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Protein

Glutamate receptor ionotropic, NMDA 2A

Gene

Grin2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium (PubMed:1374164). Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg2+. Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have higher sensitivity to glutamate and faster kinetics than channels formed by GRIN1 and GRIN2B (By similarity). Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (PubMed:7816096, PubMed:8987814).By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi44Zinc; via tele nitrogenBy similarity1
Metal bindingi128Zinc; via tele nitrogenBy similarity1
Metal bindingi266ZincBy similarity1
Metal bindingi282ZincBy similarity1
Binding sitei518GlutamateBy similarity1
Sitei614Functional determinant of NMDA receptorsBy similarity1

GO - Molecular functioni

  • calcium channel activity Source: MGI
  • cation channel activity Source: MGI
  • extracellular-glutamate-gated ion channel activity Source: InterPro
  • NMDA glutamate receptor activity Source: MGI
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • calcium ion transport Source: MGI
  • chemical synaptic transmission Source: MGI
  • directional locomotion Source: MGI
  • dopamine metabolic process Source: MGI
  • excitatory postsynaptic potential Source: MGI
  • learning Source: MGI
  • learning or memory Source: MGI
  • locomotion Source: MGI
  • locomotory behavior Source: UniProtKB
  • long-term synaptic potentiation Source: MGI
  • memory Source: MGI
  • modulation of chemical synaptic transmission Source: UniProtKB
  • negative regulation of protein catabolic process Source: MGI
  • neurogenesis Source: MGI
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of long-term synaptic potentiation Source: MGI
  • protein localization Source: MGI
  • regulation of membrane potential Source: MGI
  • regulation of postsynaptic membrane potential Source: MGI
  • regulation of sensory perception of pain Source: MGI
  • regulation of synaptic plasticity Source: UniProtKB
  • response to amphetamine Source: MGI
  • response to drug Source: MGI
  • response to ethanol Source: MGI
  • response to wounding Source: MGI
  • sensory perception of pain Source: MGI
  • serotonin metabolic process Source: MGI
  • sleep Source: MGI
  • startle response Source: MGI
  • visual learning Source: MGI

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Receptor
Biological processIon transport, Transport
LigandCalcium, Magnesium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-MMU-442729. CREB phosphorylation through the activation of CaMKII.
R-MMU-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-8849932. Synaptic adhesion-like molecules.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate receptor ionotropic, NMDA 2A
Short name:
GluN2A
Alternative name(s):
Glutamate [NMDA] receptor subunit epsilon-11 Publication
N-methyl D-aspartate receptor subtype 2A
Short name:
NMDAR2A
Short name:
NR2A1 Publication
Gene namesi
Name:Grin2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:95820. Grin2a.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 555ExtracellularCuratedAdd BLAST533
Transmembranei556 – 576HelicalBy similarityAdd BLAST21
Topological domaini577 – 600CytoplasmicCuratedAdd BLAST24
Intramembranei601 – 620Discontinuously helicalBy similarityAdd BLAST20
Topological domaini621 – 625CytoplasmicCurated5
Transmembranei626 – 645HelicalBy similarityAdd BLAST20
Topological domaini646 – 816ExtracellularCuratedAdd BLAST171
Transmembranei817 – 837HelicalBy similarityAdd BLAST21
Topological domaini838 – 1464CytoplasmicCuratedAdd BLAST627

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

Mutant mice appear grossly normal and are fertile (PubMed:7816096, PubMed:8987814). NMDA channel currents are decreased in mutant brain slices. Contrary to wild-type, where tetanic stimulation leads to a strong long-term increase in synaptic strength, only modest long-term synaptic potentiation is seen in mutant mice (PubMed:7816096). Mossy fiber granule cells from mutant mice present a decrease of the slow component of the excitatory postsynaptic current (PubMed:8987814). The slow component of the excitatory postsynaptic current is nearly abolished in mossy fiber cells from mice lacking both Grin2a and Grin2c (PubMed:8987814). Mutant mice present subtle deficits in spatial learning (PubMed:7816096). Mice lacking both Grin2a and Grin2c display subtle motor deficits; they have no visible phenotype when performing simple tasks, but have decreased ability to walk across a narrow wooden bar, and are unable to stay on a rapidly rotating rod (PubMed:8987814).2 Publications

Chemistry databases

ChEMBLiCHEMBL3832634.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000001157423 – 1464Glutamate receptor ionotropic, NMDA 2AAdd BLAST1442

