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

    Gene ID: 2904, updated on 23-Jul-2017
    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; Vega:OTTHUMG00000137373
    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
    MRD6; NR2B; hNR3; EIEE27; GluN2B; NMDAR2B
    Summary
    N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA receptor channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heteromers composed of three different subunits: NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The NR2 subunit acts as the agonist binding site for glutamate. This receptor is the predominant excitatory neurotransmitter receptor in the mammalian brain. [provided by RefSeq, Jul 2008]
    Orthologs
    Location:
    12p13.1
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 12 NC_000012.12 (13537337..13982012, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (13713684..14133022, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene RNA, 5S ribosomal pseudogene 353 Neighboring gene RNA, U6 small nuclear 590, pseudogene Neighboring gene uncharacterized LOC105369668 Neighboring gene RNA, 7SK small nuclear pseudogene 162 Neighboring gene uncharacterized LOC105369667 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 23 Neighboring gene mitochondrial ribosomal protein S18C pseudogene 4

    • 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 Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Epileptic encephalopathy, early infantile, 27
    MedGen: C4015316 OMIM: 616139 GeneReviews: Not available
    Compare labs
    Mental retardation, autosomal dominant 6
    MedGen: C3151411 OMIM: 613970 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated (2013-07-18)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated (2013-07-18)

    ClinGen Genome Curation PagePubMed

    NHGRI GWAS Catalog

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

    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

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    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • Dopaminergic synapse, organism-specific biosystem (from KEGG)
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    • Dopaminergic synapse, conserved biosystem (from KEGG)
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    • Downstream signal transduction, organism-specific biosystem (from REACTOME)
      Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
    • EPH-Ephrin signaling, organism-specific biosystem (from REACTOME)
      EPH-Ephrin signaling, organism-specific biosystemDuring the development process cell migration and adhesion are the main forces involved in morphing the cells into critical anatomical structures. The ability of a cell to migrate to its correct dest...
    • EPHB-mediated forward signaling, organism-specific biosystem (from REACTOME)
      EPHB-mediated forward signaling, organism-specific biosystemMultiple EPHB receptors contribute directly to dendritic spine development and morphogenesis. These are more broadly involved in post-synaptic development through activation of focal adhesion kinase ...
    • ErbB4 signaling events, organism-specific biosystem (from Pathway Interaction Database)
      ErbB4 signaling events, organism-specific biosystem
      ErbB4 signaling events
    • FCERI mediated MAPK activation, organism-specific biosystem (from REACTOME)
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    • Fc epsilon receptor (FCERI) signaling, organism-specific biosystem (from REACTOME)
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    • Frs2-mediated activation, organism-specific biosystem (from REACTOME)
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    • GRB2 events in EGFR signaling, organism-specific biosystem (from REACTOME)
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    • Glutamatergic synapse, organism-specific biosystem (from KEGG)
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    • Glutamatergic synapse, conserved biosystem (from KEGG)
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    • Huntington's disease, conserved biosystem (from KEGG)
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    • IRS-related events triggered by IGF1R, organism-specific biosystem (from REACTOME)
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    • Long-term potentiation, organism-specific biosystem (from KEGG)
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    • Long-term potentiation, conserved biosystem (from KEGG)
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    • SOS-mediated signalling, organism-specific biosystem (from REACTOME)
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      Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystemBinding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS...
    • Signaling by VEGF, organism-specific biosystem (from REACTOME)
      Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • Signalling to ERKs, organism-specific biosystem (from REACTOME)
      Signalling to ERKs, organism-specific biosystemNeurotrophins utilize multiple pathways to activate ERKs (ERK1 and ERK2), a subgroup of the large MAP kinase (MAPK) family, from the plasma membrane. The major signalling pathways to ERKs are via RAS...
    • Signalling to RAS, organism-specific biosystem (from REACTOME)
      Signalling to RAS, organism-specific biosystemSignalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation...
    • Signalling to p38 via RIT and RIN, organism-specific biosystem (from REACTOME)
      Signalling to p38 via RIT and RIN, organism-specific biosystemRIT and RIN are two small guanine nucleotide binding proteins that share more than 50% sequence identity with RAS, including highly conserved core effector domains. Unlike RAS, the C termini of RIT a...
    • Systemic lupus erythematosus, organism-specific biosystem (from KEGG)
      Systemic lupus erythematosus, organism-specific biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
    • Systemic lupus erythematosus, conserved biosystem (from KEGG)
      Systemic lupus erythematosus, conserved biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
    • Transmission across Chemical Synapses, organism-specific biosystem (from REACTOME)
      Transmission across Chemical Synapses, organism-specific biosystemChemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron,...
    • Unblocking of NMDA receptor, glutamate binding and activation, organism-specific biosystem (from REACTOME)
      Unblocking of NMDA receptor, glutamate binding and activation, organism-specific biosystemAt resting membrane potential the NMDA receptor is blocked by extracellular Mg2+ ions and therefore is not activated in this state by ligands (glutamate, glycine, NMDA). The voltage block is removed ...
    • VEGFA-VEGFR2 Pathway, organism-specific biosystem (from REACTOME)
      VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...
    • VEGFR2 mediated cell proliferation, organism-specific biosystem (from REACTOME)
      VEGFR2 mediated cell proliferation, organism-specific biosystemVEGFR2 stimulates ERK not via GRB2-SOS-RAS, but via pY1175-dependent phosphorylation of PLC gamma and subsequent activation of PKCs. PKC plays an important mediatory role in the proliferative Ras/Raf...
    • cAMP signaling pathway, organism-specific biosystem (from KEGG)
      cAMP signaling pathway, organism-specific biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
    • cAMP signaling pathway, conserved biosystem (from KEGG)
      cAMP signaling pathway, conserved biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • MGC142178, MGC142180

