HOME2_RAT
ID HOME2_RAT Reviewed; 354 AA.
AC O88801; O88802;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Homer protein homolog 2 {ECO:0000305};
DE Short=Homer-2;
DE AltName: Full=Cupidin {ECO:0000250|UniProtKB:Q9QWW1};
DE AltName: Full=VASP/Ena-related gene up-regulated during seizure and LTP 2;
DE Short=Vesl-2;
GN Name=Homer2 {ECO:0000312|RGD:620705}; Synonyms=Vesl2;
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] (ISOFORMS 1 AND 2).
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RX PubMed=9727012; DOI=10.1074/jbc.273.37.23969;
RA Kato A., Ozawa F., Saitoh Y., Fukazawa Y., Sugiyama H., Inokuchi K.;
RT "Novel members of the Vesl/Homer family of PDZ-proteins that bind
RT metabotropic glutamate receptors.";
RL J. Biol. Chem. 273:23969-23975(1998).
RN [2]
RP INTERACTION WITH AGAP2.
RX PubMed=14528310; DOI=10.1038/nn1134;
RA Rong R., Ahn J.-Y., Huang H., Nagata E., Kalman D., Kapp J.A., Tu J.,
RA Worley P.F., Snyder S.H., Ye K.;
RT "PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing
RT neuronal apoptosis.";
RL Nat. Neurosci. 6:1153-1161(2003).
RN [3]
RP INTERACTION WITH DAGLA, AND SUBCELLULAR LOCATION.
RX PubMed=17584991; DOI=10.1124/mol.107.037796;
RA Jung K.M., Astarita G., Zhu C., Wallace M., Mackie K., Piomelli D.;
RT "A key role for diacylglycerol lipase-alpha in metabotropic glutamate
RT receptor-dependent endocannabinoid mobilization.";
RL Mol. Pharmacol. 72:612-621(2007).
CC -!- FUNCTION: Postsynaptic density scaffolding protein. Binds and cross-
CC links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2,
CC SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-
CC associated ITPR1 receptors, it aids the coupling of surface receptors
CC to intracellular calcium release. May also couple GRM1 to PI3 kinase
CC through its interaction with AGAP2. Isoforms can be differently
CC regulated and may play an important role in maintaining the plasticity
CC at glutamatergic synapses. Required for normal hearing (By similarity).
CC Negatively regulates T cell activation by inhibiting the calcineurin-
CC NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT
CC protein binding, hence preventing NFAT activation by PPP3CA (By
CC similarity). {ECO:0000250|UniProtKB:Q9NSB8}.
CC -!- SUBUNIT: Isoform 1 and isoform 2 encode coiled-coil structures that
CC mediate homo- and heteromultimerization. Interacts with NFATC2;
CC interaction is reduced by AKT activation. Interacts with NFATC1 and
CC NFATC4 (By similarity). Interacts with DAGLA (via PPXXF motif); this
CC interaction is required for the cell membrane localization of DAGLA
CC (Probable). {ECO:0000250|UniProtKB:Q9NSB8,
CC ECO:0000305|PubMed:17584991}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17584991}. Cell
CC membrane {ECO:0000269|PubMed:17584991}. Postsynaptic density. Synapse.
CC Cell projection, stereocilium {ECO:0000250|UniProtKB:Q9QWW1}.
CC Note=Postsynaptic density of neuronal cells. The stabilization and
CC clustering of the metabotropic glutamate receptors appears to be
CC mediated by isoform 1 and isoform 2 at the cell surface.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O88801-1; Sequence=Displayed;
CC Name=2; Synonyms=Vesl-2(delta 11);
CC IsoId=O88801-2; Sequence=VSP_009072;
CC -!- TISSUE SPECIFICITY: Constitutively expressed in the adult hippocampus.
CC -!- DEVELOPMENTAL STAGE: In the developing hippocampus, expression is high
CC at P8, then decreased along with hippocampal development.
CC -!- DOMAIN: The WH1 domain interacts with the PPXXF motif in GRM1, GRM5,
CC RYR1, RYR2, ITPR1, SHANK 1 and SHANK3.
