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)

Identity

HGNC
LOCATION
6p21.32
IMAGE
Atlas Image
LOCUSID
ALIAS
BING2,DAP6,EAP1,SMIM40
FUSION GENES

DNA/RNA

Atlas Image

Description

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

Transcription

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:
696-740: SSLCIPSPARLSQTPHSQPPRPGTCKTSVATQCDPEEIIVLSDSDPAKNLGRRRSKQDQG

Proteins

Atlas Image

Description

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).

Expression

Ubiquitous.

Localisation

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.

Function

  • 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%).

    Mutations

    Note

    Substitutions (see the external links).

    Implicated in

    Disease
    Daxx is a component of the promyelocytic leukemia protein (PML) nuclear bodies (NBs).
    Entity name
    Alpha-thalassemia
    Disease
    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
    Leukemia
    Disease
    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.

    Article Bibliography

    Pubmed IDLast YearTitleAuthors

    Other Information

    Locus ID:

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

    Variants:

    dbSNP: 1616
    ClinVar: 1616
    TCGA: ENSG00000204209
    COSMIC: DAXX

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000204209ENST00000266000Q9UER7
    ENSG00000204209ENST00000266000A0A024RCS3
    ENSG00000204209ENST00000374542Q9UER7
    ENSG00000204209ENST00000374542A0A024RCS3
    ENSG00000204209ENST00000414083Q9UER7
    ENSG00000204209ENST00000446403Q4VX54
    ENSG00000204209ENST00000446511A2AB94
    ENSG00000204209ENST00000620164Q9UER7

    Expression (GTEx)

    0
    10
    20
    30
    40
    50
    60
    70
    80

    Pathways

    PathwaySourceExternal ID
    MAPK signaling pathwayKEGGko04010
    ApoptosisKEGGko04210
    Amyotrophic lateral sclerosis (ALS)KEGGko05014
    MAPK signaling pathwayKEGGhsa04010
    ApoptosisKEGGhsa04210
    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
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    380382522024DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks.0
    380382522024DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks.0
    356912892023DAXX, ATRX, and MSI in PanNET and Their Metastases: Correlation with Histopathological Data and Prognosis.0
    368682282023DAXX adds a de novo H3.3K9me3 deposition pathway to the histone chaperone network.18
    373967462023The Impact of Human Mammary Tumor Virus (HMTV) on the Expression of Epidermal Growth Factor Receptor (EGFR) and Death-Domain Associated Protein (DAXX) in Breast Carcinoma Tissues.0
    378718532023HPV16 E7 protein antagonizes TNF-α-induced apoptosis of cervical cancer cells via Daxx/JNK pathway.1
    356912892023DAXX, ATRX, and MSI in PanNET and Their Metastases: Correlation with Histopathological Data and Prognosis.0
    368682282023DAXX adds a de novo H3.3K9me3 deposition pathway to the histone chaperone network.18
    373967462023The Impact of Human Mammary Tumor Virus (HMTV) on the Expression of Epidermal Growth Factor Receptor (EGFR) and Death-Domain Associated Protein (DAXX) in Breast Carcinoma Tissues.0
    378718532023HPV16 E7 protein antagonizes TNF-α-induced apoptosis of cervical cancer cells via Daxx/JNK pathway.1
    357188182022Reciprocal regulation of Daxx and PIK3CA promotes colorectal cancer cell growth.5
    361625102022Death domain-associated protein DAXX regulates noncoding RNA transcription at the centromere through the transcription regulator ZFAT.1
    357188182022Reciprocal regulation of Daxx and PIK3CA promotes colorectal cancer cell growth.5
    361625102022Death domain-associated protein DAXX regulates noncoding RNA transcription at the centromere through the transcription regulator ZFAT.1
    326942502021Direct Interaction of Daxx and Androgen Receptor Is Required for Their Regulatory Activity in Cholesterol Biosynthesis.3

    Citation

    Eunhee Kim

    DAXX (death-associated protein 6)

    Atlas Genet Cytogenet Oncol Haematol. 2009-01-01

    Online version: http://atlasgeneticsoncology.org/gene/40265/meetings/favicon/css/template-card.css