Q01097 (NMDE2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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=NMDAR2B
Short name=NR2B

Gene names

Name:

Grin2b

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	1482 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 with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. 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. Ref.12
Subunit structure	Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B). Found in a complex with GRIN1 and GRIN3B. Found in a complex with GRIN1, GRIN3A and PPP2CB. Interacts with PDZ domains of INADL, DLG4 and MAGI3 By similarity. Interacts with HIP1 and NETO1. Interacts with DAPK1. Ref.5 Ref.6 Ref.8 Ref.11 Ref.12
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein.
Post-translational modification	Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity.
Sequence similarities	Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2B/GRIN2B subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Domain	Signal Transmembrane Transmembrane helix
Ligand	Calcium Magnesium Metal-binding Zinc
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	behavioral fear response Inferred from mutant phenotype PubMed 16710293. Source: MGI behavioral response to pain Inferred from mutant phenotype PubMed 11711849. Source: MGI detection of mechanical stimulus involved in sensory perception of pain Inferred from mutant phenotype PubMed 16190898. Source: MGI in utero embryonic development Inferred from mutant phenotype PubMed 9147327. Source: MGI learning Inferred from direct assay PubMed 10485705. Source: MGI memory Inferred from direct assay PubMed 10485705. Source: MGI regulation of excitatory postsynaptic membrane potential Inferred from mutant phenotype PubMed 10634899PubMed 11530236PubMed 12832518PubMed 16045501PubMed 16157280PubMed 9147327. Source: MGI regulation of neuronal synaptic plasticity Traceable author statement PubMed 14622581. Source: UniProtKB response to ethanol Inferred from mutant phenotype PubMed 11530236. Source: MGI sensory organ development Inferred from mutant phenotype PubMed 8789948. Source: MGI startle response Inferred from mutant phenotype PubMed 11488959. Source: MGI suckling behavior Inferred from mutant phenotype PubMed 8789948. 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 outer membrane-bounded periplasmic space Inferred from electronic annotation. Source: InterPro postsynaptic density Inferred from direct assay PubMed 21664258. Source: BHF-UCL postsynaptic membrane Inferred from direct assay PubMed 12890763. Source: MGI presynaptic membrane Inferred from direct assay PubMed 16157280. Source: UniProtKB synaptic vesicle Inferred from direct assay PubMed 10846156PubMed 20418887. Source: MGI
Molecular_function	N-methyl-D-aspartate selective glutamate receptor activity Inferred from mutant phenotype PubMed 10634899PubMed 12816890PubMed 12832518PubMed 9458051. Source: MGI calcium channel activity Inferred from mutant phenotype PubMed 12816890. Source: MGI extracellular-glutamate-gated ion channel activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Dapk1	Q80YE7	8	EBI-400125,EBI-2584874
Dlg4	Q62108	12	EBI-400125,EBI-300895

