HOME2_MOUSE
ID HOME2_MOUSE Reviewed; 354 AA.
AC Q9QWW1; O89025; Q9Z0E4;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Homer protein homolog 2 {ECO:0000305};
DE Short=Homer-2;
DE AltName: Full=Cupidin {ECO:0000303|Ref.2};
DE AltName: Full=VASP/Ena-related gene up-regulated during seizure and LTP 2;
DE Short=Vesl-2;
GN Name=Homer2 {ECO:0000312|MGI:MGI:1347354}; Synonyms=Vesl2;
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Forebrain;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
RA Shiraishi Y., Mizutani A., Furuichi T.;
RT "Cupidin, a gene transiently expressed in developing cerebellar granule
RT cells.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-192.
RA Keen J., Inglehearn C.;
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INTERACTION WITH GRM1; GRM5; DYN3 AND ITPR1, AND TISSUE SPECIFICITY.
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 FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=25816005; DOI=10.1371/journal.pgen.1005137;
RA Azaiez H., Decker A.R., Booth K.T., Simpson A.C., Shearer A.E.,
RA Huygen P.L., Bu F., Hildebrand M.S., Ranum P.T., Shibata S.B., Turner A.,
RA Zhang Y., Kimberling W.J., Cornell R.A., Smith R.J.;
RT "HOMER2, a stereociliary scaffolding protein, is essential for normal
RT hearing in humans and mice.";
RL PLoS Genet. 11:E1005137-E1005137(2015).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 2-111.
RX PubMed=11491285; DOI=10.1006/jmbi.2001.4640;
RA Barzik M., Carl U.D., Schubert W.-D., Frank R., Wehland J., Heinz D.W.;
RT "The N-terminal domain of Homer/Vesl is a new class II EVH1 domain.";
RL J. Mol. Biol. 309:155-169(2001).
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 (By similarity). Isoforms can be
CC differently regulated and may play an important role in maintaining the
CC plasticity at glutamatergic synapses (By similarity) Required for
CC normal hearing (PubMed:25816005). 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q9NSB8, ECO:0000269|PubMed:25816005}.
CC -!- SUBUNIT: Forms coiled-coil structures 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 (By
CC similarity). {ECO:0000250|UniProtKB:O88801,
CC ECO:0000250|UniProtKB:Q9NSB8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9NSB8}. Cell
CC membrane {ECO:0000250|UniProtKB:O88801}. Postsynaptic density. Synapse.
CC Cell projection, stereocilium {ECO:0000269|PubMed:25816005}.
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; Synonyms=2b;
CC IsoId=Q9QWW1-1; Sequence=Displayed;
CC Name=2; Synonyms=2a;
CC IsoId=Q9QWW1-2; Sequence=VSP_009071;
CC -!- TISSUE SPECIFICITY: Expressed in olfactory bulb, hippocampus, thalamus
CC and heart (PubMed:9808459). Expressed in the cochlea, organ of Corti.
CC Expression is particularly enriched in the tips of stereocilia of both
CC inner and outer hair cells (PubMed:25816005).
CC {ECO:0000269|PubMed:25816005, ECO:0000269|PubMed:9808459}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice exhibit early onset
CC progressive hearing loss. {ECO:0000269|PubMed:25816005}.
CC -!- SIMILARITY: Belongs to the Homer family. {ECO:0000305}.
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DR EMBL; AF093259; AAC71023.1; -; mRNA.
DR EMBL; AF093260; AAC71024.1; -; mRNA.
DR EMBL; AB017136; BAA37088.1; -; mRNA.
DR EMBL; AJ012076; CAA09909.1; -; mRNA.
DR CCDS; CCDS40009.1; -. [Q9QWW1-1]
DR CCDS; CCDS85329.1; -. [Q9QWW1-2]
DR RefSeq; NP_001157558.1; NM_001164086.1. [Q9QWW1-2]
DR RefSeq; NP_001157559.1; NM_001164087.1.
DR RefSeq; NP_036113.1; NM_011983.2. [Q9QWW1-1]
DR PDB; 1I7A; X-ray; 2.24 A; A/B/C/D=1-111.
DR PDB; 5ZZ9; X-ray; 2.30 A; A/B/C=1-115.
DR PDBsum; 1I7A; -.
DR PDBsum; 5ZZ9; -.
DR AlphaFoldDB; Q9QWW1; -.
DR SMR; Q9QWW1; -.
DR BioGRID; 205015; 13.
DR IntAct; Q9QWW1; 2.
DR MINT; Q9QWW1; -.
DR STRING; 10090.ENSMUSP00000026922; -.
DR iPTMnet; Q9QWW1; -.
DR PhosphoSitePlus; Q9QWW1; -.
DR MaxQB; Q9QWW1; -.
DR PaxDb; Q9QWW1; -.
DR PeptideAtlas; Q9QWW1; -.
DR PRIDE; Q9QWW1; -.
