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 | MODIFY | Summary: Ada2-like positive coactivator activity should be generalized to sign-neutral transcription coregulator activity for the divergent Fun19/Laf SWIRM-only branch. Reason: PTN000271860 correctly captures Ada2-family coactivator biology, but the Fun19 lineage is a divergent SF21 branch that explicitly lost SAGA-type complex membership and retained only SWIRM, lacking the Ada2 ZZ/SANT architecture used with Gcn5/Ada3 in the SAGA HAT module. The focused report and PMID:36965704 show that the retained SWIRM is a SAGA-HAT tether in Ada2, not an autonomous activation module, while the retained PTN000271931 complex context is Rpd3L-Expanded rather than SAGA. Together this argues that the PAINT placement over-propagates the activation-specific molecular function, but not the sign-neutral transcription coregulator parent retained at the Fun19 leaf. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE COMPARTMENT OR COMPLEX MISMATCH REGULATORY SIGN INVERSION Sources checked: PANTHER:PTN000271860 · PTN000271860 SUPPORTS SOURCE BUT NOT TARGET The source node supports Ada2/SAGA-family coactivator activity, but the Fun19/Laf SF21 branch lost SAGA-type complex membership and Fun19 lacks the Ada2 ZZ/SANT HAT-module effector architecture. Proposed replacements: transcription coregulator activity Supporting Evidence: PMID:36965704 This depletion of just the HAT module proteins from the SAGA complex upon deletion of the Ada2 SWIRM domain indicates that the SWIRM domain plays a central role in tethering all four HAT module subunits to the rest of the SAGA complex. file:yeast/FUN19/FUN19-hypotheses/transcription-coactivation-after-ada2-saga-divergence/openscientist.md Retaining the "docking" piece while losing the "business end" is not a conservative basis for inferring retained activation. |
| 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 | REMOVE | Summary: Positive transcriptional regulation is a derived over-propagation from unsupported Fun19 coactivator activity. Reason: This inter-ontology assertion derives from GO:0003713 coactivator activity. The focused Fun19 report found no direct transcription-activation assay for Fun19 and the comparative evidence now argues against Ada2/SAGA-like coactivation after loss of SAGA-type complex membership, so the positive-direction biological process inherits the same propagation defect. Direction-neutral Pol II regulation remains a plausible PAINT inference. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE REGULATORY SIGN INVERSION Sources checked: GO:0003713 · transcription coactivator activity SUPPORTS SOURCE BUT NOT TARGET The logical positive-regulation inference is appropriate for bona fide transcription coactivators, but the underlying coactivator assignment to Fun19 is rejected for target-specific Ada2/SAGA divergence. Supporting Evidence: file:yeast/FUN19/FUN19-hypotheses/transcription-coactivation-after-ada2-saga-divergence/openscientist.md Retaining the "docking" piece while losing the "business end" is not a conservative basis for inferring retained activation. |
| 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. The literature-search record in FUN19-notes.md finds no study of this S. cerevisiae gene product that identifies a molecular function. Supporting Evidence: file:yeast/FUN19/FUN19-notes.md - **Molecular function**: unknown. No enzymatic activity; no demonstrated binding partner/substrate. |
| 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. The literature-search record in FUN19-notes.md finds no study of this S. cerevisiae gene product that identifies a cellular location. Supporting Evidence: file:yeast/FUN19/FUN19-notes.md - **Cellular localization**: not experimentally established |
| 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. The literature-search record in FUN19-notes.md finds no study of this S. cerevisiae gene product that identifies a biological process. Supporting Evidence: file:yeast/FUN19/FUN19-notes.md - **Biological process**: unknown. No pathway assignment from direct evidence. |
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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):
Non-essential protein of unknown function; expression induced in response to heat stress; FUN19 has a paralog, YOR338W, that arose from the whole genome duplication
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