DAXX (death-associated protein 6)

2009-01-01   Eunhee Kim 

School of Bioscience & Biotechnology, Chungnam National University, 220 Goong-dong, Yusung-gu, Daejeon, 305-764, Korea (South)


Atlas Image


Atlas Image


Daxx gene has 8 exons on chromosome 6. The sizes of the exons are 66, 256, 832, 212, 214, 475, 223 and 191 bps.


2,477 bp mRNA.
Two alternative transcripts:
1. Isoform 1 has been chosen as the canonical sequence
2. Isoform 2 differs from the canonical sequence as follows:


Atlas Image


740 amino acids, 82.2 kDa; contains in 3 coiled coils (residues 180-217, 358-399 and 430-489), and 2 nuclear localisation signals (residues 391-395 and 628-634).




Nucleus and cytoplasm.
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 the cytoplasmic punctate structures.
Translocated from the nucleus to the cytoplasm upon glucose deprivation or ischemic stress.


  • Interaction with Fas death domain and induces Fas-mediated cell death.
  • Establishes Fas-Daxx-ASK1-JNK axis.
  • Implicated in ischemic cell death. Daxx translocates from the nucleus to the cytoplasm upon ischemic stress. Cytoplasmic Daxx interacts with NHE1 and stimulates the NHE1 transporter activity and suppresses the NHE1-ezrin-AKT1 pathway.
  • Associated with the PML body in the nucleus.
  • Interacts with SUMO1 and UBC9 and is sumorylated at K630 and 631. However, the sumoylation status does not determine its localization onto the PML body.
  • Mediates SUMO-dependent transcriptional control and subnuclear compartmentalization.
  • Suppresses cell death in the early embryo.
  • Daxx silencing sensitizes cells to Fas- and stress-induced cell death through caspase activation, cytochrome C release and JNK activation.
  • Homology

    Holomogy with Pan troglodytes (99%); Canis lupus familiaris (89%); Bos taurus (83%); Mus musculus (70%), Rattus norvegicus (73%).



    Substitutions (see the external links).

    Implicated in

    Daxx is a component of the promyelocytic leukemia protein (PML) nuclear bodies (NBs).
    Entity name
    Daxx complex is a novel ATP-dependent chromatin-remodeling complex, with alpha-thalassaemia syndrome protein (ATRX) being the core ATPase subunit and Daxx being the targeting subunit.
    Entity name
    Daxx protein was expressed in 38.0% of 50 children with acute leukemia, which was significantly higher than that of the control group (5.0%) (P < 0.05). Daxx expression is abnormal in children with acute leukemia and associated with some clinical features of acute leukemia, suggesting that it may play an important role in the genesis and development of acute leukemia.


    Pubmed IDLast YearTitleAuthors
    159290992005Survival role of protein kinase C (PKC) in chronic lymphocytic leukemia and determination of isoform expression pattern and genes altered by PKC inhibition.Alkan S et al
    117033232001Histone deacetylase inhibitors induce caspase-dependent apoptosis and downregulation of daxx in acute promyelocytic leukaemia with t(15;17).Amin HM et al
    184560012008Self-regulatory role of 4-hydroxynonenal in signaling for stress-induced programmed cell death.Awasthi YC et al
    153029352004Large-scale characterization of HeLa cell nuclear phosphoproteins.Beausoleil SA et al
    147222672004Nuclear localization but not PML protein is required for incorporation of the papillomavirus minor capsid protein L2 into virus-like particles.Becker KA et al
    153596462004In the erythroleukemic cell line HEL Prostate-apoptosis-response-gene-4 (par-4) fails to down-regulate Bcl-2 and to promote apoptosis.Boehrer S et al
    156837512005Expression of Daxx sensitizes Jurkat T-cells to the apoptosis-inducing effect of chemotherapeutic agents.Boehrer S et al
    151831202004In bcr-abl-positive myeloid cells resistant to conventional chemotherapeutic agents, expression of Par-4 increases sensitivity to imatinib (STI571) and histone deacetylase-inhibitors.Brieger A et al
    167319592006Human cytomegalovirus (HCMV) UL82 gene product (pp71) relieves hDaxx-mediated repression of HCMV replication.Cantrell SR et al
    117730672002Molecular mechanisms involved in CD43-mediated apoptosis of TF-1 cells. Roles of transcription Daxx expression, and adhesion molecules.Cermák L et al
    156370792005Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4.Chang CC et al
    97435011998Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx.Chang HY et al
    99900101999Dissecting Fas signaling with an altered-specificity death-domain mutant: requirement of FADD binding for apoptosis but not Jun N-terminal kinase activation.Chang HY et al
    114936002001A kinase-independent function of Ask1 in caspase-independent cell death.Charette SJ et al
    164751842006SUMO regulates the cytoplasmonuclear transport of its target protein Daxx.Chen A et al
    170989292006DAXX interacts with phage PhiC31 integrase and inhibits recombination.Chen JZ et al
    145172822003Daxx silencing sensitizes cells to multiple apoptotic pathways.Chen LY et al
    166382112006[Expression of apoptosis-related proteins in the human bone marrow hematopoietic cells treated by Panax Notoginosides].Chen XH et al
    184804072008Live cell dynamics of promyelocytic leukemia nuclear bodies upon entry into and exit from mitosis.Chen YC et al
    147619632004Positive regulation of apoptosis signal-regulating kinase 1 by hD53L1.Cho S et al
    129488512003Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation.Chow KU et al
    169827442006Daxx represses expression of a subset of antiapoptotic genes regulated by nuclear factor-kappaB.Croxton R et al
    125294002003Homeodomain-interacting protein kinase 1 modulates Daxx localization, phosphorylation, and transcriptional activity.Ecsedy JA et al
    117991272002The interaction of Pax5 (BSAP) with Daxx can result in transcriptional activation in B cells.Emelyanov AV et al
    117165412001Interferon-induced antiviral Mx1 GTPase is associated with components of the SUMO-1 system and promyelocytic leukemia protein nuclear bodies.Engelhardt OG et al
    176708332007Herpes simplex virus type 1 genomes are associated with ND10 nuclear substructures in quiescently infected human fibroblasts.Everett RD et al
    120337692002Reorganization of nuclear domain 10 induced by papillomavirus capsid protein l2.Florin L et al
    110994842001HIV induces lymphocyte apoptosis by a p53-initiated, mitochondrial-mediated mechanism.Genini D et al
    154893342004The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).Gerhard DS et al
    114200432001An essential role for Daxx in the inhibition of B lymphopoiesis by type I interferons.Gongora R et al
    153399332004The transcriptional repressor hDaxx potentiates p53-dependent apoptosis.Gostissa M et al
    157952472005The cellular protein daxx interacts with avian sarcoma virus integrase and viral DNA to repress viral transcription.Greger JG et al
    179475142007Knockdown of hDaxx in normally non-permissive undifferentiated cells does not permit human cytomegalovirus immediate-early gene expression.Groves IJ et al
    169553922006Gene expression profiling of human synovial sarcoma cell line (Hs701.T) in response to IL-1beta stimulation.Ha WY et al
    95210531998Genomic analysis of the Tapasin gene, located close to the TAP loci in the MHC.Herberg JA et al
    119920052002Functional interaction between the pp71 protein of human cytomegalovirus and the PML-interacting protein human Daxx.Hofmann H et al
    146789852003HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in human hepatoma cells.Hofmann TG et al
    121402632002Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek.Hollenbach AD et al
    175904042007Proteasome-dependent, ubiquitin-independent degradation of Daxx by the viral pp71 protein in human cytomegalovirus-infected cells.Hwang J et al