DR ProteomicsDB; 273126; -. [Q9QWW1-1]
DR ProteomicsDB; 273127; -. [Q9QWW1-2]
DR Antibodypedia; 28153; 261 antibodies from 22 providers.
DR DNASU; 26557; -.
DR Ensembl; ENSMUST00000026922; ENSMUSP00000026922; ENSMUSG00000025813. [Q9QWW1-2]
DR Ensembl; ENSMUST00000207983; ENSMUSP00000146787; ENSMUSG00000025813. [Q9QWW1-1]
DR GeneID; 26557; -.
DR KEGG; mmu:26557; -.
DR UCSC; uc009ich.2; mouse. [Q9QWW1-1]
DR UCSC; uc009ici.2; mouse. [Q9QWW1-2]
DR CTD; 9455; -.
DR MGI; MGI:1347354; Homer2.
DR VEuPathDB; HostDB:ENSMUSG00000025813; -.
DR eggNOG; ENOG502QR3K; Eukaryota.
DR GeneTree; ENSGT00940000157324; -.
DR HOGENOM; CLU_033940_0_0_1; -.
DR InParanoid; Q9QWW1; -.
DR OMA; PVTKKSW; -.
DR OrthoDB; 1251658at2759; -.
DR PhylomeDB; Q9QWW1; -.
DR TreeFam; TF325627; -.
DR Reactome; R-MMU-6794361; Neurexins and neuroligins.
DR BioGRID-ORCS; 26557; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Homer2; mouse.
DR EvolutionaryTrace; Q9QWW1; -.
DR PRO; PR:Q9QWW1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9QWW1; protein.
DR Bgee; ENSMUSG00000025813; Expressed in lacrimal gland and 240 other tissues.
DR ExpressionAtlas; Q9QWW1; baseline and differential.
DR Genevisible; Q9QWW1; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IMP:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0043229; C:intracellular organelle; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0032426; C:stereocilium tip; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:MGI.
DR GO; GO:0035256; F:G protein-coupled glutamate receptor binding; ISO:MGI.
DR GO; GO:0035254; F:glutamate receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0030160; F:synaptic receptor adaptor activity; IDA:MGI.
DR GO; GO:0048148; P:behavioral response to cocaine; IMP:MGI.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IMP:MGI.
DR GO; GO:0048875; P:chemical homeostasis within a tissue; IMP: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:0008277; P:regulation of G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:2001256; P:regulation of store-operated calcium entry; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; IMP: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 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Coiled coil; Cytoplasm; Hearing; Membrane; Reference proteome; Synapse.
FT CHAIN 1..354
FT /note="Homer protein homolog 2"
FT /id="PRO_0000191009"
FT DOMAIN 1..110
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT REGION 110..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 160..329
FT /evidence="ECO:0000255"
FT COMPBIAS 124..150
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..166
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 130..140
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9808458, ECO:0000303|Ref.2"
FT /id="VSP_009071"
FT CONFLICT 191..192
FT /note="RE -> VP (in Ref. 3; CAA09909)"
FT /evidence="ECO:0000305"
FT STRAND 6..15
FT /evidence="ECO:0007829|PDB:1I7A"
FT TURN 18..20
FT /evidence="ECO:0007829|PDB:5ZZ9"
FT STRAND 24..27
FT /evidence="ECO:0007829|PDB:5ZZ9"
FT STRAND 32..39
FT /evidence="ECO:0007829|PDB:1I7A"
FT TURN 40..43
FT /evidence="ECO:0007829|PDB:1I7A"
FT STRAND 44..51
FT /evidence="ECO:0007829|PDB:1I7A"
FT STRAND 54..61
FT /evidence="ECO:0007829|PDB:1I7A"
FT STRAND 67..79
FT /evidence="ECO:0007829|PDB:1I7A"
FT TURN 80..83
FT /evidence="ECO:0007829|PDB:1I7A"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:1I7A"
FT HELIX 93..110
FT /evidence="ECO:0007829|PDB:1I7A"
SQ SEQUENCE 354 AA; 40570 MW; 18AF2F22EA8E1D06 CRC64;
MGEQPIFTTR AHVFQIDPST KKNWVPASKQ AVTVSYFYDV TRNSYRIISV DGAKVIINST
ITPNMTFTKT SQKFGQWADS RANTVFGLGF SSELQLTKFA EKFQEVREAA RLARDKSQEK
TETSSNHSQE SGCETPSSTQ ASSVNGTDDE KASHASPADT HLKSENDKLK IALTQSAANV
KKWEMELQTL RESNARLTTA LQESAASVEQ WKRQFSICRD ENDRLRSKIE ELEEQCSEIN
REKEKNTQLK RRIEELESEV RDKEMELKDL RKQSEIIPQL MSECEYVSEK LEAAERDNQN
LEDKVRSLKT DIEESKYRQR HLKGELKSFL EVLDGKIDDL HDFRRGLSKL GTDN
