HOME3_MOUSE
ID HOME3_MOUSE Reviewed; 356 AA.
AC Q99JP6; D3Z6N9; Q9Z215;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Homer protein homolog 3 {ECO:0000305};
DE Short=Homer-3;
GN Name=Homer3 {ECO:0000312|MGI:MGI:1347359};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary tumor;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-356 (ISOFORM 2).
RC STRAIN=C3H/HeJ; TISSUE=Myotube;
RX PubMed=9808458; DOI=10.1016/s0896-6273(00)80588-7;
RA Xiao B., Tu J.C., Petralia R.S., Yuan J.P., Doan A., Breder C.D.,
RA Ruggiero A., Lanahan A.A., Wenthold R.J., Worley P.F.;
RT "Homer regulates the association of group 1 metabotropic glutamate
RT receptors with multivalent complexes of homer-related, synaptic proteins.";
RL Neuron 21:707-716(1998).
RN [4]
RP INTERACTION WITH METABOTROPIC GLUTAMATE AND ITPR1 RECEPTORS.
RX PubMed=9808459; DOI=10.1016/s0896-6273(00)80589-9;
RA Tu J.C., Xiao B., Yuan J.P., Lanahan A.A., Leoffert K., Li M., Linden D.J.,
RA Worley P.F.;
RT "Homer binds a novel proline-rich motif and links group 1 metabotropic
RT glutamate receptors with IP3 receptors.";
RL Neuron 21:717-726(1998).
RN [5]
RP INTERACTION WITH GRM1 AND GRM5.
RX PubMed=11418862; DOI=10.1038/35082096;
RA Ango F., Prezeau L., Muller T., Tu J.C., Xiao B., Worley P.F., Pin J.P.,
RA Bockaert J., Fagni L.;
RT "Agonist-independent activation of metabotropic glutamate receptors by the
RT intracellular protein Homer.";
RL Nature 411:962-965(2001).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [7]
RP INTERACTION WITH NFATC2, AND DISRUPTION PHENOTYPE.
RX PubMed=18218901; DOI=10.1126/science.1151227;
RA Huang G.N., Huso D.L., Bouyain S., Tu J., McCorkell K.A., May M.J., Zhu Y.,
RA Lutz M., Collins S., Dehoff M., Kang S., Whartenby K., Powell J., Leahy D.,
RA Worley P.F.;
RT "NFAT binding and regulation of T cell activation by the cytoplasmic
RT scaffolding Homer proteins.";
RL Science 319:476-481(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, and Spleen;
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 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. Isoforms can be differently regulated
CC and may play an important role in maintaining the plasticity at
CC glutamatergic synapses (By similarity). Negatively regulates T cell
CC activation by inhibiting the calcineurin-NFAT pathway. Acts by
CC competing with calcineurin/PPP3CA for NFAT protein binding, hence
CC preventing NFAT activation by PPP3CA (PubMed:18218901).
CC {ECO:0000250|UniProtKB:Q9NSC5, ECO:0000269|PubMed:18218901}.
CC -!- SUBUNIT: Tetramer (By similarity). Isoform 1 and isoform 2 encode
CC coiled-coil structures that mediate homo- and heteromultimerization.
CC Interacts with NFATC2; interaction is calcium independent; interaction
CC competes with PPP3CA for NFATC2 binding; interaction is reduced by AKT
CC activation (PubMed:18218901). Interacts with NFATC1 and NFATC4.
CC Interacts with SHANK1; forms a high-order complex at least composed of
CC SHANK1 and HOMER3; the complex formation is regulated by CAMK2A-
CC mediated phosphorylation (By similarity).
CC {ECO:0000250|UniProtKB:Q9NSC5, ECO:0000269|PubMed:18218901}.
CC -!- INTERACTION:
CC Q99JP6; Q14517: FAT1; Xeno; NbExp=2; IntAct=EBI-6272061, EBI-1171918;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Postsynaptic density
CC {ECO:0000250}. Synapse {ECO:0000250}. Note=Postsynaptic density of
CC neuronal cells. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99JP6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99JP6-2; Sequence=VSP_009078;
CC -!- TISSUE SPECIFICITY: Expressed in the cerebellum, hippocampus, lung and
CC thymus.
CC -!- DOMAIN: The WH1 domain interacts with the PPXXF motif in GRM1, GRM5,
CC RYR1, RYR2, ITPR1, SHANK 1 and SHANK3.
CC -!- DISRUPTION PHENOTYPE: Knockout mice show severe autoimmune phenotypes,
CC with lymphocyte infiltration of multiple organs and hyperplasia in
CC lymph nodes by 10 weeks of age. {ECO:0000269|PubMed:18218901}.
CC -!- SIMILARITY: Belongs to the Homer family. {ECO:0000305}.
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DR EMBL; AC158553; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005773; AAH05773.1; -; mRNA.
DR EMBL; AF093261; AAC71025.1; -; mRNA.
