P42260 (GRIK2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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 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 junction › synapse › postsynaptic 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 process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	RNA editing
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Ion channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 synaptic transmission Inferred from mutant phenotype Ref.1. Source: RGD
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW dendrite cytoplasm Inferred from direct assay PubMed 15844209. Source: RGD ionotropic glutamate receptor complex Inferred from direct assay PubMed 10627597. Source: UniProtKB perikaryon Inferred from direct assay PubMed 15844209. Source: RGD postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell terminal bouton Inferred from direct assay PubMed 15844209. Source: RGD
Molecular_function	extracellular-glutamate-gated ion channel activity Inferred from electronic annotation. Source: InterPro kainate selective glutamate receptor activity Inferred from direct assay Ref.1. Source: RGD protein homodimerization activity Inferred from direct assay Ref.1. Source: RGD
Complete GO annotation...

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_0000011546

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

Region

689 – 690

2

Glutamate binding

Sites

Binding site

523

1

Glutamate

Binding site

738

1

Glutamate

Amino acid modifications

Modified residue

846

1

Phosphoserine; by PKC By similarity

Modified residue

868

1

Phosphoserine; by PKC By similarity

Glycosylation

67

1

N-linked (GlcNAc...) Ref.11

Glycosylation

73

1

N-linked (GlcNAc...) Potential

Glycosylation

275

1

N-linked (GlcNAc...) Potential

Glycosylation

378

1

N-linked (GlcNAc...) Ref.11

Glycosylation

412

1

N-linked (GlcNAc...) Ref.11

Glycosylation

423

1

N-linked (GlcNAc...) Ref.9

Glycosylation

430

1

N-linked (GlcNAc...) Potential

Glycosylation

546

1

N-linked (GlcNAc...) Potential

Glycosylation

751

1

N-linked (GlcNAc...) Ref.9

Disulfide bond

96 ↔ 347

Ref.11

Cross-link

886

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) Ref.6

Natural variations

Natural variant

567

1

I → C 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

Mutagenesis

883

1

V → A: Abolishes interaction with KLHL17. Abolishes actinfilin-mediated degradation. Ref.5

Mutagenesis

884

1

I → A: Abolishes interaction with KLHL17. Abolishes actinfilin-mediated degradation. Ref.5

Mutagenesis

886

1

K → R: Abolishes sumoylation. Loss of kainate-mediated endocytosis. Ref.6

Secondary structure

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908

Helix Strand Turn

Details...

