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Q12879 (NMDE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutamate [NMDA] receptor subunit epsilon-1
Alternative name(s):
N-methyl D-aspartate receptor subtype 2A
Short name=NMDAR2A
Short name=NR2A
Short name=hNR2A
Gene names
Name:GRIN2A
Synonyms:NMDAR2A
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length1464 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Interacts with HIP1 and NETO1 By similarity. Interacts with LRFN2 By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein.

Involvement in disease

Defects in GRIN2A are the cause of epilepsy with neurodevelopmental defects (EPND) [MIM:613971]. EPND is a neurodevelopmental defect characterized by mental retardation, with behavioral problems, associated with epilepsy, learning difficuties and variable degree of cognitive impairment. Note=A chomosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2). Ref.5

Sequence similarities

Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2A/GRIN2A subfamily. [View classification]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 14641442Glutamate [NMDA] receptor subunit epsilon-1
PRO_0000011573

Regions

Topological domain23 – 555533Extracellular Potential
Transmembrane556 – 57621Helical; Potential
Topological domain577 – 63357Cytoplasmic Potential
Transmembrane634 – 65421Helical; Potential
Topological domain655 – 816162Extracellular Potential
Transmembrane817 – 83721Helical; Potential
Topological domain838 – 1464627Cytoplasmic Potential
Region511 – 5133Glutamate binding By similarity
Region689 – 6902Glutamate binding By similarity
Motif1462 – 14643PDZ-binding By similarity

Sites

Metal binding1281Zinc By similarity
Metal binding2831Zinc By similarity
Binding site5181Glutamate By similarity
Binding site7311Glutamate; via amide nitrogen By similarity
Site6141Functional determinant of NMDA receptors By similarity

Amino acid modifications

Modified residue8881Phosphothreonine By similarity
Modified residue9121Phosphoserine Ref.4
Modified residue9171Phosphoserine Ref.4
Modified residue9291Phosphoserine By similarity
Modified residue9431Phosphotyrosine By similarity
Modified residue10251Phosphoserine By similarity
Modified residue13371Phosphoserine Ref.3
Modified residue14591Phosphoserine By similarity
Glycosylation751N-linked (GlcNAc...) Potential
Glycosylation3401N-linked (GlcNAc...) Potential
Glycosylation3801N-linked (GlcNAc...) Potential
Glycosylation4431N-linked (GlcNAc...) Potential
Glycosylation4441N-linked (GlcNAc...) Potential
Glycosylation5411N-linked (GlcNAc...) Potential
Disulfide bond87 ↔ 320 By similarity

Natural variations

Natural variant2701K → E. Ref.1
VAR_010938
Natural variant6151N → K in EPND; the mutant receptor has decreased calcium permeability; shows a dominant-negative effect. Ref.5
VAR_065899

Secondary structure

1 .. 1464
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q12879 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: AF5EDD599EC0B1E3

FASTA1,464165,283
        10         20         30         40         50         60 
MGRVGYWTLL VLPALLVWRG PAPSAAAEKG PPALNIAVML GHSHDVTERE LRTLWGPEQA 

        70         80         90        100        110        120 
AGLPLDVNVV ALLMNRTDPK SLITHVCDLM SGARIHGLVF GDDTDQEAVA QMLDFISSHT 

       130        140        150        160        170        180 
FVPILGIHGG ASMIMADKDP TSTFFQFGAS IQQQATVMLK IMQDYDWHVF SLVTTIFPGY 

       190        200        210        220        230        240 
REFISFVKTT VDNSFVGWDM QNVITLDTSF EDAKTQVQLK KIHSSVILLY CSKDEAVLIL 

       250        260        270        280        290        300 
SEARSLGLTG YDFFWIVPSL VSGNTELIPK EFPSGLISVS YDDWDYSLEA RVRDGIGILT 

       310        320        330        340        350        360 
TAASSMLEKF SYIPEAKASC YGQMERPEVP MHTLHPFMVN VTWDGKDLSF TEEGYQVHPR 

       370        380        390        400        410        420 
LVVIVLNKDR EWEKVGKWEN HTLSLRHAVW 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 KGVEDALVSL 

       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 
AKNISSMSNM NSSRMDSPKR AADFIQRGSL IMDMVSDKGN LMYSDNRSFQ GKESIFGDNM 

       970        980        990       1000       1010       1020 
NELQTFVANR QKDNLNNYVF QGQHPLTLNE SNPNTVEVAV STESKANSRP RQLWKKSVDS 

      1030       1040       1050       1060       1070       1080 
IRQDSLSQNP VSQRDEATAE NRTHSLKSPR YLPEEMAHSD ISETSNRATC HREPDNSKNH 

      1090       1100       1110       1120       1130       1140 
KTKDNFKRSV ASKYPKDCSE VERTYLKTKS SSPRDKIYTI DGEKEPGFHL DPPQFVENVT 

