NMDE3_RAT
ID NMDE3_RAT Reviewed; 1237 AA.
AC Q00961;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Glutamate receptor ionotropic, NMDA 2C;
DE Short=GluN2C;
DE AltName: Full=Glutamate [NMDA] receptor subunit epsilon-3;
DE AltName: Full=N-methyl D-aspartate receptor subtype 2C;
DE Short=NMDAR2C {ECO:0000303|PubMed:8428958};
DE Short=NR2C {ECO:0000303|PubMed:1350383};
DE Flags: Precursor;
GN Name=Grin2c;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=1350383; DOI=10.1126/science.256.5060.1217;
RA Monyer H., Sprengel R., Schoepfer R., Herb A., Higuchi M., Lomeli H.,
RA Burnashev N., Sakmann B., Seeburg P.H.;
RT "Heteromeric NMDA receptors: molecular and functional distinction of
RT subtypes.";
RL Science 256:1217-1221(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=8428958; DOI=10.1016/s0021-9258(18)53849-7;
RA Ishii T., Moriyoshi K., Sugihara H., Sakurada K., Kadotani H., Yokoi M.,
RA Akazawa C., Shigemoto R., Mizuno N., Masu M., Nakanishi S.;
RT "Molecular characterization of the family of the N-methyl-D-aspartate
RT receptor subunits.";
RL J. Biol. Chem. 268:2836-2843(1993).
RN [3]
RP INTERACTION WITH DLG4.
RX PubMed=7569905; DOI=10.1126/science.7569905;
RA Kornau H.C., Schenker L.T., Kennedy M.B., Seeburg P.H.;
RT "Domain interaction between NMDA receptor subunits and the postsynaptic
RT density protein PSD-95.";
RL Science 269:1737-1740(1995).
RN [4]
RP INTERACTION WITH PATJ.
RX PubMed=9647694; DOI=10.1006/mcne.1998.0679;
RA Kurschner C., Mermelstein P.G., Holden W.T., Surmeier D.J.;
RT "CIPP, a novel multivalent PDZ domain protein, selectively interacts with
RT Kir4.0 family members, NMDA receptor subunits, neurexins, and
RT neuroligins.";
RL Mol. Cell. Neurosci. 11:161-172(1998).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-912, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF MET-815.
RX PubMed=28126851; DOI=10.1124/mol.116.106781;
RA Chen W., Tankovic A., Burger P.B., Kusumoto H., Traynelis S.F., Yuan H.;
RT "Functional evaluation of a de novo GRIN2A mutation identified in a patient
RT with profound global developmental delay and refractory epilepsy.";
RL Mol. Pharmacol. 91:317-330(2017).
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:1350383, PubMed:8428958, PubMed:28126851). Sensitivity to
CC glutamate and channel kinetics depend on the subunit composition
CC (Probable). Plays a role in regulating the balance between excitatory
CC and inhibitory activity of pyramidal neurons in the prefrontal cortex.
CC Contributes to the slow phase of excitatory postsynaptic current, long-
CC term synaptic potentiation, and learning (By similarity).
CC {ECO:0000250|UniProtKB:Q01098, ECO:0000269|PubMed:1350383,
CC ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:8428958, 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:1350383, PubMed:8428958,
CC PubMed:28126851). 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 (PubMed:7569905, PubMed:9647694).
CC Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the
CC interaction is required for recycling to the plasma membrane when
CC endocytosed and prevent degradation in lysosomes (By similarity).
CC {ECO:0000250|UniProtKB:Q14957, ECO:0000269|PubMed:1350383,
CC ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:7569905,
CC ECO:0000269|PubMed:8428958, ECO:0000269|PubMed:9647694, ECO:0000305}.
CC -!- INTERACTION:
CC Q00961; Q63ZW7: Patj; Xeno; NbExp=2; IntAct=EBI-631045, EBI-8366894;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1350383,
CC ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:8428958}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q14957}. Postsynaptic cell
CC membrane {ECO:0000250|UniProtKB:Q14957}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q14957}.
CC -!- TISSUE SPECIFICITY: Detected in cerebellum.
CC {ECO:0000269|PubMed:1350383, ECO:0000269|PubMed:8428958}.
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 -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. NR2C/GRIN2C subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA02499.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M91563; AAA41713.1; -; mRNA.
DR EMBL; D13212; BAA02499.1; ALT_INIT; mRNA.
DR RefSeq; NP_036707.3; NM_012575.3.
DR RefSeq; XP_006247769.1; XM_006247707.2.
DR RefSeq; XP_006247771.1; XM_006247709.3.
DR RefSeq; XP_017452475.1; XM_017596986.1.
DR RefSeq; XP_017452476.1; XM_017596987.1.
DR RefSeq; XP_017452477.1; XM_017596988.1.
DR RefSeq; XP_017452478.1; XM_017596989.1.
DR RefSeq; XP_017452479.1; XM_017596990.1.
DR RefSeq; XP_017452480.1; XM_017596991.1.
DR RefSeq; XP_017452481.1; XM_017596992.1.
DR AlphaFoldDB; Q00961; -.
DR SMR; Q00961; -.
DR BioGRID; 246576; 6.
DR ComplexPortal; CPX-287; NMDA receptor complex, GluN1-GluN2C.
