ID 1433E_MOUSE Reviewed; 255 AA. AC P62259; P29360; P42655; Q63631; DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 27-MAR-2024, entry version 181. DE RecName: Full=14-3-3 protein epsilon; DE Short=14-3-3E; GN Name=Ywhae; 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 DEVELOPMENTAL STAGE. RC STRAIN=SWR/J; TISSUE=Kidney; RX PubMed=7750640; DOI=10.1006/dbio.1995.1139; RA McConnell J.E., Armstrong J.F., Bard J.B.; RT "The mouse 14-3-3 epsilon isoform, a kinase regulator whose expression RT pattern is modulated in mesenchyme and neuronal differentiation."; RL Dev. Biol. 169:218-228(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=129/Sv; RA Takihara Y., Irie K., Nomura M., Motaleb M., Matsumoto K., Shimada K.; RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=ILS, and ISS; RX PubMed=11471062; DOI=10.1007/s00335-001-1001-x; RA Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J., RA Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.; RT "High-throughput sequence identification of gene coding variants within RT alcohol-related QTLs."; RL Mamm. Genome 12:657-663(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; 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 PROTEIN SEQUENCE OF 131-141; 154-170 AND 197-215, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RC TISSUE=Brain, and Hippocampus; RA Lubec G., Klug S., Friebe K., Yang J.W., Zigmond M.; RL Submitted (JUL-2007) to UniProtKB. RN [6] RP INTERACTION WITH KSR1. RX PubMed=10409742; DOI=10.1128/mcb.19.8.5523; RA Stewart S., Sundaram M., Zhang Y., Lee J., Han M., Guan K.L.; RT "Kinase suppressor of Ras forms a multiprotein signaling complex and RT modulates MEK localization."; RL Mol. Cell. Biol. 19:5523-5534(1999). RN [7] RP INTERACTION WITH BEX3. RX PubMed=11278287; DOI=10.1074/jbc.m005453200; RA Kimura M.T., Irie S., Shoji-Hoshino S., Mukai J., Nadano D., Oshimura M., RA Sato T.-A.; RT "14-3-3 is involved in p75 neurotrophin receptor-mediated signal RT transduction."; RL J. Biol. Chem. 276:17291-17300(2001). RN [8] RP INTERACTION WITH ARHGEF28. RX PubMed=11533041; DOI=10.1074/jbc.m107709200; RA Zhai J., Lin H., Shamim M., Schlaepfer W.W., Canete-Soler R.; RT "Identification of a novel interaction of 14-3-3 with p190RhoGEF."; RL J. Biol. Chem. 276:41318-41324(2001). RN [9] RP INTERACTION WITH NDEL1. RX PubMed=12796778; DOI=10.1038/ng1169; RA Toyo-oka K., Shionoya A., Gambello M.J., Cardoso C., Leventer R., RA Ward H.L., Ayala R., Tsai L.-H., Dobyns W., Ledbetter D., Hirotsune S., RA Wynshaw-Boris A.; RT "14-3-3epsilon is important for neuronal migration by binding to NUDEL: a RT molecular explanation for Miller-Dieker syndrome."; RL Nat. Genet. 34:274-285(2003). RN [10] RP INTERACTION WITH GRB10. RX PubMed=15722337; DOI=10.1074/jbc.m501477200; RA Urschel S., Bassermann F., Bai R.Y., Munch S., Peschel C., Duyster J.; RT "Phosphorylation of grb10 regulates its interaction with 14-3-3."; RL J. Biol. Chem. 280:16987-16993(2005). RN [11] RP INTERACTION WITH TIAM2. RX PubMed=17320046; DOI=10.1016/j.bbrc.2007.02.028; RA Takefuji M., Mori K., Morita Y., Arimura N., Nishimura T., Nakayama M., RA Hoshino M., Iwamatsu A., Murohara T., Kaibuchi K., Amano M.; RT "Rho-kinase modulates the function of STEF, a Rac GEF, through its RT phosphorylation."; RL Biochem. Biophys. Res. Commun. 355:788-794(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC 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 [13] RP INTERACTION WITH ZFP36. RX PubMed=21078877; DOI=10.1128/mcb.00717-10; RA Clement S.L., Scheckel C., Stoecklin G., Lykke-Andersen J.; RT "Phosphorylation of tristetraprolin by MK2 impairs AU-rich element mRNA RT decay by preventing deadenylase recruitment."; RL Mol. Cell. Biol. 31:256-266(2011). RN [14] RP INTERACTION WITH DAPK2. RX PubMed=26047703; DOI=10.1016/j.bbrc.2015.05.105; RA Yuasa K., Ota R., Matsuda S., Isshiki K., Inoue M., Tsuji A.; RT "Suppression of death-associated protein kinase 2 by interaction with 14-3- RT 3 proteins."; RL Biochem. Biophys. Res. Commun. 