Protein

Glutamate receptor ionotropic, NMDA 2A

Gene

GRIN2A

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: -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. 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⁺ (PubMed:8768735, PubMed:26919761, PubMed:26875626, PubMed:28105280). 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 (PubMed:26919761, PubMed:26875626). Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity).By similarity4 Publications

Sites

Feature key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	44	Zinc; via tele nitrogenBy similarity	1
Metal bindingⁱ	128	Zinc; via tele nitrogenBy similarity	1
Metal bindingⁱ	266	ZincBy similarity	1
Metal bindingⁱ	282	ZincBy similarity	1
Binding siteⁱ	518	GlutamateCombined sources3 Publications	1
Siteⁱ	614	Functional determinant of NMDA receptorsBy similarity	1

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Ion channel, Ligand-gated ion channel, Receptor
Biological process	Ion transport, Transport
Ligand	Calcium, Magnesium, Metal-binding, Zinc

Enzyme and pathway databases

Reactomeⁱ	R-HSA-438066 Unblocking of NMDA receptors, glutamate binding and activation R-HSA-6794361 Neurexins and neuroligins R-HSA-8849932 Synaptic adhesion-like molecules R-HSA-9022699 MECP2 regulates neuronal receptors and channels R-HSA-9609736 Assembly and cell surface presentation of NMDA receptors R-HSA-9617324 Negative regulation of NMDA receptor-mediated neuronal transmission R-HSA-9620244 Long-term potentiation
SignaLinkⁱ	Q12879
SIGNORⁱ	Q12879

Protein family/group databases

TCDBⁱ	1.A.10.1.20 the glutamate-gated ion channel (gic) family of neurotransmitter receptors

TCDBⁱ

1.A.10.1.20 the glutamate-gated ion channel (gic) family of neurotransmitter receptors

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Glutamate receptor ionotropic, NMDA 2A Short name: GluN2A Alternative name(s): Glutamate [NMDA] receptor subunit epsilon-1 N-methyl D-aspartate receptor subtype 2A Short name: NMDAR2A1 Publication Short name: NR2A Short name: hNR2A1 Publication
Gene namesⁱ	Name:GRIN2A Synonyms:NMDAR2A
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 16

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:4585 GRIN2A
MIMⁱ	138253 gene
neXtProtⁱ	NX_Q12879

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	23 – 555	ExtracellularBy similarityAdd BLAST	533
Transmembraneⁱ	556 – 576	HelicalBy similarityAdd BLAST	21
Topological domainⁱ	577 – 600	CytoplasmicBy similarityAdd BLAST	24
Intramembraneⁱ	601 – 620	Discontinuously helicalBy similarityAdd BLAST	20
Topological domainⁱ	621 – 625	CytoplasmicBy similarity	5
Transmembraneⁱ	626 – 645	HelicalBy similarityAdd BLAST	20
Topological domainⁱ	646 – 816	ExtracellularBy similarityAdd BLAST	171
Transmembraneⁱ	817 – 837	HelicalBy similarityAdd BLAST	21
Topological domainⁱ	838 – 1464	CytoplasmicBy similarityAdd BLAST	627