    160384112005C-terminus of heat shock protein 70-interacting protein facilitates degradation of apoptosis signal-regulating kinase 1 and inhibits apoptosis signal-regulating kinase 1-dependent apoptosis.Hwang JR et al
    157813412005Differential effects of a novel IFN-zeta/limitin and IFN-alpha on signals for Daxx induction and Crk phosphorylation that couple with growth control of megakaryocytes.Ishida N et al
    105255301999PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1.Ishov AM et al
    152521192004Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX.Ishov AM et al
    121509772002Modification of Daxx by small ubiquitin-related modifier-1.Jang MS et al
    181965342008Critical roles for JNK, c-Jun, and Fas/FasL-Signaling in vitamin E analog-induced apoptosis in human prostate cancer cells.Jia L et al
    180036192008Physical interactions and functional coupling between Daxx and sodium hydrogen exchanger 1 in ischemic cell death.Jung YS et al
    159833812005Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death.Junn E et al
    97408011998Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade.Juo P et al
    182421852008Proteasome inhibitor MG132 blocks viral DNA replication and assembly of human cytomegalovirus.Kaspari M et al
    129173392003ZIP kinase triggers apoptosis from nuclear PML oncogenic domains.Kawai T et al
    158611942005Daxx is required for stress-induced cell death and JNK activation.Khelifi AF et al
    129547722003Identification of Daxx interacting with p73, one of the p53 family, and its regulation of p53 activity by competitive interaction with PML.Kim EJ et al
    160889322005Upregulation of Daxx mediates apoptosis in response to oxidative stress.Kim KS et al
    146371552003Long form of cellular FLICE-inhibitory protein interacts with Daxx and prevents Fas-induced JNK activation.Kim YY et al
    94070011997Cloning and expression of primate Daxx cDNAs and mapping of the human gene to chromosome 6p21.3 in the MHC region.Kiriakidou M et al
    168103182006Release of RASSF1C from the nucleus by Daxx degradation links DNA damage and SAPK/JNK activation.Kitagawa D et al
    114959192001Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm.Ko YG et al
    162879802005SUMO modification negatively modulates the transcriptional activity of CREB-binding protein via the recruitment of Daxx.Kuo HY et al
    165248762006BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase.Kwon JE et al
    152401132004Daxx-mediated transcriptional repression of MMP1 gene is reversed by SPOP.La M et al
    118420832002The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx. Two proteins with capacity to bind Ubc9 and conjugated to SUMO1.Lalioti VS et al
    112445002001Regulation of Pax3 transcriptional activity by SUMO-1-modified PML.Lehembre F et al
    166795342006CGI-55 interacts with nuclear proteins and co-localizes to p80-coilin positive-coiled bodies in the nucleus.Lemos TA et al
    173842622006HGF/SF regulates expression of apoptotic genes in MCF-10A human mammary epithelial cells.Leroy C et al
    106697542000Sequestration and inhibition of Daxx-mediated transcriptional repression by PML.Li H et al
    106984922000EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes.Li R et al
    119073242002Hantavirus nucleocapsid protein interacts with the Fas-mediated apoptosis enhancer Daxx.Li XD et al
    165669462006Effect of sinomenine on gene expression of the IL-1 beta-activated human synovial sarcoma.Li XJ et al
    177073452007Sensitization to Fas-mediated apoptosis by dengue virus capsid protein.Limjindaporn T et al
    155726612004Negative modulation of androgen receptor transcriptional activity by Daxx.Lin DY et al
    170819862006Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors.Lin DY et al
    125955262003Promyelocytic leukemia protein (PML) functions as a glucocorticoid receptor co-activator by sequestering Daxx to the PML oncogenic domains (PODs) to enhance its transactivation potential.Lin DY et al
    119481832002Essential role of the 58-kDa microspherule protein in the modulation of Daxx-dependent transcriptional repression as revealed by nucleolar sequestration.Lin DY et al
    174045972007Axin bridges Daxx to p53.Lin SC et al
    174710232007Daxx shortens mitotic arrest caused by paclitaxel.Lindsay CR et al
    173060742007[Expression of Daxx in children with acute leukemia].Liu J et al
    121869182002Overexpression of promyelocytic leukemia protein precludes the dispersal of ND10 structures and has no effect on accumulation of infectious herpes simplex virus 1 or its proteins.Lopez P et al
    119719792002Gene control in germinal differentiation: RNF6, a transcription regulatory protein in the mouse sertoli cell.Lopez P et al
    81252981994Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.Maruyama K et al
    182647182008Differences between mouse and human cytomegalovirus interactions with their respective hosts at immediate early times of the replication cycle.Maul GG et al
    173603862007Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts.Meinecke I et al
    124829202003RNAi reveals anti-apoptotic and transcriptionally repressive activities of DAXX.Michaelson JS et al