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 1482	1456	Glutamate receptor ionotropic, NMDA 2B		PRO_0000011578
Regions
	Topological domain	27 – 557	531	Extracellular Potential
	Transmembrane	558 – 578	21	Helical; Potential
	Topological domain	579 – 634	56	Cytoplasmic Potential
	Transmembrane	635 – 655	21	Helical; Potential
	Topological domain	656 – 817	162	Extracellular Potential
	Transmembrane	818 – 838	21	Helical; Potential
	Topological domain	839 – 1482	644	Cytoplasmic Potential
	Region	1292 – 1304	13	Interaction with DAPK1
	Motif	1480 – 1482	3	PDZ-binding By similarity
	Compositional bias	984 – 989	6	Poly-His
Sites
	Metal binding	127	1	Zinc By similarity
	Metal binding	284	1	Zinc By similarity
	Site	615	1	Functional determinant of NMDA receptors By similarity
Amino acid modifications
	Modified residue	917	1	Phosphoserine Ref.10
	Modified residue	930	1	Phosphoserine Ref.9
	Modified residue	932	1	Phosphotyrosine Ref.9
	Modified residue	949	1	Phosphotyrosine Ref.9
	Modified residue	962	1	Phosphotyrosine Ref.9
	Modified residue	1039	1	Phosphotyrosine Ref.9
	Modified residue	1049	1	Phosphotyrosine Ref.9
	Modified residue	1061	1	Phosphoserine Ref.9
	Modified residue	1065	1	Phosphothreonine Ref.9
	Modified residue	1070	1	Phosphotyrosine Ref.9
	Modified residue	1109	1	Phosphotyrosine Ref.9
	Modified residue	1155	1	Phosphotyrosine Ref.9
	Modified residue	1166	1	Phosphoserine Ref.7
	Modified residue	1252	1	Phosphotyrosine Ref.9
	Modified residue	1303	1	Phosphoserine; by DAPK1 Ref.7 Ref.9 Ref.10 Ref.12
	Modified residue	1472	1	Phosphotyrosine Ref.4
	Glycosylation	74	1	N-linked (GlcNAc...) Potential
	Glycosylation	341	1	N-linked (GlcNAc...) Potential
	Glycosylation	348	1	N-linked (GlcNAc...) Potential
	Glycosylation	444	1	N-linked (GlcNAc...) Potential
	Glycosylation	491	1	N-linked (GlcNAc...) Potential
	Glycosylation	542	1	N-linked (GlcNAc...) Potential
	Glycosylation	688	1	N-linked (GlcNAc...) Potential
	Disulfide bond	86 ↔ 321		By similarity
Experimental info
	Sequence conflict	99	1	L → F in BAB22483. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q01097 [UniParc]. Last modified June 20, 2001. Version 3. Checksum: B8C3FA10E9A4B36D	FASTA	1,482	165,959
	10 20 30 40 50 60 MKPSAECCSP KFWLVLAVLA VSGSKARSQK SAPSIGIAVI LVGTSDEVAI KDAHEKDDFH 70 80 90 100 110 120 HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVLA DDTDQEAIAQ ILDFISAQTL 130 140 150 160 170 180 TPILGIHGGS SMIMADKDES SMFFQFGPSI EQQASVMLNI MEEYDWYIFS IVTTYFPGYQ 190 200 210 220 230 240 DFVNKIRSTI ENSFVGWELE EVLLLDMSLD DGDSKIQNQL KKLQSPIILL YCTKEEATYI 250 260 270 280 290 300 FEVANSVGLT GYGYTWIVPS LVAGDTDTVP SEFPTGLISV SYDEWDYGLP ARVRDGIAII 310 320 330 340 350 360 TTAASDMLSE HSFIPEPKSS CYNTHEKRIY QSNMLNRYLI NVTFEGRNLS FSEDGYQMHP 370 380 390 400 410 420 KLVIILLNKE RKWERVGKWK DKSLQMKYYV WPRMCPETEE QEDDHLSIVT LEEAPFVIVE 430 440 450 460 470 480 SVDPLSGTCM RNTVPCQKRI ISENKTDEEP GYIKKCCKGF CIDILKKISK SVKFTYDLYL 490 500 510 520 530 540 VTNGKHGKKI NGTWNGMIGE VVMKRAYMAV GSLTINEERS EVVDFSVPFI ETGISVMVSR 550 560 570 580 590 600 SNGTVSPSAF LEPFSADVWV MMFVMLLIVS AVAVFVFEYF SPVGYNRCLA DGREPGGPSF 610 620 630 640 650 660 TIGKAIWLLW GLVFNNSVPV QNPKGTTSKI MVSVWAFFAV IFLASYTANL AAFMIQEEYV 670 680 690 700 710 720 DQVSGLSDKK FQRPNDFSPP FRFGTVPNGS TERNIRNNYA EMHAYMGKFN QRGVDDALLS 730 740 750 760 770 780 LKTGKLDAFI YDAAVLNYMA GRDEGCKLVT IGSGKVFAST GYGIAIQKDS GWKRQVDLAI 790 800 810 820 830 840 LQLFGDGEME ELEALWLTGI CHNEKNEVMS SQLDIDNMAG VFYMLGAAMA LSLITFICEH 850 860 870 880 890 900 LFYWQFRHCF MGVCSGKPGM VFSISRGIYS CIHGVAIEER QSVMNSPTAT MNNTHSNILR 910 920 930 940 950 960 LLRTAKNMAN LSGVNGSPQS ALDFIRRESS VYDISEHRRS FTHSDCKSYN NPPCEENLFS 970 980 990 1000 1010 1020 DYISEVERTF GNLQLKDSNV YQDHYHHHHR PHSIGSTSSI DGLYDCDNPP FTTQPRSISK 1030 1040 1050 1060 1070 1080 KPLDIGLPSS KHSQLSDLYG KFSFKSDRYS GHDDLIRSDV SDISTHTVTY GNIEGNAAKR 1090 1100 1110 1120 1130 1140 RKQQYKDSLK KRPASAKSRR EFDEIELAYR RRPPRSPDHK RYFRDKEGLR DFYLDQFRTK 1150 1160 1170 1180 1190 1200 ENSPHWEHVD LTDIYKERSD DFKRDSVSGG GPCTNRSHLK HGTGDKHGVV GGVPAPWEKN 1210 1220 1230 1240 1250 1260 LTNVDWEDRS GGNFCRSCPS KLHNYSSTVA GQNSGRQACI RCEACKKAGN LYDISEDNSL 1270 1280 1290 1300 1310 1320 QELDQPAAPV AVSSNASTTK YPQSPTNSKA QKKNRNKLRR QHSYDTFVDL QKEEAALAPR 