DR CCDS; CCDS22363.1; -. [Q99JP6-1]
DR CCDS; CCDS52569.1; -. [Q99JP6-2]
DR RefSeq; NP_001139625.1; NM_001146153.1. [Q99JP6-2]
DR RefSeq; NP_036114.2; NM_011984.2. [Q99JP6-1]
DR AlphaFoldDB; Q99JP6; -.
DR BMRB; Q99JP6; -.
DR SMR; Q99JP6; -.
DR BioGRID; 205016; 17.
DR IntAct; Q99JP6; 12.
DR MINT; Q99JP6; -.
DR STRING; 10090.ENSMUSP00000117033; -.
DR iPTMnet; Q99JP6; -.
DR PhosphoSitePlus; Q99JP6; -.
DR EPD; Q99JP6; -.
DR MaxQB; Q99JP6; -.
DR PaxDb; Q99JP6; -.
DR PeptideAtlas; Q99JP6; -.
DR PRIDE; Q99JP6; -.
DR ProteomicsDB; 273161; -. [Q99JP6-1]
DR ProteomicsDB; 273162; -. [Q99JP6-2]
DR DNASU; 26558; -.
DR Ensembl; ENSMUST00000003669; ENSMUSP00000003669; ENSMUSG00000003573. [Q99JP6-2]
DR Ensembl; ENSMUST00000110124; ENSMUSP00000105751; ENSMUSG00000003573. [Q99JP6-2]
DR Ensembl; ENSMUST00000140212; ENSMUSP00000117033; ENSMUSG00000003573. [Q99JP6-1]
DR GeneID; 26558; -.
DR KEGG; mmu:26558; -.
DR UCSC; uc009lzs.2; mouse. [Q99JP6-1]
DR UCSC; uc009lzt.2; mouse. [Q99JP6-2]
DR CTD; 9454; -.
DR MGI; MGI:1347359; Homer3.
DR VEuPathDB; HostDB:ENSMUSG00000003573; -.
DR eggNOG; ENOG502R3T0; Eukaryota.
DR GeneTree; ENSGT00940000158081; -.
DR HOGENOM; CLU_033940_0_0_1; -.
DR InParanoid; Q99JP6; -.
DR OMA; KICDLKD; -.
DR OrthoDB; 1251658at2759; -.
DR PhylomeDB; Q99JP6; -.
DR TreeFam; TF325627; -.
DR Reactome; R-MMU-6794361; Neurexins and neuroligins.
DR BioGRID-ORCS; 26558; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Homer3; mouse.
DR PRO; PR:Q99JP6; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q99JP6; protein.
DR Bgee; ENSMUSG00000003573; Expressed in cerebellar cortex and 126 other tissues.
DR ExpressionAtlas; Q99JP6; baseline and differential.
DR Genevisible; Q99JP6; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0045178; C:basal part of cell; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0035256; F:G protein-coupled glutamate receptor binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:MGI.
DR GO; GO:0019904; F:protein domain specific binding; IPI:MGI.
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:0098962; P:regulation of postsynaptic neurotransmitter receptor activity; IDA:SynGO.
DR GO; GO:2001256; P:regulation of store-operated calcium entry; IBA:GO_Central.
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; Coiled coil; Cytoplasm; Phosphoprotein;
KW Reference proteome; Synapse.
FT CHAIN 1..356
FT /note="Homer protein homolog 3"
FT /id="PRO_0000191012"
FT DOMAIN 1..113
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT REGION 1..80
FT /note="Required for interaction with NFATC2"
FT /evidence="ECO:0000250|UniProtKB:Q9NSC5"
FT REGION 136..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 244..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 94..122
FT /evidence="ECO:0000255"
FT COILED 191..353
FT /evidence="ECO:0000255"
FT COMPBIAS 250..278
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X5"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 267
FT /note="Q -> QEIQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9808458"
FT /id="VSP_009078"
FT CONFLICT 308
FT /note="S -> A (in Ref. 2; AAH05773 and 3; AAC71025)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 356 AA; 39694 MW; 7E75F910EE1D0F3F CRC64;
MSTAREQPIF STRAHVFQID PTTKRNWIPA GKHALTVSYF YDATRNVYRI ISIGGAKAII
NSTVTPNMTF TKTSQKFGQW ADSRANTVYG LGFASEQQLT QFAEKFQEVK EAARLAREKS
QDGGEFTSTG LALASHQVPP SPLVSTNGPG EEKLFRSQSA DTPGPTERER LKKMLSEGSV
GEVQWEAEFF ALQDSNQRLA GALREANAAA TQWRQQLEVQ RAEAELLRQR VAELEAQVAV
EPVRAGEKEA TSQSVEQLEA RVQTKDQTLK NQSTGTREAP DTAEREETQQ QVQDLETRNA
ELEQQLRSME CNLEEARAER ERARAEVGRA AQLLDVRLFE LSELREGLAR LAEAAP