    150873952004Overexpression of a dominant-negative mutant Ubc9 is associated with increased sensitivity to anticancer drugs.Mo YY et al
    145744042003The DNA sequence and analysis of human chromosome 6.Mungall AJ et al
    168612372006Ets-1-dependent expression of vascular endothelial growth factor receptors is activated by latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus through interaction with Daxx.Murakami Y et al
    163312682006Physical and functional interactions between Daxx and STAT3.Muromoto R et al
    164550552006Evidence for the interaction of the regulatory protein Ki-1/57 with p53 and its interacting proteins.Nery FC et al
    178911702008Proapoptotic role of Hsp90 by its interaction with c-Jun N-terminal kinase in lipid rafts in edelfosine-mediated antileukemic therapy.Nieto-Miguel T et al
    124829842003Inhibition of stress-inducible kinase pathways by tumorigenic mutant p53.Ohiro Y et al
    170819832006Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.Olsen JV et al
    173629892007Inhibition of NF-kappaB acetylation and its transcriptional activity by Daxx.Park J et al
    114839552001TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation.Perlman R et al
    96459501998Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death.Pluta AF et al
    180941922008Identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response.Poleshko A et al
    166035112006Role of the cellular protein hDaxx in human cytomegalovirus immediate-early gene expression.Preston CM et al
    184137142008Daxx represses RelB target promoters via DNA methyltransferase recruitment and DNA hypermethylation.Puto LA et al
    144996222003Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport.Reuter TY et al
    110346062000FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation.Rochat-Steiner V et al
    179381712007A suppressive role of the prolyl isomerase Pin1 in cellular apoptosis mediated by the death-associated protein Daxx.Ryo A et al
    111124092000Interaction of Daxx, a Fas binding protein, with sentrin and Ubc9.Ryu SW et al
    175963072007Human cytomegalovirus gene expression is silenced by Daxx-mediated intrinsic immune defense in model latent infections established in vitro.Saffert RT et al
    164065232006Daxx: death or survival protein?Salomoni P et al
    1806980020084-Hydroxynonenal self-limits fas-mediated DISC-independent apoptosis by promoting export of Daxx from the nucleus to the cytosol and its binding to Fas.Sharma R et al
    180312302007Daxx mediates SUMO-dependent transcriptional control and subnuclear compartmentalization.Shih HM et al
    159987992005Dissociation of Akt1 from its negative regulator JIP1 is mediated through the ASK1-MEK-JNK signal transduction pathway during metabolic oxidative stress: a negative feedback loop.Song JJ et al
    118811502001[Monoclonal antibodies against protein Daxx and its localization in nuclear domains 10].Sotnikov AG et al
    124779322002Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.Strausberg RL et al
    173701202007Anti-apoptotic effects of probucol are associated with downregulation of Daxx expression in THP-1 macrophage.Su B et al
    93731491997Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.Suzuki Y et al
    150771452004PML nuclear bodies and apoptosis.Takahashi Y et al
    158781632005The death domain-associated protein modulates activity of the transcription co-factor Skip/NcoA62.Tang J et al
    149905862004A novel transcription regulatory complex containing death domain-associated protein and the ATR-X syndrome protein.Tang J et al
    179425422008Nuclear domain 10 components promyelocytic leukemia protein and hDaxx independently contribute to an intrinsic antiviral defense against human cytomegalovirus infection.Tavalai N et al
    105451151999Human Daxx regulates Fas-induced apoptosis from nuclear PML oncogenic domains (PODs).Torii S et al
    182006672008Effect of Daxx on cholesterol accumulation in hepatic cells.Tuo QH et al
    165696392006Physiological and functional interactions between Tcf4 and Daxx in colon cancer cells.Tzeng SL et al
    109037352000Fas ligand-induced c-Jun kinase activation in lymphoid cells requires extensive receptor aggregation but is independent of DAXX, and Fas-mediated cell death does not involve DAXX, RIP, or RAIDD.Villunger A et al
    170352422006Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter.Woodhall DL et al
    124074422002Ultraviolet radiation-induced apoptosis is mediated by Daxx.Wu S et al
    129531022003The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies.Xue Y et al
    92156291997Daxx, a novel Fas-binding protein that activates JNK and apoptosis.Yang X et al
    120868722002Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling.Yeoh EJ et al
    176613482008Daxx contains two nuclear localization signals and interacts with importin alpha3.Yeung PL et al
    145576652003Adenovirus E1B 55-kilodalton oncoprotein binds to Daxx and eliminates enhancement of p53-dependent transcription by Daxx.Zhao LY et al
    106848552000Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis.Zhong S et al
    173890202007Sequence variation within the major histocompatibility complex subregion centromeric of HLA class II in type 1 diabetes.van der Slik AR et al