Keywords - Cellular componentⁱ

Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Epilepsy, focal, with speech disorder and with or without mental retardation (FESD)12 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA highly variable neurologic disorder with features ranging from severe early-onset seizures associated with delayed psychomotor development, persistent speech difficulties, and mental retardation to a more benign entity characterized by childhood onset of mild or asymptomatic seizures associated with transient speech difficulties followed by remission of seizures in adolescence and normal psychomotor development. The disorder encompasses several clinical entities, including Landau-Kleffner syndrome, epileptic encephalopathy with continuous spike and wave during slow-wave sleep, autosomal dominant rolandic epilepsy, mental retardation and speech dyspraxia, and benign epilepsy with centrotemporal spikes.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_070345	79	P → R in FESD. 1 PublicationCorresponds to variant dbSNP:rs1250662891EnsemblClinVar.	1
Natural variantⁱVAR_070346	184	I → S in FESD; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_070347	231	C → Y in FESD; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_070348	243	A → V in FESD; results in reduced high-affinity zinc mediated inhibition. 1 Publication	1
Natural variantⁱVAR_070349	290	A → V in FESD. 1 PublicationCorresponds to variant dbSNP:rs199528312EnsemblClinVar.	1
Natural variantⁱVAR_070350	295	G → S in FESD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs568484876EnsemblClinVar.	1
Natural variantⁱVAR_070351	370	R → W in FESD. 1 PublicationCorresponds to variant dbSNP:rs761168789Ensembl.	1
Natural variantⁱVAR_070352	436	C → R in FESD; decreased protein abundance; loss of localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency and decreased glycine potency. 2 PublicationsCorresponds to variant dbSNP:rs1555496111EnsemblClinVar.	1
Natural variantⁱVAR_070353	483	G → R in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency. 2 Publications	1
Natural variantⁱVAR_070354	504	R → W in FESD; decreased protein abundance; decreased localization to the cell membrane; no significant effect on calcium ion transmembrane import into cytosol. 2 PublicationsCorresponds to variant dbSNP:rs1360906241Ensembl.	1
Natural variantⁱVAR_079933	506	V → A in FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency. 1 PublicationCorresponds to variant dbSNP:rs796052543EnsemblClinVar.	1
Natural variantⁱVAR_070355	518	R → H in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by affected receptor kinetics. 2 PublicationsCorresponds to variant dbSNP:rs397518470EnsemblClinVar.	1
Natural variantⁱVAR_070356	531	T → M in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by affected receptor kinetics. 2 PublicationsCorresponds to variant dbSNP:rs397518468EnsemblClinVar.	1
Natural variantⁱVAR_070357	547	Missing in FESD. 1 Publication	1
Natural variantⁱVAR_070358	548	A → T in FESD; no effect on localization to the cell membrane; loss of glutamate-gated calcium ion channel activity. 2 Publications	1
Natural variantⁱVAR_069382	552	P → R in FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency with delay in rise time and slower deactivation time course. 2 PublicationsCorresponds to variant dbSNP:rs397518450EnsemblClinVar.	1
Natural variantⁱVAR_065899	615	N → K in FESD; the mutant receptor has decreased calcium permeability; shows a dominant-negative effect. 1 PublicationCorresponds to variant dbSNP:rs397518447EnsemblClinVar.	1
Natural variantⁱVAR_069383	649	L → V in FESD. 1 PublicationCorresponds to variant dbSNP:rs397514557EnsemblClinVar.	1
Natural variantⁱVAR_070359	652	F → V in FESD; affects receptor kinetics. 1 PublicationCorresponds to variant dbSNP:rs397518471EnsemblClinVar.	1
Natural variantⁱVAR_070360	669	K → N in FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency. 2 Publications	1
Natural variantⁱVAR_079935	685	V → G in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency. 1 PublicationCorresponds to variant dbSNP:rs796052548EnsemblClinVar.	1
Natural variantⁱVAR_070361	694	I → T in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and decreased open probability. 2 Publications	1
Natural variantⁱVAR_070362	699	P → S in FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency and decreased open probability. 2 PublicationsCorresponds to variant dbSNP:rs1555491648EnsemblClinVar.	1
Natural variantⁱVAR_070363	705	M → V in FESD; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and decreased open probability. 2 Publications	1
Natural variantⁱVAR_070364	714	E → K in FESD; decreased protein abundance; no effect on localization to the cell membrane; no significant effect on calcium ion transmembrane import into cytosol. 2 Publications	1
Natural variantⁱVAR_078110	716	A → D in FESD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057519552EnsemblClinVar.	1
Natural variantⁱVAR_070365	716	A → T in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency. 2 PublicationsCorresponds to variant dbSNP:rs762659685EnsemblClinVar.	1
Natural variantⁱVAR_070366	727	A → T in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and decreased open probability. 2 PublicationsCorresponds to variant dbSNP:rs1555488144EnsemblClinVar.	1
Natural variantⁱVAR_070367	731	D → N in FESD; decreased protein abundance; decreased localization to the cell membrane; decreased glutamate-gated calcium ion channel activity characterized by drastically decreased glutamate agonist potency, decreased glycine agonist potency, reduced amplitude of current response, shortened synaptic-like response time course, decreased channel open probability and enhanced sensitivity to negative allosteric modulators. 3 PublicationsCorresponds to variant dbSNP:rs796052549EnsemblClinVar.	1
Natural variantⁱVAR_070368	734	V → L in FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency. 2 Publications	1
Natural variantⁱVAR_070369	772	K → E in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and decreased open probability. 2 Publications	1
Natural variantⁱVAR_072750	812	L → M in FESD; increase in receptor response to agonists; decrease in the actions of endogenous negative modulators; increase in channel open probability; prolonged deactivation time course. 1 Publication	1
Natural variantⁱVAR_070370	814	I → T in FESD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs780654733EnsemblClinVar.	1
Natural variantⁱVAR_071626	817	M → V in FESD; gain-of-function characterized by enhanced agonist potency, reduced sensitivity to endogenous negative inhibitors, prolonged synaptic-like response time course, increased single-channel mean open time and increased channel open probability. 2 PublicationsCorresponds to variant dbSNP:rs796052551EnsemblClinVar.	1
Natural variantⁱVAR_070371	904	I → F in FESD. 1 PublicationCorresponds to variant dbSNP:rs1555482933EnsemblClinVar.	1
Natural variantⁱVAR_070372	933	D → N in FESD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs933322445Ensembl.	1
Natural variantⁱVAR_070373	976	N → S in FESD. 1 PublicationCorresponds to variant dbSNP:rs886039239EnsemblClinVar.	1
Natural variantⁱVAR_070374	1251	D → N in FESD. 1 Publication	1

