Reviewed, UniProtKB/Swiss-Prot Q00959 (NMDE1_RAT)

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

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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, GRIN3A and PPP2CB. Interacts with AIP1. Found in a complex with GRIN1 and GRIN3B By similarity. Interacts with PDZ domains of INADL and DLG4.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the glutamate-gated ion channel (TC 1.A.10) family. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Domain	Signal Transmembrane
Ligand	Calcium Magnesium
Molecular function	Ionic channel Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	memory Inferred from direct assay. Source: UniProtKB
Cellular component	N-methyl-D-aspartate selective glutamate receptor complex Inferred from direct assay. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW neuron projection Inferred from direct assay. Source: UniProtKB postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW presynaptic membrane Inferred from direct assay. Source: UniProtKB
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW extracellular-glutamate-gated ion channel activity Inferred from electronic annotation. Source: InterPro glutamate binding Inferred from mutant phenotype. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Dlg4	P31016	2	EBI-630970,EBI-375655

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_0000011576

Regions

Topological domain

23 – 555

533

Extracellular Potential

Transmembrane

556 – 576

21

Potential

Topological domain

577 – 633

57

Cytoplasmic Potential

Transmembrane

634 – 654

21

Potential

Topological domain

655 – 816

162

Extracellular Potential

Transmembrane

817 – 837

21

Potential

Topological domain

838 – 1464

627

Cytoplasmic Potential

Region

511 – 513

3

Glutamate binding

Region

689 – 690

2

Glutamate binding

Motif

1462 – 1464

3

PDZ-binding

Sites

Binding site

518

1

Glutamate

Binding site

731

1

Glutamate; via amide nitrogen

Site

614

1

Functional determinant of NMDA receptors By similarity

Amino acid modifications

Modified residue

888

1

Phosphothreonine By similarity

Modified residue

912

1

Phosphoserine By similarity

Modified residue

917

1

Phosphoserine By similarity

Modified residue

929

1

Phosphoserine By similarity

Modified residue

943

1

Phosphotyrosine By similarity

Modified residue

1025

1

Phosphoserine By similarity

Modified residue

1459

1

Phosphoserine By similarity

Glycosylation

75

1

N-linked (GlcNAc...) Potential

Glycosylation

340

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

Experimental info

Sequence conflict

246

1

L → F in BAA02498. Ref.3

Sequence conflict

758

1

S → T in BAA02498. Ref.3

Sequence conflict

758

1

S → T in AAB58801. Ref.4

Sequence conflict

990

1

E → D in AAB58801. Ref.4

Secondary structure

1

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1464

Helix Strand Turn

Details...

