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GRIN2A glutamate ionotropic receptor NMDA type subunit 2A [ Homo sapiens (human) ]

Gene ID: 2903, updated on 10-May-2020

Summary

Official Symbol
GRIN2Aprovided by HGNC
Official Full Name
glutamate ionotropic receptor NMDA type subunit 2Aprovided by HGNC
Primary source
HGNC:HGNC:4585
See related
Ensembl:ENSG00000183454 MIM:138253
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
LKS; EPND; FESD; NR2A; GluN2A; NMDAR2A
Summary
This gene encodes a member of the glutamate-gated ion channel protein family. The encoded protein is an N-methyl-D-aspartate (NMDA) receptor subunit. NMDA receptors are both ligand-gated and voltage-dependent, and are involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. These receptors are permeable to calcium ions, and activation results in a calcium influx into post-synaptic cells, which results in the activation of several signaling cascades. Disruption of this gene is associated with focal epilepsy and speech disorder with or without cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
Expression
Biased expression in brain (RPKM 9.5), heart (RPKM 0.9) and 2 other tissues See more
Orthologs

Genomic context

See GRIN2A in Genome Data Viewer
Location:
16p13.2
Exon count:
16
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 16 NC_000016.10 (9753404..10182928, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (9847265..10276611, complement)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101927026 Neighboring gene RNA, 5S ribosomal pseudogene 403 Neighboring gene RNA, 5S ribosomal pseudogene 404 Neighboring gene uncharacterized LOC105371077 Neighboring gene uncharacterized LOC105371076 Neighboring gene inosine monophosphate dehydrogenase 1 pseudogene 11 Neighboring gene uncharacterized LOC107984900 Neighboring gene RNA, 7SL, cytoplasmic 493, pseudogene

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 (2013-06-19)

ClinGen Genome Curation Page
Haploinsufficency

Little evidence for dosage pathogenicity (Last evaluated (2013-06-19)

ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
A genome-wide association study with DNA pooling identifies the variant rs11866328 in the GRIN2A gene that affects disease progression of chronic HBV infection.
NHGRI GWA Catalog
A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
NHGRI GWA Catalog
Biological insights from 108 schizophrenia-associated genetic loci.
NHGRI GWA Catalog
Common genetic variation and the control of HIV-1 in humans.
NHGRI GWA Catalog
Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans.
NHGRI GWA Catalog
Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population.
NHGRI GWA Catalog
Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 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 Ca(2+) influx through the NMDA receptor is necessary for HIV-1 Tat-induced synapse loss PubMed
tat HIV-1 Tat increases in inhibitory synapse number in neurons are dependent on LRP binding and GluN2A-containing NMDAR activation but not PSD95 ubiquitination 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 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 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 Tat treatment causes activation of neuronal nitric oxide synthase (nNOS) through association with NMDA receptors PubMed
tat HIV-1 Tat treatment of human neurons results in tyrosine (Y) phosphorylation at position 1325 of the NMDAR subunit 2A (NR2A) in a src kinase-dependent manner PubMed
tat HIV-1 Tat treatment of primary differentiated human neurons induces extensive apoptosis through increased amounts of NMDAR2A expression, but only low levels of apoptosis in primary immature human neurons result from low or minimal expression of NMDAR2A 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

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
NMDA glutamate receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
NMDA glutamate receptor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
NMDA glutamate receptor activity TAS
Traceable Author Statement
more info
PubMed 
amyloid-beta binding TAS
Traceable Author Statement
more info
PubMed 
glutamate receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
glutamate-gated calcium ion channel activity IDA
Inferred from Direct Assay
more info
PubMed 
glutamate-gated calcium ion channel activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
ligand-gated ion channel activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
zinc ion binding ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
activation of cysteine-type endopeptidase activity TAS
Traceable Author Statement
more info
PubMed 
brain development NAS
Non-traceable Author Statement
more info
PubMed 
calcium ion transmembrane import into cytosol IDA
Inferred from Direct Assay
more info
PubMed 
calcium ion transmembrane import into cytosol IMP
Inferred from Mutant Phenotype
more info
PubMed 
calcium-mediated signaling IEA
Inferred from Electronic Annotation
more info
 
NOT cellular response to amyloid-beta IGI
Inferred from Genetic Interaction
more info
PubMed 
chemical synaptic transmission TAS
Traceable Author Statement
more info
PubMed 
directional locomotion IEA
Inferred from Electronic Annotation
more info
 
dopamine metabolic process IEA
Inferred from Electronic Annotation
more info
 
excitatory chemical synaptic transmission NAS
Non-traceable Author Statement
more info
PubMed 
excitatory postsynaptic potential IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
glutamate receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
ionotropic glutamate receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
learning or memory TAS
Traceable Author Statement
more info
PubMed 
long-term synaptic potentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
memory IEA
Inferred from Electronic Annotation
more info
 
modulation of chemical synaptic transmission IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of protein catabolic process IEA
Inferred from Electronic Annotation
more info
 
neurogenesis IEA
Inferred from Electronic Annotation
more info
 
positive regulation of apoptotic process IEA
Inferred from Electronic Annotation
more info
 
protein localization to postsynaptic membrane IEA
Inferred from Electronic Annotation
more info
 
regulation of NMDA receptor activity TAS
Traceable Author Statement
more info
 
regulation of synaptic plasticity NAS
Non-traceable Author Statement
more info
PubMed 
response to amphetamine IEA
Inferred from Electronic Annotation
more info
 
