Human Gene GRIA4 (ENST00000282499.10) from GENCODE V44
  Description: Homo sapiens glutamate ionotropic receptor AMPA type subunit 4 (GRIA4), transcript variant 1, mRNA. (from RefSeq NM_000829)
RefSeq Summary (NM_000829): 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. Some haplotypes of this gene show a positive association with schizophrenia. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000282499.10
Gencode Gene: ENSG00000152578.15
Transcript (Including UTRs)
   Position: hg38 chr11:105,610,073-105,982,090 Size: 372,018 Total Exon Count: 17 Strand: +
Coding Region
   Position: hg38 chr11:105,610,998-105,979,739 Size: 368,742 Coding Exon Count: 16 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr11:105,610,073-105,982,090)mRNA (may differ from genome)Protein (902 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Glutamate receptor 4; Short=GluR-4; Short=GluR4; AltName: Full=AMPA-selective glutamate receptor 4; AltName: Full=GluR-D; AltName: Full=Glutamate receptor ionotropic, AMPA 4; Short=GluA4; Flags: Precursor;
FUNCTION: Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L- glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist.In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
SUBUNIT: Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Interacts with EPB41L1 via its C-terminus (By similarity). Found in a complex with GRIA1, GRIA2, GRIA3, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5 and PRKCG (By similarity).
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Cell projection, dendrite. Note=Interaction with CNIH2, CNIH3 and PRKCG promotes cell surface expression (By similarity).
PTM: Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-611 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-837 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity).
PTM: Phosphorylated at Ser-862 by PRKCG; phosphorylation increases plasma membrane-associated GRI4 expression (By similarity).
MISCELLANEOUS: The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate.
SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA4 subfamily.

-  Primer design for this transcript

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: GRIA4
Diseases sorted by gene-association score: schizophrenia (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 22.35 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 101.75 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -191.10446-0.428 Picture PostScript Text
3' UTR -601.502351-0.256 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001828 - ANF_lig-bd_rcpt
IPR019594 - Glu_rcpt_Glu/Gly-bd
IPR001320 - Iontro_glu_rcpt
IPR001508 - NMDA_rcpt

Pfam Domains:
PF01094 - Receptor family ligand binding region
PF00060 - Ligand-gated ion channel
PF10613 - Ligated ion channel L-glutamate- and glycine-binding site

ModBase Predicted Comparative 3D Structure on P48058
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004970 ionotropic glutamate receptor activity
GO:0004971 AMPA glutamate receptor activity
GO:0005216 ion channel activity
GO:0005231 excitatory extracellular ligand-gated ion channel activity
GO:0005234 extracellular-glutamate-gated ion channel activity
GO:0038023 signaling receptor activity

Biological Process:
GO:0006811 ion transport
GO:0007215 glutamate receptor signaling pathway
GO:0034220 ion transmembrane transport
GO:0035235 ionotropic glutamate receptor signaling pathway
GO:0060079 excitatory postsynaptic potential

Cellular Component:
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030054 cell junction
GO:0030425 dendrite
GO:0030666 endocytic vesicle membrane
GO:0032281 AMPA glutamate receptor complex
GO:0042995 cell projection
GO:0043025 neuronal cell body
GO:0043197 dendritic spine
GO:0045202 synapse
GO:0045211 postsynaptic membrane
GO:1903561 extracellular vesicle

-  Descriptions from all associated GenBank mRNAs
  BC045546 - Homo sapiens glutamate receptor, ionotrophic, AMPA 4, mRNA (cDNA clone IMAGE:5265048), complete cds.
BC142654 - Homo sapiens glutamate receptor, ionotrophic, AMPA 4, mRNA (cDNA clone IMAGE:40148067), complete cds.
BC150209 - Homo sapiens glutamate receptor, ionotrophic, AMPA 4, mRNA (cDNA clone IMAGE:40148893), complete cds.
AB209092 - Homo sapiens mRNA for glutamate receptor, ionotrophic variant protein.
BC146816 - Homo sapiens glutamate receptor, ionotrophic, AMPA 4, mRNA (cDNA clone IMAGE:8860412), complete cds.
BC167786 - Synthetic construct Homo sapiens clone IMAGE:100068176, MGC:195793 glutamate receptor, ionotrophic, AMPA 4 (GRIA4) mRNA, encodes complete protein.
U16129 - Human glutamate receptor (GluR4) mRNA, complete cds.
BC114549 - Homo sapiens glutamate receptor, ionotrophic, AMPA 4, mRNA (cDNA clone IMAGE:40034913), partial cds.
BC015199 - Homo sapiens glutamate receptor, ionotrophic, AMPA 4, mRNA (cDNA clone IMAGE:4277248), with apparent retained intron.
BC035610 - Homo sapiens glutamate receptor, ionotrophic, AMPA 4, mRNA (cDNA clone IMAGE:5199898), with apparent retained intron.
FJ947075 - Homo sapiens clone 204-H glutamate receptor 4 variant (GRIA4) mRNA, partial cds, alternatively spliced.
FJ947076 - Homo sapiens clone 604-o-A glutamate receptor 4 variant (GRIA4) mRNA, partial cds, alternatively spliced.
JN547407 - Homo sapiens AMPA-selective glutamate receptor 4 (GRIA4) mRNA, partial cds, alternatively spliced.
AK311193 - Homo sapiens cDNA, FLJ18235.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein P48058 (Reactome details) participates in the following event(s):

R-HSA-420977 Ca permeable AMPA receptor ligand binding
R-HSA-399712 Activation of Ca permeable AMPA receptors
R-HSA-416320 Trafficking of GluR1-containing AMPA receptors
R-HSA-420980 Activation of Ca permeable AMPA receptors
R-HSA-416985 Trafficking of GluR2-containing AMPA receptors to synapse
R-HSA-420975 Ca impermeable AMPA receptor ligand binding
R-HSA-438037 Membrane depolarization upon activation of Ca impermeable AMPA receptors
R-HSA-399711 Activation of Ca impermeable AMPA receptors
R-HSA-416639 Trafficking of GluR2-containing AMPA receptors to extrasynaptic sites
R-HSA-421007 Endocytosis of Ca impermeable AMPA receptors
R-HSA-8849881 SALM2 associate with AMPA and NMDA receptors
R-HSA-432162 Unblocking of NMDA receptor
R-HSA-399710 Activation of AMPA receptors
R-HSA-399719 Trafficking of AMPA receptors
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors
R-HSA-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-HSA-8849932 Synaptic adhesion-like molecules
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity
R-HSA-442755 Activation of NMDA receptor and postsynaptic events
R-HSA-6794362 Protein-protein interactions at synapses
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112316 Neuronal System
R-HSA-112315 Transmission across Chemical Synapses

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000282499.1, ENST00000282499.2, ENST00000282499.3, ENST00000282499.4, ENST00000282499.5, ENST00000282499.6, ENST00000282499.7, ENST00000282499.8, ENST00000282499.9, GLUR4, GRIA4_HUMAN, NM_000829, P48058, Q86XE8, uc001pix.1, uc001pix.2, uc001pix.3
UCSC ID: ENST00000282499.10
RefSeq Accession: NM_000829
Protein: P48058 (aka GRIA4_HUMAN or GLR4_HUMAN)
CCDS: CCDS8333.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.