GRIP2_RAT
ID GRIP2_RAT Reviewed; 1043 AA.
AC Q9WTW1; O88961; Q9WU36;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Glutamate receptor-interacting protein 2;
DE Short=GRIP-2;
DE AltName: Full=AMPA receptor-interacting protein GRIP2;
GN Name=Grip2;
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] (ISOFORM 3), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, SUBCELLULAR LOCATION, AND INTERACTION WITH GRIA2 AND GRIA3.
RX PubMed=9768844; DOI=10.1016/s0896-6273(00)80568-1;
RA Srivastava S., Osten P., Vilim F.S., Khatri L., Inman G., States B.,
RA Daly C., DeSouza S., Abagyan R., Valtschanoff J.G., Weinberg R.J.,
RA Ziff E.B.;
RT "Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA
RT receptor-binding protein ABP.";
RL Neuron 21:581-591(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE, AND
RP INTERACTION WITH EFNB1 AND EFNB3.
RC TISSUE=Hippocampus;
RX PubMed=10197531; DOI=10.1016/s0896-6273(00)80706-0;
RA Brueckner K., Pablo Labrador J., Scheiffele P., Herb A., Seeburg P.H.,
RA Klein R.;
RT "EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft
RT membrane microdomains.";
RL Neuron 22:511-524(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND SUBCELLULAR LOCATION.
RC TISSUE=Hippocampus;
RX PubMed=10436050; DOI=10.1523/jneurosci.19-16-06930.1999;
RA Dong H., Zhang P., Song I., Petralia R.S., Liao D., Huganir R.L.;
RT "Characterization of the glutamate receptor-interacting proteins GRIP1 and
RT GRIP2.";
RL J. Neurosci. 19:6930-6941(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND
RP INTERACTION WITH GRIA2 AND GRIA3.
RX PubMed=10414981; DOI=10.1523/jneurosci.19-15-06528.1999;
RA Wyszynski M., Valtschanoff J.G., Naisbitt S., Dunah A.W., Kim E.,
RA Standaert D.G., Weinberg R., Sheng M.;
RT "Association of AMPA receptors with a subset of glutamate receptor-
RT interacting protein in vivo.";
RL J. Neurosci. 19:6528-6537(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND PALMITOYLATION AT CYS-11 (ISOFORM 4).
RX PubMed=11978826; DOI=10.1523/jneurosci.22-09-03493.2002;
RA DeSouza S., Fu J., States B.A., Ziff E.B.;
RT "Differential palmitoylation directs the AMPA receptor-binding protein ABP
RT to spines or to intracellular clusters.";
RL J. Neurosci. 22:3493-3503(2002).
RN [6]
RP INTERACTION WITH GRIPAP1.
RX PubMed=10896157; DOI=10.1016/s0896-6273(00)81198-8;
RA Ye B., Liao D., Zhang X., Zhang P., Dong H., Huganir R.L.;
RT "GRASP-1: a neuronal RasGEF associated with the AMPA receptor/GRIP
RT complex.";
RL Neuron 26:603-617(2000).
RN [7]
RP INTERACTION WITH CSGP4, AND DOMAIN.
RX PubMed=12458226; DOI=10.1074/jbc.m210010200;
RA Stegmueller J., Werner H., Nave K.-A., Trotter J.;
RT "The proteoglycan NG2 is complexed with alpha-amino-3-hydroxy-5-methyl-4-
RT isoxazolepropionic acid (AMPA) receptors by the PDZ glutamate receptor
RT interaction protein (GRIP) in glial progenitor cells. Implications for
RT glial-neuronal signaling.";
RL J. Biol. Chem. 278:3590-3598(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: May play a role as a localized scaffold for the assembly of a
CC multiprotein signaling complex and as mediator of the trafficking of
CC its binding partners at specific subcellular location in neurons.
CC -!- SUBUNIT: Interacts with the C-terminal tail of PRLHR (By similarity).
