Description: Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide (YWHAE), transcript variant 1, mRNA. RefSeq Summary (NM_006761): This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the mouse ortholog. It interacts with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer. Two transcript variants, one protein-coding and the other non-protein-coding, have been found for this gene. [provided by RefSeq, Aug 2008]. Transcript (Including UTRs) Position: hg19 chr17:1,247,834-1,303,556 Size: 55,723 Total Exon Count: 6 Strand: - Coding Region Position: hg19 chr17:1,248,741-1,303,404 Size: 54,664 Coding Exon Count: 6
ID:1433E_HUMAN DESCRIPTION: RecName: Full=14-3-3 protein epsilon; Short=14-3-3E; FUNCTION: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. SUBUNIT: Homodimer. Heterodimerizes with YWHAZ. Interacts with NDEL1, ARHGEF28 and TIAM2 (By similarity). Interacts with HCV core protein. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm. Weakly interacts with CDKN1B. Interacts with GAB2. Interacts with phosphorylated GRB10. Interacts with PKA-phosphorylated AANAT. Interacts with the phosphorylated (by AKT1) form of SRPK2. INTERACTION: O00257-3:CBX4; NbExp=2; IntAct=EBI-356498, EBI-4392727; O94921:CDK14; NbExp=3; IntAct=EBI-356498, EBI-1043945; Q9UKT5:FBXO4; NbExp=5; IntAct=EBI-356498, EBI-960409; Q14678-2:KANK1; NbExp=3; IntAct=EBI-356498, EBI-6173812; P61981:YWHAG; NbExp=4; IntAct=EBI-356498, EBI-359832; SUBCELLULAR LOCATION: Cytoplasm (By similarity). Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. SIMILARITY: Belongs to the 14-3-3 family.
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): YWHAE CDC HuGE Published Literature: YWHAE Positive Disease Associations: suicide Related Studies:
suicide Yanagi, M. et al. 2005, Association of 14-3-3 epsilon gene haplotype with completed suicide in Japanese., Journal of human genetics. 2005 ;50(4):210-6.
[PubMed 15838597]
This finding suggests that 14-3-3 epsilon is a potential suicide susceptibility gene and implies that dysregulation of neurogenesis may be involved in suicide.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P62258
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000086 G2/M transition of mitotic cell cycle GO:0000165 MAPK cascade GO:0001764 neuron migration GO:0003064 regulation of heart rate by hormone GO:0006605 protein targeting GO:0010389 regulation of G2/M transition of mitotic cell cycle GO:0016032 viral process GO:0021762 substantia nigra development GO:0021766 hippocampus development GO:0021987 cerebral cortex development GO:0034605 cellular response to heat GO:0035308 negative regulation of protein dephosphorylation GO:0035329 hippo signaling GO:0035556 intracellular signal transduction GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0046827 positive regulation of protein export from nucleus GO:0051480 regulation of cytosolic calcium ion concentration GO:0060306 regulation of membrane repolarization GO:0061024 membrane organization GO:0086013 membrane repolarization during cardiac muscle cell action potential GO:0086091 regulation of heart rate by cardiac conduction GO:0097711 ciliary basal body docking GO:1900034 regulation of cellular response to heat GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:1901016 regulation of potassium ion transmembrane transporter activity GO:1901020 negative regulation of calcium ion transmembrane transporter activity GO:1902309 negative regulation of peptidyl-serine dephosphorylation
Protein P62258 (Reactome details) participates in the following event(s):
R-HSA-8863674 CDC25C binds YWHAE (14-3-3-epsilon) R-HSA-204981 14-3-3epsilon attentuates NADE-related apoptosis R-HSA-2028651 YWHAE (14-3-3 epsilon) dimer binds phosphorylated WWTR1 (TAZ) R-HSA-4793925 p-S303,307-HSF1 binds YWHAE (14-3-3) R-HSA-8933452 YWHAE dimer binds phosphorylated DENND1 proteins R-HSA-380272 Plk1-mediated phosphorylation of Nlp R-HSA-380283 Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome R-HSA-380294 Loss of C-Nap-1 from centrosomes R-HSA-380311 Recruitment of Plk1 to centrosomes R-HSA-380455 Recruitment of CDK11p58 to the centrosomes R-HSA-380303 Dissociation of Phospho-Nlp from the centrosome R-HSA-5626220 C2CD3 binds the mother centriole R-HSA-75016 Association of p-S216-CDC25C with 14-3-3 proteins R-HSA-139899 Sequestration of BAD protein by 14-3-3 R-HSA-1445149 14-3-3 binds p-5S,T642-AS160 (TBC1D4) R-HSA-1454689 14-3-3 Binds p-S237-TBC1D1 R-HSA-5632732 p-S939,T1462-TSC2 binding to 14-3-3 dimer is negatively regulated by DDIT4 R-HSA-5632738 DDIT4 binds 14-3-3 dimer R-HSA-139906 Activation of BAD by calcineurin R-HSA-380508 Translocation of NuMA to the centrosomes R-HSA-2574845 AJUBA binds centrosome-associated AURKA R-HSA-8853405 TPX2 binds AURKA at centrosomes R-HSA-3000319 BORA binds PLK1 and AURKA R-HSA-2574840 AJUBA facilitates AURKA autophosphorylation R-HSA-3000310 AURKA phosphorylates PLK1 R-HSA-5626223 C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole R-HSA-5626681 Recruitment of transition zone proteins R-HSA-5626227 CP110 and CEP97 dissociate from the centriole R-HSA-380316 Association of NuMA with microtubules R-HSA-8853419 TPX2 promotes AURKA autophosphorylation R-HSA-5626228 The distal appendage proteins recruit TTBK2 R-HSA-5638009 CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body R-HSA-8877612 DENND1s exchange GTP for GDP on RAB35 R-HSA-5626699 MARK4 binds ODF2 in the centriole R-HSA-5617816 RAB3IP stimulates nucleotide exchange on RAB8A R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-205025 NADE modulates death signalling R-HSA-2028269 Signaling by Hippo R-HSA-3371453 Regulation of HSF1-mediated heat shock response R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs R-HSA-380259 Loss of Nlp from mitotic centrosomes R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome R-HSA-5620912 Anchoring of the basal body to the plasma membrane R-HSA-8863678 Neurodegenerative Diseases R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex R-HSA-5625740 RHO GTPases activate PKNs R-HSA-111447 Activation of BAD and translocation to mitochondria R-HSA-1445148 Translocation of GLUT4 to the plasma membrane R-HSA-5628897 TP53 Regulates Metabolic Genes R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE R-HSA-162582 Signal Transduction R-HSA-3371556 Cellular response to heat stress R-HSA-9007101 Rab regulation of trafficking R-HSA-380320 Recruitment of NuMA to mitotic centrosomes R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition R-HSA-8854518 AURKA Activation by TPX2 R-HSA-380287 Centrosome maturation R-HSA-5617833 Cilium Assembly R-HSA-1643685 Disease R-HSA-69473 G2/M DNA damage checkpoint R-HSA-195258 RHO GTPase Effectors R-HSA-114452 Activation of BH3-only proteins R-HSA-199991 Membrane Trafficking R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-193704 p75 NTR receptor-mediated signalling R-HSA-2262752 Cellular responses to stress R-HSA-68877 Mitotic Prometaphase R-HSA-69275 G2/M Transition R-HSA-1852241 Organelle biogenesis and maintenance R-HSA-69481 G2/M Checkpoints R-HSA-194315 Signaling by Rho GTPases R-HSA-109606 Intrinsic Pathway for Apoptosis R-HSA-5653656 Vesicle-mediated transport R-HSA-212436 Generic Transcription Pathway R-HSA-73887 Death Receptor Signalling R-HSA-8953897 Cellular responses to external stimuli R-HSA-68886 M Phase R-HSA-453274 Mitotic G2-G2/M phases R-HSA-69620 Cell Cycle Checkpoints R-HSA-109581 Apoptosis R-HSA-73857 RNA Polymerase II Transcription R-HSA-69278 Cell Cycle (Mitotic) R-HSA-1640170 Cell Cycle R-HSA-5357801 Programmed Cell Death R-HSA-74160 Gene expression (Transcription)
US Server
