GRID2_HUMAN
ID GRID2_HUMAN Reviewed; 1007 AA.
AC O43424; E9PH24; Q4KKU8; Q4KKU9; Q4KKV0; Q59FZ1;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Glutamate receptor ionotropic, delta-2;
DE Short=GluD2;
DE Short=GluR delta-2 subunit;
DE Flags: Precursor;
GN Name=GRID2; Synonyms=GLURD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
RX PubMed=9465309; DOI=10.1006/geno.1997.5108;
RA Hu W., Zuo J., De Jager P.L., Heintz N.;
RT "The human glutamate receptor delta 2 gene (GRID2) maps to chromosome
RT 4q22.";
RL Genomics 47:143-145(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-68.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [5]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 24-440, DISULFIDE BONDS,
RP INTERACTION WITH CBLN1, MUTAGENESIS OF ASP-24; SER-25; ILE-26; THR-60;
RP GLU-61; PHE-76; LEU-342; GLU-343; ASP-344; ARG-345; LYS-346; HIS-348;
RP SER-349; MET-350; SER-352; GLN-364 AND LEU-434, SUBUNIT, FUNCTION, REGION,
RP SITE, AND CHARACTERIZATION OF VARIANT SCAR18 THR-654.
RX PubMed=27418511; DOI=10.1126/science.aae0104;
RA Elegheert J., Kakegawa W., Clay J.E., Shanks N.F., Behiels E., Matsuda K.,
RA Kohda K., Miura E., Rossmann M., Mitakidis N., Motohashi J., Chang V.T.,
RA Siebold C., Greger I.H., Nakagawa T., Yuzaki M., Aricescu A.R.;
RT "Structural basis for integration of GluD receptors within synaptic
RT organizer complexes.";
RL Science 353:295-299(2016).
RN [6]
RP INVOLVEMENT IN SCAR18.
RX PubMed=23611888; DOI=10.1177/0883073813484967;
RA Utine G.E., Haliloglu G., Salanci B., Cetinkaya A., Kiper P.O., Alanay Y.,
RA Aktas D., Boduroglu K., Alikasifoglu M.;
RT "A homozygous deletion in GRID2 causes a human phenotype with cerebellar
RT ataxia and atrophy.";
RL J. Child Neurol. 28:926-932(2013).
RN [7]
RP INVOLVEMENT IN SCAR18.
RX PubMed=24078737; DOI=10.1212/wnl.0b013e3182a841a3;
RA Hills L.B., Masri A., Konno K., Kakegawa W., Lam A.T., Lim-Melia E.,
RA Chandy N., Hill R.S., Partlow J.N., Al-Saffar M., Nasir R., Stoler J.M.,
RA Barkovich A.J., Watanabe M., Yuzaki M., Mochida G.H.;
RT "Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and
RT tonic upgaze in humans.";
RL Neurology 81:1378-1386(2013).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-209.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [9]
RP VARIANTS SCAR18 ASP-654; THR-654 AND VAL-656.
RX PubMed=25841024; DOI=10.1212/wnl.0000000000001524;
RA Coutelier M., Burglen L., Mundwiller E., Abada-Bendib M., Rodriguez D.,
RA Chantot-Bastaraud S., Rougeot C., Cournelle M.A., Milh M., Toutain A.,
RA Bacq D., Meyer V., Afenjar A., Deleuze J.F., Brice A., Heron D.,
RA Stevanin G., Durr A.;
RT "GRID2 mutations span from congenital to mild adult-onset cerebellar
RT ataxia.";
RL Neurology 84:1751-1759(2015).
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 (PubMed:27418511). {ECO:0000269|PubMed:27418511}.
CC -!- SUBUNIT: Tetramer; dimer of dimers (PubMed:27418511). Interacts with
CC EML2, MAGI2 (via PDZ domains) and AP4M1 (By similarity). Interacts with
CC BECN1, GOPC, GRID2IP, SHANK1 and SHANK2. Interacts with CBLN2, but not
CC with CBLN4 (By similarity). 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:27418511). {ECO:0000250|UniProtKB:Q61625,
CC ECO:0000250|UniProtKB:Q63226, ECO:0000269|PubMed:27418511}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43424-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43424-2; Sequence=VSP_054704;
CC -!- DOMAIN: The PDZ-binding motif mediates interaction with GOPC.
CC {ECO:0000250}.
CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 18 (SCAR18)
CC [MIM:616204]: A form of spinocerebellar ataxia, a clinically and
CC genetically heterogeneous group of cerebellar disorders. Patients show
CC progressive incoordination of gait and often poor coordination of
CC hands, speech and eye movements, due to degeneration of the cerebellum
CC with variable involvement of the brainstem and spinal cord. SCAR18
CC features include progressive cerebellar atrophy, delayed psychomotor
CC development, severely impaired gait, ocular movement abnormalities, and
CC intellectual disability. {ECO:0000269|PubMed:23611888,
CC ECO:0000269|PubMed:24078737, ECO:0000269|PubMed:25841024,
CC ECO:0000269|PubMed:27418511}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. GRID2 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92555.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF009014; AAC39579.1; -; mRNA.
DR EMBL; AB209318; BAD92555.1; ALT_INIT; mRNA.
DR EMBL; AC020699; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022317; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093596; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC095059; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096769; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC105315; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC105452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108158; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110800; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC112695; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC115111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC115537; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC099652; AAH99652.1; -; mRNA.
DR EMBL; BC099653; AAH99653.1; -; mRNA.
DR EMBL; BC099654; AAH99654.1; -; mRNA.
DR CCDS; CCDS3637.1; -. [O43424-1]
DR CCDS; CCDS68758.1; -. [O43424-2]
DR RefSeq; NP_001273767.1; NM_001286838.1. [O43424-2]
DR RefSeq; NP_001501.2; NM_001510.3. [O43424-1]
DR PDB; 5KC8; X-ray; 1.75 A; A=24-440.
DR PDB; 5KCA; X-ray; 3.10 A; A=24-440.
DR PDBsum; 5KC8; -.
DR PDBsum; 5KCA; -.
DR AlphaFoldDB; O43424; -.
DR SMR; O43424; -.
DR BioGRID; 109152; 8.
DR MINT; O43424; -.
DR STRING; 9606.ENSP00000282020; -.
DR ChEMBL; CHEMBL4524129; -.
DR GlyGen; O43424; 4 sites.
DR iPTMnet; O43424; -.
DR PhosphoSitePlus; O43424; -.
DR BioMuta; GRID2; -.
DR EPD; O43424; -.
DR jPOST; O43424; -.
DR MassIVE; O43424; -.
DR MaxQB; O43424; -.
DR PaxDb; O43424; -.
DR PeptideAtlas; O43424; -.
DR PRIDE; O43424; -.
DR ProteomicsDB; 20442; -.
DR ProteomicsDB; 48936; -. [O43424-1]
DR Antibodypedia; 25698; 116 antibodies from 27 providers.
DR DNASU; 2895; -.
DR Ensembl; ENST00000282020.9; ENSP00000282020.4; ENSG00000152208.13. [O43424-1]
DR Ensembl; ENST00000510992.5; ENSP00000421257.1; ENSG00000152208.13. [O43424-2]
DR GeneID; 2895; -.
DR KEGG; hsa:2895; -.
DR MANE-Select; ENST00000282020.9; ENSP00000282020.4; NM_001510.4; NP_001501.2.
DR UCSC; uc011cdt.4; human. [O43424-1]
DR CTD; 2895; -.
DR DisGeNET; 2895; -.
DR GeneCards; GRID2; -.
DR HGNC; HGNC:4576; GRID2.
DR HPA; ENSG00000152208; Group enriched (brain, testis).
DR MalaCards; GRID2; -.
DR MIM; 602368; gene.
DR MIM; 616204; phenotype.
DR neXtProt; NX_O43424; -.
DR OpenTargets; ENSG00000152208; -.
DR Orphanet; 363432; Autosomal recessive congenital cerebellar ataxia due to GRID2 deficiency.
DR PharmGKB; PA28971; -.
DR VEuPathDB; HostDB:ENSG00000152208; -.
DR eggNOG; KOG1052; Eukaryota.
DR GeneTree; ENSGT00940000155192; -.
DR InParanoid; O43424; -.
DR OMA; CWNPITG; -.
DR OrthoDB; 122304at2759; -.
DR PhylomeDB; O43424; -.
DR TreeFam; TF352434; -.
DR PathwayCommons; O43424; -.
DR SignaLink; O43424; -.
DR SIGNOR; O43424; -.
DR BioGRID-ORCS; 2895; 6 hits in 1071 CRISPR screens.
