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FLASH GENE
Symbol ARX contributors: mct/pgu - updated : 08-02-2014
HGNC name aristaless related homeobox
HGNC id 18060
DNA
TYPE functioning gene
SPECIAL FEATURE component of a cluster
STRUCTURE 11.56 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence cytosine-phosphate-guanine/HTF
motif repetitive sequence   triplet
text structure
  • expanded polyalanine
  • a high overall GC content of 72.5p100 that codes for a multidomain protein
  • MAPPING cloned Y linked N status provisional
    Map pter - DXS6717 - DXS1432 - ARX - DXS6714 - DXS8056 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2885 - 562 - 1996 8826457
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Nervousbrainforebraincerebral cortex highly
     brainbasal nucleistriatum  
    Reproductivefemale systemovary   
     male systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text brain, forebrain, floor plate, testis, strongly expressed in differentiating embryonic muscle
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two independent repression domains: an N-terminal octapeptide motif/engrailed homology domain, necessary for Groucho-dependent repression activity
  • a high overall GC content of 72.5p100 that codes for a multidomain protein, including the octapeptide domain, that binds DNA
  • three nuclear localization sequences
  • four polyalanine tracts (pA1-4)
  • two repression domains, the OP and a second domain located in the C-terminus at amino acids (398-448) of the protein, termed ORD (for other repression domain)
  • C-terminal Aristaless domain, a novel octapeptide motif/engrailed homology domain, and four polyalanine (polyA) tracts, and missense mutations in the ARX homeodomain represent loss-of-function mutations, which lead to a reduced or complete loss of DNA binding and as a consequence, a loss of transcriptional repression
  • HOMOLOGY
    interspecies ortholog to murine Arx
    Homologene
    FAMILY
  • paired homeobox family
  • bicoid subfamily
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    text restricted to regions that are known to be rich in GABAergic neurons
    basic FUNCTION
  • playing a role in the differentiation, radial and tangential migration and maintenance of specific neuronal subtypes in the cerebral cortex (crucial for the development of cognitive function) and a secondary role in the differentiation of the testes (controlling the function of Leydig cells)
  • acting as a novel positive regulator of embryonic myogenesis by synergizing with MEF2C and MYOD1 and by establishing an activating loop with myogenin
  • can function as a transcriptional repressor
  • important for many developmental processes, including proper migration of GABA-ergic cortical interneurons and neuronal cell differentiation and proliferation, and for proper pancreatic endocrine cell specification through the inhibition of PAX4
  • plays multiple roles in forebrain development, both dependent and independent of DLX1/2
  • may play a role in controlling cell cycle exit of neural progenitors within the subpallium
  • not directly involved in GABAergic cell fate specification, but having multiple and distinct cell-autonomous roles for ARX in corticogenesis
  • required for the normal development of human enteroendocrine cells, and in the progenitor for enteroendocrine cell development
  • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with IPO13 (with the C-terminal nuclear localization sequences in the homeodomain of ARX is required for correct nuclear localization)
  • interaction between ARX and the co-repressors Groucho and CtBP
  • EBF3, LMO1 and SHOX2 are direct transcriptional targets of ARX (can bind to the putative enhancers of EBF3, LMO1 and SHOX2)
  • genetic interactions between NKX2-2 and ARX within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells
  • LMO1 and SHOX2, are ARX targets (mutations in the ARX homeodomain disrupt repression of LMO1 and SHOX2, direct targets of ARX transcription repression)
  • KDM5C is directly regulated by ARX through the binding in a conserved noncoding element (ARX transactivates the 5prime KDM5C regulatory element by binding to the two “TAAT/ATTA” boxes (BD1 and BD2)
  • ARX is a direct target of NKX6.1
  • LHX6 directly binds to an ARX enhancer and to an intronic CXCR7 enhancer that remains active in mature interneurons
  • EBF3 is a downstream transcriptional target of aristaless-related homeobox (ARX) and is thought to be transcriptionally repressed by ARX
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) ISSX , PRTS , XLAG , MRX54 , EIEE1
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS