NMDE4_MOUSE
ID NMDE4_MOUSE Reviewed; 1323 AA.
AC Q03391; C9K0Z5;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Glutamate receptor ionotropic, NMDA 2D;
DE Short=GluN2D;
DE AltName: Full=Glutamate [NMDA] receptor subunit epsilon-4 {ECO:0000303|PubMed:1385220, ECO:0000303|PubMed:8774946};
DE AltName: Full=N-methyl D-aspartate receptor subtype 2D;
DE Short=NMDAR2D;
DE Short=NR2D;
DE Flags: Precursor;
GN Name=Grin2d; Synonyms=GluN2D;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ddY; TISSUE=Spinal cord;
RA Nishizwa M., Ito S.;
RT "Expression of mRNA in mouse spinal cord.";
RL Submitted (OCT-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RC TISSUE=Brain;
RX PubMed=1385220; DOI=10.1016/0014-5793(92)81178-o;
RA Ikeda K., Nagasawa M., Mori H., Araki K., Sakimura K., Watanabe M.,
RA Inoue Y., Mishina M.;
RT "Cloning and expression of the epsilon 4 subunit of the NMDA receptor
RT channel.";
RL FEBS Lett. 313:34-38(1992).
RN [3]
RP SEQUENCE REVISION.
RA Ikeda K., Nagasawa M., Mori H., Araki K., Sakimura K., Watanabe M.,
RA Inoue Y., Mishina M.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=8774946; DOI=10.1016/0169-328x(95)00107-4;
RA Ikeda K., Araki K., Takayama C., Inoue Y., Yagi T., Aizawa S., Mishina M.;
RT "Reduced spontaneous activity of mice defective in the epsilon 4 subunit of
RT the NMDA receptor channel.";
RL Brain Res. Mol. Brain Res. 33:61-71(1995).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1313, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1303, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Component of NMDA receptor complexes that function as
CC heterotetrameric, ligand-gated ion channels with high calcium
CC permeability and voltage-dependent sensitivity to magnesium. Channel
CC activation requires binding of the neurotransmitter glutamate to the
CC epsilon subunit, glycine binding to the zeta subunit, plus membrane
CC depolarization to eliminate channel inhibition by Mg(2+)
CC (PubMed:1385220). Sensitivity to glutamate and channel kinetics depend
CC on the subunit composition (Probable). {ECO:0000269|PubMed:1385220,
CC ECO:0000305}.
CC -!- SUBUNIT: Heterotetramer. Forms heterotetrameric channels composed of
CC two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B,
CC GRIN2C or GRIN2D) (in vitro) (PubMed:1385220). In vivo, the subunit
CC composition may depend on the expression levels of the different
CC subunits (Probable). Interacts with PDZ domains of PATJ and DLG4 (By
CC similarity). {ECO:0000250|UniProtKB:Q62645, ECO:0000269|PubMed:1385220,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1385220};
CC Multi-pass membrane protein {ECO:0000305}. Postsynaptic cell membrane
CC {ECO:0000305|PubMed:8774946}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in neonate brain synaptosomes (at protein
CC level). {ECO:0000269|PubMed:8774946}.
CC -!- DOMAIN: A hydrophobic region that gives rise to the prediction of a
CC transmembrane span does not cross the membrane, but is part of a
CC discontinuously helical region that dips into the membrane and is
CC probably part of the pore and of the selectivity filter.
CC {ECO:0000250|UniProtKB:Q00960}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate, are
CC viable and fertile. Their brains appear grossly normal. Mutant mice
CC show reduced spontaneous locomotion activity, but have no visible
CC impairment of motor skills. They have normal exploratory behavior, but
CC their behavior in a new situation suggests increased novelty
CC preference. {ECO:0000269|PubMed:8774946}.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. NR2D/GRIN2D subfamily. {ECO:0000305}.
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DR EMBL; AB154245; BAI44630.1; -; mRNA.
DR EMBL; D12822; BAA02254.1; -; mRNA.
DR CCDS; CCDS21267.1; -.
DR PIR; S27224; S27224.
DR RefSeq; NP_032198.2; NM_008172.2.