DR ChiTaRS; GRID2; human.
DR GeneWiki; GRID2; -.
DR GenomeRNAi; 2895; -.
DR Pharos; O43424; Tbio.
DR PRO; PR:O43424; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O43424; protein.
DR Bgee; ENSG00000152208; Expressed in right testis and 75 other tissues.
DR ExpressionAtlas; O43424; baseline and differential.
DR Genevisible; O43424; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043197; C:dendritic spine; ISS:BHF-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0008328; C:ionotropic glutamate receptor complex; ISS:BHF-UCL.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; ISS:BHF-UCL.
DR GO; GO:0008066; F:glutamate receptor activity; IBA:GO_Central.
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; ISS:BHF-UCL.
DR GO; GO:0097110; F:scaffold protein binding; ISS: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; ISS:BHF-UCL.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISS:BHF-UCL.
DR GO; GO:1904861; P:excitatory synapse assembly; IMP:UniProtKB.
DR GO; GO:0007215; P:glutamate receptor signaling pathway; TAS:ProtInc.
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; IMP:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IMP:UniProtKB.
DR GO; GO:0060134; P:prepulse inhibition; ISS:BHF-UCL.
DR GO; GO:0008104; P:protein localization; ISS:BHF-UCL.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; ISS:BHF-UCL.
DR GO; GO:0010975; P:regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0099151; P:regulation of postsynaptic density assembly; IEA:Ensembl.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; ISS:BHF-UCL.
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; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel;
KW Membrane; Neurodegeneration; Phosphoprotein; Postsynaptic cell membrane;
KW Receptor; Reference proteome; Signal; Synapse; Transmembrane;
KW 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_0000011564"
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:0000269|PubMed:27418511"
FT REGION 921..991
FT /note="Interaction with AP4M1"
FT /evidence="ECO:0000250|UniProtKB:Q63226"
FT MOTIF 1005..1007
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT SITE 76
FT /note="Essential for dimerization"
FT /evidence="ECO:0000269|PubMed:27418511"
FT MOD_RES 883
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61625"
FT MOD_RES 886
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q61625"
FT MOD_RES 890
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61625"
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:0000269|PubMed:27418511,
FT ECO:0007744|PDB:5KC8, ECO:0007744|PDB:5KCA"
FT DISULFID 99..131
FT /evidence="ECO:0000269|PubMed:27418511,
FT ECO:0007744|PDB:5KC8, ECO:0007744|PDB:5KCA"
FT DISULFID 298..310
FT /evidence="ECO:0000269|PubMed:27418511,
FT ECO:0007744|PDB:5KC8, ECO:0007744|PDB:5KCA"
FT VAR_SEQ 82..176
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054704"
FT VARIANT 68
FT /note="T -> M (in dbSNP:rs34144324)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_055016"
FT VARIANT 209
FT /note="T -> N (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035697"
FT VARIANT 398
FT /note="F -> S (in dbSNP:rs34796082)"
FT /id="VAR_055017"
FT VARIANT 490
FT /note="V -> I (in dbSNP:rs10034345)"
FT /id="VAR_055018"
FT VARIANT 654
FT /note="A -> D (in SCAR18)"
FT /evidence="ECO:0000269|PubMed:25841024"
FT /id="VAR_074166"
FT VARIANT 654
FT /note="A -> T (in SCAR18; constitutively open the
FT extracellular-glutamate-gated ion channel)"
FT /evidence="ECO:0000269|PubMed:25841024,
FT ECO:0000269|PubMed:27418511"
FT /id="VAR_074167"
FT VARIANT 656
FT /note="L -> V (in SCAR18)"
FT /evidence="ECO:0000269|PubMed:25841024"
FT /id="VAR_074168"
FT MUTAGEN 24
FT /note="D->A: Reduces binding to CBLN1; when associated with
FT D76. Abolishes CBLN1 binding; when associated with A-26; A-
FT 61; D-76 and A-345. Abolishes synapse assembly; when
FT associated with A-26; A-61 and A-345. Abolishes cerebellar
FT parallel fiber-Purkinje cell synapse formation; when
FT associated with A-26; A-61 and A-345. Abolishes D-Serine-
FT dependent long term synaptic depression at PF-PC synapses;
FT when associated with A-26; A-61 and A-345."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 25
FT /note="S->A: Reduces binding to CBLN1; when associated with
FT D76."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 26
FT /note="I->A: Reduces binding to CBLN1; when associated with
FT D76. Abolishes CBLN1 binding; when associated with A-24; A-
FT 61; D-76 and A-345. Abolishes synapse assembly; when
FT associated with A-24; A-61 and A-345. Abolishes cerebellar
FT parallel fiber-Purkinje cell synapse formation; when
FT associated with A-24; A-61 and A-345. Abolishes D-Serine-
FT dependent long term synaptic depression at PF-PC synapses;
FT when associated with A-24; A-61 and A-345."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 60
FT /note="T->A: No effect on CBLN1 interaction; when
FT associated with D76."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 61