response to ethanol IDA
Inferred from Direct Assay
more info
PubMed 
response to wounding IEA
Inferred from Electronic Annotation
more info
 
sensory perception of pain IEA
Inferred from Electronic Annotation
more info
 
serotonin metabolic process IEA
Inferred from Electronic Annotation
more info
 
sleep IEA
Inferred from Electronic Annotation
more info
 
startle response IEA
Inferred from Electronic Annotation
more info
 
synaptic transmission, glutamatergic IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
visual learning IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
NMDA selective glutamate receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
NMDA selective glutamate receptor complex IDA
Inferred from Direct Assay
more info
PubMed 
NMDA selective glutamate receptor complex TAS
Traceable Author Statement
more info
PubMed 
cell IEA
Inferred from Electronic Annotation
more info
 
cell surface ISS
Inferred from Sequence or Structural Similarity
more info
 
cytoplasmic vesicle membrane IEA
Inferred from Electronic Annotation
more info
 
dendritic spine IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
 
glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
 
integral component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
integral component of postsynaptic density membrane IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
postsynaptic density ISS
Inferred from Sequence or Structural Similarity
more info
 
postsynaptic density membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
postsynaptic membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
presynaptic membrane IEA
Inferred from Electronic Annotation
more info
 
synaptic membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
synaptic vesicle IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
glutamate receptor ionotropic, NMDA 2A
Names
N-methyl D-aspartate receptor subtype 2A
N-methyl-D-aspartate receptor channel, subunit epsilon-1
N-methyl-D-aspartate receptor subunit 2A
glutamate receptor, ionotropic, N-methyl D-aspartate 2A

NCBI Reference Sequences (RefSeq)

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_011812.2 RefSeqGene

    Range
    4847..434347
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000833.5NP_000824.1  glutamate receptor ionotropic, NMDA 2A isoform 1 precursor

    See identical proteins and their annotated locations for NP_000824.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Transcript variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AC006531, AC007218, AC022168, U09002, U90277
    Consensus CDS
    CCDS10539.1
    UniProtKB/Swiss-Prot
    Q12879
    UniProtKB/TrEMBL
    Q547U9
    Related
    ENSP00000379818.2, ENST00000396573.6
    Conserved Domains (5) summary
    cd06378
    Location:32392
    PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
    COG0834
    Location:458541
    HisJ; ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms]
    cd13718
    Location:403802
    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:556828
    Lig_chan; Ligand-gated ion channel
    pfam10565
    Location:8391464
    NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
  2. NM_001134407.3NP_001127879.1  glutamate receptor ionotropic, NMDA 2A isoform 1 precursor

    See identical proteins and their annotated locations for NP_001127879.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Transcript variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AB209695, AC006531, AC007218, AC022168, U09002
    Consensus CDS
    CCDS10539.1
    UniProtKB/Swiss-Prot
    Q12879
    UniProtKB/TrEMBL
    Q547U9, Q59EW6
    Related
    ENSP00000332549.3, ENST00000330684.4
    Conserved Domains (5) summary
    cd06378
    Location:32392
    PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
    COG0834
    Location:458541
    HisJ; ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms]
    cd13718
    Location:403802
    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:556828
    Lig_chan; Ligand-gated ion channel
    pfam10565
    Location:8391464
    NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
  3. NM_001134408.2NP_001127880.1  glutamate receptor ionotropic, NMDA 2A isoform 2 precursor

    See identical proteins and their annotated locations for NP_001127880.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has a shorter 5' UTR and is alternatively spliced at the 3' end, which results in a frameshift, compared to variant 1. The encoded isoform (2) has a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AC007218, BC143273, U90277
    Consensus CDS
    CCDS45407.1
    UniProtKB/Swiss-Prot
    Q12879
    Related
    ENSP00000454998.1, ENST00000562109.5
    Conserved Domains (3) summary
    cd06378
    Location:32392
    PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
    cd13718
    Location:403802
    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
    pfam10565
    Location:8391258
    NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p13 Primary Assembly

    Range
    9753404..10182928 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017023173.1XP_016878662.1  glutamate receptor ionotropic, NMDA 2A isoform X2

  2. XM_017023172.1XP_016878661.1  glutamate receptor ionotropic, NMDA 2A isoform X1

  3. XM_011522461.3XP_011520763.1  glutamate receptor ionotropic, NMDA 2A isoform X4

    See identical proteins and their annotated locations for XP_011520763.1

    UniProtKB/Swiss-Prot
    Q12879
    Conserved Domains (3) summary
    cd06378
    Location:32392
    PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
    cd13718
    Location:403802
    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
    pfam10565
    Location:8391258
    NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
  4. XM_011522458.3XP_011520760.1  glutamate receptor ionotropic, NMDA 2A isoform X3

    See identical proteins and their annotated locations for XP_011520760.1

    Related
    ENSP00000441572.2, ENST00000535259.5
    Conserved Domains (5) summary
    cd06378
    Location:1235
    PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family
    COG0834
    Location:301384
    HisJ; ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms]
    cd13718
    Location:246645
    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:399671
    Lig_chan; Ligand-gated ion channel
    pfam10565
    Location:6821307
    NMDAR2_C; N-methyl D-aspartate receptor 2B3 C-terminus
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