P35438 (NMDZ1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamate receptor ionotropic, NMDA 1
Short name=GluN1

Alternative name(s):
Glutamate [NMDA] receptor subunit zeta-1
N-methyl-D-aspartate receptor subunit NR1
Short name=NMD-R1

Gene names

Name:	Grin1
Synonyms:	Glurz1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	938 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Modulated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors By similarity.
Subunit structure	Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B); disulfide-linked. Found in a complex with GRIN2A or GRIN2B and GRIN3B. Found in a complex with GRIN2A or GRIN2B, GRIN3A and PPP2CB. Interacts with DLG4 and MPDZ By similarity. Interacts with LRFN1 and LRFN2 By similarity. Interacts with MYZAP. Ref.4 Ref.5 Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Cell junction › synapse › postsynaptic cell membrane By similarity. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density By similarity. Note: Enriched in postsynaptic plasma membrane and postsynaptic densities By similarity. Ref.5
Post-translational modification	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 By similarity.
Sequence similarities	Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR1/GRIN1 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	Calcium Magnesium
Molecular function	Ion channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adult locomotory behavior Inferred from mutant phenotype PubMed 10481908PubMed 10818139. Source: MGI cellular calcium ion homeostasis Inferred from mutant phenotype PubMed 8060614. Source: MGI cellular response to manganese ion Inferred from electronic annotation. Source: Compara cerebral cortex development Inferred from mutant phenotype PubMed 10963597PubMed 12657691. Source: MGI conditioned taste aversion Inferred from mutant phenotype PubMed 16101757. Source: MGI long-term memory Inferred from mutant phenotype PubMed 15003177. Source: MGI male mating behavior Inferred from mutant phenotype PubMed 10481908. Source: MGI negative regulation of neuron apoptotic process Inferred from mutant phenotype PubMed 17077143. Source: MGI olfactory learning Inferred from mutant phenotype PubMed 10700255PubMed 11248114. Source: MGI pons maturation Inferred from mutant phenotype PubMed 8313466. Source: MGI positive regulation of apoptotic process Inferred from genetic interaction PubMed 17803966. Source: MGI positive regulation of excitatory postsynaptic membrane potential Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 7907365. Source: MGI prepulse inhibition Inferred from mutant phenotype PubMed 15265649. Source: MGI propylene metabolic process Inferred from direct assay PubMed 21795692. Source: BHF-UCL regulation of axonogenesis Inferred from mutant phenotype PubMed 15745956. Source: MGI regulation of dendrite morphogenesis Inferred from mutant phenotype PubMed 15745956. Source: MGI regulation of excitatory postsynaptic membrane potential Inferred from mutant phenotype PubMed 15003177. Source: MGI regulation of long-term neuronal synaptic plasticity Inferred from mutant phenotype PubMed 10818139PubMed 17015831PubMed 17313573. Source: MGI regulation of respiratory gaseous exchange Inferred from mutant phenotype PubMed 10777815. Source: MGI regulation of synapse assembly Inferred from mutant phenotype PubMed 12657691. Source: MGI respiratory gaseous exchange Inferred from mutant phenotype PubMed 8313466PubMed 8713451. Source: MGI response to amphetamine Inferred from mutant phenotype PubMed 15467708PubMed 16638606. Source: MGI response to calcium ion Inferred from electronic annotation. Source: Compara response to fungicide Inferred from electronic annotation. Source: Compara response to morphine Inferred from mutant phenotype PubMed 18423864. Source: MGI rhythmic process Inferred from electronic annotation. Source: Compara sensory perception of pain Inferred from mutant phenotype PubMed 12832526. Source: MGI social behavior Inferred from mutant phenotype PubMed 10481908. Source: MGI suckling behavior Inferred from mutant phenotype PubMed 10777815PubMed 8313466PubMed 8713451. Source: MGI synaptic transmission, glutamatergic Inferred from mutant phenotype PubMed 10963597PubMed 8313466. Source: MGI visual learning Inferred from mutant phenotype PubMed 10818139PubMed 16611824PubMed 17313573PubMed 8980238PubMed 9246451. Source: MGI
Cellular_component	N-methyl-D-aspartate selective glutamate receptor complex Inferred from physical interaction PubMed 9003035. Source: MGI cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from direct assay PubMed 17229826. Source: BHF-UCL dendrite membrane Inferred from electronic annotation. Source: Compara excitatory synapse Inferred from electronic annotation. Source: Compara growth cone Non-traceable author statement PubMed 10480904. Source: UniProtKB outer membrane-bounded periplasmic space Inferred from electronic annotation. Source: InterPro postsynaptic density Inferred from direct assay PubMed 15317856PubMed 15748150. Source: MGI postsynaptic membrane Inferred from direct assay PubMed 11754836PubMed 12890763PubMed 15317856. Source: MGI synaptic cleft Inferred from electronic annotation. Source: Compara synaptic vesicle Inferred from direct assay PubMed 10846156. Source: MGI terminal bouton Inferred from electronic annotation. Source: Compara
Molecular_function	N-methyl-D-aspartate selective glutamate receptor activity Inferred from direct assay PubMed 1374164PubMed 1377365PubMed 1385220Ref.1. Source: MGI calcium channel activity Inferred from direct assay PubMed 1374164Ref.1. Source: MGI calcium ion binding Inferred from direct assay PubMed 15663482. Source: MGI calmodulin binding Inferred from direct assay PubMed 15663482. Source: MGI extracellular-glutamate-gated ion channel activity Inferred from electronic annotation. Source: InterPro glutamate binding Inferred from electronic annotation. Source: Compara glycine binding Inferred from mutant phenotype PubMed 12586454. Source: UniProtKB neurotransmitter binding Inferred from electronic annotation. Source: Compara voltage-gated cation channel activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Dlg4	Q62108	8	EBI-400084,EBI-300895
Lrp8	Q924X6	4	EBI-400084,EBI-432319

