GRID2_MOUSE
ID GRID2_MOUSE Reviewed; 1007 AA.
AC Q61625; A4QPG1;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Glutamate receptor ionotropic, delta-2;
DE Short=GluD2;
DE Short=GluR delta-2 subunit;
DE Flags: Precursor;
GN Name=Grid2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=ICR; TISSUE=Brain;
RX PubMed=7506541; DOI=10.1006/bbrc.1993.2614;
RA Araki K., Meguro H., Kushiya E., Takayama C., Inoue Y., Mishina M.;
RT "Selective expression of the glutamate receptor channel delta 2 subunit in
RT cerebellar Purkinje cells.";
RL Biochem. Biophys. Res. Commun. 197:1267-1276(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH GOPC AND BECN1, AND DOMAIN.
RX PubMed=12372286; DOI=10.1016/s0896-6273(02)00861-9;
RA Yue Z., Horton A., Bravin M., DeJager P.L., Selimi F., Heintz N.;
RT "A novel protein complex linking the delta 2 glutamate receptor and
RT autophagy: implications for neurodegeneration in lurcher mice.";
RL Neuron 35:921-933(2002).
RN [4]
RP INTERACTION WITH SHANK1 AND SHANK2, MUTAGENESIS OF SER-920, AND TISSUE
RP SPECIFICITY.
RX PubMed=15207857; DOI=10.1016/j.mcn.2004.02.007;
RA Uemura T., Mori H., Mishina M.;
RT "Direct interaction of GluRdelta2 with Shank scaffold proteins in
RT cerebellar Purkinje cells.";
RL Mol. Cell. Neurosci. 26:330-341(2004).
RN [5]
RP INTERACTION WITH GRID2IP.
RX PubMed=17027646; DOI=10.1016/j.bbrc.2006.09.109;
RA Sonoda T., Mochizuki C., Yamashita T., Watanabe-Kaneko K., Miyagi Y.,
RA Shigeri Y., Yazama F., Okuda K., Kawamoto S.;
RT "Binding of glutamate receptor delta2 to its scaffold protein, Delphilin,
RT is regulated by PKA.";
RL Biochem. Biophys. Res. Commun. 350:748-752(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-883; THR-886 AND SER-890, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INTERACTION WITH CBLN1.
RX PubMed=20395510; DOI=10.1126/science.1185152;
RA Matsuda K., Miura E., Miyazaki T., Kakegawa W., Emi K., Narumi S.,
RA Fukazawa Y., Ito-Ishida A., Kondo T., Shigemoto R., Watanabe M., Yuzaki M.;
RT "Cbln1 is a ligand for an orphan glutamate receptor delta2, a bidirectional
RT synapse organizer.";
RL Science 328:363-368(2010).
RN [8]
RP INTERACTION WITH CBLN1.
RX PubMed=21410790; DOI=10.1111/j.1460-9568.2011.07638.x;
RA Matsuda K., Yuzaki M.;
RT "Cbln family proteins promote synapse formation by regulating distinct
RT neurexin signaling pathways in various brain regions.";
RL Eur. J. Neurosci. 33:1447-1461(2011).
RN [9]
RP INTERACTION WITH CBLN1 AND CBLN2.
RX PubMed=22220752; DOI=10.1111/j.1471-4159.2012.07648.x;
RA Wei P., Pattarini R., Rong Y., Guo H., Bansal P.K., Kusnoor S.V.,
RA Deutch A.Y., Parris J., Morgan J.I.;
RT "The Cbln family of proteins interact with multiple signaling pathways.";
RL J. Neurochem. 121:717-729(2012).
RN [10]
RP INTERACTION WITH CBLN1.
RX PubMed=29782851; DOI=10.1016/j.brainres.2018.05.022;
RA Rong Y., Bansal P.K., Wei P., Guo H., Correia K., Parris J., Morgan J.I.;
RT "Glycosylation of Cblns attenuates their receptor binding.";
RL Brain Res. 1694:129-139(2018).
