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O15399

- NMDE4_HUMAN

UniProt

O15399 - NMDE4_HUMAN

Protein

Glutamate receptor ionotropic, NMDA 2D

Gene

GRIN2D

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 2 (05 May 2009)
      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
    Sitei642 – 6421Functional determinant of NMDA receptorsBy similarity

    GO - Molecular functioni

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

    GO - Biological processi

    1. adult locomotory behavior Source: Ensembl
    2. ionotropic glutamate receptor signaling pathway Source: RefGenome
    3. ion transmembrane transport Source: RefGenome
    4. regulation of sensory perception of pain Source: Ensembl
    5. signal transduction Source: ProtInc
    6. startle response Source: Ensembl
    7. synaptic transmission Source: Reactome
    8. synaptic transmission, glutamatergic Source: RefGenome

    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.
    SignaLinkiO15399.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glutamate receptor ionotropic, NMDA 2D
    Short name:
    GluN2D
    Alternative name(s):
    EB11
    Glutamate [NMDA] receptor subunit epsilon-4
    N-methyl D-aspartate receptor subtype 2D
    Short name:
    NMDAR2D
    Short name:
    NR2D
    Gene namesi
    Name:GRIN2D
    Synonyms:GluN2D, NMDAR2D
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:4588. GRIN2D.

    Subcellular locationi

    GO - Cellular componenti

    1. cell junction Source: UniProtKB-KW
    2. dendrite Source: RefGenome
    3. N-methyl-D-aspartate selective glutamate receptor complex Source: RefGenome
    4. plasma membrane Source: Reactome
    5. postsynaptic membrane Source: RefGenome

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28982.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2727Sequence AnalysisAdd
    BLAST
    Chaini28 – 13361309Glutamate receptor ionotropic, NMDA 2DPRO_0000011583Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi92 – 921N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi352 – 3521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi366 – 3661N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi455 ↔ 483By similarity
    Disulfide bondi462 ↔ 484By similarity
    Glycosylationi467 – 4671N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi569 – 5691N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi773 ↔ 828By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiO15399.
    PRIDEiO15399.

    PTM databases

    PhosphoSiteiO15399.

    Expressioni

    Gene expression databases

    BgeeiO15399.
    CleanExiHS_GRIN2D.
    GenevestigatoriO15399.

    Organism-specific databases

    HPAiHPA038269.

    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).By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Dlg3Q629362EBI-1754030,EBI-349596From a different organism.

    Protein-protein interaction databases

    BioGridi109163. 4 interactions.
    IntActiO15399. 4 interactions.
    MINTiMINT-130143.
    STRINGi9606.ENSP00000263269.

    Structurei

    3D structure databases

    ProteinModelPortaliO15399.
    SMRiO15399. Positions 99-288, 429-567, 689-829.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini28 – 583556ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini605 – 65652CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini678 – 844167ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini866 – 1336471CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei584 – 60421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei657 – 67721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei845 – 86521HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi1334 – 13363PDZ-bindingBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi281 – 2866Poly-Gly
    Compositional biasi908 – 9169Poly-Pro
    Compositional biasi1035 – 10406Poly-Ala
    Compositional biasi1209 – 12135Poly-Pro
    Compositional biasi1244 – 12474Poly-Ala

    Sequence similaritiesi

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG282132.
    HOGENOMiHOG000113803.
    HOVERGENiHBG052637.
    InParanoidiO15399.
    KOiK05212.
    OMAiWDYLPPR.
    OrthoDBiEOG72ZCD1.
    PhylomeDBiO15399.
    TreeFamiTF314731.

    Family and domain databases

    InterProiIPR001828. ANF_lig-bd_rcpt.
    IPR019594. Glu_rcpt_Glu/Gly-bd.
    IPR001320. Iontro_glu_rcpt.
    IPR001508. NMDA_rcpt.
    IPR028082. Peripla_BP_I.
    IPR001638. SBP_bac_3.
    [Graphical view]
    PfamiPF01094. ANF_receptor. 1 hit.
    PF00060. Lig_chan. 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.

