Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Combined Automated Annotation using Multiple IEA Methods.
GOA annotations for S. pombe Epe1
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The fetched GOA line for the contested GO:0032452 IBA annotation propagates histone demethylase activity through PANTHER:PTN000564171 and active JHDM1/KDM2-family source entries.
"UniProtKB O94603 jhd1 enables GO:0032452 histone demethylase activity molecular_function ECO:0000318 IBA GO_REF:0000033 FB:FBgn0037659|MGI:MGI:1338034|MGI:MGI:1354737|MGI:MGI:2443388|PANTHER:PTN000564171|PomBase:SPCC622.16c|SGD:S000000853|UniProtKB:O75151|UniProtKB:Q6ZMT4|UniProtKB:Q8NHM5|UniProtKB:Q9UPP1|UniProtKB:Q9Y2K7|WB:WBGene00017920|ZFIN:ZDB-GENE-030131-9829|ZFIN:ZDB-GENE-050309-32 284812 Schizosaccharomyces pombe (strain 972 / ATCC 24843) GO_Central Putative JmjC domain-containing histone demethylation protein 1 20250412"
OpenScientist hypothesis investigation - Epe1 histone demethylase activity
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OpenScientist recommended removing the GO:0032452 IBA annotation.
"the IBA annotation of GO:0032452 (histone demethylase activity) on Epe1 should be removed"
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OpenScientist traced the contested annotation to the same PANTHER source node present in the fetched local GOA line.
"The IBA annotation on Epe1 derives from PANTHER ancestral node PTN000564171 via GO_REF:0000033."
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OpenScientist's sequence analysis found the Epe1 JmjC active-site triad diverges from the canonical histone-demethylase triad.
"Epe1 has H297-E299-Y370 vs. canonical H-D-H."
A novel jmjC domain protein modulates heterochromatization in fission yeast.
Histone demethylation by a family of JmjC domain-containing proteins.
Swi6/HP1 recruits a JmjC domain protein to facilitate transcription of heterochromatic repeats.
Interaction of Epe1 with the heterochromatin assembly pathway in Schizosaccharomyces pombe.
The JmjC domain protein Epe1 prevents unregulated assembly and disassembly of heterochromatin.
The Cul4-Ddb1(Cdt)² ubiquitin ligase inhibits invasion of a boundary-associated antisilencing factor into heterochromatin.
RNA elimination machinery targeting meiotic mRNAs promotes facultative heterochromatin formation.
Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundaries.
Rapid epigenetic adaptation to uncontrolled heterochromatin spreading.
Epigenetics. Epigenetic inheritance uncoupled from sequence-specific recruitment.
Epigenetics. Restricted epigenetic inheritance of H3K9 methylation.
The 19S proteasome regulates subtelomere silencing and facultative heterochromatin formation in fission yeast.
Anti-silencing factor Epe1 associates with SAGA to regulate transcription within heterochromatin.
Regulation of ectopic heterochromatin-mediated epigenetic diversification by the JmjC family protein Epe1.
The histone chaperone FACT facilitates heterochromatin spreading by regulating histone turnover and H3K9 methylation states.
An H3K9 methylation-dependent protein interaction regulates the non-enzymatic functions of a putative histone demethylase.
Tandemly repeated genes promote RNAi-mediated heterochromatin formation via an antisilencing factor, Epe1, in fission yeast.
Mapping the dynamics of epigenetic adaptation in S. pombe during heterochromatin misregulation.
Bioinformatics Analysis of S. pombe Epe1 Protein
Falcon deep research report on S. pombe Epe1/Jhd1 (UniProt O94603)
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Epe1 is a nuclear, Swi6/HP1-recruited JmjC-family protein that acts as a
negative regulator (anti-silencing factor) of heterochromatin assembly and
spreading, controlling heterochromatin domain stability and epigenetic
variability.
"Epe1 emerges as a **negative regulator (“anti-silencing factor”) of heterochromatin assembly and spreading**, acting at heterochromatin boundaries and within heterochromatin to control domain stability and epigenetic variability."
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Despite being annotated as a putative JmjC histone demethylase, direct in
vitro H3K9 demethylase activity is repeatedly undetectable, and influential
studies propose Epe1's dominant in vivo functions are non-enzymatic,
mediated by Swi6/HP1 interaction.
"While Epe1 is annotated as a putative 2-oxoglutarate/Fe(II) dioxygenase/histone demethylase, **direct in vitro H3K9 demethylase activity is repeatedly difficult to detect**, and several influential studies propose that Epe1’s dominant in vivo functions are **non-enzymatic**, mediated by protein–protein interactions (especially with Swi6/HP1) that antagonize histone deacetylase activity."
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Epe1's JmjC-like motif is non-canonical, lacking conserved Fe(II)-binding
residues, with a histidine-to-tyrosine substitution (Y370) at a position
normally associated with iron coordination in canonical JmjC demethylases.
"Raiymbek et al. (and related mechanistic work) highlight that Epe1 has a **non-canonical HXE…Y motif** and a **histidine-to-tyrosine substitution (Y370)** at a position typically associated with iron coordination in canonical JmjC demethylases."
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Sorida et al. define a separation-of-function: the N-terminal
transcriptional activation (NTA) domain prevents de novo ectopic H3K9
methylation, whereas the JmjC module contributes to removal of established
ectopic heterochromatin in vivo.
"an N-terminal transcriptional activation domain (NTA) can prevent de novo ectopic H3K9 methylation, whereas the JmjC module contributes to removal of established ectopic heterochromatin in vivo"
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Epe1's C-terminus directly binds Swi6 in an H3K9me-stimulated manner and
can disrupt heterochromatin by outcompeting/displacing the histone
deacetylase Clr3, framing Epe1 as a regulator of heterochromatin complex
assembly rather than only an eraser enzyme.
"Expressing Epe1’s C-terminus can disrupt heterochromatin by **outcompeting/displacing the histone deacetylase Clr3** from heterochromatin."
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This S. pombe Epe1/Jhd1 is distinct from the better-known budding-yeast
Jhd1 that demethylates H3K36, confirming the target identity (O94603;
SPCC622.16c).
"This matches the UniProt-provided identity (O94603; SPCC622.16c) and is distinct from the better-known budding-yeast “Jhd1” that demethylates H3K36."
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Epe1 abundance and localization are tuned by nutrient (cAMP-PKA
translational control) and stress (proteasome-dependent N-terminal
truncation to tEpe1) signaling, coupling environmental inputs to
heterochromatin state and adaptive epigenetic drug resistance.
"Stressors (caffeine, azoles) induce **ubiquitylation and proteasome-dependent removal of the N-terminal ~150 residues**, producing **tEpe1**."