Affinage

GRIK5

Glutamate receptor ionotropic, kainate 5 · UniProt Q16478

Length
980 aa
Mass
109.3 kDa
Annotated
2026-06-10
58 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRIK5 (GluK5/KA2) is a high-affinity kainate receptor subunit that cannot form functional homomeric ion channels and instead functions as an obligate partner subunit shaping the properties of heteromeric kainate receptors that mediate excitatory neurotransmission (PMID:1373632, PMID:20951142). Expressed alone, KA2 is retained in the endoplasmic reticulum through discrete trafficking signals—an arginine-rich ER retention/retrieval motif and a di-leucine motif in the C-terminus plus an additional motif in the intracellular loop—so that even forced surface expression yields non-functional homomers (PMID:12878702, PMID:16807331); the structural basis lies in an aberrant R1 dimer interface of its amino-terminal domain incompatible with self-assembly (PMID:20951142). ER egress requires obligate co-assembly with GluK2/GluR6 (not GluK1 or AMPA/NMDA subunits) into a fixed 2:2 'dimer of dimers' heterotetramer, which sterically masks the retention signals (PMID:12878702, PMID:16807331, PMID:22509486, PMID:31194959). This trafficking is gated by a sequential checkpoint: β-COP/COPI binds the arginine-rich signal to retain unassembled subunits, and heteromeric assembly displaces COPI in favor of 14-3-3-mediated forward trafficking, with SAP97/CASK additionally masking the retention signals to route receptors into the dendritic secretory pathway (PMID:16595684, PMID:30339823). Within the assembled receptor GluK5 confers high glutamate affinity and larger unitary conductance, and ligand binding through the GluK5 site is necessary and sufficient for surface delivery (PMID:8836240, PMID:23975096). Functionally, KA2 determines presynaptic mossy-fiber facilitation and postsynaptic EPSC decay kinetics, and CaMKII phosphorylation of three C-terminal GluK5 residues reduces PSD-95 binding to increase receptor lateral mobility and drive kainate receptor long-term depression (PMID:12533602, PMID:23288040). Beyond canonical signaling, GluK5 localizes to rod photoreceptor ribbon synapses where its loss disrupts ribbon structural integrity (PMID:28235022), and KA2 participates with GluR6 in a PSD95-MLK3-JNK signaling module mediating ischemic neuronal death (PMID:17639597).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1992 High

    Established that KA2 is not an independent channel-forming subunit but modifies the gating and pharmacology of kainate receptors only when co-assembled, defining it as an accessory subunit.

    Evidence Heterologous expression in oocytes/HEK cells with electrophysiology comparing homomers and heteromers

    PMID:1373632

    Open questions at the time
    • Stoichiometry and assembly mechanism unknown
    • Native receptor composition not yet established
  2. 1994 High

    Showed that KA2/GluR6 heteromeric complexes exist in native brain and that AMPA and kainate subunits do not appreciably co-assemble, defining the molecular boundary of native kainate receptor composition.

    Evidence Reciprocal co-immunoprecipitation from transfected cells and rat brain with radioligand binding

    PMID:8288598 PMID:8552236

    Open questions at the time
    • Subunit stoichiometry not quantified
    • Trafficking determinants of assembly not addressed
  3. 1994 Medium

    Placed KA2 at the postsynaptic density and dendritic spines, linking the subunit to synaptic signaling sites.

    Evidence EM immunostaining and immunocytochemistry in rat nervous system and cultured hippocampal neurons

    PMID:7852627 PMID:8552236

    Open questions at the time
    • Does not address later-described presynaptic localizations
    • Anchoring partners not identified at this stage
  4. 1996 High

    Quantified how KA2 incorporation alters single-channel conductance and agonist affinity, defining its contribution to receptor biophysics.

    Evidence Patch-clamp and noise analysis in transfected HEK293 cells

    PMID:8836240

    Open questions at the time
    • Conductance measured in heterologous, not native, channels
    • Structural basis of conductance change unknown
  5. 1997 High

    Confirmed that recombinant GluR5/KA2 heteromers recapitulate native kainate channels in vivo, validating the heteromeric model in real neurons.