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P35438-1)

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

Isoform 2 (identifier: P35438-2)

The sequence of this isoform differs from the canonical sequence as follows:
     864-885: DRKSGRAEPDPKKKATFRAITS → QYHPTDITGPLNLSDPSVSTVV
     886-938: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 938	920	Glutamate receptor ionotropic, NMDA 1		PRO_0000011588
Regions
	Topological domain	19 – 559	541	Extracellular Potential
	Transmembrane	560 – 580	21	Helical; Potential
	Topological domain	581 – 636	56	Cytoplasmic Potential
	Transmembrane	637 – 657	21	Helical; Potential
	Topological domain	658 – 812	155	Extracellular Potential
	Transmembrane	813 – 833	21	Helical; Potential
	Topological domain	834 – 938	105	Cytoplasmic Potential
	Region	516 – 518	3	Glycine binding By similarity
Sites
	Binding site	523	1	Glycine By similarity
	Binding site	688	1	Glycine By similarity
	Binding site	732	1	Glycine By similarity
Amino acid modifications
	Modified residue	889	1	Phosphoserine; by PKC By similarity
	Modified residue	890	1	Phosphoserine Ref.6
	Modified residue	896	1	Phosphoserine; by PKC By similarity
	Modified residue	897	1	Phosphoserine; by PKC By similarity
	Glycosylation	61	1	N-linked (GlcNAc...) Potential
	Glycosylation	203	1	N-linked (GlcNAc...) Potential
	Glycosylation	239	1	N-linked (GlcNAc...) Potential
	Glycosylation	276	1	N-linked (GlcNAc...) Potential
	Glycosylation	300	1	N-linked (GlcNAc...) Potential
	Glycosylation	350	1	N-linked (GlcNAc...) Potential
	Glycosylation	368	1	N-linked (GlcNAc...) Potential
	Glycosylation	440	1	N-linked (GlcNAc...) Potential
	Glycosylation	471	1	N-linked (GlcNAc...) Potential
	Glycosylation	491	1	N-linked (GlcNAc...) Potential
	Disulfide bond	79		Interchain By similarity
Natural variations
	Alternative sequence	864 – 885	22	DRKSG…RAITS → QYHPTDITGPLNLSDPSVST VV in isoform 2.		VSP_014222
	Alternative sequence	886 – 938	53	Missing in isoform 2.		VSP_014223
	Natural variant	936	1	R → T.

