WBP2_MOUSE
ID WBP2_MOUSE Reviewed; 261 AA.
AC P97765; A2A860;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=WW domain-binding protein 2;
DE Short=WBP-2;
GN Name=Wbp2;
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], AND INTERACTION WITH YAP1.
RX PubMed=7644498; DOI=10.1073/pnas.92.17.7819;
RA Chen H.I., Sudol M.;
RT "The WW domain of Yes-associated protein binds a proline-rich ligand that
RT differs from the consensus established for Src homology 3-binding
RT modules.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7819-7823(1995).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 [5]
RP INTERACTION WITH NEDD4, DOMAINS, AND MUTAGENESIS OF TYR-170; TYR-200 AND
RP TYR-252.
RC TISSUE=Embryo;
RX PubMed=11042109; DOI=10.1042/bj3510557;
RA Jolliffe C.N., Harvey K.F., Haines B.P., Parasivam G., Kumar S.;
RT "Identification of multiple proteins expressed in murine embryos as binding
RT partners for the WW domains of the ubiquitin-protein ligase Nedd4.";
RL Biochem. J. 351:557-565(2000).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
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).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND ALTERNATIVE
RP SPLICING.
RX PubMed=26881968; DOI=10.15252/emmm.201505523;
RA Buniello A., Ingham N.J., Lewis M.A., Huma A.C., Martinez-Vega R.,
RA Varela-Nieto I., Vizcay-Barrena G., Fleck R.A., Houston O., Bardhan T.,
RA Johnson S.L., White J.K., Yuan H., Marcotti W., Steel K.P.;
RT "Wbp2 is required for normal glutamatergic synapses in the cochlea and is
RT crucial for hearing.";
RL EMBO Mol. Med. 8:191-207(2016).
CC -!- FUNCTION: Acts as transcriptional coactivator of estrogen and
CC progesterone receptors (ESR1 and PGR) upon hormone activation. In
CC presence of estrogen, binds to ESR1-responsive promoters. Required for
CC YAP1 coactivation function on PGR activity. Synergizes with WBP2 in
CC enhancing PGR activity (By similarity). Modulates expression of post-
CC synaptic scaffolding proteins via regulation of ESR1, ESR2 and PGR
CC (PubMed:26881968). {ECO:0000250|UniProtKB:Q969T9,
CC ECO:0000269|PubMed:26881968}.
CC -!- SUBUNIT: Binds to the WW domain of YAP1, WWP1 and WWP2 (By similarity)
CC (PubMed:7644498). Interacts with NEDD4 (PubMed:11042109). Interacts
CC with ESR1 and UBE3A (By similarity). {ECO:0000250|UniProtKB:Q969T9,
CC ECO:0000269|PubMed:11042109, ECO:0000269|PubMed:7644498}.
CC -!- INTERACTION:
CC P97765; P46935: Nedd4; NbExp=5; IntAct=EBI-6304181, EBI-773516;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q969T9}. Nucleus
CC {ECO:0000250|UniProtKB:Q969T9}. Note=Translocates from cytoplasm to
CC nucleus when phosphorylated. {ECO:0000250|UniProtKB:Q969T9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P97765-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P97765-2; Sequence=VSP_059234;
CC -!- TISSUE SPECIFICITY: Expressed in the ear and the eye (PubMed:26881968).
CC Isoform 1 is expressed in brain, inner ear and organ of Corti. Isoform
CC 2 is only detected in brain (PubMed:26881968).
CC {ECO:0000269|PubMed:26881968}.
CC -!- DOMAIN: The PPxY motif 1 mediates interaction with NEDD4
CC (PubMed:11042109). The PPxY motif 2 is required for the coactivation
CC function (By similarity). {ECO:0000250|UniProtKB:Q969T9,
CC ECO:0000269|PubMed:11042109}.
CC -!- PTM: Phosphorylated in repsonse to EGF as well as estrogen and
CC progesterone hormones. Tyr-192 and Tyr-231 are phosphorylated by YES
CC and SRC inducing nuclear translocation. {ECO:0000250|UniProtKB:Q969T9}.
CC -!- DISRUPTION PHENOTYPE: Mutant animals have a progressive high-frequency
CC hearing loss (PubMed:26881968). They show swelling of afferent
CC terminals and abnormal expression of AMPA receptor subunit at post-
CC synaptic densities (PubMed:26881968). Mice are fertile and show no
CC other abnormalities (PubMed:26881968). {ECO:0000269|PubMed:26881968}.
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DR EMBL; U40826; AAB40893.1; -; mRNA.
DR EMBL; AL607108; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466558; EDL34550.1; -; Genomic_DNA.
DR EMBL; BC055058; AAH55058.1; -; mRNA.
DR CCDS; CCDS25657.1; -. [P97765-1]
DR CCDS; CCDS83934.1; -. [P97765-2]
DR RefSeq; NP_001334571.1; NM_001347642.1. [P97765-2]
DR RefSeq; NP_058548.1; NM_016852.2. [P97765-1]
DR AlphaFoldDB; P97765; -.
DR BioGRID; 204546; 9.
DR IntAct; P97765; 2.
DR MINT; P97765; -.
DR STRING; 10090.ENSMUSP00000074204; -.
DR iPTMnet; P97765; -.
DR PhosphoSitePlus; P97765; -.
DR EPD; P97765; -.
DR jPOST; P97765; -.
DR MaxQB; P97765; -.
DR PaxDb; P97765; -.
DR PeptideAtlas; P97765; -.
DR PRIDE; P97765; -.
DR ProteomicsDB; 297632; -. [P97765-1]
DR ProteomicsDB; 297633; -. [P97765-2]
DR Antibodypedia; 32285; 145 antibodies from 25 providers.
DR Ensembl; ENSMUST00000074628; ENSMUSP00000074204; ENSMUSG00000034341. [P97765-1]
DR Ensembl; ENSMUST00000106444; ENSMUSP00000102052; ENSMUSG00000034341. [P97765-2]
DR GeneID; 22378; -.
DR KEGG; mmu:22378; -.
DR UCSC; uc007mjv.1; mouse. [P97765-1]
DR CTD; 23558; -.
DR MGI; MGI:104709; Wbp2.
DR VEuPathDB; HostDB:ENSMUSG00000034341; -.
DR eggNOG; KOG3294; Eukaryota.
DR GeneTree; ENSGT00530000063718; -.
DR InParanoid; P97765; -.
DR OMA; QAPTNVF; -.
DR PhylomeDB; P97765; -.
DR TreeFam; TF314141; -.
DR BioGRID-ORCS; 22378; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Wbp2; mouse.
DR PRO; PR:P97765; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P97765; protein.
DR Bgee; ENSMUSG00000034341; Expressed in primary visual cortex and 263 other tissues.
DR ExpressionAtlas; P97765; baseline and differential.
DR Genevisible; P97765; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:MGI.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0071391; P:cellular response to estrogen stimulus; ISO:MGI.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; ISO:MGI.
DR GO; GO:0071169; P:establishment of protein localization to chromatin; ISO:MGI.
DR GO; GO:0071442; P:positive regulation of histone H3-K14 acetylation; ISO:MGI.
DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0050847; P:progesterone receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043627; P:response to estrogen; ISS:UniProtKB.
DR GO; GO:0032570; P:response to progesterone; ISS:UniProtKB.
DR InterPro; IPR004182; GRAM.
DR InterPro; IPR033598; WBP2.
DR InterPro; IPR044852; WBP2-like.
DR PANTHER; PTHR31606; PTHR31606; 1.
DR PANTHER; PTHR31606:SF4; PTHR31606:SF4; 1.
DR Pfam; PF02893; GRAM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..261
FT /note="WW domain-binding protein 2"
FT /id="PRO_0000065951"
FT DOMAIN 1..84
FT /note="GRAM"
FT REGION 196..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 196..200
FT /note="PPxY motif 1"
FT MOTIF 248..252
FT /note="PPxY motif 2"
FT COMPBIAS 196..213
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 241..261
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 192
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q969T9"
FT MOD_RES 231
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q969T9"
FT VAR_SEQ 133..177
FT /note="Missing (in isoform 2)"
FT /id="VSP_059234"
FT MUTAGEN 170
FT /note="Y->A: No effect on interaction with NEDD4."
FT /evidence="ECO:0000269|PubMed:11042109"
FT MUTAGEN 200
FT /note="Y->A: Abolishes interaction with NEDD4."
FT /evidence="ECO:0000269|PubMed:11042109"
FT MUTAGEN 252
FT /note="Y->A: No effect on interaction with NEDD4."
FT /evidence="ECO:0000269|PubMed:11042109"
SQ SEQUENCE 261 AA; 28032 MW; DA475B184F284380 CRC64;
MALNKNHSEG GGVIVNNTES ILMSYDHVEL TFNDMKNVPE AFKGTKKGTV YLTPYRVIFL
SKGKDAMQSF MMPFYLMKDC EIKQPVFGAN FIKGIVKAEA GGGWEGSASY KLTFTAGGAI
EFGQRMLQVA SQASRGEVPN GAYGYPYMPS GAYVFPPPVA NGMYPCPPGY PYPPPPPEFY
PGPPMMDGAM GYVQPPPPPY PGPMEPPVSG PSAPATPAAE AKAAEAAASA YYNPGNPHNV
YMPTSQPPPP PYYPPEDKKT Q
