Affinage

NR5A1

Steroidogenic factor 1 · UniProt Q13285

Length
461 aa
Mass
51.6 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR5A1 (Ad4BP/SF-1) is a zinc finger orphan nuclear receptor that binds Ad4/SF-1 cis-elements through a DNA-binding domain and a ligand-binding/dimerization domain homologous to the steroid receptor superfamily, acting as the master transcriptional regulator of steroidogenic cell identity and endocrine organ development (PMID:8463279). It directly drives steroidogenic gene expression in a cell-type-specific manner, activating the steroidogenic P-450 genes CYP11A and CYP11B (PMID:8247022), the cholesterol-mobilizing genes STAR and CYP11A1 (PMID:27455990, PMID:9801462), and coordinating cholesterogenic and glycolytic gene programs genome-wide so that housekeeping cholesterol synthesis and energy metabolism are matched to cell-specific steroid output (PMID:24727981, PMID:30271905). Beyond steroidogenesis, SF-1 directly governs developmental targets including Mullerian Inhibiting Substance (PMID:9165127), the orphan receptor DAX-1 (PMID:10446902), the spleen-determination factor TLX1, and the SOX9 TESCO testis enhancer—activities that map to functionally separable domains (PMID:24905461, PMID:30067310). Its transcriptional output is tuned by SUMO-1 conjugation at K119/K194, which—within the synergy control motif—represses synergistic transcription and recruits the SNF2 chromatin remodeler ARIP4 to transiently suppress target genes, while the SUMO machinery components Ubc9 and PIAS1 additionally serve as sumoylation-independent coactivators (PMID:15192080, PMID:19692572, PMID:21467194); DAX-1 represses SF-1 through direct LXXLL-mediated contact with its ligand-binding domain (PMID:12482977). SF-1 expression is itself controlled in two steps, initiated by a Hox-Pbx1-Prep1 complex at a fetal adrenal enhancer and maintained by an autoregulatory loop, with dedicated tissue-specific enhancers directing VMH and fetal Leydig cell expression (PMID:16705164, PMID:15994202, PMID:22128023). In vivo, SF-1 is required for Sertoli cell survival via the MDM2/TP53 axis (PMID:30872705), for ovarian primordial follicle reserve formation through suppression of Notch signaling and laminin matrix maintenance (PMID:37494420), and in VMH neurons for the metabolic benefits of exercise (PMID:27874828). Distinct from its nuclear role, SF-1 localizes to centrosomes and maintains centrosome homeostasis and genomic stability through a transcription-independent mechanism, as shown by a transcription-defective mutant that still rescues centrosome amplification (PMID:21566663).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 High

    Established the molecular identity of the factor controlling steroidogenic gene transcription—answering what protein binds the Ad4 cis-element and whether it can activate transcription.

    Evidence Protein purification from bovine adrenal nuclear extract, cDNA cloning, and reporter assay in CV-1 cells

    PMID:8247022 PMID:8463279

    Open questions at the time
    • Endogenous ligand undefined
    • In vivo necessity not yet shown by genetics
  2. 1994 High

    Resolved that the same Ftz-F1 locus encodes multiple isoforms with opposing activities, showing that DNA-binding strength and isoform structure tune SF-1 output.

    Evidence EMSA with in vitro synthesized proteins and reporter assays distinguishing ELP/ELP1 from Ad4BP

    PMID:8058072 PMID:8543574

    Open questions at the time
    • Physiological abundance and tissue distribution of repressor isoforms unquantified
  3. 1997 High

    Demonstrated in vivo that SF-1 is a required activator of a developmental target gene (MIS), extending it beyond steroidogenic enzymes into sex differentiation.

    Evidence Transgenic mouse MIS-reporter assay with SF-1 binding-site mutagenesis

    PMID:9165127

    Open questions at the time
    • Cofactors required for Sertoli-specific activation not defined
  4. 1999 High

    Showed SF-1 directly regulates DAX-1, defining a transcriptional node in the gonadal/adrenal regulatory network.

    Evidence EMSA, reporter assay, and Ftz-f1 knockout mouse expression analysis

    PMID:10446902

    Open questions at the time
    • Direct promoter occupancy in vivo by ChIP not shown
  5. 2003 High

    Defined the structural basis of negative feedback—how DAX-1 antagonizes SF-1—identifying LXXLL-motif contacts with the SF-1 ligand-binding domain.

    Evidence Yeast two-hybrid, in vitro pull-down, reporter assays with motif mutagenesis

    PMID:12482977

    Open questions at the time
    • Structural model of the SF-1 LBD/DAX-1 interface not solved
  6. 2004 High

    Established post-translational control of SF-1 by SUMO-1, showing sumoylation at the synergy control motif represses multi-site synergistic transcription without altering DNA binding.

