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Protein

Glutamate receptor ionotropic, delta-2

Gene

GRID2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. Promotes synaptogenesis and mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis of cerebellar parallel fiber-Purkinje cell (PF-PC) synapses through the beta-NRX1-CBLN1-GRID2 triad complex (PubMed:27418511).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei76Essential for dimerization1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Receptor
Biological processIon transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate receptor ionotropic, delta-2
Short name:
GluD2
Short name:
GluR delta-2 subunit
Gene namesi
Name:GRID2
Synonyms:GLURD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000152208.11
HGNCiHGNC:4576 GRID2
MIMi602368 gene
neXtProtiNX_O43424

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 566ExtracellularSequence analysisAdd BLAST543
Transmembranei567 – 587HelicalSequence analysisAdd BLAST21
Topological domaini588 – 635CytoplasmicSequence analysisAdd BLAST48
Transmembranei636 – 656HelicalSequence analysisAdd BLAST21
Topological domaini657 – 830ExtracellularSequence analysisAdd BLAST174
Transmembranei831 – 851HelicalSequence analysisAdd BLAST21
Topological domaini852 – 1007CytoplasmicSequence analysisAdd BLAST156

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia, autosomal recessive, 18 (SCAR18)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSpinocerebellar ataxia defines a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR18 features include progressive cerebellar atrophy, delayed psychomotor development, severely impaired gait, ocular movement abnormalities, and intellectual disability.
See also OMIM:616204
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074166654A → D in SCAR18. 1 Publication1
Natural variantiVAR_074167654A → T in SCAR18; constitutively open the extracellular-glutamate-gated ion channel. 2 Publications1
Natural variantiVAR_074168656L → V in SCAR18. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24D → A: Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-26; A-61; D-76 and A-345. Abolishes synapse assembly; when associated with A-26; A-61 and A-345. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-26; A-61 and A-345. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-26; A-61 and A-345. 1 Publication1
Mutagenesisi25S → A: Reduces binding to CBLN1; when associated with D76. 1 Publication1
Mutagenesisi26I → A: Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-24; A-61; D-76 and A-345. Abolishes synapse assembly; when associated with A-24; A-61 and A-345. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-24; A-61 and A-345. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-24; A-61 and A-345. 1 Publication1
Mutagenesisi60T → A: No effect on CBLN1 interaction; when associated with D76. 1 Publication1
Mutagenesisi61E → A: Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-24; A-26; D-76 and A-345. Abolishes synapse assembly; when associated with A-24; A-26 and A-345. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-24; A-26 and A-345. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-24; A-26 and A-345. 1 Publication1
Mutagenesisi76F → D: Monomeric form. Does not dimerize. Weakly interacts with C1q domain of CBLN1. Forms intermediate synapse. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation. Abolishes D-Serine?dependent long term synaptic depression at PF-PC synapses. Does not recover motor coordination in experiment of tranfection in Grid2-null mice. 1 Publication1
Mutagenesisi342L → A: Reduces binding to CBLN1; when associated with D76. 1 Publication1
Mutagenesisi343E → A: No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-346; A-349 and A-350. No effect on synapse assembly; when associated with A-346; A-349 and A-350. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-346; A-349 and A-350. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-346; A-349 and A-350. Does not affect motor coordination; when associated with A-346; A-349 and A-350. 1 Publication1
Mutagenesisi344D → A: No effect on CBLN1 interaction; when associated with D76. 1 Publication1
Mutagenesisi345R → A: Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-24; A-26; A-61 and D-76. Abolishes synapse assembly; when associated with A-24; A-26 and A-61. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-24; A-26 and A-61. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-24; A-26 and A-61. 1 Publication1
Mutagenesisi346K → A: No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-343; A-349 and A-350. No effect on synapse assembly; when associated with A-343; A-349 and A-350. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-343; A-349 and A-350. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-343; A-349 and A-350. Does not affect motor coordination; when associated with A-343; A-349 and A-350. 1 Publication1
Mutagenesisi348H → A: Reduces binding to CBLN1; when associated with D76. 1 Publication1
Mutagenesisi349S → A: No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-343; A-346 and A-350. No effect on synapse assembly; when associated with A-343; A-346 and A-350. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-343; A-346 and A-350. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-343; A-346 and A-350. Does not affect motor coordination; when associated with A-343; A-346 and A-350. 1 Publication1
Mutagenesisi350M → A: No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-343; A-346 and A-349. No effect on synapse assembly; when associated with A-343; A-346 and A-349. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-343; A-346 and A-349. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-343; A-346 and A-349. Does not affect motor coordination; when associated with A-343; A-346 and A-349. 1 Publication1
Mutagenesisi352S → A: Reduces binding to CBLN1; when associated with D76. 1 Publication1
Mutagenesisi364Q → A: No effect on CBLN1 interaction; when associated with D76. 1 Publication1
Mutagenesisi434L → ELSNGTDGAS: Impairs the ability of the LBD to induce pore closure. No effect on synapse assembly. No effect on cerebellar parallel fiber-Purkinje cell synapse formation. Abolishes D-Serine?dependent long term synaptic depression at PF-PC synapses. Does not affect motor coordination. 1 Publication1

