WHI5 (Q12416, YOR083W) - curation notes

Working journal for the GO annotation review of S. cerevisiae Whi5. Append; do not rewrite.

2026-09-25 - initial review

Identity and family

• UniProt Q12416, "G1-specific transcriptional repressor WHI5", 295 aa, WHI5/NRM1 family, Pfam
  PF08528 (Whi5), InterPro IPR039198 (Srl3/Whi5) and IPR013734 (TF_Nrm1/Whi5). Features are
  disordered regions (1-171, 249-295) and compositionally biased acidic/low-complexity segments;
  no DNA-binding domain. Thirteen phosphosites recorded (T47, S59, S62, S161, S262 by
  PMID:15210110 plus phosphoproteomics).
• Paralog in S. cerevisiae: Whi7/Srl3 (SGD:S000001799), the second member of PANTHER node
  PTN002000919 that seeds the IBA rows. MBF has its own corepressor, Nrm1.

Core biology (what the gene product does)

• SBF-bound G1/S corepressor. PMID:15210110 PMID:15210110
• Recruited by the transcription factor, not by DNA. PMID:15210111 PMID:19823668
• Mechanism of repression includes HDAC recruitment, redundantly with Stb1. PMID:19745812 PMID:19823668
• CDK antagonism: Cln3-Cdc28 and Pcl9-Pho85 in early/mid G1, Cln1/2-Cdc28 for the feedback
  burst. PMID:15210111 PMID:19823668
• Export is Msn5-dependent, Crm1-independent. PMID:19520826 Re-import involves Ess1 acting on phospho-Ser-Pro
  motifs in the NLS/NES. PMID:24470217
• Size control by dilution. PMID:26390151 whi5 is among the most potent size mutants genome-wide. PMID:12089449
• Caveats worth remembering: whi5 single mutants can show near-normal CLN1/2 RNA in some
  backgrounds because of Stb1 redundancy PMID:19745812; Cln3 has Whi5-independent targets
  PMID:19823669; the dilution model is contested by
  titration/network models (deep research, Ravi et al. 2024; not cached).
• Peripheral 2025 report: whi5 deletion attenuates autophagy and Atg1 phosphorylates Whi5.
  PMID:40365021 Single study, hedged by the authors; treated as non-core.

Annotation decisions and why

• GO:0000082 (8 rows, IEA/IGI/IMP): ACCEPT. Considered MODIFY to GO:2000134 (the term used for
  human RB1) but the comparator check settles it: QuickGO shows GO:2000134 on a single yeast
  gene (YGR250C), whereas SGD puts the whole Start machinery, including the repressors STB1,
  SIC1, RPD3 and SRL3/Whi7, on GO:0000082 involved_in. The obsolete terms GO:0000083 and
  GO:0071930 (regulation of transcription involved in G1/S transition) were checked and are
  not usable. Raised as a suggested question rather than overruling the convention.
• GO:0000122 (5 rows): ACCEPT; core.
• GO:0000978 IBA (sequence-specific DNA binding): MODIFY -> GO:0061629. Whi5 has no DNA-binding
  domain and reaches promoters via Swi4-Swi6; the ChIP occupancy has been read as DNA binding.
  Fallback for a DNA-occupancy row would be GO:0001012, as used for the RB1 IBA in this repo.
• GO:0003712 IBA: ACCEPT (family-level coregulator; Whi5 in its own WITH/FROM is expected).
• GO:0003714 (IDA/IGI/IMP): ACCEPT; core MF.
• GO:0005634 (5 rows): ACCEPT. GO:0005737 (4 rows): KEEP_AS_NON_CORE (exported, inactive pool).
• GO:0006357 (IBA + 2 IGI from PMID:19823668): MODIFY -> GO:0000122; the evidence is
  specifically for repression, and both node members are repressors. Kept consistent across
  evidence codes to satisfy the consistency check.
• GO:0007089 IMP (PMID:26390151): ACCEPT; Whi5 is the inhibitory node of the Start feedback
  loop and its concentration is the integrated variable.
• GO:0008361 HMP: ACCEPT; core physiological output.
• GO:0010508 IMP (PMID:40365021): KEEP_AS_NON_CORE; hedged qualifier in GOA is appropriate.
• GO:0033309 IDA: ACCEPT; GO definition of the SBF complex names Whi5 as an associated protein.
• GO:0061629 IDA: ACCEPT; the informative MF for the Whi5-SBF interaction.
• No NEW terms proposed. A chromatin (GO:0000785) location was considered for core_functions
  on the strength of promoter ChIP but dropped because no GOA row exists and the nucleus term
  plus the SBF complex term already capture the site of action.

Identifier resolution used for WITH/FROM

SGD:S000000038 = CLN3; SGD:S000002214 = MBP1; SGD:S000005952 = PHO85; SGD:S000005253 = STB1;
SGD:S000001799 = SRL3 (Whi7); SGD:S000005609 = WHI5 itself.

Cache status

Abstract-only: PMID:12089449, PMID:14562095, PMID:15210110, PMID:15210111. Full text: PMID:19520826,
PMID:19745812, PMID:19823668, PMID:19823669, PMID:24470217, PMID:26390151, PMID:40365021.
Not cached (cited in deep research only): Skotheim 2008 (positive feedback), Taberner 2009 and
Wagner 2009 (Msn5 export/phosphosites), Travesa 2013 (SBF specificity), Xiao 2024
(hypo/hyper-phosphorylation), Irvali 2023 (reversible Start), Su 2024 (meiotic entry), Ravi
2024 (START-BYCC model).

2026-09-29 - IBA project alignment

Rechecked the five IBA rows against the GOA WITH/FROM traces and the current
IBA review project convention. All are from the same ancestral
PANTHER:PTN002000919 placement over the Whi5/Whi7 family:

• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding is still MODIFY to GO:0061629; the PTN-level assertion
  role-conflates promoter occupancy with sequence-specific DNA binding.
• GO:0006357 regulation of transcription by RNA polymerase II is still MODIFY
  to GO:0000122; the family-level function is repressive, not sign-neutral.
• GO:0003712 transcription coregulator activity, GO:0005634 nucleus, and
  GO:0005737 cytoplasm now have explicit propagation_review blocks.

The extant SGD:S000001799 and SGD:S000005609 entries in GOA are valid
descendant evidence behind the PAINT placement, and Whi5 appearing in its own
WITH/FROM is not circular. Structured source_entities now record the
ancestral PTN plus the curated SGD donors that each IBA row's argument rests
on. The local PTHR28246 cache has PTHR28246-entries.csv but no
PTHR28246-paint.tsv, so the review records that local mirror limitation in
PTN comments rather than treating PTN002000919 as stale. The cytoplasm IBA
is retained as non-core despite its is_active_in qualifier because canonical
SBF corepression is nuclear but the Atg1-Whi5 starvation interaction leaves a
possible noncanonical cytoplasmic activity unresolved.

Search on 2026-09-29 found no newer published S. cerevisiae WHI5 paper that
changes the GO review beyond the already-cached 2025 Atg1/autophagy report
(PMID:40365021). Recent 2024 Start-mechanism papers are already covered by the
Falcon deep-research report as context, the 2025 Whi5/Mug54 paper concerns
fission yeast, and a 2026 SBF/Whi5 chromatin-binding result is still a preprint.