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Protein

Glutamate receptor ionotropic, NMDA 1

Gene

Grin1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 Mg2+ (PubMed:1532151, PubMed:8060614, PubMed:12008020). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:12008020).3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei523GlycineBy similarity1
Binding sitei688GlycineBy similarity1
Binding sitei732GlycineBy similarity1

GO - Molecular functioni

  • calcium channel activity Source: MGI
  • calcium ion binding Source: MGI
  • calmodulin binding Source: MGI
  • cation channel activity Source: MGI
  • extracellular-glutamate-gated ion channel activity Source: InterPro
  • glutamate binding Source: MGI
  • glutamate-gated calcium ion channel activity Source: Ensembl
  • glycine binding Source: UniProtKB
  • NMDA glutamate receptor activity Source: MGI
  • receptor binding Source: MGI
  • transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential Source: SynGO

GO - Biological processi

  • adult locomotory behavior Source: MGI
  • associative learning Source: MGI
  • calcium ion homeostasis Source: MGI
  • calcium ion transmembrane import into cytosol Source: Ensembl
  • calcium ion transport Source: MGI
  • cation transport Source: MGI
  • cellular calcium ion homeostasis Source: MGI
  • cerebral cortex development Source: MGI
  • chemical synaptic transmission Source: MGI
  • conditioned taste aversion Source: MGI
  • ephrin receptor signaling pathway Source: Reactome
  • excitatory postsynaptic potential Source: MGI
  • ionotropic glutamate receptor signaling pathway Source: MGI
  • learning Source: MGI
  • learning or memory Source: MGI
  • long-term memory Source: MGI
  • male mating behavior Source: MGI
  • memory Source: MGI
  • negative regulation of neuron apoptotic process Source: MGI
  • neuromuscular process Source: MGI
  • olfactory learning Source: MGI
  • pons maturation Source: MGI
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • prepulse inhibition Source: MGI
  • propylene metabolic process Source: BHF-UCL
  • protein heterotetramerization Source: UniProtKB
  • regulation of axonogenesis Source: MGI
  • regulation of cell communication Source: MGI
  • regulation of dendrite morphogenesis Source: MGI
  • regulation of long-term neuronal synaptic plasticity Source: MGI
  • regulation of membrane potential Source: MGI
  • regulation of neuronal synaptic plasticity Source: MGI
  • regulation of neuron apoptotic process Source: MGI
  • regulation of respiratory gaseous exchange Source: MGI
  • regulation of synapse assembly Source: MGI
  • regulation of synaptic plasticity Source: MGI
  • respiratory gaseous exchange Source: MGI
  • response to amphetamine Source: MGI
  • response to ethanol Source: MGI
  • response to glycine Source: Ensembl
  • response to morphine Source: MGI
  • sensory perception of pain Source: MGI
  • social behavior Source: MGI
  • startle response Source: MGI
  • suckling behavior Source: MGI
  • synaptic transmission, glutamatergic Source: MGI
  • visual learning Source: MGI

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Receptor
Biological processIon transport, Transport
LigandCalcium, Magnesium

Enzyme and pathway databases

ReactomeiR-MMU-3928662. EPHB-mediated forward signaling.
R-MMU-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-MMU-442729. CREB phosphorylation through the activation of CaMKII.
R-MMU-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-8849932. Synaptic adhesion-like molecules.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate receptor ionotropic, NMDA 1
Short name:
GluN1
Alternative name(s):
Glutamate [NMDA] receptor subunit zeta-1
N-methyl-D-aspartate receptor subunit NR1
Short name:
NMD-R1
Gene namesi
Name:Grin1
Synonyms:Glurz1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:95819. Grin1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 559ExtracellularCuratedAdd BLAST541
Transmembranei560 – 580HelicalBy similarityAdd BLAST21
Topological domaini581 – 602CytoplasmicCuratedAdd BLAST22
Intramembranei603 – 624Discontinuously helicalBy similarityAdd BLAST22
Topological domaini625 – 630CytoplasmicCurated6
Transmembranei631 – 647HelicalBy similarityAdd BLAST17
Topological domaini648 – 812ExtracellularCuratedAdd BLAST165
Transmembranei813 – 833HelicalBy similarityAdd BLAST21
Topological domaini834 – 938CytoplasmicCuratedAdd BLAST105

