P19491 · GRIA2_RAT
- ProteinGlutamate receptor 2
- GeneGria2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids883 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system and plays an important role in fast excitatory synaptic transmission (By similarity).
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 upon entry of monovalent and divalent cations such as sodium and calcium (PubMed:11773314, PubMed:12501192, PubMed:12730367, PubMed:12872125, PubMed:16483599, PubMed:1653450, PubMed:17018279, PubMed:19946266).
The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (PubMed:12015593, PubMed:16192394, PubMed:17018279, PubMed:19946266).
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 L-glutamate (PubMed:21172611).
Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (PubMed:16037816).
Miscellaneous
Catalytic activity
- Ca2+(in) = Ca2+(out)
- Na+(in) = Na+(out)
Features
Showing features for site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 474 | Interaction with the cone snail toxin Con-ikot-ikot | ||||
Sequence: R | ||||||
Binding site | 499 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: P | ||||||
Binding site | 501 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 506 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Site | 654 | Crucial to convey clamshell closure to channel opening | ||||
Sequence: I | ||||||
Binding site | 675 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 676 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Site | 681 | Interaction with the cone snail toxin Con-ikot-ikot | ||||
Sequence: R | ||||||
Binding site | 726 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Site | 773 | Interaction with the cone snail toxin Con-ikot-ikot | ||||
Sequence: K |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGlutamate receptor 2
- Short namesGluR-2
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP19491
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Displays a somatodendritic localization and is excluded from axons in neurons (By similarity).
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 22-543 | Extracellular | ||||
Sequence: VSSNSIQIGGLFPRGADQEYSAFRVGMVQFSTSEFRLTPHIDNLEVANSFAVTNAFCSQFSRGVYAIFGFYDKKSVNTITSFCGTLHVSFITPSFPTDGTHPFVIQMRPDLKGALLSLIEYYQWDKFAYLYDSDRGLSTLQAVLDSAAEKKWQVTAINVGNINNDKKDETYRSLFQDLELKKERRVILDCERDKVNDIVDQVITIGKHVKGYHYIIANLGFTDGDLLKIQFGGANVSGFQIVDYDDSLVSKFIERWSTLEEKEYPGAHTATIKYTSALTYDAVQVMTEAFRNLRKQRIEISRRGNAGDCLANPAVPWGQGVEIERALKQVQVEGLSGNIKFDQNGKRINYTINIMELKTNGPRKIGYWSEVDKMVVTLTELPSGNDTSGLENKTVVVTTILESPYVMMKKNHEMLEGNERYEGYCVDLAAEIAKHCGFKYKLTIVGDGKYGARDADTKIWNGMVGELVYGKADIAIAPLTITLVREEVIDFSKPFMSLGISIMIKKPQKSKPGVFSFLDPLA | ||||||
Transmembrane | 544-564 | Helical | ||||
Sequence: YEIWMCIVFAYIGVSVVLFLV | ||||||
Topological domain | 565-591 | Cytoplasmic | ||||
Sequence: SRFSPYEWHTEEFEDGRETQSSESTNE | ||||||
Intramembrane | 592-607 | Helical; Pore-forming | ||||
Sequence: FGIFNSLWFSLGAFMQ | ||||||
Intramembrane | 608-610 | |||||
Sequence: QGC | ||||||
Topological domain | 611-616 | Cytoplasmic | ||||
Sequence: DISPRS | ||||||
Transmembrane | 617-637 | Helical | ||||
Sequence: LSGRIVGGVWWFFTLIIISSY | ||||||
Topological domain | 638-812 | Extracellular | ||||
Sequence: TANLAAFLTVERMVSPIESAEDLSKQTEIAYGTLDSGSTKEFFRRSKIAVFDKMWTYMRSAEPSVFVRTTAEGVARVRKSKGKYAYLLESTMNEYIEQRKPCDTMKVGGNLDSKGYGIATPKGSSLGNAVNLAVLKLNEQGLLDKLKNKWWYDKGECGSGGGDSKEKTSALSLSN | ||||||
Transmembrane | 813-833 | Helical; Name=M4 | ||||
Sequence: VAGVFYILVGGLGLAMLVALI | ||||||
