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Q14957

- NMDE3_HUMAN

UniProt

Q14957 - NMDE3_HUMAN

Protein

Glutamate receptor ionotropic, NMDA 2C

Gene

GRIN2C

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 3 (30 Nov 2010)
      Previous versions | rss
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    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

    1. cation channel activity Source: Ensembl
    2. extracellular-glutamate-gated ion channel activity Source: RefGenome
    3. N-methyl-D-aspartate selective glutamate receptor activity Source: RefGenome
    4. protein binding Source: IntAct

    GO - Biological processi

    1. directional locomotion Source: Ensembl
    2. glutamate receptor signaling pathway Source: ProtInc
    3. ionotropic glutamate receptor signaling pathway Source: RefGenome
    4. ion transmembrane transport Source: RefGenome
    5. negative regulation of protein catabolic process Source: Ensembl
    6. neuromuscular process controlling balance Source: Ensembl
    7. protein localization Source: Ensembl
    8. regulation of excitatory postsynaptic membrane potential Source: Ensembl
    9. response to wounding Source: Ensembl
    10. synaptic transmission Source: Reactome
    11. synaptic transmission, glutamatergic Source: RefGenome
    12. transport Source: ProtInc

    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: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:4587. GRIN2C.

    Subcellular locationi

    GO - Cellular componenti

    1. cell junction Source: UniProtKB-KW
    2. dendrite Source: RefGenome
    3. integral component of plasma membrane Source: ProtInc
    4. N-methyl-D-aspartate selective glutamate receptor complex Source: RefGenome
    5. plasma membrane Source: Reactome
    6. postsynaptic density Source: Ensembl
    7. postsynaptic membrane Source: RefGenome

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28981.

    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

    ArrayExpressiQ14957.
    BgeeiQ14957.
    CleanExiHS_GRIN2C.
    GenevestigatoriQ14957.

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini20 – 553534ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini575 – 62652CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini648 – 814167ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini836 – 1233398CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei554 – 57421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei627 – 64721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei815 – 83521HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Motif

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

    Sequence similaritiesi

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

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

    Family and domain databases

    InterProiIPR001828. 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]
    PfamiPF01094. ANF_receptor. 1 hit.
    PF00060. Lig_chan. 1 hit.
    PF10565. NMDAR2_C. 1 hit.
    PF00497. SBP_bac_3. 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

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    MGGALGPALL LTSLFGAWAG LGPGQGEQGM TVAVVFSSSG PPQAQFRARL     50
    TPQSFLDLPL EIQPLTVGVN TTNPSSLLTQ ICGLLGAAHV HGIVFEDNVD 100
    TEAVAQILDF ISSQTHVPIL SISGGSAVVL TPKEPGSAFL QLGVSLEQQL 150
    QVLFKVLEEY DWSAFAVITS LHPGHALFLE GVRAVADASH VSWRLLDVVT 200
    LELGPGGPRA RTQRLLRQLD APVFVAYCSR EEAEVLFAEA AQAGLVGPGH 250
    VWLVPNLALG STDAPPATFP VGLISVVTES WRLSLRQKVR DGVAILALGA 300
    HSYWRQHGTL PAPAGDCRVH PGPVSPAREA FYRHLLNVTW EGRDFSFSPG 350
    GYLVQPTMVV IALNRHRLWE MVGRWEHGVL YMKYPVWPRY SASLQPVVDS 400
    RHLTVATLEE RPFVIVESPD PGTGGCVPNT VPCRRQSNHT FSSGDVAPYT 450
    KLCCKGFCID ILKKLARVVK FSYDLYLVTN GKHGKRVRGV WNGMIGEVYY 500
    KRADMAIGSL TINEERSEIV DFSVPFVETG ISVMVARSNG TVSPSAFLEP 550
    YSPAVWVMMF VMCLTVVAIT VFMFEYFSPV SYNQNLTRGK KSGGPAFTIG 600
    KSVWLLWALV FNNSVPIENP RGTTSKIMVL VWAFFAVIFL ASYTANLAAF 650
    MIQEQYIDTV SGLSDKKFQR PQDQYPPFRF GTVPNGSTER NIRSNYRDMH 700
    THMVKFNQRS VEDALTSLKM GKLDAFIYDA AVLNYMAGKD EGCKLVTIGS 750
    GKVFATTGYG IAMQKDSHWK RAIDLALLQF LGDGETQKLE TVWLSGICQN 800
    EKNEVMSSKL DIDNMAGVFY MLLVAMGLAL LVFAWEHLVY WKLRHSVPNS 850
    SQLDFLLAFS RGIYSCFSGV QSLASPPRQA SPDLTASSAQ ASVLKMLQAA 900
    RDMVTTAGVS SSLDRATRTI ENWGGGRRAP PPSPCPTPRS GPSPCLPTPD 950
    PPPEPSPTGW GPPDGGRAAL VRRAPQPPGR PPTPGPPLSD VSRVSRRPAW 1000
    EARWPVRTGH CGRHLSASER PLSPARCHYS SFPRADRSGR PFLPLFPELE 1050
    DLPLLGPEQL ARREALLHAA WARGSRPRHA SLPSSVAEAF ARPSSLPAGC 1100
    TGPACARPDG HSACRRLAQA QSMCLPIYRE ACQEGEQAGA PAWQHRQHVC 1150
    LHAHAHLPFC WGAVCPHLPP CASHGSWLSG AWGPLGHRGR TLGLGTGYRD 1200
    SGGLDEISRV ARGTQGFPGP CTWRRISSLE SEV 1233
    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:
    EMBL
    GenBank
    DDBJ
    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.

