Stat3 (rat) review notes

Session 1 (2026-10-28)

• just fetch-gene rat Stat3 resolved P52631 (STAT3_RAT, Swiss-Prot reviewed; RGD:3772;
  GeneID 25125). First attempt timed out on UniProt; retry succeeded. 318 GOA rows over 142
  distinct terms.
• No deep research provider available; manual synthesis in Stat3-deep-research-manual.md.
• Key experimental paper PMID:19450559 (Barry et al. 2009) read in full: Stat3
  overexpression protects neonatal rat ventricular myocytes from simulated I/R, Y705F
  dominant-negative enhances death PMID:19450559.
  Supports GO:1900037 regulation of cellular response to hypoxia (IMP) as a non-core,
  context-specific process.

Decisions of note

• Core MF: DNA-binding transcription activator activity, RNA Pol II-specific
  (GO:0001228 / GO:0000981), sequence-specific binding to cis-regulatory elements
  (GO:0000978), homodimerisation (GO:0042803). Core BP: JAK-STAT receptor signalling
  (GO:0007259) and gp130-family cytokine (IL-6) signalling; positive regulation of Pol II
  transcription (GO:0045944).
• PMID:22284190 (NMDAR-LTD) explicitly shows STAT3's role in LTD is independent of nuclear
  action PMID:22284190,
  which contradicts the SynGO row GO:0099527 postsynapse to nucleus signaling pathway.
  Marked as over-annotated rather than removed (curator may have relied on the
  pSTAT3 activation data); flagged for expert review.
• GO:0050804 modulation of chemical synaptic transmission: modified to the specific
  process actually shown, GO:0060292 long-term synaptic depression (is_a descendant via
  regulation of synaptic plasticity, checked with OAK).
• GO:0004879 nuclear receptor activity and GO:0030522 intracellular receptor signaling
  pathway: STAT3 is activated by receptor-associated kinases, not by ligand binding;
  marked as over-annotated.
• GO:0006606 protein import into nucleus: Stat3 is the cargo, not import machinery;
  marked over-annotated.
• Bare protein binding (Rac1, ephrinB1 IPIs) removed per protein-binding policy.
• GO:0035259 nuclear glucocorticoid receptor binding (GOA label says obsolete; OLS still
  lists it) modified to GO:0016922 nuclear receptor binding.
• GO:0045944 does not descend from GO:0010628 positive regulation of gene expression in the
  local GO build, so GO:0010628 rows were kept as non-core rather than modified.
• Physiological/organismal ISO terms (feeding, energy/glucose/temperature homeostasis,
  development) kept as non-core: real in mouse but downstream of the TF activity.
• No NEW terms proposed.

2026-10-28 review-fix pass

• Added structured propagation_review to 33 ISO/IBA rows with MODIFY/MARK_AS_OVER_ANNOTATED actions, derived from each row's reason: TERM_SCOPING_PROBLEM with GRANULARITY_MISMATCH for correct-but-general rows, with ROLE_CONFLATION for process terms STAT3 regulates or is the cargo of (transcription by Pol II, gene expression, proliferation, nuclear import, TGF-beta signalling), and with no failure mode for nuclear receptor activity and intracellular receptor signalling. Sources (mouse Stat3 MGI:103038, human STAT3 P40763, PANTHER PTN000927860) were not re-inspected, and the comments say so instead of asserting a status.
• Removed supported_by self-citations of the gene's own -deep-research-manual.md where a primary citation in the same block already supports the row (the reviewer's own conclusion is not independent evidence). The validator now warns that no annotation cites the deep-research file; that warning is accepted deliberately, which sets the status to DRAFT.