CC Interacts with EFNB1, EFNB3, GRIA2, GRIA3, CSGP4 and GRIPAP1. Can form
CC homomultimers and heteromultimers with GRIP1. {ECO:0000250,
CC ECO:0000269|PubMed:10197531, ECO:0000269|PubMed:10414981,
CC ECO:0000269|PubMed:10896157, ECO:0000269|PubMed:12458226,
CC ECO:0000269|PubMed:9768844}.
CC -!- INTERACTION:
CC Q9WTW1; Q8VHY0: Cspg4; Xeno; NbExp=2; IntAct=EBI-936045, EBI-8327479;
CC Q9WTW1-3; P19491: Gria2; NbExp=7; IntAct=EBI-936068, EBI-77718;
CC Q9WTW1-3; P97879: Grip1; NbExp=3; IntAct=EBI-936068, EBI-936113;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane. Postsynaptic density.
CC Note=Isoform 1 was found in synaptic plasma membrane and postsynaptic
CC density.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Membrane; Peripheral
CC membrane protein. Synapse. Note=Isoform 2 was found at excitatory
CC synapses and also at non-synaptic membranes and within intracellular
CC compartments.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane. Postsynaptic density.
CC Cell projection, dendritic spine. Endoplasmic reticulum. Cytoplasm,
CC cytoskeleton. Note=Isoform 3 was found in synaptic plasma membrane and
CC postsynaptic density. Isoform 3 was also found in dendrites where it
CC was associated with microtubules, endoplasmic reticulum and dendritic
CC spines.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Membrane; Peripheral membrane
CC protein. Note=Isoform 4 was exclusively membrane associated.
CC {ECO:0000269|PubMed:11978826}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9WTW1-1; Sequence=Displayed;
CC Name=2; Synonyms=ABP-L, ABP-L/GRIP2;
CC IsoId=Q9WTW1-2; Sequence=VSP_009761;
CC Name=3; Synonyms=ABP, ABP-S;
CC IsoId=Q9WTW1-3; Sequence=VSP_009760, VSP_009762, VSP_009763;
CC Name=4; Synonyms=pABP-L;
CC IsoId=Q9WTW1-4; Sequence=VSP_009759;
CC -!- TISSUE SPECIFICITY: Brain specific. Isoform 1 is expressed in the
CC olfactory bulb, cortex and hippocampus and was also expressed at lower
CC levels in thalamus, cerebellum and spinal cord. Isoform 3 is expressed
CC in pyramidal cells of cortex and hippocampus, striatum, thalamus,
CC hypothalamus, stellate cells of cerebellum, and brainstem. Isoform 2
CC and isoform 4 are expressed in cortex, hippocampus, thalamus,
CC cerebellum, brainstem and spinal cord. In hippocampal neurons isoform 4
CC is found abundantly in spine structures. Isoform 2 is abundant in the
CC cell body and also found in dendritic shafts.
CC {ECO:0000269|PubMed:10436050, ECO:0000269|PubMed:11978826,
CC ECO:0000269|PubMed:9768844}.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 expression was relatively low early in
CC development and increased postnatally, reaching a peak at P14. Isoform
CC 3 is detected at low levels prior to P9, whereupon its expression
CC increases, with the highest levels in the adult.
CC {ECO:0000269|PubMed:10197531, ECO:0000269|PubMed:10436050,
CC ECO:0000269|PubMed:9768844}.
CC -!- DOMAIN: PDZ 5 mediates the C-terminal binding of GRIA2 and GRIA3. PDZ 6
CC mediates interaction with the PDZ recognition motif of EFNB1. PDZ 7
CC mediates interaction with CSPG4. {ECO:0000269|PubMed:12458226}.
CC -!- PTM: Palmitoylation of isoform 4 mediates membrane location.
CC {ECO:0000269|PubMed:11978826}.
