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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
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