Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Glutamate receptor 2

Gene

Gria2

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

Functioni

Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. 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. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei471GlutamateBy similarity1
Binding sitei506GlutamateBy similarity1
Binding sitei726GlutamateBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate receptor 2
Short name:
GluR-2
Alternative name(s):
AMPA-selective glutamate receptor 2
GluR-B
GluR-K2
Glutamate receptor ionotropic, AMPA 2
Short name:
GluA2
Gene namesi
Name:Gria2
Synonyms:Glur2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:95809. Gria2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 543ExtracellularBy similarityAdd BLAST519
Transmembranei544 – 564HelicalBy similarityAdd BLAST21
Topological domaini565 – 591CytoplasmicBy similarityAdd BLAST27
Intramembranei592 – 607Helical; Pore-formingBy similarityAdd BLAST16
Intramembranei608 – 610By similarity3
Topological domaini611 – 616CytoplasmicBy similarity6
Transmembranei617 – 637HelicalBy similarityAdd BLAST21
Topological domaini638 – 812ExtracellularBy similarityAdd BLAST175
Transmembranei813 – 833Helical; Name=M4By similarityAdd BLAST21
Topological domaini834 – 883CytoplasmicBy similarityAdd BLAST50

GO - Cellular componenti

  • AMPA glutamate receptor complex Source: MGI
  • cell junction Source: UniProtKB-KW
  • endoplasmic reticulum Source: MGI
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: UniProtKB
  • membrane Source: MGI
  • neuron projection Source: BHF-UCL
  • postsynaptic membrane Source: MGI
  • synapse Source: MGI
  • synaptic membrane Source: MGI
  • synaptic vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi869Y → F: No effect on tyrosine phosphorylation. Reduced tyrosine phosphorylation; when associated with F-873 and F-876. 1 Publication1
Mutagenesisi873Y → F: No effect on tyrosine phosphorylation. Reduced tyrosine phosphorylation; when associated with F-869 and F-876. 1 Publication1
Mutagenesisi876Y → F: Loss of tyrosine phosphorylation at the C-terminus. Reduced tyrosine phosphorylation; when associated with F-869 and F-873. Interferes with accumulation at synapses. Interferes with AMPA-mediated receptor internalization. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2096617.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000001153325 – 883Glutamate receptor 2Add BLAST859

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi78 ↔ 330By similarity
Glycosylationi256N-linked (GlcNAc...)Sequence analysis1
Glycosylationi370N-linked (GlcNAc...)Sequence analysis1
Glycosylationi406N-linked (GlcNAc...)Sequence analysis1
Glycosylationi413N-linked (GlcNAc...)Sequence analysis1
Lipidationi610S-palmitoyl cysteine1 Publication1
Modified residuei683Phosphoserine; by PKCBy similarity1
Modified residuei717Phosphoserine; by PKGBy similarity1
Disulfide bondi739 ↔ 794By similarity
Lipidationi836S-palmitoyl cysteine1 Publication1
Modified residuei860PhosphoserineCombined sources1
Modified residuei863PhosphoserineCombined sources1
Modified residuei876Phosphotyrosine1 Publication1
Modified residuei880Phosphoserine1 Publication1

Post-translational modificationi

Palmitoylated. Depalmitoylated upon glutamate stimulation. ZDHHC3/GODZ specifically palmitoylates Cys-610, which 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.1 Publication
N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiP23819.
MaxQBiP23819.
PaxDbiP23819.
PeptideAtlasiP23819.
PRIDEiP23819.

PTM databases

iPTMnetiP23819.
PhosphoSitePlusiP23819.
SwissPalmiP23819.

Expressioni

Tissue specificityi

Detected in brain cortex, hippocampus and cerebellum (at protein level). Detected in hippocampus.2 Publications

Developmental stagei

Detected at low levels in newborns. Levels increase strongly and are highest in hippocampus from 7 day olds. Detected at low levels in hippocampus and olfactory bulb of 3 month olds (at protein level).1 Publication

Gene expression databases

CleanExiMM_GRIA2.

Interactioni

Subunit structurei

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. Interacts with ATAD1 in an ATP-dependent manner. ATAD1-catalyzed ATP hydrolysis disrupts binding to ATAD1 and to GRIP1 and leads to AMPAR complex disassembly. Interacts with GRIP2. Isoform 1, but not isoform 3, interacts with PICK1/PRKCABP. Interacts with GRIA1 and SYNDIG1. Interacts with LRFN1 (By similarity). Found in a complex with GRIA1, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5 (By similarity). Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes. Interacts with OLFM2 (PubMed:25218043).By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cspg4Q8VHY02EBI-77538,EBI-8327479
Gria1P238185EBI-77538,EBI-445486
Grip1Q925T65EBI-77538,EBI-537752

Protein-protein interaction databases

BioGridi200059. 8 interactors.
IntActiP23819. 30 interactors.
MINTiMINT-1776844.
STRINGi10090.ENSMUSP00000074787.

