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Protein

Glutamate receptor ionotropic, NMDA 2D

Gene

Grin2d

Organism
Rattus norvegicus (Rat)
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
Sitei639 – 6391Functional determinant of NMDA receptorsBy similarity

GO - Molecular functioni

  • cation channel activity Source: RGD
  • extracellular-glutamate-gated ion channel activity Source: InterPro
  • glutamate binding Source: RGD
  • ionotropic glutamate receptor activity Source: RGD
  • neurotransmitter binding Source: RGD
  • NMDA glutamate receptor activity Source: RGD
  • voltage-gated cation channel activity Source: RGD

GO - Biological processi

  • synaptic transmission, glutamatergic Source: RGD
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

ReactomeiR-RNO-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-RNO-442729. CREB phosphorylation through the activation of CaMKII.
R-RNO-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-8849932. SALM protein interactions at the synapse.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate receptor ionotropic, NMDA 2D
Short name:
GluN2D
Alternative name(s):
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi2740. Grin2d.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 580553ExtracellularSequence analysisAdd
BLAST
Transmembranei581 – 60121HelicalSequence analysisAdd
BLAST
Topological domaini602 – 65352CytoplasmicSequence analysisAdd
BLAST
Transmembranei654 – 67421HelicalSequence analysisAdd
BLAST
Topological domaini675 – 841167ExtracellularSequence analysisAdd
BLAST
Transmembranei842 – 86221HelicalSequence analysisAdd
BLAST
Topological domaini863 – 1323461CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • ionotropic glutamate receptor complex Source: RGD
  • NMDA selective glutamate receptor complex Source: RGD
  • postsynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2096669.
GuidetoPHARMACOLOGYi459.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence analysisAdd
BLAST
Chaini28 – 13231296Glutamate receptor ionotropic, NMDA 2DPRO_0000011585Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi89 – 891N-linked (GlcNAc...)Sequence analysis
Glycosylationi349 – 3491N-linked (GlcNAc...)Sequence analysis
Glycosylationi363 – 3631N-linked (GlcNAc...)Sequence analysis
Disulfide bondi452 ↔ 4801 Publication
Disulfide bondi459 ↔ 4811 Publication
Glycosylationi464 – 4641N-linked (GlcNAc...)Sequence analysis
Glycosylationi566 – 5661N-linked (GlcNAc...)Sequence analysis
Disulfide bondi770 ↔ 8251 Publication
Modified residuei1313 – 13131PhosphoserineBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ62645.

PTM databases

iPTMnetiQ62645.
PhosphoSiteiQ62645.

Expressioni

Tissue specificityi

Expressed in brain, mainly in the subcortical region.

Developmental stagei

Already detected in embryonic stages, peaks at postnatal day 7, and decreases thereafter to adult levels.

Gene expression databases

ExpressionAtlasiQ62645. baseline and differential.
GenevisibleiQ62645. RN.

Interactioni

Subunit structurei

Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B). Interacts with PDZ domains of INADL and DLG4.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
InadlQ63ZW73EBI-631067,EBI-8366894From a different organism.

Protein-protein interaction databases

BioGridi246577. 3 interactions.
IntActiQ62645. 4 interactions.
MINTiMINT-103662.
STRINGi10116.ENSRNOP00000028615.

Chemistry

BindingDBiQ62645.

