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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004959 7 - 3095 NP_004950 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)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine adrenal gland       highly Homo sapiens Nervous brain diencephalon hypothalamus nucleus accumbens predominantly Homo sapiens Reproductive female system ovary       Homo sapiens   male system testis       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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