UniProtKB - Q05586 (NMDZ1_HUMAN)
Protein
Glutamate receptor ionotropic, NMDA 1
Gene
GRIN1
Organism
Homo sapiens (Human)
Status
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:7685113, PubMed:28126851, PubMed:26919761, PubMed:26875626, PubMed:28105280). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:26919761).5 Publications
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Binding sitei | 523 | GlycineCombined sources3 Publications | 1 | |
| Binding sitei | 688 | GlycineCombined sources3 Publications | 1 | |
| Binding sitei | 732 | GlycineCombined sources3 Publications | 1 |
GO - Molecular functioni
- amyloid-beta binding Source: ARUK-UCL
- calcium ion binding Source: UniProtKB
- calmodulin binding Source: UniProtKB
- glutamate binding Source: UniProtKB
- glutamate-gated calcium ion channel activity Source: UniProtKB
- glycine binding Source: UniProtKB
- ligand-gated ion channel activity Source: GO_Central
- neurotransmitter binding Source: BHF-UCL
- NMDA glutamate receptor activity Source: UniProtKB
- protein-containing complex binding Source: ARUK-UCL
- signaling receptor activity Source: GO_Central
- signaling receptor binding Source: Ensembl
- transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential Source: Ensembl
GO - Biological processi
- adult locomotory behavior Source: Ensembl
- brain development Source: ARUK-UCL
- calcium ion homeostasis Source: UniProtKB
- calcium ion transmembrane import into cytosol Source: UniProtKB
- cation transport Source: UniProtKB
- cerebral cortex development Source: Ensembl
- chemical synaptic transmission Source: GO_Central
- conditioned taste aversion Source: Ensembl
- ephrin receptor signaling pathway Source: Reactome
- excitatory chemical synaptic transmission Source: ARUK-UCL
- excitatory postsynaptic potential Source: UniProtKB
- ionotropic glutamate receptor signaling pathway Source: UniProtKB
- long-term memory Source: Ensembl
- male mating behavior Source: Ensembl
- MAPK cascade Source: Reactome
- negative regulation of neuron apoptotic process Source: Ensembl
- olfactory learning Source: Ensembl
- pons maturation Source: Ensembl
- positive regulation of apoptotic process Source: Ensembl
- positive regulation of calcium ion transport into cytosol Source: ARUK-UCL
- positive regulation of cysteine-type endopeptidase activity Source: ARUK-UCL
- positive regulation of excitatory postsynaptic potential Source: BHF-UCL
- positive regulation of reactive oxygen species biosynthetic process Source: ARUK-UCL
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- prepulse inhibition Source: Ensembl
- propylene metabolic process Source: BHF-UCL
- protein heterotetramerization Source: UniProtKB
- protein localization to postsynaptic membrane Source: Ensembl
- regulation of axonogenesis Source: Ensembl
- regulation of dendrite morphogenesis Source: Ensembl
- regulation of long-term neuronal synaptic plasticity Source: Ensembl
- regulation of membrane potential Source: UniProtKB
- regulation of NMDA receptor activity Source: Reactome
- regulation of respiratory gaseous exchange Source: Ensembl
- regulation of synapse assembly Source: Ensembl
- regulation of synaptic plasticity Source: ARUK-UCL
- response to amphetamine Source: Ensembl
- response to ethanol Source: UniProtKB
- response to glycine Source: UniProtKB
- response to morphine Source: Ensembl
- sensory perception of pain Source: Ensembl
- social behavior Source: Ensembl
- suckling behavior Source: Ensembl
- synaptic transmission, glutamatergic Source: Ensembl
- visual learning Source: UniProtKB
Keywordsi
| Molecular function | Ion channel, Ligand-gated ion channel, Receptor |
| Biological process | Ion transport, Transport |
| Ligand | Calcium, Magnesium |
Enzyme and pathway databases
| PathwayCommonsi | Q05586 |
| Reactomei | R-HSA-3928662, EPHB-mediated forward signaling R-HSA-438066, Unblocking of NMDA receptors, glutamate binding and activation 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-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 | Q05586 |
Protein family/group databases
| 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 1Short name: GluN1 Alternative name(s): Glutamate [NMDA] receptor subunit zeta-1 N-methyl-D-aspartate receptor subunit NR1 Short name: NMD-R1 |
| Gene namesi | Name:GRIN1 Synonyms:NMDAR1 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000176884.14 |
| HGNCi | HGNC:4584, GRIN1 |
