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FLASH GENE
Symbol NR0B1 contributors: shn/npt - updated : 29-08-2012
HGNC name nuclear receptor subfamily 0, group B, member 1
HGNC id 7960
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a DNA-binding domain at the N terminus
  • a nuclear hormone receptor ligand-binding domain at the C terminus
  • N terminus consists of three sequence repeats that include the LXXL/ML motif thought to play a role in subcellular distribution and nuclear localization of NR0B1, and were required for the full repression of NR1H4 transactivation
  • ligand binding domain common to nuclear receptors, lacking the zinc-finger DNA binding domain, but with 3.5 repeats motifs at the N-terminus
  • . a C terminal LBD-like domain with transcriptional silencing domain, dominant negative regulator of transcription, with an amphipatic alpha-helical motif (AF2 domain), required for nuclear localization
    mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to NR0B1, Pan troglodytes
    ortholog to Nr0b1, Mus musculus
    ortholog to Nr0b1, Rattus norvegicus
    ortholog to nr0b1, Danio rerio
    Homologene
    FAMILY
  • nuclear hormone receptor superfamily
  • orphan nuclear (steroid/thyroid/retinoid) receptor
  • NR0 subfamily
  • CATEGORY regulatory , transcription factor , receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text impaired nuclear localization by mutant protein
    basic FUNCTION
  • DAX1 has a role in gonadal sex determination
  • may influence the development of spermatogenic cells in response to steroid and pituitary hormones
  • DAX1 may be one of the factors influencing the steroid biosynthesis of adrenocortical neoplasms
  • DAX1 binds DNA and acts as a powerful transcriptional repressor of steroidogenic acute regulatory protein (STAR) gene expression
  • DAX1 is essential for the development of a functioning hypothalamus-pituitary-gonadal axis
  • Sry and Dax1 are both required for normal testis determination
  • orphan nuclear (steroid/thyroid/retinoid) receptor, with a transcriptional repression activity
  • likely involved in testis development, essential for the integrity of testicular germinal epithelium
  • repressing STAR expression and NR5A1 (SF-1) transcription and suppressing steroidogenesis by binding to the STAR promoter
  • antagonizing testis determining factor SRY and synergy between FTZF1 and WT1
  • playing a role in cutaneous steroidogenesis and in hair follicle cycling
  • having pleiotropic roles in addition to its function as a negative regulator of steroidogenesis during the development and adult function of the hypothalamic-pituitary-adrenal-gonadal (HPAG) axis
  • functioning as a global negative regulator of steroid hormone production by repressing the expression of multiple genes involved in the steroidogenic pathway
  • having a function in the development of the embryo and in the maintenance of embryonic stem cell pluripotency
  • acting as a nucleocytoplasmic shuttling protein, and may be exerting additional post-transcriptional regulatory functions
  • required for the oncogenic phenotype mediated by EWS/FLI in Ewing's sarcoma
  • inhibiting the transactivity of PPARG in a dose-dependent manner
  • functioning as a ligand-independent nuclear receptor and may be as a competitive transcriptional corepressor
  • may function as a dosage-dependent SF-1 coactivator
  • play a role in steroidogenesis and adrenal biology
  • downregulates the expression of Mc2R, CYP11A1, and StAR genes
  • is critical in early embryogenesis, where it participates in the maintenance of embryonic stem cell pluripotency
  • acts as a transcriptional repressor in adrenal/gonadal development, steroidogenesis and probably spermatogenesis
  • acts as a co-repressor to negatively modulate NR1H4 transactivity
  • inhibition of its expression or activity in the liver might increase NR1H4 target gene expression and improve glucose and lipid homeostasis
  • functions as a negative regulator of ESSRB and POU5F1, and these molecules form a regulatory loop for controlling the pluripotency and self-renewal capacity of ES cells
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development , reproduction/sex
    text adrenal cortex
    PATHWAY
    metabolism
    signaling hormonal
    a component
    INTERACTION
    DNA
    RNA noncoding RNA SRA
    small molecule
    protein
  • SRY
  • negative coregulator of NR5A1
  • Steroidogenic factor 1, SF-1
  • steroid receptor RNA activator, SRA
  • p160 coactivator TIF2
  • corepressor of NR1H3, functioning as a negative regulator of lipogenic enzyme gene expression in liver
  • co-localized with NR1H4 in the nucleus and acted as a negative regulator of FXR through a physical interaction with NR1H4
  • is a novel and potent NR1I3 corepressor, suggesting that NR0B1 functions as a coordinate hepatic regulator of NR1I3 biological function
  • ESRRB is a NR0B1-interacting protein (interaction mediated through LXXLL motifs of NR0B1 and the activation- and ligand-binding domains of ESRRB)
  • cell & other
    REGULATION
    activated by SF-1
    beta-catenin
    glucocorticoids
    Other regulated by WT1 for gonadal differentiation
    dosage-sensitive sex reversal
    mediated by the retinoic receptor
    ASSOCIATED DISORDERS
    corresponding disease(s) AHC , HHG , DSS , DUPXP , DELXP21
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    lower in the SRY-negative XX testes than in XY testes (Kojima 2008)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Transgenic mice harboring an additional copy of the Dax-1 gene in a weakened Sry allelic background exhibit an overt intersex phenotype