    Evidence In vitro and cellular sumoylation assays, K194R mutagenesis, reporter assays

    PMID:15192080

    Open questions at the time
    • Physiological signals controlling SF-1 sumoylation dynamics unknown
  7. 2006 High

    Resolved how SF-1 expression itself is established and sustained, defining a two-step Hox-Pbx1-Prep1 initiation plus SF-1 autoregulatory maintenance mechanism at the fetal adrenal enhancer.

    Evidence Transgenic FAdE-lacZ reporters with binding-site mutagenesis and RT-PCR

    PMID:16705164

    Open questions at the time
    • Identity of factors triggering the initiation-to-maintenance switch unclear
  8. 2009 High

    Connected SF-1 sumoylation to chromatin remodeling, showing sumoylated SF-1 recruits and stimulates the ATPase ARIP4 to transiently suppress target genes.

    Evidence Affinity purification, SIM mapping, ATPase assay, ChIP, and siRNA knockdown

    PMID:19692572

    Open questions at the time
    • Genome-wide scope of ARIP4-mediated repression not mapped
  9. 2011 High

    Revealed a transcription-independent function of SF-1 at the centrosome safeguarding genomic stability, dissected by a transcription-defective mutant that still rescues centrosome amplification.

    Evidence Immunofluorescence/fractionation, shRNA depletion, centrosome assays, G35E rescue

    PMID:21566663

    Open questions at the time
    • Centrosomal binding partners and mechanism of duplication control unknown
  10. 2011 High

    Broadened the SF-1 regulon, establishing that it directly controls glycolytic genes and additional adrenal targets (SOAT1), coupling metabolic capacity to steroidogenesis.

    Evidence ChIP-seq, siRNA knockdown with ATP/NADPH readouts, and bidirectional manipulation in adrenocortical cells

    PMID:21239516 PMID:21467194 PMID:24727981

    Open questions at the time
    • Direct binding for some targets (e.g. SOAT1) inferred from expression, not ChIP
  11. 2014 Medium

    Showed SF-1 activities are functionally separable across organs, regulating TLX1 for spleen development independently of SOX9/TESCO synergy, and required in Sertoli cells via the MDM2/TP53 survival axis.

    Evidence Patient-mutation transactivation assays and Sertoli-specific Amh-Cre conditional knockout with apoptosis/MDM2-TP53 analysis

    PMID:24905461 PMID:30872705

    Open questions at the time
    • Direct transcriptional regulation of MDM2 by NR5A1 not proven by ChIP/reporter
    • Domain basis for target selectivity not structurally defined
  12. 2018 Medium

    Linked patient SF-1 mutations to impaired TESCO activation and aberrant localization, and expanded the regulon to cholesterogenic genes coordinating cholesterol supply with steroidogenesis.

    Evidence Reporter assays and localization on 20 patient mutants; ChIP-seq and knockdown for cholesterogenic targets

    PMID:30067310 PMID:30271905

    Open questions at the time
    • Structural consequences of mutations modeled in silico only
    • Hummr role in cholesterol transport not directly validated
  13. 2023 Medium

    Defined organ-level developmental roles in vivo—VMH neuronal control of exercise metabolism and prenatal ovarian primordial follicle reserve formation via Notch suppression and laminin matrix integrity.

    Evidence VMH-specific and prenatal ovary conditional knockouts with metabolic phenotyping, histology, and transcriptomics

    PMID:27455990 PMID:27874828 PMID:37494420

    Open questions at the time
    • Mechanistic link from SF-1 to PGC-1α induction not established
    • Direct SF-1 targets mediating Notch/laminin effects unidentified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous ligand (if any) regulating SF-1 ligand-binding-domain activity and the integration of its nuclear versus centrosomal functions remain undefined.
  • No physiological ligand established in the corpus
  • How a single protein partitions transcriptional and centrosomal roles is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 1
Pathway
GO:0140110 transcription regulator activity 1
Partners
ARIP4DAX-1PIAS1PIAS3SOX9UBC9

