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FLASH GENE
Symbol NR5A1 contributors: shn/mct - updated : 12-07-2022
HGNC name nuclear receptor subfamily 5, group A, member 1
HGNC id 7983
Corresponding disease
POF4 premature ovarian failure 4
SRA3 46,XY disorder of sex development, NR5A1 related
Location 9q33.3      Physical location : 127.243.514 - 127.269.699
Synonym name
  • steroidogenic factor 1, (STF-1) (SF-1)
  • nuclear receptor subfamily 5 group A member 1
  • adrenal 4-binding protein
  • steroid hormone receptor Ad4BP
  • Fushi tarazu factor homolog 1
    • Synonym symbol(s) FTZ1, SF-1, SF1, FTZF1, AD4BP, ELP, FTZF1, POF7, SPGF8, SRXX4, SRXY3, hSF-1
    DNA
    TYPE functioning gene
    STRUCTURE 26.19 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    alternative promoter
    MAPPING cloned Y linked N status confirmed
    Map NR5A1 was mapped to 9q33 by fluorescence in situ hybridization cen - D9S282 - D9S1881 - NR5A1 - D9S1840 - D9S282 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 3095 53 461 expressed in all primary steroidogenic tissues, including the adrenal cortex, testicular Leydig cells, and ovarian theca and granulosa cells and corpus luteum 1994 8187173
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly Homo sapiens
    Nervousbraindiencephalonhypothalamusnucleus accumbenspredominantly Homo sapiens
    Reproductivefemale systemovary    Homo sapiens
     male systemtestis    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text gonads, testis, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal modulator receptor region
  • a central bipartite (class II) zinc finger DNA binding domain
  • a C terminal ligand domain
    • conjugated PhosphoP
    mono polymer monomer
    HOMOLOGY
    interspecies homolog to Drosophila Fushi-Tarazu pair rule gene
    ortholog to NR5A1, Pan troglodytes
    ortholog to Nr5a1, Rattus norvegicus
    ortholog to Nr5a1, Mus musculus
    Homologene
    FAMILY
  • steroid/thyroid receptor superfamily
  • nuclear hormone receptor family
  • NR5 subfamily
    • CATEGORY transcription factor , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • localized to the centrosome in addition to the nucleus
  • besides functioning in the nucleus, also resides in the centrosome and controls centrosome homeostasis
    • basic FUNCTION
  • transcriptional activator involved in sex determination in synergistic with SRY
  • playing an essential role for steroid hormone-biosynthesis and endocrine development
  • nuclear receptor involved in adrenocortical and gonadal development, regulating the regression of Mullerian structures and the expression of several steroid-metabolizing enzymes
  • playing a role in cutaneous steroidogenesis and in hair follicle cycling
  • may be essential for sexual differentiation and formation of the primary steroidogenic tissues
  • SF-1 activates the expression of Dax-1
  • combinatorial expression of the paracrine factor DHH and nuclear transcription factor NR5A1 is required for Leydig cell development
  • SF-1 dosage is critically important for proper adrenal development
  • plays a pivotal role in the development and differentiation of the endocrine and reproductive systems, and also regulates the transcription of a host of genes, including those encoding several steroidogenic enzymes and gonadotropins
  • plays a major role in regulating steroidogenic enzymes, and inhibits aldosterone synthase (CYP11B2) reporter gene activity
  • induced the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into steroidogenic cells such as Leydig or adrenocortical cells
  • plays a pivotal role in the regulation of reproductive endocrine functions at multiple levels during adrenal and gonadal development and differentiation, including regulating the expression of steroidogenic genes
  • transcription factor whose expression is required for the development of the ventral medial hypothalamic nucleus
  • novel role in the control of centrosome homeostasis and genomic stability
  • directs transcriptional programs in the hypothalamus relevant to coordinated control of energy homeostasis, especially after excess caloric intake