DR RefSeq; XP_011249107.1; XM_011250805.2.
DR AlphaFoldDB; Q03391; -.
DR SMR; Q03391; -.
DR BioGRID; 200071; 6.
DR ComplexPortal; CPX-293; NMDA receptor complex, GluN1-GluN2D.
DR IntAct; Q03391; 3.
DR STRING; 10090.ENSMUSP00000002848; -.
DR ChEMBL; CHEMBL3832634; -.
DR GlyConnect; 2353; 1 N-Linked glycan (1 site).
DR GlyGen; Q03391; 7 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q03391; -.
DR PhosphoSitePlus; Q03391; -.
DR PaxDb; Q03391; -.
DR PeptideAtlas; Q03391; -.
DR PRIDE; Q03391; -.
DR ProteomicsDB; 252912; -.
DR Antibodypedia; 31709; 186 antibodies from 29 providers.
DR DNASU; 14814; -.
DR Ensembl; ENSMUST00000002848; ENSMUSP00000002848; ENSMUSG00000002771.
DR Ensembl; ENSMUST00000211713; ENSMUSP00000147663; ENSMUSG00000002771.
DR GeneID; 14814; -.
DR KEGG; mmu:14814; -.
DR UCSC; uc009gxm.1; mouse.
DR CTD; 2906; -.
DR MGI; MGI:95823; Grin2d.
DR VEuPathDB; HostDB:ENSMUSG00000002771; -.
DR eggNOG; KOG1053; Eukaryota.
DR GeneTree; ENSGT00940000159109; -.
DR HOGENOM; CLU_002039_3_1_1; -.
DR InParanoid; Q03391; -.
DR OMA; CGCPRSH; -.
DR OrthoDB; 188544at2759; -.
DR PhylomeDB; Q03391; -.
DR TreeFam; TF314731; -.
DR Reactome; R-MMU-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-8849932; Synaptic adhesion-like molecules.
DR Reactome; R-MMU-9609736; Assembly and cell surface presentation of NMDA receptors.
DR BioGRID-ORCS; 14814; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Grin2d; mouse.
DR PRO; PR:Q03391; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q03391; protein.
DR Bgee; ENSMUSG00000002771; Expressed in molecular layer of cerebellar cortex and 84 other tissues.
DR ExpressionAtlas; Q03391; baseline and differential.
DR Genevisible; Q03391; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; ISO:MGI.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IC:ComplexPortal.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0005261; F:cation channel activity; ISO:MGI.
DR GO; GO:0016595; F:glutamate binding; ISO:MGI.
DR GO; GO:0022849; F:glutamate-gated calcium ion channel activity; ISS:UniProtKB.
DR GO; GO:0004970; F:ionotropic glutamate receptor activity; ISO:MGI.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0042165; F:neurotransmitter binding; ISO:MGI.
DR GO; GO:0004972; F:NMDA glutamate receptor activity; IDA:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; ISO:MGI.
DR GO; GO:0022843; F:voltage-gated cation channel activity; ISO:MGI.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISS:UniProtKB.
DR GO; GO:0098655; P:cation transmembrane transport; ISO:MGI.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISO:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; IBA:GO_Central.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISO:MGI.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISO:MGI.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; ISO:MGI.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IC:ComplexPortal.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IMP:MGI.
DR GO; GO:0001964; P:startle response; IMP:MGI.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; ISO:MGI.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR019594; Glu/Gly-bd.
DR InterPro; IPR001508; Iono_rcpt_met.
DR InterPro; IPR001320; Iontro_rcpt.
DR InterPro; IPR028082; Peripla_BP_I.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00060; Lig_chan; 1.
DR Pfam; PF10613; Lig_chan-Glu_bd; 1.
DR PRINTS; PR00177; NMDARECEPTOR.
DR SMART; SM00918; Lig_chan-Glu_bd; 1.