CC -!- SIMILARITY: Belongs to the GRIP2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD28427.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF090113; AAC36313.1; -; mRNA.
DR EMBL; AF072509; AAD25916.1; -; mRNA.
DR EMBL; AF205193; AAF19028.1; -; mRNA.
DR EMBL; AF112182; AAD28427.1; ALT_INIT; mRNA.
DR RefSeq; NP_612544.2; NM_138535.2. [Q9WTW1-1]
DR RefSeq; XP_006236957.1; XM_006236895.3. [Q9WTW1-2]
DR AlphaFoldDB; Q9WTW1; -.
DR SMR; Q9WTW1; -.
DR IntAct; Q9WTW1; 5.
DR MINT; Q9WTW1; -.
DR STRING; 10116.ENSRNOP00000041016; -.
DR TCDB; 8.A.24.1.4; the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family.
DR iPTMnet; Q9WTW1; -.
DR PhosphoSitePlus; Q9WTW1; -.
DR SwissPalm; Q9WTW1; -.
DR PaxDb; Q9WTW1; -.
DR PRIDE; Q9WTW1; -.
DR Ensembl; ENSRNOT00000013232; ENSRNOP00000013232; ENSRNOG00000009726. [Q9WTW1-2]
DR Ensembl; ENSRNOT00000049657; ENSRNOP00000041016; ENSRNOG00000009726. [Q9WTW1-1]
DR GeneID; 171571; -.
DR KEGG; rno:171571; -.
DR UCSC; RGD:621668; rat. [Q9WTW1-1]
DR CTD; 80852; -.
DR RGD; 621668; Grip2.
DR eggNOG; KOG3528; Eukaryota.
DR GeneTree; ENSGT00940000155615; -.
DR HOGENOM; CLU_004313_0_0_1; -.
DR InParanoid; Q9WTW1; -.
DR OMA; MNHAFSC; -.
DR OrthoDB; 65191at2759; -.
DR PhylomeDB; Q9WTW1; -.
DR TreeFam; TF326909; -.
DR Reactome; R-RNO-416993; Trafficking of GluR2-containing AMPA receptors.
DR PRO; PR:Q9WTW1; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000009726; Expressed in cerebellum and 9 other tissues.
DR ExpressionAtlas; Q9WTW1; baseline and differential.
DR Genevisible; Q9WTW1; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043198; C:dendritic shaft; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0044309; C:neuron spine; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:UniProtKB.
DR GO; GO:0035254; F:glutamate receptor binding; IDA:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IEA:InterPro.
DR GO; GO:0014824; P:artery smooth muscle contraction; ISO:RGD.
DR GO; GO:0098887; P:neurotransmitter receptor transport, endosome to postsynaptic membrane; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:1904719; P:positive regulation of AMPA glutamate receptor clustering; IMP:UniProtKB.
DR GO; GO:0045777; P:positive regulation of blood pressure; ISO:RGD.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IMP:UniProtKB.
DR GO; GO:0014042; P:positive regulation of neuron maturation; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IMP:RGD.
DR GO; GO:0099003; P:vesicle-mediated transport in synapse; ISO:RGD.
DR Gene3D; 2.30.42.10; -; 7.
DR InterPro; IPR043545; GRIP1/2.
DR InterPro; IPR030029; GRIP2.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR PANTHER; PTHR46227; PTHR46227; 1.
DR PANTHER; PTHR46227:SF4; PTHR46227:SF4; 1.
DR Pfam; PF00595; PDZ; 6.
DR Pfam; PF17820; PDZ_6; 1.
DR SMART; SM00228; PDZ; 7.
DR SUPFAM; SSF50156; SSF50156; 7.
DR PROSITE; PS50106; PDZ; 7.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Endoplasmic reticulum; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Reference proteome; Repeat; Synapse.
