Grin1

A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.

The extracellular N-terminal domain (NTD) is a site of allosteric regulation to modulate overall receptor function.

The ligand-binding domain (LBD) binds to glycine (GluN1 and GluN3 subunits) and glutamate (GluN2 subunits) and control opening of the channel gate.

The transmembrane domain (TMD) harbors the channel gate and pore.

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 potasium 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).

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant

NDHMSD

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive

NDHMSR

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Developmental and epileptic encephalopathy 101

DEE101

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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).

Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR1/GRIN1 subfamily.

• Cell membrane
• Multi-pass membrane protein
• Postsynaptic cell membrane
• Postsynaptic density membrane
• Synaptic cell membrane
• Synaptic cell membrane targeting is dependent of GRIN2B/GluN2B subunit (By similarity). Association with GRIN3A occurs in the endoplasmic reticulum (By similarity).

NMDAR1, GRIN1, GluN1, Glutamate [NMDA] receptor subunit zeta-1, N-methyl-D-aspartate receptor subunit NR1, NMD-R1, hNR1

• entrezGene:2902
• omim:138249
• swissprot:Q05586

Proteins

Neuroscience

• Cardiovascular

105373Da