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Ad4BP (NR5A1) was purified from bovine adrenal cortex nuclear extract as a 53 kDa zinc finger protein that specifically binds the Ad4 cis-element in steroidogenic P-450 gene promoters (CYP11B and others), and its cDNA revealed a structure with a zinc finger DNA-binding domain and a ligand binding/dimerization domain homologous to the steroid hormone receptor superfamily; transfection of Ad4BP expression plasmid into CV-1 cells activated transcription of a CAT reporter driven by the Ad4 sequence. Protein purification from nuclear extract, cDNA cloning, sequence analysis, transient transfection/reporter assay The Journal of biological chemistry High 8463279
1993 Ad4BP activates transcription of CYP11A and CYP11B gene promoters in steroidogenic cells in a cell-type-specific manner; the Ad4 site confers steroidogenic tissue-specific (Leydig and adrenocortical cell) transcriptional activity, dependent on Ad4BP protein, as shown by cotransfection of Ad4BP expression vector into non-steroidogenic PC-12 cells restoring cAMP-dependent transcription. Transient transfection, reporter gene (beta-globin CAT), immunoblot, cotransfection with Ad4BP or protein kinase A catalytic subunit expression vectors Molecular endocrinology (Baltimore, Md.) High 8247022
1994 ELP and Ad4BP/SF-1 are isoforms encoded by the same gene (mammalian Ftz-F1 gene); they recognize the same DNA sequences but ELP has significantly weaker DNA-binding activity than Ad4BP and functions as a weak inhibitor of Ad4BP-dependent transactivation of the CYP11B gene when co-transfected. Gel shift assay (EMSA) with in vitro synthesized proteins, transient transfection/reporter assay, immunochemistry, immunohistochemistry Molecular endocrinology (Baltimore, Md.) High 8058072
1997 SF-1 directly activates Mullerian Inhibiting Substance (MIS) gene expression in vivo; a 180 bp MIS proximal promoter is sufficient for Sertoli cell and granulosa cell expression, and an intact SF-1 binding site within this promoter is required for MIS promoter activity in vivo, as shown by transgenic mouse assays with MIS/GH reporter transgenes. Transgenic mouse assay with MIS-human growth hormone reporter, site-directed mutagenesis of SF-1 binding site Development (Cambridge, England) High 9165127
1999 Ad4BP/SF-1 directly regulates transcription of the Dax-1 gene; a novel Ad4/SF-1 binding site in the mouse Dax-1 upstream region was identified by transient transfection and EMSA, and Dax-1 expression was significantly impaired in Ftz-f1 (Ad4BP/SF-1) knockout mice. Transient transfection reporter assay, electrophoretic mobility shift assay (EMSA), immunohistochemistry, knockout mouse analysis Molecular endocrinology (Baltimore, Md.) High 10446902
2003 DAX-1 represses Ad4BP/SF-1 transcriptional activity through direct protein-protein interaction mediated by three LXXLL-related motifs in DAX-1, which interact with the ligand binding domain of Ad4BP/SF-1; the interaction specificity depends on specific amino acids at defined positions within the LXXLL-related motifs. Yeast two-hybrid, in vitro pull-down, transient transfection/reporter assay, amino acid substitution analysis Molecular and cellular biology High 12482977
2004 Ad4BP/SF-1 is sumoylated (SUMO-1 conjugation) at lysines K119 and K194 by the E2 enzyme Ubc9 and E3 ligases PIAS1/PIAS3; sumoylation at K194, within the synergy control (SC) motif, represses synergistic transcription from promoters with multiple Ad4/SF-1 binding sites; SUMO modification does not affect DNA binding activity or interaction with Sox9 but regulates transcriptional synergy between Ad4BP/SF-1 and Sox9. Two-hybrid screening, cultured cell sumoylation assay, in vitro sumoylation assay, transient transfection/reporter assay, mutagenesis (K194R) Molecular endocrinology (Baltimore, Md.) High 15192080
2006 Ad4BP/SF-1 gene expression in the fetal adrenal is initiated by a Hox-Pbx1-Prep1 complex binding to a fetal adrenal enhancer (FAdE) in intron 4, and is subsequently maintained by an autoregulatory loop in which Ad4BP/SF-1 itself binds Ad4 sites within FAdE; transgenic mouse assays defined conserved Pbx/Prep and Pbx/Hox binding sites as initiating elements, while Ad4 sites (with Ad4BP/SF-1) maintain expression. Transgenic mouse assay with FAdE-lacZ reporters, site-directed mutagenesis of FAdE binding sites, RT-PCR for Hox expression in adrenal primordia Molecular and cellular biology High 16705164
2009 ARIP4 (AR interacting protein 4, a Rad54 family SNF2 chromatin remodeling factor) interacts with sumoylated Ad4BP/SF-1 through two SUMO-interacting motifs and one Ad4BP/SF-1-binding region; ARIP4 ATPase activity is stimulated by sumoylated Ad4BP/SF-1 in the presence of Ad4BP/SF-1-binding DNA; ChIP and siRNA studies show ARIP4 transiently suppresses Ad4BP/SF-1-mediated transcription upon recruitment to target genes. Affinity purification of ARIP4, co-immunoprecipitation, SUMO-interacting motif mapping, ATPase activity assay, ChIP assay, siRNA knockdown Molecular biology of the cell High 19692572
2011 SF-1 (NR5A1) localizes to centrosomes in addition to the nucleus; shRNA-mediated depletion of SF-1 causes centrosome over-duplication, aberrant mitosis, and genomic instability; a centrosome localization signal was identified in SF-1; a transcription-defective SF-1-G35E mutant rescues centrosome amplification, indicating a non-genomic (non-transcriptional) role of SF-1 in centrosome homeostasis. Immunofluorescence/subcellular fractionation, shRNA knockdown, centrosome duplication assay, mutagenesis (G35E transcription-defective mutant), rescue experiments Cell death and differentiation High 21566663
2011 Ubc9 and PIAS1 act as coactivators of SF-1-mediated transcription of steroidogenic enzyme genes (CYP17, CYP11A1, CYP11B1) in adrenocortical cells; Ubc9 and PIAS1 interact with SF-1 (co-immunoprecipitation), are recruited to the CYP17 promoter in chromatin (ChIP), and their knockdown by siRNA reduces endogenous CYP17, CYP11A1, and CYP11B1 mRNA; coactivation is independent of their sumoylation enzymatic activity. Co-immunoprecipitation, ChIP assay, siRNA knockdown, transient transfection/reporter assay, mutagenesis of sumoylation activity Endocrinology High 21467194
2011 SOAT1 (sterol O-acyltransferase 1) is a novel transcriptional target of SF-1 in the human adrenal; bidirectional manipulation of SF-1 (overexpression and knockdown) in NCI-H295R human adrenocortical cells identified SOAT1 among positively regulated SF-1 target genes, alongside established targets STAR and CYP11A. SF-1 overexpression and knockdown (siRNA) in adrenocortical cells, gene expression profiling The Journal of clinical endocrinology and metabolism Medium 21239516
2014 Nearly all genes in the glycolytic pathway are direct transcriptional targets of Ad4BP/SF-1 (NR5A1); ChIP-seq identified glycolytic gene promoters as Ad4BP/SF-1 binding sites; siRNA-mediated suppression of Ad4BP/SF-1 reduced ATP and NADPH production and decreased expression of glucose metabolism genes in steroidogenic cells. ChIP-seq (chromatin immunoprecipitation sequencing), siRNA knockdown, metabolite measurement (ATP, NADPH) Nature communications High 24727981
2014 SF-1 (NR5A1) is required in the Sertoli cell lineage for post-sex-determination testis development; Sertoli cell-specific knockout of Nr5a1 at E14.5 (using Amh-Cre) leads to Sertoli cell apoptosis via reduced MDM2 levels and elevated TP53, disruption of seminiferous cords, and loss of both Sertoli and germ cell populations; NR5A1 appears to directly regulate MDM2 expression. Conditional Sertoli cell-specific knockout (Amh-Cre × Nr5a1-flox), apoptosis assays, MDM2/TP53 protein expression analysis Scientific reports Medium 30872705
2014 SF-1 (NR5A1) is required for human spleen development via transactivation of TLX1; a recessive SF-1 R103Q mutation reduced SF-1 transactivation of TLX1 (a transcription factor essential for murine spleen development) but did not impair synergistic SF-1/SRY coactivation of the SOX9 testis development enhancer, demonstrating functionally separable domains in SF-1. Patient mutation identification, in vitro transactivation assays (luciferase reporter), functional mutagenesis comparing TLX1 vs. SOX9/TESCO activation The Journal of clinical investigation Medium 24905461
2018 Ad4BP/SF-1 regulates cholesterogenic genes and Hummr (a candidate mediator of cholesterol transport from endoplasmic reticula to mitochondria), in addition to steroidogenic and glycolytic genes; ChIP-seq and gene expression analyses demonstrate SF-1 directly coordinates housekeeping cholesterol synthesis with cell-specific steroidogenesis. ChIP-seq, gene expression analysis, siRNA knockdown Communications biology Medium 30271905
2018 SF-1 mutants found in 46,XY DSD patients show reduced transcriptional activation of the SOX9 TESCO enhancer; 15 of 20 patient-derived SF-1 mutants displayed reduced TESCO activation, with 11 showing atypical subcellular localization, and in silico analysis predicted altered DNA, ligand, or cofactor interactions in 14 mutants. Luciferase reporter assay (TESCO enhancer), protein expression analysis, subcellular localization by immunofluorescence, in silico structural modeling Human mutation Medium 30067310
