HOME2_HUMAN
ID HOME2_HUMAN Reviewed; 354 AA.
AC Q9NSB8; O95269; O95349; Q9NSB6; Q9NSB7; Q9UNT7;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Homer protein homolog 2 {ECO:0000305};
DE Short=Homer-2;
DE AltName: Full=Cupidin {ECO:0000250|UniProtKB:Q9QWW1};
GN Name=HOMER2 {ECO:0000312|HGNC:HGNC:17513};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Frontal cortex;
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] (ISOFORMS 1 AND 2), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 1-182 (ISOFORMS 1/2).
RX PubMed=10653696; DOI=10.1006/jmbi.1999.3436;
RA Soloviev M., Ciruela F., Chan W.-Y., McIlhinney R.A.J.;
RT "Molecular characterisation of two structurally distinct groups of human
RT homers, generated by extensive alternative splicing.";
RL J. Mol. Biol. 295:1185-1200(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Yoshida M., Ueno M., Nakamura H., Saya H.;
RT "Mammalian neuralized interacts with a novel protein which has a EVH1-like
RT domain.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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 [6]
RP FUNCTION.
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 [7]
RP FUNCTION, AND INTERACTION WITH NFATC1; NFATC2 AND NFATC4.
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 FUNCTION, INVOLVEMENT IN DFNA68, SUBCELLULAR LOCATION, AND VARIANT DFNA68
RP PRO-196.
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).
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 (PubMed:9808459). Required for normal hearing
CC (PubMed:25816005). Negatively regulates T cell activation by inhibiting
CC the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA
CC for NFAT protein binding, hence preventing NFAT activation by PPP3CA
CC (PubMed:18218901). {ECO:0000269|PubMed:18218901,
CC ECO:0000269|PubMed:25816005, ECO:0000269|PubMed:9808459}.
CC -!- SUBUNIT: Forms coiled-coil structures that mediate homo- and
CC heteromultimerization. Interacts with NFATC2; interaction is reduced by
CC AKT activation (PubMed:18218901). Interacts with NFATC1 and NFATC4
CC (PubMed:18218901). 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:0000269|PubMed:18218901}.
CC -!- INTERACTION:
CC Q9NSB8; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-2126733, EBI-741037;
CC Q9NSB8; Q9H4P4: RNF41; NbExp=3; IntAct=EBI-2126733, EBI-2130266;
CC Q9NSB8-2; Q9P2A4: ABI3; NbExp=3; IntAct=EBI-12017090, EBI-742038;
CC Q9NSB8-2; Q8WX93-2: PALLD; NbExp=3; IntAct=EBI-12017090, EBI-12218525;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25816005}. Cell
CC membrane {ECO:0000250|UniProtKB:O88801}. 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; Synonyms=2b;
CC IsoId=Q9NSB8-1; Sequence=Displayed;
CC Name=2; Synonyms=2a;
CC IsoId=Q9NSB8-2; Sequence=VSP_041731;
CC -!- DOMAIN: The WH1 domain interacts with the PPXXF motif in GRM1, GRM5,
CC RYR1, RYR2, ITPR1, SHANK 1 and SHANK3.
CC -!- DISEASE: Deafness, autosomal dominant, 68 (DFNA68) [MIM:616707]: A form
CC of non-syndromic sensorineural hearing loss with postlingual onset.
CC Sensorineural deafness results from damage to the neural receptors of
CC the inner ear, the nerve pathways to the brain, or the area of the
CC brain that receives sound information. {ECO:0000269|PubMed:25816005}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the Homer family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB75539.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC Sequence=CAB75540.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AF093263; AAC71027.1; -; mRNA.
DR EMBL; AF093264; AAC71028.1; -; mRNA.
DR EMBL; Y19025; CAB75537.1; -; mRNA.
DR EMBL; Y19026; CAB75538.1; -; mRNA.
DR EMBL; Y19027; CAB75539.1; ALT_SEQ; mRNA.
DR EMBL; Y19028; CAB75540.1; ALT_SEQ; mRNA.
DR EMBL; AF081530; AAD13748.1; -; mRNA.
DR EMBL; AC022558; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC044907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012109; AAH12109.1; -; mRNA.
DR CCDS; CCDS45334.1; -. [Q9NSB8-1]
DR CCDS; CCDS45336.1; -. [Q9NSB8-2]
DR RefSeq; NP_004830.2; NM_004839.3. [Q9NSB8-2]
DR RefSeq; NP_955362.1; NM_199330.2. [Q9NSB8-1]
DR AlphaFoldDB; Q9NSB8; -.
DR SMR; Q9NSB8; -.
DR BioGRID; 114844; 23.
DR IntAct; Q9NSB8; 14.
DR MINT; Q9NSB8; -.
DR STRING; 9606.ENSP00000305632; -.
DR GlyGen; Q9NSB8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NSB8; -.
DR PhosphoSitePlus; Q9NSB8; -.
DR BioMuta; HOMER2; -.
DR DMDM; 38605067; -.
DR EPD; Q9NSB8; -.
DR jPOST; Q9NSB8; -.
DR MassIVE; Q9NSB8; -.
DR MaxQB; Q9NSB8; -.
DR PaxDb; Q9NSB8; -.
DR PeptideAtlas; Q9NSB8; -.
DR PRIDE; Q9NSB8; -.
DR ProteomicsDB; 82525; -. [Q9NSB8-1]
DR ProteomicsDB; 82526; -. [Q9NSB8-2]
DR Antibodypedia; 28153; 261 antibodies from 22 providers.
DR DNASU; 9455; -.
DR Ensembl; ENST00000304231.12; ENSP00000305632.8; ENSG00000103942.13. [Q9NSB8-1]
DR Ensembl; ENST00000450735.7; ENSP00000407634.2; ENSG00000103942.13. [Q9NSB8-2]
DR GeneID; 9455; -.
DR KEGG; hsa:9455; -.
DR MANE-Select; ENST00000450735.7; ENSP00000407634.2; NM_004839.4; NP_004830.2. [Q9NSB8-2]
DR UCSC; uc002bjg.4; human. [Q9NSB8-1]
DR CTD; 9455; -.
DR DisGeNET; 9455; -.
DR GeneCards; HOMER2; -.
DR HGNC; HGNC:17513; HOMER2.
DR HPA; ENSG00000103942; Tissue enhanced (pancreas).
DR MalaCards; HOMER2; -.
DR MIM; 604799; gene.
DR MIM; 616707; phenotype.
DR neXtProt; NX_Q9NSB8; -.
DR OpenTargets; ENSG00000103942; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR PharmGKB; PA134870500; -.
DR VEuPathDB; HostDB:ENSG00000103942; -.
DR eggNOG; ENOG502QR3K; Eukaryota.
DR GeneTree; ENSGT00940000157324; -.
DR HOGENOM; CLU_033940_0_0_1; -.
DR InParanoid; Q9NSB8; -.
DR OMA; PVTKKSW; -.
DR OrthoDB; 1251658at2759; -.
DR PhylomeDB; Q9NSB8; -.
DR TreeFam; TF325627; -.
DR PathwayCommons; Q9NSB8; -.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR SignaLink; Q9NSB8; -.
DR BioGRID-ORCS; 9455; 12 hits in 1069 CRISPR screens.
DR ChiTaRS; HOMER2; human.
DR GeneWiki; HOMER2; -.
DR GenomeRNAi; 9455; -.
DR Pharos; Q9NSB8; Tbio.
DR PRO; PR:Q9NSB8; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9NSB8; protein.
DR Bgee; ENSG00000103942; Expressed in body of pancreas and 159 other tissues.
DR ExpressionAtlas; Q9NSB8; baseline and differential.
DR Genevisible; Q9NSB8; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0043229; C:intracellular organelle; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR GO; GO:0032426; C:stereocilium tip; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; IEA:Ensembl.
DR GO; GO:0035256; F:G protein-coupled glutamate receptor binding; IBA:GO_Central.
DR GO; GO:0030160; F:synaptic receptor adaptor activity; IEA:Ensembl.
DR GO; GO:0048148; P:behavioral response to cocaine; IEA:Ensembl.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IEA:Ensembl.
DR GO; GO:0048875; P:chemical homeostasis within a tissue; IEA:Ensembl.
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; IMP:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IMP:UniProtKB.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IEA:Ensembl.
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 Alternative splicing; Cell membrane; Cell projection; Coiled coil;
KW Cytoplasm; Deafness; Disease variant; Hearing; Membrane;
KW Non-syndromic deafness; Reference proteome; Synapse.
FT CHAIN 1..354
FT /note="Homer protein homolog 2"
FT /id="PRO_0000191008"
FT DOMAIN 1..110
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT REGION 112..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 92..122
FT /evidence="ECO:0000255"
FT COILED 160..329
FT /evidence="ECO:0000255"
FT COMPBIAS 112..127
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..149
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:10653696,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9808458,
FT ECO:0000303|Ref.3"
FT /id="VSP_041731"
FT VARIANT 196
FT /note="R -> P (in DFNA68; dbSNP:rs864309524)"
FT /evidence="ECO:0000269|PubMed:25816005"
FT /id="VAR_075751"
FT VARIANT 219
FT /note="R -> H (in dbSNP:rs7175005)"
FT /id="VAR_053366"
FT VARIANT 239
FT /note="I -> S (in dbSNP:rs17158223)"
FT /id="VAR_053367"
FT CONFLICT 149
FT /note="D -> E (in Ref. 1; AAC71027/AAC71028)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="H -> Q (in Ref. 1; AAC71027/AAC71028)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 354 AA; 40627 MW; 33D258177F798373 CRC64;
MGEQPIFTTR AHVFQIDPNT KKNWMPASKQ AVTVSYFYDV TRNSYRIISV DGAKVIINST
ITPNMTFTKT SQKFGQWADS RANTVFGLGF SSEQQLTKFA EKFQEVKEAA KIAKDKTQEK
IETSSNHSQE SGRETPSSTQ ASSVNGTDDE KASHAGPANT HLKSENDKLK IALTQSAANV
KKWEIELQTL RESNARLTTA LQESAASVEQ WKRQFSICRD ENDRLRNKID ELEEQCSEIN
REKEKNTQLK RRIEELEAEL REKETELKDL RKQSEIIPQL MSECEYVSEK LEAAERDNQN
LEDKVRSLKT DIEESKYRQR HLKVELKSFL EVLDGKIDDL HDFRRGLSKL GTDN
