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FLASH GENE
Symbol YWHAE contributors: mct/ - updated : 19-09-2019
HGNC name tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide
HGNC id 12851
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer homomer , dimer
HOMOLOGY
interspecies ortholog to rattus Ywhae (98.8pc)
ortholog to murine Ywhae (99.6pc)
Homologene
FAMILY
  • 14-3-3 family
  • CATEGORY adaptor , regulatory , signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,chromatin/chromosome,kinetochore
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • inhibitor of apoptosis through inhibiting the activation of p38 MAP kinase
  • multifunctional regulator required for cytoplasmic dynein function, neuronal migration and brain development
  • implicated in the regulation of a large spectrum of both general and specialized signaling pathway
  • playing a crucial role in neronal development by sustaining the effects of CDK5 phosphorylation
  • involved in the proper localization of NDEL1 and PAFAH1B1 in axons
  • YWHAE and DISC1, two schizophrenia susceptibility factors have been implicated in the regulation of spine density
  • is a key component of a DDX58 translocon required for innate antiviral immunity
  • may act as an important regulator in modulating tumor metastasis by promoting EMT as well as cell migration
  • subchondral bone soluble mediator altering cartilage homeostasis
  • CDK5, YWHAE, and CDK5 cofactor C2CD5 together promote NDEL1 phosphorylation and are essential for force adaptation
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • complex LIS1/CDK5/NDEL1/YWHAE, pathway in neuronal migration and development
  • HDAC7 directly binds to beta-catenin and forms a complex with YWHAE, YWHAZ, and YWHAH proteins
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • p38 MAP kinase
  • LIS1 and NDEL1 (maintaining phosphorylation of NDEL1)
  • KCNH2 (to control the membrane excitability and cardiac rhythm)
  • HCV core protein
  • forms a complex with DISC1 (both DISC1 and YWHAE are required for neuronal development via transport of the NUDEL/LIS1 complex
  • interaction with YWHAB, ATXN1, YWHAH, YWHAZ mediated by AKT1 to modulate the neurotoxicity of SCA1
  • regulates cardiogenesis and growth of the compact ventricular myocardium by modulating the cardiomyocyte cell cycle via both CCNE1 and CDKN1B
  • interaction between NAV2 and YWHAE could provide insight into the mechanism by which NAV2 participates in promoting cell migration and neuronal elongation
  • YWHAE interacts with the kinase domain of MAP3K5 in close proximity to its active site, thus indicating this interaction might block its accessibility and/or affect its conformation
  • cell & other
    REGULATION
    activated by Cl-channel with CLCA1
    ASSOCIATED DISORDERS
    corresponding disease(s) MDS , DEL17P13D , DUP17P13
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer
    tumoral   deletion    
    in small cell lung cancer
    constitutional     --low  
    synaptic reduction of DISC1 and YWHAE is developmentally correlated with the age-dependent decrease in striatal spine density
    Susceptibility to schizophrenia
    Variant & Polymorphism SNP SNP which influence the expression of 14-3-3 epsilon RNA and protein, is associated with schizophrenia and seems to work protectively
    Candidate gene
    Marker may serve as a novel prognostic biomarker for hepatocellular carcinoma (HCC)
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    YWHAE/ANPEP interaction could be a new therapeutic target in osteoarthritis
    cancerdigestivestomach
    may serve as a therapeutic target for hepatocellular carcinoma (HCC)
    ANIMAL & CELL MODELS
  • Ywhae knockout mouse is useful for pathophysiological analyses of neuropsychiatric disorders caused by defects during neurodevelopment 7)