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Overview

Uniprot ID	Q9UER7
Protein Name	Death domain-associated protein 6
Gene Name	DAXX
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
637	KKSRKEKKQTGSGPL

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 activation 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 a histone chaperone that facilitates deposition of histone H3.3. Acts as a 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. Upon neuronal activation associates 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). Plays a role as a positive regulator of the heat shock transcription factor HSF1 activity during the stress protein response (PubMed:15016915)

Protein Sequence

10 MATANSIIVL 20 DDDDEDEAAA 30 QPGPSHPLPN 40 AASPGAEAPS 50 SSEPHGARGS 60 SSSGGKKCYK 70 LENEKLFEEF 80 LELCKMQTAD 90 HPEVVPFLYN 100 RQQRAHSLFL 110 ASAEFCNILS 120 RVLSRARSRP 130 AKLYVYINEL 140 CTVLKAHSAK 150 KKLNLAPAAT 160 TSNEPSGNNP 170 PTHLSLDPTN 180 AENTASQSPR 190 TRGSRRQIQR 200 LEQLLALYVA 210 EIRRLQEKEL 220 DLSELDDPDS 230 AYLQEARLKR 240 KLIRLFGRLC 250 ELKDCSSLTG 260 RVIEQRIPYR 270 GTRYPEVNRR 280 IERLINKPGP 290 DTFPDYGDVL 300 RAVEKAAARH 310 SLGLPRQQLQ 320 LMAQDAFRDV 330 GIRLQERRHL 340 DLIYNFGCHL 350 TDDYRPGVDP 360 ALSDPVLARR 370 LRENRSLAMS 380 RLDEVISKYA 390 MLQDKSEEGE 400 RKKRRARLQG 410 TSSHSADTPE 420 ASLDSGEGPS 430 GMASQGCPSA 440 SRAETDDEDD 450 EESDEEEEEE 460 EEEEEEEATD 470 SEEEEDLEQM 480 QEGQEDDEEE 490 DEEEEAAAGK 500 DGDKSPMSSL 510 QISNEKNLEP 520 GKQISRSSGE 530 QQNKGRIVSP 540 SLLSEEPLAP 550 SSIDAESNGE 560 QPEELTLEEE 570 SPVSQLFELE 580 IEALPLDTPS 590 SVETDISSSR 600 KQSEEPFTTV 610 LENGAGMVSS 620 TSFNGGVSPH 630 NWGDSGPPCK 640 KSRKEKKQTG 650 SGPLGNSYVE 660 RQRSVHEKNG 670 KKICTLPSPP 680 SPLASLAPVA 690 DSSTRVDSPS 700 HGLVTSSLCI 710 PSPARLSQTP 720 HSQPPRPGTC 730 KTSVATQCDP 740 EEIIVLSDSD

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0000775	chromosome, centromeric region
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0016604	nuclear body
Cellular Component	GO:0005730	nucleolus
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0016605	PML body
Molecular Function	GO:0019899	enzyme binding
Molecular Function	GO:0031072	heat shock protein binding
Molecular Function	GO:0042393	histone binding
Molecular Function	GO:0140693	molecular condensate scaffold activity
Molecular Function	GO:0050681	nuclear androgen receptor binding
Molecular Function	GO:0002039	p53 binding
Molecular Function	GO:0042803	protein homodimerization activity
Molecular Function	GO:0030295	protein kinase activator activity
Molecular Function	GO:0019901	protein kinase binding
Molecular Function	GO:0061629	RNA polymerase II-specific DNA-binding transcription factor binding
Molecular Function	GO:0003713	transcription coactivator activity
Molecular Function	GO:0003714	transcription corepressor activity
Molecular Function	GO:0140416	transcription regulator inhibitor activity
Molecular Function	GO:0031625	ubiquitin protein ligase binding
Biological Process	GO:0030521	androgen receptor signaling pathway
Biological Process	GO:0071276	cellular response to cadmium ion
Biological Process	GO:0071280	cellular response to copper ion
Biological Process	GO:0072738	cellular response to diamide
Biological Process	GO:0034605	cellular response to heat
Biological Process	GO:1903936	cellular response to sodium arsenite
Biological Process	GO:0034620	cellular response to unfolded protein
Biological Process	GO:0006338	chromatin remodeling
Biological Process	GO:0006351	DNA-templated transcription
Biological Process	GO:0008625	extrinsic apoptotic signaling pathway via death domain receptors
Biological Process	GO:0007254	JNK cascade
Biological Process	GO:0045892	negative regulation of DNA-templated transcription
Biological Process	GO:0010629	negative regulation of gene expression
Biological Process	GO:0036480	neuron intrinsic apoptotic signaling pathway in response to oxidative stress
Biological Process	GO:0006334	nucleosome assembly
Biological Process	GO:0042981	regulation of apoptotic process
Biological Process	GO:0006355	regulation of DNA-templated transcription
Biological Process	GO:0010468	regulation of gene expression
Biological Process	GO:0031396	regulation of protein ubiquitination

Reference

[1] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.