P35436 (NMDE1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamate [NMDA] receptor subunit epsilon-1

Alternative name(s):
N-methyl D-aspartate receptor subtype 2A
Short name=NMDAR2A
Short name=NR2A

Gene names

Name:

Grin2a

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1464 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits.
Subunit structure	Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B). Found in a complex with GRIN1 and GRIN3B. Found in a complex with GRIN1, GRIN3A and PPP2CB. Interacts with PDZ domains of AIP1, INADL and DLG4 By similarity. Interacts with HIP1 and NETO1. Interacts with LRFN2 By similarity. Ref.6 Ref.9
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein Ref.4.
Sequence similarities	Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2A/GRIN2A subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Domain	Signal Transmembrane Transmembrane helix
Ligand	Calcium Magnesium Metal-binding Zinc
Molecular function	Ionic channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	directional locomotion Inferred from genetic interaction. Source: MGI dopamine metabolic process Inferred from mutant phenotype. Source: MGI locomotory behavior Traceable author statement. Source: UniProtKB memory Inferred from mutant phenotype. Source: MGI negative regulation of protein catabolic process Inferred from genetic interaction. Source: MGI neurogenesis Inferred from mutant phenotype. Source: MGI protein localization Inferred from mutant phenotype. Source: MGI regulation of excitatory postsynaptic membrane potential Inferred from mutant phenotype. Source: MGI regulation of sensory perception of pain Inferred from mutant phenotype. Source: MGI response to amphetamine Inferred from mutant phenotype. Source: MGI response to drug Inferred from mutant phenotype. Source: MGI response to ethanol Inferred from mutant phenotype. Source: MGI response to wounding Inferred from mutant phenotype. Source: MGI sensory perception of pain Inferred from mutant phenotype. Source: MGI serotonin metabolic process Inferred from mutant phenotype. Source: MGI sleep Inferred from mutant phenotype. Source: MGI startle response Inferred from mutant phenotype. Source: MGI visual learning Inferred from mutant phenotype. Source: MGI
Cellular component	N-methyl-D-aspartate selective glutamate receptor complex Inferred from physical interaction. Source: MGI cell junction Inferred from electronic annotation. Source: UniProtKB-KW outer membrane-bounded periplasmic space Inferred from electronic annotation. Source: InterPro postsynaptic density Inferred from direct assay. Source: MGI postsynaptic membrane Inferred from direct assay. Source: MGI presynaptic membrane Inferred from direct assay. Source: UniProtKB synaptosome Inferred from direct assay. Source: MGI
Molecular function	N-methyl-D-aspartate selective glutamate receptor activity Inferred from mutant phenotype. Source: MGI calcium channel activity Inferred from mutant phenotype. Source: MGI zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Dlg4	Q62108	6	EBI-400115,EBI-300895

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 1464	1442	Glutamate [NMDA] receptor subunit epsilon-1		PRO_0000011574
Regions
	Topological domain	23 – 555	533	Extracellular Potential
	Transmembrane	556 – 576	21	Helical; Potential
	Topological domain	577 – 633	57	Cytoplasmic Potential
	Transmembrane	634 – 654	21	Helical; Potential
	Topological domain	655 – 816	162	Extracellular Potential
	Transmembrane	817 – 837	21	Helical; Potential
	Topological domain	838 – 1464	627	Cytoplasmic Potential
	Region	511 – 513	3	Glutamate binding By similarity
	Region	689 – 690	2	Glutamate binding By similarity
	Motif	1462 – 1464	3	PDZ-binding By similarity
Sites
	Metal binding	128	1	Zinc By similarity
	Metal binding	283	1	Zinc By similarity
	Binding site	518	1	Glutamate By similarity
	Binding site	731	1	Glutamate; via amide nitrogen By similarity
	Site	614	1	Functional determinant of NMDA receptors By similarity
Amino acid modifications
	Modified residue	888	1	Phosphothreonine Ref.8
	Modified residue	912	1	Phosphoserine By similarity
	Modified residue	917	1	Phosphoserine Ref.5
	Modified residue	929	1	Phosphoserine Ref.8
	Modified residue	943	1	Phosphotyrosine Ref.7
	Modified residue	1025	1	Phosphoserine Ref.8
	Modified residue	1459	1	Phosphoserine Ref.8
	Glycosylation	75	1	N-linked (GlcNAc...) Potential
	Glycosylation	340	1	N-linked (GlcNAc...) Potential
	Glycosylation	380	1	N-linked (GlcNAc...) Potential
	Glycosylation	443	1	N-linked (GlcNAc...) Potential
	Glycosylation	444	1	N-linked (GlcNAc...) Potential
	Glycosylation	541	1	N-linked (GlcNAc...) Potential
	Disulfide bond	87 ↔ 320		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P35436 [UniParc]. Last modified July 19, 2004. Version 2. Checksum: 438986DD5666C152	FASTA	1,464	165,421
	10 20 30 40 50 60 MGRLGYWTLL VLPALLVWHG PAQNAAAEKG TPALNIAVLL GHSHDVTERE LRNLWGPEQA 70 80 90 100 110 120 TGLPLDVNVV ALLMNRTDPK SLITHVCDLM SGARIHGLVF GDDTDQEAVA QMLDFISSQT 130 140 150 160 170 180 FIPILGIHGG ASMIMADKDP TSTFFQFGAS IQQQATVMLK IMQDYDWHVF SLVTTIFPGY 190 200 210 220 230 240 RDFISFIKTT VDNSFVGWDM QNVITLDTSF EDAKTQVQLK KIHSSVILLY CSKDEAVLIL 250 260 270 280 290 300 SEARSLGLTG YDFFWIVPSL VSGNTELIPK EFPSGLISVS YDDWDYSLEA RVRDGLGILT 310 320 330 340 350 360 TAASSMLEKF SYIPEAKASC YGQTEKPETP LHTLHQFMVN VTWDGKDLSF TEEGYQVHPR 370 380 390 400 410 420 LVVIVLNKDR EWEKVGKWEN QTLSLRHAVW PRYKSFSDCE PDDNHLSIVT LEEAPFVIVE 430 440 450 460 470 480 DIDPLTETCV RNTVPCRKFV KINNSTNEGM NVKKCCKGFC IDILKKLSRT VKFTYDLYLV 490 500 510 520 530 540 TNGKHGKKVN NVWNGMIGEV VYQRAVMAVG SLTINEERSE VVDFSVPFVE TGISVMVSRS 550 560 570 580 590 600 NGTVSPSAFL EPFSASVWVM MFVMLLIVSA IAVFVFEYFS PVGYNRNLAK GKAPHGPSFT 610 620 630 640 650 660 IGKAIWLLWG LVFNNSVPVQ NPKGTTSKIM VSVWAFFAVI FLASYTANLA AFMIQEEFVD 670 680 690 700 710 720 QVTGLSDKKF QRPHDYSPPF RFGTVPNGST ERNIRNNYPY MHQYMTKFNQ RGVEDALVSL 730 740 750 760 770 780 KTGKLDAFIY DAAVLNYKAG RDEGCKLVTI GSGYIFATTG YGIALQKGSP WKRQIDLALL 790 800 810 820 830 840 QFVGDGEMEE LETLWLTGIC HNEKNEVMSS QLDIDNMAGV FYMLAAAMAL SLITFIWEHL 850 860 870 880 890 900 FYWKLRFCFT GVCSDRPGLL FSISRGIYSC IHGVHIEEKK KSPDFNLTGS QSNMLKLLRS 910 920 930 940 950 960 AKNISNMSNM NSSRMDSPKR AADFIQRGSL IVDMVSDKGN LIYSDNRSFQ GKDSIFGENM 970 980 990 1000 1010 1020 NELQTFVANR HKDSLSNYVF QGQHPLTLNE SNPNTVEVAV STESKGNSRP RQLWKKSMES 1030 1040 1050 1060 1070 1080 LRQDSLNQNP VSQRDEKTAE NRTHSLKSPR YLPEEVAHSD ISETSSRATC HREPDNNKNH 1090 1100 1110 1120 1130 1140 KTKDNFKRSM ASKYPKDCSE VERTYVKTKA SSPRDKIYTI DGEKEPSFHL DPPQFIENIV 1150 1160 1170 1180 1190 1200 LPENVDFPDT YQDHNENFRK GDSTLPMNRN PLHNEDGLPN NDQYKLYAKH FTLKDKGSPH 1210 1220 1230 1240 1250 1260 SEGSDRYRQN STHCRSCLSN LPTYSGHFTM RSPFKCDACL RMGNLYDIDE DQMLQETGNP 1270 1280 1290 1300 1310 1320 ATREEAYQQD WSQNNALQFQ KNKLKINRQH SYDNILDKPR EIDLSRPSRS ISLKDRERLL 1330 1340 1350 1360 1370 1380 EGNLYGSLFS VPSSKLLGNK SSLFPQGLED SKRSKSLLPD HTSDNPFLHT YGDDQRLVIG 1390 1400 1410 1420 1430 1440 RCPSDPYKHS LPSQAVNDSY LRSSLRSTAS YCSRDSRGHS DVYISEHVMP YAANKNNMYS 1450 1460 TPRVLNSCSN RRVYKKMPSI ESDV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs." Meguro H., Mori H., Araki K., Kushiya E., Kutsuwada T., Yamazaki M., Kumanishi T., Arakawa M., Sakimura K., Mishina M. Nature 357:70-74(1992) [PubMed: 1374164] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Meguro H., Mori H., Araki K., Kushiya E., Kutsuwada T., Yamazaki M., Kumanishi T., Arakawa M., Sakimura K., Mishina M. Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 384.
