Fun19 is a nonessential Saccharomyces cerevisiae SWIRM-domain protein with an inferred nuclear chromatin-regulatory role. Its conserved domain supports chromatin binding, and phylogenetic evidence places it in an Rpd3L-related chromatin-complex lineage with roles in chromatin remodeling and transcriptional regulation. Fun19 and its whole-genome-duplication paralog YOR338W differ from canonical Ada2 proteins in domain architecture and complex context. The precise Fun19 interaction partners, target genes and mechanism of transcriptional regulation remain experimentally unresolved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization is retained as the core inherited compartment of Fun19. Reason: The actual PTHR12374 tree places Fun19/PTN000271934 below the eukaryotic nuclear assertion at PTN000271860 and the fungal chromatin-complex clade. No target-specific loss of nuclear targeting is established. Lack of a direct target localization assay is not a reason to demote an otherwise supported phylogenetic core location. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000271860 · PTN000271860 SUPPORTS TRANSFER Actual treeinfo lineage and the corresponding current PAINT IBD were checked. No target-specific loss of this assertion is established. Direct target experiments are distinguished from inherited function. Supporting Evidence: PMID:16461455 The SWIRM domain is a module found in the Swi3 and Rsc8 subunits of SWI/SNF-family chromatin remodeling complexes, and the Ada2 and BHC110/LSD1 subunits of chromatin modification complexes. |
| GO:0006338 chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: Fun19 is inferred to contribute to chromatin remodeling as a chromatin-complex component. Reason: GO:0006338 is a dynamic reorganization process, not a requirement that every participant be an ATPase. Actual descent from PTN000271860 is verified, and the current node includes Laf1 as well as Ada2 evidence. The retained Rpd3L-Expanded association provides a compatible deacetylase-complex context. Lack of an ATPase or Ada2 ZZ/SANT domains does not refute this broader process. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000271860 · PTN000271860 SUPPORTS TRANSFER Actual treeinfo lineage and the corresponding current PAINT IBD were checked. No target-specific loss of this assertion is established. Direct target experiments are distinguished from inherited function. |
| GO:0003713 transcription coactivator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Transcription coactivator activity is retained as an ancestral Fun19 inference pending mechanism-specific follow-up. Reason: The actual tree retains the positive coactivator assertion from PTN000271860 in the Fun19 branch. Fun19 differs from Ada2 in ZZ/SANT architecture and the fungal clade carries a curated loss of SAGA-type membership, but neither establishes loss of every coactivation mechanism. Coactivator activity can be supplied by different chromatin complexes; absence of a target assay or a donor in the same terminal subfamily is not a negative result. Restore the inherited assertion and seek a focused assessment of functional directionality and conserved interfaces without assuming that the SAGA loss propagates to all regulatory functions. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000271860 · PTN000271860 SUPPORTS TRANSFER Actual treeinfo lineage and the corresponding current PAINT IBD were checked. No target-specific loss of this assertion is established. Direct target experiments are distinguished from inherited function. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of RNA polymerase II transcription is a supported ancestral role of Fun19. Reason: The term does not specify transcriptional activation or SAGA membership. The current tree retains this process at PTN000271860 across the Fun19 clade while separately recording loss of SAGA-type membership. Broad transcriptional regulation remains compatible with its SWIRM and inferred Rpd3-family complex context. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000271860 · PTN000271860 SUPPORTS TRANSFER Actual treeinfo lineage and the corresponding current PAINT IBD were checked. No target-specific loss of this assertion is established. Direct target experiments are distinguished from inherited function. |
| GO:0070210 Rpd3L-Expanded complex | IBA GO_REF:0000033 | ACCEPT | Summary: Fun19 is inferred to be a component of the Rpd3L-Expanded chromatin complex. Reason: The actual target lineage descends from the fungal PTN000271931 assertion seeded by Laf1/Laf2. The GO definition explicitly describes a Saccharomyces cerevisiae complex, contradicting the earlier claim that this term is fission-yeast-specific. The same node has an IRD loss of SAGA-type complex GO:0070461; it does not negate Rpd3L-Expanded membership. Preserve the supported complex inference without asserting a direct Fun19 purification. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000271931 · PTN000271931 SUPPORTS TRANSFER Actual treeinfo lineage and the corresponding current PAINT IBD were checked. No target-specific loss of this assertion is established. Direct target experiments are distinguished from inherited function. |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Chromatin binding is a supported inherited molecular function of Fun19. Reason: The current ancestral chromatin-binding assertion and retained SWIRM domain are concordant. PMID:16461455 directly assays related Swi3/Rsc8 SWIRM modules, not Fun19, and supports the domain mechanism without being misrepresented as a target assay. Missing Fun19-specific measurement does not by itself make the inherited function non-core. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000271860 · PTN000271860 SUPPORTS TRANSFER Actual treeinfo lineage and the corresponding current PAINT IBD were checked. No target-specific loss of this assertion is established. Direct target experiments are distinguished from inherited function. Supporting Evidence: PMID:16461455 the Swi3 SWIRM binds free DNA and mononucleosomes with high and comparable affinity |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | ACCEPT | Summary: Broad gene-expression regulation is compatible with Fun19 chromatin functions. Reason: This existing ARBA assertion is consistent with the independently curated chromatin-binding, Pol-II-regulation and Rpd3-family complex inferences. Breadth does not make a biologically compatible existing term an over-annotation. It remains a computational inference, not an experimental target result. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000108 | ACCEPT | Summary: Positive transcriptional regulation follows the retained coactivator inference. Reason: The inter-ontology assertion derives from GO:0003713. Since actual ancestry retains coactivator activity and no activation-specific loss has been established, the earlier removal of this derived assertion loses its stated basis. Restore it with the same inferential limits and include directionality in the focused mechanistic follow-up. |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root "molecular_function" with the ND (No biological Data available) evidence code correctly records that FUN19 has no experimentally determined molecular function. Reason: ND root annotation accurately reflects that no molecular function has been experimentally established for FUN19; appropriate placeholder for a dark gene. |
| GO:0005575 cellular_component | ND GO_REF:0000015 | ACCEPT | Summary: Root "cellular_component" with ND correctly records the absence of experimental localization data for FUN19. Reason: No subcellular localization has been experimentally determined; the ND root annotation is the correct representation. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root "biological_process" with ND correctly records that no biological process has been experimentally assigned to FUN19. Reason: No biological process is experimentally established for FUN19; the ND root annotation appropriately captures this. |
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Download this section (compressed HTML)Q: Does the FUN19 SWIRM domain bind DNA or nucleosomes in vitro, and with what specificity, as its Swi3/Rsc8 counterparts do?
