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
DAXX
LOCATION
6p21.32
IMAGE
Atlas Image
LOCUSID
1616
ALIAS
BING2,DAP6,EAP1,SMIM40
FUSION GENES
Show Gene Fusions

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

    Entity name
    Promyelocytic leukemia
    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.

    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
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    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
    cerebral cortex
    cerebellum
    hippocampus
    caudate
    thyroid gland
    parathyroid gland
    adrenal gland
    nasopharynx
    bronchus
    lung
    oral mucosa
    salivary gland
    esophagus
    stomach 1
    stomach 2
    duodenum
    small intestine
    colon
    rectum
    liver
    gallbladder
    pancreas
    kidney
    urinary bladder
    testis
    epididymis
    seminal vesicle
    prostate
    vagina
    ovary
    fallopian tube
    endometrium 1
    endometrium 2
    cervix, uterine
    placenta
    breast
    heart muscle
    smooth muscle
    skeletal muscle
    soft tissue 1
    soft tissue 2
    adipose tissue
    skin 1
    skin 2
    appendix
    spleen
    lymph node
    tonsil
    bone marrow

    References

    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

    Citation

    Eunhee Kim

    DAXX (death-associated protein 6)

    Atlas Genet Cytogenet Oncol Haematol. 2009-01-01

    Online version: http://atlasgeneticsoncology.org/gene/40265/meetings/css/lib/bootstrap.min.css