Affinage

SF1

Splicing factor 1 · UniProt Q15637

Length
639 aa
Mass
68.3 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SF1 functions both as a pre-mRNA splicing factor (SF1/mBBP/ZFM1) that recognizes intron branchpoint sequences and as a nuclear receptor transcription factor (NR5A1/SF-1) essential for steroidogenic tissue and hypothalamic development. As a splicing factor, SF1 binds the branchpoint sequence UACUAAC via its KH domain and zinc knuckle, cooperatively associates with U2AF65 to nucleate early spliceosome (E/commitment complex) formation, and recruits U2 snRNP through SURP domain interactions; this cooperative binding is positively regulated by KIS phosphorylation of the SPSP motif and negatively regulated by PKG-I phosphorylation at Ser20 (PMID:9182766, PMID:9512519, PMID:26420826, PMID:16420481, PMID:10449420). SF1 additionally acts as a transcriptional repressor of activated transcription through interactions with EWS-family proteins and the elongation factor CA150 (PMID:9506990, PMID:11604498). As the nuclear receptor NR5A1, SF-1 is essential for gonadotrope LH/FSH expression, adrenal cortex regression (regulated by SUMOylation-dependent Dax1 recruitment), and terminal differentiation of ventromedial hypothalamic neurons including BDNF transcription; its expression is controlled by WT1 and FOXL2 binding at the Sf1 promoter and its target gene selectivity is modulated by Wnt/β-catenin signaling (PMID:11124111, PMID:28893949, PMID:12727442, PMID:27888191, PMID:22128028).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1991 High

    Identifying SF1 as a distinct splicing factor required for early pre-spliceosome assembly established that spliceosome formation depends on a separable activity beyond U2AF and SF3.

    Evidence Chromatographic fractionation of HeLa nuclear extracts with in vitro splicing reconstitution

    PMID:1827409

    Open questions at the time
    • Molecular identity of SF1 was unknown
    • RNA target specificity not determined
    • Relationship to branchpoint recognition unclear
  2. 1996 High

    Cloning SF1 revealed its KH domain and zinc knuckle as RNA-binding modules and confirmed it as the essential activity required for the first ATP-dependent spliceosomal complex.

    Evidence cDNA cloning, baculovirus expression, RNA binding assays, pre-splicing complex assembly

    PMID:8752089

    Open questions at the time
    • Precise RNA recognition site not mapped
    • Relationship to yeast splicing machinery unknown
  3. 1997 High

    Demonstrating that mammalian SF1/mBBP is the ortholog of yeast BBP and specifically recognizes the branchpoint sequence UACUAAC resolved how the branchpoint is identified during early spliceosome formation.

    Evidence Recombinant protein RNA-binding assays, genetic complementation across yeast and mammalian systems

    PMID:9182766

    Open questions at the time
    • How SF1 cooperates with U2AF at the 3′ splice site unknown
    • Regulatory inputs on SF1 function uncharacterized
  4. 1998 High

    Showing that SF1 and U2AF65 cooperatively bind branchpoint-polypyrimidine tract RNA — mediated through U2AF65's third RBD — established the molecular basis of early intron definition at the 3′ splice site.

    Evidence Cooperative RNA binding assays with recombinant proteins, domain deletion mutagenesis

    PMID:9512519

    Open questions at the time
    • Whether this cooperative binding is regulated in vivo unknown
    • Structural basis of the SF1–U2AF65 interface unresolved
  5. 1998 Medium

    Identifying SF1/ZFM1 as a transcriptional repressor that interacts with EWS-family activation domains revealed a splicing-independent nuclear function, raising the question of how dual roles are coordinated.

    Evidence Yeast two-hybrid, GST pulldown, Gal4 fusion transcription repression assays in mammalian cells

    PMID:9506990 PMID:9660765

    Open questions at the time
    • Endogenous transcriptional targets of SF1/ZFM1 repression not identified
    • Whether splicing and transcription functions are mutually exclusive unclear
    • Single-lab findings without independent replication
  6. 1999 High

    PKG-I phosphorylation of SF1 at Ser20 inhibits U2AF65 binding and blocks pre-spliceosome assembly, establishing that early spliceosome formation is subject to signal-dependent kinase regulation in neuronal cells.

    Evidence In vitro kinase assay, S20A/S20T mutagenesis, co-immunoprecipitation, pre-spliceosome assembly assay, cGMP analogue treatment of neuronal cells

    PMID:10449420

    Open questions at the time
    • Endogenous splicing targets affected by PKG-I-mediated regulation not identified
    • Whether other kinases target Ser20 unknown
  7. 1999 High

    Yeast genetic studies revealed that BBP/SF1 is required for commitment complex 2 formation and also retains unspliced pre-mRNA in the nucleus, uncovering a quality-control function beyond catalytic splicing.