    Polymorphism databases

    DMDMi313104210.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L76224 mRNA. Translation: AAA88096.1 .
    AC068874 Genomic DNA. No translation available.
    BC140801 mRNA. Translation: AAI40802.1 .
    CCDSi CCDS32724.1.
    RefSeqi NP_000826.2. NM_000835.4.
    UniGenei Hs.436980.

    3D structure databases

    ProteinModelPortali Q14957.
    SMRi Q14957. Positions 401-543, 659-799.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109162. 4 interactions.
    IntActi Q14957. 3 interactions.
    MINTi MINT-1776011.
    STRINGi 9606.ENSP00000293190.

    Chemistry

    BindingDBi Q14957.
    ChEMBLi CHEMBL4109.
    DrugBanki DB00145. Glycine.
    DB00142. L-Glutamic Acid.
    DB00836. Loperamide.
    GuidetoPHARMACOLOGYi 458.

    Protein family/group databases

    TCDBi 1.A.10.1.3. the glutamate-gated ion channel (gic) family of neurotransmitter receptors.

    PTM databases

    PhosphoSitei Q14957.

    Polymorphism databases

    DMDMi 313104210.

    Proteomic databases

    PaxDbi Q14957.
    PRIDEi Q14957.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000293190 ; ENSP00000293190 ; ENSG00000161509 .
    GeneIDi 2905.
    KEGGi hsa:2905.
    UCSCi uc002jlt.1. human.

    Organism-specific databases

    CTDi 2905.
    GeneCardsi GC17M072854.
    H-InvDB HIX0039170.
    HGNCi HGNC:4587. GRIN2C.
    HPAi HPA041666.
    MIMi 138254. gene.
    neXtProti NX_Q14957.
    PharmGKBi PA28981.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG282132.
    HOVERGENi HBG052636.
    InParanoidi Q14957.
    KOi K05211.
    OMAi REACQEG.
    OrthoDBi EOG72ZCD1.
    PhylomeDBi Q14957.
    TreeFami TF314731.

    Enzyme and pathway databases

    Reactomei REACT_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.
    SignaLinki Q14957.

    Miscellaneous databases

    GeneWikii GRIN2C.
    GenomeRNAii 2905.
    NextBioi 11503.
    PROi Q14957.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14957.
    Bgeei Q14957.
    CleanExi HS_GRIN2C.
    Genevestigatori Q14957.

    Family and domain databases

    InterProi IPR001828. 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 ]
    Pfami PF01094. ANF_receptor. 1 hit.
    PF00060. Lig_chan. 1 hit.
    PF10565. NMDAR2_C. 1 hit.
    PF00497. SBP_bac_3. 1 hit.
    [Graphical view ]
    PRINTSi PR00177. NMDARECEPTOR.
    SMARTi SM00918. Lig_chan-Glu_bd. 1 hit.
    SM00079. PBPe. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53822. SSF53822. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 136 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