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Protein

Glutamate receptor ionotropic, NMDA 2C

Gene

GRIN2C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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:26875626). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable). Plays a role in regulating the balance between excitatory and inhibitory activity of pyramidal neurons in the prefrontal cortex. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity).By similarityCurated2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei511GlutamateBy similarity1
Binding sitei516GlutamateBy similarity1
Sitei612Functional determinant of NMDA receptorsBy similarity1
Binding sitei729GlutamateBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-HSA-442729 CREB phosphorylation through the activation of CaMKII
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6794361 Neurexins and neuroligins
R-HSA-8849932 Synaptic adhesion-like molecules
SignaLinkiQ14957

Protein family/group databases

TCDBi1.A.10.1.3 the glutamate-gated ion channel (gic) family of neurotransmitter receptors

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate receptor ionotropic, NMDA 2C
Short name:
GluN2C
Alternative name(s):
Glutamate [NMDA] receptor subunit epsilon-3
N-methyl D-aspartate receptor subtype 2C
Short name:
NMDAR2C
Short name:
NR2C
Gene namesi
Name:GRIN2C
Synonyms:NMDAR2C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000161509.13
HGNCiHGNC:4587 GRIN2C
MIMi138254 gene
neXtProtiNX_Q14957

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 domaini20 – 554ExtracellularBy similarityAdd BLAST535
Transmembranei555 – 573HelicalBy similarityAdd BLAST19
Topological domaini574 – 600CytoplasmicBy similarityAdd BLAST27
Intramembranei601 – 620Discontinuously helicalBy similarityAdd BLAST20
Topological domaini621 – 627CytoplasmicBy similarity7
Transmembranei628 – 643HelicalBy similarityAdd BLAST16
Topological domaini644 – 814ExtracellularBy similarityAdd BLAST171
Transmembranei815 – 834HelicalBy similarityAdd BLAST20
Topological domaini835 – 1233CytoplasmicBy similarityAdd BLAST399

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi550P → R: Changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency. 1 Publication1

Organism-specific databases

DisGeNETi2905
OpenTargetsiENSG00000161509
PharmGKBiPA28981

Chemistry databases

ChEMBLiCHEMBL4109
DrugBankiDB00659 Acamprosate
DB00289 Atomoxetine
DB00996 Gabapentin
DB06741 Gavestinel
DB00145 Glycine
DB06738 Ketobemidone
DB00142 L-Glutamic Acid
DB04896 Milnacipran
DB00312 Pentobarbital
DB00454 Pethidine
DB01174 Phenobarbital
DB01708 Prasterone
DB00418 Secobarbital
DB01520 Tenocyclidine
GuidetoPHARMACOLOGYi458

Polymorphism and mutation databases

DMDMi313104210

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001158020 – 1233Glutamate receptor ionotropic, NMDA 2CAdd BLAST1214

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi70N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi82 ↔ 317By similarity
Glycosylationi337N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi426 ↔ 453By similarity
Disulfide bondi433 ↔ 454By similarity
Glycosylationi438N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi539N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi743 ↔ 798By similarity
Modified residuei875PhosphoserineBy similarity1
Modified residuei881PhosphoserineBy similarity1
Modified residuei912PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ14957
PeptideAtlasiQ14957
PRIDEiQ14957
ProteomicsDBi60260

PTM databases

iPTMnetiQ14957
PhosphoSitePlusiQ14957

Expressioni

Tissue specificityi

Mainly expressed in brain with predominant expression is in the cerebellum, also present in the hippocampus, amygdala, caudate nucleus, corpus callosum, subthalamic nuclei and thalamus. Detected in the heart, skeletal muscle and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000161509 Expressed in 105 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_GRIN2C
ExpressionAtlasiQ14957 baseline and differential
GenevisibleiQ14957 HS

Interactioni

Subunit structurei

Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:26875626). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Interacts with PDZ domains of PATJ and DLG4 (By similarity). Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (PubMed:21300787).By similarityCurated2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109162, 3 interactors
ComplexPortaliCPX-286 NMDA receptor complex, GluN1-GluN2C
IntActiQ14957, 3 interactors
MINTiQ14957
STRINGi9606.ENSP00000293190