    Evidence Temperature-sensitive and cold-sensitive yeast mutants, in vitro spliceosome assembly, in vivo pre-mRNA nuclear export assays

    PMID:10376880 PMID:10775271

    Open questions at the time
    • Mechanism of pre-mRNA retention unknown — whether direct or via spliceosome checkpoint
    • Whether mammalian SF1 also functions in pre-mRNA retention untested
  8. 2000 High

    Demonstrating that extensive SF1 depletion only modestly impairs splicing — primarily slowing U2 snRNP binding — indicated SF1 acts as a kinetic facilitator of U2 snRNP recruitment rather than an absolutely essential catalytic factor.

    Evidence Immunodepletion from HeLa nuclear extracts, in vitro splicing and spliceosome assembly, complementation with recombinant U2AF65

    PMID:10954700

    Open questions at the time
    • Whether essential role is substrate-specific (weak introns) untested
    • Residual SF1 after depletion not quantified to rule out trace sufficiency
  9. 2001 High

    The interaction between SF1/ZFM1 and transcription elongation factor CA150 linked SF1 to RNA polymerase II elongation control, suggesting a mechanistic bridge between splicing factor recruitment and transcriptional regulation.

    Evidence GST pulldown, yeast two-hybrid, domain mutagenesis, transcription repression assays

    PMID:11604498

    Open questions at the time
    • Whether SF1–CA150 interaction occurs co-transcriptionally on endogenous genes unknown
    • No genome-wide target identification
  10. 2001 High

    Pituitary-specific SF-1 conditional knockout demonstrated that SF-1/NR5A1 is cell-autonomously required in gonadotropes for LH and FSH expression, separating its pituitary role from its known adrenal/gonadal functions.

    Evidence Conditional knockout mice (α-GSU-Cre/loxP), hormone measurements, histology, gonadotropin rescue

    PMID:11124111

    Open questions at the time
    • Direct SF-1 target genes in gonadotropes beyond LHβ/FSHβ not comprehensively identified
    • Mechanism of SF-1 action in gonadotrope specification vs. maintenance unclear
  11. 2003 High

    SF-1 knockout mice revealed that SF-1 is required for terminal differentiation of VMH neurons — including BDNF expression and axonal projections — establishing SF-1 as a neuronal terminal differentiation factor beyond its endocrine roles.

    Evidence SF-1 knockout mouse, immunohistochemistry, axon tracing, in situ hybridization

    PMID:12727442 PMID:16917842

    Open questions at the time
    • Direct versus indirect transcriptional targets in VMH neurons not fully resolved
    • Whether SF-1 continues to function in adult VMH neurons beyond development unknown
  12. 2005 High

    In vivo genetic epistasis (Sf1 heterozygous/Dax1 KO double mutants) showed that SF-1 and DAX1 cooperate rather than antagonize for Sertoli cell gene expression, revising the prevailing in vitro model of DAX1 as a pure SF-1 repressor.

    Evidence Double mutant mice, immunohistochemistry, qRT-PCR for Sertoli/Leydig markers

    PMID:15829514

    Open questions at the time
    • Molecular mechanism of cooperation in vivo unknown
    • Whether cooperation is gene-target-specific not systematically tested
  13. 2005 High

    p300-mediated acetylation of SF-1 at the KQQKK motif in response to cAMP enhances DNA binding, providing a post-translational mechanism for signal-dependent activation of steroidogenic gene transcription.

    Evidence In vitro/in vivo acetylation assays, KQQKK mutagenesis, ChIP, co-immunoprecipitation, luciferase reporters

    PMID:16287857

    Open questions at the time
    • Whether acetylation affects interaction with specific co-regulators beyond DNA binding unknown
    • Deacetylase responsible for reversing this modification not identified
  14. 2006 High

    KIS phosphorylation of the SPSP motif enhances SF1–U2AF65 interaction and ternary complex formation, establishing an opposing kinase (relative to PKG-I) that positively tunes early spliceosome assembly.

    Evidence Mass spectrometry, in vitro kinase assay, KIS UHM domain mutagenesis, co-immunoprecipitation, ternary complex assay

    PMID:16420481

    Open questions at the time
    • Endogenous splicing events regulated by KIS-SF1 axis not identified
    • Whether PKG-I and KIS compete at the same SF1 molecules unknown
  15. 2014 High

    FOXL2 directly binds and represses the Sf1 promoter, antagonizing WT1-KTS activation, which — together with the 2016 finding that WT1 represses Sf1 to prevent premature steroidogenic differentiation — defined a promoter-level regulatory circuit controlling Sf1 dosage and gonadal cell fate.

    Evidence ChIP, binding site mutagenesis, Foxl2-null mice, Wt1 conditional KO mice, reporter assays

    PMID:24451388 PMID:27888191

    Open questions at the time
    • How WT1 switches from activator (in one context) to repressor of Sf1 is not mechanistically resolved
    • Chromatin remodeling events at the Sf1 promoter not characterized
  16. 2015 High

    SF1 physically interacts with SURP domain-containing U2 snRNP proteins via a conserved region, directly recruiting U2 snRNP during E complex formation and partially explaining how SF1 accelerates the E-to-A complex transition.