2016 SF-1 expression in VMH neurons is required for beneficial metabolic effects of exercise; VMH-specific deletion of SF-1 in mice blunts exercise-induced reductions in fat mass, improvements in glycemia, increases in energy expenditure, and induction of PGC-1α in skeletal muscle. VMH-specific conditional knockout of SF-1 (Nr5a1) in mice, metabolic phenotyping during exercise training eLife Medium 27874828
2016 SF-1 deficiency in Leydig cells leads to lipid accumulation via suppression of STAR and CYP11A1; SF-1 knockdown in mouse Leydig cell lines caused reduced STAR and CYP11A1 expression, accumulation of neutral lipids and cholesterol, and reduced androgen production; knockdown of either STAR or CYP11A1 alone induced lipid accumulation, and combined knockdown was additive. Heterozygous SF-1 knockout mouse analysis, siRNA knockdown in Leydig cell lines, lipid staining, steroid hormone measurement Endocrine Medium 27455990
2023 SF-1 (Nr5a1) is required for formation of the ovarian primordial follicle reserve; conditional depletion of SF-1 (but not LRH-1) from prenatal ovaries led to smaller ovaries, fewer primordial follicles, increased oocyte death via elevated ovarian inflammation and Notch signaling, impaired ovarian laminin matrix formation, and compromised oocyte-granulosa cell communication; major dysregulated genes included Iroquois homeobox 3 and 5 and their downstream targets. Conditional knockout of Nr5a1 in prenatal ovaries, histology, oocyte counting, transcriptomic analysis, Notch signaling assays Proceedings of the National Academy of Sciences of the United States of America Medium 37494420
1995 The mouse ELP/Ad4BP/SF-1 gene generates multiple isoforms (ELP1, ELP2, ELP3, Ad4BP/SF-1) via alternative promoter usage and differential splicing; ELP1, which lacks the region III (ligand binding/activation) domain, functions as a transcriptional repressor, whereas isoforms with intact region II and III function as transactivators. cDNA library screening, genomic sequence analysis, RT-PCR, transient transfection/reporter assay Journal of biochemistry Medium 8543574
2001 Pod-1/Capsulin (a bHLH transcription factor) represses expression of Ad4BP/SF-1; in co-transfection experiments, Pod-1/Capsulin overexpression repressed a reporter driven by the Ad4BP/SF-1 upstream regulatory region, and forced Pod-1/Capsulin expression in Leydig cell-derived I-10 cells repressed endogenous Ad4BP/SF-1 expression. Co-transfection reporter assay, forced expression in cell lines, endogenous gene expression analysis Mechanisms of development Medium 11287187
1998 SF-1/Ad4BP binds specific sites in the bovine StAR gene promoter (at -1190, and weakly at -240) as shown by EMSA with nuclear proteins and in vitro transcribed/translated SF-1/Ad4BP; transfection assays showed SF-1/Ad4BP activates the bovine StAR promoter preferentially through proximal elements (-100 and -240), with a small cAMP/PKA-dependent increase. EMSA, heterologous transfection of StAR promoter-reporter constructs, cotransfection with SF-1/Ad4BP expression vector and constitutive PKA Journal of molecular endocrinology Medium 9801462
2005 A ventromedial hypothalamic nucleus (VMH)-specific enhancer for Ad4BP/SF-1 gene expression was identified in intron 6 of the mouse Ad4BP/SF-1 gene; the enhancer is conserved in mouse, human, and chick; ATTA motifs (homeobox protein binding elements) within the activating element are required for enhancer activity, as shown by transgenic mouse assays and EMSA with hypothalamic nuclear extracts. Transgenic mouse reporter (lacZ) assays, site-directed mutagenesis, EMSA with hypothalamic nuclear extracts Molecular endocrinology (Baltimore, Md.) Medium 15994202
2011 A fetal Leydig cell-specific enhancer was identified in the upstream region of the mouse Ad4BP/SF-1 gene; the enhancer contains an Ad4BP/SF-1 binding sequence (required for autoregulatory loop) and an E-box; mutation of either sequence abolished enhancer activity in transgenic mouse assays, indicating Leydig cell-specific Ad4BP/SF-1 expression requires both an unidentified E-box binding protein and SF-1 autoregulation. Transgenic mouse reporter assay, site-directed mutagenesis of Ad4 and E-box sites, comparative genomics Endocrinology Medium 22128023

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Ad4BP regulating steroidogenic P-450 gene is a member of steroid hormone receptor superfamily. The Journal of biological chemistry 321 8463279
1993 Activation of CYP11A and CYP11B gene promoters by the steroidogenic cell-specific transcription factor, Ad4BP. Molecular endocrinology (Baltimore, Md.) 211 8247022
2003 SF-1 a key player in the development and differentiation of steroidogenic tissues. Nuclear receptor 191 14594453
1996 Ad4BP/SF-1, a transcription factor essential for the transcription of steroidogenic cytochrome P450 genes and for the establishment of the reproductive function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 187 9002548
2006 Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proceedings of the National Academy of Sciences of the United States of America 184 16916933
2015 DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best practice & research. Clinical endocrinology & metabolism 156 26303087
2008 Steroidogenic factor-1 (SF-1, Ad4BP, NR5A1) and disorders of testis development. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 152 18987494
1994 Functional difference between Ad4BP and ELP, and their distributions in steroidogenic tissues. Molecular endocrinology (Baltimore, Md.) 147 8058072
1997 The nuclear receptor SF-1 mediates sexually dimorphic expression of Mullerian Inhibiting Substance, in vivo. Development (Cambridge, England) 146 9165127
2017 Elastin-like protein-hyaluronic acid (ELP-HA) hydrogels with decoupled mechanical and biochemical cues for cartilage regeneration. Biomaterials 140 28268018
2014 HSF-1-mediated cytoskeletal integrity determines thermotolerance and life span. Science (New York, N.Y.) 140 25324391
2010 Steroidogenic factor-1 (SF-1, NR5A1) and human disease. Molecular and cellular endocrinology 131 21078366
2009 Molecular aspects of steroidogenic factor 1 (SF-1). Molecular and cellular endocrinology 126 19616058
2003 LXXLL-related motifs in Dax-1 have target specificity for the orphan nuclear receptors Ad4BP/SF-1 and LRH-1. Molecular and cellular biology 126 12482977
2006 Two-step regulation of Ad4BP/SF-1 gene transcription during fetal adrenal development: initiation by a Hox-Pbx1-Prep1 complex and maintenance via autoregulation by Ad4BP/SF-1. Molecular and cellular biology 109 16705164
2001 Phenotypic spectrum of mutations in DAX-1 and SF-1. Molecular and cellular endocrinology 105 11738790
1999 Dax-1 as one of the target genes of Ad4BP/SF-1. Molecular endocrinology (Baltimore, Md.) 102 10446902
2002 Synergistic expression of Ad4BP/SF-1 and cytochrome P-450 aromatase (ovarian type) in the ovary of Nile tilapia, Oreochromis niloticus, during vitellogenesis suggests transcriptional interaction. Biology of reproduction 98 12606465
2004 Small ubiquitin-like modifier 1 (SUMO-1) modification of the synergy control motif of Ad4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1) regulates synergistic transcription between Ad4BP/SF-1 and Sox9. Molecular endocrinology (Baltimore, Md.) 97 15192080
2003 HSF-1 interacts with Ral-binding protein 1 in a stress-responsive, multiprotein complex with HSP90 in vivo. The Journal of biological chemistry 90 12621024
2000 Disruption of the gene encoding SF-1 alters the distribution of hypothalamic neuronal phenotypes. The Journal of comparative neurology 81 10880989
2006 SF-1 overexpression in childhood adrenocortical tumours. European journal of cancer (Oxford, England : 1990) 77 16574405
2008 Biochemical and functional characterization of anti-HIV antibody-ELP fusion proteins from transgenic plants. Plant biotechnology journal 72 18312505
2016 Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals. Birth defects research. Part C, Embryo today : reviews 70 28033660
2019 Mutation update for the NR5A1 gene involved in DSD and infertility. Human mutation 69 31513305
1997 Maternal oestrogen/xenoestrogen exposure alters expression of steroidogenic factor-1 (SF-1/Ad4BP) in the fetal rat testis. Molecular and cellular endocrinology 66 9099904
2014 Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1. Nature communications 59 24727981
2010 SF-1 in the ventral medial hypothalamic nucleus: a key regulator of homeostasis. Molecular and cellular endocrinology 57 21111025
1995 Ad4BP in the human adrenal cortex and its disorders. The Journal of clinical endocrinology and metabolism 55 7629233
1998 The role of SF-1/Ad4BP in the control of the bovine gene for the steroidogenic acute regulatory (StAR) protein. Journal of molecular endocrinology 53 9801462
1996 Structural characterization of human Ad4bp (SF-1) gene. Biochemical and biophysical research communications 53 8806624
1995 Genomic organization and isoforms of the mouse ELP gene. Journal of biochemistry 53 8543574
