Pax6 (mouse, P63015) curation notes

Provenance / method

• Automated deep research was NOT available for this gene (falcon provider returned HTTP 402, OpenAI 401).
  No -deep-research-<provider>.md file was created. These notes were assembled manually from the cached
  publications in publications/, the UniProt record (Pax6-uniprot.txt) and the completed human
  ortholog review (genes/human/PAX6/PAX6-ai-review.yaml).
• Many cited MGI papers are abstract-only in the cache; for those, the "do not overrule curators" rule was
  applied (developmental IMP rows kept as non-core; UNDECIDED where the abstract does not mention Pax6).

Molecular function

• Paired-box family TF; paired domain sufficient for sequence-specific DNA binding
  PMID:10197584.
• Direct target activation: Mitf RPE promoter PMID:12756174;
  alpha-cell genes MafB, cMaf, NeuroD1 PMID:20592023;
  Sox2 PMID:18287938;
  Six6 with Lhx2 PMID:19146846.
• Genome-wide cortical targets PMID:19521500;
  Pax6-Tbr2-Tbr1 cascade PMID:30186101.
• Repressor activity: PMID:23622063;
  Trap/Acp5 in osteoclast lineage PMID:23990468
  with Grg6/Tle6 PMID:23990468.
• Regulation of Pax6 activity: HIPK2/p300 PMID:16407227;
  Smad3 PMID:17251190 -- NOTE the same paper
  invalidates Smad4 binding PMID:17251190
  -> co-SMAD binding (GO:0070410) REMOVED (human review had accepted an IEA co-SMAD row; disagreement noted);
  Trim11 degradation PMID:18628401;
  SUMOylation of p32 isoform PMID:21084637;
  lncRNA Paupar PMID:24488179.

Isoforms

• Pax6(5a) vs canonical paired domain PMID:15548580;
  PD essential in brain PMID:15548580.
• Paired-less isoform PMID:16464444.

Biological roles (mostly non-core, KEEP_AS_NON_CORE)

• Eye: lens placode PMID:11069887;
  cornea PMID:16080917;
  lacrimal gland PMID:10821755.
• Telencephalon: PMID:11050125;
  PMID:15878992.
• Spinal cord/hindbrain: PMID:9230312.
• Pancreas: PMID:20592023.

Problem annotations

• GO:0003682 chromatin binding IDA PMID:23637604: cached full text is a Candida albicans/Dectin-1 paper with no Pax6 mention -> UNDECIDED, reference flagged WRONG_IDENTIFIER.
• GO:0001933 (PMID:16497297, HSP27), GO:0023019 (PMID:18462699, ER71), GO:0007224 (PMID:18590716, FKBP8), GO:0045665 (PMID:16950124),
  GO:0042462 (PMID:12648492): abstracts do not support the specific Pax6 claim -> UNDECIDED.
• GO:0007601 visual perception: Pax6 Sey-Dey eyeless mice used only as blind controls -> over-annotation.
• GO:0030216 keratinocyte differentiation -> MODIFY to GO:0160122 corneal epithelial cell differentiation.
• protein binding rows -> REMOVE, except Tle6/Grg6 row -> MODIFY to GO:0001222 transcription corepressor binding.

2026-10-12 Ortholog/family audit (human PAX6, DROME ey/toy, DANRE pax6a/pax6b)

• GOA refresh (just fetch-gene mouse Pax6): 266 rows fetched; review already covered all 242 distinct (term, evidence, reference) keys; no new or stale rows. No review actions changed in the mouse file.
• PANTHER: mouse and human both PTHR45636:SF48 (PAX-6); fly ey/toy PTHR45636:SF41. Shared family IBAs (brain/forebrain/retina development, sensory organ development, type B pancreatic cell differentiation) are KEEP_AS_NON_CORE in both mouse and human; core MF (GO:0000981, GO:0000978 accepted) agree across mouse, human, ey and toy.
• Mouse-vs-human contradictions resolved on the human side (human IEA rows are Ensembl projections of the mouse experimental rows):
• GO:0003723 RNA binding: mouse IDA KEEP_AS_NON_CORE (Paupar lncRNA association) vs human IEA REMOVE claiming no experimental support. The human projection derives from the mouse IDA PMID:24488179, so the human row was changed to KEEP_AS_NON_CORE.
• GO:0031625 ubiquitin protein ligase binding: mouse IPI KEEP_AS_NON_CORE vs human IEA ACCEPT. PAX6 is the TRIM11 substrate PMID:18628401; human changed to KEEP_AS_NON_CORE.
• Left as-is: GO:0003682 chromatin binding IDA PMID:23637604 stays UNDECIDED (PubMed confirms this PMID is a Candida albicans/dectin-1 paper, so the MGI row likely carries a wrong PMID; the function itself is accepted from other rows). GO:0007601 visual perception is MARK_AS_OVER_ANNOTATED (mouse IMP) vs KEEP_AS_NON_CORE (human TAS); both express "downstream of eye development, not core", so not harmonised.
• Zebrafish pax6a/pax6b ACCEPT several developmental IBAs that mammals keep as non-core, and pax6a REMOVEs the type B pancreatic cell differentiation IBA that pax6b accepts; flagged for the zebrafish reviewers, not edited here.