    Evidence Yeast two-hybrid, co-IP from HeLa extracts, mass spectrometry, depleted extract complementation with SF1 deletion mutants

    PMID:26420826

    Open questions at the time
    • Structural basis of SF1–SURP interaction unknown
    • Whether this recruitment is regulated by phosphorylation not tested
  17. 2017 High

    SF-1 SUMOylation enhances Dax1 co-repressor recruitment (without affecting DNA binding), controlling timing of postnatal fetal adrenal cortex regression in vivo, establishing SUMOylation as a mechanism for context-dependent transcriptional switching.

    Evidence SUMOylation-deficient Sf1 knock-in mice, Dax1 KO mice, in vitro binding, FAdE reporter assays

    PMID:28893949

    Open questions at the time
    • SUMO E3 ligase responsible for SF-1 SUMOylation in adrenal cortex not identified
    • Whether SUMOylation regulates SF-1 at other target genes unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how the splicing factor and transcription factor activities of SF1/ZFM1 are coordinated in cells that express both functions, whether specific pre-mRNA substrates are preferentially dependent on SF1 for splicing, and what structural basis underlies the SF1–U2AF65–RNA ternary complex.
  • No structural model of the mammalian SF1–U2AF65–branchpoint RNA ternary complex
  • Genome-wide identification of SF1-dependent splicing events lacking
  • Coordination between SF1 splicing and transcriptional repression functions unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003723 RNA binding 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4
Partners
DAX1EP300EWSR1PRKG1PRPF40BTCERG1U2AF2UHMK1
Complex memberships
E complex / commitment complex (spliceosome)SF1–U2AF65 heterodimer