Q: Is FUN19 a bona fide subunit of an S. cerevisiae chromatin-modifying complex (e.g. a Rpd3/Sin3-type HDAC), by analogy to the fission yeast SF21 relatives laf1/laf2, or does it act independently?
Q: Does FUN19 act redundantly with its whole-genome-duplication paralog YOR338W, such that phenotypes are only revealed in the double deletant?
Experiment: Express and purify recombinant full-length FUN19 and its isolated SWIRM domain and test binding to free DNA and reconstituted mononucleosomes by EMSA and quantitative binding assays, benchmarking against the Swi3 SWIRM domain.
Hypothesis: FUN19's SWIRM domain confers chromatin/nucleosome association.
Type: in vitro DNA/nucleosome binding
Experiment: Affinity-purify endogenously tagged FUN19 from S. cerevisiae and identify co-purifying proteins by mass spectrometry, specifically testing for Rpd3/Sin3- type HDAC or SAGA/ADA subunits, and determine subcellular localization by fluorescence microscopy.
Hypothesis: FUN19 associates with a chromatin-modifying complex in vivo.
Type: affinity purification-mass spectrometry and localization
Experiment: Construct fun19, yor338w single and fun19 yor338w double deletants and profile growth, stress responses (including heat), and genome-wide transcription to reveal phenotypes masked by paralog redundancy.
Hypothesis: FUN19 and YOR338W are functionally redundant paralogs.
Type: genetic (single/double deletion) and transcriptomic analysis
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular activity of FUN19 is unknown. No enzymatic activity, DNA/ nucleosome-binding activity, or binding partner has been demonstrated, and it is undetermined whether FUN19's own SWIRM domain binds DNA/nucleosomes as the Swi3/Rsc8 SWIRM domains do.
OPEN BIOLOGY MF_DARK
What is known: What is firmly established is only the domain architecture: a C-terminal SWIRM domain (residues 316-413; Pfam PF04433) attached to a largely disordered, low-complexity N-terminal region, placing FUN19 in the ADA2/LSD1 SWIRM superfamily.
Significance: A direct Fun19 assay would test and mechanistically refine the curated ancestral chromatin-binding inference; the current inference is not equivalent to absence of functional evidence.
What would resolve it: In vitro DNA/nucleosome-binding assays with recombinant FUN19 (and its SWIRM domain), plus affinity purification / mass spectrometry to identify partners.
Provenance (the field's own admissions):
Gap: The biological process FUN19 participates in is unknown. Family-level annotations point toward chromatin-based transcriptional regulation, but no pathway, target genes, or process have been experimentally linked to FUN19.
OPEN BIOLOGY BP_DARK
What is known: Fun19 is expressed and has a conserved SWIRM domain. Its actual phylogeny retains ancestral regulatory functions while explicitly recording loss of SAGA-type-complex membership in the fungal Fun19/Laf clade; a change of complex does not identify the direction of every transcriptional effect.
Significance: The FUN19 subfamily bridges two opposing chromatin activities in its relatives (acetylation via Ada2, deacetylation via laf1/laf2); resolving which, if either, FUN19 contributes to would clarify the evolutionary fate of a duplicated chromatin-regulatory module in budding yeast.
What would resolve it: Genome-wide expression/chromatin profiling of a fun19 (and fun19 yor338w double) deletant, and testing physical association with Rpd3/Sin3 or SAGA/ADA complex members.
Provenance (the field's own admissions):
Gap: The subcellular localization of FUN19 and its membership (if any) in a defined protein complex are unverified. It is not established whether FUN19 is nuclear, nor whether it is a subunit of any S. cerevisiae Rpd3/Sin3-type or SAGA-type complex.
OPEN BIOLOGYCURATION CC_DARK
What is known: Actual ancestry supports nucleus and Rpd3L-Expanded association, with no direct Fun19 localization/purification assay identified. GO:0070210 explicitly includes budding-yeast architecture; it is not restricted to fission yeast.
Significance: Direct localization and complex isolation would test and refine the retained phylogenetic assertions and define Fun19-specific partners.
What would resolve it: Fluorescent-protein localization of endogenous FUN19 and affinity-purification mass spectrometry to test co-purification with Rpd3/Sin3 or SAGA/ADA subunits.
Provenance (the field's own admissions):
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