Topological domain | 834-883 | Cytoplasmic | ||||
Sequence: EFCYKSRAEAKRMKVAKNPQNINPSSSQNSQNFATYKEGYNVYGIESVKI |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 504 | Promotes dimerization. Strongly reduced desensitization. | ||||
Sequence: L → Y | ||||||
Natural variant | 607 | in RNA edited version | ||||
Sequence: Q → R | ||||||
Mutagenesis | 775 | Increases rate of desensitization. | ||||
Sequence: N → D | ||||||
Mutagenesis | 851-852 | Strongly reduces interaction with NSF. | ||||
Sequence: NP → AA | ||||||
Mutagenesis | 875 | Almost abolishes interaction with IQSEC1; when associated with V-876. Abolishes activation of ARF6 by IQSEC1; when associated with V-876. | ||||
Sequence: V → Y | ||||||
Mutagenesis | 876 | Strongly decreases interaction with IQSEC1. Abolishes activation of ARF6 by IQSEC1. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 876 | No effect on interaction with IQSEC1. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 876 | Almost abolishes interaction with IQSEC1; when associated with Y-875. Abolishes activation of ARF6 by IQSEC1; when associated with Y-875. | ||||
Sequence: Y → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1 variant from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, lipidation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MQKIMHISVLLSPVLWGLIFG | ||||||
Chain | PRO_0000011535 | 22-883 | Glutamate receptor 2 | |||
Sequence: VSSNSIQIGGLFPRGADQEYSAFRVGMVQFSTSEFRLTPHIDNLEVANSFAVTNAFCSQFSRGVYAIFGFYDKKSVNTITSFCGTLHVSFITPSFPTDGTHPFVIQMRPDLKGALLSLIEYYQWDKFAYLYDSDRGLSTLQAVLDSAAEKKWQVTAINVGNINNDKKDETYRSLFQDLELKKERRVILDCERDKVNDIVDQVITIGKHVKGYHYIIANLGFTDGDLLKIQFGGANVSGFQIVDYDDSLVSKFIERWSTLEEKEYPGAHTATIKYTSALTYDAVQVMTEAFRNLRKQRIEISRRGNAGDCLANPAVPWGQGVEIERALKQVQVEGLSGNIKFDQNGKRINYTINIMELKTNGPRKIGYWSEVDKMVVTLTELPSGNDTSGLENKTVVVTTILESPYVMMKKNHEMLEGNERYEGYCVDLAAEIAKHCGFKYKLTIVGDGKYGARDADTKIWNGMVGELVYGKADIAIAPLTITLVREEVIDFSKPFMSLGISIMIKKPQKSKPGVFSFLDPLAYEIWMCIVFAYIGVSVVLFLVSRFSPYEWHTEEFEDGRETQSSESTNEFGIFNSLWFSLGAFMQQGCDISPRSLSGRIVGGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAEDLSKQTEIAYGTLDSGSTKEFFRRSKIAVFDKMWTYMRSAEPSVFVRTTAEGVARVRKSKGKYAYLLESTMNEYIEQRKPCDTMKVGGNLDSKGYGIATPKGSSLGNAVNLAVLKLNEQGLLDKLKNKWWYDKGECGSGGGDSKEKTSALSLSNVAGVFYILVGGLGLAMLVALIEFCYKSRAEAKRMKVAKNPQNINPSSSQNSQNFATYKEGYNVYGIESVKI | ||||||
Disulfide bond | 78↔330 | |||||
Sequence: CSQFSRGVYAIFGFYDKKSVNTITSFCGTLHVSFITPSFPTDGTHPFVIQMRPDLKGALLSLIEYYQWDKFAYLYDSDRGLSTLQAVLDSAAEKKWQVTAINVGNINNDKKDETYRSLFQDLELKKERRVILDCERDKVNDIVDQVITIGKHVKGYHYIIANLGFTDGDLLKIQFGGANVSGFQIVDYDDSLVSKFIERWSTLEEKEYPGAHTATIKYTSALTYDAVQVMTEAFRNLRKQRIEISRRGNAGDC | ||||||
Glycosylation | 256 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 370 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 406 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 413 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Lipidation | 610 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 683 | Phosphoserine; by PKC | ||||
Sequence: S | ||||||
Modified residue | 717 | Phosphoserine; by PKG | ||||
Sequence: S | ||||||
Disulfide bond | 739↔794 | |||||
Sequence: CDTMKVGGNLDSKGYGIATPKGSSLGNAVNLAVLKLNEQGLLDKLKNKWWYDKGEC | ||||||
Lipidation | 836 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 860 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 863 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 876 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 880 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Depalmitoylated upon L-glutamate stimulation (By similarity).
Cys-610 palmitoylation leads to Golgi retention and decreased cell surface expression (By similarity).
In contrast, Cys-836 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in dendrites of neuronal cells (PubMed:9697855).
Expressed in the pyramidal cell layers of CA1 and CA3 and in the granule cell layer of the dentate gyrus (PubMed:12657670).
Induction
Developmental stage
Interaction
Subunit
Tetramers may be formed by the dimerization of dimers (PubMed:12015593, PubMed:19946266, PubMed:21317873).
May interact with MPP4 (By similarity).
Forms a ternary complex with GRIP1 and CSPG4 (By similarity).
Interacts with ATAD1 in an ATP-dependent manner (PubMed:21496646).
ATAD1-catalyzed ATP hydrolysis disrupts binding to ATAD1 and to GRIP1 and leads to AMPAR complex disassembly (PubMed:21496646).
Interacts with GRIP2 (By similarity).
Interacts with GRIP1 (PubMed:9069286).
Interacts with NSF via its C-terminus (PubMed:9697855).
Interacts with CACNG2, PICK1 and GRIP2 (PubMed:10027300, PubMed:10414981, PubMed:16793768, PubMed:27756895).
Interacts with GRIA1 and SYNDIG1 (By similarity).
Part of a complex containing GRIA2, NSF and NAPA and/or NAPB (PubMed:9697855).
Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (By similarity).
Interacts with LRFN1 (PubMed:16630835).
Found in a complex with GRIA1, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 (PubMed:19265014).
Interacts with CACNG5 (PubMed:18817736, PubMed:19234459).
Interacts with OLFM2 (By similarity).
Interacts with AP4B1, AP4E1 and AP4M1; probably indirect it mediates the somatodendritic localization of GRIA2 in neurons (By similarity).
Forms a complex with GRIP1, NSG1 and STX12; controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (PubMed:16037816).
Interacts with IQSEC1; the interaction is required for ARF6 activation (PubMed:20547133).