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi75N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi87 ↔ 320By similarity
Glycosylationi340N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi380N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi429 ↔ 455By similarity
Disulfide bondi436 ↔ 456By similarity
Glycosylationi443N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi444N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi541N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi745 ↔ 800By similarity
Modified residuei882PhosphoserineCombined sources1
Modified residuei890PhosphoserineCombined sources1
Modified residuei929PhosphoserineCombined sources1
Modified residuei1025PhosphoserineBy similarity1
Modified residuei1059PhosphoserineCombined sources1
Modified residuei1062PhosphoserineBy similarity1
Modified residuei1198PhosphoserineBy similarity1
Modified residuei1291PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP35436.
PeptideAtlasiP35436.
PRIDEiP35436.

PTM databases

iPTMnetiP35436.
PhosphoSitePlusiP35436.

Expressioni

Tissue specificityi

Detected in forbrain (PubMed:7816096). Detected in cerebellum (at protein level) (PubMed:8987814). Detected in brain cortex, piriform cortex, hippocampus, caudate-putamen, dentate gyrus and granule cell layer (PubMed:1374164, PubMed:7816096).3 Publications

Gene expression databases

BgeeiENSMUSG00000059003.
GenevisibleiP35436. MM.

Interactioni

Subunit structurei

Heterotetramer (By similarity). Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:1374164). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (PubMed:12008020). In vivo, the subunit composition may depend on the expression levels of the different subunits. Found in a complex with GRIN1, GRIN3A and PPP2CB (By similarity). Found in a complex with GRIN1 and GRIN3B (PubMed:12008020). Interacts with AIP1 (By similarity). Interacts with HIP1 and NETO1 (PubMed:17329427, PubMed:19243221). Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (PubMed:23524343). Interacts with PDZ domains of PATJ and DLG4. Interacts with LRFN2 (By similarity).By similarity5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi200068. 19 interactors.
CORUMiP35436.
DIPiDIP-31567N.
IntActiP35436. 7 interactors.
MINTiMINT-103939.
STRINGi10090.ENSMUSP00000032331.

Structurei

3D structure databases

ProteinModelPortaliP35436.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni511 – 513Glutamate bindingBy similarity3
Regioni599 – 620Pore-formingBy similarityAdd BLAST22
Regioni689 – 690Glutamate bindingBy similarity2
Regioni730 – 731Glutamate bindingBy similarity2

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1462 – 1464PDZ-bindingCurated3

Domaini

Contains an N-terminal domain, a ligand-binding domain and a transmembrane domain. Agonist binding to the extracellular ligand-binding domains triggers channel gating.By similarity
A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1053. Eukaryota.
ENOG410XNUR. LUCA.
GeneTreeiENSGT00760000119186.
HOGENOMiHOG000113802.
HOVERGENiHBG052635.
InParanoidiP35436.
KOiK05209.
OMAiRDFISFI.
OrthoDBiEOG091G09KH.
PhylomeDBiP35436.
TreeFamiTF314731.