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Mutant mice are born at the expected Mendelian rate, appear grossly normal and have apparently normal brain structure, but the pups do not feed and all die during the first day after birth. Cerebellum granule cells and hippocampus pyramidal neurons from mutants lack NMDA-induced Ca2+influx and membrane currents, contrary to wild-type.1 Publication

Chemistry databases

ChEMBLiCHEMBL3832634.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001158819 – 938Glutamate receptor ionotropic, NMDA 1Add BLAST920

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi61N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi79 ↔ 308By similarity
Glycosylationi203N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi239N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi276N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi300N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi350N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi368N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi420 ↔ 454By similarity
Disulfide bondi436 ↔ 455By similarity
Glycosylationi440N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi471N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi491N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi744 ↔ 798By similarity
Modified residuei889Phosphoserine; by PKCBy similarity1
Modified residuei890PhosphoserineBy similarity1
Modified residuei896Phosphoserine; by PKCBy similarity1
Modified residuei897Phosphoserine; by PKCBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP35438.
PaxDbiP35438.
PeptideAtlasiP35438.
PRIDEiP35438.

PTM databases

iPTMnetiP35438.
PhosphoSitePlusiP35438.

Expressioni

Tissue specificityi

Detected in brain (at protein level). Detected in brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000026959.
CleanExiMM_GRIN1.
ExpressionAtlasiP35438. baseline and differential.
GenevisibleiP35438. MM.

Interactioni

Subunit structurei

Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B) (PubMed:12008020, PubMed:14602821). Found in a complex with GRIN2A or GRIN2B and GRIN3B (PubMed:12008020, PubMed:14602821). Found in a complex with GRIN2A or GRIN2B, GRIN3A and PPP2CB (By similarity). Interacts with DLG4 and MPDZ (By similarity). Interacts with LRFN1 and LRFN2 (By similarity). Interacts with MYZAP (PubMed:18849881). Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (PubMed:23524343). Found in a complex with DLG4 and PRR7 (By similarity). Found in a complex with GRIN2B and PRR7 (By similarity). Interacts with PRR7; the interaction is reduced following NMDA receptor activity (By similarity).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • calmodulin binding Source: MGI
  • receptor binding Source: MGI

Protein-protein interaction databases

BioGridi200067. 82 interactors.
DIPiDIP-31577N.
IntActiP35438. 126 interactors.
MINTiMINT-135802.
STRINGi10090.ENSMUSP00000028335.

Structurei

3D structure databases

ProteinModelPortaliP35438.
SMRiP35438.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni516 – 518Glycine bindingBy similarity3
Regioni603 – 624Pore-formingBy similarityAdd BLAST22

Domaini

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.By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1053. Eukaryota.
ENOG410XNUR. LUCA.
GeneTreeiENSGT00760000119186.
HOGENOMiHOG000231491.
HOVERGENiHBG052638.
InParanoidiP35438.
KOiK05208.
TreeFamiTF351405.