    Evidence RT-PCR, whole-cell patch-clamp and pharmacology in dissociated trigeminal ganglion neurons

    PMID:9254673

    Open questions at the time
    • Does not establish trafficking control of native assembly
    • Limited to one neuronal population
  6. 1997 Medium

    Mapped transcriptional control elements of grik5, including intronic negative regulatory and neural-specific promoter/silencer elements governing its expression.

    Evidence Reporter assays, footprinting, EMSA and transgenic lacZ reporters

    PMID:11533047 PMID:9079693

    Open questions at the time
    • Trans-acting factors only partially identified
    • Physiological regulation in vivo not demonstrated
  7. 2003 High

    Defined the molecular basis of obligate heteromerization: ER retention motifs in the C-terminus retain KA2 until heteromeric assembly masks them, explaining why KA2 cannot reach the surface alone.

    Evidence Surface biotinylation, mutagenesis, immunofluorescence and electrophysiology in heterologous cells and neurons

    PMID:12878702 PMID:12950450 PMID:14511640

    Open questions at the time
    • Loop-region retention signal not yet found
    • Identity of proteins reading the retention signals unknown
  8. 2003 High

    Assigned physiological consequences to KA2 in vivo, showing it controls presynaptic mossy-fiber facilitation and postsynaptic EPSC decay kinetics.

    Evidence Slice electrophysiology in KA2-/- knockout mice

    PMID:12533602

    Open questions at the time
    • Molecular mechanism of affinity contribution not resolved here
    • Behavioral consequences not addressed
  9. 2006 High

    Completed the trafficking model by identifying a second retention motif and the sequential COPI-to-14-3-3 checkpoint, and demonstrated genetically that GluR6 specifically drives KA2 surface delivery.

    Evidence Mutagenesis, biotinylation, peptide pulldown, COPI degradation, co-IP from cerebellum/COS-7 and knockout mouse analysis

    PMID:16595684 PMID:16807331

    Open questions at the time
    • How heteromerization mechanically displaces COPI not fully resolved
    • 14-3-3 binding site mapping incomplete
  10. 2007 Medium

    Linked the GluR6/KA2 module to a pathological signaling cascade, implicating it in ischemic neuronal death via PSD95-MLK3-JNK signaling.

    Evidence In vivo antisense knockdown in a rat ischemia model with Western blot and survival counting

    PMID:17639597

    Open questions at the time
    • Antisense specificity not exhaustively controlled
    • Direct vs indirect role of KA2 in the module not dissected
  11. 2010 High

    Provided the structural explanation for assembly incompatibility, showing the GluK5 amino-terminal domain forms an aberrant R1 dimer interface.

    Evidence X-ray crystallography of the isolated GluK5 ATD

    PMID:20951142

    Open questions at the time
    • Isolated domain may not reflect full-length assembly
    • Heteromeric interface not crystallized
  12. 2012 High

    Determined the fixed 2:2 GluK2:GluK5 stoichiometry of the heterotetramer, constraining all functional models.

    Evidence Single-molecule bleaching step counting in live-cell membranes

    PMID:22509486

    Open questions at the time
    • Spatial arrangement of subunits not yet defined
    • Stoichiometry in native synapses not directly measured
  13. 2013 High

    Identified CaMKII phosphorylation of GluK5 as the molecular switch for kainate receptor LTD, coupling phosphorylation to reduced PSD-95 binding and increased lateral mobility.

    Evidence Molecular replacement, single-particle tracking/FRAP, phosphorylation assays and mossy-fiber electrophysiology

    PMID:23288040

    Open questions at the time
    • Direct phospho-dependent PSD-95 affinity change not structurally resolved
    • Upstream activity triggers in vivo not defined
  14. 2013 Medium

    Established that agonist binding specifically through the GluK5 subunit is necessary and sufficient for heteromer surface trafficking, identifying a ligand-gated biosynthetic checkpoint.

    Evidence Ligand-binding domain mutagenesis with surface expression and electrophysiology in heterologous cells

    PMID:23975096

    Open questions at the time
    • Single lab, two methods
    • Endogenous ligand source during biosynthesis unclear
  15. 2014 Medium

    Showed that GluK2 and GluK5 subunits can gate the channel independently and that domoate causes prolonged GluK5-specific inhibition, revealing functional autonomy within the tetramer.

    Evidence Whole-cell electrophysiology of wild-type and binding-affinity mutant recombinant receptors

    PMID:24859608

    Open questions at the time
    • Single primary method
    • Structural basis of long-lasting inhibition unresolved
  16. 2017 Medium

    Revealed a non-canonical structural role for GluK5 at rod photoreceptor ribbon synapses, where it organizes presynaptic ribbon integrity.

    Evidence Double-immunofluorescence, EM and GluK5 knockout mouse retina analysis

    PMID:28235022

    Open questions at the time
    • Molecular partners at the ribbon not identified
    • Whether channel function is required for the structural role unknown
  17. 2018 Medium

    Defined the SAP97/CASK mechanism that masks GluK5 retention signals and routes assembled receptors into the dendritic secretory pathway.

    Evidence Co-IP, conformational analysis, mutagenesis and neuronal trafficking assays

    PMID:30339823

    Open questions at the time
    • Abstract-level mechanistic detail only
    • Interplay with COPI/14-3-3 checkpoint not integrated
  18. 2019 Medium

    Resolved the conformational arrangement and dynamics of GluK2/GluK5 heteromers, including a defined dimer-of-dimers geometry and subunit-specific responses to agonists.

    Evidence Single-molecule FRET on full-length receptors in resting, glutamate- and AMPA-bound states

    PMID:31194959 PMID:37526035

    Open questions at the time
    • Single lab
    • Functional coupling of conformational states to gating not fully mapped
  19. 2019 Low

    Implicated GRIK5 in eye vascular biology, expanding its potential roles beyond glutamatergic signaling.

    Evidence Morpholino knockdown in zebrafish with vascular imaging

    PMID:30827500

    Open questions at the time
    • Single-organism knockdown with limited mechanistic follow-up
    • Morpholino off-target effects not excluded
    • No mammalian validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the channel-function, synaptic-organizing, and non-neural vascular roles of GRIK5 are mechanistically unified, and whether the ribbon-organizing and vascular roles require ion-channel activity, remains unresolved.
  • No structure of the assembled heterotetramer
  • Channel-independent functions mechanistically undefined
  • Disease relevance of human GRIK5 variants not established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-9609507 Protein localization 4 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 2
Partners
14-3-3CAMK2CASKCOPB1DLG1DLG4GRIK1GRIK2
Complex memberships
GluK2/GluK5 (GluR6/KA2) heterotetrameric kainate receptorGluR6/KA2-PSD95-MLK3 signaling module

