NMDE3_MOUSE
ID NMDE3_MOUSE Reviewed; 1239 AA.
AC Q01098;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Glutamate receptor ionotropic, NMDA 2C;
DE Short=GluN2C;
DE AltName: Full=Glutamate [NMDA] receptor subunit epsilon-3 {ECO:0000303|PubMed:1377365};
DE AltName: Full=N-methyl D-aspartate receptor subtype 2C;
DE Short=NMDAR2C;
DE Short=NR2C {ECO:0000303|PubMed:8987814};
DE Flags: Precursor;
GN Name=Grin2c;
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], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND
RP TISSUE SPECIFICITY.
RX PubMed=1377365; DOI=10.1038/358036a0;
RA Kutsuwada T., Kashiwabuchi N., Mori H., Sakimura K., Kushiya E., Araki K.,
RA Meguro H., Masaki H., Kumanishi T., Arakawa M., Mishina M.;
RT "Molecular diversity of the NMDA receptor channel.";
RL Nature 358:36-41(1992).
RN [2]
RP SEQUENCE REVISION.
RA Kashiwabuchi N.;
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8987814; DOI=10.1523/jneurosci.16-24-07859.1996;
RA Kadotani H., Hirano T., Masugi M., Nakamura K., Nakao K., Katsuki M.,
RA Nakanishi S.;
RT "Motor discoordination results from combined gene disruption of the NMDA
RT receptor NR2A and NR2C subunits, but not from single disruption of the NR2A
RT or NR2C subunit.";
RL J. Neurosci. 16:7859-7867(1996).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-875 AND SER-881, AND
RP IDENTIFICATION BY 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 [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=27922130; DOI=10.1038/srep38321;
RA Gupta S.C., Ravikrishnan A., Liu J., Mao Z., Pavuluri R., Hillman B.G.,
RA Gandhi P.J., Stairs D.J., Li M., Ugale R.R., Monaghan D.T., Dravid S.M.;
RT "The NMDA receptor GluN2C subunit controls cortical excitatory-inhibitory
RT balance, neuronal oscillations and cognitive function.";
RL Sci. Rep. 6:38321-38321(2016).
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:1377365). Sensitivity to glutamate and channel kinetics depend
CC on the subunit composition (PubMed:1377365). Plays a role in regulating
CC the balance between excitatory and inhibitory activity of pyramidal
CC neurons in the prefrontal cortex (PubMed:27922130). Contributes to the
CC slow phase of excitatory postsynaptic current, long-term synaptic
CC potentiation, and learning (PubMed:8987814).
CC {ECO:0000269|PubMed:1377365, ECO:0000269|PubMed:27922130,
CC ECO:0000269|PubMed:8987814}.
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:1377365). Can also form
CC heterotetrameric channels that contain at least one zeta subunit
CC (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (By
CC similarity). In vivo, the subunit composition may depend on the
CC expression levels of the different subunits (Probable). Interacts with
CC PDZ domains of PATJ and DLG4 (By similarity). Interacts (via PDZ-
CC binding motif) with SNX27 (via PDZ domain); the interaction is required
CC for recycling to the plasma membrane when endocytosed and prevent
CC degradation in lysosomes (By similarity).
CC {ECO:0000250|UniProtKB:Q00961, ECO:0000250|UniProtKB:Q14957,
CC ECO:0000269|PubMed:1377365, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1377365};
CC Multi-pass membrane protein {ECO:0000305}. Postsynaptic cell membrane;
CC Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Detected in cerebellum (at protein level)
CC (PubMed:8987814). Detected in the granule cell layer of the cerebellum
CC (PubMed:1377365). {ECO:0000269|PubMed:1377365,
CC ECO:0000269|PubMed:8987814}.
