Ste11 is an HMG-box DNA-binding transcription factor that is the master regulator of sexual differentiation (mating/conjugation and meiotic entry) in the fission yeast Schizosaccharomyces pombe. It binds sequence-specifically, via its single N-terminal HMG box, to T-rich TR-box elements (consensus TTCTTTGTTY) in the promoters of genes required for mating and meiosis, where it bends DNA and activates RNA polymerase II transcription. Direct Ste11 targets include the mating-type genes mat1-Pc/mat1-Mc, the meiotic master-switch gene mei2, the M-factor pheromone genes (mfm1/2/3), pheromone-pathway genes such as map3, mam2, ste6 and rgs1, and meiotic recombination genes (dmc1/rad24); Ste11 also positively autoregulates its own promoter. Ste11 expression and activity are controlled by nutrient signaling: nitrogen/carbon starvation lowers cAMP and PKA activity, relieving repression of the upstream activator Rst2 and activating the Sty1 SAPK/Atf1 pathway, both of which induce ste11 transcription; the PKA and TORC1 (Tor2) pathways together repress Ste11 by blocking its nuclear accumulation, and Ste11 protein shuttles between the cytoplasm and the nucleus, accumulating in the nucleus upon starvation and pheromone stimulation. Ste11 activity is further gated by phosphorylation: it is a substrate of the meiosis-repressing Pat1/Ran1 kinase (antagonized by the Mei3 pseudosubstrate inhibitor) and a target of the pheromone-pathway MAPK Spk1, and it cooperates with the M-cell HMG-box protein Mat1-Mc to drive M-cell-specific transcription.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. Ste11 is a sequence-specific HMG-box transcription factor that activates RNA polymerase II transcription of sexual-development genes. The phylogenetic (IBA) call is fully supported by direct experimental evidence in S. pombe. Reason: Ste11 is experimentally established as a DNA-binding transcription factor regulating sexual development; this is its central molecular function. Supporting Evidence: PMID:1657709 Schizosaccharomyces pombe ste11 encodes a member of the family of HMG-box proteins. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Ste11 acts as a transcription factor in the nucleus, where it accumulates upon nitrogen starvation and pheromone signaling. The phylogenetic nuclear call is supported by direct experimental localization. Reason: Nucleus is the site of Ste11 transcription-factor activity. Supporting Evidence: PMID:20634885 Under nitrogen deprivation, Ste11-GFP accumulated in the nucleus |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process. Ste11 regulates RNA polymerase II transcription of mating and meiotic genes. The more specific positive regulation term is also annotated and represents the predominant direction of action. Reason: Ste11 is a Pol II transcriptional regulator of sexual-development genes. Supporting Evidence: PMID:1657709 Ste11 protein regulates positively transcription of the following genes required for sexual development: the mating type genes, matP and matM, and the mei2 gene, which is essential for commitment to meiosis. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. Ste11 binds sequence-specifically to TR-box cis-regulatory elements in target-gene promoters. Strongly supported by direct in vitro binding data. Reason: Direct experimental evidence for sequence-specific promoter DNA binding. Supporting Evidence: PMID:1657709 Ste11 protein synthesized in vitro binds specifically to a DNA fragment carrying a 10-base motif TTCTTTGTTY that is an essential cis-acting element for the induction of mei2 and is commonly seen in the upstream regions of the genes inducible by nitrogen starvation. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus localization from UniProt subcellular-location mapping. Consistent with experimental data; the nucleus is where Ste11 functions as a TF. Reason: Supported by experimental localization and TF function. Supporting Evidence: PMID:21879336 Rst2 and Ste11 proteins were induced and localized to the nucleus of sam5 and sam7 mutants even under rich glucose conditions |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasm localization from UniProt subcellular-location mapping. Ste11 shuttles between the cytoplasm and nucleus and is largely cytoplasmic in growing cells; this is a regulatory reservoir rather than its site of transcription-factor action. Reason: Cytoplasmic pool reflects nucleocytoplasmic shuttling and PKA/TOR-mediated nuclear exclusion, not the site of TF function. Supporting Evidence: PMID:20634885 Ste11 shuttles between the nucleus and the cytoplasm. In growing cells, Ste11 is present at low levels and is pancellular. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | HDA PMID:40015273 A comprehensive Schizosaccharomyces pombe atlas of physical ... | ACCEPT | Summary: High-throughput genome-wide chromatin/TF atlas confirming Ste11 binding to RNA polymerase II cis-regulatory regions. Redundant with multiple direct low-throughput annotations of the same term but corroborates the core DNA-binding function. Reason: Genome-scale TF-chromatin atlas confirms sequence-specific promoter binding. Supporting Evidence: PMID:40015273 A comprehensive Schizosaccharomyces pombe atlas of physical transcription factor interactions with proteins and chromatin. |
