Q13224 (NMDE2_HUMAN) 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
N-methyl-D-aspartate receptor subunit 3
Short name=NR3
Short name=hNR3

Gene names

Name:	GRIN2B
Synonyms:	NMDAR2B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1484 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 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). Found in a complex with GRIN1 and GRIN3B. Found in a complex with GRIN1, GRIN3A and PPP2CB. Interacts with PDZ domains of INADL and DLG4. Interacts with HIP1 and NETO1 By similarity. Interacts with MAGI3. Interacts with DAPK1 By similarity. Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein.
Tissue specificity	Primarily found in the fronto-parieto-temporal cortex and hippocampus pyramidal cells, lower expression in the basal ganglia. Ref.6
Post-translational modification	Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity By similarity.
Involvement in disease	Mental retardation, autosomal dominant 6 (MRD6) [MIM:613970]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 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.
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
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Disease mutation Mental retardation
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	behavioral fear response Inferred from electronic annotation. Source: Compara behavioral response to pain Inferred from electronic annotation. Source: Compara detection of mechanical stimulus involved in sensory perception of pain Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara learning Inferred from electronic annotation. Source: Compara learning or memory Traceable author statement PubMed 10485705. Source: ProtInc memory Inferred from electronic annotation. Source: Compara regulation of excitatory postsynaptic membrane potential Inferred from electronic annotation. Source: Compara regulation of synaptic plasticity Inferred from electronic annotation. Source: Compara response to ethanol Inferred from direct assay PubMed 18445116. Source: UniProtKB sensory organ development Inferred from electronic annotation. Source: Compara startle response Inferred from electronic annotation. Source: Compara suckling behavior Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	N-methyl-D-aspartate selective glutamate receptor complex Inferred from direct assay PubMed 10480938PubMed 17047094. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from sequence or structural similarity. Source: BHF-UCL neuron projection Inferred from sequence or structural similarity. Source: BHF-UCL outer membrane-bounded periplasmic space Inferred from electronic annotation. Source: InterPro postsynaptic density Inferred from electronic annotation. Source: Compara postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell synaptic vesicle Inferred from electronic annotation. Source: Compara
Molecular_function	N-methyl-D-aspartate selective glutamate receptor activity Traceable author statement Ref.2. Source: ProtInc calcium channel activity Inferred from electronic annotation. Source: Compara extracellular-glutamate-gated ion channel activity Inferred from electronic annotation. Source: InterPro glycine binding Inferred from direct assay PubMed 17047094. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Potential

Chain

27 – 1484

1458

Glutamate receptor ionotropic, NMDA 2B

PRO_0000011577

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 – 1484

646

Cytoplasmic Potential

Region

1292 – 1304

13

Interaction with DAPK1 By similarity

Motif

1482 – 1484

3

PDZ-binding By similarity

Compositional bias

984 – 989

6

Poly-His

Compositional bias

1361 – 1364

4

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 By similarity

Modified residue

930

1

Phosphoserine By similarity

Modified residue

932

1

Phosphotyrosine By similarity

Modified residue

949

1

Phosphotyrosine By similarity

Modified residue

962

1

Phosphotyrosine By similarity

Modified residue

1039

1

Phosphotyrosine By similarity

Modified residue

1049

1

Phosphotyrosine By similarity

Modified residue

1061

1

Phosphoserine By similarity

Modified residue

1065

1

Phosphothreonine By similarity

Modified residue

1070

1

Phosphotyrosine By similarity

Modified residue

1109

1

Phosphotyrosine By similarity

Modified residue

1155

1

Phosphotyrosine By similarity

Modified residue

1166

1

Phosphoserine By similarity

Modified residue

1252

1

Phosphotyrosine By similarity

Modified residue

1303

1

Phosphoserine; by DAPK1 By similarity

Modified residue

1474

1

Phosphotyrosine By similarity

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

Natural variations

Natural variant

407

1

S → N. Ref.1

VAR_011317

Natural variant

682

1

R → C in MRD6; analysis of agonist dose-response curves reveal no differences in the affinities of wild-type and mutant receptors for glutamate and glycine. Ref.8