[3]	"Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability." Matsuda K., Kamiya Y., Matsuda S., Yuzaki M. Brain Res. Mol. Brain Res. 100:43-52(2002) [PubMed: 12008020] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH GRIN1 AND GRIN3B.
[4]	"Specific assembly with the NMDA receptor 3B subunit controls surface expression and calcium permeability of NMDA receptors." Matsuda K., Fletcher M., Kamiya Y., Yuzaki M. J. Neurosci. 23:10064-10073(2003) [PubMed: 14602821] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH GRIN1 AND GRIN3B.
[5]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed: 16452087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-917, MASS SPECTROMETRY. Tissue: Brain.
[6]	"NMDA receptor function and NMDA receptor-dependent phosphorylation of huntingtin is altered by the endocytic protein HIP1." Metzler M., Gan L., Wong T.P., Liu L., Helm J., Liu L., Georgiou J., Wang Y., Bissada N., Cheng K., Roder J.C., Wang Y.T., Hayden M.R. J. Neurosci. 27:2298-2308(2007) [PubMed: 17329427] [Abstract] Cited for: INTERACTION WITH HIP1.
[7]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-943, MASS SPECTROMETRY. Tissue: Brain.
[8]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-888; SER-929; SER-1025 AND SER-1459, MASS SPECTROMETRY. Tissue: Brain cortex.
[9]	"Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning." Ng D., Pitcher G.M., Szilard R.K., Sertie A., Kanisek M., Clapcote S.J., Lipina T., Kalia L.V., Joo D., McKerlie C., Cortez M., Roder J.C., Salter M.W., McInnes R.R. PLoS Biol. 7:E41-E41(2009) [PubMed: 19243221] [Abstract] Cited for: INTERACTION WITH NETO1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D10217 mRNA. Translation: BAA01069.2.
IPI	IPI00118380.
PIR	S29159.
RefSeq	NP_032196.2. NM_008170.2.
UniGene	Mm.2953.
3D structure databases
ProteinModelPortal	P35436.
SMR	P35436. Positions 31-392, 404-801.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31567N.
IntAct	P35436. 4 interactions.
MINT	MINT-103939.
STRING	P35436.
PTM databases
PhosphoSite	P35436.
Proteomic databases
PRIDE	P35436.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000032331; ENSMUSP00000032331; ENSMUSG00000059003. ENSMUST00000115835; ENSMUSP00000111501; ENSMUSG00000059003.
GeneID	14811.
KEGG	mmu:14811.
UCSC	uc007ydc.1. mouse.
Organism-specific databases
CTD	2903.
MGI	MGI:95820. Grin2a.
Phylogenomic databases
eggNOG	roNOG08083.
GeneTree	ENSGT00540000070221.
HOGENOM	HBG717736.
HOVERGEN	HBG052635.
InParanoid	P35436.
OMA	KMPSIES.
OrthoDB	EOG4X0MRG.
PhylomeDB	P35436.
Gene expression databases
ArrayExpress	P35436.
Bgee	P35436.
Genevestigator	P35436.
GermOnline	ENSMUSG00000059003. Mus musculus.
Family and domain databases
InterPro	IPR001828. ANF_lig-bd_rcpt. IPR019594. Glu_rcpt_Glu/Gly-bd. IPR001320. Iontro_glu_rcpt. IPR001508. NMDA_rcpt. IPR018884. NMDAR2_C. IPR001638. SBP_bac_3. [Graphical view]
KO	K05209.
Pfam	PF01094. ANF_receptor. 1 hit. PF00060. Lig_chan. 1 hit. PF10565. NMDAR2_C. 1 hit. PF00497. SBP_bac_3. 1 hit. [Graphical view]
PRINTS	PR00177. NMDARECEPTOR.
SMART	SM00918. Lig_chan-Glu_bd. 1 hit. SM00079. PBPe. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	286999.
SOURCE	Search...

Entry information

Entry name

NMDE1_MOUSE

Accession

Primary (citable) accession number: P35436

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	July 19, 2004
Last modified:	November 16, 2011
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program