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P42260 (GRIK2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutamate receptor ionotropic, kainate 2

Short name=GluK2
Alternative name(s):
Glutamate receptor 6
Short name=GluR-6
Short name=GluR6
Gene names
Name:Grik2
Synonyms:Glur6
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length908 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Ref.6 Ref.10

Subunit structure

Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Assembles into a kainate-gated homomeric channel that does not bind AMPA By similarity. GRIK2 associated to GRIK5 forms functional channels that can be gated by AMPA. Interacts with DLG4. Interacts with NETO2. Interacts (via C-terminus) with KLHL17 (via kelch repeats); the interaction targets GRIK2 for degradation via ubiquitin-proteasome pathway. Ref.4 Ref.5 Ref.7 Ref.9 Ref.10 Ref.11

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein Ref.6.

Tissue specificity

Highest expression is found in the olfactory lobe, piriform cortex, dentate gyrus, hippocampus, granular cell layer of the cerebellum, and in caudate-putamen.

Post-translational modification

Sumoylation mediates kainate receptor-mediated endocytosis and regulates synaptic transmission. Sumoylation is enhanced by PIAS3 and desumoylated by SENP1. Ref.6

Ubiquitinated. Ubiquitination regulates the GRIK2 levels at the synapse by leading kainate receptor degradation through proteasome. Ref.5

Phosphorylated by PKC at Ser-868 upon agonist activation, this directly enhance sumoylation By similarity.

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 > glutamate. It does not bind AMPA without coexpression with GRIK5.

Sequence similarities

Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK2 subfamily. [View classification]

RNA editing

Edited at positions 567, 571 and 621.
Partially edited. The presence of Gln at position 621 (non-edited) determines channels with low calcium permeability, whereas an arginine residue (edited) determines a higher calcium permeability especially if the preceding sites are fully edited. This receptor is nearly completely edited in all gray matter structures (90% of the receptors). Ref.3

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityRNA editing
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionIon channel
Ligand-gated ion channel
Receptor
   PTMDisulfide bond
Glycoprotein
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_procession transmembrane transport

Inferred from Biological aspect of Ancestor. Source: GOC

ionotropic glutamate receptor signaling pathway

Inferred from direct assay Ref.1. Source: GOC

negative regulation of synaptic transmission, glutamatergic

Inferred from direct assay PubMed 16420445. Source: UniProtKB

neuron apoptotic process

Inferred from mutant phenotype PubMed 11152698. Source: UniProtKB

positive regulation of neuron apoptotic process

Inferred from mutant phenotype PubMed 17639597. Source: RGD

receptor clustering

Inferred from direct assay PubMed 9808460. Source: UniProtKB

regulation of JNK cascade

Inferred from mutant phenotype PubMed 11152698. Source: UniProtKB

signal transduction

Inferred from direct assay PubMed 10627597. Source: GOC

synaptic transmission

Inferred from mutant phenotype Ref.1. Source: RGD

   Cellular_componentaxon

Inferred from direct assay PubMed 15844209. Source: RGD

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

dendrite

Inferred from direct assay PubMed 9808460. Source: UniProtKB

dendrite cytoplasm

Inferred from direct assay PubMed 15844209. Source: RGD

integral component of plasma membrane

Inferred from direct assay PubMed 9808460. Source: UniProtKB

ionotropic glutamate receptor complex

Inferred from direct assay PubMed 10627597. Source: UniProtKB

kainate selective glutamate receptor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

perikaryon

Inferred from direct assay PubMed 15844209. Source: RGD

postsynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

presynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

synapse

Inferred from direct assay Ref.6. Source: RGD

terminal bouton

Inferred from direct assay PubMed 15844209. Source: RGD

   Molecular_functionPDZ domain binding

Inferred from physical interaction PubMed 1127911PubMed 9808460. Source: UniProtKB

extracellular-glutamate-gated ion channel activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

glutamate receptor activity

Inferred from direct assay PubMed 10627597. Source: UniProtKB

identical protein binding

Inferred from direct assay Ref.1. Source: RGD

ionotropic glutamate receptor activity

Traceable author statement Ref.1. Source: RGD

kainate selective glutamate receptor activity

Inferred from direct assay Ref.1. Source: RGD

protein homodimerization activity

Inferred from direct assay Ref.1. Source: RGD

ubiquitin conjugating enzyme binding

Inferred from physical interaction Ref.6. Source: RGD

ubiquitin protein ligase binding

Inferred from physical interaction Ref.6. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Map3k11Q66HA12EBI-7809795,EBI-4279420

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Potential
Chain32 – 908877Glutamate receptor ionotropic, kainate 2
PRO_0000011546

Regions

Topological domain32 – 561530Extracellular Potential
Transmembrane562 – 58221Helical; Potential
Topological domain583 – 63856Cytoplasmic Potential
Transmembrane639 – 65921Helical; Potential
Topological domain660 – 819160Extracellular Potential
Transmembrane820 – 84021Helical; Potential
Topological domain841 – 90868Cytoplasmic Potential
Region516 – 5183Glutamate binding
Region689 – 6902Glutamate binding

Sites

Binding site5231Glutamate
Binding site7381Glutamate

Amino acid modifications

Modified residue8461Phosphoserine; by PKC By similarity
Modified residue8681Phosphoserine; by PKC By similarity
Glycosylation671N-linked (GlcNAc...) Ref.11
Glycosylation731N-linked (GlcNAc...) Potential
Glycosylation2751N-linked (GlcNAc...) Potential
Glycosylation3781N-linked (GlcNAc...) Ref.11
Glycosylation4121N-linked (GlcNAc...) Ref.11
Glycosylation4231N-linked (GlcNAc...) Ref.9
Glycosylation4301N-linked (GlcNAc...) Potential
Glycosylation5461N-linked (GlcNAc...) Potential
Glycosylation7511N-linked (GlcNAc...) Ref.9
Disulfide bond96 ↔ 347 Ref.11
Cross-link886Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) Ref.6

Natural variations

Natural variant5671I → C in RNA edited version.
Natural variant5711Y → C in RNA edited version.
Natural variant6211Q → R in RNA edited version.

Experimental info

Mutagenesis8831V → A: Abolishes interaction with KLHL17. Abolishes actinfilin-mediated degradation. Ref.5
Mutagenesis8841I → A: Abolishes interaction with KLHL17. Abolishes actinfilin-mediated degradation. Ref.5
Mutagenesis8861K → R: Abolishes sumoylation. Loss of kainate-mediated endocytosis. Ref.6

Secondary structure

........................................................................................................................ 908
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42260 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: 7F430E2D8B2E982B

FASTA908102,470
        10         20         30         40         50         60 
MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA 

        70         80         90        100        110        120 
VNTINRNRTL LPNTTLTYDT QKINLYDSFE ASKKACDQLS LGVAAIFGPS HSSSANAVQS 

       130        140        150        160        170        180 
ICNALGVPHI QTRWKHQVSD NKDSFYVSLY PDFSSLSRAI LDLVQFFKWK TVTVVYDDST 

       190        200        210        220        230        240 
GLIRLQELIK APSRYNLRLK IRQLPADTKD AKPLLKEMKR GKEFHVIFDC SHEMAAGILK 

       250        260        270        280        290        300 
QALAMGMMTE YYHYIFTTLD LFALDVEPYR YSGVNMTGFR ILNTENTQVS SIIEKWSMER 

       310        320        330        340        350        360 
LQAPPKPDSG LLDGFMTTDA ALMYDAVHVV SVAVQQFPQM TVSSLQCNRH KPWRFGTRFM 

       370        380        390        400        410        420 
SLIKEAHWEG LTGRITFNKT NGLRTDFDLD VISLKEEGLE KIGTWDPASG LNMTESQKGK 

       430        440        450        460        470        480 
PANITDSLSN RSLIVTTILE EPYVLFKKSD KPLYGNDRFE GYCIDLLREL STILGFTYEI 

       490        500        510        520        530        540 
RLVEDGKYGA QDDVNGQWNG MVRELIDHKA DLAVAPLAIT YVREKVIDFS KPFMTLGISI 

       550        560        570        580        590        600 
LYRKPNGTNP GVFSFLNPLS PDIWMYILLA YLGVSCVLFV IARFSPYEWY NPHPCNPDSD 

       610        620        630        640        650        660 
VVENNFTLLN SFWFGVGALM QQGSELMPKA LSTRIVGGIW WFFTLIIISS YTANLAAFLT 

       670        680        690        700        710        720 
VERMESPIDS ADDLAKQTKI EYGAVEDGAT MTFFKKSKIS TYDKMWAFMS SRRQSVLVKS 

       730        740        750        760        770        780 
NEEGIQRVLT SDYAFLMEST TIEFVTQRNC NLTQIGGLID SKGYGVGTPM GSPYRDKITI 

       790        800        810        820        830        840 
AILQLQEEGK LHMMKEKWWR GNGCPEEESK EASALGVQNI GGIFIVLAAG LVLSVFVAVG 

       850        860        870        880        890        900 
EFLYKSKKNA QLEKRSFCSA MVEELRMSLK CQRRLKHKPQ APVIVKTEEV INMHTFNDRR 


LPGKETMA 

« Hide

References

[1]"Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA."
Egebjerg J., Bettler B., Hermans-Borgmeyer I., Heinemann S.F.
Nature 351:745-748(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"High-affinity kainate and domoate receptors in rat brain."
Lomeli H., Wisden W., Koehler M., Keinaenen K., Sommer B., Seeburg P.H.
FEBS Lett. 307:139-143(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"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.
Tissue: Brain.
[4]"The PDZ1 domain of SAP90. Characterization of structure and binding."
Piserchio A., Pellegrini M., Mehta S., Blackman S.M., Garcia E.P., Marshall J., Mierke D.F.
J. Biol. Chem. 277:6967-6973(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DLG4.
[5]"Actinfilin is a Cul3 substrate adaptor, linking GluR6 kainate receptor subunits to the ubiquitin-proteasome pathway."
Salinas G.D., Blair L.A., Needleman L.A., Gonzales J.D., Chen Y., Li M., Singer J.D., Marshall J.
J. Biol. Chem. 281:40164-40173(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KLHL17, UBIQUITINATION, MUTAGENESIS OF VAL-883 AND ILE-884.
[6]"SUMOylation regulates kainate-receptor-mediated synaptic transmission."
Martin S., Nishimune A., Mellor J.R., Henley J.M.
Nature 447:321-325(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-886, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-886.
[7]"A transmembrane accessory subunit that modulates kainate-type glutamate receptors."
Zhang W., St-Gelais F., Grabner C.P., Trinidad J.C., Sumioka A., Morimoto-Tomita M., Kim K.S., Straub C., Burlingame A.L., Howe J.R., Tomita S.
Neuron 61:385-396(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NETO2.
[8]"Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity."
Mayer M.L.
Neuron 45:539-552(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 429-806 IN COMPLEXES WITH GLUTAMATE; KAINATE; METHYLGLUTAMATE AND QUISQUALATE.
[9]"Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid."
Nanao M.H., Green T., Stern-Bach Y., Heinemann S.F., Choe S.
Proc. Natl. Acad. Sci. U.S.A. 102:1708-1713(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.11 ANGSTROMS) OF 419-819 IN COMPLEX WITH DOMOATE, SUBUNIT, GLYCOSYLATION AT ASN-423 AND ASN-751.
[10]"Conformational restriction blocks glutamate receptor desensitization."
Weston M.C., Schuck P., Ghosal A., Rosenmund C., Mayer M.L.
Nat. Struct. Mol. Biol. 13:1120-1127(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 663-806, FUNCTION, SUBUNIT.
[11]"Structure and assembly mechanism for heteromeric kainate receptors."
Kumar J., Schuck P., Mayer M.L.
Neuron 71:319-331(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.91 ANGSTROMS) OF 32-420 IN COMPLEX WITH GRIK5, DISULFIDE BONDS, GLYCOSYLATION AT ASN-67; ASN-378 AND ASN-412, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z11548 mRNA. Translation: CAA77647.1.
Z11715 mRNA. Translation: CAA77778.1.
PIRS19098.
RefSeqNP_062182.1. NM_019309.2.
UniGeneRn.87696.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S50X-ray1.65A429-806[»]
1S7YX-ray1.75A/B429-806[»]
1S9TX-ray1.80A/B429-806[»]
1SD3X-ray1.80A/B429-806[»]
1TT1X-ray1.93A/B429-806[»]
1YAEX-ray3.11A/B/C/D/E/F419-819[»]
2I0BX-ray1.96A/B/C429-806[»]
2I0CX-ray2.25A/B429-805[»]
2XXRX-ray1.60A/B429-806[»]
2XXTX-ray1.90A/B429-806[»]
2XXUX-ray1.50A/B429-806[»]
2XXVX-ray1.70A/B429-806[»]
2XXWX-ray2.30A/B429-806[»]
2XXXX-ray2.10A/B/C/D429-806[»]
2XXYX-ray3.00A/B/C/D429-806[»]
3G3FX-ray1.38A/B429-806[»]
3G3GX-ray1.30A/B429-806[»]
3G3HX-ray1.50A/B429-806[»]
3G3IX-ray1.37A/B429-806[»]
3G3JX-ray1.32A/B429-806[»]
3G3KX-ray1.24A/B429-806[»]
3H6GX-ray2.70A/B32-420[»]
3H6HX-ray2.90A/B32-420[»]
3QLTX-ray2.99A/B32-420[»]
3QLUX-ray2.91C/D32-420[»]
3QLVX-ray3.94C/D/F/H/J32-420[»]
4BDLX-ray1.75A/B429-806[»]
4BDMX-ray3.40A/B/C/D429-806[»]
4BDNX-ray2.50A/B/C/D429-806[»]
4BDOX-ray2.55A/B/C/D429-806[»]
4BDQX-ray1.90A/B429-806[»]
4BDRX-ray1.65A/B429-806[»]
4H8IX-ray2.00A/B667-806[»]
ProteinModelPortalP42260.
SMRP42260. Positions 423-546, 668-804.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248480. 3 interactions.
DIPDIP-29256N.
IntActP42260. 3 interactions.
MINTMINT-8359884.
STRING10116.ENSRNOP00000000415.

Chemistry

BindingDBP42260.
ChEMBLCHEMBL2094119.

Protein family/group databases

TCDB1.A.10.1.11. the glutamate-gated ion channel (gic) family of neurotransmitter receptors.

PTM databases

PhosphoSiteP42260.

Proteomic databases

PaxDbP42260.
PRIDEP42260.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID54257.
KEGGrno:54257.
UCSCRGD:2733. rat.

Organism-specific databases

CTD2898.
RGD2733. Grik2.

Phylogenomic databases

eggNOGNOG316680.
HOGENOMHOG000234371.
HOVERGENHBG051839.
InParanoidP42260.
KOK05202.
PhylomeDBP42260.

Gene expression databases

GenevestigatorP42260.

Family and domain databases

InterProIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view]
PRINTSPR00177. NMDARECEPTOR.
SMARTSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMSSF53822. SSF53822. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP42260.
NextBio610770.
PROP42260.

Entry information

Entry nameGRIK2_RAT
AccessionPrimary (citable) accession number: P42260
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 15, 1998
Last modified: April 16, 2014
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references