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FLASH GENE
Symbol NR0B2 contributors: mct - updated : 09-10-2018
HGNC name nuclear receptor subfamily 0, group B, member 2
HGNC id 7961
Location 1p36.11      Physical location : 27.237.975 - 27.240.567
Synonym name
  • small heterodimer partner
  • short heterodimer partner
  • orphan nuclear receptor SHP
    • Synonym symbol(s) SHP, SHP1, FLJ17090
    DNA
    TYPE functioning gene
    STRUCTURE 2.48 kb     2 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D1S2843 - D1S2732 - D1S478 - D1S2864 - RAP1GA1 - D1S482 - D1S2674 - D1S2749 - NR0B2 - D1S449 - SLC9A1 - D1S2639 - D1S247 - D1S513 - D1S2676 - D1S201 - D1S2830 - D1S2783 - D1S255 - POU3F1 - D1S432 - D1S2645 - D1S2861 - D1S443 - D1S2720 - D1S197 - D1S2661 - D1S417 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1277 - 257 - 2009 19322021
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   predominantly
    Digestiveintestinesmall intestine  moderately
     liver   highly
     stomach   highly
    Endocrineadrenal gland   specific
    Lymphoid/Immunespleen   moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text liver
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal AAs 1–92 AAs is sufficient to interact with SIRT1
  • a putative ligand-binding domain
  • a LXXLL motif and AF-2 domain involved in NR0B2 homodimerization and DAX1-NROB2 heterodimerization
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Nr0b2 (78.6pc)
    homolog to murine Nr0b2 (79pc)
    Homologene
    FAMILY
  • nuclear hormone receptor family
  • NR0 subfamily
    • CATEGORY enzyme , regulatory , receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • acting as an orphan nuclear (steroid/thyroid/retinoid) receptor
  • potential negative regulator of receptor dependent signaling pathways
  • regulator of beta acid synthesis
  • being an important component of the feedback regulatory cascade controling the conversion of cholesterol to bile acids
  • specifically inhibiting transactivation of the nuclear receptor with whom it interacts
  • acting as a steroid hormone receptor
  • acting as a transcription corepressor
  • playing an essential role in negative regulation of immune cell activity
  • having an inhibitory effect on insulin activation of hepatic fatty acid synthesis which constitutes a mechanism that would explain the beneficial effect of FGF19 on metabolic syndrome
  • having a role in mediating the reduction in lipogenic enzyme expression caused by FGF19
  • inhibits apoptosis during the monocytic differentiation by inducing CDKN1A and prolongs a cellular survival of differentiating monocytes through the transcriptional regulation of target genes of cell survival and differentiation
  • nuclear receptor that decreases the expression of Gli target genes by repressing the transcriptional activity of GLI1 and inhibiting its nuclear localization
  • can play a negative role in Hedgehog/GLI1 signaling
  • recruits SIRT1 and utilizes SIRT1 deacetylase activity to inhibit NR5A2 mediated transcriptional activation
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text negative regulation of transcription from RNA polymerase II promoter
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    cholesterol metabolism
    a component
  • heterodimerizing with many members of receptor superfamily including RAR, RXR, small heterodimer partner interacting with PPARx
  • heterodimerizing with LXRA leading to promoter specific repression of LXRA and CYP7A1
  • heterodimerizing with TR and NR1I3
  • DAX1-NROB2 heterodimerization
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • inhibiting C17A1 and NR5A2 expression
  • RARA
  • RXRA
  • THRB
  • NR5A1
  • NR5A2
  • NR1I3
  • PPARA
  • PPARG
  • HNF4A
  • ONECUT1 is a novel target of NR0B2 in the regulation of gluconeogenesis
  • interacting with CREBZF (entire N-terminus of NR0B2 and the middle region of SMILE-L are involved in this interaction)
  • interacts and co-localizes specifically with SIRT1 (inhibition of SIRT1 activity significantly reversed NR0B2-mediated inhibition of bile-acid synthesis by NR5A2 overexpression)
  • activation of the VDR represses hepatic NR0B2 to increase levels on CYP7A1 and reduce cholesterol
  • NPAS2 controlled the circadian rhythm of NR0B2 expression by binding rhythmically to the NR0B2 promoter, which was enhanced by nicotinamide adenine dinucleotide
    • cell & other
    REGULATION
    induced by FXR (NR1H4)
    Other regulation involving phosphorylation of its C-terminal Ser591 by associated protein kinase Calpha
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation     loss of function
    loss of function and mutation leading to in maturity onset diabetes of the young (MODY) mild obesity in Japenese subjects
    constitutional     --over  
    of NR1H4, NR0B2, SLC10A1 and ABCB11 was significantly up-regulated in the non-alcoholic steatohepatitis (NASH) in comparison with simple steatosis (SS) patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS