GRID2
entrez
2895
canonical
uniprot
O43424
canonical
ensembl
ENSG00000152208
resolver
ensp
ENSP00000282020
resolver
ensp
ENSP00000421257
resolver
ensp
ENSP00000483084
resolver
genesymbol
GRID2
resolver
genesymbol_syn
GLURD2
resolver
hgnc
HGNC:4576
resolver
uniprot
E9PH24
resolver
uniprot
Q4KKU8
resolver
uniprot
Q4KKU9
resolver
uniprot
Q4KKV0
resolver
uniprot
Q59FZ1
resolver
uniprot_entry
GRID2_HUMAN
resolver
uniprot_sec
E9PH24
resolver
uniprot_sec
Q4KKU8
resolver
uniprot_sec
Q4KKU9
resolver
uniprot_sec
Q4KKV0
resolver
uniprot_sec
Q59FZ1
resolver
activity_regulation
ACTIVITY REGULATION: Activated by the binding of D-serine or GABA (gamma-aminobutyric acid), which results in the asymmetric opening of the ion channel for conductance (PubMed:40957579). Its ligand-gated cation channel activity was previously disputed due to a lack of evidence for direct ligand-gated ion channel activity (PubMed:39052831). {ECO:0000269|PubMed:39052831, ECO:0000269|PubMed:40957579}.
uniprot
proteins
amino_acid_sequence
MEVFPFLLVLSVWWSRTWDSANADSIIHIGAIFDESAKKDDEVFRTAVGDLNQNEEILQTEKITFSVTFVDGNNPFQAVQEACELMNQGILALVSSIGCTSAGSLQSLADAMHIPHLFIQRSTAGTPRSGCGLTRSNRNDDYTLSVRPPVYLHDVILRVVTEYAWQKFIIFYDSEYDIRGIQEFLDKVSQQGMDVALQKVENNINKMITTLFDTMRIEELNRYRDTLRRAILVMNPATAKSFITEVVETNLVAFDCHWIIINEEINDVDVQELVRRSIGRLTIIRQTFPVPQNISQRCFRGNHRISSTLCDPKDPFAQNMEISNLYIYDTVLLLANAFHKKLEDRKWHSMASLSCIRKNSKPWQGGRSMLETIKKGGVSGLTGELEFGENGGNPNVHFEILGTNYGEELGRGVRKLGCWNPVTGLNGSLTDKKLENNMRGVVLRVVTVLEEPFVMVSENVLGKPKKYQGFSIDVLDALSNYLGFNYEIYVAPDHKYGSPQEDGTWNGLVGELVFKRADIGISALTITPDRENVVDFTTRYMDYSVGVLLRRAEKTVDMFACLAPFDLSLWACIAGTVLLVGLLVYLLNWLNPPRLQMGSMTSTTLYNSMWFVYGSFVQQGGEVPYTTLATRMMMGAWWLFALIVISSYTANLAAFLTITRIESSIQSLQDLSKQTEIPYGTVLDSAVYEHVRMKGLNPFERDSMYSQMWRMINRSNGSENNVLESQAGIQKVKYGNYAFVWDAAVLEYVAINDPDCSFYTIGNTVADRGYGIALQHGSPYRDVFSQRILELQQNGDMDILKHKWWPKNGQCDLYSSVDTKQKGGALDIKSFAGVFCILAAGIVLSCFIAMLETWWNKRKGSRVPSKEDDKEIDLEHLHRRVNSLCTDDDSPHKQFSTSSIDLTPLDIDTLPTRQALEQISDFRNTHITTTTFIPEQIQTLSRTLSAKAASGFTFGNVPEHRTGPFRHRAPNGGFFRSPIKTMSSIPYQPTPTLGLNLGNDPDRGTSI
uniprot
proteins
disease_involvement
DISEASE: Spinocerebellar ataxia, autosomal recessive, 18 (SCAR18) [MIM:616204]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR18 features include progressive cerebellar atrophy, delayed psychomotor development, severely impaired gait, ocular movement abnormalities, and intellectual disability. {ECO:0000269|PubMed:23611888, ECO:0000269|PubMed:24078737, ECO:0000269|PubMed:25841024, ECO:0000269|PubMed:27418511}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Member of the ionotropic glutamate receptor family, which plays a crucial role in synaptic organization and signal transduction in the central nervous system (PubMed:34936451, PubMed:27418511, PubMed:40957579). Although it shares structural features with ionotropic glutamate receptors, does not bind glutamate as a primary ligand (PubMed:34936451). Promotes synaptogenesis and mediates the D-serine-dependent long term depression signals and AMPA receptor endocytosis of cerebellar parallel fiber-Purkinje cell (PF-PC) synapses through the NRX1B-CBLN1-GRID2 triad complex (PubMed:27418511). In the presence of neurexins and cerebellins, forms cation-selective channels that are proposed to be gated by glycine and D-serine (PubMed:34936451). Cation-selective ion channel activity can be triggered by GRM1 in Purkinje cells (PubMed:24357660, PubMed:27276689). {ECO:0000269|PubMed:24357660, ECO:0000269|PubMed:27276689, ECO:0000269|PubMed:27418511, ECO:0000269|PubMed:34936451, ECO:0000269|PubMed:40957579}.
