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1: GRIN2A glutamate receptor, ionotropic, N-methyl D-aspartate 2A [ Homo sapiens ]

GeneID: 2903 updated 12-Nov-2008

[Top][Help]Summary

Official Symbol: GRIN2Aprovided by HGNC
Official Full Name: glutamate receptor, ionotropic, N-methyl D-aspartate 2Aprovided by HGNC
Primary source: HGNC:4585
See related: Ensembl:ENSG 00000183454; HPRD:00698; 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: NR2A; NMDAR2A; GRIN2A
Summary: N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate-gated ion channels. These receptors have 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 the key receptor subunit NMDAR1 (GRIN1) and 1 or more of the 4 NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C) and NMDAR2D (GRIN2D). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq]

[Top][Help]Genomic regions, transcripts, and products

(minus strand) Go to reference sequence details Try our new Sequence Viewer

Genomic context[Top][Help]

chromosome: 16; Location: 16p13.2See GRIN2A in MapViewer

[Top][Help]Bibliography

GeneRIFs: Gene References Into FunctionWhat's a GeneRIF?

1. Observational study of gene-disease association. (HuGE Navigator)

2. NR2A and NR2B receptor gene variations modify age at onset in Huntington disease in a sex-specific manner.

3. NMDAR2A is commonly hypermethylated in primary human colorectal carcinoma and possesses tumor-suppressive activity.

4. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)

5. Observational study of gene-disease association. (HuGE Navigator)

6. Observational study of gene-disease association. (HuGE Navigator)

7. Observational study of gene-disease association. (HuGE Navigator)

8. Observational study of gene-disease association. (HuGE Navigator)

9. Observational study of gene-disease association. (HuGE Navigator)

10. Observational study of gene-disease association. (HuGE Navigator)

11. Observational study of gene-disease association. (HuGE Navigator)

12. laser capture microdissection combined with quantitative PCR was used to examine the expression of AMPA (GRIA1-4) and NMDA (GRIN1, 2A and 2B) subunit mRNA levels in Layer II/III and Layer V pyramidal cells in the DLPFC.

13. The results of the present study, thus, suggest that blockage of NMDA receptors including the NR2A subunit suppresses MKN45 cell proliferation due to cell cycle arrest at the G(1) phase.

14. NR2A(F637) influences NMDA receptor affinity, ion channel gating, and ethanol sensitivity; the changes in NMDA receptor affinity are likely to be the result of altered ion channel gating

15. a probable genetic effect for the GRIN2A promoter (GT)n variation on the predisposition to schizophrenia in Japanese cohorts.

16. genetic variation in GRIN2A may confer increased risk for attention deficit disorder with hyperactivity

17. Owing to its role in aspects of cognition, linkage of 4 GRIN2A polymorphisms was studied in inhibitory control, verbal short-term memory and verbal working memory. There was no significant evidence of linkage between GRIN2A and these phenotypes.

18. N-methyl-d-aspartate receptor subunit messenger ribonucleic acids are differentially expressed during postnatal development of the human hippocampus

19. human cerebral endothelial cells express the message and protein for NMDA receptors.

20. Analysis of the autistic disorder susceptibility locus suggests an association on chromosome 16p between GRIN2A and ABAT.

21. the three amino acid tail following the TM4 region of the N-methyl-D-aspartate receptor (NR) 2 subunits is sufficient to overcome endoplasmic reticulum retention of NR1-1a subunit

22. the conformation of NR1 subunit homodimers is affected by the partner NR2 subunits during the formation of heteromeric receptor complexes

23. In schizophrenia, analysis of the GRIN2A gene detected four single nucleotide polymorphisms, and a variable (GT)(n) repeat in the promoter region.

24. The levels of NR2A mRNA are decreased in Alzheimer disease hippocampus and entorhinal cortex compared to controls.

25. NR2A subtypes mainly expressed in the striatum, may influence the variability in age of onset of Huntington disease.

26. GRIN2A and TCERG1 may show true association with residual age of onset for Huntington's disease in genetic association tests in 443 affected people from a large set of kindreds from Venezuela.

