GRIA4

Protein identityUniProt · HPA

UniProt accession

P48058

Gene

GRIA4

Ensembl

ENSG00000152578

Chromosome

11

Canonical length

902 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Focal adhesion sites

Secretome location

Intracellular and membrane

Quaternary structure

Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

902 residues, UniProt reviewed canonical sequence.

>P48058|GRIA4
     1  MRIISRQIVL LFSGFWGLAM GAFPSSVQIG GLFIRNTDQE YTAFRLAIFL HNTSPNASEA
    61  PFNLVPHVDN IETANSFAVT NAFCSQYSRG VFAIFGLYDK RSVHTLTSFC SALHISLITP
   121  SFPTEGESQF VLQLRPSLRG ALLSLLDHYE WNCFVFLYDT DRGYSILQAI MEKAGQNGWH
   181  VSAICVENFN DVSYRQLLEE LDRRQEKKFV IDCEIERLQN ILEQIVSVGK HVKGYHYIIA
   241  NLGFKDISLE RFIHGGANVT GFQLVDFNTP MVIKLMDRWK KLDQREYPGS ETPPKYTSAL
   301  TYDGVLVMAE TFRSLRRQKI DISRRGNAGD CLANPAAPWG QGIDMERTLK QVRIQGLTGN
   361  VQFDHYGRRV NYTMDVFELK STGPRKVGYW NDMDKLVLIQ DVPTLGNDTA AIENRTVVVT
   421  TIMESPYVMY KKNHEMFEGN DKYEGYCVDL ASEIAKHIGI KYKIAIVPDG KYGARDADTK
   481  IWNGMVGELV YGKAEIAIAP LTITLVREEV IDFSKPFMSL GISIMIKKPQ KSKPGVFSFL
   541  DPLAYEIWMC IVFAYIGVSV VLFLVSRFSP YEWHTEEPED GKEGPSDQPP NEFGIFNSLW
   601  FSLGAFMQQG CDISPRSLSG RIVGGVWWFF TLIIISSYTA NLAAFLTVER MVSPIESAED
   661  LAKQTEIAYG TLDSGSTKEF FRRSKIAVYE KMWTYMRSAE PSVFTRTTAE GVARVRKSKG
   721  KFAFLLESTM NEYIEQRKPC DTMKVGGNLD SKGYGVATPK GSSLRTPVNL AVLKLSEAGV
   781  LDKLKNKWWY DKGECGPKDS GSKDKTSALS LSNVAGVFYI LVGGLGLAML VALIEFCYKS
   841  RAEAKRMKLT FSEAIRNKAR LSITGSVGEN GRVLTPDCPK AVHTGTAIRQ SSGLAVIASD
   901  LP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRIA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

3

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

60 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GRIA4.

Disease | AllUniProt

Conditions GRIA4 is implicated in, by any mechanism.

• Neurodevelopmental disorder with or without seizures and gait abnormalities (NEDSGA) MIM:617864

Disease | GeneticClinVar

11 pathogenic / likely-pathogenic of 266 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with or without seizures and gait abnormalities
• Intellectual disability
• See cases
• Inborn genetic diseases
• Obesity

Disease | ImmuneIEDB

Conditions an epitope on GRIA4 was assayed in.

• glioblastoma T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.43

gnomAD pLI

0.02

gnomAD missense Z

3.42

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• glutamate receptor signaling pathway
• modulation of chemical synaptic transmission
• negative regulation of smooth muscle cell apoptotic process
• synaptic transmission, glutamatergic

Molecular functions

• AMPA glutamate receptor activity
• amyloid-beta binding
• glutamate-gated receptor activity
• ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
• transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential

Cellular components

• AMPA glutamate receptor complex
• dendrite
• dendritic spine
• endocytic vesicle membrane
• extracellular vesicle
• neuronal cell body
• plasma membrane
• postsynaptic density membrane

Protein domainsUniProt · Pfam · InterPro

• Ionotropic glutamate receptor, C-terminal
• Ionotropic glutamate receptor, metazoa
• Receptor, ligand binding region
• Ionotropic glutamate receptor
• Ionotropic glutamate receptor, L-glutamate and glycine-binding domain
• Periplasmic binding protein-like I
• Ligand-gated ion channel
• Receptor family ligand binding region
• Ligated ion channel L-glutamate- and glycine-binding site

KeywordsUniProt

• Cell membrane
• Cell projection
• Disulfide bond
• Glycoprotein
• Intellectual disability
• Ion channel
• Ion transport
• Ligand-gated ion channel
• Lipoprotein
• Membrane
• Palmitate
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• Signal
• Synapse
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of GRIA4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CACNG5
• EPB41L1
• PICK1
• PRKCG