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Q14957 (NMDE3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:GRIN2C
Synonyms:NMDAR2C
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1233 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

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. Ref.4

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein.

Tissue specificity

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.

Sequence similarities

Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2C/GRIN2C subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandCalcium
Magnesium
   Molecular functionIon channel
Ligand-gated ion channel
Receptor
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdirectional locomotion

Inferred from electronic annotation. Source: Ensembl

glutamate receptor signaling pathway

Traceable author statement PubMed 9798920. Source: ProtInc

ion transmembrane transport

Inferred from Biological aspect of Ancestor. Source: RefGenome

ionotropic glutamate receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of protein catabolic process

Inferred from electronic annotation. Source: Ensembl

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

protein localization

Inferred from electronic annotation. Source: Ensembl

regulation of excitatory postsynaptic membrane potential

Inferred from electronic annotation. Source: Ensembl

response to wounding

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

synaptic transmission, glutamatergic

Inferred from Biological aspect of Ancestor. Source: RefGenome

transport

Traceable author statement PubMed 9798920. Source: ProtInc

   Cellular_componentN-methyl-D-aspartate selective glutamate receptor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

dendrite

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of plasma membrane

Traceable author statement PubMed 9798920. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

postsynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionN-methyl-D-aspartate selective glutamate receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

cation channel activity

Inferred from electronic annotation. Source: Ensembl

extracellular-glutamate-gated ion channel activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction PubMed 11937501. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Dlg3Q629366EBI-8285963,EBI-349596From a different organism.
DLG4P783524EBI-8285963,EBI-80389
Dlg4P310162EBI-8285963,EBI-375655From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 12331214Glutamate receptor ionotropic, NMDA 2C
PRO_0000011580

Regions

Topological domain20 – 553534Extracellular Potential
Transmembrane554 – 57421Helical; Potential
Topological domain575 – 62652Cytoplasmic Potential
Transmembrane627 – 64721Helical; Potential
Topological domain648 – 814167Extracellular Potential
Transmembrane815 – 83521Helical; Potential
Topological domain836 – 1233398Cytoplasmic Potential
Motif1231 – 12333PDZ-binding

Sites

Site6121Functional determinant of NMDA receptors By similarity

Amino acid modifications

Glycosylation701N-linked (GlcNAc...) Potential
Glycosylation3371N-linked (GlcNAc...) Potential
Glycosylation4381N-linked (GlcNAc...) Potential
Glycosylation5391N-linked (GlcNAc...) Potential

Natural variations

Natural variant12091R → S.
Corresponds to variant rs3744215 [ dbSNP | Ensembl ].
VAR_037634

Experimental info

Sequence conflict10481E → EPPE in AAI40802. Ref.3
Sequence conflict10571P → K in AAA88096. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q14957 [UniParc].

Last modified November 30, 2010. Version 3.
Checksum: 7B1F2F7995C0D689

FASTA1,233134,209
        10         20         30         40         50         60 
MGGALGPALL LTSLFGAWAG LGPGQGEQGM TVAVVFSSSG PPQAQFRARL TPQSFLDLPL 

        70         80         90        100        110        120 
EIQPLTVGVN TTNPSSLLTQ ICGLLGAAHV HGIVFEDNVD TEAVAQILDF ISSQTHVPIL 

       130        140        150        160        170        180 
SISGGSAVVL TPKEPGSAFL QLGVSLEQQL QVLFKVLEEY DWSAFAVITS LHPGHALFLE 

       190        200        210        220        230        240 
GVRAVADASH VSWRLLDVVT LELGPGGPRA RTQRLLRQLD APVFVAYCSR EEAEVLFAEA 

       250        260        270        280        290        300 
AQAGLVGPGH VWLVPNLALG STDAPPATFP VGLISVVTES WRLSLRQKVR DGVAILALGA 

       310        320        330        340        350        360 
HSYWRQHGTL PAPAGDCRVH PGPVSPAREA FYRHLLNVTW EGRDFSFSPG GYLVQPTMVV 

       370        380        390        400        410        420 
IALNRHRLWE MVGRWEHGVL YMKYPVWPRY SASLQPVVDS RHLTVATLEE RPFVIVESPD 

       430        440        450        460        470        480 
PGTGGCVPNT VPCRRQSNHT FSSGDVAPYT KLCCKGFCID ILKKLARVVK FSYDLYLVTN 

       490        500        510        520        530        540 
GKHGKRVRGV WNGMIGEVYY KRADMAIGSL TINEERSEIV DFSVPFVETG ISVMVARSNG 

       550        560        570        580        590        600 
TVSPSAFLEP YSPAVWVMMF VMCLTVVAIT VFMFEYFSPV SYNQNLTRGK KSGGPAFTIG 

