GRIA3

Protein identityUniProt · HPA

UniProt accession

P42263

Gene

GRIA3

Ensembl

ENSG00000125675

Chromosome

X

Canonical length

894 aa

Protein class

Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

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 at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

894 residues, UniProt reviewed canonical sequence.

>P42263|GRIA3
     1  MARQKKMGQS VLRAVFFLVL GLLGHSHGGF PNTISIGGLF MRNTVQEHSA FRFAVQLYNT
    61  NQNTTEKPFH LNYHVDHLDS SNSFSVTNAF CSQFSRGVYA IFGFYDQMSM NTLTSFCGAL
   121  HTSFVTPSFP TDADVQFVIQ MRPALKGAIL SLLGHYKWEK FVYLYDTERG FSILQAIMEA
   181  AVQNNWQVTA RSVGNIKDVQ EFRRIIEEMD RRQEKRYLID CEVERINTIL EQVVILGKHS
   241  RGYHYMLANL GFTDILLERV MHGGANITGF QIVNNENPMV QQFIQRWVRL DEREFPEAKN
   301  APLKYTSALT HDAILVIAEA FRYLRRQRVD VSRRGSAGDC LANPAVPWSQ GIDIERALKM
   361  VQVQGMTGNI QFDTYGRRTN YTIDVYEMKV SGSRKAGYWN EYERFVPFSD QQISNDSASS
   421  ENRTIVVTTI LESPYVMYKK NHEQLEGNER YEGYCVDLAY EIAKHVRIKY KLSIVGDGKY
   481  GARDPETKIW NGMVGELVYG RADIAVAPLT ITLVREEVID FSKPFMSLGI SIMIKKPQKS
   541  KPGVFSFLDP LAYEIWMCIV FAYIGVSVVL FLVSRFSPYE WHLEDNNEEP RDPQSPPDPP
   601  NEFGIFNSLW FSLGAFMQQG CDISPRSLSG RIVGGVWWFF TLIIISSYTA NLAAFLTVER
   661  MVSPIESAED LAKQTEIAYG TLDSGSTKEF FRRSKIAVYE KMWSYMKSAE PSVFTKTTAD
   721  GVARVRKSKG KFAFLLESTM NEYIEQRKPC DTMKVGGNLD SKGYGVATPK GSALRNAVNL
   781  AVLKLNEQGL LDKLKNKWWY DKGECGSGGG DSKDKTSALS LSNVAGVFYI LVGGLGLAMM
   841  VALIEFCYKS RAESKRMKLT KNTQNFKPAP ATNTQNYATY REGYNVYGTE SVKI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRIA3 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)

0.3

Highest tissue expression

39 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GRIA3.

Disease | AllUniProt

Conditions GRIA3 is implicated in, by any mechanism.

• Intellectual developmental disorder, X-linked, syndromic, Wu type (MRXSW) MIM:300699

Disease | GeneticClinVar

40 pathogenic / likely-pathogenic of 742 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Syndromic X-linked intellectual disability 94
• Inborn genetic diseases
• GRIA3-related disorder
• Seizure
• See cases

Disease | AutoantibodyPubMed

Conditions in which antibodies against GRIA3 are reported. Each links to that disease's full target list.

• Encephalitis 20
• Epilepsy 8
• Seizures 5

ReferencesPubMed · IEDB

Publications for GRIA3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.19

gnomAD pLI

1

gnomAD missense Z

4.23

DepMap mean gene effect

0.06

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
• long-term synaptic potentiation
• modulation of chemical synaptic transmission
• protein heterotetramerization
• protein homotetramerization
• synaptic transmission, glutamatergic

Molecular functions

• AMPA glutamate receptor activity
• amyloid-beta binding
• glutamate-gated calcium ion channel activity
• 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
• dendritic spine
• endocytic vesicle membrane
• parallel fiber to Purkinje cell synapse
• plasma membrane
• postsynaptic density membrane
• postsynaptic 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
• 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 GRIA3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CACNG5
• GRIP1
• GRIP2
• PICK1