RN [11]
RP VARIANT LURCHER THR-654.
RC TISSUE=Purkinje cell;
RX PubMed=9285588; DOI=10.1038/42009;
RA Zuo J., De Jager P.L., Takahashi K.A., Jiang W., Linden D.J., Heintz N.;
RT "Neurodegeneration in Lurcher mice caused by mutation in delta2 glutamate
RT receptor gene.";
RL Nature 388:769-773(1997).
CC -!- FUNCTION: Receptor for glutamate. L-glutamate acts as an excitatory
CC neurotransmitter at many synapses in the central nervous system. The
CC postsynaptic actions of Glu are mediated by a variety of receptors that
CC are named according to their selective agonists. Promotes
CC synaptogenesis and mediates the D-Serine-dependent long term depression
CC signals and AMPA receptor endocytosis of cerebellar parallel fiber-
CC Purkinje cell (PF-PC) synapses through the beta-NRX1-CBLN1-GRID2 triad
CC complex. {ECO:0000250|UniProtKB:O43424}.
CC -!- SUBUNIT: Tetramer; dimer of dimers (By similarity). Interacts with
CC EML2, MAGI2 (via PDZ domains) and AP4M1 (By similarity). Interacts with
CC BECN1, GOPC, GRID2IP, SHANK1 and SHANK2 (PubMed:12372286,
CC PubMed:15207857, PubMed:17027646). Interacts with CBLN2, but not with
CC CBLN4 (PubMed:22220752). Interacts with CBLN1 (via C1q domain); the
CC interaction is CBLN1-NRX1 complex formation-dependent; CBLN1-binding is
CC calcium-independent; CBLN1 hexamers anchor GRID2 N-terminal domain
CC dimers to monomeric NRXN1 isoform beta; promotes synaptogenesis and
CC mediates the D-Serine-dependent long term depression signals and AMPA
CC receptor endocytosis (PubMed:20395510, PubMed:21410790,
CC PubMed:22220752, PubMed:29782851). {ECO:0000250|UniProtKB:O43424,
CC ECO:0000250|UniProtKB:Q63226, ECO:0000269|PubMed:12372286,
CC ECO:0000269|PubMed:15207857, ECO:0000269|PubMed:17027646,
CC ECO:0000269|PubMed:20395510, ECO:0000269|PubMed:21410790,
CC ECO:0000269|PubMed:22220752, ECO:0000269|PubMed:29782851}.
CC -!- INTERACTION:
CC Q61625; Q9R171: Cbln1; NbExp=8; IntAct=EBI-2794106, EBI-2794140;
CC Q61625; Q8BH60: Gopc; NbExp=5; IntAct=EBI-2794106, EBI-296357;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Postsynaptic cell membrane {ECO:0000250}; Multi-
CC pass membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed selectively in cerebellar Purkinje cells
CC where it is localized in dendritic spines.
CC {ECO:0000269|PubMed:15207857, ECO:0000269|PubMed:7506541}.
CC -!- DOMAIN: The PDZ-binding motif mediates interaction with GOPC.
CC {ECO:0000269|PubMed:12372286}.
CC -!- DISEASE: Note=Defects in Grid2 are the cause of the Lurcher phenotype.
CC Heterozygous animals display a characteristic swaying of the hind
CC quarters and jerky up and down movements following cerebellar Purkinje
CC cell degeneration during postnatal development. Homozygous animals die
CC shortly after birth because of a massive loss of midbrain and hindbrain
CC neurons during late embryogenesis.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. GRID2 subfamily. {ECO:0000305}.
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DR EMBL; D13266; BAA02524.1; -; mRNA.
DR EMBL; BC139823; AAI39824.1; -; mRNA.
DR CCDS; CCDS20202.1; -.
DR PIR; PN0156; PN0156.
DR RefSeq; NP_032193.1; NM_008167.2.
