O15399 (NMDE4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamate receptor ionotropic, NMDA 2D
Short name=GluN2D

Alternative name(s):
EB11
Glutamate [NMDA] receptor subunit epsilon-4
N-methyl D-aspartate receptor subtype 2D
Short name=NMDAR2D
Short name=NR2D

Gene names

Name:	GRIN2D
Synonyms:	GluN2D, NMDAR2D

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	1336 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.
Subunit structure	Interacts with PDZ domains of INADL and DLG4 By similarity. Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B).
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2D/GRIN2D subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	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 electronic annotation. Source: Compara ionotropic glutamate receptor signaling pathway Inferred from electronic annotation. Source: GOC regulation of sensory perception of pain Inferred from electronic annotation. Source: Compara startle response Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW outer membrane-bounded periplasmic space Inferred from electronic annotation. Source: InterPro plasma membrane Traceable author statement. Source: Reactome postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	N-methyl-D-aspartate selective glutamate receptor activity Inferred from electronic annotation. Source: Compara extracellular-glutamate-gated ion channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 1336	1309	Glutamate receptor ionotropic, NMDA 2D		PRO_0000011583
Regions
	Topological domain	28 – 583	556	Extracellular Potential
	Transmembrane	584 – 604	21	Helical; Potential
	Topological domain	605 – 656	52	Cytoplasmic Potential
	Transmembrane	657 – 677	21	Helical; Potential
	Topological domain	678 – 844	167	Extracellular Potential
	Transmembrane	845 – 865	21	Helical; Potential
	Topological domain	866 – 1336	471	Cytoplasmic Potential
	Motif	1334 – 1336	3	PDZ-binding By similarity
	Compositional bias	281 – 286	6	Poly-Gly
	Compositional bias	908 – 916	9	Poly-Pro
	Compositional bias	1035 – 1040	6	Poly-Ala
	Compositional bias	1209 – 1213	5	Poly-Pro
	Compositional bias	1244 – 1247	4	Poly-Ala
Sites
	Site	642	1	Functional determinant of NMDA receptors By similarity
Amino acid modifications
	Modified residue	1326	1	Phosphoserine By similarity
	Glycosylation	92	1	N-linked (GlcNAc...) Potential
	Glycosylation	352	1	N-linked (GlcNAc...) Potential
	Glycosylation	366	1	N-linked (GlcNAc...) Potential
	Glycosylation	467	1	N-linked (GlcNAc...) Potential
	Glycosylation	569	1	N-linked (GlcNAc...) Potential
	Disulfide bond	455 ↔ 483		By similarity
	Disulfide bond	462 ↔ 484		By similarity
	Disulfide bond	773 ↔ 828		By similarity
Natural variations
	Natural variant	140	1	P → S in a breast cancer sample; somatic mutation. Ref.3		VAR_035698
	Natural variant	286	1	G → R in a breast cancer sample; somatic mutation. Ref.3		VAR_035699
	Natural variant	527	1	E → G in a breast cancer sample; somatic mutation. Ref.3		VAR_035700
Experimental info
	Sequence conflict	924	1	R → G in AAC15910. Ref.1
	Sequence conflict	1005	1	P → A in AAC15910. Ref.1
	Sequence conflict	1097	1	R → C in AAC15910. Ref.1
	Sequence conflict	1130	1	E → D in AAC15910. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O15399 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 0DB7559056AE4593	FASTA	1,336	143,752
