FUN19 (YAL034C) — Curation notes

UniProt: P28003 · SGD: S000002134 · Systematic name: YAL034C · Standard name: FUN19 ("Function UNknown 19")
Organism: Saccharomyces cerevisiae S288C (NCBITaxon:559292)
Length: 413 aa; 47 kDa; non-essential.

This is a genuinely UNDERSTUDIED ("dark") gene. There is no direct experimental
characterization of FUN19 molecular function. The primary deliverable of this review is an
honest knowledge_gaps section plus a domain/orthology-grounded, carefully hedged
description/core_functions.

Journal

2026-07-05 — Initial data gather

KNOWN (well-supported facts)

  1. Non-essential ORF originally of unknown function. FUN19 was defined during the molecular
    analysis of chromosome I. PMID:1583694 and, at the
    time, PMID:1583694 The gene name literally encodes "Function UNknown."

  2. Contains a single SWIRM domain (residues 316–413). UniProt FT DOMAIN 316..413 "SWIRM"
    (Pfam PF04433, PROSITE PS50934, InterPro IPR007526); the rest of the protein (1–315) is
    largely low-complexity/disordered (MobiDB-lite disordered REGIONs 35–55, 189–211, 249–271;
    COMPBIAS low-complexity 35–51, 200–211). RecName in UniProt: "SWIRM domain-containing protein
    FUN19".

  3. What SWIRM domains do (domain-level, general). The SWIRM domain is a ~85-residue four-helix
    bundle with a helix-turn-helix motif found in chromatin-regulatory subunits — Swi3/Rsc8
    (SWI/SNF-family remodelers), Ada2 (SAGA/ADA HAT), and BHC110/LSD1 (KDM1A demethylase).
    PMID:16461455 It can bind DNA/nucleosomes and mediate complex assembly:
    PMID:16461455 and PMID:16461455 So the domain is a strong hint
    toward a chromatin-associated / nucleic-acid-binding role, but it is a shared module that by
    itself does not specify which complex or which activity.

  4. Phosphoprotein (large-scale MS). Phosphorylated at Thr-194, Ser-207, Ser-211
    PMID:18407956 and Ser-207 is a Cdk1 substrate site PMID:19779198. Evidence at protein
    level (UniProt PE 1) — i.e. the protein is expressed. These are proteome-scale, not
    function-specific.

  5. WGD paralog = YOR338W. FUN19 and YOR338W (S000005865) are ohnologs from the whole-genome
    duplication; both are also SF21 "FUN19-related". YOR338W is likewise uncharacterized. (SGD)

  6. Heat-stress-induced expression; non-essential null with mild fitness/chemical-response
    phenotypes     (SGD phenotype summaries). No specific molecular process is implicated.

Orthology / subfamily reasoning (basis for judging the IBA transfers)

PANTHER PTHR12374 splits into:
- SF20 = TRANSCRIPTIONAL ADAPTER 2-ALPHA — the bona fide ADA2 orthologs: S. cerevisiae
ADA2 (Q02336, SGD:S000002856), human TADA2A (O75478), S. pombe ada2 (Q9P7J7), plant/fly ADA2.
These are SAGA/ADA co-activator subunits with SWIRM + ZZ-type zinc finger + SANT/Myb domains.
- SF21 = "SWIRM DOMAIN-CONTAINING PROTEIN FUN19-RELATED" — FUN19 (P28003), its WGD paralog
YOR338W (Q99326), and S. pombe laf1 (O13719) / laf2 (O74443). These are shorter proteins
carrying essentially only the SWIRM module (FUN19 = 413 aa but mostly disordered N-term; laf1
272 aa; laf2 297 aa) — they LACK the ZZ finger and SANT/Myb domains that give ADA2 its SAGA
coactivator identity.

Consequence for the GOA IBA transfers:
- Terms whose with/from cite ADA2 (SGD:S000002856) — "transcription coactivator activity"
(GO:0003713), "chromatin binding" (GO:0003682), "chromatin remodeling" (GO:0006338, also cites
ADA2), "regulation of transcription by RNA Pol II" (GO:0006357, cites ADA2) — are transfers from
the sibling ADA2 subfamily (SF20), NOT from within SF21. FUN19 lacks the ZZ/SANT domains that
underlie ADA2's coactivator activity, so "transcription coactivator activity" in particular is
a likely over-propagation across the subfamily boundary.
- The "Rpd3L-Expanded complex" (GO:0070210) IBA has with/from PomBase laf1 / laf2, i.e.
it IS a within-SF21 transfer. laf1/laf2 have been reported as components of S. pombe SIN3/Rpd3-
type (SIN3L) histone-deacetylase complexes (WebSearch, Two-assembly-modes / SIN3 HDAC
literature). This makes an HDAC-complex association the most biologically defensible of the
propagated terms for FUN19 — although still IBA, not experimental, and not verified in budding
yeast. NOTE: the specific complex "Rpd3L-Expanded" is a fission-yeast complex name; whether
S. cerevisiae FUN19 is part of Rpd3L is unverified (FUN19 is not among the established Rpd3L
subunit set).

Net interpretation: FUN19 is best described as a SWIRM-domain protein of the ADA2/LSD1 chromatin
superfamily whose own molecular function is uncharacterized; the least-unreasonable inference is
a chromatin/nucleosome-associated role (possibly linked to a Rpd3/Sin3-type HDAC module via its
SF21 relatives), but the specific SAGA-type "transcription coactivator" identity of ADA2 should
NOT be transferred wholesale.

NOT known (knowledge gaps — primary deliverable)

Deep research status

Automated deep research was attempted but is unavailable for this review:
- just deep-research-falcon yeast FUN19 --fallback perplexity-lite: falcon timed out
after 600s; the perplexity-lite fallback returned HTTP 401 (insufficient_quota — API
quota exceeded). A subsequent clean falcon retry (just deep-research-falcon yeast FUN19) also hung on the network (0% CPU, ~2s CPU time over >12 min elapsed) and was
terminated.

No -deep-research-{provider}.md file was produced, and none was fabricated. Per project
policy, the review is instead grounded in the UniProt record, the GOA annotations and their
with/from provenance, the PANTHER PTHR12374 family/subfamily data
(interpro/panther/PTHR12374/), and cached primary literature (PMID:1583694, PMID:16461455,
PMID:18407956, PMID:19779198), supplemented by targeted web/PubMed lookups recorded above.

References to cite in review

2026-09-21: full-gene re-review with actual tree and term definitions

All eleven original rows reviewed. Actual PTHR12374 treeinfo lineage places Fun19/P28003 leaf PTN000271934 below both PTN000271860 ancestral nuclear/chromatin/regulatory assertions and fungal PTN000271931 Rpd3L-Expanded assertion. The latter has a separate IRD loss of GO:0070461 SAGA-type complex; there is no corresponding negation of chromatin binding, coactivation or broad Pol-II regulation. Treat that selective loss as a specific evolutionary judgment, not permission to erase every ancestor function.

Current GO:0070210 explicitly describes an S. cerevisiae complex, so the old fission-yeast-only exclusion is false. GO:0006338 describes chromatin reorganization and does not require every participant to contain an ATPase. A SWIRM-bearing structural/regulatory subunit can contribute to a deacetylase/remodeling complex. Restore nucleus, chromatin binding, remodeling, Pol-II regulation, Rpd3L-Expanded membership and the compatible broad gene-expression assertion. Restore coactivator and derived positive-regulation assertions as inherited functions because Ada2 ZZ/SANT/SAGA divergence does not demonstrate loss of every activation mechanism. A neutral focused report is queued to examine directionality and functional interfaces; it does not treat absent target assays or sibling-subfamily donors as refutation.

The 1992 gene-discovery abstract (PMID:1583694) establishes nonessentiality; PMID:16461455 assays Swi3/Rsc8 SWIRM domains, not Fun19; phosphoproteomics establishes expression/modification rather than this regulatory mechanism. All source fields and ND rows are preserved. Core functions explicitly distinguish phylogenetic inference from direct target experimentation. No NEW annotation was needed. Existing notes' categorical rejection statements are superseded by this assessment.

Repository and global OpenScientist cache searches for FUN19, P28003 and YAL034C found no prior report. Tree path, node assertions and current definitions are retained in projects/IBA_REVIEW/rereview-2026-09-20/ecm30-fun19-paint-and-terms.json. Independent reviewer reasoning check confirmed that SAGA loss cannot by itself negate coactivation.