A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2).

GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma.2 Publications

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	552	P → A: Changed glutamate-gated calcium ion channel activity characterized by increased desensitization. 1 Publication	1
Mutagenesisⁱ	552	P → G: Changed glutamate-gated calcium ion channel activity characterized by accelerated response activation time and increased desensitization. 1 Publication	1
Mutagenesisⁱ	552	P → I: Changed glutamate-gated calcium ion channel activity characterized by increased desensitization. 1 Publication	1
Mutagenesisⁱ	552	P → K: Changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency with delay in rise time and slower deactivation time course. 1 Publication	1
Mutagenesisⁱ	552	P → L: No effect on localization to the cell membrane. Changed glutamate-gated calcium ion channel activity characterized by increased desensitization. 1 Publication	1
Mutagenesisⁱ	552	P → Q: No effect on localization to the cell membrane. Changed glutamate-gated calcium ion channel activity characterized by decreased response amplitude and changed desensitization without effect on response rise time or deactivation time course. 1 Publication	1

Keywords - Diseaseⁱ

Disease mutation, Epilepsy

Organism-specific databases

DisGeNET More...DisGeNETⁱ	2903
GeneReviewsⁱ	GRIN2A
MalaCards human disease database More...MalaCardsⁱ	GRIN2A
MIMⁱ	245570 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000183454
Orphanetⁱ	725 Continuous spikes and waves during sleep 289266 Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation 98818 Landau-Kleffner syndrome 1945 Rolandic epilepsy 163721 Rolandic epilepsy-speech dyspraxia syndrome
PharmGKBⁱ	PA28979

Chemistry databases

ChEMBLⁱ	CHEMBL1972
Drug and drug target database More...DrugBankⁱ	DB00659 Acamprosate DB06151 Acetylcysteine DB00289 Atomoxetine DB00949 Felbamate DB00996 Gabapentin DB06741 Gavestinel DB00145 Glycine DB01159 Halothane DB06738 Ketobemidone DB00142 L-Glutamic Acid DB01043 Memantine DB04896 Milnacipran DB00312 Pentobarbital DB00454 Pethidine DB01174 Phenobarbital DB01708 Prasterone DB00418 Secobarbital DB01520 Tenocyclidine
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	456