| MIMi | 138249, gene |
| neXtProti | NX_Q05586 |
Subcellular locationi
Plasma membrane
- Cell membrane 5 Publications; Multi-pass membrane protein By similarity
- postsynaptic cell membrane By similarity
Other locations
- postsynaptic density By similarity
Note: Enriched in postsynaptic plasma membrane and postsynaptic densities.By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: Ensembl
Extracellular region or secreted
- synaptic cleft Source: BHF-UCL
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- integral component of postsynaptic density membrane Source: Ensembl
- NMDA selective glutamate receptor complex Source: UniProtKB
- plasma membrane Source: UniProtKB
- postsynaptic membrane Source: UniProtKB
- synaptic membrane Source: ARUK-UCL
Other locations
- cell surface Source: BHF-UCL
- cytoplasm Source: ARUK-UCL
- dendrite Source: UniProtKB
- dendritic spine Source: BHF-UCL
- excitatory synapse Source: BHF-UCL
- glutamatergic synapse Source: Ensembl
- neuron projection Source: UniProtKB
- postsynaptic density Source: UniProtKB
- synapse Source: UniProtKB
- synaptic vesicle Source: UniProtKB
- synaptic vesicle membrane Source: Ensembl
- terminal bouton Source: BHF-UCL
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Topological domaini | 19 – 559 | ExtracellularBy similarityAdd BLAST | 541 | |
| Transmembranei | 560 – 580 | HelicalBy similarityAdd BLAST | 21 | |
| Topological domaini | 581 – 602 | CytoplasmicBy similarityAdd BLAST | 22 | |
| Intramembranei | 603 – 624 | Discontinuously helicalBy similarityAdd BLAST | 22 | |
| Topological domaini | 625 – 630 | CytoplasmicBy similarity | 6 | |
| Transmembranei | 631 – 647 | HelicalBy similarityAdd BLAST | 17 | |
| Topological domaini | 648 – 812 | ExtracellularBy similarityAdd BLAST | 165 | |
| Transmembranei | 813 – 833 | HelicalBy similarityAdd BLAST | 21 | |
| Topological domaini | 834 – 938 | CytoplasmicBy similarityAdd BLAST | 105 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, SynapsePathology & Biotechi
Involvement in diseasei
Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (NDHMSD)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant neurodevelopmental disorder characterized by severe mental retardation and developmental delay, absent speech, muscular hypotonia, dyskinesia, and hyperkinetic movements. Cortical blindness, cerebral atrophy, and seizures are present in some patients.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_079989 | 552 | D → E in NDHMSD; changed localization to the cell membrane; decreased glutamate-gated calcium ion channel activity. 3 PublicationsCorresponds to variant dbSNP:rs1554770054EnsemblClinVar. | 1 | |
| Natural variantiVAR_079991 | 557 | P → R in NDHMSD; changed localization to the cell membrane; loss of glutamate-gated calcium ion channel activity. 3 PublicationsCorresponds to variant dbSNP:rs878853143EnsemblClinVar. | 1 | |
| Natural variantiVAR_066597 | 560 | S → SS in NDHMSD; there is near abolition of the activity of the NMDA receptor in Xenopus oocytes; alters the 3-dimensional structure at the receptor's channel pore entrance. 1 Publication | 1 | |
| Natural variantiVAR_079992 | 618 | G → R in NDHMSD; loss of function in calcium ion transmembrane import into cytosol. 1 Publication | 1 | |
| Natural variantiVAR_079993 | 620 | G → R in NDHMSD; decreased localization to the plasma membrane of GRIN1/GRIN2B NMDA receptor complexes; changed glutamate-gated calcium ion channel activity; decreased activation by glutamate and glycine; decreased sensitivity to magnesium block; loss of function in calcium ion transmembrane import into cytosol. 2 PublicationsCorresponds to variant dbSNP:rs797045047EnsemblClinVar. | 1 | |
| Natural variantiVAR_079994 | 641 | M → I in NDHMSD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1060500046EnsemblClinVar. | 1 | |
| Natural variantiVAR_079995 | 645 | A → S in NDHMSD; unknown pathological significance; no effect on glutamate-gated calcium ion channel activity. 1 Publication | 1 | |
| Natural variantiVAR_079996 | 647 | Y → S in NDHMSD; loss of glutamate-gated calcium ion channel activity. 1 Publication | 1 | |
| Natural variantiVAR_079997 | 650 | N → K in NDHMSD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs771610568EnsemblClinVar. | 1 | |
| Natural variantiVAR_066598 | 662 | E → K in NDHMSD; this mutation produces a significant increase in NMDA receptor-induced calcium currents; excessive calcium influx through NMDA receptor could lead to excitotoxic neuronal cell damage. 1 PublicationCorresponds to variant dbSNP:rs387906635EnsemblClinVar. | 1 | |
