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Protein

Glutamate receptor ionotropic, kainate 2

Gene

Grik2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus. Modulates cell surface expression of NETO2.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei523 – 5231GlutamateBy similarity
Binding sitei738 – 7381GlutamateBy similarity

GO - Molecular functioni

  • extracellular-glutamate-gated ion channel activity Source: InterPro
  • ionotropic glutamate receptor activity Source: UniProtKB
  • kainate selective glutamate receptor activity Source: MGI

GO - Biological processi

  • behavioral fear response Source: MGI
  • cellular calcium ion homeostasis Source: MGI
  • excitatory postsynaptic potential Source: MGI
  • inhibitory postsynaptic potential Source: MGI
  • intracellular protein transport Source: MGI
  • modulation of synaptic transmission Source: MGI
  • negative regulation of neuron apoptotic process Source: MGI
  • negative regulation of synaptic transmission, glutamatergic Source: MGI
  • neuronal action potential Source: MGI
  • neuron apoptotic process Source: Ensembl
  • positive regulation of neuron apoptotic process Source: Ensembl
  • positive regulation of synaptic transmission Source: MGI
  • receptor clustering Source: Ensembl
  • regulation of JNK cascade Source: Ensembl
  • regulation of long-term neuronal synaptic plasticity Source: MGI
  • regulation of membrane potential Source: MGI
  • regulation of short-term neuronal synaptic plasticity Source: MGI
  • synaptic transmission Source: MGI
  • synaptic transmission, glutamatergic Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-MMU-451307. Activation of Na-permeable Kainate Receptors.
R-MMU-451308. Activation of Ca-permeable Kainate Receptor.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate receptor ionotropic, kainate 2
Short name:
GluK2
Alternative name(s):
Glutamate receptor 6
Short name:
GluR-6
Short name:
GluR6
Glutamate receptor beta-2
Short name:
GluR beta-2
Gene namesi
Name:Grik2
Synonyms:Glur6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:95815. Grik2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini32 – 561530ExtracellularSequence analysisAdd
BLAST
Transmembranei562 – 58221HelicalSequence analysisAdd
BLAST
Topological domaini583 – 63856CytoplasmicSequence analysisAdd
BLAST
Transmembranei639 – 65921HelicalSequence analysisAdd
BLAST
Topological domaini660 – 819160ExtracellularSequence analysisAdd
BLAST
Transmembranei820 – 84021HelicalSequence analysisAdd
BLAST
Topological domaini841 – 90868CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • dendrite cytoplasm Source: Ensembl
  • ionotropic glutamate receptor complex Source: MGI
  • kainate selective glutamate receptor complex Source: MGI
  • membrane Source: MGI
  • neuronal cell body Source: MGI
  • perikaryon Source: Ensembl
  • postsynaptic density Source: MGI
  • postsynaptic membrane Source: MGI
  • presynaptic membrane Source: MGI
  • synapse Source: UniProtKB
  • terminal bouton Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131Sequence analysisAdd
BLAST
Chaini32 – 908877Glutamate receptor ionotropic, kainate 2PRO_0000011545Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi67 – 671N-linked (GlcNAc...)Sequence analysis
Glycosylationi73 – 731N-linked (GlcNAc...)Sequence analysis
Disulfide bondi96 ↔ 347By similarity
Glycosylationi275 – 2751N-linked (GlcNAc...)Sequence analysis
Glycosylationi378 – 3781N-linked (GlcNAc...)Sequence analysis
Glycosylationi412 – 4121N-linked (GlcNAc...)Sequence analysis
Glycosylationi423 – 4231N-linked (GlcNAc...)Sequence analysis
Glycosylationi430 – 4301N-linked (GlcNAc...)Sequence analysis
Glycosylationi546 – 5461N-linked (GlcNAc...)Sequence analysis
Modified residuei846 – 8461Phosphoserine; by PKCBy similarity
Modified residuei868 – 8681Phosphoserine; by PKCBy similarity
Cross-linki886 – 886Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity

Post-translational modificationi

Sumoylation mediates kainate receptor-mediated endocytosis and regulates synaptic transmission. Sumoylation is enhanced by PIAS3 and desumoylated by SENP1 (By similarity).By similarity
Ubiquitinated. Ubiquitination regulates the GRIK2 levels at the synapse by leading kainate receptor degradation through proteasome (By similarity).By similarity
Phosphorylated by PKC at Ser-868 upon agonist activation, this directly enhance sumoylation.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP39087.
PaxDbiP39087.
PRIDEiP39087.

PTM databases

iPTMnetiP39087.
PhosphoSiteiP39087.

Expressioni

Tissue specificityi

Most abundant in the cerebellum and the hypothalamus.

Developmental stagei

Expressed during brain development. Expression drops in the adult.

Gene expression databases

BgeeiP39087.
ExpressionAtlasiP39087. baseline and differential.
GenevisibleiP39087. MM.

Interactioni

Subunit structurei

Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers (Probable). Assembles into a kainate-gated homomeric channel that does not bind AMPA. GRIK2 associated to GRIK5 forms functional channels that can be gated by AMPA. Interacts with DLG4 (By similarity). Interacts (via C-terminus) with KLHL17 (via kelch repeats); the interaction targets GRIK2 for degradation via ubiquitin-proteasome pathway (By similarity). Interacts with NETO2.By similarityCurated1 Publication

Protein-protein interaction databases

BioGridi200064. 5 interactions.
IntActiP39087. 4 interactions.
STRINGi10090.ENSMUSP00000101124.

Structurei

3D structure databases

ProteinModelPortaliP39087.
SMRiP39087. Positions 33-842.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni516 – 5183Glutamate bindingBy similarity
Regioni689 – 6902Glutamate bindingBy similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1054. Eukaryota.
ENOG410XPSH. LUCA.
GeneTreeiENSGT00760000118920.
HOGENOMiHOG000234371.
HOVERGENiHBG051839.
InParanoidiP39087.
OMAiFRILNIE.
OrthoDBiEOG71G9W6.
PhylomeDBiP39087.
TreeFamiTF334668.

Family and domain databases

InterProiIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu/Gly-bd.
IPR001508. Iono_rcpt_met.
IPR001320. Iontro_rcpt.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view]
PRINTSiPR00177. NMDARECEPTOR.
SMARTiSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMiSSF53822. SSF53822. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform GluR6 Beta2 (identifier: P39087-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM
60 70 80 90 100
GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSFE ASKKACDQLS
110 120 130 140 150
LGVAAIFGPS HSSSANAVQS ICNALGVPHI QTRWKHQVSD NKDSFYVSLY
160 170 180 190 200
PDFSSLSRAI LDLVQFFKWK TVTVVYDDST GLIRLQELIK APSRYNLRLK
210 220 230 240 250
IRQLPADTKD AKPLLKEMKR GKEFHVIFDC SHEMAAGILK QALAMGMMTE
260 270 280 290 300
YYHYIFTTLD LFALDVEPYR YSGVNMTGFR ILNTENTQVS SIIEKWSMER
310 320 330 340 350
LQAPPKPDSG LLDGFMTTDA ALMYDAVHVV SVAVQQFPQM TVSSLQCNRH
360 370 380 390 400
KPWRFGTRFM SLIKEAHWEG LTGRITFNKT NGLRTDFDLD VISLKEEGLE
410 420 430 440 450
KIGTWDPSSG LNMTESQKGK PANITDSLSN RSLIVTTILE EPYVLFKKSD
460 470 480 490 500
KPLYGNDRFE GYCIDLLREL STILGFTYEI RLVEDGKYGA QDDVNGQWNG
510 520 530 540 550
MVRELIDHKA DLAVAPLAIT YVREKVIDFS KPFMTLGISI LYRKPNGTNP
560 570 580 590 600
GVFSFLNPLS PDIWMYILLA YLGVSCVLFV IARFSPYEWY NPHPCNPDSD
610 620 630 640 650
VVENNFTLLN SFWFGVGALM QQGSELMPKA LSTRIVGGIW WFFTLIIISS
660 670 680 690 700
YTANLAAFLT VERMESPIDS ADDLAKQTKI EYGAVEDGAT MTFFKKSKIS
710 720 730 740 750
TYDKMWAFMS SRRQSVLVKS NEEGIQRVLT SDYAFLMEST TIEFVTQRNC
760 770 780 790 800
NLTQIGGLID SKGYGVGTPM GSPYRDKITI AILQLQEEGK LHMMKEKWWR
810 820 830 840 850
GNGCPEEESK EASALGVQNI GGIFIVLAAG LVLSVFVAVG EFLYKSKKNA
860 870 880 890 900
QLEKRSFCSA MVEELRMSLK CQRRLKHKPQ APVIVKTEEV INMHTFNDRR

LPGKETMA
Length:908
Mass (Da):102,486
Last modified:January 9, 2007 - v4
Checksum:iEF430E2D8E0A87D4
GO
Isoform GluR6-2 (identifier: P39087-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     855-908: RSFCSAMVEELRMSLKCQRRLKHKPQAPVIVKTEEVINMHTFNDRRLPGKETMA → ESSIWLVPPYHPDTV

Show »
Length:869
Mass (Da):97,884
Checksum:iDA4DE3E1A78267DA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti611 – 6111S → G in CAA46907 (PubMed:8260617).Curated
Sequence conflicti849 – 86416NAQLE…AMVEE → TLNWKRGPSVAPWWKN in BAA00943 (PubMed:1379666).CuratedAdd
BLAST

RNA editingi

Edited at positions 567, 571 and 621.1 Publication
Partially edited. The presence of Gln at position 621 (non-edited) determines channels with low calcium permeability, whereas Arg (edited) determines a higher calcium permeability especially if the preceding sites are fully edited (By similarity).By similarity

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti567 – 5671I → V in RNA edited version.
Natural varianti571 – 5711Y → C in RNA edited version.
Natural varianti621 – 6211Q → R in RNA edited version.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei855 – 90854RSFCS…KETMA → ESSIWLVPPYHPDTV in isoform GluR6-2. 2 PublicationsVSP_000133Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66117 mRNA. Translation: CAA46907.1.
D10054 mRNA. Translation: BAA00943.1.
U31443 Genomic DNA. Translation: AAA85221.1.
AC113305 Genomic DNA. No translation available.
CCDSiCCDS23830.1. [P39087-2]
CCDS48554.1. [P39087-1]
PIRiA43954.
S35792.
UniGeneiMm.332838.

Genome annotation databases

EnsembliENSMUST00000079751; ENSMUSP00000078687; ENSMUSG00000056073. [P39087-2]
ENSMUST00000105484; ENSMUSP00000101124; ENSMUSG00000056073. [P39087-1]
ENSMUST00000105485; ENSMUSP00000101125; ENSMUSG00000056073. [P39087-2]
ENSMUST00000105487; ENSMUSP00000101127; ENSMUSG00000056073. [P39087-1]

Keywords - Coding sequence diversityi

Alternative splicing, RNA editing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66117 mRNA. Translation: CAA46907.1.
D10054 mRNA. Translation: BAA00943.1.
U31443 Genomic DNA. Translation: AAA85221.1.
AC113305 Genomic DNA. No translation available.
CCDSiCCDS23830.1. [P39087-2]
CCDS48554.1. [P39087-1]
PIRiA43954.
S35792.
UniGeneiMm.332838.

3D structure databases

ProteinModelPortaliP39087.
SMRiP39087. Positions 33-842.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200064. 5 interactions.
IntActiP39087. 4 interactions.
STRINGi10090.ENSMUSP00000101124.

PTM databases

iPTMnetiP39087.
PhosphoSiteiP39087.

Proteomic databases

MaxQBiP39087.
PaxDbiP39087.
PRIDEiP39087.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000079751; ENSMUSP00000078687; ENSMUSG00000056073. [P39087-2]
ENSMUST00000105484; ENSMUSP00000101124; ENSMUSG00000056073. [P39087-1]
ENSMUST00000105485; ENSMUSP00000101125; ENSMUSG00000056073. [P39087-2]
ENSMUST00000105487; ENSMUSP00000101127; ENSMUSG00000056073. [P39087-1]

Organism-specific databases

MGIiMGI:95815. Grik2.

Phylogenomic databases

eggNOGiKOG1054. Eukaryota.
ENOG410XPSH. LUCA.
GeneTreeiENSGT00760000118920.
HOGENOMiHOG000234371.
HOVERGENiHBG051839.
InParanoidiP39087.
OMAiFRILNIE.
OrthoDBiEOG71G9W6.
PhylomeDBiP39087.
TreeFamiTF334668.

Enzyme and pathway databases

ReactomeiR-MMU-451307. Activation of Na-permeable Kainate Receptors.
R-MMU-451308. Activation of Ca-permeable Kainate Receptor.

Miscellaneous databases

PROiP39087.
SOURCEiSearch...

Gene expression databases

BgeeiP39087.
ExpressionAtlasiP39087. baseline and differential.
GenevisibleiP39087. MM.

Family and domain databases

InterProiIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu/Gly-bd.
IPR001508. Iono_rcpt_met.
IPR001320. Iontro_rcpt.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view]
PRINTSiPR00177. NMDARECEPTOR.
SMARTiSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMiSSF53822. SSF53822. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6."
    Gregor P., O'Hara B.F., Yang X., Uhl G.R.
    NeuroReport 4:1343-1346(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GLUR6-2).
    Strain: BALB/cJ.
    Tissue: Brain.
  2. "Cloning and functional expression of a cDNA encoding the mouse beta 2 subunit of the kainate-selective glutamate receptor channel."
    Morita T., Sakimura K., Kushiya E., Yamazaki M., Meguro H., Araki K., Abe T., Mori K.J., Mishina M.
    Brain Res. Mol. Brain Res. 14:143-146(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-864 (ISOFORM GLUR6-2).
  3. "Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences."
    Herb A., Higuchi M., Sprengel R., Seeburg P.H.
    Proc. Natl. Acad. Sci. U.S.A. 93:1875-1880(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 584-695, RNA EDITING OF POSITION 621.
    Strain: BALB/cJ.
  4. "Determinants of Ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: diversity by RNA editing."
    Koehler M., Burnashev N., Sakmann B., Seeburg P.H.
    Neuron 10:491-500(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 560-585, RNA EDITING OF POSITIONS 567; 571 AND 621.
    Tissue: Brain.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 855-908.
    Strain: C57BL/6J.
  6. "Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
    Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
    Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.
  7. Cited for: FUNCTION, INTERACTION WITH NETO2.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.

Entry informationi

Entry nameiGRIK2_MOUSE
AccessioniPrimary (citable) accession number: P39087
Secondary accession number(s): Q60933
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 9, 2007
Last modified: June 8, 2016
This is version 157 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate > quisqualate > 6-cyano-7-nitroquinoxaline-2,3-dione > L-glutamate = 6,7-dinitroquinoxaline-2,3-dione > dihydrokainate (By similarity).By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.