Affinage

GRIK5

Glutamate receptor ionotropic, kainate 5 · UniProt Q16478

Round 2 corrected
Length
980 aa
Mass
109.3 kDa
Annotated
2026-04-28
114 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRIK5 encodes GluK5 (KA2), a high-affinity kainate receptor subunit that binds kainate with ~15 nM affinity but cannot form functional homomeric channels; it obligately co-assembles with GluK1–3 subunits—preferentially GluK2 in brain—to produce heteromeric receptors with distinct biophysical properties including AMPA responsiveness, slow deactivation kinetics matching native KAR-EPSCs, and bell-shaped concentration-response curves arising from subunit-specific high- and low-affinity agonist sites (PMID:1373632, PMID:18562611, PMID:20026616). ER retention of GluK5 homomers is enforced by arginine-rich and di-leucine motifs in its C-terminus and an intracellular loop, recognized by COPI coat proteins; heteromeric assembly masks these signals (aided by SAP97/CASK engagement), and ligand occupancy of the GluK5 binding site serves as a quality-control checkpoint for forward trafficking (PMID:12878702, PMID:16595684, PMID:15583001, PMID:30339823). At synapses, GluK5 is scaffolded by PSD-95 family members via its SH3/GK-binding C-terminal domain, and CaMKII-dependent phosphorylation of three GluK5 C-terminal residues increases lateral receptor mobility and drives kainate receptor long-term depression at mossy fiber–CA3 synapses (PMID:9808460, PMID:23288040). Beyond ionotropic neurotransmission, GluK5 organizes photoreceptor ribbon synapse architecture, tonically regulates neuroblast migration speed, and contributes to vascular integrity in the eye (PMID:28235022, PMID:18565997, PMID:30827500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 High

    The fundamental question of whether KA2 functions as an ion channel was resolved: GluK5 binds kainate with high affinity but requires co-assembly with GluK1–3 subunits to produce functional channels, establishing its obligate heteromeric nature and showing it confers AMPA sensitivity and altered desensitization to heteromers.

    Evidence Heterologous expression in oocytes/HEK cells with electrophysiology and radioligand binding across multiple subunit combinations

    PMID:1373632

    Open questions at the time
    • Stoichiometry of heteromeric assemblies unknown
    • Mechanism of ER retention not yet addressed
    • Native receptor composition in specific brain regions undetermined
  2. 1994 High

    Whether GluK5/GluK2 heteromers exist in native brain was established by reciprocal co-immunoprecipitation from rat brain membranes, confirming the GluR6/KA2 complex as a physiologically relevant entity.

    Evidence Reciprocal co-immunoprecipitation from HEK cells and native rat brain membranes with deglycosylation analysis

    PMID:8288598

    Open questions at the time
    • Subunit stoichiometry within native complexes unknown
    • Regional and cell-type specificity of heteromer expression not resolved
  3. 1996 High

    How GluK5 alters the biophysical fingerprint of heteromeric channels was quantified: GluK5 incorporation increases unitary conductance of edited GluK2(R)/GluK5 channels ~2–3-fold, modifies burst kinetics, and confers AMPA sensitivity, explaining functional diversity of native KARs.

    Evidence Single-channel and noise analysis patch-clamp electrophysiology on defined recombinant channels in HEK293 cells

    PMID:8730589 PMID:8836240

    Open questions at the time
    • Whether these biophysical properties match native synaptic KAR-EPSCs not yet tested
    • Structural basis for conductance increase unknown
  4. 1997 High

    Native KARs in trigeminal ganglion neurons were shown to match recombinant GluR5(R)/KA2 heteromers pharmacologically and kinetically, providing the first strong evidence that GluK5-containing heteromers are the predominant native KAR in a defined neuronal population.

    Evidence RT-PCR plus patch-clamp electrophysiology and pharmacological profiling in acutely dissociated trigeminal neurons

    PMID:9254673

    Open questions at the time
    • Heteromeric identity inferred pharmacologically rather than by direct biochemical isolation from these neurons
  5. 1998 High

    The scaffolding mechanism linking GluK5 to the postsynaptic density was identified: PSD-95/SAP90 binds GluK5's C-terminus via SH3 and GK domains (not PDZ domains), and this interaction modulates channel desensitization, establishing how GluK5 is anchored and regulated at synapses.

    Evidence Co-immunoprecipitation from neurons, yeast two-hybrid, and electrophysiology in transfected cells

    PMID:9808460

    Open questions at the time
    • Phosphorylation-dependent regulation of this interaction not yet explored
    • Whether SAP90 binding is required for synaptic localization in vivo untested
  6. 2003 High

    The mechanism preventing GluK5 homomeric surface expression was dissected: arginine-rich and di-leucine C-terminal motifs plus an intracellular loop signal mediate ER retention; heteromeric assembly masks these signals. In parallel, GluK5 knockout mice revealed that GluK5 sets presynaptic agonist affinity and postsynaptic decay kinetics at mossy fiber–CA3 synapses.

    Evidence Surface biotinylation, mutagenesis, immunofluorescence, electrophysiology in transfected cells and neurons; hippocampal slice electrophysiology in KA2−/− mice

    PMID:12533602 PMID:12878702 PMID:12950450

    Open questions at the time
    • Identity of the coat protein machinery mediating ER retention not yet known
    • Role of GluK5 agonist binding in trafficking not addressed
  7. 2004 High

    A quality-control checkpoint was identified: intact glutamate binding to the GluK5 ligand-binding domain (T675) is required for surface delivery of heteromeric GluK2/GluK5 receptors, even though assembly with GluK2 still occurs, revealing that agonist occupancy at GluK5 gates forward trafficking independently of assembly.

    Evidence Site-directed mutagenesis of binding residue T675, surface biotinylation, radioligand binding, and pulse-chase degradation in transfected cells and neurons

    PMID:15583001

    Open questions at the time
    • Whether endogenous ER glutamate concentration is sufficient for this checkpoint in vivo unknown
    • ER chaperone partners mediating the checkpoint unidentified
  8. 2006 High

    The molecular machinery enforcing GluK5 ER retention was identified as COPI vesicle coat proteins, which directly bind the arginine-rich signal; heteromeric assembly displaces COPI and recruits 14-3-3 proteins for forward trafficking. Additionally, GluK6 (not GluK5) knockout specifically abolishes native GluK5 surface expression, confirming GluK2/GluK6 as the obligate partner for ER egress in vivo.

