Reviewed, UniProtKB/Swiss-Prot P19491 (GRIA2_RAT)

Names and origin

Protein names

Glutamate receptor 2 [Precursor]
Also known as:
     GluR-2
     GluR-B
     GluR-K2
     Glutamate receptor ionotropic, AMPA 2
     AMPA-selective glutamate receptor 2

Gene names

Name:	Gria2
Synonyms:	Glur2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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.
Subunit structure	Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. May interact with MPP4. Forms a ternary complex with GRIP1 and CSPG4 By similarity. Interacts with CACNG2, PRKCABP, GRIP1 and GRIP2. Interacts with NSF via its C-terminus. Part of a complex containing GRIA2, NSF and NAPA and/or NAPB.
Subcellular location	Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Note=Interaction with CACNG2 promotes cell surface expression.
Tissue specificity	Detected in forebrain. Detected in dendrites of neuronal cells.
Developmental stage	Detected at low levels in newborns. Levels increase strongly and are highest in hippocampus from 8 to 14 day old animals. Detected at intermediate levels at day 42 (at protein level).
Post-translational modification	Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-610 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-836 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis 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 AMPA (quisqualate) > glutamate > kainate.
Sequence similarities	Belongs to the glutamate-gated ion channel (TC 1.A.10) family. [View classification]
RNA editing	Edited at position 607. Fully edited in the brain. Heteromerically expressed edited GLUR2 (R) receptor complexes are impermeable to calcium, whereas the unedited (Q) forms are highly permeable to divalent ions (By similarity).

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Endoplasmic reticulum Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing RNA editing
Domain	Signal Transmembrane
Molecular function	Ionic channel Receptor
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	establishment of protein localization Inferred from mutant phenotype. Source: UniProtKB positive regulation of synaptic transmission Inferred from mutant phenotype. Source: UniProtKB receptor internalization Inferred from direct assay. Source: UniProtKB regulation of receptor recycling Inferred from mutant phenotype. Source: UniProtKB regulation of synaptic transmission, glutamatergic Inferred from mutant phenotype. Source: UniProtKB response to lithium ion Inferred from expression pattern. Source: UniProtKB
Cellular component	cell soma Ref.10 Inferred from direct assay. Source: UniProtKB dendritic shaft Ref.10 Inferred from direct assay. Source: UniProtKB dendritic spine Inferred from direct assay. Source: UniProtKB ionotropic glutamate receptor complex Traceable author statement. Source: UniProtKB synapse Ref.6 Inferred from direct assay. Source: UniProtKB
Molecular function	PDZ domain binding Ref.6 Inferred from direct assay. Source: UniProtKB receptor activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Grip2	Q9WTW1-3	4	EBI-77718,EBI-936068
Mpp4	Q9QYH1	1	EBI-77718,EBI-937554
NSF	P18708	1	EBI-77718,EBI-925742	From a different organism.
Nsf	Q9QUL6	4	EBI-77718,EBI-925794
Pick1	Q9EP80	6	EBI-77718,EBI-77728

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Flop (identifier: P19491-1)
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 Flip (identifier: P19491-2)
The sequence of this isoform differs from the canonical sequence as follows:
     765-766 NA → TP
     775-775 N → S
     779-779 L → V
     796-800 SGGGD → AKDSG

Isoform 3 (identifier: P19491-3)
Also known as Long;
The sequence of this isoform differs from the canonical sequence as follows:
     848-883 VAKNPQNINP...NVYGIESVKI → MTLSDVMRSK...GMNVSVTDLS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 883

