GRIN1
entrez
2902
canonical
uniprot
Q05586
canonical
ensembl
ENSG00000176884
resolver
ensp
ENSP00000360601
resolver
ensp
ENSP00000360605
resolver
ensp
ENSP00000360608
resolver
ensp
ENSP00000360610
resolver
ensp
ENSP00000360614
resolver
ensp
ENSP00000360615
resolver
ensp
ENSP00000360616
resolver
ensp
ENSP00000672909
resolver
enst
ENST00000371555
resolver
genesymbol
GRIN1
resolver
genesymbol_syn
NMDAR1
resolver
hgnc
HGNC:4584
resolver
uniprot
A6NED8
resolver
uniprot
A6NGR6
resolver
uniprot
A6NLK7
resolver
uniprot
A6NLR1
resolver
uniprot
C9K0X1
resolver
uniprot
P35437
resolver
uniprot
Q12867
resolver
uniprot
Q12868
resolver
uniprot
Q59GW0
resolver
uniprot
Q5VSF3
resolver
uniprot
Q5VSF4
resolver
uniprot
Q5VSF5
resolver
uniprot
Q5VSF6
resolver
uniprot
Q5VSF7
resolver
uniprot
Q5VSF8
resolver
uniprot
Q5VSF9
resolver
uniprot
Q9UPF8
resolver
uniprot
Q9UPF9
resolver
uniprot_entry
NMDZ1_HUMAN
resolver
uniprot_entry
Q59GW0_HUMAN
resolver
uniprot_entry
Q5VSF9_HUMAN
resolver
uniprot_sec
A6NED8
resolver
uniprot_sec
A6NGR6
resolver
uniprot_sec
A6NLK7
resolver
uniprot_sec
A6NLR1
resolver
uniprot_sec
C9K0X1
resolver
uniprot_sec
P35437
resolver
uniprot_sec
Q12867
resolver
uniprot_sec
Q12868
resolver
uniprot_sec
Q5VSF3
resolver
uniprot_sec
Q5VSF4
resolver
uniprot_sec
Q5VSF5
resolver
uniprot_sec
Q5VSF6
resolver
uniprot_sec
Q5VSF7
resolver
uniprot_sec
Q5VSF8
resolver
uniprot_sec
Q9UPF8
resolver
uniprot_sec
Q9UPF9
resolver
activity_regulation
ACTIVITY REGULATION: NMDA glutamate receptor activity is inhibited by Mg2(+) in a voltage-dependent manner; Mg2(+)-induced blockade occurs only at negative potentials and decreases with membrane depolarization (PubMed:7679115, PubMed:7681588, PubMed:7685113). 7-chlorokynurenate (50 uM) or Zn2(+) (100 uM) partially inhibit the NMDA glutamate receptor activity, while acide 2-amino-5-phosphonovalerique(100 uM) almost completely blocked the NMDA glutamate receptor activity (PubMed:7679115, PubMed:7685113). Dizocilpine (1 uM) results in long lasting and almost complete block of the NMDA glutamate receptor activity (PubMed:7679115, PubMed:7685113). {ECO:0000269|PubMed:7679115, ECO:0000269|PubMed:7681588, ECO:0000269|PubMed:7685113}.
uniprot
proteins
amino_acid_sequence
MSTMRLLTLALLFSCSVARAACDPKIVNIGAVLSTRKHEQMFREAVNQANKRHGSWKIQLNATSVTHKPNAIQMALSVCEDLISSQVYAILVSHPPTPNDHFTPTPVSYTAGFYRIPVLGLTTRMSIYSDKSIHLSFLRTVPPYSHQSSVWFEMMRVYSWNHIILLVSDDHEGRAAQKRLETLLEERESKAEKVLQFDPGTKNVTALLMEAKELEARVIILSASEDDAATVYRAAAMLNMTGSGYVWLVGEREISGNALRYAPDGILGLQLINGKNESAHISDAVGVVAQAVHELLEKENITDPPRGCVGNTNIWKTGPLFKRVLMSSKYADGVTGRVEFNEDGDRKFANYSIMNLQNRKLVQVGIYNGTHVIPNDRKIIWPGGETEKPRGYQMSTRLKIVTIHQEPFVYVKPTLSDGTCKEEFTVNGDPVKKVICTGPNDTSPGSPRHTVPQCCYGFCIDLLIKLARTMNFTYEVHLVADGKFGTQERVNNSNKKEWNGMMGELLSGQADMIVAPLTINNERAQYIEFSKPFKYQGLTILVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVMLYLLDRFSPFGRFKVNSEEEEEDALTLSSAMWFSWGVLLNSGIGEGAPRSFSARILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGINDPRLRNPSDKFIYATVKQSSVDIYFRRQVELSTMYRHMEKHNYESAAEAIQAVRDNKLHAFIWDSAVLEFEASQKCDLVTTGELFFRSGFGIGMRKDSPWKQNVSLSILKSHENGFMEDLDKTWVRYQECDSRSNAPATLTFENMAGVFMLVAGGIVAGIFLIFIEIAYKRHKDARRKQMQLAFAAVNVWRKNLQDRKSGRAEPDPKKKATFRAITSTLASSFKRRRSSKDTSTGGGRGALQNQKDTVLPRRAIEREEGQLQLCSRHRES
uniprot
proteins
disease_involvement
DISEASE: Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (NDHMSD) [MIM:614254]: An autosomal dominant neurodevelopmental disorder characterized by severe intellectual disability and developmental delay, absent speech, muscular hypotonia, dyskinesia, and hyperkinetic movements. Cortical blindness, cerebral atrophy, and seizures are present in some patients. {ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:25167861, ECO:0000269|PubMed:25864721, ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28228639, ECO:0000269|PubMed:28389307, ECO:0000269|PubMed:38538865}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive (NDHMSR) [MIM:617820]: An autosomal recessive neurodevelopmental disorder characterized by severe intellectual disability and psychomotor developmental delay, involuntary and stereotypic movements, spasticity, and inability to walk without support. Intractable seizures manifest in some patients. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28051072}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 101 (DEE101) [MIM:619814]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE101 is an autosomal recessive, severe form characterized by onset of seizures in early infancy. Death in infancy may occur. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:34611970}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:21376300, PubMed:26875626, PubMed:26919761, PubMed:28126851, PubMed:28228639, PubMed:36959261, PubMed:7679115, PubMed:7681588, PubMed:7685113). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the long-term potentiation (LTP) (PubMed:26875626). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:21376300, PubMed:26875626, PubMed:26919761, PubMed:27164704, PubMed:28095420, PubMed:28105280, PubMed:28126851, PubMed:28228639, PubMed:36959261, PubMed:38538865, PubMed:7679115, PubMed:7681588, PubMed:7685113). NMDARs mediate simultaneously the potassium efflux and the influx of calcium and sodium (By similarity). Each GluN2 or GluN3 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626, PubMed:26919761, PubMed:36309015, PubMed:38598639). {ECO:0000250|UniProtKB:P35438, ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:28228639, ECO:0000269|PubMed:36309015, ECO:0000269|PubMed:36959261, ECO:0000269|PubMed:38538865, ECO:0000269|PubMed:38598639, ECO:0000269|PubMed:7679115, ECO:0000269|PubMed:7681588, ECO:0000269|PubMed:7685113}.