Family and domain databases

InterProiView protein in InterPro
IPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu/Gly-bd.
IPR001508. Iono_rcpt_met.
IPR001320. Iontro_rcpt.
IPR018884. NMDAR2_C.
IPR028082. Peripla_BP_I.
PfamiView protein in Pfam
PF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
PF10565. NMDAR2_C. 1 hit.
PRINTSiPR00177. NMDARECEPTOR.
SMARTiView protein in SMART
SM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
SUPFAMiSSF53822. SSF53822. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P35436-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRLGYWTLL VLPALLVWHG PAQNAAAEKG TPALNIAVLL GHSHDVTERE
60 70 80 90 100
LRNLWGPEQA TGLPLDVNVV ALLMNRTDPK SLITHVCDLM SGARIHGLVF
110 120 130 140 150
GDDTDQEAVA QMLDFISSQT FIPILGIHGG ASMIMADKDP TSTFFQFGAS
160 170 180 190 200
IQQQATVMLK IMQDYDWHVF SLVTTIFPGY RDFISFIKTT VDNSFVGWDM
210 220 230 240 250
QNVITLDTSF EDAKTQVQLK KIHSSVILLY CSKDEAVLIL SEARSLGLTG
260 270 280 290 300
YDFFWIVPSL VSGNTELIPK EFPSGLISVS YDDWDYSLEA RVRDGLGILT
310 320 330 340 350
TAASSMLEKF SYIPEAKASC YGQTEKPETP LHTLHQFMVN VTWDGKDLSF
360 370 380 390 400
TEEGYQVHPR LVVIVLNKDR EWEKVGKWEN QTLSLRHAVW PRYKSFSDCE
410 420 430 440 450
PDDNHLSIVT LEEAPFVIVE DIDPLTETCV RNTVPCRKFV KINNSTNEGM
460 470 480 490 500
NVKKCCKGFC IDILKKLSRT VKFTYDLYLV TNGKHGKKVN NVWNGMIGEV
510 520 530 540 550
VYQRAVMAVG SLTINEERSE VVDFSVPFVE TGISVMVSRS NGTVSPSAFL
560 570 580 590 600
EPFSASVWVM MFVMLLIVSA IAVFVFEYFS PVGYNRNLAK GKAPHGPSFT
610 620 630 640 650
IGKAIWLLWG LVFNNSVPVQ NPKGTTSKIM VSVWAFFAVI FLASYTANLA
660 670 680 690 700
AFMIQEEFVD QVTGLSDKKF QRPHDYSPPF RFGTVPNGST ERNIRNNYPY
710 720 730 740 750
MHQYMTKFNQ RGVEDALVSL KTGKLDAFIY DAAVLNYKAG RDEGCKLVTI
760 770 780 790 800
GSGYIFATTG YGIALQKGSP WKRQIDLALL QFVGDGEMEE LETLWLTGIC
810 820 830 840 850
HNEKNEVMSS QLDIDNMAGV FYMLAAAMAL SLITFIWEHL FYWKLRFCFT
860 870 880 890 900
GVCSDRPGLL FSISRGIYSC IHGVHIEEKK KSPDFNLTGS QSNMLKLLRS
910 920 930 940 950
AKNISNMSNM NSSRMDSPKR AADFIQRGSL IVDMVSDKGN LIYSDNRSFQ
960 970 980 990 1000
GKDSIFGENM NELQTFVANR HKDSLSNYVF QGQHPLTLNE SNPNTVEVAV
1010 1020 1030 1040 1050
STESKGNSRP RQLWKKSMES LRQDSLNQNP VSQRDEKTAE NRTHSLKSPR
1060 1070 1080 1090 1100
YLPEEVAHSD ISETSSRATC HREPDNNKNH KTKDNFKRSM ASKYPKDCSE
1110 1120 1130 1140 1150
VERTYVKTKA SSPRDKIYTI DGEKEPSFHL DPPQFIENIV LPENVDFPDT
1160 1170 1180 1190 1200
YQDHNENFRK GDSTLPMNRN PLHNEDGLPN NDQYKLYAKH FTLKDKGSPH
1210 1220 1230 1240 1250
SEGSDRYRQN STHCRSCLSN LPTYSGHFTM RSPFKCDACL RMGNLYDIDE
1260 1270 1280 1290 1300
DQMLQETGNP ATREEAYQQD WSQNNALQFQ KNKLKINRQH SYDNILDKPR
1310 1320 1330 1340 1350
EIDLSRPSRS ISLKDRERLL EGNLYGSLFS VPSSKLLGNK SSLFPQGLED
1360 1370 1380 1390 1400
SKRSKSLLPD HTSDNPFLHT YGDDQRLVIG RCPSDPYKHS LPSQAVNDSY
1410 1420 1430 1440 1450
LRSSLRSTAS YCSRDSRGHS DVYISEHVMP YAANKNNMYS TPRVLNSCSN
1460
RRVYKKMPSI ESDV
Length:1,464
Mass (Da):165,421
Last modified:July 19, 2004 - v2
Checksum:i438986DD5666C152
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10217 mRNA. Translation: BAA01069.2.
CCDSiCCDS27943.1.
PIRiS29159.
RefSeqiNP_032196.2. NM_008170.2.
XP_006521857.1. XM_006521794.3.
UniGeneiMm.2953.

Genome annotation databases

EnsembliENSMUST00000032331; ENSMUSP00000032331; ENSMUSG00000059003.
ENSMUST00000115835; ENSMUSP00000111501; ENSMUSG00000059003.
ENSMUST00000199708; ENSMUSP00000142900; ENSMUSG00000059003.
GeneIDi14811.
KEGGimmu:14811.
UCSCiuc007ydc.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiNMDE1_MOUSE
AccessioniPrimary (citable) accession number: P35436
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: July 19, 2004
Last modified: October 25, 2017
This is version 178 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families