Chemistry databases

BindingDBiQ14957

Structurei

3D structure databases

ProteinModelPortaliQ14957
SMRiQ14957
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni509 – 511Glutamate bindingBy similarity3
Regioni601 – 620Pore-formingBy similarityAdd BLAST20
Regioni687 – 688Glutamate bindingBy similarity2

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1231 – 1233PDZ-binding3

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
GeneTreeiENSGT00910000143978
HOVERGENiHBG052636
InParanoidiQ14957
KOiK05211
OMAiREACQEG
OrthoDBiEOG091G09KH
PhylomeDBiQ14957
TreeFamiTF314731

Family and domain databases

InterProiView protein in InterPro
IPR001828 ANF_lig-bd_rcpt
IPR019594 Glu/Gly-bd
IPR001508 Iono_rcpt_met
IPR001320 Iontro_rcpt
IPR018884 NMDAR2_C
IPR028082 Peripla_BP_I
PfamiView protein in Pfam
PF01094 ANF_receptor, 1 hit
PF00060 Lig_chan, 1 hit
PF10613 Lig_chan-Glu_bd, 1 hit
PF10565 NMDAR2_C, 1 hit
PRINTSiPR00177 NMDARECEPTOR
SMARTiView protein in SMART
SM00918 Lig_chan-Glu_bd, 1 hit
SM00079 PBPe, 1 hit
SUPFAMiSSF53822 SSF53822, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