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: Mutant mice appear grossly normal
CC (PubMed:8987814). Mossy fiber granule cells from mutant mice present a
CC decrease of the slow component of the excitatory postsynaptic current
CC (PubMed:8987814). Pyramidal neurons in the prefrontal cortex display a
CC reduced dendritic spine density (PubMed:27922130). Besides, the
CC prefrontal cortex has an altered pattern of excitatory and inhibitory
CC synapses (PubMed:27922130). Pyramidal neurons in the prefrontal cortex
CC display a reduced frequency of miniature excitatory postsynaptic
CC currents (mEPSC), together with an increased frequency of miniature
CC inhibitory postsynaptic currents (mIPSC), indicative of a shift in the
CC balance between excitatory and inhibitory membrane currents
CC (PubMed:27922130). The slow component of the excitatory postsynaptic
CC current is nearly abolished in mossy fiber cells from mice lacking both
CC Grin2a and Grin2c (PubMed:8987814). Mice lacking both Grin2a and Grin2c
CC display subtle motor deficits; they have no visible phenotype when
CC performing simple tasks, but have decreased ability to walk across a
CC narrow wooden bar, and are unable to stay on a rapidly rotating rod
CC (PubMed:8987814). {ECO:0000269|PubMed:27922130,
CC ECO:0000269|PubMed:8987814}.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. NR2C/GRIN2C subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D10694; BAA01536.1; -; mRNA.
DR CCDS; CCDS25624.1; -.
DR PIR; I49705; I49705.
DR RefSeq; NP_034480.2; NM_010350.2.
DR AlphaFoldDB; Q01098; -.
DR SMR; Q01098; -.
DR BioGRID; 200070; 6.
DR ComplexPortal; CPX-292; NMDA receptor complex, GluN1-GluN2C.
DR IntAct; Q01098; 1.
DR MINT; Q01098; -.
DR STRING; 10090.ENSMUSP00000102164; -.
DR ChEMBL; CHEMBL3832634; -.
DR GlyConnect; 2352; 1 N-Linked glycan (1 site).
DR GlyGen; Q01098; 6 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q01098; -.
DR PhosphoSitePlus; Q01098; -.
DR PaxDb; Q01098; -.
DR PRIDE; Q01098; -.
DR ProteomicsDB; 293865; -.
DR ABCD; Q01098; 3 sequenced antibodies.
DR Antibodypedia; 19474; 286 antibodies from 35 providers.
DR DNASU; 14813; -.
DR Ensembl; ENSMUST00000003351; ENSMUSP00000003351; ENSMUSG00000020734.
DR Ensembl; ENSMUST00000106554; ENSMUSP00000102164; ENSMUSG00000020734.
DR GeneID; 14813; -.
DR KEGG; mmu:14813; -.
DR UCSC; uc007mgx.1; mouse.
DR CTD; 2905; -.
DR MGI; MGI:95822; Grin2c.
DR VEuPathDB; HostDB:ENSMUSG00000020734; -.
DR eggNOG; KOG1053; Eukaryota.
DR GeneTree; ENSGT00940000156964; -.
DR HOGENOM; CLU_002039_1_0_1; -.
DR InParanoid; Q01098; -.
DR OMA; VENQARH; -.
DR OrthoDB; 188544at2759; -.
DR PhylomeDB; Q01098; -.
DR TreeFam; TF314731; -.
DR Reactome; R-MMU-438066; Unblocking of NMDA receptors, glutamate binding and activation.
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; 14813; 4 hits in 75 CRISPR screens.
DR PRO; PR:Q01098; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q01098; protein.
DR Bgee; ENSMUSG00000020734; Expressed in cerebellum lobe and 88 other tissues.
DR ExpressionAtlas; Q01098; baseline and differential.
DR Genevisible; Q01098; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; IPI:MGI.
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:0005261; F:cation channel activity; IMP: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:0004972; F:NMDA glutamate receptor activity; IMP:MGI.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO: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; IDA:SynGO.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISS:UniProtKB.
DR GO; GO:0098655; P:cation transmembrane transport; IC:ComplexPortal.
DR GO; GO:0033058; P:directional locomotion; IGI:MGI.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IMP: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:0042177; P:negative regulation of protein catabolic process; IGI:MGI.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IMP:MGI.
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:1903539; P:protein localization to postsynaptic membrane; IMP:MGI.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; ISO:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IC:ComplexPortal.
DR GO; GO:0009611; P:response to wounding; IGI: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; IPR018884; NMDAR2_C.
