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FLASH GENE
Symbol PHOX2B contributors: mct - updated : 14-01-2011
HGNC name paired-like homeobox 2b
HGNC id 9143
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineadrenal gland    
Nervousbrain   moderately
Reproductivemale systemprostate  moderately
Respiratorylung   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialsecretoryglandularendocrine 
Nervouscentral   
Nervousperipherous   
cells
SystemCellPubmedSpeciesStageRna symbol
nervousneuron
cell lineage
cell lines neuroblastoma cell lines
fluid/secretion
at STAGE
physiological period embryo
Text expressed during neural development in central autonomic circuits and perpheral neural crest deerivatives
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a paired-like homeodomain protein
  • two short and stable polyalanine repeats of 9 and 20n residues, respectively
  • five putative DNA sites that potentially bind homeodomain proteins, including PHOX2B itself
  • HOMOLOGY
    intraspecies homolog to ARIX
    Homologene
    FAMILY
  • paired homeobox family
  • CATEGORY transcription factor , signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    text mutants carrying alanine expansion retained in the cytoplasm, both in widespread diffuse and in aggregated forms
    basic FUNCTION
  • involved in the signal-mediated expression in developing and mature catecholaminergic cells and neuradrenergic neurons and regulating ARIX during nervous system development
  • playing a major role in the patterning of the autonomous ventilation system and in the autonomic nervous system
  • transcription factors crucial in the development of neural-crest-derived cells, leading to ANS (autonomic nervous system) specific neuronal lineages
  • regulates its own expression by a transcriptional auto-regulatory mechanism
  • master regulator genes for peripheral SNS differentiation
  • drives ALK gene transcription by directly binding its promoter, which therefore represents a novel PHOX2B target)
  • recruited to different nodes in the genetic architecture of cell differentiation, while maintaining control over a visceral program
  • visceral sensory ganglia and the nucleus of the solitary tract all depend for their formation on the pan-visceral homeodomain transcription factor PHOX2B, also required in efferent neurons to the viscera
  • HOXB5 and PHOX2B, regulating enteric neural crest cells (ENCCs) proliferation, migration and differentiation could be risk factors for Hirschsprung disease (HSCR)
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS nervous system
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with PHOX2A (for its transcriptional regulation) and with DBH (role in the catecholamine biosynthesis)
  • needed for RET expression
  • able to bind the cell-specific element in the 5 prime regulatory region of the TLX2 gene, determining its transactivation in neuroblastoma cells (involved in the cascade leading to TLX2 transactivation and presumably in the intestinal neuronal differentiation)
  • interacting with MSX1 (downstream target of PHOX2B that activates the Delta-Notch pathway in neuroblastoma
  • HAND2 interacted with TCF3, and bound to the PHOX2B promoter region in sympathetic nervous system (SNS) differentiation
  • HAND2 can activate the SNS differentiation program by induction of SNS-related genes, including PHOX2B, ASCL1, DBH and TH
  • TRIM11 plays a critical role in the clearance of mutant PHOX2B through the proteasome
  • SOX10 regulation by PHOX2B is pivotal for the development and pathogenesis of the autonomic ganglia
  • TWIST1 interacts with the pro-neural factor SOX10 via its Twist-box domain and binds to the PHOX2B promoter to repress transcriptional activity
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CCHS3 , NBL4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in familiar and sporadic neuroblastomas
    constitutional        
    schizophrenia with strabismus
    Susceptibility
  • to neuroblastoma
  • to Parkinson disease (in association with ASCL1)
  • Variant & Polymorphism other variation in the 20-alanine homopolymer
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    murine b-/- death in utero