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FLASH GENE
Symbol NR1I2 contributors: mct/npt - updated : 10-01-2016
HGNC name nuclear receptor subfamily 1, group I, member 2
HGNC id 7968
DNA
TYPE functioning gene
STRUCTURE 38.01 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure
  • proximal region of 1.5-kb from the transcription start site conferred a promoter activity
  • putative HNF1 binding element is essential for the transcriptional activity
  • MAPPING cloned Y linked N status provisional
    Physical map
    IGSF11 3q21.2 immunoglobulin superfamily, member 11 FLJ32859 3q13.33 hypothetical protein FLJ32859 UPK1B 3q13.3-q21 uroplakin 1B B4GALT4 3q13.3 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 4 CDGAP 3q13.33 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 4 FLJ10902 3q13.33 hypothetical protein FLJ10902 MDS010 3q13.33 x 010 protein C3orf1 3q13.33 chromosome 3 open reading frame 1 CD80 3q13.3-q21 CD80 antigen (CD28 antigen ligand 1, B7-1 antigen) CSRP2P 3q21.1 cysteine and glycine-rich protein 2 pseudogene ADPRH 3q13.31-q13.33 ADP-ribosylarginine hydrolase PLA1A 3q13.13-q13.2 phospholipase A1 member A LOC391569 3 similar to 60S ribosomal protein L10 (QM protein) (Tumor suppressor QM) (Laminin receptor homolog) POPDC2 3q13.33 popeye domain containing 2 COX17 3p14.3-p14.1 COX17 homolog, cytochrome c oxidase assembly protein (yeast) AAT1 3q12-q13.3 AAT1-alpha NR1I2 3q12-q13.3 nuclear receptor subfamily 1, group I, member 2 GSK3B 3q13.3 glycogen synthase kinase 3 beta LOC389143 3 LOC389143 GPR156 3q13.33 G protein-coupled receptor 156 LOC116064 3q13.33 hypothetical protein LOC116064 FSTL1 3q13.33 follistatin-like 1 NDUFB4 3q13.33 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 4, 15kDa HGD 3q21-q23 homogentisate 1,2-dioxygenase (homogentisate oxidase) MGC23920 GTF2E1 3q21-q24 general transcription factor IIE, polypeptide 1, alpha 56kDa
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 2772 - 473 - 2006 16328955
  • isoform 2
  • 9 - 4446 49.7 434 - 2006 16328955
  • isoform 1
  • 9 - 4335 - 397 - 2006 16328955
  • isoform 3
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
     stomach    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a nuclear receptor DNA-binding domain
  • a ligand binding domain (LBD) that uses a novel sequence insert to form a homodimer unique to the nuclear receptor superfamily
  • a AF2 domain necessary for binding with PROX1
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Nr1i2 (77.4pc)
    homolog to rattus Nr1i2 (76.9pc)
    Homologene
    FAMILY
  • nuclear hormone receptor family
  • nuclear receptor superfamily
  • CATEGORY transcription factor , receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text nuclear translocation observed as an essential regulatory event for transcription of its target genes such as CYP3A4
    basic FUNCTION
  • detoxification of cholestatic bile acids
  • regulating the expression of genes involved in the biosynthesis transport and metabolism of bile acids
  • playing a key role in the regulation of both drug metabolism and efflux by inducing the expression of CYP3A4 and MDR1 gene
  • key regulator of genes encoding several major cytochrome P450 enzymes and transporters
  • potential role in breast cancer resistance to drug treatments
  • ligand-activated transcription factor regulating genes central to drug and hormone metabolism in the liver
  • necessary for IL6-mediated repression of the CYP3A4 expression in human hepatocytes
  • transcription factor that induces hepatic drug metabolism by activating cytochrome P450 genes (21127053)
  • may have a function in prediction and treatment of esophageal disease
  • important regulator of xenobiotic metabolism and intestinal integrity
  • co-ordinately up-regulates drug metabolism, transport, and antioxidant genes to protect the vasculature from endogenous and exogenous insults, thus representing a novel gatekeeper for vascular defence
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • an FGF21-NR1I2 signaling pathway may be involved in decreased hepatic CYP3A4 metabolic activity in Nonalcoholic fatty liver disease (NAFLD)
  • a component
  • heterodimerizing with RXR
  • forms a tryptophan zipper-mediated homodimer, playing a role in the function of this nuclear xenobiotic receptor
  • NR1I2 and RXRA form a heterotetramer unprecedented in the nuclear receptor family of ligand-regulated transcription factors
  • INTERACTION
    DNA binding to a response element in CYP3A4
    RNA
    small molecule
    protein
  • immune-regulatory role in T lymphocytes and SOCS1 is an early signal in NR1I2-mediated T lymphocyte suppression
  • GADD45B is a direct target for NR1I2, eliciting cell signals to regulate various cellular functions
  • eliciting MAPK14 phosphorylation for cell migration
  • NR1I2 promoter methylation is involved in the regulation of intestinal NR1I2 and CYP3A4 mRNA expression and might be associated with the inter-individual variability of the drug responses of colon cancer cells
  • NR1I2 represses SULT1E1, possibly attenuating the inactivation of estrogen
  • PROX1 could negatively regulate NR1I2 signals in some tumor cells, such as hepatocellular carcinoma (HCC) cells, where both NR1I2 and PROX1 are expressed
  • RBCK1 ubiquitinates NR1I2, and this may target NR1I2 for degradation by the ubiquitin-proteasome pathway
  • both ELANE and PRTN3 cleave the human NR1I2 N terminus at sites distinct from the thrombin cleavage site
  • regulates innate immunity via activation of NLRP3 inflammasome in vascular endothelial cells
  • cross-talk between NR1I2 and AHR plays a role in the regulation of CYP3A4 gene expression
  • NR1I2 plays a central role in cortisol-mediated induction of CYP3A4 activity during pregnancy
  • cell & other
    REGULATION
    activated by pregnanes, toxic bile acid, lithocholic acid
    induced by catatoxic steroids
    Other SUMOylated to repress the inflammatory response
    post-translational regulation of NR1I2 via phosphorylation-facilitated ubiquitination by DYRK2 and UBR5
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in adenocarcinoma tissue and columnar Barrett epithelium
    Susceptibility to ulcerative colitis (UC)
    Variant & Polymorphism SNP
  • rs2276707 was weakly associated with UC susceptibility
  • Candidate gene
    Marker
  • prognostic factor in epithelial ovarian cancer and may represent a useful marker to identify patients at risk of recurrence or death
  • Therapy target
    ANIMAL & CELL MODELS
  • Pxr-deficient mice exhibit an exaggerated T lymphocyte proliferation and increased CD25 expression