| Natural variantiVAR_079998 | 688 | S → Y in NDHMSD. 1 Publication | 1 | |
| Natural variantiVAR_079999 | 815 | G → R in NDHMSD; loss of glutamate-gated calcium ion channel activity. 2 PublicationsCorresponds to variant dbSNP:rs797044925EnsemblClinVar. | 1 | |
| Natural variantiVAR_080000 | 815 | G → V in NDHMSD. 1 Publication | 1 | |
| Natural variantiVAR_080001 | 817 | F → L in NDHMSD; decreased glutamate-gated calcium ion channel activity. 1 PublicationCorresponds to variant dbSNP:rs1554770624EnsemblClinVar. | 1 | |
| Natural variantiVAR_080002 | 827 | G → R in NDHMSD; loss of function in calcium ion transmembrane import into cytosol. 2 PublicationsCorresponds to variant dbSNP:rs1451230055EnsemblClinVar. | 1 | |
| Natural variantiVAR_080003 | 844 | R → C in NDHMSD; no effect on glutamate-gated calcium ion channel activity. 1 PublicationCorresponds to variant dbSNP:rs1554770667EnsemblClinVar. | 1 |
Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive (NDHMSR)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive neurodevelopmental disorder characterized by severe mental retardation and psychomotor developmental delay, involuntary and stereotypic movements, spasticity, and inability to walk without support. Intractable seizures manifest in some patients.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_079984 | 217 | R → W in NDHMSR; changed glutamate-gated calcium ion channel activity; increased inhibition by zinc. 1 PublicationCorresponds to variant dbSNP:rs200777850EnsemblClinVar. | 1 | |
| Natural variantiVAR_079985 | 227 | D → H in NDHMSR; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs869312865Ensembl. | 1 | |
| Natural variantiVAR_079990 | 556 – 938 | Missing in NDHMSR; loss of function in calcium ion transmembrane import into cytosol. 1 PublicationAdd BLAST | 383 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 813 | M → V: Slight decrease in glycine agonist potency; no effect on glutamate agonist potency. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, Mental retardationOrganism-specific databases
| DisGeNETi | 2902 |
| MalaCardsi | GRIN1 |
| MIMi | 614254, phenotype 617820, phenotype |
| OpenTargetsi | ENSG00000176884 |
| Orphaneti | 178469, Autosomal dominant non-syndromic intellectual disability 208447, Bilateral generalized polymicrogyria |
| PharmGKBi | PA28978 |
Miscellaneous databases
| Pharosi | Q05586, Tclin |
Chemistry databases
| ChEMBLi | CHEMBL2015 |
| DrugBanki | DB01931, 5,7-Dichlorokynurenic acid DB00659, Acamprosate DB06151, Acetylcysteine DB08838, Agmatine DB01238, Aripiprazole DB00289, Atomoxetine DB05824, CNS-5161 DB04620, Cycloleucine DB03929, D-Serine DB00843, Donepezil DB11823, Esketamine DB13146, Fluciclovine (18F) DB06741, Gavestinel DB00142, Glutamic acid DB00874, Guaifenesin DB08954, Ifenprodil DB06738, Ketobemidone DB09409, Magnesium acetate tetrahydrate DB09481, Magnesium carbonate DB01043, Memantine DB00454, Meperidine DB00333, Methadone DB04896, Milnacipran DB01173, Orphenadrine DB00312, Pentobarbital DB01174, Phenobarbital DB01708, Prasterone DB00418, Secobarbital DB00193, Tramadol |
| DrugCentrali | Q05586 |
| GuidetoPHARMACOLOGYi | 455 |
Polymorphism and mutation databases
| BioMutai | GRIN1 |
| DMDMi | 548377 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Signal peptidei | 1 – 18 | Sequence analysisAdd BLAST | 18 | |
| ChainiPRO_0000011587 | 19 – 938 | Glutamate receptor ionotropic, NMDA 1Add BLAST | 920 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Glycosylationi | 61 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Disulfide bondi | 79 ↔ 308 | By similarity | ||
| Glycosylationi | 203 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 239 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 276 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 300 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 350 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 368 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Disulfide bondi | 420 ↔ 454 | Combined sources3 Publications | ||
| Disulfide bondi | 436 ↔ 455 | Combined sources3 Publications | ||
| Glycosylationi | 440 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 471 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 491 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 674 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Disulfide bondi | 744 ↔ 798 | Combined sources3 Publications | ||
| Glycosylationi | 771 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Modified residuei | 889 | Phosphoserine; by PKC1 Publication | 1 | |
| Modified residuei | 890 | Phosphoserine; by PKC1 Publication | 1 | |
| Modified residuei | 896 | Phosphoserine; by PKC1 Publication | 1 | |
| Modified residuei | 897 | Phosphoserine; by PKC1 Publication | 1 |
Post-translational modificationi
NMDA is probably regulated by C-terminal phosphorylation of an isoform of NR1 by PKC. Dephosphorylated on Ser-897 probably by protein phosphatase 2A (PPP2CB). Its phosphorylated state is influenced by the formation of the NMDAR-PPP2CB complex and the NMDAR channel activity.1 Publication
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
| MassIVEi | Q05586 |
| PaxDbi | Q05586 |
| PeptideAtlasi | Q05586 |
| PRIDEi | Q05586 |
| ProteomicsDBi | 58336 [Q05586-1] 58337 [Q05586-2] 58338 [Q05586-3] 58339 [Q05586-4] 58340 [Q05586-5] 65258 65259 |
PTM databases
| GlyGeni | Q05586, 10 sites |
| iPTMneti | Q05586 |
| PhosphoSitePlusi | Q05586 |
Expressioni
Gene expression databases
| Bgeei | ENSG00000176884, Expressed in anterior cingulate cortex and 199 other tissues |
| ExpressionAtlasi | Q05586, baseline and differential |
| Genevisiblei | Q05586, HS |
Organism-specific databases
| HPAi | ENSG00000176884, Tissue enriched (brain) |
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:7685113, PubMed:28126851, PubMed:26919761, PubMed:26875626, PubMed:28105280). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), an epsilon subunit, plus GRIN3A or GRIN3B (in vitro). In vivo, the subunit composition may vary in function of the expression levels of the different subunits.
Found in a complex with GRIN2A or GRIN2B, GRIN3A and PPP2CB (By similarity).
Found in a complex with GRIN2A or GRIN2B and GRIN3B (By similarity).
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 DLG4 and MPDZ.
Interacts with LRFN1 and LRFN2 (By similarity).
Interacts with MYZAP (PubMed:18849881).
Found in a complex with DLG4 and PRR7 (By similarity).
Found in a complex with GRIN2B and PRR7 (PubMed:27458189).
Interacts with PRR7; the interaction is reduced following NMDA receptor activity (PubMed:27458189).
By similarity7 PublicationsBinary interactionsi
Isoform 1 [Q05586-2]
| With | #Exp. | IntAct |
|---|---|---|
| Dlg3 [Q62936] from Rattus norvegicus. | 3 | EBI-8286218,EBI-349596 |
GO - Molecular functioni
- calmodulin binding Source: UniProtKB
- signaling receptor binding Source: Ensembl
Protein-protein interaction databases
| BioGRIDi | 109159, 24 interactors |
| ComplexPortali | CPX-2202, NMDA receptor complex, GluN1-GluN2A CPX-285, NMDA receptor complex, GluN1-GluN2B CPX-286, NMDA receptor complex, GluN1-GluN2C CPX-289, NMDA receptor complex, GluN1-GluN2D CPX-294, NMDA receptor complex, GluN1-GluN2A-GluN2B |
| CORUMi | Q05586 |
| IntActi | Q05586, 9 interactors |
| MINTi | Q05586 |
| STRINGi | 9606.ENSP00000360608 |
Chemistry databases
| BindingDBi | Q05586 |
Miscellaneous databases
| RNActi | Q05586, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| SMRi | Q05586 |
| ModBasei | Search... |
| PDBe-KBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | Q05586 |
Family & Domainsi
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 516 – 518 | Glycine bindingCombined sources3 Publications | 3 | |
| Regioni | 603 – 624 | Pore-formingBy similarityAdd BLAST | 22 |
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
Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR1/GRIN1 subfamily. [View classification]Curated
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
| eggNOGi | KOG4440, Eukaryota |
| GeneTreei | ENSGT00940000158016 |
| HOGENOMi | CLU_007257_2_0_1 |
| InParanoidi | Q05586 |
| KOi | K05208 |
| OMAi | SGFYHIP |
| OrthoDBi | 188544at2759 |
| PhylomeDBi | Q05586 |
| TreeFami | TF351405 |
Family and domain databases
| InterProi | View protein in InterPro IPR001828, ANF_lig-bd_rcpt IPR018882, CaM-bd_C0_NMDA_rcpt_NR1 IPR019594, Glu/Gly-bd IPR001508, Iono_rcpt_met IPR001320, Iontro_rcpt IPR028082, Peripla_BP_I |
| Pfami | View protein in Pfam PF01094, ANF_receptor, 1 hit PF10562, CaM_bdg_C0, 1 hit PF00060, Lig_chan, 1 hit PF10613, Lig_chan-Glu_bd, 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 (7+)i
Sequence statusi: Complete.