    Other Information

    Locus ID:

    NCBI: 1616
    MIM: 603186
    HGNC: 2681
    Ensembl: ENSG00000204209


    dbSNP: 1616
    ClinVar: 1616
    TCGA: ENSG00000204209


    Gene IDTranscript IDUniprot

    Expression (GTEx)



    PathwaySourceExternal ID
    MAPK signaling pathwayKEGGko04010
    Amyotrophic lateral sclerosis (ALS)KEGGko05014
    MAPK signaling pathwayKEGGhsa04010
    Amyotrophic lateral sclerosis (ALS)KEGGhsa05014
    Herpes simplex infectionKEGGko05168
    Herpes simplex infectionKEGGhsa05168
    Gene ExpressionREACTOMER-HSA-74160
    Generic Transcription PathwayREACTOMER-HSA-212436
    Transcriptional Regulation by TP53REACTOMER-HSA-3700989
    Regulation of TP53 ActivityREACTOMER-HSA-5633007
    Regulation of TP53 Expression and DegradationREACTOMER-HSA-6806003
    Regulation of TP53 DegradationREACTOMER-HSA-6804757

    Protein levels (Protein atlas)

    Not detected


    Pubmed IDYearTitleCitations
    212523152011DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.498
    217196412011Altered telomeres in tumors with ATRX and DAXX mutations.331
    205049012010The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3.271
    92156291997Daxx, a novel Fas-binding protein that activates JNK and apoptosis.209
    170819862006Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors.182
    129531022003The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies.143
    121402632002Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek.113
    230758512012DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.105
    201473992010Regulation of ICP0-null mutant herpes simplex virus type 1 infection by ND10 components ATRX and hDaxx.103
    245303022014Mislocalization of the centromeric histone variant CenH3/CENP-A in human cells depends on the chaperone DAXX.95


    Eunhee Kim

    DAXX (death-associated protein 6)

    Atlas Genet Cytogenet Oncol Haematol. 2009-01-01

    Online version: http://atlasgeneticsoncology.org/gene/40265/daxx-(death-associated-protein-6)