    Evidence Peptide pulldown, co-immunoprecipitation from cerebellum, surface expression assays, analysis of GluR5 and GluR6 KO mice

    PMID:16595684 PMID:16807331

    Open questions at the time
    • Whether 14-3-3 binding is phosphorylation-dependent not resolved
    • Which COPI subunit(s) directly contact the arginine motif not determined at atomic resolution
  9. 2008 High

    How GluK5 shapes synaptic current kinetics was resolved: GluK2/GluK5 heteromers produce slowly deactivating currents matching native KAR-EPSCs, with kinetic modeling attributing this to stabilization of partially liganded open states by GluK5, directly explaining the characteristically slow KAR-EPSC decay. Separately, GluK5-containing receptors were shown to tonically restrain neuroblast migration speed in the SVZ.

    Evidence Fast glutamate application to outside-out patches with Markov modeling; time-lapse migration imaging and calcium imaging in whole-mount SVZ with selective pharmacology

    PMID:18562611 PMID:18565997

    Open questions at the time
    • In vivo confirmation that GluK5 determines KAR-EPSC kinetics at defined synapses beyond mossy fiber–CA3 not shown
    • Signaling pathway linking GluK5 activation to migration speed regulation unknown
  10. 2010 High

    Structural determinants of obligate heteromeric assembly were revealed: the GluK5 ATD crystal structure showed a unique R1 dimer interface incompatible with stable homodimerization, and subsequent GluK2/GluK5 ATD heterodimer structures demonstrated ~32,000-fold preferential heterodimerization (Kd ~11 nM), providing the thermodynamic basis for obligate heteromeric assembly.

    Evidence X-ray crystallography of GluK5 ATD homo- and heterodimers; analytical ultracentrifugation measuring homo- vs. heterodimer affinities

    PMID:20951142 PMID:21791290

    Open questions at the time
    • Full-length heteromeric receptor structure not yet available
    • How ATD heterodimerization communicates to transmembrane domain assembly unclear
  11. 2012 High

    The stoichiometry question was definitively answered: GluK2/GluK5 receptors assemble with 2:2 stoichiometry at the plasma membrane, as measured by single-molecule subunit counting, though later work showed 3:1 stoichiometry and tri/tetra-heteromeric assemblies are also possible.

    Evidence Single-molecule fluorescence photobleaching step-counting in live cells; multi-color single-molecule imaging

    PMID:22509486 PMID:34706237

    Open questions at the time
    • Functional consequences of 3:1 vs. 2:2 stoichiometry on channel properties not systematically characterized
    • Whether stoichiometric flexibility is regulated in vivo unknown
  12. 2013 High

    A synaptic plasticity mechanism was established: CaMKII directly phosphorylates three GluK5 C-terminal residues, increasing lateral mobility of KARs away from synapses (likely by disrupting PSD-95 binding) and driving KAR long-term depression at mossy fiber synapses—confirmed by molecular replacement with phosphodeficient GluK5.

    Evidence In vitro kinase assay, single-particle tracking of lateral mobility, molecular replacement in neurons, hippocampal slice LTD recordings

    PMID:23288040

    Open questions at the time
    • Identity of the phosphatase(s) reversing CaMKII phosphorylation unknown
    • Whether this mechanism operates at synapses other than mossy fiber–CA3 not tested
  13. 2017 Medium

    A non-ionotropic structural role for GluK5 was discovered: GluK5 localizes presynaptically to rod photoreceptor ribbon synapses, and GluK5 knockout disrupts ribbon synapse architecture, revealing a function independent of postsynaptic glutamate signaling.

    Evidence Double-immunofluorescence and electron microscopy in wild-type and GluK5 KO mouse retina

    PMID:28235022

    Open questions at the time
    • Molecular partners mediating GluK5's structural role at ribbons unidentified
    • Whether this is ion-channel-independent confirmed functionally
    • Single lab observation
  14. 2018 Medium

    The ER retention masking mechanism was refined: SAP97 (in an extended conformation facilitated by CASK) rather than GluK2 co-assembly per se masks the GluK5 C-terminal retention signals, and these signals double as dendritic sorting determinants, reframing ER retention as a targeting mechanism for local dendritic secretory trafficking.

    Evidence Co-immunoprecipitation, in vitro binding, surface expression assays, live-cell imaging of dendritic secretory pathway in neurons

    PMID:30339823

    Open questions at the time
    • Relative contributions of SAP97/CASK masking vs. heteromeric assembly masking in vivo not quantified
    • Whether dendritic sorting is synapse-type specific unknown
  15. 2023 Medium

    Subunit-specific conformational dynamics underlying partial agonism were resolved: in GluK2/GluK5 receptors, AMPA produces intermediate cleft closure at GluK2 but not GluK5, and fails to decouple the agonist-binding domain dimer interface, establishing distinct conformational contributions of each subunit to partial vs. full agonism.

    Evidence Single-molecule FRET with subunit-specific labeling on purified full-length GluK2/GluK5 receptors

    PMID:37526035

    Open questions at the time
    • Cryo-EM structures of partial vs. full agonist-bound states not available
    • Whether these conformational differences extend to other partial agonists untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the high-resolution full-length structure of a GluK2/GluK5 heteromeric receptor in defined functional states; the molecular mechanism by which GluK5 organizes photoreceptor ribbon synapses; whether variable stoichiometries (2:2 vs. 3:1) are regulated and functionally distinct in vivo; and how GluK5 contributes to vascular integrity and non-neuronal phenotypes.
  • No full-length heteromeric cryo-EM structure published
  • Non-ionotropic signaling mechanisms of GluK5 uncharacterized
  • Vascular phenotype observed only in zebrafish with morpholino knockdown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0060089 molecular transducer activity 3
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005886 plasma membrane 4
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-9609507 Protein localization 5 R-HSA-162582 Signal Transduction 2
Partners
CASKDLG1DLG3DLG4GRIK1GRIK2GRIK3
Complex memberships
GluK2/GluK5 heteromeric kainate receptorGluK5-PSD-95/SAP90 complexGluR6/KA2-PSD95-MLK3 signaling module