Sequence processingi: The displayed sequence is further processed into a mature form.
This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basketThis entry has 7 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 3 (identifier: Q05586-1) [UniParc]FASTAAdd to basket
Also known as: Long, NR1-3
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.
10 20 30 40 50
MSTMRLLTLA LLFSCSVARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN
60 70 80 90 100
KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYAI LVSHPPTPND
110 120 130 140 150
HFTPTPVSYT AGFYRIPVLG LTTRMSIYSD KSIHLSFLRT VPPYSHQSSV
160 170 180 190 200
WFEMMRVYSW NHIILLVSDD HEGRAAQKRL ETLLEERESK AEKVLQFDPG
210 220 230 240 250
TKNVTALLME AKELEARVII LSASEDDAAT VYRAAAMLNM TGSGYVWLVG
260 270 280 290 300
EREISGNALR YAPDGILGLQ LINGKNESAH ISDAVGVVAQ AVHELLEKEN
310 320 330 340 350
ITDPPRGCVG NTNIWKTGPL FKRVLMSSKY ADGVTGRVEF NEDGDRKFAN
360 370 380 390 400
YSIMNLQNRK LVQVGIYNGT HVIPNDRKII WPGGETEKPR GYQMSTRLKI
410 420 430 440 450
VTIHQEPFVY VKPTLSDGTC KEEFTVNGDP VKKVICTGPN DTSPGSPRHT
460 470 480 490 500
VPQCCYGFCI DLLIKLARTM NFTYEVHLVA DGKFGTQERV NNSNKKEWNG
510 520 530 540 550
MMGELLSGQA DMIVAPLTIN NERAQYIEFS KPFKYQGLTI LVKKEIPRST
560 570 580 590 600
LDSFMQPFQS TLWLLVGLSV HVVAVMLYLL DRFSPFGRFK VNSEEEEEDA
610 620 630 640 650
LTLSSAMWFS WGVLLNSGIG EGAPRSFSAR ILGMVWAGFA MIIVASYTAN
660 670 680 690 700
LAAFLVLDRP EERITGINDP RLRNPSDKFI YATVKQSSVD IYFRRQVELS
710 720 730 740 750
TMYRHMEKHN YESAAEAIQA VRDNKLHAFI WDSAVLEFEA SQKCDLVTTG
760 770 780 790 800
ELFFRSGFGI GMRKDSPWKQ NVSLSILKSH ENGFMEDLDK TWVRYQECDS
810 820 830 840 850
RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH KDARRKQMQL
860 870 880 890 900
AFAAVNVWRK NLQDRKSGRA EPDPKKKATF RAITSTLASS FKRRRSSKDT
910 920 930
STGGGRGALQ NQKDTVLPRR AIEREEGQLQ LCSRHRES
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| Q5VSF9 | Q5VSF9_HUMAN | Glutamate receptor ionotropic, NMDA... | GRIN1 | 922 | Annotation score: | ||
| A2AVK2 | A2AVK2_HUMAN | Glutamate receptor ionotropic, NMDA... | GRIN1 | 356 | Annotation score: |
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 389 | P → S in AAB25917 (PubMed:7681588).Curated | 1 | |
| Sequence conflicti | 488 | E → K in AAB59361 (PubMed:8406025).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_079984 | 217 | R → W in NDHMSR; changed glutamate-gated calcium ion channel activity; increased inhibition by zinc. 1 PublicationCorresponds to variant dbSNP:rs200777850EnsemblClinVar. | 1 | |
| Natural variantiVAR_079985 | 227 | D → H in NDHMSR; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs869312865Ensembl. | 1 | |
| Natural variantiVAR_079986 | 306 | R → Q Found in a patient with schizophrenia; unknown pathological significance. 1 Publication | 1 | |
| Natural variantiVAR_079987 | 349 | A → S1 PublicationCorresponds to variant dbSNP:rs148008303EnsemblClinVar. | 1 | |
| Natural variantiVAR_079988 | 419 | T → A1 PublicationCorresponds to variant dbSNP:rs763133592Ensembl. | 1 | |
| Natural variantiVAR_049187 | 540 | I → M1 PublicationCorresponds to variant dbSNP:rs3181457Ensembl. | 1 | |
| Natural variantiVAR_079989 | 552 | D → E in NDHMSD; changed localization to the cell membrane; decreased glutamate-gated calcium ion channel activity. 3 PublicationsCorresponds to variant dbSNP:rs1554770054EnsemblClinVar. | 1 | |
| Natural variantiVAR_079990 | 556 – 938 | Missing in NDHMSR; loss of function in calcium ion transmembrane import into cytosol. 1 PublicationAdd BLAST | 383 | |