862

Glutamate receptor 2

Regions

Topological domain

22 – 543

522

Extracellular Potential

Transmembrane

544 – 564

21

Potential

Topological domain

565 – 624

60

Cytoplasmic Potential

Transmembrane

625 – 645

21

Potential

Topological domain

646 – 812

167

Extracellular Potential

Transmembrane

813 – 833

21

Potential

Topological domain

834 – 883

50

Cytoplasmic Potential

Region

499 – 501

3

Glutamate binding

Region

675 – 676

2

Glutamate binding

Sites

Binding site

506

1

Glutamate

Binding site

726

1

Glutamate

Amino acid modifications

Modified residue

683

1

Phosphoserine; by PKC

Modified residue

717

1

Phosphoserine; by PKG

Modified residue

869

1

Phosphotyrosine By similarity

Modified residue

876

1

Phosphotyrosine

Modified residue

880

1

Phosphoserine By similarity

Lipidation

610

1

S-palmitoyl cysteine By similarity

Lipidation

836

1

S-palmitoyl cysteine By similarity

Glycosylation

256

1

N-linked (GlcNAc...) Potential

Glycosylation

370

1

N-linked (GlcNAc...) Potential

Glycosylation

406

1

N-linked (GlcNAc...) Potential

Glycosylation

413

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

765 – 766

2

NA → TP in isoform Flip.

Alternative sequence

775

1

N → S in isoform Flip.

Alternative sequence

779

1

L → V in isoform Flip.

Alternative sequence

796 – 800

5

SGGGD → AKDSG in isoform Flip.

Alternative sequence

848 – 883

36

VAKNP…ESVKI → MTLSDVMRSKARLSITGSTG ENGRVMTPEFPKAVHAVPYV SPGMGMNVSVTDLS in isoform 3.

Natural variant

607

1

Q → R in RNA edited version. By similarity

Experimental info

Mutagenesis

504

1

L → Y: Promotes dimerization. Strongly reduced desensitization

Mutagenesis

775

1

N → D: Increases rate of desensitization

Mutagenesis

851 – 852

2

NP → AA: Strongly reduces interaction with NSF

Secondary structure

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883

Helix Strand Turn

Details...