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 GluK5 (KA-2) binds [3H]kainate with high affinity (KD ~15 nM) but does not form functional homomeric channels; coexpression with GluR5(R) or GluR6 subunits produces agonist-gated currents, demonstrating that GluK5 requires heteromeric assembly with low-affinity subunits for channel function. Heteromeric GluR5(Q)/KA-2 channels show more rapid desensitization and altered current-voltage relations compared to GluR5(Q) homomers, and GluR6/KA-2 channels gain responsiveness to AMPA. Heterologous expression in Xenopus oocytes/HEK cells, electrophysiology, radioligand binding Neuron High 1373632
1994 GluK5 (KA2) and GluR6 subunits co-assemble into heteromeric complexes in transfected HEK cells and in native rat brain membranes, as demonstrated by reciprocal co-immunoprecipitation. KA2 runs at ~123 kDa (glycosylated) and ~109 kDa (deglycosylated), confirming it is a glycoprotein. Antibodies to GluR6 co-immunoprecipitate KA2 and vice versa from detergent-solubilized brain membranes, establishing the GluR6/KA2 heteromeric complex as a native brain entity. Co-immunoprecipitation, immunoblot, deglycosylation assay, [3H]kainate binding The Journal of biological chemistry High 8288598
1994 GRIK5 (encoding KA2) maps to human chromosome 19q13.2, mouse chromosome 7, and rat chromosome 1, establishing its chromosomal localization as distinct from GRIK4 (KA1) on human chromosome 11q22.3. Southern analysis of somatic cell hybrid panels, fluorescence in situ hybridization, interspecific backcross mapping Proceedings of the National Academy of Sciences of the United States of America High 7527545
1995 KA2 (GluK5) is enriched at synaptic sites in hippocampal neurons, co-localizing with the synaptic vesicle marker synaptophysin in dendritic spines after ~14 days in culture. Despite co-localization with AMPA subunit GluR1 in the same spines, co-immunoprecipitation shows no direct interaction between GluR1 and KA2, confirming that AMPA and kainate receptor complexes remain distinct at synapses. Immunocytochemistry, co-immunoprecipitation in cultured hippocampal neurons Neuroscience Medium 8552236
1996 Heteromeric GluR6(R)/KA2 channels have a ~2–3-fold larger unitary conductance (~572 fS) than homomeric GluR6(R) channels (~231–264 fS), as measured by noise analysis. GluR6(R)/KA2 heteromers are additionally activated by AMPA (which fails to gate homomeric GluR6), and show higher EC50 for kainate (~1.62 µM) compared to homomers (~0.47 µM). Patch-clamp electrophysiology (whole-cell noise analysis), transfected HEK293 cells Journal of neurophysiology High 8836240
1996 RNA editing at the Q/R site of GluR5 and GluR6 dramatically reduces homomeric single-channel conductance. Coexpression of KA2 with GluR5(Q) dramatically shortens channel burst length, while coexpression with edited GluR5(R) or GluR6(R) increases mean single-channel conductance (~950 fS for GluR5(R)/KA2; ~700 fS for GluR6(R)/KA2) relative to the respective homomers. Outside-out patch-clamp single-channel recording and spectral/variance analysis, transfected HEK293 cells The Journal of physiology High 8730589
1997 In rat trigeminal ganglion (TG) neurons, GluR5 and KA2 mRNAs are co-expressed at high levels, and the pharmacological, kinetic, rectification, and ion-permeability properties of native kainate currents closely match those of recombinant GluR5(R)/KA2 heteromeric channels, providing strong evidence that GluR5/KA2 heteromers are the predominant native kainate receptor in TG neurons. RT-PCR, patch-clamp electrophysiology of acutely dissociated neurons, pharmacological characterization The Journal of neuroscience High 9254673
1997 The rat GRIK5 gene spans >54 kb and is composed of 20 exons. The 5'-flanking region confers tissue-specific expression, and the first intron contains a negative regulatory element (silencer) located within 500 bp of the intron's 3' end that inhibits transcription in an orientation- and distance-independent manner; a 24-nucleotide sequence within this region binds nuclear proteins and mediates silencer activity. Reporter gene (CAT) transfection assay, genomic library screening, footprinting, gel shift assays The Journal of biological chemistry Medium 9079693
1998 SAP90 (PSD-95) and SAP102 co-immunoprecipitate with KA2 (GluK5) from neurons. The KA2 C-terminal region binds specifically to the SH3 and GK domains of SAP90 (not the PDZ domains that bind GluR6). Co-expression of SAP90 with GluR6/KA2 receptors reduces desensitization of kainate-evoked currents, demonstrating that SAP90/PSD-95 family members modulate the electrophysiological properties of KA2-containing kainate receptors. Co-immunoprecipitation, yeast two-hybrid, transfected cell electrophysiology Neuron High 9808460
2001 The intramolecular interaction of the SAP97 N-terminus with its own SH3 domain occludes the KA2-binding site on SAP97, explaining why SAP97 associates weakly with KA2 in vivo compared to SAP90. The individual SH3 and GK domains of SAP97 can bind KA2's C-terminal tail in vitro, but specific intramolecular contacts in full-length SAP97 prevent this interaction, revealing a mechanism for differential subcellular targeting of kainate receptors by distinct SAP family members. GFP-chimera expression, co-immunoprecipitation in HEK293 cells, in vitro binding assays with deletion mutants The Journal of biological chemistry Medium 11279111
2001 The GRIK5 promoter is TATA-less and GC-rich with multiple initiator sequences. A 1200 bp 5'-flanking region sustains neural cell-specific promoter activity via a TFIID-containing complex at an initiator sequence ~1100 bp upstream of intron 1. A 77-bp intronic/exonic sequence functions as a silencer in non-neural cells, containing a functional SP1-binding site and a neuron-restrictive silencer element-like sequence that suppresses GRIK5 expression in fibroblasts. Transgenic mouse lacZ reporter, reporter transfection assays, gel shift/EMSAs, deletion analysis The Journal of biological chemistry Medium 11533047
2003 KA2 (GluK5) homomers are retained in the endoplasmic reticulum (ER) and do not reach the plasma membrane. ER retention is mediated by an arginine-rich ER retention/retrieval motif and a di-leucine endocytic sequence in the KA2 C-terminus. Disruption of both motifs allows KA2 surface expression, but these homomers remain non-functional ion channels. During heteromeric assembly, the ER retention signal is sterically masked, permitting delivery of functional GluR6/KA2 receptors to the plasma membrane. Surface biotinylation, immunofluorescence, site-directed mutagenesis, electrophysiology in transfected cells and neurons The Journal of neuroscience High 12878702
2003 Genetic ablation of KA2 (GluK5, KA2-/-) in mice reduces the agonist affinity of presynaptic facilitatory autoreceptors at mossy-fiber terminals and abolishes heterosynaptic kainate receptor-mediated facilitation driven by glutamate spillover from CA3 collateral synapses. Postsynaptic kainate-mediated EPSCs also show shorter half-decay times in KA2-/- neurons, identifying KA2 as a determinant of both presynaptic and postsynaptic kainate receptor function at mossy-fiber–CA3 synapses. Hippocampal slice electrophysiology in genetic knockout mice, field and whole-cell recordings The Journal of neuroscience High 12533602
