motifs/domains
| a N terminal containing a PHD type (C4-H-C3) zinc finger motif |
|
two functional nuclear localization signals |
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two domains that target ATRX to nuclear speeckles |
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a central region with ATPase helicase motifs homologous to RAD54 |
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ATRX-DNMT3-DNMT3L (ADD) domain, playing a role in normal pattern of DNA methylation with an N-terminal GATA-like zinc finger, a plant homeodomain finger, and a long C-terminal -helix |
|
C terminal GLN rich domain with homology to SNF2, polyQ domain |
SUBCELLULAR LOCALIZATION
| intracellular
|
|
| intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
|
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| intracellular,nucleus,nucleoplasm,nuclear bodies,PML
|
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| intracellular,nucleus,chromatin/chromosome,euchromosome
|
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| intracellular,nucleus,chromatin/chromosome,heterochromosome
|
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| intracellular,nucleus,chromatin/chromosome,telomere
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| intracellular,nucleus,chromatin/chromosome,centromere
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| text
| associated with pericentromeric heterochromatin during interphase and mitosis |
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associated with condensed chromatin at the onset of mitosis |
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located at G-rich tandem repeats (TRs) in telomeres and euchromatin where it may recognize unusual DNA structures |
| basic FUNCTION
| chromatin-remodeling protein, regulating gene expression via an effect on chromatin structure and/or function, at interphase and chromosomal segregation at mitosis |
|
helicase involved in DNA recombination and repair and transcription regulation, down-regulator of the alpha-globin locus, playing a role in the regulation of globin gene expression |
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binding to the short arms of acrocentric chromosomes where the arrays of ribosomal DNA are located |
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involved in DNA methylation, in brain development and facial morphogenesis |
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may play an important role in transcription regulation, and involved in chromatin remodelling |
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critical mediator of cell survival during early neuronal differentiation during and corticogenesis |
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plays an important role in the recombinational repair of double-strand DNA (dsDNA) breaks |
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play important roles during homologous recombination |
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stimulates MUS81–EME1 endonuclease activity on various holliday junction-like intermediates (may cooperate in the processing of Holliday junction-like intermediates during homologous recombination or DNA repair) |
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switch/sucrose nonfermenting-type ATPase localized at pericentromeric heterochromatin  |
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contributes to chromosome dynamics during mitosis and provide a possible cellular explanation for reduced cortical size and abnormal brain development associated with ATRX deficiency |
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transcriptional regulator, playing a novel function, working in conjunction with H3F3B, H3F3A and CBX5, as a key regulator of embryonic stem-cell telomere chromatin |
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with DAXX are required for H3F3A deposition onto pericentric DNA repeats outside the S phase, and the DAXX/ATRX complex uses H3F3A to modulate the transcription from these repeats |
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may be involved in recruitment of the complex DAXX/ATRX to telomeres |
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essential for the maintenance of chromosome stability during female meiosis, and required to recruit the transcriptional regulator DAXX to pericentric heterochromatin at prophase I of meiosis |
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chromatin-remodeling factor known to regulate DNA methylation at repetitive sequences of the human genome |
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required for heterochromatin formation and maintenance of chromosome stability during meiosis |
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required for centromere stability and the epigenetic control of heterochromatin function during meiosis and the transition to the first mitosis |
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plays a critical role in the functional differentiation of chromatin structure during oogenesis and underscore the importance of chromatin remodeling proteins in the control of chromosome segregation during meiosis |
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essential epigenetic component of pericentric heterochromatin for the repression of centromere mitotic rearrangements, DNA breaks and chromosome missegregation and hence as an important guardian of centromere integrity and function |
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role of ATRX may be to recognize unusual forms of DNA and facilitate their resolution in several contexts |
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required for the timely accumulation of the homologous recombination proteins RAD51 and BRCA2 at double-strand breaks |
CELLULAR PROCESS
 |
nucleotide, chromatin organization, remodeling
|
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| nucleotide, chromatin organization, methylation
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| nucleotide, recombination
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| nucleotide, repair
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| nucleotide, transcription, regulation
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| a component
| chromatin-remodeling complex with DAXX, through their paired amphipathic alpha helices domains (ATP-dependent chromatin-remodeling complex, with ATRX being the core ATPase subunit and DAXX being the targeting subunit) |
| small molecule
|
nucleotide,
|
|
| ATP |
| protein
| EZH2 |
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interacting with MECP2 (interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation) |
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binds histone H3 |
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interacts with a DNA structure-specific endonuclease, MUS81–EME1 (might function together in the repair of damaged DNA) |
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partner with cohesin and MECP2 and contributes to developmental silencing of imprinted genes in the brain |
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interacts with H3F3A in maintaining telomere structural integrity in pluripotent embryonic stem cells) |
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with DAXX are specifically associated with the H3F3A deposition machinery |
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in euchromatin the predominant targets of ATRX are sequences containing VNTRs |
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ATRX can directly enhance the expression of androgen-dependent genes through physical interaction with AR |
|
ATRX and MUS81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway |
| Other morbid association(s)
|
| Type | Gene Modification | Chromosome rearrangement | Protein expression | Protein Function
|
|---|
| constitutional
| somatic mutation
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|
|
| |
in alpha-thalassemia myelodysplasia syndrome with poor prognosis, germinal mutations associated with besser prognosis | | tumoral
| fusion
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| |
with DAXX in promyelocytic leukemia (localization in nuclear bodies) | | constitutional
|
|
| --low
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| |
results in the transmission of aneuploidy and the occurrence of centromeric breaks leading to a high incidence of structural and numerical chromosome aberrations in the pre-implantation embryo | | tumoral
| somatic mutation
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|
| |
in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain-associated protein) and ATRX, in pancreatic neuroendocrine tumors | |
Variant & Polymorphism
| 
| |
Candidate gene
Marker
Therapy target
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| | | |
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| overexpression of ATRX in transgenic mice was associated with growth retardation, neural tube defects, and a high incidence of embryonic death, transgenic mice that survived to birth exhibited a high incidence of perinatal death as well as seizures, mild craniofacial anomalies, and abnormal behavior, in conclusion ATRX dosage is crucial for normal development and organization of the cortex | |
loss of ATRX function during reproductive senescence may contribute to the onset of aneuploidy in the female gamete, and the reduced fertility observed in ATRX knockdown female mice underscores the importance of this model to determine the molecular mechanisms of aneuploidy and its effects on female fertility |
|
ScAtrxKO mice developed small testes and discontinuous tubules, due to prolonged G2/M phase and apoptosis of proliferating Sertoli cells during fetal life |