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: C610632DD3E06171	FASTA	938	105,481
	10 20 30 40 50 60 MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL 70 80 90 100 110 120 NATSVTHKPN AIQMALSVCE DLISSQVYAI LVSHPPTPND HFTPTPVSYT AGFYRIPVLG 130 140 150 160 170 180 LTTRMSIYSD KSIHLSFLRT VPPYSHQSSV WFEMMRVYNW NHIILLVSDD HEGRAAQKRL 190 200 210 220 230 240 ETLLEERESK AEKVLQFDPG TKNVTALLME ARDLEARVII LSASEDDAAT VYRAAAMLNM 250 260 270 280 290 300 TGSGYVWLVG EREISGNALR YAPDGIIGLQ LINGKNESAH ISDAVGVVAQ AVHELLEKEN 310 320 330 340 350 360 ITDPPRGCVG NTNIWKTGPL FKRVLMSSKY ADGVTGRVEF NEDGDRKFAN YSIMNLQNRK 370 380 390 400 410 420 LVQVGIYNGT HVIPNDRKII WPGGETEKPR GYQMSTRLKI VTIHQEPFVY VKPTMSDGTC 430 440 450 460 470 480 KEEFTVNGDP VKKVICTGPN DTSPGSPRHT VPQCCYGFCV DLLIKLARTM NFTYEVHLVA 490 500 510 520 530 540 DGKFGTQERV NNSNKKEWNG MMGELLSGQA DMIVAPLTIN NERAQYIEFS KPFKYQGLTI 550 560 570 580 590 600 LVKKEIPRST LDSFMQPFQS TLWLLVGLSV HVVAVMLYLL DRFSPFGRFK VNSEEEEEDA 610 620 630 640 650 660 LTLSSAMWFS WGVLLNSGIG EGAPRSFSAR ILGMVWAGFA MIIVASYTAN LAAFLVLDRP 670 680 690 700 710 720 EERITGINDP RLRNPSDKFI YATVKQSSVD IYFRRQVELS TMYRHMEKHN YESAAEAIQA 730 740 750 760 770 780 VRDNKLHAFI WDSAVLEFEA SQKCDLVTTG ELFFRSGFGI GMRKDSPWKQ NVSLSILKSH 790 800 810 820 830 840 ENGFMEDLDK TWVRYQECDS RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH 850 860 870 880 890 900 KDARRKQMQL AFAAVNVWRK NLQDRKSGRA EPDPKKKATF RAITSTLASS FKRRRSSKDT 910 920 930 STGGGRGALQ NQKDTVLPRR AIEREEGQLQ LCSRHRES
	Isoform 2 [UniParc]. Checksum: 283AA14096E81558	FASTA	885	99,423
	10 20 30 40 50 60 MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL 70 80 90 100 110 120 NATSVTHKPN AIQMALSVCE DLISSQVYAI LVSHPPTPND HFTPTPVSYT AGFYRIPVLG 130 140 150 160 170 180 LTTRMSIYSD KSIHLSFLRT VPPYSHQSSV WFEMMRVYNW NHIILLVSDD HEGRAAQKRL 190 200 210 220 230 240 ETLLEERESK AEKVLQFDPG TKNVTALLME ARDLEARVII LSASEDDAAT VYRAAAMLNM 250 260 270 280 290 300 TGSGYVWLVG EREISGNALR YAPDGIIGLQ LINGKNESAH ISDAVGVVAQ AVHELLEKEN 310 320 330 340 350 360 ITDPPRGCVG NTNIWKTGPL FKRVLMSSKY ADGVTGRVEF NEDGDRKFAN YSIMNLQNRK 370 380 390 400 410 420 LVQVGIYNGT HVIPNDRKII WPGGETEKPR GYQMSTRLKI VTIHQEPFVY VKPTMSDGTC 430 440 450 460 470 480 KEEFTVNGDP VKKVICTGPN DTSPGSPRHT VPQCCYGFCV DLLIKLARTM NFTYEVHLVA 490 500 510 520 530 540 DGKFGTQERV NNSNKKEWNG MMGELLSGQA DMIVAPLTIN NERAQYIEFS KPFKYQGLTI 550 560 570 580 590 600 LVKKEIPRST LDSFMQPFQS TLWLLVGLSV HVVAVMLYLL DRFSPFGRFK VNSEEEEEDA 610 620 630 640 650 660 LTLSSAMWFS WGVLLNSGIG EGAPRSFSAR ILGMVWAGFA MIIVASYTAN LAAFLVLDRP 670 680 690 700 710 720 EERITGINDP RLRNPSDKFI YATVKQSSVD IYFRRQVELS TMYRHMEKHN YESAAEAIQA 730 740 750 760 770 780 VRDNKLHAFI WDSAVLEFEA SQKCDLVTTG ELFFRSGFGI GMRKDSPWKQ NVSLSILKSH 790 800 810 820 830 840 ENGFMEDLDK TWVRYQECDS RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH 850 860 870 880 KDARRKQMQL AFAAVNVWRK NLQQYHPTDI TGPLNLSDPS VSTVV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression and modulation of a mouse NMDA receptor subunit." Yamazaki M., Mori H., Araki K., Mori K.J., Mishina M. FEBS Lett. 300:39-45(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Eye.