2003 Co-expression of KA2 with GluR5, GluR6, or GluR7 (but not GluR1 or NMDA receptor NR1) dramatically increases KA2 cell-surface expression in HEK293 cells, indicating a specific assembly requirement. KA2 expressed alone is retained in the ER, while synaptic kainate receptors in native neocortex have relatively high KA2 content compared to microsomal fractions, consistent with synaptic enrichment of KA2-containing heteromers. Surface biotinylation, cobalt uptake assay, subcellular fractionation of neocortex Journal of neurochemistry Medium 12950450
2003 An ER-retention motif in the KA2 cytosolic C-terminus (containing RRRRR sequence) mediates intracellular retention, but unlike the NMDA receptor NR1 motif, disruption of this arginine stretch alone (by glutamate substitution) is insufficient to relieve ER retention of KA2, indicating a unique and more complex retention mechanism for KA2. Chimeric reporter protein assay, immunofluorescence, mutagenesis in transfected cells Biochemical and biophysical research communications Medium 14511640
2004 Intact glutamate binding to the KA2 subunit (threonine 675 in the ligand-binding domain) is required for plasma membrane expression of heteromeric GluR6/KA2 receptors. Mutation of T675 to alanine or glutamate eliminates kainate and glutamate affinity and markedly reduces surface expression of GluR6/KA2 in transfected cells and cultured neurons, even though KA2 T675 mutants still co-assemble with GluR5 and GluR6. This establishes ligand binding as a quality-control checkpoint for forward trafficking of kainate receptors. Site-directed mutagenesis, surface biotinylation, [3H]kainate binding, immunoprecipitation, pulse-chase degradation assay The Journal of biological chemistry High 15583001
2006 COPI vesicle coat proteins mediate ER retention of KA2 by directly interacting with the arginine-rich retention/retrieval determinant in the KA2 cytoplasmic tail. Beta-COP interacts directly with immobilized KA2 peptides containing the arginine-rich signal; alanine substitution of this signal reduces COPI–KA2 association and increases plasma membrane localization. Assembly into GluR6a/KA2 heteromers markedly reduces COPI binding, coinciding with increased association with 14-3-3 proteins that promote forward trafficking. Co-immunoprecipitation from cerebellum and COS-7 cells, in vitro peptide pulldown, temperature-sensitive COPI degradation, surface localization assay The Journal of biological chemistry High 16595684
2006 An additional ER retention motif exists in an intracellular loop region of KA2, distinct from the C-terminal motifs. Mutation of both the loop motif and C-terminal motifs together significantly increases KA2 homomeric surface expression beyond mutation of C-terminal motifs alone, but surface-expressed KA2 homomers remain non-functional. In GluR6 knockout mice, native KA2 surface expression is dramatically reduced relative to wild-type, while KA2 trafficking is unaffected in GluR5 knockout mice, demonstrating that GluR6 oligomerization is specifically required for KA2 ER egress in neurons. Site-directed mutagenesis, surface biotinylation, immunofluorescence, electrophysiology, analysis of GluR5 and GluR6 knockout mice The Journal of neuroscience High 16807331
2008 Heteromeric GluR6/KA2 receptors, but not homomeric GluR6 receptors, produce slowly deactivating currents in response to brief glutamate applications with kinetics matching native KAR-EPSCs. Model simulations indicate the slow deactivation of GluR6/KA2 results from stabilization of partially glutamate-bound open states after rapid agonist removal, identifying the KA2 subunit as responsible for the characteristically slow decay of synaptic kainate receptor currents. Fast glutamate application (piezo-driven) to outside-out patches from transfected cells, kinetic modeling The Journal of neuroscience High 18562611
2009 Glutamate binding to the ligand-binding domain (LBD) of GluR6 acts as a molecular chaperone for proper folding of nascent kainate receptor subunits in the ER. Mutations that eliminate glutamate binding impair subunit folding and assembly, while mutations that lock the LBD in a closed conformation decrease surface expression and alter oligomeric assembly but do not impair folding. These results establish that LBDs must access multiple conformations (including open and partially closed states) for efficient kainate receptor biogenesis. Site-directed mutagenesis (including engineered disulfide bridges), surface biotinylation, secretion of soluble LBD proteins, oligomeric assembly analysis The Journal of biological chemistry Medium 19342380
2010 The crystal structure of the GluK5 amino-terminal domain (ATD) was solved, revealing that it crystallizes as a dimer with a strikingly different dimer assembly at the R1 interface compared to low-affinity kainate receptor ATDs (GluK1-3). Both R1 and R2 domain dimer assemblies were characterized; the R2 assembly resembles other non-NMDA iGluRs, while the R1 interface is distinct. These structural differences at the R1 dimer interface are consistent with GluK5 being an obligate heteromer that cannot form functional homomeric channels. X-ray crystallography (high-resolution crystal structure) Journal of molecular biology High 20951142
2009 GluK2/GluK5 (GluR6/KA2) heteromeric kainate receptor channels exhibit bell-shaped steady-state concentration-response curves to both glutamate and AMPA, indicating two distinct agonist binding sites with markedly different affinities within the same receptor. The high-affinity site (GluK5) leads to channel opening, while the low-affinity site (GluK2) leads to strong desensitization upon agonist binding. This was confirmed by the GluK2(E738D) mutation, which selectively right-shifted the desensitization phase of the concentration-response curve. Two-electrode voltage clamp in Xenopus oocytes, site-directed mutagenesis, Markov model fitting The Journal of physiology High 20026616
2011 The GluR6/KA2 ATD assembles as a heterodimer with extremely high affinity (Kd ~11 nM), ~32,000-fold tighter than KA2 ATD homodimer formation. Crystal structures of the GluR6/KA2 ATD heterodimer and heterotetramer assemblies revealed the molecular basis for obligate heteromeric assembly. Mutant cycle analysis confirmed that high-affinity ATD interactions are required for biosynthesis of functional heteromeric receptors. Sedimentation velocity analytical ultracentrifugation, X-ray crystallography, mutant cycle analysis, electrophysiology Neuron High 21791290
2012 GluK2 and GluK5 subunits assemble with 2:2 stoichiometry in heteromeric kainate receptors at the plasma membrane of live cells, as directly measured by single-molecule imaging with subunit counting. This definitively establishes the tetrameric architecture of GluK2/GluK5 receptors. Single-molecule fluorescence imaging with step-photobleaching for subunit counting in live cell plasma membranes Cell reports High 22509486
2013 CaMKII directly phosphorylates three residues in the C-terminal domain of GluK5 (GRIK5 protein), markedly increasing the lateral mobility of kainate receptors (KARs) at hippocampal mossy fiber synapses, likely by decreasing GluK5 binding to PSD-95. CaMKII activation promotes surface expression of KARs at extrasynaptic sites while simultaneously decreasing synaptic KAR content, mediating long-term depression of KAR-mediated responses (KAR-LTD). Molecular replacement with phosphorylation-deficient GluK5 confirms that direct GluK5 phosphorylation by CaMKII is necessary for KAR-LTD. In vitro kinase assay, single-particle tracking (lateral mobility), molecular replacement in neurons, hippocampal slice electrophysiology (LTD), Ca2+ imaging The EMBO journal High 23288040
