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1.A.10.1.20
Heteromeric ionotropic NMDA receptor (NMDAR) consisting of two subunits, GluN1 (938 aas) and GluN2A (1464 aas).  Positions of the Mg2+ and Ca2+ ions in the ion channel divalent cation binding site have been proposed, and differences in the structural and dynamic behavior of the channel proteins in the presence of Mg2+ or Ca2+ have been analyzed (Mesbahi-Vasey et al. 2017). GRIN variants in receptor M2 channel pore-forming loop are associated with neurological diseases (Li et al. 2019). Disease-associated variants have revealed mechanistic aspect of the NMDA receptor (Amin et al. 2021). Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors (Iacobucci et al. 2021). The gating mechanism and a modulatory niche of human GluN1-GluN2A NMDA receptors have been reported (Wang et al. 2021). GluN2A and GluN2B NMDA receptors apparently use distinct allosteric routes (Tian et al. 2021). A negative allosteric modulatory site in the GluN1 M4 determines the efficiency of neurosteroid modulation (Langer et al. 2021). Excitatory signaling mediated by NMDAR is critical for brain development and function, as well as for neurological diseases and disorders. Channel blockers of NMDARs can be used for treating depression, Alzheimer's disease, and epilepsy. Chou et al. 2022 monitored the binding of three clinically important channel blockers: phencyclidine, ketamine, and memantine in GluN1-2B NMDARs at local resolutions of 2.5-3.5 Å around the binding site. The channel blockers form interactions with pore-lining residues, which control mostly off-speeds but not on-speeds (Chou et al. 2022).  NMDAR channel blockers include MK-801, phencyclidine, ketamine, and the Alzheimer's disease drug memantine, can bind and unbind only when the NMDAR channel is open. NMDAR channel blockers can enter the channel through two routes: the well-known hydrophilic path from extracellular solution to channel through the open channel gate, and also a hydrophobic path from plasma membrane to channel through a gated fenestration (Wilcox et al. 2022). Pregnane-based steroids are  positive NMDA receptor modulators that may compensate for the effect of loss-of-function disease-associated GRIN mutations (Kysilov et al. 2022). The NMDA receptor C-terminal domain signals in development, maturity, and disease (Haddow et al. 2022). Blood tissue Plasminogen Activator (tPA) of liver origin contributes to neurovascular coupling involving brain endothelial N-Methyl-D-Aspartate (NMDA) receptors (Furon et al. 2023). Two gates mediate NMDA receptor activity and are under subunit-specific regulation (Amin et al. 2023). One of the main molecular mechanisms of ketamine action is the blockage of NMDA-activated glutamate receptors (Pochwat 2022). The S1-M1 linker of the NMDA receptor controls channel opening (Xie et al. 2023).

Accession Number:Q05586
Protein Name:Glutamate receptor ionotropic, NMDA 1
Length:938
Molecular Weight:105373.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:3
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

OMIM: 138249  gene
Structure:
2NR1   3BYA   2HQW   5H8F   5H8H   5H8N   5H8Q   5I2K   5I2N   5KCJ   [...more]

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MSTMRLLTLA LLFSCSVARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL 
61:	NATSVTHKPN AIQMALSVCE DLISSQVYAI LVSHPPTPND HFTPTPVSYT AGFYRIPVLG 
121:	LTTRMSIYSD KSIHLSFLRT VPPYSHQSSV WFEMMRVYSW NHIILLVSDD HEGRAAQKRL 
181:	ETLLEERESK AEKVLQFDPG TKNVTALLME AKELEARVII LSASEDDAAT VYRAAAMLNM 
241:	TGSGYVWLVG EREISGNALR YAPDGILGLQ LINGKNESAH ISDAVGVVAQ AVHELLEKEN 
301:	ITDPPRGCVG NTNIWKTGPL FKRVLMSSKY ADGVTGRVEF NEDGDRKFAN YSIMNLQNRK 
361:	LVQVGIYNGT HVIPNDRKII WPGGETEKPR GYQMSTRLKI VTIHQEPFVY VKPTLSDGTC 
421:	KEEFTVNGDP VKKVICTGPN DTSPGSPRHT VPQCCYGFCI DLLIKLARTM NFTYEVHLVA 
481:	DGKFGTQERV NNSNKKEWNG MMGELLSGQA DMIVAPLTIN NERAQYIEFS KPFKYQGLTI 
541:	LVKKEIPRST LDSFMQPFQS TLWLLVGLSV HVVAVMLYLL DRFSPFGRFK VNSEEEEEDA 
601:	LTLSSAMWFS WGVLLNSGIG EGAPRSFSAR ILGMVWAGFA MIIVASYTAN LAAFLVLDRP 
661:	EERITGINDP RLRNPSDKFI YATVKQSSVD IYFRRQVELS TMYRHMEKHN YESAAEAIQA 
721:	VRDNKLHAFI WDSAVLEFEA SQKCDLVTTG ELFFRSGFGI GMRKDSPWKQ NVSLSILKSH 
781:	ENGFMEDLDK TWVRYQECDS RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH 
841:	KDARRKQMQL AFAAVNVWRK NLQDRKSGRA EPDPKKKATF RAITSTLASS FKRRRSSKDT 
901:	STGGGRGALQ NQKDTVLPRR AIEREEGQLQ LCSRHRES