GRIA2 glutamate ionotropic receptor AMPA type subunit 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRIA2provided by HGNC
Official Full Name: glutamate ionotropic receptor AMPA type subunit 2provided by HGNC
Primary source: HGNC:HGNC:4572
See related: Ensembl:ENSG00000120251 MIM:138247; AllianceGenome:HGNC:4572
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: GLUR2; GLURB; GluA2; HBGR2; NEDLIB; gluR-2; gluR-B; GluR-K2
Summary: Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. These channels are assembled from 4 related subunits, GRIA1-4. The subunit encoded by this gene (GRIA2) is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to render the channel impermeable to Ca(2+). Human and animal studies suggest that pre-mRNA editing is essential for brain function, and defective GRIA2 RNA editing at the Q/R site may be relevant to amyotrophic lateral sclerosis (ALS) etiology. Alternative splicing, resulting in transcript variants encoding different isoforms, (including the flip and flop isoforms that vary in their signal transduction properties), has been noted for this gene. [provided by RefSeq, Jul 2008]
Expression: Restricted expression toward brain (RPKM 36.3) See more
Orthologs: mouse all
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Genomic context

Location:: 4q32.1

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (157220120..157366075)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (160550597..160711660)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (158141272..158287227)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Internalization of AMPA-type Glutamate Receptor in the MIN6 Pancreatic beta-cell Line.
Title: Internalization of AMPA-type Glutamate Receptor in the MIN6 Pancreatic β-cell Line.
Nanoscale mobility of resting AMPA receptors predetermines responsiveness to neurotransmitter, allosteric anions and TARP auxiliary subunits. Mobility at rest is regulated by alternative splicing of the flip/flop cassette of the ligand-binding domain, which controls motions in the distant AMPA receptor N-terminal domain (NTD).
Title: Nanoscale Mobility of the Apo State and TARP Stoichiometry Dictate the Gating Behavior of Alternatively Spliced AMPA Receptors.
he current study investigated novel curcumin derivatives on the biophysical properties of AMPA receptors, specifically on the homomeric GluA2 and the heteromeric GluA2/A3 subunits and assessed for inhibitory actions
Title: Inhibition and assessment of the biophysical gating properties of GluA2 and GluA2/A3 AMPA receptors using curcumin derivatives.
Study reports heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability and neurodevelopmental abnormalities. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification.
Title: AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.
Reduced expression of Gria2 increased Ca(2+) influx through Ca(2+)-permeable AMPA receptors which increased the vulnerability and affected the differentiation and migration of distinct cell populations and interfered with normal circuit formation in fragile X syndrome.
Title: Functional changes of AMPA responses in human induced pluripotent stem cell-derived neural progenitors in fragile X syndrome.
a dramatic reduction of expression of the GluA2 subunit occurs concomitantly with its hyper-phosphorylation on Serine 880 and increased ubiquitination. Consequently, Cdkl5 silencing skews the composition of membrane-inserted AMPA-Rs towards the GluA2-lacking calcium-permeable form
Title: The antidepressant tianeptine reverts synaptic AMPA receptor defects caused by deficiency of CDKL5.
This review showed that the mutation GR1A protein associate with Obsessive-compulsive disorder.
Title: Obsessive-compulsive disorder, which genes? Which functions? Which pathways? An integrated holistic view regarding OCD and its complex genetic etiology.
Measured the expression of GRIA2 and GABRA1 in patients with methamphetamine-use disorder. Also examined whether miR-181a down-regulates GRIA2 and GABRA1 in a cell-based assay. We further examined the effects of chronic methamphetamine exposure on the expression of miR-181a, GRIA2 and GABRA1. The results demonstrated that serum GRIA2 is higher in patients with methamphetamine-use disorder than in healthy controls.
Title: miR-181a is a negative regulator of GRIA2 in methamphetamine-use disorder.
This study demonstrated that a significant decrease in the protein level of GluN2A in major depression disorder.
Title: Zinc transporters protein level in postmortem brain of depressed subjects and suicide victims.
both the intracellular C-terminal domain (CTD) and the loop region between the M1 and M2 helices move during activation and the CTD is detached from the membrane
Title: Structural rearrangement of the intracellular domains during AMPA receptor activation.