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    NMDA glutamate receptor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    Ras guanyl-nucleotide exchange factor activity TAS
    Traceable Author Statement
    more info
     
    extracellular-glutamate-gated ion channel activity IEA
    Inferred from Electronic Annotation
    more info
     
    glycine binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    zinc ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Process Evidence Code Pubs
    MAPK cascade TAS
    Traceable Author Statement
    more info
     
    chemical synaptic transmission TAS
    Traceable Author Statement
    more info
    PubMed 
    ephrin receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    excitatory postsynaptic potential IEA
    Inferred from Electronic Annotation
    more info
     
    glutamate receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
     
    ionotropic glutamate receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    learning or memory TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of GTPase activity IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
     
    response to ethanol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transport TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    NMDA selective glutamate receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell junction IEA
    Inferred from Electronic Annotation
    more info
     
    cell surface ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    integral component of plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    intracellular IEA
    Inferred from Electronic Annotation
    more info
     
    neuron projection ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    postsynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
     
    Preferred Names
    glutamate receptor ionotropic, NMDA 2B
    Names
    N-methyl D-aspartate receptor subtype 2B
    N-methyl-D-aspartate receptor subunit 3
    NR3
    glutamate [NMDA] receptor subunit epsilon-2
    glutamate receptor subunit epsilon-2
    glutamate receptor, ionotropic, N-methyl D-aspartate 2B

    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_031854.1 RefSeqGene

      Range
      5001..423613
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000834.3NP_000825.2  glutamate receptor ionotropic, NMDA 2B precursor

      See identical proteins and their annotated locations for NP_000825.2

      Status: REVIEWED

      Source sequence(s)
      AC007535, U88963, U90278
      Consensus CDS
      CCDS8662.1
      UniProtKB/Swiss-Prot
      Q13224
      Related
      ENSP00000477455.1, OTTHUMP00000174410, ENST00000609686.3, OTTHUMT00000268014
      Conserved Domains (5) summary
      cd06378
      Location:33393
      PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
      COG0834
      Location:459542
      HisJ; ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms]
      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
      pfam00060
      Location:557829
      Lig_chan; Ligand-gated ion channel
      pfam10565
      Location:8401484
      NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p7 Primary Assembly

      Range
      13537337..13982012 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011520629.2XP_011518931.1  glutamate receptor ionotropic, NMDA 2B isoform X1

      See identical proteins and their annotated locations for XP_011518931.1

      UniProtKB/Swiss-Prot
      Q13224
      Conserved Domains (5) summary
      cd06378
      Location:33393
      PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
      COG0834
      Location:459542
      HisJ; ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms]
      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
      pfam00060
      Location:557829
      Lig_chan; Ligand-gated ion channel
      pfam10565
      Location:8401484
      NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
    2. XM_011520628.2XP_011518930.1  glutamate receptor ionotropic, NMDA 2B isoform X1

      See identical proteins and their annotated locations for XP_011518930.1

      UniProtKB/Swiss-Prot
      Q13224
      Conserved Domains (5) summary
      cd06378
      Location:33393
      PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
      COG0834
      Location:459542
      HisJ; ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms]
      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
      pfam00060
      Location:557829
      Lig_chan; Ligand-gated ion channel
      pfam10565
      Location:8401484
      NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
    3. XM_017019219.1XP_016874708.1  glutamate receptor ionotropic, NMDA 2B isoform X1

      UniProtKB/Swiss-Prot
      Q13224
      Conserved Domains (5) summary
      cd06378
      Location:33393
      PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
      COG0834
      Location:459542
      HisJ; ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms]
      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
      pfam00060
      Location:557829
      Lig_chan; Ligand-gated ion channel
      pfam10565
      Location:8401484
      NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
    4. XM_005253351.3XP_005253408.1  glutamate receptor ionotropic, NMDA 2B isoform X2

      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 CHM1_1.1

    Genomic

    1. NC_018923.2 Alternate CHM1_1.1

      Range
      13679406..14098101 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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