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FLASH GENE
Symbol DAXX contributors: mct - updated : 19-11-2018
HGNC name death-domain associated protein
HGNC id 2681
DNA
TYPE functioning gene
STRUCTURE 4.46 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
text a predominant transcript ubiquitously expressed, a truncated transcript in placenta and pancreas and an extended transcript in heart and skeletal muscle
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 2563 - 752 - 1997 9407001
  • isoform b
  • 8 - 2629 - 740 - 1997 9407001
  • isoform a
  • 8 - 2632 81.4 740 - 1997 9407001
  • isoform a
  • EXPRESSION
    Type ubiquitous
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveesophagus   highly
     pharynx   highly
    Endocrinepancreas    
     thyroid   highly
    Reproductivefemale systembreastmammary gland  
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, all fetal tissues
    PROTEIN
    PHYSICAL PROPERTIES acid
    STRUCTURE
    motifs/domains
  • N terminus interacts directly with variant-specific residues in the H3F3A, and H3F3B core
  • two predicted paired amphipathic helices (PAH1 and PAH2)
  • a glutamic acid-rich domain
  • two separate nuclear localizing domains, NLS1, NLS2
  • a Ser/Pro/Thr (SPT)-rich domain
  • a coiled-coil (CC), an acidic domain (acidic)
  • and an rtt106-like domain (rtt106)
  • N- and/or C-terminal SUMO-interacting motifs (SIM-N and SIM-C)
  • HOMOLOGY
    interspecies homolog to murine Daxx
    Homologene
    FAMILY
  • DAXX family
  • CATEGORY regulatory , transcription factor , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    text component of the promyelocytic leukemia protein (PML) nuclear bodies
    basic FUNCTION
  • enhancing Fas-mediated apoptosis through the JNK signal transduction pathway
  • potential regulator of FAS-induced apoptosis from nuclear oncogenic domains POD in which it colocalizes with PML
  • mediating its pro and antiapoptotic function in part or entirely through its activating effect on HSF1 and the stress protein response
  • functioning as a transcriptional regulator
  • involved in the repression of transcriptional activation of the MMP1 and BCL2 genes
  • multi-functional protein modulating both apoptosis and transcription
  • promotes Fas-mediated cell death through activation of apoptosis signal-regulating kinase 1, leading to the activation of the MAPKs JNK and p38
  • critical regulator of T-lymphocyte homeostasis by decreasing TCR-induced cell proliferation and by promoting Fas-mediated cell death
  • plays a major role in several important signaling pathways including transcription and cell death
  • inhibits stress-induced apoptosis in cardiac myocytes
  • inhibits E2A function, and it recruits histone deacetylase activity to E2A-dependent promoters
  • functions as a positive coregulator in modulating the beta-catenin/TCF4-dependent transcriptional potential via TCF4 interaction
  • functions as a bona fide histone chaperone involved in the replication-independent deposition of H3F3A
  • required for assembly of H3F3A nucleosomes onto pericentric DNA repeats
  • with ATRX are required for H3F3A deposition onto pericentric DNA repeats outside the S phase, and the DAXX/ATRX complex uses H3F3A to modulate the transcription from these repeats
  • functions as an H3F3-specific chaperone and facilitates the deposition of H3F3a and H3F3B at heterochromatin loci in the context of the ATRX–DAXX complex
  • essential scaffold protein with key roles in diverse cellular processes spanning transcription to apoptosis and mitosis
  • FTH1 and DAXX are able to participate in apoptosis pathway through JNK signal molecule and FTH1 can inhibit this pathway
  • functioned as a signal transducer linking cAMP-stimulated HIPK3 activity with JNK/JUN phosphorylation and NR5A1-dependent CYP11A1 transcription for steroid synthesis
  • is essential for NR5A1-dependent transcription of CYP11A1
  • histone chaperone specific to the evolutionarily conserved histone variant H3F3A
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    JNK pathway
    a component
  • acting as a bridge between FAS and ASK1
  • complexing with TSG101 through its coiled-coil domain and co-localized in the nucleus
  • forming a complex with MDM2 and USP7
  • ATRX–DAXX complex catalyzes the deposition and remodeling of H3F3A, and H3F3B-containing nucleosomes
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to FAS (APT1) cell surface receptor,(ASK1), MAP3K5 and ETS1
  • affecting PAX5 roles as an activator or a repressor of B cells
  • mediator of HSF1 activation
  • PAX3
  • interacting with TSG101
  • binding to ATRX through its paired amphipathic alpha helices domains (a novel ATP-dependent chromatin-remodeling complex)
  • can modulate the function of MDM2 regulating therefore DNA damage-induced TP53 activation
  • nuclear localization of DAXX is controlled by two independent signals and KPNA4, through its NLS1 and NLS2 sequences
  • interacting with AIRE and exerting a strong repressive role on the transcriptional activity of AIRE
  • with ATRX are specifically associated with the H3F3A deposition machinery
  • H3F3A histone chaperone (associates with pericentric DNA repeats, and modulates the transcription from these repeats through assembly of H3F3A nucleosomes)
  • CEBPB directly interact with DAXX after overexpression as well as on the endogenous level, and its activity is negatively regulated by the transcriptional co-repressor DAXX
  • interaction of a C-terminal fragment of DAXX with an N-terminal fragment of the sumoylated ETS1 transcription factor mediated by SIM-C
  • participated in NR5A1-dependent CYP11A1 expression
  • enhancement of NR5A1 activity by DAXX required JNK and JUN phosphorylation
  • participates in cAMP-stimulated steroidogenic CYP11A1 transcription by mediating the effect of HIPK3
  • novel function for TP53 in the methylation of RASSF1 promoter by its interaction with DAXX
  • selectively represses IL6 transcription through HDAC1-mediated histone deacetylation in LPS-induced macrophages
  • DPPA3 controls the expression of DAXX and ensures chromatin reorganization in early embryos
  • alternative lengthening of telomeres (ALT) activation is an adaptive response to ATRX/DAXX loss-induced telomere replication dysfunction
  • ATRX has an effect on telomeric DSB repair and this role involves both telomere cohesion and a DAXX-dependent pathway
  • cell & other
    REGULATION
    Phosphorylated by HIPK3 at Ser-669 in response to cAMP stimulation
    ATM (phosphorylation of DAXX by ATM upon DNA damage disrupts the DAXX-MDM2 interaction and facilitates TP53 activation)
    Other DAXX-dependent transcriptional repression is modulated by MCRS1 (MSP58)
    ubiquitinated by MDM2, reducing DAXX expression upon over-expression and deubiquitinated by USP7
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    overexpressed in prostate tumor
    tumoral fusion      
    with ATRX in promyelocytic leukemia (in nuclear bodies)
    tumoral somatic mutation      
    in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain-associated protein) and ATRX, in pancreatic neuroendocrine tumors
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • EIF4B, DAXX and ERCC5 are identified as novel prognostic markers for poor survival in diffuse large B-cell lymphoma (DLBCL)
  • Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    link between abrogation of DAXX-CEBPB complex formation and acute promyelocytic leukemia remission
    ANIMAL & CELL MODELS