  • regulates transcriptional programs that play a critical role in mediating diet-induced thermogenesis in the brown adipose tissues
  • nuclear receptor that controls adrenogenital cell growth and differentiation
  • plays a central role in gonadal development and steroidogenesis
  • NR5A1 regulates the TP53 pathway during development, is essential for fetal Sertoli cell survival and controls the cell cycle of Sertoli cells during differentiation
  • orphan nuclear receptor, important for sexual differentiation and the development of multiple endocrine organs, as well as cell proliferation in cancer cells
  • plays a central role in the development of steroidogenic tissues and their ability to produce steroid hormones
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text hypothalamic-pituitary-adrenal/gonadal axes
    PATHWAY
    metabolism
    signaling
    role of CITED2 during sex determination through a WT1/NR5A1 regulatory pathway
    a component
  • SF-1 is an RNA binding protein and that both SF-1 and Dax-1 bind to the noncoding RNA SRA
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • cooperation between the orphan nuclear receptors COUP-TFII and SF1 in the regulation of Insl3 gene expression in Leydig cells . associating with WT1 for promoting AMH expression
  • regulating CYP11A, CYP21, HSD3B antagonized by DAX1, STAR
  • controlling the transcription of NR01
  • target of MAMLD1
  • interacting with CITED2, WT1
  • can bind both sphingolipids and phospholipids (it is likely that multiple bioactive lipids are ligands for NR5A1 and that these lipids will differentially act to control its activity in a context-dependent manner)
  • CYP11A, CYP11B, CYP21B, CYP17, SFPQ, NONO and NCOA2
  • CTNNB1 1, EDF1, JUN, NCOA1, NRIP1, NR0B1, GATA4, GTF2B, PITX1, SOX9, SP1, WT1, TRERF1 and ZNF653
  • BRCA1/BARD1 complex interacts with NR5A1 (interaction between NR5A1 and BRCA1/BARD1 may recruit BRCA1/BARD1 complex to the aromatase PII promoter for BRCA1/BARD1-mediate transcriptional repression)
  • SRY and NR5A1 co-operate to activate the human SOX9 homologous TES, a process dependent on phosphorylated NR5A1
  • enhancement of NR5A1 activity by DAXX required JNK and JUN phosphorylation
  • is a direct FOXO1 transcriptional target in the ventromedial hypothalamus
  • NR5A1 restricts centrosome overduplication by inhibiting aberrant activation of DNA-dependent protein kinase (PRKDC) in the centrosome
  • NR5A1 could bind to the FDX1 promoter in differentiated hMSCs
  • FDXR is a novel NR5A1 target gene
  • FOXL2 is an essential activator of NR5A1-induced transcriptional regulation of anti-müllerian hormone in granulosa cells
  • binding of ESR1 is crucial for chromatin remodeling of NR5A1 enhancer and promoter, leading to RNA polymerase recruitment and transcription
  • NR5A1 may interact with ATF3, activates ATF3 transcriptional activity and plays a functional role in cancer development
  • activity of the EHD3 promoter was positively regulated by NR5A1, which occupied the conserved sequence "AGGTCA" in the EHD3 promoter
  • interaction between Clock NR5A1/NR5A2 and BMP15 is likely to be involved in the fine-tuning of steroidogenesis by ovarian granulosa cells
  • cooperation between the orphan nuclear receptors NR2F2 and NR5A1 in the regulation of INSL3 gene expression in Leydig cells
    • cell & other
    REGULATION
    activated by acetylation
    phosphorylation
    SOX15, TEAD4, KIAA1257, ADAMTS6, JOSD1, that activate NR5A1 gene expression
    inhibited by sumoylation
    repressed by DAX1
    ASSOCIATED DISORDERS
    corresponding disease(s) SRA3 , POF4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    lower in the SRY-negative XX testes than in XY testes
    constitutional       loss of function
    abrogates the testicular pathway and induces the ectopic ovarian pathway, resulting in postnatal partial/complete male-to-female gonadal sex reversal
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Ovaries of NR5A1+ females presented defects such as multi-oocyte follicles and an accumulation of corpora lutea