| Natural variantiVAR_079991 | 557 | P → R in NDHMSD; changed localization to the cell membrane; loss of glutamate-gated calcium ion channel activity. 3 PublicationsCorresponds to variant dbSNP:rs878853143EnsemblClinVar. | 1 | |
| Natural variantiVAR_066597 | 560 | S → SS in NDHMSD; there is near abolition of the activity of the NMDA receptor in Xenopus oocytes; alters the 3-dimensional structure at the receptor's channel pore entrance. 1 Publication | 1 | |
| Natural variantiVAR_079992 | 618 | G → R in NDHMSD; loss of function in calcium ion transmembrane import into cytosol. 1 Publication | 1 | |
| Natural variantiVAR_079993 | 620 | G → R in NDHMSD; decreased localization to the plasma membrane of GRIN1/GRIN2B NMDA receptor complexes; changed glutamate-gated calcium ion channel activity; decreased activation by glutamate and glycine; decreased sensitivity to magnesium block; loss of function in calcium ion transmembrane import into cytosol. 2 PublicationsCorresponds to variant dbSNP:rs797045047EnsemblClinVar. | 1 | |
| Natural variantiVAR_079994 | 641 | M → I in NDHMSD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1060500046EnsemblClinVar. | 1 | |
| Natural variantiVAR_079995 | 645 | A → S in NDHMSD; unknown pathological significance; no effect on glutamate-gated calcium ion channel activity. 1 Publication | 1 | |
| Natural variantiVAR_079996 | 647 | Y → S in NDHMSD; loss of glutamate-gated calcium ion channel activity. 1 Publication | 1 | |
| Natural variantiVAR_079997 | 650 | N → K in NDHMSD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs771610568EnsemblClinVar. | 1 | |
| Natural variantiVAR_066598 | 662 | E → K in NDHMSD; this mutation produces a significant increase in NMDA receptor-induced calcium currents; excessive calcium influx through NMDA receptor could lead to excitotoxic neuronal cell damage. 1 PublicationCorresponds to variant dbSNP:rs387906635EnsemblClinVar. | 1 | |
| Natural variantiVAR_069057 | 682 | A → S1 PublicationCorresponds to variant dbSNP:rs1126448Ensembl. | 1 | |
| Natural variantiVAR_079998 | 688 | S → Y in NDHMSD. 1 Publication | 1 | |
| Natural variantiVAR_079999 | 815 | G → R in NDHMSD; loss of glutamate-gated calcium ion channel activity. 2 PublicationsCorresponds to variant dbSNP:rs797044925EnsemblClinVar. | 1 | |
| Natural variantiVAR_080000 | 815 | G → V in NDHMSD. 1 Publication | 1 | |
| Natural variantiVAR_080001 | 817 | F → L in NDHMSD; decreased glutamate-gated calcium ion channel activity. 1 PublicationCorresponds to variant dbSNP:rs1554770624EnsemblClinVar. | 1 | |
| Natural variantiVAR_080002 | 827 | G → R in NDHMSD; loss of function in calcium ion transmembrane import into cytosol. 2 PublicationsCorresponds to variant dbSNP:rs1451230055EnsemblClinVar. | 1 | |
| Natural variantiVAR_080003 | 844 | R → C in NDHMSD; no effect on glutamate-gated calcium ion channel activity. 1 PublicationCorresponds to variant dbSNP:rs1554770667EnsemblClinVar. | 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_011777 | 190 | K → KSKKRNYENLDQLSYDNKRG PK in isoform 5, isoform 6 and isoform 7. 2 Publications | 1 | |
| Alternative sequenceiVSP_045464 | 864 – 938 | DRKSG…RHRES → QYHPTDITGPLNLSDPSVST VV in isoform 7. 1 PublicationAdd BLAST | 75 | |
| Alternative sequenceiVSP_000139 | 864 – 900 | Missing in isoform 2. 1 PublicationAdd BLAST | 37 | |
| Alternative sequenceiVSP_000137 | 864 – 885 | DRKSG…RAITS → QYHPTDITGPLNLSDPSVST VV in isoform 1. 2 PublicationsAdd BLAST | 22 | |
| Alternative sequenceiVSP_000138 | 886 – 938 | Missing in isoform 1. 2 PublicationsAdd BLAST | 53 | |