Polymorphism and mutation databases

BioMutaⁱ	GRIN2A
DMDMⁱ	14285603

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 22	Sequence analysisAdd BLAST		22
ChainⁱPRO_0000011573	23 – 1464	Glutamate receptor ionotropic, NMDA 2AAdd BLAST		1442

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Glycosylationⁱ	75	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	87 ↔ 320	By similarity
Glycosylationⁱ	340	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	380	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	429 ↔ 455	Combined sources3 Publications
Disulfide bondⁱ	436 ↔ 456	Combined sources3 Publications
Glycosylationⁱ	443	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	444	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	541	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	745 ↔ 800	By similarity
Modified residueⁱ	882	PhosphoserineBy similarity	1
Modified residueⁱ	890	PhosphoserineBy similarity	1
Modified residueⁱ	929	PhosphoserineBy similarity	1
Modified residueⁱ	1025	PhosphoserineBy similarity	1
Modified residueⁱ	1059	PhosphoserineBy similarity	1
Modified residueⁱ	1062	PhosphoserineBy similarity	1
Modified residueⁱ	1198	PhosphoserineBy similarity	1
Modified residueⁱ	1291	PhosphoserineBy similarity	1

Keywords - PTMⁱ

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

jPOSTⁱ	Q12879
PaxDbⁱ	Q12879
PeptideAtlas More...PeptideAtlasⁱ	Q12879
PRIDEⁱ	Q12879
ProteomicsDBⁱ	58998 [Q12879-1] 61175

PTM databases

iPTMnetⁱ	Q12879
PhosphoSitePlusⁱ	Q12879

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000183454 Expressed in 135 organ(s), highest expression level in primary visual cortex
ExpressionAtlasⁱ	Q12879 baseline and differential
Genevisibleⁱ	Q12879 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB022725

HPAⁱ

CAB022725

Interactionⁱ

Subunit structureⁱ

Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:8768735, PubMed:26919761, PubMed:26875626, PubMed:28105280). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B. 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 (By similarity).

Interacts with AIP1 (By similarity).

Interacts with HIP1 and NETO1.

Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (By similarity).

Interacts with PDZ domains of PATJ and DLG4.

Interacts with LRFN2 (By similarity).

Interacts with RPH3A and DLG4; this ternary complex regulates NMDA receptor composition at postsynaptic membranes (By similarity).

Interacts with SORCS2 (By similarity).

Interacts with ARC; preventing ARC oligomerization (By similarity).

By similarity4 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
Dlg3	Q62936	5	EBI-7249937,EBI-349596	From Rattus norvegicus.
DLG4	P78352	5	EBI-7249937,EBI-80389
Dlg4	P31016	2	EBI-7249937,EBI-375655	From Rattus norvegicus.
LRP1	Q07954	2	EBI-7249937,EBI-1046087

Protein-protein interaction databases

BioGridⁱ	109160, 49 interactors
ComplexPortalⁱ	CPX-2202 NMDA receptor complex, GluN1-GluN2A CPX-294 NMDA receptor complex, GluN1-GluN2A-GluN2B
CORUMⁱ	Q12879
Database of interacting proteins More...DIPⁱ	DIP-40798N
IntActⁱ	Q12879, 6 interactors
Molecular INTeraction database More...MINTⁱ	Q12879
STRINGⁱ	9606.ENSP00000379818