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Mammalian SF1 (mBBP) is the ortholog of yeast BBP and binds specifically to the branchpoint sequence UACUAAC in pre-mRNA, functioning as a branchpoint binding protein in early splicing complex (E complex) formation. Recombinant protein RNA-binding assays, genetic complementation, E complex assembly Cell High 9182766
1996 Mammalian SF1 is encoded by alternatively spliced variant cDNAs; the protein contains a KH domain and a zinc knuckle mediating RNA binding, and is required for the first ATP-dependent spliceosomal complex formation. SF1 binds RNA directly with preference for G/U-rich sequences. cDNA cloning, baculovirus expression, RNA binding assays, pre-splicing complex assembly assay RNA High 8752089
1991 SF1 (splicing factor 1) functions early in splicing, is essential for pre-splicing complex assembly, and is required for production of spliced RNA; it is distinct from SF3 and U2AF by chromatographic properties and biochemical sensitivities. Chromatographic fractionation of HeLa nuclear extracts, in vitro splicing reconstitution, heat/NEM sensitivity assays The EMBO journal High 1827409
1998 SF1 (mBBP) and U2AF65 cooperatively bind a branchpoint sequence-polypyrimidine tract-containing RNA; the third RBD of U2AF65 is essential for the SF1-U2AF65 protein-protein interaction both in the presence and absence of RNA. Cooperative RNA binding assays with recombinant proteins, domain deletion mutagenesis, gel-shift assays Genes & development High 9512519
1999 SF1 is phosphorylated at Ser20 by cGMP-dependent protein kinase I (PKG-I); this phosphorylation inhibits the SF1-U2AF65 interaction and blocks pre-spliceosome assembly. Ser20 is essential for U2AF65 binding, and phosphorylation of SF1 occurs in neuronal cells in response to cGMP. In vitro kinase assay, site-directed mutagenesis (S20A, S20T), co-immunoprecipitation, pre-spliceosome assembly assay, cGMP analogue treatment of neuronal cells The EMBO journal High 10449420
2006 SF1 is highly phosphorylated in mammalian cells on two serines within an SPSP motif by the kinase KIS; the UHM domain of KIS is required for interaction with SF1 and efficient phosphorylation; SPSP phosphorylation by KIS increases SF1 binding to U2AF65 and enhances formation of the ternary SF1-U2AF65-RNA complex. Mass spectrometry of in-vivo phosphorylation, in vitro kinase assay, domain deletion mutagenesis of KIS UHM, co-immunoprecipitation, ternary complex formation assay The FEBS journal High 16420481
2000 Extensive depletion of SF1/mBBP from HeLa nuclear extracts causes only modest reduction in spliceosome assembly and splicing, primarily affecting the kinetics of U2 snRNP binding; SF1/mBBP has a role in U2 snRNP recruitment distinct from promoting U2AF65 binding. Immunodepletion of SF1 from HeLa nuclear extracts, in vitro splicing and spliceosome assembly assays, complementation with recombinant U2AF65 The Journal of biological chemistry High 10954700
2015 SF1 interacts with SURP domain-containing U2 snRNP proteins (identified by yeast two-hybrid and co-immunoprecipitation from HeLa cells); a short evolutionarily conserved region of SF1 mediates SURP domain interactions. SF1 can recruit U2 snRNP to the spliceosome during E complex formation, and deletion of the SURP-interaction domain of SF1 partially impairs A complex rescue. Yeast two-hybrid, co-immunoprecipitation from HeLa cell extracts, mass spectrometry, SF1-depleted extract complementation with recombinant SF1 deletion mutants Nucleic acids research High 26420826
2001 SF1 (ZFM1) interacts directly with transcription elongation factor CA150 through CA150 WW1 and WW2 domains binding a novel proline-rich motif in the C-terminal half of SF1; this interaction is required for efficient CA150-mediated repression of RNA polymerase II transcription elongation. GST pulldown, yeast two-hybrid, domain mutagenesis, transcription repression assays in mammalian cells Molecular and cellular biology High 11604498
1998 ZFM1/SF1 acts as a transcriptional repressor; it interacts with the transcription activation domain of EWS (Ewing sarcoma protein), TLS, and hTAFII68 by GST pulldown and two-hybrid assays, and overexpression of ZFM1 represses Gal4-EWS-NTD-driven transcription. Yeast two-hybrid, GST pulldown, transcription repression assay in HepG2 cells The Journal of biological chemistry Medium 9660765
1998 ZFM1/SF1 is a transcriptional repressor; it represses activated (not basal) transcription and requires an N-terminal repression domain (first 137 amino acids) plus a GQC-interaction region; it interacts with and represses the SSAP transcription activation domain. Yeast two-hybrid, Gal4 fusion transcription assay in mammalian cells, deletion mutagenesis The Journal of biological chemistry Medium 9506990
1999 In S. cerevisiae, BBP/SF1 (MSL5 gene product) is required for commitment complex 2 (CC2) formation; temperature-sensitive and cold-sensitive mutants block at CC2, and BBP depletion leads to pre-mRNA leakage from the nucleus (up to 40-fold increase), revealing a dual role in nuclear pre-mRNA retention and splicing. Temperature-sensitive and cold-sensitive yeast mutants, in vitro spliceosome assembly assays, in vivo pre-mRNA nuclear export assays The EMBO journal High 10775271
1999 Yeast BBP (SF1 ortholog) is present with Mud2 in commitment complex 2 (CC2) but not CC1, is required for CC2 formation, and is released during transition to the pre-spliceosome; BBP and Mud2 are recycled during spliceosome assembly. Supershift assays, coprecipitation from yeast splicing reactions, genetic depletion of BBP, biochemical fractionation of splicing complexes RNA High 10376880
2005 SF-1 (NR5A1) transcriptional activity is regulated by p300-mediated acetylation at the KQQKK motif in the Ftz-F1 box; cAMP stimulation increases p300 expression, SF-1 association with p300, acetylation of SF-1, and SF-1 DNA-binding activity, and promotes SF-1 colocalization with p300 in nuclear foci. In vitro and in vivo acetylation assays, site-directed mutagenesis of KQQKK motif, ChIP, immunofluorescence, co-immunoprecipitation, luciferase reporter assays Molecular and cellular biology High 16287857
2017 SF-1 SUMOylation, although not directly affecting DNA binding, increases binding of Dax1 to Sf1 to enhance transcriptional repression of the fetal adrenal enhancer (FAdE); Sf1 SUMOylation and Dax1 cooperatively control timing of postnatal fetal adrenal cortex regression. SUMOylation-deficient Sf1 knock-in mice, Dax1 knockout mice, in vitro binding assays, FAdE reporter assays, immunohistochemistry Development High 28893949