| GO:0005654 nucleoplasm | EXP PMID:37788281 A dominant negative 14-3-3 mutant in Schizosaccharomyces pom... | ACCEPT | Summary: Nucleoplasm is a refined nuclear localization where Ste11 acts as a TF, consistent with its nuclear accumulation during sexual differentiation. Reason: Refined nuclear (nucleoplasm) location consistent with TF activity. Supporting Evidence: PMID:37788281 A dominant negative 14-3-3 mutant in Schizosaccharomyces pombe distinguishes the binding proteins involved in sexual differentiation and check point. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:11554925 The RGS domain-containing fission yeast protein, Rgs1p, regu... | ACCEPT | Summary: Core molecular function. Ste11 acts as a transcriptional activator; rgs1 was identified as a direct Ste11 target gene whose expression requires Ste11-mediated nitrogen-starvation signaling. Reason: Ste11 activates transcription of target genes such as rgs1. Supporting Evidence: PMID:11554925 rgs1, a member of the Regulator of G-protein Signalling (RGS) family, as a novel Ste11 target gene. rgs1 expression requires both an Ste11-mediated nitrogen starvation signal and the pheromone-induced activation of the Byr2/Byr1/Spk1 MAPK pathway. |
| GO:0031139 positive regulation of conjugation with cellular fusion | IMP PMID:8196631 Analysis of the structural genes encoding M-factor in the fi... | ACCEPT | Summary: Core biological process. Ste11 is required for transcription of the M-factor pheromone (mfm) genes essential for mating, supporting its role in positively regulating conjugation. Reason: Ste11 is required for transcription of mating/conjugation genes; ste11 loss abolishes mating. Supporting Evidence: PMID:8196631 Their transcription is limited to M cells and requires the mat1-Mc and ste11 gene products. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:9233811 Cell differentiation by interaction of two HMG-box proteins:... | ACCEPT | Summary: Direct evidence that Ste11 binds the TR-box cis-regulatory element of the mfm1 promoter; Mat1-Mc enhances Ste11 binding to weak TR-boxes. Core DNA-binding function. Reason: Direct DNA-binding to the mfm1 TR-box cis-regulatory site. Supporting Evidence: PMID:9233811 The Mat1-Mc protein caused a dramatic increase in the DNA-binding of Ste11 to this box |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:9233811 Cell differentiation by interaction of two HMG-box proteins:... | ACCEPT | Summary: Core molecular function. Ste11, cooperating with Mat1-Mc, activates M-cell-specific transcription from TR-box-containing promoters. Reason: Ste11 acts as a transcriptional activator of M-cell-specific genes. Supporting Evidence: PMID:9233811 This regulation requires two HMG-box proteins: the ubiquitous Ste11 transcription factor and the M cell-controlling protein Mat1-Mc. |
| GO:0005515 protein binding | IPI PMID:9233811 Cell differentiation by interaction of two HMG-box proteins:... | MARK AS OVER ANNOTATED | Summary: This IPI annotation (WITH PomBase:SPBC23G7.09 = mat1-Mc) records the physical cooperation between Ste11 and the HMG-box protein Mat1-Mc that promotes Ste11 binding to weak M-cell TR-boxes. Bare "protein binding" is uninformative per curation guidelines; the functional consequence of this interaction is better captured by the RNA polymerase II transcription regulator complex annotation (GO:0090575) from the same paper. Reason: Bare protein binding is uninformative; the biologically meaningful Ste11-Mat1-Mc cooperation is captured by the transcription regulator complex term. Supporting Evidence: PMID:9233811 A DNA fragment containing both the TR- and the M-box allowed the formation of a complex containing both Ste11 and Mat1-Mc. |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:9233811 Cell differentiation by interaction of two HMG-box proteins:... | ACCEPT | Summary: Ste11 acts within a Pol II transcription regulator complex, cooperating with Mat1-Mc on M-cell-specific promoters. Supported by formation of a Ste11-Mat1-Mc-DNA complex. Reason: Ste11 participates in a transcription regulator complex with Mat1-Mc on target promoters. Supporting Evidence: PMID:9233811 A DNA fragment containing both the TR- and the M-box allowed the formation of a complex containing both Ste11 and Mat1-Mc. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:10982411 A zinc-finger protein, Rst2p, regulates transcription of the... | ACCEPT | Summary: Direct evidence that Ste11 binds a TR-box in its own promoter (autoregulation). Core DNA-binding function. Reason: Direct evidence of Ste11 binding the TR box of the ste11 promoter. Supporting Evidence: PMID:10982411 A complete Ste11p-binding motif (TR box) found in the promoter region was necessary for the full expression of ste11, suggesting that Ste11p is involved in the activation of ste11. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:10982411 A zinc-finger protein, Rst2p, regulates transcription of the... | ACCEPT | Summary: Core molecular function. Ste11 positively autoregulates its own promoter and activates target genes, acting as a transcriptional activator. Reason: Ste11 acts as a transcriptional activator, including autoactivation. Supporting Evidence: PMID:10982411 we conclude that transcription of ste11 is under autoregulation in addition to control through the PKA-Rst2p pathway. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:7975894 Mating pheromone-induced expression of the mat1-Pm gene of S... | ACCEPT | Summary: Core biological process. ste11 is required for, and overexpression increases, pheromone-induced mat1-Pm transcription via the TR-box. Strong genetic evidence for positive transcriptional regulation. Reason: ste11 loss abolishes, and overexpression boosts, mat1-Pm expression. Supporting Evidence: PMID:7975894 Almost no expression of mat1-Pm was detected in a ste11 deletion mutant, whereas overproduction of Ste11 greatly increased the expression. |
| GO:0005634 nucleus | IDA PMID:20634885 TOR and PKA pathways synergize at the level of the Ste11 tra... | ACCEPT | Summary: Direct evidence (Ste11-GFP) that Ste11 accumulates in the nucleus upon nitrogen starvation, where it acts as a TF. Core localization. Reason: Direct imaging shows nuclear accumulation of Ste11 under starvation. Supporting Evidence: PMID:20634885 Under nitrogen deprivation, Ste11-GFP accumulated in the nucleus |
| GO:0005737 cytoplasm | IDA PMID:20634885 TOR and PKA pathways synergize at the level of the Ste11 tra... | KEEP AS NON CORE | Summary: Direct evidence that Ste11 is pancellular (including cytoplasm) in growing cells. This reflects nucleocytoplasmic shuttling and nuclear exclusion by PKA/TOR, not a site of transcription-factor activity; the is_active_in qualifier overstates a functional cytoplasmic role. Reason: Cytoplasmic pool is a shuttling reservoir under active PKA/TOR signaling, not the site of TF function. Supporting Evidence: PMID:20634885 In growing cells, Ste11 is present at low levels and is pancellular. |
| GO:0005634 nucleus | IDA PMID:8945514 Molecular mimicry in development: identification of ste11+ a... | ACCEPT | Summary: Nucleus localization consistent with Ste11 TF function. This paper's primary finding is that Ste11 is a substrate of the Pat1/Ran1 kinase (inhibited by the Mei3 pseudosubstrate), an important regulatory input. Reason: Nuclear localization consistent with TF activity. Supporting Evidence: PMID:8945514 the ste11+ transcription factor is a substrate for ran1+ in vitro and that this reaction is directly inhibited by mei3+. |
| GO:0005515 protein binding | IPI PMID:15713656 Constitutive activation of the fission yeast pheromone-respo... | MARK AS OVER ANNOTATED | Summary: This IPI annotation (WITH PomBase:SPAC31G5.09c = spk1) records the physical interaction between Ste11 and the pheromone-pathway MAPK Spk1, which phosphorylates Ste11. Bare "protein binding" is uninformative per curation guidelines; the meaningful relationship is that Ste11 is a kinase substrate regulating meiotic entry. Reason: Bare protein binding is uninformative; the Ste11-Spk1 interaction is a kinase-substrate relationship better described by phosphorylation/meiotic regulation context. Supporting Evidence: PMID:15713656 we show that Spk1 can interact physically with Ste11 and also phosphorylate the transcription factor in vitro. |
| GO:0031139 positive regulation of conjugation with cellular fusion | IMP PMID:15713656 Constitutive activation of the fission yeast pheromone-respo... | ACCEPT | Summary: Core biological process. Constitutive Ste11 expression drives pheromone-gene expression and ectopic meiosis, and ste11 is required for pheromone-induced G1 arrest, supporting its positive role in conjugation. Reason: ste11 is required for pheromone response and conjugation. Supporting Evidence: PMID:15713656 we demonstrate that ste11 is required for pheromone-induced G1 arrest. |
| GO:0003690 double-stranded DNA binding | IDA PMID:1657709 Schizosaccharomyces pombe ste11+ encodes a transcription fac... | ACCEPT | Summary: Direct in vitro binding of Ste11 to a double-stranded DNA fragment carrying the TR-box motif. A correct but more general parent of the sequence-specific Pol II cis-regulatory DNA-binding term. Reason: Direct dsDNA binding demonstrated; correct, though the cis-regulatory sequence-specific term is more informative. Supporting Evidence: PMID:1657709 Ste11 protein synthesized in vitro binds specifically to a DNA fragment carrying a 10-base motif TTCTTTGTTY |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:1657709 Schizosaccharomyces pombe ste11+ encodes a transcription fac... | ACCEPT | Summary: Direct evidence of sequence-specific binding to the TR-box cis-regulatory element of target promoters (e.g., mei2). Core DNA-binding function. Reason: Direct sequence-specific binding to TR-box promoter elements. Supporting Evidence: PMID:1657709 Ste11 protein synthesized in vitro binds specifically to a DNA fragment carrying a 10-base motif TTCTTTGTTY that is an essential cis-acting element for the induction of mei2 |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IMP PMID:1657709 Schizosaccharomyces pombe ste11+ encodes a transcription fac... | ACCEPT | Summary: Core molecular function. ste11 is essential for induction of sexual development genes and its ectopic expression drives uncontrolled mating and sporulation, demonstrating transcriptional activator activity. Reason: ste11 positively activates transcription of sexual-development genes. Supporting Evidence: PMID:1657709 Expression of ste11 is essential for induction of sexual development, and its ectopic expression stimulates uncontrolled mating and sporulation. |
| GO:0031139 positive regulation of conjugation with cellular fusion | IMP PMID:1657709 Schizosaccharomyces pombe ste11+ encodes a transcription fac... | ACCEPT | Summary: Core biological process. ste11 is essential for sexual development including mating/conjugation; loss abolishes and ectopic expression promotes mating. Reason: ste11 is essential for and promotes conjugation/sexual development. Supporting Evidence: PMID:1657709 Expression of ste11 is essential for induction of sexual development, and its ectopic expression stimulates uncontrolled mating and sporulation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:1435723 Functional conservation between Schizosaccharomyces pombe st... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II is the defining, core function of the ste11 HMG transcription factor, supported by extensive experimental evidence (it activates mat-Pc/Pm, mei2, mfm pheromone genes, etc.). This PomBase IMP annotation cites Styrkarsdottir et al. 1992, a study of the pheromone signaling pathway that induces mat1-Pm transcription; our cached abstract foregrounds the upstream kinase ste8 (= byr2) in that pathway, and the full text is not available in our cache. Because the function is unambiguously core for ste11 and PomBase made an experimental (IMP) assignment, the annotation is accepted; we lack the full text to second-guess the curator's choice of evidence. Reason: Positive regulation of Pol II transcription is the core, well-established function of the ste11 transcription factor. The cited PomBase IMP comes from a study of the pheromone-induced mat1-Pm transcription pathway in which ste11 is the master activator; the full text is not in our cache, so we defer to the curator rather than overrule the annotation. (An earlier REMOVE call asserting "wrong gene / name confusion" was based only on the cached abstract and is retracted.) Supporting Evidence: PMID:1435723 the mat1-Pm gene, which is required for entry into meiosis, is expressed in response to a pheromone signal |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:1657709 Schizosaccharomyces pombe ste11+ encodes a transcription fac... | ACCEPT | Summary: Core biological process. ste11 positively regulates transcription of sexual-development genes including the mating-type genes and mei2. Reason: ste11 positively regulates Pol II transcription of mating/meiotic genes. Supporting Evidence: PMID:1657709 Ste11 protein regulates positively transcription of the following genes required for sexual development: the mating type genes, matP and matM, and the mei2 gene, which is essential for commitment to meiosis. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | EXP PMID:10908327 Dmc1 of Schizosaccharomyces pombe plays a role in meiotic re... | ACCEPT | Summary: Ste11 controls induction of the meiosis-specific dmc1/rad24 bicistronic transcript, consistent with sequence-specific binding to its cis-regulatory region. Corroborates the core DNA-binding function. Reason: Ste11 regulates meiotic recombination genes via cis-regulatory binding. Supporting Evidence: PMID:10908327 Induction of the bicistronic transcript is under the control of a meiosis-specific transcription factor, Ste11. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:10908327 Dmc1 of Schizosaccharomyces pombe plays a role in meiotic re... | ACCEPT | Summary: Core molecular function. Ste11 activates the meiosis-specific dmc1/rad24 transcript, acting as a transcriptional activator of meiotic genes. Reason: Ste11 activates transcription of meiotic recombination genes. Supporting Evidence: PMID:10908327 Induction of the bicistronic transcript is under the control of a meiosis-specific transcription factor, Ste11. |
| GO:0044377 RNA polymerase II cis-regulatory region sequence-specific DNA binding, bending | IDA PMID:10867006 Sequence-specific high mobility group box factors recognize ... | ACCEPT | Summary: Direct evidence that Ste11's HMG box bends DNA upon binding its extended minor-groove TR-box motif. A characteristic HMG-box molecular function that contributes to transcriptional activation. Reason: Direct evidence of sequence-specific DNA binding and bending by Ste11. Supporting Evidence: PMID:10867006 The sequence-specific interaction of Ste11 with these 3' base pairs contributes significantly to binding and bending of the DNA motif. |
| GO:0005737 cytoplasm | IDA PMID:21879336 Multistep regulation of protein kinase A in its localization... | KEEP AS NON CORE | Summary: Cytoplasmic localization of Ste11 (PKA-regulated). This represents the shuttling/sequestered pool under active PKA rather than the site of TF action; the is_active_in qualifier overstates a functional cytoplasmic role. Reason: Cytoplasmic pool reflects PKA-dependent nuclear exclusion, not the site of transcription-factor function. Supporting Evidence: PMID:21879336 Rst2 and Ste11 proteins were induced and localized to the nucleus of sam5 and sam7 mutants even under rich glucose conditions |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:8196631 Analysis of the structural genes encoding M-factor in the fi... | ACCEPT | Summary: Core biological process. Ste11 is required for transcription of the M-factor pheromone (mfm) genes, demonstrating positive transcriptional regulation of mating genes. Reason: ste11 is required for transcription of the mfm mating-pheromone genes. Supporting Evidence: PMID:8196631 Their transcription is limited to M cells and requires the mat1-Mc and ste11 gene products. |
| GO:0005634 nucleus | IDA PMID:21879336 Multistep regulation of protein kinase A in its localization... | ACCEPT | Summary: Direct evidence of nuclear Ste11 in PKA-null (sam) mutants, where Ste11 is induced and nuclear even in rich medium. Core localization for TF activity. Reason: Direct evidence of nuclear localization where Ste11 acts as a TF. Supporting Evidence: PMID:21879336 Rst2 and Ste11 proteins were induced and localized to the nucleus of sam5 and sam7 mutants even under rich glucose conditions |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: High-throughput GFP localization assigning Ste11 to the nucleus. Consistent with experimental low-throughput data and core TF function. Reason: High-throughput localization consistent with nuclear TF function. Supporting Evidence: PMID:16823372 ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe. |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: High-throughput GFP localization detecting a cytosolic Ste11 pool. This reflects the shuttling/cytoplasmic reservoir rather than the site of TF action; the is_active_in qualifier overstates a functional cytosolic role. Reason: Cytosolic pool reflects nucleocytoplasmic shuttling, not the site of TF function. Supporting Evidence: PMID:16823372 ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe. |
| GO:0034064 Tor2-Mei2-Ste11 complex | IDA PMID:17046992 Fission yeast Tor2 promotes cell growth and represses cell d... | ACCEPT | Summary: Ste11 is a component of a Tor2-Mei2-Ste11 assembly; Tor2 (TORC1) represses sexual differentiation by interfering with the functions of Ste11 and Mei2. Well-documented regulatory complex membership. Reason: Documented physical/functional association of Ste11 with Tor2 and Mei2 in repression of differentiation. Supporting Evidence: PMID:17046992 This newly revealed function of Tor2 appears to operate by interfering with the functions of the transcription factor Ste11 and the meiosis-promoting RNA-binding protein Mei2. |
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Download this section (compressed HTML)Q: What is the precise composition and stoichiometry of the Ste11-containing transcription regulator complexes at different target promoters (e.g., with Mat1-Mc, Mat1-Pc, Atf1/Pcr1, Mediator)?
Q: How do the Pat1/Ran1 and Spk1 (MAPK) phosphorylation events mechanistically switch Ste11 between inactive and active states during the transition from mating to meiosis?
Experiment: Genome-wide ChIP-seq of Ste11 under vegetative growth, nitrogen starvation and pheromone stimulation to define the complete direct target gene set and TR-box occupancy dynamics.
Experiment: Phospho-site mapping and phosphomutant analysis (Pat1/Ran1 and Spk1/MAPK sites) combined with nuclear-localization and target-gene reporter assays to quantify how each modification gates Ste11 activity and nuclear accumulation.
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