2013 Ligand binding to only the GluK5 subunit (not the GluK2 subunit) is both necessary and sufficient for surface expression of heteromeric GluK2/GluK5 receptors. Mutations that reduce agonist affinity in GluK5 decrease functional heteromeric receptor surface expression and cannot be rescued by wild-type GluK2 or competitive antagonists, while analogous GluK2 mutations can be rescued by co-assembly with wild-type GluK5. This reveals a distinct quality-control role for GluK5 agonist binding in heteromeric KAR trafficking. Site-directed mutagenesis of ligand-binding domain, electrophysiology, surface expression assays in transfected cells Cellular and molecular neurobiology Medium 23975096
2014 Domoate produces a long-lasting inhibition specifically of the GluK5 subunit: brief exposure to domoate prevents GluK5 activation by other agonists for several minutes. In heteromeric GluK2/K5 receptors, the domoate-bound GluK5 state is not a desensitized or blocked conformation, as the receptor can still be fully activated through the GluK2 subunit. A mutation in GluK5 that reduces agonist binding affinity prevents this long-lasting inhibition, establishing its site-specificity. Whole-cell electrophysiology in transfected cells expressing homomeric and heteromeric kainate receptors, site-directed mutagenesis Neuropharmacology Medium 24859608
2017 GluK5 (encoded by GRIK5) is localized presynaptically to the ribbon synapses of rod photoreceptors in the mouse retina, as shown by double-immunofluorescence and electron microscopy. In GluK5-deficient mice, the structural integrity of synaptic ribbons is severely altered, revealing a novel non-ionotropic function of GluK5 in organizing synaptic ribbons in rod photoreceptor presynaptic terminals. Immunofluorescence, electron microscopy, GluK5 knockout mouse analysis PloS one Medium 28235022
2018 Two ER retention signals in the GluK5 C-terminus (an arginine-based signal and a di-leucine motif) are masked not primarily by GluK2 co-assembly but by the scaffold proteins SAP97 and CASK. SAP97 in an extended conformation (facilitated by CASK) engages both its SH3 and GK domains to sterically block the ER retention signals in GluK5. SAP97 and CASK are also required for sorting GluK5-containing receptor complexes into the local dendritic secretory pathway in neurons, revealing that ER retention signals in GluK5 function as dendritic sorting signals rather than simply preventing homomeric export. Co-immunoprecipitation, in vitro binding, surface expression assays, live-cell imaging of dendritic secretory pathway in neurons, site-directed mutagenesis Biochimica et biophysica acta. Molecular cell research Medium 30339823
2019 Single-molecule FRET reveals that in full-length heteromeric GluK2/GluK5 receptors, GluK2 and GluK5 subunits adopt a specific arrangement within the dimer-of-dimers tetramer, with GluK5 occupying defined positions at the amino-terminal domain interface. The conformational dynamics of both the amino-terminal domain and agonist-binding domain interfaces differ between resting and desensitized states, and these dynamics differ between homomeric and heteromeric receptors, providing insight into how GluK5 incorporation alters gating. Single-molecule FRET (smFRET) on purified full-length receptors Biochimica et biophysica acta. Biomembranes Medium 31194959
2019 Depletion of the GRIK5 ortholog in zebrafish reduces blood vessel numbers and integrity in the eye and increases vascular permeability, demonstrating a role for GluK5 in vascular biology and eye development beyond classical neurotransmission. Reduced genetically predicted expression of GRIK5 in humans is associated with comorbid vascular and eye diseases in electronic health records. Zebrafish morpholino knockdown, vascular integrity and permeability assays, electronic health record phenome-wide analysis American journal of human genetics Medium 30827500
2021 GluK5 (GluK5 KO mice on C57BL/6N background) share behavioral phenotypes with GluK2 KO mice including reduced locomotor activity, impaired motor function, and enhanced depressive-like behavior. GluK5 KO mice specifically show enhanced contextual memory, identifying a subunit-specific role for GluK5 in regulating contextual memory encoding and depressive-like behavior. Behavioral battery in genetic knockout mice (open field, rotarod, forced swim, contextual fear conditioning, etc.) Behavioural brain research Medium 33631192
2021 GluK1/K5, GluK2/K5, and GluK3/K5 heteromeric kainate receptors can form with either 3:1 or 2:2 stoichiometry as assessed by single-molecule fluorescence, and tri- and tetra-heteromeric KARs containing three or four different subunit types (including GluK5) can be detected. This establishes that GluK5-containing receptors have greater compositional diversity than previously appreciated. Single-molecule fluorescence imaging (multi-color), single-particle counting in live cells Cell reports Medium 34706237
2023 In heteromeric GluK2/GluK5 receptors, partial agonism by AMPA is mediated primarily through conformational differences at the GluK2 agonist-binding domain cleft: AMPA binding produces intermediate cleft closure at GluK2 (between apo/open and glutamate/closed states), while the GluK5 agonist-binding domain cleft shows no significant difference between AMPA- and glutamate-bound states. Additionally, the agonist-binding domain dimer interface is not decoupled by AMPA (unlike with full agonist glutamate), establishing distinct subunit contributions to partial agonism. Single-molecule FRET (smFRET) on full-length GluK2/GluK5 receptors with subunit-specific labeling Proteins Medium 37526035
2017 Preferential heterodimer formation of GluK5 ATD with GluK1-3 ATDs is energetically favored over GluK5 homodimerization, with heterodimer affinities spanning many orders of magnitude above homodimer stabilities. This thermodynamic framework explains the observed physiological receptor subunit combinations and suggests an assembly pathway in which high-affinity ATD heterodimerization drives GluK5 incorporation into functional heteromers. Fluorescence-detected sedimentation velocity analytical ultracentrifugation (systematic thermodynamic measurement of homo- and heterodimer affinities) eLife High 29058671
2008 GLIK5 (GLU(K5))-containing kainate receptors tonically reduce the speed of neuroblast migration along the lateral ventricle in the postnatal subventricular zone. Application of GLU(K5) receptor antagonists (NS3763 for homomeric; UB302 for heteromeric GLU(K5)) increased neuroblast migration speed by ~38% in whole-mount preparations, while GLU(K5) activation increased intracellular Ca2+ in ~60% of neuroblasts. This establishes a tonic, non-synaptic role for GluK5-containing receptors in regulating neural progenitor migration. Whole-mount lateral ventricle preparation with time-lapse imaging, patch-clamp electrophysiology, Ca2+ imaging, selective pharmacological antagonists, RT-PCR from single aspirated cells The Journal of physiology Medium 18565997
2007 KA2 antisense oligodeoxynucleotide knockdown in vivo reduces expression of both KA2 and GluR6 subunits, suppresses assembly of the GluR6/KA2-PSD95-MLK3 signaling module, inhibits JNK activation and c-jun phosphorylation after cerebral ischemia/reperfusion, and increases neuronal survival in CA1 after 5 days reperfusion. Combined KA2 and GluR6 knockdown has additive neuroprotective effects, establishing functional cooperation between these subunits in activating the PSD95-MLK3-MKK4/7-JNK3 death pathway. Intracerebroventricular antisense oligodeoxynucleotide infusion, co-immunoprecipitation, immunoblot, neuronal survival counting in rat ischemia model Journal of neuroscience research Medium 17639597