27. disulfide bridging and structural integrity within the NR1 N-terminal domain is requisite for cell surface N-methyl-D-aspartate receptor expression

28. The C-terminus of NR2A is critical for modulation of desensitization by calcineurin.

29. analysis of the role of the glutamate binding pocket in agonist affinity and efficacy of N-methyl-D-aspartate receptor activation

Submit: New GeneRIF Correction

[Top][Help]HIV-1 protein interactions

Protein Interaction

1.Envelope surface glycoprotein gp120 HIV-1 gp120 activates NMDA receptor directly and phosphorylates JNK through a gp120-mediated apoptotic pathway in human neuroblastoma cells PubMed

2. 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

3. HIV-1 gp120 causes an activation of phospholipase A2, resulting in the increased release of arachidonic acid, which may sensitize the NMDA receptor PubMed

4. HIV-1 gp120-mediated human cell death involves the NMDA receptor complex; antagonists of the NMDA receptor reverse the gp120-mediated effects PubMed

5.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 Protein Interaction Database

[Top][Help]Interactions

Description ..........

Product Interactant Other Gene Complex Source Pubs

N-methyl D-aspartate receptor subunit 2A NP_015566.1 GRIN1 HPRD PubMed

N-methyl D-aspartate receptor subunit 2A NP_733750.2 INADL HPRD PubMed

N-methyl D-aspartate receptor subunit 2A NP_055530.2 RICS HPRD PubMed

NP_000824.1 NP_001093.1 ACTN1 HPRD PubMed

NP_000824.1 Synapse associated protein 97 DLG1 HPRD PubMed

NP_000824.1 Channel associated protein of synapse 110 DLG2 HPRD PubMed

NP_000824.1 Synapse associated protein 102 DLG3 HPRD PubMed

NP_000824.1 NP_001356.1 DLG4 HPRD PubMed

NP_000824.1 NP_004737.2 DLGAP1 HPRD PubMed

NP_000824.1 Fyn FYN HPRD PubMed

NR1a interacts with NR2A.

NP_000824.1 NP_015566.1 GRIN1 BIND PubMed

npro-IL-16 interacts with NR2A.

NP_000824.1 AAQ86961.1 IL16 BIND PubMed

NP_000824.1 Interleukin 16 IL16 HPRD PubMed

NP_000824.1 Focal adhesion kinase 2 PTK2B HPRD PubMed

NP_000824.1 NP_002821.1 PTPN4 HPRD PubMed

NP_000824.1 c-Src SRC HPRD PubMed

NP_000824.1 CIPP HPRD PubMed

NP_000824.1 NR1 HPRD PubMed

NP_000824.1 NR3A HPRD PubMed

NP_000824.1 NR3B HPRD PubMed

NP_000824.1 PLC gamma HPRD PubMed

SCP1-REST complex interacts with the GRIN2A RE-1.

NT_010393.15 BIND PubMed

in vivo

BioGRID:109160 BioGRID:106602 ACTN1 BioGRID PubMed

Affinity Capture-Western; Reconstituted Complex

BioGRID:109160 BioGRID:108083 DLG1 BioGRID PubMed

in vivo

BioGRID:109160 BioGRID:108084 DLG2 BioGRID PubMed

in vitro; in vivo

BioGRID:109160 BioGRID:108085 DLG3 BioGRID PubMed

in vitro; in vivo; Two-hybrid

BioGRID:109160 BioGRID:108086 DLG4 BioGRID PubMed

in vivo

BioGRID:109160 BioGRID:114660 DLGAP1 BioGRID PubMed

Affinity Capture-Western; in vitro; in vivo

BioGRID:109160 BioGRID:108810 FYN BioGRID PubMed

in vivo

BioGRID:109160 BioGRID:125508 GRIN3A BioGRID PubMed

Affinity Capture-Western

BioGRID:109160 BioGRID:125509 GRIN3B BioGRID PubMed

in vivo; Two-hybrid

BioGRID:109160 BioGRID:109816 IL16 BioGRID PubMed

Affinity Capture-Western; in vivo

BioGRID:109160 BioGRID:108480 PTK2B BioGRID PubMed

Affinity Capture-Western

BioGRID:109160 BioGRID:111741 PTPN4 BioGRID PubMed

Affinity Capture-Western; in vitro; in vivo

BioGRID:109160 BioGRID:112592 SRC BioGRID PubMed

[Top][Help]General gene information

Markers

D16S3064(e-PCR): Links: UniSTS:2188; Alternate names: A312WA5; AFMA312WA5; AFMa312wa5; GDB:608670; HSA312WA5; W6021
SHGC-18386(e-PCR): Links: UniSTS:2749; Alternate name: RH83435
D16S2596E(e-PCR): Links: UniSTS:19233; Alternate names: Cdazrc09; GDB:447222; RH10972; RH85117; RH85185; SHGC-61030; SHGC-61223
D16S732(e-PCR): Links: UniSTS:27113; Alternate names: GDB:354835; MR120; RH34727; RH85412; SHGC-6487; SX-53_05.SEQ; WI-1311
D16S3126(e-PCR): Links: UniSTS:28448; Alternate names: AFMA041YF1; AFMa041yf1; GDB:613410; HSA041YF1
D16S407(e-PCR): Links: UniSTS:37252; Alternate names: 113XE3; AFM113xe3; GDB:187997; HS113XE3; RH3996; RH42090; RH54473
D16S407(e-PCR): Links: UniSTS:38533; Alternate names: AFM113xe3; RH241; RH97236; SHGC-27
G17910(e-PCR): Links: UniSTS:44284; Alternate name: SHGC-5859
G01525(e-PCR): Links: UniSTS:45101; Alternate name: UC9
RH69953(e-PCR): Links: UniSTS:56126; Alternate name: R53954
SHGC-12942(e-PCR): Links: UniSTS:56536; Alternate names: G00-677-762; GDB:677762; GRIN2A; RH14116; RH54776; RH77635; RH85334; SHGC-60976; UTR-05505; WI-7968
D16S407(e-PCR): Links: UniSTS:57503; Alternate names: AFM113xe3; RH13248; SHGC-27; stSG560
G10721(e-PCR): Links: UniSTS:65875; Alternate names: CHLC.UTR_05505_U09002; CHLC.UTR_05505_U09002.P65612
SHGC-83077(e-PCR): Links: UniSTS:101305; Alternate name: RH110340
Grin2a(e-PCR): Links: UniSTS:143261
D16S2608E(e-PCR): Links: UniSTS:151676; Alternate name: GDB:447261
SHGC-111612(e-PCR): Links: UniSTS:168431
SHGC-149675(e-PCR): Links: UniSTS:177157
GRIN2A_118(e-PCR): Links: UniSTS:277296
GRIN2A(e-PCR): Links: UniSTS:480253

Genotypes

See GRIN2A SNP GeneView Report
See GRIN2A SNP Genotype Report

Pathways

KEGG pathway: Calcium signaling pathway: 04020
KEGG pathway: Long-term potentiation: 04720
KEGG pathway: Neuroactive ligand-receptor interaction: 04080

Homology

Mouse, Rat: Map Viewer

GeneOntology Provided by GOA

Function Evidence

N-methyl-D-aspartate selective glutamate receptor activity
PubMed 8768735 TAS PubMed

calcium channel activity IEA

calcium ion binding IEA

extracellular-glutamate-gated ion channel activity IEA

glutamate receptor binding IEA

ion channel activity IEA

ionotropic glutamate receptor activity IEA

magnesium ion binding IEA

protein binding
PubMed 17997397 IPI PubMed

receptor activity IEA

Process Evidence

calcium ion transport IEA

directional locomotion IEA

dopamine metabolic process IEA

glutamate signaling pathway
PubMed 8768735 TAS PubMed

ion transport IEA

memory IEA

negative regulation of protein catabolic process IEA

neurogenesis IEA

protein localization IEA

regulation of excitatory postsynaptic membrane potential IEA

regulation of sensory perception of pain IEA

regulation of synaptic plasticity IEA

response to amphetamine IEA

response to drug IEA

response to ethanol
PubMed 18445116 IDA PubMed

response to wounding IEA

serotonin metabolic process IEA

sleep IEA

startle response IEA

visual learning IEA

Component Evidence

N-methyl-D-aspartate selective glutamate receptor complex
PubMed 10480938 IDA PubMed

cell junction IEA

cytoplasm
PubMed 18029348 IDA PubMed

integral to membrane IEA

integral to plasma membrane
PubMed 8768735 TAS PubMed

plasma membrane IEA

postsynaptic density IEA

postsynaptic membrane IEA

presynaptic membrane IEA

synapse IEA

synaptosome IEA

[Top][Help]General protein information

Preferred Names: N-methyl-D-aspartate receptor subunit 2A

Names: N-methyl-D-aspartate receptor subunit 2A; OTTHUMP00000160135; OTTHUMP00000174531; NMDA receptor subtype 2A; N-methyl-D-aspartate receptor channel, subunit epsilon-1

[Top][Help]NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

mRNA and Protein(s)

NM_000833.3→NP_000824.1 N-methyl-D-aspartate receptor subunit 2A isoform 1 precursor

Description

Transcript Variant: This variant (2) is alternatively spliced at the 5' end, hence contains a different 5' UTR compared to variant 1. Transcript variants 1 and 2 encode the same isoform (1).

Source sequence(s)

AC007218,R43097,U09002,U90277

Consensus CDS

CCDS10539.1

UniProtKB/Swiss-Prot

Q12879

UniProtKB/TrEMBL

Q547U9

Conserved Domains (4) summary

cd00134 Location:458–547 Blast Score:121 Location:681–796 Blast Score:118: PBPb; Bacterial periplasmic transport systems use membrane-bound complexes and substrate-bound, membrane-associated, periplasmic binding proteins (PBPs) to transport a wide variety of substrates, such as, amino acids, peptides, sugars, vitamins and...
pfam00060 Location:554–838 Blast Score:656: Lig_chan; Ligand-gated ion channel. This family includes the four transmembrane regions of the ionotropic glutamate receptors and NMDA receptors.
cd06378 Location:32–392 Blast Score:1645: PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family. The ionotropic N-methyl-d-asparate (NMDA) subtype of glutamate receptor serves critical functions in neuronal development, functioning...

NM_001134407.1→NP_001127879.1 N-methyl-D-aspartate receptor subunit 2A isoform 1 precursor

Description

Transcript Variant: This variant (1) represents the longest transcript. Transcript variants 1 and 2 encode the same isoform (1).

Source sequence(s)

AB209695,AC007218,R43097,U09002,U90277

UniProtKB/Swiss-Prot

Q12879

UniProtKB/TrEMBL

Q547U9

UniProtKB/TrEMBL

Q59EW6

Conserved Domains (4) summary

cd00134 Location:458–547 Blast Score:121 Location:681–796 Blast Score:118: PBPb; Bacterial periplasmic transport systems use membrane-bound complexes and substrate-bound, membrane-associated, periplasmic binding proteins (PBPs) to transport a wide variety of substrates, such as, amino acids, peptides, sugars, vitamins and...
pfam00060 Location:554–838 Blast Score:656: Lig_chan; Ligand-gated ion channel. This family includes the four transmembrane regions of the ionotropic glutamate receptors and NMDA receptors.
cd06378 Location:32–392 Blast Score:1645: PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family. The ionotropic N-methyl-d-asparate (NMDA) subtype of glutamate receptor serves critical functions in neuronal development, functioning...

NM_001134408.1→NP_001127880.1 N-methyl-D-aspartate receptor subunit 2A isoform 2 precursor

Description

Transcript Variant: This variant (3) is alternatively spliced at the 3' end compared to variant 1, resulting in a frame-shift and a shorter isoform (2) with a different C-terminus compared to isoform 1.

Source sequence(s)

AK295620,BC117131,U90277

UniProtKB/Swiss-Prot

Q12879

UniProtKB/TrEMBL

Q17RZ6

Conserved Domains (4) summary

cd00134 Location:458–547 Blast Score:121 Location:681–796 Blast Score:117: PBPb; Bacterial periplasmic transport systems use membrane-bound complexes and substrate-bound, membrane-associated, periplasmic binding proteins (PBPs) to transport a wide variety of substrates, such as, amino acids, peptides, sugars, vitamins and...
pfam00060 Location:554–838 Blast Score:650: Lig_chan; Ligand-gated ion channel. This family includes the four transmembrane regions of the ionotropic glutamate receptors and NMDA receptors.
cd06378 Location:32–392 Blast Score:1643: PBP1_iGluR_NMDA_NR2; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the NR2 subunit of NMDA receptor family. The ionotropic N-methyl-d-asparate (NMDA) subtype of glutamate receptor serves critical functions in neuronal development, functioning...