Beta strand

406 – 410

5

Turn

414 – 416

3

Beta strand

417 – 421

5

Beta strand

434 – 447

14

Beta strand

449 – 458

10

Helix

459 – 471

13

Beta strand

475 – 479

5

Beta strand

482 – 485

4

Helix

495 – 501

7

Beta strand

506 – 508

3

Helix

516 – 519

4

Beta strand

522 – 524

3

Beta strand

529 – 531

3

Beta strand

533 – 538

6

Helix

668 – 671

4

Helix

673 – 675

3

Beta strand

676 – 678

3

Helix

689 – 695

7

Helix

699 – 705

7

Helix

706 – 708

3

Helix

713 – 721

9

Beta strand

726 – 731

6

Helix

732 – 740

9

Beta strand

747 – 751

5

Helix

755 – 757

3

Beta strand

759 – 761

3

Beta strand

764 – 766

3

Helix

772 – 784

13

Helix

787 – 795

9

Sequences

	Sequence		Length	Mass (Da)
	Q00959-1 [UniParc]. Last modified December 15, 1998. Version 2. Checksum: DC1528E1898DECA4	FASTA	1,464	165,469
	10 20 30 40 50 60 MGRLGYWTLL VLPALLVWRD PAQNAAAEKG PPALNIAVLL 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 YGQAEKPETP 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 MHQYMTRFNQ RGVEDALVSL 730 740 750 760 770 780 KTGKLDAFIY DAAVLNYKAG RDEGCKLVTI GSGYIFASTG 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 ATDFIQRGSL IVDMVSDKGN LIYSDNRSFQ GKDSIFGDNM 970 980 990 1000 1010 1020 NELQTFVANR HKDNLSNYVF QGQHPLTLNE SNPNTVEVAV STESKGNSRP RQLWKKSMES 1030 1040 1050 1060 1070 1080 LRQDSLNQNP VSQRDEKTAE NRTHSLKSPR YLPEEVAHSD ISETSSRATC HREPDNNKNH 1090 1100 1110 1120 1130 1140 KTKDNFKRSM ASKYPKDCSD VDRTYMKTKA SSPRDKIYTI DGEKEPSFHL DPPQFVENIT 1150 1160 1170 1180 1190 1200 LPENVGFPDT YQDHNENFRK GDSTLPMNRN PLHNEDGLPN NDQYKLYAKH FTLKDKGSPH 1210 1220 1230 1240 1250 1260 SEGSDRYRQN STHCRSCLSN LPTYSGHFTM RSPFKCDACL RMGNLYDIDE DQMLQETGNP 1270 1280 1290 1300 1310 1320 ATREEVYQQD WSQNNALQFQ KNKLRINRQH SYDNILDKPR EIDLSRPSRS ISLKDRERLL 1330 1340 1350 1360 1370 1380 EGNLYGSLFS VPSSKLLGNK SSLFPQGLED SKRSKSLLPD HASDNPFLHT YGDDQRLVIG 1390 1400 1410 1420 1430 1440 RCPSDPYKHS LPSQAVNDSY LRSSLRSTAS YCSRDSRGHS DVYISEHVMP YAANKNTMYS 1450 1460 TPRVLNSCSN RRVYKKMPSI ESDV

References

[1]	"Heteromeric NMDA receptors: molecular and functional distinction of subtypes." Monyer H., Sprengel R., Schoepfer R., Herb A., Higuchi M., Lomeli H., Burnashev N., Sakmann B., Seeburg P.H. Science 256:1217-1221(1992) [PubMed: 1350383] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	Monyer H., Sprengel R., Schoepfer R., Herb A., Higuchi M., Lomeli H., Burnashev N., Sakmann B., Seeburg P.H. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 595 AND 597-598.
[3]	"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: 8428958] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Forebrain.
[4]	"Nucleotide sequence of rat NMDA receptor gene NMDAR2A." Boulter J. Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley.
[5]	"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: 7569905] [Abstract] Cited for: INTERACTION WITH DLG4.
[6]	"A novel multiple PDZ domain-containing molecule interacting with N-methyl-d-aspartate receptors and neuronal cell adhesion proteins." Hirao K., Hata Y., Ide N., Takeuchi M., Irie M., Yao I., Deguchi M., Toyoda A., Suedhof T.C., Takai Y. J. Biol. Chem. 273:21105-21110(1998) [PubMed: 9694864] [Abstract] Cited for: INTERACTION WITH AIP1.
[7]	"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: 9647694] [Abstract] Cited for: INTERACTION WITH INADL.
[8]	"Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors." Perez-Otano I., Schulteis C.T., Contractor A., Lipton S.A., Trimmer J.S., Sucher N.J., Heinemann S.F. J. Neurosci. 21:1228-1237(2001) [PubMed: 11160393] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH GRIN1 AND GRIN3A.
[9]	"An NMDA receptor signaling complex with protein phosphatase 2A." Chan S.F., Sucher N.J. J. Neurosci. 21:7985-7992(2001) [PubMed: 11588171] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH GRIN1; GRIN3A AND PPP2CB.
[10]	"Association of NR3A with the N-methyl-D-aspartate receptor NR1 and NR2 subunits." Al-Hallaq R.A., Jarabek B.R., Fu Z., Vicini S., Wolfe B.B., Yasuda R.P. Mol. Pharmacol. 62:1119-1127(2002) [PubMed: 12391275] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH GRIN1 AND GRIN3A.
[11]	"Characterization and comparison of the NR3A subunit of the NMDA receptor in recombinant systems and primary cortical neurons." Sasaki Y.F., Rothe T., Premkumar L.S., Das S., Cui J., Talantova M.V., Wong H.-K., Gong X., Chan S.F., Zhang D., Nakanishi N., Sucher N.J., Lipton S.A. J. Neurophysiol. 87:2052-2063(2002) [PubMed: 11929923] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH GRIN1 AND GRIN3A.
[12]	"Subunit arrangement and function in NMDA receptors." Furukawa H., Singh S.K., Mancusso R., Gouaux E. Nature 438:185-192(2005) [PubMed: 16281028] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 401-802 IN COMPLEXES WITH GRIN1 AND GLUTAMATE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M91561 mRNA. Translation: AAC03565.1.
D13211 mRNA. Translation: BAA02498.1.
AF001423 mRNA. Translation: AAB58801.1.

PIR

A43274.

RefSeq

NP_036705.3.

UniGene

Rn.9710

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2A5S	X-ray	1.70	A	401-802	[»]