2001 SF-1 is essential for pituitary gonadotrope function: pituitary-specific conditional knockout of SF1 (using alpha-GSU-Cre) causes sterility, hypoplastic gonads, and markedly decreased LH and FSH expression, establishing a direct role for SF-1 in gonadotrope cells. Conditional knockout mice (Cre-loxP), hormone measurements by RIA, histology, gonadotropin stimulation rescue experiment Development High 11124111
2003 SF-1 is required for terminal differentiation of ventromedial hypothalamic (VMH) neurons: sf-1 null mice retain VMN precursors but fail to express late VMH markers (BDNF), misexpress NKX2-1, and completely lack projections to the bed nucleus of stria terminalis and amygdala. SF-1 knockout mouse analysis, immunohistochemistry, axon tracing, in situ hybridization Molecular and cellular neurosciences High 12727442
2006 SF-1 regulates BDNF expression in the ventromedial hypothalamus (VMH): SF-1 activates bdnf exon I and IV promoters in cell-based assays; sf-1 heterozygous mice show reduced bdnf I and IV mRNA in the VMH, diet-induced obesity, and impaired sympathetic activity. Sf-1 heterozygous mice, luciferase reporter assays (SF-1 activation of bdnf promoters), qRT-PCR, immunofluorescence colocalization The Journal of comparative neurology High 16917842
1999 Egr-1 interacts directly with both Ptx1 and SF-1, leading to synergistic enhancement of Ptx1- and SF-1-induced LHbeta transcription; GnRH specifically induces Egr-1 (not SF-1 or Ptx1), and this is mediated through PKC activation. Co-immunoprecipitation/direct protein interaction assays, luciferase reporter assays, PKC inhibitors, GnRH stimulation of gonadotrope cells Molecular and cellular biology Medium 10082522
2014 SF1 forms nuclear bodies (CS bodies) that colocalize with Celf3 in neuroblastoma cells; the lncRNA Gomafu sequesters SF1 and Celf3 into separate distinct nuclear bodies, suggesting indirect modulation of SF1/Celf3 splicing function through nuclear compartmentalization. Cross-link RNA precipitation (CLIP), immunofluorescence/confocal microscopy, knockdown of Celf3/Gomafu Genes to cells Medium 25145264
2015 PRPF40B directly interacts with SF1 and associates with U2AF65; PRPF40B colocalizes with SF1 in nuclear speckles; PRPF40B modulates alternative splice site selection and depletion increases Fas receptor expression and apoptosis. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence colocalization, splicing reporter minigene assays, siRNA knockdown with apoptosis readout RNA Medium 25605964
2016 WT1 represses Sf1 expression by directly binding to the Sf1 promoter region; in the absence of Wt1, Sf1 is upregulated and gonadal somatic cells differentiate into steroidogenic cells instead of supporting cells (Sertoli/granulosa), demonstrating that Wt1-mediated repression of Sf1 is required for supporting cell lineage specification. Wt1 conditional knockout mice, chromatin immunoprecipitation, Sf1 promoter reporter assay with WT1 binding site mutagenesis, immunohistochemistry Development High 27888191
2014 FOXL2 transcriptionally represses Sf1 by antagonizing WT1-KTS activation; a conserved FOXL2 binding site in the Sf1 proximal promoter is required for negative regulation; Foxl2-null mice show 2-fold increased Sf1 expression in XX fetal gonads. Luciferase reporter assays, in vitro ChIP, FOXL2 binding site mutagenesis, Foxl2-null mouse qRT-PCR FASEB journal High 24451388
2011 Activation of Wnt/β-catenin signaling inhibits SF1 binding to the Tesco Sox9 enhancer (but not to the Cyp11a1 promoter), thereby blocking Sox9 expression and Sertoli cell differentiation, without altering SF1 mRNA or protein levels. Chromatin immunoprecipitation (ChIP) in male gonad cultures with Wnt/β-catenin activation, gene expression analysis, embryonic gonad culture models Endocrinology Medium 22128028
2001 Cytokine (IL-1β, TNF-α) treatment of vascular smooth muscle cells downregulates ZFM1/SF1 expression; antisense suppression of ZFM1 mimics cytokine-stimulated SMC proliferation and MCP-1/VCAM-1 expression, identifying SF1 as a counter-regulatory factor in smooth muscle cell proliferation. Suppression subtractive hybridization, antisense oligonucleotide knockdown, cell proliferation assays, in vivo atherosclerosis model (immunohistochemistry) The Journal of biological chemistry Medium 11748220
1999 Drosophila SF1 (DmSF1) and C. elegans SF1 (CeSF1) contain an N-terminal RS domain absent in yeast/mammalian SF1; both interact with HsU2AF65 and DmU2AF50; DmSF1 lacking its N terminus is functional in prespliceosome formation in HeLa splicing extracts; CeSF1 is essential for embryonic viability (RNAi lethality). cDNA cloning, interaction assays with U2AF homologs, prespliceosome assembly in HeLa extracts, C. elegans RNAi RNA High 10606272
2008 In budding yeast, BBP (SF1 ortholog) forms a heterodimer with Mud2p (U2AF65 ortholog) without a U2AF35-like third factor; the BBP-Mud2p complex bridges interactions with Prp39p, Mer1p, Clf1p, and Smy2p; the bbpΔ56 mutation impairs branchpoint binding, splicing, and pre-mRNA nuclear retention. Gel filtration, affinity selection, mass spectrometry, yeast two-hybrid, genetic analysis of BBP/MUD2 mutants, pre-mRNA nuclear export assay Nucleic acids research High 18375978
2018 In ovarian granulosa cells, Mdm2 suppresses p53, which in turn transcriptionally controls SF1 expression; conditional Mdm2 deletion in granulosa cells reduces SF1 levels and causes infertility through impaired oocyte maturation, ovulation, and fertilization; this Mdm2-p53-SF1 axis is relevant in human cumulus cells for oocyte quality. Conditional knockout mice (Mdm2-loxP/Pgr-Cre and double Mdm2/p53 knockout), fertility assays, gene expression analysis, human cumulus cell correlation analysis FASEB journal Medium 30260703
2005 SF1 and DAX1 function cooperatively in vivo during testis development: Sf1/Dax1 double mutants show further reduction of Dhh and Amh expression (not rescue), demonstrating cooperation rather than antagonism for these Sertoli cell targets in vivo, despite their known transcriptional antagonism in vitro. Sf1 heterozygous / Dax1 knockout double mutant mice, immunohistochemistry, qRT-PCR for Sertoli/Leydig cell markers Development High 15829514
2017 SF1 and cJUN interact and cooperate to activate the Fdx1 (Ferredoxin 1) promoter in Leydig cells; SF1 is recruited to the Fdx1 promoter region (-124 to -306bp); RNA interference confirms SF1 is essential for Fdx1 transcription while cJUN acts as a cooperative partner. Co-immunoprecipitation, luciferase reporter assays with Fdx1 promoter deletions, ChIP, siRNA knockdown in MA-10 and TM3 Leydig cells The Journal of steroid biochemistry and molecular biology Medium 28274746

