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Protein

Glutamate receptor ionotropic, NMDA 2C

Gene

GRIN2C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei612 – 6121Functional determinant of NMDA receptorsBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Calcium, Magnesium

Enzyme and pathway databases

ReactomeiREACT_20546. Ras activation uopn Ca2+ infux through NMDA receptor.
REACT_20594. Unblocking of NMDA receptor, glutamate binding and activation.
REACT_20642. CREB phosphorylation through the activation of CaMKII.
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
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:4587. GRIN2C.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 553534ExtracellularSequence AnalysisAdd
BLAST
Transmembranei554 – 57421HelicalSequence AnalysisAdd
BLAST
Topological domaini575 – 62652CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei627 – 64721HelicalSequence AnalysisAdd
BLAST
Topological domaini648 – 814167ExtracellularSequence AnalysisAdd
BLAST
Transmembranei815 – 83521HelicalSequence AnalysisAdd
BLAST
Topological domaini836 – 1233398CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28981.

Chemistry

DrugBankiDB00659. Acamprosate.
DB00289. Atomoxetine.
DB00996. Gabapentin.
DB00145. Glycine.
DB06738. Ketobemidone.
DB04896. Milnacipran.
DB00312. Pentobarbital.
DB00454. Pethidine.
DB01174. Phenobarbital.
DB00418. Secobarbital.

Polymorphism and mutation databases

DMDMi313104210.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence AnalysisAdd
BLAST
Chaini20 – 12331214Glutamate receptor ionotropic, NMDA 2CPRO_0000011580Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi70 – 701N-linked (GlcNAc...)Sequence Analysis
Glycosylationi337 – 3371N-linked (GlcNAc...)Sequence Analysis
Glycosylationi438 – 4381N-linked (GlcNAc...)Sequence Analysis
Glycosylationi539 – 5391N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ14957.
PRIDEiQ14957.

PTM databases

PhosphoSiteiQ14957.

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.

Gene expression databases

BgeeiQ14957.
CleanExiHS_GRIN2C.
ExpressionAtlasiQ14957. baseline and differential.
GenevisibleiQ14957. HS.

Organism-specific databases

HPAiHPA041666.

Interactioni

Subunit structurei

Interacts with PDZ domains of INADL and DLG4 (By similarity). Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B). 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.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Dlg3Q629366EBI-8285963,EBI-349596From a different organism.
DLG4P783524EBI-8285963,EBI-80389
Dlg4P310162EBI-8285963,EBI-375655From a different organism.

Protein-protein interaction databases

BioGridi109162. 4 interactions.
IntActiQ14957. 3 interactions.
MINTiMINT-1776011.
STRINGi9606.ENSP00000293190.

Structurei

3D structure databases

ProteinModelPortaliQ14957.
SMRiQ14957. Positions 401-543, 659-799.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1231 – 12333PDZ-binding

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG282132.
GeneTreeiENSGT00760000119186.
HOVERGENiHBG052636.
InParanoidiQ14957.
KOiK05211.
OMAiREACQEG.
OrthoDBiEOG72ZCD1.
PhylomeDBiQ14957.
TreeFamiTF314731.

Family and domain databases

InterProiIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu/Gly-bd.
IPR001508. Iono_rcpt_met.
IPR001320. Iontro_rcpt.
IPR018884. NMDAR2_C.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10565. NMDAR2_C. 1 hit.
[Graphical view]
PRINTSiPR00177. NMDARECEPTOR.
SMARTiSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMiSSF53822. SSF53822. 1 hit.

Sequencei

Sequence statusi: Complete.

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

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1048 – 10481E → EPPE in AAI40802 (PubMed:15489334).Curated
Sequence conflicti1057 – 10571P → K in AAA88096 (PubMed:9037519).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1209 – 12091R → S.
Corresponds to variant rs3744215 [ dbSNP | Ensembl ].
VAR_037634

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.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ14957.
SMRiQ14957. Positions 401-543, 659-799.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109162. 4 interactions.
IntActiQ14957. 3 interactions.
MINTiMINT-1776011.
STRINGi9606.ENSP00000293190.

Chemistry

BindingDBiQ14957.
ChEMBLiCHEMBL2094124.
DrugBankiDB00659. Acamprosate.
DB00289. Atomoxetine.
DB00996. Gabapentin.
DB00145. Glycine.
DB06738. Ketobemidone.
DB04896. Milnacipran.
DB00312. Pentobarbital.
DB00454. Pethidine.
DB01174. Phenobarbital.
DB00418. Secobarbital.
GuidetoPHARMACOLOGYi458.

Protein family/group databases

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

PTM databases

PhosphoSiteiQ14957.

Polymorphism and mutation databases

DMDMi313104210.

Proteomic databases

PaxDbiQ14957.
PRIDEiQ14957.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000293190; ENSP00000293190; ENSG00000161509.
GeneIDi2905.
KEGGihsa:2905.
UCSCiuc002jlt.1. human.

Organism-specific databases

CTDi2905.
GeneCardsiGC17M072839.
H-InvDBHIX0039170.
HGNCiHGNC:4587. GRIN2C.
HPAiHPA041666.
MIMi138254. gene.
neXtProtiNX_Q14957.
PharmGKBiPA28981.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG282132.
GeneTreeiENSGT00760000119186.
HOVERGENiHBG052636.
InParanoidiQ14957.
KOiK05211.
OMAiREACQEG.
OrthoDBiEOG72ZCD1.
PhylomeDBiQ14957.
TreeFamiTF314731.

Enzyme and pathway databases

ReactomeiREACT_20546. Ras activation uopn Ca2+ infux through NMDA receptor.
REACT_20594. Unblocking of NMDA receptor, glutamate binding and activation.
REACT_20642. CREB phosphorylation through the activation of CaMKII.
SignaLinkiQ14957.

Miscellaneous databases

GeneWikiiGRIN2C.
GenomeRNAii2905.
NextBioi11503.
PROiQ14957.
SOURCEiSearch...

Gene expression databases

BgeeiQ14957.
CleanExiHS_GRIN2C.
ExpressionAtlasiQ14957. baseline and differential.
GenevisibleiQ14957. HS.

Family and domain databases

InterProiIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu/Gly-bd.
IPR001508. Iono_rcpt_met.
IPR001320. Iontro_rcpt.
IPR018884. NMDAR2_C.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10565. NMDAR2_C. 1 hit.
[Graphical view]
PRINTSiPR00177. NMDARECEPTOR.
SMARTiSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMiSSF53822. SSF53822. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of the cDNA for the human NMDA receptor NR2C subunit and its expression in the central nervous system and periphery."
    Lin Y.J., Bovetto S., Carver J.M., Giordano T.
    Brain Res. Mol. Brain Res. 43:57-64(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. "Deficiency of sorting nexin 27 (SNX27) leads to growth retardation and elevated levels of N-methyl-D-aspartate receptor 2C (NR2C)."
    Cai L., Loo L.S., Atlashkin V., Hanson B.J., Hong W.
    Mol. Cell. Biol. 31:1734-1747(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SNX27.

Entry informationi

Entry nameiNMDE3_HUMAN
AccessioniPrimary (citable) accession number: Q14957
Secondary accession number(s): B2RTT1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 30, 2010
Last modified: June 24, 2015
This is version 144 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.