Source papers

Stage 0 corpus · 114 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1992 The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron 496 1373632
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
1994 Histological and ultrastructural localization of the kainate receptor subunits, KA2 and GluR6/7, in the rat nervous system using selective antipeptide antibodies. The Journal of comparative neurology 279 7852627
1998 SAP90 binds and clusters kainate receptors causing incomplete desensitization. Neuron 211 9808460
1996 Effect of RNA editing and subunit co-assembly single-channel properties of recombinant kainate receptors. The Journal of physiology 151 8730589
2009 Arabidopsis protein kinases GRIK1 and GRIK2 specifically activate SnRK1 by phosphorylating its activation loop. Plant physiology 143 19339507
1997 Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia. Brain research 139 9099808
2008 Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of mania. Molecular psychiatry 136 18332879
2007 A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation. American journal of human genetics 127 17847003
2003 Loss of kainate receptor-mediated heterosynaptic facilitation of mossy-fiber synapses in KA2-/- mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 127 12533602
1994 Biochemical and assembly properties of GluR6 and KA2, two members of the kainate receptor family, determined with subunit-specific antibodies. The Journal of biological chemistry 108 8288598
1997 Glutamate receptor subunits GluR5 and KA-2 are coexpressed in rat trigeminal ganglion neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 9254673
2003 Multiple trafficking signals regulate kainate receptor KA2 subunit surface expression. The Journal of neuroscience : the official journal of the Society for Neuroscience 101 12878702
2011 Structure and assembly mechanism for heteromeric kainate receptors. Neuron 99 21791290
2009 Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 81 19086053
2008 GluR6/KA2 kainate receptors mediate slow-deactivating currents. The Journal of neuroscience : the official journal of the Society for Neuroscience 67 18562611
2021 Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy. Acta pharmaceutica Sinica. B 66 35256949
2001 Molecular mechanisms regulating the differential association of kainate receptor subunits with SAP90/PSD-95 and SAP97. The Journal of biological chemistry 63 11279111
2001 Improvement of desulfurization activity in Rhodococcus erythropolis KA2-5-1 by genetic engineering. Bioscience, biotechnology, and biochemistry 63 11302154
2006 Pharmacological characterization of the competitive GLUK5 receptor antagonist decahydroisoquinoline LY466195 in vitro and in vivo. The Journal of pharmacology and experimental therapeutics 60 16690725
1996 Homomeric and heteromeric ion channels formed from the kainate-type subunits GluR6 and KA2 have very small, but different, unitary conductances. Journal of neurophysiology 59 8836240
2007 Synthesis and pharmacological characterization of N3-substituted willardiine derivatives: role of the substituent at the 5-position of the uracil ring in the development of highly potent and selective GLUK5 kainate receptor antagonists. Journal of medicinal chemistry 58 17348638
2006 Identification of an endoplasmic reticulum-retention motif in an intracellular loop of the kainate receptor subunit KA2. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 16807331
2013 Influence of polymorphisms in genes SLC1A1, GRIN2B, and GRIK2 on clozapine-induced obsessive-compulsive symptoms. Psychopharmacology 54 23660601
2011 Convergent genomic studies identify association of GRIK2 and NPAS2 with chronic fatigue syndrome. Neuropsychobiology 52 21912186
2004 Ligand binding is a critical requirement for plasma membrane expression of heteromeric kainate receptors. The Journal of biological chemistry 52 15583001
1994 Human GluR6 kainate receptor (GRIK2): molecular cloning, expression, polymorphism, and chromosomal assignment. Genomics 49 8034316
2008 Tonic activation of GLUK5 kainate receptors decreases neuroblast migration in whole-mounts of the subventricular zone. The Journal of physiology 47 18565997
1998 Expression and heteromeric interactions of non-N-methyl-D-aspartate glutamate receptor subunits in the developing and adult cerebellum. Neuroscience 47 9466455
1995 Synaptic expression of the high-affinity kainate receptor subunit KA2 in hippocampal cultures. Neuroscience 47 8552236
2012 Assembly stoichiometry of the GluK2/GluK5 kainate receptor complex. Cell reports 45 22509486
2003 Assembly and cell surface expression of KA-2 subunit-containing kainate receptors. Journal of neurochemistry 45 12950450
1996 The effect of chronic haloperidol treatment on glutamate receptor subunit (GluR1, GluR2, KA1, KA2, NR1) mRNAs and glutamate binding protein mRNA in rat forebrain. Neuroscience letters 45 8843098
2013 CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors. The EMBO journal 42 23288040
2017 A gain-of-function mutation in the GRIK2 gene causes neurodevelopmental deficits. Neurology. Genetics 41 28180184
2006 Intracellular trafficking of KA2 kainate receptors mediated by interactions with coatomer protein complex I (COPI) and 14-3-3 chaperone systems. The Journal of biological chemistry 41 16595684
2005 Association study of polymorphisms in the GluR7, KA1 and KA2 kainate receptor genes (GRIK3, GRIK4, GRIK5) with schizophrenia. Psychiatry research 40 16325263
2009 Subunit-specific desensitization of heteromeric kainate receptors. The Journal of physiology 39 20026616
2010 Crystal structures of the glutamate receptor ion channel GluK3 and GluK5 amino-terminal domains. Journal of molecular biology 38 20951142