2008 Hsf-1 and POB1 induce drug sensitivity and apoptosis by inhibiting Ralbp1. The Journal of biological chemistry 51 18474607
2004 SF-1/Ad4BP transforms primary long-term cultured bone marrow cells into ACTH-responsive steroidogenic cells. Genes to cells : devoted to molecular & cellular mechanisms 51 15569155
2001 Pod-1/Capsulin shows a sex- and stage-dependent expression pattern in the mouse gonad development and represses expression of Ad4BP/SF-1. Mechanisms of development 51 11287187
2019 SF-1 mediates reproductive toxicity induced by Cerium oxide nanoparticles in male mice. Journal of nanobiotechnology 50 30894193
2016 SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise. eLife 48 27874828
2011 Identification of an enhancer in the Ad4BP/SF-1 gene specific for fetal Leydig cells. Endocrinology 48 22128023
2006 Heat shock and genetic activation of HSF-1 enhance immunity to bacteria. Cell cycle (Georgetown, Tex.) 48 17106259
2011 Sterol O-acyltransferase 1 (SOAT1, ACAT) is a novel target of steroidogenic factor-1 (SF-1, NR5A1, Ad4BP) in the human adrenal. The Journal of clinical endocrinology and metabolism 47 21239516
2009 Transgenic expression of Ad4BP/SF-1 in fetal adrenal progenitor cells leads to ectopic adrenal formation. Molecular endocrinology (Baltimore, Md.) 47 19628584
2008 Potent, selective and cell penetrant inhibitors of SF-1 by functional ultra-high-throughput screening. Molecular pharmacology 47 18334597
2010 Adrenocortical development and cancer: focus on SF-1. Journal of molecular endocrinology 42 20200142
2014 Testicular differentiation factor SF-1 is required for human spleen development. The Journal of clinical investigation 41 24905461
2001 SF-1: a critical mediator of steroidogenesis. Molecular and cellular endocrinology 41 11165004
2000 Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology 41 10963870
2012 ELP-z and ELP-zz capturing scaffolds for the purification of immunoglobulins by affinity precipitation. Journal of biotechnology 40 23089730
2016 SF-1 deficiency causes lipid accumulation in Leydig cells via suppression of STAR and CYP11A1. Endocrine 39 27455990
2010 Expression and purification of ELP-intein-tagged target proteins in high cell density E. coli fermentation. Microbial cell factories 37 20959011
2010 Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function. Endocrine development 37 21164257
2002 SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis. Endocrine research 37 12530669
1998 Adrenocortical and gonadal expression of the mammalian Ftz-F1 gene encoding Ad4BP/SF-1 is independent of pituitary control. Journal of biochemistry 37 9644266
2020 HSB-1/HSF-1 pathway modulates histone H4 in mitochondria to control mtDNA transcription and longevity. Science advances 36 33087356
1995 Function and distribution of a steroidogenic cell-specific transcription factor, Ad4BP. The Journal of steroid biochemistry and molecular biology 36 7626521
2012 Expression of 3β-hydroxysteroid dehydrogenase (hsd3b), star and ad4bp/sf-1 during gonadal development in medaka (Oryzias latipes). General and comparative endocrinology 35 22330050
2005 Ventromedial hypothalamic nucleus-specific enhancer of Ad4BP/SF-1 gene. Molecular endocrinology (Baltimore, Md.) 35 15994202
2012 Beyond steroidogenesis: novel target genes for SF-1 discovered by genomics. Molecular and cellular endocrinology 33 23168267
2001 Transcriptional regulators of steroidogenesis, DAX-1 and SF-1, are expressed in human skin. The Journal of investigative dermatology 32 11886523
2016 HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans. eLife 31 26952214
2006 Differential gene dosage effects of Ad4BP/SF-1 on target tissue development. Biochemical and biophysical research communications 31 16458255
2010 Update--steroidogenic factor 1 (SF-1, NR5A1). Minerva endocrinologica 30 20595937
2019 Steroidogenic Factor 1 (Nr5a1) is Required for Sertoli Cell Survival Post Sex Determination. Scientific reports 29 30872705
2011 Steroidogenic Factor 1 (NR5A1) resides in centrosomes and maintains genomic stability by controlling centrosome homeostasis. Cell death and differentiation 29 21566663
1999 Steroidogenic factor 1 (SF-1) is essential for endocrine development and function. The Journal of steroid biochemistry and molecular biology 27 10418976
2022 Icariin promotes mouse Leydig cell testosterone synthesis via the Esr1/Src/Akt/Creb/Sf-1 pathway. Toxicology and applied pharmacology 26 35259346
2019 HSB-1 Inhibition and HSF-1 Overexpression Trigger Overlapping Transcriptional Changes To Promote Longevity in Caenorhabditis elegans. G3 (Bethesda, Md.) 26 30894454
2019 Purification of proteins using peptide-ELP based affinity precipitation. Journal of biotechnology 26 31874207
