GRD2I_MOUSE
ID GRD2I_MOUSE Reviewed; 1203 AA.
AC Q0QWG9; Q6DID0; Q9ESJ5;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Delphilin;
DE AltName: Full=Glutamate receptor, ionotropic, delta 2-interacting protein 1;
GN Name=Grid2ip;
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] (ISOFORM 2), TISSUE SPECIFICITY, AND INTERACTION
RP WITH GRID2.
RC STRAIN=BALB/cJ;
RX PubMed=11826110; DOI=10.1523/jneurosci.22-03-00803.2002;
RA Miyagi Y., Yamashita T., Fukaya M., Sonoda T., Okuno T., Yamada K.,
RA Watanabe M., Nagashima Y., Aoki I., Okuda K., Mishina M., Kawamoto S.;
RT "Delphilin: a novel PDZ and formin homology domain-containing protein that
RT synaptically colocalizes and interacts with glutamate receptor delta 2
RT subunit.";
RL J. Neurosci. 22:803-814(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, PALMITOYLATION
RP AT CYS-3 (ISOFORM 2), AND INTERACTION WITH GRID2.
RC TISSUE=Cerebellum;
RX PubMed=16835239; DOI=10.1074/jbc.m602044200;
RA Matsuda K., Matsuda S., Gladding C.M., Yuzaki M.;
RT "Characterization of the delta2 glutamate receptor-binding protein
RT delphilin: splicing variants with differential palmitoylation and an
RT additional PDZ domain.";
RL J. Biol. Chem. 281:25577-25587(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-184 (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA]
RP OF 1-183 (ISOFORM 3), INTERACTION WITH GRID2, DEVELOPMENTAL STAGE, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16168524; DOI=10.1016/j.molbrainres.2005.08.006;
RA Yamashita T., Miyagi Y., Ono M., Ito H., Watanabe K., Sonoda T.,
RA Tsuzuki K., Ozawa S., Aoki I., Okuda K., Mishina M., Kawamoto S.;
RT "Identification and characterization of a novel Delphilin variant with an
RT alternative N-terminus.";
RL Brain Res. Mol. Brain Res. 141:83-94(2005).
RN [5]
RP INTERACTION WITH GRID2.
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 INTERACTION WITH GRID2.
RX PubMed=17425562; DOI=10.1111/j.1460-9568.2007.05412.x;
RA Kohda K., Kakegawa W., Matsuda S., Nakagami R., Kakiya N., Yuzaki M.;
RT "The extreme C-terminus of GluRdelta2 is essential for induction of long-
RT term depression in cerebellar slices.";
RL Eur. J. Neurosci. 25:1357-1362(2007).
RN [7]
RP INTERACTION WITH SLC16A7.
RX PubMed=17496809; DOI=10.1097/wnr.0b013e3280586821;
RA Watanabe-Kaneko K., Sonoda T., Miyagi Y., Yamashita T., Okuda K.,
RA Kawamoto S.;
RT "The synaptic scaffolding protein Delphilin interacts with monocarboxylate
RT transporter 2.";
RL NeuroReport 18:489-493(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303; SER-572; SER-613;
RP SER-644 AND SER-647, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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).
CC -!- FUNCTION: Postsynaptic scaffolding protein at the Purkinje cell
CC synapse, where it may serve to link GRID2 with actin cytoskeleton and
CC various signaling molecules.
CC -!- SUBUNIT: Interacts with C-terminus of the glutamate receptor GRID2 via
CC PDZ domain. Isoform 2 interacts also with Profilin-2/PFN2 and with the
CC monocarboxylate transporter SLC16A7 via PDZ domain. The interaction of
CC isoform 2 with GRID2 is dependent on GRID2 phosphorylation by PKA.
CC {ECO:0000269|PubMed:11826110, ECO:0000269|PubMed:16168524,
CC ECO:0000269|PubMed:16835239, ECO:0000269|PubMed:17027646,
CC ECO:0000269|PubMed:17425562, ECO:0000269|PubMed:17496809}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Postsynaptic cell membrane. Cell
CC projection, dendritic spine. Note=Localized to the postsynaptic
CC junction site of the parallel fiber-Purkinje cell synapse. Highly
CC present in the dendritic spines.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Synapse. Cell projection, dendritic
CC spine. Cell membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}.
CC Note=Localized at the dendritic spines, but also in dendritic shafts
CC apart fron spines.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=L-delphilin;
CC IsoId=Q0QWG9-1; Sequence=Displayed;
CC Name=2; Synonyms=S-delphilin, delphilin alpha;
CC IsoId=Q0QWG9-2; Sequence=VSP_033275, VSP_033278;
CC Name=3; Synonyms=delphilin beta;
CC IsoId=Q0QWG9-3; Sequence=VSP_033276, VSP_033277;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in the cerebellum, but not
CC in the cerebral cortex. Isoform 2 is expressed in the cell body of
CC purkinge cells of the cerebellum and weakly expressed in the cerebrum
CC and the brainstem as well as various nuclei of the thalamus. Isoform 2
CC is highly expressed in the cerebral cortex than in the cerebellum.
CC Isoform 3 is expressed in the cerebellum and cerebrum.
CC {ECO:0000269|PubMed:11826110, ECO:0000269|PubMed:16835239}.
CC -!- DEVELOPMENTAL STAGE: Isoform 3 expression is maintained throughout
CC cerebellar development, while isoform 2 expression gradually decrease
CC following the first postnatal week. {ECO:0000269|PubMed:16168524}.
CC -!- DOMAIN: PDZ 1 domain is responsible for cytoplasmic clustering of
CC isoform 1.
CC -!- PTM: Isoform 2 is palmitoylated. Palmitoylation of isoform 2 is
CC necessary for the enhanced cell surface expression of GRID2, and is
CC also responsible for the accumulation of isoform 2 within dendritic
CC spines. Isoform 1 and isoform 2 are differentially localized, probably
CC modulating GRID2 signaling in neurons.
CC -!- MISCELLANEOUS: Isoform 1 shows a punctate distribution throughout the
CC cytoplasm when expressed in COS cells, whereas isoform 2 is enriched at
CC the edges of the plasma membranes. When expressed in cultured
CC hippocampal neurons, isoform 1 forms clusters mainly in the dendritic
CC shafts, whereas isoform 2 is preferentially expressed in spines.
CC -!- MISCELLANEOUS: [Isoform 1]: Not palmitoylated.
CC -!- MISCELLANEOUS: [Isoform 2]: When Cys-3 is mutated to Ala-3, isoform 2
CC is not palmitoylated anymore. {ECO:0000305}.
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DR EMBL; DQ193535; ABB04525.1; -; mRNA.
DR EMBL; AF099933; AAG31020.1; -; mRNA.
DR EMBL; BC075624; AAH75624.1; -; mRNA.
DR EMBL; AY377834; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY377835; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS19841.1; -. [Q0QWG9-2]
DR CCDS; CCDS51689.1; -. [Q0QWG9-1]
DR CCDS; CCDS84992.1; -. [Q0QWG9-3]
DR RefSeq; NP_001152793.1; NM_001159321.1. [Q0QWG9-1]
DR RefSeq; NP_001334458.1; NM_001347529.1. [Q0QWG9-3]
DR RefSeq; NP_579933.1; NM_133355.1. [Q0QWG9-2]
DR AlphaFoldDB; Q0QWG9; -.
DR SMR; Q0QWG9; -.
DR BioGRID; 228467; 4.
DR STRING; 10090.ENSMUSP00000106361; -.
DR iPTMnet; Q0QWG9; -.
DR PhosphoSitePlus; Q0QWG9; -.
DR SwissPalm; Q0QWG9; -.
DR MaxQB; Q0QWG9; -.
DR PaxDb; Q0QWG9; -.
DR PeptideAtlas; Q0QWG9; -.
DR PRIDE; Q0QWG9; -.
DR ProteomicsDB; 271086; -. [Q0QWG9-1]
DR ProteomicsDB; 271087; -. [Q0QWG9-2]
DR ProteomicsDB; 271088; -. [Q0QWG9-3]
DR Antibodypedia; 49924; 85 antibodies from 17 providers.
DR DNASU; 170935; -.
DR Ensembl; ENSMUST00000010969; ENSMUSP00000010969; ENSMUSG00000010825. [Q0QWG9-2]
DR Ensembl; ENSMUST00000110733; ENSMUSP00000106361; ENSMUSG00000010825. [Q0QWG9-1]
DR Ensembl; ENSMUST00000120825; ENSMUSP00000113443; ENSMUSG00000010825. [Q0QWG9-3]
DR GeneID; 170935; -.
DR KEGG; mmu:170935; -.
DR UCSC; uc009akd.1; mouse. [Q0QWG9-1]
DR UCSC; uc009ake.1; mouse. [Q0QWG9-2]
DR UCSC; uc009akf.1; mouse. [Q0QWG9-3]
DR CTD; 392862; -.
DR MGI; MGI:2176213; Grid2ip.
DR VEuPathDB; HostDB:ENSMUSG00000010825; -.
DR eggNOG; KOG1922; Eukaryota.
DR eggNOG; KOG3528; Eukaryota.
DR eggNOG; KOG3589; Eukaryota.
DR GeneTree; ENSGT00940000157625; -.
DR HOGENOM; CLU_002818_0_0_1; -.
DR InParanoid; Q0QWG9; -.
DR OMA; CENVPPS; -.
DR OrthoDB; 790964at2759; -.
DR PhylomeDB; Q0QWG9; -.
DR TreeFam; TF329416; -.
DR BioGRID-ORCS; 170935; 2 hits in 69 CRISPR screens.
DR ChiTaRS; Grid2ip; mouse.
DR PRO; PR:Q0QWG9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q0QWG9; protein.
