GRID2_RAT
ID GRID2_RAT Reviewed; 1007 AA.
AC Q63226; Q62641;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Glutamate receptor ionotropic, delta-2;
DE Short=GluD2;
DE Short=GluR delta-2 subunit;
DE Flags: Precursor;
GN Name=Grid2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8422924; DOI=10.1016/0014-5793(93)81186-4;
RA Lomeli H., Sprengel R., Laurie D., Khr G., Herb A., Seeburg P., Wisden W.;
RT "The rat delta-1 and delta-2 subunits extend the excitatory amino acid
RT receptor family.";
RL FEBS Lett. 315:318-322(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Boulter J., Pecht G.;
RT "Nucleotide sequence of rat glutamate receptor subunit gene delta2.";
RL Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH EML2.
RX PubMed=11829466; DOI=10.1006/bbrc.2002.6413;
RA Ly C.D., Roche K.W., Lee H.K., Wenthold R.J.;
RT "Identification of rat EMAP, a delta-glutamate receptor binding protein.";
RL Biochem. Biophys. Res. Commun. 291:85-90(2002).
RN [4]
RP INTERACTION WITH MAGI2.
RX PubMed=12589829; DOI=10.1016/s0006-291x(03)00070-6;
RA Yap C.C., Muto Y., Kishida H., Hashikawa T., Yano R.;
RT "PKC regulates the delta2 glutamate receptor interaction with S-SCAM/MAGI-2
RT protein.";
RL Biochem. Biophys. Res. Commun. 301:1122-1128(2003).
RN [5]
RP INTERACTION WITH AP4M1, AND MUTAGENESIS OF SER-945; PHE-952; PHE-954;
RP VAL-957; 965-PHE-ARG-966 AND 975-PHE-ARG-976.
RX PubMed=14572453; DOI=10.1016/s1044-7431(03)00164-7;
RA Yap C.C., Murate M., Kishigami S., Muto Y., Kishida H., Hashikawa T.,
RA Yano R.;
RT "Adaptor protein complex-4 (AP-4) is expressed in the central nervous
RT system neurons and interacts with glutamate receptor delta2.";
RL Mol. Cell. Neurosci. 24:283-295(2003).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-883; SER-890 AND SER-1006,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 440-813 IN COMPLEX WITH SERINE.
RX PubMed=17715062; DOI=10.1073/pnas.0703718104;
RA Naur P., Hansen K.B., Kristensen A.S., Dravid S.M., Pickering D.S.,
RA Olsen L., Vestergaard B., Egebjerg J., Gajhede M., Traynelis S.F.,
RA Kastrup J.S.;
RT "Ionotropic glutamate-like receptor delta2 binds D-serine and glycine.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:14116-14121(2007).
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 AP4M1 (PubMed:14572453). Interacts with EML2 (PubMed:11829466).
CC Interacts with MAGI2 (via PDZ domains) (PubMed:12589829). Interacts
CC with BECN1, GOPC, GRID2IP, SHANK1 and SHANK2. Interacts with CBLN2, but
CC not with CBLN4 (By similarity). Interacts with CBLN1 (via C1q domain);
CC the interaction is CBLN1-NRX1 complex formation-dependent; CBLN1-
CC binding is calcium-independent; CBLN1 hexamers anchor GRID2 N-terminal
CC domain dimers to monomeric NRXN1 isoform beta; promotes synaptogenesis
CC and mediates the D-Serine-dependent long term depression signals and
CC AMPA receptor endocytosis (By similarity).
CC {ECO:0000250|UniProtKB:O43424, ECO:0000250|UniProtKB:Q61625,
CC ECO:0000269|PubMed:11829466, ECO:0000269|PubMed:12589829,
CC ECO:0000269|PubMed:14572453}.
CC -!- INTERACTION:
CC Q63226; Q63226: Grid2; NbExp=2; IntAct=EBI-6988699, EBI-6988699;
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 at high levels in the cerebellar Purkinje
CC cell layer, almost absent in the forebrain.
CC {ECO:0000269|PubMed:8422924}.
CC -!- DOMAIN: The PDZ-binding motif mediates interaction with GOPC.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. GRID2 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Z17239; CAA78937.1; -; mRNA.
DR EMBL; U08256; AAA17829.1; -; mRNA.
DR PIR; S28858; S28858.
DR RefSeq; NP_077355.1; NM_024379.1.
DR PDB; 2V3T; X-ray; 2.75 A; A/B=440-551, A/B=664-813.
DR PDB; 2V3U; X-ray; 1.74 A; A=440-551, A=664-813.
DR PDB; 5CC2; X-ray; 2.50 A; A=440-551, A=664-813.
DR PDB; 5L2E; X-ray; 4.15 A; A/B/C=24-551, A/B/C=664-813.
DR PDB; 6LU9; EM; 8.80 A; A/B/C/D=24-893.
DR PDBsum; 2V3T; -.
DR PDBsum; 2V3U; -.
DR PDBsum; 5CC2; -.
DR PDBsum; 5L2E; -.
DR PDBsum; 6LU9; -.
DR AlphaFoldDB; Q63226; -.
DR SMR; Q63226; -.
DR BioGRID; 249429; 1.
DR DIP; DIP-40709N; -.
DR IntAct; Q63226; 4.
DR MINT; Q63226; -.
DR STRING; 10116.ENSRNOP00000060322; -.
DR GlyGen; Q63226; 4 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q63226; -.
DR PhosphoSitePlus; Q63226; -.
DR PaxDb; Q63226; -.
DR PRIDE; Q63226; -.
DR Ensembl; ENSRNOT00000116787; ENSRNOP00000084985; ENSRNOG00000006174.
DR GeneID; 79220; -.
DR KEGG; rno:79220; -.
DR UCSC; RGD:68368; rat.
DR CTD; 2895; -.
DR RGD; 68368; Grid2.
DR eggNOG; KOG1052; Eukaryota.
DR GeneTree; ENSGT00940000155192; -.
DR InParanoid; Q63226; -.
DR OrthoDB; 122304at2759; -.
DR PhylomeDB; Q63226; -.
DR TreeFam; TF352434; -.
DR EvolutionaryTrace; Q63226; -.
DR PRO; PR:Q63226; -.
DR Proteomes; UP000002494; Chromosome 4.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043197; C:dendritic spine; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:RGD.
DR GO; GO:0036477; C:somatodendritic compartment; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0008066; F:glutamate receptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:UniProtKB.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
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; ISS:BHF-UCL.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISO:RGD.
DR GO; GO:1904861; P:excitatory synapse assembly; ISO:RGD.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; ISS: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:RGD.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:RGD.
DR GO; GO:0060134; P:prepulse inhibition; ISO:RGD.
DR GO; GO:0008104; P:protein localization; ISS:BHF-UCL.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0010975; P:regulation of neuron projection development; ISO:RGD.
DR GO; GO:0099151; P:regulation of postsynaptic density assembly; ISO:RGD.
DR GO; GO:1905606; P:regulation of presynapse assembly; IDA:SynGO.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; ISO:RGD.
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 3D-structure; Cell membrane; 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_0000011566"
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:0000269|PubMed:14572453"
FT MOTIF 1005..1007
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
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:22673903"
FT MOD_RES 886
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q61625"
FT MOD_RES 890
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1006
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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 MUTAGEN 945
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:14572453"
FT MUTAGEN 952
FT /note="F->A: Loss of interaction with AP4M1."
FT /evidence="ECO:0000269|PubMed:14572453"
FT MUTAGEN 954
FT /note="F->A: Loss of interaction with AP4M1."
FT /evidence="ECO:0000269|PubMed:14572453"
FT MUTAGEN 957
FT /note="V->E: Loss of interaction with AP4M1."
FT /evidence="ECO:0000269|PubMed:14572453"
FT MUTAGEN 965..966
FT /note="FR->AA: Loss of interaction with AP4M1."
FT /evidence="ECO:0000269|PubMed:14572453"
FT MUTAGEN 975..976
FT /note="FR->AA: Loss of interaction with AP4M1."
FT /evidence="ECO:0000269|PubMed:14572453"
FT CONFLICT 109..111
FT /note="ADA -> GRLT (in Ref. 1; CAA78937)"
FT /evidence="ECO:0000305"
FT CONFLICT 324..326
FT /note="NLY -> HLC (in Ref. 1; CAA78937)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="T -> A (in Ref. 1; CAA78937)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="E -> Q (in Ref. 2; AAA17829)"
FT /evidence="ECO:0000305"
FT CONFLICT 950
FT /note="S -> F (in Ref. 2; AAA17829)"
FT /evidence="ECO:0000305"
FT STRAND 442..447
FT /evidence="ECO:0007829|PDB:2V3U"
FT TURN 451..453
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 454..457
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 466..469
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 470..482
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 485..490
FT /evidence="ECO:0007829|PDB:2V3U"
FT TURN 501..503
FT /evidence="ECO:0007829|PDB:2V3T"
FT HELIX 507..513
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 528..531
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 540..543
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 545..550
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 668..672
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 675..677
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 686..695
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 704..712
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 714..717
FT /evidence="ECO:0007829|PDB:5CC2"
FT STRAND 722..724
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 725..734
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 738..742
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 743..752
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 758..761
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 768..770
FT /evidence="ECO:0007829|PDB:2V3U"
FT STRAND 773..775
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 781..793
FT /evidence="ECO:0007829|PDB:2V3U"
FT HELIX 796..804
FT /evidence="ECO:0007829|PDB:2V3U"
SQ SEQUENCE 1007 AA; 113259 MW; 6583C31357C9402C CRC64;
MEVFPLLFFL SFWWSRTWDL ATSDSIIHIG 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
GNHRISSTLC 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 GFTFGSVPEH
RTGPFRHRAP NGGFFRSPIK TMSSIPYQPT PTLGLNLGND PDRGTSI