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 KA-2 (GRIK5) does not form functional homomeric ion channels when expressed alone, but coexpression with GluR5 or GluR6 subunits produces agonist-gated currents. GluR5(R)/KA-2 heteromers show more rapid desensitization and different current-voltage relations compared to GluR5(Q) homomers; GluR6/KA-2 heteromers are gated by AMPA, which fails to gate homomeric GluR6 channels. Heterologous expression in Xenopus oocytes or HEK cells with electrophysiological recording Neuron High 1373632
1994 KA2 and GluR6 subunits co-assemble into heteromeric complexes in both transfected cells and native rat brain, as demonstrated by co-immunoprecipitation with subunit-specific antibodies. Each antibody selectively immunoprecipitated [3H]kainate binding activity but not [3H]AMPA binding activity. GluR1 and GluR2 (AMPA subunits) also co-immunoprecipitated with GluR6 in co-transfected cells, but such mixed complexes appeared limited in brain. Co-immunoprecipitation from transfected HEK cells and detergent-solubilized rat brain membranes; immunoblot; deglycosylation assay The Journal of biological chemistry High 8288598
1994 KA2 protein is localized postsynaptically in the rat nervous system, with immunostaining concentrated in postsynaptic densities apposed by unstained presynaptic terminals, and in associated dendrites. Immunohistochemistry and electron microscopic ultrastructural localization using affinity-purified anti-KA2 C-terminus antibody The Journal of comparative neurology Medium 7852627
1995 KA2 is expressed in hippocampal neurons, is enriched in dendritic spines after ~14 days in culture, and co-localizes with synaptophysin indicating synaptic localization. Co-immunoprecipitation showed no direct interaction between KA2 and AMPA subunit GluR1, confirming AMPA and kainate subunits do not co-assemble into mixed receptor complexes despite co-localizing at synapses. Immunocytochemistry in cultured hippocampal neurons; co-immunoprecipitation Neuroscience Medium 8552236
1996 Homomeric GluR6(R) channels have a very small unitary conductance (~231–264 fS by noise analysis). Heteromeric GluR6(R)/KA2 channels have a two- to threefold larger unitary conductance (~572 fS), different KA affinity (EC50 ~1.62 µM vs 0.47 µM for GluR6 homomers), and can be activated by AMPA unlike GluR6 homomers. Patch-clamp electrophysiology and noise analysis in transfected HEK293 cells Journal of neurophysiology High 8836240
1997 GluR5 and KA-2 subunits are co-expressed at high levels in trigeminal ganglion (TG) neurons and form functional heteromeric channels in vivo. Native kainate receptor channels in TG neurons closely resemble recombinant GluR5(R)/KA-2 heteromers in pharmacological properties, desensitization, rectification, ion permeability, and mean channel conductance. RT-PCR, whole-cell patch-clamp electrophysiology, pharmacological characterization of acutely dissociated TG neurons The Journal of neuroscience High 9254673
1997 The rat grik5 gene has 20 exons spanning >54 kb. The first intron contains a negative regulatory element (within 500 bp of the 3'-end of intron 1) that inhibits transcription in an orientation- and distance-independent manner; a 24-nucleotide sequence within this region binds nuclear proteins from neural and non-neural cells. Reporter gene (CAT) assays, footprinting, gel shift assays, genomic library screening The Journal of biological chemistry Medium 9079693
2001 The GRIK5 promoter is TATA-less and GC-rich with multiple consensus initiator sequences. Neural-cell-specific promoter activity maps to a 1200-bp 5'-flanking region; transcriptional activity involves a TFIID-containing complex on an initiator sequence 1100 bp upstream of the first intron. A 77-bp intragenic sequence within the first exon acts as a silencer in non-neural cells via an SP1-binding site and a neuron-restrictive silencer element-like sequence. Transgenic mouse lacZ reporter assays, transfection reporter assays in neural (CG-4) and non-neural cells, EMSA The Journal of biological chemistry Medium 11533047
2003 KA2 homomeric receptors fail to reach the plasma membrane and are retained in the endoplasmic reticulum (ER). This retention is mediated by discrete trafficking signals: an arginine-rich ER retention/retrieval motif and a di-leucine endocytic sequence in the C-terminus. Disruption of both motifs allows ER exit and surface expression of KA2 homomers that remain non-functional. The ER retention signal is sterically shielded upon heteromeric assembly, allowing delivery of functional heteromeric receptors to the plasma membrane. Surface biotinylation, immunofluorescence, mutagenesis, electrophysiology in heterologous expression systems and primary neurons The Journal of neuroscience High 12878702
2003 KA2 is retained in the ER when expressed alone; co-expression with GluR5-7 (but not with GluR1 or NR1) dramatically increases surface expression of KA2. Synaptic KARs from neocortex have a relatively high KA2 content compared to microsomal fractions, indicating preferential synaptic targeting of heteromeric KA2-containing receptors. Surface biotinylation, cobalt uptake assay, subcellular fractionation of neocortex in HEK293 cells Journal of neurochemistry Medium 12950450
2003 In KA2-/- (GluK5 knockout) mice, presynaptic mossy-fiber kainate receptor facilitation by heterosynaptic spillover of glutamate from CA3 collaterals is absent, while homosynaptic facilitation is normal. Postsynaptic kainate-mediated EPSCs show shorter half-decay times. These results identify KA2 as a determinant of both presynaptic affinity for glutamate and postsynaptic EPSC kinetics at mossy-fiber-CA3 synapses. Electrophysiological recordings in hippocampal slices from KA2-/- knockout mice The Journal of neuroscience High 12533602
2003 A chimeric reporter approach identified an ER-retention motif within the KA2 cytosolic C-terminal domain (RRRRR stretch). However, mutation of this arginine motif alone (with alternating glutamic acid residues) was insufficient to disrupt ER-retention of KA2, suggesting a unique mechanism distinct from the NR1 RRR motif. Chimeric reporter protein, mutagenesis, immunofluorescence in heterologous cells Biochemical and biophysical research communications Medium 14511640
2006 An additional ER retention motif in the intracellular loop region of KA2 was identified. Mutation of this loop motif together with C-terminal motifs significantly increases KA2 surface expression; however, surface-expressed KA2 homomers still do not form functional ion channels. In GluR6 knockout mice, native KA2 surface expression is dramatically reduced, whereas it is unaffected in GluR5 knockout mice, demonstrating that GluR6 oligomerization is specifically required for KA2 ER egress and cell-surface transport. Site-directed mutagenesis, immunofluorescence, surface biotinylation, electrophysiology, knockout mouse analysis The Journal of neuroscience High 16807331