DR SMART; SM00079; PBPe; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Disulfide bond; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Magnesium; Membrane; Methylation;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..1323
FT /note="Glutamate receptor ionotropic, NMDA 2D"
FT /id="PRO_0000011584"
FT TOPO_DOM 28..581
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 582..600
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 601..627
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 628..647
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 648..654
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 655..670
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 671..841
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 842..861
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 862..1323
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 628..647
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT REGION 897..952
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 977..1112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1201..1323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1321..1323
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 899..930
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1016..1033
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1077..1096
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1213..1243
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 536..538
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 538
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT BINDING 543
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT BINDING 714..715
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 756
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT SITE 639
FT /note="Functional determinant of NMDA receptors"
FT /evidence="ECO:0000250"
FT MOD_RES 1303
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 1313
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 349
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 381
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 712
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 101..345
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 452..480
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 459..481
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 770..825
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT CONFLICT 1087
FT /note="A -> T (in Ref. 2; BAA02254)"
FT /evidence="ECO:0000305"
FT CONFLICT 1208..1209
FT /note="PR -> AP (in Ref. 2; BAA02254)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1323 AA; 142963 MW; 3DF8860D19677586 CRC64;
MRGAGGPRGP RGPAKMLLLL ALACASPFPE EVPGPGAAGG GTGGARPLNV ALVFSGPAYA
AEAARLGPAV AAAVRSPGLD VRPVALVLNG SDPRSLVLQL CDLLSGLRVH GVVFEDDSRA
PAVAPILDFL SAQTSLPIVA VHGGAALVLT PKEKGSTFLQ LGSSTEQQLQ VIFEVLEEYD
WTSFVAVTTR APGHRAFLSY IEVLTDGSLV GWEHRGALTL DPGAGEAVLG AQLRSVSAQI
RLLFCAREEA EPVFRAAEEA GLTGPGYVWF MVGPQLAGGG GSGVPGEPLL LPGGAPLPAG
LFAVRSAGWR DDLARRVAAG VAVVARGAQA LLRDYGFLPE LGHDCRAQNR THRGESLHRY
FMNITWDNRD YSFNEDGFLV NPSLVVISLT RDRTWEVVGS WEQQTLRLKY PLWSRYGRFL
QPVDDTQHLT VATLEERPFV IVEPADPISG TCIRDSVPCR SQLNRTHSPP PDAPRPEKRC
CKGFCIDILK RLAHTIGFSY DLYLVTNGKH GKKIDGVWNG MIGEVFYQRA DMAIGSLTIN
EERSEIVDFS VPFVETGISV MVARSNGTVS PSAFLEPYSP AVWVMMFVMC LTVVAVTVFI
FEYLSPVGYN RSLATGKRPG GSTFTIGKSI WLLWALVFNN SVPVENPRGT TSKIMVLVWA
FFAVIFLASY TANLAAFMIQ EEYVDTVSGL SDRKFQRPQE QYPPLKFGTV PNGSTEKNIR
SNYPDMHSYM VRYNQPRVEE ALTQLKAGKL DAFIYDAAVL NYMARKDEGC KLVTIGSGKV
FATTGYGIAL HKGSRWKRPI DLALLQFLGD DEIEMLERLW LSGICHNDKI EVMSSKLDID
NMAGVFYMLL VAMGLSLLVF AWEHLVYWRL RHCLGPTHRM DFLLAFSRGM YSCCSAEAAP
PPAKPPPPPQ PLPSPAYPAA RPPPGPAPFV PRERAAADRW RRAKGTGPPG GAALADGFHR
YYGPIEPQGL GLGEARAAPR GAAGRPLSPP TTQPPQKPPP SYFAIVREQE PAEPPAGAFP
GFPSPPAPPA AAAAAVGPPL CRLAFEDESP PAPSRWPRSD PESQPLLGGG AGGPSAGAPT
APPPRRAAPP PCAYLDLEPS PSDSEDSESL GGASLGGLEP WWFADFPYPY AERLGPPPGR
YWSVDKLGGW RAGSWDYLPP RGGPAWHCRH CASLELLPPP RHLSCSHDGL DGGWWAPPPP
PWAAGPPPRR RARCGCPRPH PHRPRASHRA PAAAPHHHRH RRAAGGWDLP PPAPTSRSLE
DLSSCPRAAP TRRLTGPSRH ARRCPHAAHW GPPLPTASHR RHRGGDLGTR RGSAHFSSLE
SEV