Keywords - Diseasei

Neurodegeneration

Organism-specific databases

DisGeNETi2895
MalaCardsiGRID2
MIMi616204 phenotype
OpenTargetsiENSG00000152208
Orphaneti363432 Autosomal recessive congenital cerebellar ataxia due to GRID2 deficiency
PharmGKBiPA28971

Chemistry databases

DrugBankiDB00142 L-Glutamic Acid

Polymorphism and mutation databases

BioMutaiGRID2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000001156424 – 1007Glutamate receptor ionotropic, delta-2Add BLAST984

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi83 ↔ 355Combined sources1 Publication
Disulfide bondi99 ↔ 131Combined sources1 Publication
Glycosylationi293N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi298 ↔ 310Combined sources1 Publication
Glycosylationi426N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei883PhosphoserineBy similarity1
Modified residuei886PhosphothreonineBy similarity1
Modified residuei890PhosphoserineBy similarity1
Modified residuei1006PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiO43424
MaxQBiO43424
PaxDbiO43424
PeptideAtlasiO43424
PRIDEiO43424

PTM databases

iPTMnetiO43424
PhosphoSitePlusiO43424

Expressioni

Gene expression databases

BgeeiENSG00000152208
CleanExiHS_GRID2
ExpressionAtlasiO43424 baseline and differential
GenevisibleiO43424 HS

Organism-specific databases

HPAiHPA056253
HPA058538

Interactioni

Subunit structurei

Tetramer; dimer of dimers (PubMed:27418511). Interacts with EML2, MAGI2 (via PDZ domains) and AP4M1 (By similarity). Interacts with BECN1, GOPC, GRID2IP, SHANK1 and SHANK2. Interacts with CBLN2, but not with CBLN4 (By similarity). Interacts with CBLN1 (via C1q domain); the interaction is CBLN1-NRX1 complex formation-dependent; CBLN1-binding is calcium-independent; CBLN1 hexamers anchor GRID2 N-terminal domain dimers to monomeric NRXN1 isoform beta; promotes synaptogenesis and mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (PubMed:27418511).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Magi2O883822EBI-8604158,EBI-696179From Rattus norvegicus.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109152, 7 interactors
IntActiO43424, 1 interactor
MINTiO43424
STRINGi9606.ENSP00000282020

Structurei

Secondary structure

11007
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 34Combined sources8
Helixi38 – 53Combined sources16
Beta strandi63 – 70Combined sources8
Helixi75 – 88Combined sources14
Beta strandi93 – 97Combined sources5
Helixi99 – 112Combined sources14
Beta strandi116 – 120Combined sources5
Beta strandi137 – 139Combined sources3
Beta strandi143 – 145Combined sources3
Helixi152 – 162Combined sources11
Beta strandi167 – 172Combined sources6
Helixi178 – 181Combined sources4
Helixi182 – 190Combined sources9
Beta strandi194 – 199Combined sources6
Helixi204 – 214Combined sources11
Helixi217 – 226Combined sources10
Beta strandi229 – 234Combined sources6
Helixi236 – 248Combined sources13
Beta strandi257 – 261Combined sources5
Helixi267 – 276Combined sources10
Beta strandi279 – 287Combined sources9
Helixi294 – 297Combined sources4
Beta strandi298 – 300Combined sources3
Helixi307 – 310Combined sources4
Helixi315 – 318Combined sources4
Helixi322 – 343Combined sources22
Beta strandi355 – 357Combined sources3
Helixi366 – 374Combined sources9
Beta strandi377 – 380Combined sources4
Beta strandi383 – 386Combined sources4
Beta strandi397 – 402Combined sources6
Beta strandi414 – 420Combined sources7
Turni421 – 423Combined sources3
Beta strandi424 – 427Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5KC8X-ray1.75A24-440[»]
5KCAX-ray3.10A24-440[»]
ProteinModelPortaliO43424
SMRiO43424
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni24 – 345Interaction with CBLN1 homotrimer1 PublicationAdd BLAST322
Regioni921 – 991Interaction with AP4M1By similarityAdd BLAST71

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1005 – 1007PDZ-bindingBy similarity3

Domaini

The PDZ-binding motif mediates interaction with GOPC.By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ISR9 Eukaryota
ENOG410YYDD LUCA
GeneTreeiENSGT00910000143978
HOGENOMiHOG000264260
HOVERGENiHBG051840
InParanoidiO43424
KOiK05207
OMAiGVRKLGC
OrthoDBiEOG091G010L
PhylomeDBiO43424
TreeFamiTF352434

Family and domain databases

InterProiView protein in InterPro
IPR001828 ANF_lig-bd_rcpt
IPR019594 Glu/Gly-bd
IPR001508 Iono_rcpt_met
IPR001320 Iontro_rcpt
IPR028082 Peripla_BP_I
PfamiView protein in Pfam
PF01094 ANF_receptor, 1 hit
PF00060 Lig_chan, 1 hit
PF10613 Lig_chan-Glu_bd, 1 hit
PRINTSiPR00177 NMDARECEPTOR
SMARTiView protein in SMART
SM00918 Lig_chan-Glu_bd, 1 hit
SM00079 PBPe, 1 hit
SUPFAMiSSF53822 SSF53822, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43424-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEVFPFLLVL SVWWSRTWDS ANADSIIHIG AIFDESAKKD DEVFRTAVGD
60 70 80 90 100
LNQNEEILQT EKITFSVTFV DGNNPFQAVQ EACELMNQGI LALVSSIGCT
110 120 130 140 150
SAGSLQSLAD AMHIPHLFIQ RSTAGTPRSG CGLTRSNRND DYTLSVRPPV
160 170 180 190 200
YLHDVILRVV TEYAWQKFII FYDSEYDIRG IQEFLDKVSQ QGMDVALQKV
210 220 230 240 250
ENNINKMITT LFDTMRIEEL NRYRDTLRRA ILVMNPATAK SFITEVVETN
260 270 280 290 300
LVAFDCHWII INEEINDVDV QELVRRSIGR LTIIRQTFPV PQNISQRCFR
310 320 330 340 350
GNHRISSTLC DPKDPFAQNM EISNLYIYDT VLLLANAFHK KLEDRKWHSM
360 370 380 390 400
ASLSCIRKNS KPWQGGRSML ETIKKGGVSG LTGELEFGEN GGNPNVHFEI
410 420 430 440 450
LGTNYGEELG RGVRKLGCWN PVTGLNGSLT DKKLENNMRG VVLRVVTVLE
460 470 480 490 500
EPFVMVSENV LGKPKKYQGF SIDVLDALSN YLGFNYEIYV APDHKYGSPQ
510 520 530 540 550
EDGTWNGLVG ELVFKRADIG ISALTITPDR ENVVDFTTRY MDYSVGVLLR
560 570 580 590 600
RAEKTVDMFA CLAPFDLSLW ACIAGTVLLV GLLVYLLNWL NPPRLQMGSM
610 620 630 640 650
TSTTLYNSMW FVYGSFVQQG GEVPYTTLAT RMMMGAWWLF ALIVISSYTA
660 670 680 690 700
NLAAFLTITR IESSIQSLQD LSKQTEIPYG TVLDSAVYEH VRMKGLNPFE
710 720 730 740 750
RDSMYSQMWR MINRSNGSEN NVLESQAGIQ KVKYGNYAFV WDAAVLEYVA
760 770 780 790 800
INDPDCSFYT IGNTVADRGY GIALQHGSPY RDVFSQRILE LQQNGDMDIL
810 820 830 840 850
KHKWWPKNGQ CDLYSSVDTK QKGGALDIKS FAGVFCILAA GIVLSCFIAM
860 870 880 890 900
LETWWNKRKG SRVPSKEDDK EIDLEHLHRR VNSLCTDDDS PHKQFSTSSI
910 920 930 940 950
DLTPLDIDTL PTRQALEQIS DFRNTHITTT TFIPEQIQTL SRTLSAKAAS
960 970 980 990 1000
GFTFGNVPEH RTGPFRHRAP NGGFFRSPIK TMSSIPYQPT PTLGLNLGND

