GRIK2

Protein identityUniProt · HPA

UniProt accession

Q13002

Gene

GRIK2

Ensembl

ENSG00000164418

Chromosome

6

Canonical length

908 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

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. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

908 residues, UniProt reviewed canonical sequence.

>Q13002|GRIK2
     1  MKIIFPILSN PVFRRTVKLL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA
    61  VNTINRNRTL LPNTTLTYDT QKINLYDSFE ASKKACDQLS LGVAAIFGPS HSSSANAVQS
   121  ICNALGVPHI QTRWKHQVSD NKDSFYVSLY PDFSSLSRAI LDLVQFFKWK TVTVVYDDST
   181  GLIRLQELIK APSRYNLRLK IRQLPADTKD AKPLLKEMKR GKEFHVIFDC SHEMAAGILK
   241  QALAMGMMTE YYHYIFTTLD LFALDVEPYR YSGVNMTGFR ILNTENTQVS SIIEKWSMER
   301  LQAPPKPDSG LLDGFMTTDA ALMYDAVHVV SVAVQQFPQM TVSSLQCNRH KPWRFGTRFM
   361  SLIKEAHWEG LTGRITFNKT NGLRTDFDLD VISLKEEGLE KIGTWDPASG LNMTESQKGK
   421  PANITDSLSN RSLIVTTILE EPYVLFKKSD KPLYGNDRFE GYCIDLLREL STILGFTYEI
   481  RLVEDGKYGA QDDANGQWNG MVRELIDHKA DLAVAPLAIT YVREKVIDFS KPFMTLGISI
   541  LYRKPNGTNP GVFSFLNPLS PDIWMYILLA YLGVSCVLFV IARFSPYEWY NPHPCNPDSD
   601  VVENNFTLLN SFWFGVGALM QQGSELMPKA LSTRIVGGIW WFFTLIIISS YTANLAAFLT
   661  VERMESPIDS ADDLAKQTKI EYGAVEDGAT MTFFKKSKIS TYDKMWAFMS SRRQSVLVKS
   721  NEEGIQRVLT SDYAFLMEST TIEFVTQRNC NLTQIGGLID SKGYGVGTPM GSPYRDKITI
   781  AILQLQEEGK LHMMKEKWWR GNGCPEEESK EASALGVQNI GGIFIVLAAG LVLSVFVAVG
   841  EFLYKSKKNA QLEKRSFCSA MVEELRMSLK CQRRLKHKPQ APVIVKTEEV INMHTFNDRR
   901  LPGKETMA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRIK2 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)

0.29

Highest tissue expression

10 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GRIK2.

Disease | AllUniProt

Conditions GRIK2 is implicated in, by any mechanism.

• Intellectual developmental disorder, autosomal recessive 6 (MRT6) MIM:611092
• Neurodevelopmental disorder with impaired language and ataxia and with or without seizures (NEDLAS) MIM:619580

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 300 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with impaired language and ataxia and with or without seizures
• Intellectual disability
• Intellectual disability, autosomal recessive 6
• Severe global developmental delay
• GRIK2-related neurodevelopmental disorder

ReferencesPubMed · IEDB

Publications for GRIK2 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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)

0.26

gnomAD pLI

1

gnomAD missense Z

2.91

DepMap mean gene effect

0.1

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

• behavioral fear response
• chemical synaptic transmission
• glutamate receptor signaling pathway
• inhibitory postsynaptic potential
• intracellular calcium ion homeostasis
• modulation of chemical synaptic transmission
• modulation of excitatory postsynaptic potential
• negative regulation of neuron apoptotic process
• negative regulation of synaptic transmission, glutamatergic
• neuron apoptotic process
• neuronal action potential
• positive regulation of neuron apoptotic process
• positive regulation of synaptic transmission
• presynaptic modulation of chemical synaptic transmission
• receptor clustering
• regulation of JNK cascade
• regulation of long-term neuronal synaptic plasticity
• regulation of short-term neuronal synaptic plasticity
• synaptic transmission, glutamatergic
• detection of cold stimulus involved in thermoception

Molecular functions

• glutamate-gated calcium ion channel activity
• glutamate-gated receptor activity
• identical protein binding
• kainate selective glutamate receptor activity
• ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
• PDZ domain binding
• scaffold protein binding
• SNARE binding
• transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
• ubiquitin conjugating enzyme binding
• ubiquitin protein ligase binding
• extracellularly glutamate-gated ion channel activity

Cellular components

• dendrite cytoplasm
• glutamatergic synapse
• hippocampal mossy fiber to CA3 synapse
• kainate selective glutamate receptor complex
• perikaryon
• plasma membrane
• postsynaptic density membrane
• presynaptic membrane
• terminal bouton
• mossy fiber rosette

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
• Epilepsy
• Glycoprotein
• Intellectual disability
• Ion channel
• Ion transport
• Isopeptide bond
• Ligand-gated ion channel
• Membrane
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• RNA editing
• Signal
• Synapse
• Transmembrane
• Transmembrane helix
• Transport
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of GRIK2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DLG4
• NETO2
• KLHL24