	10 20 30 40 50 60 MRGAGGPRGP RGPAKMLLLL ALACASPFPE EAPGPGGAGG PGGGLGGARP LNVALVFSGP 70 80 90 100 110 120 AYAAEAARLG PAVAAAVRSP GLDVRPVALV LNGSDPRSLV LQLCDLLSGL RVHGVVFEDD 130 140 150 160 170 180 SRAPAVAPIL DFLSAQTSLP IVAVHGGAAL VLTPKEKGST FLQLGSSTEQ QLQVIFEVLE 190 200 210 220 230 240 EYDWTSFVAV TTRAPGHRAF LSYIEVLTDG SLVGWEHRGA LTLDPGAGEA VLSAQLRSVS 250 260 270 280 290 300 AQIRLLFCAR EEAEPVFRAA EEAGLTGSGY VWFMVGPQLA GGGGSGAPGE PPLLPGGAPL 310 320 330 340 350 360 PAGLFAVRSA GWRDDLARRV AAGVAVVARG AQALLRDYGF LPELGHDCRA QNRTHRGESL 370 380 390 400 410 420 HRYFMNITWD NRDYSFNEDG FLVNPSLVVI SLTRDRTWEV VGSWEQQTLR LKYPLWSRYG 430 440 450 460 470 480 RFLQPVDDTQ HLTVATLEER PFVIVEPADP ISGTCIRDSV PCRSQLNRTH SPPPDAPRPE 490 500 510 520 530 540 KRCCKGFCID ILKRLAHTIG FSYDLYLVTN GKHGKKIDGV WNGMIGEVFY QRADMAIGSL 550 560 570 580 590 600 TINEERSEIV DFSVPFVETG ISVMVARSNG TVSPSAFLEP YSPAVWVMMF VMCLTVVAVT 610 620 630 640 650 660 VFIFEYLSPV GYNRSLATGK RPGGSTFTIG KSIWLLWALV FNNSVPVENP RGTTSKIMVL 670 680 690 700 710 720 VWAFFAVIFL ASYTANLAAF MIQEEYVDTV SGLSDRKFQR PQEQYPPLKF GTVPNGSTEK 730 740 750 760 770 780 NIRSNYPDMH SYMVRYNQPR VEEALTQLKA GKLDAFIYDA AVLNYMARKD EGCKLVTIGS 790 800 810 820 830 840 GKVFATTGYG IALHKGSRWK RPIDLALLQF LGDDEIEMLE RLWLSGICHN DKIEVMSSKL 850 860 870 880 890 900 DIDNMAGVFY MLLVAMGLSL LVFAWEHLVY WRLRHCLGPT HRMDFLLAFS RGMYSCCSAE 910 920 930 940 950 960 AAPPPAKPPP PPQPLPSPAY PAPRPAPGPA PFVPRERASV DRWRRTKGAG PPGGAGLADG 970 980 990 1000 1010 1020 FHRYYGPIEP QGLGLGLGEA RAAPRGAAGR PLSPPAAQPP QKPPPSYFAI VRDKEPAEPP 1030 1040 1050 1060 1070 1080 AGAFPGFPSP PAPPAAAATA VGPPLCRLAF EDESPPAPAR WPRSDPESQP LLGPGAGGAG 1090 1100 1110 1120 1130 1140 GTGGAGGGAP AAPPPCRAAP PPCPYLDLEP SPSDSEDSES LGGASLGGLE PWWFADFPYP 1150 1160 1170 1180 1190 1200 YAERLGPPPG RYWSVDKLGG WRAGSWDYLP PRSGPAAWHC RHCASLELLP PPRHLSCSHD 1210 1220 1230 1240 1250 1260 GLDGGWWAPP PPPWAAGPLP RRRARCGCPR SHPHRPRASH RTPAAAAPHH HRHRRAAGGW 1270 1280 1290 1300 1310 1320 DLPPPAPTSR SLEDLSSCPR AAPARRLTGP SRHARRCPHA AHWGPPLPTA SHRRHRGGDL 1330 GTRRGSAHFS SLESEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Functional characterization of human N-methyl-D-aspartate subtype 1A/2D receptors." Hess S.D., Daggett L.P., Deal C., Lu C.-C., Johnson E.C., Velicelebi G. J. Neurochem. 70:1269-1279(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-140; ARG-286 AND GLY-527.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U77783 mRNA. Translation: AAC15910.1. AC008403 Genomic DNA. No translation available. AC011527 Genomic DNA. No translation available.
IPI	IPI00006217.
RefSeq	NP_000827.2. NM_000836.2.
UniGene	Hs.445015.
3D structure databases
ProteinModelPortal	O15399.
ModBase	Search...
Protein-protein interaction databases
IntAct	O15399. 1 interaction.
MINT	MINT-130143.
STRING	9606.ENSP00000263269.
PTM databases
PhosphoSite	O15399.
Proteomic databases
PaxDb	O15399.
PRIDE	O15399.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263269; ENSP00000263269; ENSG00000105464.
GeneID	2906.
KEGG	hsa:2906.
UCSC	uc002pjc.4. human.
Organism-specific databases
CTD	2906.
GeneCards	GC19P048898.
H-InvDB	HIX0040164.
HGNC	HGNC:4588. GRIN2D.
HPA	HPA038269.
MIM	602717. gene.
neXtProt	NX_O15399.
PharmGKB	PA28982.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG282132.
HOGENOM	HOG000113803.
HOVERGEN	HBG052637.
InParanoid	O15399.
KO	K05212.
OMA	ARCGCPR.
OrthoDB	EOG42RD6M.
PhylomeDB	O15399.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	O15399.
CleanEx	HS_GRIN2D.
Genevestigator	O15399.
GermOnline	ENSG00000105464. 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. IPR001638. SBP_bac_3. [Graphical view]
Pfam	PF01094. ANF_receptor. 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	O15399.
ChEMBL	CHEMBL2591.
DrugBank	DB00142. L-Glutamic Acid. DB00836. Loperamide. DB01173. Orphenadrine.
GenomeRNAi	2906.
NextBio	11507.
SOURCE	Search...

Entry information

Entry name

NMDE4_HUMAN

Accession

Primary (citable) accession number: O15399

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 29, 2001
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 120 of the entry and version 2 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.