Beta strand

416 – 420

5

Turn

424 – 426

3

Beta strand

427 – 429

3

Helix

433 – 435

3

Helix

438 – 441

4

Beta strand

442 – 444

3

Helix

445 – 457

13

Beta strand

461 – 465

5

Turn

476 – 478

3

Helix

483 – 489

7

Beta strand

494 – 496

3

Helix

504 – 507

4

Beta strand

510 – 512

3

Beta strand

516 – 519

4

Beta strand

521 – 526

6

Helix

657 – 662

6

Beta strand

664 – 671

8

Helix

675 – 682

8

Helix

686 – 697

12

Beta strand

704 – 706

3

Helix

707 – 716

10

Turn

717 – 719

3

Beta strand

720 – 726

7

Helix

727 – 733

7

Beta strand

741 – 745

5

Beta strand

751 – 753

3

Beta strand

756 – 758

3

Helix

764 – 776

13

Helix

779 – 788

10

Turn

789 – 791

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Flop [UniParc]. Last modified July 15, 1998. Version 2. Checksum: DEFA817027C1CCD1	FASTA	883	98,688
	10 20 30 40 50 60 MQKIMHISVL LSPVLWGLIF GVSSNSIQIG GLFPRGADQE YSAFRVGMVQ FSTSEFRLTP 70 80 90 100 110 120 HIDNLEVANS FAVTNAFCSQ FSRGVYAIFG FYDKKSVNTI TSFCGTLHVS FITPSFPTDG 130 140 150 160 170 180 THPFVIQMRP DLKGALLSLI EYYQWDKFAY LYDSDRGLST LQAVLDSAAE KKWQVTAINV 190 200 210 220 230 240 GNINNDKKDE TYRSLFQDLE LKKERRVILD CERDKVNDIV DQVITIGKHV KGYHYIIANL 250 260 270 280 290 300 GFTDGDLLKI QFGGANVSGF QIVDYDDSLV SKFIERWSTL EEKEYPGAHT ATIKYTSALT 310 320 330 340 350 360 YDAVQVMTEA FRNLRKQRIE ISRRGNAGDC LANPAVPWGQ GVEIERALKQ VQVEGLSGNI 370 380 390 400 410 420 KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVVTLT ELPSGNDTSG LENKTVVVTT 430 440 450 460 470 480 ILESPYVMMK KNHEMLEGNE RYEGYCVDLA AEIAKHCGFK YKLTIVGDGK YGARDADTKI 490 500 510 520 530 540 WNGMVGELVY GKADIAIAPL TITLVREEVI DFSKPFMSLG ISIMIKKPQK SKPGVFSFLD 550 560 570 580 590 600 PLAYEIWMCI VFAYIGVSVV LFLVSRFSPY EWHTEEFEDG RETQSSESTN EFGIFNSLWF 610 620 630 640 650 660 SLGAFMQQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM VSPIESAEDL 670 680 690 700 710 720 SKQTEIAYGT LDSGSTKEFF RRSKIAVFDK MWTYMRSAEP SVFVRTTAEG VARVRKSKGK 730 740 750 760 770 780 YAYLLESTMN EYIEQRKPCD TMKVGGNLDS KGYGIATPKG SSLGNAVNLA VLKLNEQGLL 790 800 810 820 830 840 DKLKNKWWYD KGECGSGGGD SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR 850 860 870 880 AEAKRMKVAK NPQNINPSSS QNSQNFATYK EGYNVYGIES VKI
	Isoform Flip [UniParc]. Checksum: 3B70561B4F9E1C61		883	98,745
	10 20 30 40 50 60 MQKIMHISVL LSPVLWGLIF GVSSNSIQIG GLFPRGADQE YSAFRVGMVQ FSTSEFRLTP 70 80 90 100 110 120 HIDNLEVANS FAVTNAFCSQ FSRGVYAIFG FYDKKSVNTI TSFCGTLHVS FITPSFPTDG 130 140 150 160 170 180 THPFVIQMRP DLKGALLSLI EYYQWDKFAY LYDSDRGLST LQAVLDSAAE KKWQVTAINV 190 200 210 220 230 240 GNINNDKKDE TYRSLFQDLE LKKERRVILD CERDKVNDIV DQVITIGKHV KGYHYIIANL 250 260 270 280 290 300 GFTDGDLLKI QFGGANVSGF QIVDYDDSLV SKFIERWSTL EEKEYPGAHT ATIKYTSALT 310 320 330 340 350 360 YDAVQVMTEA FRNLRKQRIE ISRRGNAGDC LANPAVPWGQ GVEIERALKQ VQVEGLSGNI 370 380 390 400 410 420 KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVVTLT ELPSGNDTSG LENKTVVVTT 430 440 450 460 470 480 ILESPYVMMK KNHEMLEGNE RYEGYCVDLA AEIAKHCGFK YKLTIVGDGK YGARDADTKI 490 500 510 520 530 540 WNGMVGELVY GKADIAIAPL TITLVREEVI DFSKPFMSLG ISIMIKKPQK SKPGVFSFLD 550 560 570 580 590 600 PLAYEIWMCI VFAYIGVSVV LFLVSRFSPY EWHTEEFEDG RETQSSESTN EFGIFNSLWF 610 620 630 640 650 660 SLGAFMQQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM VSPIESAEDL 670 680 690 700 710 720 SKQTEIAYGT LDSGSTKEFF RRSKIAVFDK MWTYMRSAEP SVFVRTTAEG VARVRKSKGK 730 740 750 760 770 780 YAYLLESTMN EYIEQRKPCD TMKVGGNLDS KGYGIATPKG SSLGTPVNLA VLKLSEQGVL 790 800 810 820 830 840 DKLKNKWWYD KGECGAKDSG SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR 850 860 870 880 AEAKRMKVAK NPQNINPSSS QNSQNFATYK EGYNVYGIES VKI
	Isoform 3 (Long) [UniParc]. Checksum: 13CE9B51B120A799		901	100,409
	10 20 30 40 50 60 MQKIMHISVL LSPVLWGLIF GVSSNSIQIG GLFPRGADQE YSAFRVGMVQ FSTSEFRLTP 70 80 90 100 110 120 HIDNLEVANS FAVTNAFCSQ FSRGVYAIFG FYDKKSVNTI TSFCGTLHVS FITPSFPTDG 130 140 150 160 170 180 THPFVIQMRP DLKGALLSLI EYYQWDKFAY LYDSDRGLST LQAVLDSAAE KKWQVTAINV 190 200 210 220 230 240 GNINNDKKDE TYRSLFQDLE LKKERRVILD CERDKVNDIV DQVITIGKHV KGYHYIIANL 250 260 270 280 290 300 GFTDGDLLKI QFGGANVSGF QIVDYDDSLV SKFIERWSTL EEKEYPGAHT ATIKYTSALT 310 320 330 340 350 360 YDAVQVMTEA FRNLRKQRIE ISRRGNAGDC LANPAVPWGQ GVEIERALKQ VQVEGLSGNI 370 380 390 400 410 420 KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVVTLT ELPSGNDTSG LENKTVVVTT 430 440 450 460 470 480 ILESPYVMMK KNHEMLEGNE RYEGYCVDLA AEIAKHCGFK YKLTIVGDGK YGARDADTKI 490 500 510 520 530 540 WNGMVGELVY GKADIAIAPL TITLVREEVI DFSKPFMSLG ISIMIKKPQK SKPGVFSFLD 550 560 570 580 590 600 PLAYEIWMCI VFAYIGVSVV LFLVSRFSPY EWHTEEFEDG RETQSSESTN EFGIFNSLWF 610 620 630 640 650 660 SLGAFMQQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM VSPIESAEDL 670 680 690 700 710 720 SKQTEIAYGT LDSGSTKEFF RRSKIAVFDK MWTYMRSAEP SVFVRTTAEG VARVRKSKGK 730 740 750 760 770 780 YAYLLESTMN EYIEQRKPCD TMKVGGNLDS KGYGIATPKG SSLGNAVNLA VLKLNEQGLL 790 800 810 820 830 840 DKLKNKWWYD KGECGSGGGD SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR 850 860 870 880 890 900 AEAKRMKMTL SDVMRSKARL SITGSTGENG RVMTPEFPKA VHAVPYVSPG MGMNVSVTDL S

