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FLASH GENE
Symbol ATRX contributors: mct - updated : 23-01-2019
HGNC name alpha thalassemia/mental retardation syndrome X-linked
HGNC id 886
RNA
TRANSCRIPTS type messenger
text alternative splicing transcripts in the 5' region
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
35 - 11202 282.5 2492 - 2008 18409179
exons 1 to 4
34 splicing 11088 278 2454 widely 2008 18409179
lacks exon 2 within the coding region (exons 1,3,4 )
- splicing 10452 - 2288 brain, fibroblasts and kidney 2008 18409179
an additional region leads to a translation frameshift, resulting in a N-terminal truncated protein (exons 2, 3, 4)
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
blood / hematopoieticthymus   highly
Endocrineneuroendocrinepituitary  highly
Hearing/Equilibriumear   highly
Lymphoid/Immunelymph node   highly
Reproductivefemale systembreastmammary gland highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Lymphoid    
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal containing a PHD type (C4-H-C3) zinc finger motif
  • two functional nuclear localization signals
  • two domains that target ATRX to nuclear speeckles
  • a central region with ATPase helicase motifs homologous to RAD54
  • 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
  • HOMOLOGY
    interspecies homolog to yeast SNF2/SWI2 (sucrase non fermenting)
    homolog to Drosophila brama (brm)
    homolog to murine Atrx
    Homologene
    FAMILY
  • family of helicase/ATPase (SNF2/SWI2 family)
  • SNF2/RAD54 helicase family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    intracellular,nucleus,chromatin/chromosome,euchromosome
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    intracellular,nucleus,chromatin/chromosome,telomere
    intracellular,nucleus,chromatin/chromosome,centromere
    text
  • associated with pericentromeric heterochromatin during interphase and mitosis
  • associated with condensed chromatin at the onset of mitosis
  • 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
  • binding to the short arms of acrocentric chromosomes where the arrays of ribosomal DNA are located
  • involved in DNA methylation, in brain development and facial morphogenesis
  • may play an important role in transcription regulation, and involved in chromatin remodelling
  • critical mediator of cell survival during early neuronal differentiation during and corticogenesis
  • plays an important role in the recombinational repair of double-strand DNA (dsDNA) breaks
  • play important roles during homologous recombination
  • 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)
  • switch/sucrose nonfermenting-type ATPase localized at pericentromeric heterochromatin
  • contributes to chromosome dynamics during mitosis and provide a possible cellular explanation for reduced cortical size and abnormal brain development associated with ATRX deficiency
  • transcriptional regulator, playing a novel function, working in conjunction with H3F3B, H3F3A and CBX5, as a key regulator of embryonic stem-cell telomere chromatin
  • 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
  • may be involved in recruitment of the complex DAXX/ATRX to telomeres
  • 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
  • chromatin-remodeling factor known to regulate DNA methylation at repetitive sequences of the human genome
  • required for heterochromatin formation and maintenance of chromosome stability during meiosis
  • required for centromere stability and the epigenetic control of heterochromatin function during meiosis and the transition to the first mitosis
  • 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
  • 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
  • role of ATRX may be to recognize unusual forms of DNA and facilitate their resolution in several contexts
  • required for the timely accumulation of the homologous recombination proteins RAD51 and BRCA2 at double-strand breaks
  • CELLULAR PROCESS nucleotide, chromatin organization, remodeling
    nucleotide, chromatin organization, methylation
    nucleotide, recombination
    nucleotide, repair
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    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)
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • EZH2
  • interacting with MECP2 (interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation)
  • binds histone H3
  • interacts with a DNA structure-specific endonuclease, MUS81–EME1 (might function together in the repair of damaged DNA)
  • partner with cohesin and MECP2 and contributes to developmental silencing of imprinted genes in the brain
  • interacts with H3F3A in maintaining telomere structural integrity in pluripotent embryonic stem cells)
  • with DAXX are specifically associated with the H3F3A deposition machinery
  • in euchromatin the predominant targets of ATRX are sequences containing VNTRs
  • 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
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) ATRX , JMS , SFMS , CWS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional somatic mutation      
    in alpha-thalassemia myelodysplasia syndrome with poor prognosis, germinal mutations associated with besser prognosis
    tumoral fusion      
    with DAXX in promyelocytic leukemia (localization in nuclear bodies)
    constitutional     --low  
    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      
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • 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