P39087 (GRIK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamate receptor, ionotropic kainate 2

Alternative name(s):
Glutamate receptor 6
Short name=GluR-6
Short name=GluR6
Glutamate receptor beta-2
Short name=GluR beta-2

Gene names

Name:	Grik2
Synonyms:	Glur6

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	908 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Ref.6
Subunit structure	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. Ref.6
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein.
Tissue specificity	Most abundant in the cerebellum and the hypothalamus.
Developmental stage	Expressed during brain development. Expression drops in the adult.
Post-translational modification	Sumoylation mediates kainate receptor-mediated endocytosis and regulates synaptic transmission. Sumoylation is enhanced by PIAS3 and desumoylated by SENP1 By similarity. Ubiquitinated. Ubiquitination regulates the GRIK2 levels at the synapse by leading kainate receptor degradation through proteasome 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 > 6-cyano-7-nitroquinoxaline-2,3-dione > L-glutamate = 6,7-dinitroquinoxaline-2,3-dione > dihydrokainate By similarity.
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 Arg (edited) determines a higher calcium permeability especially if the preceding sites are fully edited By similarity. Ref.3 Ref.4

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing RNA editing
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Ionic channel Ligand-gated ion channel Receptor
PTM	Glycoprotein Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	behavioral fear response Inferred from mutant phenotype. Source: MGI cellular calcium ion homeostasis Inferred from mutant phenotype. Source: MGI intracellular protein transport Inferred from direct assay. Source: MGI negative regulation of neuron apoptosis Inferred from genetic interaction. Source: MGI negative regulation of synaptic transmission, glutamatergic Inferred from genetic interaction. Source: MGI regulation of action potential in neuron Inferred from mutant phenotype. Source: MGI regulation of excitatory postsynaptic membrane potential Inferred from mutant phenotype. Source: MGI regulation of inhibitory postsynaptic membrane potential Inferred from mutant phenotype. Source: MGI regulation of long-term neuronal synaptic plasticity Inferred from mutant phenotype. Source: MGI regulation of membrane potential Inferred from direct assay. Source: MGI regulation of short-term neuronal synaptic plasticity Inferred from mutant phenotype. Source: MGI synaptic transmission Inferred from mutant phenotype. Source: MGI synaptic transmission, glutamatergic Inferred from mutant phenotype. Source: MGI
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW intracellular Inferred from direct assay. Source: GOC kainate selective glutamate receptor complex Inferred from physical interaction. Source: MGI membrane Inferred from direct assay. Source: MGI membrane fraction Inferred from direct assay. Source: MGI postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell presynaptic membrane Inferred from direct assay. Source: MGI
Molecular function	extracellular-glutamate-gated ion channel activity Inferred from electronic annotation. Source: InterPro kainate selective glutamate receptor activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform GluR6 Beta2 (identifier: P39087-1)

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.

Isoform GluR6-2 (identifier: P39087-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Potential
	Chain	32 – 908	877	Glutamate receptor, ionotropic kainate 2		PRO_0000011545
Regions
	Topological domain	32 – 561	530	Extracellular Potential
	Transmembrane	562 – 582	21	Helical; Potential
	Topological domain	583 – 638	56	Cytoplasmic Potential
	Transmembrane	639 – 659	21	Helical; Potential
	Topological domain	660 – 819	160	Extracellular Potential
	Transmembrane	820 – 840	21	Helical; Potential
	Topological domain	841 – 908	68	Cytoplasmic Potential
	Region	516 – 518	3	Glutamate binding By similarity
	Region	689 – 690	2	Glutamate binding By similarity
Sites
	Binding site	523	1	Glutamate By similarity
	Binding site	738	1	Glutamate By similarity
Amino acid modifications
	Glycosylation	67	1	N-linked (GlcNAc...) Potential
	Glycosylation	73	1	N-linked (GlcNAc...) Potential
	Glycosylation	275	1	N-linked (GlcNAc...) Potential
	Glycosylation	378	1	N-linked (GlcNAc...) Potential
	Glycosylation	412	1	N-linked (GlcNAc...) Potential
	Glycosylation	423	1	N-linked (GlcNAc...) Potential
	Glycosylation	430	1	N-linked (GlcNAc...) Potential
	Glycosylation	546	1	N-linked (GlcNAc...) Potential
	Cross-link	886		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) By similarity
Natural variations
	Alternative sequence	855 – 908	54	RSFCS…KETMA → ESSIWLVPPYHPDTV in isoform GluR6-2.		VSP_000133
	Natural variant	567	1	I → V in RNA edited version.
	Natural variant	571	1	Y → C in RNA edited version.
	Natural variant	621	1	Q → R in RNA edited version.
Experimental info
	Sequence conflict	611	1	S → G in CAA46907. Ref.1
	Sequence conflict	849 – 864	16	NAQLE…AMVEE → TLNWKRGPSVAPWWKN in BAA00943. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform GluR6 Beta2 [UniParc]. Last modified January 9, 2007. Version 4. Checksum: EF430E2D8E0A87D4	FASTA	908	102,486
	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 KIGTWDPSSG 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
	Isoform GluR6-2 [UniParc]. Checksum: DA4DE3E1A78267DA	FASTA	869	97,884
	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 KIGTWDPSSG 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 EFLYKSKKNA QLEKESSIWL VPPYHPDTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 8260617] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GLUR6-2). Strain: BALB/c. 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: 1379666] [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: 8700852] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 584-695, RNA EDITING OF POSITION 621. Strain: BALB/c.
[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: 7681676] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 560-585, RNA EDITING OF POSITIONS 567; 571 AND 621. Tissue: Brain.
[5]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 855-908. Strain: C57BL/6J.
[6]	"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: 19217376] [Abstract] Cited for: FUNCTION, INTERACTION WITH NETO2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X66117 mRNA. Translation: CAA46907.1. D10054 mRNA. Translation: BAA00943.1. U31443 Genomic DNA. Translation: AAA85221.1. AC113305 Genomic DNA. No translation available.
IPI	IPI00131566. IPI00223171.
PIR	A43954. S35792.
UniGene	Mm.332838.
3D structure databases
ProteinModelPortal	P39087.
SMR	P39087. Positions 33-415, 424-804.
ModBase	Search...
Protein-protein interaction databases
IntAct	P39087. 4 interactions.
STRING	P39087.
PTM databases
PhosphoSite	P39087.
Proteomic databases
PRIDE	P39087.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000078692; ENSMUSP00000077758; ENSMUSG00000056073. ENSMUST00000079751; ENSMUSP00000078687; ENSMUSG00000056073. ENSMUST00000105485; ENSMUSP00000101125; ENSMUSG00000056073. ENSMUST00000105487; ENSMUSP00000101127; ENSMUSG00000056073.
Organism-specific databases
MGI	MGI:95815. Grik2.
Phylogenomic databases
GeneTree	ENSGT00590000083056.
HOGENOM	HBG381523.
HOVERGEN	HBG051839.
InParanoid	P39087.
OMA	GVQQFPQ.
OrthoDB	EOG41C6VH.
PhylomeDB	P39087.
Gene expression databases
ArrayExpress	P39087.
Bgee	P39087.
Genevestigator	P39087.
GermOnline	ENSMUSG00000056073. Mus musculus.
Family and domain databases
InterPro	IPR001828. ANF_lig-bd_rcpt. IPR019594. Glu_rcpt_Glu/Gly-bd. IPR001320. Iontro_glu_rcpt. IPR001508. NMDA_rcpt. [Graphical view]
Pfam	PF01094. ANF_receptor. 1 hit. PF00060. Lig_chan. 1 hit. PF10613. Lig_chan-Glu_bd. 1 hit. [Graphical view]
PRINTS	PR00177. NMDARECEPTOR.
SMART	SM00918. Lig_chan-Glu_bd. 1 hit. SM00079. PBPe. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

GRIK2_MOUSE

Accession

Primary (citable) accession number: P39087
Secondary accession number(s): Q60933

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	January 9, 2007
Last modified:	November 16, 2011
This is version 115 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program