       610        620        630        640        650        660 
KSVWLLWALV FNNSVPIENP RGTTSKIMVL VWAFFAVIFL ASYTANLAAF MIQEQYIDTV 

       670        680        690        700        710        720 
SGLSDKKFQR PQDQYPPFRF GTVPNGSTER NIRSNYRDMH THMVKFNQRS VEDALTSLKM 

       730        740        750        760        770        780 
GKLDAFIYDA AVLNYMAGKD EGCKLVTIGS GKVFATTGYG IAMQKDSHWK RAIDLALLQF 

       790        800        810        820        830        840 
LGDGETQKLE TVWLSGICQN EKNEVMSSKL DIDNMAGVFY MLLVAMGLAL LVFAWEHLVY 

       850        860        870        880        890        900 
WKLRHSVPNS SQLDFLLAFS RGIYSCFSGV QSLASPPRQA SPDLTASSAQ ASVLKMLQAA 

       910        920        930        940        950        960 
RDMVTTAGVS SSLDRATRTI ENWGGGRRAP PPSPCPTPRS GPSPCLPTPD PPPEPSPTGW 

       970        980        990       1000       1010       1020 
GPPDGGRAAL VRRAPQPPGR PPTPGPPLSD VSRVSRRPAW EARWPVRTGH CGRHLSASER 

      1030       1040       1050       1060       1070       1080 
PLSPARCHYS SFPRADRSGR PFLPLFPELE DLPLLGPEQL ARREALLHAA WARGSRPRHA 

      1090       1100       1110       1120       1130       1140 
SLPSSVAEAF ARPSSLPAGC TGPACARPDG HSACRRLAQA QSMCLPIYRE ACQEGEQAGA 

      1150       1160       1170       1180       1190       1200 
PAWQHRQHVC LHAHAHLPFC WGAVCPHLPP CASHGSWLSG AWGPLGHRGR TLGLGTGYRD 

      1210       1220       1230 
SGGLDEISRV ARGTQGFPGP CTWRRISSLE SEV 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L76224 mRNA. Translation: AAA88096.1.
AC068874 Genomic DNA. No translation available.
BC140801 mRNA. Translation: AAI40802.1.
CCDSCCDS32724.1.
RefSeqNP_000826.2. NM_000835.4.
UniGeneHs.436980.

3D structure databases

ProteinModelPortalQ14957.
SMRQ14957. Positions 401-543, 659-799.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109162. 4 interactions.
IntActQ14957. 3 interactions.
MINTMINT-1776011.
STRING9606.ENSP00000293190.

Chemistry

BindingDBQ14957.
ChEMBLCHEMBL4109.
DrugBankDB00145. Glycine.
DB00142. L-Glutamic Acid.
DB00836. Loperamide.
GuidetoPHARMACOLOGY458.

Protein family/group databases

TCDB1.A.10.1.3. the glutamate-gated ion channel (gic) family of neurotransmitter receptors.

PTM databases

PhosphoSiteQ14957.

Polymorphism databases

DMDM313104210.

Proteomic databases

PaxDbQ14957.
PRIDEQ14957.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000293190; ENSP00000293190; ENSG00000161509.
GeneID2905.
KEGGhsa:2905.
UCSCuc002jlt.1. human.

Organism-specific databases

CTD2905.
GeneCardsGC17M072854.
H-InvDBHIX0039170.
HGNCHGNC:4587. GRIN2C.
HPAHPA041666.
MIM138254. gene.
neXtProtNX_Q14957.
PharmGKBPA28981.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG282132.
HOVERGENHBG052636.
InParanoidQ14957.
KOK05211.
OMAREACQEG.
OrthoDBEOG72ZCD1.
PhylomeDBQ14957.
TreeFamTF314731.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
SignaLinkQ14957.

Gene expression databases

ArrayExpressQ14957.
BgeeQ14957.
CleanExHS_GRIN2C.
GenevestigatorQ14957.

Family and domain databases

InterProIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
IPR018884. NMDAR2_C.
IPR028082. Peripla_BP_I.
IPR001638. SBP_bac_3.
[Graphical view]
PfamPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10565. NMDAR2_C. 1 hit.
PF00497. SBP_bac_3. 1 hit.
[Graphical view]
PRINTSPR00177. NMDARECEPTOR.
SMARTSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMSSF53822. SSF53822. 1 hit.
ProtoNetSearch...

Other

GeneWikiGRIN2C.
GenomeRNAi2905.
NextBio11503.
PROQ14957.
SOURCESearch...

Entry information

Entry nameNMDE3_HUMAN
AccessionPrimary (citable) accession number: Q14957
Secondary accession number(s): B2RTT1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 30, 2010
Last modified: July 9, 2014
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM