toy (twin of eyeless) - curation notes

UniProt: Q9V490 (unreviewed TrEMBL canonical, 543 aa); FlyBase FBgn0019650.
Domains (UniProt/InterPro): N-terminal paired domain (PF00292, IPR001523), paired-type homeodomain
(PF00046, IPR001356); PANTHER PTHR45636:SF41 (PAX6-related). Subcellular location: nucleus (ARBA/ProRule).

Automated deep research failed for this gene (falcon provider returned HTTP 402, OpenAI returned 401),
so these notes are from my own reading of cached PubMed records (publications/) and a web check of
Blanco et al. 2005 full text. No -deep-research-<provider>.md file was produced.

Identity and evolution

• toy is the second Drosophila Pax6 gene, arising by an insect-lineage duplication
  PMID:10198632.
• Toy is closer to vertebrate Pax6 than Ey PMID:10198632.
• The ey/toy redundancy is ancient in arthropods PMID:28993201.

Molecular function: sequence-specific DNA-binding transcription factor

• Directly regulates the eye-specific enhancer of ey PMID:10198632.
• Binds the so10 enhancer of sine oculis at sites distinct from Ey PMID:11830564.
• Binds multiple paired-domain sites at the Clock locus by EMSA PMID:24916389.
• Blanco et al. 2005 (abstract-only in cache; full text checked online): His-TOY binds the chicken
  delta1-crystallin DC5 enhancer in EMSA and, together with SoxN, activates DC5 in S2 cells and in vivo;
  however D-Pax2 is the physiological regulator of DC5 in cone cells
  PMID:15790965.
  This supports a generic Pax6-type DNA-binding TF activity for Toy (IDA for GO:0000981).
• Paired domain of Toy has DNA-binding properties distinct from Ey, and the C-terminal region differs in
  transactivation PMID:15253940.
• Phosphorylated by Hipk in paired domain and C-terminal transactivation domain PMID:29205612.

Biological roles

• Compound eye: acts upstream of ey; required for ey initiation; ectopic Toy induces eyes via Ey
  PMID:10198632.
  Toy can also induce eyes in ey mutants PMID:15253940.
• Eye-antennal disc / head: strong toy mutants are headless PMID:11861484;
  ey+toy together promote proliferation/survival of the whole disc via tsh and eyg PMID:28584125.
• Ocelli (dorsal head simple eyes): toy is the main Pax6 for ocelli; it initiates eya/so in ocellar
  primordium with hh PMID:21104743;
  effect on so is largely eya-mediated PMID:20580700;
  TOY binding sites in so10 are required for ocellus development PMID:11830564.
• Brain: toy mutants show embryonic neuromere and mushroom body defects PMID:19901536.
  Earlier, null/RNAi showed no gross embryonic CNS defects PMID:11335113.
• Circadian pacemaker neurons: regulates Clk in s-LNvs PMID:24916389. Not in GOA; not proposed as NEW (single study; process would be "regulation of gene expression" in a cell type rather than circadian rhythm execution).
• Partial interchangeability with ey PMID:19484263.
• Upstream regulation of toy: oc and salm positive, ems repressive PMID:26976323.

Curation summary

Core: Pol II DNA-binding TF (paired + homeodomain), positive regulator of transcription of eye
determination genes (ey, so, eya); compound eye specification upstream of ey; ocellus development;
eye-antennal disc development. Non-core: brain/mushroom body development, sensory organ morphogenesis.
Generic ARBA terms (post-embryonic development, cell differentiation, system development) and
"DNA-templated transcription" judged over-annotations.