2006 COPI vesicle coat subunits co-immunoprecipitate with KA2 subunits from cerebellum and COS-7 cells; β-COP protein interacts directly with KA2 peptides containing the arginine-rich retention/retrieval determinant. Alanine substitution of this signal reduces COPI–KA2 association. Assembly of heteromeric GluR6a/KA2 receptors reduces COPI binding and concomitantly increases association with 14-3-3 proteins, which mediate forward trafficking, representing a checkpoint for functional KAR biosynthesis. Co-immunoprecipitation from cerebellum and COS-7 cells, GST peptide pulldown, temperature-sensitive COPI degradation, surface localization assay The Journal of biological chemistry High 16595684
2010 Crystal structures of the GluK5 amino-terminal domain (ATD) were determined at high resolution. GluK5 ATD crystallizes as a dimer with a strikingly different dimer assembly at the R1 interface compared to GluK3 ATD, while the R2 domain dimer assembly is similar to other non-NMDA iGluRs. The aberrant R1 dimer interface is consistent with GluK5 being unable to form functional homomeric channels and requiring obligate co-assembly with GluK1-3 subunits. X-ray crystallography of isolated ATD domain Journal of molecular biology High 20951142
2012 GluK2 and GluK5 subunits assemble into heterotetrameric receptors with a fixed 2:2 stoichiometry, as determined by direct single-molecule counting of each subunit type in the plasma membrane of live cells. Single-molecule imaging (single-molecule bleaching step counting) in live cell plasma membranes Cell reports High 22509486
2013 CaMKII phosphorylates three residues in the C-terminal domain of GluK5, markedly increasing lateral mobility of kainate receptors (KARs), likely by decreasing GluK5 binding to PSD-95. CaMKII activation promotes surface expression of KARs at extrasynaptic sites but decreases synaptic KAR content. This CaMKII-dependent phosphorylation of GluK5 is necessary for long-term depression of KAR-mediated responses at hippocampal mossy fiber synapses (KAR-LTD), established using a molecular replacement strategy. Molecular replacement, lateral mobility (single-particle tracking/FRAP), phosphorylation assays, electrophysiology at mossy fiber synapses in hippocampal slices The EMBO journal High 23288040
2013 Ligand binding to the GluK5 subunit (not GluK2) is both necessary and sufficient for surface trafficking of heteromeric GluK2/GluK5 receptors. Mutations reducing agonist affinity in GluK5 prevent functional surface expression and cannot be rescued by wild-type GluK2 or antagonist, whereas GluK2 binding-site mutations can be rescued by co-assembly with wild-type GluK5. Site-directed mutagenesis of ligand-binding domain, surface expression assays, electrophysiology in heterologous cells Cellular and molecular neurobiology Medium 23975096
2014 Domoate causes long-lasting inhibition of the GluK5 subunit in heteromeric GluK2/K5 receptors: brief domoate exposure prevents GluK5 activation by other agonists for several minutes. A mutation in GluK5 that reduces agonist binding affinity prevents this inhibition. Domoate-bound GluK2/K5 heteromers can still be fully activated through the GluK2 subunit, demonstrating that the two subunits within the tetramer can function independently to open the ion channel. Electrophysiology (whole-cell recordings) in heterologous cells expressing wild-type or mutant recombinant kainate receptors Neuropharmacology Medium 24859608
2017 GluK5 (GRIK5) is localized presynaptically to the ribbon synapses of rod photoreceptor terminals in the mouse retina. In GluK5-deficient mice, the structural integrity of synaptic ribbons is severely altered, indicating a novel role for GluK5 in organizing presynaptic ribbon structure. Double-immunofluorescence, electron microscopy, GluK5 knockout mice analysis PloS one Medium 28235022
2018 Two ER retention signals in the GluK5 C-terminus (arginine-based signal and di-leucine motif) are physically masked by SAP97 in the presence of CASK: SAP97 adopts an extended conformation making its SH3 and GuK domains available to bind and sterically block both ER retention signals. SAP97 and CASK are necessary for sorting GluK2/GluK5 receptor complexes into the local dendritic secretory pathway in neurons, rather than the somatic Golgi pathway. Co-immunoprecipitation, conformational analysis, mutagenesis, neuronal trafficking assays Biochimica et biophysica acta. Molecular cell research Medium 30339823
2019 smFRET studies established that GluK2 and GluK5 subunits arrange within the heterotetrameric receptor in a defined 'dimer of dimers' configuration. The heteromeric GluK2/GluK5 receptor shows distinct conformational dynamics at the amino-terminal and agonist-binding domain interfaces compared to homomeric GluK2, particularly in resting versus desensitized states. Single-molecule FRET (smFRET) on full-length receptors Biochimica et biophysica acta. Biomembranes Medium 31194959
2007 KA2 antisense knockdown in vivo suppresses the assembly of the GluR6/KA2-PSD95-MLK3 signaling module, inhibits JNK activation and c-jun phosphorylation, and increases neuronal survival in hippocampal CA1 after ischemia/reperfusion. Combined KA2 and GluR6 knockdown has greater neuroprotective effect than either alone, indicating functional cooperation between KA2 and GluR6 in mediating ischemic neuronal death through the PSD95-MLK3-MKK4/7-JNK3 pathway. Intracerebroventricular antisense oligodeoxynucleotide injection in rat ischemia model; Western blot for signaling components; neuronal survival counting Journal of neuroscience research Medium 17639597
2019 Knockdown of the GRIK5 ortholog in zebrafish caused reduced blood vessel numbers, reduced vascular integrity in the eye, and increased vascular permeability, indicating a role for GRIK5 in eye vascular biology beyond classical glutamate receptor function. Morpholino knockdown in zebrafish, vascular imaging American journal of human genetics Low 30827500
2023 In heteromeric GluK2/GluK5 receptors, partial agonism by AMPA is mediated primarily through the GluK2 subunit: AMPA induces intermediate cleft closure states at the GluK2 agonist-binding domain (between apo and full-agonist glutamate-bound conformations), while the GluK5 agonist-binding domain shows no significant difference in cleft closure between AMPA and glutamate conditions. Additionally, the agonist-binding domain dimer interface is not decoupled in the AMPA-bound state, unlike the glutamate-bound state. Single-molecule FRET (smFRET) on full-length heteromeric GluK2/GluK5 receptors Proteins Medium 37526035

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron 497 1373632
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 280 7852627
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
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
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
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 59 17348638
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
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
2008 Tonic activation of GLUK5 kainate receptors decreases neuroblast migration in whole-mounts of the subventricular zone. The Journal of physiology 47 18565997
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
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
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
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
2000 Increase in desulfurization activity of Rhodococcus erythropolis KA2-5-1 using ethanol feeding. Journal of bioscience and bioengineering 33 16232759
2001 Long-term repeated biodesulfurization by immobilized Rhodococcus erythropolis KA2-5-1 cells. Applied microbiology and biotechnology 29 11341322
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
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 28 16837561
2003 Trafficking and surface expression of the glutamate receptor subunit, KA2. Biochemical and biophysical research communications 27 14511640
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
2007 Anxiolytic-like effects through a GLUK5 kainate receptor mechanism. Neuropharmacology 20 17418283
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
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
2021 A comparative analysis of kainate receptor GluK2 and GluK5 knockout mice in a pure genetic background. Behavioural brain research 15 33631192
2019 The structural arrangement and dynamics of the heteromeric GluK2/GluK5 kainate receptor as determined by smFRET. Biochimica et biophysica acta. Biomembranes 15 31194959
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
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
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
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
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
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
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
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
2023 Partial agonism in heteromeric GLUK2/GLUK5 kainate receptor. Proteins 3 37526035
2017 [Polymorphic Variants of Glutamate Receptor (GRIK5, GRIN2B) and Serotonin Receptor (HTR2A) Genes Are Associated with Chronic Obstructive Pulmonary Disease]. Molekuliarnaia biologiia 2 28900078
2024 Domoic Acid as a Lead for the Discovery of the First Selective Ligand for Kainate Receptor Subtype 5 (GluK5). Journal of medicinal chemistry 1 39133077

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