Structurei

Secondary structure

1
1323
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi428 – 4336Combined sources
Turni437 – 4393Combined sources
Beta strandi440 – 4445Combined sources
Turni447 – 4493Combined sources
Beta strandi457 – 4637Combined sources
Beta strandi478 – 4836Combined sources
Helixi484 – 49613Combined sources
Beta strandi499 – 5046Combined sources
Beta strandi507 – 5104Combined sources
Helixi520 – 5267Combined sources
Beta strandi529 – 5335Combined sources
Helixi541 – 5444Combined sources
Beta strandi547 – 5493Combined sources
Beta strandi554 – 56310Combined sources
Helixi693 – 6964Combined sources
Helixi698 – 7003Combined sources
Beta strandi701 – 7033Combined sources
Helixi714 – 7229Combined sources
Helixi724 – 7307Combined sources
Helixi731 – 7333Combined sources
Helixi738 – 7469Combined sources
Beta strandi751 – 7566Combined sources
Helixi757 – 76610Combined sources
Helixi768 – 7703Combined sources
Beta strandi772 – 7743Combined sources
Helixi775 – 7784Combined sources
Beta strandi781 – 7866Combined sources
Beta strandi789 – 7913Combined sources
Helixi797 – 80913Combined sources
Helixi812 – 82110Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3OEKX-ray1.90A424-564[»]
A686-827[»]
3OELX-ray1.90A424-564[»]
A686-827[»]
3OEMX-ray1.90A424-564[»]
A686-827[»]
3OENX-ray1.80A424-564[»]
A686-827[»]
4JWYX-ray2.00A424-564[»]
A686-827[»]
ProteinModelPortaliQ62645.
SMRiQ62645. Positions 428-580, 687-826.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62645.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1321 – 13233PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi278 – 2836Poly-Gly
Compositional biasi905 – 9139Poly-Pro
Compositional biasi1030 – 10356Poly-Ala
Compositional biasi1197 – 12015Poly-Pro

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1053. Eukaryota.
ENOG410XNUR. LUCA.
GeneTreeiENSGT00760000119186.
HOGENOMiHOG000113803.
HOVERGENiHBG052637.
InParanoidiQ62645.
KOiK05212.
PhylomeDBiQ62645.

Family and domain databases

InterProiIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu/Gly-bd.
IPR001508. Iono_rcpt_met.
IPR001320. Iontro_rcpt.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view]
PRINTSiPR00177. NMDARECEPTOR.
SMARTiSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMiSSF53822. SSF53822. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: Q62645-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRGAGGPRGP RGPAKMLLLL ALACASPFPE EVPGPGAVGG GTGGARPLNV
60 70 80 90 100
ALVFSGPAYA AEAARLGPAV AAAVRSPGLD VRPVALVLNG SDPRSLVLQL
110 120 130 140 150
CDLLSGLRVH GVVFEDDSRA PAVAPILDFL SAQTSLPIVA VHGGAALVLT
160 170 180 190 200
PKEKGSTFLQ LGSSTEQQLQ VIFEVLEEYD WTSFVAVTTR APGHRAFLSY
210 220 230 240 250
IEVLTDGSLV GWEHRGALTL DPGAGEAVLG AQLRSVSAQI RLLFCAREEA
260 270 280 290 300
EPVFRAAEEA GLTGPGYVWF MVGPQLAGGG GSGVPGEPLL LPGGSPLPAG
310 320 330 340 350
LFAVRSAGWR DDLARRVAAG VAVVARGAQA LLRDYGFLPE LGHDCRTQNR
360 370 380 390 400
THRGESLHRY FMNITWDNRD YSFNEDGFLV NPSLVVISLT RDRTWEVVGS
410 420 430 440 450
WEQQTLRLKY PLWSRYGRFL QPVDDTQHLT VATLEERPFV IVEPADPISG
460 470 480 490 500
TCIRDSVPCR SQLNRTHSPP PDAPRPEKRC CKGFCIDILK RLAHTIGFSY
510 520 530 540 550
DLYLVTNGKH GKKIDGVWNG MIGEVFYQRA DMAIGSLTIN EERSEIVDFS
560 570 580 590 600
VPFVETGISV MVARSNGTVS PSAFLEPYSP AVWVMMFVMC LTVVAVTVFI
610 620 630 640 650
FEYLSPVGYN RSLATGKRPG GSTFTIGKSI WLLWALVFNN SVPVENPRGT
660 670 680 690 700
TSKIMVLVWA FFAVIFLASY TANLAAFMIQ EEYVDTVSGL SDRKFQRPQE
710 720 730 740 750
QYPPLKFGTV PNGSTEKNIR SNYPDMHSYM VRYNQPRVEE ALTQLKAGKL
760 770 780 790 800
DAFIYDAAVL NYMARKDEGC KLVTIGSGKV FATTGYGIAL HKGSRWKRPI
810 820 830 840 850
DLALLQFLGD DEIEMLERLW LSGICHNDKI EVMSSKLDID NMAGVFYMLL
860 870 880 890 900
VAMGLSLLVF AWEHLVYWRL RHCLGPTHRM DFLLAFSRGM YSCCSAEAAP
910 920 930 940 950
PPAKPPPPPQ PLPSPAYPAA RPPPGPAPFV PRERAAADRW RRAKGTGPPG
960 970 980 990 1000
GAAIADGFHR YYGPIEPQGL GLGEARAAPR GAAGRPLSPP TTQPPQKPPP
1010 1020 1030 1040 1050
SYFAIVREQE PTEPPAGAFP GFPSPPAPPA AAAAAVGPPL CRLAFEDESP
1060 1070 1080 1090 1100
PAPSRWPRSD PESQPLLGGG AGGPSAGAPT APPPRRAAPP PCAYLDLEPS
1110 1120 1130 1140 1150
PSDSEDSESL GGASLGGLEP WWFADFPYPY AERLGPPPGR YWSVDKLGGW
1160 1170 1180 1190 1200
RAGSWDYLPP RGGPAWHCRH CASLELLPPP RHLSCSHDGL DGGWWAPPPP
1210 1220 1230 1240 1250
PWAAGPPPRR RARCGCPRPH PHRPRASHRA PAAAPHHHRH RRAAGGWDFP
1260 1270 1280 1290 1300
PPAPTSRSLE DLSSCPRAAP TRRLTGPSRH ARRCPHAAHW GPPLPTASHR
1310 1320
RHRGGDLGTR RGSAHFSSLE SEV
Length:1,323
Mass (Da):143,101
Last modified:August 29, 2001 - v2
Checksum:i40F7D60192579564
GO
Isoform 1 (identifier: Q62645-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1265-1323: CPRAAPTRRL...AHFSSLESEV → RPCPPHRTGD...APTPFALGEL