FT /note="E->A: Reduces binding to CBLN1; when associated with
FT D76. Abolishes CBLN1 binding; when associated with A-24; A-
FT 26; D-76 and A-345. Abolishes synapse assembly; when
FT associated with A-24; A-26 and A-345. Abolishes cerebellar
FT parallel fiber-Purkinje cell synapse formation; when
FT associated with A-24; A-26 and A-345. Abolishes D-Serine-
FT dependent long term synaptic depression at PF-PC synapses;
FT when associated with A-24; A-26 and A-345."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 76
FT /note="F->D: Monomeric form. Does not dimerize. Weakly
FT interacts with C1q domain of CBLN1. Forms intermediate
FT synapse. Abolishes cerebellar parallel fiber-Purkinje cell
FT synapse formation. Abolishes D-Serine?dependent long term
FT synaptic depression at PF-PC synapses. Does not recover
FT motor coordination in experiment of transfection in Grid2-
FT null mice."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 342
FT /note="L->A: Reduces binding to CBLN1; when associated with
FT D76."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 343
FT /note="E->A: No effect on CBLN1 interaction; when
FT associated with D76. No effect on CBLN1 binding; when
FT associated with D-76; A-346; A-349 and A-350. No effect on
FT synapse assembly; when associated with A-346; A-349 and A-
FT 350. No effect on cerebellar parallel fiber-Purkinje cell
FT synapse formation; when associated with A-346; A-349 and A-
FT 350. Does not affect D-Serine?dependent long term synaptic
FT depression at PF-PC synapses; when associated with A-346;
FT A-349 and A-350. Does not affect motor coordination; when
FT associated with A-346; A-349 and A-350."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 344
FT /note="D->A: No effect on CBLN1 interaction; when
FT associated with D76."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 345
FT /note="R->A: Reduces binding to CBLN1; when associated with
FT D76. Abolishes CBLN1 binding; when associated with A-24; A-
FT 26; A-61 and D-76. Abolishes synapse assembly; when
FT associated with A-24; A-26 and A-61. Abolishes cerebellar
FT parallel fiber-Purkinje cell synapse formation; when
FT associated with A-24; A-26 and A-61. Abolishes D-Serine-
FT dependent long term synaptic depression at PF-PC synapses;
FT when associated with A-24; A-26 and A-61."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 346
FT /note="K->A: No effect on CBLN1 interaction; when
FT associated with D76. No effect on CBLN1 binding; when
FT associated with D-76; A-343; A-349 and A-350. No effect on
FT synapse assembly; when associated with A-343; A-349 and A-
FT 350. No effect on cerebellar parallel fiber-Purkinje cell
FT synapse formation; when associated with A-343; A-349 and A-
FT 350. Does not affect D-Serine?dependent long term synaptic
FT depression at PF-PC synapses; when associated with A-343;
FT A-349 and A-350. Does not affect motor coordination; when
FT associated with A-343; A-349 and A-350."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 348
FT /note="H->A: Reduces binding to CBLN1; when associated with
FT D76."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 349
FT /note="S->A: No effect on CBLN1 interaction; when
FT associated with D76. No effect on CBLN1 binding; when
FT associated with D-76; A-343; A-346 and A-350. No effect on
FT synapse assembly; when associated with A-343; A-346 and A-
FT 350. No effect on cerebellar parallel fiber-Purkinje cell
FT synapse formation; when associated with A-343; A-346 and A-
FT 350. Does not affect D-Serine?dependent long term synaptic
FT depression at PF-PC synapses; when associated with A-343;
FT A-346 and A-350. Does not affect motor coordination; when
FT associated with A-343; A-346 and A-350."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 350
FT /note="M->A: No effect on CBLN1 interaction; when
FT associated with D76. No effect on CBLN1 binding; when
FT associated with D-76; A-343; A-346 and A-349. No effect on
FT synapse assembly; when associated with A-343; A-346 and A-
FT 349. No effect on cerebellar parallel fiber-Purkinje cell
FT synapse formation; when associated with A-343; A-346 and A-
FT 349. Does not affect D-Serine?dependent long term synaptic
FT depression at PF-PC synapses; when associated with A-343;
FT A-346 and A-349. Does not affect motor coordination; when
FT associated with A-343; A-346 and A-349."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 352
FT /note="S->A: Reduces binding to CBLN1; when associated with
FT D76."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 364
FT /note="Q->A: No effect on CBLN1 interaction; when
FT associated with D76."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 434
FT /note="L->ELSNGTDGAS: Impairs the ability of the LBD to
FT induce pore closure. No effect on synapse assembly. No
FT effect on cerebellar parallel fiber-Purkinje cell synapse
FT formation. Abolishes D-Serine?dependent long term synaptic
FT depression at PF-PC synapses. Does not affect motor
FT coordination."
