Protein Details: Glutamate receptor ionotropic; NMDA 2A

Protein ID

ICDB_Pro_0493

Protein Name

Glutamate receptor ionotropic; NMDA 2A

Gene Name

Grin2a

Organism

Mus musculus (Mouse)

Length

1464 amino acids

AlphaFoldDB

AF-P35436-F1-model_v4.pdb

Function

Component of NMDA receptor complexes that function as heterotetrameric; ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit; glycine binding to the zeta subunit; plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have lower sensitivity to glutamate and faster deactivation kinetics than channels formed by GRIN1 and GRIN2B (By similarity). Contributes to the slow phase of excitatory postsynaptic current; long-term synaptic potentiation; and learning. Participates in the synaptic plasticity regulation through activation by the L-glutamate released by BEST1; into the synaptic cleft; upon F2R/PAR-1 activation in astrocyte.

Sequence

MGRLGYWTLLVLPALLVWHGPAQNAAAEKGTPALNIAVLLGHSHDVTERELRNLWGPEQATGLPLDVNVVALLMNRTDPKSLITHVCDLMSGARIHGLVFGDDTDQEAVAQMLDFISSQTFIPILGIHGGASMIMADKDPTSTFFQFGASIQQQATVMLKIMQDYDWHVFSLVTTIFPGYRDFISFIKTTVDNSFVGWDMQNVITLDTSFEDAKTQVQLKKIHSSVILLYCSKDEAVLILSEARSLGLTGYDFFWIVPSLVSGNTELIPKEFPSGLISVSYDDWDYSLEARVRDGLGILTTAASSMLEKFSYIPEAKASCYGQTEKPETPLHTLHQFMVNVTWDGKDLSFTEEGYQVHPRLVVIVLNKDREWEKVGKWENQTLSLRHAVWPRYKSFSDCEPDDNHLSIVTLEEAPFVIVEDIDPLTETCVRNTVPCRKFVKINNSTNEGMNVKKCCKGFCIDILKKLSRTVKFTYDLYLVTNGKHGKKVNNVWNGMIGEVVYQRAVMAVGSLTINEERSEVVDFSVPFVETGISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIVSAIAVFVFEYFSPVGYNRNLAKGKAPHGPSFTIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVWAFFAVIFLASYTANLAAFMIQEEFVDQVTGLSDKKFQRPHDYSPPFRFGTVPNGSTERNIRNNYPYMHQYMTKFNQRGVEDALVSLKTGKLDAFIYDAAVLNYKAGRDEGCKLVTIGSGYIFATTGYGIALQKGSPWKRQIDLALLQFVGDGEMEELETLWLTGICHNEKNEVMSSQLDIDNMAGVFYMLAAAMALSLITFIWEHLFYWKLRFCFTGVCSDRPGLLFSISRGIYSCIHGVHIEEKKKSPDFNLTGSQSNMLKLLRSAKNISNMSNMNSSRMDSPKRAADFIQRGSLIVDMVSDKGNLIYSDNRSFQGKDSIFGENMNELQTFVANRHKDSLSNYVFQGQHPLTLNESNPNTVEVAVSTESKGNSRPRQLWKKSMESLRQDSLNQNPVSQRDEKTAENRTHSLKSPRYLPEEVAHSDISETSSRATCHREPDNNKNHKTKDNFKRSMASKYPKDCSEVERTYVKTKASSPRDKIYTIDGEKEPSFHLDPPQFIENIVLPENVDFPDTYQDHNENFRKGDSTLPMNRNPLHNEDGLPNNDQYKLYAKHFTLKDKGSPHSEGSDRYRQNSTHCRSCLSNLPTYSGHFTMRSPFKCDACLRMGNLYDIDEDQMLQETGNPATREEAYQQDWSQNNALQFQKNKLKINRQHSYDNILDKPREIDLSRPSRSISLKDRERLLEGNLYGSLFSVPSSKLLGNKSSLFPQGLEDSKRSKSLLPDHTSDNPFLHTYGDDQRLVIGRCPSDPYKHSLPSQAVNDSYLRSSLRSTASYCSRDSRGHSDVYISEHVMPYAANKNNMYSTPRVLNSCSNRRVYKKMPSIESDV

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

BINDING 44; /ligand="Zn(2+)"; BINDING 128; /ligand="Zn(2+)"; BINDING 266; /ligand="Zn(2+)"; BINDING 282; /ligand="Zn(2+)"; BINDING 511..513; /ligand="L-glutamate"; BINDING 518; /ligand="L-glutamate"; BINDING 689..690; /ligand="L-glutamate"; BINDING 730..731; /ligand="L-glutamate"

Disease

Location

Detected in striatum (PubMed:28469074). Detected in forbrain (PubMed:7816096). Detected in cerebellum (at protein level) (PubMed:8987814). Detected in cerebellum (at protein level) (PubMed:8987814). Detected in cerebellum (at protein level) (PubMed:8987814). Detected in brain cortex; piriform cortex; hippocampus; caudate-putamen; dentate gyrus and granule cell layer (PubMed:1374164; PubMed:7816096)

DOI ID

10.1038/357070a0; 10.1038/373151a0; 10.1523/jneurosci.16-24-07859.1996; 10.1016/s0169-328x(02)00173-0; 10.1523/jneurosci.5175-06.2007; 10.1074/mcp.m600046-mcp200; 10.1371/journal.pbio.1000041; 10.1016/j.cell.2010.12.001; 10.1038/nm.3117; 10.1186/s13041-015-0097-y; 10.1172/jci.insight.88995; 10.1016/j.bbrc.2019.05.087

RefSeq

NP_032196.2; XP_006521857.1