464:70-75(2015). RN [15] RP INTERACTION WITH CRTC1; CRTC2 AND CRTC3. RX PubMed=30611118; DOI=10.1016/j.isci.2018.12.012; RA Sonntag T., Ostojic J., Vaughan J.M., Moresco J.J., Yoon Y.S., RA Yates J.R. III, Montminy M.; RT "Mitogenic Signals Stimulate the CREB Coactivator CRTC3 through PP2A RT Recruitment."; RL IScience 11:134-145(2018). RN [16] RP DISRUPTION PHENOTYPE. RX PubMed=30973865; DOI=10.1371/journal.pbio.3000194; RA Ingham N.J., Pearson S.A., Vancollie V.E., Rook V., Lewis M.A., Chen J., RA Buniello A., Martelletti E., Preite L., Lam C.C., Weiss F.D., Powis Z., RA Suwannarat P., Lelliott C.J., Dawson S.J., White J.K., Steel K.P.; RT "Mouse screen reveals multiple new genes underlying mouse and human hearing RT loss."; RL PLoS Biol. 17:E3000194-E3000194(2019). CC -!- FUNCTION: Adapter protein implicated in the regulation of a large CC spectrum of both general and specialized signaling pathways. Binds to a CC large number of partners, usually by recognition of a phosphoserine or CC phosphothreonine motif. Binding generally results in the modulation of CC the activity of the binding partner. Positively regulates CC phosphorylated protein HSF1 nuclear export to the cytoplasm. CC {ECO:0000250|UniProtKB:P62258, ECO:0000250|UniProtKB:P62261}. CC -!- SUBUNIT: Homodimer (By similarity). Heterodimerizes with YWHAZ (By CC similarity). Interacts with PKA-phosphorylated AANAT (By similarity). CC Interacts with ABL1 (phosphorylated form); the interaction retains it CC in the cytoplasm (By similarity). Interacts with ARHGEF28 CC (PubMed:11533041). Interacts with BEX3 (PubMed:11278287). Weakly CC interacts with CDKN1B (By similarity). Interacts with the 'Thr-369' CC phosphorylated form of DAPK2 (PubMed:26047703). Interacts with DENND1A CC (By similarity). Interacts with GAB2 (By similarity). Interacts with CC phosphorylated GRB10 (PubMed:15722337). Interacts with KSR1 CC (PubMed:10409742). Interacts with NDEL1 (PubMed:12796778). Interacts CC with PI4KB, TBC1D22A and TBC1D22B (By similarity). Interacts with the CC phosphorylated (by AKT1) form of SRPK2 (By similarity). Interacts with CC TIAM2 (PubMed:17320046). Interacts with the 'Ser-1134' and 'Ser-1161' CC phosphorylated form of SOS1 (By similarity). Interacts with ZFP36 (via CC phosphorylated form) (PubMed:21078877). Interacts with SLITRK1 (By CC similarity). Interacts with HSF1 (via phosphorylated form); this CC interaction promotes HSF1 sequestration in the cytoplasm in a ERK- CC dependent manner (By similarity). Interacts with RIPOR2 (By CC similarity). Interacts with KLHL22; required for the nuclear CC localization of KLHL22 upon amino acid starvation (By similarity). CC Interacts with CRTC1 (PubMed:30611118). Interacts with CRTC2 (probably CC when phosphorylated at 'Ser-171') (PubMed:30611118). Interacts with CC CRTC3 (probably when phosphorylated at 'Ser-162' and/or 'Ser-273') CC (PubMed:30611118). Interacts with ATP2B1 and ATP2B3; this interaction CC inhibits calcium-transporting ATPase activity (By similarity). CC Interacts with MEFV (By similarity). Interacts with RNF115 (By CC similarity). {ECO:0000250|UniProtKB:P62258, CC ECO:0000250|UniProtKB:P62260, ECO:0000269|PubMed:10409742, CC ECO:0000269|PubMed:11278287, ECO:0000269|PubMed:11533041, CC ECO:0000269|PubMed:12796778, ECO:0000269|PubMed:15722337, CC ECO:0000269|PubMed:17320046, ECO:0000269|PubMed:21078877, CC ECO:0000269|PubMed:26047703, ECO:0000269|PubMed:30611118}. CC -!- INTERACTION: CC P62259; Q8CHQ0: Fbxo4; NbExp=2; IntAct=EBI-356480, EBI-3895153; CC P62259; Q8C2B3: Hdac7; NbExp=5; IntAct=EBI-356480, EBI-643830; CC P62259; Q5S006: Lrrk2; NbExp=4; IntAct=EBI-356480, EBI-2693710; CC P62259; Q9ERR1: Ndel1; NbExp=7; IntAct=EBI-356480, EBI-646668; CC P62259; Q64163-4: Tfdp2; NbExp=6; IntAct=EBI-356480, EBI-8077763; CC P62259; O35244: Prdx6; Xeno; NbExp=2; IntAct=EBI-356480, EBI-915490; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P62258}. Cytoplasm CC {ECO:0000250|UniProtKB:P62258}. Melanosome CC {ECO:0000250|UniProtKB:P62258}. CC -!