2002 Characterisation of the effects of ATPA, a GLU(K5) receptor selective agonist, on excitatory synaptic transmission in area CA1 of rat hippocampal slices. Neuropharmacology 38 12069899
1992 Molecular structure and pharmacological characterization of humEAA2, a novel human kainate receptor subunit. Molecular pharmacology 38 1321949
2018 KAP1 facilitates reinstatement of heterochromatin after DNA replication. Nucleic acids research 37 29955894
2002 A novel enzyme, 2'-hydroxybiphenyl-2-sulfinate desulfinase (DszB), from a dibenzothiophene-desulfurizing bacterium Rhodococcus erythropolis KA2-5-1: gene overexpression and enzyme characterization. Biochimica et biophysica acta 37 12147352
2010 Association between polymorphisms in GRIK2 gene and obsessive-compulsive disorder: a family-based study. CNS neuroscience & therapeutics 36 20370803
2021 Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders. American journal of human genetics 34 34375587
2018 E3 ubiquitin ligase RNF123 targets lamin B1 and lamin-binding proteins. The FEBS journal 33 29676528
2000 Increase in desulfurization activity of Rhodococcus erythropolis KA2-5-1 using ethanol feeding. Journal of bioscience and bioengineering 33 16232759
2007 Human herpesvirus 6 (HHV-6) induces dysregulation of glutamate uptake and transporter expression in astrocytes. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 30 18247129
2003 Heteromer formation of delta2 glutamate receptors with AMPA or kainate receptors. Brain research. Molecular brain research 29 12573530
2001 Long-term repeated biodesulfurization by immobilized Rhodococcus erythropolis KA2-5-1 cells. Applied microbiology and biotechnology 29 11341322
2021 Structural and compositional diversity in the kainate receptor family. Cell reports 28 34706237
2019 GRIK5 Genetically Regulated Expression Associated with Eye and Vascular Phenomes: Discovery through Iteration among Biobanks, Electronic Health Records, and Zebrafish. American journal of human genetics 28 30827500
2011 Genome-wide association study on bipolar disorder in the Bulgarian population. Genes, brain, and behavior 28 21771265
2004 Maternal transmission disequilibrium of the glutamate receptor GRIK2 in schizophrenia. Neuroreport 28 15305151
2001 Genomic organization of the human GRIK2 gene and evidence for multiple splicing variants. Gene 28 11675011
2017 Preferential assembly of heteromeric kainate and AMPA receptor amino terminal domains. eLife 27 29058671
2007 Glutamate receptor 6 gene (GluR6 or GRIK2) polymorphisms in the Indian population: a genetic association study on autism spectrum disorder. Cellular and molecular neurobiology 27 17712621
2006 Antiallodynic and antihyperalgesic effects of selective competitive GLUK5 (GluR5) ionotropic glutamate receptor antagonists in the capsaicin and carrageenan models in rats. The Journal of pharmacology and experimental therapeutics 27 16837561
2003 Trafficking and surface expression of the glutamate receptor subunit, KA2. Biochemical and biophysical research communications 27 14511640
2009 Glutamate binding and conformational flexibility of ligand-binding domains are critical early determinants of efficient kainate receptor biogenesis. The Journal of biological chemistry 26 19342380
2002 The cbs mutant strain of Rhodococcus erythropolis KA2-5-1 expresses high levels of Dsz enzymes in the presence of sulfate. Archives of microbiology 26 12375103
2021 Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data. Cellular and molecular life sciences : CMLS 24 34100982
2007 Anxiolytic-like effects through a GLUK5 kainate receptor mechanism. Neuropharmacology 20 17418283
1995 Refinement of map position of the human GluR6 kainate receptor gene (GRIK2) and lack of association and linkage with idiopathic generalized epilepsies. Neurology 20 7675232
2012 Association of genes on chromosome 6, GRIK2 , TMEM217 and TMEM63B (linked to MRPL14 ) with diabetic retinopathy. Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde 19 23037145
2005 A pharmacological investigation of the role of GLUK5-containing receptors in kainate-driven hippocampal gamma band oscillations. Neuropharmacology 19 16153668
1994 The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat. Proceedings of the National Academy of Sciences of the United States of America 19 7527545
2002 Association study of polymorphisms in the GluR6 kainate receptor gene (GRIK2) with schizophrenia. Psychiatry research 18 12467946
2004 Characterisation of the effects of ATPA, a GLU(K5) kainate receptor agonist, on GABAergic synaptic transmission in the CA1 region of rat hippocampal slices. Neuropharmacology 17 15275825
2002 Developmental distribution of the glutamate receptor subunits KA2, GluR6/7, and delta 1/2 in the rat medial nucleus of the trapezoid body. A quantitative image analysis. Cell and tissue research 17 12012203
2019 The structural arrangement and dynamics of the heteromeric GluK2/GluK5 kainate receptor as determined by smFRET. Biochimica et biophysica acta. Biomembranes 15 31194959
2012 TAA repeat variation in the GRIK2 gene does not influence age at onset in Huntington's disease. Biochemical and biophysical research communications 15 22771793
2005 Effect of sulfur sources on specific desulfurization activity of Rhodococcus erythropolis KA2-5-1 in exponential fed-batch culture. Journal of bioscience and bioengineering 15 16233786
1997 Gene structure of the rat kainate receptor subunit KA2 and characterization of an intronic negative regulatory region. The Journal of biological chemistry 15 9079693
2021 A comparative analysis of kainate receptor GluK2 and GluK5 knockout mice in a pure genetic background. Behavioural brain research 14 33631192