References

[1]	"A family of AMPA-selective glutamate receptors." Keinaenen K., Wisden W., Sommer B., Werner P., Herb A., Verdoorn T.A., Sakmann B., Seeburg P.H. Science 249:556-560(1990) [PubMed: 2166337] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS FLIP AND FLOP). Tissue: Brain.
[2]	"Molecular cloning and functional expression of glutamate receptor subunit genes." Boulter J., Hollmann M., O'Shea-Greenfield A., Hartley M., Deneris E.S., Maron C., Heinemann S.F. Science 249:1033-1037(1990) [PubMed: 2168579] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FLOP).
[3]	"A family of glutamate receptor genes: evidence for the formation of heteromultimeric receptors with distinct channel properties." Nakanishi N., Schneider N.A., Axel R. Neuron 5:569-581(1990) [PubMed: 1699567] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FLIP). Tissue: Brain cortex and Hippocampus.
[4]	"N-glycosylation is not a prerequisite for glutamate receptor function but is essential for lectin modulation." Everts I., Villmann C., Hollmann M. Mol. Pharmacol. 52:861-873(1997) [PubMed: 9351977] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FLIP), FUNCTION. Strain: Sprague-Dawley.
[5]	"The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha- and beta-SNAPs." Osten P., Srivastava S., Inman G.J., Vilim F.S., Khatri L., Lee L.M., States B.A., Einheber S., Milner T.A., Hanson P.I., Ziff E.B. Neuron 21:99-110(1998) [PubMed: 9697855] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH NSF, IDENTIFICATION IN A COMPLEX WITH NSF; NAPA AND NAPB, MUTAGENESIS OF 851-ASN-PRO-852.
[6]	"Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1." Xia J., Zhang X., Staudinger J., Huganir R.L. Neuron 22:179-187(1999) [PubMed: 10027300] [Abstract] Cited for: INTERACTION WITH PRKCABP.
[7]	"Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS." Sommer B.,