DR Bgee; ENSMUSG00000010825; Expressed in rostral migratory stream and 38 other tissues.
DR Genevisible; Q0QWG9; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:MGI.
DR GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; TAS:MGI.
DR GO; GO:0060292; P:long-term synaptic depression; IMP:MGI.
DR Gene3D; 1.20.58.2220; -; 1.
DR Gene3D; 2.30.42.10; -; 2.
DR InterPro; IPR015425; FH2_Formin.
DR InterPro; IPR042201; FH2_Formin_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR Pfam; PF02181; FH2; 1.
DR Pfam; PF00595; PDZ; 2.
DR SMART; SM00498; FH2; 1.
DR SMART; SM00228; PDZ; 2.
DR SUPFAM; SSF50156; SSF50156; 2.
DR PROSITE; PS51444; FH2; 1.
DR PROSITE; PS50106; PDZ; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Postsynaptic cell membrane;
KW Reference proteome; Repeat; Synapse.
FT CHAIN 1..1203
FT /note="Delphilin"
FT /id="PRO_0000331625"
FT DOMAIN 1..79
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 268..345
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 812..1203
FT /note="FH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00774"
FT REGION 215..270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 466..541
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 563..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 611..656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 710..821
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..232
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 485..508
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 611..634
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 710..740
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 741..759
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 767..782
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 783..804
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 572
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 644
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 647
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..179
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11826110,
FT ECO:0000303|PubMed:16168524"
FT /id="VSP_033275"
FT VAR_SEQ 1..172
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16168524"
FT /id="VSP_033276"
FT VAR_SEQ 173..183
FT /note="SEAQGPVLDNL -> MGKDQGFSRHF (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16168524"
FT /id="VSP_033277"
FT VAR_SEQ 180..184
FT /note="LDNLR -> MSCLG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11826110,
FT ECO:0000303|PubMed:16168524"
FT /id="VSP_033278"
FT LIPID Q0QWG9-2:3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:16835239"
SQ SEQUENCE 1203 AA; 132021 MW; 79AFAA7E869731C1 CRC64;
MPATNQGWPE DFGFQLGGSG PCFVIEVAEG SSAHAGGLRP GDQILEVEGL AVGGLSRERI
VRLARRCPRV PPSLGVLPGP EGGPTALTAA WLTRRFGRSL PLSRELLRLA GGPRPDAVHR
ERRRKAQEFS CQVDDILGDR LTAKEQVFTA LKQFAAEQRV DELVWTLTLV LPSEAQGPVL
DNLRIFIPKK HRARFDEVVS QGLLGKLCRA RRAQGAQRLR RSRSEERPER LLVSTRASAA
PRRPDEPPPR KATSLLGGRT GPGGPRRTVR VYKGNKSFGF TLRGHGPVWI ESVLPGSPAE
NASLKSGDRI LFLNGLDMRN CSHDKVVSML QGSGAMPTLV VEEGPVPFAS DSDSLDSPTR
ASALTSLQWV ADILPSSIRV QGRTFSQQLD HLLTPPERYG VCRALERFFQ HRNIDTLIVD
VYPVLDTPAK QVLWQFLYQL LTYEEQELCQ EKIACFLGYT AMTEPESSLD LEPESTPEPT
PEPQPRSSLR ASSMCRRSLR SQGLETSLSC GPGDCPEMPL PLIPGERQAG DGTSLPETPN
PKMMSAVYAE LESRLNSSFK GKIGTMSKSR ASPPVPSLVG TSGPRTLSGV SWPSDRLLPS
PCYDPLCSGG LASPSSSESH PYASLDSSRA PSPQPGLGSI HADSPPSPDP IRPPSRRKLF
AFSRPVRSRD TDRFLDALSE QLGPRLSIVD DFLTPENDYE EMSFHDDQGS FVTNERSSAS
ECVSSSEEGS SLTYSSISDH IPPPPLSPPP PPPLPFHDPK PSSRTSDGPR GPPQSLTKPL
TQINHPVPPP PPPPLPPPVP CAPPMLSRGV GHRRSETSHM SVKRLRWEQV ENSEGTIWGQ
LGEDSDYDKL SDMVKYLDLE LHFGTQKPPK PVPGPEPFRK KEVVEILSHK KAYNTSILLA
HLKLTPGELR QVLMSMEPRR LEPAHLAQLL LFAPDADEEQ RYQAFREAPG RLSEPDQFVL
QMLSVPEYKT RLRSLHFQAT LQEKTEEIRG SLECLRQASL ELKNSRKLAK ILEFVLAMGN
YLNDGQPKTN KTTGFKINFL TELNSTKTVD GKSTFLHILA KSLSQHFPEL LGFAQDLPTV
PLAAKVNQRA LTGDLADLHD TVSEIQVACQ SMAPSSEDRF AVVMASFLET AQPALRALDG
LQREAMEELG KALAFFGEDS KATTSEAFFG IFSEFMSKFE RALSDLQAGD GPRSSGMVSP
LAW