FT CHAIN 1..1043
FT /note="Glutamate receptor-interacting protein 2"
FT /id="PRO_0000083853"
FT DOMAIN 53..136
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 153..239
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 253..337
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 458..547
FT /note="PDZ 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 559..643
FT /note="PDZ 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 658..740
FT /note="PDZ 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 942..1024
FT /note="PDZ 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 371..450
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 745..769
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 786..863
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 383..407
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 786..823
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9768844"
FT /id="VSP_009760"
FT VAR_SEQ 1..18
FT /note="MLAVSLKWRLGVVRRRPK -> MRGWRRNLALCLQRLPDE (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:11978826"
FT /id="VSP_009759"
FT VAR_SEQ 349..390
FT /note="VRIQRSEQLHHWDPCVPSCHSPRPSHCRAPTWAPGGQDQSRS -> A (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:10414981"
FT /id="VSP_009761"
FT VAR_SEQ 859..874
FT /note="SPAPGPAREEGFWRVL -> RHPVSPLSTPSHLPLF (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9768844"
FT /id="VSP_009762"
FT VAR_SEQ 875..1043
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9768844"
FT /id="VSP_009763"
FT CONFLICT 450
FT /note="Q -> H (in Ref. 4; AAD28427)"
FT /evidence="ECO:0000305"
FT LIPID Q9WTW1-4:11
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:11978826"
SQ SEQUENCE 1043 AA; 112488 MW; C463C36ADC459A3C CRC64;
MLAVSLKWRL GVVRRRPKDD GPYSKGGKDT AGTDGALVCR RQSIPEEFRG ITMVELIKRE
GSTLGLTISG GTDKDGKPRV SNLRPGGLAA RSDLLNVGDY IRSVNGIRLT RLRHDEIITL
LKNVGERVVL EVEYELPPPA PENNPRIISK TVDVSLYKEG NSFGFVLRGG AHEDLHKSRP
LVLTYVRPGG PADREGSLKV GDRLLSIDGI PLHGASHATA IATLQQCSHE ALFQVEYDVA
TPDTVANASG PLVVEIAKTP GSALGISLTT GSHRNKPAIT IDRIKPASVV DRSGALHAGD
HILAIDGTST EHCSLVEATK LLASVTEKVR LEILPAPQSR RPLKPPEAVR IQRSEQLHHW
DPCVPSCHSP RPSHCRAPTW APGGQDQSRS VSSTPFSSPT MNPAFPCANA STLPRGPMSP
RTTAGRRRQR RKEHRSSLSL ASSTVGPGGQ IVHTETTEVV LCGDPLSGFG LQLQGGIFAT
ETLSSPPLVR FIEPDSPAER CGLLQVGDRV LAINGIATED GTMEEANQLL RDAALARKVV
LEIEFDVAES VIPSSGTFHV KLPKRRGVEL GITISSASRK RGEPLIISDI KKGSVAHRTG
TLEPGDKLLA IDNIRLDHCP MEYAVQILRQ CEDLVKLKIR KDEDNSDEQE SSGAVSYTVE
LKRYGGPLGI TISGTEEPFD PIIISGLTKR GLAERTGAIH VGDRILAINS VSLKGRPLSE
AIHLLQVAGE TVTLKIKKQL DRPLLPRQSG SLSEASDVDE DPPEALKGGL LTTHFSPAVP
SVDSAVESWG SSATEGGFGG SGSYTPQVAV RSVTPQEWRS SRLKSSPPPL EPRRTSYTPG
PTDESFPEEE EGDWEPPMSP APGPAREEGF WRVLGEALED LESCGQSELL RELEASIMTG
TVQSVAVDGR PGSRPWRRSR EVGTSPEDLQ ELLLPTPLEM HRVTLHKDPV RNDFGFSVSD
GLLEKGVYVH TVRIDGPAQH GGLQPFDRLL QVNHVRTRDF DCCLAVPLLA EAGDILELVV
SRNPLAQSRR TPGAPGPSSP QMI
