Gria4 glutamate ionotropic receptor AMPA type subunit 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Gria4provided by RGD
Official Full Name: glutamate ionotropic receptor AMPA type subunit 4provided by RGD
Primary source: RGD:61863
See related: Ensembl:ENSRNOG00000006957 AllianceGenome:RGD:61863
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: GluA4; GluR4; GluR-D
Summary: Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing of this gene results in transcript variants encoding different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]
Expression: Restricted expression toward (RPKM 345.6) See more
Orthologs: human mouse all
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Genomic context

Location:: 8q11

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	8	NC_086026.1 (9845421..10320021, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	8	NC_051343.1 (1562118..2035035, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	8	NC_005107.4 (1548145..2045874, complement)

Chromosome 8 - NC_086026.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hippocampal GluA2 and GluA4 protein but not corresponding mRNA and promoter methylation levels are modulated at retrieval in spatial learning of the rat.
Title: Hippocampal GluA2 and GluA4 protein but not corresponding mRNA and promoter methylation levels are modulated at retrieval in spatial learning of the rat.
Data show that PKA activation leads to insertion of GluA4 to synaptic sites with initially weak or silent AMPAR-mediated transmission. This suggests that the GluA4-mediated activation of silent synapses is a critical mechanism facilitating the functional maturation of glutamatergic circuitry during the critical period of experience-dependent fine-tuning.
Title: Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses.
The results of this study support the local translation of GluA1-4 mRNAs in dendrites of hippocampal pyramidal cells and CA1 interneurons but not in granule cells of the dentate gyrus.
Title: Differential dendritic targeting of AMPA receptor subunit mRNAs in adult rat hippocampal principal neurons and interneurons.
Here we examine whether hypoxia in the developing retina would cause activation of the AMPA GluRs and increase in Ca(2+) influx into retinal ganglion cells (RGCs) that might ultimately lead to their death.
Title: Hypoxia-induced retinal ganglion cell damage through activation of AMPA receptors and the neuroprotective effects of DNQX.
Similar to clozapine, JL 13 does not alter levels of NMDA and AMPA receptors in hippocampus and entorhinal cortex.
Title: Long-term effects of JL 13, a potential atypical antipsychotic, on ionotropic glutamate receptors.
Several interactors of GluR4 AMPA receptor subunit were id'd, most of which are novel AMPA receptor partners, namely, cytoskeleton proteins, motor proteins, RNA processing proteins which are part of neuronal RNA granules, and kinases, among others.
Title: Proteomic analysis of an interactome for long-form AMPA receptor subunits.
results show that synaptic AMPA receptors on the dendrites of the lamina III/IV neurokinin 1 receptor projection neurons contain GluR2, GluR3 and GluR4, but not GluR1 subunits
Title: Neurokinin 1 receptor-expressing projection neurons in laminae III and IV of the rat spinal cord have synaptic AMPA receptors that contain GluR2, GluR3 and GluR4 subunits.
synapse-specific AMPA-R trafficking coarsely sets and synaptic activity finely tunes transmission kinetics and integration properties at different synapses in central neurons
Title: Activity level-dependent synapse-specific AMPA receptor trafficking regulates transmission kinetics.
the GluR4 subunit exhibits a different correlation between receptor activation and ligand-binding domain cleft closure than does GluR2
Title: Correlating AMPA receptor activation and cleft closure across subunits: crystal structures of the GluR4 ligand-binding domain in complex with full and partial agonists.
Our results also provide the first evidence that postsynaptic GluR4-containing AMPA receptors are involved in spinal nociceptive transmission.
Title: Large projection neurons in lamina I of the rat spinal cord that lack the neurokinin 1 receptor are densely innervated by VGLUT2-containing axons and possess GluR4-containing AMPA receptors.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8Got3 (e-PCR)
- UniSTS:115799

UniSTS:25220 (e-PCR)
- UniSTS:25220

AW531802 (e-PCR)
- UniSTS:260537

D8Rat228 (e-PCR), detects polymorphism
- UniSTS:228293

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables AMPA glutamate receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables AMPA glutamate receptor activity	IEA Inferred from Electronic Annotation more info
enables AMPA glutamate receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables AMPA glutamate receptor activity	ISO Inferred from Sequence Orthology more info
enables AMPA glutamate receptor activity	TAS Traceable Author Statement more info	PubMed
enables glutamate-gated receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
enables ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential	ISO Inferred from Sequence Orthology more info
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 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in chemical synaptic transmission	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chemical synaptic transmission	ISO Inferred from Sequence Orthology more info
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within chemical synaptic transmission, postsynaptic	ISO Inferred from Sequence Orthology more info
involved_in ionotropic glutamate receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in modulation of chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in modulation of chemical synaptic transmission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of smooth muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of smooth muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of synaptic transmission, glutamatergic	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of postsynaptic membrane potential	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of postsynaptic membrane potential	ISO Inferred from Sequence Orthology more info
involved_in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in regulation of synapse structure or activity	TAS Traceable Author Statement more info	PubMed
involved_in response to fungicide	IEP Inferred from Expression Pattern more info	PubMed
involved_in synaptic transmission, glutamatergic	IBA Inferred from Biological aspect of Ancestor more info

