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Protein

Glutamate receptor ionotropic, NMDA 2B

Gene

GRIN2B

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:28126851). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:8768735, PubMed:26875626). In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity (By similarity).By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi127ZincBy similarity1
Metal bindingi284ZincBy similarity1
Binding sitei514GlutamateBy similarity1
Binding sitei519GlutamateBy similarity1
Sitei615Functional determinant of NMDA receptorsBy similarity1
Binding sitei732GlutamateBy similarity1

GO - Molecular functioni

  • extracellularly glutamate-gated ion channel activity Source: InterPro
  • glutamate binding Source: UniProtKB
  • glutamate-gated calcium ion channel activity Source: UniProtKB
  • glycine binding Source: UniProtKB
  • NMDA glutamate receptor activity Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • brain development Source: ARUK-UCL
  • calcium ion transmembrane import into cytosol Source: UniProtKB
  • chemical synaptic transmission Source: ProtInc
  • ephrin receptor signaling pathway Source: Reactome
  • excitatory chemical synaptic transmission Source: ARUK-UCL
  • glutamate receptor signaling pathway Source: ProtInc
  • learning or memory Source: ARUK-UCL
  • MAPK cascade Source: Reactome
  • multicellular organism development Source: ARUK-UCL
  • negative regulation of dendritic spine maintenance Source: ARUK-UCL
  • positive regulation of cysteine-type endopeptidase activity Source: ARUK-UCL
  • positive regulation of neuron death Source: ARUK-UCL
  • protein heterotetramerization Source: UniProtKB
  • regulation of synaptic plasticity Source: ARUK-UCL
  • response to ethanol Source: UniProtKB

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-3928662 EPHB-mediated forward signaling
R-HSA-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-HSA-442729 CREB phosphorylation through the activation of CaMKII
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6794361 Neurexins and neuroligins
R-HSA-8849932 Synaptic adhesion-like molecules
R-HSA-9032500 Activated NTRK2 signals through FYN
SignaLinkiQ13224
SIGNORiQ13224

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate receptor ionotropic, NMDA 2B
Short name:
GluN2B
Alternative name(s):
Glutamate [NMDA] receptor subunit epsilon-2
N-methyl D-aspartate receptor subtype 2B
Short name:
NMDAR2B1 Publication
Short name:
NR2B
N-methyl-D-aspartate receptor subunit 3
Short name:
NR3
Short name:
hNR31 Publication
Gene namesi
Name:GRIN2B
Synonyms:NMDAR2B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000273079.4
HGNCiHGNC:4586 GRIN2B
MIMi138252 gene
neXtProtiNX_Q13224

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 domaini27 – 557ExtracellularBy similarityAdd BLAST531
Transmembranei558 – 576HelicalBy similarityAdd BLAST19
Topological domaini577 – 603CytoplasmicBy similarityAdd BLAST27
Intramembranei604 – 623Discontinuously helicalBy similarityAdd BLAST20
Topological domaini624 – 630CytoplasmicBy similarity7
Transmembranei631 – 646HelicalBy similarityAdd BLAST16
Topological domaini647 – 817ExtracellularBy similarityAdd BLAST171
Transmembranei818 – 837HelicalBy similarityAdd BLAST20
Topological domaini838 – 1484CytoplasmicBy similarityAdd BLAST647

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Mental retardation, autosomal dominant 6, with or without seizures (MRD6)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD6 additional features may include seizures, hypotonia, abnormal movements, such as dystonia, and autistic features.
See also OMIM:613970
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079947413E → G in MRD6; 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:rs527236034EnsemblClinVar.1
Natural variantiVAR_079948436C → R in MRD6; decreased protein abundance; decreased localization to the cell membrane. 1 Publication1
Natural variantiVAR_076764456C → Y in MRD6; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency and increased open probability. 2 PublicationsCorresponds to variant dbSNP:rs397514555EnsemblClinVar.1
Natural variantiVAR_079949461C → F in MRD6; decreased protein abundance; decreased localization to the cell membrane; decreased glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and increased glycine potency. 1 Publication1
Natural variantiVAR_069384553P → L in MRD6; no effect on localization to the cell membrane; loss of glutamate-gated calcium ion channel activity. 2 PublicationsCorresponds to variant dbSNP:rs397514556EnsemblClinVar.1
Natural variantiVAR_065900682R → C in MRD6; decreased protein abundance; no effect on localization to the cell membrane; no significant effect on calcium ion transmembrane import into cytosol; analysis of agonist dose-response curves for glutamate and glycine are not consistent. 2 PublicationsCorresponds to variant dbSNP:rs387906636EnsemblClinVar.1
Natural variantiVAR_079950696R → H in MRD6; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency. 1 Publication1
Natural variantiVAR_078647820G → E in MRD6. 1 Publication1
Epileptic encephalopathy, early infantile, 27 (EIEE27)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent.
See also OMIM:616139
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07823515V → M in EIEE27; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057519553Ensembl.1
Natural variantiVAR_072663540R → H in EIEE27; decreased protein abundance; decreased localization to the cell membrane; increased glutamate-gated calcium ion channel activity via an allosteric effect which is characterized by increased glutamate and glycine potency and increased open probability; the mutant channel is less sensitive to magnesium inhibition and has increased calcium permeability compared to wild-type. 2 PublicationsCorresponds to variant dbSNP:rs672601378EnsemblClinVar.1
Natural variantiVAR_072664615N → I in EIEE27; severe phenotype with early onset seizures; gain of function mutation; results in neuronal hyperexcitability; the mutant channel is not inhibited by magnesium and has increased calcium permeability compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs672601377EnsemblClinVar.1
Natural variantiVAR_072665618V → G in EIEE27; severe phenotype with early onset seizures; gain of function mutation; results in neuronal hyperexcitability; the mutant channel is not inhibited by magnesium and has increased calcium permeability compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs672601376EnsemblClinVar.1
A chromosomal aberrations involving GRIN2B has been found in patients with mental retardation. Translocations t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint in 12p13.1.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi553P → R: Changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency and slowed response rise time and deactivation time course. 1 Publication1
Mutagenesisi818M → V: Increased glutamate and glycine agonist potency. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation

Organism-specific databases

DisGeNETi2904
MalaCardsiGRIN2B
MIMi613970 phenotype
616139 phenotype
OpenTargetsiENSG00000273079
Orphaneti178469 Autosomal dominant non-syndromic intellectual disability
3451 West syndrome
PharmGKBiPA28980

Chemistry databases

ChEMBLiCHEMBL1904
DrugBankiDB00659 Acamprosate
DB06151 Acetylcysteine
DB00289 Atomoxetine
DB00949 Felbamate
DB00996 Gabapentin
DB06741 Gavestinel
DB00502 Haloperidol
DB08954 Ifenprodil
DB06738 Ketobemidone
DB00142 L-Glutamic Acid
DB01043 Memantine
DB04896 Milnacipran
DB00312 Pentobarbital
DB00454 Pethidine
DB01174 Phenobarbital
DB01708 Prasterone
DB00418 Secobarbital
DB01520 Tenocyclidine

Polymorphism and mutation databases

BioMutaiGRIN2B
DMDMi14548162

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000001157727 – 1484Glutamate receptor ionotropic, NMDA 2BAdd BLAST1458

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi74N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi86 ↔ 321By similarity
Glycosylationi341N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi348N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi429 ↔ 456By similarity
Disulfide bondi436 ↔ 457By similarity
Glycosylationi444N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi491N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi542N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi688N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi746 ↔ 801By similarity
Modified residuei882PhosphoserineBy similarity1
Modified residuei886PhosphoserineBy similarity1
Modified residuei917PhosphoserineBy similarity1
Modified residuei920PhosphoserineBy similarity1
Modified residuei962PhosphotyrosineBy similarity1
Modified residuei1039PhosphotyrosineBy similarity1
Modified residuei1058PhosphoserineBy similarity1
Modified residuei1061PhosphoserineBy similarity1
Modified residuei1064PhosphoserineBy similarity1
Modified residuei1109PhosphotyrosineBy similarity1
Modified residuei1133PhosphotyrosineBy similarity1
Modified residuei1143PhosphoserineBy similarity1
Modified residuei1155PhosphotyrosineBy similarity1
Modified residuei1255PhosphoserineBy similarity1
Modified residuei1259PhosphoserineBy similarity1
Modified residuei1303Phosphoserine; by DAPK1By similarity1
Modified residuei1474PhosphotyrosineBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residues (By similarity). Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ13224
PeptideAtlasiQ13224
PRIDEiQ13224
ProteomicsDBi59232

PTM databases

iPTMnetiQ13224
PhosphoSitePlusiQ13224

Expressioni

Tissue specificityi

Primarily found in the fronto-parieto-temporal cortex and hippocampus pyramidal cells, lower expression in the basal ganglia.1 Publication

Gene expression databases

BgeeiENSG00000273079
CleanExiHS_GRIN2B
ExpressionAtlasiQ13224 baseline and differential
GenevisibleiQ13224 HS

Organism-specific databases

HPAiHPA069762

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:28126851, PubMed:26912815). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (By similarity). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Found in a complex with GRIN1 and GRIN3B. Found in a complex with GRIN1, GRIN3A and PPP2CB. Interacts with PDZ domains of PATJ, DLG3 and DLG4. Interacts with HIP1 and NETO1 (By similarity). Interacts with MAGI3 (PubMed:10748157). Interacts with DAPK1 (By similarity). Found in a complex with GRIN1 and PRR7 (PubMed:27458189). Interacts with PRR7 (PubMed:27458189).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109161, 26 interactors
ComplexPortaliCPX-285 NMDA receptor complex, GluN1-GluN2B
CPX-294 NMDA receptor complex, GluN1-GluN2A-GluN2B
DIPiDIP-41002N
IntActiQ13224, 15 interactors
MINTiQ13224
STRINGi9606.ENSP00000279593

Chemistry databases

BindingDBiQ13224

Structurei

Secondary structure

11484
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi34 – 44Combined sources11
Helixi47 – 50Combined sources4
Beta strandi62 – 73Combined sources12
Helixi78 – 91Combined sources14
Beta strandi94 – 100Combined sources7
Helixi107 – 119Combined sources13
Beta strandi123 – 127Combined sources5
Helixi128 – 131Combined sources4
Beta strandi143 – 147Combined sources5
Helixi150 – 164Combined sources15
Beta strandi168 – 173Combined sources6
Helixi179 – 191Combined sources13
Beta strandi193 – 195Combined sources3
Beta strandi198 – 204Combined sources7
Helixi215 – 221Combined sources7
Beta strandi226 – 232Combined sources7
Helixi234 – 246Combined sources13
Beta strandi255 – 258Combined sources4
Helixi260 – 263Combined sources4
Beta strandi278 – 282Combined sources5
Turni284 – 286Combined sources3
Helixi289 – 311Combined sources23
Beta strandi321 – 323Combined sources3
Helixi324 – 327Combined sources4
Helixi328 – 330Combined sources3
Helixi336 – 339Combined sources4
Beta strandi355 – 359Combined sources5
Beta strandi362 – 367Combined sources6
Beta strandi373 – 379Combined sources7
Beta strandi384 – 387Combined sources4

3D structure databases

ProteinModelPortaliQ13224
SMRiQ13224
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni604 – 623Pore-formingBy similarityAdd BLAST20
Regioni690 – 691Glutamate bindingBy similarity2
Regioni1292 – 1304Interaction with DAPK1By similarityAdd BLAST13

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1482 – 1484PDZ-bindingBy similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi984 – 989Poly-His6
Compositional biasi1361 – 1364Poly-His4

Domaini

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
GeneTreeiENSGT00910000143978
HOGENOMiHOG000113802
HOVERGENiHBG052635
InParanoidiQ13224
KOiK05210
OMAiRNNYPEM
OrthoDBiEOG091G09KH
PhylomeDBiQ13224
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.

Q13224-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKPRAECCSP KFWLVLAVLA VSGSRARSQK SPPSIGIAVI LVGTSDEVAI
60 70 80 90 100
KDAHEKDDFH HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVFA
110 120 130 140 150
DDTDQEAIAQ ILDFISAQTL TPILGIHGGS SMIMADKDES SMFFQFGPSI
160 170 180 190 200
EQQASVMLNI MEEYDWYIFS IVTTYFPGYQ DFVNKIRSTI ENSFVGWELE
210 220 230 240 250
EVLLLDMSLD DGDSKIQNQL KKLQSPIILL YCTKEEATYI FEVANSVGLT
260 270 280 290 300
GYGYTWIVPS LVAGDTDTVP AEFPTGLISV SYDEWDYGLP ARVRDGIAII
310 320 330 340 350
TTAASDMLSE HSFIPEPKSS CYNTHEKRIY QSNMLNRYLI NVTFEGRNLS
360 370 380 390 400
FSEDGYQMHP KLVIILLNKE RKWERVGKWK DKSLQMKYYV WPRMCPETEE
410 420 430 440 450
QEDDHLSIVT LEEAPFVIVE SVDPLSGTCM RNTVPCQKRI VTENKTDEEP
460 470 480 490 500
GYIKKCCKGF CIDILKKISK SVKFTYDLYL VTNGKHGKKI NGTWNGMIGE
510 520 530 540 550
VVMKRAYMAV GSLTINEERS EVVDFSVPFI ETGISVMVSR SNGTVSPSAF
560 570 580 590 600
LEPFSADVWV MMFVMLLIVS AVAVFVFEYF SPVGYNRCLA DGREPGGPSF
610 620 630 640 650
TIGKAIWLLW GLVFNNSVPV QNPKGTTSKI MVSVWAFFAV IFLASYTANL
660 670 680 690 700
AAFMIQEEYV DQVSGLSDKK FQRPNDFSPP FRFGTVPNGS TERNIRNNYA
710 720 730 740 750
EMHAYMGKFN QRGVDDALLS LKTGKLDAFI YDAAVLNYMA GRDEGCKLVT
760 770 780 790 800
IGSGKVFAST GYGIAIQKDS GWKRQVDLAI LQLFGDGEME ELEALWLTGI
810 820 830 840 850
CHNEKNEVMS SQLDIDNMAG VFYMLGAAMA LSLITFICEH LFYWQFRHCF
860 870 880 890 900
MGVCSGKPGM VFSISRGIYS CIHGVAIEER QSVMNSPTAT MNNTHSNILR
910 920 930 940 950
LLRTAKNMAN LSGVNGSPQS ALDFIRRESS VYDISEHRRS FTHSDCKSYN
960 970 980 990 1000
NPPCEENLFS DYISEVERTF GNLQLKDSNV YQDHYHHHHR PHSIGSASSI
1010 1020 1030 1040 1050
DGLYDCDNPP FTTQSRSISK KPLDIGLPSS KHSQLSDLYG KFSFKSDRYS
1060 1070 1080 1090 1100
GHDDLIRSDV SDISTHTVTY GNIEGNAAKR RKQQYKDSLK KRPASAKSRR
1110 1120 1130 1140 1150
EFDEIELAYR RRPPRSPDHK RYFRDKEGLR DFYLDQFRTK ENSPHWEHVD
1160 1170 1180 1190 1200
LTDIYKERSD DFKRDSVSGG GPCTNRSHIK HGTGDKHGVV SGVPAPWEKN
1210 1220 1230 1240 1250
LTNVEWEDRS GGNFCRSCPS KLHNYSTTVT GQNSGRQACI RCEACKKAGN
1260 1270 1280 1290 1300
LYDISEDNSL QELDQPAAPV AVTSNASTTK YPQSPTNSKA QKKNRNKLRR
1310 1320 1330 1340 1350
QHSYDTFVDL QKEEAALAPR SVSLKDKGRF MDGSPYAHMF EMSAGESTFA
1360 1370 1380 1390 1400
NNKSSVPTAG HHHHNNPGGG YMLSKSLYPD RVTQNPFIPT FGDDQCLLHG
1410 1420 1430 1440 1450
SKSYFFRQPT VAGASKARPD FRALVTNKPV VSALHGAVPA RFQKDICIGN
1460 1470 1480
QSNPCVPNNK NPRAFNGSSN GHVYEKLSSI ESDV
Length:1,484
Mass (Da):166,367
Last modified:June 20, 2001 - v3
Checksum:i40AEB12BE6E50CEF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti434V → A in AAD00659 (Ref. 3) Curated1
Sequence conflicti745G → A in AAA69920 (PubMed:7959773).Curated1
Sequence conflicti773K → N in AAA69920 (PubMed:7959773).Curated1
Sequence conflicti773K → N in AAA74930 (PubMed:7959773).Curated1
Sequence conflicti796W → C in AAA69920 (PubMed:7959773).Curated1
Sequence conflicti796W → C in AAA74930 (PubMed:7959773).Curated1
Sequence conflicti888T → P in AAA69920 (PubMed:7959773).Curated1
Sequence conflicti888T → P in AAA74930 (PubMed:7959773).Curated1
Sequence conflicti902L → V in AAA69920 (PubMed:7959773).Curated1
Sequence conflicti902L → V in AAA74930 (PubMed:7959773).Curated1
Sequence conflicti920 – 921SA → RP in AAB60368 (PubMed:7999784).Curated2
Sequence conflicti958L → S in AAA69920 (PubMed:7959773).Curated1
Sequence conflicti958L → S in AAA74930 (PubMed:7959773).Curated1
Sequence conflicti980 – 982VYQ → DHY in AAA69920 (PubMed:7959773).Curated3
Sequence conflicti1056I → M in AAA69920 (PubMed:7959773).Curated1
Sequence conflicti1167V → I in AAB49993 (PubMed:8768735).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07823515V → M in EIEE27; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1057519553Ensembl.1
Natural variantiVAR_07994318V → I1 PublicationCorresponds to variant dbSNP:rs201094029EnsemblClinVar.1
Natural variantiVAR_07994450I → N Found in a patient with schizophrenia; unknown pathological significance. 1 Publication1
Natural variantiVAR_079945271A → V1 PublicationCorresponds to variant dbSNP:rs138098032EnsemblClinVar.1
Natural variantiVAR_079946362L → M Found in a patient with schizophrenia; unknown pathological significance. 1 Publication1
Natural variantiVAR_011317407S → N1 Publication1
Natural variantiVAR_079947413E → G in MRD6; 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:rs527236034EnsemblClinVar.1
Natural variantiVAR_079948436C → R in MRD6; decreased protein abundance; decreased localization to the cell membrane. 1 Publication1
Natural variantiVAR_076764456C → Y in MRD6; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency and increased open probability. 2 PublicationsCorresponds to variant dbSNP:rs397514555EnsemblClinVar.1
Natural variantiVAR_079949461C → F in MRD6; decreased protein abundance; decreased localization to the cell membrane; decreased glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and increased glycine potency. 1 Publication1
Natural variantiVAR_072663540R → H in EIEE27; decreased protein abundance; decreased localization to the cell membrane; increased glutamate-gated calcium ion channel activity via an allosteric effect which is characterized by increased glutamate and glycine potency and increased open probability; the mutant channel is less sensitive to magnesium inhibition and has increased calcium permeability compared to wild-type. 2 PublicationsCorresponds to variant dbSNP:rs672601378EnsemblClinVar.1
Natural variantiVAR_069384553P → L in MRD6; no effect on localization to the cell membrane; loss of glutamate-gated calcium ion channel activity. 2 PublicationsCorresponds to variant dbSNP:rs397514556EnsemblClinVar.1
Natural variantiVAR_072664615N → I in EIEE27; severe phenotype with early onset seizures; gain of function mutation; results in neuronal hyperexcitability; the mutant channel is not inhibited by magnesium and has increased calcium permeability compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs672601377EnsemblClinVar.1
Natural variantiVAR_072665618V → G in EIEE27; severe phenotype with early onset seizures; gain of function mutation; results in neuronal hyperexcitability; the mutant channel is not inhibited by magnesium and has increased calcium permeability compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs672601376EnsemblClinVar.1
Natural variantiVAR_065900682R → C in MRD6; decreased protein abundance; no effect on localization to the cell membrane; no significant effect on calcium ion transmembrane import into cytosol; analysis of agonist dose-response curves for glutamate and glycine are not consistent. 2 PublicationsCorresponds to variant dbSNP:rs387906636EnsemblClinVar.1
Natural variantiVAR_079950696R → H in MRD6; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency. 1 Publication1
Natural variantiVAR_078647820G → E in MRD6. 1 Publication1
Natural variantiVAR_079951825L → V Probable disease-associated mutation found in a patient with autism spectrum disorder. 1 Publication1
Natural variantiVAR_0799521014Q → R Found in a patient with schizophrenia; unknown pathological significance. 1 Publication1
Natural variantiVAR_0799531026G → S1 PublicationCorresponds to variant dbSNP:rs201963596EnsemblClinVar.1
Natural variantiVAR_0799541342M → R1 Publication1
Natural variantiVAR_0799551415S → L Found in a patient with autism spectrum disorder; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201463390Ensembl.1
Natural variantiVAR_0799561424L → F1 PublicationCorresponds to variant dbSNP:rs748128078Ensembl.1
Natural variantiVAR_0782361439P → A Found in a patient with Landau-Kleffner syndrome; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs758042475EnsemblClinVar.1
Natural variantiVAR_0799571452S → F Found in a patient with schizophrenia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs756790727EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U90278 mRNA Translation: AAB49993.1
U88963 mRNA Translation: AAD00659.1
U11287 mRNA Translation: AAB60368.1
BC113618 mRNA Translation: AAI13619.1
BC113620 mRNA Translation: AAI13621.1
U28758 mRNA Translation: AAA74930.1
U28861 mRNA Translation: AAA69919.1
U28862 mRNA Translation: AAA69920.1
CCDSiCCDS8662.1
PIRiI39066
S52086
RefSeqiNP_000825.2, NM_000834.3
XP_011518930.1, XM_011520628.2
XP_011518931.1, XM_011520629.2
XP_016874708.1, XM_017019219.1
UniGeneiHs.504844
Hs.632856
Hs.654430

Genome annotation databases

EnsembliENST00000609686; ENSP00000477455; ENSG00000273079
GeneIDi2904
KEGGihsa:2904
UCSCiuc001rbt.3 human

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNMDE2_HUMAN
AccessioniPrimary (citable) accession number: Q13224
Secondary accession number(s): Q12919
, Q13220, Q13225, Q14CU4, Q9UM56
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: June 20, 2001
Last modified: July 18, 2018
This is version 189 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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