Interacts (heterotetramer form) with CNIH2 and CNIH3; this interaction promotes expression at the plasma membrane and extensively modulates their gating properties by slowing deactivation and desensitization kinetics (PubMed:19265014).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P19491 | Agap2 Q8CGU4 | 4 | EBI-77718, EBI-4409108 | |
BINARY | P19491 | Ap2m1 P84092 | 2 | EBI-77718, EBI-297693 | |
BINARY | P19491 | Atad1 Q505J9 | 3 | EBI-77718, EBI-4280289 | |
BINARY | P19491 | Cacng2 Q71RJ2 | 2 | EBI-77718, EBI-8538384 | |
BINARY | P19491 | Gria1 P19490 | 3 | EBI-77718, EBI-371642 | |
BINARY | P19491 | Gria2 P19491 | 12 | EBI-77718, EBI-77718 | |
BINARY | P19491 | Grip1 P97879 | 15 | EBI-77718, EBI-936113 | |
BINARY | P19491 | Grip2 Q9WTW1-3 | 7 | EBI-77718, EBI-936068 | |
BINARY | P19491 | Nsf Q9QUL6 | 5 | EBI-77718, EBI-925794 | |
BINARY | P19491 | Pick1 Q9EP80 | 13 | EBI-77718, EBI-77728 | |
XENO | P19491 | PPFIA1 Q13136 | 2 | EBI-77718, EBI-745426 | |
BINARY | P19491 | Ppfia4 Q91Z80 | 3 | EBI-77718, EBI-8276907 | |
BINARY | P19491 | Syt3 P40748 | 3 | EBI-77718, EBI-458106 | |
BINARY | P19491-2 | Gria1 P19490-2 | 2 | EBI-15817825, EBI-26900830 | |
BINARY | P19491-2 | Gria2 P19491-2 | 18 | EBI-15817825, EBI-15817825 | |
BINARY | P19491-2 | Gria3 P19492-2 | 6 | EBI-15817825, EBI-16201849 | |
BINARY | P19491-2 | Gria4 P19493-2 | 2 | EBI-15817825, EBI-15852899 | |
XENO | P19491-2 | P0CB20 | 2 | EBI-15817825, EBI-16116011 | |
BINARY | P19491-3 | Mapk8 P49185 | 2 | EBI-9118256, EBI-7456505 |
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 867-877 | Required for interaction with IQSEC1 | ||||
Sequence: ATYKEGYNVYG |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
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.
- NameFlop
- Length883
- Mass (Da)98,688
- Last updated1998-07-15 v2
- ChecksumDEFA817027C1CCD1
P19491-2
- NameFlip
P19491-3
- Name3
- SynonymsLong
- Differences from canonical
- 848-883: VAKNPQNINPSSSQNSQNFATYKEGYNVYGIESVKI → MTLSDVMRSKARLSITGSTGENGRVMTPEFPKAVHAVPYVSPGMGMNVSVTDLS
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6AKP3 | A0A8I6AKP3_RAT | Gria2 | 805 | ||
F1LNE4 | F1LNE4_RAT | Gria2 | 883 | ||
A0A8I6AC88 | A0A8I6AC88_RAT | Gria2 | 878 | ||
A0A8I6AFJ3 | A0A8I6AFJ3_RAT | Gria2 | 903 | ||
A0A8I6GB39 | A0A8I6GB39_RAT | Gria2 | 813 | ||
G3V914 | G3V914_RAT | Gria2 | 883 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_000111 | 765-766 | in isoform Flip | |||
Sequence: NA → TP | ||||||
Alternative sequence | VSP_000112 | 775 | in isoform Flip | |||
Sequence: N → S | ||||||
Alternative sequence | VSP_000113 | 779 | in isoform Flip | |||
Sequence: L → V | ||||||
Alternative sequence | VSP_000114 | 796-800 | in isoform Flip | |||
Sequence: SGGGD → AKDSG | ||||||
Alternative sequence | VSP_029310 | 848-883 | in isoform 3 | |||
Sequence: VAKNPQNINPSSSQNSQNFATYKEGYNVYGIESVKI → MTLSDVMRSKARLSITGSTGENGRVMTPEFPKAVHAVPYVSPGMGMNVSVTDLS |
RNA Editing
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M36419 EMBL· GenBank· DDBJ | AAA41244.1 EMBL· GenBank· DDBJ | mRNA | ||
M38061 EMBL· GenBank· DDBJ | AAC37652.1 EMBL· GenBank· DDBJ | mRNA | ||
M85035 EMBL· GenBank· DDBJ | AAA41240.1 EMBL· GenBank· DDBJ | mRNA | ||
X54655 EMBL· GenBank· DDBJ | CAA38465.1 EMBL· GenBank· DDBJ | mRNA | ||
AF164344 EMBL· GenBank· DDBJ | AAD51284.1 EMBL· GenBank· DDBJ | mRNA |