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 SF1 and SF2 helicases: family matters. Current opinion in structural biology 758 20456941
1997 The splicing factor BBP interacts specifically with the pre-mRNA branchpoint sequence UACUAAC. Cell 286 9182766
1998 The pan-pituitary activator of transcription, Ptx1 (pituitary homeobox 1), acts in synergy with SF-1 and Pit1 and is an upstream regulator of the Lim-homeodomain gene Lim3/Lhx3. Molecular endocrinology (Baltimore, Md.) 240 9514159
1999 Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with Ptx1 and SF-1 to enhance luteinizing hormone beta gene transcription. Molecular and cellular biology 225 10082522
1998 A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition. Genes & development 213 9512519
1987 Molecular structure of the bilin binding protein (BBP) from Pieris brassicae after refinement at 2.0 A resolution. Journal of molecular biology 200 3430616
2001 Steroidogenic factor 1 (SF1) is essential for pituitary gonadotrope function. Development (Cambridge, England) 180 11124111
2015 DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best practice & research. Clinical endocrinology & metabolism 154 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 151 18987494
1996 Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA. RNA (New York, N.Y.) 148 8752089
2009 Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation. Cancer research 134 19549922
2010 Steroidogenic factor-1 (SF-1, NR5A1) and human disease. Molecular and cellular endocrinology 130 21078366
2000 Expression and subcellular localization of SF-1, SOX9, WT1, and AMH proteins during early human testicular development. Developmental dynamics : an official publication of the American Association of Anatomists 127 10741423
1999 The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly. The Journal of cell biology 110 10085284
2014 Transactivation of micrornA-320 by microRNA-383 regulates granulosa cell functions by targeting E2F1 and SF-1 proteins. The Journal of biological chemistry 107 24828505
2002 Different patterns of anti-Müllerian hormone expression, as related to DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9 expression, in the chick differentiating gonads. Developmental dynamics : an official publication of the American Association of Anatomists 107 12412004
2001 The transcription elongation factor CA150 interacts with RNA polymerase II and the pre-mRNA splicing factor SF1. Molecular and cellular biology 105 11604498
2001 Phenotypic spectrum of mutations in DAX-1 and SF-1. Molecular and cellular endocrinology 105 11738790
2008 Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency. Human mutation 103 17694559
2007 The Sf1-related nuclear hormone receptor Hr39 regulates Drosophila female reproductive tract development and function. Development (Cambridge, England) 103 18077584
1998 Comparisons between the structures of HCV and Rep helicases reveal structural similarities between SF1 and SF2 super-families of helicases. Protein science : a publication of the Protein Society 98 9541392
2009 DSIF, the Paf1 complex, and Tat-SF1 have nonredundant, cooperative roles in RNA polymerase II elongation. Genes & development 95 19952111
1991 Three protein factors (SF1, SF3 and U2AF) function in pre-splicing complex formation in addition to snRNPs. The EMBO journal 94 1827409
1997 Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells. The Journal of biological chemistry 88 9374518
2000 Temperature-dependent sex determination in the American alligator: expression of SF1, WT1 and DAX1 during gonadogenesis. Gene 87 10675033
2000 A dual role for BBP/ScSF1 in nuclear pre-mRNA retention and splicing. The EMBO journal 86 10775271
1998 The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription. The Journal of biological chemistry 84 9660765
1999 Transient interaction of BBP/ScSF1 and Mud2 with the splicing machinery affects the kinetics of spliceosome assembly. RNA (New York, N.Y.) 79 10376880
2003 Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons. Molecular and cellular neurosciences 77 12727442
2001 Mutations in NR0B1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita. Human mutation 76 11748841
1999 Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent protein kinase regulates spliceosome assembly. The EMBO journal 76 10449420
2014 CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin. Molecular metabolism 72 25352999
2011 Fibrinogen is a ligand for the Staphylococcus aureus microbial surface components recognizing adhesive matrix molecules (MSCRAMM) bone sialoprotein-binding protein (Bbp). The Journal of biological chemistry 71 21642438
2005 SF-1 (nuclear receptor 5A1) activity is activated by cyclic AMP via p300-mediated recruitment to active foci, acetylation, and increased DNA binding. Molecular and cellular biology 71 16287857
2016 Wt1 directs the lineage specification of sertoli and granulosa cells by repressing Sf1 expression. Development (Cambridge, England) 70 27888191