uniprot
proteins
mass_dalton
105373
uniprot
proteins
mutagenesis
MUTAGEN 642; /note="I->L: Slight decrease in glutamate and glycine agonist potency; mutant channels are activated at 2-fold higher glutamate and glycine concentrations."; /evidence="ECO:0000269|PubMed:38538865"; MUTAGEN 644; /note="V->M: Increase in glutamate and glycine agonist potency; mutant channels are activated lower glutamate and glycine concentrations."; /evidence="ECO:0000269|PubMed:38538865"; MUTAGEN 653; /note="A->G: Increase in glutamate and glycine agonist potency; mutant channels are activated lower glutamate and glycine concentrations."; /evidence="ECO:0000269|PubMed:38538865"; MUTAGEN 813; /note="M->V: Slight decrease in glycine agonist potency; no effect on glutamate agonist potency."; /evidence="ECO:0000269|PubMed:28126851"; MUTAGEN 860; /note="K->R: Complete loss of ubiquitination by KCTD13."; /evidence="ECO:0000269|PubMed:37142655
uniprot
proteins
post_translational_modification
PTM: NMDA is probably regulated by C-terminal phosphorylation of an isoform of GRIN1 by PKC (PubMed:8316301). Dephosphorylated on Ser-897 probably by protein phosphatase 2A (PPP2CB) (PubMed:8316301). Its phosphorylated state is influenced by the formation of the NMDAR-PPP2CB complex and the NMDAR channel activity (PubMed:8316301). {ECO:0000269|PubMed:8316301}.; PTM: Ubiquitinated via 'Lys-48'-linked ubiquitin chains by the E3 ubiquitin ligase complex, at least composed of CUL3, KCTD13 and RBX1; leading to proteasomal degradation. {ECO:0000269|PubMed:37142655}.
uniprot
proteins
protein_family
Glutamate-gated ion channel (TC 1.A.10.1) family
uniprot
proteins
protein_family
NR1/GRIN1 subfamily
uniprot
proteins
pubmed
10201407
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
18849881
uniprot
proteins
pubmed
21376300
uniprot
proteins
pubmed
22833210
uniprot
proteins
pubmed
25167861
uniprot
proteins
pubmed
25864721
uniprot
proteins
pubmed
26875626
uniprot
proteins
pubmed
26919761
uniprot
proteins
pubmed
27164704
uniprot
proteins
pubmed
27458189
uniprot
proteins
pubmed
28051072
uniprot
proteins
pubmed
28095420
uniprot
proteins
pubmed
28105280
uniprot
proteins
pubmed
28126851
uniprot
proteins
pubmed
28228639
uniprot
proteins
pubmed
28389307
uniprot
proteins
pubmed
34186027
uniprot
proteins
pubmed
34321660
uniprot
proteins
pubmed
34611970
uniprot
proteins
pubmed
36309015
uniprot
proteins
pubmed
36959261
uniprot
proteins
pubmed
37142655
uniprot
proteins
pubmed
38538865
uniprot
proteins
pubmed
38598639
uniprot
proteins
pubmed
7622053
uniprot
proteins
pubmed
7679115
uniprot
proteins
pubmed
7681588
uniprot
proteins
pubmed
7685113
uniprot
proteins
pubmed
7926821
uniprot
proteins
pubmed
8316301
uniprot
proteins
pubmed
8406025
uniprot
proteins
pubmed
9231706
uniprot
proteins
sequence_length
938
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:28228639, ECO:0000269|PubMed:38538865, ECO:0000269|PubMed:7685113}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P35439}. Postsynaptic cell membrane {ECO:0000250|UniProtKB:P35438}. Postsynaptic density membrane {ECO:0000250|UniProtKB:P35439}. Synaptic cell membrane {ECO:0000250|UniProtKB:P35438}. Note=Synaptic cell membrane targeting is dependent of GRIN2B/GluN2B subunit (By similarity). Association with GRIN3A occurs in the endoplasmic reticulum (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P35438, ECO:0000250|UniProtKB:P35439}.
uniprot
proteins
transmembrane_region
TRANSMEM 560..580; /note="Helical"; /evidence="ECO:0000269|PubMed:34186027, ECO:0007744|PDB:7EOQ"; TRANSMEM 628..648; /note="Helical"; /evidence="ECO:0000269|PubMed:34186027, ECO:0007744|PDB:7EOQ"; TRANSMEM 812..835; /note="Helical"; /evidence="ECO:0000269|PubMed:34186027, ECO:0007744|PDB:7EOQ
uniprot
proteins