1330 1340 1350 1360 1370 1380 SVSLKDKGRF MDGSPYAHMF EMPAGESSFA NKSSVTTAGH HHNNPGSGYM LSKSLYPDRV 1390 1400 1410 1420 1430 1440 TQNPFIPTFG DDQCLLHGSK SYFFRQPTVA GASKTRPDFR ALVTNKPVVS ALHGAVPGRF 1450 1460 1470 1480 QKDICIGNQS NPCVPNNKNP RAFNGSSNGH VYEKLSSIES DV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular diversity of the NMDA receptor channel." Kutsuwada T., Kashiwabuchi N., Mori H., Sakimura K., Kushiya E., Araki K., Meguro H., Masaki H., Kumanishi T., Arakawa M., Mishina M. Nature 358:36-41(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Kutsuwada T., Kashiwabuchi N., Mori H., Sakimura K., Kushiya E., Araki K., Meguro H., Masaki H., Kumanishi T., Arakawa M., Mishina M. Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-337. Strain: C57BL/6J. Tissue: Brain.
[4]	"Regulation of NMDA receptor function by Fyn-mediated tyrosine phosphorylation." Nakazawa T., Tezuka T., Yamamoto T. Nihon Shinkei Seishin Yakurigaku Zasshi 22:165-167(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-1472.
[5]	"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 GRIN1 AND GRIN3B.
[6]	"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: IDENTIFICATION IN A COMPLEX WITH GRIN1 AND GRIN3B.
[7]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1166 AND SER-1303, MASS SPECTROMETRY. Tissue: Brain.
[8]	"NMDA receptor function and NMDA receptor-dependent phosphorylation of huntingtin is altered by the endocytic protein HIP1." Metzler M., Gan L., Wong T.P., Liu L., Helm J., Liu L., Georgiou J., Wang Y., Bissada N., Cheng K., Roder J.C., Wang Y.T., Hayden M.R. J. Neurosci. 27:2298-2308(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIP1.
[9]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-930; TYR-932; TYR-949; TYR-962; TYR-1039; TYR-1049; SER-1061; THR-1065; TYR-1070; TYR-1109; TYR-1155; TYR-1252; SER-1303 AND TYR-1304, MASS SPECTROMETRY. Tissue: Brain.
[10]	"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-917 AND SER-1303, MASS SPECTROMETRY. Tissue: Brain cortex.
[11]	"Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning." Ng D., Pitcher G.M., Szilard R.K., Sertie A., Kanisek M., Clapcote S.J., Lipina T., Kalia L.V., Joo D., McKerlie C., Cortez M., Roder J.C., Salter M.W., McInnes R.R. PLoS Biol. 7:E41-E41(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NETO1.
[12]	"DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in stroke." Tu W., Xu X., Peng L., Zhong X., Zhang W., Soundarapandian M.M., Balel C., Wang M., Jia N., Zhang W., Lew F., Chan S.L., Chen Y., Lu Y. Cell 140:222-234(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-1303, INTERACTION WITH DAPK1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D10651 mRNA. Translation: BAA01498.2. AK002963 mRNA. Translation: BAB22483.1.
IPI	IPI00321320.
PIR	I49704.
RefSeq	NP_032197.3. NM_008171.3.
UniGene	Mm.436649.
3D structure databases
ProteinModelPortal	Q01097.
SMR	Q01097. Positions 33-836.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31568N.
IntAct	Q01097. 185 interactions.
MINT	MINT-135847.
PTM databases
PhosphoSite	Q01097.
Proteomic databases
PaxDb	Q01097.
PRIDE	Q01097.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	14812.
KEGG	mmu:14812.
UCSC	uc009elq.1. mouse.
Organism-specific databases
CTD	2904.
MGI	MGI:95821. Grin2b.
Phylogenomic databases
eggNOG	NOG282132.
HOGENOM	HOG000113802.
HOVERGEN	HBG052635.
InParanoid	Q01097.
KO	K05210.
OrthoDB	EOG4Z8XVM.
Gene expression databases
Genevestigator	Q01097.
GermOnline	ENSMUSG00000030209. Mus musculus.
Family and domain databases
InterPro	IPR001828. ANF_lig-bd_rcpt. IPR019594. Glu_rcpt_Glu/Gly-bd. IPR001320. Iontro_glu_rcpt. IPR001508. NMDA_rcpt. IPR018884. NMDAR2_C. IPR001638. SBP_bac_3. [Graphical view]
Pfam	PF01094. ANF_receptor. 1 hit. PF00060. Lig_chan. 1 hit. PF10565. NMDAR2_C. 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	Q01097.
ChEMBL	CHEMBL3442.
NextBio	287003.
SOURCE	Search...

Entry information

Entry name

NMDE2_MOUSE

Accession

Primary (citable) accession number: Q01097
Secondary accession number(s): Q9DCB2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 20, 2001
Last modified:	May 1, 2013
This is version 136 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program