DR AlphaFoldDB; Q61625; -.
DR SMR; Q61625; -.
DR BioGRID; 200062; 6.
DR CORUM; Q61625; -.
DR IntAct; Q61625; 37.
DR MINT; Q61625; -.
DR STRING; 10090.ENSMUSP00000093536; -.
DR TCDB; 1.A.10.1.8; the glutamate-gated ion channel (gic) family of neurotransmitter receptors.
DR GlyConnect; 2346; 4 N-Linked glycans (2 sites).
DR GlyGen; Q61625; 4 sites, 4 N-linked glycans (2 sites).
DR iPTMnet; Q61625; -.
DR PhosphoSitePlus; Q61625; -.
DR SwissPalm; Q61625; -.
DR MaxQB; Q61625; -.
DR PaxDb; Q61625; -.
DR PeptideAtlas; Q61625; -.
DR PRIDE; Q61625; -.
DR ProteomicsDB; 271018; -.
DR Antibodypedia; 25698; 116 antibodies from 27 providers.
DR DNASU; 14804; -.
DR Ensembl; ENSMUST00000095852; ENSMUSP00000093536; ENSMUSG00000071424.
DR GeneID; 14804; -.
DR KEGG; mmu:14804; -.
DR UCSC; uc009cdz.1; mouse.
DR CTD; 2895; -.
DR MGI; MGI:95813; Grid2.
DR VEuPathDB; HostDB:ENSMUSG00000071424; -.
DR eggNOG; KOG1052; Eukaryota.
DR GeneTree; ENSGT00940000155192; -.
DR HOGENOM; CLU_007257_9_0_1; -.
DR InParanoid; Q61625; -.
DR OMA; CWNPITG; -.
DR OrthoDB; 122304at2759; -.
DR PhylomeDB; Q61625; -.
DR TreeFam; TF352434; -.
DR BioGRID-ORCS; 14804; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Grid2; mouse.
DR PRO; PR:Q61625; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q61625; protein.
DR Bgee; ENSMUSG00000071424; Expressed in cerebellum lobe and 110 other tissues.
DR ExpressionAtlas; Q61625; baseline and differential.
DR Genevisible; Q61625; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043197; C:dendritic spine; IDA:BHF-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0008328; C:ionotropic glutamate receptor complex; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:BHF-UCL.
DR GO; GO:0036477; C:somatodendritic compartment; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0008066; F:glutamate receptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004970; F:ionotropic glutamate receptor activity; IEA:InterPro.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0030165; F:PDZ domain binding; IPI:BHF-UCL.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0021707; P:cerebellar granule cell differentiation; IGI:BHF-UCL.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IMP:MGI.
DR GO; GO:1904861; P:excitatory synapse assembly; ISO:MGI.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IGI:BHF-UCL.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1900454; P:positive regulation of long-term synaptic depression; ISO:MGI.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:MGI.
DR GO; GO:0060134; P:prepulse inhibition; IMP:MGI.
DR GO; GO:0008104; P:protein localization; IDA:BHF-UCL.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0010975; P:regulation of neuron projection development; IMP:MGI.
DR GO; GO:0099151; P:regulation of postsynaptic density assembly; IDA:SynGO.
DR GO; GO:1905606; P:regulation of presynapse assembly; ISO:MGI.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IMP:MGI.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR019594; Glu/Gly-bd.
DR InterPro; IPR001508; Iono_rcpt_met.
DR InterPro; IPR001320; Iontro_rcpt.
DR InterPro; IPR028082; Peripla_BP_I.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00060; Lig_chan; 1.
DR Pfam; PF10613; Lig_chan-Glu_bd; 1.
DR PRINTS; PR00177; NMDARECEPTOR.
DR SMART; SM00918; Lig_chan-Glu_bd; 1.