2021 GRIK2 is a target for bladder cancer stem-like cell-targeting immunotherapy. Cancer immunology, immunotherapy : CII 14 34405274
2007 Improvement of 2'-hydroxybiphenyl-2-sulfinate desulfinase, an enzyme involved in the dibenzothiophene desulfurization pathway, from Rhodococcus erythropolis KA2-5-1 by site-directed mutagenesis. Bioscience, biotechnology, and biochemistry 14 17986771
1997 Rat chromosome 1: regional localization of seven genes (Slc9a3, Srd5a1, Esr, Tcp1, Grik5, Tnnt3, Jak2) and anchoring of the genetic linkage map to the cytogenetic map. Mammalian genome : official journal of the International Mammalian Genome Society 14 9271667
2022 Music alleviates pain perception in depression mouse models by promoting the release of glutamate in the hippocampus of mice to act on GRIK5. Nucleosides, nucleotides & nucleic acids 13 35357273
2007 Activation of kainate GLU(K5) transmission rescues kindling-induced impairment of LTP in the rat lateral amygdala. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 13 18046310
2001 Characterization of the rat GRIK5 kainate receptor subunit gene promoter and its intragenic regions involved in neural cell specificity. The Journal of biological chemistry 13 11533047
1996 Contrasting effects of electroconvulsive shock on mRNAs encoding the high affinity kainate receptor subunits (KA1 and KA2) and cyclophilin in the rat. Brain research 12 8963683
2006 Genetic analysis of the GRIK2 modifier effect in Huntington's disease. BMC neuroscience 11 16959037
2002 Enhancement and stabilization of desulfurization activity of Rhodococcus erythropolis KA2-5-1 by feeding ethanol and sulfur components. Journal of bioscience and bioengineering 11 16233332
2024 A novel AAV9-dual microRNA-vector targeting GRIK2 in the hippocampus as a treatment for mesial temporal lobe epilepsy. Molecular therapy. Methods & clinical development 9 39429724
2017 Presynaptic localization of GluK5 in rod photoreceptors suggests a novel function of high affinity glutamate receptors in the mammalian retina. PloS one 9 28235022
2023 GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling. Cell biology international 8 36959746
2016 A pharmacological profile of the high-affinity GluK5 kainate receptor. European journal of pharmacology 8 27373850
2009 Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia. Psychiatric genetics 8 19125103
2007 Functional cooperation between KA2 and GluR6 subunits is involved in the ischemic brain injury. Journal of neuroscience research 8 17639597
2001 Selective cleavage of the two CS bonds in asymmetrically alkylated dibenzothiophenes by Rhodococcus erythropolis KA2-5-1. Journal of bioscience and bioengineering 8 16233063
1997 Kainate/AMPA receptors expressed on human fetal astrocytes in long-term culture. Journal of neuroscience research 8 9039653
2012 Synaptic Pattern of KA1 and KA2 upon the Direction-Selective Ganglion Cells in Developing and Adult Mouse Retina. Acta histochemica et cytochemica 7 22489103
2019 Isoforms of Ionotropic Glutamate Receptor GRIK2 Induce Senescence of Carcinoma Cells. Cancer genomics & proteomics 6 30587499
2019 Correlation between GRIK2 rs6922753, rs2227283 polymorphism and aggressive behaviors with Bipolar Mania in the Chinese Han population. Brain and behavior 6 31631587
2014 The neurotoxin domoate causes long-lasting inhibition of the kainate receptor GluK5 subunit. Neuropharmacology 6 24859608
2013 Agonist binding to the GluK5 subunit is sufficient for functional surface expression of heteromeric GluK2/GluK5 kainate receptors. Cellular and molecular neurobiology 6 23975096
2020 Truncated RUNX1 Generated by the Fusion of RUNX1 to Antisense GRIK2 via a Cryptic Chromosome Translocation Enhances Sensitivity to Granulocyte Colony-Stimulating Factor. Cytogenetic and genome research 5 32544910
2004 Refined linkage to the RDP/DYT12 locus on 19q13.2 and evaluation of GRIK5 as a candidate gene. Movement disorders : official journal of the Movement Disorder Society 5 15254951
2018 A novel function for the ER retention signals in the C-terminus of kainate receptor subunit, GluK5. Biochimica et biophysica acta. Molecular cell research 4 30339823
2020 A Novel Susceptibility Locus Near GRIK2 Associated With Erosive Esophagitis in a Korean Cohort. Clinical and translational gastroenterology 3 32132452
2019 Interaction among GRIK2 gene on epilepsy susceptibility in Chinese children. Acta neurologica Scandinavica 3 30908586
2023 Partial agonism in heteromeric GLUK2/GLUK5 kainate receptor. Proteins 2 37526035
2020 Senescence of Normal Human Fibroblasts Relates to the Expression of Ionotropic Glutamate Receptor GluR6/Grik2. Cancer genomics & proteomics 2 33099472
2017 [Polymorphic Variants of Glutamate Receptor (GRIK5, GRIN2B) and Serotonin Receptor (HTR2A) Genes Are Associated with Chronic Obstructive Pulmonary Disease]. Molekuliarnaia biologiia 2 28900078
2011 Non-syndromic autosomal recessive mental retardation in Tunisian families : exclusion of GRIK2 and TUSC3 genes. La Tunisie medicale 2 21557188
2025 Pathological gain-of-function human variants in the GRIK2 kainate receptor gene cause wide-ranging behavioral dysfunction and seizures in mouse models. Neurobiology of disease 1 41391686
2023 Epigenetic signature discriminates lymphatic metastasis in BRAF wild-type thyroid carcinoma: methylation role of GRIK2. Epigenomics 1 37990886
2022 Alternative Promoters of GRIK2 (GluR6) Gene in Human Carcinoma Cell Lines Are Regulated by Differential Methylation of CpG Dinucleotides. Genes 1 35328043
2024 Domoic Acid as a Lead for the Discovery of the First Selective Ligand for Kainate Receptor Subtype 5 (GluK5). Journal of medicinal chemistry 0 39133077