Q14957-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGGALGPALL LTSLFGAWAG LGPGQGEQGM TVAVVFSSSG PPQAQFRARL
60 70 80 90 100
TPQSFLDLPL EIQPLTVGVN TTNPSSLLTQ ICGLLGAAHV HGIVFEDNVD
110 120 130 140 150
TEAVAQILDF ISSQTHVPIL SISGGSAVVL TPKEPGSAFL QLGVSLEQQL
160 170 180 190 200
QVLFKVLEEY DWSAFAVITS LHPGHALFLE GVRAVADASH VSWRLLDVVT
210 220 230 240 250
LELGPGGPRA RTQRLLRQLD APVFVAYCSR EEAEVLFAEA AQAGLVGPGH
260 270 280 290 300
VWLVPNLALG STDAPPATFP VGLISVVTES WRLSLRQKVR DGVAILALGA
310 320 330 340 350
HSYWRQHGTL PAPAGDCRVH PGPVSPAREA FYRHLLNVTW EGRDFSFSPG
360 370 380 390 400
GYLVQPTMVV IALNRHRLWE MVGRWEHGVL YMKYPVWPRY SASLQPVVDS
410 420 430 440 450
RHLTVATLEE RPFVIVESPD PGTGGCVPNT VPCRRQSNHT FSSGDVAPYT
460 470 480 490 500
KLCCKGFCID ILKKLARVVK FSYDLYLVTN GKHGKRVRGV WNGMIGEVYY
510 520 530 540 550
KRADMAIGSL TINEERSEIV DFSVPFVETG ISVMVARSNG TVSPSAFLEP
560 570 580 590 600
YSPAVWVMMF VMCLTVVAIT VFMFEYFSPV SYNQNLTRGK KSGGPAFTIG
610 620 630 640 650
KSVWLLWALV FNNSVPIENP RGTTSKIMVL VWAFFAVIFL ASYTANLAAF
660 670 680 690 700
MIQEQYIDTV SGLSDKKFQR PQDQYPPFRF GTVPNGSTER NIRSNYRDMH
710 720 730 740 750
THMVKFNQRS VEDALTSLKM GKLDAFIYDA AVLNYMAGKD EGCKLVTIGS
760 770 780 790 800
GKVFATTGYG IAMQKDSHWK RAIDLALLQF LGDGETQKLE TVWLSGICQN
810 820 830 840 850
EKNEVMSSKL DIDNMAGVFY MLLVAMGLAL LVFAWEHLVY WKLRHSVPNS
860 870 880 890 900
SQLDFLLAFS RGIYSCFSGV QSLASPPRQA SPDLTASSAQ ASVLKMLQAA
910 920 930 940 950
RDMVTTAGVS SSLDRATRTI ENWGGGRRAP PPSPCPTPRS GPSPCLPTPD
960 970 980 990 1000
PPPEPSPTGW GPPDGGRAAL VRRAPQPPGR PPTPGPPLSD VSRVSRRPAW
1010 1020 1030 1040 1050
EARWPVRTGH CGRHLSASER PLSPARCHYS SFPRADRSGR PFLPLFPELE
1060 1070 1080 1090 1100
DLPLLGPEQL ARREALLHAA WARGSRPRHA SLPSSVAEAF ARPSSLPAGC
1110 1120 1130 1140 1150
TGPACARPDG HSACRRLAQA QSMCLPIYRE ACQEGEQAGA PAWQHRQHVC
1160 1170 1180 1190 1200
LHAHAHLPFC WGAVCPHLPP CASHGSWLSG AWGPLGHRGR TLGLGTGYRD
1210 1220 1230
SGGLDEISRV ARGTQGFPGP CTWRRISSLE SEV
Length:1,233
Mass (Da):134,209
Last modified:November 30, 2010 - v3
Checksum:i7B1F2F7995C0D689
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y2V8H0Y2V8_HUMAN
Glutamate receptor ionotropic, NMDA...
GRIN2C hCG_29832
873Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1048E → EPPE in AAI40802 (PubMed:15489334).Curated1
Sequence conflicti1057P → K in AAA88096 (PubMed:9037519).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07995818 – 1233Missing Found in a patient with autism spectrum disorder; unknown pathological significance. 1 PublicationAdd BLAST1216
Natural variantiVAR_07995990V → I1 PublicationCorresponds to variant dbSNP:rs192960268Ensembl.1
Natural variantiVAR_079960166A → V1 PublicationCorresponds to variant dbSNP:rs201199917Ensembl.1
Natural variantiVAR_079961573M → T1 Publication1
Natural variantiVAR_079962641A → T1 PublicationCorresponds to variant dbSNP:rs746610735Ensembl.1
Natural variantiVAR_079963679R → C Found in a patient with schizophrenia; unknown pathological significance. 1 Publication1
Natural variantiVAR_079964863I → T Found in a patient with autism spectrum disorder; unknown pathological significance. 1 Publication1
Natural variantiVAR_079965871Q → R1 PublicationCorresponds to variant dbSNP:rs765016248Ensembl.1
Natural variantiVAR_079966877P → S1 PublicationCorresponds to variant dbSNP:rs139011774Ensembl.1
Natural variantiVAR_079967911S → I1 PublicationCorresponds to variant dbSNP:rs370546831Ensembl.1
Natural variantiVAR_079968982P → A1 PublicationCorresponds to variant dbSNP:rs960726960Ensembl.1
Natural variantiVAR_079969989S → P Found in a patient with schizophrenia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs552196496Ensembl.1
Natural variantiVAR_079970995S → L Found in a patient with schizophrenia; unknown pathological significance. 1 Publication1
Natural variantiVAR_0799711079H → Y1 PublicationCorresponds to variant dbSNP:rs889196426Ensembl.1
Natural variantiVAR_0799721141P → A1 PublicationCorresponds to variant dbSNP:rs751640851Ensembl.1
Natural variantiVAR_0799731180G → R1 PublicationCorresponds to variant dbSNP:rs115230539Ensembl.1
Natural variantiVAR_0799741196T → I1 PublicationCorresponds to variant dbSNP:rs143282101Ensembl.1
Natural variantiVAR_0376341209R → S. Corresponds to variant dbSNP:rs3744215Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76224 mRNA Translation: AAA88096.1
AC068874 Genomic DNA No translation available.
BC140801 mRNA Translation: AAI40802.1
CCDSiCCDS32724.1
RefSeqiNP_000826.2, NM_000835.4
UniGeneiHs.436980

Genome annotation databases

EnsembliENST00000293190; ENSP00000293190; ENSG00000161509
GeneIDi2905
KEGGihsa:2905
UCSCiuc002jlt.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNMDE3_HUMAN
AccessioniPrimary (citable) accession number: Q14957
Secondary accession number(s): B2RTT1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 30, 2010
Last modified: September 12, 2018
This is version 172 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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