Family and domain databases

InterProiView protein in InterPro
IPR001828. ANF_lig-bd_rcpt.
IPR018882. CaM-bd_C0_NMDA_rcpt_NR1.
IPR019594. Glu/Gly-bd.
IPR001508. Iono_rcpt_met.
IPR001320. Iontro_rcpt.
IPR028082. Peripla_BP_I.
PfamiView protein in Pfam
PF01094. ANF_receptor. 1 hit.
PF10562. CaM_bdg_C0. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
PRINTSiPR00177. NMDARECEPTOR.
SMARTiView protein in SMART
SM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
SUPFAMiSSF53822. SSF53822. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35438-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN
60 70 80 90 100
KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYAI LVSHPPTPND
110 120 130 140 150
HFTPTPVSYT AGFYRIPVLG LTTRMSIYSD KSIHLSFLRT VPPYSHQSSV
160 170 180 190 200
WFEMMRVYNW NHIILLVSDD HEGRAAQKRL ETLLEERESK AEKVLQFDPG
210 220 230 240 250
TKNVTALLME ARDLEARVII LSASEDDAAT VYRAAAMLNM TGSGYVWLVG
260 270 280 290 300
EREISGNALR YAPDGIIGLQ LINGKNESAH ISDAVGVVAQ AVHELLEKEN
310 320 330 340 350
ITDPPRGCVG NTNIWKTGPL FKRVLMSSKY ADGVTGRVEF NEDGDRKFAN
360 370 380 390 400
YSIMNLQNRK LVQVGIYNGT HVIPNDRKII WPGGETEKPR GYQMSTRLKI
410 420 430 440 450
VTIHQEPFVY VKPTMSDGTC KEEFTVNGDP VKKVICTGPN DTSPGSPRHT
460 470 480 490 500
VPQCCYGFCV DLLIKLARTM NFTYEVHLVA DGKFGTQERV NNSNKKEWNG
510 520 530 540 550
MMGELLSGQA DMIVAPLTIN NERAQYIEFS KPFKYQGLTI LVKKEIPRST
560 570 580 590 600
LDSFMQPFQS TLWLLVGLSV HVVAVMLYLL DRFSPFGRFK VNSEEEEEDA
610 620 630 640 650
LTLSSAMWFS WGVLLNSGIG EGAPRSFSAR ILGMVWAGFA MIIVASYTAN
660 670 680 690 700
LAAFLVLDRP EERITGINDP RLRNPSDKFI YATVKQSSVD IYFRRQVELS
710 720 730 740 750
TMYRHMEKHN YESAAEAIQA VRDNKLHAFI WDSAVLEFEA SQKCDLVTTG
760 770 780 790 800
ELFFRSGFGI GMRKDSPWKQ NVSLSILKSH ENGFMEDLDK TWVRYQECDS
810 820 830 840 850
RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH KDARRKQMQL
860 870 880 890 900
AFAAVNVWRK NLQDRKSGRA EPDPKKKATF RAITSTLASS FKRRRSSKDT
910 920 930
STGGGRGALQ NQKDTVLPRR AIEREEGQLQ LCSRHRES
Length:938
Mass (Da):105,481
Last modified:June 1, 1994 - v1
Checksum:iC610632DD3E06171
GO
Isoform 2 (identifier: P35438-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     864-885: DRKSGRAEPDPKKKATFRAITS → QYHPTDITGPLNLSDPSVSTVV
     886-938: Missing.

Show »
Length:885
Mass (Da):99,423
Checksum:i283AA14096E81558
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti936R → T. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014222864 – 885DRKSG…RAITS → QYHPTDITGPLNLSDPSVST VV in isoform 2. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_014223886 – 938Missing in isoform 2. 1 PublicationAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10028 mRNA. Translation: BAA00920.1.
AL732309 Genomic DNA. Translation: CAM14685.1.
AL732309 Genomic DNA. Translation: CAM14688.1.
BC039157 mRNA. Translation: AAH39157.1.
CCDSiCCDS15764.1. [P35438-1]
CCDS50528.1. [P35438-2]
PIRiS21104.
RefSeqiNP_001171127.1. NM_001177656.2.
NP_001171128.1. NM_001177657.2. [P35438-2]
NP_032195.1. NM_008169.3. [P35438-1]
UniGeneiMm.278672.

Genome annotation databases

EnsembliENSMUST00000028335; ENSMUSP00000028335; ENSMUSG00000026959. [P35438-1]
ENSMUST00000114312; ENSMUSP00000109951; ENSMUSG00000026959. [P35438-2]
GeneIDi14810.
KEGGimmu:14810.
UCSCiuc008iri.3. mouse. [P35438-2]
uc008irk.3. mouse. [P35438-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNMDZ1_MOUSE
AccessioniPrimary (citable) accession number: P35438
Secondary accession number(s): A2AI15, A2AI18, Q8CFS4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 22, 2017
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families