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FLASH GENE
Symbol NR1H4 last update : 12-09-2009
HGNC name nuclear receptor subfamily 1, group H, member 4
HGNC id 7967
Location 12q23.1
Synonym name
  • farnesoid-X activated receptor
  • bile acid receptor
  • RXR-interacting protein 14
  • farnesol receptor HRR-1
    • Synonym symbol(s) FXR, BAR, HRR-1, HRR1, RIP14, MGC163445
    DNA RNA EXP/sub-loc PROTEIN PATHOLOGY
    DNABack to top
    TYPE functioning gene
    STRUCTURE 89.96 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    Map cen - D12S1671 - D12S332 - NR1H4 - D12S1030 - D12S1572 - D12S1962 - D12S1607 - qter
    Authors GeneMap (98)
    Physical map
    LOC121456 12q23.1 similar to solute carrier family 9, member 7; nonselective sodium potassium/proton exchanger; sodium/hydrogen exchanger 7 TMPO 12q22-q23.1 thymopoietin LOC341457 12q23.1 similar to peptidyl-Pro cis trans isomerase SLC25A3 12q22-q23.1 solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 3 LOC387877 FLJ31051 APAF1 12q23 apoptotic protease activating factor EB-1 12q23.1-q23.2 E2a-Pbx1-associated protein MGC39520 12q23.2 hypothetical protein MGC39520 LOC387878 12 similar to ribosomal protein S4, X-linked KIAA0701 12q23.1-q23.3 similar to ribosomal protein S4, X-linked DKFZp434M0331 12q23.3 hypothetical protein DKFZp434M0331 ACTR6 12q23.3 actin-related protein 6 FLJ33505 12q23.3 hypothetical protein FLJ33505 FLJ10074 12q23.3 hypothetical protein FLJ10074 SLC17A8 12q23.3 solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 8 NR1H4 12q21.3 nuclear receptor subfamily 1, group H, member 4 LOC283431 12q23.3 hypothetical protein LOC283431 PIGAP1 12q21 phosphatidylinositol glycan, class A, pseudogene 1 TMEM16D 12q23.3 transmembrane protein 16D (eight membrane-spanning domains) SLC5A8 12q23.3 solute carrier family 5 (iodide transporter), member 8 DRIM 12q23 down-regulated in metastasis ARL1 12q23.3 ADP-ribosylation factor-like 1 SPIC 12q23.3 likely ortholog of mouse Spi-C transcription factor (Spi-1/PU.1 related) MYBPC1 12q22-q23 myosin binding protein C, slow type CHPT1 12q11 choline phosphotransferase 1 SYCP3 12q24.2-q24.3 synaptonemal complex protein 3 MGC4170 12q23.3 synaptonemal complex protein 3 LOC387880 12 similar to 10 KD HEAT SHOCK PROTEIN, MITOCHONDRIAL (HSP10) (10 KD CHAPERONIN) (CPN10) FLJ11259 12q23.3 hypothetical protein FLJ11259 LOC390353 12 similar to ribosomal protein L9 CGI-116 12q23.3 CGI-116 protein Nup37 12q23.3 nucleoporin Nup37 FLJ20641 12q23.3 hypothetical protein FLJ20641 PMCH 12q23.1 pro-melanin-concentrating hormone IGF1 12q23.1 insulin-like growth factor 1 (somatomedin C)
    RNABack to top
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionauthors
    NM_005123 11 - 2213 NP_005114 54.3 472 - Renga (2009)
    EXPRESSION / SUBCELLULAR LOCALIZATIONBack to top
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan 1organ 2organ 3organ 4level
    Cardiovascularvessel    
    Digestiveintestinesmall intestine   
     liver    
    Endocrineadrenal gland    
    Urinarykidney    
    tissue
    SystemTissueS_TissueSs_Tissuelevel
    Epithelialsecretoryglandularendocrine 
    Muscularsmoothvessel  
    Muscularstriatumskeletal  
    cells
    SystemCell
    Cardiovascularendothelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    PROTEINBack to top
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • receptor composed of a central bipartite (class II C4) zinc finger DNA binding domain
  • a N terminal modulator domain
  • a C terminal ligand binding domain of hormone receptor
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies
     
    intraspecies
     
    Homologene
    FAMILY
  • nuclear hormone receptor family
  • NR1 subfamily
    • CATEGORY regulatory , transcription factor , receptor nuclear
    basic FUNCTION
  • plays an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol (Zhang 2008)
  • inhibiting CYP7A1 synthesis when bound to bile acids
  • bile acid sensor regulating the expression of a number of genes the products of which control bile acid and cholesterol homeostasis
  • regulates expression of liver cystathionase (CSE), hydrogen sulfide production and hepatic microcirculation (Fenga 2009)
  • mediates important signaling functions of bile acids in diverse cell types including those residing in the vascular wall (Das 2009)
  • regulated 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) expression in adrenocortical cells (Xing 2009)
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • heterodimerizing with RXRs(retinoic X receptors)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with DCN (activation in vascular smooth muscle cells) (He 2008)
  • interacting with AGTR2 (upregulates AGTR2 expression at a transcriptional level and play a role in the NR1H4-mediated inhibition of ERK activation via upregulation of PTPN6) (Zhang 2008)
  • interacting with PTK2 (pivotal role for PTK2 in the process of NR1H4-induced and MMP9-dependent endothelial cell motility and vascular tube formation)(Das 2009)
    • cell & other
  • binding bile acids
    • REGULATION
    activated by retinoids,farnesol metabolites
    by bile acids such as chenodeoxycholic acid, or synthetic ligands such as GW4064 (Gineste 2008)
    other phosphorylated by PRKCA (phosphorylation induced by PKCalpha directly modulates the ability of agonists to activate NR1H4) (Gineste 2008)
    ASSOCIATED DISORDERSBack to top
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     low  
    in the liver in PFIC1 with severe cholestasis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • NR1H4 agonists may increase gallbladder fluid secretion through transcriptional activation of VIPR1, which may contribute to the regulation of bile secretion by bile salts and to a protective effect of NR1H4 pharmacological agonists in gallstone disease
  • emerging role of NR1H4 agonists as therapeutic treatment of diabetes and certain liver diseases (Xing 2009)
  • NR1H4-NR0B2 way may be a novel therapeutic target for vascular inflammation, remodeling, and atherosclerotic plaque stability (Li 2007)
  • in smooth muscle cells may serve as a novel molecular target for modulating AGTR2 signalling in the vasculature (Zhang 2008)
    • animal or cellular model