DR SMART; SM00079; PBPe; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Disulfide bond; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Phosphoprotein;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1007
FT /note="Glutamate receptor ionotropic, delta-2"
FT /id="PRO_0000011565"
FT TOPO_DOM 24..566
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 567..587
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 588..635
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 636..656
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 657..830
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 831..851
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 852..1007
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 24..345
FT /note="Interaction with CBLN1 homotrimer"
FT /evidence="ECO:0000250|UniProtKB:O43424"
FT REGION 921..991
FT /note="Interaction with AP4M1"
FT /evidence="ECO:0000250|UniProtKB:Q63226"
FT MOTIF 1005..1007
FT /note="PDZ-binding"
FT SITE 76
FT /note="Essential for dimerization"
FT /evidence="ECO:0000250|UniProtKB:O43424"
FT MOD_RES 883
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 886
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 890
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1006
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63226"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 713
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 716
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 83..355
FT /evidence="ECO:0000250|UniProtKB:O43424"
FT DISULFID 99..131
FT /evidence="ECO:0000250|UniProtKB:O43424"
FT DISULFID 298..310
FT /evidence="ECO:0000250|UniProtKB:O43424"
FT VARIANT 654
FT /note="A -> T (in Lurcher)"
FT /evidence="ECO:0000269|PubMed:9285588"
FT MUTAGEN 920
FT /note="S->A: Abolishes interaction with SHANK1 and SHANK2."
FT /evidence="ECO:0000269|PubMed:15207857"
SQ SEQUENCE 1007 AA; 113082 MW; A456166CC782A44B CRC64;
MEVFPLLLFL SFCWSRTWDL ATADSIIHIG AIFDESAKKD DEVFRTAVGD LNQNEEILQT
EKITFSVTFV DGNNPFQAVQ EACELMNQGI LALVSSIGCT SAGSLQSLAD AMHIPHLFIQ
RSTAGTPRSG CGLTRSNRND DYTLSVRPPV YLNEVILRVV TEYAWQKFII FYDSEYDIRG
IQEFLDKVSQ QGMDVALQKV ENNINKMITT LFDTMRIEEL NRYRDTLRRA ILVMNPATAK
SFISEVVETN LVAFDCHWII INEEINDVDV QELVRRSIGR LTIIRQTFPV PQNISQRCFR
GNHRISSSLC DPKDPFAQNM EISNLYIYDT VLLLANAFHK KLEDRKWHSM ASLSCIRKNS
KPWQGGRSML ETIKKGGVNG LTGDLEFGEN GGNPNVHFEI LGTNYGEELG RGVRKLGCWN
PVTGLNGSLT DKKLENNMRG VVLRVVTVLE EPFVMVSENV LGKPKKYQGF SIDVLDALSN
YLGFNYEIYV APDHKYGSPQ EDGTWNGLVG ELVFKRADIG ISALTITPDR ENVVDFTTRY
MDYSVGVLLR RAEKTVDMFA CLAPFDLSLW ACIAGTVLLV GLLVYLLNWL NPPRLQMGSM
TSTTLYNSMW FVYGSFVQQG GEVPYTTLAT RMMMGAWWLF ALIVISSYTA NLAAFLTITR
IESSIQSLQD LSKQTDIPYG TVLDSAVYQH VRMKGLNPFE RDSMYSQMWR MINRSNGSEN
NVLESQAGIQ KVKYGNYAFV WDAAVLEYVA INDPDCSFYT VGNTVADRGY GIALQHGSPY
RDVFSQRILE LQQSGDMDIL KHKWWPKNGQ CDLYSSVDAK QKGGALDIKS LAGVFCILAA
GIVLSCLIAV LETWWSRRKG SRVPSKEDDK EIDLEHLHRR VNSLCTDDDS PHKQFSTSSI
DLTPLDIDTL PTRQALEQIS DFRNTHITTT TFIPEQIQTL SRTLSAKAAS GFAFGSVPEH
RTGPFRHRAP NGGFFRSPIK TMSSIPYQPT PTLGLNLGND PDRGTSI