DR IntAct; Q00961; 5.
DR MINT; Q00961; -.
DR STRING; 10116.ENSRNOP00000004477; -.
DR BindingDB; Q00961; -.
DR ChEMBL; CHEMBL401; -.
DR DrugCentral; Q00961; -.
DR GuidetoPHARMACOLOGY; 458; -.
DR GlyGen; Q00961; 6 sites.
DR iPTMnet; Q00961; -.
DR PhosphoSitePlus; Q00961; -.
DR PaxDb; Q00961; -.
DR PRIDE; Q00961; -.
DR ABCD; Q00961; 3 sequenced antibodies.
DR GeneID; 24411; -.
DR KEGG; rno:24411; -.
DR CTD; 2905; -.
DR RGD; 2739; Grin2c.
DR eggNOG; KOG1053; Eukaryota.
DR InParanoid; Q00961; -.
DR OrthoDB; 188544at2759; -.
DR PhylomeDB; Q00961; -.
DR TreeFam; TF314731; -.
DR Reactome; R-RNO-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-RNO-8849932; Synaptic adhesion-like molecules.
DR Reactome; R-RNO-9609736; Assembly and cell surface presentation of NMDA receptors.
DR PRO; PR:Q00961; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0022849; F:glutamate-gated calcium ion channel activity; ISS:UniProtKB.
DR GO; GO:0004970; F:ionotropic glutamate receptor activity; IDA:RGD.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0004972; F:NMDA glutamate receptor activity; IDA:RGD.
DR GO; GO:0030165; F:PDZ domain binding; IPI:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:RGD.
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:RGD.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISS:UniProtKB.
DR GO; GO:0033058; P:directional locomotion; ISO:RGD.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISO:RGD.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; IDA:ComplexPortal.
DR GO; GO:0060291; P:long-term synaptic potentiation; IBA:GO_Central.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IDA:ComplexPortal.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IDA:ComplexPortal.
DR GO; GO:1903539; P:protein localization to postsynaptic membrane; ISO:RGD.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; IDA:ComplexPortal.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:RGD.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IC:ComplexPortal.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
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..1237
FT /note="Glutamate receptor ionotropic, NMDA 2C"
FT /id="PRO_0000011582"
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..1237
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 907..990
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1235..1237
FT /note="PDZ-binding"
FT COMPBIAS 907..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 COMPBIAS 967..981
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:Q00960"
FT SITE 612
FT /note="Functional determinant of NMDA receptors"
FT /evidence="ECO:0000250"
FT MOD_RES 875
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01098"
FT MOD_RES 881
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01098"
FT MOD_RES 912
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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"
FT MUTAGEN 815
FT /note="M->V: Increased glutamate and glycine agonist
FT potency."
FT /evidence="ECO:0000269|PubMed:28126851"
SQ SEQUENCE 1237 AA; 135271 MW; B175993804B337A4 CRC64;
MGGALGPALL LTSLLGAWAR LGAGQGEQAV TVAVVFGSSG PLQTQARTRL TSQNFLDLPL
EIQPLTVGVN 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 GYLVRPTMVV
IALNRHRLWE MVGRWDHGVL YMKYPVWPRY STSLQPVVDS RHLTVATLEE RPFVIVESPD
PGTGGCVPNT VPCRRQSNHT FSSGDLTPYT KLCCKGFCID ILKKLAKVVK FSYDLYLVTN
GKHGKRVRGV WNGMIGEVYY KRADMAIGSL TINEERSEII DFSVPFVETG ISVMVSRSNG
TVSPSAFLEP YSPAVWVMMF VMCLTVVAIT VFMFEYFSPV SYNQNLTKGK KPGGPSFTIG
KSVWLLWALV FNNSVPIENP RGTTSKIMVL VWAFFAVIFL ASYTANLAAF MIQEQYIDTV
SGLSDKKFQR PQDQYPPFRF GTVPNGSTER NIRSNYRDMH THMVKFNQRS VEDALTSLKM
GKLDAFIYDA AVLNYMAGKD EGCKLVTIGS GKVFATTGYG IAMQKDSHWK RAIDLALLQL
LGDGETQKLE TVWLSGICQN EKNEVMSSKL DIDNMAGVFY MLLVAMGLAL LVFAWEHLVY
WKLRHSVPNS SQLDFLLAFS RGIYSCFNGV QSLPSPARPP SPDLTADSAQ ANVLKMLQAA
RDMVNTADVS SSLDRATRTI ENWGNNRRVP APTASGPRSS TPGPPGQPSP SGWGPPGGGR
TPLARRAPQP PARPATCGPP LPDVSRPSCR HASDARWPVR VGHQGPHVSA SERRALPERS
LLPAHCHYSS FPRAERSGRP YLPLFPEPPE PDDLPLLGPE QLARREAMLR AAWARGPRPR
HASLPSSVAE AFTRSNPLPA RCTGHACACP CPQSRPSCRH LAQAQSLRLP SYPEACVEGV
PAGVATWQPR QHVCLHAHTR LPFCWGTVCR HPPPCTSHSP WLIGTWEPPA HRVRTLGLGT
GYRDSGVLEE VSREACGTQG FPRSCTWRRV SSLESEV
