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FLASH GENE
Symbol YWHAZ contributors: mct/npt/pgu - updated : 27-01-2016
HGNC name tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide
HGNC id 12855
Location 8q22.3      Physical location : 101.930.803 - 101.965.623
Synonym name
  • 14-3-3 zeta protein
  • phospholipase A2
  • protein kinase C inhibitor protein 1
  • 14-3-3 protein/cytosolic phospholipase A2
  • Synonym symbol(s) KCIP-1, 14-3-3-zeta, MGC126532, MGC138156, MGC111427, HEL-S-3, HEL-S-93, HEL4, YWHAD
    DNA
    TYPE functioning gene
    STRUCTURE 34.82 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    RPL30 8q22-q24 ribosomal protein L30 FLJ39553 8q22.2 hypothetical protein FLJ39553 UK114 8q22 hypothetical protein FLJ39553 POP1 8q22.1 processing of precursors 1 FLJ13955 8q22.2 hypothetical protein FLJ13955 KCNS2 8q23.3-q24.11 potassium voltage-gated channel, delayed-rectifier, subfamily S, member 2 STK3 8q22.2 serine/threonine kinase 3 (STE20 homolog, yeast) MRP63P7 8q22.2 mitochondrial ribosomal protein 63 pseudogene 7 OSR2 8q22.2 odd-skipped-related 2A protein COH1 8q22.2 Cohen syndrome 1 COX6C 8q22-q23 cytochrome c oxidase subunit VIc DKFZP434I092 8q22.3 DKFZP434I092 protein LOC286151 8q22.3 similar to RIKEN cDNA 4930533G20 POLR2K 8q22 polymerase (RNA) II (DNA directed) polypeptide K, 7.0kDa SPAG1 8q22 sperm associated antigen 1 RNF19 8q22 ring finger protein 19 LOC157567 8q22.3 hypothetical protein LOC157567 MGC39715 8q22.3 hypothetical protein MGC39715 PABPC1 8q22.2-q23 poly(A) binding protein, cytoplasmic 1 LOC392256 YWHAZ 2p25.2-p25.1 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide LOC51123 8q22.3 HSPC038 protein FKSG17 8q22.3 HSPC038 protein TFCP2L3 8q22.3 HSPC038 protein NCALD 8q22-q23 neurocalcin delta LOC392257 8 similar to IAP-associated factor VIAF1; phosducin-like 2 RRM2B 8q23.1 ribonucleotide reductase M2 B (TP53 inducible) DD5 8q22 ribonucleotide reductase M2 B (TP53 inducible) ODF1 8q22.3 outer dense fiber of sperm tails 1 TIEG 8q22.2 TGFB inducible early growth response OAZIN 8q22.3 ornithine decarboxylase antizyme inhibitor LOC389679 8 similar to hypothetical protein ATP6V1C1 8q22.3 ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C, isoform 1 LOC389680 8 similar to MGC39526 protein BAALC 8q22.3 brain and acute leukemia, cytoplasmic FZD6 8q22.3-q23.1 frizzled homolog 6 (Drosophila) CTHRC1 8q22.3 collagen triple helix repeat containing 1 MFTC 8q22.3 mitochondrial folate transporter/carrier DKFZP564O0463 8q22.3 DKFZP564O0463 protein TARBP2P 8q22-q24 TAR (HIV) RNA binding protein 2 pseudogene
    RNA
    TRANSCRIPTS type messenger
    text all transcripts encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 3003 27 245 - 2004 15225635
  • variant 1
  • containing a different 5' UTR compared to variant 2
  • both variants encode the same protein, however, they are differentially expressed in hematopoietic cells
  • 6 splicing 3077 27 245 - 2004 15225635
  • variant 2
  • using a different exon in the 5' UTR compared to variant 1
  • both variants encode the same protein, however, they are differentially expressed in hematopoietic cells
  • 6 - 3042 - 245 - 2004 15225635
    variant 6
    6 - 3023 - 245 - 2004 15225635
    variant 5
    6 - 2974 - 245 - 2004 15225635
    variant 4
    6 - 3020 - 245 - 2004 15225635
    variant 3
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
     mouthtongue (see gustatory)  highly
    Reproductivefemale systemuteruscervix highly
     male systemtestis   
    Skin/Tegumentskin   highly
    Urinarybladder   highly
    Visualeyeanterior segmentcornea  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • 14-3-3 family
  • CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • multifunctional regulator involved in cell-cyle control (checkpoint) cellular proliferation and apoptosis by binding and sequestering phosphoserine containing proteins and by inhibiting the activation of p38 MAP kinase
  • playing a role in in EGF receptor signaling or regulation
  • forms a molecular complex with HSPD1 and PRNP in the CNS under physiological conditions and this complex might become disintegrated in the pathologic process of prion diseases
  • candidate proto-oncogene and may have a role in head and neck squamous cell carcinoma.carcinogenesis
  • antiapoptotic protein
  • YWHAZ controls PCYT1A nuclear import in response to calcium signals, thereby regulating mammalian phospholipid synthesis
  • YWHAZ and possibly other 14-3-3 isoforms may have additional functional roles conducted by the monomeric state
  • has a role in the fibrillization of MAPT in Alzheimer brain, and MAPT phosphorylation does not affect YWHAZ-induced MAPT aggregation
  • essential role for YWHAZ in the regulation of macropinocytosis in macrophages upon cytokine stimulation through modulation of the localization of CORO1A
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • HDAC7 directly binds to beta-catenin and forms a complex with YWHAE, YWHAZ, and YWHAH proteins
  • novel function of YWHAZ/CTNNB1 axis in promoting epithelial-mesenchymal transition and lung cancer metastasis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • IL9R alpha chain
  • p38 MAP kinase
  • tuberin/14-3-3zeta interaction is regulated by Akt-mediated phosphorylation of tuberin
  • EGF receptor interacting protein
  • interaction with YWHAB, YWHAE, YWHAH, ATXN1 mediated by AKT1 to modulate the neurotoxicity of SCA1
  • interacting with ADAM22,(can regulate cell adhesion and spreading, therefore it has a potential role in neural development and function)
  • interacts with nuclear localization sequence of forkhead transcription factor FOXO4
  • interaction between CENPJ and 14-3-3, and this interaction appears to be phosphorylation and cell cycle dependent
  • YWHAZ-KH1 interaction regulates the mRNA-decay activity of KHSRP by sequestering the protein in a separate functional pool
  • PCYT1A nuclear import was associated with binding to YWHAZ, a key regulator of protein trafficking
  • monomeric form interacts with MAPT and with the HSPB6 protein
  • YWHAZ is a direct binding partner of GNB2L1
  • interacts physically with STAT3 and regulates its constitutive activation in multiple myeloma cells (
  • may be an endogenous physiologic regulator of HNF1A
  • binds to PPP1CA and causes its retention in the cytosol which suggests that YWHAZ regulates nuclear trafficking of PPP1CA in mammalian cells
  • binding of AXL to YWHAZ, which is essentially required for AXL-mediated cell invasion, transendothelial migration, and resistance against TGFB1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    age-down regulated in the frontal cortex
    tumoral     --over  
    contribute to de novo chemoresistance to anthracyclines and are permissive for metastatic recurrence
    constitutional     --over  
    protects cells from drug-induced apoptosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • YWHAZ driven contextual changes of Smad partners from TP53 to GLI2 may serve as biomarkers and therapeutic targets of TGFB1-mediated cancer progression
  • Therapy target
    ANIMAL & CELL MODELS
  • locomotor hyperactivity in Ywhaz KO mice is associated with dopamine transporter dysfunction
  • deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating