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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
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
2 - 1.591 - 470 sertoli cells of rat testis - in the cytoplasm and nucleus of human adrenal cortex and mouse Leydig tumor cells Tamai et al, 1996; Lalli et al 2000
- - - - - testis, in addition to Sertoli cells, DAX-1/DAX-1A is expressed in germ cells from spermatogonia to round spermatids 2011 21775412
  • inhibitory effect on NR0B1 transcriptional function
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly
    endocrinebraindiencephalonpituitary  
    Nervousbrain   moderately
     braindiencephalonhypothalamus highly
    Reproductivefemale systemovary   
     male systemtestis  highly Homo sapiens
    Respiratorylung   highly
    Skin/Tegumentskin appendagesskin glandsweat glandapocrine sweat gland 
     skin appendagesskin glandsebaceous gland  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegranulosa cell
    ReproductiveLeydig cell Homo sapiens
    ReproductiveSertoli cell Homo sapiens
    Reproductivespermatid Homo sapiens
    Skin/Tegumentepidermal secretory cell
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines teratocarcinoma cell line (N-TERA-2)
    NCL-H295
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain and adrenal
    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