Grin1

Domain

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 (ATD) 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.

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:1350383, PubMed:1388270, PubMed:1834949, PubMed:8428958). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the long-term potentiation (LTP) (By similarity). 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:11823786, PubMed:1350383, PubMed:1388270, PubMed:15996549, PubMed:18177891, PubMed:1834949, PubMed:24876489, PubMed:27135925, PubMed:27618671, PubMed:28384476, PubMed:28468946, PubMed:8428958). 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:10436042, PubMed:11160393, PubMed:11929923, PubMed:28384476, PubMed:9463421). Forms excitatory glycinergic receptor complexes with GluN3 alone which are activated by glycine binding to the GluN1 and GluN3 subunits (PubMed:11823786, PubMed:11929923, PubMed:12391275).

Post-translational modifications

NMDA is probably regulated by C-terminal phosphorylation of an isoform of NR1 by PKC (PubMed:11588171, PubMed:15936117). Dephosphorylated on Ser-897 probably by protein phosphatase 2A (PPP2CB) (PubMed:11588171). Its phosphorylated state is influenced by the formation of the NMDAR-PPP2CB complex and the NMDAR channel activity (PubMed:11588171).

Sequence Similarities

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

Tissue Specificity

Detected throughout the brain, in brain cortex, cerebellum, thalamus and olfactory bulb.

Cellular localization

• Cell membrane
• Multi-pass membrane protein
• Postsynaptic cell membrane
• Synaptic cell membrane
• Postsynaptic density membrane
• Synaptic cell membrane targeting is dependent of GRIN2B/GluN2B subunit (By similarity). Association with GRIN3A occurs in the endoplasmic reticulum (PubMed:11160393).

Alternative names

Nmdar1, Grin1, GluN1, Glutamate [NMDA] receptor subunit zeta-1, N-methyl-D-aspartate receptor subunit NR1, NMD-R1

Database links

swissprot:P35439 entrezGene:24408

Other research areas

• Cardiovascular