[4]	"Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability." Matsuda K., Kamiya Y., Matsuda S., Yuzaki M. Brain Res. Mol. Brain Res. 100:43-52(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH GRIN2A OR GRIN2B AND GRIN3B.
[5]	"Specific assembly with the NMDA receptor 3B subunit controls surface expression and calcium permeability of NMDA receptors." Matsuda K., Fletcher M., Kamiya Y., Yuzaki M. J. Neurosci. 23:10064-10073(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH GRIN2A OR GRIN2B AND GRIN3B.
[6]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-890, MASS SPECTROMETRY. Tissue: Brain cortex.
[7]	"GRINL1A colocalizes with N-methyl D-aspartate receptor NR1 subunit and reduces N-methyl D-aspartate toxicity." Roginski R.S., Goubaeva F., Mikami M., Fried-Cassorla E., Nair M.R., Yang J. NeuroReport 19:1721-1726(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MYZAP.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D10028 mRNA. Translation: BAA00920.1. AL732309 Genomic DNA. Translation: CAM14685.1. AL732309 Genomic DNA. Translation: CAM14688.1. BC039157 mRNA. Translation: AAH39157.1.
IPI	IPI00118385. IPI00608056.
PIR	S21104.
RefSeq	NP_001171127.1. NM_001177656.1. NP_001171128.1. NM_001177657.1. NP_032195.1. NM_008169.2.
UniGene	Mm.278672.
3D structure databases
ProteinModelPortal	P35438.
SMR	P35438. Positions 24-838.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31577N.
IntAct	P35438. 121 interactions.
MINT	MINT-135802.
PTM databases
PhosphoSite	P35438.
Proteomic databases
PaxDb	P35438.
PRIDE	P35438.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000028335; ENSMUSP00000028335; ENSMUSG00000026959. ENSMUST00000114312; ENSMUSP00000109951; ENSMUSG00000026959.
GeneID	14810.
KEGG	mmu:14810.
UCSC	uc008iri.2. mouse. uc008irk.2. mouse.
Organism-specific databases
CTD	2902.
MGI	MGI:95819. Grin1.
Phylogenomic databases
eggNOG	NOG282132.
GeneTree	ENSGT00700000104113.
HOGENOM	HOG000231491.
HOVERGEN	HBG052638.
KO	K05208.
Gene expression databases
ArrayExpress	P35438.
Bgee	P35438.
CleanEx	MM_GRIN1.
Genevestigator	P35438.
GermOnline	ENSMUSG00000026959. Mus musculus.
Family and domain databases
InterPro	IPR001828. ANF_lig-bd_rcpt. IPR018882. CaM-bd_C0_NMDA_rcpt_NR1. IPR019594. Glu_rcpt_Glu/Gly-bd. IPR001320. Iontro_glu_rcpt. IPR001508. NMDA_rcpt. IPR001638. SBP_bac_3. [Graphical view]
Pfam	PF01094. ANF_receptor. 1 hit. PF10562. CaM_bdg_C0. 1 hit. PF00060. Lig_chan. 1 hit. PF00497. SBP_bac_3. 1 hit. [Graphical view]
PRINTS	PR00177. NMDARECEPTOR.
SMART	SM00918. Lig_chan-Glu_bd. 1 hit. SM00079. PBPe. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P35438.
ChEMBL	CHEMBL2895.
NextBio	286995.
SOURCE	Search...

Entry information

Entry name

NMDZ1_MOUSE

Accession

Primary (citable) accession number: P35438
Secondary accession number(s): A2AI15, A2AI18, Q8CFS4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	May 1, 2013
This is version 142 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program