2005 Mouse Polycomb M33 is required for splenic vascular and adrenal gland formation through regulating Ad4BP/SF1 expression. Blood 69 15899914
2007 Gonadal expression of Sf1 and aromatase during sex determination in the red-eared slider turtle (Trachemys scripta), a reptile with temperature-dependent sex determination. Differentiation; research in biological diversity 68 17490415
2000 Synergy of SF1 and RAR in activation of Oct-3/4 promoter. The Journal of biological chemistry 68 10692469
2005 Nuclear receptors Sf1 and Dax1 function cooperatively to mediate somatic cell differentiation during testis development. Development (Cambridge, England) 67 15829514
2006 Diminished hypothalamic bdnf expression and impaired VMH function are associated with reduced SF-1 gene dosage. The Journal of comparative neurology 66 16917842
2013 Structure and Mechanisms of SF1 DNA Helicases. Advances in experimental medicine and biology 62 23161005
2015 The plasticizer benzyl butyl phthalate (BBP) alters the ecdysone hormone pathway, the cellular response to stress, the energy metabolism, and several detoxication mechanisms in Chironomus riparius larvae. Chemosphere 61 25725395
2015 Microcystic Stromal Tumor: A Distinctive Ovarian Sex Cord-Stromal Neoplasm Characterized by FOXL2, SF-1, WT-1, Cyclin D1, and β-catenin Nuclear Expression and CTNNB1 Mutations. The American journal of surgical pathology 61 26200099
2007 Mastermind-like domain-containing 1 (MAMLD1 or CXorf6) transactivates the Hes3 promoter, augments testosterone production, and contains the SF1 target sequence. The Journal of biological chemistry 60 18162467
2014 Formation of nuclear bodies by the lncRNA Gomafu-associating proteins Celf3 and SF1. Genes to cells : devoted to molecular & cellular mechanisms 58 25145264
2001 Expression of AMH, SF1, and SOX9 in gonads of genetic female chickens during sex reversal induced by an aromatase inhibitor. Developmental dynamics : an official publication of the American Association of Anatomists 56 11668600
2002 The role of SF1 in adrenal and reproductive function: insight from naturally occurring mutations in humans. Molecular genetics and metabolism 55 12083805
2003 SF1 in the development of the adrenal gland and gonads. Hormone research 54 12566727
2011 Wnt signaling in ovarian development inhibits Sf1 activation of Sox9 via the Tesco enhancer. Endocrinology 53 22128028
2012 JNK-dependent Atg4 upregulation mediates asperphenamate derivative BBP-induced autophagy in MCF-7 cells. Toxicology and applied pharmacology 51 22668848
1999 Tat-SF1 protein associates with RAP30 and human SPT5 proteins. Molecular and cellular biology 49 10454543
2006 Major phosphorylation of SF1 on adjacent Ser-Pro motifs enhances interaction with U2AF65. The FEBS journal 48 16420481
2016 SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise. eLife 47 27874828
2008 Potent, selective and cell penetrant inhibitors of SF-1 by functional ultra-high-throughput screening. Molecular pharmacology 47 18334597
2000 Kinetic role for mammalian SF1/BBP in spliceosome assembly and function after polypyrimidine tract recognition by U2AF. The Journal of biological chemistry 47 10954700
2013 MicroRNA23a and microRNA23b deregulation derepresses SF-1 and upregulates estrogen signaling in ovarian endometriosis. The Journal of clinical endocrinology and metabolism 46 23450049
2015 Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins. Nucleic acids research 43 26420826
2010 Adrenocortical development and cancer: focus on SF-1. Journal of molecular endocrinology 42 20200142
2014 FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during ovarian development in mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 41 24451388
2006 BBP: Brucella genome annotation with literature mining and curation. BMC bioinformatics 41 16842628
2000 Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology 41 10963870
2016 Leptin and insulin engage specific PI3K subunits in hypothalamic SF1 neurons. Molecular metabolism 40 27656404
1999 Splicing factor SF1 from Drosophila and Caenorhabditis: presence of an N-terminal RS domain and requirement for viability. RNA (New York, N.Y.) 38 10606272
2003 Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed patients. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 37 14689056
2002 SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis. Endocrine research 37 12530669
2018 Mdm2-p53-SF1 pathway in ovarian granulosa cells directs ovulation and fertilization by conditioning oocyte quality. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 35 30260703
2018 The pre-mRNA splicing and transcription factor Tat-SF1 is a functional partner of the spliceosome SF3b1 subunit via a U2AF homology motif interface. The Journal of biological chemistry 35 30567737
2008 A BBP-Mud2p heterodimer mediates branchpoint recognition and influences splicing substrate abundance in budding yeast. Nucleic acids research 33 18375978