      1150       1160       1170       1180       1190       1200 
LPENVDFPDP YQDPSENFRK GDSTLPMNRN PLHNEEGLSN NDQYKLYSKH FTLKDKGSPH 

      1210       1220       1230       1240       1250       1260 
SETSERYRQN STHCRSCLSN MPTYSGHFTM RSPFKCDACL RMGNLYDIDE DQMLQETGNP 

      1270       1280       1290       1300       1310       1320 
ATGEQVYQQD WAQNNALQLQ KNKLRISRQH SYDNIVDKPR ELDLSRPSRS ISLKDRERLL 

      1330       1340       1350       1360       1370       1380 
EGNFYGSLFS VPSSKLSGKK SSLFPQGLED SKRSKSLLPD HTSDNPFLHS HRDDQRLVIG 

      1390       1400       1410       1420       1430       1440 
RCPSDPYKHS LPSQAVNDSY LRSSLRSTAS YCSRDSRGHN DVYISEHVMP YAANKNNMYS 

      1450       1460 
TPRVLNSCSN RRVYKKMPSI ESDV

« Hide

References

« Hide 'large scale' references
[1]"Human N-methyl-D-aspartate receptor modulatory subunit hNR2A: cloning and sequencing of the cDNA and primary structure of the protein."
Foldes R.L., Adams S.L., Fantaske R.P., Kamboj R.K.
Biochim. Biophys. Acta 1223:155-159(1994) [PubMed: 8061049] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-270.
[2]"Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors."
Hess S.D., Daggett L.P., Crona J., Deal C., Lu C.-C., Urrutia A., Chavez-Noriega L., Ellis S.B., Johnson E.C., Velicelebi G.
J. Pharmacol. Exp. Ther. 278:808-816(1996) [PubMed: 8768735] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Cerebellum.
[3]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1337, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[4]"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry."
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-912 AND SER-917, MASS SPECTROMETRY.
Tissue: Embryonic kidney.
[5]"Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes."
Endele S., Rosenberger G., Geider K., Popp B., Tamer C., Stefanova I., Milh M., Kortum F., Fritsch A., Pientka F.K., Hellenbroich Y., Kalscheuer V.M., Kohlhase J., Moog U., Rappold G., Rauch A., Ropers H.H., von Spiczak S. expand/collapse author list , Tonnies H., Villeneuve N., Villard L., Zabel B., Zenker M., Laube B., Reis A., Wieczorek D., Van Maldergem L., Kutsche K.
Nat. Genet. 42:1021-1026(2010) [PubMed: 20890276] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION, VARIANT EPND LYS-615, CHARACTERIZATION OF VARIANT EPND LYS-615.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U09002 mRNA. Translation: AAB60343.1.
U90277 mRNA. Translation: AAB49992.1.
IPIIPI00029768.
PIRS47555.
RefSeqNP_000824.1. NM_000833.3.
NP_001127879.1. NM_001134407.1.
NP_001127880.1. NM_001134408.1.
UniGeneHs.411472.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3NFLX-ray1.91E/F/G/H1449-1464[»]
ProteinModelPortalQ12879.
SMRQ12879. Positions 31-393, 404-801.
ModBaseSearch...

Protein-protein interaction databases

MINTMINT-414776.
STRINGQ12879.

PTM databases

PhosphoSiteQ12879.

Polymorphism databases

DMDM14285603.

Proteomic databases

PRIDEQ12879.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330684; ENSP00000332549; ENSG00000183454.
ENST00000396573; ENSP00000379818; ENSG00000183454.
ENST00000396575; ENSP00000379820; ENSG00000183454.
GeneID2903.
KEGGhsa:2903.
UCSCuc002czp.1. human.

Organism-specific databases

CTD2903.
GeneCardsGC16M009762.
H-InvDBHIX0038671.
HGNCHGNC:4585. GRIN2A.
HPACAB022725.
MIM138253. gene.
613971. phenotype.
neXtProtNX_Q12879.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG08955.
HOVERGENHBG052635.
InParanoidQ12879.
OMAKMPSIES.
OrthoDBEOG4X0MRG.
PhylomeDBQ12879.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressQ12879.
BgeeQ12879.
CleanExHS_GRIN2A.
GenevestigatorQ12879.
GermOnlineENSG00000183454. Homo sapiens.

Family and domain databases

InterProIPR001828. 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]
KOK05209.
PfamPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10565. NMDAR2_C. 1 hit.
PF00497. SBP_bac_3. 1 hit.
[Graphical view]
PRINTSPR00177. NMDARECEPTOR.
SMARTSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB00949. Felbamate.
DB00145. Glycine.
DB00142. L-Glutamic Acid.
DB00836. Loperamide.
DB01043. Memantine.
NextBio11495.
SOURCESearch...

Entry information

Entry nameNMDE1_HUMAN
AccessionPrimary (citable) accession number: Q12879
Secondary accession number(s): O00669
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: November 1, 1996
Last modified: December 14, 2011
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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