DAXX - Death domain-associated protein 6 - human protein (Function)
 
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DAXX »  Death domain-associated protein 6
 
Protein also known as:  Fas death domain-associated protein.
Gene name:  DAXX
Family name: DAXX
Entry whose protein(s) existence is based on evidence at protein level
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1 193 5
GENE REF ISO

Function

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Overview 
Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activatiopn of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Acts as histone chaperone that facilitates deposition of histone H3.3. Acts as targeting component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Does not affect the ATPase activity of ATRX but alleviates its transcription repression activity. Upopn neuronal activation asociates with regulatory elements of selected immediate early genes where it promotes deposition of histone H3.3 which may be linked to transcriptional induction of these genes. Required for the recruitment of histone H3.3:H4 dimers to PML-nuclear bodies (PML-NBs); the process is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested to function as regulatory sites for the incorporation of newly synthesized histone H3.3 into chromatin. In case of overexpression of centromeric histone variant CENPA (as found in various tumors) is involved in its mislocalization to chromosomes; the ectopic localization involves a heterotypic tetramer containing CENPA, and histones H3.3 and H4 and decreases binding of CTCF to chromatin. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Shows restriction activity towards human cytomegalovirus (HCMV).  
12
  • UniProtKB
GO molecular function 
Androgen receptor bindingdefinition[GO:0050681]  
1
  • UniProtKB
Enzyme bindingdefinition[GO:0019899]  
1
  • UniProtKB
Heat shock protein bindingdefinition[GO:0031072]  
1
  • UniProtKB
Histone bindingdefinition[GO:0042393]  
2
  • UniProtKB
P53 bindingdefinition[GO:0002039]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
41
  • IntAct
  • UniProtKB
Isoform  Iso 1   Protein homodimerization activitydefinition[GO:0042803]  
1
  • UniProtKB
Protein kinase activator activitydefinition[GO:0030295]  
1
  • ParkinsonsUK-UCL
Protein kinase bindingdefinition[GO:0019901]  
1
  • ParkinsonsUK-UCL
Protein N-terminus bindingdefinition[GO:0047485]  
2
  • UniProtKB
Receptor signaling protein activitydefinition[GO:0005057]  
1
  • PINC
Transcription corepressor activitydefinition[GO:0003714]  
1
  • UniProtKB
Isoform  Iso 1   Transcription factor bindingdefinition[GO:0008134]  
1
  • UniProtKB
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • UniProtKB
GO biological process 
Activation of JUN kinase activitydefinition[GO:0007257]  
1
  • PINC
Androgen receptor signaling pathwaydefinition[GO:0030521]  
1
  • UniProtKB
Apoptotic processdefinition[GO:0006915]  
1
  • UniProtKB
Chromatin remodelingdefinition[GO:0006338]  
1
  • UniProtKB
Extrinsic apoptotic signaling pathway via death domain receptorsdefinition[GO:0008625]  
1
  • PINC
Mitotic cytokinesisdefinition[GO:0000281] silver  
1
  • Ortholog Compara
Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
3
  • UniProtKB
Nucleosome assemblydefinition[GO:0006334]  
2
  • UniProtKB
Positive regulation of apoptotic signaling pathwaydefinition[GO:2001235] silver  
1
  • Ortholog Compara
Positive regulation of neuron deathdefinition[GO:1901216]  
1
  • ParkinsonsUK-UCL
Positive regulation of protein kinase activitydefinition[GO:0045860]  
1
  • ParkinsonsUK-UCL
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • ParkinsonsUK-UCL
Regulation of protein ubiquitinationdefinition[GO:0031396]  
1
  • UniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • MGI
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB KW
Viral processdefinition[GO:0016032]  
1
  • UniProtKB KW
Enzymatic activity 
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Amyotrophic lateral sclerosis (ALS)  hsa05014+1616  
Herpes simplex infection  hsa05168+1616  
MAPK signaling pathway  hsa04010+1616  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Host-virus interaction  definition   [KW-0945]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Chaperone  definition   [KW-0143]
Chromatin regulator  definition   [KW-0156]
Repressor  definition   [KW-0678]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: Death-associated_protein_6
GenomeRNAi: 1616
PRO: PR:Q9UER7