HAP2 (P06774, YGL237C) notes

2026-10-21 — Full re-review, independent of the ProtNLM2 predictions

Context: HAP2 is reviewed as the experimentally characterised reference for transfer to
N. crassa NCU03033 (Q7SGY4). ProtNLM2 outputs were not consulted.

Deep research

just deep-research-falcon yeast HAP2 --fallback perplexity-lite failed: the Edison (falcon)
API returned "Failed to authenticate" (HTTP 403), and the perplexity-lite fallback also
failed. No deep-research file exists. The review is based on the cached abstracts
(all abstract-only) and the curated UniProt record.

Evolutionary grounding

• PANTHER 19 places P06774, Q7SGY4 and human NFYA (P23511) in the same subfamily,
  PTHR12632:SF6 (see HAP2-bioinformatics/RESULTS.md). UniProt/InterPro cross-references show
  only the family PTHR12632 for both proteins.
• PAINT: the IBA rows come from PTN000290575 (MF/BP: GO:0000981, GO:0006357) and
  PTN000290576 (CC: GO:0016602). SGD:S000003206 (HAP2) is a donor to both nodes.
• PAINT propagated only the generic family-level terms (TF activity, regulation of transcription
  by Pol II, CCAAT-binding factor complex). It did NOT propagate the yeast-specific "positive
  regulation" / respiration terms. I treat that omission as deliberate: NF-Y can activate or
  repress, and the respiratory regulon depends on the HAP4 activation subunit.

Experimentally established in S. cerevisiae

• Nuclear localisation of HAP2-lacZ fusion; lexA-HAP2 activates transcription
  PMID:3547076.
• HAP2 and HAP3 associate without DNA to form an activation complex at CYC1 UAS2
  PMID:2832951.
• HAP2/3/5 heterotrimer is required and sufficient for CCAAT binding
  PMID:7828851.
• HAP2 DNA-binding domain: 21 residues; R199L changes specificity; it forms a hybrid DNA-binding domain
  with HAP3 PMID:8223474.
• One-step assembly of Hap2/3/5; Hap4 joins only after DNA binding; Hap4 supplies the activation domain
  PMID:16278450.
• hap2 mutants: cytochromes about 40-50% of wild type, slow growth on glycerol PMID:2182199.

Inferred only (not shown in yeast)

• The generic NF-Y activator/repressor duality; the yeast complex is only shown as an activator.

Protein binding

The five GO:0005515 IPI rows (all with HAP5, Q02516) come from high-throughput two-hybrid/MS screens.
They are removed under the protein-binding policy. The interaction is real, and the
CCAAT-binding factor complex CC term captures it.