ID:DAXX_HUMAN DESCRIPTION: RecName: Full=Death domain-associated protein 6; AltName: Full=Daxx; Short=hDaxx; AltName: Full=ETS1-associated protein 1; Short=EAP1; AltName: Full=Fas death domain-associated protein; FUNCTION: Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. 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. 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. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6- dependent apoptosis thereby. Down-regulates basal and activated transcription. Seems to act as a transcriptional corepressor and inhibits PAX3 and ETS1 through direct protein-protein interaction. Modulates PAX5 activity. 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. SUBUNIT: Homomultimer. Binds to the TNFRSF6 death domain via its C-terminus and to PAX5. Binds to SLC2A4/GLUT4, MAP3K5, TGFBR2, phosphorylated dimeric HSPB1/HSP27, CENPC1, ETS1, sumoylated PML, UBE2I and MCRS1. Is part of a complex containing PAX5 and CREBBP. Interacts with HIPK2 and HIPK3 via its N-terminus. Interacts with HIPK1, which induces translocation from PML/POD/ND10 nuclear bodies to chromatin and enhances association with HDAC1 (By similarity). The non-phosphorylated form binds to PAX3, PAX7, DEK, HDAC1, HDAC2, HDAC3, acetylated histone H4 and histones H2A, H2B, H3 and H4. Interacts with SPOP. Part of a complex consisting of DAXX, CUL3 and SPOP. Interacts with CBP; the interaction is dependent the sumoylation of CBP and suppresses CBP transcriptional activity via recruitment of HDAC2 directly in the complex with TP53 and HIPK2. Interacts with AXIN1; the interaction stimulates the interaction of DAXX with TP53, stimulates 'Ser-46' phosphorylation of TP53 on and induces cell death on UV irradiation. Interacts with HCMV tegument phosphoprotein pp71. Part of a complex with MDM2, DAXX, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts (via N-terminus) with RASSF1 (via C-terminus); the interaction is independent of MDM2 and TP53. Interacts with MDM2; the interaction is direct. Interacts with USP7; the interaction is direct and independent of MDM2 and TP53. Interacts with TP53. Interacts with human cytomegalovirus/HHV-5 protein UL123. INTERACTION: P03243:- (xeno); NbExp=4; IntAct=EBI-77321, EBI-1561361; O43918:AIRE; NbExp=5; IntAct=EBI-77321, EBI-1753081; P10275:AR; NbExp=5; IntAct=EBI-77321, EBI-608057; P46100:ATRX; NbExp=3; IntAct=EBI-77321, EBI-396461; Q8N726:CDKN2A; NbExp=8; IntAct=EBI-77321, EBI-625922; Q92793:CREBBP; NbExp=2; IntAct=EBI-77321, EBI-81215; P03244:E1B (xeno); NbExp=4; IntAct=EBI-77321, EBI-1561155; P14921-1:ETS1; NbExp=3; IntAct=EBI-287635, EBI-913224; P14921-2:ETS1; NbExp=2; IntAct=EBI-287635, EBI-913228; P25445:FAS; NbExp=2; IntAct=EBI-77321, EBI-494743; P25446:Fas (xeno); NbExp=4; IntAct=EBI-77321, EBI-296206; P02794:FTH1; NbExp=5; IntAct=EBI-77321, EBI-713259; Q13547:HDAC1; NbExp=2; IntAct=EBI-77321, EBI-301834; Q92769:HDAC2; NbExp=2; IntAct=EBI-77321, EBI-301821; O88904:Hipk1 (xeno); NbExp=3; IntAct=EBI-77321, EBI-692945; P04792:HSPB1; NbExp=3; IntAct=EBI-77321, EBI-352682; P15991:HSPB1 (xeno); NbExp=3; IntAct=EBI-77321, EBI-1559114; Q99683:MAP3K5; NbExp=6; IntAct=EBI-77321, EBI-476263; Q96EZ8:MCRS1; NbExp=7; IntAct=EBI-77321, EBI-348259; Q00987:MDM2; NbExp=14; IntAct=EBI-77321, EBI-389668; Q99497:PARK7; NbExp=3; IntAct=EBI-77321, EBI-1164361; Q02650:Pax5 (xeno); NbExp=4; IntAct=EBI-77321, EBI-296260; P29590:PML; NbExp=6; IntAct=EBI-77321, EBI-295890; P14672:SLC2A4; NbExp=7; IntAct=EBI-77321, EBI-367146; O43791:SPOP; NbExp=5; IntAct=EBI-77321, EBI-743549; P40763:STAT3; NbExp=4; IntAct=EBI-77321, EBI-518675; P63165:SUMO1; NbExp=5; IntAct=EBI-77321, EBI-80140; Q9NQB0:TCF7L2; NbExp=5; IntAct=EBI-77321, EBI-924724; P37173:TGFBR2; NbExp=2; IntAct=EBI-77321, EBI-296151; P04637:TP53; NbExp=11; IntAct=EBI-77321, EBI-366083; Q99816:TSG101; NbExp=4; IntAct=EBI-77321, EBI-346882; Q93009:USP7; NbExp=10; IntAct=EBI-77321, EBI-302474; SUBCELLULAR LOCATION: 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 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. TISSUE SPECIFICITY: Ubiquitous. INDUCTION: Upon mitogenic stimulation by concanavalin-A. DOMAIN: The Sumo interaction motif mediates Sumo binding, and is required both for sumoylation and binding to sumoylated targets. PTM: Sumoylated with SUMO1 on multiple lysine residues. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated by HIPK1 upon glucose deprivation. PTM: Polyubiquitinated; which is promoted by CUL3 and SPOP and results in proteasomal degradation. Ubiquitinated by MDM2; inducing its degradation. Deubiquitinated by USP7; leading to stabilize it. SIMILARITY: Belongs to the DAXX family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org//Genes/DAXXID40265ch6p21.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UER7
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001934 positive regulation of protein phosphorylation GO:0006325 chromatin organization 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:0034605 cellular response to heat GO:0034620 cellular response to unfolded protein GO:0045860 positive regulation of protein kinase activity GO:0045892 negative regulation of transcription, DNA-templated GO:0071276 cellular response to cadmium ion GO:0071280 cellular response to copper ion GO:0072738 cellular response to diamide GO:1901216 positive regulation of neuron death GO:1903936 cellular response to sodium arsenite
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
