10         20         30         40         50         60
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MATDDSIIVL DDDDEDEAAA QPGPSNLPPN PASTGPGPGL SQQATGLSEP RVDGGSSNSG - 60
SRKCYKLDNE KLFEEFLELC KTETSDHPEV VPFLHKLQQR AQSVFLASAE FCNILSRVLA - 120
RSRKRPAKIY VYINELCTVL KAHSIKKKLN LAPAASTTSE ASGPNPPTEP PSDLTNTENT - 180
ASEASRTRGS RRQIQRLEQL LALYVAEIRR LQEKELDLSE LDDPDSSYLQ EARLKRKLIR - 240
LFGRLCELKD CSSLTGRVIE QRIPYRGTRY PEVNRRIERL INKPGLDTFP DYGDVLRAVE - 300
KAATRHSLGL PRQQLQLLAQ DAFRDVGVRL QERRHLDLIY NFGCHLTDDY RPGVDPALSD - 360
PTLARRLREN RTLAMNRLDE VISKYAMMQD KTEEGERQKR RARLLGTAPQ PSDPPQASSE - 420
SGEGPSGMAS QECPTTSKAE TDDDDDDDDD DDEDNEESEE EEEEEEEEKE ATEDEDEDLE - 480
QLQEDQGGDE EEEGGDNEGN ESPTSPSDFF HRRNSEPAEG LRTPEGQQKR GLTETPASPP - 540
GASLDPPSTD AESSGEQLLE PLLGDESPVS QLAELEMEAL PEERDISSPR KKSEDSLPTI - 600
LENGAAVVTS TSVNGRVSSH TWRDASPPSK RFRKEKKQLG SGLLGNSYIK EPMAQQDSGQ - 660
NTSVQPMPSP PLASVASVAD SSTRVDSPSH ELVTSSLCSP SPSLLLQTPQ AQSLRQCIYK - 720
TSVATQCDPE EIIVLSDSD

Function: 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 (By similarity). Interacts with CBP; the interaction is dependent on the sumoylation of CBP and suppresses CBP transcriptional activity via recruitment of HDAC2.
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. 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 AXIN1; the interaction stimulates the interaction of DAXX with TP53, stimulates \'Ser-46\' phosphorylation of TP53 on and induces cell death on UV irradiation. 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 (By similarity). O43293:DAPK3 (xeno); NbExp=1; IntAct=EBI-77304, EBI-77293; O54784:Dapk3; NbExp=1; IntAct=EBI-77304, EBI-77359; P25446:Fas; NbExp=2; IntAct=EBI-77304, EBI-296206; Q86Z02:HIPK1 (xeno); NbExp=1; IntAct=EBI-77304, EBI-692891; O88904:Hipk1; NbExp=2; IntAct=EBI-77304, EBI-692945; Q9ERH7:Hipk3; NbExp=1; IntAct=EBI-77304, EBI-524356; P37173:TGFBR2 (xeno); NbExp=1; IntAct=EBI-77304, EBI-296151;


Subcellular Location: Cytoplasm (By similarity). Nucleus, nucleoplasm (By similarity). Nucleus, PML body (By similarity). Nucleus, nucleolus (By similarity). 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 (By similarity).
PTM: Sumoylated (By similarity).
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR (By similarity). Repressor activity is down-regulated upon Ser-669 phosphorylation.
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 (By similarity).
SIMILARITY: Belongs to the DAXX family.
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