Chemistry databases

BindingDBⁱ	Q12879

BindingDBⁱ

Q12879

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	405 – 410	Combined sources	6
Turnⁱ	414 – 416	Combined sources	3
Beta strandⁱ	417 – 421	Combined sources	5
Turnⁱ	424 – 426	Combined sources	3
Beta strandⁱ	434 – 442	Combined sources	9
Beta strandⁱ	449 – 458	Combined sources	10
Helixⁱ	459 – 471	Combined sources	13
Beta strandⁱ	474 – 479	Combined sources	6
Beta strandⁱ	482 – 485	Combined sources	4
Beta strandⁱ	487 – 489	Combined sources	3
Beta strandⁱ	492 – 494	Combined sources	3
Helixⁱ	495 – 501	Combined sources	7
Beta strandⁱ	506 – 508	Combined sources	3
Helixⁱ	516 – 519	Combined sources	4
Beta strandⁱ	522 – 524	Combined sources	3
Beta strandⁱ	528 – 538	Combined sources	11
Helixⁱ	668 – 671	Combined sources	4
Helixⁱ	673 – 675	Combined sources	3
Beta strandⁱ	676 – 678	Combined sources	3
Beta strandⁱ	686 – 688	Combined sources	3
Helixⁱ	689 – 697	Combined sources	9
Helixⁱ	699 – 705	Combined sources	7
Helixⁱ	706 – 708	Combined sources	3
Helixⁱ	713 – 721	Combined sources	9
Beta strandⁱ	726 – 731	Combined sources	6
Helixⁱ	732 – 740	Combined sources	9
Helixⁱ	743 – 745	Combined sources	3
Beta strandⁱ	747 – 750	Combined sources	4
Turnⁱ	751 – 753	Combined sources	3
Beta strandⁱ	756 – 761	Combined sources	6
Beta strandⁱ	764 – 766	Combined sources	3
Helixⁱ	772 – 784	Combined sources	13
Helixⁱ	787 – 795	Combined sources	9
Beta strandⁱ	1461 – 1464	Combined sources	4

Show more details

3D structure databases

SMRⁱ	Q12879
ModBaseⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q12879

EvolutionaryTraceⁱ

Q12879

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	511 – 513	Glutamate bindingCombined sources3 Publications	3
Regionⁱ	599 – 620	Pore-formingBy similarityAdd BLAST	22
Regionⁱ	689 – 690	Glutamate bindingBy similarity	2
Regionⁱ	730 – 731	Glutamate bindingBy similarity	2

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	1462 – 1464	PDZ-bindingCurated		3

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

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

Keywords - Domainⁱ

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG1053 Eukaryota ENOG410XNUR LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000156222
HOGENOMⁱ	HOG000113802
InParanoidⁱ	Q12879
KEGG Orthology (KO) More...KOⁱ	K05209
OMAⁱ	HHSHSAE
Database of Orthologous Groups More...OrthoDBⁱ	188544at2759
PhylomeDBⁱ	Q12879
TreeFamⁱ	TF314731

Family and domain databases

InterProⁱ	View 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
Pfam protein domain database More...Pfamⁱ	View 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
PRINTSⁱ	PR00177 NMDARECEPTOR
SMARTⁱ	View protein in SMART SM00918 Lig_chan-Glu_bd, 1 hit SM00079 PBPe, 1 hit
SUPFAMⁱ	SSF53822 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. Align Add to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: Q12879-1) [UniParc]FASTA Add to basket

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

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        10         20         30         40         50
MGRVGYWTLL VLPALLVWRG PAPSAAAEKG PPALNIAVML GHSHDVTERE 
        60         70         80         90        100
LRTLWGPEQA AGLPLDVNVV ALLMNRTDPK SLITHVCDLM SGARIHGLVF 
       110        120        130        140        150
GDDTDQEAVA QMLDFISSHT FVPILGIHGG ASMIMADKDP TSTFFQFGAS 
       160        170        180        190        200
IQQQATVMLK IMQDYDWHVF SLVTTIFPGY REFISFVKTT VDNSFVGWDM 
       210        220        230        240        250
QNVITLDTSF EDAKTQVQLK KIHSSVILLY CSKDEAVLIL SEARSLGLTG 
       260        270        280        290        300
YDFFWIVPSL VSGNTELIPK EFPSGLISVS YDDWDYSLEA RVRDGIGILT 
       310        320        330        340        350
TAASSMLEKF SYIPEAKASC YGQMERPEVP MHTLHPFMVN VTWDGKDLSF 
       360        370        380        390        400
TEEGYQVHPR LVVIVLNKDR EWEKVGKWEN HTLSLRHAVW 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 KGVEDALVSL 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
AKNISSMSNM NSSRMDSPKR AADFIQRGSL IMDMVSDKGN LMYSDNRSFQ 
       960        970        980        990       1000
GKESIFGDNM NELQTFVANR QKDNLNNYVF QGQHPLTLNE SNPNTVEVAV 
      1010       1020       1030       1040       1050
STESKANSRP RQLWKKSVDS IRQDSLSQNP VSQRDEATAE NRTHSLKSPR 
      1060       1070       1080       1090       1100
YLPEEMAHSD ISETSNRATC HREPDNSKNH KTKDNFKRSV ASKYPKDCSE 
      1110       1120       1130       1140       1150
VERTYLKTKS SSPRDKIYTI DGEKEPGFHL DPPQFVENVT LPENVDFPDP 
      1160       1170       1180       1190       1200
YQDPSENFRK GDSTLPMNRN PLHNEEGLSN NDQYKLYSKH FTLKDKGSPH 
      1210       1220       1230       1240       1250
SETSERYRQN STHCRSCLSN MPTYSGHFTM RSPFKCDACL RMGNLYDIDE 
      1260       1270       1280       1290       1300
DQMLQETGNP ATGEQVYQQD WAQNNALQLQ KNKLRISRQH SYDNIVDKPR 
      1310       1320       1330       1340       1350
ELDLSRPSRS ISLKDRERLL EGNFYGSLFS VPSSKLSGKK SSLFPQGLED 
      1360       1370       1380       1390       1400
SKRSKSLLPD HTSDNPFLHS HRDDQRLVIG RCPSDPYKHS LPSQAVNDSY 
      1410       1420       1430       1440       1450
LRSSLRSTAS YCSRDSRGHN DVYISEHVMP YAANKNNMYS TPRVLNSCSN 
      1460 
RRVYKKMPSI ESDV

Length:1,464

Mass (Da):165,283

Last modified:November 1, 1996 - v1

Checksum:ⁱAF5EDD599EC0B1E3

Isoform 2 (identifier: Q12879-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1259-1464: NPATGEQVYQ...KKMPSIESDV → MTNAWLLGDAPRTLTNTRCHPRR

« Hide

        10         20         30         40         50
MGRVGYWTLL VLPALLVWRG PAPSAAAEKG PPALNIAVML GHSHDVTERE 
        60         70         80         90        100
LRTLWGPEQA AGLPLDVNVV ALLMNRTDPK SLITHVCDLM SGARIHGLVF 
       110        120        130        140        150
GDDTDQEAVA QMLDFISSHT FVPILGIHGG ASMIMADKDP TSTFFQFGAS 
       160        170        180        190        200
IQQQATVMLK IMQDYDWHVF SLVTTIFPGY REFISFVKTT VDNSFVGWDM 
       210        220        230        240        250
QNVITLDTSF EDAKTQVQLK KIHSSVILLY CSKDEAVLIL SEARSLGLTG 
       260        270        280        290        300
YDFFWIVPSL VSGNTELIPK EFPSGLISVS YDDWDYSLEA RVRDGIGILT 
       310        320        330        340        350
TAASSMLEKF SYIPEAKASC YGQMERPEVP MHTLHPFMVN VTWDGKDLSF 
       360        370        380        390        400
TEEGYQVHPR LVVIVLNKDR EWEKVGKWEN HTLSLRHAVW 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 KGVEDALVSL 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
AKNISSMSNM NSSRMDSPKR AADFIQRGSL IMDMVSDKGN LMYSDNRSFQ 
       960        970        980        990       1000
GKESIFGDNM NELQTFVANR QKDNLNNYVF QGQHPLTLNE SNPNTVEVAV 
      1010       1020       1030       1040       1050
STESKANSRP RQLWKKSVDS IRQDSLSQNP VSQRDEATAE NRTHSLKSPR 
      1060       1070       1080       1090       1100
YLPEEMAHSD ISETSNRATC HREPDNSKNH KTKDNFKRSV ASKYPKDCSE 
      1110       1120       1130       1140       1150
VERTYLKTKS SSPRDKIYTI DGEKEPGFHL DPPQFVENVT LPENVDFPDP 
      1160       1170       1180       1190       1200
YQDPSENFRK GDSTLPMNRN PLHNEEGLSN NDQYKLYSKH FTLKDKGSPH 
      1210       1220       1230       1240       1250
SETSERYRQN STHCRSCLSN MPTYSGHFTM RSPFKCDACL RMGNLYDIDE 
      1260       1270       1280 
DQMLQETGMT NAWLLGDAPR TLTNTRCHPR R