FT /evidence="ECO:0000269|PubMed:27418511"
FT CONFLICT 6
FT /note="F -> L (in Ref. 1; AAC39579 and 4; AAH99652/
FT AAH99653/AAH99654)"
FT /evidence="ECO:0000305"
FT CONFLICT 8
FT /note="L -> F (in Ref. 4; AAH99652)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="V -> I (in Ref. 1; AAC39579)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="G -> C (in Ref. 1; AAC39579)"
FT /evidence="ECO:0000305"
FT CONFLICT 557
FT /note="D -> E (in Ref. 4; AAH99652)"
FT /evidence="ECO:0000305"
FT CONFLICT 752
FT /note="N -> Y (in Ref. 1; AAC39579)"
FT /evidence="ECO:0000305"
FT STRAND 27..34
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 38..53
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 63..70
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 75..88
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 99..112
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:5KCA"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 152..162
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 167..172
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 178..181
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 182..190
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 204..214
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 217..226
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 229..234
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 236..248
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 267..276
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 279..287
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 294..297
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 307..310
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 315..318
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 322..343
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:5KC8"
FT HELIX 366..374
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 397..402
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 414..420
FT /evidence="ECO:0007829|PDB:5KC8"
FT TURN 421..423
FT /evidence="ECO:0007829|PDB:5KC8"
FT STRAND 424..427
FT /evidence="ECO:0007829|PDB:5KC8"
SQ SEQUENCE 1007 AA; 113356 MW; 8EF938AB7F1D6D26 CRC64;
MEVFPFLLVL SVWWSRTWDS ANADSIIHIG AIFDESAKKD DEVFRTAVGD LNQNEEILQT
EKITFSVTFV DGNNPFQAVQ EACELMNQGI LALVSSIGCT SAGSLQSLAD AMHIPHLFIQ
RSTAGTPRSG CGLTRSNRND DYTLSVRPPV YLHDVILRVV TEYAWQKFII FYDSEYDIRG
IQEFLDKVSQ QGMDVALQKV ENNINKMITT LFDTMRIEEL NRYRDTLRRA ILVMNPATAK
SFITEVVETN LVAFDCHWII INEEINDVDV QELVRRSIGR LTIIRQTFPV PQNISQRCFR
GNHRISSTLC DPKDPFAQNM EISNLYIYDT VLLLANAFHK KLEDRKWHSM ASLSCIRKNS
KPWQGGRSML ETIKKGGVSG LTGELEFGEN 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 LSKQTEIPYG TVLDSAVYEH VRMKGLNPFE RDSMYSQMWR MINRSNGSEN
NVLESQAGIQ KVKYGNYAFV WDAAVLEYVA INDPDCSFYT IGNTVADRGY GIALQHGSPY
RDVFSQRILE LQQNGDMDIL KHKWWPKNGQ CDLYSSVDTK QKGGALDIKS FAGVFCILAA
GIVLSCFIAM LETWWNKRKG SRVPSKEDDK EIDLEHLHRR VNSLCTDDDS PHKQFSTSSI
DLTPLDIDTL PTRQALEQIS DFRNTHITTT TFIPEQIQTL SRTLSAKAAS GFTFGNVPEH
RTGPFRHRAP NGGFFRSPIK TMSSIPYQPT PTLGLNLGND PDRGTSI
