GRIA2

Protein identityUniProt · HPA

UniProt accession

P42262

Gene

GRIA2

Ensembl

ENSG00000120251

Chromosome

4

Canonical length

883 aa

Protein class

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

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. 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]

Canonical amino-acid sequenceUniProt

883 residues, UniProt reviewed canonical sequence.

>P42262|GRIA2
     1  MQKIMHISVL LSPVLWGLIF GVSSNSIQIG GLFPRGADQE YSAFRVGMVQ FSTSEFRLTP
    61  HIDNLEVANS FAVTNAFCSQ FSRGVYAIFG FYDKKSVNTI TSFCGTLHVS FITPSFPTDG
   121  THPFVIQMRP DLKGALLSLI EYYQWDKFAY LYDSDRGLST LQAVLDSAAE KKWQVTAINV
   181  GNINNDKKDE MYRSLFQDLE LKKERRVILD CERDKVNDIV DQVITIGKHV KGYHYIIANL
   241  GFTDGDLLKI QFGGANVSGF QIVDYDDSLV SKFIERWSTL EEKEYPGAHT TTIKYTSALT
   301  YDAVQVMTEA FRNLRKQRIE ISRRGNAGDC LANPAVPWGQ GVEIERALKQ VQVEGLSGNI
   361  KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVVTLT ELPSGNDTSG LENKTVVVTT
   421  ILESPYVMMK KNHEMLEGNE RYEGYCVDLA AEIAKHCGFK YKLTIVGDGK YGARDADTKI
   481  WNGMVGELVY GKADIAIAPL TITLVREEVI DFSKPFMSLG ISIMIKKPQK SKPGVFSFLD
   541  PLAYEIWMCI VFAYIGVSVV LFLVSRFSPY EWHTEEFEDG RETQSSESTN EFGIFNSLWF
   601  SLGAFMQQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM VSPIESAEDL
   661  SKQTEIAYGT LDSGSTKEFF RRSKIAVFDK MWTYMRSAEP SVFVRTTAEG VARVRKSKGK
   721  YAYLLESTMN EYIEQRKPCD TMKVGGNLDS KGYGIATPKG SSLRNAVNLA VLKLNEQGLL
   781  DKLKNKWWYD KGECGSGGGD SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR
   841  AEAKRMKVAK NAQNINPSSS QNSQNFATYK EGYNVYGIES VKI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRIA2 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

79 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GRIA2.

Disease | AllUniProt

Conditions GRIA2 is implicated in, by any mechanism.

• Neurodevelopmental disorder with language impairment and behavioral abnormalities (NEDLIB) MIM:618917

Disease | GeneticClinVar

42 pathogenic / likely-pathogenic of 242 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with language impairment and behavioral abnormalities
• Neurodevelopmental delay
• Inborn genetic diseases
• GRIA2-related disorder

ReferencesPubMed · IEDB

Publications for GRIA2 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)

0.25

gnomAD pLI

1

gnomAD missense Z

4.56

DepMap mean gene effect

0.08

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ionotropic glutamate receptor signaling pathway
• modulation of chemical synaptic transmission
• synaptic transmission, glutamatergic

Molecular functions

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

Cellular components

• AMPA glutamate receptor complex
• asymmetric synapse
• dendrite
• dendritic spine
• endocytic vesicle membrane
• excitatory synapse
• external side of plasma membrane
• neuronal cell body
• plasma membrane
• postsynapse
• postsynaptic density
• postsynaptic density membrane
• postsynaptic endocytic zone

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

• Autism spectrum disorder
• Cell membrane
• Disulfide bond
• Epilepsy
• Glycoprotein
• Intellectual disability
• Ion channel
• Ion transport
• Ligand-gated ion channel
• Lipoprotein
• Membrane
• Palmitate
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• RNA editing
• Signal
• Synapse
• Transmembrane
• Transmembrane helix
• Transport
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of GRIA2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AP4B1
• AP4E1
• AP4M1
• ATAD1
• CACNG2
• CACNG5
• GRIA1
• GRIP1
• GRIP2
• IQSEC1
• LRFN1
• NSF
• OLFM2
• PICK1
• SNX27
• SYNDIG1
• TMUB1
• ARF1
• SHISA8
• CSPG4