VAR_065900

Experimental info

Sequence conflict

434

1

V → A in AAD00659. Ref.3

Sequence conflict

745

1

G → A in AAA69920. Ref.5

Sequence conflict

773

1

K → N in AAA69920. Ref.5

Sequence conflict

773

1

K → N in AAA74930. Ref.5

Sequence conflict

796

1

W → C in AAA69920. Ref.5

Sequence conflict

796

1

W → C in AAA74930. Ref.5

Sequence conflict

888

1

T → P in AAA69920. Ref.5

Sequence conflict

888

1

T → P in AAA74930. Ref.5

Sequence conflict

902

1

L → V in AAA69920. Ref.5

Sequence conflict

902

1

L → V in AAA74930. Ref.5

Sequence conflict

920 – 921

2

SA → RP in AAB60368. Ref.1

Sequence conflict

958

1

L → S in AAA69920. Ref.5

Sequence conflict

958

1

L → S in AAA74930. Ref.5

Sequence conflict

980 – 982

3

VYQ → DHY in AAA69920. Ref.5

Sequence conflict

1056

1

I → M in AAA69920. Ref.5

Sequence conflict

1167

1

V → I in AAB49993. Ref.2

Secondary structure

1

.

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1484

Helix Strand Turn

Details...

Turn

423 – 426

4

Beta strand

429 – 431

3

Beta strand

440 – 442

3

Helix

448 – 453

6

Helix

461 – 472

12

Helix

496 – 502

7

Beta strand

507 – 509

3

Helix

517 – 520

4

Beta strand

529 – 535

7

Helix

666 – 670

5

Helix

673 – 675

3

Turn

678 – 680

3

Helix

690 – 698

9

Helix

700 – 706

7

Helix

714 – 723

10

Beta strand

724 – 727

4

Helix

733 – 740

8

Turn

743 – 745

3

Beta strand

757 – 762

6

Helix

773 – 785

13

Helix

789 – 797

9

Sequences

	Sequence		Length	Mass (Da)
	Q13224 [UniParc]. Last modified June 20, 2001. Version 3. Checksum: 40AEB12BE6E50CEF	FASTA	1,484	166,367
	10 20 30 40 50 60 MKPRAECCSP KFWLVLAVLA VSGSRARSQK SPPSIGIAVI LVGTSDEVAI KDAHEKDDFH 70 80 90 100 110 120 HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVFA 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 AEFPTGLISV 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 VTENKTDEEP 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 PHSIGSASSI DGLYDCDNPP FTTQSRSISK 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 GPCTNRSHIK HGTGDKHGVV SGVPAPWEKN 1210 1220 1230 1240 1250 1260 LTNVEWEDRS GGNFCRSCPS KLHNYSTTVT GQNSGRQACI RCEACKKAGN LYDISEDNSL 1270 1280 1290 1300 1310 1320 QELDQPAAPV AVTSNASTTK YPQSPTNSKA QKKNRNKLRR QHSYDTFVDL QKEEAALAPR 1330 1340 1350 1360 1370 1380 SVSLKDKGRF MDGSPYAHMF EMSAGESTFA NNKSSVPTAG HHHHNNPGGG YMLSKSLYPD 1390 1400 1410 1420 1430 1440 RVTQNPFIPT FGDDQCLLHG SKSYFFRQPT VAGASKARPD FRALVTNKPV VSALHGAVPA 1450 1460 1470 1480 RFQKDICIGN QSNPCVPNNK NPRAFNGSSN GHVYEKLSSI ESDV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human N-methyl-D-aspartate receptor modulatory subunit hNR3: cloning and sequencing of the cDNA and primary structure of the protein." Adams S.L., Foldes R.L., Kamboj R.K. Biochim. Biophys. Acta 1260:105-108(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-407. Tissue: Fetal brain.
[2]	"Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors." Hess S.D., Daggett L.P., Crona J., Deal C., Lu C.-C., Urrutia A., Chavez-Noriega L., Ellis S.B., Johnson E.C., Velicelebi G. J. Pharmacol. Exp. Ther. 278:808-816(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[3]	"Cloning of GRIN2B human subunit." Mandich P., Schito A.M., Pizzuti A., Ratti A. Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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]. Tissue: Cerebellum.
[5]	"Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12." Mandich P., Schito A.M., Bellone E., Antonacci R., Finelli P., Rocchi M., Ajmar F. Genomics 22:216-218(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-294 AND 661-1089.
[6]	"mRNA distribution in adult human brain of GRIN2B, a N-methyl-D-aspartate (NMDA) receptor subunit." Schito A.M., Pizzuti A., Di Maria E., Schenone A., Ratti A., Defferrari R., Bellone E., Mancardi G.L., Ajmar F., Mandich P. Neurosci. Lett. 239:49-53(1997) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase." Wu Y., Dowbenko D., Spencer S., Laura R., Lee J., Gu Q., Lasky L.A. J. Biol. Chem. 275:21477-21485(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAGI3.
[8]	"Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes." Endele S., Rosenberger G., Geider K., Popp B., Tamer C., Stefanova I., Milh M., Kortum F., Fritsch A., Pientka F.K., Hellenbroich Y., Kalscheuer V.M., Kohlhase J., Moog U., Rappold G., Rauch A., Ropers H.H., von Spiczak S. , Tonnies H., Villeneuve N., Villard L., Zabel B., Zenker M., Laube B., Reis A., Wieczorek D., Van Maldergem L., Kutsche K. Nat. Genet. 42:1021-1026(2010) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATIONS, VARIANT MRD6 CYS-682.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00297933.

PIR

I39066.
S52086.

RefSeq

NP_000825.2. NM_000834.3.

UniGene

Hs.654430.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S11	model	-	A	403-543	[»]
			B	660-801	[»]
1S2S	model	-	A	405-543	[»]
			B	660-801	[»]
2IPV	model	-	X	404-768	[»]

ProteinModelPortal

Q13224.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13224. 5 interactions.

MINT

MINT-127466.

STRING

9606.ENSP00000279593.

PTM databases

PhosphoSite

Q13224.

Polymorphism databases

DMDM

14548162.

Proteomic databases

PaxDb

Q13224.

PeptideAtlas

Q13224.

PRIDE

Q13224.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000279593; ENSP00000279593; ENSG00000150086.

GeneID

2904.

KEGG

hsa:2904.

UCSC

uc001rbt.2. human.

Organism-specific databases

CTD

2904.

GeneCards

GC12M013614.

H-InvDB

HIX0036873.

HGNC

HGNC:4586. GRIN2B.

MIM

138252. gene.
613970. phenotype.

neXtProt

NX_Q13224.

Orphanet

178469. Autosomal dominant nonsyndromic intellectual deficit.

PharmGKB

PA28980.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG282132.

HOGENOM

HOG000113802.

HOVERGEN

HBG052635.

InParanoid

Q13224.

KO

K05210.

OMA

CTNRSHL.

OrthoDB

EOG4Z8XVM.

PhylomeDB

Q13224.

Enzyme and pathway databases

Pathway_Interaction_DB

reelinpathway. Reelin signaling pathway.

Reactome

REACT_13685. Neuronal System.

SignaLink

Q13224.

Gene expression databases

ArrayExpress

Q13224.

Bgee

Q13224.

CleanEx

HS_GRIN2B.

Genevestigator

Q13224.

GermOnline

ENSG00000150086. Homo sapiens.

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

Q13224.

ChEMBL

CHEMBL1904.

DrugBank

DB00949. Felbamate.
DB00502. Haloperidol.
DB00142. L-Glutamic Acid.
DB00836. Loperamide.
DB01043. Memantine.

GenomeRNAi

2904.

NextBio

11499.

SOURCE

Search...

Entry information

Entry name

NMDE2_HUMAN

Accession

Primary (citable) accession number: Q13224
Secondary accession number(s): Q12919 , Q13220, Q13225, Q14CU4, Q9UM56

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	June 20, 2001
Last modified:	May 29, 2013
This is version 138 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.