Structurei

3D structure databases

ProteinModelPortaliP23819.
SMRiP23819.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The M4 transmembrane segment mediates tetramerization and is required for cell surface expression.By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1054. Eukaryota.
ENOG410XPSH. LUCA.
HOGENOMiHOG000234372.
HOVERGENiHBG051839.
InParanoidiP23819.
KOiK05198.
PhylomeDBiP23819.

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 (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P23819-1) [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
MQKIMHISVL LSPVLWGLIF GVSSNSIQIG GLFPRGADQE YSAFRVGMVQ
60 70 80 90 100
FSTSEFRLTP HIDNLEVANS FAVTNAFCSQ FSRGVYAIFG FYDKKSVNTI
110 120 130 140 150
TSFCGTLHVS FITPSFPTDG THPFVIQMRP DLKGALLSLI EYYQWDKFAY
160 170 180 190 200
LYDSDRGLST LQAVLDSAAE KKWQVTAINV GNINNDKKDE TYRSLFQDLE
210 220 230 240 250
LKKERRVILD CERDKVNDIV DQVITIGKHV KGYHYIIANL GFTDGDLLKI
260 270 280 290 300
QFGGANVSGF QIVDYDDSLV SKFIERWSTL EEKEYPGAHT ATIKYTSALT
310 320 330 340 350
YDAVQVMTEA FRNLRKQRIE ISRRGNAGDC LANPAVPWGQ GVEIERALKQ
360 370 380 390 400
VQVEGLSGNI KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVVTLT
410 420 430 440 450
ELPSGNDTSG LENKTVVVTT ILESPYVMMK KNHEMLEGNE RYEGYCVDLA
460 470 480 490 500
AEIAKHCGFK YKLTIVGDGK YGARDADTKI WNGMVGELVY GKADIAIAPL
510 520 530 540 550
TITLVREEVI DFSKPFMSLG ISIMIKKPQK SKPGVFSFLD PLAYEIWMCI
560 570 580 590 600
VFAYIGVSVV LFLVSRFSPY EWHTEEFEDG RETQSSESTN EFGIFNSLWF
610 620 630 640 650
SLGAFMQQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM
660 670 680 690 700
VSPIESAEDL SKQTEIAYGT LDSGSTKEFF RRSKIAVFDK MWTYMRSAEP
710 720 730 740 750
SVFVRTTAEG VARVRKSKGK YAYLLESTMN EYIEQRKPCD TMKVGGNLDS
760 770 780 790 800
KGYGIATPKG SSLGNAVNLA VLKLNEQGLL DKLKNKWWYD KGECGSGGGD
810 820 830 840 850
SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR AEAKRMKVAK
860 870 880
NAQNINPSSS QNSQNFATYK EGYNVYGIES VKI
Length:883
Mass (Da):98,662
Last modified:August 2, 2002 - v3
Checksum:iC44B317027C1CCC1
GO
Isoform 2 (identifier: P23819-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     761-761: S → T
     765-767: NAV → WVE
     768-883: Missing.

Show »
Length:767
Mass (Da):86,181
Checksum:i822F17FD67E4820E
GO
Isoform 3 (identifier: P23819-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     802-802: K → KTPVNLAVLKLSEQGVLDKLKNKWWYDKGECGAKDSGSK
     848-883: VAKNAQNINP...NVYGIESVKI → MTLSAATRNK...GMNVSVTDLS

Show »
Length:939
Mass (Da):104,523
Checksum:i2600BEDAF2C0583D
GO
Isoform 4 (identifier: P23819-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     802-802: K → KTPVNLAVLKLSEQGVLDKLKNKWWYDKGECGAKDSGSK

Show »
Length:921
Mass (Da):102,851
Checksum:iE38D8C26ED029219
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti264D → V in CAA40735 (PubMed:1699805).Curated1
Sequence conflicti270V → A in CAA40735 (PubMed:1699805).Curated1
Sequence conflicti282E → G in CAA40735 (PubMed:1699805).Curated1
Sequence conflicti374N → H in BAB29316 (PubMed:16141072).Curated1
Sequence conflicti482N → K in BAC31557 (PubMed:16141072).Curated1
Sequence conflicti552F → L in BAB29316 (PubMed:16141072).Curated1
Sequence conflicti764G → R in AAC37653 (PubMed:7545935).Curated1

