DAXX (death-associated protein 6)

2009-01-01 Eunhee Kim Affiliation

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

Identity

HGNC

DAXX

LOCATION

6p21.32

IMAGE

LOCUSID

1616

ALIAS

BING2,DAP6,EAP1,SMIM40

FUSION GENES

Show Gene Fusions

DNA/RNA

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

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 ID	Last Year	Title	Authors
17596307	2007	Human cytomegalovirus gene expression is silenced by Daxx-mediated intrinsic immune defense in model latent infections established in vitro.	Saffert RT et al
16406523	2006	Daxx: death or survival protein?	Salomoni P et al
18069800	2008	4-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
18031230	2007	Daxx mediates SUMO-dependent transcriptional control and subnuclear compartmentalization.	Shih HM et al
15998799	2005	Dissociation 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
11881150	2001	[Monoclonal antibodies against protein Daxx and its localization in nuclear domains 10].	Sotnikov AG et al
12477932	2002	Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.	Strausberg RL et al
17370120	2007	Anti-apoptotic effects of probucol are associated with downregulation of Daxx expression in THP-1 macrophage.	Su B et al
9373149	1997	Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.	Suzuki Y et al
15077145	2004	PML nuclear bodies and apoptosis.	Takahashi Y et al
15878163	2005	The death domain-associated protein modulates activity of the transcription co-factor Skip/NcoA62.	Tang J et al
14990586	2004	A novel transcription regulatory complex containing death domain-associated protein and the ATR-X syndrome protein.	Tang J et al
17942542	2008	Nuclear domain 10 components promyelocytic leukemia protein and hDaxx independently contribute to an intrinsic antiviral defense against human cytomegalovirus infection.	Tavalai N et al
10545115	1999	Human Daxx regulates Fas-induced apoptosis from nuclear PML oncogenic domains (PODs).	Torii S et al
18200667	2008	Effect of Daxx on cholesterol accumulation in hepatic cells.	Tuo QH et al
16569639	2006	Physiological and functional interactions between Tcf4 and Daxx in colon cancer cells.	Tzeng SL et al
10903735	2000	Fas 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
17035242	2006	Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter.	Woodhall DL et al
12407442	2002	Ultraviolet radiation-induced apoptosis is mediated by Daxx.	Wu S et al
12953102	2003	The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies.	Xue Y et al
9215629	1997	Daxx, a novel Fas-binding protein that activates JNK and apoptosis.	Yang X et al
12086872	2002	Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling.	Yeoh EJ et al
17661348	2008	Daxx contains two nuclear localization signals and interacts with importin alpha3.	Yeung PL et al
14557665	2003	Adenovirus E1B 55-kilodalton oncoprotein binds to Daxx and eliminates enhancement of p53-dependent transcription by Daxx.	Zhao LY et al
10684855	2000	Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis.	Zhong S et al
17389020	2007	Sequence 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

Variants:

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

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000204209	ENST00000266000	Q9UER7
ENSG00000204209	ENST00000266000	A0A024RCS3
ENSG00000204209	ENST00000374542	Q9UER7
ENSG00000204209	ENST00000374542	A0A024RCS3
ENSG00000204209	ENST00000414083	Q9UER7
ENSG00000204209	ENST00000446403	Q4VX54
ENSG00000204209	ENST00000446511	A2AB94
ENSG00000204209	ENST00000620164	Q9UER7

Expression (GTEx)

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

Pathway	Source	External ID
MAPK signaling pathway	KEGG	ko04010
Apoptosis	KEGG	ko04210
Amyotrophic lateral sclerosis (ALS)	KEGG	ko05014
MAPK signaling pathway	KEGG	hsa04010
Apoptosis	KEGG	hsa04210
Amyotrophic lateral sclerosis (ALS)	KEGG	hsa05014
Herpes simplex infection	KEGG	ko05168
Herpes simplex infection	KEGG	hsa05168
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
Regulation of TP53 Activity	REACTOME	R-HSA-5633007
Regulation of TP53 Expression and Degradation	REACTOME	R-HSA-6806003
Regulation of TP53 Degradation	REACTOME	R-HSA-6804757

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
21252315	2011	DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.	498
21719641	2011	Altered telomeres in tumors with ATRX and DAXX mutations.	331
20504901	2010	The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3.	271
9215629	1997	Daxx, a novel Fas-binding protein that activates JNK and apoptosis.	209
17081986	2006	Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors.	182
12953102	2003	The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies.	143
12140263	2002	Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek.	113
23075851	2012	DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.	105
20147399	2010	Regulation of ICP0-null mutant herpes simplex virus type 1 infection by ND10 components ATRX and hDaxx.	103
24530302	2014	Mislocalization 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/cancer-prone-explorer/gene-explorer/