| Alternative sequenceiVSP_011778 | 901 – 922 | STGGG…PRRAI → QYHPTDITGPLNLSDPSVST VV in isoform 4 and isoform 6. 2 PublicationsAdd BLAST | 22 | |
| Alternative sequenceiVSP_011779 | 923 – 938 | Missing in isoform 4 and isoform 6. 2 PublicationsAdd BLAST | 16 |
Sequence databases
Genome annotation databases
| Ensembli | ENST00000371546; ENSP00000360601; ENSG00000176884 [Q05586-5] ENST00000371550; ENSP00000360605; ENSG00000176884 [Q05586-3] ENST00000371553; ENSP00000360608; ENSG00000176884 [Q05586-6] ENST00000371559; ENSP00000360614; ENSG00000176884 [Q05586-2] ENST00000371560; ENSP00000360615; ENSG00000176884 [Q05586-7] ENST00000371561; ENSP00000360616; ENSG00000176884 [Q05586-1] |
| GeneIDi | 2902 |
| KEGGi | hsa:2902 |
| UCSCi | uc004clk.4, human [Q05586-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
| Wikipedia NMDA receptor entry |
Sequence databases
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 2HQW | X-ray | 1.90 | B | 875-898 | [»] | |
| 2NR1 | NMR | - | A | 599-621 | [»] | |
| 3BYA | X-ray | 1.85 | B | 875-898 | [»] | |
| 5H8F | X-ray | 1.81 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 5H8H | X-ray | 2.23 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 5H8N | X-ray | 2.50 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 5H8Q | X-ray | 1.90 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 5I2K | X-ray | 2.86 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 5I2N | X-ray | 2.12 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 5KCJ | X-ray | 2.09 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 5KDT | X-ray | 2.44 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 5TP9 | X-ray | 2.40 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 5TPA | X-ray | 2.48 | B | 394-544 | [»] | |
| B | 663-800 | [»] | ||||
| 6IRA | electron microscopy | 4.50 | A/C | 1-847 | [»] | |
| 6IRF | electron microscopy | 5.10 | A/C | 1-847 | [»] | |
| 6IRG | electron microscopy | 5.50 | A/C | 1-847 | [»] | |
| 6IRH | electron microscopy | 7.80 | A/C | 1-847 | [»] | |
| SMRi | Q05586 | |||||
| ModBasei | Search... | |||||
| PDBe-KBi | Search... | |||||
Protein-protein interaction databases
| BioGRIDi | 109159, 24 interactors |
| ComplexPortali | CPX-2202, NMDA receptor complex, GluN1-GluN2A CPX-285, NMDA receptor complex, GluN1-GluN2B CPX-286, NMDA receptor complex, GluN1-GluN2C CPX-289, NMDA receptor complex, GluN1-GluN2D CPX-294, NMDA receptor complex, GluN1-GluN2A-GluN2B |
| CORUMi | Q05586 |
| IntActi | Q05586, 9 interactors |
| MINTi | Q05586 |
| STRINGi | 9606.ENSP00000360608 |
Chemistry databases
| BindingDBi | Q05586 |
| ChEMBLi | CHEMBL2015 |
| DrugBanki | DB01931, 5,7-Dichlorokynurenic acid DB00659, Acamprosate DB06151, Acetylcysteine DB08838, Agmatine DB01238, Aripiprazole DB00289, Atomoxetine DB05824, CNS-5161 DB04620, Cycloleucine DB03929, D-Serine DB00843, Donepezil DB11823, Esketamine DB13146, Fluciclovine (18F) DB06741, Gavestinel DB00142, Glutamic acid DB00874, Guaifenesin DB08954, Ifenprodil DB06738, Ketobemidone DB09409, Magnesium acetate tetrahydrate DB09481, Magnesium carbonate DB01043, Memantine DB00454, Meperidine DB00333, Methadone DB04896, Milnacipran DB01173, Orphenadrine DB00312, Pentobarbital DB01174, Phenobarbital DB01708, Prasterone DB00418, Secobarbital DB00193, Tramadol |
| DrugCentrali | Q05586 |
| GuidetoPHARMACOLOGYi | 455 |
Protein family/group databases
| TCDBi | 1.A.10.1.20, the glutamate-gated ion channel (gic) family of neurotransmitter receptors |
PTM databases
| GlyGeni | Q05586, 10 sites |
| iPTMneti | Q05586 |
| PhosphoSitePlusi | Q05586 |
Polymorphism and mutation databases
| BioMutai | GRIN1 |
| DMDMi | 548377 |
Proteomic databases
| MassIVEi | Q05586 |
| PaxDbi | Q05586 |
| PeptideAtlasi | Q05586 |
| PRIDEi | Q05586 |
| ProteomicsDBi | 58336 [Q05586-1] 58337 [Q05586-2] 58338 [Q05586-3] 58339 [Q05586-4] 58340 [Q05586-5] 65258 65259 |
Protocols and materials databases
| Antibodypediai | 3475, 1232 antibodies |
Genome annotation databases
| Ensembli | ENST00000371546; ENSP00000360601; ENSG00000176884 [Q05586-5] ENST00000371550; ENSP00000360605; ENSG00000176884 [Q05586-3] ENST00000371553; ENSP00000360608; ENSG00000176884 [Q05586-6] ENST00000371559; ENSP00000360614; ENSG00000176884 [Q05586-2] ENST00000371560; ENSP00000360615; ENSG00000176884 [Q05586-7] ENST00000371561; ENSP00000360616; ENSG00000176884 [Q05586-1] |
| GeneIDi | 2902 |
| KEGGi | hsa:2902 |
| UCSCi | uc004clk.4, human [Q05586-1] |
Organism-specific databases
| CTDi | 2902 |
| DisGeNETi | 2902 |
| EuPathDBi | HostDB:ENSG00000176884.14 |
| GeneCardsi | GRIN1 |
| HGNCi | HGNC:4584, GRIN1 |
| HPAi | ENSG00000176884, Tissue enriched (brain) |
| MalaCardsi | GRIN1 |
| MIMi | 138249, gene 614254, phenotype 617820, phenotype |
| neXtProti | NX_Q05586 |
| OpenTargetsi | ENSG00000176884 |
| Orphaneti | 178469, Autosomal dominant non-syndromic intellectual disability 208447, Bilateral generalized polymicrogyria |
| PharmGKBi | PA28978 |
| GenAtlasi | Search... |
Phylogenomic databases
| eggNOGi | KOG4440, Eukaryota |
| GeneTreei | ENSGT00940000158016 |
| HOGENOMi | CLU_007257_2_0_1 |
| InParanoidi | Q05586 |
| KOi | K05208 |
| OMAi | SGFYHIP |
| OrthoDBi | 188544at2759 |
| PhylomeDBi | Q05586 |
| TreeFami | TF351405 |
Enzyme and pathway databases
| PathwayCommonsi | Q05586 |
| Reactomei | R-HSA-3928662, EPHB-mediated forward signaling R-HSA-438066, Unblocking of NMDA receptors, glutamate binding and activation 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-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 | Q05586 |
Miscellaneous databases
| BioGRID-ORCSi | 2902, 3 hits in 869 CRISPR screens |
| ChiTaRSi | GRIN1, human |
| EvolutionaryTracei | Q05586 |
| GeneWikii | GRIN1 |
| GenomeRNAii | 2902 |
| Pharosi | Q05586, Tclin |
| PROi | PR:Q05586 |
| RNActi | Q05586, protein |
| SOURCEi | Search... |
Gene expression databases
| Bgeei | ENSG00000176884, Expressed in anterior cingulate cortex and 199 other tissues |
| ExpressionAtlasi | Q05586, baseline and differential |
| Genevisiblei | Q05586, HS |
Family and domain databases
| InterProi | View protein in InterPro IPR001828, ANF_lig-bd_rcpt IPR018882, CaM-bd_C0_NMDA_rcpt_NR1 IPR019594, Glu/Gly-bd IPR001508, Iono_rcpt_met IPR001320, Iontro_rcpt IPR028082, Peripla_BP_I |
| Pfami | View protein in Pfam PF01094, ANF_receptor, 1 hit PF10562, CaM_bdg_C0, 1 hit PF00060, Lig_chan, 1 hit PF10613, Lig_chan-Glu_bd, 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 |
| ProtoNeti | Search... |
| MobiDBi | Search... |
Entry informationi
| Entry namei | NMDZ1_HUMAN | |
| Accessioni | Q05586Primary (citable) accession number: Q05586 Secondary accession number(s): A6NLK7 Q9UPF9 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 1994 |
| Last sequence update: | June 1, 1994 | |
| Last modified: | October 7, 2020 | |
| This is version 235 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - 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 - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
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