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	IDA Inferred from Direct Assay more info	PubMed
part_of AMPA glutamate receptor complex	ISO Inferred from Sequence Orthology more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in dendritic spine	IBA Inferred from Biological aspect of Ancestor more info
located_in dendritic spine	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
part_of ionotropic glutamate receptor complex	TAS Traceable Author Statement more info	PubMed
part_of kainate selective glutamate receptor complex	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic density	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynaptic density membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in postsynaptic density membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic active zone membrane	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in synapse	ISO Inferred from Sequence Orthology more info
located_in terminal bouton	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: glutamate receptor 4

Names: AMPA-selective glutamate receptor 4; glutamate receptor, ionotrophic, AMPA 4; glutamate receptor, ionotropic, AMPA 4; glutamate receptor, ionotropic, AMPA4 (alpha 4)

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_001113184.1 → NP_001106655.1 glutamate receptor 4 isoform 2 precursor

See identical proteins and their annotated locations for NP_001106655.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate internal coding exon compared to transcript variant 1, and encodes an isoform (2, also known as flop isoform) that is the same length, but with a few amino acid differences compared to isoform 1. RNA editing (AGA->GGA) changes Arg765Gly.

Source sequence(s)

BC093608, BF390245, BF390683, BF413680, CB761818, CK598329, M36421, M85037

UniProtKB/Swiss-Prot

P19493, Q64241

UniProtKB/TrEMBL

A6KQJ7, G3V6W1

Related

ENSRNOP00000009542.6, ENSRNOT00000009542.6

Conserved Domains (4) summary

cd06388
Location:28 → 398

PBP1_iGluR_AMPA_GluR4; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor

cd13727
Location:414 → 795

PBP2_iGluR_AMPA_GluR4; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR4 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

pfam00060
Location:546 → 825

Lig_chan; Ligand-gated ion channel

pfam01094
Location:39 → 380

ANF_receptor; Receptor family ligand binding region
NM_001113185.1 → NP_001106656.1 glutamate receptor 4 isoform 3 precursor

See identical proteins and their annotated locations for NP_001106656.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) is missing several coding exons at the 3' end, and contains a novel 3' terminal exon compared to transcript variant 1. This results in a shorter isoform (3) with a different C-terminus compared to isoform 1.

Source sequence(s)

BC093608, CB761818, DV726151

UniProtKB/TrEMBL

A0A8I5ZUN6, Q566D4

Related

ENSRNOP00000068876.1, ENSRNOT00000078765.2

Conserved Domains (2) summary

cd06388
Location:28 → 398

PBP1_iGluR_AMPA_GluR4; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor

pfam01094
Location:39 → 380

ANF_receptor; Receptor family ligand binding region
NM_017263.2 → NP_058959.2 glutamate receptor 4 isoform 1 precursor

See identical proteins and their annotated locations for NP_058959.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1 (also known as flip isoform). RNA editing (AGA->GGA) changes Arg765Gly.

Source sequence(s)

BC093608, BF390245, BF390683, BF413680, CB761818, M38063, M85037

UniProtKB/Swiss-Prot

P19493, Q64241

UniProtKB/TrEMBL

A0A0G2JU28, A6KQJ6

Related

ENSRNOP00000068940.1, ENSRNOT00000081171.2

Conserved Domains (4) summary

cd06388
Location:28 → 398

PBP1_iGluR_AMPA_GluR4; N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor

cd13727
Location:414 → 795

PBP2_iGluR_AMPA_GluR4; The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR4 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily

pfam00060
Location:546 → 825

Lig_chan; Ligand-gated ion channel

pfam01094
Location:39 → 380

ANF_receptor; Receptor family ligand binding region

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086026.1 Reference GRCr8

Range

9845421..10320021 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063265032.1 → XP_063121102.1 glutamate receptor 4 isoform X4
XM_063265033.1 → XP_063121103.1 glutamate receptor 4 isoform X5
XM_063265031.1 → XP_063121101.1 glutamate receptor 4 isoform X1
XM_017595511.3 → XP_017451000.1 glutamate receptor 4 isoform X2

UniProtKB/Swiss-Prot

P19493, Q64241
XM_017595510.3 → XP_017450999.1 glutamate receptor 4 isoform X3

UniProtKB/Swiss-Prot

P19493, Q64241
XM_039080969.2 → XP_038936897.1 glutamate receptor 4 isoform X6

UniProtKB/Swiss-Prot

P19493, Q64241

Conserved Domains (2) summary

cd06388
Location:28 → 400

PBP1_iGluR_AMPA_GluR4; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the GluR4 subunit of the AMPA receptor

cl21456
Location:414 → 765

Periplasmic_Binding_Protein_Type_2; Type 2 periplasmic binding fold superfamily