RNA editingi

Edited at position 607.1 Publication
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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti607Q → R in RNA edited version. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000106761S → T in isoform 2. 1 Publication1
Alternative sequenceiVSP_000107765 – 767NAV → WVE in isoform 2. 1 Publication3
Alternative sequenceiVSP_000108768 – 883Missing in isoform 2. 1 PublicationAdd BLAST116
Alternative sequenceiVSP_000109802K → KTPVNLAVLKLSEQGVLDKL KNKWWYDKGECGAKDSGSK in isoform 3 and isoform 4. Curated1
Alternative sequenceiVSP_000110848 – 883VAKNA…ESVKI → MTLSAATRNKARLSITGSTG ENGRVMTPEFPKAVHAVPYV SPGMGMNVSVTDLS in isoform 3. CuratedAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57498 mRNA. Translation: CAA40735.1.
L32204
, L32189, L32190, L32192, L32194, L32196, L32198, L32200, L32202, L32203, L32201, L32199, L32197, L32195, L32193, L32191 Genomic DNA. Translation: AAC37653.1.
L32372
, L32189, L32190, L32191, L32192, L32193, L32194, L32195, L32196, L32197, L32198, L32199, L32200, L32201, L32202, L32203, L32204 Genomic DNA. Translation: AAC37654.1.
AK014389 mRNA. Translation: BAB29316.1.
AK043490 mRNA. Translation: BAC31557.1.
AK044574 mRNA. Translation: BAC31986.1.
AK046861 mRNA. Translation: BAC32899.1.
CCDSiCCDS17423.1. [P23819-1]
PIRiI49695.
I49696.
RefSeqiNP_001034284.1. NM_001039195.1.
NP_001077275.1. NM_001083806.1.
NP_038568.2. NM_013540.2.
UniGeneiMm.220224.

Genome annotation databases

GeneIDi14800.
KEGGimmu:14800.
UCSCiuc008pof.1. mouse. [P23819-1]

Keywords - Coding sequence diversityi

Alternative splicing, RNA editing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57498 mRNA. Translation: CAA40735.1.
L32204
, L32189, L32190, L32192, L32194, L32196, L32198, L32200, L32202, L32203, L32201, L32199, L32197, L32195, L32193, L32191 Genomic DNA. Translation: AAC37653.1.
L32372
, L32189, L32190, L32191, L32192, L32193, L32194, L32195, L32196, L32197, L32198, L32199, L32200, L32201, L32202, L32203, L32204 Genomic DNA. Translation: AAC37654.1.
AK014389 mRNA. Translation: BAB29316.1.
AK043490 mRNA. Translation: BAC31557.1.
AK044574 mRNA. Translation: BAC31986.1.
AK046861 mRNA. Translation: BAC32899.1.
CCDSiCCDS17423.1. [P23819-1]
PIRiI49695.
I49696.
RefSeqiNP_001034284.1. NM_001039195.1.
NP_001077275.1. NM_001083806.1.
NP_038568.2. NM_013540.2.
UniGeneiMm.220224.

3D structure databases

ProteinModelPortaliP23819.
SMRiP23819.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200059. 8 interactors.
IntActiP23819. 30 interactors.
MINTiMINT-1776844.
STRINGi10090.ENSMUSP00000074787.

Chemistry databases

ChEMBLiCHEMBL2096617.

PTM databases

iPTMnetiP23819.
PhosphoSitePlusiP23819.
SwissPalmiP23819.

Proteomic databases

EPDiP23819.
MaxQBiP23819.
PaxDbiP23819.
PeptideAtlasiP23819.
PRIDEiP23819.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi14800.
KEGGimmu:14800.
UCSCiuc008pof.1. mouse. [P23819-1]

Organism-specific databases

CTDi2891.
MGIiMGI:95809. Gria2.

Phylogenomic databases

eggNOGiKOG1054. Eukaryota.
ENOG410XPSH. LUCA.
HOGENOMiHOG000234372.
HOVERGENiHBG051839.
InParanoidiP23819.
KOiK05198.
PhylomeDBiP23819.

Miscellaneous databases

PROiP23819.
SOURCEiSearch...

Gene expression databases

CleanExiMM_GRIA2.

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...

Entry informationi

Entry nameiGRIA2_MOUSE
AccessioniPrimary (citable) accession number: P23819
Secondary accession number(s): Q61604
, Q61605, Q8BG69, Q8BXU3, Q9D6D3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: August 2, 2002
Last modified: November 2, 2016
This is version 170 of the entry and version 3 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 AMPA (quisqualate) > glutamate > kainate.

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.