Show »

Length:1,281

Mass (Da):144,431

Checksum:ⁱ7454CF24F5BE8373

Computationally mapped potential isoform sequencesⁱ

There are 4 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

F5GZ52	F5GZ52_HUMAN	Glutamate receptor ionotropic, NMDA... Glutamate receptor ionotropic, NMDA 2A	GRIN2A	1,144	Annotation score:
A0A1B0GUT1	A0A1B0GUT1_HUMAN	Glutamate receptor ionotropic, NMDA... Glutamate receptor ionotropic, NMDA 2A	GRIN2A	200	Annotation score:
A0A1B0GVW1	A0A1B0GVW1_HUMAN	Glutamate receptor ionotropic, NMDA... Glutamate receptor ionotropic, NMDA 2A	GRIN2A	19	Annotation score:
A0A1B0GU35	A0A1B0GU35_HUMAN	Glutamate receptor ionotropic, NMDA... Glutamate receptor ionotropic, NMDA 2A	GRIN2A	10	Annotation score:

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_067725	57	P → L Found in a cutaneous malignant melanoma sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_070345	79	P → R in FESD. 1 PublicationCorresponds to variant dbSNP:rs1250662891EnsemblClinVar.	1
Natural variantⁱVAR_079929	143	T → I Found in a patient with autism spectrum disorder; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_067726	183	F → I Found in a cutaneous malignant melanoma sample; somatic mutation; also found in a patient with benign epilepsy with centrotemporal spike. 2 PublicationsCorresponds to variant dbSNP:rs587780353EnsemblClinVar.	1
Natural variantⁱVAR_070346	184	I → S in FESD; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_079930	189	T → N Found in a patient with schizophrenia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1377082706Ensembl.	1
Natural variantⁱVAR_070347	231	C → Y in FESD; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_070348	243	A → V in FESD; results in reduced high-affinity zinc mediated inhibition. 1 Publication	1
Natural variantⁱVAR_067727	252	D → N Found in a cutaneous malignant melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs868215122Ensembl.	1
Natural variantⁱVAR_010938	270	K → E1 Publication	1
Natural variantⁱVAR_067728	278	S → F Found in a cutaneous malignant melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs148531310Ensembl.	1
Natural variantⁱVAR_070349	290	A → V in FESD. 1 PublicationCorresponds to variant dbSNP:rs199528312EnsemblClinVar.	1
Natural variantⁱVAR_070350	295	G → S in FESD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs568484876EnsemblClinVar.	1
Natural variantⁱVAR_079931	336	P → S1 PublicationCorresponds to variant dbSNP:rs148511104EnsemblClinVar.	1
Natural variantⁱVAR_071624	349	S → F Found in a cutaneous malignant melanoma sample. 1 Publication	1
Natural variantⁱVAR_070351	370	R → W in FESD. 1 PublicationCorresponds to variant dbSNP:rs761168789Ensembl.	1
Natural variantⁱVAR_067729	371	E → K Found in a cutaneous malignant melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs149344082Ensembl.	1
Natural variantⁱVAR_067730	373	E → K Found in a cutaneous malignant melanoma sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_078109	380	N → D Found in a patient with neonatal onset epileptic encephalopathy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057519551EnsemblClinVar.	1
Natural variantⁱVAR_070352	436	C → R in FESD; decreased protein abundance; loss of localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency and decreased glycine potency. 2 PublicationsCorresponds to variant dbSNP:rs1555496111EnsemblClinVar.	1
Natural variantⁱVAR_067731	449	G → E Found in a cutaneous malignant melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs139033056Ensembl.	1
Natural variantⁱVAR_079932	452	V → M No effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency. 2 PublicationsCorresponds to variant dbSNP:rs145956175EnsemblClinVar.	1
Natural variantⁱVAR_067732	459	F → S Found in a cutaneous malignant melanoma sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_070353	483	G → R in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency. 2 Publications	1
Natural variantⁱVAR_070354	504	R → W in FESD; decreased protein abundance; decreased localization to the cell membrane; no significant effect on calcium ion transmembrane import into cytosol. 2 PublicationsCorresponds to variant dbSNP:rs1360906241Ensembl.	1
Natural variantⁱVAR_079933	506	V → A in FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency. 1 PublicationCorresponds to variant dbSNP:rs796052543EnsemblClinVar.	1
Natural variantⁱVAR_070355	518	R → H in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by affected receptor kinetics. 2 PublicationsCorresponds to variant dbSNP:rs397518470EnsemblClinVar.	1
Natural variantⁱVAR_070356	531	T → M in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by affected receptor kinetics. 2 PublicationsCorresponds to variant dbSNP:rs397518468EnsemblClinVar.	1
Natural variantⁱVAR_070357	547	Missing in FESD. 1 Publication	1
Natural variantⁱVAR_070358	548	A → T in FESD; no effect on localization to the cell membrane; loss of glutamate-gated calcium ion channel activity. 2 Publications	1
Natural variantⁱVAR_069382	552	P → R in FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency with delay in rise time and slower deactivation time course. 2 PublicationsCorresponds to variant dbSNP:rs397518450EnsemblClinVar.	1
Natural variantⁱVAR_079934	576	F → S1 Publication	1
Natural variantⁱVAR_067733	595	H → R Found in a cutaneous malignant melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs551688681Ensembl.	1
Natural variantⁱVAR_067734	598	S → F Found in a cutaneous malignant melanoma sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_065899	615	N → K in FESD; the mutant receptor has decreased calcium permeability; shows a dominant-negative effect. 1 PublicationCorresponds to variant dbSNP:rs397518447EnsemblClinVar.	1
Natural variantⁱVAR_069383	649	L → V in FESD. 1 PublicationCorresponds to variant dbSNP:rs397514557EnsemblClinVar.	1
Natural variantⁱVAR_070359	652	F → V in FESD; affects receptor kinetics. 1 PublicationCorresponds to variant dbSNP:rs397518471EnsemblClinVar.	1
Natural variantⁱVAR_067735	653	M → I Found in a cutaneous malignant melanoma sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_070360	669	K → N in FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency. 2 Publications	1
Natural variantⁱVAR_079935	685	V → G in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency. 1 PublicationCorresponds to variant dbSNP:rs796052548EnsemblClinVar.	1
Natural variantⁱVAR_070361	694	I → T in FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and decreased open probability. 2 Publications	1
Natural variantⁱVAR_070362	699	P → S in FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency and decreased open probability. 2 PublicationsCorresponds to variant dbSNP:rs1555491648EnsemblClinVar.	1
Natural variantⁱVAR_070363	705	M → V in FESD; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and decreased open probability. 2 Publications

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UniProtKB - Q12879 (NMDE1_HUMAN)

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Glutamate receptor ionotropic, NMDA 2A

GRIN2A

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