    more info
     
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in postsynaptic density ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in postsynaptic density membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in postsynaptic membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in postsynaptic membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in synaptic membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     

    General protein information

    Preferred Names
    glutamate receptor ionotropic, NMDA 2B
    Names
    GluN2B(alt_5'UTR)
    N-methyl D-aspartate receptor subtype 2B
    N-methyl-D-aspartate receptor subunit 3
    glutamate [NMDA] receptor subunit epsilon-2
    glutamate receptor subunit epsilon-2
    glutamate receptor, ionotropic, N-methyl D-aspartate 2B

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_031854.2 RefSeqGene

      Range
      5411..449676
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000834.5NP_000825.2  glutamate receptor ionotropic, NMDA 2B isoform a precursor

      See identical proteins and their annotated locations for NP_000825.2

      Status: REVIEWED

      Source sequence(s)
      AC007527, AC007535, AC007916, U88963, U90278
      Consensus CDS
      CCDS8662.1
      UniProtKB/Swiss-Prot
      Q12919, Q13220, Q13224, Q13225, Q14CU4, Q9UM56
      UniProtKB/TrEMBL
      A0A8D9PHB2
      Related
      ENSP00000477455.1, ENST00000609686.4
      Conserved Domains (3) summary
      cd13718
      Location:403803
      PBP2_iGluR_NMDA_Nr2; The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily
      cd06378
      Location:33388
      PBP1_iGluR_NMDA_NR2; N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
      pfam10565
      Location:8401484
      NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
    2. NM_001413992.1NP_001400921.1  glutamate receptor ionotropic, NMDA 2B isoform a precursor

      Status: REVIEWED

      Source sequence(s)
      AC007397, AC007527, AC007535, AC007784, AC007916
      UniProtKB/Swiss-Prot
      Q12919, Q13220, Q13224, Q13225, Q14CU4, Q9UM56
      UniProtKB/TrEMBL
      A0A8D9PHB2
      Related
      ENSP00000486677.3, ENST00000630791.3
    3. NM_001413993.1NP_001400922.1  glutamate receptor ionotropic, NMDA 2B isoform b precursor

      Status: REVIEWED

      Source sequence(s)
      AC007397, AC007784, AC007916
    4. NM_001413994.1NP_001400923.1  glutamate receptor ionotropic, NMDA 2B isoform b precursor

      Status: REVIEWED

      Source sequence(s)
      AC007397, AC007784, AC007916
    5. NM_001413995.1NP_001400924.1  glutamate receptor ionotropic, NMDA 2B isoform b precursor

      Status: REVIEWED

      Source sequence(s)
      AC007397, AC007784, AC007916

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      13537337..13982134 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005253351.3XP_005253408.1  glutamate receptor ionotropic, NMDA 2B isoform X1

      Conserved Domains (2) summary
      pfam10565
      Location:102746
      NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
      cl21456
      Location:165
      Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      13411758..13856548 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371855.1XP_054227830.1  glutamate receptor ionotropic, NMDA 2B isoform X2

      UniProtKB/Swiss-Prot
      Q12919, Q13220, Q13224, Q13225, Q14CU4, Q9UM56
      UniProtKB/TrEMBL
      A0A8D9PHB2
    2. XM_054371854.1XP_054227829.1  glutamate receptor ionotropic, NMDA 2B isoform X2

      UniProtKB/Swiss-Prot
      Q12919, Q13220, Q13224, Q13225, Q14CU4, Q9UM56
      UniProtKB/TrEMBL
      A0A8D9PHB2
    3. XM_054371856.1XP_054227831.1  glutamate receptor ionotropic, NMDA 2B isoform X1