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FLASH GENE
Symbol NR5A2 contributors: mct - updated : 19-02-2018
HGNC name nuclear receptor subfamily 5, group A, member 2
HGNC id 7984
Location 1q32.1      Physical location : 199.996.769 - 200.146.548
Synonym name
  • fetoprotein -alpha 1(AFP) transcription factor
  • liver receptor homolog -1
  • hepatocyte B1-binding factor
  • CYP7A promoter-binding factor
  • b1-binding factor, hepatocyte transcription factor which activates enhancer II of hepatitis B virus
    • Synonym symbol(s) FTF, HB1F, LRH1, FTZF1, HB1F2, CPF, B1F, NR52, LRH-1
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 149.78 kb     8 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    Binding site   transcription factor
    text structure
  • binding sites for liver-specific and ubiquitous tanscription factors
  • transcriptionally regulated by the ESR1
    • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 5054 - 541 - 2001 11595170
    7 - 4916 - 495 - 2001 11595170
    7 - 4787 - 469 - 2001 11595170
    - - - - - expressed in the human ovary but not the liver 2013 23471216
    transcribed from a novel transcription start site, termed exon 2o, located 41 bp upstream of the reported exon 2
    EXPRESSION
    Rna function mRNA is expressed at much higher levels than NR5A1 mRNA in the human gonad
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine   moderately Homo sapiens
     liver   moderately Homo sapiensFetal
     pancreas exocrine   moderately Homo sapiens
    Endocrinepancreas     Homo sapiensFetal
    Nervousbraindiencephalonhypothalamus highly
    Reproductivefemale systemovary  moderately Homo sapiens
     male systemtestis  highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose    Homo sapiens
    Epithelialsecretoryglandularexocrine  Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegranulosa cell Homo sapiens
    ReproductiveLeydig cell Homo sapiens
    Reproductivespermatozoa Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text yolk sac, liver
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal modulator domain
  • nuclear localization of the NR5A2 is mediated by two nuclear localization signals (NLSs) that are karyopherin/importin-dependent
  • a central bipartite zinc finger
  • calreticulin (CRT)-dependent NES (nuclear export signal) which is not only required for cytoplasmic trafficking, but also essential for correct protein folding to avoid misfolding-induced aggregation
  • DNA binding domain
  • one FTZ-F1 box
  • a C terminal ligand domain
    • HOMOLOGY
    interspecies homolog to drosophila Ftz-f1
    intraspecies homolog to orphan receptor fushi tarazu factor 1 (FTZF1)
    Homologene
    FAMILY
  • nuclear receptor subfamily 5,group A
  • fushi tarazu factor subfamily
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • contributing to the regulation of pancreas specific genes and to the embryonic development
  • nuclear receptor, activating the alpha 1 fetoprotein gene in early differentiating hepatocytes
  • activating the enhancer II of hepatitis B virus
  • playing an important role in the regulation of gonadal function
  • playing a role in the initiation of intestinal tumorigenesis both by affecting cell cycle control as well as through its impact on inflammatory pathways
  • may be playing an essential role in embryogenesis and cholesterol homeostasis
  • playing an important role in the development of breast carcinomas
  • involved in intestinal lipid homeostasis and cell proliferation
  • regulates intestinal immunity by triggering local glucocorticoid production
  • playing an essential roles in cholesterol homeostasis
  • could exert potential oncogenic effects during breast cancer formation
  • indispensable to maintaining the pluripotent state of embryonic stem cells
  • transcription factor that mainly participates in the homeostasis of bile acid production in the liver
  • broad role in regulating bile acid homeostasis but is either not involved in the feedback regulation of bile acid synthesis or is compensated for by other factors
  • implicated in the regulation of cholesterol, bile acid, and steroid hormone homeostasis
  • could represent another key regulator of the steroidogenic lineage inmesenchymal stem cells and play a vital role in steroid hormone production in human Leydig cells
  • shares many common gene targets with SOX2 and KLF4, which suggests that the transcription factor trio works in concert to mediate reprogramming
  • activates NR0B2 gene promoter and transcription
  • playing potentially an important role in the regulation of testicular aromatase expression
  • NR5A2 and NR5A1, similarly induce changes to chromatin structure at the STAR gene promoter and the distal control region and suggesting that NR5A2 and NR5A1 work together in steroidogenic tissues, especially in the ovary, to regulate steroid hormone production
  • controls cell differentiation in the developing pancreas and maintains cholesterol homeostasis in adults
  • has a major role in development of pancreatic cancer
  • NR5A2 is an essential regulator of gene transcription, critical for maintenance of cell pluripotency in early development and imperative for the proper functions of the liver, pancreas, and intestines during the adult life
  • is necessary for maintenance of the corpus luteum, for promotion of decidualization and for formation of the placenta, and has multiple, indispensible roles in establishing and sustaining pregnancy
  • RARG and NR5A2 promote conversion of fibroblasts to functional neurons
  • initiates a novel pathway of ER stress resolution that is independent of the unfolded protein response (UPR), yet equivalently required
  • plays crucial regulatory roles during organogenesis
  • controls several temporally distinct stages of pancreatic development that involve regulatory mechanisms relevant to pancreatic oncogenesis and the maintenance of the exocrine phenotype
  • likely in spermatozoa the NR5A2 effects are closely integrated with the estrogen signaling, supporting NR5A2 as a downstream effector of the estradiol pathway on some sperm functions
  • orphan nuclear receptor that has been shown to play a role in the transcriptional regulation of pathways involved in cancer
  • may be important in the pathophysiology of Preterm birth (PTB)
  • critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis
  • could play a role in cancer stem cell (CSC) stemness and epithelial-mesenchymal transition (EMT) in pancreatic cancer, which may contribute to the worse clinical outcome
  • is a transcription factor and either activates or inhibits transcription through actions at hundreds of enhancers
  • is involved in the regulation of development, lipid metabolism and proliferation and is predominantly expressed in epithelial tissues
  • is essential for granulosa cell proliferation, but its depletion does not alter the frequency of apoptosis nor autophagy
  • participates in a wide variety of processes, including cholesterol and glucose metabolism in the liver, resolution of endoplasmic reticulum stress, intestinal glucocorticoid production, pancreatic development and acinar differentiation
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • NR5A2/NR0B1 complex provides the molecular mechanism for the function of NR0B1 as a potent transcriptional repressor
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • expression in human granulosa cells is regulated by CYP11A1
  • may be involved both in stimulating basal CYP7A1 and CYP8B1 transcription and in repressing their expression as part of the nuclear bile acid receptor [farnesoid X receptor (FXR)]-small heterodimer partner signaling cascade
  • bound to the distal control region and promoter of STAR
  • NR5A2 controls CYP7A1 expression from two distinct sites, i.e., liver and ileum, in the enterohepatic circulation
  • in breast cancer cells, NR5A2 promotes cell proliferation by enhancing ESR1 mediated transcription of target genes such as GREB1
  • NR5A2 acts as a transcriptional activator in the regulation of POU5F1 gene expression through the cooperative interaction with three binding sites directly or/and indirectly
  • binds directly to the kisspeptin (KISS1) promoter and stimulates KISS1 transcription
  • NR5A2 cooperates with FOXA1 and binds directly to CDKN1A promoter and a distal regulatory region found at -62&
    • 8201;kb from its transcriptional start sites, allowing repression of CDKN1A transcription
  • SERBP1 and ILF3 were identified as NR5A2 interacting partners
  • directly binds to its binding sites in the FASLG promoter, and thereby drives FASLG promoter activity
  • NR5A2 regulates FASLG transcription and associated T-cell effector functions
  • interaction between Clock NR5A1/NR5A2 and BMP15 is likely to be involved in the fine-tuning of steroidogenesis by ovarian granulosa cells
    • cell & other
    REGULATION
    activated by HNF1 and HNF3B
    repressed by NR0B2 (NR0B2 recruits SIRT1 deacetylase to inhibit NR5A2-mediated target gene activation)
    Other regulated by a DR4 element
    activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer cell lines expressing ESR1
    tumoral       gain of function
    in pancreatic cancer cells compared to normal pancreatic ductal epithelium
    tumoral     --over  
    in pancreatic tumors
    Susceptibility to inflammatory bowel disease (IBD)
    Variant & Polymorphism protective role against the onset of IBD, intimately linked with its commanding role on glucocorticoid synthesis in the intestinal epithelium
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerendocrinepancreas
    might be a plausible therapeutic target for treatment of pancreatic cancer
    cancer  
    targeting NR5A2 may provide an attractive prospect for treatment of tumors that are resistant to hormonal and targeted therapy
    ANIMAL & CELL MODELS