- DEVELOPMENTAL STAGE: In the 8.5 dpc embryo, expressed throughout the CC embryo. Within a day, expression was more marked in mesenchyme than CC elsewhere (e.g. epithelial tissue, where it was generally low), CC although levels in neural tissue rose again by about 12.5 dpc. This CC difference was maintained until 15.5 dpc when expression levels started CC to drop in most tissues, with those of the nervous system, tooth, and CC kidney being exceptions. Strongly expressed in early mesenchyme. The CC expression decreased as the mesenchyme differentiated. CC {ECO:0000269|PubMed:7750640}. CC -!- DISRUPTION PHENOTYPE: Knockouts show reduced viability with reduced CC growth and a shortened skull (PubMed:30973865). Mutants show increased CC thresholds across all frequencies associated with variable amounts of CC accumulated fluid and exudate containing inflammatory cells in the CC middle ear, suggesting predisposition to otitis media. The middle ear CC mucosa appear thickened with granulation tissue in sections and the CC luminal surface show an open Eustachian tube but abundant clusters of CC goblet cells with fewer ciliated epithelial cells (PubMed:30973865). CC {ECO:0000269|PubMed:30973865}. CC -!- SIMILARITY: Belongs to the 14-3-3 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z19599; CAA79659.1; -; mRNA. DR EMBL; D87663; BAA13424.1; -; mRNA. DR EMBL; AF483478; AAL90752.1; -; mRNA. DR EMBL; AF483479; AAL90753.1; -; mRNA. DR EMBL; BC058686; AAH58686.1; -; mRNA. DR CCDS; CCDS25056.1; -. DR PIR; I48337; S31975. DR RefSeq; NP_033562.3; NM_009536.4. DR AlphaFoldDB; P62259; -. DR SMR; P62259; -. DR BioGRID; 204619; 329. DR IntAct; P62259; 44. DR MINT; P62259; -. DR STRING; 10090.ENSMUSP00000070993; -. DR GlyGen; P62259; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P62259; -. DR MetOSite; P62259; -. DR PhosphoSitePlus; P62259; -. DR SwissPalm; P62259; -. DR REPRODUCTION-2DPAGE; P62259; -. DR EPD; P62259; -. DR jPOST; P62259; -. DR PaxDb; 10090-ENSMUSP00000070993; -. DR PeptideAtlas; P62259; -. DR ProteomicsDB; 285810; -. DR Pumba; P62259; -. DR Antibodypedia; 1898; 612 antibodies from 40 providers. DR DNASU; 22627; -. DR Ensembl; ENSMUST00000067664.10; ENSMUSP00000070993.4; ENSMUSG00000020849.14. DR GeneID; 22627; -. DR KEGG; mmu:22627; -. DR UCSC; uc007ket.2; mouse. DR AGR; MGI:894689; -. DR CTD; 7531; -. DR MGI; MGI:894689; Ywhae. DR VEuPathDB; HostDB:ENSMUSG00000020849; -. DR eggNOG; KOG0841; Eukaryota. DR GeneTree; ENSGT01090000260061; -. DR HOGENOM; CLU_058290_0_0_1; -. DR InParanoid; P62259; -. DR OMA; KGCQLAR; -. DR OrthoDB; 920089at2759; -. DR PhylomeDB; P62259; -. DR TreeFam; TF102003; -. DR Reactome; R-MMU-111447; Activation of BAD and translocation to mitochondria. DR Reactome; R-MMU-2028269; Signaling by Hippo. DR Reactome; R-MMU-205025; NADE modulates death signalling. DR Reactome; R-MMU-2565942; Regulation of PLK1 Activity at G2/M Transition. DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-MMU-3371511; HSF1 activation. DR Reactome; R-MMU-380259; Loss of Nlp from mitotic centrosomes. DR Reactome; R-MMU-380270; Recruitment of mitotic centrosome proteins and complexes. DR Reactome; R-MMU-380284; Loss of proteins required for interphase microtubule organization from the centrosome. DR Reactome; R-MMU-380320; Recruitment of NuMA to mitotic centrosomes. DR Reactome; R-MMU-5620912; Anchoring of the basal body to the plasma membrane. DR Reactome; R-MMU-5625740; RHO GTPases activate PKNs. DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-MMU-75035; Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex. DR Reactome; R-MMU-8854518; AURKA Activation by TPX2. DR Reactome; R-MMU-8876198; RAB GEFs exchange GTP for GDP on RABs. DR BioGRID-ORCS; 22627; 19 hits in 116 CRISPR screens. DR ChiTaRS; Ywhae; mouse. DR PRO; PR:P62259; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; P62259; Protein. DR Bgee; ENSMUSG00000020849; Expressed in metanephric ureteric bud and 279 other cell types or tissues. DR ExpressionAtlas; P62259; baseline and differential. DR GO; GO:0030424; C:axon; ISO:MGI. DR GO; GO:0090724; C:central region of growth cone; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0005871; C:kinesin complex; ISO:MGI. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; HDA:MGI. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0045202; C:synapse; ISO:MGI. DR GO; GO:0005246; F:calcium channel regulator activity; ISO:MGI. DR GO; GO:0019899; F:enzyme binding; ISO:MGI. DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI. DR GO; GO:0050815; F:phosphoserine residue binding; ISO:MGI. DR GO; GO:0015459; F:potassium channel regulator activity; ISO:MGI. DR GO; GO:0019904; F:protein domain specific binding; IDA:MGI. DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI. DR GO; GO:0019903; F:protein phosphatase binding; IPI:MGI. DR GO; GO:0140311; F:protein sequestering activity; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI. DR GO; GO:0035591; F:signaling adaptor activity; ISO:MGI. DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB. DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI. DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; ISO:MGI. DR GO; GO:0021766; P:hippocampus development; IMP:MGI. DR GO; GO:0006886; P:intracellular protein transport; IEA:UniProt. DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB. DR GO; GO:1905913; P:negative regulation of calcium ion export across plasma membrane; ISO:MGI. DR GO; GO:1902309; P:negative regulation of peptidyl-serine dephosphorylation; ISO:MGI. DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; IDA:MGI. DR GO; GO:0001764; P:neuron migration; IMP:MGI. DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISS:UniProtKB. DR GO; GO:0034504; P:protein localization to nucleus; ISS:UniProtKB. DR GO; GO:0006605; P:protein targeting; IDA:MGI. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:0060306; P:regulation of membrane repolarization; ISO:MGI. DR GO; GO:0007346; P:regulation of mitotic cell cycle; IBA:GO_Central. DR GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; ISO:MGI. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR CDD; cd10020; 14-3-3_epsilon; 1. DR Gene3D; 1.20.190.20; 14-3-3 domain; 1. DR InterPro; IPR000308; 14-3-3. DR InterPro; IPR023409; 14-3-3_CS. DR InterPro; IPR036815; 14-3-3_dom_sf. DR InterPro; IPR023410; 14-3-3_domain. DR PANTHER; PTHR18860; 14-3-3 PROTEIN; 1. DR PANTHER; PTHR18860:SF17; 14-3-3 PROTEIN EPSILON; 1. DR Pfam; PF00244; 14-3-3; 1. DR PIRSF; PIRSF000868; 14-3-3; 1. DR PRINTS; PR00305; 1433ZETA. DR SMART; SM00101; 14_3_3; 1. DR SUPFAM; SSF48445; 14-3-3 protein; 1. DR PROSITE; PS00796; 1433_1; 1. DR PROSITE; PS00797; 1433_2; 1. DR Genevisible; P62259; MM. PE 1: Evidence at protein level; KW Acetylation; Cytoplasm; Direct protein sequencing; Isopeptide bond; KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..255 FT /note="14-3-3 protein epsilon" FT /id="PRO_0000058619" FT REGION 234..255 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 238..255 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 57 FT /note="Interaction with phosphoserine on interacting FT protein" FT /evidence="ECO:0000250" FT SITE 130 FT /note="Interaction with phosphoserine on interacting FT protein" FT /evidence="ECO:0000250" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:P62258" FT MOD_RES 50 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P62258" FT MOD_RES 65 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P62260" FT MOD_RES 69 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P62258" FT MOD_RES 118 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P62258" FT MOD_RES 123 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P62258" FT MOD_RES 131 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P62260" FT MOD_RES 137 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P62260" FT MOD_RES 210 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 232 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P62258" FT CROSSLNK 50 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:P62258" SQ SEQUENCE 255 AA; 29174 MW; 07817CCBD1F75B26 CRC64; MDDREDLVYQ AKLAEQAERY DEMVESMKKV AGMDVELTVE ERNLLSVAYK NVIGARRASW RIISSIEQKE ENKGGEDKLK MIREYRQMVE TELKLICCDI LDVLDKHLIP AANTGESKVF YYKMKGDYHR YLAEFATGND RKEAAENSLV AYKAASDIAM TELPPTHPIR LGLALNFSVF YYEILNSPDR ACRLAKAAFD DAIAELDTLS EESYKDSTLI MQLLRDNLTL WTSDMQGDGE EQNKEALQDV EDENQ //