CC -!- SIMILARITY: Belongs to the Homer family. {ECO:0000305}.
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DR EMBL; AB007689; BAA32478.1; -; mRNA.
DR EMBL; AB007690; BAA32479.1; -; mRNA.
DR RefSeq; NP_445761.1; NM_053309.1. [O88801-1]
DR AlphaFoldDB; O88801; -.
DR SMR; O88801; -.
DR BioGRID; 248181; 3.
DR IntAct; O88801; 2.
DR STRING; 10116.ENSRNOP00000026158; -.
DR iPTMnet; O88801; -.
DR PhosphoSitePlus; O88801; -.
DR jPOST; O88801; -.
DR PaxDb; O88801; -.
DR PRIDE; O88801; -.
DR Ensembl; ENSRNOT00000087785; ENSRNOP00000070858; ENSRNOG00000061450. [O88801-1]
DR GeneID; 29547; -.
DR KEGG; rno:29547; -.
DR UCSC; RGD:620705; rat. [O88801-1]
DR CTD; 9455; -.
DR RGD; 620705; Homer2.
DR eggNOG; ENOG502QR3K; Eukaryota.
DR GeneTree; ENSGT00940000157324; -.
DR HOGENOM; CLU_033940_0_0_1; -.
DR InParanoid; O88801; -.
DR OMA; PVTKKSW; -.
DR OrthoDB; 1251658at2759; -.
DR PhylomeDB; O88801; -.
DR TreeFam; TF325627; -.
DR Reactome; R-RNO-6794361; Neurexins and neuroligins.
DR PRO; PR:O88801; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000061450; Expressed in pancreas and 18 other tissues.
DR Genevisible; O88801; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0043229; C:intracellular organelle; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0032426; C:stereocilium tip; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; ISO:RGD.
DR GO; GO:0035256; F:G protein-coupled glutamate receptor binding; IPI:UniProtKB.
DR GO; GO:0035254; F:glutamate receptor binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IMP:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0030160; F:synaptic receptor adaptor activity; ISO:RGD.
DR GO; GO:0048148; P:behavioral response to cocaine; ISO:RGD.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISO:RGD.
DR GO; GO:0048875; P:chemical homeostasis within a tissue; ISO:RGD.
DR GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; ISS:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; ISS:UniProtKB.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:2001256; P:regulation of store-operated calcium entry; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; ISS:UniProtKB.
DR CDD; cd01206; EVH1_Homer_Vesl; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR045027; Homer.
DR InterPro; IPR044100; Homer_EVH1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR PANTHER; PTHR10918; PTHR10918; 1.
DR Pfam; PF00568; WH1; 1.
DR SMART; SM00461; WH1; 1.
DR PROSITE; PS50229; WH1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Coiled coil;
KW Cytoplasm; Hearing; Membrane; Reference proteome; Synapse.
FT CHAIN 1..354
FT /note="Homer protein homolog 2"
FT /id="PRO_0000191010"
FT DOMAIN 1..110
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT REGION 114..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 92..120
FT /evidence="ECO:0000255"
FT COILED 160..329
FT /evidence="ECO:0000255"
FT COMPBIAS 124..150
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 130..140
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9727012"
FT /id="VSP_009072"
SQ SEQUENCE 354 AA; 40563 MW; 205FA6358F9D198E CRC64;
MGEQPIFTTR AHVFQIDPST KKNWVPASKQ AVTVSYFYDV TRNSYRIISV DGAKVIINST
ITPNMTFTKT SQKFGQWADS RANTVFGLGF SSEQQLTKFA EKFQEVREAA RLARDKSQEK
IETSSNHSQE SGCETPSSTQ ASSVNGTDDE KASHASPADT HLKSENDKLK IALTQSAANV
KKWEIELQTL RESNARLTTA LQESAASVEQ WKRQFSICRD ENDRLRSKIE ELEEQCGEIN
REKEKNTQLK RRIEELESEV REKEMELKDL RKQSEIIPQL MSECEYVSEK LEAAERDNQN
LEDKVRSLKT DIEESKYRQR HLKGELKSFL EVLDGKIDDL HDFRRGLSKL GTDN