PDRGTSI
Length:1,007
Mass (Da):113,356
Last modified:May 5, 2009 - v2
Checksum:i8EF938AB7F1D6D26
GO
Isoform 2 (identifier: O43424-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     82-176: Missing.

Show »
Length:912
Mass (Da):102,822
Checksum:iA82226A9B772131B
GO

Sequence cautioni

The sequence BAD92555 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6F → L in AAC39579 (PubMed:9465309).Curated1
Sequence conflicti6F → L in AAH99652 (PubMed:15489334).Curated1
Sequence conflicti6F → L in AAH99653 (PubMed:15489334).Curated1
Sequence conflicti6F → L in AAH99654 (PubMed:15489334).Curated1
Sequence conflicti8L → F in AAH99652 (PubMed:15489334).Curated1
Sequence conflicti290V → I in AAC39579 (PubMed:9465309).Curated1
Sequence conflicti462G → C in AAC39579 (PubMed:9465309).Curated1
Sequence conflicti557D → E in AAH99652 (PubMed:15489334).Curated1
Sequence conflicti752N → Y in AAC39579 (PubMed:9465309).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05501668T → M1 PublicationCorresponds to variant dbSNP:rs34144324Ensembl.1
Natural variantiVAR_035697209T → N in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_055017398F → S. Corresponds to variant dbSNP:rs34796082Ensembl.1
Natural variantiVAR_055018490V → I. Corresponds to variant dbSNP:rs10034345Ensembl.1
Natural variantiVAR_074166654A → D in SCAR18. 1 Publication1
Natural variantiVAR_074167654A → T in SCAR18; constitutively open the extracellular-glutamate-gated ion channel. 2 Publications1
Natural variantiVAR_074168656L → V in SCAR18. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05470482 – 176Missing in isoform 2. 1 PublicationAdd BLAST95

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF009014 mRNA Translation: AAC39579.1
AB209318 mRNA Translation: BAD92555.1 Different initiation.
AC020699 Genomic DNA No translation available.
AC022317 Genomic DNA No translation available.
AC093596 Genomic DNA No translation available.
AC093733 Genomic DNA No translation available.
AC095059 Genomic DNA No translation available.
AC096769 Genomic DNA No translation available.
AC104077 Genomic DNA No translation available.
AC105315 Genomic DNA No translation available.
AC105452 Genomic DNA No translation available.
AC108158 Genomic DNA No translation available.
AC110800 Genomic DNA No translation available.
AC112695 Genomic DNA No translation available.
AC115111 Genomic DNA No translation available.
AC115537 Genomic DNA No translation available.
BC099652 mRNA Translation: AAH99652.1
BC099653 mRNA Translation: AAH99653.1
BC099654 mRNA Translation: AAH99654.1
CCDSiCCDS3637.1 [O43424-1]
CCDS68758.1 [O43424-2]
RefSeqiNP_001273767.1, NM_001286838.1 [O43424-2]
NP_001501.2, NM_001510.3 [O43424-1]
UniGeneiHs.162727
Hs.480281

Genome annotation databases

EnsembliENST00000282020; ENSP00000282020; ENSG00000152208 [O43424-1]
ENST00000510992; ENSP00000421257; ENSG00000152208 [O43424-2]
GeneIDi2895
KEGGihsa:2895
UCSCiuc011cdt.4 human [O43424-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGRID2_HUMAN
AccessioniPrimary (citable) accession number: O43424
Secondary accession number(s): E9PH24
, Q4KKU8, Q4KKU9, Q4KKV0, Q59FZ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: May 5, 2009
Last modified: March 28, 2018
This is version 162 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health