uniprot
proteins
mass_dalton
113356
uniprot
proteins
mutagenesis
MUTAGEN 24; /note="D->A: Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-26; A-61; D-76 and A-345. Abolishes synapse assembly; when associated with A-26; A-61 and A-345. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-26; A-61 and A-345. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-26; A-61 and A-345."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 25; /note="S->A: Reduces binding to CBLN1; when associated with D76."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 26; /note="I->A: Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-24; A-61; D-76 and A-345. Abolishes synapse assembly; when associated with A-24; A-61 and A-345. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-24; A-61 and A-345. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-24; A-61 and A-345."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 60; /note="T->A: No effect on CBLN1 interaction; when associated with D76."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 61; /note="E->A: Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-24; A-26; D-76 and A-345. Abolishes synapse assembly; when associated with A-24; A-26 and A-345. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-24; A-26 and A-345. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-24; A-26 and A-345."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 76; /note="F->D: Monomeric form. Does not dimerize. Weakly interacts with C1q domain of CBLN1. Forms intermediate synapse. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation. Abolishes D-Serine?dependent long term synaptic depression at PF-PC synapses. Does not recover motor coordination in experiment of transfection in Grid2-null mice."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 342; /note="L->A: Reduces binding to CBLN1; when associated with D76."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 343; /note="E->A: No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-346; A-349 and A-350. No effect on synapse assembly; when associated with A-346; A-349 and A-350. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-346; A-349 and A-350. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-346; A-349 and A-350. Does not affect motor coordination; when associated with A-346; A-349 and A-350."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 344; /note="D->A: No effect on CBLN1 interaction; when associated with D76."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 345; /note="R->A: Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-24; A-26; A-61 and D-76. Abolishes synapse assembly; when associated with A-24; A-26 and A-61. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-24; A-26 and A-61. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-24; A-26 and A-61."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 346; /note="K->A: No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-343; A-349 and A-350. No effect on synapse assembly; when associated with A-343; A-349 and A-350. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-343; A-349 and A-350. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-343; A-349 and A-350. Does not affect motor coordination; when associated with A-343; A-349 and A-350."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 348; /note="H->A: Reduces binding to CBLN1; when associated with D76."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 349; /note="S->A: No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-343; A-346 and A-350. No effect on synapse assembly; when associated with A-343; A-346 and A-350. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-343; A-346 and A-350. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-343; A-346 and A-350. Does not affect motor coordination; when associated with A-343; A-346 and A-350."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 350; /note="M->A: No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-343; A-346 and A-349. No effect on synapse assembly; when associated with A-343; A-346 and A-349. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-343; A-346 and A-349. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-343; A-346 and A-349. Does not affect motor coordination; when associated with A-343; A-346 and A-349."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 352; /note="S->A: Reduces binding to CBLN1; when associated with D76."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 364; /note="Q->A: No effect on CBLN1 interaction; when associated with D76."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 434; /note="L->ELSNGTDGAS: Impairs the ability of the LBD to induce pore closure. No effect on synapse assembly. No effect on cerebellar parallel fiber-Purkinje cell synapse formation. Abolishes D-Serine?dependent long term synaptic depression at PF-PC synapses. Does not affect motor coordination."; /evidence="ECO:0000269|PubMed:27418511"; MUTAGEN 617; /note="V->R: Abolishes activation by GRIA1 of cation-channel activity."; /evidence="ECO:0000269|PubMed:24357660
uniprot
proteins
protein_family
GRID2 subfamily
uniprot
proteins
protein_family
Glutamate-gated ion channel (TC 1.A.10.1) family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
23611888
uniprot
proteins
pubmed
24078737
uniprot
proteins
pubmed
24357660
uniprot
proteins
pubmed
25841024
uniprot
proteins
pubmed
27276689
uniprot
proteins
pubmed
27418511
uniprot
proteins
pubmed
34936451
uniprot
proteins
pubmed
39052831
uniprot
proteins
pubmed
40957579
uniprot
proteins
pubmed
9465309
uniprot
proteins
sequence_length
1007
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q61625}; Multi-pass membrane protein {ECO:0000269|PubMed:40957579}.
uniprot
proteins
transmembrane_region
TRANSMEM 567..587; /note="Helical; Name=M1"; /evidence="ECO:0000269|PubMed:40957579, ECO:0007744|PDB:9NWO, ECO:0007744|PDB:9NWP, ECO:0007744|PDB:9NWQ, ECO:0007744|PDB:9OOO"; TRANSMEM 625..653; /note="Helical; Name=M3"; /evidence="ECO:0000269|PubMed:40957579, ECO:0007744|PDB:9NWO, ECO:0007744|PDB:9NWP, ECO:0007744|PDB:9NWQ, ECO:0007744|PDB:9OOO"; TRANSMEM 831..851; /note="Helical; Name=M4"; /evidence="ECO:0000269|PubMed:40957579, ECO:0007744|PDB:9NWO, ECO:0007744|PDB:9NWP, ECO:0007744|PDB:9NWQ, ECO:0007744|PDB:9OOO
uniprot
proteins