2018 Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity. Scientific reports 26 29567944
2023 Steroidogenic factor 1 (SF-1; Nr5a1) regulates the formation of the ovarian reserve. Proceedings of the National Academy of Sciences of the United States of America 25 37494420
2018 Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids. Communications biology 25 30271905
2013 NR5A1 (SF-1) mutations are not a major cause of primary ovarian insufficiency. The Journal of clinical endocrinology and metabolism 23 23543655
2008 Involvement of Ad4BP/SF-1, DAX-1, and COUP-TFII transcription factor on steroid production and luteinization in ovarian theca cells. Molecular and cellular biochemistry 23 18409030
2000 Identification of novel first exons in Ad4BP/SF-1 (NR5A1) gene and their tissue- and species-specific usage. Biochemical and biophysical research communications 23 11071856
2020 Anti-CD99 scFv-ELP nanoworms for the treatment of acute myeloid leukemia. Nanomedicine : nanotechnology, biology, and medicine 22 32535112
2020 Coordination of Multiple Cellular Processes by NR5A1/Nr5a1. Endocrinology and metabolism (Seoul, Korea) 22 33397036
1998 Molecular cloning and expression of the SF-1/Ad4BP gene in the frog, Rana rugosa. Gene 22 9831646
2020 ELP-dependent expression of MCL1 promotes resistance to EGFR inhibition in triple-negative breast cancer cells. Science signaling 21 33203722
2023 DHX37 and NR5A1 Variants Identified in Patients with 46,XY Partial Gonadal Dysgenesis. Life (Basel, Switzerland) 20 37240737
2022 Sex-specific splicing of Z- and W-borne nr5a1 alleles suggests sex determination is controlled by chromosome conformation. Proceedings of the National Academy of Sciences of the United States of America 19 35074916
2018 Elastin-like Polypeptide (ELP) Charge Influences Self-Assembly of ELP-mCherry Fusion Proteins. Biomacromolecules 19 29791150
2014 Vanin-1 inactivation antagonizes the development of adrenocortical neoplasia in Sf-1 transgenic mice. Endocrinology 19 24712878
2009 Transcriptional Suppression by Transient Recruitment of ARIP4 to Sumoylated nuclear receptor Ad4BP/SF-1. Molecular biology of the cell 19 19692572
1996 SF-1: a key regulator of development and function in the mammalian reproductive system. Acta paediatrica Japonica : Overseas edition 19 8840555
2022 HSF-1: Guardian of the Proteome Through Integration of Longevity Signals to the Proteostatic Network. Frontiers in aging 18 35874276
2011 Coactivation of SF-1-mediated transcription of steroidogenic enzymes by Ubc9 and PIAS1. Endocrinology 18 21467194
2006 Role of transcription factors Ad4bp/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia. International journal of urology : official journal of the Japanese Urological Association 17 16834661
1996 Expression of steroidogenic factor-1 (SF-1) mRNA and protein in the human placenta. Molecular human reproduction 17 9238716
2020 Extension of Survival in Bilaterally Adrenalectomized Mice by Implantation of SF-1/Ad4BP-Induced Steroidogenic Cells. Endocrinology 16 31950150
2011 SF-1 expression during adrenal development and tumourigenesis. Molecular and cellular endocrinology 16 22024498
2010 NR5A1/SF-1 and development and function of the ovary. Annales d'endocrinologie 16 20394914
2000 Transcriptional regulation of the human FTZ-F1 gene encoding Ad4BP/SF-1. Journal of biochemistry 16 10965053
2022 Application of elastin-like polypeptide (ELP) containing extra-cellular matrix (ECM) binding ligands in regenerative medicine. International journal of biological macromolecules 15 35276294
2022 Combinatorial Use of Therapeutic ELP-Based Micelle Particles in Tissue Engineering. Advanced healthcare materials 15 35373501
2020 NR5A1 Gene Variants: Variable Phenotypes, New Variants, Different Outcomes. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 15 32369823
2019 Radiosensitization of HSF-1 Knockdown Lung Cancer Cells by Low Concentrations of Hsp90 Inhibitor NVP-AUY922. Cells 15 31569342
2018 Mutant NR5A1/SF-1 in patients with disorders of sex development shows defective activation of the SOX9 TESCO enhancer. Human mutation 15 30067310
2024 Role of NR5A1 Gene Mutations in Disorders of Sex Development: Molecular and Clinical Features. Current issues in molecular biology 14 38785542
2020 Enantiomer-specific activities of an LRH-1 and SF-1 dual agonist. Scientific reports 14 33335203
2016 Effect of ELP Sequence and Fusion Protein Design on Concentrated Solution Self-Assembly. Biomacromolecules 14 26927835
1998 Pref-1, SF-1 and adrenocortical zonation. Endocrine research 14 9888610

Missed literature

Know a paper Affinage missed for NR5A1? Flag it for the maintainers and the community.

No submissions yet.