Note: No experimental confirmation available.
Show »
Length:1,356
Mass (Da):145,929
Checksum:i7FCCCEBBFD212D75
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251A → V in AAA17833 (Ref. 3) Curated
Sequence conflicti47 – 471P → Q in AAA17833 (Ref. 3) Curated
Sequence conflicti67 – 671G → V in AAC37646 (PubMed:7512349).Curated
Sequence conflicti94 – 941R → P in AAC37646 (PubMed:7512349).Curated
Sequence conflicti94 – 941R → P in AAC37647 (PubMed:7512349).Curated
Sequence conflicti305 – 3051R → A in AAC37646 (PubMed:7512349).Curated
Sequence conflicti305 – 3051R → A in AAC37647 (PubMed:7512349).Curated
Sequence conflicti635 – 6351A → G in AAA17833 (Ref. 3) Curated
Sequence conflicti974 – 9741E → D in AAA17833 (Ref. 3) Curated
Sequence conflicti1253 – 12531A → G in AAA17833 (Ref. 3) Curated
Sequence conflicti1266 – 12672PR → TT in AAA17833 (Ref. 3) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1265 – 132359CPRAA…LESEV → RPCPPHRTGDTGAGTWAHAG ALRISPAWSPRYDAAPAPTP TPAAPSVSAGHGPRGRAKWT GPSWVGKDRNGPGRTPPGAA SCAPTPFALGEL in isoform 1. 1 PublicationVSP_000136Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13213 mRNA. Translation: BAA02500.1.
D13214 mRNA. Translation: BAA02501.1.
L31611 mRNA. Translation: AAC37646.1.
L31612 mRNA. Translation: AAC37647.1.
U08260 mRNA. Translation: AAA17833.1.
PIRiI78557.
RefSeqiNP_073634.1. NM_022797.1.
XP_008757539.1. XM_008759317.1. [Q62645-2]
UniGeneiRn.91209.

Genome annotation databases

EnsembliENSRNOT00000028615; ENSRNOP00000028615; ENSRNOG00000021063. [Q62645-1]
GeneIDi24412.
KEGGirno:24412.
UCSCiRGD:2740. rat. [Q62645-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13213 mRNA. Translation: BAA02500.1.
D13214 mRNA. Translation: BAA02501.1.
L31611 mRNA. Translation: AAC37646.1.
L31612 mRNA. Translation: AAC37647.1.
U08260 mRNA. Translation: AAA17833.1.
PIRiI78557.
RefSeqiNP_073634.1. NM_022797.1.
XP_008757539.1. XM_008759317.1. [Q62645-2]
UniGeneiRn.91209.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3OEKX-ray1.90A424-564[»]
A686-827[»]
3OELX-ray1.90A424-564[»]
A686-827[»]
3OEMX-ray1.90A424-564[»]
A686-827[»]
3OENX-ray1.80A424-564[»]
A686-827[»]
4JWYX-ray2.00A424-564[»]
A686-827[»]
ProteinModelPortaliQ62645.
SMRiQ62645. Positions 428-580, 687-826.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246577. 3 interactions.
IntActiQ62645. 4 interactions.
MINTiMINT-103662.
STRINGi10116.ENSRNOP00000028615.

Chemistry

BindingDBiQ62645.
ChEMBLiCHEMBL2096669.
GuidetoPHARMACOLOGYi459.

PTM databases

iPTMnetiQ62645.
PhosphoSiteiQ62645.

Proteomic databases

PaxDbiQ62645.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000028615; ENSRNOP00000028615; ENSRNOG00000021063. [Q62645-1]
GeneIDi24412.
KEGGirno:24412.
UCSCiRGD:2740. rat. [Q62645-1]

Organism-specific databases

CTDi2906.
RGDi2740. Grin2d.

Phylogenomic databases

eggNOGiKOG1053. Eukaryota.
ENOG410XNUR. LUCA.
GeneTreeiENSGT00760000119186.
HOGENOMiHOG000113803.
HOVERGENiHBG052637.
InParanoidiQ62645.
KOiK05212.
PhylomeDBiQ62645.

Enzyme and pathway databases

ReactomeiR-RNO-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-RNO-442729. CREB phosphorylation through the activation of CaMKII.
R-RNO-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-8849932. SALM protein interactions at the synapse.

Miscellaneous databases

EvolutionaryTraceiQ62645.
PROiQ62645.

Gene expression databases

ExpressionAtlasiQ62645. baseline and differential.
GenevisibleiQ62645. RN.

Family and domain databases

InterProiIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu/Gly-bd.
IPR001508. Iono_rcpt_met.
IPR001320. Iontro_rcpt.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 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

  1. "Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits."
    Ishii T., Moriyoshi K., Sugihara H., Sakurada K., Kadotani H., Yokoi M., Akazawa C., Shigemoto R., Mizuno N., Masu M., Nakanishi S.
    J. Biol. Chem. 268:2836-2843(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE OF 1265-1356 (ISOFORM 2).
    Strain: Sprague-Dawley.
    Tissue: Forebrain.
  2. "Developmental and regional expression in the rat brain and functional properties of four NMDA receptors."
    Monyer H., Burnashev N., Laurie D.J., Sakmann B., Seeburg P.H.
    Neuron 12:529-540(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Brain.
  3. Boulter J., Pecht G.
    Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Strain: Sprague-Dawley.
    Tissue: Brain.
  4. "Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95."
    Kornau H.C., Schenker L.T., Kennedy M.B., Seeburg P.H.
    Science 269:1737-1740(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DLG4.
  5. "CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins."
    Kurschner C., Mermelstein P.G., Holden W.T., Surmeier D.J.
    Mol. Cell. Neurosci. 11:161-172(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH INADL.
  6. "Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors."
    Vance K.M., Simorowski N., Traynelis S.F., Furukawa H.
    Nat. Commun. 2:294-294(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 424-827, DISULFIDE BONDS.

Entry informationi

Entry nameiNMDE4_RAT
AccessioniPrimary (citable) accession number: Q62645
Secondary accession number(s): Q63381
, Q63382, Q63729, Q63730
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: August 29, 2001
Last modified: July 6, 2016
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.