Submit: New GeneRIF Correction See all GeneRIFs (62)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Neurodevelopmental disorder with language impairment and behavioral abnormalities MedGen: C5394502 OMIM: 618917 GeneReviews: GRIA2-Related Neurodevelopmental Disorder	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of glutamate receptor, ionotropic, AMPA 2 (GRIA2) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D4S2841 (e-PCR)
- UniSTS:15410

RH25939 (e-PCR)
- UniSTS:89940

SHGC-67298 (e-PCR)
- UniSTS:89435

SHGC-106423 (e-PCR)
- UniSTS:169834

BB085555 (e-PCR)
- UniSTS:207513

SHGC-30802 (e-PCR)
- UniSTS:24753

D4S2322 (e-PCR)
- UniSTS:75735

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables AMPA glutamate receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables AMPA glutamate receptor activity	ISS Inferred from Sequence or Structural Similarity more info
contributes_to AMPA glutamate receptor activity	NAS Non-traceable Author Statement more info	PubMed
enables amyloid-beta binding	ISS Inferred from Sequence or Structural Similarity more info
enables amyloid-beta binding	NAS Non-traceable Author Statement more info	PubMed
enables glutamate-gated receptor activity	IDA Inferred from Direct Assay 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

Process	Evidence Code	Pubs
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in ionotropic glutamate receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in modulation of chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of postsynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic transmission, glutamatergic	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of AMPA glutamate receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of AMPA glutamate receptor complex	ISS Inferred from Sequence or Structural Similarity more info
located_in asymmetric synapse	ISS Inferred from Sequence or Structural Similarity more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
is_active_in dendritic spine	IBA Inferred from Biological aspect of Ancestor more info
located_in dendritic spine	NAS Non-traceable Author Statement more info	PubMed
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in excitatory synapse	NAS Non-traceable Author Statement more info	PubMed
located_in external side of plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in neuronal cell body	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	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynapse	TAS Traceable Author Statement more info	PubMed
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 endocytic zone	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: glutamate receptor 2

Names: AMPA receptor subunit GluA2; AMPA-selective glutamate receptor 2; glutamate receptor, ionotropic, AMPA 2

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_000826.6 → NP_000817.5 glutamate receptor 2 isoform 1 precursor

Status: REVIEWED

Source sequence(s)

AC079233, AC112240

Consensus CDS

CCDS3797.1

UniProtKB/TrEMBL

A0A994J4G8

Related

ENSP00000296526.7, ENST00000296526.12

Conserved Domains (2) summary

cd13715
Location:413 → 794

PBP2_iGluR_AMPA; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtypes of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

cd06389
Location:28 → 398

PBP1_iGluR_AMPA_GluR2; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the GluR2 subunit of the AMPA receptor
NM_001083619.3 → NP_001077088.2 glutamate receptor 2 isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AC079233, AC112240

Consensus CDS

CCDS43274.1

UniProtKB/Swiss-Prot

A8MT92, I6L997, P42262, Q96FP6

UniProtKB/TrEMBL

A0A994J4G8

Related

ENSP00000264426.9, ENST00000264426.14

Conserved Domains (2) summary

cd13715
Location:413 → 794

PBP2_iGluR_AMPA; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtypes of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

cd06389
Location:28 → 398

PBP1_iGluR_AMPA_GluR2; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the GluR2 subunit of the AMPA receptor
NM_001083620.3 → NP_001077089.2 glutamate receptor 2 isoform 3

Status: REVIEWED

Source sequence(s)

AC079233, AC112240

Consensus CDS

CCDS43275.1

UniProtKB/TrEMBL

B7Z288

Related

ENSP00000377403.2, ENST00000393815.6

Conserved Domains (2) summary

cd13715
Location:366 → 747

PBP2_iGluR_AMPA; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtypes of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

cl10011
Location:1 → 351

Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily
NM_001379000.3 → NP_001365929.3 glutamate receptor 2 isoform 4

Status: REVIEWED

Source sequence(s)

AC079233, AC112240

Consensus CDS

CCDS93659.1

UniProtKB/TrEMBL

A0A994J4F1, B7Z288

Related

ENSP00000515446.1, ENST00000703717.1

Conserved Domains (2) summary

cd13715
Location:366 → 747

PBP2_iGluR_AMPA; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtypes of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

cl10011
Location:1 → 351

Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily
NM_001379001.3 → NP_001365930.3 glutamate receptor 2 isoform 3

Status: REVIEWED

Source sequence(s)

AC079233, AC112240

Consensus CDS

CCDS43275.1

UniProtKB/TrEMBL

B7Z288

Related

ENSP00000426845.1, ENST00000507898.5

Conserved Domains (2) summary

cd13715
Location:366 → 747

PBP2_iGluR_AMPA; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtypes of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

cl10011
Location:1 → 351

Periplasmic_Binding_Protein_type1; Type 1 periplasmic binding fold superfamily

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

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

157220120..157366075

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047450131.1 → XP_047306087.1 glutamate receptor 2 isoform X1

UniProtKB/TrEMBL

A0A994J4F1

RNA

XR_007096394.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

160550597..160711660

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054349815.1 → XP_054205790.1 glutamate receptor 2 isoform X1

UniProtKB/TrEMBL

A0A994J4F1
XM_054349816.1 → XP_054205791.1 glutamate receptor 2 isoform X1

UniProtKB/TrEMBL

A0A994J4F1
XM_054349814.1 → XP_054205789.1 glutamate receptor 2 isoform X1

UniProtKB/TrEMBL

A0A994J4F1
XM_054349817.1 → XP_054205792.1 glutamate receptor 2 isoform X2