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 Pfam; PF10565; NMDAR2_C; 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;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1239
FT /note="Glutamate receptor ionotropic, NMDA 2C"
FT /id="PRO_0000011581"
FT TOPO_DOM 20..554
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TRANSMEM 555..573
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 574..600
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT INTRAMEM 601..620
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 621..627
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TRANSMEM 628..643
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 644..814
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TRANSMEM 815..834
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 835..1239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT REGION 601..620
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT REGION 918..988
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1237..1239
FT /note="PDZ-binding"
FT COMPBIAS 918..936
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 937..952
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 509..511
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 511
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT BINDING 516
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 687..688
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 729
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT SITE 612
FT /note="Functional determinant of NMDA receptors"
FT /evidence="ECO:0000250"
FT MOD_RES 875
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 881
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 912
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00961"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 438
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 539
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 685
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 82..317
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 426..453
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 433..454
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 743..798
FT /evidence="ECO:0000250|UniProtKB:Q00959"
SQ SEQUENCE 1239 AA; 135420 MW; 793E8E731E20C3C9 CRC64;
MGGALGPALL LTSLLGAWAG LGAGQGEQAV TVAVVFGSSG PLQAQARTRL TPQNFLDLPL
EIQPLTIGVN NTNPSSILTQ ICGLLGAARV HGIVFEDNVD TEAVAQLLDF VSSQTHVPIL
SISGGSAVVL TPKEPGSAFL QLGVSLEQQL QVLFKVLEEY DWSAFAVITS LHPGHALFLE
GVRAVADASY LSWRLLDVLT LELGPGGPRA RTQRLLRQVD APVLVAYCSR EEAEVLFAEA
AQAGLVGPGH VWLVPNLALG STDAPPAAFP VGLISVVTES WRLSLRQKVR DGVAILALGA
HSYRRQYGTL PAPAGDCRSH PGPVSPAREA FYRHLLNVTW EGRDFSFSPG GYLVQPTMVV
IALNRHRLWE MVGRWDHGVL YMKYPVWPRY STSLQPVVDS RHLTVATLEE RPFVIVESPD
PGTGGCVPNT VPCRRQSNHT FSSGDITPYT KLCCKGFCID ILKKLAKVVK FSYDLYLVTN
GKHGKRVRGV WNGMIGEVYY KRADMAIGSL TINEERSEII DFSVPFVETG ISVMVARSNG
TVSPSAFLEP YSPAVWVMMF VMCLTVVAIT VFMFEYFSPV SYNQNLTKGK KSGGPSFTIG
KSVWLLWALV FNNSVPIENP RGTTSKIMVL VWAFFAVIFL ASYTANLAAF MIQEQYIDTV
SGLSDKKFQR PQDQYPPFRF GTVPNGSTER NIRSNYRDMH THMVKFNQRS VEDALTSLKM
GKLDAFIYDA AVLNYMAGKD EGCKLVTIGS GKVFATTGYG IAMQKDSHWK RAIDLALLQF
LGDGETQKLE TVWLSGICHN EKNEVMSSKL DIDNMAGVFY MLLVAMGLAL LVFAWEHLVY
WKLRHSVPSS SQLDFLLAFS RGIYSCFNGV QSLPSPARPP SPDLTAGSAQ ANVLKMLQAA
RDMVSTADVS GSLDRATRTI ENWGNNRRAP APTTSGPRSC TPGPPGQPSP SGWRPPGGGR
TPLARRAPQP PARPATCAGS PQPDVSRASC RHAWDARWPV RVGHQGSHLS ASERRALPER
SLLHAHCHYS SFPRAERSGR PFLPLFPEPP EPDDLPLLGP EQLARREALL RAAWARGPRP
RHASLPSSVA EAFTRSNPLP ARCTGHACAC PCPQSRPSCR HVAQTQSLRL PSYREACVEG
VPAGVAATWQ PRQHVCLHTH THLPFCWGTV CRHPPPCSSH SPWLIGTWEP PSHRGRTLGL
GTGYRDSGVL EEVSREACGT QGFPRSCTWR RISSLESEV
