death domain-associated protein 6; Daxx; hDaxx; ETS1-associated protein 1; EAP1; Fas death domain-associated protein (DAXX, BING2, DAP6)

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 & enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thus promoting TP53 ubiquitination & subsequent proteasomal degradation
• upon DNA damage, its association with MDM2 & USP7 is disrupted, resulting in increased MDM2 autoubiquitination & MDM2 degradation, which leads to TP53 stabilization
• proposed to mediate activation of the JNK pathway & apoptosis via MAP3K5 in response to signaling from TNFRSF6 & TGFBR2
• interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 & MAP3K5 & block DAXX-mediated apoptosis
• in contrast, in lymphoid cells JNC activation & TNFRSF6- mediated apoptosis may not involve DAXX
• seems to regulate transcription in PML nuclear bodies together with PML & may influence TNFRSF6-dependent apoptosis
• down-regulates basal & activated transcription
• seems to act as a transcriptional corepressor & inhibits PAX3 & 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 nuclear bodies through interactions with MCSR1 & PML, respectively
• sumoylated
• phosphorylated upon DNA damage, probably by ATM or ATR
• phosphorylated by HIPK1 upon glucose deprivation
• polyubiquitinated; which is promoted by CUL3 & SPOP & results in proteasomal degradation
• ubiquitinated by MDM2 inducing its degradation
• deubiquitinated by USP7; leading to stabilization
• homomultimer
• binds to the TNFRSF6 death domain via its C-terminus & to PAX5
• binds to SLC2A4/GLUT4, MAP3K5, TGFBR2, phosphorylated dimeric HSPB1/HSP27, CENPC1, ETS1, sumoylated PML, UBE2I & MCRS1
• part of a complex containing PAX5 & CREBBP
• interacts with HIPK2 & HIPK3 via its N-terminus
• interacts with HIPK1, which induces translocation from PML nuclear bodies to chromatin & enhances association with HDAC1
• the non-phosphorylated form binds to PAX3, PAX7, DEK, HDAC1, HDAC2, HDAC3, acetylated histone H4 & histones H2A, H2B, H3 & H4
• interacts with SPOP
• part of a complex consisting of DAXX, CUL3 & SPOP
• interacts with CBP; the interaction is dependent sumoylation of CBP & suppresses CBP transcriptional activity via recruitment of HDAC2 directly in the complex with TP53 & HIPK2
• interacts with AXIN1; the interaction stimulates interaction of DAXX with TP53
• stimulates Ser-46 phosphorylation of TP53
• induces cell death on UV irradiation
• interacts with HCMV tegument phosphoprotein pp71
• part of a complex with MDM2, DAXX, RASSF1 & USP7
• part of a complex with DAXX, MDM2 & USP7
• interacts (via N-terminus) with RASSF1 (via C-terminus); the interaction is independent of MDM2 & TP53
• interacts with MDM2; the interaction is direct
• interacts with USP7; the interaction is direct & independent of MDM2 & TP53
• interacts with TP53

Structure

belongs to the DAXX family

Compartment

• cytoplasm, nucleus, nucleoplasm, PML nuclear body, nucleolus
• chromosome, centromere
• dispersed throughout the nucleoplasm, in PML nuclear bodies, & 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 nucleoplasm with accumulation in nuclear speckles

Alternative splicing

named isoforms=2

Expression

• ubiquitous
• upon mitogenic stimulation by concanavalin-A

More general terms

• nuclear protein
• pro apoptotic protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1616
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1616
• OMIM: https://mirror.omim.org/entry/603186
• UniProt: http://www.uniprot.org/uniprot/Q9UER7.html