InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DAXX

Summary

InnateDB Protein

IDBP-82728.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DAXX

Protein Name

death-domain associated protein

Synonyms

BING2; DAP6; EAP1;

Species

Homo sapiens

Ensembl Protein

ENSP00000363668

InnateDB Gene

IDBG-82726 (DAXX)

Protein Structure

UniProt Annotation

Function

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). {ECO:0000269PubMed:12140263, ECO:0000269PubMed:14990586, ECO:0000269PubMed:15364927, ECO:0000269PubMed:16845383, ECO:0000269PubMed:17081986, ECO:0000269PubMed:17942542, ECO:0000269PubMed:20504901, ECO:0000269PubMed:20651253, ECO:0000269PubMed:23222847, ECO:0000269PubMed:24200965, ECO:0000269PubMed:24530302}.

Subcellular Localization

Cytoplasm. Nucleus, nucleoplasm. Nucleus, PML body. Nucleus, nucleolus. Chromosome, centromere. Note=Dispersed throughout the nucleoplasm, in PML/POD/ND10 nuclear bodies, and in nucleoli. Colocalizes with histone H3.3, ATRX, HIRA and ASF1A at PML-nuclear bodies. Colocalizes with a subset of interphase centromeres, but is absent from mitotic centromeres. Detected in cytoplasmic punctate structures. Translocates from the nucleus to the cytoplasm upon glucose deprivation or oxidative stress. Colocalizes with RASSF1 in the nucleus. Colocalizes with USP7 in nucleoplasma with accumulation in speckled structures.

Disease Associations

Tissue Specificity

Ubiquitous.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 177 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.

Experimentally validated
Total	177 [view]
Protein-Protein	174 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	12 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002039	p53 binding
GO:0003714	transcription corepressor activity
GO:0005057	receptor signaling protein activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0030295	protein kinase activator activity
GO:0031072	heat shock protein binding
GO:0031625	ubiquitin protein ligase binding
GO:0042393	histone binding
GO:0042803	protein homodimerization activity
GO:0047485	protein N-terminus binding
GO:0050681	androgen receptor binding

Biological Process

GO:0000281	mitotic cytokinesis
GO:0001934	positive regulation of protein phosphorylation
GO:0006334	nucleosome assembly
GO:0006338	chromatin remodeling
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006915	apoptotic process
GO:0007257	activation of JUN kinase activity
GO:0008625	extrinsic apoptotic signaling pathway via death domain receptors
GO:0016032	viral process
GO:0030521	androgen receptor signaling pathway
GO:0031396	regulation of protein ubiquitination
GO:0045860	positive regulation of protein kinase activity
GO:0045892	negative regulation of transcription, DNA-templated
GO:0097190	apoptotic signaling pathway
GO:1901216	positive regulation of neuron death
GO:2001235	positive regulation of apoptotic signaling pathway

Cellular Component

GO:0000775	chromosome, centromeric region
GO:0000792	heterochromatin
GO:0005634	nucleus
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016605	PML body
GO:0070603	SWI/SNF superfamily-type complex