    O15399-1 [UniParc]FASTAAdd to Basket

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    MRGAGGPRGP RGPAKMLLLL ALACASPFPE EAPGPGGAGG PGGGLGGARP     50
    LNVALVFSGP AYAAEAARLG PAVAAAVRSP GLDVRPVALV LNGSDPRSLV 100
    LQLCDLLSGL RVHGVVFEDD SRAPAVAPIL DFLSAQTSLP IVAVHGGAAL 150
    VLTPKEKGST FLQLGSSTEQ QLQVIFEVLE EYDWTSFVAV TTRAPGHRAF 200
    LSYIEVLTDG SLVGWEHRGA LTLDPGAGEA VLSAQLRSVS AQIRLLFCAR 250
    EEAEPVFRAA EEAGLTGSGY VWFMVGPQLA GGGGSGAPGE PPLLPGGAPL 300
    PAGLFAVRSA GWRDDLARRV AAGVAVVARG AQALLRDYGF LPELGHDCRA 350
    QNRTHRGESL HRYFMNITWD NRDYSFNEDG FLVNPSLVVI SLTRDRTWEV 400
    VGSWEQQTLR LKYPLWSRYG RFLQPVDDTQ HLTVATLEER PFVIVEPADP 450
    ISGTCIRDSV PCRSQLNRTH SPPPDAPRPE KRCCKGFCID ILKRLAHTIG 500
    FSYDLYLVTN GKHGKKIDGV WNGMIGEVFY QRADMAIGSL TINEERSEIV 550
    DFSVPFVETG ISVMVARSNG TVSPSAFLEP YSPAVWVMMF VMCLTVVAVT 600
    VFIFEYLSPV GYNRSLATGK RPGGSTFTIG KSIWLLWALV FNNSVPVENP 650
    RGTTSKIMVL VWAFFAVIFL ASYTANLAAF MIQEEYVDTV SGLSDRKFQR 700
    PQEQYPPLKF GTVPNGSTEK NIRSNYPDMH SYMVRYNQPR VEEALTQLKA 750
    GKLDAFIYDA AVLNYMARKD EGCKLVTIGS GKVFATTGYG IALHKGSRWK 800
    RPIDLALLQF LGDDEIEMLE RLWLSGICHN DKIEVMSSKL DIDNMAGVFY 850
    MLLVAMGLSL LVFAWEHLVY WRLRHCLGPT HRMDFLLAFS RGMYSCCSAE 900
    AAPPPAKPPP PPQPLPSPAY PAPRPAPGPA PFVPRERASV DRWRRTKGAG 950
    PPGGAGLADG FHRYYGPIEP QGLGLGLGEA RAAPRGAAGR PLSPPAAQPP 1000
    QKPPPSYFAI VRDKEPAEPP AGAFPGFPSP PAPPAAAATA VGPPLCRLAF 1050
    EDESPPAPAR WPRSDPESQP LLGPGAGGAG GTGGAGGGAP AAPPPCRAAP 1100
    PPCPYLDLEP SPSDSEDSES LGGASLGGLE PWWFADFPYP YAERLGPPPG 1150
    RYWSVDKLGG WRAGSWDYLP PRSGPAAWHC RHCASLELLP PPRHLSCSHD 1200
    GLDGGWWAPP PPPWAAGPLP RRRARCGCPR SHPHRPRASH RTPAAAAPHH 1250
    HRHRRAAGGW DLPPPAPTSR SLEDLSSCPR AAPARRLTGP SRHARRCPHA 1300
    AHWGPPLPTA SHRRHRGGDL GTRRGSAHFS SLESEV 1336
    Length:1,336
    Mass (Da):143,752
    Last modified:May 5, 2009 - v2
    Checksum:i0DB7559056AE4593
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti924 – 9241R → G in AAC15910. (PubMed:9489750)Curated
    Sequence conflicti1005 – 10051P → A in AAC15910. (PubMed:9489750)Curated
    Sequence conflicti1097 – 10971R → C in AAC15910. (PubMed:9489750)Curated
    Sequence conflicti1130 – 11301E → D in AAC15910. (PubMed:9489750)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti140 – 1401P → S in a breast cancer sample; somatic mutation. 1 Publication
    VAR_035698
    Natural varianti286 – 2861G → R in a breast cancer sample; somatic mutation. 1 Publication
    VAR_035699
    Natural varianti527 – 5271E → G in a breast cancer sample; somatic mutation. 1 Publication
    VAR_035700

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U77783 mRNA. Translation: AAC15910.1.
    AC008403 Genomic DNA. No translation available.
    AC011527 Genomic DNA. No translation available.
    CCDSiCCDS12719.1.
    RefSeqiNP_000827.2. NM_000836.2.
    UniGeneiHs.445015.

    Genome annotation databases

    EnsembliENST00000263269; ENSP00000263269; ENSG00000105464.
    GeneIDi2906.
    KEGGihsa:2906.
    UCSCiuc002pjc.4. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U77783 mRNA. Translation: AAC15910.1 .
    AC008403 Genomic DNA. No translation available.
    AC011527 Genomic DNA. No translation available.
    CCDSi CCDS12719.1.
    RefSeqi NP_000827.2. NM_000836.2.
    UniGenei Hs.445015.

    3D structure databases

    ProteinModelPortali O15399.
    SMRi O15399. Positions 99-288, 429-567, 689-829.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109163. 4 interactions.
    IntActi O15399. 4 interactions.
    MINTi MINT-130143.
    STRINGi 9606.ENSP00000263269.

    Chemistry

    BindingDBi O15399.
    ChEMBLi CHEMBL3038505.
    DrugBanki DB00142. L-Glutamic Acid.
    DB00836. Loperamide.
    DB01173. Orphenadrine.
    GuidetoPHARMACOLOGYi 459.

    PTM databases

    PhosphoSitei O15399.

    Proteomic databases

    PaxDbi O15399.
    PRIDEi O15399.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000263269 ; ENSP00000263269 ; ENSG00000105464 .
    GeneIDi 2906.
    KEGGi hsa:2906.
    UCSCi uc002pjc.4. human.

    Organism-specific databases

    CTDi 2906.
    GeneCardsi GC19P048898.
    H-InvDB HIX0040164.
    HGNCi HGNC:4588. GRIN2D.
    HPAi HPA038269.
    MIMi 602717. gene.
    neXtProti NX_O15399.
    PharmGKBi PA28982.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG282132.
    HOGENOMi HOG000113803.
    HOVERGENi HBG052637.
    InParanoidi O15399.
    KOi K05212.
    OMAi WDYLPPR.
    OrthoDBi EOG72ZCD1.
    PhylomeDBi O15399.
    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 O15399.

    Miscellaneous databases

    GeneWikii GRIN2D.
    GenomeRNAii 2906.
    NextBioi 11507.
    PROi O15399.
    SOURCEi Search...

    Gene expression databases

    Bgeei O15399.
    CleanExi HS_GRIN2D.
    Genevestigatori O15399.

    Family and domain databases

    InterProi IPR001828. ANF_lig-bd_rcpt.
    IPR019594. Glu_rcpt_Glu/Gly-bd.
    IPR001320. Iontro_glu_rcpt.
    IPR001508. NMDA_rcpt.
    IPR028082. Peripla_BP_I.
    IPR001638. SBP_bac_3.
    [Graphical view ]
    Pfami PF01094. ANF_receptor. 1 hit.
    PF00060. Lig_chan. 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. "Functional characterization of human N-methyl-D-aspartate subtype 1A/2D receptors."
      Hess S.D., Daggett L.P., Deal C., Lu C.-C., Johnson E.C., Velicelebi G.
      J. Neurochem. 70:1269-1279(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal brain.
    2. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-140; ARG-286 AND GLY-527.

    Entry informationi

    Entry nameiNMDE4_HUMAN
    AccessioniPrimary (citable) accession number: O15399
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 29, 2001
    Last sequence update: May 5, 2009
    Last modified: October 1, 2014
    This is version 133 of the entry and version 2 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 19
      Human chromosome 19: 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