2001 Transcriptional regulators of steroidogenesis, DAX-1 and SF-1, are expressed in human skin. The Journal of investigative dermatology 32 11886523
2024 Pituitary neuroendocrine tumors with PIT1/SF1 co-expression show distinct clinicopathological and molecular features. Acta neuropathologica 30 38228887
2015 Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF65 and modulates alternative pre-mRNA splicing in vivo. RNA (New York, N.Y.) 30 25605964
2021 BBSome ablation in SF1 neurons causes obesity without comorbidities. Molecular metabolism 29 33722691
1997 Steroidogenic factor-1 (SF-1) and the regulation of expression of luteinising hormone and follicle stimulating hormone b-subunits in the sheep anterior pituitary in vivo. The international journal of biochemistry & cell biology 28 9570145
2023 Multilineage Pituitary Neuroendocrine Tumors (PitNETs) Expressing PIT1 and SF1. Endocrine pathology 27 37268858
2016 The plasticizer BBP selectively inhibits epigenetic regulator sirtuin during differentiation of C3H10T1/2 stem cell line. Toxicology in vitro : an international journal published in association with BIBRA 24 27923775
2007 Increased susceptibility of Sf1(+/-) mice to azoxymethane-induced colon tumorigenesis. Cancer science 24 17900258
1997 The plasticizer benzyl butyl phthalate (BBP) inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary DNA adduct formation and tumorigenesis. Carcinogenesis 23 9276647
1998 Human ZFM1 protein is a transcriptional repressor that interacts with the transcription activation domain of stage-specific activator protein. The Journal of biological chemistry 22 9506990
2021 Copper exposure disrupts ovarian steroidogenesis in human ovarian granulosa cells via the FSHR/CYP19A1 pathway and alters methylation patterns on the SF-1 gene promoter. Toxicology letters 21 34871762
2010 SEDLIN forms homodimers: characterisation of SEDLIN mutations and their interactions with transcription factors MBP1, PITX1 and SF1. PloS one 21 20498720
2004 LBP proteins modulate SF1-independent expression of P450scc in human placental JEG-3 cells. Molecular endocrinology (Baltimore, Md.) 21 15471945
2001 Cytokine-induced down-regulation of zfm1/splicing factor-1 promotes smooth muscle cell proliferation. The Journal of biological chemistry 21 11748220
2017 Timing of adrenal regression controlled by synergistic interaction between Sf1 SUMOylation and Dax1. Development (Cambridge, England) 20 28893949
2016 Gonadotropin and sf-1 regulation of cyp19a1a gene and aromatase activity during oocyte development in the rohu, L. rohita. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 20 26916215
2005 Phosphorylation of p27(BBP)/eIF6 and its association with the cytoskeleton are developmentally regulated in Xenopus oogenesis. Cellular and molecular life sciences : CMLS 20 15990955
2017 BBP-Functionalized Biomimetic Nanofibrous Scaffold Can Capture BMP2 and Promote Osteogenic Differentiation. Journal of materials chemistry. B 19 29250330
2015 The plasticizer BBP selectively inhibits epigenetic regulator sirtuins. Toxicology 19 26520405
1996 SF-1: a key regulator of development and function in the mammalian reproductive system. Acta paediatrica Japonica : Overseas edition 19 8840555
2015 The ribosome biogenesis pathway as an early target of benzyl butyl phthalate (BBP) toxicity in Chironomus riparius larvae. Chemosphere 18 26539713
2013 Neonatal expression of amh, sox9 and sf-1 mRNA in Caiman latirostris and effects of in ovo exposure to endocrine disrupting chemicals. General and comparative endocrinology 18 23747749
2013 Complement regulator C4BP binds to Staphylococcus aureus surface proteins SdrE and Bbp inhibiting bacterial opsonization and killing. Results in immunology 18 24600566
2017 Transcription factors SF1 and cJUN cooperate to activate the Fdx1 promoter in MA-10 Leydig cells. The Journal of steroid biochemistry and molecular biology 17 28274746
2015 Genome-wide identification of SF1 and SF2 helicases from archaea. Gene 17 26456193
2011 Identification of novel SRY mutations and SF1 (NR5A1) changes in patients with pure gonadal dysgenesis and 46,XY karyotype. Molecular human reproduction 17 21242195
2007 Structure and characterization of a novel chicken biotin-binding protein A (BBP-A). BMC structural biology 17 17343730
1996 Expression of steroidogenic factor-1 (SF-1) mRNA and protein in the human placenta. Molecular human reproduction 17 9238716
2015 Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen α. Protein & cell 16 26349459
2014 Influence of BBP exposure on nervous system and antioxidant system in zebrafish. Ecotoxicology (London, England) 16 25239577
2011 SF-1 expression during adrenal development and tumourigenesis. Molecular and cellular endocrinology 16 22024498
2023 Mechanisms of Surfactin from Bacillus subtilis SF1 against Fusarium foetens: A Novel Pathogen Inducing Potato Wilt. Journal of fungi (Basel, Switzerland) 15 36983535