Beta strand

34 – 47

14

Helix

52 – 66

15

Beta strand

68 – 84

17

Helix

88 – 101

14

Helix

112 – 124

13

Beta strand

129 – 131

3

Beta strand

145 – 151

7

Helix

153 – 166

14

Beta strand

170 – 178

9

Helix

180 – 184

5

Helix

186 – 189

4

Helix

191 – 193

3

Beta strand

198 – 203

6

Helix

208 – 211

4

Helix

212 – 220

9

Beta strand

225 – 230

6

Helix

232 – 244

13

Beta strand

249 – 251

3

Beta strand

253 – 256

4

Helix

261 – 263

3

Turn

267 – 271

5

Beta strand

275 – 280

6

Helix

287 – 298

12

Beta strand

309 – 311

3

Helix

318 – 335

18

Beta strand

347 – 349

3

Helix

356 – 365

10

Beta strand

367 – 370

4

Beta strand

373 – 376

4

Turn

379 – 381

3

Beta strand

382 – 384

3

Beta strand

389 – 395

7

Beta strand

398 – 406

9

Turn

407 – 409

3

Beta strand

410 – 413

4

Turn

425 – 428

4

Beta strand

433 – 437

5

Turn

441 – 443

3

Beta strand

444 – 446

3

Helix

455 – 458

4

Beta strand

459 – 461

3

Helix

462 – 474

13

Beta strand

478 – 482

5

Turn

493 – 495

3

Helix

500 – 506

7

Beta strand

511 – 513

3

Helix

521 – 524

4

Beta strand

527 – 529

3

Beta strand

533 – 536

4

Beta strand

538 – 544

7

Beta strand

665 – 667

3

Helix

671 – 675

5

Beta strand

678 – 685

8

Helix

689 – 696

8

Helix

700 – 711

12

Helix

713 – 716

4

Beta strand

717 – 720

4

Helix

721 – 730

10

Beta strand

731 – 738

8

Helix

739 – 748

10

Beta strand

752 – 757

6

Beta strand

762 – 764

3

Beta strand

767 – 769

3

Helix

774 – 787

14

Helix

790 – 799

10

Sequences

	Sequence		Length	Mass (Da)
	P42260 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 7F430E2D8B2E982B	FASTA	908	102,470
	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

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.

IPI

IPI00324708.

PIR

S19098.

RefSeq

NP_062182.1. NM_019309.2.

UniGene

Rn.87696.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S50	X-ray	1.65	A	429-806	[»]
1S7Y	X-ray	1.75	A/B	429-806	[»]
1S9T	X-ray	1.80	A/B	429-806	[»]
1SD3	X-ray	1.80	A/B	429-806	[»]
1TT1	X-ray	1.93	A/B	429-806	[»]
1YAE	X-ray	3.11	A/B/C/D/E/F	419-819	[»]
2I0B	X-ray	1.96	A/B/C	429-806	[»]
2I0C	X-ray	2.25	A/B	429-805	[»]
2XXR	X-ray	1.60	A/B	429-806	[»]
2XXT	X-ray	1.90	A/B	429-806	[»]
2XXU	X-ray	1.50	A/B	429-806	[»]
2XXV	X-ray	1.70	A/B	429-806	[»]
2XXW	X-ray	2.30	A/B	429-806	[»]
2XXX	X-ray	2.10	A/B/C/D	429-806	[»]
2XXY	X-ray	3.00	A/B/C/D	429-806	[»]
3G3F	X-ray	1.38	A/B	429-806	[»]
3G3G	X-ray	1.30	A/B	429-806	[»]
3G3H	X-ray	1.50	A/B	429-806	[»]
3G3I	X-ray	1.37	A/B	429-806	[»]
3G3J	X-ray	1.32	A/B	429-806	[»]
3G3K	X-ray	1.24	A/B	429-806	[»]
3H6G	X-ray	2.70	A/B	32-420	[»]
3H6H	X-ray	2.90	A/B	32-420	[»]
3QLT	X-ray	2.99	A/B	32-420	[»]
3QLU	X-ray	2.91	C/D	32-420	[»]
3QLV	X-ray	3.94	C/D/F/H/J	32-420	[»]

ProteinModelPortal

P42260.

SMR

P42260. Positions 423-546, 668-804.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29256N.

STRING

10116.ENSRNOP00000000415.

PTM databases

PhosphoSite

P42260.

Proteomic databases

PaxDb

P42260.

PRIDE

P42260.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

54257.

KEGG

rno:54257.

UCSC

RGD:2733. rat.

Organism-specific databases

CTD

2898.

RGD

2733. Grik2.

Phylogenomic databases

eggNOG

NOG316680.

HOGENOM

HOG000234371.

HOVERGEN

HBG051839.

InParanoid

P42260.

KO

K05202.

OrthoDB

EOG41C6VH.

Gene expression databases

ArrayExpress

P42260.

Genevestigator

P42260.

GermOnline

ENSRNOG00000000368. Rattus norvegicus.

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

BindingDB

P42260.

ChEMBL

CHEMBL3607.

EvolutionaryTrace

P42260.

NextBio

610770.

Entry information

Entry name

GRIK2_RAT

Accession

Primary (citable) accession number: P42260

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	July 15, 1998
Last modified:	April 3, 2013
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program